I've always wished I had big chewy problems like this to work on, in the way de Grey does... something I can think about, make some progress with, and then put aside and come back to later. Many great scientific thinkers (Feynman, Hawking, Erdos, etc.) spend hours just thinking about problems, turning them in their heads, nibbling away at the bits they can deal with...
I've never been one to work that way. I'm way more of a "flash of brilliance" kind of guy... I set myself up to address a problem, look at it, weigh options, and BAM, have the solution. Then I do it. (Much of my experience with this is physical things. How do I rearrange the bathroom plumbing to make room for a larger tub? Or what order should I put in the wiring, insulation, and wallboard, to make sure everything lines up right?)
The difference, as I see it, is they are working on big problems that require many smaller solutions, to get to the solution to the Big Problem. They chew on it for months, years, decades. They can pick up where predecessors have left off.
The kinds of problems I think about are more atomic: they solve a specific issue, but are not a part of a bigger solution I am working towards.
If I went back and did it all over again, I'd probably spend more time on maths. Probably.