Paul Smith (Cardiff University)

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Intro/Outro (00:00:01):
Welcome to Flow Stars candid conversations between Dr. Peter O'Toole and the big hitters of Flow Cytometry brought to you by Beckman Coulter at Bitesize Bio.

Peter O'Toole (00:00:12):
In today's episode of Flow Stars, I'm joined by Paul Smith from Cardiff University who shares his advice, buying children's toys

Paul Smith (00:00:20):
That stuck with me that did the fact that technology can stop you having to sleep in the lab. Definitely.

Peter O'Toole (00:00:28):
And his experience of working at a nuclear laboratory,

Paul Smith (00:00:32):
Not us. We were in the biology branch. We were playing with cells, but in other parts, and if that happened, there was, there would be a massive radiation flash. And basically you were dead at that point.

Peter O'Toole (00:00:45):
All in this episode, of the Flow Stars.

Speaker 3 (00:00:51):
Hi, I'm Peter O'Toole and today I'm joined by Paul Smith from the University of Cardiff afternoon, Paul.

Paul Smith (00:00:58):
Good afternoon, Peter. How are you?

Peter O'Toole (00:01:00):
I'm Good. Thank you. It's been a while since we've met. So usually either conferences or grant committees.

Paul Smith (00:01:07):
That's right. Yeah. Where you're pleading for money. How's it going?

Peter O'Toole (00:01:11):
Uh, on the money sides. Okay. But the the but maybe I just got lucky on that front recently. Well done thinking of which I, I, this is going to throw out today. We're going to chat about all sorts of, and you know, some of the questions I've never been able to ask you before, probably because we've been around people where we shouldn't maybe talking quite so openly. So I thought what better than other recorded chats to discuss it? And I know I I've, I've, I've been fortunate in funding, uh, getting research funding and having it from, uh, EPSRC BBSRC MRC. So that the whole, a lot of the UK that were associated with it, but you're equally competitive in all those different funding bodies from Cancer Research, UK BBSRC EPSRC, is that your science being so diverse that enables you to apply for all those different, different funding bodies. Most people are restricted to one, and yet here you are. And you're able to go down all these different branches of funding avenues.

Paul Smith (00:02:16):
I think it's the people, you know, and you collaborate with that's the reality. You become inspired by as well. But I tell you, um, if you look out there, there are people who can solve your problems for you and you can work with that's, what I've found. And the people I admire, the people, I don't understand that mathematicians, right. I really don't understand them. It's another species, but in sum them up one at a time. So, but I think engineers have a superb way of thinking, um, bioengineers as well in terms of putting projects together, how to push them through. So I've been very lucky to work in a multidisciplinary sort of science in many ways Cytometry has to reach out to instrumentation, um, biology, applications, clinic, et cetera. So I enjoy that. I get bored too easily as well. So I get inspired by other people's interests.

Peter O'Toole (00:03:10):
Well, if you look at the way the, so in, in the UK, uh, we have the government funds a variety of different funding bodies within it. That puts it for more basic biological to the medical and research, the engineering and physics you search. So they're all sort of split out into these different pots, which tends to be working more and more together. Do you think that's the right way forward?

Paul Smith (00:03:36):
Um, if it's focused on something they want to commonly achieve. Yes. I think a good example of that was the relationship between the EPSRC and CRUK for advanced imaging centers. You know, that you, you can't do everything yourself. Um, science is multidisciplinary whichever way you look at it. And so, um, I think as long as there's a clear focus and a strategic need for something you can assemble the people, um, the groups and the research councils as there used to be called, shall we say together to achieve that, but you have to look in the, all of those situations on not what is presented now, what's going to happen in the future. And that's where the risk element has to come in. Right? And that's why I think, um, groups like, um, Innovate UK should be partnering more with some of these organizations because let's face it. They're the ones that should have a strategic view, as well as taking some degree of a brief from government as well. So it's, it's for the longer view those, um, uh, strategic alliances. And I've tried to do that with my science as well, rather than just what the immediate is,

Peter O'Toole (00:04:49):
That, that, that partly answers actually what my next question was going to be. You you've obviously sat on many, many, many grant panels. I'm not saying you really don't when I say many, many,

Paul Smith (00:04:59):
I'm just looking at your gray hair, uh, and no black eyebrows what's going on there. My wife looks at me and I do that. And she, she, she burst into tears of laughter every time. So there you go. It must be good genes.

Peter O'Toole (00:05:17):
It'll be interesting to see what happens is I'm going on the ground. See what happens with these anyway, I was going to ask, but you've also chaired, uh, many grant panels as well. And through that, I've been fortunate to be on the panels that you've chaired. And I found you an exceptionally good chair, but you must have some top tips of what makes a good grant application and what doesn't. So what would be your top tip to make it sell? And what is the biggest thing you shouldn't do when you're writing your grant application for anyone looking to get their next grant application?

Paul Smith (00:05:50):
Okay. I, I think it can say that without doubt that the PE thing people fail most on is the impact side of their science, where you have to fill in. And it's usually the last thing you fill in on the grant application for, you know, what's going to be the impact, et cetera, et cetera, translation in some way. And people think that's an added afterthought and you, and I know on grant panels, very often the decision to go with one of our class one higher than another is a cost that longer view that impact. And very often you can almost write the impact statement for the people having read their grant. So why on earth don't they do it themselves, right? You see that, that they're not thinking that way, or they're not playing the game, or they're not really answering the question that's being asked. And that's the major failing point. I think the science let's face it. Most people present their science in a way that essentially they should be the best person in the world to do it in reality. They should know more about their area than anybody else. Right. I always say that to PhD students, remember you've been immersed in this area, so, so don't take it up and examiner it too much, you know? So I think that's the one thing, the impact and the longer view, because let's face it, that's where the grant call comes from trying to achieve something, not just give money out.

Peter O'Toole (00:07:19):
That kind of comes on to the next point. We, as a grant panel we give money out, they get that funding. Do you expect that researcher to carry out the research exactly as they have proposed within their grant application?

Paul Smith (00:07:32):
Um, from my, uh, experience of what's happening to me, if you suddenly come across something that means you can pivot to advantage and still stay, should we say on the rails of interest for that grant? I think that's perfect. A good example, I think was a BBSRC grant that we had, that we were following then suddenly something appears, and you could not ignore this. So what do you do? Put it to one side, apply for another grant, examine it in 18 months time or capture the moment in some way. Right? So capturing the moment of, uh, not going against the principles of the grant, certainly sometimes a really good idea just to talk to the grant, awarding body and practice that, um, that, uh, pitch that it's worthwhile doing this. It should otherwise you're undertaking contract research, something that can be done, but you're the one to do it. And you complete it, right? Mean it's not contract research. Is it from research councils? It should be innovation, right. All the way through.

Peter O'Toole (00:08:41):
I think it comes back to what you said at the start impact. And if you carry on down what you first, a PhD thesis, you never, you never end up in the third year where you thought you were going to be on year one. And it's the same with a grant application don't really ever finish up in exactly the same spot. Yes, it's got that, that area, but it's not a narrow line. It is broad.

Paul Smith (00:09:03):
A PhD is a driving test, isn't it, it, wasn't not your, you can be allowed out there with other people's money to pursue science that you have some inspiration behind, but also a need for that. So, um, it's a driving test really,

Peter O'Toole (00:09:19):
So cool. What got you into science to start with?

Paul Smith (00:09:23):
Oh gosh. Um, it sounds a bit strange to say this, but, uh, I wanted to be an astronomer when I was nine and 10 that's because my parents bought me a telescope when suddenly the world opens up to you and you've got an instrument to handle. It's fantastic. Right. I remember talking to my, um, what would have been about 10, I guess the teacher and the primary skill set. I really want to be an astronomer. And they said, no, there's no, there's no careers in that. There's no jobs, you know, do not take careers advice from any teacher whatsoever just don't do it. Right. Because we've, cause they don't know what jobs are out there in reality. And I've got lots of examples of that. Um, it's tongue in cheek that by, by tongue in cheek. But the next step was that I read books on microbiology. Um, you know, uh, the biography basically, uh, by, um, of Louis Pasteur. So by the time I was 13, I wanted to be microbiologist, which is ridiculous. Really isn't it, you know, sort of, and that's because I was bought a microscope. So be careful what you buy your child because you can suddenly get them fixated on something. So I ended up doing medical microbiology as a first degree. So that's what inspired me in science, having access to instruments that you can play with and use. Yeah. So

Peter O'Toole (00:10:59):
If anyone gives you a toy, you get into it. So they bought you a telescope, you got into astronomy, you got into the micro microbiology cure, bought a microscope, I guess that was about the age of 13. 14. So when you're 17, you got bought a car. Does that mean you go into cars as well?

Paul Smith (00:11:16):
That's right. Yeah. I'm looking forward to the electric wheelchair as well. I'm sure that's really quite an interesting technology. So, um, yeah. Be careful what you buy your child will tell you that

Peter O'Toole (00:11:27):
You are a car fanatic

Paul Smith (00:11:29):
a little bit. Yes. I know to my little, um, car as it were, which is a 350z amazingly polluting these days, you know, we do trips. There's one to Lamont in 2012. For example, when, uh, I looked a bit, uh, younger. Yes. And been very lucky in many ways. We've sought out living in places where there's a nice community. So there was a group of about seven of us in open-top sports cars. Oh God. Going on a long trip together. Great fun. So I wrap my interests into like people in the community, which is a great thing, you know? So enjoy that very much

Peter O'Toole (00:12:10):
I suppose if you've all got drop tops, you have to kind of open top cars. You have to go some miles just to be able to use it binge

Paul Smith (00:12:17):
That's Right? Yeah, absolutely. Oh, well sometimes I just sit in the garage with it off, you know, and the fan heater on it works really well for me. So there you go. I can believe that actually policy, but sometimes my wife makes me go up there. I don't know why, but then we'll say, okay,

Peter O'Toole (00:12:37):
So far from being in microbiology. So I think you did your degree in microbiology. Yeah. But then you went over to Canada.

Paul Smith (00:12:47):
Oh yeah. That was a no, not quite. I ended up at the Paterson Labs doing a PhD studentship with the MRC and infact, believe it or not. I'd heard about the MRC, you know, from being in my teams because I used to subscribe to the new scientist. So you see these adverts coming through all the time. You know, I used to look at the adverts and when I was in sixth form and I think, oh yeah, that's the thing to work for the MRC, you know, they're really focused. They know what they're doing, et cetera. And so I w what happened was I sought out MRC studentships when I finished my first degree. And they ended up at the Paterson Labs in Manchester. And the last little lighter was there, but talking about inspirations, amazing. Alma Howard was the, um, head of the radiology department basically. Now Alma Howard and Pelc of course named the cell cycle. So I, so I got caught at that point into interest in the cell cycle. Let's face it, it's the most important thing. Um, you know, in human existence a cell only has to do what three things decide whether or not to replicate its DNA, decide whether or not to divide and decide whether or not to die. Everything else is in a dormant on that in terms of biology. So understanding the basic principles of the cell cycle and its central importance was something I sort of gripped me at that point. You know, in fact, that was my first exposure when I was a student to flow cytometry because we didn't have a flow cytometer, obviously the Paterson Labs at the time, but my supervisor came along and waved this, um, uh, article in front of me from, uh, nature. And it was the first DNA histogram generated by a flow. This is early seventies. And, uh, I just finished three days of measuring pulse label mytosis by sleeping in the lab, you know, uh, measuring them to get a full two full cell cycles as it were a friend analyzed. And he was grinning at me say, see, you can do it in minutes. That stuck with me that did the fact that technology can stop you having to sleep in the lab. Definitely that we, uh, I actually ended up, um, in Canada post docing there. I think it's because of the old boy network in reality, in those days, because your supervisor would know people typically in the state, you had to have a north American experience and they would say, you know, I've been in touch with some, so how about possible fellowship there? So there was much more guidance in those days. I was so excited because I was going to a large national laboratory and I thought that's the way science was done, a big national lab, everybody working together. And I can tell you a bit more about that if you're interested.

Peter O'Toole (00:15:48):
Was it not like that when you got there?

Paul Smith (00:15:51):
Well, I hadn't realized that there were armed guards walking around the place for a start because it was the charter of the nuclear labs and that's bit of an exaggeration, about armed guards, but there was plutonium on side and a whole series of things. So, um, even though I was in the biology branch, we had to, uh, be careful of where we were on the sight, because there were a couple of reactors that sort of thing. And, uh, interestingly, my first exposure to that place in a non Radiobiological way, uh, the first exposure was, uh, the safety lecture where they decided to tell you about the different sirens that are involved in an emergency. And there was about 15 of them that you have to learn different types of sirens. And the worst one was, it was a typical ones such as, Ooh, you know, you had to close the windows and do various things. This is in case a release of radioactive material, which never happened by the way, but they'd have to think about these things. And then, um, and then there's this awful sound that was a little like this, uh, uh, absolutely like a sound from hell as it were. And that was in, uh, uh, a flux detector, basically. Not other words when you got the neutral flux. So when you, you artificially put together a pile of radioactive material, not us, we were in the biology branch, we were playing with cells, but in other parts, and if that happened, there was, there would be a massive radiation flash. And basically you were dead at that point. So your first job was to make sure nobody else came into the area. That was the safety routine. You know, this never happened of course, but they, I think they did this deliberately just to scare you. Yeah.

Peter O'Toole (00:17:46):
How did you find go now? it's a big change going from the UK over to Canada. How were you daunted just from the personal experience of not the science, but actually just moving countries to do your science.

Paul Smith (00:17:59):
Yeah. There's two ways of looking at that. First off all Canada is wonderful. It's the most British thing in North America. So you fed straight in and it's a, it's a land of immigrants in many ways as well, welcoming people. It's superb, we have, we have business there as well. Even today. I have some great friends there, but very welcoming and they make a point of not being American in the nicest possible way as it were. And, uh, what is somebody say once, uh, Canada is like, um, living in an upstairs apartment with the great party going on below, you know, that's the idea, but we loved Canada and fell in love with the place, had two children out there as well, Canadians. And, uh, the other side, we lived in a rather strange town called Deep River, which we love dearly. But have you seen twin peaks? See these areas about strange, um, uh, town in North America? It was like that because everybody in the place worked at the plant. So they were either metallic or physicists or engineers or mathematicians. So you can imagine what it was like at the local high school when they had the parents evening, because the nuclear physicist would come in and ask the teacher why his child wasn't a prodigy, et cetera. So it was rather strange place, just rammed full of professional people. It's like having an Oxford or a Cambridge dropped into the middle of a North American forest, really weird, but we liked it.

Peter O'Toole (00:19:41):
So on that note, I presume you weren't bought up in a similar type of location

Paul Smith (00:19:48):
The time French. No, I'm from the north of England, uh, Warrington. That's why I love rugby league by the way I used to play union, but I, I watched rugby league. And, uh, so I can't, you can't take the north out of the man. I don't think I just feel it, not so much at home there, but I have certain resonances and, uh, yeah, which you crammed between Liverpool and Manchester. Of course, you know, two very industrial cities, Warrington as a family. We come from silk weavers originally and a very interesting background because it's a history of the industrial revolution, how people moved around, even within relatively small areas, our ancestors shall we say, moved to Warrington because of the sudden up term in the industrial revolution in engineering there and metalwork, et cetera. So, yeah, really interesting that

Peter O'Toole (00:20:47):
We should follow that thread. Another time pool can help it. So you're now in Cardiff, uh, by, uh, was it MRC, down in You went back to the MRC.

Speaker 2 (00:21:02):
I went to, yeah, it was the MRC center in Cambridge for many years as well, very happy there, but at some point in your life, you have to change and shift. And, uh, I was made aware of Cardiff and, uh, um, I moved down what, 95, 97. So yeah, it's always difficult when you got children because they're, you know, at school doing exams and things. And so I had to make the move over a period of two years. Which is uh, you know, oh, it's difficult, but it's worthwhile doing

Peter O'Toole (00:21:35):
So take your children stayed back in Cambridge.

Paul Smith (00:21:39):
One did and one didn't Yeah. So, uh, yeah, so, uh, one came with me, uh, well I went first, then one came as they went into the sixth form, then the next one came et cetera. So you had to go move to as a family, 95, which for that time I used to commute. I used to commute when the six former started what happened, what happened then?

Peter O'Toole (00:22:08):
Yeah, because if you've got one in six form and the other, one's not in sixth form I presume,

Paul Smith (00:22:11):
We've got a place in, in a little town called Cowbridge and the Vale of Glamorgan lovely place. And then we would go home for the long week for the weekends, then come back, et cetera. So there's lots of shuttling did quite a bit, quite a bit of driving, but that's, uh, that's what parents have to do to make sure that the children get through. Okay. So, well, if you

Peter O'Toole (00:22:33):
Weren't driving back to Cambridge, you'd probably been driving to a rugby match or football match or cricket match practice.

Paul Smith (00:22:39):
There you go.

Peter O'Toole (00:22:42):
That tends to be all our weekends. I was driving one and then the other, and in winter months that isn't much fun standing in the middle of nowhere.

Paul Smith (00:22:49):
Yeah. And then you've got the taxi service as all parents have to, we should all be registered Uber drivers for our family, I think. Yeah.

Peter O'Toole (00:23:00):
Let's not go down that path. We'll that time. So you've obviously been MRC Cambridge. You've been at Cardiff. You've been at Paterson, you've been Kent. You've been into mega places who are your biggest inspirations.

Paul Smith (00:23:16):
Okay. I can either be logical about this or I can be emotional or I can be, uh, rather, um, uh, embarrassing. W what would you prefer?

Peter O'Toole (00:23:27):
It's going to go emotional, but then you said embarrassing. So we've got to start there.

Paul Smith (00:23:30):
Okay. Well, it's, it's almost embarrassing to say that you're inspired by a teacher, right. But in reality, it's my biology teacher who came from Cardiff University, believe it or not originally, uh, Di Reese as we used to call him Mr. Reese. And he was one of these people who, uh, would just highly motivating, strange individual in many ways, but we all sort of, uh, anybody who was interested in biology thought he was super, he would do things like when you're in, when you're 16 or so, you've arranged for a group of us to go away to the Institute of biology lectures. So we, we were visiting university campuses at that age, not just on an open day to go listen to lectures and ask questions. Right. Which was amazing really, because I got this insight into what universities looked like, felt like how they operated the types of people who were in there usually long hair mustaches, uh, you know, bad breath and, um, uh, sandals, you know, was the sort of sixties let's face it. And, um, so in that, in that way, I sort of homed in on university as our academic life relatively early. And he would, he was quite inspirational. So any of these pupils that would go away to university would send their practical, um, uh, sheets back. And he would reproduce the university practical's in the school lab. So when I'm 16 and I'm making slides on extracting DNA, I'm doing, God knows what, in reality, not all sure of what you're doing, but being exposed to those, that sort of lab work. So that was, that kicked me off really. And then the different places I went to there was old somebody inspirational. And I was very lucky, very lucky I can go through those, but, you know, there's one person that stands out amongst anybody else. And that's Jim Watson, the real Jim Watson, the cytometry, Jim Watson, the medic, the real one and um at Cambridge. And that was the reason I actually went to Cambridge. Yeah. Oh God. You're actually using that are you. Of course. Yeah. That's the Jim Watson, everybody knows to the, uh, with the, uh, glass in the hand, the drawing was actually done by the MRC, um, art department at the MRC century in that Allenby and in Cambridge. And that's what people felt about him. He just melted everywhere. Amazing. I heard about flow cytometry in its real sense. I think when I was in Canada and I saw this opportunity for a position in, um, Cambridge, and I'd missed the deadline for the application, of course, you should completely ignore that. Any deadlines, you know? So I immediately sent, I believe it's a telex that shows you something, doesn't it a telex saying that hold everything I'm putting in an application, you know as it were and it brings people your attention to people. So, um, that was interesting. I'd looked at some of the early publications, what they were starting to do there. And I just thought it was a wonderful technology. You mean, you can look at individual cells at high speed and analyze them. And, uh, you had an early instrument there, but he was building his own system. So I got in on that basically when I arrived, we even shared an office together as well. And, um, there you go. It's uh, and I've got so much time for the, he's a real polymath they're inspirations who sit in silos because they're very good at something. They usually like role models or people who can help you or inspire you. But real polymath is somebody like Jim, who would design equipment, um, uh, work with people with experiments, go off and run a, an oncology clinic, uh, go into, um, uh, uh, the operating theater handled Brackey therapy, and then coming back and teach himself coding and software and engineering zone, um, programs, you know, it's just, it was an inspiration to be with really well. And I, regard him as my, um, you know, great colleague from those days, you know? Yeah. On a very personal note, if you don't mind me touching on this, um, Jim had an episode of, uh, not being well at one point. And, um, uh, his wife actually was phone me as one of the first people to phone. So I could go along and see him in our hospital at a particular moment of crisis in which he completely recovered. But, um, that was very touching because, uh, we, at some point your colleagues become friends and then they become something else as well. You know? So, um, anyway, a lot of time for Jim and he's still doing his bit in different ways in different places, so, yeah.

Peter O'Toole (00:28:40):
Hmm. So you were there at the, not quite the birth, but around the birth of flow cytometry, I guess, but at the same time, same as [inaudible] Brad Amos was there.

Paul Smith (00:28:52):
Oh yeah. Well, cells, it Cesar, Cesar Milstein used to come into my lab there. The nice thing about there, you can have your own lab, you got on them and did what you wanted to do, you know, and you, you looked around this, there was first talk I went to, there were four Nobel prizes. It sat on the front seats of that, you know, the, the auditorium that tells you something, doesn't it. And Cesar Milstein who I knew very well, he used to come into my lab and use my equipment as well. And, um, but of course, um, how should we say international profile or fame mean nothing when you're in labs, you just get on and do things you interact normally. And I do remember one day Cesar came in, you know, um, and, uh, he said, he said, Paul, Argentinian as you remember. And he said, Paul, um, I can't get the, the, uh, spectral, photometer your spectrophotometer to work. And I was busy. So I went, uh, I need close the shutter by mistake. So there's no light coming to them. Oh, there you go. Then I realized who I was, as I walked out, I realized who I was talking to, you know, but you just saw it was people in the lab as it were, you know, that sort of very good example of that. Brad was a good example of a problem solver. You know, he, and he introduced me well, what happened with some work with Jim Watson, that we were exploring the far red part of the spectrum for flourals, because that was underrepresented. And so we, we organize the flow cytometer system to be able to detect in the far red. Um, I modify the spectrum for Tom Mitchell as well and discover fluorescent signatures in the far red of different probes and drugs. We were very interested in drugs because we were interested in oncology and then went to Brad. And basically he was setting up his Bio-Rad type system as it were with far red detection. And that just opened up a whole series of experiments for us. And he just loved the idea of being able to modify technology to enable another door to be opened for you. Remember, Brad remember is somebody who would walk around a supermarket with a small, um, spectral analyzer in his pocket to pick out things and just have a quick look at them to see if there's anything interesting that it could pursue. That's true. I didn't know that. Did you know he was a diamond polisher? He, um, is a gem polisher as well. Yeah. So here's somebody who had a very refined set of interests. I tell you,

Peter O'Toole (00:31:45):
There are some bizarre hobbies amongst in, in Brad's case, by feces microscopist, I guess. And, uh, uh, with, with what was then the first proper confocal microscope.

Paul Smith (00:31:58):
Yeah. Well, of course, yeah, you have to pay due respect as well to the MRC workshops. You know, that's an example of an MRC workshop engineering. These are the, I inherited parts of Jim Watson's, uh, uh, uh, flow cytometer systems when we took it apart. And I tried to reassemble it for that say in, um, in Cardiff in various ways, but that's an example of MRC engineering in those days. So precise, so beautiful. In fact, you can just fumble these they're wonderful. I keep them on my desk as a reminder of those days, but, uh, the MRC workshops were something special, uh, there in Cambridge, because you would go with an idea and they'll say, yep, we'll build that. And the engineering was superb. So Jen was had that capacity of being able to conceive of something, then having translated on site until a working instrument and surrounded like lesser mortals, like myself who wanted to use those pieces of equipment in different ways. And then they would modify them according to what you wanted to pursue. So it's not like buying off the shelf anymore and being convinced about somebody else's, um, capacity to do something. Maybe it was live engineering, just wonderful. Wonderful. Yeah. And, and

Peter O'Toole (00:33:18):
As you just illustrated, even design paperweights, especially for your desktop Paul.

Paul Smith (00:33:22):
Yeah. Well, I have this idea. I keep looking at these things I must have meant. Let me show you, just bear with me one second. There you go. There you go. It's a mother, a father, and a little small child, isn't it? Oh, it's the first, second. And third of some cytometry award who wouldn't want one of these mounted as an award. Yeah. So that third place, very nice, you know, beam, there's a unit for bringing in it. I think it was the red beam at that time. That's the runner up. And there you go. And there's the full Monte for the winner of the award. You never know. I think that's a good idea for an award sometimes getting touch with the RMS on that.

Peter O'Toole (00:34:14):
Or ISAC Thinking of ISAC, you will also ISAC president. Yes. Oh gosh.

Paul Smith (00:34:23):
1962. Yeah. No, it wasn't 12. It's about 12. Yeah. About 12 yes. I've been involved for a while actually because, uh, Jim Watson introduced me to SAC the original society. Well, the morphed society anyway, and we had the SAC conference in Cambridge. So we were all recruited into this, of course, to help out. Uh, Jim was great, but he was useless to organizing big events in reality because he, he thought they were basically lab parties just on a bigger scale. And so he, uh, for example, thought I'm not going to bring a caters in to do coffee and tea at the breaks. I'll just put a couple of kettles there and some sachets of, and people can help themselves to coffee. Well, if you calculate it out 800 people trying to help themselves to coffee and, uh, you know, 15 minutes doesn't work. So, but that was Jim for you. And that was my introduction to SAC then became ISAC. So yeah. And enjoy the time it was, um, it's joining an international rather than a domestic society. It does open up your potential for staying in places and, um, overnight, if you ever get stuck anywhere because you knows so many people. Um, but in reality, it's a great way to explore the views of your science as well. And not so much collaboration, but learning from others. I know that sounds a little corny, but that's the truth. And at the time, of course, there was a lots of exciting things happening in the large national labs in, uh, like Lawrence Livermore and, um, et cetera, um, and Los Alamos. And, uh, it was a way of understanding what was happening there and the people behind them and their motivation as well. And of course you can translate that thinking into how you pursue grants as well and how you organize your research because you want it to be competitive, but not following as it were. If it's not, you wanted to be competitive and almost parallel so that you can learn from others and progress together as well, which is slightly different from how some of the post-docs used to be organized in a North American labs where basically people would be given more than one person would we begin the same project and the first one to publish won, you know, it's a different attitudes. So yeah.

Peter O'Toole (00:36:58):
Yeah, no, I think as you mentioned at the start collaborating and team sciences is really important, probably more important now than ever before you bought Cyto innovation.

Paul Smith (00:37:07):

Peter O'Toole (00:37:10):
Cyto innovation. Yes. What are your innovations? Wasn't it?

Paul Smith (00:37:16):
Yes, it was actually, yeah, people forget this and CYTO I branded, I was driving along one day and uh, I thought we've got to change the name of the society. I think it was president intellect at the time we can't have the XXIV the international Congress of the international society for analytical cytology, I anymore, as it used to be called, that is not catchy in any way. So I thought in reality, with cytometry as a, uh, as a publication, the party, we have ownership in some ways and recognition of our own scientific domain. Right? So why not capture that as the brand, as it were for, uh, the international Congress? I thought CYTO so I immediately thought that's the way to go. And everybody thought it was a good idea. And so the original idea in fact, was to have a umbrella name for an international meeting in which you could partner with other organizations without them feeling that they're attending your meeting as it were as an annual Congress. Right? So it allowed you to partner under the umbrella of CYT, even though we own that, as it were without feeling that you're joining somebody else's Congress. So that was the concept to make it easier to partner with different groups in different times. Yeah.

Peter O'Toole (00:38:46):
What'd you do in your part, in your spare time then

Paul Smith (00:38:48):
What spare time? It's, it's it's one long list of interviews with different interesting people. Uh, I made an exception today, Peter, and yeah cheers Paul. So now I have this horror, not horror, pleasure and amusement. I'm becoming like my father, my father could build things and create things as it were. And so in my spare time, if it's raining, I have my own workshop and I build interesting furniture as it were out of quirky things will move that time. I'm not supplying any photographs in there. You can't

Peter O'Toole (00:39:33):
Move your camera to show us any of that quirky furniture.

Paul Smith (00:39:37):
There's one behind me. No, you can't see it now. That's just a coffee table. Two coffee tables, actually. Yeah. And of course my wife thinks, oh my God, another coffee table, you know, that sort of thing. So I'm thinking about making so they can stack now, but anyway, but you know how to an old white board of my sons, I converted into a table looks really cool. So I liked doing that. I like fixing things. I like, uh, I prefer to do things myself and get somebody else in to do them. I only bring people in when I've made a mess of something. We have to fix it basically. Yeah. So there's that enjoy messing around in cars and with cars, et cetera. But I think it's things to do with your hands and, you know, achieving things, something that has a product at the end of it as well. So like

Peter O'Toole (00:40:28):
In that case, do you cook or wash up then if you like making things with your hands?

Paul Smith (00:40:34):
I didn't know there was a choice. I must, I must go into this a bit more closely. I didn't know that there's a choice I had to. I thought you had to do both. Right. If you don't mind me saying, so I do all the cooking. Yeah. I've done all the cooking for years as it were. And uh, cause I like to eat well. And um, so yeah, but then what you're saying, are you saying you don't know, is this going public? Um, so I like cooking Italian and uh, experimenting. I never follow recipes. And I think that's a bit of my failing actually. Um, I don't like being told the right way to do something. I'd rather work it out. You can never follow

Peter O'Toole (00:41:22):
Recipes or there is a guideline. You never follow it to the, to the letter

Paul Smith (00:41:25):
Exactly. Exactly. Except, but that's that's um, yeah, that's the thing I have. So I don't even know what I'm going to produce at the start, but I'm cooking cause I'll change my mind halfway as it were. So yeah, we haven't lost anybody yet though. That's the main thing.

Peter O'Toole (00:41:45):
So it's clear Italian is your preferred style what do you not like cooking?

Paul Smith (00:41:50):
What do I not like cooking? I won't touch baking at all. That's because you have to follow a recipe for that, you don' t immediately see if it's worked. You have to wait until the darn thing comes out to the oven, you know? And then the anticipation of failure is just too much for me basically. I, I

Peter O'Toole (00:42:12):
Struggled to cook Asian food,

Paul Smith (00:42:15):
Asian food. Yeah. I really struggled to cook Asian food. Yeah. I think it's, I think it's having the right ingredients and the range of them and understanding how they're put together. That's that's my failing. I think I don't look into that, but I like the chemistry of cooking as well. You know, I do things I think I wonder if that will work. Oh, no, it doesn't wonder why, you know, so this is probably because I'll have to get into formulations recently. That's the problem?

Peter O'Toole (00:42:43):
Well, I was going to say thinking, thinking of chemistry and don't forget get you started out as a, as a microscopist to a hobby scientist at home, through to a microbiologist. Now, arguably you've had a lot of chemistry influence as well.

Paul Smith (00:42:56):
I can bluff my way in chemistry. I can really, I've got some great people in the background. One of which is of course, a Lawrence Patterson, a long time colleague of mine. Um, and, uh, he's a superb medicinal chemist as well. Um, in the next lab to me was Paul Workman course in, um, in, uh, in, uh, Cambridge. And he was quite inspiration. There's somebody works really hard for him and, and uh, he really does. And, um, understanding that understanding how chemistry can direct you in the right dose, in the right way to a solution in biology, whether or not it's a probe, a report or a drug, a modifier or whatever. It's, um, it's in your hands to, to create these molecular tools to investigate biology and, uh, talk about inspirations. One of the early things I read about was the history, Paul Ehrlich, of course Salvarsan and, um, developing, um, really the first chemotherapeutic, I guess, in some ways. And, um, that was an inspiration as well in that you can, you can think about molecules and create them in a way that can be used as those tools or medicines And it's that duality of purpose that interested me in many ways. Okay.

Peter O'Toole (00:44:18):
So this is Draq 5.

Paul Smith (00:44:21):
Yeah. That's one of the answer Quinones, um, probes that we'd developed. And, uh, I remember looking down the microscope the first time I saw this and, um, we were going a serious of anthracyclinones modified drugs and hypoxia activated prodrug. I was working at their mechanisms of action and this is right all the way through to Cardiff. And, um, I looked down the microscope one day where we'd modified one of the molecules in a, in a unique way. And, um, suddenly it was just lighting up all the nuclei, right. Then we understood some of the rules associated with molecular targeting within the cell, just at that moment, which was quite something. But the main background to this, I guess, was my understanding of far red florals as well because having the instrumentation to look in the far red, allow you to look for signatures in that area. And also, um, getting rid of this idea in my head at the time that all probes and florals have to be brighter and brighter and brighter. You know, the closer you are to one for a quantum yield, the better as it were gusting up the case detect it's all about signal to noise and affinity. That's the reality. So if you have a high affinity binder, even if it's got a low quantum yield, you'll still get a signal. In fact, the signal rises above noise very nicely at that point. So looking for low quantum yields florals with high affinity, with a medicinal chemistry background that allow you to understand how they enter and, and target objects within cells, it was the key to the, uh, our work in the area.

Peter O'Toole (00:46:08):
So I'm presuming from that. This was never, you never set out to design a live cell DNA stain.

Paul Smith (00:46:15):
You're not the DNA stain, but a DNA targeting drug, right? So we went to the drugs, look in fact, what we were doing. I previously in Cambridge, I had decided to get into, um, molecular targets and looking at, um, uh, DNA top-line summarizes, which I found fascinating molecules that can unlink, unknot and detwist DNA as part of the natural process. And also as part of, um, regulating whether or not the integrity of DNA is sufficient to allow a cell to divide.

Peter O'Toole (00:46:50):
Have you been practicing that hand move? What you do on the dance floor? Is that one of your, did

Paul Smith (00:46:59):
I looked back with embarrassment because one of the easy ways to do this, I used to, yeah, I'm just, this is just a cable running the computer, but I used to do this with the microphone cable when I was giving a talk DNA, double stranded, do that. And then you got a super helical twist. So how do you unknot that when you want to translate a molecule along it, and in one go, you show people how to apply, summarize his work. And, uh, and the fact that there were certain drugs that could track these molecules on. Um, cause a lot of disruption is the basis of a lot of chemotherapeutic agents, of course, Adriamycin, BP60, and the top of side, things like that. And we were looking at a new range of drugs and I was Lawrence and I were trying to identify ways of targeting those more succinctly to selectively to DNA. So they would track the consensus sequences that took by summarizes used to bind. So it was a molecular targeting targeting exercise then because I was involved in far red flow flow cytometry because the Hercs dyes and things like that, it's suddenly appeared to me that these could be modified in some ways to produce probes and stains. Yeah. Just

Peter O'Toole (00:48:17):
Serendipitous in a way

Paul Smith (00:48:21):
To come across. Louis Pasteur said Louis Pasteur said, it's a chance favors the mind that is prepared. Right. And that is, and being prepared, it's usually been the right place at the right time with the right people. So it's nothing to do with you in the end. It's just sheer luck.

Peter O'Toole (00:48:42):
But then you have to ride your luck because if I could just get one more background, which I think I, I didn't realize this. I really had no idea, but you spun out too. So you actually, you had this dye, it's no good having that track five in your own lab, you need to make it available to people in a support, reliable manner, hence spun out and you've got bio status which or actually I'm quite fond of as a company we've used quite a lot of work, quite closely with Roy Edwards and he's been a great help, but I didn't know you had all these other spin outs

Paul Smith (00:49:16):
You get to that point where you, um, if you're in cancer research for so many years, you have to deliver and not just live off the career. Right. And if you're involved in trying to develop therapeutics, if, if you believe in something and you want to see through to the clinic, you've got to sort of commit to doing that in some way and not just handed time as a Baton race.

Peter O'Toole (00:49:42):
Well, that was about to ask you cause a lot, I think a lot of academics see that they've got a compound. It's interesting, it's good. They think a company should then just buy it off them and do something with it. And it doesn't often work like that.

Paul Smith (00:49:55):
That's because there's a valid valley of death. There's an abyss between the great ideas and they they being translated or handed onto it, some sort of vehicle that can take it forward. So by a state to set up basically to, um, uh, invent new dyes because we use them in the lab, you know, is nothing best than inventing things that you want to use, not just sell as it works. And we have an inspirational CEO in Stefan Ogrodzinski as well as super background, he's flown, you know, um, he's flown supplies into areas in Africa, under fire, et cetera. You know, there's, there's lots of stories they're telling you is a very special individual anyway. And, um, very credible and ethical individual sort of person. You want that your side in any endeavor. And so the three of us started Lawrence Paterson, Stefan Ogrodzinski and myself, started BioStatus with the idea of not being a lifestyle company, just enjoying the ride, but trying to achieve something real in business. And we got to Royal Society of Chemistry award for it as well. And, um, however also as an opportunity for other things, in other words, create your own environment in which to innovate just don't rely on other research councils. So we've eventually spun out three different companies, all based on our own input of venture, not receiving money from anybody else, no those to yourself. And that means two things happen. First of all, you go in the direction you believe. And secondly, you start to learn the process as you go along, you know, experience is something you need just after you experience is something you get just after you need it. If you put it that way. So you learn about things as you go along by trying to do them. And so we created these opportunities and one that we're very, uh, committed to at the moment is certainly on cathartic, which is a new class of anticancer drugs that we're pushing forward. And we've been relatively successful thus far so far. And we're hoping to push this into the clinic one way or another over the next 12 months, if not 18 months.

Peter O'Toole (00:52:17):
SohHow I, it's a huge step to go from the world of academia and actually taking that step to start to spin out. It takes a lot of effort and time and I'd imagine, was it not a fear that your academic career would suffer because you had to put effort and time in there.

Paul Smith (00:52:33):
That is a choice in the end. So I stepped down from the University. I'm now a Emeritus right? Because in my head I didn't want any conflicts as well. So I decided you reached that point in your life, I guess, where you have to make positive decisions. And the best way to make a positive decision is not when you're forced to, but when you've got other people around, you are thinking the same way. So having those sort of helps,

Peter O'Toole (00:52:59):
But did you do that at the started Biostatus or once Biostatus published?

Paul Smith (00:53:02):
Yeah. It became clear that BioStatus was teaching us things about spin out about business, about how to approach things, how to have relationships with different larger organizations, et cetera. And in teaching yourself these skills, I'll give you it. De-risks what you want to do in some ways, because your eyes are a bit more open. And I think this is why ISAC. Um, I was interested in introducing innovation as one of the tranches, shall we say within this, this society, because there are lots of people out there who want to take these steps and what to learn from others and know that it's worthwhile as well. It's a great journey.

Peter O'Toole (00:53:46):
So you have, like, I've got to think about this carefully, you, you, you balanced your academic life with the startup of your first company and you managed to do that and go through how do you then balance having an academic career, a starter and your Family?

Paul Smith (00:54:01):
It's very easy. I w I used to work late until about one two in the morning, right? First of all, I was always able to work late, but that's the wrong thing to do. Um, make sure you engage with family things. That's what we, we've always done on our local community as well. But I tell you, it's having people around you who think the same way that you can share and delegate and share tasks together as well. So doing it by yourself is probably something I wouldn't have done if I hadn't have created BioStatus, is this sort of, um, uh, first step opportunity to see how to do these things as well, but it's definitely having the right people around you, but that's my family, very proud of my daughter. They're very shy and retiring one with the hand in the air. And she's leading on environmental matters for Scottish power on, on the large wind farms. Now, you know, she's somebody special

Peter O'Toole (00:55:05):
If she works for Scottish Power can you get me a discount on my electric and gas? Because they just put up my price at the most. We

Paul Smith (00:55:10):
Can just set up the extension leg and she'll start you out. And the guy in the white that's Anthony very proud of. He really is a bit of an entrepreneur himself pushing himself forward. So he's at that side of my spectrum as it were, I think Elouise is in the middle of my daughter and the guy, just above. Um, Eloise is, uh, Adrian, our middle son. And he's more sort of, um, he loves excel sheets and data and wonder. So he's a bit closer to me in, in, in many ways it's got to show, see that some of you have genes get sliced, sliced up and you know, shared out. And that's my wife, Barbara and our daughter-in-law's behind. That's my wonderful father who passed away earlier this year. Uh, no semi natural causes as it were during lockdown, but he was living with us and that's my mother who passed away previously. But my father was taught me how to be patient and I'm very impatient person, but he is, uh, he was rock solid in that. And he was a frustrated technologist as well. He was a precision engineer and of course the w the war disturbed his career path, but he was responsible for building the air braking systems on some of the RAFs fighters, things like that. So it was a, and of course he did buy me toys. He bought me for example, a full working model of a conveyancer forklift truck when it was nine, because he thought it was really cute. And they were working on comparison trucks at the time as it were. So I tell you, it's what you, you buy your children's starts to set them up in potentially just the right direction.

Peter O'Toole (00:56:57):
My dad bought me all sorts of tools as a builder, and I didn't want to go in the building trade.

Paul Smith (00:57:01):
You want, you want to been able to hack it? I'm sure

Peter O'Toole (00:57:06):
Which I can't hang a shelf up straight. There's no point

Paul Smith (00:57:11):
I can see that from the background.

Peter O'Toole (00:57:13):
That's just the angle. Oh, I've got my dad to do

Paul Smith (00:57:15):
Okay. I'm

Peter O'Toole (00:57:17):
Not retina idea. Actually. I think I might've done that one myself. I've got to, I've got to ask some more personal questions actually. What sort of music are you into?

Paul Smith (00:57:26):
Oh, no. Okay. Right. Um, I'm unfortunately being a northerner at that time of my life, um, R&B and soul was part of my upbringing. Right. So I couldn't even remember all the code numbers on all the different records as it were, you know, pathetic really. Yeah. So R and B and soul, then as it went into the seventies, especially having the north American experience, you discovered west coast folk, et cetera. So it was quite an eclectic mix. Actually. I have a passion for opera as well. So it's everything, you know, my daughter Elouise is actually, she's inherited that ability to just explore different genres of music and, uh, and, uh, we go to live concerts, but I'm deliberately not going to tell you which ones I go to otherwise. You'll quote from

Peter O'Toole (00:58:18):
What's your favorite album?

Paul Smith (00:58:20):
What's your favorite? Oh, gosh. It must be a Neil Young album After the Gold Rush, because that opened up things in terms of west coast, um, music and American folk, et cetera. And it just hit at the right time. I'll say, After the Gold Rush, Neil young,

Peter O'Toole (00:58:36):
At home at the moment, what would you do? We watch read a book or watch TV.

Paul Smith (00:58:40):
I read papers. Avidly. Keep up to date. Yeah, write papers. I read virtually online. Most of the time I must admit for spots of sanity. I read the independent I, um, now and then, but, um, I, I tend to take different news feeds because I like to check things, believe it or not to make sure I'm getting the right information balance. The more important to do that these days. I

Peter O'Toole (00:59:11):
Think you look at the British press. I always look at the head. I always look at the front pages in the morning. If you could get the website and look at all the fronts headlines, and then there could be one story, two sides. I do like getting that balance.

Paul Smith (00:59:23):
Yeah, absolutely. You got to be careful what you release though, because remember Paul Workman saying once to some reporters that, um, they had a really interesting lead compound, so it went on the wire throughout the states, and then you get people phoning him up and say, you've got a compound for treating cancer. That's made of lead. Yeah, no, I'm already there.

Peter O'Toole (00:59:48):
So, so you read newspapers if you, so if you were to have the tea, do you ever watch TV? If you do TV or film, what's

Paul Smith (00:59:55):
Your preference, but I'm, I'm very much a factual program person because it's a bit boring, but I like to learn something from the programs as well, but, um, like Comedy I have my favorite comedians, you know, that sort of thing. Milton, Milton Jones, for example, I think I liked the, I liked the working of the mind there any one liner is in a play on words and puns, correct? Yeah. Well, I, I, I've taken various tests to understand what your, your personality is. And apparently I'm a word master, not with Northern accent. I could never be a word master, but, um, I do enjoy manipulation and use of words, which sometimes getting my way of saying things simply. So it's not always the best characteristic to have.

Peter O'Toole (01:00:44):
So I I've got two more questions because we are out of time. First one is what is your favorite science? And if you can't think of a science one, just, what is your favorite joke?

Paul Smith (01:00:56):
Favorite joke? Um, am I allowed to plagiarize? Yeah, of course. Okay. And Milton Jones, Joke, I love the expectation in a joke and the visual image and then the twist and you should be able to get the, um, the punchline at the end, right before it's delivered. Then it's even funny when it's delivered. So forgive me for this. This is nothing to do with me. I give my respect, respect Milton Jones here. So he was saying about his father who was, um, unfortunately had a, for being a peeping Tom. And, um, he died recently and apparently, uh, he used to drill a hole in the floor of this house and spy on people below in the apartment below, but he died recently. And I like to think he's up there somewhere looking down upon us, but there's no delivering that, but that's that play on words and favorite science, favorite science? Yeah, maybe science joke, famous science joke. Oh, I don't find anything funny in science. It's far too serious and I'll leave it at that.

Okay. Very finally. What is the next big thing or what is the biggest unmet challenge that we need? Address insights,

The harnessing of big data, collective knowledge to effectively build highly predictive models so that money is not wasted on wrong directions in research, right? Because lots of people pursue research and I'm guilty of this myself. Research avenues, which if you knew more about that area, you would pursue, it has the advantages of uncovering unexpected findings by chance. But I think we have to have a more, how should we say, um, a more efficient way of using research money for purpose? Yeah. The drug and pharma industry know this, certainly in terms of trying to predict early failure, but I would say that's the biggest step forward effective, um, modeling, uh, using big data or appropriate data, not just fumbling around in the dark to see something comes out about AI, but actually a real predictive approach to modeling. So I think that's where we're going. I, in fact, in reality, that's exactly what's happening in real life. When you buy something, people can predict what you're going to buy next, et cetera. Why not harness these, these thinking to navigate a better and more awake, efficient way through science.

Peter O'Toole (01:03:49):
Nice answer. Paul on that note, I will. Thank you. Thanks for taking the time today to talk to us.

Paul Smith (01:03:54):
Pleasure. I was, I was great to see you, Peter. Bye-bye.

Creators and Guests

Paul Smith (Cardiff University)