Some people think it is corny, but I like the tradition. These days, at the end of each year, I still enjoy taking stock of my work and personal life. What was I excited about? What could I have done better?

I thought I would share a few of these thoughts as 2018 concludes.

One thing that occurs to me is that the questions I am asking myself at age 63 are very different from the ones I would have asked when I was in my 20s.

Back then, an end-of-year assessment would amount to just one question: Is Microsoft software making the personal-computing dream come true?

Today of course I still assess the quality of my work. But I also ask myself a whole other set of questions about my life. Did I devote enough time to my family? Did I learn enough new things? Did I develop new friendships and deepen old ones? These would have been laughable to me when I was 25, but as I get older, they are much more meaningful.

Melinda has helped broaden my thinking on this point. So has Warren Buffett, who says his measure of success is, “Do the people you care about love you back?” I think that is about as good a metric as you will find.

It may sound grand, but I think the world is slowly going through a similar transition to a broader understanding of well-being. For most of human history, we have been focused on living longer by fighting disease and trying to grow enough food for everyone. As a result, life spans have gone up dramatically. Technology has played a key role in that through vaccines, medicines, and improved sanitation.

We still need a lot of innovation to solve problems like malaria or obesity, but we are also going to be focusing more on improving the quality of life. I think this will be the thrust of many big breakthroughs of the future. For example, software will be able to notice when you’re feeling down, connect you with your friends, give you personalized tips for sleeping and eating better, and help you use your time more efficiently.

There are not the same clear measures of these things as there are for diseases, and there may never be. But there is nascent work in this field and I think it is going to accelerate.

As I look back on the year, I am also thinking about the specific areas I work on. Some of this is done through our foundation but a lot of it (such as my work on energy and Alzheimer’s work) is not. What connects it all is my belief that innovation can save lives and improve everyone’s well-being. A lot of people underestimate just how much innovation will make life better.

Here are a few updates on what’s going well and what isn’t with innovation in some areas where I work.

Alzheimer’s disease

I saw two positive trends in Alzheimer’s research in 2018.

One is that researchers focused on a new set of ideas about how to stop Alzheimer’s.

The first generation of theories, which dominated the field for years, emphasized two proteins called amyloid and tau. These proteins cause plaques and tangles in the brain, clogging up and killing brain cells. The idea was to stop the plaques and tangles from forming. I hope these approaches pay off, but we have not seen much evidence that they will.

In the past year, researchers have doubled down on a second generation of hypotheses. One theory is that a patient’s brain cells break down because their energy producers (called mitochondria) wear out. Another is that brain cells break down because part of the immune system gets overactivated and attacks them.

This is a great example of how improving our understanding of biology will reduce both medical costs and human suffering.

The other trend this year is that the Alzheimer’s community focused on getting more and better access to data. We’re working with researchers to make it easier for them to share information from their studies broadly so that we can better understand questions like how the disease progresses.

Over the past few years, the U.S. government has dramatically stepped up funding for Alzheimer’s research, from $400 million a year to over $2 billion a year. There is also a big push to create better diagnostics.

The only problem where I don’t yet see a clear path forward yet is how to develop more efficient ways to recruit patients for clinical trials. Without a simple and reliable diagnostic for Alzheimer’s, it’s hard to find eligible people early enough in the disease’s progression who can participate in trials. It can take years to enroll enough patients. If we could find a way to pre-screen participants, we could start new trials more quickly.

But there is so much momentum in other areas—scientific tools, better diagnostics, improved access to data—that as long as we can solve the recruitment problem, I am confident that we will make substantial progress in the next decade or two.

Polio

I thought we would be closer to eradicating polio today than we are. Unfortunately, there were more cases in 2018 than in 2017 (29 versus 22).

I underestimated how hard it would be to vaccinate children in places where there’s political violence and war. Families move around to escape fighting, which makes it hard to keep track of children and make sure they get all the doses of the vaccine. Or sewage systems get destroyed, allowing the virus to spread as children come into contact with an infected person’s excrement.

This is a key reason why Afghanistan and Pakistan have never been free of polio—in fact they are the only two countries that have never been free of polio.

I spend a lot of time on polio, part of it talking to the funders to make sure they continue their commitment even though eradication is taking longer than any of us would like. I remind them of the huge benefits of success, and the risk that the disease will return in a big way if we don’t finish the job.

I also remind them what a difference innovation is making. We’re now able to test sewage samples to track the virus and find the source before an outbreak starts. And the global health community is finding creative ways to work in war zones, having stopped outbreaks in Syria and Somalia in recent years.

Finally, I am hopeful about a new oral vaccine being tested in Belgium and Panama. The results should be out in 2019, and if this one proves effective, it would overcome some of the problems with previous oral vaccines when they’re used in places where few children are immunized. The new vaccine could be in use as soon as 2020.

Despite all the challenges, I am still optimistic that we can eradicate polio soon.

Energy

Global emissions of greenhouse gases went up in 2018. For me, that just reinforces the fact that the only way to prevent the worst climate-change scenarios is to get some breakthroughs in clean energy.

Some people think we have all the tools we need, and that driving down the cost of renewables like solar and wind solves the problem. I am glad to see solar and wind getting cheaper and we should be deploying them wherever it makes sense.

But solar and wind are intermittent sources of energy, and we are unlikely to have super-cheap batteries anytime soon that would allow us to store sufficient energy for when the sun isn’t shining or the wind isn’t blowing. Besides, electricity accounts for only 25% of all emissions. We need to solve the other 75% too.

This year Breakthrough Energy Ventures, the clean-energy investment fund I’m involved with, announced the first companies we’re putting money into. You can see the list at http://www.b-t.energy/ventures/our-investment-portfolio/. We are looking at all the major drivers of climate change. The companies we chose are run by brilliant people and show a lot of promise for taking innovative clean-energy ideas out of the lab and getting them to market.

Next year I will speak out more about how the U.S. needs to regain its leading role in nuclear power research. (This is unrelated to my work with the foundation.)

Nuclear is ideal for dealing with climate change, because it is the only carbon-free, scalable energy source that’s available 24 hours a day. The problems with today’s reactors, such as the risk of accidents, can be solved through innovation.

The United States is uniquely suited to create these advances with its world-class scientists, entrepreneurs, and investment capital.

Unfortunately, America is no longer the global leader on nuclear energy that it was 50 years ago. To regain this position, it will need to commit new funding, update regulations, and show investors that it’s serious.

There are several promising ideas in advanced nuclear that should be explored if we get over these obstacles. TerraPower, the company I started 10 years ago, uses an approach called a traveling wave reactor that is safe, prevents proliferation, and produces very little waste. We had hoped to build a pilot project in China, but recent policy changes here in the U.S. have made that unlikely. We may be able to build it in the United States if the funding and regulatory changes that I mentioned earlier happen.

The world needs to be working on lots of solutions to stop climate change. Advanced nuclear is one, and I hope to persuade U.S. leaders to get into the game.

The next epidemic

In 1918, the Spanish flu killed 50 million people worldwide. It still ranks as one of the deadliest natural disasters ever.

I had hoped that hitting the 100^th anniversary of this epidemic would spark a lot of discussion about whether we’re ready for the next global epidemic. Unfortunately, it didn’t, and we still are not ready.

People rightly worry about dangers like terrorism and climate change (and, more remotely, an asteroid hitting the Earth). But if anything is going to kill tens of millions of people in a short time, it will probably be a global epidemic. And the disease would most likely be a form of the flu, because the flu virus spreads easily through the air. Today a flu as contagious and lethal as the 1918 one would kill nearly 33 million people in just six months.

I have been studying this for several years. To be prepared, we need a plan for national governments to work together. We need to think through how to handle quarantines, make sure supply chains will reach affected areas, decide how to involve the military, and so on. There was not much progress on these questions in 2018.

The good news is that there has been progress toward a vaccine that would protect you from every strain of the flu. This year I visited the U.S. National Institutes of Health in Maryland and got an update from some of the people leading this work.

The challenges of making a universal flu vaccine are fascinating. All strains of the virus have certain structures in common. If you’ve never been exposed to the flu, it’s possible to make a vaccine that teaches your immune system to look for those structures and attack them. But once you’ve had the flu, your body obsesses over the strain that got you sick. That makes it really hard to get your immune system to look for the common structures.

So it is clear how we could make a universal vaccine that would protect anyone (such as the very young) who has never been exposed to the flu before. But for anyone who has already had the virus, it is a lot harder. The problem is a long way from being solved, but new research money is coming in and more scientists are working on it.

To make the most of these scientific efforts (some of which our foundation is funding), the world needs to develop a global system for monitoring and responding to epidemics. That is a political matter that requires international cooperation among government leaders. This issue deserves a lot more focus.

Gene editing

Gene editing made the news in November when a Chinese scientist announced that he had altered the genes of two baby girls when they were embryos. What is unprecedented about his work is that he edited their germline cells, meaning the changes will be passed down to their children. (The other, less controversial type of gene editing involves somatic cells, which aren’t inherited by future generations.)

I agree with those who say this scientist went too far. But something good can come from his work if it encourages more people to learn and talk about gene editing. This might be the most important public debate we haven’t been having widely enough.

The ethical questions are enormous. Gene editing is generating a ton of optimism for treating and curing diseases, including some that our foundation works on (though we fund work on altering crops and insects, not humans). But the technology could make inequity worse, especially if it is available only for wealthy people.

I am surprised that these issues haven’t generated more attention from the general public. Today, artificial intelligence is the subject of vigorous debate. Gene editing deserves at least as much of the spotlight as AI.

I encourage you to read up on it whenever you have a chance. Keep an eye out for articles in your news feed. If you are willing to read a whole book, The Gene by Siddhartha Mukherjee is very well done. This story is one to follow, because big breakthroughs—some good, some worrisome—are coming.

Looking ahead

I am making a resolution for 2019.

Although I have never been one for New Year’s resolutions, I have always been committed to setting clear goals and making plans to achieve them. As I get older, these two things look more and more like the same exercise. So I am making a resolution for 2019. I am committing to learn and think about two key areas where technology has the potential to make an enormous impact on the quality of our lives, but also raises complex ethical and social considerations.

One is the balance between privacy and innovation. How can we use data to gain insights into education (like which schools do the best job of teaching low-income students) or health (like which doctors provide the best care for a reasonable price) while protecting people’s privacy?

The other is the use of technology in education. How much can software improve students’ learning? For years we have been hearing overheated claims about the huge impact that technology would have on education. People have been right to be skeptical. But I think things are finally coming together in a way that will deliver on the promises.

I will be posting updates on these and other issues on the Gates Notes.

In the meantime, Melinda and I are working on our next Annual Letter. The theme is a surprise, though it is safe to say we’ll be sharing some positive trends that make us optimistic about the future. We’ll send the letter out in February.

I hope you have a happy and healthy start to 2019.