A better banana and a less-toxic cassava, childhood vaccines hidden in spores and drunk with fruit juice, mice that develop AIDS and many other exotic dreams of public health scientists will share $437 million in grant money, the William and Melinda Gates Foundation announced yesterday.
The 43 projects were the winners of a competition announced by Mr. Gates two years ago to find new ways to attack the greatest health challenges facing people in poor countries; the contest attracted 1,500 proposals from 70 countries.
The projects, which will get five-year grants of up to $20 million each, are "very visionary and very, very high risk," said Dr. Richard D. Klausner, a former director of the National Cancer Institute who now runs the Gates Foundation's global health program. "But if any of them are successful, it will be well worth the investment."
The foundation, which in just a few years has become one of the driving forces in global health, has in the past given grants of $1.5 billion to help existing vaccines reach more of the world's children, $150 million to find a malaria vaccine, $127 million to find an AIDS vaccine and $200 million to stop the spread of AIDS in India.
In this case, the 14 goals that the foundation wanted scientists to pursue included: vaccines that need no refrigeration and can be given without needles; vaccines that create immunity with one dose and are safe for newborns; new ways to kill or cripple mosquitoes; more nutritious staple crops; better animal models for human diseases; blood tests that can be done in villages without electricity; and new ways to attack diseases like tuberculosis and hepatitis when they are dormant.
As part of receiving a grant, the researchers are allowed to patent anything they invent, but they must guarantee that it will be made available to poor countries at low cost or free.
The Gates grants are "an exceptional commitment to global health research," said Dr. Timothy Evans, assistant director general for policy at the World Health Organization. "One shouldn't expect results this year or next, but in 10 or 15 years, I'd expect very interesting results that could transform the way we think about vaccines, diagnostics and other issues."
In some cases, several teams are competing, taking different paths to the same goal.
Six, for example, are working on ways to deliver vaccines through nasal sprays, inhalers, skin patches or drinks.
Three - one based at Yale, one in Germany and one in China - are trying to make mice more immunologically human so AIDS vaccines can be tested on them.
Two technologies will compete for making vaccines that do not need to be kept chilled, overcoming a major obstacle to vaccinating children in rural Africa. One envisions encapsulating vaccines in bacterial spores, another in a protective coating already used in cosmetics.
Many winning teams combine researchers from universities, biotech companies and government agencies like the Centers for Disease Control and Prevention.
Some are headed by very prominent scientists who, "were it not for the funding source," might not have been able to concentrate on projects for the world's poorest people, said Dr. Elias A. Zerhouni, director of the National Institutes of Health, who is on the Gates Foundation's Grand Challenges board and helped pick the winners.
The $20 million grants are much bigger than typical grants from Dr. Zerhouni's agency, which is the world's largest backer of medical research. The N.I.H. hands out about $22 billion a year in grants, but they average about $1.2 million each, said Dr. Daniel J. Carucci, director of a program at the N.I.H. Foundation that coordinates with the Gates Foundation. The projects will also be more closely supervised. Each can be cut off if periodic goals are not met.
"A typical government grant is much more hands-off," Dr. Carucci said. "It's reviewed at the end of the grant, usually in one to three years."
Also, he said, any patents for inventions created under an N.I.H. grant normally go to the university involved, with no requirement that poor countries get any benefit.
Without the Gates Foundation, some of the recipients said, there would have been no financing for their ideas.
Dr. David Baltimore, who won a Nobel Prize at 37 for his genetics work and is now president of the California Institute of Technology, was granted $14 million for a radical idea: to create stem cells that could be safely injected into anyone, would populate the immune system and would contain the genetic instructions for initiating attacks on many diseases. If successful, they would make vaccines obsolete.
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"I imagined this proposal into existence, but I never imagined we could get money for it," Dr. Baltimore said yesterday. "It's not the kind of thing the N.I.H. would fund. It's too big, it's too chancy, it's too focused on a particular product. If this was 15 years ago in the biotech industry, this could be the basis of a company, but venture capitalists now are looking for a much quicker payoff."
Dr. Richard T. Sayre, a plant biologist at Ohio State University, won a $7.5 million grant to develop a better cassava.
Cassava, a starchy root that is the staple food for 250 million people in Africa, Latin America and Asia, has serious drawbacks. It contains cyanide, so it must be pounded and soaked repeatedly to leach the poison out before cooking, and it provides less than a third of the protein a human needs.
Dr. Sayre's team has a plan to genetically redirect the cyanide-making process to make more protein, so the cassava is more nutritious, less toxic and can be stored longer.
"Over the years, we've gotten grants from the Rockefeller Foundation, USAid and private companies," he said. "But the biggest was $1 million. This is the largest program ever to target cassava, and will probably have the largest impact."
Other grants are for a more nutritious banana, better rice and more digestible sorghum.
Dr. Nirmal Kumar Ganguly, director-general of the Indian Council for Medical Research and a member of the scientific board for the Grand Challenges project, said he was most excited by the seven projects that attacked mosquitoes.
One envisions creating dominant genes to shorten mosquitoes' lives just enough so that they could still reproduce, but could not transmit dengue fever. Another plans to change the dengue virus so it kills the mosquito. Two others envisioned blocking a mosquito's sense of smell so it cannot find a human.
Dr. Ganguly said he was also excited by the business opportunities the grants would mean for small biotechnology companies in countries like India. If grant recipients do not want to develop their own inventions in poor countries, they can license them to companies that will.
The Gates Foundation issued its original call for "Grand Challenges" proposals in late 2003. Mr. Gates originally committed $200 million to the project but raised that to $450 million this year when many promising proposals came in. The Wellcome Trust, the largest backer of health research in Britain, contributed $27 million, and the Canadian Institutes of Health Research put in $4.5 million.