Steve Hardy at Creative Generalist comments on Few and Far Between: Black Swans and the Impossibility of Prediction, a ChangeThis manifesto that I found interesting as well.
Author Nassim Nicholas Taleb says that extreme events are impossible to predict, yet important to understand (in the sense that we don't know what we don't know) and more likely to occur going forward. The world is getting ever more complex.
Though he doesn't mention it explicitly, Taleb would appear comfortable with a very old method of reasoning about the unknown called apophasis, which triangulates knowledge rather than picking it apart directly. As a technique, it's not going to engineer a new propulsion system, map the human genome or predict the future, but it's certainly comfortable with the unknown.
James Surowiecki interviews the author in this brief Wired article. Taleb is also the author of Fooled by Randomness, and a Dean’s Professor in the Sciences of Uncertainty (how's that for a title?) at the University of Massachusetts, Amherst.
I'd be remiss if I didn't mention that Steve has also contributed a manifesto of his own, called, appropriately enough, The Creative Generalist: How Broad Thinking Leads to Big Ideas. Check it out.