Warren Buffett's pledge of US$37 billion (odd) is said to be the biggest act of philanthropy in history.
It's generous. But He's actually pledged US$1.5 billion per year to the Gates foundation on the priviso that it's spent in the year it's given.
It sounds like Buffett didn't know what to do with his money. I wouldn't exactly know either. I'd be concerned that the money wouldn't be used carefully enough - at this magnitude, a few hundred million tends to get dropped here and there. Look what happened when the US poured cash into Iraq. A lot of it spilt all over the ground. Metaphorically.
But with money of that magnitude, surely something structural can be achieved, rather than a few band-aids. Despite poor aid records for the western world in recent times, government aid dwarfs the Buffet billions. And that's generally band-aid, with some minor structural tinkering (eg micro-loans to women). Curing 20 diseases is laudable, but what if you could put the structures in place such that fundamental issues are addressed more permanently?
Perhaps the Gates Foundation is doing a little of that? I heard one of their briefs was to improve U.S. education outcomes.
First thing I'd do: reverse the tide of false information put out by vested interests regarding global warming. There's surely enough money there to influence world opinion and put the issue at the top of the international agenda.
What other structural changes could be effected with such massive sums? Issues spring to mind such as sanitation, education, biodiversity, over-population, etc. That last one is problematic. The cure for overpopulation has been well proven to be escape from poverty. (people have fewer children as wealth increases.)
But that requires a wholesale redistribution of wealth, and that's a bit trickier. And a bit Marxist.