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Intro/Outro (00:01):
Welcome to The Microscopists, a Bitesize Bio podcast hosted by Peter O'Toole, sponsored by Zeiss Microscopy. Today on The Microscopists.

Peter O'Toole (00:14):
Today on The Microscopists, I'm joined by Ed Boyden from MIT and a HHMI investigator and we discuss his very early work in the lab.

Ed Boyden (00:24):
So I started college really young. I was 14 years old and I worked in a laboratory that was trying to create life in a test tube, which of course didn't happen, or you would've heard about it

Peter O'Toole (00:33):
And how he manages one of the largest neuroscience groups in the world.

Ed Boyden (00:37):
Right now we have 56 full-time researchers in the group split half and half between graduate students and postdocs or staff Scientists

Peter O'Toole (00:46):
Might seem hard to believe, but despite his current success, Ed admit, he's struggled to get his first permanent role in academia.

Ed Boyden (00:54):
It was hard getting a faculty job actually. So I wanted to start the first group that just did technology for reading and writing to the, you know, to the brain and yeah, a lot of places didn't like that. So I was rejected by the majority of the places I've applied to

Peter O'Toole (01:12):
And how he's now using expansion microscopy to explore new, exciting grounding neuroscience.

Ed Boyden (01:19):
You know, we have a technique that we call expansion microscopy, where, you know, for literally 300 years, people have been zooming in with a lens. We started thinking, why don't we just take the darn thing and make it bigger

Peter O'Toole (01:29):
All in this episode of The Microscopists. Hi, I'm Peter O'Toole and welcome to The Microscopists. Today I'm joined by Ed Boyd from MIT at Stanford University. Ed, how are you today

Ed Boyden (01:49):
Doing right. Doing right. Good to see you.

Peter O'Toole (01:52):
Yeah, likewise, ed, I, I, I looked at your background and I was trying to figure out how you got to where you are today. Cause, cause it's what, I don't think you were heading into where you are today. So if, if we go right back, when you were a child, what did you want to be?

Ed Boyden (02:16):
Well, when I was a child, I was I was very philosophical. I really wanted to understand the meaning of life. And I went through a very religious phase, for example, when I was about eight years old or so, and, and around age nine, I really got obsessed with this idea that, you know, science might help us understand what it means to be human and maybe to alleviate suffering of the human condition. So two things happened, I became very ambitious. I wanted to, to learn everything. And and then secondly, I decided to work on towards scientific projects that connect to philosophy. So I started college really young. I was 14 years old and I worked in a laboratory that was trying to create life in a test tube, which of course didn't happen or you would've heard about it. Um and then I transferred to a different school and switched majors and ended up working on quantum computing, another project that sort of blends the mysterious and the scientific and that also was really hard. Right. You know, it's been decades since, and we still don't have very good quantum computers. And third times a charm in 1998 or so I decided to work on the brain and it turned out that, you know, the chemistry and physics that I learned from those early projects had prepared me to take a, a different tack on the brain. So yeah, that was what sort of the pivot into neuroscience.

Peter O'Toole (03:39):
So to what degrees did you do

Ed Boyden (03:42):
As an undergraduate?

Peter O'Toole (03:43):
Yeah, undergraduate.

Ed Boyden (03:45):
I was an undergraduate for six years, so I studied chemistry for two years at the University of North Texas. They have a program for high school. Students can skip the last two years of high school and go right to college called Tams, Texas academy of math and science. And then I transferred to MIT and spent four years there where I majored in electrical engineering, computer science and physics. So I ended up kind of knowing a pretty broad swath of science and and importantly fundamental sciences things that, you know, stand the test of time and that really can be applied in any direction you want. So and then I, for my PhD went on to to neuroscience at Stanford.

Peter O'Toole (04:25):
So I said that that, which, which is obviously a bio biological side of it. So you've done your chemistry, you've done your physics, you've done your math, you've done your compute science. And then you ended up going to a PhD and, or I know it's related, but a different subject again. How did you find that leap from chemistry, physics, math, where things are, maybe you do B and you get C to life sciences where you do a twice over and you get a different answer.

Ed Boyden (04:54):
Well, that's part of why I really enjoyed the path that I took, where I learned the fundamental sciences as an undergraduate. And then I started working on the more emergent sciences where there's still a lot of art as well as science in it for my PhD. And that was a great sort of, you know, one, two transition where I had a lot of skills and now I could apply those skills to problems that, that you know, are widely regarded as UN unsolvable currently, you know, trying understand how the brain generates the mind, what happens during thinking, what is a feeling, you know, can we cure Alzheimer's disease? The list goes on and on.

Peter O'Toole (05:28):
How did you find a supervisor to take you on being as you hadn't got the biology background to do a neuroscience PhD?

Ed Boyden (05:36):
My co-advisors Jennifer Raymond and Dick Chen at Stanford had made similar transitions. Actually Jennifer had studied mathematics before entering neuroscience and Dick had also studied electrical engineering before switching into, into biology. So it was great to, to have mentors who understood that transition and, and it was a fantastic environment in their two groups at Stanford where I did my, my graduate work on motor learning. So he tried to study how motor memories are encoded in the brain using a variety of molecular and behavioral approaches.

Peter O'Toole (06:09):
And, and I, I, I think Dan Davis, who I did a podcast with some time ago did exactly the same. He, he went from physics undergraduates and then went over to the states and did a PhD in immunology. But I, I think it's amazing actually that you find supervisors that are, that are willing to do that. And I think, yeah, look at your career, look at Dan's career, they're amazingly successful careers. And I think, yeah, I, I think he, maybe it's a good lesson that people should be open to who they're recruiting as their PhDs.

Ed Boyden (06:37):
If I recall properly, I could be wrong, but there were five undergraduates who graduated my year at MIT. This is 1999 who became MIT faculty. And if I recall all five of us trained in physics, electrical engineering, or math or something like that, and all five of us ended up working on biology. So there's a, there's a big, I think, transition now where the life sciences are, you know, full of unknowns desperately in need of technology. And so these is more mature sciences. You know, people are, are leaving them and trying to go to the, the, the unknown. So

Peter O'Toole (07:11):
I, I, it is a stellar career, as you say, you know, after year two, as your undergraduate then went to MIT and I don't think you've left MIT. I think you've been there most of the time. Haven't you? Since all the way through?

Ed Boyden (07:24):
Oh, yeah after I finished at Stanford in 2005. I post for several months, but then joined MIT in the fall of 2006. And yeah, I've been running my group here ever since 16 years.

Peter O'Toole (07:38):
And, and, and I've got to ask cuz you, you look insanely young and you've been there since 2006, which must mean you were exceptionally young when you started out on that career path.

Ed Boyden (07:50):
Yeah. Well starting college when I was 14, I always thought, Hey, I've got a couple extra years. I can use those years to take risks and try bold, ambitious things. But then I kept getting lucky. And so yeah. The luck continued. I kind of think of the core disciplined I'm trying to, to apply here is sort of luck engineering, right? You know, biology car is lots of luck. You know, people discovered CRISPR, the people who discovered penicillin, a lot of biology is luck, but then how can we be lucky on purpose? And that's kind of what I like to do. And we like to train our group members on.

Peter O'Toole (08:22):
Yeah. And you, and you have to be looking for the lucky answer maybe. So, so it's not complete luck. You've, you've had to create some of that luck. I, I would say so. So don't, don't do yourself down.

Ed Boyden (08:33):
Oh no, no luck is learnable and teachable. In fact, when I got tenure, my group made post-it notes with all the things that I say all the time. And so they, these are some of the post-it notes that they commissioned. And so it has things like, you know, let's go for the ground truth, right. You know, you have to think backwards from the goal. You know, don't make assumptions and so forth. And these, these are all skills that can be applied to be lucky. And, and we, I actually have published two papers on, on other skills that can be applied. So for example, one thought is, you know, if everybody's doing one thing, do the opposite of it. Right. You know, we have a technique that we call expansion microscopy where, you know, for literally 300 years, people have been zooming in with a lens. We started thinking, why do we just take the darn thing and make it bigger? And so there, there are, again, I think luck is a learnable teachable thing.

Peter O'Toole (09:17):
And, and so, so I, I obviously know your work around expansion might cross be fairly well. And we just dying to dabbling it at the moment to ourselves. How on earth can you take something so small? How, how big have you expanded things now what's the limit you've reached?

Ed Boyden (09:34):
I don't think there really is a limit. I mean, you can take something and expand it. So for those who don't know what expansion microscopy is, we take a specimen, we infuse it with baby diaper, polymer, add water, and we can make the specimen much bigger. And because it's a precise expansion, it lets you use ordinary microscopes to do nano imaging. So hundreds and hundreds of studies have already con doing expansion. It's spreading very, very quickly. But up to the rental question, you can take a specimen, put the baby diaper polymer in and expand it, make a second round of baby diaper infusion and expand it again. And you can do it over and over and over again. We've done up to one millionfold volumetric expansion.

Peter O'Toole (10:13):
I I'm just trying to get my head around the scale that that would actually be at that point.

Ed Boyden (10:18):
Yeah. I

Peter O'Toole (10:19):
Think there can't be anything left of a cell to see at that point. It's gonna be so diffuse

Ed Boyden (10:24):
That well, we do Fluorescence microscopy, so we always add fluorescent tags anyway, to decorate the things we want to see. So actually expanding it and making diffuse is awesome because now it's completely transparent. And we had a joint paper with Eric Betzig who won the Nobel prize for his work on nano imaging, where we expanded and then did this light sheet imaging strategy that they did called Lattice lightsheet imaging. And, you know, in lightsheet you illuminate a two dimensional section, take a picture at a 90, 90 degree angle. So you can go blazing fast speeds. And we estimated in that paper, which is in, in the journal science in early 2019, that we could go about a thousand times faster than the nearest competing nano imagery method

Peter O'Toole (11:05):
For the, the Lattice lightsheet. And I, I slide sheet. And as you say, when you get something so big, you then need to image faster, you image in a much bigger area or using your low magnification ends, I guess, as a compromise.

Ed Boyden (11:21):
Well, so the ordinary micro, the vast majority of people are still using ordinary microscopes to do the imaging. I mean the, you know, of the hundreds of papers that have been coming out so far, I think mostly just use a regular confocal microscope. You might not need a huge volume to be imaged, to get a lot of insights into a biological process. You know, people are looking at the set of skeleton. People are looking at the nucleus. People are looking at motor proteins, people looking at synapses, sometimes a little bit of nano imaging will tell you something fundamental. And you might not to image an entire tumor or an entire brain with nanoscale precision to get a huge insight into a biological process.

Peter O'Toole (12:01):
I don't wanna go too geeky at point, but I've got to ask the question cuz one of the things you often hear is how does it stay in proportion X, Y, Z? How does it, how does it not distort those dimensions? So you've got a precise measurement of the cell.

Ed Boyden (12:17):
Yeah, well the polymer is very dense, right? The spacing between polymer threads is only one to two nanometers, smaller than most biomolecules right. Or many biomolecules. Anyway. we also anchor the biomolecules to the polymers as the poly expands, the biomolecules are dragged apart. And then finally we soft the specimen using enzymes or detergent or heat so that when the pull part happens, it's a smooth process. So by design it's an isotropic process, but we've also validated it's very extensively.

Peter O'Toole (12:49):
Yeah, no, no, I I'm. I'm well aware. It's just, you know, you mention it and people go, oh no, it must, you know, distort in some dimension and everything else. So I thought it was good to get it directly from you that it is as it does expand completely proportionately.

Ed Boyden (13:03):
Yeah. The distortion is not zero, but it's really, really small. It's like a few percent over a typical microscope field of view and turns out for the vast, vast majority of biological and medical problems. That's totally okay.

Peter O'Toole (13:15):
Yeah. And maybe we shouldn't ignore the fact that when we do super resolution techniques, there's, there's, there's operations in the image also distorted when you get down to that type of resolution. So, you know, nothing is perfect. That's for sure. Yeah. So you got into expansion microscopy, but I, I think you first made your name, your career really around optogenetics.

Ed Boyden (13:41):
Yeah, that was a side project that was done in parallel to my PhD. So I met a fellow student, Carl Reistrov when I was just starting out at Stanford who was in the same lab. We started brainstorming about how we could control the brain with light. And so it was sort of a parallel collaboration, not in my thesis at all for my PhD, but in fact we published the first light controlled neurons before I turned in my PhD on motor learning. And yeah, it started to take off very fast.

Peter O'Toole (14:08):
So again, I guess that would be what you call one of your lucks a as it were, but again, right place, right time and right. Solution to it.

Ed Boyden (14:17):
Yeah. But lots of examples of, of, of again, luck generating skills, right? So one thing that is very useful to look at something that people can do, but it might not be so easy to use by everybody. And then can you make something that is deployable and that works for everybody, right. You know, CRISPR was not the first genome editing method, right? Google was not the first search engine, but if you look for something that somebody's doing and you could make it work in everybody's hands, that can be great. And so many people had developed ways of controlling neurons of life before optogenetic, but they all were either complicated or had, you know, they required ultraviolet light, which biologists don't like, or they would require chemicals to be administered, which biologists don't like. And, and so if we just had a visible light driven all off the shelf, you know, protein that didn't require chemical supplementation, then that would be great. And that's what optogenetic is. We take these genes, put them into, into neurons shine, light, the gene product converse the light to electricity.

Peter O'Toole (15:12):
I I've got to ask, you mentioned Google. Wasn't the first search engine. What was the first search engine you used? Can you remember?

Ed Boyden (15:19):
Oh, there was Alta Vista and, and I can't remember all the other ones, but I do remember like writing searches in multiple engines to try to find out which kind having them vote so

Peter O'Toole (15:31):
Yeah, no, I certain remember Alta Vista at the one that was the default that we go to and then, then Google came along and I dunno, you kind of felt loyal to Alta Vista for a while. And then, then, then you kind of thought, oh no, Google is better and switch,

Ed Boyden (15:46):

Peter O'Toole (15:47):
Explain strange emotions to something you've got very little control over. Yeah. How big is your lab at the moment? How many PhDs and postdocs do you have? Oh,

Ed Boyden (15:58):
Right now we have 56 fulltime researchers in the group split half and half between grad students and postdocs or staff scientists. And yeah, it's it's maybe I dunno, is it the biggest neuroscience group on earth? I'm not sure, but it's, it's very large, but importantly, a lot of the people in our group are co-advised they work between my group and another group. And that's how we've been helping people discover new potential treatments for Alzheimer's disease. New ways of understanding schizophrenia, you know, new methods of, of you know all, all sorts of stuff, ways of seeing things and new ways, ways of controlling things in new ways. Yeah, I'm a big fan of this co-advising strategy.

Peter O'Toole (16:38):
How do you manage, how do you cope with the diversity of those projects that are going on in your environment?

Ed Boyden (16:47):
Yeah. I try to run the group on a three week block. So I meet with everybody for half an hour during that period. So if you have 10 hours a day, times, five days a week, that's 50 half hour slots. Right. and 50 hour slots, excuse me, 100 half hour slots. Is that right? Wow. That's a lot of meeting slots. So yeah. So if you, if you manage your time, well it's possible to, to get one on one meetings with everybody and, and, and, and lots of time to think and work and write and plan

Peter O'Toole (17:16):
And your, your energy levels are obviously they look endless. How do you keep your energy levels and your enthusiasm so high? Cause you must be enthusiasm, your students, you know, they, they, they're gonna be motivated. They're gonna be motivated by you. How do you actually keep those energy levels? So high?

Ed Boyden (17:34):
Hmm. Good question. Well, I think it's important to sleep a lot. I drink lots of coffee. And but I think for me, it's maybe the course that I am motivated, you know, it goes back to this long standing obsession. And I really think that maybe we could help understand what it means to be human and to help people who have, oh, it's what, over a billion people around the world have some kind of, of brain condition. And as the population, the world ages, it's getting more and more so. Yeah.

Peter O'Toole (18:06):
And so, so you, you do the 10 hours a day. Fine. You said you sleep a lot. What do you do between work and sleep?

Ed Boyden (18:15):
Well I have a family let's see, two children ages nine and 12. Yeah, my wife is a professor at BU she runs Boston University neurotechnology group. We used to collaborate on many projects, still have a few collaborations ongoing. I like to travel. I probably give at this point over 500 lectures over the years and I love meeting interesting people and going new places. And yeah, so I just spent a couple days in Houston at the Rice Neuroengineering Conference and at UT and before that I was in Denmark at Aarhus University at their annual conference. Yeah. Again, as a believer in luck, you know, connecting the dots between ideas and fields is a way of being more deliberately lucky.

Peter O'Toole (19:02):
And your nine and 12 year old. Is that correct? Boy, girl, boy, boy, girl, girl,

Ed Boyden (19:08):
12 year old boy and nine year old girl.

Peter O'Toole (19:10):
Yeah. And are they showing signs of following the same footsteps steps to yourself and your wife?

Ed Boyden (19:18):
We're all rapidly changes. You know they're, they're both interested in many things, you know, art and science and, you know business and writing and, and all sorts of things. So, yeah,

Peter O'Toole (19:31):
That's cool. And I I've gotta say, are they into anything? What, what are they, what are their hobbies? Is they into their soccer, their hockey, their, you

Ed Boyden (19:42):
Let's see. Yeah. I mean they both like different arts like you know, painting and drawing and, and writing and that kind of thing. They both like math, they both take math after school classes yeah, we try to do more outdoors things you know hiking and exploring and so forth.

Peter O'Toole (20:07):
That's cool. I've got some quick fire questions for you. I think you probably answered some of these already, but we're gonna go anyway.

Ed Boyden (20:15):
Sure.

Peter O'Toole (20:16):
PC or Mac,

Ed Boyden (20:18):
I'll just switch to Mac. Yeah. I had a PC, but it died and then all they were back ordered the ones that I, I wanted with a, a lot of storage. So I bought a Mac. That's the only thing that's around that I had enough solid state disc. So I've been learning unlearning 31 years of keyboard shortcuts slightly.

Peter O'Toole (20:37):
How you coping with that?

Ed Boyden (20:40):
It's slow. It's slow. Yeah.

Peter O'Toole (20:43):
Okay. So McDonald's or burger king?

Ed Boyden (20:49):
Let's see, I guess recently we've been getting burgers from shake shack, so yeah, every Tuesday that's gonna become our new family tradition.

Peter O'Toole (20:58):
sounds fun. I, I, I might, I think I know this straight off tea or coffee.

Ed Boyden (21:05):
Yeah, I drink coffee every hour and a half before four o'clock and then at four o'clock I'll switch to tea.

Peter O'Toole (21:10):
Oh, okay. And are they espressos Americanos, Milky coffees?

Ed Boyden (21:16):
I have an espresso machine over there and I try, yeah, I take two shots about every 90 minutes or so starting from when I wake up and yeah,

Peter O'Toole (21:23):
It's a lot of coffee in a day. I, I, I, I guess, yeah, you're becoming immune to parts of it and just feed off it.

Ed Boyden (21:31):
Yeah. And I like the ritual of it too, you know, making the coffee and smelling it and, yeah, it's just it's very meditative.

Peter O'Toole (21:38):
So do you grind your own coffee in the office or is it pods?

Ed Boyden (21:42):
We used to have our own machine that would grind things and, and so forth, but it's hard to clean. So recently we switched to, to pods. Once we got convinced that the pods were recyclable,

Peter O'Toole (21:51):
So okay. And at home

Ed Boyden (21:54):
At home we have a lot of different coffee machines two espresso machines. Yeah. One in my office upstairs is one of the kitchen a, a coffee machine and then a drip coffee machine. So I guess you have four and a French press if that counts. So five of them.

Peter O'Toole (22:10):
Okay. I also have two expresso machines at home and two at work.

Ed Boyden (22:15):
Oh, wow.

Peter O'Toole (22:15):
One pod, one that I grind in. Can't be it fresh.

Ed Boyden (22:22):
I know.

Peter O'Toole (22:22):
Yeah. So you do just, just, yeah, no, absolutely. Is the best wine or beer.

Ed Boyden (22:28):
What's that

Peter O'Toole (22:29):
That wine or beer?

Ed Boyden (22:31):
Oh, definitely wine. Yeah. Yeah.

Peter O'Toole (22:34):
Red or white?

Ed Boyden (22:35):
Red. Yeah. I like deep reds that yeah. Yeah. I don't know why, but I've always been just drawn to that.

Peter O'Toole (22:43):
Any favorite? Grape?

Ed Boyden (22:45):
Grape. Oh, like Cabernet, I guess I've had to pick one, but you know, blends are great too. I'm not that into the technical details, I guess. So but but yeah, like dry red wines, I guess.

Peter O'Toole (23:00):
Okay. So after your, after your coffee, you hit the deep red wines, chocolate or cheese to accompany it.

Ed Boyden (23:08):
I don't eat much sugar anymore. So if they, if we get like the extremely dark chocolate that's coarsely ground I like that stuff, but yeah, definitely cheese would be my default.

Peter O'Toole (23:17):
Okay. That's cool. So going back onto the more serious stuff and onto work, have you had any really difficult or challenging times at work?

Ed Boyden (23:28):
It was hard getting a faculty job actually. So I wanted to start the first group that just did technology for reading and writing to the, you know, to the brain and yeah, a lot of places didn't like that. So I was rejected by the majority of the places I applied to. And I started out as a professor in MIT school of architecture of all things. If I recall properly, they had a faculty search on a different topic and we're about to close it. If I recall they didn't hire anybody. And, and I had been a teaching assistant for one of the faculty, I guess, on the committee. And they said, oh, why don't you apply to this? So I, I applied there and that's where I was until two years ago when my group fully moved into the neuroscience building. And now I'm a professor in, in brain and cognitive sciences as my home department as of, of about two years ago.

Peter O'Toole (24:18):
So how so we sound remarkable. Cause obviously your career has been stellar. It was stellar from the, from the offset before you even got there, but you, because of what you wanted to study, you couldn't find an academic, you know, sort of leading post.

Ed Boyden (24:33):
I have to remember brain technology was not cool back then, you know the number of brain technologies that had been developed was was a handful, right. You know, two photo microscopy functional MRI patch, clamp, you know, there are a handful of ones that were regarded as, as really pioneering, but that was, you know, over a two decade period. So yeah, I really wanted to start a group that just focused on that all day long. And and so yeah, people were quite skeptical of it back then.

Peter O'Toole (24:58):
And when you started your group, how did you find it going for sort of being someone who was, I doubt you were ever properly supervised? I think you were probably very self motivated anyway, but how did you find it having that responsibility of having your own students and postdocs working for you?

Ed Boyden (25:13):
Oh, it was great. Yeah. I mean, having trained in physics and electrical engineering, I think I've always been a bit more of a theoretically mind person and I was able to do really great experiments, but I, I love thinking I love analyzing data and that kind of thing. So I, it was wonderful. You know, it's not like you get training on it. So it did take a couple years for me to, to learn you know sometimes that's by experimenting a bit, you know, how to run a scientific group and that tradition continues, continues to stay where many of my students now for their last chapter of their PhD will write a whole chapter about how they would change science if they were in charge. And, and many of them have started their own institutions one of them right outta graduate school. Many of them started companies, many have gone to faculty jobs, some of them right. Outta graduate school. And as we have a real tradition to think about how people would reform science,

Peter O'Toole (26:04):
It's, it's just incredible. so I, I'm gonna ask question now, do you prefer the biological question, the technology development or the backend analysis of what's coming out from that

Ed Boyden (26:17):
In terms of my own day to day work or what I appreciate reading, yeah.

Peter O'Toole (26:21):
Yourself, what, where's your passion? Where, where would you, if you think all your time, if you had to sync all your time into just all of those fo, whether it be the biologic that's coming through the technology development to look at the biology or the analysis that's coming at, what would you choose?

Ed Boyden (26:38):
Well, I guess that's not how I think what I, I, I want to see biology become a mature science, right? And so our group is morphin, right? We used to be pure tools, but now we're about one third application, two thirds tools, and that's gonna continue to evolve. I mean, I probably spend this fall learning some computer science to get more into machine learning and analysis of the data too. My dream is for biology to be a mature science, you know, physics after quantum mechanics. And now you can make lasers and microchips of the internet and land on the moon and so forth, right. Chemistry after the periodic table. And then you can make Teflon and nylon and who knows what else? Right. My, my dream is that biology undergoes a similar transition where we can, we can see everything and control everything. And that leads to a mature science where you can design the solution to a problem. And yeah, so I, I think fr now it's, it's been different by tools, right? We wanna see everything and control everything in the brain and in the body, but now the tools are getting so good that we are applying them more and more, you know, projects that our group initiated or help others initiate are now have now led to treatments in clinical trials for blindness, for, for Alzheimer's you know startup companies and so forth, you know, showing potential human benefit. And, and, and, and now, you know, now we're like, Hey, you know, the world's changing, we're gonna change as well. Right.

Peter O'Toole (28:01):
So we thought about the difficult times, the challenges you've had. What about the most fun time? Well, why, if you could think about any time in your career to date, what has been the most, the, the best time, the most enjoyable time of that career? So far,

Ed Boyden (28:16):
It's so much fun to see something for the first time. You know, when we first, when I did the first light activated neuron at one o'clock in the morning and it, it just worked, you know and you know, with all the work that we've done in expansion, it was so beautiful to see the first expanded brain, you know, that was kind of a shock and just delightful. Yeah. I think it's just one of the reasons why science is so much fun is you do get to see, you know, something for the first time in history, quite often, if you, if you, you know, pick problems strategically and you then, you know, use these learnable teachable skills to, to drive creative problem solving.

Peter O'Toole (28:53):
So you've got a team of over 50 people, and I'm just thinking here, you've got so many techniques at your disposal. Do you have a favorite technique?

Ed Boyden (29:04):
So again, that's not really how I think about it, just because, you know, I always wanna start with the question, right. And I think there's really two big questions right now. How do we see everything and how do we control everything right into the brain and in the body. Now, the current means to do that is to build tools, right? So seeing includes expansion, microscopy S spatial, multiplexing, and so forth control includes optogenetic and, and all sorts of methods for perturbing systems. And then of course, we apply that when, you know, if there's an opportunity, we have a collaboration led by Li-Huei Tsai MIT to try to, you know, tackle Alzheimer's disease, right? One of the most intractable diseases of our time, you know, node disease, modifying treatments, much less cures. My own grandmother has, has Alzheimer's disease. You know, if we can make a dent in that, let's do it. So I guess I think it more is just, you know, here, the end goal is we want biology to be mature science, so that like physics or chemistry before it, people can just get stuff done, right. Solve the problem. And, and that requires us to, to work on these multiple levels, to technology, application analysis and theory.

Peter O'Toole (30:07):
And what about favorite publication that you've authored or co-authored, do you have a, a favorite one for whatever reason?

Ed Boyden (30:17):
So again, I guess they're all puzzle pieces of a, of a larger hole, right. You know, if you see something, you know so expansion across could be lets you do nano imaging for cheap, but it doesn't work on a living thing. Right. More recently published a paper it's spatially multiplex, live imaging, where you take a cell and image different signals from different places in the cell that gives you high speed, live imaging of many things at once, but its spatial precision is not as good. So I find it hard to pick just one thing. I see it more as like a, an overarching landscape of possibility, right? So you have physics and chemistry, right? I like to study the history of science. Cause I think you can learn a lot about the future. You in physics, you have quantum mechanics, right? Where you have wave functions and, and, and matrix algebra and so forth. And you also have those certain things that you can do, like make semiconductors and so forth, which led to the micro ship. You on chemistry, you have the pure table, but you also have the theory of the molecular bond. You have thermodynamics and you have certain reactions, right. You kind of need all of them. So the way I think about it is if you wanna de-risk biology, make it a very mature science. We have to see control, right? See and control things. And those tools have to be integrated in a way that yields actionable, you know, insights that are therapeutic and theories that de-risk the future of science. That's how I think about it, you know, by analogy to the structure of the scientific fields of chemistry and physics.

Peter O'Toole (31:35):
So I I'm, again, a quick, a quick Google can tell me quite a lot, but you have won so many awards and, and it's not surprising. It really isn't. So I think discover magazine top 20 scientists under 40, and you've probably only about 20 at the time. You've got the one, the MIT technical TR35 for top innovator under 35 national academy of scientists, 2019. I, I, I only picked three cuz otherwise I could, the podcast doesn't last that long to list them all. How did you find the awards? Are, are you, does that give you a sense of achievement reward? Are you nonplused by it? What's your, what's your emotions towards the awards? There's so many of them.

Ed Boyden (32:24):
It's a good question. I think rewards have two practical outcomes. One is that it does sort of legitimize the work and, and make it more classical, you know, going, you know, going from the rebellious phase to, wow, this is part of science it's I think awards are part of that and other things too, like, you know, when Obama then president US president Obama announced the brain initiative in 2013, I went to the white house for the announcement and several of the people in the committee, they were like, oh yeah, ed, we want more groups like yours. This is the, one of the goals of the brain initiative would be to, to, you know, help more people like you get into brain science from engineering and so forth. And so I was very gratified to hear that as well. The other practical outcome of course, is that you know it can, you know, raise the profile of a field, you know, if, if people from different fields we can bring them into neuroscience. That helps a lot. Right. Yeah. And and some of the, the awards, like the Richter prize which is a, a 3 million prize, I think it's the largest neuro, not the largest neuroscience prize, the largest science prize on earth. You know, it gets just got such attention from people that people would be like, Hey you know, this, I hadn't heard of this thing before. I I've been an expert in this field. How can I help? You know? And that's also been really exciting to see all the talent pouring into this area where we just need so much help.

Peter O'Toole (33:41):
So, and that's, yeah, I can't find the right word, you know, all that different, all that you just said is not about you, is it it's all about it's it's not about you. Yeah. You just said there was, you have won, but you see them as just a great way of actually inspiring others and getting other people to be aware of the importance of the research that you are undertaking, which I, I think is you a really honorable approach to this and really well deserved,

Ed Boyden (34:10):
Well thought about being driven by the ultimate goal for me. And that, that for me is the understanding of human existence and, you know and then remedying it and making it better. And so, yeah, I, I even, I guess I even see the awards as a kind of technology that drives the greater goal, I guess.

Peter O'Toole (34:26):
So moving back into some quick fire questions, are you an early bird or night owl?

Ed Boyden (34:31):
Definitely early. Yeah. I'm usually in bed by nine and up by by five or six.

Peter O'Toole (34:36):
Okay. See, they're pretty sensible hours. I, I would say early bird, definitely. But you know, you're, as you say, you're getting a good sleep.

Ed Boyden (34:44):
Absolutely. So important sleep drives creativity. I'm pretty convinced.

Peter O'Toole (34:48):
Oh, I've gotta ask question. Now, when your head hits the pillow, do you, do you go asleep, switch off really fast?

Ed Boyden (34:54):
Yeah. I usually meditate for a few minutes, but then yeah.

Peter O'Toole (34:57):
Yeah. Which, which is healthy and good, Book or TV.

Ed Boyden (35:03):
It depends. Yeah. kind of on the circumstance. I like books, but I write so much that I often am tired by the time I can read them. But yeah, I've been reading books that are about meditation and mindfulness recently, and it's been very interesting

Peter O'Toole (35:18):
And TV. You said both.

Ed Boyden (35:20):
If there's something really good, then I'll watch it. I, I, I don't watch that much. I maybe only completed one or two whole series in my, my life, but, but but yeah, if there's something good.

Peter O'Toole (35:32):
And what about a favorite film? Favorite movie?

Ed Boyden (35:36):
Hmm, good question. I find it hard to pick cuz some movies I, I watch because I think they can serve some kind of role or function like they motivate me or and then those are just fun and, and so forth. Yeah. I I'd have to think about that. I guess mind. Sorry.

Peter O'Toole (36:01):
As we go on, you might one might pop into here. Go. No, actually I'll, I'll settle on that one. What about

Ed Boyden (36:07):
Original matrix? I found very inspiring. Okay. Yeah, actually that was around the time that I was thinking abouts genitics and this whole idea of brain control,uyou know,uI think that did influence me some that movie. Uof course we want to,uuse genetics to ease suffering and the matrix of versus very dystopian. But, but I remember watching the movie and thinking, Hmm, this is,uyou know,uthis is an example of, you know, neurotechnology gone wrong, you know, but what could, could we make one that would be beneficial to people?

Peter O'Toole (36:38):
It's amazing. Isn't it? The things that just in life, little things that you don't think about necessarily, but actually are a trigger or an inspiration to take to that next step. Have you had many inspirations in your career,

Ed Boyden (36:51):
Many what

Peter O'Toole (36:52):
Inspirations any mentors or people you've looked up to and thought? Ah, yes. And that's kind of inspired you to take a career step or change or development.

Ed Boyden (37:03):
I try to take inspiration from everyone and everything and to learn from every interaction. Yeah, but I think reading two biographies one of Seymour Benzer and one of Max Delbruck right as I was pivoting from physics into biology was very helpful. Cause these are examples of people who also made that transition. And Max Delbruck, you know, basically helped found molecular biology, Seymour Benzer discovered genes at [inaudible] behavior. It was, it was very helpful to learn how to think through the transition.

Peter O'Toole (37:37):
I, I, I think that's really good advice and looking for those inspirations, I, I apologize. You probably won't get much inspiration off me personally today, but, but, but certainly it's working the other way around. Do you have a favorite Christmas movie,

Ed Boyden (37:52):
Christmas movie? Does Die Hard count? Oh,

Peter O'Toole (37:55):
Absolutely. It counts. Of course it counts. Yeah.

Ed Boyden (37:59):
This it can cannot.

Peter O'Toole (38:00):
Oh, it definitely can. Can't it surely,

Ed Boyden (38:03):
Yeah. I'm trying to think of any other Christmas movies I know of, but yeah, I, I, yeah, Die Hard, I like it just also just, is it, I just, it is actually influenced a little bit how I try to tell scientific stories cuz it's, it will set up a plot and then it answers the plot question with an answer later and it and many people talked about how just tightly scripted it is and, and and but yeah, I think, I, I think if I had to pick like an unusual inspiration I, I definitely think reading the script for Die Hard shaped how I think about scientific storytelling.

Peter O'Toole (38:40):
OK. And yeah, I love the movie, its one of the best movies. I think. What about music? What's your favorite genre of music?

Ed Boyden (38:49):
I'm mostly like to listen to classical music, but I've listened for it so long that I've, I've recently been listening more to like electronic music. Yeah. So let's see. I listened to some Chopan and, and Beethoven and I was just listening to some Broms piano pieces last week, but also been really not reading, listening to a lot of electronic music from like different, you know, French and, and German producers and so forth recently as well.

Peter O'Toole (39:14):
Okay. Have your children got that same passion or are they getting you into more pop dance, rock music?

Ed Boyden (39:22):
They listen to a lot of the stuff that I listen to cuz you know, we, and they both play music. They play string instruments and piano as well. And so we'll yeah, we have a lot of music in the family.

Peter O'Toole (39:34):
Do you play any musical instruments?

Ed Boyden (39:36):
Not, well. I like to mess around with the piano.

Peter O'Toole (39:38):
Okay. Yeah. I, I fear that you say not well, but it's probably absolutely brilliant just on your own standards. Not well

Ed Boyden (39:45):

Peter O'Toole (39:48):
So is it genuinely not well about as bad as my piano, I've got a piano just behind me, but trust me, I it's, I, I get so infrequently. I have, do you know what people say? It's like a bike you never forget, like I'm scared to go on a bike cause I've really forgotten how to play it.

Ed Boyden (40:04):
Yeah. Yeah. Fair enough. Fair enough.

Peter O'Toole (40:06):
But yourself. So and just so just the piano that you learned,

Ed Boyden (40:12):
I learned French horn, but I haven't touched that in many, many, many, many years

Peter O'Toole (40:17):
That reminds me Petra Schwille. She, she, she she's one person banded the number of instruments that she plays with her family. So he's quite very cool sorry.

Ed Boyden (40:30):
Very cool.

Peter O'Toole (40:31):
Yeah. No, yeah, it is. Do you have any other hobbies?

Ed Boyden (40:35):
I like the outdoors. I love hiking and exploring and yeah. I love nature as a kid. I, my dad and I go camping every month for a while and it was always, yeah, I love exploring waterfalls and forests and deserts and all sorts of stuff.

Peter O'Toole (40:53):
Oh, there there's a good question. So you travel a lot. Do you prefer to go to a hot location, tempera or cold location? Do you actually have a preference if you could choose one holiday, would it be somewhere hot, somewhere moderate or somewhere? That's actually icy snowy cold.

Ed Boyden (41:14):
I try to mix it up. Yeah. For the last several years. Our family's tried to go spend the week between Christmas and new years on a beach somewhere, but I also like skiing and being in cold places too.

Peter O'Toole (41:26):
Ah, so if, so here, if you go to a beach you actually unwind and actually stop thinking or are you always after going sight, seeing, going to see something different or do you actually chill out and relax?

Ed Boyden (41:38):
A bit of both. Yeah. I really tried to relax. Usually by day three or four though, of the week, then I start wanting to read and write again. So

Peter O'Toole (41:46):
, it sounds like your, your has similar passions. So

Ed Boyden (41:53):
Brain technology group at BU and yeah, works on all sorts of wonderful brain interfacing stimulation and recording and imaging methods and applies them to different diseases.

Peter O'Toole (42:04):
So you obviously do teaching as well as a research. Do, do you have the same passion for teaching as you do for your research?

Ed Boyden (42:13):
Well, I, I teach classes that I designed or co-designed so yes. I teach, I teach classes which are very much about creativity and problem solving. We actually try to simulate what, how I teach people in my group to solve problems, but compressed to a class. And the students do projects where they have to invent new tools and or at least in, in a, in a class format do that. And yeah, it's, it's kind of a microcosm of the group that's been rendered in classroom forums. So it's a lot of fun

Peter O'Toole (42:40):
Actually does sound really cool. So I can't think of many places that would enable that to be taught. I'm trying to think it's not an easy subject to be teaching that type of skill. I think it's a really important skill.

Ed Boyden (42:58):
Our alumni are applying this way of thinking all over the map. Now, you know, one of my graduate students, Sarah Scarscit the PhD. And then in in a matter of months really raised over a hundred million US dollars to go and, and fight climate change. And then in several of my alumni are now working on all sorts of things, you know we spun out a 3d nano printing company actually. We had a paper in science in 2018 on you know, the expansion method we run in reverse, take a baby diaper polymer and laser print things at it and shrink it down dirt cheap way of making nanotechnology. So I'm very excited that the, the way we think about problems, excuse me, ground truth, oriented technology oriented, you know thinking backwards through problems, you know, welcoming creativity and luck. That's being applied to different fields now.

Peter O'Toole (43:48):
So if those classes that you teach and students, do you actually many come into your lab afterwards and actually start to do a PhD in your lab?

Ed Boyden (43:58):
Not that often it's happened a couple times. Yeah. yeah, actually one of the students who co spearheaded the expansion microscopy project took my class and then ended up joining my group later

Peter O'Toole (44:12):
And coming sort of to end my questions, I think in a minute. But where were you heading that you can tell us about where, where do you see actually, what is the biggest problem that is yet to be solved and you're still haven't found a solution for maybe that's a good answer question.

Ed Boyden (44:32):
Well, the biggest problem that I think is a big struggle is is consciousness, you know, subjective experience the feeling of feeling. And I think the big one problem is that we can't measure it. Right. I mean, it's not even clear whether I'm a conscious being, right. Maybe I'm just a very accurate robot and the real Ed is over on a beach, you know, somewhere just lying in the sun. Right. So yeah, I mean, what we can't measure, it's really hard to study. Right. And so yeah, something I've been wondering about is can we build a way to measure consciousness in some way?

Peter O'Toole (45:04):
Okay. And I, I'm gonna ask this on behalf of any young scientists who's listening. How on earth do you get a place to work in your lab? Cause I, I know far young I'd be wanting to be in there.

Ed Boyden (45:17):
Yeah. Well, we take graduate students from many different departments at MIT brain and cognitive science, biological engineering, electrical engineering, and computer science and so forth. Students at different Harvard departments can also work in our, our group as well, cuz MIT and Harvard have a several joint programs and what not for post-doctoral scholars, you know usually we interact to see if there's some mutual path that looks interesting. And as noted though like almost half the group, probably this point's co-advised. So we also have a lot of people we work closely with you know, Li-Huei Tsai I mentioned earlier where she's spearheading this attack on Alzheimer's disease. We have several joint students and now it's just a joint postdoc joint who are building tools with me and then we're applying them to Alzheimer's with, with her.

Peter O'Toole (46:04):
And one final question, you've been at MIT pretty much all your career, if you could move your lab. And so assuming you could move the lab and all the support, cause you've got an incredibly environment which does enable you to flourish. So, so successfully do you regret not moving somewhere else and, and sampling a different environment. And would you like to do that at any point?

Ed Boyden (46:30):
Oh, I, I don't see how that could be possible. So again, our group is not just alone, right? Almost half the group have co-advisors all over MIT and Harvard place. So if we move, we have to move like the entire city of Boston. So I, I Boston's really a great place. Right. Cuz you don't just have your university, you have Harvard and Tufts and BU and Brandeis and Wellesley and Mass general hospital and brig women's and Beth Israel. And it's like being in this gigantic university, that's the size of a city. And if you want an expert on any topic of any kind, you can find them. And our group is so like a like spiderwebs or the rays of the sun or connected with so many other things. So I really feel like we're like a, a hub and we're surrounded by spokes. But you know, it's it's, it's almost like an ecosystem at this point, not a group,

Peter O'Toole (47:17):
But that's surely not just Boston. Surely got those spokes going out to nodes internationally as well.

Ed Boyden (47:23):
Oh absolutely. Yeah. Yeah. We have collaborators all over the world that we work very closely with. Yeah, probably the number of groups that we work closely with is over a hundred groups at this point. Several of our papers will have like eight groups working together, you know, a Swiss group that studies the retina and a Georgia tech group that makes robots and you know, then, and then all these people come together for a study.

Peter O'Toole (47:49):
Okay. Ed, I don't think I've ever met anyone that has so much going on with so much diversity and just has a grasp of it. I think that's utterly incredible. You are an incredible person. Oh, thank so. Thank you for joining me today. Thank you for taking the time. I hope I haven't taken away your, your slots with some of your students for those who watched or listened to microscopist. Don't forget to subscribe and watched some of the previous back episodes for Ed. Just inspirational. Thank you so much.

Ed Boyden (48:23):
Thank you. Really appreciate it. So great talking to you today and yeah, stay in touch. And if anybody listening wants to work on something together, you know, again, I'm a big believer in luck. And one way to optimize luck is to connect people who have never talked across fields across disciplines, across all these, you know, these boundaries to, to bring people together.

Peter O'Toole (48:43):
Ed, thank you.

Ed Boyden (48:44):
Have a great day.

Intro/Outro (48:48):
Thank you for listening to The Microscopists, a Bitesizebio podcast sponsored by Zeiss microscopy to view all audio and video recordings from this series, please visit bitesizebio.com/themicroscopist