As a computational biologist, I'm not so confident that Simons can make a huge impact in my field. At best, I would expect his institute to find a niche and impact on the scale of a typical lab, but this pales in comparison to, say, the Broad institute which is a better peer with the Flatiron, what with lavish funding and a distinctive research philosophy than following NSF/NIH grants.

He prefers problems that aren't hopelessly complicated, but I suspect this is exactly where computational biology falls into if you don't have the ability to perform causal experiments. And wet lab experiments aren't being funded by the Flatiron.