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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.”

Risky ideas

Grand Challenges, which targets risky, far-out ideas with potentially huge payoffs, has always represented a small fraction of Gates Foundation spending, which exceeded $3 billion this year.

When the program was conceived, few top scientists were working on global health, Gates said. One of the goals was to draw more people into the field, and on that score, the program has been a clear success. “Many, many smart minds are getting involved,” Gates said.

All of the original projects yielded good science, and many produced new understanding or tools likely to prove valuable down the road. But the foundation estimates only 20 percent are on track to have a real-world impact — a rate Gates said is in line with what he expected going in.

Among his favorite projects is an effort to eliminate Dengue fever by infecting mosquitoes with bacteria that block disease transmission. Another is a spinoff biotech working on a probiotic to cure cholera.

But critics say projects like those demonstrate the foundation’s continuing emphasis on technological fixes, rather than on the social and political roots of poverty and disease.

“The main harm is in the opportunity cost,” said Dr. David McCoy, a public-health expert at Queen Mary University, London. “It’s in looking constantly for new solutions, rather than tackling the barriers to existing solutions.”

The toll of many diseases could be lowered simply by strengthening health systems in developing countries, he said. Instead, programs like Grand Challenges — heavily promoted by the Gates Foundation’s PR machine — divert the global community’s attention from such needs, McCoy argues.

The disconnect between laboratory science and the field was apparent in one of the Grand Challenges projects the foundation largely abandoned. An effort to develop vaccines that don’t need refrigeration yielded good ideas, but it didn’t make sense to commercialize the technology because the entire vaccine-distribution system in Africa is built around the use of refrigeration.

“One element we found very difficult was this translational aspect,” Gates acknowledged.

When several Gates-funded, high-tech toilets were installed in the Indian city of Raichur last year, at a cost of about $8,000 each, residents refused to use them. Many of the other toilet prototypes funded through Grand Challenges are so complex, with solar panels and combustion chambers, they would never prove practical, said Jason Kass, founder of Toilets for People, a company that sells simple, composting toilets to nonprofits in the developing world.

“If the many failed development projects of the past 60 years have taught us anything, it’s that complicated, imported solutions do not work,” Kass wrote in a New York Times Op-Ed entitled “Bill Gates Can’t Build a Toilet.”

But senior program officer Doulaye Koné said the foundation is looking beyond technology this time. The goal is to mass-produce the toilets to bring the price down, then foster a self-sustaining system in which private companies install and service the units for a small fee.

Practical bent

At the anniversary event, Gates vowed to continue backing risky, cutting-edge science — in addition to scores of more traditional research efforts, like work on malaria and AIDS vaccines.

Most of the new Grand Challenges grants also have a decidedly practical bent, with milestones built in and a focus on impact. Many don’t involve new technology at all, including recent calls for better ways to get drugs to people suffering from parasitic infections and to empower women and girls.

More of the new grants are also going to organizations and scientists in the developing world.

Always eager to pull in other players, the Gates Foundation has also exported the Grand Challenges approach. Canada, Brazil and India adopted similar programs, as did the U.S. Agency for International Development.

While the Gates version is still looking for its first home run, some of the spinoffs have already logged modest successes.

Production is expected to start soon on a USAID-backed device invented by an Argentine car mechanic to ease difficult births. And the agency estimates that 5,000 young lives in Nepal have already been saved by a low-cost antiseptic gel used to swab the umbilical cord after birth.

USAID Administrator Raj Shah, a former top Gates Foundation official, said he and his staff applied lessons learned at the foundation to ensure their version would yield payoffs.

“We proudly borrowed the idea,” Shah said. “But we designed our Grand Challenges program to have impact quickly, at scale.”

Sandi Doughton at: 206-464-2491 or