I've been re-reading Francis Crick's memoir What Mad Pursuit, and this passage struck me:

". . .it is important not to believe too strongly in one's own arguments. This particularly applies to negative arguments, arguments that suggest that a particular approach should certainly not be tried since it is bound to fail. . .While one should certainly try to think which lines are worth pursuing and which are not, it is wise to be very cautious about one's own arguments, especially when the subject is an important one, since then the cost of missing a useful approach is high. . .

Be sensible but don't be too impressed by negative arguments. If at all possible, try it and see what turns up. Theorists almost always dislike this sort of approach."

Right on target. In my field, there is hardly an experiment worth doing that can't be objected to right at the start. Counterexamples abound, theoretical reasons why things won't work out are everywhere. Too sterically hindered, not nucleophilic enough, an interfering functional group somewhere else in the molecule, wrong solvent, wrong catalyst, wrong temperature, wrong everything. If you listen to every one of these objections, even when they're coming from inside your head, you'll never do anything at all. True, you'll never be wrong, but only at the cost of never being right.

This is on my mind tonight, because I'm getting close to a revival of a series of experiments that I've been messing around with for nearly three years now. It's a very interesting idea whose details, painfully, I'm not at liberty to lay out. Not yet. I'm reposting my writings on this work over in the Birth of an Idea category at the right, in case you're interested in seeing what scientific excitement does to a person.

The whole time, I've hardly had the tiniest bit of experimental success, it pains me to say. But I'm back with another variation. Every time I'm more sure that things are going to work. Perhaps, after two years of being quite wrong, I might make the switch to quite right. . .