Engineering Serendipity

Three Short Stories About How to Increase Luck Through Skill

On May 8, 2025, I gave the commencement address for my high school, the Texas Academy of Mathematics and Science (TAMS), a residential high school based at the University of North Texas, in Denton, Texas. TAMS is a unique program run by the state of Texas, where each year ~150 students from across the state skip the last two years of high school, and go straight to college. (I ended up skipping 4 grades, graduating in the class of 1995.)

Attending TAMS was life-changing. Indeed, I’m amazed more states don’t make their own versions of TAMS. I got to do chemistry research on the origins of life (working on the hypothesis that DNA was assembled by clay), study advanced mathematics, volunteer to help build a playground, dive deep into philosophical and humanistic questions, and make lifelong friends.

Here is what I wrote (slightly edited to accommodate the transition from spoken to written form; original video here; longer, more science-oriented version with slides, delivered at U Iowa in 2018, posted here):

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It is a great honor to be here with you today. 30 years ago, I was sitting where you are now - about to cross the stage, and receive my diploma from TAMS.

Today, I’m a professor at MIT, where I lead a research group inventing tools to understand and repair the brain. The brain is a mystery. We can’t explain how the brain generates our thoughts and feelings. We can’t fully cure any brain disease – which affect over a billion people around the world. The group I lead has developed molecules that let us control brain cells with light, to repair the brain. We’ve used the swellable material in baby diapers, to make brain specimens a thousand times bigger, so we can trace how brain cells form networks.

Our inventions are leading to therapies showing promise in human trials – helping blind people see again, revealing how to clean up junk in the brain in Alzheimer’s disease. We share all our tools freely, helping thousands of scientists confront brain diseases, and to explore the mysteries of thought and feeling. My hope is that we can build computer simulations of the brain, and watch thoughts and feelings as they take shape. Maybe we can confront the nature of consciousness. And, maybe we can end brain diseases for good.

But 30 years ago, as I was graduating from TAMS, the path was murky. There was no textbook, or recipe, telling me what to do. I was fascinated about confronting philosophy through science. I wanted to understand the nature of human existence, and to engineer improvements thereupon. But, when you are confronting a problem that big, where do you even begin?

When you do anything for the first time, there is no recipe, no textbook. You’re at the mercy of luck. I began to wonder – can you increase your luck, through skill? Can you engineer serendipity?

I think you can – and in a post-internet, AI-embracing, world, it might be the most valuable skill you can have. Going forward, following recipes and textbooks just might not be as interesting, anymore. Nor is it up to the task of confronting the intractable problems of our world, the list of which seems to grow in number every day.

Today I’ll tell you three short stories about ways to be lucky on purpose. As a professor, I teach, and I like to think that you can take art forms, like being lucky, and turn them into learnable, teachable skills. Today I hope to persuade you that some forms of luck can be learned and taught.

My first story is about optogenetics, how we control the brain with light. Brain cells compute by firing electrical pulses. In your brain right now, as you hear me speak, certain cells are firing electrical pulses, in language areas of your brain. Brain diseases often involve corrupted electrical pulses. If you could control them, you might be able to repair the brain. But how can you do that?

There have been many attempts to control the brain. Drugs can alter brain activity, but can be slow and messy. Electrical stimulation can help, but electricity spreads in all directions. Can we be more precise? In optogenetics, we deliver light to the brain. And to make brain cells sense light, we borrow molecules from nature. Some microbes have special molecules, that act like little solar panels, and convert sunlight into electricity. We took one of these molecules, put it in a brain cell, and aimed light at it. Amazingly, the cell fired an electrical pulse. Now, this was serendipity. It didn’t have to work. The molecule could have been toxic, and killed the brain cell. Or it might have done nothing at all.

Today, thousands of scientists use this technology, which we call optogenetics – opto for light, and genetics because the molecule is encoded by a small piece of DNA - to study the brain. Using animal models common in neuroscience, people have used optogenetics to find cells that trigger the recall of a memory, cells that when activated can slow the progression of Alzheimer’s, and cells that when activated can improve mood. It’s even showing promise in human trials, as a treatment for blindness – helping people whose eyes have lost their light-sensing cells, to sense light again.

How did we make ourselves so lucky? Well, we used a strategy so powerful, that I use it to this day. Simply put, try to think of every way of solving a problem. This is easier than it sounds! In this case, we made a list of all the forms of energy you can deliver to the brain – there’s light, sound, radio waves, a few other things. You can write the whole list down in a couple minutes. I liked light because it’s faster than anything else, and you can aim it precisely. Next question: how do you make brain cells sense light? Well, you can either design a tiny solar panel, or you can try to find one. That’s the whole list, just two cases. Finding one sounded easier. So we started emailing people, asking anyone who would listen - could you send us the light-driven molecule that you are studying, so we could put it into brain cells? And some people replied. We were in business! We took one molecule, put it in a brain cell, and as I told you, we could activate it with light. By writing down every way of solving a problem, in a systematic way, you can hone in on the best path. You may even find ideas you wouldn’t ordinarily think about. It helps you make a map of your own, when none is given to you.

My second story is about failure. Failure can be useful, if it’s the right kind. It needs to be a constructive failure – a failure you can trust. If you fail because you lacked basic skill, or didn’t try, that may not be helpful. But if you failed because you encountered a fundamental difficulty, you might have found a secret of the universe.

We wanted to map the brain. That way you could figure out where in the brain to intervene, to help somebody. Maybe we could simulate thoughts and feelings in a computer. This is hard - the brain is wired up via tiny, nanoscale connections. The brain itself, of course, is gigantic, relatively speaking. We thought – there are lots of high-resolution imaging methods out there, let’s use them to map the brain. How hard could it be? A year later, we were struggling – the methods we tried were difficult, slow, and expensive. How could you ever map a whole brain?

We were failing. But we trusted our failure – we had learned a secret, which is that nanoimaging, despite all the big announcements, was really hard. And it was hard because of fundamental physical limitations. That means that really new ideas would be needed. This was an example where failure helped us learn the truth. So, we tried another of my favorite serendipity-boosting methods – imagining what would happen, if we did the opposite of everyone else.

For literally 300 years, the way that you imaged in biology, was with some kind of lens. You magnify an image of an object. We wondered – what is the most opposite thing we could do? What if we made the object, itself, bigger? We decided to take a brain - preserved, not living - and infuse it with the kind of material you find in baby diapers – swellable polymers. Do it just right, add water, and the baby diaper material would swell, making the brain bigger. We call this technology expansion microscopy. It allows you to map the brain with cheap imaging devices. And not just the brain – all of biology is made of nanoscale building blocks, or biomolecules, which interact with each other with nanoscale precision. Now anyone can map these building blocks. It’s being used to analyze parasites, in labs in resource-poor environments. It’s being used to see if you can detect cancer in a biopsy, earlier. And of course, we’re heading down the path of using it to make a map of the brain so detailed, that we can simulate it in a computer.

This time, we failed. But you don’t always have to fail yourself - there’s failure all around. Revolutions are often hiding in plain sight - the big idea is out there, but one thing is holding it back. You fix that one thing, and you get the revolution. Facebook wasn’t the first social network. CRISPR wasn’t the first genome editor. Google wasn’t the first search engine. In each case, there were predecessor technologies. And an additional insight, caused the revolution. I call this method “failure rebooting.” Give it a try :)

My last story is about people. After I finished my PhD at Stanford, I applied for faculty jobs. I wanted to start a ground truth-oriented research group focused just on making brain technology. Neurotechnology is a cool, fast-growing field these days. But back then, neurotechnology was not yet cool. The very department at MIT that is my home base today, rejected my job application. Actually, most places I applied to, rejected my job application.

Then luck kicked in. Years before, I had been a teaching assistant for a professor in an interdisciplinary center at MIT, full of designers and multidisciplinary thinkers and creative misfits who didn’t fit into traditional academic buckets. He had an idea for how to teach quantum physics to freshmen, and I volunteered to help. In the lab of another professor there, I did research on quantum computing. These two professors alerted me, during my job search struggles, to a job opening they had, that was going unfilled. They encouraged me to apply, and I got the job. The lesson: if I was helpful to others, I could nurture serendipity in return.

I have countless examples of this kind– finding the optogenetic molecules now in human trials for blindness, getting funding for the expansion microscopy project, being invited to give my first TED talk – all of these resulted from people-serendipity, sometimes after chains of events transpiring over many years. Once I started my lab, I decided that our group would share all our tools as freely as possible – and as people used the tools, and benefited from them, more and more serendipity came my way.

The toughest problems do not come with textbooks or recipes to tell us what to do. We must master serendipity as a skill, to make progress on such problems. I hope I’ve shown you that some forms of luck can be taught and learned.

There’s an old saying, perhaps going back to ancient Rome: fortune favors the bold. But perhaps today we can do better: the bold can engineer fortune.

And so as we part ways today I wish you good luck. But don’t just wait for it – go make it happen. Thank you.