Self-described "impatient optimists" Bill and Melinda Gates remain resolutely sanguine about the future and the progress it will bring. Still, in their  annual letter they note a few things that surprised them. Some global problems are so intractable that momentum has been slow, while others have been less difficult to overcome than they had originally thought.

For instance, pollution remains a vexing issue that will likely continue to devastate the environment. Curbing malaria in the developing world, however, has been a bright spot. They had once thought minimizing the toll of the mosquito-borne disease would require a long-lasting vaccine, but the Gates were buoyed by the benefits of the widespread use of bed nets. Malaria deaths are down 42 percent since 2000, reports the couple.? 

In their 11th annual letter, released Tuesday and entitled "We Didn't See This Coming," the billionaire philanthropists, who co-chair the Kirkland, Washington-based Bill & Melinda Gates Foundation, list nine things that proved confounding in 2018 and how they hope to address them in the year ahead.

Both the nonprofit and for-profit worlds pore over the letter--which has been co-written by Melinda Gates since 2014--for clues as to how the philanthropists will direct their sizable influence and an endowment of more than $50 billion. The couple maintains separate investment vehicles, too. Bill operates Cascade Investment, through which he has a stake in everything from hospitality firms to a Canadian railroad operator, while Melinda's Pivotal Ventures aims to empower women and girls. They both, however, maintain a keen interest in supporting the expansion of technology globally. 

"We believe in the power of innovation," writes the couple, explaining their optimism. They also emphasize the import of human grit. "We've seen firsthand that for every challenge we've written about in this letter, there are people devoting their ideas, their resources, and even their lives to solving them."

Here are three of the most compelling ideas on the minds of the Gates.

DNA Sleuthing

At-home DNA testing services led to the capture of the Golden State Killer in April of last year. While that's compelling in its own right, so too is the potential for how those tests, more generally, can be used to better understand gene-related health issues and treatment options. In particular, the duo point to a 2017 23andMe study of premature births, which the foundation helped fund.

Using 40,000 samples that were volunteered by 23andMe users, the Mountain View-California-based DNA-testing service says it established a link between preterm labor and six genes, one of which is tasked with regulating how the body uses a mineral called selenium. The study suggests that expecting mothers carrying this gene, which prevents them from processing selenium properly, are more likely to deliver early.

"This connection is one of several breakthroughs we've made in recent years," writes the Microsoft co-founder. "Better tools and more data sharing mean that we're finally starting to understand what causes babies to be born early--and what we can do to keep them in the womb longer."

Toilets of the Future

Another breakthrough? Self-contained toilets. As Bill and Melinda note in their letter, you can't export "rich-world" sanitation solutions, because they require a sewer system that may be too costly to build.

At a 2018 toilet fair in Beijing, where Bill appeared onstage with a jar of human feces, he saw firsthand the promise of next-generation toilets, which can render urine and feces into useful byproducts like fertilizer. The focus in the near term is making commodes more affordable so people in the developing world might use them. Melinda notes the need is particularly urgent for girls and women in the developing world, who often stay home from work and school while they menstruate rather than face public ridicule.

"If you're anything like me, I'm guessing toilets aren't your favorite topic of conversation," writes Melinda. "But if you care about keeping girls in school, expanding women's economic participation, and protecting them against violence, then we have to be willing to talk about toilets."

"Sexist" Data

The philanthropists also want to make sure people start measuring women's economic vitality. Specifically, they want to know how much women earn, how much property they own, and how many hours they spend on household chores.

That data simply doesn't exist, writes Melinda. And the data that does exist, which is used by policymakers, can be flawed or downright "sexist," as Melinda calls it.

"We like to think of data as being objective, but the answers we get are often shaped by the questions we ask. When those questions are biased, the data is too," Melinda writes, adding that three years ago, the foundation she runs with her husband started investing in resolving the gender-data gap. In time, by empowering new data collection methods and recasting existing data by gender, a clearer image of women should form.

"What we choose to measure is a reflection of what society values," writes Melinda. "That's why when it comes to understanding the lives of women and girls, the world can't accept 'I don't know' as an answer."