Here's how I guarantee they will not make a "breakthrough": Almost half of their awardees are already Howard Hughes Investigators, and all of them appear to be senior faculty at very well funded institutions. My point being that they already have a shitload of money. If you want a breakthrough you have to throw money at young people with ideas but no cash who are willing to work their asses off to prove that they belong with the big boys. Maybe Zuckerberg and Brin forgot that their companies were founded by young people.