One hundred years ago, an aggressive flu virus killed 675,000 Americans in just 3 weeks. The virus, known as Spanish Influenza or the flu of 1918, went on to kill more than 50 million people worldwide and is still the deadliest pandemic in modern history.

Today, an increasingly connected world makes the risk of a deadly global pandemic like the 1918 flu higher than ever before — and we need to prepare.

That’s the message delivered Friday by Microsoft co-founder and philanthropist Bill Gates. Delivering the New England Journal of Medicine’s annual Shattuck Lecture in Boston, Gates also announced the launch of a $12 million grand challenge that will fund research into universal flu vaccines, something he says is essential to preparing for the next flu pandemic.

The world needs to prepare for pandemics the way the military prepares for war.

“The goal is to encourage bold thinking by the world’s best scientists across disciplines, including those new to the field,” Gates will say, according to a draft of his prepared remarks. The challenge will be funded by the Bill and Melinda Gates Foundation and the family of Google co-founder and Alphabet CEO Larry Page.

It’s a response to a growing concern among health experts that we are unprepared for a global pandemic. Recent outbreaks of Ebloa, Zika and even the seasonal flu virus have revealed a shaky global infrastructure for detecting and containing easily spread pathogens.

“We can’t predict when. But given the continual emergence of new pathogens, the increasing risk of a bioterror attack, and how connected our world is through air travel, there is a significant probability of a large and lethal, modern-day pandemic occurring in our lifetimes,” Gates said.

“The world needs to prepare for pandemics the way the military prepares for war. This includes simulations, war games and other preparedness exercises so we can better understand how diseases will spread and how to deal with things like quarantine and communications to minimize panic,” he said.

Watch Gates’ speech in the live stream below:

Gates Foundation President of Global Health Trevor Mundel told GeekWire that the flu is a worrying virus when it comes to global outbreaks.

“Flu, by anybody’s account, is one of the next pathogens,” he said.

The flu is a smart virus. It’s constantly changing and adapting, rewriting parts of its genetic code to better invade our bodies.

That’s why the flu vaccine from one flu season won’t protect well against next year’s version of the virus. It’s also why new strains of the flu — like the 2009 outbreak of H1N1, or Swine Flu — can be so deadly.

If another ultra-aggressive flu virus like the one seen in 1918 were to arrive on the scene today, “nearly 33 million people worldwide would die in just six months,” Gates said.

A universal flu vaccine has long been a holy grail for epidemiologists. In theory, the vaccine could target a part of the virus that doesn’t change quickly and therefore will hold stable over several years. Emerging science — such as two early efforts at the University of Washington — may hold the key to making that a reality.

“If we get three great ideas — different from what’s out there already — that would be a fantastic return,” Mundel said.

The grand challenge will accept submissions from researchers working on universal vaccine technology and fund several with small seed grants. Successful projects will have a chance to apply for $10 million in funding to further develop them.

A universal flu vaccine could be stockpiled in case of a pandemic and could also protect against the seasonal virus better than current vaccines. Some scientists predict that a universal flu vaccine could protect someone for up to five years.

But science isn’t the only thing that we need to combat pandemics. In his speech, Gates emphasized the need for more international collaboration to innovate on health technology and prepare for outbreaks.

Unlike military conflicts, there isn’t much of a protocol for responding to a pandemic. It isn’t even completely clear who is in charge of international responses to pandemics or what part governments, NGOs, drugmakers and health service workers each play.

“At the end of the day, you need to understand how the whole system works together,” Mundel said.

That will be a focus for the Gates Foundation and other organizations going forward, Gates said. He called out several projects that are working towards that goal, including the public-private Coalition for Epidemic Preparedness Innovations (CEPI), which is partially funded by the Gates Foundation.

He also called out a computer modeling program being developed at the Institute for Health Metrics and Evaluation at the University of Washington, which aims to predict the risk and spread of pandemics and infectious diseases.

Technology like that program along with an army of well-trained volunteer health workers, better science and clear protocols are all important to preventing huge casualties in the event of a pandemic, Gates said.

“At my core, I’m an optimist,” he said. “In this case my optimism comes from the progress we’re making in developing new tools, and in the world’s proven ability to tackle other pandemics. We eradicated smallpox, a disease that killed an estimated 300 million people in the 20th century alone.”

“Somewhere in the history of these collective efforts is a roadmap to create a comprehensive pandemic preparedness and response system. We must find it and follow it because lives – in numbers too great to comprehend – depend on it.”