Gates said he was startled to learn some years ago that half a million children die each year from rotavirus, which causes severe diarrhea and dehydration in infants. He said he was even more shocked to discover that vaccines and treatments that could prevent millions of deaths around the world weren't being pursued because they weren't problems for rich countries.

The latest amount brings to $450 million the Gates Foundation will award researchers to tackle 14 specific public-health challenges in developing countries -- challenges ranging from the development of vaccines that need no refrigeration to creating a single staple crop to help alleviate malnutrition.

Microsoft Chairman Bill Gates announced the grant yesterday at the annual World Health Assembly in Geneva, Switzerland. The Gates Foundation committed the initial $200 million in 2003 to its Grand Challenges in Global Health, an initiative to fight diseases that, while uncommon in rich nations, kill millions of people in poor countries. The foundation expects to award the first of the $450 million worth of grants late next month.

Gates said that science and technology can be harnessed to achieve more groundbreaking advances in global health over the next decade than in all of the past 50 years.

"We are on the verge of taking historic steps to reduce disease in the developing world," Gates said. "I believe we can do this, and if we do it will be the best thing humanity has ever done."

The Gates Foundation's Grand Challenges are modeled after a call by the German mathematician David Hilbert, who in 1900 listed the two-dozen greatest unsolved problems in mathematics. In 2003, an international panel of scientists culled 14 modern Grand Challenges in global health from hundreds of ideas submitted from around the world.

Since then, some 1,500 proposals to tackle the 14 problems have been submitted from more than 70 countries; nearly 450 scientists have been asked to submit grant proposals.

The Grand Challenges initiative is administered jointly by the Gates Foundation and the Foundation for the National Institutes of Health.

Gates said he was startled to learn some years ago that half a million children die each year from rotavirus, which causes severe diarrhea and dehydration in infants. He said he was even more shocked to discover that vaccines and treatments that could prevent millions of deaths around the world weren't being pursued because they weren't problems for rich countries.

Gates said that he and his wife, Melinda, decided to make erasing this inequity a priority in their giving. Their foundation's largest grant recipient is the Global Alliance for Vaccines and Immunization, which has received a total of $1.5 billion to promote childhood immunization in developing countries.

The Gates Foundation approach to the world's health problems has its critics.

A recent article in The Lancet, a respected British medical journal, criticized the premise that a Grand Challenge to scientific and technological know-how is the best route to combating malaria, HIV/AIDS, tuberculosis and other diseases that kill millions of people each year.

Anne-Emanuelle Birn, an associate professor with the department of public-health sciences at the University of Toronto, argued that many of the 14 Grand Challenges failed to incorporate economic, social and political context in seeking solutions and were shortsighted and even potentially harmful.

For instance, Birn said, developing single-dose or needle-free vaccines might reduce the number of well-baby visits, which are essential for monitoring a child's growth. Or developing a genetic or chemical strategy to wipe out mosquitoes or other disease-carrying insects might make extending clean water and sanitation services to poor areas less urgent, he said.

Birn urged Gates to adopt a broader approach to global health problems than just searching for a scientific solution.

In his speech in Geneva, Gates was unapologetic about his foundation's focus on health breakthroughs.

He noted that some patients with AIDS used to take 20 pills daily; now they might take three.

"Today, we have tuberculosis drugs that you have to take for nine months," he said. "Why can't we find one that works in three days?

"Some point to the better health in the developed world and say we can only improve health when we eliminate poverty. And eliminating poverty is an important goal. But we have a different view. The world didn't have to eliminate poverty in order to eliminate smallpox -- and we don't have to eliminate poverty before we reduce malaria."

Ann Marie Kimball, professor of epidemiology at the University of Washington, said legitimate debate exists about the Gates Foundation approach. But she said any criticisms should not overshadow its deep financial commitment to often-neglected parts of the world.

"The fact that these investments are being made is extraordinarily important," Kimball said.

Since its creation in January 2000, the Gates Foundation has pledged nearly $8 billion in grants for global health, education and public libraries as well as community programs in the Pacific Northwest. The foundation, the world's largest, has nearly $29 billion in endowments, bankrolled by the Gateses' Microsoft stock.

By law, U.S. foundations are required to give away at least 5 percent of their assets each year, which for the Gates Foundation totals $1.5 billion annually.