Dr. Mike Klymkowsky Transcript:
Hello, and welcome to Ask a Scientist, the podcast for kids and adults to ask scientists questions about anything they want to know. There are so many scientists out there doing a lot of cool scientific research. In the news, we’re constantly hearing about scientists and their ideas and where those ideas are going to take us in the future. But just who are these scientists? In this podcast, we will learn a little more about who they are and what inspires them as scientists.
I’m your host, Victoria. Every other week, I’ll sit down and ask a different scientist questions written by you, the listeners, and by students from classrooms throughout the country.
Victoria:
Hello listeners. Welcome back to the next episode of Ask a Scientist. This week we have Dr. Mike Klymkowsky. He is a professor of Molecular Cellular and Developmental Biology at the University of Colorado Boulder.
Dr. Klymkowsky, thank you so much for being here today.
Dr. Klymkowsky:
Thanks for inviting me.
Victoria:
Well, we’ve got a lot of great questions for you today, but before we get into the questions, would you mind just telling us a little bit about yourself and your research and what you do?
Dr. Klymkowsky:
Oh, well, so I’ve gotten to be basically a cell biologist and I also study how students learn. So we do, I do, both two things. I got into cell biology in a circuitous way. I worked in a lab as an undergraduate at Penn State, which I found phenomenally helpful to me. I recommend it to all college students, if you can manage it. And I started working on virus structure. I worked as a graduate student on the structure of various acetylcholine receptor isoforms, and then I went to work in London, looking at the behavior of very structural proteins in cells. And what’s happened to me over the years, as I moved from studying cells grown in culture, to cells within embryos, because embryos are more realistic setting.
During that same time, I developed my interest in education research. And so thinking about why it is, what we teach, and what’s the point of most of it, and working with Melanie Cooper, who’s now at Michigan State, we’ve developed what we think are way better curriculum for chemistry and biology. And the key, I think guiding principle is teaching things that you think the student needs to use, and then give them a chance to use them. And so that idea that you don’t learn things for the sake of a test, you learned because you can use them.
So since, you know, since I’ve been here in Boulder, I moved here in 1984, which is a long time ago, I’ve been working on frogs and students, as experimental organisms.
Victoria:
(Ms. Abdallah’s 4th graders – How do neurotransmitters work?)
Well, we have some great questions about both your work with frogs and your work with students. And with that, we can get into the questions. So this is a good question, I think, to start off with getting at, you know, basic biology. This is a question from Ms. Abdallah’s 4th graders. How do neurotransmitters work?
Dr. Klymkowsky:
So this is one of these questions that the answer all depends on what you already know. And so this is a big problem in science, because much of what we learn in science is sort of not obvious and not actually, it doesn’t sound reasonable when you first think about it.
So we’re going to start talking about, you know, so we’re talking about how cells talk to each other, basically. So how neuronal cells talk to each other. Neuronal cells can send signals through their membrane, through their surfaces. And those signals lead to the release of various chemicals. Those chemicals can then move away from the cell that released them, and bind to receptors on neighboring cell. Typically, that occurs at a synapse. What’s called a synapse is a specialized structure. And when those chemicals bind, they bind a specific receptor, specific protein molecule on the surface of other cells. And in the case of most neurotransmitters, they work by opening a channel.
So the cell is like a little battery and it’s closed until the receptor molecule binds a neuro-transmitter which opens it and sends a little current running into the cell, and that activates the next cell down. And so you have a cascade of signals from one cell to the other. So it’s all based on release of chemicals and binding of chemicals.
That’s the common form of communication course. In biology, there are alternative forms, but that’s the simplest one.
And so what happens is in a network of cells, that pattern of activity will lead to various behaviors. Because cells are normally, one cell may be connected to multiple target cells and may receive inputs from multiple upstream cells. So we got networks of interacting cells firing away.
Victoria:
Okay, that’s really interesting.
Dr. Klymkowsky:
Part of understanding it is realizing that the cell is all ready to respond to these signals. There are electrical and chemical gradients, ion gradients across the membrane surface. And as soon as he opened the channel, ions flow through the channel and caught change the behavior of the cell that responds.
And so, you know, if you were studying neurobiology and you would be going on to see how the cell signal is propagated down the axon. So that’s another interesting reaction. That’s distinct from how the neuro-transmitter works, though.
Victoria:
(Ms. Abdallah’s 4th graders – How do chemicals work? What are the causes of the chemical reaction for vinegar and baking soda?)
Okay. That’s cool. And you mentioned chemicals. So this is a good follow-up question, again from Ms. Abdallah’s 4th grade class. How do chemicals work? And then specifically they’re interested in the chemical reaction for vinegar and baking soda and what causes that reaction.
Dr. Klymkowsky:
Okay. So that’s, you know, so the idea that, I mean, do chemicals work? That’s an interesting question. But what are chemicals, is basically their collections of atoms in various combinations and the atoms are connected to each other via what we would call bonds. And those bonds, we can think of bonds is basically two, two atoms are connected, and the bond strength is actually determined by how much energy you have to add to the system to break it. Right. So normal molecules that have chemicals that are stable, the amount of energy in the environment is not enough to break the bonds. So they sit there. If we put and so that’s a, you know, a chemical basically would be a molecule of a certain composition because the atoms are connected to one another in a particular way, different atoms have different behaviors.
So we now can think about in the question of a particular chemical reaction of vinegar, which is acetic acid, and baking soda which is sodium bicarbonate. But the reality is what’s happening in that reaction is these two chemicals are basically stable by themselves, if I put them into water, I’m creating a reaction system. And so they’re now possibilities of reorganizing atoms that have stronger bonds between them. So, and what’s happening is that, as the molecule sort of rearrange, so this is a tricky question. It depends on how much you know about acids and bases and chemical bonds. But the simplest way is to say the two molecules that we add rearrange, and they rearrange into molecules that are extremely stable. The molecules, they rearrange into our water, which is very stable, and carbon dioxide, which is what the bubbles are. And the bubbles, because you have a lot of bicarbonate of soda, and as you form carbon dioxide, it’s not that soluble in water, so it bubbles out. Right. And so that reaction is all being caused by the fact that water and carbon dioxide have much stronger bonds than do the original molecules. And so, bonds are being broken and formed. And so they’ll end up with these stable components. So that’s a simple way. The complex way requires you to take chemistry, probably at the college level.
Victoria:
Yeah. Something that the fourth graders can do in the future when they get older.
Dr. Klymkowsky:
Something to let me look forward to.
Victoria:
(Michelle – Since you do research on neuron cell communication, do you know the status of spinal cord research with regard to repairing breaks?)
Yeah. All right. And let’s get back to some questions more about cell communication. This question is from Michelle. Since you do research on neuron cell communication, do you know the status of spinal cord research with regard to repairing breaks?
Dr. Klymkowsky:
Right. So this is not my direct area of study, but I do know something about it in the sense that in many organisms, the problem is that all of this partly depends on the nature of the damage to the spinal cord.
So you have to realize that in humans and most mammals, neurons, once they’re born, cannot replicate anymore. They are what’s called terminally differentiated. And there are no cells generally that produce new neurons in the central nervous system, which is your spinal cord and your brain.
So the problem becomes when I make a large damage to the spinal cord, I kill a lot of neurons. And the neurons are connected to one another through what are known as axons. So there are, for example, in your spinal cord, there are cell bodies in the spinal cord that send these axons down out of the spinal cord to your muscles controlling, whether they fire or not. And those neurons are getting inputs from your brain, telling you whether to fire or not. And you can imagine that’s a pretty long distance, and cells are small, the body of the cel would be small, the small 50 microns, a hundred microns across, you’re talking maybe three or four feet between your head, you know, part of your spinal cord in your brain.
And the problem in organisms that can, some organisms can regenerate a lot of function from such damages; mammals like humans cannot, in general. And part of the problem is when you have a damage to your spinal cord, there’s a lot of scarring that occurs. Certain cells start to proliferate. They make barriers that axons cannot climb through again. So these glial scars make it very difficult for neurons to come back and reconnect to their original targets. The damage will break the connections and either the neurons will die or they’ll, mostly they’ll die.
So to get regeneration, you would want to have neurons. You’d have to put in neurons, new neurons, that connect correctly to the brain and send their processes correctly to their targets. Now that’s a process that normally occurs as the fetus is developing, as you are developing in your mother’s womb, and later as you growing. And you can imagine it’s difficult to do it when you’re already an adult, the sizes involved are much larger, and yeah. So it’s a really difficult problem. People are looking at various ways to control muscles, you know, using electronics and various things, but that’s a very difficult biological problem.
I mean the organisms like newts, which have been used for a long time that can regenerate whole limb. Right. So you can cut off the leg of a newt and it grows back. And that’s, you know, that’s part of their evolutionary wiring that allows them to do that. And mammals don’t do that generally. There’s very little regeneration of that order in mammals. So it’s a tricky problem. People are working on it, but you can see that where the problem is coming from. Since those connections are initially built during the early development, when you are very small.
Victoria:
Yeah. Wow. Is that something that like stem cell research can do?
Dr. Klymkowsky:
So the idea of using stem cells would be to say, okay, so I can engineer cells. So people, what would, so with various ways of engineering cell, they can engineer cells so that they are like me. One of the problems with doing cells added to your body is your immune system is extremely good at detecting foreign objects, foreign organisms. Why? Because bacteria and viruses like to grow inside you and that’s not good. So you develop your immune system, which itself is extremely complex, can recognize you and not attack you, but it can attack foreign thing. That’s why, you know, organ transplants are tricky that you have to have a match, what’s called a match so that the surface looks the same.
It’s now possible to take cells from your body to re-engineer them. And those cells can go back to a state where they can produce various other types of cells, so that those are called fully potent cells. And the idea that many people, what we are exploring would be, can I take cells from your body? Can I differentiate them in culture? Can I make neurons or say, can I make a new kidney? Can I make any kind of cell I want and then implant them and hopefully allow them to grow to where they should belong? Now, of course, I have to get rid of the scarring tissue.
And normally I read up a little bit about this when I first saw the question, you know, if you can stop the scarring occurs very quickly after the damage. So you have to intervene very quickly. And then the question is, well, do we have the technology to repair it at the moment? You know, but you can see how people would start being able to do that more and more efficiently by growing neurons that they could transplant in. Now, the trick is to grow the right kinds of neurons that make the right kinds of connections and behave the right way.
Victoria:
Oh, wow. That seems very complicated, very challenging.
Dr. Klymkowsky:
It’s tricky, right? Because biological systems are extremely complicated, and because they’re the product of evolutionary processes, which are not based on, you know, an intelligent designer, but occur through a random mutation and selection, they can be very weird. Right. And so. To know how you can deduce how it works from first principle, you have to sort of go in and figure out how it works. Right? What’s there? What genes are there? What proteins are there? And this makes it inherently a trickier problem. Although modern methods are making it easier to do, right.
So, the question is how do you essentially poke and prod and replace parts of a system so that you fix it while it’s running, like fixing your car when you’re driving down, you know driving down the interstate. So, it will get there eventually, but it’s not a trivial problem.
Victoria:
(Sierra – In terms of neuron communication, is there research being done on stroke victims to establish new neuro pathways to restore lost abilities in stroke victims?)
Yeah. Speaking of other non-trivial problems. This next question is from Sierra. Again, in terms of neuron communication, is there research being done on stroke victims to establish new neuro pathways to restore lost abilities in stroke victims?
Dr. Klymkowsky:
Right. This is a question very much like repairing the spinal cord because your brain and spinal cord are similar tissues. Your brain is more complicated, but they’re both part of what’s called the central nervous system. And again, your problem is there are many different cell types in the brain. You recognize them and you recognize more and more of them because people are characterizing them at higher and higher molecular resolution.
And when you have a stroke, you’re essentially cutting off blood flow to a specific area of the brain. And neuron are, because they’re so active sending signals and responding to signal, they use a lot of energy, they need a lot of oxygen, they’re very sensitive, then they start to die when there’s a stroke, when blood flow to a region of the brain is interrupted.
So you have a lot of cell death and you essentially have to do the same thing we talked about before. You have to essentially have to rewire around that damage in a way that reproduces the original behavior.
It’s probably, you know, so we’re moving in a way from biology and neurobiology to what you might call biological engineering. And so now you’re sitting there saying, okay, so I basically sort of understand how the system works now. How do I engineer it, to fix it? Now you might do that by trying to replace the cell, or you might do it by sort of using electrodes and various stimuli to turn on and regions of the brain that are undamaged and essentially detour around the damage regions. And in some cases, people do show response after a stroke, they adapt to the damage. So you imagine like maybe I can engineered system that allows for better sort of indirect non biological control, but I could control it with my own brain. Right. I could say, I want to do this. And I take that signal and I use it to fire neurons in a specific area.
So that’s, I think, I mean, there, I am not a neurosurgeon or a neurologist. So, but that idea is the same basic problem. How do I circumvent the circuits that are damaged, so I can get the outcome I want.
Victoria:
(Chris – Is neuron communication research part of dementia and Alzheimer research?)
Okay. That makes sense. And then this next question is also about brain related things. Chris wants to know is neuron communication research part of dementia and Alzheimer research?
Dr. Klymkowsky:
Absolutely. So, what happens as you got older and this can be influenced by various factors, but again, what happens is various defects start to occur inside the nervous system for various reasons, or there’re accumulations of proteins that are not behaving correctly. You have a whole lot of cellular systems whose function is to deal with proteins that are unfolding if you.
So this depends on if you understand how proteins work. They’re the product, they’re encoded for by genes, they fold up to make various little molecular machines that do various little tasks, but they’re fragile. You know, they’re not like rocks. They’re more like elastic machines. And so, they can unfold in various ways. You have lots of systems in your cells that are designed to find unfolded proteins and get rid of them, repair them. What happens as you get older is those damaged proteins accumulate more and more, and they start interrupting neuronal communication. They cause cells to die. Right. And they block normal function.
And you know, there’re genetic dispositions, there’s all kinds of causes. Most many of which are not clearly known. but that idea of maintaining the balance of functioning molecules inside the cytoplasm is critical.
And that’s another very difficult problem to solve because you’re talking about a number of complicated interacting systems. So you have to manipulate that system in a way.
Victoria:
Yikes.
Dr. Klymkowsky:
You got to engineer it. You have to re-engineer it in a way, which means that you, when you perturb the cell, you don’t always know what. You may think you’re pretty sure you know what’s going to do, and then you do it. It does something else.
Victoria:
Oh man. Yeah. And then I bet you have to go back to the drawing board and come up with a different.
Dr. Klymkowsky:
You go to another idea. You think, you know, you go study it a little bit more. You see how it went wrong and decide whether you can get around that problem.
Victoria:
(Mackenzie – How does the organization of structures within a cell effect it’s function, behavior and efficacy of communication with other cells and biological components?)
Yep. And switching gears a little bit, getting back to some cell structure questions.
Mackenzie wants to know how does the organization of structures within a cell effect it’s function, behavior and efficacy of communication with other cells and biological components?
Dr. Klymkowsky:
Sure. Well, so the reality is thinking about the cells are, you know, so cells are these amazing objects, right?
So if you’ve learned some biology, maybe you’ve heard about the cell theory. So the cell theory is cells always come from other cells, right? Maybe a few billion years ago, there was an event where cells came into existence. That’s the current scientific model. How that worked exactly is not clear. But, since that time, you can show that all cells are related essentially. So there’s an uninterrupted flow of cell to cell, to cell, to cell from that original, those original cells to every cell in your body. So essentially every cell in your body has like a 3-billion-year-old history. And so, which is an amazing, an amazing thought.
So, inside the cell, there’s all these molecular machines, which are encoded for by genes. There are little proteins. I thought this is part of the thing, right? So the genes are present in the cell. They don’t mean anything without the machinery that they’re to decode them. That machinery is encoded by genes. So the question is, so the system is always running. And running of the system allows the information of the genes to be read out and use, but it’s not like the genes make the cell. The cell was already there. The cell was there running, the genes providing information for what to do.
So those genes, many of them encode polypeptides, which make proteins, which make little molecular machines, right. They are machines that control ion flow across the membrane. There are machines that control the replication of DNA; or machines that control which genes are expressed right, which ones are used, which ones are not used.
The whole behavior of the cell, everything has does, is controlled by these molecular machines. And when the cell itself is getting signals from itself, it’s talking to itself, and it’s talking to the cells around it. Right. So, it’s environment. So those, all those cell communications will lead to particular behaviors.
So we talk about cells that are differentiated. So you know that your body has neurons, which I’ve been talking about, or muscle cells or cells that line your skin, or the cells in your eye, or. So there are all kinds of cells. They differ from one another, because they express different genes and various combinations. And which genes they’re expressing will determine which machines they’re building and what behaviors the cells are doing. And there’ll be behaving depending on who’s talking to them. And, you know, they make signals, which they secrete to talk to other cells. They have receptors so that other cells can talk to them. Right. So you have this system with all these feedback systems going on that are producing the sort of behavior.
So, it’s hard to talk about it in generalities. What behavior are you interested in? Right. You know, so, and then you start breaking down the molecules involved in that behavior. Right? And so you start to see how the cell puts together those molecules in various ways to produce the behavior that you’re talking about. And that’s it.
And part of the reason that people study cells inside organisms, as opposed to just inside a laboratory dishes, is that cells tend to do things depending on where they are and who they’re talking to. So it all depends on what they’re supposed to be doing, and what signals they’re getting was what they’ll do, to a large extent.
Victoria:
Okay. The next set of questions is all about the work that you do with frogs.
Dr. Klymkowsky:
Right.
Victoria:
(Sydney – What kinds of experiments do you do on the frogs?)
So these will be, these sound kind of fun to me. This first question about frogs comes from Sydney. What kinds of experiments do you do on the frogs?
Dr. Klymkowsky:
We try to make sure. So we use frogs as a system in which to study the behavior of specific types of cells and specific types of cellular components.
So normally when we’re doing a frog experiment, we’re fertilizing a frog egg. And we are then putting in various reagents to manipulate the behavior of the egg, right, which will then divide and produce an embryo.
So we use reagents, for example, that will block the expression of a particular gene. And so we ask, well, what happens if we block the expression of that gene? Right. And we use various like microscopy techniques. You know, the cells form normally are proteins that should be made, you know, are genes that should be expressed, do structures like the heart or the kidney form correctly. Right. And so that’s the kind of study we’ve been doing for the most part, because we’re trying to understand how many different functions a certain protein may or may not have, what components are required to build a particular system, how does disrupting a particular component affect the building of that system?
Many of the genes that we look at have already been identified in human because frogs and humans are related by about 90 million years since that, or let’s say probably 250 million years since they differ. But that idea is that often the functions of proteins in the human will be similar to that in a frog, until we can draw a basic thing. It’s very much for basic research, as opposed to targeted research. If you really wanted to cure a human disease, it’s possible that information from frogs would be interesting, but at the end of the day, not useful because the process may be slightly different. Right. This is where you’re thinking about you’re re-engineering a system, you know, even little details, you know, a piston from a Ford engine will not necessarily fit into a Mazda engine, right? So it’s all a matter of how the parts have become specialized. And we started looking at it because we were working on a little system, part of the cell that gives it rigidity. That in experiments we did in culture, there were very little effects for knocking this out. So it’s like, well, it’s gotta be doing something. So let’s go into a more complicated system. That’s the major reason we use frog. Not everything could be studied effectively in cultured cells.
Victoria:
(Kelly – Why do you use frogs instead of mice?)
And this is a good next question. And something that I was thinking too while listening. Kelly wants to know, why do you use frogs instead of mice?
Dr. Klymkowsky:
So this was a great question. And this goes to the whole point of what are called model systems, right? So most people, I mean, the American people have been very generous to the scientific community, because they’re interested in curing diseases.
Right. So if you really wanted to be curing diseases, you’d study it in humans. And that’s not always, you can’t do that, right, for a wide range of reasons. One, because when you’re first starting, you have no idea what you should be doing and you’re going to cause more harm than good. If you were sure that what you were doing was cure everybody. It would be easy. There’s a, you know, so that’s the practical.
So for the practical reason, you can’t study humans. So you study organisms that are related to human. We study frogs because they develop very rapidly. So within three days of a fertilized egg, they’re little swimming around tadpole. And that means that we can do experiments very quickly.
Mice take 21 days from fertilization to be born. And most of the time you have to start building with that techniques used. You generate what it called, transgenic mice. You change the genes in the mouse, and then you look for the effects, and you have to then breed them and all kinds of shenanigans. So it can take a long time and they’re expensive. They’re expensive to maintain.
So we use frogs mainly because they’re really fast in development and you can do certain experiments very quickly. Right.
So every model system that people use, and that could be fruit flies, and nematode worms, and mice, and you know, zebrafish, they all have strengths and weaknesses. And so you use them because for specific case.
If you’re really interested in human, you eventually have to do humans because there are enough differences between even say our closest relatives, which would be chimpanzees or primates and mice. Although they’re both mammals, there are enough differences that say therapy built in a mouse may or may not work in humans. So you can see this in the example of the COVID vaccine, you may do original safety trials in mice. Just to make sure it doesn’t, you know, cause them to fall over dead. But you have to also do similar trials in humans because there are significant differences in physiological behaviors between different systems, because they’re adapted to different things. You know, mice live in one environment, humans live in another, but we use frogs because they’re very convenient and fast and easily manipulatable.
Victoria:
(Audrey – Where do you get the frogs that you experiment on?)
Cool. And another good follow up question about frogs. Audrey wants to know where do you get the frogs that you experiment on?
Dr. Klymkowsky:
So these are commercial breeders. We use a frog that was originally from South Africa. It’s called Xenopus laevis. And the interesting thing is it was originally used for pregnancy testing. because the way we, and they escaped it to California. So they were all over the place in California. But nevertheless. So if the urine of a pregnant women have a hormone in it, which will induce frogs to lay eggs. And so, that allows you to tell whether a woman is pregnant, and that’s an early pregnancy test.
But the frogs we use are commercial. We use them because they are very tough, and they resist diseases. So frogs should be fragile because pathogens can get through their skin. They normally have a mucus layer on their skin, which is why, if you pick one up, it’s slippery. And so toads are a little different, cause toads are live on land. Xenopus is sort of like a toad that went back. It was a frog, it went became a toad, then it went back to be a frog, a little confused.
Victoria:
Oh man.
Dr. Klymkowsky:
They’re pretty. We got them commercially.
Victoria:
(Limetra – How do you “perturb” a cell or organism?)
Okay. All right. This next set of questions are all about perturbing cells. So, the first question is from Limetra. How do you “perturb” a cell or organism?
Dr. Klymkowsky:
Well, this is this is a standard question. So the cell is a system, right? This is a very good question in the sense that a cell is as ystem.
So you have to do something that changes the behavior of the system. Now the simplest way is to put a drug on, you know. So drugs are a small molecule, typically that will bind to a specific protein in the cell or get through the membrane of the cell or they’ll bind to the membrane of the cell. And they’ll bind to a specific target protein, they’re like drugs, right. And so, you know, a drug, and that will affect the function of that protein or that system. And so you ask, well, what if I inhibit this enzyme, right? So an enzyme will catalyze a specific biological process. If I inhibit that enzyme, what happens? How does the cell, how does the behavior of the cell change? So you’re always doing some kind of perturbation.
In the new world of high technology, and you may have heard of CRISPR-Cas, mutagenesis, or any of these things. You can target genes in cells and induce mutations where you want them. Those mutations can affect the behavior of the targeted gene. And now you’re going to look at what’s the effect of that mutation. And , and you look at that with increasing levels of sophisticated analyses. So now we can take a single cell and basically determine which genes are being expressed in it. And so you say, okay, just does affecting this gene, how does it change the behavior of the cell? What molecules are active? What molecules are present? You can use microscopic techniques and say, well, where are things in the cell? Or have I changed that? You can watch the cell. Does it behave? Is his behavior different? So is it shape, morphology, different? All that kinds of stuff.
But the perturbation is basically anything where you go in and you change something from the way it was, very often it’s removing a gene, essentially, or changing a gene in a way that stops it from functioning normally.
Victoria:
That’s super cool.
Dr. Klymkowsky:
Yep. It is super cool.
Victoria:
(Jane – What are the typical reactions when they are “perturbed”?)
This is a good question, a good follow-up from Jane. What are the typical reactions when they are “perturbed”?
Dr. Klymkowsky:
Yeah. And this is a great question. And of course, it all depends on what you’re targeting. Right?
So for example, I can target a protein that’s required to turn on a specific gene, right? So if I say, I’m going to knock this gene out. Often people use the term knocking a gene out, which means that you’ve made the mutation so that that gene doesn’t function anymore. So that means the gene product that encodes is not made anymore. So let’s say if that gene product is a protein that regulates the expression of other genes. Then, I will see what happens when I change that.
So it all depends on what your targeted, right? If I target a cell surface receptor, a gene encoding its cell surface receptor, or that protein, I can affect how the cell responds to signal while its signal molecules released by other cells. Right. If I could target a gene that’s involved in, you know, so essentially capturing energy from the environment and using it to drive various reactions. I could, you know.
So remember there are about 24,000 different genes inside cells at least, and you know, they’re interconnected in various ways. So, it’s always a matter of what you think you focus on, what the process you think the gene is involved in and you target your, basically you target your analysis of the effects based on what you think the gene does.
The nice thing now is because you can look at every gene whose expression is affected, you can see things that you didn’t anticipate. Right? So let’s say I targeted gene and I thought, for sure, it’s doing this process. And then I see that if I knock it out, these other genes, which I never would have suspected are changing. Okay. So that’s part of the interconnectedness of the system, right? Genes are controlled by transcription factors, which control by multiple genes.
So it’s always a matter of looking. You think you know what you’re looking for to begin with, and you target your search there. But the nice thing about the modern world is now you can look at almost the whole cell. So you can look at what proteins are there by mass spectrometry. You know, there’s a lot of different possibilities now that didn’t exist before.
So you’re, all in all it depends on what you think the gene does, to begin with or the process. And then of course it’s the same kind of question, right? Does a cell, what is the context in which you manipulate the cell? Okay. If I’m manipulating the cell, let’s say I take a cardiac cell, a heart cell. Well, what does it do? If it’s in cultural, it doesn’t beat, if you could beat or not beat. So you could look at the rate at which it beat. And if it’s in the heart, you know, it’s part of a coordinated system. It’s talking to the cells around it, and it’s integrated with the cells around. It doesn’t beat independently. That’s not good, if the heart cells are beating independently of each other. Okay. And so, now you can look at more sophisticated effect, you know. What behaviors are occurring there.
For example, what happens if you do that to a neuron? Right. So the question is, can you see the effect of manipulating a single neuron? You know, these are all, you know, how does the nervous system work? It’s not one neuron, it’s probably many neurons in the network behaving in a certain way. So the context will also matter. But you could change the rate at which a neuron fires. You can change the rate at which it responds. It’s always context dependent.
Victoria:
Okay. Yeah. That makes sense. That seems kind of overwhelming in the number of things you can look at and the number of questions you can answer.
Dr. Klymkowsky:
Right. And that’s, and so people would normally really try to focus down on one question, because you can’t deal, you can generate so much data and it’s very difficult to make sense of it, right?
Because something changes. So say you do a perturbation. I knock out this gene. And I look, and I see the 300 or 400 genes, the level of their expression is changing. And it’s not uncommon for 300 or 400 genes to change their levels of expression. It’s not like I knock out this gene and that only that gene changes, like lots of things happen. Well, how do you know whether this change is meaningful, is physiologically significant, it has a functional effect? Or just because it just happens to occur, and there’s no really bad consequence for it happening? Right. So if it doesn’t really do any damage, there’s no reason to stop it. Right. And so, then you started talking about, you know, how is the wiring diagram of the cell organized, which is tricky.
Victoria:
(Amy – What kinds of viruses infect what types of bacteria?)
Yeah. And speaking of things that might perturb the cell or perturb the system, Amy wants to know what kinds of viruses infect what types of bacteria?
Dr. Klymkowsky:
So this is, again, a very, this is a very complicated question or a very simple question, right?
So essentially every cell type. If you want to be too general, there are viruses that infect every kind of cell. Okay. Bacterial viruses are called bacteria phage, because phage means to eat. So bacteria phage is viruses that eat bacteria. They don’t really eat them, but they go in, they take them over, and they use well, they do eat them in the sense that they use the bacteria to make new viruses. And so that’s what viruses normally do. Cause viruses are not alive, but a little selfish molecular machine. They exploit aspects of so cell behavior to make a machine that can replicate itself and carry a gene from place to place, or genes from place to place. So they’re completely dependent on the cell they infect.
And so there are lots of viruses that infect lots of bacteria. And essentially, you know, you asked your question, well, what makes one virus different from another? Well, the surface of the bacteria are different. So I need a molecular machine that could recognize this bacteria versus that one. Bacteria have lots of antiviral systems. Okay. So you have to fit, you know, so there’s a constant sort of interplay between viruses and bacteria. So what the CRISPR CAS system, for which people just got the Nobel Prize, is essentially bacterial immune system, derived from a bacterial immune system to fight off invading viruses.
So, every species probably has some set of viruses that are infected, and it’s all determined by, you know, you have to rec, by molecular interactions. The virus has to recognize the kinds of bacteria that it can infect. If it binds through the wrong bacteria, it’ll just won’t be able to replicate.
Victoria:
(Joe – What are molecular machines? Can they be modified to help people with paralysis?)
Okay. Yeah. That makes sense. I can see that.
And speaking of molecular machines that you mentioned when talking about the viruses, Joe wants to know what are molecular machines, and can they be modified to help people with paralysis?
Dr. Klymkowsky:
Ah, so this is sort of two different questions.
So molecular machines are. The simplest way of thinking of them is there, I mean, if you saw pictures of them, they do specific things, right? So the classic one that people really, I think, captured the imagination is the machine that catalyzes the generation of ATP, the energy store in the cell. And it sits in the membrane. And as ion flow through it, it turns this machine, and as it turns the machine, it brings the phosphate group, adenosine diphosphate. Yeah. See, this is where we could add a image of this. You could put in an image of this machine how it turns.
Victoria:
Yeah.
Dr. Klymkowsky:
It’s turning, and it’s catalyzing the catalysis of a phosphate group, and then the adenosine diphosphate molecule, and it releases that adenosine triphosphate molecule.
And it can run backwards. It causes the breakdown of the adenosine triphosphate molecule, and it pumps ions out of the cell. So you can get ions flow through it and just do one thing, capture energy, and then you can use that energy to pump ions out.
So there are a number of these machines, right? The way DNA is replicated is a little machine. That’s going to crawl along the DNA. It’s going to capture a nucleotide, complimentary to the one with DNA, and catalyzes addition.
So if you think about machine is basically anything that does something, it does some form of work. So these, you know, uses energy in those forms. It does a form of work. So there are a lot of them.
Now, the idea of making a machine that can help with paralysis would be something that would be able to, it’s almost the idea of a nanobot where you would build some little thing that might recognize and say, if you were talking about glial scarring, maybe you make a little machine that can recognize a glial scar and digest it. Right. So it would be specific for the scar and it would eat away at the scar tissue and allow neurons to grow back. That would be sort of an idea of a machine.
But they really are a little machine. You can see pictures of them, because now there are methods that make it a lot easier to see pictures of substructures.
And even a classic one would be the ribosome, which is the molecular machine that takes an RNA molecule, that’s the product made by complimentary to a gene and then translates it into a polypeptide. So it grabs along the thing and it ratches its way along and it synthesizes the polypeptide. You know, so it’s a really little machine. Right.
And so, that idea of thinking about, well, how they work, how I could modify them, how I could target them to do specific tasks. That would be what Joe’s thinking about. What if I want to try with paralysis? Well, maybe I need machines that clear the scar. So I inject these little nanobots, which I built, you know, atom by atom or whoever I want to build them. And now they start breaking down the scar tissue and in a controlled way. That would be a sort of idea of how you would do that.
Victoria:
Okay. and just to clarify, the non-modified machines, the regular machines in the cell, those are made by, they’re coded for by specific genes, is that right?
Dr. Klymkowsky:
They’re coded for by sets of genes. Right. So it’s important to realize that, you know, so they’re often coded for by multiple genes, right? Because they’re proteins, which can have multiple subunits. Each subunit is encoded for by one gene. Right? So for example, one subunit may be involved in recognizing a particular region where the machine should be in the cell. Right. So it has a little recognition sequence on it, and it recognizes the machine. So if we think about a standard eukaryotic cell, which has a nucleus, right? So proteins are made in the cytoplasm. Some proteins stay in the cytoplasm, some proteins go into the nucleus. There’s a little machine that controls which ones enter, and that machine can actually partially unfold proteins so that they can get through the pore, there’s a nuclear pore, get through the pore into the nucleus.
Right. So. Every task can be broken down into, I need to do this, and I need to move this here. I need to, you know, move that there. I need to assemble this structure. I need this structure do this process. Right.
Victoria:
Oh, cool. Okay.
So now we are going to switch gears a little bit, and there’s a bunch of questions all about you and your career and what you like to do. These are always fun.
Dr. Klymkowsky:
These will be harder.
Victoria:
(Jen – What has been your most exciting discovery?)
This question comes from Jen. What has been your most exciting discovery?
Dr. Klymkowsky:
What’s my most exciting discovery. Hard to say. Or any of them exciting?
I mean, exciting discovery. I mean, you know, in science you’re always trying to do a puzzle, right. So essentially, they’re all puzzles. Right. And you’re trying to figure out how to manipulate the system to answer a specific question, or you’re trying to look at the specific behavior.
The one I particularly liked was when we were studying a molecule that’s normally involved in anchoring two cells together, and this was a molecule, the family of protein, and it also a related protein is involved in controlling cell behavior. And so it turns out here’s the protein that you think is in the cytoplasm doing this thing about cell-cell adhesion. And you discover, oh, look, it’s in the nucleus and it’s controlling gene expression. Right? So often you think a protein does one thing, you discover it does something else. Right.
You know, so my career has been full of looking at little tricks and trying to figure out, well, what’s going on here. Right. So how does this work? And, that was, you know, you always find interesting things, I think. And sometimes, you know, some people are driven by curing a disease. That’s trickier because you only have one good answer, which is curing the disease. Because we’re always trying to figure out how various parts of cells work. And to me, that’s, you know, those kinds of things become very interesting.
And the other things that we’ve been doing, you know, that I like or thinking about how best to teach people and really start thinking about what does it mean to learn something, why you teach one thing not the other, what is the students supposed to do with it, how do you simplify what can be seen as way too complicated to sort of basic principles, which are good for understanding, you know, a certain level. The trick is, you know, if you want to, re-engineer a system, you have to go into these amazing details, right, which you don’t need, most people don’t need.
Victoria:
Yeah, unless they’re the ones that are doing that.
Dr. Klymkowsky:
So that’s very right. Unless they’re doing the engineering, they don’t really need it.
Victoria:
(Jane – What is the most interesting thing you are working on now?)
Yeah. That makes sense.
Let’s see, this next question comes from Jane. What is the most interesting thing you were working on right now?
Dr. Klymkowsky:
Well, this actually comes from early work I did when I was a post-doctoral student, which was that I was looking at the function of these or what disrupting these intermediate filaments we’re doing and so. Not much was happening. And then recently I’ve been reading the work of Yassemi Capetanaki, who’s a Greek person studying these proteins in various systems in mouse. And she’s been finding that the cells are generally full of proteins that help other proteins fold, they called chaperones. Right? So they’re called chaperones because what they’re doing is they’re trying to make sure that proteins don’t make inappropriate relationships. So what a chaperone does is keep you from doing, you know, hanging out with the wrong people. So chaperones will take proteins that are unfolded or misfolded, and they’ll unfold them and let them refold again. They have to fold on their own. The chaperone can’t do everything. But that idea that when you disrupt the system, you perturb all the interactions in the system. And sometimes, the phenotype, the effect you see is not due to the absence of the function of the protein you deleted. It’s due to the fact that proteins are now making inappropriate interactions. They’re breaking systems that they shouldn’t be involved in. Because their partner’s not there or whatever, all these kinds of components.
So what I’m particularly interested right now is just looking at how widespread this effect is, what happens if we increase the amount of chaperones in the cell where we’ve made a genetic modification, and does it rescue the phenotype or does it not? So you know, we’re a very small lab at the moment, but nevertheless, we’re having fun, trying to get this to work. So we’ll see.
Victoria:
(Sam – What is your favorite thing to study?)
That’s really cool.
Okay. This next question is from Sam. What is your favorite thing to study?
Dr. Klymkowsky:
Well, that’s tricky because, you know, partly it’s, I like looking at mechanisms, I like looking at the effects of perturbation, you know, I like trying to see what happens when you break one system, what does it do to behavior. In Xenopus, we can, what’s nice about xenopus is that it develops very fast, and the signaling process that are involved in essentially taking a circle egg and turning it into a little tadpole are reasonably well known. And so it gives you, you can see where you affect various behaviors, much more easily. So I like that.
The other thing I like is thinking about how students think, right? So and trying to identify these key ideas that explain a lot, or at least provide a context in which you can explain a lot. Right? So you can understand a lot, if you want to go further, this gives you the foundation. So looking for those biological foundational processes, and how you teach them, like what’s important for a student to know. That’s again, another, that’s another thing that gets my interest.
Victoria:
(Chris – Why did you choose biology?)
Yeah.
This next question comes from Chris. Why did you choose biology?
Dr. Klymkowsky:
Partly what people, you know, it’s like, what resonates with you? You know, what do you find interesting when you do it? I got lucky. I got into working in a lab when I was an undergrad and I just loved doing it. Right. There’s something about it. There’s something about making predictions. It wasn’t so abstract, like much of physics seemed to me to be abstract. At least my view of it was. Chemistry, you know, it’s hard to know why, you know, it’s like, that’s part of why. If you’re a student, the best thing to do is to test out various kinds of things and see which one works for you. It’s not like most people have a really good reason for what they do, what they do. They sort of stumbled into it, they discovered they liked it, they were pretty good at it, and it was rewarding. Right.
And so do I choose biology? I got lucky, you know, I found myself in a situation where I could have fun, you know, and it was interesting. That is really important to testing because, you know, we have an issue that some people really love biology, but they don’t like working at the bench. They don’t like doing experiments. Right. And that’s something really important to know. There are a lot of careers. For example, if you were interested in science and biology, they were a lot of careers that you could follow that are based in biology, but don’t necessarily mean you’re working at the bench. I like it, experiment works. It’s like, oh, cool. And the problem is often experiments don’t work. So you have to do them multiple times, and you have to, you have to be interested enough to be able to get back and do it again when it doesn’t work. Right. And so you, I don’t think you pick it, you know.
On the other side, there are people who really want to address a certain problem. Right. I never felt that way. I felt like I was just like to do biology. I admire people who want to solve a particular problem, but, you know, and I think that’s why you really want to seek out experiences, volunteer and things like that, because you may discover that you think it’s a great idea, but you don’t like doing it. Or there’s something that you really like doing, you never would have thought of.
Victoria:
Yeah. Yeah. I’ve heard a lot of that story in particular, you did something that you never thought you’re going to like, and then it became your career. That’s pretty common.
Dr. Klymkowsky:
Yeah. It’s a very common, it’s very common because a lot of things are interesting. And biology can, is sort of more hands-on. And you know, when I first went, you know, for a long time, it’s also been something that you could do more or less by yourself in a way, right. You didn’t need a big group. Now, if you think about people doing high energy physics, you know, they’re not colliding things in their backyard by themselves. Right. They’re working in teams of hundreds, of thousands of people. They depend on expensive machines, you know. So there’s a lot of factors that go in, and some of it, a lot of it’s just luck, you know. Where did you find an opportunity to do something and did it work?
Victoria:
(Kelly – If you could be the size of something only seen under a microscope, what biology thing would you go look at up close?)
Yeah.
Okay, this next question is one of my favorites. It’s a really, really cool question. Kelly wants to know if you could be the size of something only seen under a microscope, what biology thing would you go look at up close?
Victoria:
Well, this is two different things. One is which one would I want to be. The other is which one would I like to look at.
I’d love to be able to go sort of looking inside the nucleus and watching all the things that are running around and going. Because that’s one of those things where people get this feeling, that everything is so deterministic, that things know what they’re doing. But in fact, you know, at the molecular level, everything is being driven by random noise. It’s like thermal motion is driving. And a lot of times when people illustrate something, they don’t do it correctly. Like, there are many, many collisions between molecules that don’t do anything. You know, when you’re waiting for the right collision to do something. Now they, things are going really fast.
I’m trying to think of what’s my favorite microscopic organism would be, I don’t know. There’re so many cool ones. There’s a great video by a guy at UCSF, I will find and send it to you. And there are all these weird, you know, unicellular organisms that are just too cool for words. Right. Rotifers are particularly wacky, you know. And there’s a lot of those that you would love to, I don’t know whether you want to be them. They don’t seem to have much of a personal life. But nevertheless, you know, there are a lot of really amazing structures that the organisms that do phenomenal things. And, so I think, there would be a lot to see at that level.
Victoria:
(Limetra – Do you teach classes?)
Nice.
And now we’ll switch gears a little bit and we’ll talk about your work on how people learn. So the first question to kind of lead us into this topic is from Limetra. Do you teach classes?
Dr. Klymkowsky:
Yes, I do. I’ve been teaching, most recently, teaching what’s called Developmental Biology. That’s the way systems of cells and organisms develop. Right? So the way I teach it, as people often think of cell like microbes as being individuals, but often they can collaborate and the processes by which they collaborate are very similar. And so started looking at all those, talking about those processes, how did they work? How do cells talk to each other? How do they form different structures? And then that translates into how embryos develop? How animals and plants develop? I mainly talk about, I mainly teach about animals, cause I don’t know anything about plants.
So, yeah, those are fun because you’re trying to think about what’s the real important thing to know. It’s always about, what’s the really important thing to take away as opposed to the details of fruit fly development. You may never ever use them again. Right? But you can learn about processes that are similar in various organisms. This is like a theme, right? This is one way something can work. And so you can see those ways things can work and you anchor them, essentially anchor them in the sort of molecular cellular behaviors that you know about, that you may have learned before. It’s like, the last course that our students are required to take molecular biology.
And I have taught Introductory Biology, which is also fun to teach because once again, you’re thinking about what’s really important, what’s not important, you know. What am I, you know, don’t make me memorize, you know, the amino acid names, right? It’s just a waste of time. It’s particularly a waste of time now because you can look them up. Right. And so, you would only memorize them if you were using them all the time to do something. Right, because then it would just make you more efficient. The only reason to memorize them would be to become more efficient at a task you’re doing over and over and over again.
Victoria:
(Joe – In terms of learning biology and other sciences, what do you believe are the biggest roadblocks hampering people’s understanding? What can be done to reduce or remove these roadblocks?)
Yeah.
This next question from Joe is a good follow-up to this discussion. Joe wants to know in terms of learning biology and other sciences, what do you believe are the biggest roadblocks hampering people’s understanding? And what can be done to reduce or remove these roadblocks?
Dr. Klymkowsky:
This is a great question, you know. And my considered opinion, which is not reflected in the way everybody teaches, is that you want to strip away unnecessary detail, and you really want to focus on making sure people really understand the core ideas. Right?
So, you want to identify what those core ideas are, what they’re used for, why they matter, and then really make sure a student understands them by letting them use them in a number of contexts. And I think some of the biggest obstacles is when you take a class, and you’re taught things that don’t seem to have any relevance to what you’re interested in.
And I know that it can be difficult. I didn’t really like classes, in part because I didn’t always understand why I was being forced to learn something that didn’t seem relevant to me. And I think that all this comes from my background. My parents are immigrants to this country and I’m the first person in my family to go to college. And, you know, I think there’s a, you learn almost by osmosis from your family. What’s expected, you know, what’s normal, what isn’t. And if you don’t come from, you know, certain people come from certain backgrounds, they can think that the problem is with them, not with the design of the course. And, I’ve come to believe that it’s almost always in the design of the course.
Right. But you know that the course hasn’t been really, the course is teaching things because they were taught before, not because they make sense to teach or they’re necessary. And so I think a big obstacle is getting people to see the relevance. One the story I normally, I also tell them, is that how you experienced something is very, very personal. So when somebody tells you that something is really interesting, That’s not good enough. In fact, it can be sort of exclusionary. You may usually not find it interesting, because you don’t have the background necessarily to find it interesting. It’s the instructor’s job to tell you why it’s interesting. So they have to prepare you. And you know, if they’re presenting a surprising behavior, they actually have to prepare you for why it’s surprising. Because if you don’t find it surprising, it doesn’t have any impact then. Right. So you know, the instructor has to think beyond their own experience. Why is this valuable? Why is it important? Why is it interesting? Where does it come from? And. You know, that’s sadly not present all the time.
And sometimes a big obstacle is when people think they have to cover something in a class. Right. But the course has to get through certain material rather than taking time to really go back and explain when you discover that, there’s something that people didn’t understand. That requires sort of a foundation of other things to get why it’s happening. Right. So you’ve got to back up. So you can’t feel like you were in a race to finish the course. And so that’s one of the advantages of being a professor, which is that, you know, you’re allowed to do whatever you want in a way. And don’t tell anybody, that’s a secret. But it also gives you the flexibility to really value learning, because you’re not being told that you have to finish, you know, this content doesn’t really have to be completed. Mainly in part from a realistic position, most people don’t rely on you finishing it anyway. You know, if you’re taking a subsequent course, if it’s really important, they’ll go over it again. But more important from a practical point of view, there’s no point in covering something if students don’t understand it, or they don’t understand it’s relevant.
And, so to me, that’s the big obstacle is thinking about what’s needed to really understand something, and let people practice it, and giving them feedback about it. And, you know, that’s the trickiest part. It’s like getting students to tell you, I didn’t get this. And even more to coerce them into telling you what they did think. I thought this. Because you can’t help them fix it unless you know where they’re coming from. So the more people, you know, it’s not a sign of ignorance, it’s a sign of, this is what I thought. You know, why does it, or does it not work for this problem? And what do I have to do to fix that? Right. And we’re all in that. Right? All experimental scientists run into things that they’re pretty sure they understand how they work and then they discover they don’t. Right. And so you should, in your learning, it seems to be, you should take a scientific perspective, which is, I think I know what’s going on, but I’m not sure, let’s test it. Right. And you tell me if it works or not, and if it doesn’t work, why doesn’t it work, right. So to me that I think those obstacles are basically presuming that people know why something is important, rather than telling them why or showing them why what was important to tell them, it’s more important to show them why.
It’s like assuming that you’re, you know, don’t treat students as if they’re already part of the club, show them how to become part of the club if that’s what they want to do. Right. But don’t let them think that they’re excluded from the club. The entrance to the club is because you want to be part of it. Right. And you know, and so think about the course, think about what you’re teaching that way. I think that’s the biggest obstacle.
Victoria:
(Sam – Within the context of science and science fiction, l was once told that anything that humans can imagine will one day come true. Do you believe that is true?)
Yeah. Yeah. That makes sense. That makes a lot of sense.
All right. And then this is our very last question from Sam. Within the context of science and science fiction, I was once told that anything that humans can imagine will someday come true. Do you believe that’s true?
Dr. Klymkowsky:
Sadly, I don’t. And the world is constrained. Right. That’s part of what’s hard about existence, right? I’m not particularly that excited about getting older. You can look up at the stars, and see how cool they are, and realize you never getting there. And nothing that happens on them is going to affect you. It’s like real. I mean, there are amazing observation. Probably the most, for me, aside from recognizing how old the earth is, is there’s a Hubble Deep Field image where you look at a smaller part of the sky and you see billions of galaxies, each of which with billions of stars. They have no impact on you whatsoever. You know, so, the world is constraint, right? Certain things are not possible. The laws of thermodynamics seem pretty rigorously established. You can’t make a perpetual motion machine, organisms don’t live forever, the speed of light is, you know, as fast as you can go, basically, you know. And there’s sort of, there are things you can do, I mean. That said, what can be done is pretty amazing.
Victoria:
Yeah.
Dr. Klymkowsky:
Right. So how, you know, how people start to bend, you know, and manipulate the universe is pretty, we were just talking about a while ago, you know, little nanobots or whatever, where you can imagine, you know, building little molecular machines that could do things.
You know, what the limits are. It seemed to be more than broad enough. I mean, the problems with the universe is we live with other people who are not necessarily rational. And, the world doesn’t nor will always work the way it should in quotation marks. You can’t, you can’t fix everything. Right. And you can’t reverse like, you know, life itself is one of those things, you know, it’s like you can’t, once something is dead, it’s dead. It isn’t coming back. Right. And. That’s one of those amazing things, you know, that continuity of cells from the origin to now is unbelievable, but that, you know, once that’s lost its heart, you can’t reverse it. Right. And, it’s probably, that’s probably one of those impossible things. It’s hard to always say what they are, but in physics they’re fairly straightforward, and physics and chemistry, you know what those rules are. Right. You know how gravity works, basically. I mean, at least you may not know it in the perfect theoretical view, but you know, basically what’s going on. You know how fast things can go. You know which way reactions will go. And so certain things can’t be circumvented, right, by just imagination.
I mean, that’s one of the problems with science fiction is that if you think too much, you realize, oh, you’re not going from one place to another that fast, you know. By the time you get there and you probably don’t know why you wanted to go there to begin with.
So, yeah, no, I think that the fact that the world is constrained is one thing. The fact that we haven’t even come close to a lot of the limits is another.
Victoria:
Yeah. All right. Well, that is all of those questions.
Dr. Klymkowsky:
That was pretty amazing.
Victoria:
Do you have any questions of your own for the listeners?
Dr. Klymkowsky:
Oh, no, I don’t think I have questions, but I am interested in how people understand science. So I’m interested in what things people find most mysterious, right. Or what people are confused about. I mean, that’s the kind of stuff I’m really interested. What are the top things you think are true, that aren’t true.
Victoria:
Oh yeah. I bet there’s a lot of really great things out there that people think that aren’t true.
Dr. Klymkowsky:
Yeah, I know it’s, you know, and we live in, you know, so it’s like, it’s harder and harder to disconnect, because you live in this world of the science fictiony world or this weird claims world. Right.
Victoria:
Thank you. This is fantastic!
Dr. Klymkowsky:
Thanks! That was fun.
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