When he took the stage this fall to celebrate the 10th anniversary of his signature global health research initiative, Bill Gates used the word “naive” — four times — to describe himself and his charitable foundation.

It was a surprising admission coming from the world’s richest man.

But the Microsoft co-founder seemed humbled that, despite an investment of $1 billion, none of the projects funded under the Gates Foundation’s “Grand Challenges” banner has yet made a significant contribution to saving lives and improving health in the developing world.

“I was pretty naive about how long that process would take,” Gates told a gathering of nearly 1,000 people in Seattle.

Launched with fanfare a decade ago, the original Grand Challenges program mobilized leading scientists to tackle some of the toughest problems in global health. Gates handed out nearly half a billion dollars in grants to 45 “dream teams” of researchers working on everything from tuberculosis drugs and new vaccine strategies to advanced mosquito repellents and bananas genetically engineered to boost nutrition.

But five years in, Gates said he could see that it would be at least another decade before even the most promising of those projects paid off.

Not only did he underestimate some of the scientific hurdles, Gates said. He and his team also failed to adequately consider what it would take to implement new technologies in countries where millions of people lack access to basic necessities such as clean water and medical care.

While continuing to support a handful of the “big science” projects, the foundation in 2008 introduced a program of small, highly focused grants called Grand Challenges Explorations.

With headline-grabbing goals like condoms that feel good and waste-to-energy toilets, the explorations initiative has probably garnered more media attention than anything else the giant philanthropy has undertaken.

But none of those projects has yet borne fruit, either.

At the 10th anniversary meeting, Nobel Prize-winning biologist Harold Varmus urged a foundation known for its obsession with metrics to undertake a critical evaluation of Grand Challenges.

“Was the program actually a success?” asked Varmus, who served on the founding board. “We don’t know.”