Episode Transcript

Summary

Dr. Thomas Pollard, a renowned molecular biologist, discussed the molecular basis of cellular motility and cytokinesis. He highlighted the importance of cell motility in processes like immune response and brain development and its role in cancer metastasis. Pollard explained the historical shift from observational biology to biochemical and genetic approaches, emphasizing the role of reductionism and computational models. He shared his personal journey, including his work on actin and the impact of federal funding on scientific advancements. Pollard also touched on the potential for healthy longevity and the importance of interdisciplinary training for young scientists.

Tom Pollard
In principle, it’s possible if we could find a particular vulnerability in the cancer cells and target that without targeting the motility in the rest of the body, it would be a dream come true, but we haven’t got there yet.

Tan Deleon
On behalf of the members of the Academy, welcome to this episode of Living and Learning stem in Connecticut, the podcast of the Connecticut Academy of Science and Engineering. My name is Tanimu Deleon. I’m an elected member of the Academy and serve as an officer for its Governing Council. For more information about the Academy, visit ctcase.org, Our topic today is the molecular basis of cellular motility and cytokinesis. Here to discuss what we should know about this is Dr Thomas Pollard, the Sterling Professor Emeritus of Molecular Cellular and Developmental Biology, professor emeritus of cell biology and of molecular biophysics and biochemistry at Yale University. He is also the 2025 Connecticut Medal of Science winner and a corresponding member of the Academy. Welcome, Tom.

Tom Pollard
Hello. Good morning.

Tan Deleon
Can you tell us a bit about yourself?

Tom Pollard
Sure.I grew up in Southern California. Both of my parents studied science in college, but having a career in science during the Depression was unthinkable. However, they were very gratified that I and all three of my brothers became professional scientists, and so their dream, in some way, was fulfilled by their children. I had a wonderful, rewarding career myself as a professor, as a research scientist, as an author, and a institutional leader at Harvard Medical School, the Johns Hopkins Medical School, the Salk Institute, and for the time since 2001, at Yale University. So I’ve had just as a dream like professional experience. It’s been fantastic.

Tan Deleon
No, that’s, great to hear. Yeah, you’ve, you’ve certainly accomplished quite a great deal, and we’re very lucky to be able to have a discussion with you today. So, thank you for the time. So, let’s just jump right into this. So you graduated, as you said, from Harvard Medical School, but you decided to focus on researching cells. What was the impetus for the shift from traditional medicine in the late 60s?

Tom Pollard
Okay, well, I hope this is an interesting story. It starts when I was in high school, and my high school biology teacher showed us amoebas crawling around in a microscope. I was absolutely thrilled by this and wondered how it worked, but nothing was known actually, or there were fairy tales about how it worked, but not actually how it worked. And then, as a college student, one summer, I worked in a laboratory where they made time lapse movies of nerve cells in tissue culture, and nerve cells would send out long processes trying to find another cell to talk to. And this, this was equally amazing. And so I went to the library and tried to find out what was known about how it worked. And it turned out nothing was known about the molecular basis of these movements. So I thought that would be a really interesting thing to work on. It was a big opportunity, since nothing was known, I was going to would get in on the ground floor. So when I was a medical student, I found a very dear professor friend of mine who took me into his lab and helped me do experiments on how cells move. This was remarkable, because he was his research was on a completely different topic, but he thought it would be fun to work on my project, so he helped me do it, and we actually discovered some very interesting fundamental things during my spare time in medical school. And then I did a medical internship at the Massachusetts General Hospital and intended to become a neurologist, but it was the middle of Vietnam War, and all of us doctors were being drafted. An alternative to serving in the military as a doctor was to work for the Public Health Service, and I obtained a position at the National Institutes of Health, which allowed me to do research for my military service. So I found I was very fortunate to find a lab that was interested in what I wanted to do, and once again, we had a very, very productive time for three years. Discovered some very fundamental things about the molecular basis of cell movements and I was about to go off for my residency at University of California in San Francisco, when my friends at Harvard Medical School phoned up and said, what are you doing next year? I said, oh, we’re happy. We’re going back to California our home. And they said, Well, have you ever considered being a basic scientist? I said, well, not really, but they said, come on up and visit us. And they talked me into giving up medicine and becoming a cell biologist. So that’s how I became a scientist. I’m a chance scientist.

Tan Deleon
Wow. Well, it’s lucky for us, right? I mean, because some of your discoveries have been very fundamental, so…

Tom Pollard
Yeah, well, lucky for me too, because I was able to advance through my career much more rapidly than I would have if I’d spent five years training as a neurologist. So at the end of five years at Harvard, I was already asked to start up a new department of cell biology at the Johns Hopkins Medical School. So it turned out just wonderfully. But at the beginning, we actually had very limited tools for studying the things I was interested in. But at Harvard we still were able to make some pretty important discoveries. Things are much better now, the technology allows us to move much faster.

Tan Deleon
Okay, okay, so okay, so then, so that would lead me to to ask you what actually makes cellular motility so important then?

Tom Pollard
Well, that’s fun thing to talk about. I mean, in some ways, being able to move is sort of the definition of living organisms. When the organisms stop moving, people usually say they’re dead. So it’s very fundamental but it’s important for us as human beings as well. The thing people usually think about first is white blood cells, which migrate around in the body and track down bacteria that might have invaded the tissues and eat them to protect us from bacterial infections. But the most spectacular example is our brain. Our brain has 1 million miles of connections between the nerve cells, and all these connections are formed, as I observed when I was an undergraduate student, by nerve cells growing out a long process and finding their target. The movements of these processes uses exactly the same machinery as an amoeba or a white blood cell. So it’s fantastic. So a million miles of connections in your brain were formed by the pushing forward of these processes from the cells. And on the dark side, there is the spread of cancer cells. If the cancers just stayed put in the organism organ where they formed this or you could a surgeon could cut them out and cure you. The trouble is that the cancer cells tend to escape from the primary tumor and go to other places in the body, like lungs or liver or brain, and and that’s what kills cancer patients. So cell motility not only has lots of benefits, but it has this dark side as well.

Tan Deleon
Okay, so, so if the same fundamentals enable malignant cells from primary tumors to secondary sites to spread, leading to a major cause of death in cancer patients, as you just said, right? Once the cells are identified, could they turn off the motility ability? Or am I just not making sense?

Tom Pollard
That would be a dream. But let’s think about this… the machinery that’s making the cells move is really fundamental to life itself. And so if you stop the movements, the movement mechanism, and stop those cancer cells from getting into mischief, you also stop the movement ofthe white blood cells and any remodeling of the brain which depends on these movements as well. So it’s that particular goal has not been achieved. In principle, it’s possible if we could find a particular vulnerability in the cancer cells and target that without targeting the motility in the rest of the body, it would be a dream come true, but we haven’t got there yet.

Tan Deleon
Okay.

Tom Pollard
That make sense?

Tan Deleon
Yeah, no, no, that does make sense, you know, like, because you tend to think, like, you know, if you could, I don’t know, isolate and then inject some type of paralytic or something. But I guess that would, that would seep into, into other cells and cause problems elsewhere.

Tom Pollard
The side effects would be, uh, deadly.

Tan Deleon
Okay.

Tom Pollard
But that, but you’re on the right track. That’s the dream of everybody who works on on cell motility in the human context.

Tan Deleon
Okay, all right, so motility is quintessential. So then, why is cytokinesis so important then?

Tom Pollard
Okay, let’s think about that. That’s sort of fun, too. Now, in order to make you or me or a sequoia tree, it’s necessary to start with one cell, the fertilized egg or a seed, and divide many times. In humans, the egg, fertilized egg, divides in two. That’s the first division, and the two cells have to pinch apart like that, and then each of those cells pinch apart, and now you’ve got four cells. And 38 rounds of successive divisions gives you 1 trillion cells, which is enough to make a baby. So that’s pretty important. And if the cell division process goes bad, then you get congenital defects and one thing and another. So it’s super, just like motility, it’s super fundamental to to multicellular life and or unicellular life, for that matter, to be able to divide in two.

Tan Deleon
Okay, okay, no, that definitely makes sense from intrinsic and fundamental perspective. And as you said, all life for the most part, even tree, sequoia trees, as you, as you mentioned, would do the exact same thing. So, so then you have the cell that splits apart, right? But, you know, human beings are always looking at things to have, like specific symmetry, right? In pretty much every facet of life, you know. So, so why is an asymmetric cell division fundamental to the development of oocytes?

Tom Pollard
Okay, that’s a great question. You are right. Virtually all cell divisions are symmetrical like this. But there are some very special cell divisions that are not symmetrical. For example, stem cells in the body, which which allow for regeneration of tissues and so on, sort of hide here and there in the body and when necessary for them to proliferate and to regenerate the tissue, they divide in two. Now it looks like the two cells are the same, but they’re not. One of them has the information to remain as a stem cell, and the other one has the information necessary to proliferate into many cells to regenerate the tissue. So that’s an example – a spectacular, fundamental, important example – of an asymmetrical cell division. On the surface, the two cells look the same, but inside they’re different.

Tan Deleon
I see, I see, okay, so it’s the shape is the same, but the but the actual information is different.

Tom Pollard
Yeah, the molecules in the two cells are largely the same, but there’s some special molecules for the cell that stays behind as a stem cell, and for the other cell that goes on and regenerates, for example, skin if you have a skin wound.

Tan Deleon
Okay, okay. Interesting. So, so then, okay, so you’ve, you came across all this, you know, discovered all this information. You know, how was it possible to discover the molecular mechanisms of cell movements and cytokinesis, like, how did you go about doing this?

Tom Pollard
So, you can’t understand the mechanism by just looking at the cells, which is what people did for several hundred years, up until the 1960s. In the 1960s people overcame the prejudice that motility was something magical about live cells. They were vitalists, not chemists and physicists. And at that point, I and a few other people got our field started by attacking the problem with chemistry and physics. And in the case of cell motility, all of the important protein molecules required to make the cell move were discovered by biochemists who ground up cells and purified proteins that they thought might be involved with cell motility. One by one, and now we have maybe 100 different proteins that are involved with cell motility, and each one of those has been purified by a biochemist, and so you could study its structure and its interactions with other molecules, its location in cells. And from all of that, you get some idea about how the system works. For cytokinesis, a different strategy was required. We initially started out doing our biochemical approach, but we stalled out in about 1980 and we didn’t know why, until about 15 years later, when people working on yeast did genetics experiments that identified a very large number of proteins that are required for cytokinesis – more than 150. Now, finding all those proteins was impossible in the biochemistry lab, but now we knew their identity from the genetics, so we started with the genetic identification of the proteins, and went back and looked in the cells and found out where each one was located during the process of cell division. And from that we came up with ideas about how it might work. And then at that point, we went back to being biochemists. Identified the ones that looked like they were the most important, determined their structures, how they interacted with their partners and so on, and came up with a hypothesis to explain the process. Now this is called reductionism. This is a triumph – in the both of these cases – a triumph of reductionism. Making a catalog of all the parts, isolating the parts, putting the parts back together to see how they worked. And in both of these cases, we took a lead in going a step further. All of us cell biologists and biochemists love to make little cartoons about how we think this molecule and that molecule interact with each other and do something, and the cartoon has some value, and they’re correct in most cases, to some extent, but only to some extent. So how do you find out whether your cartoon is any good? And computers came to our rescue. These processes are way, way too complicated to understand intuitively. You simply can’t understand the interactions of, you know, even five or six proteins in the cellular context without a little help. So the computers helped us, because we could make mathematical models of what we thought was going on. And then run a computer simulation of what we thought was going on and compare it with what we observed in live cells. And almost every time you do this, it fails. Okay, so your cartoon wasn’t strictly correct.Ah, but then you’re in business, you can go say, okay, what’s wrong here? Am I missing a part, or have I made an incorrect measurement about how the proteins interact with each other, or some other assumption’s wrong? And you test all those ideas, update your mathematical model, rerun your computer simulation and see whether you’ve improved the performance of your simulation. And it’s worked fantastically by making a few relatively simple corrections, we could take our model for how the cell did cytokinesis and turn it from a complete dud into something that not only correctly reproduced what you see in cells, which isn’t too hard, but we got the timing right from the from the basic information about the molecules and the rates of their interaction, which physicists tell me is almost impossible to do a bottom up analysis and get the timing right. But we got the timing right, so we think we’re on the right track thanks to a lot of hard work in the biochemistry lab. A lot of very, very insightful microscopy, and then the computer simulations.

Tan Deleon
What was the duration, what was the epoch, from the yeast cells – because you said guys had a hiatus because you stalled out. Then some folks were doing work with yeast cells. What was the epoch from the yeast cells to to the to the revelation?

Tom Pollard
Okay, we switched to working on the yeast cells. We were working on human cells and tissue culture, and it was too complicated for us to figure out what was going on although we published papers, we didn’t really make that much progress. But we switched to yeast, and we didn’t actually tell our funders we were switching. We just switched and came back a couple years later to renew our grant, and suddenly we were a yeast lab. But that was important, because being a yeast lab enabled us to do experiments we couldn’t do in animal cells. One of the very most important things for people in this field has been to put fluorescent proteins as tags on our proteins we’re interested in the cell. This was a Nobel Prize winning experiment by others, but we took advantage of this right away, and because in the yeast, it’s easy to manipulate the genome. At the time, it was impossible to manipulate the human genome, but in yeast, it was simple. We’d go in there and put a green tag on one protein and a red tag on another one, and go back look at these cells in the microscope and figure out the time when all the proteins appeared at the scene of the crime, and what they did during the pinching of the cells in two and so on. And that was our benchmark, that we tested our computer simulations against and at the beginning, the simulations didn’t really reproduce the process, but eventually it actually didn’t require that many adjustments. The simulations work fantastically. So that’s how you know you’ve got to you can come up a lot of good ideas on science, but it’s often difficult to prove that they’re correct. In fact, the Hans Popper, philosopher of science, says you could never prove your hypothesis is correct. All you could do is disprove your hypothesis. Okay, which we do all the time. Okay?

Tan Deleon
Very true, yeah.

Tom Pollard
But Hans Popper didn’t have computers available at the time, 100 years ago, and so I think he’d be very happy to see that you can actually do a pretty rigorous test of complicated hypothesis and to reassure yourselves that your hypothesis is correct. As an aside, let me add on point here.

Tan Deleon
Sure.

Tom Pollard
Your viewers here would appreciate this, but in a little yeast cell, little yeast cells shaped like a hot dog. There’s about half a million protein molecules that gather together to form a little ring around the middle of the cell. The little ring has many features of our muscles, and so the little ring constricts and pinches the cell in two. So there are half a million molecules there, roughly. And so that’s why the computers are important, because the computer can keep track of all those molecules that you’re trying to simulate to reproduce what you see in the cell.

Tan Deleon
Okay, okay. And it, I mean, it’s certainly, you know, not only the computers help, but you definitely have to have a lot of perseverance, which is, which is a characteristic of great scientists. Clearly.

Tom Pollard
Great. Well, I’m a marathon runner, so I’ve got a lot of perseverance. And I must say that many of our, many of my friends, questioned what we were doing along the way, because we were going one step at a time, one protein at a time, patiently trying to understand every single one of them until we could get to our final goal, and our funders understood this. Thank goodness. They understood that what we were doing was a very long range project. It was – that’s the case of cytokinesis. That was a 40 year project to get from the beginning to this very satisfying computer simulation at the end of what I was doing. And there were, you know, dozens of proteins involved, and we’ve purified of those proteins, each one of them required hard work by a grad student or a postdoc, a whole PhD Career, perhaps just to isolate one of these proteins. Then the whole careers of additional scientists in my lab to determine the atomic structures, to measure the rates of the interactions of the protein with other proteins, and to do all the microscopy to give us a benchmark against which we can test our ideas. So every one of these proteins has a tricky mechanism of action. They’re none of them simple, okay, the main protein in the system is actin, a little protein called actin that polymerizes into filaments that push the front end of the cell forward and make the ring for dividing the cell in two. I’ve been working on actin for more than, gosh, 50 years, 60 years, and even today, I was working on a new paper about actin that I’m doing with some collaborators at Chicago, and we’ve suddenly realized we can explain something we never understood before. Even today, there’s still secrets to be, to be learned about these, these molecules. So for your viewers this, this is a task. It is, I should emphasize, my lab alone did not do this.

Tan Deleon
Okay.

Tom Pollard
There are hundreds of labs who now work on cell motility and cytokinesis. At the beginning, there were two. Now there are hundreds, with many people in the labs chipping away at it. And it’s, it’s, it’s, it’s not like Einstein have to have a theoretical insight that would change the world. Biology – it’s hard spade work. There’s a lot of detailed experiments that need to be done. At the end, you collect enough information to explain how things work. You know, when I was a high school student and a college student, I had a dream that I wished I could be a little gremlin, get inside the cell and look around and see what was going on.

Tan Deleon
Okay.

Tom Pollard
And we’ve darned near achieved that with our computer simulations of these processes.

Tan Deleon
Wow. That reminds me of Magic School Bus with Mrs. Frizzle. When I when I was, when I was a lad. That’s, that’s fantastic. So then, yeah, I mean, so computers have been fundamental in this discovery, right? And you know in over 50 years, right, they’ve afforded vast abilities for current researchers in molecular biology. However, you had to be creative. And I just wonder if computers today might stymie creativity to some extent…

Tom Pollard
Oh, I think they enhance it actually.

Tan Deleon
Okay.

Tom Pollard
Because you could, you could use the computers to test out things that you can’t think – you’re not clever enough to think about.

Tan Deleon
Okay, okay.

Tom Pollard
Okay, so you still have to come up with good ideas, sure, and then you use the computer to test them.

Tan Deleon
I see, okay. So, you’re saying, the creative, the creative part is, is the idea that you come up with, and you’re just the computer is just the tool you’re testing with.

Tom Pollard
Yep, yep, it’s, but I should emphasize that the reductionist strategy is extremely powerful. Extremely powerful. If we’re willing to put in the time and effort to do all the different things, find the proteins, do their structures, measure their interactions, and a lot of this is physical chemistry, measuring the rate constants for reactions and equilibrium constants and things. If you’re willing to do all that, that information, almost inevitably gives you a good idea about what’s going on.

Tan Deleon
Okay.

Tom Pollard
Okay, so you build this, this edifice, all this information, and then many people could could figure out what was going on if they knew all that. But if they didn’t know any of that, like I was in high school or college, you were clueless. You couldn’t even start to make a guess. So this big monument of of hard work by a lot of people over decades is, is what, what makes the creativity possible. So maybe that’s disappointing, and what I’m saying is a lot of hard work allows you to be creative.

Tan Deleon
Okay. So yeah, so you’re taking it from a different vantage point. Okay, all right, that’s fair. That’s right, and was the reductionist strategy, is that something that you and your cohorts came up with, or is that something you guys took from, from, from, from a different area?

Tom Pollard
That was something that developed slowly over about 100 years during the 20th century. At the beginning of the 20th century, virtually nothing was known about the molecules of life. There was no structure of DNA. People didn’t know how big proteins would work. They could have been as small as a pinhead or as large as this room. They really didn’t know. It’s amazing what people didn’t know even up until the 1940s so but once again, some hard working chemists and physicists took this on and eventually found were able to purify and characterize proteins and then find out what they were doing and to support life. But speaking of support, I need to make another very important point.

Tan Deleon
Okay, please do.

Tom Pollard
Along with all the other scientists who work on these interesting and important biological questions, and that extends to engineering, chemistry, physics, astronomy.. we’re all exceedingly grateful to the taxpayers in the United States for providing the money for the Federal Science Agencies to support this work. It wouldn’t happen without really generous support.

Tan Deleon
Okay, no, that’s fundamental, yeah.

Tom Pollard
And I’m not alone. There are a lot of other people doing this work, and we’re all grateful to the taxpayers. Taxpayers should understand when they pay their taxes, they may grumble a little bit, but they are doing some very important things to advance civilization.

Tan Deleon
Yeah, yeah, no, and you know, that’s a very good point. I’m glad you brought that up, because, you know, it makes the connection for people, because, people tend to miss that connection, right? And they don’t really see that you know, all this basic science, this basic research has a path that leads back to them at some at some point in their lives. And you know that connection is quintessential to how humans have been able to evolve as much as we have, and to be able to do, I mean, if you look around, some of the things that we have. If I dropped someone here from 120 100 years ago, and just put them, you know, in 2025 they would think they’re in like a, like a sci-fi movie or something. It’s, it’s amazing. It really is amazing.

Tom Pollard
Well, I am a living example of how important basic research is. I’ve had life threatening cancer twice. The surgeon saved me the first time when I was 44. When I was 78, five years ago, I came down with a disease called acute myeloid leukemia. For a 78 year old, this was a deadly disease. Only 1% of 78 year olds survived for one year, and here I am five years later. So what happened? Two months before my diagnosis, a very important paper based on fundamental cell biology was published with a tricky new approach to treating acute myeloid leukemia, and I was fortunate enough to get this treatment. It was very mild, nothing like the horrible chemotherapy they used to do. And in one month, it removed all the leukemia cells from my bone marrow.

Tan Deleon
Wow.

Tom Pollard
There were still, well, I should say, almost all. There were still a few hiding there. We could tell from sequencing the DNA in the bone marrow sample. Second round of treatment got rid of the mutated genes, and here I am today.

Tan Deleon
Wow. I mean…

Tom Pollard
It improved the outcome from 1% to about 90%.

Tan Deleon
My goodness. I mean, you’re a walking testament. You know.

Tom Pollard
Absolutely. And this was basic cell biology that the treatment was based on, that I’ve been teaching my students in my cell biology class about for 20 years or so. And finally, somebody put the pieces together and took advantage of a vulnerability in these leukemia cells that allowed the the treatment to kill the leukemia cells without killing the normal cells.

Tan Deleon
That is, that’s fantastic. I mean, there you go, folks. I mean, you just, that’s a real-life example for you, you know, so…

Tom Pollard
So that’s what, that’s what your taxpayer dollars have been paying for. I’m a beneficiary.

Tan Deleon
No, that’s absolutely wonderful, absolutely wonderful. It actually holds more weight coming from you as someone that basically started, you know, this, this entire field. So it’s, it’s pretty, pretty fundamental. So let’s, let’s look so you know, it’s been, you know, 50 years plus or so. So where do you see molecular biology heading in the next 50 years?

Tom Pollard
Okay, thank you for asking that question. This is something I love to tell the politicians. Okay, when I started, we didn’t have the tools required to understand the molecular basis of life. We were sort of wandering around in the dark. But over the last 50 years, the technology has improved so much, that we – I know we can understand any biological process at the molecular level. The only question – the rate limiting factor – is how much resources that are put into this? So if we want to not make any progress, we put in no dollars. We have a decent amount of support now. So we’re making wonderful progress. If society decided that that solving the cancer problem, or any other biomedical problem, was a high priority and put, let’s say, twice as much money into medical research, we’d get there twice as fast. So it’s a simple, simple engineering problem. It’s that we’re limited by by the resources we have available to do the work. We’re not limited by the technology.

Tan Deleon
Okay.

Tom Pollard
So we’ve gotten to a point where politicians can make the decision.

Tan Deleon
Okay. So, I got a bit of a like, I guess it’s kind of out in left field question for you, but I think it’s probably fairly relevant, you know. Do you think with all the advances right that we’ve made thus far, and the potential going forward, you know, do you think one day science will afford humans the ability to be amortal?

Tom Pollard
Right? I was surprised by that question when you gave me your script and it gave me something to think about. I don’t think anybody knows the answer to that. Okay. I mean, we don’t really understand aging all that well, but having been around here for more than 80 years, I can see how aging reduces one’s abilities to do things over the years. And I don’t know whether stopping that is is possible, but that would be a question that would be a decent question for somebody to investigate, and there was a moral question about whether you’d actually want to act on the information.

Tan Deleon
Yeah, no, that is true. That is definitely true. I think the benefit would be if, is if everyone was able to be amortal, as opposed to just a select few, right?

Tom Pollard
Exactly, but I don’t know where we put all of us.

Tan Deleon
Yeah, we’d have a, we certainly have a resource issue from from a climate perspective, right?

Tom Pollard
Yeah, well, just from a housing perspective, but which is very acute here in San Francisco. But, you know, the new generations are very important, and I can really see that in science, the new generations of people coming along have are starting from a much stronger position than I did after I went to medical school. I had no formal training in scientific research, just a little practical experience and a good undergraduate degree in chemistry and zoology. But now, now the students coming along are afforded a much better platform from which to start thinking about the scientific problems for the future. And I think that they can, they can reach higher, because they’re starting at a higher level. And so it’s always important to have new generations coming along. I’ll use my daughter as an example. She’s a very successful computational biologist working on genomes. Yeah, and she’s knows how to do things, and it’s achieved things that I can’t even imagine. And I wonder what her kids are going to do, how they’re going to get way beyond their mom?

Tan Deleon
Well, yeah, I mean, with technology, and the way it’s advancing. The sky isn’t the limit, as they would say.

Tom Pollard
So I’m not, not sure immortality is such a good thing. I think having new generations of of abled people starting from a higher level at the beginning of their careers is going to be very helpful for civilization.

Tan Deleon
Yeah, yeah. Well, yeah. I mean, yeah, immortality is definitely not, not achievable. But you know, there are certainly lots of people out there that want to double or triple their life expectancy. And you know, they’re playing around with a lot of things, if you get my drift, yeah, so…

Tom Pollard
I’d say that the important thing would be healthy, healthy longevity. Okay, people use that term, and that would be great if people could live into their 80s or 90s and be able to perform on a level that they used to now. I’m a long distance runner, so I have a quantitative appreciation of the aging process. In the half marathon, which I’ve run many times during my career, I’ve lost about one minute per mile every 10 years. Okay, okay, I slowed down by that amount, okay, at a pretty steady rate. Now it’d be great if I could still run a marathon in 2:40 like I did when I was 40 years old.

Tan Deleon
Wow. Okay.

Tom Pollard
But I can’t even, I can’t run 100 yards that fast now, but so with healthy longevity, it would be great if I could still run that fast. Yeah, well, you know, I would say maybe you can’t do the things you used to do, but I’m sure you’re at a level when compared to people your age, you’re probably doing much better than folks your age, I would imagine so… Well, I think you’re exactly right. When I was 75 I won the national championship for my age in the 20 kilometer road race, you know. So that was, was great to be able to perform at a high level for so long.

Tan Deleon
Good, good genes, as they say, right? Good genes and, and a lot of hard work, as you said, a lot of hard work.

Tom Pollard
Just like, just like, scientific research.

Tan Deleon
Yeah, very true, very true. So, so let’s, let’s just switch topics a bit. And you know, you’re retired…you know, how are you spending your time? What things are you doing, and how are you enjoying yourself?

Tom Pollard
Good! I’m sort of doing the same things I always did. I don’t have my own lab with people I’m responsible for, which is, as I miss a little bit. But being responsible only for myself has certain advantages. So what do I do? I’m a visiting professor at the University of California Berkeley, and I go to the lab of one of my friends, and I try to be helpful, giving advice and other ways. And I have a laboratory at home where I’ve started up a new research project on a different topic than the one I spent so long working on. And I spent a couple of years troubleshooting the equipment, and I’ve just last week, I was able to do pretty much the experiment I wanted to do. So that’s that’ll keep me busy – my little home lab, but I also have professional responsibilities to scientific societies, and particularly the National Academy of Sciences and reviewing papers and other professional responsibilities. So the good thing about being retired, I control my my time. I can do what I want to do, but I still enjoy doing the the things that brought me to gratification all along. And I’m still exercising too, so and having fun with my wife. I’ve been married for 62 years…

Tan Deleon
Congratulations.

Tom Pollard
So we’ve done a lot of things together. We still have a lot of fun together.

Tan Deleon
Yeah, no, that’s phenomenal. Absolutely phenomenal. Is your, is your home science, your home lab, is it top secret what you’re working on?

Tom Pollard
No. Oh no, I’m working on another part of the cytoskeleton.

Tan Deleon
Ah, okay.

Tom Pollard
That’s another whole field. We’ve dabbled in that from time to time,and made some contributions of that field. But I’m lucky, because the people doing that work left behind untouched, some very fundamental questions, and they’ve just sort of ignored it because answering those questions is pretty hard. But based on what we did on actin, I know how to do the experiments to answer those questions, so I’m setting out to answer those questions in my little home lab, and the only instrument I need is a microscope. And I’ve got a microscope that I’ve had for more than 50 years, it was abandoned on a shelf in my lab for the last 25 years, but I’ve I’ve hopped it up so it can do, do what I need it to do, and now I can have fun collecting some data and trying to understand that mysterious process.

Tan Deleon
So always, always curious, and never stop being curious. That’s, uh…

Tom Pollard
Well, you got it. That’s what makes a scientist successful. You got to be quite curious and always questioning things.

Tan Deleon
Is that the type of advice you’d give a young, a young scientist today, or someone, someone aspiring, potentially in your footsteps, I would say, I would add.

Tom Pollard
Yes, well, that’s what I emphasize to the students and postdocs. In my lab, I had 50 postdocs and 30 graduate students who got PhDs, and I always insisted they think about what they were doing, not just do it, but think about, what does it mean? What is the next question? How can I get there and so on. And I think that’s really important. It’s also important for a second piece of advice is to try to frame an important biological question that can actually be addressed experimentally. So those questions in the 1960s were completely different from the ones now, because our tools are so much better now. But think on a question that’s important and that you can answer, it’s practical, so please be practical about it. The other piece of advice I have, and this is based on my own experience, is that you could never know enough chemistry and physics and math, if you’re a biologist. So all this because I advised that over the years as undergraduates at Yale, they’re trying to decide what courses to take. I said they want to take another biology class. I said, No, don’t take another biology class. If you want to be a biologist, you’ve got a whole lifetime to do that. You should take another physics class or another chemistry class or another math class or computer science, because you’re never going to go back to that after you leave college. You’ve got plenty of time to learn more biology later, but you never know enough chemistry, physics, math and now computer science.

Tan Deleon
Yeah, no, that’s uh, those are really, really good words to live by, and clearly, you know, you got to think beyond what your focus is because that will help you focus even more, potentially down, down the line so…

Tom Pollard
It helps you frame good questions, and it helps you do the experimental work to know what experiments to do and and so you’re right, absolutely right. Now, one other thing that I learned way back when, when I was a medical student, everybody in my department at Harvard Medical School was doing electron microscopy. They all did exactly the same experiment. They took some interesting biological material, they preserved it, put it in a block of plastic, and cut little sections off the surface so they could look at these thin sections in the electron microscope. They discovered all sorts of important things, and became famous. But by the time I got back there after my internship and time at the National Institutes of Health where I learned to be a biochemist, I realized that they were stuck. They only knew how to do electron microscopy. And so one of the things I tell my trainees, and anybody else is willing to listen, is you’ve got to be able to to expand your repertoire of things you know how to do. So over the years, I’ve learned how to become a biochemist. Then I learned how to become a biophysicist, learned how to do structural biology for X ray crystallography and electron microscopy, learned how to do chemical kinetics, learned how to do fancy light microscopy. None of these things I was trained to do. But I had had to, had to do those things to make progress on my my research. And so I tell people, don’t get stuck in a corner doing just one kind of thing when you get when you get cornered, you’ve got to reach out and try some new approach, even if you don’t have any training, you can train yourself. Ask friends you’ve got a new postdoc in the lab who knows how to do it. There’s lots of tricks for getting beyond the limits of what you know how to do. So that’s another piece of advice that I give often.

Tan Deleon
No, yeah, no. That’s, uh, that is absolutely sound and clearly that you not only give advice, but you also adhere to the advice that you give. So that’s that’s even more fundamental in its nature. So.. well, you know, I’d like to you know this has been a great conversation and, and on behalf of all of us living in Connecticut and others tuning in from other states, thank you, Tom, for sharing with us information about the molecular basis of cellular motility and cytokinesis. You’ve given us a lot to think about.

Tom Pollard
It’s been a pleasure talking to you.

Tan Deleon
Listeners. I encourage you to subscribe to this podcast on Apple Podcasts, Spotify, Amazon Music, or YouTube, and visit the Academy’s website at ctcase.org, to learn more about our guests, read the episode transcript and access additional resources, as well as to sign up for the CASE Bulletin. Thanks again, Tom, and congratulations on winning the 2025 Connecticut Medal of Science.

Tom Pollard
And thank you for the opportunity to talk to the audience. Thank you.