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Modeling the Brain?

That neuroscience business came up, I guess, because I have a minor background in it. I broke into the drug business doing work on schizophrenia, and followed that with several years on Alzheimer’s.

If some of the people in the field read this – well, don’t take it the wrong way – but I’d almost as soon have a job breaking concrete with my nose. The central nervous system is a very, very hard area to work in. That’s partly because brain function is hideously complex: it’s an interesting question whether a human brain even has enough ability to comprehend its own workings. But it’s partly because a key part of the drug-testing cascade is often missing.

That’s animal testing. (And it really is a key part – eventually I’ll get into it with the anti-in vivopeople, and I’ll argue that position as long as it takes.) The problem with many central nervous system targets is that the animal models either don’t exist, or (even worse) exist but are untrustworthy. That last situation is a killer: the models persist because there is a constituency that believe in their relevance. You’ll be running into those folks over and over if you try to do without, and they’re going to refuse to believe in your drug candidate unless it’s been through the wildebeest swim maze, the platypus tail flick assay, whatever.

The models are so hard because you’re often trying to affect behavior that is unique to humans – like remembering phone numbers. Whether a rat can remember not to run into the electrified part of the cage is of doubtful relevance. I think that there are many kinds of memory storage, and I don’t believe that rats partake of the kinds that we’re most worried about. It’s true that there must be common molecular mechanisms for all types of memory (at some level) but messing with those processes indiscriminately (the only way we know how, in many cases) is a recipe for trouble. Let’s not even get started on the topic of animal models for schizophrenia.

There’s been a lot of progress in Alzheimer’s the last two or three years. I enjoy reading about it, and I wish everyone working there all the luck in the world. I may need your compounds some day, guys, so keep banging away. But I’m glad that I’m not having to bang away with you.