Eric Betzig (University of California)

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Intro/Outro (00:00:02):
Welcome to The Microscopists, a Bitesize Bio podcast hosted by Peter O'Toole sponsored by Zeiss Microscopy. Today on The Microscopists.

Peter O'Toole (00:00:18):
In this episode of The Microscopist, this is different. Okay. This, we're going to be joined live by the enigmatic Nobel Laureate, Eric Betzig himself, hopefully depending on the questions, we'll get to know Eric on a more personal level from his favorite foods to his TV shows?

Eric Betzig (00:00:36):
I like diversity in what I eat, but I don't really care where I eat it.

Peter O'Toole (00:00:40):
And it's not all been smooth sailing. And for time Eric was unemployed and felt as though he failed as an academic and in his industrial career, but he bounced back from that showing there's always an opportunity, no matter what life throws at you,

Eric Betzig (00:00:57):
Pretty much everything I've done since then. It's just implementing the events that came about during the period.

Peter O'Toole (00:01:03):
And hopefully you will also get to hear about his legendary friendship with Harald Hess, who was clearly more safety conscious than Eric either that or scared of Eric. We'll find out, hopefully during the chat,

Eric Betzig (00:01:14):
You know we've been tied together for many years

Peter O'Toole (00:01:17):
And together how these two best mates actually built one of the world's first super resolution, single molecule localisation microscopes, which was actually found in Harald's living room.

Eric Betzig (00:01:29):
My canonical joke from my talks is we could do it there instead of the garage because Harold wasn't married

Peter O'Toole (00:01:35):
This work ultimately led to Eric winning the 2014 Nobel prize in chemistry, which is quite an achievement for someone who claims to know very little chemistry itself.

Eric Betzig (00:01:46):
There are levels upon levels of fame. And let me just say, I'm already uncomfortable with the level of fame I'm at.

Peter O'Toole (00:01:53):
All in this episode of The Microscopists.

Peter O'Toole (00:02:03):
All right. Welcome everyone. So welcome to the first live Microscopists Podcast. So before I introduce a really special guest today, I'd like to welcome all of you. And thank you actually for coming here today. I think we had interest from at least 75 different countries, looking at the stats, first thing this morning over 500 registered for the meeting itself and it is pre recorded. So hopefully many more. We'll see it including my mum, actually I and dad who I think are actually tuning in or hopefully tuning in, never as it is technically competent as I feel sometimes. So hopefully they've got into this meeting as well, so welcome everyone if you've not been to or seen The Microscopist podcast before, a really important essence of it is quite personal. It's not really going through someone's CV and talking science. This is about the person up close and personal to get to know them better. And because it's life, this gives you a unique chance to actually ask the questions yourself. So there should be a Q and a part within zoom. Please access that pop in your questions and if they're appropriate, we'll see them. Not technical questions. No, let's keep this light funny. Let's get to know Eric in even more details. So let's start Eric. Good, good morning. Your side. Isn't it. Good morning.

Eric Betzig (00:03:34):
Morning. Yes.

Peter O'Toole (00:03:36):
So actually we were recently together for the virtual launch of a, of a microscope system and that, that was a surreal experience I thought.

Eric Betzig (00:03:47):
Yeah. Yeah. That's how you did a great job. I mean, you're the guy who had to deal with the virtual aspect of it and seeing the final product looked like you were there.

Peter O'Toole (00:03:58):
Yeah. But it was all your hard work. That meant there was a product to launch to start with.

Eric Betzig (00:04:02):
Yeah, well, yeah, mine was the start, but Zeiss obviously put in a lot of blood, sweat and tears to get to the point where they are today. Yeah.

Peter O'Toole (00:04:12):
I think that was just to the virtual launch,

Eric Betzig (00:04:17):
The product itself.

Peter O'Toole (00:04:20):
Okay. So let's start up. As everyone knows, you won the Nobel prize for chemistry. I think everyone knows that, so we won't dwell too much on that, but actually I've always wondered. Once you'd been awarded that? Did that make a change to the way you viewed science or even just your life? How big a change did it make?

Eric Betzig (00:04:39):
I mean the way I've used science, not so much, you know, I, I mean, I've, I've, I've known plenty of laureates prior to my getting a prize. I kinda know what it's about. In terms of the personal change, it's unfortunately gigantic. It's and it's, it's good and bad. I mean, there, I keep weighing in my head, is it overall a net plus or minus, and, you know, just has on my personal mood as to which way I feel at that day. But you know, the pluses are, you know, there's lots of perks, right. You know, people listen to you you feel like you have some kind of stamp of approval or something, so you don't feel as insecure. The it, it opens doors that, you know, would not necessarily be open otherwise. So that's all good. The the, the downs are just, again that I don't feel like I've ever been seen productive scientists that I was prior to the Nobel, the amount of distractions and so forth are just, you know, overwhelming at the beginning. It's really overwhelming. And then kind of make sure you say no more often and you kind of get closer to normalicy, but there's no question that my life today is completely different than what it would be if I hadn't. Yeah. And in some aspects better in some aspects worse. Yeah.

Peter O'Toole (00:06:16):
So, so I, I note that you, it's quite hard to say no. And I apologize for,

Eric Betzig (00:06:22):
I think you had to twist my arm quite a bit to do this.

Peter O'Toole (00:06:28):
Well, I've never been so cheeky and asked so many times I was dumbfounded when you actually, you came back and said, yes that final time, which is

Eric Betzig (00:06:39):
I was in a sweet spot after that Zeiss launch, you know, you kinda hit me. They had a good time.

Peter O'Toole (00:06:47):
I got very lucky then, but thank you for agreeing to, it was interesting in that conversation, you've been how it gave you a, a bit more security. You feel more secure in yourself. So does that mean, I guess everyone feels moments of insecurity or doubts themselves in some way, but yeah. You've had a prolific successful career, but you still struggle with that sort of thing.

Eric Betzig (00:07:08):
Totally. Yeah, of course. So, so there, you know you know, I was an abject failure up to about age 45. Okay. So I faced a lot of, you know, when I was 45, I think there's an alternative universe close to here in which I'm an unemployed, divorced mechanical engineer living in Michigan. Okay. It's just a very bizarre set of circumstances that took me to that. So an insecurity, you know, I think the more you live in a bubble and the more you get comfortable in a bubble, the more you feel secure. But I've had to live outside of bubbles at times. And as a result of that I feel I'm aware that I'm in a bubble and I'm aware of how fragile the bubble is. And that there are so many things that could change, you know, in an instant, or like take a guy like [inaudable], you know, who was brilliant microscopist.

Eric Betzig (00:08:14):
I think he was going to change the world with what he had and then just as he's kind of hitting his stride and peak a bit, dies glioblastoma, you know, you just never, never know what's coming in the future. And so Carpe Diem, and, you know, just, just, just take the most you can out every day. So I've never lost this kind of insecurity that, and the other thing about security is great. I mean, it's nice to have a paycheck. It's nice to, to have, you know, recognition and all of that, but it's also it's a double-edged sword. It's, it's the more security you, the less likely you are to want to leave that security and take risks. Okay. The risks I've taken in life, there have been because I've had my back to the wall and I've been insecure and you just have to kind of throw caution to the wind.

Eric Betzig (00:09:09):
So a Nobel prize and, you know, a good stable job at HHMI like that, all of that has a corrosive influence on my ability to take risks. And it's just, you know, it's a battle I have in my head all the time, you know, should I quit my HHMI job, you know? I mean, it's great. The benefits are great. The money's great. Security's great. I never have written a grant in my life and I hope never to have to write a grant in my life, but I also feel like it's a handcuff. That's been constraining me to Main, to stay in an area where frankly I'm getting quite bored. So, you know, it's, well, I have the guts at my age to make that change again. I don't know.

Peter O'Toole (00:09:51):
So you mentioned going back to about age 45 or now I think you're younger here. Surely.

Eric Betzig (00:09:57):
I think I was 42 in that picture. Yeah.

Peter O'Toole (00:10:00):
So this is when I think you load loads of pictures. So I'm going to try and get as many on as possible today, so you can share those pictures with us, but I think this is this, if I'm correct. This is when you were unemployed. Yes. At the age of 42 and unemployed. And I think that for a lot of people I'm thinking, Oh my goodness, that's a big risk. And I actually I think I've got a question actually from someone here, which, which ties in perfectly from Nick. Do you think that taking time off work gave you the space to think, and would you have even been able to develop PALM without that?

Eric Betzig (00:10:35):
Good question. And yes, absolutely. There's no question that the two periods of unemployment I had once I left Bell labs, and then once I left my dad's machine tool company were by far the most productive and influential times in my career. They were also the most scary, but they go hand in hand. Okay. the, my, particularly when I left my dad's company, you know, I hadn't really done any physics for nearly a decade. And you know, almost all the knowledge had filtered out of my skull. I didn't know anything. And so I actually went back to my freshmen textbooks and my freshmen homework sets that I, that I'd saved and you know, eventually I became a far more complete and sound physicist than I was ever before by having the time and particularly the paper that I wrote on the theory of optical lattices, you know, that's been one of my least cited papers.

Eric Betzig (00:11:38):
I think it has like 20 cents or something. It's probably one of the papers I'm most proud of in my career. It's the one time I was actually like a theoretical physicist. And I felt like I had an original elegant contribution to, to optics with that. And you know, both PALM and Lattice Light-sheet were basically founded during that period of unemployment when I was at our cottage, just thinking and pretty much everything I've done since then, it's just implementing the papers that came about during that period. So, yeah, it's, it's freaking scary and it's scary to not have any money coming in and you watch your bank balance dwindle and all the rest, and you don't know, you don't know what's going to be the end. You have no idea. And, you know, I remember once I first submitted the patent on lattices, and this was like end of 2004 I once I had the patent submitted, I decided I'm going to start to look for a job to do lattice lattice microscopy. And I remember applying to NIST are actually Jila and getting the rejection letter. And I think that was my lowest point. It was like, nobody's going to ever give me a chance again. And I'm just, I'm just screwed. And I, you know, all of this work and I don't know what's what I'm going to do. Right. And so, yeah, there's there and that could have happened. I mean, you know, we then stumbled on Palm and then, you know, by another crazy set of circumstances. And so I got lucky.

Peter O'Toole (00:13:16):
Yeah, it takes a company. My virtual backgrounds have actually stopped working all the days for that to happen. Like, I'm completely lost without the virtual backgrounds now, but how did, how did you stumble across PALM? And then there's a question actually from one of the delegates, just, just on the audience that we've got how did you?. So from Shiraz, great wine, by the way as well, how did you stumble across photo activated fluorescent proteins in there and that they could be used for PALM?

Eric Betzig (00:13:49):
Yeah, well, so, so again I've told this story, like, you know, my Nobel address and stuff, so you can see it there too. But the, the, there was in two phases, right? The first phase was after I left Bell and I realized based, you know, at Bell, I was the first person to localize single molecules to fractionable wavelengths, and the first person seeing them at ambient temperatures. And so I had that localization idea from that. And then Harald and I did the cryogenic experiment where we could separate points of exciton emission inside a quantum well, by the fact that they all glowed in different colors, even though their blobs were on top of one another. And I just, once I was pushing my baby in the stroller, I combined those two ideas and had this idea about, if you can just take molecules, isolate them in a multi-dimensional space and then find the centers of their mission.

Eric Betzig (00:14:45):
You got super resig there just, wasn't a really good way to do with that. So when fast forward a decade to when I was trying to get Harald to come in with me to do my optical lattice microscope, either as a company or whatever, and, you know, he wasn't really sold on the idea and he said, well, it's your idea. And I don't want to choose somebody else's cut. So but he helped me to start looking for a place where somebody would give me lab space or a job in order to do it. And he had been after he left and went in industry there was the National High Magnetic Field Laboratory in Tallahassee was run by an old friend of his called Greg Boebinger from Bell labs. And Greg had been trying to recruit Harald is to be a scientist there.

Eric Betzig (00:15:35):
And Harald had met this guy, Mike Davidson, who was kind of an oddball guy who came up with these, had an army of undergraduates making flourescent protein fusions. And, you know, the thing that got me back to doing lattice microscopy was I didn't read Chalfie paper about GFP until 2004. I had left science months before Chalfie's paper came out. If I had hung on, I might've stayed in science because I found that the mouth, my jaw was hanging down for a week. So anyway, so we, we visited Mike cause he had all these microscopes for, for testing out these fusions. And it was from Mike. We heard about photo activated fluorescent proteins, which had just come on the scene. And so another step of my trying to get a job is I was calling all my old Bell labs contacts to see, use that network to try to get a job.

Eric Betzig (00:16:27):
And one of them was a guy named Rob Tycko, who was now NIH in his own lab. And so he invited me there to talk about lattice microscope, but that trip was like two weeks after we visited Mike. And so when I went there, we were all filled with his PALM idea because as soon as we heard about photo activate proteins and say, you know, that idea needed 10 years ago, we can do it so good. God, it's so simple. You know, we, we gotta do this. And so we have the divine fire in us, at that point. And and so those two weeks later when I went to, to there, I said to Rob, you know, can you please, please, please invite Jen Jennifer Lippincott Schwartz and George Patterson to come to my talk. I really, really, really want to talk to them. So I talked lattice and the talk and I invited them to launch. And I said, we need your help. We're chief physicist we don't know any biology. We don't have your fusions. Would you please collaborate with us on this? And Jennifer was exactly the right person to approach because Jennifer's whole career has been about being an early adopter of new technologies to reveal biology. And so it was divine intervention or something, I don't know, but, you know,

Peter O'Toole (00:17:41):
Yeah, yeah, because Jennifer is really good at adopting new technologies. Right? Well, lots of scientists out there, very risk averse and not wanting cause cause it might not succeed. And then they're not going to get the publication and the next grant. So they're very worried about it. So how have you met that type of biologists is very wary of adopting new technology.

Eric Betzig (00:18:04):
I met them there they're the dominant species. I mean, particularly in the near-field days now my goal and dream with near-field was to do biology. You know? I mean, that's what I thought, you know, would be the, you know, having, having something with the resolution of electron microscope to look at live cells, that's what I wanted to do from grad school. But you know, when we started doing thick cells, it was like pulling teeth to find people to work with us, you know, and it was, it was a struggle. And with every new microscope, it's a struggle, you know every bite and even, even lattice, you know, I mean, as successful as I believe lattice is I'm hoping, you know, the commercial instrument from Zeiss will change this, this dynamic, but you know, I'm just been amazed at how slow the biologists have been to kind of come on to it because it really is a step change. I mean, it doesn't time what PALM did in space in terms of in terms of a big step jump in performance. So

Peter O'Toole (00:19:06):
We even, I, I'm not going to belittle Palm or storm for a second. I think it may have a more profound effect because it's, it's a much wider, it's a much bigger market that can readily access it really important. Your Palm and storm, you have to engineer it slightly differently. You have to present it slightly differently, takes a bit of effort. And a lot of biologists they're not lazy. They just don't want to put the effort in because it's time that they're losing. Whereas actually now you can go straight from your microscope sampling, put it on the lattice light-sheet.

Eric Betzig (00:19:35):
Yeah. I, I, the, the other, there's two other differences between Palm and Lattice in terms of, of, of biologist adoption. Okay. On the one hand, Palm is easy to do you can do and not living, right. I mean that tells you it's easy to do. The hard part of Palm has nothing to do with the instrument, has everything to do with the sample preparation. And so there's just an amazing amount of work to do this properly in terms of developing fusions, testing the fusions to make sure they're physiological, you know, making sure they're expressed at high enough density to do the fixation without screwing up the ultra structure. All of that is on the biologist. There's nothing that the instrument can do to help you with that. The instrument itself is easy. And as a result, you know, there's probably just as many, if not more home-built palms and some of them, there are commercial systems, but lattice is different. It's the other way around. Okay. in that, you know, the instrumentation is complex, but once you have it down, like in the Zeiss product, it becomes easy to do. And so there's a hope that, you know, I've worked very, very hard since we started the lattice to try

Eric Betzig (00:20:48):
To get it in the hands of people as quickly and as broadly as possible. But I know that the only way that happens in the end is commercialization because most biologists don't have the chops to do it otherwise. So, yeah.

Peter O'Toole (00:21:05):
So just changing tack a little bit, where do you fit when you got that job? With Janelia? I don't think you had a Lab open, so you work with Harald to start with, and I believe you actually, I say I don't want to use my backgrounds cause that's what just crashed it. I've got actually, it was a famous, there's a picture of you with Harald and Harald is stood outside, your labs with not one hard hat,

Eric Betzig (00:21:30):
But two hats, hard hats.

Peter O'Toole (00:21:32):
And you had known a, he he's a tough nut to crack. Were you a tougher nut to crack or you're very scary to work with if he's got to wear two hard?

Eric Betzig (00:21:43):
Well, well basically I'm just, I'm just put my hat on his to take a picture of this for a laugh. So that was actually in the housing village. So once we both got jobs there right at the beginning, actually our apartments were right next to each other. So, you know, we've been tied together for many years.

Peter O'Toole (00:22:05):
So moving forward from that, you actually built the first system actually in his living room, is that correct?

Eric Betzig (00:22:14):
Yeah. Yeah. That's right. Yeah. So, you know, again, my canonical joke from my talks is we could do it there instead of the garage because Harald wasn't married. So but yeah, it was, you know, it's small. I would, you know, there are many ways in which I've been lucky. I mean, luck is the thing that's defined my career. But, but I was lucky to latch on the Harold as a friend from the first day I walked in the Bell. I was lucky that when I left Bell, I told them to all go, go to hell. But when Harald left bell, he took all his equipment with them. So all that was in his shed. So a lot of, you know, in particularly that last experiment of the quantum well, we did, there's a lot of optics, so he had a lot of optics still that we could scrounge.

Eric Betzig (00:23:00):
And then you know, if beyond what he already had, it didn't require, you know, we probably put about 50 cage into building the microscope. BMCC was big. Ouch. but other than that yeah, it was, I mean, I'll tell you another story about that time to tell you how much of a bachelor Harald was that we had this idea of actually bringing in light beams from different directions with optical fibers in the back of the objective. And so we were making our own fiber collimators, you know, gluing on lenses and, and, and putting epoxy on it and to cure the epoxy. We said, well, let's just put it in your oven. Well, Harald had been living in that apartment for five years and when I opened the oven to put these things in, it was clear that the oven had never been used once in 5 years. So what's he eating, take out.

Peter O'Toole (00:23:59):
Well, that'd be asking you some quick three quick questions today. Would you rather get a takeaway or, or eat out,

Eric Betzig (00:24:09):
Oh, take away or eat out me? I don't understand.

Peter O'Toole (00:24:13):
Take in. So buy your food in or would you rather be out of the restaurant?

Eric Betzig (00:24:17):
I, I mean, I like diversity in what I eat, but I don't really care where I get, I get, you know, in, in fancier restaurants and like that I get, I get annoyed if the service isn't quick. I mean, one of my defining characteristics is I always feel like there's a clock ticking and I've tried to be really real. I just have so many things going on. I just try to be really, really efficient with my time. And I, I do get a little impatient in restaurants, particularly fancy ones. Do you cook at home? I do cook some at home. So again my wife, Na Ji her parents live with us and so dada does the bulk of the Chinese cooking, but one of my little ones he's 10 and I tend to, you know, get our fill of Chinese. So then it's, then it's up to me to, to cook and, you know, I'll do fajita's or, you know, last night we had steak on the grill or something, you know, more, more hearty American, you know, and then I do the cooking for that.

Peter O'Toole (00:25:26):
So I'd say that the answer next one, what is your favorite type well? I know. What is your type favourite type of food that that's what you're cooking. What is your favorite type of food?

Eric Betzig (00:25:34):
Oh, I don't know if I have a favorite you know, one of the great things about modern society is diversity, right? I mean, there's, you know, I love Indian food. I love Chinese food. I love Mediterranean food. I love food. So, and it can be simple, you know, I mean, you know, I mean, this is another thing I was thinking like that about the Nobel I was thinking as we were, you know, they have this and on the, on the night after you give the talks, they have this huge thing in the town hall with like a thousand people at dinner, you know, and you're seated with the royalty and like that. And I'm, and the food is just immaculately presented. Right. I mean, it's like, but you know, you eat it. And it's like, yeah, that's good food. It's like, you know, a hundred years ago, 200 years ago, they couldn't still eat like that while everybody else is eating garbage. Right. And modern society has made us as, as, as affluent, as royalty in terms of our dining choices were, you know, so, yeah, that was a, okay. So to wash down, beer or wine

Eric Betzig (00:26:45):
I'm not a drinker. I will drink socially a little bit with other people, but I mean, I get drunk incredibly fast, particularly for my body weight. Nobody can believe I will have a quarter of a beer and I will be plastered, but it's like a Delta function and comes and goes fairly quick, but I just don't really enjoy alcohol. Yeah. It's just not my thing. So tea or coffee coffee, for sure. Yeah. Having coffee drinker. Yeah. Good man.

Peter O'Toole (00:27:18):
Mean the right way to go with it. And so, so you've had your dinner back. Well, you got, you gotta read a book or watch TV

Eric Betzig (00:27:30):
Kick back. There's no such thing. My house consists of three children, ages two, eight and 10, it consists of a dog and a cat. It consists of my wife and two grandparents. There is no kickback when I come home. It's, you know you know, cook dinner for ed and I, if it's one of those nights you know, check their homework, make sure they've done their homework, go over their homework with them, play with the baby the two year old who wants to do Play-Doh or, you know, a, a puzzle or whatever, you know, play tug and catch with the dog a little bit, like, that there's no time for reading and tv. And then once my head hits the pillow, it's, it's, you know, one minute I'm gone, thats it. So are you a morning bird or a night owl. I am a morning person. Yeah. The only time I get to myself in the house is the morning periods. So yeah. I typically get up around five. So,

Peter O'Toole (00:28:35):
Okay. That's really, I tell you, I get up early. I get up around six. I like my exercise, so I get my exercise out the way work, and then whenever it's good to go out and do some exercise, but five that is a

Eric Betzig (00:28:51):
Nine 30, 10, something like that. At my age, I usually also have sort of a sleepless period in the middle. I just think about things. If I'm lucky, it's one hour, if I'm unlucky, it'll be three hours cracking, get myself back to sleep, but yeah.

Peter O'Toole (00:29:08):
Some of the best ideas are created.

Eric Betzig (00:29:10):
Yeah, of course. Yeah. I mean, you know, I follow a decaying exponential of creativity during the day. So, you know, either ideas I have night I use when I'm, when I first opened my eyes would have been percolating in the subconscious or in the shower. Right. I mean, that's where the, the, the getting past the roadblocks usually happens. And then I, then, you know, one of the things that I do now fairly uniformly is to take a hike in the morning, too. So usually after I drop off the baby at daycare, there's a nice park very close to where we live and I'll go for a hike there. And the good hikes are the ones where you kind of get out of the car and then, you know, an hour and a half later, you're back in the car and you don't know, you just have the running conversation, your head and going over things for the whole time. Right. Is that by yourself when you do those hikes? I'll totally. Yeah. I mean, it wouldn't be the same with other people. Yeah.

Peter O'Toole (00:30:15):
So how many children do you have?

Eric Betzig (00:30:17):
Five? So I, from my first marriage, I am two. So the oldest is 27 and elementary or not elementary high school teacher, math in Brooklyn. My 21 year old is a financial options trader in Chicago. And then three little ones.

Peter O'Toole (00:30:42):
And we'll any follow in your footsteps. Do you think

Eric Betzig (00:30:46):
None have really showed any interest in science, maybe Mia, the eight year old? She, she has potentially the leanings of a doctor, but I've, I've learned not to predict with kids. One of the things I've learned with kids is each one of them comes out of the box wired differently. And, you know, in terms of that whole nature versus nurture thing, I am firmly in the nature camp that, you know, anything that we as adults do to our children is just tinkering around the edges from, you know, what's kind of built into their brains from get-go.

Peter O'Toole (00:31:21):
So it's a great question actually from [Inaudible]. So the question there is how do they feel about you winning the Nobel prize? And actually I'm going to go one further. Cause look, I didn't realize you got there. You can correct my pronunciation. I'm useless at pronunciation, Pontifical Academy of sciences, which was awarded by Pope Francis himself. And that's a really select group of scientific advisors.

Eric Betzig (00:31:45):
Yeah, yeah. I, well, so I don't know what the question is. So first you have two questions first. What are, what are the kids think of the Nobel? And the second is about the Pontifical Academy. So in terms of what the kids think you know, at first it's like, you know, they don't really understand, I mean the older, you know, I guess yeah, the oldest was at NYU, then the second was still in high school. And then the young ones, max was like five and Mia was like two. So, you know, we took the like younger ones. In fact, we took all of them to Stockholm. I don't know, it's, it's something that isn't really real to them because they're not in the, in the field and like that they know that yeah, some people know dad as being sort of famous for what he does. And, but it's, it's not something that, you know, is an everyday job. If your

Peter O'Toole (00:32:40):
Kids are watching this now, very famous, we're not

Eric Betzig (00:32:46):
In the Kardashians,

Peter O'Toole (00:32:50):
They're not watching it

Eric Betzig (00:32:51):
Levels upon levels of fame. And let me just say, I'm already uncomfortable with the level of shame I have

Peter O'Toole (00:33:00):
Pope Francis and the advisor.

Eric Betzig (00:33:02):
So, yeah, so I, I turned down many, many, many, many things. Again, I just asked a few people, if this is something I should do. And when I was asked and, and I did, and you know, there's only been one meeting so far because COVID killed the one for this year since I've joined it, again, it's, it's, it's meant to, they, they put out in the, in the yearly meeting, they'll have a topic and they want everybody to see, to talk about how their particular expertise influences that topic. And and then every now and then I'll have another specific topic in which they want to write a report for, for the Pope. And it's similar to national Academy in that regard where, you know, there will be, you can volunteer to work on a committee for something that goes to to Congress or whatever, to help, you know, you know, inform them about signing the policy. So it hasn't been a big deal. Just, you know, it's just one of those things that, you know, after talking to people I trust, I figured, well, okay. It doesn't look like a big time team,

Peter O'Toole (00:34:18):
So I've got to ask, are you religious yourself?

Eric Betzig (00:34:20):
No. I I'm stone cold agnostic. Okay. I'm I, you know, I, I I'm enough of a scientist to believe that there isn't enough evidence to completely re it's hard to refute something like ideate. Right. There's but it's also hard to prove something like ideate, right. From the scientific sort of, you know, Karl popper, falsification type, what I consider real science. And so I think the only intellectually honest point of view for someone of my beliefs is agnostic.

Peter O'Toole (00:35:03):
So you mentioned earlier when you mentioned you had no downtime or very little downtime to rest at home, and you've just started up a new, well, actually not, maybe not that new, relatively new a company, Icon Therapeutics, thats another other big venture on the back of everything else you're doing it them.

Eric Betzig (00:35:22):
Yeah. But again, this is, this is one of those things, you know, once you have the Nobel prize, most of our people want as your name more than your time. So actually Icon's an interesting story. That's the company that, that, that we found. So I was kind of dragged into this by two of my collaborators Bob Tiegen, who was at Berkeley and [inaudible] is here too, but at one time at Janelia, we had what was called the transcription imaging consortium. And we collaborated there imaging transcription factors and live cells and teach himself. He was president of HHMI, he's a huge polar in of money at Berkeley. He's a big deal. He's, you know, on all sorts, he's, he's got fingers in thousands of pods and he's wealthy besides because he had a drug startup in the late nineties.

Eric Betzig (00:36:19):
But in the and doing these experiments from his biochemical, he's a biochemist by trade. And they had come up with this model about how transcription starts by all of these transcription factors coming to the start of a gene to create a transcription initiation complex, and then recruits this, this preliminaries PALM which then zips along the DNA and spits out. And they have this model in their head where you have each piece individually coming in. And the stable thing forming that might last for minutes or hours when we actually started damaging by SPT PALM and the individual molecules, we realized they were only binding to any particular spot for seconds or less. That's like, well, crap.

Eric Betzig (00:37:07):
So this was really a paradigm shift in transcription. And it's kind of related also to the whole concept of of, you know, phase condensation which is now kind of a hot field inside of cells and so forth, but on a much more molecular level. And so Teigen thought, well, gee, this might actually be able to be used as a drug screen because what we, what they found was that the reason the molecules bind to one another, or particularly these transcription factors is they have intrinsically disordered regions. And these regions act as binding agents, either the DNA or to other partners. And so so, and it turns out in certain diseases like Ewing sarcoma you'll have a particular gene, which is transposed during cell division and end up getting a intrinsically disordered region grafted on it to make it go into overdrive.

Eric Betzig (00:38:10):
And so that leads to cancer for children that's lethal. And so the idea is if you could find chemical compounds that modify the binding affinity of these intrinsically disordered regions, you could potentially have a drugs. And in fact, it's target most all other drugs target sort of the conventional pocket lock and key type approach and mediating that. So it's actually then targeting all of the proteomics posted the 2% of the proteome that has been targeted so far. So it's, it's really kind of a very high risk. None of this is my ideas. This is their ideas. My, my, my use is I know how to build microscopes. I know how to build microscopes for high throughput screening and they provide all of the biology and the medicine, and then having the shiny metal to help attract investors. And so, but once it's kind of set up large, it's not a big, big strain on my time.

Peter O'Toole (00:39:17):
Overall over all these period. There's a question actually from, I aren't going to pronounce this wrong Phazer. How have you balanced your work with your personal life? I think that's really important, actually. I think it's really important to make a balance somehow.

Eric Betzig (00:39:31):
Yeah, that's a good question. And the balance is not a static one. It's based on, based on opportunity and need. Okay. So I, in some ways I consider myself a serial father and serial entrepreneur in that, for example you know, obviously I worked very, very hard when I was at Bell labs. You know, 15 hour days were the norm, you know, at least six days a week. Right. Harald and I just worked like crazy. But when I left, I'm a house husband, right. So I'm not working at all. I'm trying to figure out what I'm going to do. And I focus on, you know, on the kid. And then I started working for my dad's company and eventually it became the same thing. Right. hyper-focused on that. And then once I left that, it was again, back to being more connected with the kids, but, you know, and then, you know, once Harald and I got the idea for Palm, it was like, I'm either in San Diego at his place or I'm in Bethesda, that Jennifer's place. Right. And so I'm gone again. And so it's, that's rough on the kids. That's kind of, you know,

Peter O'Toole (00:40:53):
Any regrets then on that side.

Eric Betzig (00:40:55):
Well, I always have regrets, right. I mean, I think it's certainly contributed to the disillusion of my first marriage. And you know, there were rough years maybe, maybe it's just because it kind of coincided with, you know, particularly the oldest being in the teen years when I'm not around a lot. But there were some, yeah. I mean, it's not all fun and games all the time. I tell you between unemployment and between, you know, problems with raising children. And, you know, I don't know, I don't know how old your kids are, but you know, what are you got any teenagers?

Peter O'Toole (00:41:30):
I've got a hat trick. So 13, 17, 19.

Eric Betzig (00:41:35):
Okay. So you, you know what I'm talking about, right? I mean, when kids are finding themselves as teens, I think that's the hardest time babies are trivial compared to teenagers, you know and little kids are wonderful, but when they start getting, you know, developing their own independence and stuff it's, it's, you know, it's challenging as a parent.

Peter O'Toole (00:41:57):
It does it great questioning. I actually, I can't see who it's from. I'm really sorry. But how did you find being a house husband?

Eric Betzig (00:42:06):
I mean, it's great. I mean, look, I love kids. I mean, you know, there are some people who told me I was nuts to get remarried and have kids when I'm near sixty. And sometimes I might agree with them, but I wouldn't change it for a minute. I mean, there's, you know, there's no entertainment greater than having kids and playing with kids and kids see the world with new eyes. You know, every child has, if there's one instinct, humans have it's curiosity and all of them are born with that curiosity. All of them are scientists. And they're whether it's whether it's like sticking a fork in the electrical socket to see what happens or whatever, right. They are always experimenting. And they're just hilarious. I mean, they constantly making, see things that you have. You're, you're a fish in water and you don't notice the water and then the kids point out the water and you just laugh. So I love it. You know, I, I could, you know, if I really got disappointed, I'd be happy being just a stay at home dad for the rest of the career. Yeah.

Peter O'Toole (00:43:10):
As long as you teach them properly, because when they put that fork in the electrical socket, as long as you don't tell them, that's what the big bang is.

Eric Betzig (00:43:20):
Yeah. Yeah. So it's great. Yeah.

Peter O'Toole (00:43:22):
Okay. Teach them properly. That's brilliant. So I think you've also got a Jack Russell. I'm not going to try my virtual backgrounds. I'd say I crashed out last time. So your Jack Russell, what have you called it

Eric Betzig (00:43:34):
Bessel? So, so, you know, Na in her work,ucame up with this really clever idea of using two photon vessel beams. Udon't, she's she studies the visual system and the mouse with usually two photon. And the problem with two photon again, is it's a great optical sectioning technique, but it's too slow to get 3d volumes by doing that. Ubut oftentimes you're looking at mouse brains that have sparse expression of G camp or something. And so there's no reason not to take that all as sort of a maximum intensity projection. So she uses Bessel beans in her work. Bessel beans were the start leading the lattice microscopes. So,uso, and we also have a cat, a Bengal cat. And so with both animals, when we got,uwe put up a white board and everybody in the family starts listing names, and then we put a vote and Bessel had a unanimous, unanimous selection. So

Peter O'Toole (00:44:33):
Yeah, that's a cool, I can imagine that quite a few other dogs being called Bessel. Yeah.

Eric Betzig (00:44:37):
Yeah. Well, it certainly runs in a fast and a straight line for long distances. So,

Peter O'Toole (00:44:44):
So looking at, so look, let's look, start looking towards the future. You said that in a way that you become less risk averse. Okay. So unshackle yourself.

Eric Betzig (00:44:54):
I would say I've become more risk adverse in my later years. Okay. I'm constrained by the golden handcuffs of HHMI. I'm constrained by the fact that I have three young children I still need to support. Right.

Peter O'Toole (00:45:12):
It is my, my poor English said, unshackle yourself.

Eric Betzig (00:45:16):
Yes. I want to one check with myself. What would you do? My dream is to work on space transportation. You know, there are, I have a very negative view of the state of the world today. And what I latch on is things that are positive. And I am in freaking ore of what Elon Musk has done in his career. I worked in the auto industry for my dad. I tried to change that industry and the part that he works in, I failed miserably. I know how conservative that industry is and reluctant to change. Being at Tesla, changed the conversation about what the future of the automobile is. Okay. After doing PayPal and then doing that, that's enough for anybody's career, but doing space X as well, and taking another incredibly conservative moribund industry and turning it on its ear as he has done and not resting on his laurels with the Falcon nine, but moving on to Starship is just amazing.

Eric Betzig (00:46:29):
And you know, there are times in which I just, I just say, I hate the world. I want to quit. I'm going to go, you know, live in my my second house and I'm going to become a farmer, but every now and then there's somebody who will lift me out of that and say, it, that is inspirational to me. Maybe people are inspired by me. I don't know, but I'm inspired by a guy like Elon Musk. And what he's done is he's the Howard Hughes of the 21st century. Just no question. And so you know, I wanted to be an astronaut as a kid. I've always, I've always followed this field. And when the space shuttle came along, I knew it was a mistake from the beginning. And it was a horrible mistake and people aren't willing to acknowledge the mistake it was.

Eric Betzig (00:47:17):
But and I do believe with Musk that we have to get past the great filter if we don't become a multiplanetary species, I think our time, our days are numbered. And so I would like to contribute to that. I mean, because I'm a physicist because I like big ideas. I want to do something really disruptive. Look, I have even if I quit my job, I have reasonable security. I can go out and give talks and get honoraria, whatever, you know, my wife has a good job and works. You know, she's, she's a professor here at the U, right. So, I mean, it's just a question of how much money is a shackle. Okay. Money is a drug, okay. Salary is a drug. And you have to decide when you're going to kind of go cold Turkey. But I would like to work towards nuclear propulsion. I want to go back to 1938 and look at every nuclear reaction since then. I think we've become too locked into uranium. And plutonium is sources of energy when there's many, many nuclear reactions, one potentially. So I want to do what I did in 2002 and start from ground zero and just start learning and reading and see if there any, there might not be, but I'm going to learn a lot if I did that, I would love to do that. But you know what go to ask

Peter O'Toole (00:48:42):
Very quick answer. I'll kind of come back to this. So the Rita actually asks, have you ever managed to take time off to visit space X?

Eric Betzig (00:48:48):
No, I haven't. I would like to rather than re visiting Hawthorne, I would love to go to Boca Chica and actually watch one, one of the star ships launch. And I'm sure I'll have the opportunity is everybody will eventually to do that. Cause they're going to be launching a zillion of them if Musk gets his way.

Peter O'Toole (00:49:10):
It's really actually my son's really into it as well. So he's a computer maths, computer scientist, but really loves the thing. So actually on a clear night, when they're launching the rockets, usually you can gets to see, the glow, as it goes over, you actually go out and we watched that as a family cause we love to do that. So back to where you are, come on, what's stopping you.

Eric Betzig (00:49:36):
That I have five kids. We spend a lot of money. You know, we live in upper middle-class lifestyle and one of the most expensive places to live in the country we'd have to cut back. So my indulging myself means, you know, I mean we could easily do it. It's just that, you know, there would be more anxious than the house about money. There'd be, you know, you know, and I'm, I'm, money-wise, I'm a conservative guy. This is why I've been able to take time off. Right. I was able to take time off after, after my dad's company because, and after Bell, because I'm, I'm a crazy saver. Okay. I mean, I, you know, I just like to the purpose of money, isn't isn't to show yourself as well, but money equals freedom. Okay. And more money you have, the more freedom you have up to a point beyond that it becomes a burden. So there's kind of a, a sweet spot of where you want to go. And I just have a lot of the other thing that's still keeping me here is we're still working on the final microscope, which is taking bloody forever and I have a responsibility to get that microscope done. So that's actually,

Peter O'Toole (00:50:50):
I'm Diana to ask just that. Are you developing a new microscope?

Eric Betzig (00:50:54):
Yeah. So, so, you know, so again for me, because I've been in, I think one of the most valuable times I had was working in my dad's company for, for years thereafter, I thought it was a complete waste of time. Cause it was so orthogonal wouldn't transfer to, but what I've learned is that there is almost no utility to making new microscopes, like what we make, unless they can be commercialized in the end. Because again, biologists, I don't care, you know, so, but it's a pipeline because it can't be, let's say you have a good idea for a microscope. You patent, whatever, no company is going to take the risk on that, unless they know there's a market because it's probably a five, $10 million investment. Right. And so you have to prove it to them. There's a market. So you start doing stuff in your own lab and you start doing, you know, Janelia was great for this because it was easy to bring in outside visitors.

Eric Betzig (00:51:52):
So we've had over a hundred outside, visitors use the loudest light sheet that we had. And we got a lot of papers and a lot of attention, and that was great. That was a great microscope. But it's too small bottleneck. And so we spent months, six months at least of our own effort, not designing the next microscope, documenting the existing microscope. So other early adopters could build it themselves. And so there's probably, there's a hundred research licenses, demand sign, maybe between three eyes, microscope and other, maybe 50 actually operational. And they, again, start to create this, this buzz and, and desire for this microscope. And then you get, you know, company like Zeiss to buy in on it and then they develop the turnkey instrument. And then it's basically at that point, I was so relieved to do that launch insights because to me this was job done.

Eric Betzig (00:52:46):
I could kind of finally say, you know, lattices is a baby, that's gone to college, it's out the door. My responsibility is done. Whatever they do now is, is their business. I don't have any role in that. And so I'm so, so the new microscope is basically after the lattice, we started going multicellular with it and random the aberration problems starting from with now, when, when she was in my lab, we had a long program under the adaptive optics deal with that. We had put the adaptive optics on the lattice light sheet. We had a nice paper with that in 2018. But it's, you know, it was attempt 10 foot optical table filled with hardware and nobody's going to build that. Nobody's gonna align that. So then we had so we said just like with the same thing happened with the lattice, there was an early version of last young made.

Eric Betzig (00:53:41):
And then we made the second generation that others can replicate. We started doing that with, with the lattice state, with adaptive optics, about two or three years ago. And we realized that, well, by the time you buy all of the equipment needed to do lattice say, you know, cause it requires a Ty Sapphire laser for the GuideStar. You basically have all the equipment that goes into a confocal microscope, a two photon microscope, a Bessel B microscope, an image scanning microscope, a 3d semi-pro scope of phase contrast microscope, a lattice light sheet microscope on about 10 different modes. And we say, well, you know, why have to have 10 microscopes? Why not just make them a Swiss army knife where they can all use the same hardware? So that's, what's become this mosaic project. And it's a great microscope. Great design is by far the most complicated thing we've ever done.

Eric Betzig (00:54:40):
We've been working like the bejesus to document everything as we go along. Sadly, we had an initial group of seven people trying to build this, but enough people got wind of it and want to do themselves that we're up to like, I think 28 licenses now. And we still haven't really finished number one in terms of getting all the modes running. So, you know, in COVID certainly hasn't helped. So, and it's a complicated beast, so we'll get there, but I have a big responsibility to get that over the hump because there's, there's 28 different groups who popped down half a million bucks each in order to do this and I owe it to them in order to get it done. So

Peter O'Toole (00:55:24):
I'm gonna take you back to the start when you talked about it's no longer your responsibility, you got rid of Zeiss, took it on and commercialized it. I would say the other, the other rewarding side of that is because it's now on a turn key system with software support and everything else. It also opens up the real scientific impact because the much larger field of users. So actually to an end user perspective, you know, it's profoundly a big step. Did you ever think that getting on an invert just, just very quickly,

Eric Betzig (00:56:01):
I mean, it was obvious from the beginning that this was the way to go. What was less obvious was how to get it done, right. That's optically challenging. You know, I'm, I'm, you know, I'm, I find this for the experts listening, this DUNS be approach, you know, of, of the single objective reverted kind of thing is it's a very clever idea, but man, it isn't as clever or as versatile as Zeiss solution. Zeiss solution is really 21st century to use the freeform optics to do the correction from the bottom. I mean, that's, that's a whole nother level than anything you're going to do in an academic environment. And that's the power. I mean, the thing I've never been, I've never been comfortable unemployed. I've never been comfortable in industry. I've never been comfortable in academia, but I see the roles that all three of those things have in the innovation pipeline to the point of impact.

Eric Betzig (00:57:01):
And so if I think there's one way in which I've been successful is by moving from one of those things to the other, as I go along, you know, just working alone and coming up with the idea for optical lattices is not enough. It's just going to be dormant going to a lab and actually demonstrating that it's useful and getting some biology is great, but it's going to die on the vine there if nobody else can do it. And so nobody else is going to provide the level of refinement and support that a commercial company can do. And that's exactly what biologists insist upon in order to be able to use these technologies. So you have to go through the whole type. So this is hopefully my first example in which well, I guess Palm was another, but you know, again, so much was on the hands of the, of, of the sample prep, which is the biologists and lattice is different.

Eric Betzig (00:57:58):
The other thing that, that, you know, I know I'm pulling the subject in my direction, but the other thing that, that that I still don't get is how many biologists are still focused on structure and still focus. You know, that there's a big, you know, not to take anything away from Harald because he's brilliant, but his and his work with, you know, the fifth sound, the 3d EM, it's just phenomenal. But I have looked at enough, I've looked at more cells and more biological systems live in ways that nobody has ever seen before. I honestly feel like Lehmanan most of the time, you know, I've seen things nobody has ever seen. And I've seen enough to know that you will never understand the living cell by looking at it in a dead state. The dynamics is what's central to the cell, not the structure, the structure comes out of the dynamics. And so, you know, SPT column will be the most important part upon in the end, not the, not the dead cell, you know, looking at the structure and lattice light sheet. I still believe that if lattice light sheet is appropriately adopted, it will have, it can transform biology. I really believe that. That's not just my, that's not just my ego talking. That's my true, you know, also independent belief on what is needed to understand the cell

Peter O'Toole (00:59:25):
At this point. I'll tell you what I, one day we're going to have to get yourself and Harald to argue the toss on this. Cause that'd be,

Eric Betzig (00:59:31):
That'd be great. We argue all the time. That's the best part of our dynamic.

Peter O'Toole (00:59:36):
So lovely to have that discussion because I can see exactly why you need the ultra structure as well as a live. I think you can maybe make more profound discoveries faster in a live approach because the ultra structure is really tight, but

Eric Betzig (00:59:48):
Yeah. Yeah, I totally agree. You need the ultra structure, but, but yes, there there's a much greater opportunity on the live end I really think that it's such a step jump in terms of what we can see that, you know, I think there's so many low hanging fruit that biologists can pick with this.

Peter O'Toole (01:00:07):
You love it. We are going to get through some questions quickly cause we were up to an hour. But if we were allowed to you, okay, for just a bit longer Eric

Eric Betzig (01:00:13):
Here, as long as you like,

Peter O'Toole (01:00:15):
Really I did lose some questions, but if we get through as many as possible, I apologize to anyone who sends a question. I don't get to ask in some way, shape or form and actually I'm going to be selfish. And I couldn't cause I lost it at some point. I can't see what the question was from somebody actually, same question. I'd have what's the next beyond the mosaic. What's the big thing microscopy has to do. What, how, what future, the impossible microscope and nothing's impossible. Just so one day, what would that microscope do?

Eric Betzig (01:00:42):
All right. So I keep talking, there's, there's two sides of this. There's what is, what is needed right now and certainly doable. And then there's the Holy grails. Okay. To me the Holy grails, the things that would potentially pull me back into my cross would be to have protein specific contrast label-free at high resolution noninvasively. Okay. I don't know how to do it. All right. The other option, the other Holy grail would be, I don't care whether it's by fluorescence or whatever. But to be able to see all the molecular players involved in a biological process at the same time, not just one at a time, two at a time, three at a time. So the whole endosytic pathway, everything from clathrin adapter, proteins, rabb you know, the whole thing to see the whole mechanism going on. And once, all right, those are the Holy grails.

Eric Betzig (01:01:42):
I don't know how to get to those. Holy grails, extremely narrow line with labels with orthogonal labeling of 30 things would get you there be chemistry, crazy nightmare to get to that. But maybe there are better ways. I don't know in terms of the, what the field needs now. So yeah, this is going to piss off a lot of people. My feeling is so one of the reasons I want to get out of microscopy is I feel, I feel that fields of technological development goes through cycles, just like a farmer's field. Okay. There are fertile times after you've, after you've put in the nitrogen fixing plants and you can grow your corn, but after a while you've grown enough corn and it needs sort of a regeneration period. I think the, you know, you look at something like the mosaic, there's nothing technically novel in it at all.

Eric Betzig (01:02:42):
It's a lot of engineering, but there's nothing different. Same with the lattice. Say it was combining two microscopes. We already had them, right. It's necessary to do one like that, but it's not, you know, I feel like lattice light sheet and Palm, those were step changes. Right. In terms of same thing with near-field when I did near-field those were step genes. Okay. the rest is just, you know, throwing ingredients together in different permutations. So microscopy in terms of the hardware development to me is increasingly uninteresting because I think it needs to, you know, again, one of the things that was amazing about starting to work with Harald in 2005, when, you know, we had the idea for Palm, but at that time I didn't even know what a EMCCD camera was because I had never seen one. I used to work with an argon ion laser.

Eric Betzig (01:03:32):
And when I was doing near-field, it was eight feet long. When I saw that you can get things, dialed pumps, lasers, pagans. I felt like rip van Winkle and all the filters, all like the summer filters and like that the filters back then sucked in the nineties. Okay. So it was like, Oh my God, this is going to be so trivial. There's all this technology. So again, you know, things, things get developed. And the beautiful thing about technology is you never know how it can be combined with all the other pieces of technology that around to doing things. But right now I feel like every time there's a new, tiny little thing, whether it's a new mirror or a new wrankle, everybody in the fields. So it's not that interest. So to me, the frontiers of microscopy today that are doable, one is I'm very enamored and impressed by what people have been doing with deep learning.

Eric Betzig (01:04:26):
And I think there's, it's very, very dangerous. You've got to have a good training set and you have to validate it. And I'm really afraid there's going to be a lot of garbage because people are not going to do the right type of validation of what they're doing, but when applied, right. I can really see how that can make a big jump. Basically you're using priors, right? I mean, Palm is kind of using a prior right column is saying I'm prior know that this is a single molecule and not more than one, right. Priors can take you a long way. So I think that's got a lot of wheels to go. The other problem in the hard intractable problem. And the thing that depresses me about still lattice light sheet and lattice say, Oh, is the data. I mean, everybody knows this. Okay.

Eric Betzig (01:05:14):
I mean, with the modern CA you know, I've got on computer now, I'm trying to render a 24 terabyte dataset, right? So it's with even I got a $30,000 workstation. We have a million dollar cluster that it spoke too, and it's still an enormous pain in the to deal with the data. You know, you can easily get 10 terabytes a day. No problem. You can get 20 terabytes a day. And you know, this kind of brings up, I keep going on these tandems, but it reminded me of, I watched parts of the one you did with with Jeff, Jeff Lichtman at Harvard. And so you had an

Peter O'Toole (01:05:56):
Ultra structures, nothing.

Eric Betzig (01:05:58):
Well, no, no, no. But, but he had it, you had an interest. He had an interesting discussion at the end of that, about the value of the connectome. I have always been very suspicious about the value of the connectome. It's a very complete set of information, but even if it were not, again, you've got tens of thousands of connections from every neuron and you've got hundreds of millions of neurons, even if there were some way of mapping all of that out, can we ever really understand what it means? I really worry, even at the single cell level and at the start of chemical networks, biochemical networks that exists and how much I believe that's the casting processes are the Bay. I think brown emotion is the real engine of the cell. It's not ATP in the mitochondria that it's the organization of the cell happens because of Brown emotion and differential sticking coefficients.

Eric Betzig (01:06:53):
And it's organized in the same way, the gravity organizes galaxies in the universe. And the, our ability to understand even a bacterium, I question, and you carry out Xcel, it's going to be, it's going to be a challenge. So, you know, this was something that science is bumping up against, and maybe we can even put it all in a computer and have an AI kind of replicate, you know, what's going on. But that doesn't mean we understand it. That doesn't mean it's reduceable to principles that we can really put our hands around it. Yeah. But the data problem itself is just gigantic. Yeah.

Peter O'Toole (01:07:36):
So there's a really quick few questions cause we've got about seven minutes over. So very quickly really, really short IP issues. We might cost be innovations and corporate involvements, easy, any very quick tips

Eric Betzig (01:07:51):
For this. Oh, get lucky. It all depends on how it, it depends on if you're doing it yourself or doing it through somebody else who's putting the bill. Right. I mean, those are two very different tasks, but let me say a little bit about IP. Yeah. Okay. Well, it's hard for me to ever give a short answer, but anyway, so a patent is nothing than anting in a game, a very long poker game. Okay. And it's just the anty, you know, let's face it. Come on. Do you expect that the, that the, that the patent people in the us patent office are experts on everything that you're writing and can truly vet that in a way and compare it to all the prior patents that are out there. No, they do sort of a rough check. They kind of, it's kind of a pro forma thing rejects some, you reply and do what you can patent anything except maybe a perpetual motion machine.

Eric Betzig (01:08:49):
You can patent just about it, but it's just the beginning. Okay. Because people will all over your patents if they don't actually have, are enforceable or worthy of being enforced. So like Palm, we have Palm pads, the Palm market isn't big enough for Zeiss to go after other people. Now, the attorney's fees would far exceed any value would get what's that it's, it's, it's, it's so broad. There's so many users, so many infringers it's like, you know, and that's fine. So there's a, I'm sorry, I'm going to keep you on longer than you want. There was one very influential book for me called The Laser. I forgotten wrote it, but it was about the story of the patenting of the laser. So there's this, this so you know, most of the credit for the laser goes to Charles Townes when he was in Columbia, but there was another graduate student in another group, Gordon Gould who actually wrote down in his notebook, had it notarized all of this before Townes was talking you know, like fabric, row mirrors, optical, cavity, all of that.

Eric Betzig (01:09:58):
He, he patented that idea. He patented all the applications up to an inertial, laser fusion and metal cutting and all of these things as a graduate student. And he fought those patents for years and years and years. And it went through many, many cycles. He had to bring in attorneys. Other companies has shared, got diluted and diluted. And ultimately in the 1980s, he finally won a patent that finally won patent battles. Everything went his way. It wasn't worth it. He got millions and millions of dollars, but he was a bitter bastard for that entire time. He was a Hab with the whale. Okay. That affected me deeply. I don't want to be a Hab with the whale, with any patents I have. If I get some royalty income, Hey, that's great. Okay. But I'm not counting on it. And I highly recommend that anybody who thinks they're going to get rich off of a patent microscopy had better think again,

Peter O'Toole (01:10:59):
But it doesn't mean you shouldn't be developing stuff cause it's actually

Eric Betzig (01:11:04):
Yeah. Wrong. The other, the primary, the primary reason I Patent now is so that people don't patent ideas that we've been using for 10 years. Right. and they think they come up with it and like Jesus man,

Peter O'Toole (01:11:18):
Important for a company to have that, to commercialize it.

Eric Betzig (01:11:20):
Yes, absolutely. You know, you want to have all sorts of barriers to competition. Patents are a part, but I'll tell you the real barrier to competition Zeiss ads now is that freeform optics. It's going to be tough for anybody come along and immediately compete with them on that one. Okay. So

Peter O'Toole (01:11:40):
The next question from Kirti's, so again, really short, really out of time, what did you want to become when you were 10 years old? Astronaut, Oh, you said earlier, what about when you were 20? Astronaut, but what about when you're 70, 70, what do you think you want to be

Eric Betzig (01:12:01):
An astronaut? You have to start if star ship got to the point where they were doing tourism and it got down to the point where I could afford it and you know, the kids are taken care of and some of the blows up I'm not worried. Absolutely. I swear if there was a one chance in three of them blowing up, but I would go on it. Totally. I I've already told my wife that when I die if I haven't made it to space by then, and if there's enough money after all the bills, shoot my ashes to space. Okay. That's where I want me to go.

Peter O'Toole (01:12:37):
I, I, I'm just going through the other question. This one's a really it's this is a curve ball. Okay. So this is would you say you usually have a plant-based environmentally friendly diet,

Eric Betzig (01:12:48):
A plant-based environment? What?

Peter O'Toole (01:12:50):
A based environmentally friendly diet and that's from Catarina,

Eric Betzig (01:12:55):
Why? Hell no,

Peter O'Toole (01:12:58):
That's a good question though.

Eric Betzig (01:13:00):
That's fine. Yeah, no, I mean, you know, yeah, no, I'm an omnivore. Okay. I like plants. I like beans.

Peter O'Toole (01:13:10):
You had your steak last night. So, so we, we know that I, and you know, some of the other questions are quite in-depth actually, so we will we'll skip those. I think I'm going to get a blank on this last question. And I've asked a few different guests that are chatting too. So do you have a favorite science joke or do you just have a favorite joke? If not a science joke?

Eric Betzig (01:13:34):
No, I don't have a favorite joke. I have favorite comedians and fav, so, you know, I like, I like either self-deprecating humor, cynical humor. So Rodney Dangerfield. So one of his jokes is my wife and I made a pact to only smoke after sex. The trouble, the thing that worries me is that I'm on the same pack since 1975. And she's up to three packs a day.

Peter O'Toole (01:14:12):
I'd like to thank the audience actually for loads of questions. I'm sorry. We couldn't get through them all. It's just too many questions to actually get through all of those questions. If you like today's podcast or the microscopies go to the YouTube website, go to the Bitesize Bio website, but there's loads of great videos with backgrounds, which worked on most cases which is great to see the different pictures you to seen Bessel and stuff like that. Honest, but, and subscribe to the channel please. So you see when the latest ones come out, I hope you've enjoyed it. And Eric you've been a suit you've been out of this world. There you are. You've made it as an astronauts and thank you very much for taking the day. Thank you everyone. Bye.

Intro/Outro (01:14:56):
Thank you for listening to The Microscopists, a Bitesize Bio podcast, sponsored by Zeiss Microscopy to view all audio and video recordings from this series, please visit

Creators and Guests

Eric Betzig (University of California)