Gates says the IBM hiring manager “stopped me dead in my tracks and asked, ‘Do you want my advice? IBM has a fantastic career track, but you have to go up each ladder of the chain.” Microsoft, said the recruiter, is a young, rapidly growing company with the promise of faster advancement for women.

She took the Microsoft (MSFT) job—and history was made. Bill Gates asked her out in the company parking lot one Saturday morning, a skeptical Melinda finally agreed (more on that later), and now—a quarter century and three children later—she is co-steering a $42.3 billion foundation widely recognized as a game-changer in global poverty.

Melinda Gates appeared on stage with me for a 90-minute interview Tuesday at the Center for Strategic and International Studies, as part of our CSIS-Fortune “Smart Women Smart Power” series. She unveiled steps the Gates Foundation is taking to realign its enormous resources to make investment in women and girls a top priority. “We are making strides for women and girls, but not on a global scale,” she said.

That effort will include a renewed effort to disperse contraception, though the foundation will not fund abortion. “I believe in and use contraceptives,” said the devout Catholic, who called family planning “vital in developing countries.”

In our wide-ranging conversation, Gates defended genetically-modified crops—increasingly the target of protests here and in Europe—as critical to eradicating hunger in poor countries. She also criticized the anti-vaccine movement and offered this positive bit of news: “We are getting very close in polio eradication. This would be an amazing success in global health.”

To hear the entire interview, click here.

Our disussion provided a rare glimpse into the modest childhood, as well as the intellect and drive, of the woman who is married to the richest man in the world, yet is also on a first name basis with some of the poorest villagers on the planet.

Melinda French Gates grew up in Dallas—one of four children—with a homemaker mother who regretted never going to college and an aerospace engineer father. Gates says her dad valued having women on his engineering teams, noting that she met female engineers who worked on Apollo projects at her father’s company picnics. She herself joined a computer science club at her Catholic girls school. “I love logic,” she says. “Computer science to me was like a puzzle. I like the logic of it and working your way through.”

Her parents, determined to send all four kids away to college, ran a real estate company on the side so they could afford tuition. Melinda and her sister were assigned to keep the books on their Apple 3 computer and painted the company’s rental properties on weekends. “I learned the flows of money, profit and loss. I knew what my parents bought [the homes] for and hoped to get,” she recalled. When she attended Duke, she added an MBA to her computer science and economics degrees—and made a speedy climb up the Microsoft ladder for nine years.

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When Bill Gates asked her out in that parking lot, the 23-year-old was put off by his suggestion that they plan dinner two weeks in the future. “I had no idea what I was going to be doing then. I said, ‘that’s not spontaneous enough for me,’” she recalls. She gave him her phone number and suggested they talk closer to the day. Instead, he called that night and the relationship bloomed even though “my mom didn’t think it was a good idea.”

The seeds of the Gates Foundation can be glimpsed in those dating years. Bill Gates would tote bags of mostly biology books along on their vacations. “Bill feels like he knows he [understands] something deeply only if he can explain it or teach it to someone,” she says. “I wasn’t going to read a whole biology book, but I was going to listen. I learned a lot of about the immune system.”

Decades later, science and biology are central to the Gates Foundation work on immunizations and other health treatments. The number of children who die by age five has been cut in half since 1990, with the foundation playing a central role in more recent years.

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Melinda Gates didn’t even have a passport when she met Bill. She took her first trip to Africa when they were engaged. The journey was meant to be a fun and adventurous safari with other couples, but ended up offering painful life lessons as well.

“We loved the animals and the savannah, but you couldn’t help but ask questions—like why whole towns were shut down,” she says. In a Maasai cooking tent, the group bonded with villagers so well that one young man asked: “Can you come back in a few weeks? We are going to have a cutting ceremony for my sister.”

“We were all devastated” by the reference to genital mutilation, Gates says. “It made me realize I knew nothing about that culture. It started Bill and me on a series of learning journeys and questions.”

Now, though, she and her husband have said they plan to double down on the poverty-eradicating bet they made 15 years ago. They argue that over the next 15 years, the lives of people in poor countries will improve more than at any other time in history. “When I look at Africa, I don’t just see the destitute stories,” Melinda Gates says. “I focus on the ingenuity and change of the communities.”