Bill Gates fancies himself an optimist. Global health, he feels, is on an upward trajectory. Childhood deaths are plummeting. Polio is on the verge of eradication.

But if there’s one issue that punctures his positivity, it’s the possibility that the world will face a serious pandemic—and the near certainty that we aren’t prepared for it.

“This is a rare case of me being the bearer of bad news,” he says. “My general narrative is: Hey, we’re making great progress and we just need to accelerate it. Here, I’m bringing more of: Hey, you thought this was bad? [You should] really feel bad.”

In 2015, Gates said at the TED conference that “if anything kills over 10 million people in the next few decades, it’s most likely to be a highly infectious virus.” Three years later, he stands by that assessment. “It would take a heck of a meteor or volcano or earthquake to get you to 10 million,” he tells me. “Even a nuclear weapon going off in New York City wouldn’t be 10 million.” By contrast, in 1918, when an H1N1 flu virus swept the world, it killed between 50 and 100 million people, and slashed U.S. life expectancy by 12 years.

Medicine has advanced considerably since then, but those advances are spread thinly (as this year’s non-pandemic flu season showed), and they depend on convoluted and precarious supply chains. The world is far more populated than in 1918—7.6 billion people today versus around 2 billion then—as well as more densely populated. Based on that, the Institute for Disease Modeling predicts that a severe flu pandemic could kill more than 33 million people in just 250 days. Several concerning strains are already circulating.

Institute of Disease Modeling and the Bill and Melinda Gates Foundation To help prepare the world for the next pandemic, the Bill and Melinda Gates Foundation, together with Alphabet’s Larry Page and his family, are launching a $12 million grand challenge to spur research into a universal flu vaccine—one that will be effective against all strains of this frustratingly diverse virus. Gates announced the new initiative at the Shattuck Lecture in Boston on Friday, on the centennial of the 1918 flu.

Vaccines against measles, mumps, or rubella provide lifelong protection. But the flu comes in a large number of subtypes—H1N1, H5N1, H7N9, and so on—and many strains within those. The viruses also change constantly, which is why the flu vaccine must be constantly updated to target the strains that are most likely to cause problems next. A universal vaccine, which would protect against all possible subtypes and strains, would change that. It would effectively take flu off the table as a major threat, protecting people against future pandemics, while reducing the need for annual vaccination campaigns.