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Harald Hess (HHMI Janelia Research Campus)

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About this episode

#25 — Harald Hess is a pioneer in the fields of high-throughput electron microscopy and super-resolution 3D microscopy, and today we’ll discover more about what inspired him, his move from academia to industry and back again, and who comes off best in his tennis matches with Eric Betzig. We’ll hear how Harald and Eric built the first super-resolution microscope for PALM microscopy in Harald’s front room, what his mother thought of the first PALM images, and why science needs different approaches to progress.

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This is an automated transcript and may not be 100% accurate.

Peter O’Toole

00:01:31

Hi and welcome to this new episode of The Microscopists and today. I’m joined by Harald Hess from the Howard Hughes Medical Institute Janelia Research Campus. How are you Harald?

 

Harald Hess

00:01:42

I’m doing great, that’s our campus right back there.

 

Peter O’Toole

00:01:46

And it is a beautiful, it looks beautiful sunny out there at the moment as well.

 

Harald Hess

00:01:50

It is beautiful day here, perfect summer, one of the perfect summer days.

 

Peter O’Toole

00:01:55

How did you, this is gonna be a long story isn’t it so i’m going to break, I was gonna say how did you end up Janelia Research campus because it is an inspiring place but. Do you know let’s take you right back i’m going to ask why science what got you into science to start with.?

 

Harald Hess

00:02:10

Oh gosh yeah i’d say for me it’s been a really long long path and not straightforward to ending up in a beautiful place like this. I can say i’ve been interested in science, certainly, since elementary middle school I guess. It started out very curious like you know what is the biggest thing in the world, typically what you’d ask, as a young boy. You know and astronomy looking at the stars, galaxies was there, and after a while, so I went in the other direction okay what’s what’s the smallest. And then he started keep going and you learn about atoms and you know a little bit later protons and electrons you think Okay, this is what what’s the fundamental stuff that we’re you know made out of and, later on, as I got into High School you know it was allowed to have a little bit of independent freedom, now I sort of grew up in a small town in the Midwest. And you know I learned about these things, called science fairs. And I sort of  just got into building various projects for that, and along with model airplanes and other stuff I just love going down to the basement and start putting stuff together.

 

Peter O’Toole

00:03:35

So ho on what sort of stuff we putting together.

 

Harald Hess

00:03:38

um it was all over the place, I was inspired by you know Scientific American use long time ago had some articles about doing your own experiments, so you know just to see atomic particles like electrons you know built actually a little cloud chamber. You know, sent my parents off to a truck stops to get dry ice and build it out of a inverted pots, and you know my gosh get a little bit of radium source somewhere from the local watchmaker radium, radium dials and then you can see the particle tracks, so that was like Okay, that was the warm up project and.

 

Peter O’Toole

00:04:19

This was in your parents basements did you say?

 

Harald Hess

00:04:23

Parents, Wherever there was space, so that was starting and I sort of  just kept going there was just all these cool instruments that particle physicists were making just to see like what’s the universe made out of you know that’s far chambers bubble chambers particle accelerators simulation counters so I ended up again like Scientific American had these articles on how to build your own particle accelerator and follow that to a certain extent, you know you need vacuum pumps so being in a small town you just go to the junkyard get a refrigerator cut out the compressor fix it up a little bit inside so it’ll open, which takes a couple days to solve with a hacksaw. And you know put things together, gradually, and you know that time is a youngster you could buy mercury diffusion pumps and things like that and

 

Peter O’Toole

00:05:24

That’s a lot of physics and engineering put together, so I guess it was a physics path.

 

Harald Hess

00:05:29

It was very physics yeah because I just really love the idea of like what are the fundamental constituents of what matter is, and so, and also being in you know, an environment where you could just make this a project. You know, in a small town and putting things together, you know, I think it gave me a very early sense of experimental physics, you know that many, many people don’t have.

 

Peter O’Toole

00:05:57

So as a school boy you got into physics.

 

Harald Hess

00:06:02

mm hmm.

 

Peter O’Toole

00:06:03

Where did you see at that at that age where did you see your career going. What did you want to be, what did you aspire to be when you grew up and got a job?

 

Harald Hess

00:06:12

i’m not, I was very scientifically inclined, I remember taking one of these career tests in high school where they try to assess your skills and things like that, and they said I should become a watchmaker. I didn’t follow that path. But I did like tinkering with the things a lot. So I think from there it’s you know it might have been engineering or science I at that point, I wasn’t sure exactly but. You know that some point that I, you know went on to the University of Chicago and which was quite formative for me too and

 

Peter O’Toole

00:06:58

How so as I don’t know where you were bought up to how big a change was moving to Chicago.

 

Harald Hess

00:07:05

Oh, it was traumatic I grew up in a small town in the Midwest. yep just a few thousand population, so I was a little bit the nerd, odd person there. And you know I had a chance to go take a little more engineering a little bit more committed direction originally but I thought okay let’s keep options open. And I thought okay let’s get a little bit more liberal arts see everything the sciences, the engineering and all that to not commit to quickly to a path ended up at the University Chicago there And just try to catch on again, you know coming up from the Midwest small town, then you go to a big city place where they really have a you know fluorescent lights and all these crazy things it was a bit of a change being away from home is a bit of a change to that struggle for a while, but I think managed to get into the groove after about a year or two.

 

Peter O’Toole

00:08:01

And you just said before you know you have a bit of a small town couple of thousand, the nerd I think was the phrase you you. Definitely yeah, suddenly you’re going to be in a cohort of many like minded people as well, maybe not all but some of them would have been very similar what was that, like finding people that were similarly passionate about physics.

 

Harald Hess

00:08:23

and for me it was scary and I was, I was shy to approach any of these professors i’m there like way up there and what am I just just another person entering this world, but there was one counselor who recommended that you know I should go and you know talk to some of the professors, you know get involved in some of their lab research and so then sort of took that maybe maybe said direction to go into but certainly started out with you know heavy physics load That was the average nothing special. yeah initially. I did really get into the lab side of doing the physics problems and and some of the professors, I found could be just so modest, I mean Nobel Prize winner level like Jim Cronin who you know found you know parody violation. You know, he was teaching solid state physics, which was new to him and he was approaching it like another student and just beginning to feel like a common interest at that point, I think, was really inspiring as opposed to a very high top down yeah kind of approach.

 

Peter O’Toole

00:09:40

So it’s actually a good question, who, who has inspired you that throughout your career there’s been any single person or.

 

Harald Hess

00:09:52

I think a lot of people have been just critically enabling I think almost had my own little sense of direction. But you know just countless people were enabling, opening up the world in this direction, getting past barriers or just showing you know, showing new areas. So at the University of Chicago eventually decided to do a little bit of extra lab work with the Elmer Zeitler and, at the time the University Chicago was like a really big place for electron microscopy you know the guy who invented the diamond knife was there earlier. There was yeah Elmer Zeitler 

yeah number of others were just sort of developing various forms of microscopy you know, in the scanning microscopes too at the time i’ll.

 

Peter O’Toole

00:10:57

Microscopy started quite early.

 

Harald Hess

00:10:59

yeah microscopy started very early, but then there was another form of microscopy, scanning electron microscopy it was also developed early, but maybe not quite as refined as in the mainstream and University Chicago under Albert Crewe was sort of had a group of people.

or like minded scientists there developing it pushing it to its limits and there was early were people saying X particle physicist saying Oh, we can, maybe make proton microscopes shooting protons down trying to get the limit of you know other kinds of microscopes certainly the electron or scanning microscopes was you know, was a topic i’d say yeah maybe one thing that sort of inspired me was actually attending. A colloquium remember sitting, all the way at the back, and I think was Albert Crewe at the time, and he was describing some of the electron microscope work that they were doing at the time. And this is one where they were refined it trying to get what’s the ultimate resolution really building the thing from first principles and they were able, at that point to see single atoms. And that was really you know something where I said okay wow you know before single atoms and that was really, you know, something worth a OK wow field, you know before single atoms had been seen on microscope so you just see atoms on a tip of the tungsten tip yeah, but these were now pictures of different heavy metal atoms I think thorium uranium indium. And, and you could just sort of see them just literally sitting there on a piece of graphite. And they would just light up, and you know, and this was like an exciting time.

 

Peter O’Toole

00:13:05

Like yeah. This. Is So these are actually two of those pictures from that time.

 

Harald Hess

00:13:13

that these were like very original to me like this is like this is groundbreaking.

 

Peter O’Toole

00:13:18

And the scale bar on the images that i’ve got the background, for those listening, the scale bars, one nanometre which is, which is tiny and the particles we’re looking at are less than a nanometer.

 

Harald Hess

00:13:32

Oh yeah, and these are individual heavy metals i’m not sure if this was indium or uranium, or you know they were able to look at various atoms in even to certain extent from spectral loss trying to get their identity directly to so this to me, this was just amazing, and on top of that you’ll notice there’s like a timescale.

 

Peter O’Toole

00:13:55

yep.

 

Harald Hess

00:13:56

They weren’t sitting there you know they would move, so these were like movies of these guys moving around in time.

 

Peter O’Toole

00:14:05

So the scale bar here again zero seconds 15 seconds 45 seconds.

 

Harald Hess

00:14:11

Right.

 

Peter O’Toole

00:14:12

And this is under vacuum.

 

Harald Hess

00:14:14

This is under vacuum.

 

Peter O’Toole

00:14:14

And the movie.

 

Harald Hess

00:14:16

yeah sort of idealized I mean this is mid 70s, so making movies, was a little bit of a different enterprise back then than it would be today and building scanning electronics and things like that this is almost before computers were really there that’s all very analog based So there’s.

 

Peter O’Toole

00:14:38

So this is different again tho,so

 

Harald Hess

00:14:43

Yes, so this is after I saw those movie pictures, I thought Okay, I really need to get a little bit more involved with this, and this is a 1 million volt electron microscope microscope i’m gonna go my first visit with the you know, Professor Zeitler at the time I mentioned, building a half million volts particle accelerator, and I guess he took that as an endorsement and signed me up, so I was lucky enough to participate in this, this is a big sewer tank. Filled with the Sulfur hexafluoride for high pressures to act as an insulator and inside was a 1 million volts structure.

And it was a it was a major construction project, because everything is built on its own.

 

Peter O’Toole

00:15:34

How tall is this, just just, to just give an impression, so this is actually a much taller image than I, then I have.

 

Harald Hess

00:15:41

Yeah I think eye high level is maybe about even with that large horizontal bar that you see in there.

 

Peter O’Toole

00:15:49

Just here.

 

Harald Hess

00:15:50

yeah yeah or If you look over at the side, you can see what looks like a typical lab cabinet.

 

Peter O’Toole

00:15:56

Oh yes.

 

Harald Hess

00:15:57

Yes, in the lab bench yeah so it’s taller than a human, but eye  level is maybe at the bottom of yeah somewhere somewhere in that range.

 

Peter O’Toole

00:16:08

it’s big If you look at today’s electron microscopes to be prior electron microscopes.

 

Harald Hess

00:16:14

yeah.

 

Peter O’Toole

00:16:15

This dwarfs it, for some of those.

 

Harald Hess

00:16:17

yeah well this was at the very beginning of really exploring get scanning electron microscopy um there’s work on field admission in those early days, it was so shared with the Hitachi long time ago and I remember being part of, the beauty of it once part of just the groundwork of everything you know the electronics you build a circuit board, resistors, amplifiers to do rotational rotate the scan you know you’d have special Rotary trim pots. Again, computers weren’t an option, back then, you know, there are other ways of trying to record what’s going on with the scans. And I know so that’s still from that you really get a, You know, empowering sense that you know you can build these things yeah it’s not something that you’re stuck buying or constrained about.

 

Peter O’Toole

00:17:14

Was that after your PhD.

 

Harald Hess

00:17:17

i’m actually no, that was my undergraduate.

 

Peter O’Toole

00:17:21

That was your undergraduate wow.

 

Harald Hess

00:17:23

Then, this was a very forward looking microscope and, unfortunately, at the time. It wasn’t clear what biology it was going to be able to impact, and so it never got fully funded on it. Which is a shame, because it was just so forward looking. So I left Chicago. And the project stopped unfortunate, but it was a you know I think I feel so lucky to have been part of that effort 

 

Peter O’Toole

00:17:48

That’s quite interesting with your target, was your ambition to to use this for biology then, rather than for material science.

 

Harald Hess

00:17:57

Erm at the moment, I think I just loved the technology I didn’t have any agenda, I think I always had an interest in, Okay, what are interesting physics style problems there was intense interest in biology at the time with with this. Okay, you know sequence DNA. Can you label each base with a certain heavy metal that this motion that you saw earlier in the picture that’s something I was going to haunt the field forever and even today, you know the electron induced motion. But that time that project, unfortunately, stop. My Professor Zeitler went off to Berlin. You know I went off to go yet another direction of trying to go, initially, I thought okay particle physics, again, you know let’s get to the fundamental nature of matter and work at Fermilab for for a little while from first year there. But I was a little disturbed by the fact that these particle physics efforts are just huge team efforts and they’re they’re fun you’re part of something really, really big. That I really liked the sense of doing something a little bit more table top a little bit more intimate you know where you can sort of see the beginnings, and the end and everything you can walk around your experiment, you know and instead of being. You know, a component of it.

 

Peter O’Toole

00:19:27

So i’ve got to ask you said you had lots of good guidance, yeah lots of good tutors that you looked up to, how good was the career advice that they gave you over those.

 

Harald Hess

00:19:41

I don’t know I think I probably ignored everything. I sort of was just driven by my interests and my passion. I know, for example in [Inaudible] Princeton, and I just wanted to do you know, again I mentioned sort of a small experiment and then I thought okay low temperature physics. That was sort of like the kind of experiments that one could do you know, on on a small scale, and you know and had a good time out that. I think the guidance normally at that time was. Not explicit it was like okay here’s an option, you can go either up the postdoc track and go into the academic career, or one can sort of go into more engineering path still get involved with the semiconductor industry, you know join IBM or other places like that which were super big. And I think I was exploring both really not really biased toward one or the other rather rather neutral and rather accommodating of you know what’s available, I remember you know when I was finishing. You know my postdoc then of course the question comes up where where do I go, so I really applied to both both areas.

 

Peter O’Toole

00:21:03

Where did you end up going?

 

Harald Hess

00:21:06

Actually I ended up going to MIT. To. To what I thought was like one of the most amazing problems that one could sort of go after. I was working as a PhD I was working at low temperature property of glasses and I thought, no glasses are messy they’re just organized and the project, they had at MIT was I thought the ultimate physics thing, the ultimate thing and simplicity, it was like the hydrogen atom. Just it by itself, and they had a great plan at the time to turn super cold hydrogen atom gas into something called a bose-einstein condensate. And and and, for me, this was amazing I mean like from physics you learn that there are. Like about four states of matter. You know there’s. You know there’s earth water, air and fire and this bose condensate this is supposed to be like the absolute new state of matter you know, this is a fifth state of matter, so I felt like wow i’m going to be part of this. And so I got there and the head of scheme, you know again tech heavy you work on this special dilution refrigerator and they had a scheme where you just fill it up with this hydrogen gas who push a piston up nice squeeze a tighter and then poof it’s supposed to turn into. The bose-einstein condensate but really what happened, it just exploded and burned like crazy.

 

Peter O’Toole

00:22:46

explosive research.

 

Harald Hess

00:22:47

explosive yeah yeah hydrogen atoms love to combine to make molecular hydrogen.

 

Peter O’Toole

00:22:53

To keep part of that concept.

 

Harald Hess

00:22:56

yeah well, so what happened that was actually when it exploded, you know my little dreams, that this could be part of a future career sort of evaporated with it. So. You know, in the stuff the hydrogen burns on the walls, if you squeeze it too much burns and gas, and you know and so write it up as a paper but yeah like okay that’s. That’s. Not fully, You know solves the problem, and I remember being pretty depressed by it and sort of going home and then started thinking about the hyper fine energy levels of the hydrogen and magnetic bottles and and how to cool it and then just at home largely in isolation, I wasn’t going to conferences or anything like that, and I think that was actually a virtue. I came up with this idea that you just had in the background, a second ago of this evaporated cooling, so you can have a gas have it in a magnetic bottle and if high energy atoms get out of the get out of that deep trap they take away a lot of energy and then the rest of stuff in the middle gets colder and colder and you could write an equation for that and find that it’s amazingly powerful cool the cooling tool to work, and you know at that time I was ecstatic again, you know it’s things going fluctuations, you know from ecstasy to depression and back and forth.

 

Peter O’Toole

00:24:30

So actually just dwelling on that point.  You say you’ve had highs and lows. How low are the lows, how high are the highs

 

Harald Hess

00:24:40

super.

 

Peter O’Toole

00:24:43

How do you cope with both extremes, because actually extreme high can be equally risky as extreme lows.

 

Harald Hess

00:24:50

Yeah. I think this one was a high, but it was a little bit of a self contained one I felt like I was in you know owned this secrets of the universe, but you know couldn’t go further on it or execute and then, finally I realized okay. Maybe time to open up. Maybe other people know more, and you know mentioned it eventually to my advisor you know, few months later, and you know and they sort of developed the idea and then and actually one very interesting thing. My advisors, Father in law is was John Bardeen and he’s a double Nobel laureate, who invented the transistor and understood superconductivity and so invited me to sit down with him and I explained this thing and then just he just asked one little question. Like, how do you make the high energy atoms that evaporated really cool and that was like so key and so to the heart to the problem you know it gets into scattering cross sections and physics and then he sort of from the high you go all the way back down to the low and it’s only when you’re at the bottom that you fight to build yourself back up again. And then you think Okay, how can you get around this dilemma, you obsess, out out and then figured out some scheme to evaporate and compress and combine things and eventually made what was a usable technique to go forward now one one thing you know you asking about the lows. A little bit after this, I decided, sort of need to move on from you know, this area. It was a small part of the Science Foundation budgets were there wasn’t like a second budget available for me to start off doing this at some other University. So basically I got lucky enough to be accepted at Bell Laboratories, but at the same time, I felt like Okay, I have to say goodbye to that field. So I think what was, that was, super painful you know because I sort of developed something committed to it, put my heart into it as much as he ever could and then and could participate, a little bit at the tail end of it. But now had to go off, you know, in a place with super smart people all with established careers and try to find a new niche from nothing and I couldn’t really you know go from what I had in the past. And that’s that’s.

 

Peter O’Toole

00:27:38

Tough ask to, I guess, be very specialist, very expert in one area, and then I guess change and become experts in another area to lot of background to pick up and yeah daunting challenge, I guess.

 

Harald Hess

00:27:52

yeah and and to know that whatever you go into is the right thing to you know, because you want to make sure it works out and in the future. So that was very tough, I mean going in, a place with high standards, I think I was lucky. On many in in these cases to have other people around with very high standards. And then you have to say okay I got to meet this thing, and it was like I said earlier, it was very, very demanding very soul searching I put literally my whole life into that just to get a toehold on being a scientist and not sort of slipping down and managed to sort of switch directions, but I built on my background I had low temperature experimental fingers, you know that good sort of build on from that and, at the time, then I sort of went in. I was trying to think what’s what’s new and the time scan probe microscopy was just coming on.

And also, I knew I had a background in low temperature experimental techniques and I said okay let’s just put those two together. I was thinking I go to Bell Labs they don’t do atoms, but they do electrons that a place like that so let’s do evaporating cooling of electron so that was my first. You know I still had evaporation on my mind and couldn’t get it off so but anyway, so it was evaporating electrons off of a tip into a material. And then just built a little bit of a experimental infrastructure. Where I started just to explore different kinds of physical phenomena, you know that you can actually look at using you know, using these probes so at that point, you could say I sort of return to microscopy, but this is a very physicist sort of microscopy. Using these you know these probe instruments, you know that can go in and you know and in the end I sort of caught on and managed to sort of define my own little space my own little field, I always think that should be a goal of people, you know to what extent it’s getting harder and harder to do that. That to say, can you sort of open up a little field here or there as as a measure of success and that’s sort of what they expected to Bell Labs. You know, it was you’re literally a one person in a lab if you’re lucky you got a technician and if you even luckier you might have one postdoc to help you out on things. But you really learned then to rely on other people in terms of collaboration. You know, some people, you know they might know what a laser is so you say hey you know what about this and then within hours you can get together with another collaborator. And you know and reconfigure labs in different ways to do different kinds of experiments just using you know their expertise.

 

Peter O’Toole

00:31:07

So this image that you sent me yeah me too, by the way, and I could see this being walmart.

So the if i’m right when you kindly sent through some of these pictures and this one is some of the images from the scanning microscope from the Bell Labs I think.

 

Harald Hess

00:31:23

Yes, that’s correct. So, like I was always after seeing the Chicago work of seeing individual atoms, okay, I got to see individual somethings, and so the one with the colorful blue hexagonal arrangement. You know about the size of those three spots that’s about the size of a nuclear pore you know a little over 100 nanometers and each spot is one magnetic flux quanta. You know, like one unit of magnetic flux and there’s like and you can visualize these things are like lucky to be the first person that gets visualize these things with the scanning tunneling microscope and they were like super experiments, you know you’d spend months, putting together the apparatus, it would fail, you persist, you know, and you keep going and eventually get it, you know eventually get picture like that.

 

Peter O’Toole

00:32:22

How exciting is it when you see when you see that image and you see it come come in front of you how excited you get to that point.

 

Harald Hess

00:32:32

Well, at this point it’s a transition you’re coming from a low from just feeling totally incompetent to you know the other end it’s it’s you know it’s satisfying I wouldn’t say get overly excited because that wears off pretty quickly and then you worry about the next thing. But you know those satisfying to be there, see this thing, this is a very curious electron structure. You know, you know, for the first time, and then you think Okay, where can this continue what can be next, and in this ended up being a little bit of a works on this sample under these special you know sub one kelvin conditions and So I thought okay let’s try some more scan probes and I image those with a teeny little magnetic sensor. The picture that’s right behind you, in the middle that’s trying to use a single electron transistor which scans the surface so i’m seeing fields, and those are like individual atoms charged up with either plus one electron or the dark spots or minus. And so you can actually see you know electric fields, from a one electron sensitivity. In there, I was collaborating with the person at Bell Labs who invented the single electron transistor and we just said, can we make one of these on the end of a little needle and use this as a microscope and said sure we got together and about a year and a half later the picture came out. 

 

Peter O’Toole

00:34:10

You think the it’s strange but, but the image step is very much like a single molecule image as well.

 

Harald Hess

00:34:15

Yeah. Very much 

 

Peter O’Toole

00:34:15

I early ones, so these that image from myself.

 

Harald Hess

00:34:20

That might be the.

 

Peter O’Toole

00:34:21

[Inaudible] was full of images like that, but from a microscope a light microscope.

 

Harald Hess

00:34:26

And the light microscope. Similar similar.

 

Peter O’Toole

00:34:28

yeah it’s a similar but but pretty much the same they look the doctor intensity on a grainy background.

 

Harald Hess

00:34:35

yeah yeah you like to play with color scales, which is always cool. And red and black is always sort of a very you know powerful color scale people like to use. The picture, on the other side yeah that one yeah that was. You know at Bell Labs I met you know, a colleague Eric Betzig who you interviewed earlier, and he was just taking pictures of single molecules at the time yeah we became good friends, we play tennis at, you know, sunrise almost every morning when we’re at Bell Labs.

 

Peter O’Toole

00:35:15

How early sunrise at Bell Labs.

 

Harald Hess

00:35:18

We’d be actually pretty competitive, you know who is the first one in to Bell Labs who works, the hardest. Okay, and you know and we’d be often in the lab before it even got light, you know, and if I saw his car in the parking lot before mine, I would just sort of touch the hood to see how warm it is you know get a sense of how many minutes he beat me by.

 

Peter O’Toole

00:35:42

Not at all competitive then Harald.? No

 

Harald Hess

00:35:44

Yes, yeah good competitive not bad competitive.

 

Peter O’Toole

00:35:47

Whose better tennis player.

 

Harald Hess

00:35:49

um I think I run more. But he just gets the ball back and just wins every time without exerting too much energy. Or if I play ping pong with them, you know he’ll just sort of sit down and yawn and read a book and the same time play ping pong and i’m running back and forth on the table and.

 

Peter O’Toole

00:36:12

You need to watch his tactics and then play against them.

 

Harald Hess

00:36:15

Yes.

 

Peter O’Toole

00:36:16

You still play tennis with Eric.

 

Harald Hess

00:36:18

um that’s sort of, he left to go to Berkeley so you know, on the occasion that he’s here, you know we try to find time for that you know, but I do miss it, I mean it’s sort of like a good. Time to unwind you know put things back in perspective.

 

Peter O’Toole

00:36:37

More. More the tennis than the table tennis.

 

Harald Hess

00:36:41

yeah probably more than yeah more real tennis than the the table tennis you know yeah that’s that’s true.

 

Peter O’Toole

00:36:48

I guess on grass on hard court on.

 

Harald Hess

00:36:52

erm usually it’s whatever is available, you know, on asphalt with grass growing and all the cracks you know it’s whatever works, you know we’re not too picky.

 

Peter O’Toole

00:37:03

That sounds familiar as well.

 

Harald Hess

00:37:05

But, or you know swatting bugs while you’re sweating tennis balls. It all you know all works out well. So it doesn’t say that yeah oh sorry.

 

Peter O’Toole

00:37:15

So that’s where you met Eric to start with.

 

Harald Hess

00:37:18

Yes, yes.

 

Peter O’Toole

00:37:19

You then formed quite a formidable team don’t go forward so i’d say a team you’re both independent of each other.

 

Harald Hess

00:37:28

Oh yeah.

 

Peter O’Toole

00:37:29

Worked extremely closely together, how similar how how similar your personalities.

 

Harald Hess

00:37:36

um I think we’re both very intense scientists and physicists. I think we’re just highly driven, you know what’s what really needs to be answered, I think we have a lot in common in terms of the world view of what matters what doesn’t matters. Technology we’d be very fluid, you know talking to each other about this or that issue he was working on single molecules and I was doing low temperature bizarre things. You know I thought okay my stuff seeing a single electron is smaller and better than him seeing a molecule but really seeing the molecules actually a little bit more important than seeing a single electron, in the end, so what we did at the end largely were like a parallel effort and at the end, we did collaborate on one one experiment, and that was that last picture which you had up there just to the right of your face which looked like lots of little rings. You know, he knew how to make yeah exactly that one yeah he knew how to make these special nearfield tips. I could make a low temperature environment, we brought in another person Tim Harris who knew what a laser was. And you know and within a few weeks, though, so like the magic of having independent collaboration teams, we just sort of put everything together and we’re able to see like individual luminescent centers and you know, in a semi conductor and So.

 

Peter O’Toole

00:39:14

It was important that that teamwork, you know, Bell Labs encouraged that your a lab to yourself and installation, but actually working as a team and bringing in collaborators was was obviously really important. I presume, obviously you’re now at Janelia but didn’t go straight to Janelia from Bell Labs.

 

Harald Hess

00:39:33

Erm, no Bell Labs was undergoing a little bit of a you know soul searching at the time and the message coming in from the very top was well you guys are great physicists scientists and you publish. Can you guys do something real to help the bottom line 18 T wasn’t a monopoly anymore yeah it was becoming much more competitive, and you know both the telecommunications technology needed help to stay abreast on this competition and with the time, for example, I think even 18 T bought up NCR which stands for national cash register company, so they make you know check out tools and machines. You know, for you know the whole retail industry And then sort of ended up using and I was very sensitive this and so just are running off to the academic world, I thought oh here’s a new challenge. And you know, try to understand okay what’s you know where where can we go with this and you know, so we did some trips to NCR and they described in a grocery store, you know, on the checkout most things are barcoded which is great. You know that, vegetables and fruit aren’t. And so we’re supposed to be good scientists, how can we identify it, you know, can we go in there, you know either smell the fruit or identify shape or things like that. And, and so, at some point, then we just got. A few bags of groceries and brought him in and we had a really nice spectrometer setup for doing all the nearfield microscopy and we repurposed it to look at, you can see right there looking at pears and Granny Smith apples and then trying to do was probably very early machine learning on how can you sort of separate out one from the other.

 

Peter O’Toole

00:41:49

So your ambition at this stage, you have a spectrum. spectrometer on every check out to know who to which type of apple to pay for it.

 

Harald Hess

00:42:00

Right right exactly that was the goal.

 

Peter O’Toole

00:42:03

That is nuts.

 

Harald Hess

00:42:07

In it were partially I mean I think other people were coming into our lab at the time and wanted to learn about how we’re doing nearfield of quantum wells and and then somebody else in the background, was you know pulling an apple out of the fruit and attaching to the spectrometer saying okay let’s get the spectrum of the MacIntosh apple now you know recorded good next.

 

Peter O’Toole

00:42:32

I say nuts, either either NUTS or still ahead of its time, one of the other yeah because I don’t know what the future holds.

 

Harald Hess

00:42:43

i’d say yeah sorry.

 

Peter O’Toole

00:42:46

yeah so after that you went into industry I guess that was semi industry, but very academic still in the bell labs but then you went into industries that right, we phased metrics.

 

Harald Hess

00:42:58

Phased metrics yeah this whole tail and experience from Bell Labs it’s sort of really said there’s something else going on, you know we really need to learn where’s technology or science, useful and I really took that to heart and I thought well Bell Labs they aren’t really instrument builders, you know it’s a telecommunication company and on top of that, just sort of watching what was happening in the Silicon Valley, I was thinking there’s a another paradigm here. Doing microscopy was trying to understand Okay, I can look at the nanometers scale which is great. But I look at it very slowly this other world the semiconductors looking at massive numbers millions of transistors you know, thousands of you know, thousands is understatement billions of you know bits or you know it was I just felt that there’s something important in the massive numbers that was missing from this very slow imaging kind of stuff that I was doing in a more academic context. And I thought well and, besides, a lot of people were leaving Bell Labs bound for these little companies, which are all poised to be the next Hewlett Packard or the next Bell Labs of the world, so I left you know I joined this little company that you mentioned Phased Metrics yeah I remember walking in the door that morning and the receptionist said oh you’re the new scientists they hired welcome we just laid off 100 people yesterday. Oh, and. And I said okay sign me up. And so you know, while the rats were leaving the ship, you know i’ve worked on work walked on board and and ever since I joined it more or less kept going down. But it was the the industry to me seemed like the perfect embodiment of sort of what I wanted to learn, this is a hard disk drive industry. And I really wanted to see you know, can we characterize like I said earlier, you know the the billions of information, can you make scanning equipment that scans cheap fast high throughput very different than academic paradigm. And then I was just sort of committed you know blindsided a little bit and I just sort of went ahead with that You know, made multi-phase interfere metric structure, you know they measured heights of the Read head they’re measuring disk quality are there defects, you know, can you spend through a disc find all the defects reject good or bad and had a really cool technology and that, what do you see, there is a multi phase interferometer right now on the semiconductor way for there to see how well it applies for that you know the little arm that sticks right over your head is based on fiber optics telecommunication technology, and it has nanometers sensitivity can map these things you know within a minute. And it was, I think, by all scientific standards of success, but basically it was a big failure.

 

Peter O’Toole

00:46:31

So. What happened to the end.

 

Harald Hess

00:46:34

um I was a little naive. I didn’t fully understand one keyword, customer. Then it was sort of like evident on the first day that I joined, you know the customers for these kinds of instruments. You know they’re hard disk manufacturers. They were basically broke, they had no money, and so the last thing that they wanted to do was have some microscope like thing which is going to reject a bunch of disks and make for lower throughput and plus it costs extra to yeah, and so I was, I think the experience there really. You know, really drilled into me so the importance of the you know the word customer and having microscopes or techniques that are relevant. And then, after this phased metrics experiments, I was fired that sort of got rehired KLA Tencor which does semi conductor, and they had a very similar big challenge there and we ended up playing with some other colleagues, on some darker grants doing high throughput imaging or writing and got some very nice funding for some pretty innovative lithography stuff. But after a while, you know that didn’t quite feel like it was the right direction, either and

 

Peter O’Toole

00:48:11

Eric was.

 

Harald Hess

00:48:13

Well Eric Betzig had also gone through a similar cycle, you know, trying to save the American auto industry from other destruction and he didn’t quite save it and was like was sort of unemployed also.

 

Peter O’Toole

00:48:31

He left that job.

 

Harald Hess

00:48:33

yeah so I left it I resigned, I mean he was encouraging me, he said, you know jump and I said then, what and then you sort of quoted Ray Bradbury and said build your wings on the way down.

 

Peter O’Toole

00:48:43

Oh, I like that, because.

 

Harald Hess

00:48:45

yeah.

 

Peter O’Toole

00:48:46

You sent this picture actually.

 

Harald Hess

00:48:48

So yeah that that’s that’s Eric and they’re sort of found something that you know sort described, you know this was a some welded up beetle with wings on it.

 

Peter O’Toole

00:48:58

things yeah.

 

Harald Hess

00:49:01

which was, I think, obviously, on the way down, this is a picture that we took when we were in Tallahassee Florida, and there were both trying to look we’re trying to find you know where the opportunities where’s where some new science. And through a colleague, we ended up. At the Magnet Lab, which is in Tallahassee Florida And there, there was a rather interesting self-made man, person. Mike Davidson and he had his own biology laboratory and he had just written a paper with Jennifer Lippincott-Schwartz about optical highlighters and so within his lab he didn’t really write papers and the academic sense but always did the website. Had a big library of fluorophores and it was like the go to place for biologists to sort of get the latest of the GFPs or other things which were there.

 

Peter O’Toole

00:50:03

Just just pausing one second day so Eric has left his job and he’s unemployed, yes, and he then encouraged you to leave your job and become unemployed. Yes, and you did that’s a hugely brave move.

 

Harald Hess

00:50:19

yeah I i’ll tell you the day I finished my last day at the company. It was, I remember coming off the plane going back home, and it was like this huge weight was gone, you know the sky was blue you know you could hear the birds tweeting again, you know smell the flowers, it was like okay there’s this whole focus ordain was just sort of removed. But now there’s, of course, other fear like what to do next.

 

Peter O’Toole

00:50:53

Which is my next question no you’re not scared witless at this stage.

 

Harald Hess

00:50:57

Yes, we both were and I think that was part of the magic of it to you know when you don’t have anything else to fall back on you’re forced to be creative or forced to do new things, and then. We explored like what you see we’re both trying to build our ways wings on the way down and we ended up in Tallahassee there and you know and got lucky actually i’m there’s a lucky to meet the right people and lucky also to have eyes open and be aware and we learned then of these blinking fluorophores and you know things move forward pretty pretty quickly from there.

 

Peter O’Toole

00:51:41

Did I did, too, I did this picture, is also in Eric’s recording. This is your lounge correct.

 

Harald Hess

00:51:50

Yes, my living room in La jolla that’s right.

 

Peter O’Toole

00:51:52

And were you unemployed when you made this.

 

Harald Hess

00:51:54

Oh definitely yeah.

 

Peter O’Toole

00:51:56

So. That that looks rather expensive as well.

 

Harald Hess

00:52:01

yeah this is, I basically when I left Bell Labs I was able sort of take my lab with it went to Phased Metrics and then, when Phased Metrics. You know, found a lot of this equipment, not that useful they sold it to me for $1 and then I set some of these leftover toys up and you’re seeing, there is the first Palm microscope that we’re just beginning to try out I think off to the side of the picture I think Eric is sitting on the couch but he’s not visible right there in this picture, but it was it was great I mean the ability. To just go and do things getting super cheap off of eBay it’s not that much of an epidement time people spend more remodeling their bathrooms or kitchens, you know, then we did playing around you know with the with these things.

 

Peter O’Toole

00:52:58

Yeah. You needed a basement you started in your parents basement and you moved out the basement and teams into your own lounge. 

 

Harald Hess

00:53:06

Yes, Yes. exactly, so you just set up total freedom to do to do everything in that.

 

Peter O’Toole

00:53:13

It’s like you hadn’t grown up really at that point.

 

Harald Hess

00:53:15

Exactly exactly never grow up.

 

Peter O’Toole

00:53:23

Still still working I guess really do it so obviously this, this is a big thing and were you I guess we’re coming to kind of come at times with the palm side of things, and obviously that lead.

More of your work, then led to a Nobel Prize through through that stage i’ve got some other images so actually this this is now.

 

Harald Hess

00:53:47

Oh yes, this is, we then connected up to Jennifer Lippincott-Schwartz and you know both of us, you know I think Eric met her first we both flew over to her lab met on the airplane and because he was living in Michigan I was in San Diego and she amazingly enough listened to us. And said okay here’s a dark room here’s a corner and gave us some space to set up the thing, so it was wintertime when we were doing this experiments. George Patterson was there, and he had provided the fluorophores and we were working from before sunrise to after sunset in that little lab and it was cold in there in the winter too. But you know we just persisted and

 

Peter O’Toole

00:54:42

looks like a basement.

 

Harald Hess

00:54:44

yeah yeah. Concrete floor. And yeah and that was that was the focus there for a while. That yeah.

 

Peter O’Toole

00:54:57

And these up anyone who hasn’t seen a palm image.

 

Harald Hess

00:55:02

Oh yeah yeah that was that was our very first or I shouldn’t say the very first but among the first PALM images and you know and that’s the one that we eventually with a lot of fighting you know got into science magazine there’s one interesting little story behind that picture I really haven’t told any you know many other people about it, but I shared this photo you know with my with my mother. And you know, and she took a look at look at it, she was medical technician sort of by by training. And you know and southern German language you know the [inaudible] and she said. Ich bin nicht sehr beeindruckt, translated, means. She wasn’t very impressed by it and then I asked her why. You know I said Oh, this is better than the resolution of microscope so but she was you know doing bacteriology in the lab sort of after World War Two and a lot of people were dying with TB and one of the standards at the time was can you see TB, so you know I asked her why why why isn’t this good and she said, well, can you see TB with it and TB are really tiny very hard to see, and then I was thinking well, can we somehow label these and then she had to you know, can you see it in the sputum And this is getting a little bit too real for me, but the one big story behind it really relates to where a lot of Micro, microscopy comes from, because in the early 1900s or Robert Koch you’re the first person to really see individual TB bacteria. Using at the time it was like the most advanced you know microscopes you know from abby where they really learned how to optimize it, you know, there Zeiss microscopes at the time. And they learn to staining you know so that was tremendously relevant you know to society, back then, so in a way it’s sort of sets you know this is cool. But you know from standards from 100 years ago. You know what they were seeing with the advances of my microscopy really a major impact and I always think well Okay, you know really need to go, you know what’s, how far can you go with these you know so that’s I think that’s not the end.

 

Peter O’Toole

00:57:39

To obviously that that’s with light, we will always be limited, I think, with what we can achieve with light, but obviously you’ve now moved a lot into electron while coming back to the electrons again.

 

Harald Hess

00:57:52

Right Right.

 

Peter O’Toole

00:57:53

Bringing those together which, which is a big area actually have a big emerging area I don’t think it’s I think it’s telling a.

 

Harald Hess

00:58:02

Oh yeah yeah.

 

Peter O’Toole

00:58:03

innovator stage.

 

Harald Hess

00:58:05

yeah I feel that’s right and I feel tremendously lucky after that Janelia came up to as a place to be now this place back here is just came out of the mud about 15 years ago and you know, and there was just a confluence of ideas, you know high throughput imaging from the semiconductor and hard disk drive was becoming relevant for biology, the electron microscopy was coming together. The light microscopy the super resolution. I am, you know, I was just lucky that all of these factors that I just happened to you know pass through and touch on were just convening at the same time, so it just sort of made it, you know natural to you know, try to pull all of that together. Get the electron microscopes going try to do it together with the you know the best possible optical microscopy I recycle some of the multi-phase interferometry from hard disk drives to biology applications And so you know, so as far as the technology goes, I think a lot, a lot of things are coming together but.

 

Peter O’Toole

00:59:20

One of the challenges are what’s the next steps for the electron microscopy side.

 

Harald Hess

00:59:27

Um. Oh gosh there’s sort of a big open area right now on trying to explore, I think trying to combine two frontiers. One is larger and larger structures, I mean biology structures are big you know you can see pieces of them nicely with high resolution microscopes the TEMS but sometimes you don’t get the whole ecosystem of a big piece of organ or organism or something like that And at the other end, you can see large stuff with light microscopy maybe it’s a much better resolution with a somewhat compromised form of electron microscopy but trying to sort of bridge the two extremes, and so I just pulled out the maximal information is important and they’re also complimentary I mean biology is so rich in the information content that it has in there, you know, there are thousands of different proteins, you know he only get a hint of a small fraction of that with electron microscope fluorescence also just or it gives you just a fleeting glimpse of the richness that’s in there and

 

Peter O’Toole

01:00:49

So. What is the electron microscope. Describe your ideal, your dream electron microscope or you achieve your dream microscope.

 

Harald Hess

01:01:00

Oh well. yeah the dream is, I think you have to sort of parsify what’s the information content that comes out. So you know. Like to sort of really develop this a little bit with the biological guidance, at the same time, you know, so you don’t face like a bankrupt kind of customer situation. That it seems like the microscopes they should be able to sort of see a combination of genetic expression. High resolution on the proteins, maybe protein confirmation and the first place, to ask is you know from the biological side, what are sort of the desires and then he come back to the other side, the tool kit you know, because people do what you know how to do. And, and then he tries to case there’s some space where you can try to encompass both of those and I I think they sort of aligned pretty much with what people are thinking about right now in terms of the challenges I mean. Getting genetic expression information out getting protein labels trying to see a protein confirmation state in a native environment is a big. You know holy grail of right now for a lot of people. Now, always look a little bit to the edges of the field, you know, often this is Bell Labs when sort of comes in with this mind they’re all these people occupying spaces in the field, and then you try to find the white space what’s what’s not touched on. Quite yet and and usually find that sometimes but trying to get a little innovation on the on the microscopy side which might allow you to sort of go a little deeper in one dimension or another and and nowadays, this is all so tied up with the analyzing the data we’re right now in a world where you can’t just look at an image and understand it anymore. I mean it’s we’re really going to see the world through the eyes of a computer going forward because it’s you know the terabits that describe an experiment and getting that through a two dimensional projection of the I you know there’s some massive distillation and we have to be very careful about what that distillation is so it doesn’t bias us, in one way or the other, so I think there’s there’s a big challenge and just trying to answer questions, you know how what What do we want to see what do we want to pull out so it’s you know it’s it’s a pretty rich area right now.

 

Peter O’Toole

01:03:51

It would be the, I guess, a lot of other guests have also commented it’s the data analysis it’s to machine learning. hmm and to actually help us understand our data. Right yep, then we can visually extract and the speed of that as well. yeah I also really like the fact that you brought back. Again, the customer focus so you’re actually the customer now I guess he’s the biologist. Oh yeah questions, it needs to be answered so you’ve been informed that they’re know your customer base, I guess, and you are.

 

Harald Hess

01:04:26

Exactly.

 

Peter O’Toole

01:04:27

working for them that sounds wrong.

 

Harald Hess

01:04:30

You know it’s totally I mean that that’s sort of the ultimate goal, I mean, in the end can one have some impact on society like Robert Koch and discovering TB i’m used to be disease was everywhere. And now, because he can see it, I mean that’s if you look back on the history microscopy has really done a lot for human society, you know before you’d be looking at the. You know, rather crude description of you know, the human body and you know and what’s wrong with it, I forgot what there’s a name four no passes my head right now yeah. But. You know there’s I think there’s a lot of, potential for a lot of impact, but you know I think biologists can say it, but sometimes and we have to of course work with them to say what can you from the physics side potentially dream about and explore and maybe make a case for it.

 

Peter O’Toole

01:05:36

And there’s a long way to go, I think. You know, when we look at electron microscope she said you got to look at the big picture, but on an electron microscope scale anything we look at his timing. You know it’s it’s such a tiny representation of the of the bigger picture that it doesn’t it’s useful but it’s missing so much And I think that maybe detracts in the in the field, even that may say that, actually, what is the point, because actually I think even Eric said, you need that look the live side of things. So so but.

 

Harald Hess

01:06:12

yeah 

 

Peter O’Toole

01:06:14

it is today, I think the future could be different, and as we many things, even if you go back to your first electron microscope that that was the one mega value is never he never made it into the bio well particularly right that field has moved and developed to solve.

 

Harald Hess

01:06:34

All tremendously yeah very much according to those original dreams that you’re right the time dimensions are important it’s all about just pulling out information, you know, maybe emphasis on the resolution, maybe emphasis on the time the biology is just such a fun rich system to think about.

 

Peter O’Toole

01:06:56

You mentioned time and we’ve actually gone over one hour already. I’ve got more questions, but I.

 

Harald Hess

01:07:04

OK.

 

Peter O’Toole

01:07:04

I guess we’ll have to shelve some of those places. I would like to ask so just because time time is quite sure what would you say your biggest weaknesses and, what is your biggest strength.

 

Harald Hess

01:07:16

I think they go together a little bit. It tends to be, I think, very responsive so. You know, do what other people want, in the end, you know. And you know ended up going into directions like looking at fruit which maybe didn’t bear any fruit in the end so to say. And, but at the same time. You know, being very open and listening. You know you just get a chance, I mean I think i’ve been lucky just to have a chance, through all of these ups and downs failures, unemployment and that have had the opportunity to sort of explore a rich combination of different fields and different ways of looking at it. And so I think that gives me a little perspective, which I think is you know is you know is useful. And and and also a set of experience and tools, you know by having passed through all these different areas, I think, is useful, I mean it didn’t make for a you know super smooth secure life or anything like that, but it. Taking the risks, you know for me at least you know worked out. Yes, this distance. 

 

Peter O’Toole

01:08:42

And what is what boys your pet hate.

 

Harald Hess

01:08:52

Pet hate um. I think sometimes I get a little bit annoyed by doing science, sometimes for the sake of security or not going far enough. You know it’s like trying to do this for next paper i’m sometimes I think people get wrapped up with a lot of parts of the biological culture or I should say, science, culture where the certain expectations on publishing and talks, and you know things like that. which to me, sometimes are a little bit that the odds of going your own way, with a passion in your own direction you know, sometimes you know the nail that sticks up sort of gets hammered down and I think, having a little accommodation, for that is good, I think the world really thrives by having different approaches different ecosystems and trying to unify it too much is good, you really need to sort of the diversity of approaches that are out there. Okay, so yeah, so I think i’m yeah I think the pet hate to sort of combined with the sort of pet desire to have these. You know very diverse approaches for trying to go after science and take very non standard paths to get there.

 

Peter O’Toole

01:10:41

Well you’ve exemplified quite nicely throughout your career. Harald we have to call it there as we have ran over. Thank you so much for your time today. It’s been fascinating to hear about your track record throughout this. It’s been quite amazing, and I think lots of will find it quite inspiring. And to have the confidence to take a risk every now and then, because if you really want to succeed, I guess, you have to follow your passions that’s exactly what you’ve done and bought them all together very nicely, so thank you very much for your time and you don’t you chime so much with Jeff Lichtman work with the big [Inaudible], which I know you’re very connected to but that’s really not the right way to to work with you Eric and Jennifer just how much all these very different people working on very different areas are actually come together to solve and to help the customer.

 

Harald Hess

01:11:38

Oh yes. Yes, yes that’s yeah it’s been an absolute pleasure yeah.

 

Peter O’Toole

01:11:42

Harald, thank you very much.

 

Harald Hess

01:11:44

Thank you, thank you so much.

 

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