Kendall Squared brings you dispatches from the world’s epicenter for biotechnology and drug discovery.
Neuroscience hasn’t been the same since Ed Boyden arrived on the scene. As a trainee at Stanford, Boyden helped develop a technique that allows scientists to control brain activity with light with exquisite precision. But back when he was looking for faculty positions, the young scientist couldn’t land a job.
Boyden eventually found a home at the MIT Media Lab, where his blend of brain science and engineering was embraced, and in November he won a $3 million Breakthrough Prize, an award started and funded by dot-com billionaires to celebrate scientific achievements.
He recently met with STAT reporters and editors, and what follows are edited excerpts from the conversation. Now 36 and head of the Media Lab’s synthetic neurobiology group, Boyden spoke about how he and his wife, Boston University brain scientist Xue Han, are spending the Breakthrough Prize money, how he keeps track of all his ideas, and how technology he’s had a hand in developing — including optogenetics and expansion microscopy — could move from a research tool to helping patients.
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What are you doing with the $3 million?
My wife and I have been discussing a lot of things. Part of it we’re using to try to support research that’s too crazy to get funded by normal means. Could we make an optimal way of prospecting for treasure in the natural world? Can we find unknown things that could have revolutionary diagnostic, therapeutic, or scientific impact?
If you look at a lot of great biotechnologies, they’re often stumbled across from curiosity or wondering why jellyfish glow green or looking for enzymes in hot springs, all sorts of stuff. That stuff, in peer-reviewed settings, often doesn’t sound cool — you want to look at jellyfish all day?
Aren’t you spending any of the money on yourself?
Certainly my wife and I put some aside for our kids’ college education. But I spend most of my time in the lab working or at my desk thinking. Everything’s either thinking science or taking care of kids at this point.
How do you spend your day?
I tend to get up really early, like around 4 or 5 in the morning, get a couple hours of thinking done, and then most of the day is spent working with students and postdocs on reviewing projects, thinking of ideas, analyzing data, writing manuscripts, and so forth. And then I try to go bed early [8 or 9 p.m.], at the same time as the kids do. And my wife has the opposite schedule, she stays up late, and that’s when she gets her stuff done. So we do occasionally see each other.
Are you and your wife constantly nerding out on this stuff?
We rarely talk about science, in part because we collaborated a lot in the past. She was one of the key players in optogenetic neural silencing. Occasionally I do start talking about some topic and try to learn more about it, and she’s like, “Oh, we published a paper on that a year ago.”
Optogenetics allows scientists to control cell activity with light by introducing light-sensitive genes from algae or bacteria into living cells. It has mostly been used in research settings, but the first human clinical trial using the tool, which is aiming to treat a disease that can cause blindness, is underway. What do you think about optogenetics as a therapeutic?
They’ve picked the retina to work on, which I think is a very appropriate first step since we know a lot about the retina. We don’t know enough about the brain. We don’t even have a list of the cell types of the human brain, and using optogenetics, which is a cell-type specific strategy, really does require some knowledge of the circuitry.
Do you see any applications outside the eye in the next, say, 10 years?
There are no FDA-approved gene therapies right now, but there are lots of FDA-approved cell therapies. Imagine you could deliver a cell to the body and when you trigger it with light, it releases a hormone or a growth factor or some kind of biologic. And because you made that cell and you engineered it you could also put in a kill switch if you wanted as well. This could potentially be an avenue to a wide variety of ultraprecise control of bodily function.
It’s been about a year since your big expansion microscopy paper was published in Science. Can you give us the basic primer on what expansion microscopy is?
A couple years ago, we started thinking how you could really map the brain. This is not a new quest, but the methods from prior attempts have proven to be difficult to scale up to the large 3-D nature of brain circuits. So we started thinking, why don’t we do the opposite? Let’s actually take a brain — preserved, of course — and physically swell it and make it bigger, move the molecules apart from each other to the point where we can tell them apart.
Pretty rapidly we were able to invent a method to do it. What we do is take a sample and wash in building blocks that once they’re varied evenly throughout the tissue, we trigger them to form polymer chains, and the polymers are very similar chemically, almost identical, to the swellable polymers in baby diapers. You add water, and the polymer swells, as millions of kids prove every day. And then as it swells, it takes the molecules of the tissue with it, to the point where you can move them far enough apart that you can distinguish them. Now we’re applying it to all sorts of stuff — bacteria, cancer, biopsies, virology questions. There’s a huge pent-up demand for ways of seeing large objects with nanoscale precision.
Are there foreseeable applications in medicine?
One dream that’s emerging is take a sample from a patient and you can physically expand it for a small amount of money and then take a picture with a cheap piece of optics, like a cellphone camera. Could this be a way of revolutionizing the ability to analyze clinical samples with shape information and all sorts of other information that gets lost if you do, say, just genome sequencing?
What do you read?
I’ve kind of gotten obsessed in recent years with reading very old papers, from the 1950s to the 1970s, for example. There’s a lot of old treasure in the scientific literature, and they worked on a project and they hit a brick wall in 1965. But you know what? Nowadays, with genome sequencing and better computers and so forth, that’s the seed of an idea that could be transformative.
How do you keep track of all the ideas buzzing around in your head?
I’ve always been a compulsive notetaker. In having conversations or running meetings, I’m scribbling on pieces of paper constantly, and then every couple of weeks I go back and mine all those “conversation summaries,” as I call them, to see if I can notice things I didn’t notice at the time, or refresh my memory, or try to look at it from a different point of view. I also try to come up with ways to slow down and think about problems from different angles. I think that’s important.
There’s a huge push to do things quickly, but after I got tenure at MIT, my group members made a bunch of Post-it notes with things that apparently I say all the time, and one of them was, “Follow the principle of applied laziness” — which is, sometimes you’re doing a lot of work to be busy, and that isn’t necessarily the right thing to do when you could be thinking of a better idea that has more transformative power.