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Who Discovers and Why

Easy Parts and Hard Parts

I’ve been reading George Dyson’s interesting history of Project Orion, the late-1950s attempt to design a spacecraft powered by sequential nuclear explosions. (A borderline crazy idea, it very likely would have worked. The big question became whether it should be allowed to work at all.)

He quotes his father, Freeman Dyson, about the early days of the project:

“Everybody did a little of everything. There was no division of the staff into phgysicists and engineers. The ethos of engineering is very different from that of physics. A good physicist is a man with original ideas. A good engineer is a man who makes a design that works with as few original ideas as possible.”

There’s a lot of truth to that. So in which category is work in medicinal chemistry? The answer isn’t immediately obvious, especially for people just starting out in the business. In graduate school, the emphasis is (rightly) on the pure science: as many original ideas as possible (as long as you can get them to work, one way or another.) So when freshly coined PhDs or post-docs join a drug company, they’re sometimes under the illusion that unusual new chemistry is what’s called for at every opportunity.

And nothing could be further from the truth. From an organic chemistry standpoint, medicinal chemistry can be downright boring. The sooner that new researchers figure that out, the better off they are. You can do perfectly respectable medicinal chemistry using nothing but reactions and ideas from an undergraduate textbook. (As I’ve pointed out, those reactions got to be classics because they tend to work, which is just what you need.)

The point of medicinal chemistry isn’t chemistry; that’s just the means to the end. We do just as much cutting-edge chemistry as we have to, and no more. That stuff takes a lot of time to figure out – and we have plenty of other problems that are waiting to take plenty of our time. The chemistry had better just quietly work for the most part, if you’re going to have a chance.

The original ideas come when it’s time to decide what molecules to make, and when it’s time to figure out why you’re getting the biological effects from them that you are. In those areas, we’ll take all the original thinking that anyone can provide. Any weird brainstorms about how to make a compound more potent or more selective are welcome. And if making those new molecules calls for nothing more than ancient reactions, yawners that bore the pants off everyone who does them, then so much the better: that means that the molecules will be made quickly and in a good quantity. (One of the worst binds you can be caught in is to have a wonderful lead structure that you can’t find a way to make enough of.)

So, when it comes to chemistry, we’re engineers. When it comes to medicines, though, we’d better be the next best thing to poets.