Half a billion dollars is not to be sneezed at, even when divided 43 ways. And that, give or take a few million, was the sum at stake when a committee of the medical world's great and good decided who will take on what have become known as the Grand Challenges in Global Health. Most of the money to meet these challenges―$450 million of it―comes from the Bill and Melinda Gates Foundation, the world's richest charity. The Welcome Trust, Britain's richest, has chipped in $27 million. The 43 winners were announced on June 28. The Grand Challenges are 14 serious technical obstacles to a healthier world that were picked by the committee in the autumn of 2003, after its members had gone through several thousand submissions from the world's medical scientists. The specific challenges are, in turn, grouped under seven goals that range from the speculative (create new vaccines) to the mundane (measure health status accurately and economically in developing countries). They do not, of course, address what many might see as the biggest obstacles of all to better health―poverty and misgovernment. But they represent an imaginative approach to what medical science might do to alleviate the problem.   The winning projects are all, if not entirely new, at least still in their preliminary phases, and the sponsors expect a lot of attrition along the way. Indeed, they will be leading the culling themselves, since many proposals have to meet “milestone” objectives by particular dates, otherwise they will have their funding cut off. Some of the winning proposals sound truly wacky. Putting bacterial spores into people to prevent disease is probably top of that list. Yet it is a clever idea. One of the biggest obstacles to a healthier world is a lack of so-called cold chains for transporting temperature-sensitive medicines―Vaccines, in particular, need to be kept refrigerated if they are to remain effective. That is not easy in places where fridges are far apart and the electricity is unreliable. Abraham Sonenshein, of Tufts University in Massachusetts, thinks that one way to overcome this problem is to incorporate vaccines into bacterial spores, which are famously resistant to changes in temperature. He proposes doing this through genetic engineering. Genes for proteins from disease organisms will be added to the bacteria in question in a way that will cause the proteins to be incorporated into the spore's coat, so they are visible to the immune system.