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September 15, 2005
Pretty Much the Reason You'd Think
I wrote the other day about having a hypothesis in mind when you make new drug analogs (as opposed to just trying a few to see what happens.) A colleague of mine and I were talking about this, and he offered a suggestion about why some people are much more "by the book" than others when it comes to running an analoging program. It's all, he said, about covering your anatomy.
And I think he's right. If you confine yourself to just the sorts of structures that people have had success with before, no one can question your selection. And it's also true that people who insist on a hypothesis behind every new analog also have a strong inclination toward the hypotheses that are already thought to be important (or at least fashionable.) If upper management gets convinced that the smell of your compounds is a key component for clinical success, you can expect these folks to make sure that everything gets made with the sniff test in mind.
So if you're one of these people and your project runs into the ditch - most do, you know - you're still going to be OK. You did everything the way that everyone else thinks that it should be done, and you have concrete reasons to point to if anyone asks you why a particular compound was made. It's an insurance policy.
But if you have some weird ones in there, though, or tried some things that aren't in the usual playbook, the tendency will be to blame those for anything that went wrong. Well, actually, people will blame the person who thought up or OKed these things in the first place - you. I'm not arguing that projects switch over to complete wild-blue-yonder mode, not any more than I think a pot of soup needs a pound of pepper in it. But for seasoning, I think that a drug discovery program needs a small (but real) effort to make some things just because no one's made them. These are the kinds of ideas that go on to breed new projects themselves.
I once came across an analogous effect in the financial world. An article I read about the money management industry pointed out that many fund managers tend to cluster together for safety. If everyone's going up and down roughly in tandem, there's not as much room for irate customers who demand to know why you aren't keeping up. If you buy a million dollars of IBM and it goes down, the author pointed out, people will ask "What's wrong with that IBM?" But if you buy a millions dollars worth of Zarkotronics and it tanks, people will ask "What's wrong with you?"
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