I-5 as a metaphor for targets in drug development

All opinions are my own and not necessarily those of my employer.

Yesterday a jack-knifed FedEx truck heading south on I-5 crashed as it passed Seattle’s downtown.  Traffic backups spread for miles north, and spilled onto all the other routes leading from the north of the city.  Tens and maybe hundreds of thousands of people had their days disrupted.  My commute, which should have taken 15 minutes, took most of an hour.  It occurred to me, as I sighed and listened to KUOW, that the situation was a nice metaphor for how I’ve been thinking about drug development lately.

We work to discover targets that will have a substantial effect on human biology, hopefully in the direction of improved health.  But health is a complex phenotype, arising from a network of interactions at all kinds of levels–molecular, cellular, physiological.  One thing we know from network theory is that interconnected networks are stable and redundant.  Seattle, or any city, is also a network of networks, and for the most part damaging one part of the network (pothole repair in Ballard, say) might cause some local effects but no real change to the overall phenotype. But there are a few nodes, like I-5, that can have a substantial effect on the whole when something happens to affect  them.

I’m starting to think of drug targets this way.  We talk about finding better targets with fewer side effects, but I wonder if that’s possible.  It’s kind of a yin-yang thing.  Any gene with a large enough effect when targeted  to disrupt the networks and subsequently the phenotype will by its nature have multiple effects.  I’m probably wrong, but it will be interesting to see what new drugs and new approaches come out in the years ahead.

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