Sandi Doughton
Seven years ago, the Gates Foundation launched an ambitious effort to enlist scientists in solving some of the developing world's most vexing health problems.
The brightest minds brainstormed priorities. More than 1,500 proposals poured in from researchers around the world — including several Nobel laureates.
The 45 winning ideas were dizzying in their variety: From creating more nutritious bananas to developing vaccines that need no refrigeration and credit-card-sized "labs" to diagnose disease in villages with no electricity.
Nearly $460 million later, the foundation isn't exactly pulling the plug on the original Grand Challenges in Global Health program. But recession and a sense of urgency have drained much of Gates' enthusiasm for large, speculative research endeavors.
Most of the projects have used up their money and aren't receiving any more. Many with continued funding are receiving far less than before.
Some disappointed scientists say the loss of funding will slow progress on research that has lifesaving potential — but needs more time to mature.
"It's left most of us a bit frustrated about the whole thing," said Brett Finlay, a molecular biologist from the University of British Columbia. With the $8.7 million his team received to develop medicines that boost the body's general defenses against disease, the researchers discovered a potential drug for a severe form of malaria. "Now we're looking at each other, asking: 'How are we going to take this forward?' "
Foundation officials say the program was an experiment that's simply running its intended course. Most grants were for five years. There was never a guarantee of more funding, although many scientists assumed promising projects would be continued.
At the program's final conference in Seattle last week, Gates Foundation global health Director Dr. Tachi Yamada made it clear the megaphilanthropy approach is sharpening its focus on technologies with the biggest health payoffs and near-term applications.
"We've changed the way we work," he said. "In the very earliest days, honestly I don't know if we knew what we were doing. We were giving away money as fast as we could. ... Now we're trying to be more strategic."
Grand Challenges has always represented a small proportion of the Gates Foundation's spending, which now exceeds $2 billion a year. Much of that money goes to support the Global Fund, which distributes AIDS medications and fights malaria and tuberculosis, and GAVI, which provides childhood vaccines. The foundation also funds tightly focused efforts to develop and test vaccines and drugs for malaria, TB and other diseases.
In fact, vaccines are now the foundation's top priority, Yamada said. And it's not enough to develop something new. It must get to the people who need it — the sooner the better.
Changing strategy
With more than 70 vaccines, drugs and other health technologies in development, the foundation is putting more thought — and money — into what it will take to manufacture those new products affordably, and have them accepted and approved by governments and distributed to people in developing countries.
The hunt is still on for the type of game-changing breakthroughs the Grand Challenges program sought. Instead of committing millions of dollars to megaprojects, however, the foundation now is doling out small grants to lots of researchers, in the hope of spurring innovation. Additional funding follows for ideas that appear to be panning out. The goal of the second-generation program, called Grand Challenges Explorations, is quick results.
"I think they learned a lot from spending a lot of money on big projects, and in some cases it wasn't the right way to go," said University of Washington bioengineer Paul Yager, whose team received $15.4 million to develop lab-on-a-card diagnostics.
Committing large chunks of money over multiple years hampered the foundation's ability to change course quickly or embrace new approaches, said Steve Buchsbaum, deputy director for discovery at the foundation.
As originally conceived, the Grand Challenges program was not geared to churn out useful products, but to break the intellectual log jams that stymie progress in treating disease and improving health care for the world's poorest inhabitants.
The grants were large — some up to $20 million — which helped attract "dream teams" of scientists. The problems were ones traditional research funders passed over as too complex, too risky or too far out — such as building an artificial mosquito nose in an attempt to block the bugs' ability to sniff out human prey.
At the start, Bill Gates said he expected no more than 20 percent of the projects would succeed.
In terms of boosting scientific knowledge, the vast majority were winners, Buchsbaum said. In terms of having a health impact, about one-fifth are "on a pretty clear path in that direction," he said.
But even many of the most successful groups won't see additional money. That includes scientists who set out to develop a powdered, inhalable measles vaccine — and did it.
Measles isn't high on the foundation's priority list today, Buchsbaum said. And since a manufacturer in India may be willing to develop the vaccine, it makes sense for the foundation to step aside, he said.
Commercial support
The foundation always envisioned that many of the projects would receive future funding from other sources, including the private sector, Buchsbaum said. Some collaborations included commercial partners at the start. The scientists who studied the mosquito nose are negotiating with a pharmaceutical company to screen for "confusant" compounds that disorient the bloodsuckers.
One project in which Gates remains invested is development of a genetically engineered banana rich in the essential nutrient vitamin A. The original $4 million grant was followed by $4.5 million to conduct field trials under way in Australia and Uganda.
But a more typical level of follow-on funding is the $500,000 David Kelso received to conduct clinical trials on a dipstick-type test that reveals whether babies born to HIV-infected women have the virus.
"If they've been infected, you can get them into treatment right away," said Kelso, a professor of biomedical engineering at Northwestern University. If trials go well, a company is standing by to distribute the test kits, at a cost of less than $1 each.
Some researchers who now find themselves with no Gates money fear collaborations formed during Grand Challenges will dissolve.
"There clearly were synergies in these bigger projects that won't happen now," said David Sherman, a tuberculosis expert at the nonprofit research lab Seattle BioMed. He was part of a group that received $20 million to develop drugs against the "silent" TB infections harbored by nearly one-third of the world's population.
Their work led to a new understanding of why some people with latent infections get sick while others don't. But it didn't lead to a drug — or any follow-on funding for the team.
Lots of groundwork
Yamada praised the progress made by all of the Grand Challenges researchers. "This was a big, big program for the foundation," he said. "Our ambitions were justified."
But many of the problems tackled were so tough, it was unrealistic to expect solutions in five years, Finlay said. "They really did lay the groundwork" in many areas, he said. "It's a shame they're not going forward."
One of Grand Challenges' original aims was to entice top scientists to work on the developing world's health problems, said Dr. Rick Klausner, the foundation's global health chief when the program started. "It really made global health exciting and sexy ... and captured the imagination of the basic-science community," he said.
Before he received a Grand Challenges grant, Yager hadn't considered the challenge of correctly diagnosing fever in African villages with no health-care facilities. His project led to a prototype "lab-on-a-card" that was passed on to a commercial company.
While he would have liked more Gates funding to improve the product's performance and usefulness, Yager remains committed to the work. His entire lab now is focused on low-cost diagnostics for the developing world.
"I have really drunk the Kool-Aid," he said.
Several other fields, including energy and climate, have adopted the "grand challenges" approach to catalyze research, Klausner noted. And the director of the National Institutes of Health has made global health one of his top five priorities.
But some scientists, having experienced the way Gates can give, then take away, are wary of pinning their research programs to the interests of one very rich man.
"The Gates Foundation has really raised the profile of global health all over the world," one researcher said. "But what happens if Bill Gates comes out tomorrow and says, 'I've just read a book on global warming,' and this whole global-health thing is done?"
Sandi Doughton: 206-464-2491 or sdoughton@seattletimes.com
http://seattletimes.nwsource.com/html/localnews/2013381611_challenges09m.html
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