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Intro/Outro (00:00:03):
Welcome to The Microscopists a Bitesize Bio podcast hosted by Peter O'Toole, sponsored by Zeiss Microscopy. Today on The Microscopists:

Jason Swedlow (00:00:18):
I have pretty long arms. I barely could be. So if you were looking down the binocular, I could barely adjust the field diaphragm cause it's actually on the back of that huge tower. So it wasn't I shouldn't say, but it was the best microcsope that I've laid my hands on for many, many years.

Peter O'Toole (00:00:45):
Welcome to The Microscopists. Today, I chat to Jason Swedlow from the University of Dundee whose open source tools are revolutionizing microscopy. Well, I've known Jason personally for many years. This is a great opportunity to find out more about Jason on a personal level, everything from his decisions to stop competitive road cycling through to his travels around the world. Catch Jason at home and hear about what motivates him. You'll discover some great tips and tricks for getting to the top, as well as hear about his first microscope experiences, which are quite entertaining to hear about.

Peter O'Toole (00:01:26):
Hi, I'm Peter O'Toole and today in The Microscopist, I'm actually meeting with Jason Swedlow from the Wellcome Trust Bio Center at the University of Dundee, Jason.

Jason Swedlow (00:01:33):
Hi, Pete. Good to see you.

Peter O'Toole (00:01:36):
Yeah. Likewise seems to be seeing you a lot of you these days with the different initiatives going on.

Jason Swedlow (00:01:42):
That does lots of meetings, lots of zooms.

Peter O'Toole (00:01:44):
It's a lot, a lot. Yes. A lot. And here's another one. You are a traveling, man. Very much known, certainly on the circuit. You're always very seldom have I ever met you when you've come from Dundee? Usually you've come from somewhere completely different en route back to Dundee via somewhere else as well.

Peter O'Toole (00:02:09):
So actually this lockdown must be terrible. You're stuck at home. How are you? How's your family coping?

Jason Swedlow (00:02:17):
Well, first of all, I love it. Absolutely love being at home. This has been fabulous. I've been locked down for, I think it's 11 or 12 weeks now. So I, I absolutely love meeting people on these trips. I love the talking and the ideas and the exchange. I hate the airports. I detest the hotels, the planes I'm okay with. Cause it's usually quiet and I could work and there's, you know, I'm not in, you know, 17 meetings and all of that stuff. So I don't mind the flights because I can get work done. But I have this thing with my kids you know, texting back and forth, you know, you know, where are you? Where are you dad? You know, who knows? In yet another anonymous orange hotel room. So, you know, traveling is part of the job, but also I think it's part of a way of connecting with the community. So that's why.

Peter O'Toole (00:03:28):
I think talking to other people as well, it could be great. It's been very productive, very efficient timewise, but it's kind of using the existing networks. I'm really not sure that you don't necessarily develop close new networks. You don't have that same interaction. I don't know what your thoughts are around that.

Jason Swedlow (00:03:49):
There is, there is an element of that and it is something I've thought about, which is you often get invited to meetings from people who know you, which is great. And it's always great to see those people and interact, reinforce those connections. An awful lot of great collaborations, exchanges of ideas come out of that. But yes, there's a certain I don't want to say redundancy a bit of repetitiveness you know, I, I'm sure you find the same thing. You do see an awful lot of the same people giving talks over and over again. My father was an academic and he was, you know, his view was you never gave the same talk twice. You know, and that's, if you think about that, what that means, it's actually pretty, it's a pretty high bar to set for yourself. I have to say I haven't, I have given the same talk twice, but definitely, you know, seeing the same things over and over again, sometimes it's good to reinforce things. You hear things a few times that helps, but on the other hand, yeah, there's it would be nice. I'm not what I really enjoy is going to meetings in communities. I know nothing about it. So I'm, I'm walking in, I'm literally struggling to keep up with the vocabulary, just to understand the words that people are using. That, that, you know, that ends up being quite fresh. It's challenging, but it's also an awful lot of time.

Peter O'Toole (00:05:30):
I totally agree. And you do get invited to give the same talk. I think we get invited to give the same talk and it's the same material time and time again, but a slightly different audience. Yeah. Well, well each talk is slightly spun slightly differently. Yes.

Speaker 3 (00:05:43):
But thank goodness they're a different audience. Otherwise I'd run out of jokes Keep me thinking.

Peter O'Toole (00:05:48):
I think I heard all your jokes Pete.

Peter O'Toole (00:05:51):
Oh, you haven't, haven't seen what I've got lined up for you yet.

Jason Swedlow (00:05:54):
Okay.

Peter O'Toole (00:05:57):
That's make it kind of refreshing that you can have different audiences. And I think technology moves on that enables that opens to different markets. Microscopy is great for moving from market to market. The height, the high plex imaging, the spatial profiling has just opened up a whole new area for microscopists to be talking to and impacting that we weren't previously, you know, on our agenda.

Jason Swedlow (00:06:23):
It's an unbelievably powerful and flexible technology and it just keeps extending its scope. Yeah. I, my version of what you just said, which is very similar, which the whole single cell profiling explosion you know, and that's for a lot of people, the adoption of of imaging truly imaging in that, in that world is just started. There's a massive, I mean, will be, it is becoming, and it will be transformational.

Peter O'Toole (00:06:56):
I know we've talked a bit about this in the past, but actually I'll get, I'm going to skip. I'm not gonna look at the past. Just think about the now, IDR, the timeliness for this and the explosion. And if this is surely, if this is, this is how I think it's not one innovation is it's innovations in parallel that come together that really enabled this to tell us a bit about IDR and where you see that fitting into it all. Jason, you just cut out there for a second for me. Sorry, but you wish you could do that to me all the time. Just kind of annex me, Jason, tell me a bit about IDR.

Jason Swedlow (00:07:31):
Okay. So IDR - Image Data Resource built upon, you know, informed and built and at least initially with the ideas that are coming out of the genomics and the structural biology community, that data sets that are associated with peer reviewed publications are valuable. They're valuable for integrity. They're invaluable for reuse, they're invaluable for just reinforcing the the concepts that are being presented in a publication. And so in a very naive way, you know, can we do the same thing for bio imaging data? The problem is, and so, you know, if you, if you put it that way, it's easy to say, Oh yes, we should. And so that's fine, but right, as you well know, but the plethora of different modalities, the data sizes, the annotations, there's a huge amount of complexity in all of this. And so IDR starts I started the project in 2015, it was built upon some ideas that we worked on through Glencoe, the company.

Jason Swedlow (00:08:48):
I run with the JCB data viewer that was built with Rockefeller University Press. Then we, you know, thinking about rather than doing a journal specific resource now doing effectively the community resource. And so we were fortunate fortunate enough to get some funding from BBSRC to support that work. And in collaboration with the European Bioinformatics Institute EBI, we started building that and around, I think mid 2016 or so IDR has been in production, taking data sets from the community, working through the annotations, et cetera, and then publish them online. And it's just taken off from there. And so, you know, the the ramp up I think initially it was people thought, well, you know, will this work? And, you know, we, we still have a long way to go before this is publishing imaging data is routine and is happening for the majority of studies that used imaging, but definitely making progress there. I think pretty important step was 2018, I guess, publishing a paper with our colleagues at the EMBL and EBI, trying to lay out ideas around. What about archiving data annotating data making targeted databases, so called added value databases and trying to think about linking all of those together and to imagine what a mature image data the word we use there is ecosystem, you know, or, you know, a community of data of data resources would look like. So

Peter O'Toole (00:10:52):
One of the biggest challenges is surely going to be getting the user community to know about it. It's easy to get the likes of cores to know about it, microscopy geeks to know about it, but actually we're not the ones generating tons of relevant data. It's the users and to get them engaged and to buy into it, that's going to be a huge challenge,

Jason Swedlow (00:11:13):
Right? So, I mean, there's, there's a, a slightly trivial answer and there's a serious answer. The trivial answer is, yeah, that's why I'm on the road. And that's why, you know, as we were talking about before the salesman, well, part of science is, you know, communicating your idea is, but more seriously actually what's happening now and where adoption is coming from has less to do with us directly and more to do with journal editors. And so,uNature Springer journals have recommended, you know, have, have on their website, IDRs are recommended repository for these data, which is great, but something else is happening where specific editors in journals are targeting papers. So paper that has significant amount of imaging data is sent to us. And literally several times a week, now we get an email that reads more or less word for word, 'Dear IDR, I have a paper about to be accepted in, fill in the blank name of the journal. The editor has told me, I must deposit the data in IDR. Uplease help' you know and then you know, we go from there,

Peter O'Toole (00:12:27):
Like, I guess, look at your analogy, being a salesman. I can see your lovely bi-fold doors behind you. I can imagine the salesman coming in. And you're saying, that's one way, that's what you're doing. And yet you've also got the building regulators coming back and telling you, you have to buy double glazing.

Jason Swedlow (00:12:44):
Yeah. I mean we,

Peter O'Toole (00:12:47):
And Jason, we forget that is sunshine. Isn't it? Are you actually really in Dundee?

Jason Swedlow (00:12:53):
This is Scotland. Okay. And yes, I am in Dundee welcome to my house and I will tell you one lovely thing about living all the way up here on the East coast of Scotland is you know, I listen to every morning to you know, the rate, the weather forecast on the radio and it's atrocious down in England and, you know, there'll be storms coming in and even on the West coast of Scotland, but here on the East coast. It's it's great.

Peter O'Toole (00:13:24):
I've got some quick fire questions for you, Jason, see how this go? So you just got to answer one or the other, no hesitation. Okay. So don't think about it. Tidy or messy.

Jason Swedlow (00:13:37):
Oh, definitely messy.

Peter O'Toole (00:13:38):
Tea or coffee?

Jason Swedlow (00:13:39):
Always coffee and large amounts.

Peter O'Toole (00:13:42):
Book or TV?

Jason Swedlow (00:13:45):
Uh I, it has to be one of the other depends when time of day

Peter O'Toole (00:13:54):
Eat in or eat out?

Jason Swedlow (00:13:57):
Both.

Peter O'Toole (00:13:59):
UK or U S?

New Speaker (00:14:01):
UUK.

Peter O'Toole (00:14:03):
Ooh. There goes your American passport.

Jason Swedlow (00:14:07):
I wish it were that easy. I've lived in Europe for 20. I think it's coming up to 22 years now and it's been great. I love living here.

Peter O'Toole (00:14:22):
Yeah. So, so yeah, back in 98, I think he was when you joined and set up and start to develop. So let's look back at that because you came to the UK Wellcome Trust Bio Center up at the University of Dundee and develop that into what it is today. And, you know, it's very well known, internationally for its imaging, which is very much driven by yourself, Adopting new technologies, but you're not a biologist from your first degree, are you? I love that look of confusion of when I say you're not a biologist.

Jason Swedlow (00:14:54):
Biologist? Where is this going?

Peter O'Toole (00:15:02):
What was your degree?

Jason Swedlow (00:15:03):
Bachelor's degree chemistry five years racing bicycles and

Peter O'Toole (00:15:17):
From your degree. You then spent five years racing bicycles before going back into science.

Jason Swedlow (00:15:22):
Yeah.

Peter O'Toole (00:15:24):
So how serious was your cycling?

Jason Swedlow (00:15:27):
Pretty. Um so finished university was really enjoying racing. My parents, my dad was an academic. My mom was a nurse. We weren't exactly sure what to do with someone who was devoting themselves to going down hills very fast and things like that. And actually I've had subsequently had some discussions with my mother. I was, she was pretty worried. But initially in Boston and then in San Francisco I was racing had a job in San Francisco at UCSF working in a laboratory and I was learning a lot about pretty kind of hardcore biochemistry, protein purification, and UCSF at the time was this amazing place. There was just so much going on. It's still is it's still amazing research environment. And I, I got the bug and admittedly going fast, downhills is a lot is pretty, but you start thinking about the longevity, you know, at some point you start thinking, you know, start seeing, well, okay, this is fun, but you know what, there's a eventually, you know, a neuron fires and says, okay, time to be serious.

New Speaker (00:16:54):
You must have been pro? Semi pro?

Jason Swedlow (00:17:00):
No, all amateur, all amateur. And so the problem with that in the least, at that time in the bicycling world, the transition from amateur to I was on a team, we had some sponsorships, et cetera, but it was pretty lean. So you have to work to you know, for your food and your tires basically. And I know to make the transition to being a full pros, is a big step, and I was racing against guys. So I was getting up at five in the morning doing 40 or 50 miles getting home, going to work coming back in the evening, going out for another 30, 40, sometimes much longer just to get the miles on the legs. But in fact, we had, we had pros staying with us in our apartment and they were doing more miles, but they were getting up at nine o'clock and going out and coming home, you know, coming home and having lunch, have a nap going out again. And that that's the difference. It's just impossible to compete.

Peter O'Toole (00:18:14):
So you say you got the bug when you were at UCSF. Is that the first, I guess as a chemist, you're never really using light microscopes, I'd be guessing obviously a lot of your career has been based around the use and application and data of microscopy. So when was the first time you used a microscope?

Jason Swedlow (00:18:34):
My first rotation in graduate school, it was complete accident. So we'll try to make this as concise as possible, 1986, 1987. The first examples of what was called site directed mutagenesis were published. And so, you know, you could look at the sequence of of a protein mutate, an amino acid, and then look at what happened then assay that effect. And so this was being done on enzymes, but, you know, the idea, the technology to make a point mutation

Jason Swedlow (00:19:16):
In a, in a cDNA had just been developed. And the protein expression was in the very early days. And Dave Agard's group at UCSF was if not the first, then definitely one of the first to make a mutation that just didn't just kill the enzymes. So but in fact, they had they had switched the specificity of of a bacterial protease from small hydrophobics amino acids. And, and just by changing the binding site, they had broadened the specificity of the enzyme, so rational design and it was mind blowing that, you know, you could do such a thing. And so that's what I was going to do. That was my, that was my career goal at how I wanted to join Dave's lab and I was interviewing him interviewing with him. And we talked an awful lot about the various projects and at the end of about an hour discussion one evening, he said, you know, I, I I have this other side of my lab, you know, do you want to hear about that?

Jason Swedlow (00:20:32):
And I thought it would be rude to say no. So I said, sure. And he said, yeah, we do a lot of three dimensional structures of cells using microscopy. I had no idea what he was talking about, but after a few discussions, it seemed like so UCSF at that time was one of the few graduate programs that was doing rotations. So you would spend a year as a graduate student, your first year sampling different laboratories that at that time it was a very novel idea. So I just thought, well, Hey, you know, I'll just, I'll do a rotation of this just to learn about it just because it sounds cool. And short version is, you know, that was it. It was over I was a microscopist.

Peter O'Toole (00:21:17):
Yeah. Aye, congratulations. Welcome to the club. I think a lot of us were very late to the club were relatively late to the club. So just thinking a bit more about the microscopes themselves, tell us about this one.

Jason Swedlow (00:21:35):
Well, that's a Zeiss Axiomat there's a few people in the world who have seen those. So that was a design that came out of Zeiss in the eighties that celebrate the retirement of one of their senior engineers, at least the way I heard this story, I haven't verified this with anybody in Zeiss, but this was effectively their retirement gift design your, your microscope and sort of see in the image behind you, it has various modules. But you can also see that you can't see the whole thing. And so the, this is an inverted microscope, the objective lens and turret are way at the top. I have pretty long arms. I barely could be. So if you are looking down the binocular, I could barely adjust the field diaphragm cause it's actually on the back of that huge tower.

Jason Swedlow (00:22:25):
So it wasn't how should we say easy to use, but it was the best microscope that I've laid my hands on for many, many years. It was the darkest microscope. So no stray light. And so fluorescence just to get just the images were incrediblly crisp, and in my PhD lab. So [inaudible] are the were one of two labs. And I think they were leading the way to get a CCD camera and put it a microscope on that. They have Zeiss that John had this Zeiss Aiomat and they got a CCD camera from Tektronix. And they put it on that microscope and it was one of the first digital microscopes in the world. That was my PhD.

Peter O'Toole (00:23:09):
That's cool. I've got to say, it's got one of the longest focus stalks that I've seen on a microscope as well. And that is huge, like a magic wand.

Jason Swedlow (00:23:19):
Yeah. Well, it has to be right, because actually you are, you know, you need a way, you know, your arms are kind of reaching around it's it's yeah. It wasn't ergonomically designed that wasn't his point

Peter O'Toole (00:23:34):
In its own microscope lab or in the open bench?

Jason Swedlow (00:23:40):
No, in a positive pressure room filtered air [inaudible] the whole thing.

Peter O'Toole (00:23:45):
That's a filtered air, which sounds quite good. Cause I could have sworn you told me something in the past about microscope rooms maybe not being the best place in the world.

Jason Swedlow (00:23:53):
Yeah. So, okay. Here's the story. So you imagine this is a positive pressure. So all filtered tacky mass on the outside special room for this microscope and there's various computers in the room as well. Controlling the CCE and, and the other revolutionary thing about those microscope. Again, you have to remember when this was like eighties your Sushi Horoka in John's and John's lab had managed to get a stepper motor onto the onto the objective turret. So now you had a three dimensional optical sectioning microscope. So it's stuff that we now take for granted. No one would even think twice about the novelty of that. This was extraordinary. So yeah. Amazing lenses, all of that stuff. Before at that time to collect a three dimensional set of optical sections through a dappy stain nucleus was an amazing feat and took an awful lot of time on the computer, et cetera.

Jason Swedlow (00:25:10):
So you would sit there collecting these datasets. And, you know, I was sitting in the, in the microscope room collecting some data and John Sonought another PhD advisor, opened the door and said, you know, everything is going okay. I said, yeah, I said, you kind of sniffed the room. And he said, did you fart? I said no, I definitely didn't fart, and he said, are you sure? John, believe me, you know, if I farted, we would know it. He said, okay, we don't fart in the microscope room. The forecasters condense on the on the lenses. And and that is a true story. And but it also, I would just say it speaks to the exacting standards that John had for his microscopy and the way that, so just to, you know, it would, it would be hours to talk about how all everything was integrated on that microscope.

Peter O'Toole (00:26:13):
That's another science behind that, how the gas is collected.

Jason Swedlow (00:26:19):
Sorry, sorry, Pete.

Peter O'Toole (00:26:22):
Just switching tack a bit. You came to Dundee in 98. How did you find the trans? That's quite a big move to, to go from one country to another country. How was that? How did you find that? You know, we, were you nervous about switching countries, confident. What were the problems with that that actually brought about in itself?

Jason Swedlow (00:26:44):
Ah, probably the short version Pete, is that you're in a, you're in a place where people are normally speaking the same language. So they use the same words, but everything is different. And so you don't, you really have no idea what's going on around you. And so, you know, the decision to leave the US was complex, had job offers in the US, had job offers and the offer for Dundee here in the UK. And it seemed like a bit of an adventure. But you know, arriving in a place where people say things to you and you're conscious that you have no idea what someone is saying, and you don't even know what questions to ask to clarify. That's that's, that was the challenge. And that's, that was that's true in social settings. True. You know, trying to find schools for your kids, it's trying, you know, and it's true in the scientific environment as well. So yeah, I mean, it's hard to move, but I think like most of the scientists that have helped.

Peter O'Toole (00:27:52):
And you recommend a big switch?

Jason Swedlow (00:27:58):
Yes. Yeah.

Peter O'Toole (00:27:59):
Well, I guess I've so, as you chose UK over US,

Jason Swedlow (00:28:03):
I mean, but you know, it's right. It was right for myself. I was right for my family. So yeah, it's worked out, that's my view. That's a very personal view.

Peter O'Toole (00:28:15):
So that's one challenge. You've got quite a big career. You've had lots of diversity to it. What's when have you found the most challenging time? That's a big sigh.

Jason Swedlow (00:28:28):
Yeah. I mean, I challenging there's lots of different types of challenges. And so I guess know, I can ask back, okay, well, what kind of challenge do you mean Pete? But I think probably the hardest time is really that transition. And I, I, that this was my experience. I think it's true for an awful lot of academics. It's that transition where you're going from you know, junior independent investigator into, into a tenured position or, or whatever that is. It's different names for it in different worlds. It's a really tough time. It is really, really tough. And it's tough on your head. It's quite demanding just, you know, what you have to deliver. Yeah, I would say that would, that was one of the toughest times.

Peter O'Toole (00:29:25):
And that's mostly, I presume down to pressure and self pressure. A lot of it.

Jason Swedlow (00:29:31):
Yeah. I mean, when I came to Dundee, like I said, my dad was an academic and I had seen an awful lot of rough and tumble of academia and an awful, I have to say a lot of the things I see happening around me and happening to my colleagues. I remember my father talking about, you know, in the sixties, right over, you know, over dinner, you know, things that would happen. So I'm not in no way. Do I need you to say that, you know, to diminish the challenges of being an academic it's hard, but it definitely is something it's just, there's a lot of, it seems to be intrinsic to the system that we've built. But yeah. I don't know. I'm sorry.

Peter O'Toole (00:30:24):
Yeah. A tough time. I think, I think that, I think you'll have a lot of people listening or watching that.

Jason Swedlow (00:30:30):
I possibly feeling that now as well. Yeah. I mean, I will, I will say, You know, I'm now I'm now officially old. Right. And so I can say these things, but it took me decades to learn that how tough it is is related directly to a, a commitment to being you know, world-class and excellent and being world-class and excellent is really hard. Right. And when I came to Dundee, cause I was an academic, I said, okay, instead of myself, I have to schedule a meeting with the department chair at that time, a guy named Pete Downes. And I need to talk with them about the requirements for tenure and get this all clear. And I, I scheduled that appointment and I said, you know, I was very polite, you know, thank you for meeting me. I'd like to know how you plan on evaluating me for tenure so I can properly organize my my targets, you know, all of the things around org, you know, focus and organization and planning and Pete said, international reputation. I didn't say this, but I thought ax murderer.

Peter O'Toole (00:32:05):
And you have a lot of citations at that point.

Jason Swedlow (00:32:08):
Exactly. And I said, well, okay, we have this discussion, but I, it took me awhile to understand what Pete was saying was part of this was a Dundee thing. Dundee, had a desire to put itself on the map to be a world class research institution. And what that meant was that when, for example, Pete or any of the other senior staff would go to meetings, they wanted to, they wanted to hear people talking about you, frankly, you know, why would people, why would people be talking about you? Okay, well maybe ax murderer, but more serious, more seriously world-class science. Right. And so I think that's, that's what makes it so hard is that the aspiration is to be absolutely world class.

Peter O'Toole (00:33:01):
Yeah. Making significant contributions.

Jason Swedlow (00:33:03):
Yeah. And, and we now all live in a global community and a global scientific enterprise. And so by definition, what we, what we do when you, you know, you use the word significant or significance, it has to be on that scale. That's incredibly challenging. And it's really, really super hard. It, it, it puts all of us at a very high bar.

Peter O'Toole (00:33:34):
So this is interesting because you can do it, you can make a significant impact, but you can't just make one significant impact. You know, eventually that wave will come to the end and you then have to look for the next wave and you have to keep looking to make those significant impacts. And actually, so you started off with a chemistry, as a degree, you went into your biophysics, you moved into far more cell biology. And now actually a lot of your work is data analysis through the microscopy era. And so actually you you've been surfing all sorts of different oceans, not even just different waves. So it seems to me is that actually opportunistic is the wrong term to use, but you see where there's an opportunity and where your strengths are and you've followed them and you've not been scared to change tack.

Jason Swedlow (00:34:26):
Yeah, I wish I, I wish that all sounds great, Pete. I wish I could say that there's any kind of foresight or even thought about, Oh, am I changing a tack? I think in all cases, it's, you know, wow, this is an interesting problem. And this problem I'm facing is stopping me from making progress. And so I guess I'd have to think about it and address it. And that's about the depth. I'll confess, that's the depth of analysis or kind of reflection before embarking on any of these things,

Peter O'Toole (00:35:07):
But you've never left it to say, well, there's a problem. I need someone to solve it so I can carry on my research. You've seen a problem and shifted to solve the problem. You've taken it upon yourself to move it.

Jason Swedlow (00:35:19):
Well, the problems I've chosen to do engage with yes. I mean, not all, not all you can't solve all problems. And so I think there is a bit of you know, is this, so this was, this was a big discussion. I remember in graduate school, it was just, is this an important problem? Right. We would have these discussions about, you know, is this an important question? And you know, is this a fundamental question that is important to solve? And I think one of the things that was around UCSF and definitely definitely in Dave and John's lab is marrying a scientific problem with the technological capabilities to solve that problem and understanding that the two go hand in hand and, and sometimes you don't need new technologies, but sometimes you do. And when you do, you have to, you can't pretend that you don't because you do so sorry, that's kind of trite, but that's true. And the other one is to figure out how to, how to know, okay, what is the technological steps that you need to deliver?

Peter O'Toole (00:36:37):
You say about following goals. I mentioned following opportunities here. It's been kind of just, I've had to take the opportunity, but actually you've got your own spin out company as well. So for the Open Microscopy Environments and moving that forward. So tell us a bit more about that, because at that that's not trivial either setting up a successful spin out.

Jason Swedlow (00:36:58):
Well, yeah, I mean, so, OME started as an open source project and we had made some progress. So OME started 2000, 2002 first two grants were from the Wellcome Trust here in the UK late in 2002. And we started making some progress and by about 2005 we had some commercial commercial companies coming to us and saying, well, this is all great, but there's these open source licenses we need, we need a commercial, we need a commercial version. And so Glencoe Software was founded explicitly with the goal of, of having another way to deliver the technology, to expand the audience or expand the user base or expand the adoption because we have pharmaceutical companies and technology companies saying we want to engage with us. We, you know, especially at that time, it's changed an awful lot of the last several years, but you know, you know, 2005, 2006, I guess these discussions where we were having discussions year or so before that, you know, no pharmaceutical company would allow an open source library inside their operation, or at least they would say they, they wouldn't, sometimes they didn't know they were actually using open source libraries.

Jason Swedlow (00:38:33):
And I actually in the very early days, we were talking to some of the microscope microscope manufacturers we're talking to some of the old, you might remember Metamorph. Yeah, of course. So we visited their their offices in Eastern Pennsylvania and their president, Jeff Stuckey, were in this meeting, we said, well, this is all fine, but you know, we absolutely absolutely cannot use open source software. We will not allow open source software through the door. His CTO was sitting there and he said, well, actually we use open source software to run all our mail servers.

Jason Swedlow (00:39:21):
And he looked at him, said we do. Yeah, absolutely. It's the best stuff out there. So so part of it was education, but part of it was also providing a a choice for a broader community to access this technology.

Peter O'Toole (00:39:39):
So that's being successful. Your research has obviously been fantastically successful. How do you balance will spinning out a company and your academic research, great face.

Jason Swedlow (00:39:53):
Balance is not something that is not a word that I would really bring to the table on this one. It's a, how do you survive is probably more the best answer that has look, you know, I told you why, you know, there's reasons that we do these things. I work with an amazing group of people. My colleagues are absolutely world class. They're just the best. And that's probably the best way is not probably the best question is not how do you balance anything like this?

Jason Swedlow (00:40:33):
Because you know, everything is it's, it's an awful lot of work, but I have an amazing group of colleagues that are on the team that work with us and have now worked with, for some cases approaching 15, 18 years are just incredibly dedicated, incredibly capable, you know, expert and passionate boy, oh boy do we argue? We get in each other's faces. We will, we'll go to the mat. You know, I mean, we will argue quite vociferously because what you're, and that's the passion.

Peter O'Toole (00:41:17):
Um do you always win those discussions?

Jason Swedlow (00:41:23):
Never. That's not true. I think one of the things I most enjoy about OME and Glencoe both is that no one in the organization is, is right all the time or is the, you know, this singular voice or view. Right, right. You know, I, I can't, you know, I can't participate in those projects without my colleagues and they can't participate in, without me. I bring a lot of biological knowhow and domain expertise on that side. They bring a lot of expertise in informatics. Yeah.

Peter O'Toole (00:42:06):
They've got expertise outside of your own expertise. Hence, they're a good team. Actually, we ended up, one of my contributions is actually one of my ex PhDs, Mark Cole was there. So Roger Lee is up there with you arguing with you. I can see him not listening to you.

Jason Swedlow (00:42:29):
I mean, you know, Roger worked with us for many years and incredibly productive, you know, I don't, you know, we don't run an organization. That's about, you know, listening to me listening is one thing, you know, taking commands is that's not, that's not how the system wants to work.

Peter O'Toole (00:42:46):
So with all those stresses balancing it. I know it's not easy. And actually you did give me some some photos at this point. So this one Jason, this picture is brilliant. Your face on the picture itself and your hair. Wow. It's all over the place, mate.

Jason Swedlow (00:43:11):
Beautiful day. In Santoriniin Greece yeah, lovely day with my family. My wife kids my sisters, my mom. Yeah. All those.

Peter O'Toole (00:43:30):
Wow. One minute, so you go to Greece with your family, your children, your mom, and you call that winding down.

Jason Swedlow (00:43:40):
Oh, absolutely.

Peter O'Toole (00:43:42):
We, we with all of them together. And then, and then there's these pictures of you. Wait, where is it, Jason? This picture.

Jason Swedlow (00:43:50):
That's the, Isle of Harris, the Hebrides in Scotland. And that's October in the Hebrides. Is there anybody who knows anything about the seasons in the UK? It's getting pretty rough at that time. And yeah, so that's the autumn holidays. And I had a brilliant idea to drag the family out to the island.

Peter O'Toole (00:44:15):
I'm just looking at your daughter. They're propped up, leaning against you thinking this was not such a smart idea. Dad, dad, do you think this isn't one of your best ideas?

Jason Swedlow (00:44:25):
We talk about it fondly at the time. And still we refer to it as the holiday of death marches because we walked up and down the Island, across, and the kids were like, this is, I guess, I'm not allowed to swear. So I'm not allowed to actually say what this was.

Peter O'Toole (00:44:45):
They look, they look too nice to swear. I'm sure neither your son or your daughter be swearing at that point. He looks like he's enjoying the nature and looking down and see,

Jason Swedlow (00:44:58):
Here we go, walking again. No, it was a lovely time. Harris is beautiful. It's one of the, it's my life,

Peter O'Toole (00:45:07):
Jason. I love this picture because I can give you an even bigger quiff and now I've got a different wife, that's it? It's a perfect size.

Jason Swedlow (00:45:16):
Well, it should be, she'll be back in about half and hour. That's in Singapore. And actually, I mean,

Peter O'Toole (00:45:25):
I know where that is actually in Singapore as well.

Jason Swedlow (00:45:30):
It's in the Marina Bay gardens, I think. Yeah,

Peter O'Toole (00:45:32):
Just by the race circuit, isn't it for the formula One is a pit lane to just the other side of there.

Jason Swedlow (00:45:39):
I was on an advisory board there for many years at the A Star, one of the A Star institutes and would go out there once a year. And a couple of times Melpi came out with me. We have a lovely time after, after meeting. So I guess that's, you know, on the travel side, I quite deliberately don't add any extra days almost ever, except if I'm with my family.

Peter O'Toole (00:46:02):
So that's considered it. They get to go out occasionally with you then. So LME has never been in a good enough location to bring your family. Is that what you're saying? So I've never seen them at an LME meeting, for example. Now you've just offended half of the people around Europe and all the places that it's taken.

Jason Swedlow (00:46:24):
I know I'm going to get it for that one.

Peter O'Toole (00:46:28):
You've offended the US and you've offended the rest of Europe.

Jason Swedlow (00:46:32):
Oh, well. Honestly I yeah, what can I say? Okay.

Peter O'Toole (00:46:40):
How'd you remain motivated because you know, you've had so much, you've had so much success. You keep moving forward. I think we'll talk next about bioimaging UK. You were bioimaging global bioimaging the amount of effort and energy you must, it must take out of you to you've got Glencoe, you've got your research group. You've got these initiatives on the go. What keeps you motivated? How on earth do you keep the momentum going?

Jason Swedlow (00:47:15):
I mean, it's kinda hard to answer that question because I almost don't recognize how do I, I haven't even, I wouldn't even know how to answer that question

Peter O'Toole (00:47:26):
Just do,

Jason Swedlow (00:47:27):
I mean, the science is so darn important. Um I think it's one of the privileges of being a research scientist is what you're doing is by its nature contribution to your society. You know, it's, it's a real privilege to have such a position. So yeah, that that's enough. I don't, I don't know how to answer the question beyond that.

Peter O'Toole (00:47:57):
I I'll put words in your mouth, you mentioned earlier. You've got a really good support team that that was

Jason Swedlow (00:48:07):
Maybe a way of answering your question. I have an amazing team. I feel duty bound to do my job for them to, to deliver for them. And often too, you know, if you strip it down, you know, my job is to work with them and, and for us together to do important work. But my job also going back to what we were just saying before my job is to, you know, market, to present the work, to show the world what we're doing to hopefully see how that our work can impact their work. My job is also to continue to raise the funds, to fund the work right, to, to write the grants, etc. So they're, you know, there's motivation for funding. You're feeding an awful lot of families. I mean, to put it very bluntly,

Peter O'Toole (00:49:05):
Well, you accepted this interview now. There's just to keep the message out there, keep it going. So yeah Pete, I'll do it with you. At least you'll tweet about it when it comes out.

Jason Swedlow (00:49:22):
Yeah. I'll, I'll, I'll, I'll do my job on Twitter from here.

Peter O'Toole (00:49:27):
So moving through it, I've got a couple of other bits. What is your favorite publication? It doesn't have to be that you've authored or coauthored. It doesn't have to be your stellar publications. Which one are you most bombed off?

Jason Swedlow (00:49:47):
I think probably two for two different reasons. The first is the main paper that came out of my PhD. And I think if anybody read it now, which is that a pathetic piece of work, but it was one of the first live imaging experiments and it was, and you know, I remember clearly there, there was a huge question in the field about how chromosomes were constructed and how various proteins acting on the on chromosomes. And, you know, there was decades of work looking at different types of looking at chromosomes from different preparation that those different fixation methods and so on. And this was one of the first experiments to look at in a live organism and the results were astounding. It was the results, you know, the first time I got the results, so I'm sitting at a microscope, but very late one or two in the morning and the way the protein was moving on and off the chromosomes, no one had ever predicted before anything could happen.

Jason Swedlow (00:51:04):
And in fact, our cameras weren't so sensitive. And so basically there was this moment in the cell cycle where the protein I was looking at topoisomerase 2 completely diffused off of the chromosomes. What that meant is the signal is diffused below the detection limit of the camera. And basically the signal when all I had was dark noise. And I was just sitting there thinking, what happened? How did, how did this system break? Now, I'm looking at dark noise, right? Why, how could it possibly, what could have gone wrong? And then the signal came back as the protein relocalized. And then I fell out of my chair and bruised my arm really, badly, but you know, it was, it was a profound scientific result. So there's one

Peter O'Toole (00:51:49):
Then Jason, I'm going to ask you about the first publication that was in the days you had to write it, print it and post it, wasn't it?

Jason Swedlow (00:51:58):
Oh yeah. I mean,

Peter O'Toole (00:51:59):
Do you actually recall? I recall my first, my first one, I remember going with it in a brown envelope and putting it, wishing it well as you post it through. Can you remember that moment?

Jason Swedlow (00:52:09):
Well, there's, I think two copies of the printed manuscript, two copies of the,uall of the made up figures on storyboards, et cetera. Right. And I think on that one, I think we probably had them photographed and submitted the photographs. Uand all of that is in that big brown manilla, envelope. Absolutely.

Peter O'Toole (00:52:30):
It's so different though. You don't remember clicking, send, putting it through that letterbox, kissing it, praying and putting it through saying, please listen, please. Like it,

Jason Swedlow (00:52:40):
I think this is too old then, you know, they can remember again,

Peter O'Toole (00:52:43):
Oh, wait, wait, less of the old this side, the cheek of it man.

Jason Swedlow (00:52:52):
Yeah, so that one, and then I think the other one is our paper that was we published, we've the first paper we published on OMERO, the status management system that we built over many years that work started in 2004, 2005 paper that was published in 2012, I think. And just an enormous amount of work from a whole bunch of different people and brought in contributions from the community. It was, it was just, it was just a great example of what we were trying to do with LME.

Peter O'Toole (00:53:25):
That's eight years of work to get to that the key paper for that work

Jason Swedlow (00:53:29):
I mean in person years. Big, Well, many, many times eight,

Peter O'Toole (00:53:38):
Which, which I think is actually a credit you've mentioned a couple of the funders already say, BBSRC, Wellcome Trust and so forth. I know there's been funding from other avenues. They put a lot of trust in scientists. They've put a lot of trust in you. For these ideas are very holistic. They're very community driven and not in some of these cases, they're not to solve a specific biological question. We should fit kind of a bit outside their remit at some cases, but they put the faith in it. It's taken eight years to get to the big impact paper of 2012. IDR was an incredibly fast turnaround. I did, you know, that was within a year or so of coming through, but I think our funders, we've got to give them credit. They've put in faith because this is where the big impacts are made. And sometimes it doesn't happen overnight. You've got to keep going and have faith in your work.

Jason Swedlow (00:54:27):
Yeah. I mean yeah, I've been very, very fortunate to have here in the UK quite forward looking funding bodies. I don't, and I, you know, they don't, I'm sure they don't, I know they don't do this with all of their funding. They are willing to take chances and willing to have that Longer view. Yeah. And you know, we we've been the beneficiary of, I think, a, a great funding movement here in the UK

Peter O'Toole (00:55:02):
And, and I would actually rewind back almost to the starter today, that international profile, you have to be a salesman. You have to make sure that people know and are aware that there's a need in the market. So its all good and well to come out with the idea, but the community has to be ready to have that foresight. So when it goes to reviewers, they already are kind of aware that this is a need. And so it does come back. It takes a salesman type person an international profile getting messages across and checking its real and needed.

Jason Swedlow (00:55:33):
I think, I mean, I am a little concerned about the stat that the state of science. So, you know, you're talking about giving talks at meetings, et cetera. The pace of publication now is so high that, you know, keeping track at all and reading things deeply, it's super hard. It's just, you know, speaking for myself, it's beyond the no physical cabability,

Jason Swedlow (00:56:03):
You know, so I mean, you know, there's an awful lot of science on Twitter. There's an enormous amount of imaging on Twitter. So people are exchanging ideas in that media, I think that there's a reason people are doing that right now. So I think there's a reason that we have this proliferation of, of meetings and symposia, etc, and all of that's great. But yeah, I think it does serve a purpose in condensed in two and a half or three days, you or I, or our colleagues can sit it through a very dense, packed presentation and get a sample of what's going on. Right.

Peter O'Toole (00:56:42):
Um I think that fits the bioimaging community in general. It's very collegial we beat against each other, but everyone supports and helps each other. I think that's quite exceptional across there's one or two other technologies. Lots of other communities are far more divided.

Peter O'Toole (00:57:04):
And I think, yeah, there's been several initiatives. Bioimaging UK is one initiative that's really brought the UK certainly closer together and follows across Europe and to global biomaging as well. And you'd think behind a lot of that in the UK and Europe as well. And so just briefly before, before we wrap up, it'd be good just to hear a snippet cause not everyone will have heard it bioimaging UK. Euro bioimaging, global bioimaging. So actually salesman, I'm going to give you 10 minutes to pitch on this.

Jason Swedlow (00:57:37):
Okay. So, okay. The sales pitch, this is all about research infrastructure. And again, I'm kind of going back to what we say, what we were talking about. These are about capabilities, about open access to those capabilities that then underpin a scientific discovery and advances. One of the principles is that imaging is an absolutely key component to a modern biological and biomedical science, but, you know, Pete you know, this as well as anyone, you know, over the last couple of decades, the rapid development of new technologies and critically.

Jason Swedlow (00:58:21):
So, you know, you guys at York, you know, maintaining that capability for your, you know, even for your local community is really hard, right? And it's basically impossible to have enough funding and enough expertise. And actually, I mean, nominally, you know, maybe somebody could provide the funding, but I don't think there's the expertise to, to deliver that technology at all sites say in the UK or even Europe, worldwide, etc. And I think that that realization started to appear that there was a challenge emerging there sort of 2005, 2000 eight, something like that. Jan Ellenberg gets from EMBL Heidelberg gets an awful lot of credit for leading the charge on neurobiology imaging, starting to decide idea of a common open access research infrastructure that would provide those capabilities to the scientific community. And the short version is a European scientist should be able to identify the technologies that he or she needs to do the experiment that they need for to answer their question.

Jason Swedlow (00:59:38):
They need to be able to understand what those technologies are. They need to be able to identify who has those technologies. Then through some review process, access, those technologies run the appropriate experiments, get the data, go home, do the analysis, they need publish the paper, right? And that that's a democratization of those of those technologies realizing that they're too expensive to put in all peoples physical hands at all times, and that we don't have the staffing and expertise to deliver those technologies. And so we have to be, you have to, there has to be a smarter way than just I'll have mine and you'll have yours. And I think that smarter way idea ends up playing out at different levels, possibly at different geographical scales. So at the level of the country, like the UK, the way of thinking about how you would do that, then on the continental level would you do that? And even on the global level, so how do we bring up and have that kind of exchange and access at the global level?

Peter O'Toole (01:00:54):
So maybe not so dissimilar to data sharing and actually we're living now in a time where we can have, we've just come out of a period of austerity. Supposedly we just go into another financial crisis and the more cost effective we can be, the better it will be and the more we can share. Okay. So from a UK side, obviously we have Brexit which everyone knows about ultimately science doesn't recognize borders. And it's really important to move that because we can work far more efficiently together than we can compete against each other and duplicating efforts. I think we're going to have to do more of that to respond quicker, to, to address scientific needs. And I think actually the latest outbreak is a perfect example of that.

Jason Swedlow (01:01:42):
Yeah, I agree. I mean, you know, there's the fiscal aspect to this. I think we have a responsibility to our community to be as efficient and powerful as we can with the technologies that are ultimately funded by our society. So yes to that. But I also think the exchange of information and ideas is key to advancing, you know, moving our scientific advances as quickly as possible. So yeah, completely agree.

Peter O'Toole (01:02:16):
I've I quite like and finding about people, what car they drive, but what was your first car?

Jason Swedlow (01:02:23):
Yeah. I can see where these questions are going. A VW golf.

Peter O'Toole (01:02:32):
Gosh, she was successful early on weren't you either, you didn't get a car to you're much older.

Jason Swedlow (01:02:35):
You had to see it. This was a cast off from cast off from a sort of friend who became less of a friend when I discovered how he had temporarily tweaked the engine. So that would get me home and after that fell apart.

Peter O'Toole (01:02:55):
Well, it was very community minded of him though know this, but what are you driving at the moment Jason,

Jason Swedlow (01:03:03):
That would be a VW golf.

Peter O'Toole (01:03:07):
Tell me it's not the same one.

Jason Swedlow (01:03:10):
Definitely not the first one. Yeah, it it's somewhere in a junkyard and San Francisco, I'm glad to see the last of it, but yeah, it's still Golf.

Peter O'Toole (01:03:29):
So actually that's surprising to me. I thought we do a passion for walking with a family living up in near, near the Highlands in Scotland. You might have at least had a 4x4 or have you had that in the past?

Jason Swedlow (01:03:39):
I haven't, but cars has gotten us where we needed to go.

Peter O'Toole (01:03:44):
Yeah. I actually, I'm kind of surprised you didn't say it was an airplane. Is your current car, Jason, you've been brilliant to talk to.

Jason Swedlow (01:03:55):
It's been great.

Jason Swedlow (01:03:57):
It's been good. Fun. I, I, yeah, that microscope room, that, that image is going to last with me for a long time. I will, I will see you on zoom. No doubt.

Jason Swedlow (01:04:11):
So can I ask you a question, Pete?

Peter O'Toole (01:04:13):
Oh go on.

Jason Swedlow (01:04:15):
So how many of these interviews have you done?

Peter O'Toole (01:04:17):
Done, done so far. We've done. This is number four. There's another two already scheduled and yeah, my list is quite long. Actually. I on starting with yeah, close, close friends first, I think. But there's some, yeah, some really good ones also lined up.

Jason Swedlow (01:04:42):
And so why are you, why are you doing this? What's your motivation?

Peter O'Toole (01:04:46):
Do you know, I, one of the, one of the people I'm going to be talking to and hopefully both of them Scott Fraser inspired this idea Elmi Dublin. You know, I actually hate introducing people, which is perverse considering what I'm doing here. So if you're one of the organizers you have to up and introduce the pleneries, and I'm worried about getting their background, wrong, quoting stats and just going through their CV and actually in the audience, I find that I don't find that terribly interesting. So I sat down with Scott and so actually let's just talk to him. Let's find out what he's interested or let's introduce him. Scott, not, not the scientist, but Scott himself. And he has such an amazing background, really entertaining it just shows. Actually, I think we always see the stella stars, in science like yourself. Like Jen Lippencott-Schwarz.

Peter O'Toole (01:05:35):
Like Tony Wilson. We see them as these people who have got a focus, they know where they're going and that's where they get to. And they work night and day at it where it's actually, they're in a completely different place to where they started out. They have an amazing stories outside. They have excitement outside of work and it's balancing that. And I think that's a great message to get to a PhDs and postdocs that are thinking, I have to do this, this, this well, no, you know, as you said earlier, you follow a path, you don't know where it's going and you fall away, you can deliver.

Jason Swedlow (01:06:12):
That's the thing. I mean Scott is an, you know, an amazing scientist consider him a friend. I mean, he's so much fun to be around cause it's very quick and very imaginative. And so I'm sure that, you know, that was a fun interview. I think one of the most important, you know, well, you know, you, I feel a little bit I don't want to say intimidated, but you talk about yes. My group that I have been successful, Jennifer Schwartz's group has been incredibly successful, but boy, Oh boy. With we, you know, we all have a lot of failures as well. And I think there's I, and I, and I know Scott has as well and you know, but that's part of science and part of recognizing that, you know, what you're doing is you're trying things and you're, you're looking for opportunities, some things pan out and they're great.

Jason Swedlow (01:07:12):
And going back to your question about salesmen, you know? Yeah. So all of us will stand up at the podium and present those stories as well as we possibly can. Part of are we selling okay. Maybe, but really what we're doing is exchanging our ideas about art as it are our ideas about the science that we're working on about the systems that we're interested in. And so that, that appears like, Oh, they have been so successful and that's true, but that's because of, you know through lots of things that haven't worked out so well,

Peter O'Toole (01:07:51):
I've got a question

Jason Swedlow (01:07:52):
Recognizing when a failure, when something is just not working, okay, it's not working, but you know, okay, what can I learn from that? Right. You know, that actually in the old case we had, I'll just tell, this is a very personal story, but we started down the technical path around 2001, 2002. And and I and I had managed to get the first batch of funding for all of these work late 2002 from the Wellcome Trust. Talk about taking a gamble by about two, we had to, we were working down this path and, but we were running, we could start seeing the limitations of what we were doing and by about 2004 and I was going to have to get the next round of funding round about 2005. And I received an email from a guy at Stanford who had who was really trying to use the work that we were doing is picking up the software and working it through.

Jason Swedlow (01:09:11):
And he said, you know, he wrote him this email. I said, you know, I'm really amazed what you guys are doing is so incredible. You know, it's really impressive what you've been able to achieve. I have to say it took me six months of reading all the documentation code to actually understand what you guys have done. But now that I have, I think I see what's going on. And at that point I realized, you know, we were sunk, right. The words I used at the time were much more profane. Right. You know, so that was, that was we, we were failing. And so, okay. We're, we're, we're not doing, we're not delivering for our community now. And that's a failure, especially given them the, you know, what had been invested. So what are we going to do about that? Right? How do we, how do we figure out how to move forward?

Jason Swedlow (01:10:13):
Right out of the, out of that conversation, out of the recognition that we had failed was born the ideas around OMERO discussions with Josh Moore, Chris Allen, etc. And, and then an idea of a new idea, which then we stuck to, I think that's, I don't know if that's, that's probably more, you know, probably worth remembering that,uthose successes come from are hard won.

Peter O'Toole (01:10:41):
And I think there's always regret things. You've had to leave behind that. You wish you could have solved, but maybe technology or selling counts just wasn't in place at the time. And doesn't mean it's not be worth revisiting 10 years later, things move on things that weren't possible or didn't seem right. Things do change in that. That's a key thing is never to say, I've tried that done. That didn't work. I tried that done. That didn't work 10 years ago, but actually it might do.

Jason Swedlow (01:11:09):
Now. We're actually at such a moment, in OME, we're looking at some new technologies that re recast a lot of those early ideas, but now with the completely new ways of implementation, which makes it maybe possible to do some distance.

Peter O'Toole (01:11:27):
Jason, I know that one of the ways you relax, he's doing yoga after giving you a good workout for the last hour or so, I'll let you get back to your yoga mat and very different to cycling. May I point out?

Jason Swedlow (01:11:42):
Yes, but I'm going head first. Very fast down a hill has a certain set of risks at some point. No, that's, this is safer.

Peter O'Toole (01:11:55):
I'm not sure going head first onto a mat doing yoga, I think has it's equally a risk. Jason. Thanks very much. Thank you.

Intro/Outro (01:12:08):
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 bitesizebio.com/the-microscopists.