Making Life Happen

Dr. Biology:

This is Ask A Biologist. A program about the living world. And I'm Dr. Biology. On this podcast, we talk a lot about DNA - deoxyribonucleic acid. It seems to grab our attention because it stores all the information about living things. It is the ultimate instruction manual, packaged in an unbelievably small size inside almost every living cell. But DNA is only the start of the story of 'life' because it needs something to actually help build things and give instructions to do the work inside living organisms. It needs RNA - ribonucleic acid.

Our guest today is a big fan of RNA and he is also a scientist who has a storyteller writing for Wired magazine The Atlantic, as well as other publications. And I found out yesterday he is a fan of history. Brandon Ogbunu is a professor at Yale University. He's a computational biologist who spends his time researching ecology and evolutionary biology. His work explores a wide range of areas, including the causes of disease. His career path and his numerous accomplishments are worth a visit to Wikipedia, and we'll include a link in the show notes. So, you can read about them.

Today, we're fortunate to have him in the studio because he is visiting ASU to give a talk titled “Interactions versus Everything Complexity, Disease, Contact Genes (and the space in between). I'm looking forward to our conversation and I hope we learn a bit more about the story of RNA. We might even get into some wordplay in this episode.

Welcome to Ask a Biologist. Brandon, I really appreciate you sitting down and talking with us.

Brandon:

Dr. Biology Great to be here. Thank you for having me.

Dr. Biology:

Let's just start off with the big question. We talked about DNA and more importantly, RNA, but not about the important job that RNA has in cell function and the evolution of life. So, can we talk a little bit about RNA? Can we set the stage? So to speak, as a storyteller?

Brandon:

Yeah. And to this, you know, I hearken back to my undergraduate thesis, right, which is entitled The Liberation of RNA, which some of you have become familiar with. And part of the reason why I called it that when I was in college and part of the reason why I think about RNA in that way is because you think about the way we talk about certain aspects of biology in life. 

And I feel like DNA has always been center stage. Everybody loves DNA. Your DNA is on the marquee at the show. DNA feature in DNA. DNA is on the cover of the magazine. Everybody knows DNA. And I feel like RNA has been this kid sibling that hasn't quite gotten the attention it deserves. And I think the good news is, in the last 20 years, that's begun to change. People now understand what makes it so powerful and important because we have a new understanding now of the way information works in life.

Dr. Biology:

Right. You know, you go back to your DNA and I said, you know, it's an instruction set, it's an encyclopedia. But if it sits in the library and never gets used, what good is it? So here we bring in RNA and messenger RNA, and they're actually doing the work.

Brandon:

That's exactly right. So, like long-term storage DNA is powerful. And you know what? I'll go ahead and say it. DNA, I think, is the most powerful and important piece of information in the universe. So, I’m not against DNA. I'm on its team. I love it. I'm with it. There’s a reason why It's the basis for all cellular life on Earth that we know of at the moment because it does this remarkable job of encoding this information, but by itself, it just sits in the cell and doesn't do anything. 

We think about the exciting and dynamic process of the way a cell works and the way a person works and the way a plant works and the way a microbe works. That's because biology is dictated by turning things on and off at very particular times. From the breakfast that you ate to the dinner that you eat to sleeping and walking, it requires that you turn genes on and off in these very, very rapid ways in response to the world that we're living in. And RNA is really a very critical component to taking that information in DNA and actualizing it and animating it. Right. So, that we can actually do these things. 

Dr. Biology:

Right. For example, RNA is out there, but especially messenger RNA goes out working with ribosomes. What are we going to do? We're going to make things right. We're going to make some proteins without those proteins, without those signals, without those things that are going throughout your cell and then outside of your cell to the rest of the organism, whether it be a human, a cat, a plant, you know, fungi, whatever you want to talk about, without that, it all stops.

Brandon:

Yeah. So, when we think about the flow of information from DNA to RNA to protein, and you might have seen a picture where you have DNA with an arrow to RNA with an arrow to protein. We call that the central dogma of molecular biology. And really all it means is just a picture that tells you how information flow happens in a cell. And so protein is another one that's gotten a lot of attention. You know, we know about protein from our diet. They're actually doing the work in the cell. They're the ones that are actually breaking down the sugar in your diet. And they're the ones that are doing a lot of the heavy lifting physically in a cell. 

So, we know them. RNA has been caught in the middle, and that's one of the reasons why it's been underappreciated. And part of the reason why it's under-appreciated is that like messenger RNA, it, relatively speaking, short-lived DNA is engineered to last a long time. That's why it's the basis of heredity. RNA on the other hand is relatively short-lived. It does its job; it provides instructions for proteins to make typically and has other functions as well. But the main one is messenger RNA is basically saying, hey, this is what we need to make protein-wise, let's make it. And then RNA disappears. Right.

Dr. Biology:

Unsung hero.

Brandon:

That's right. You don't see it, even though it's responsible for all the things that are happening.

Dr. Biology:

That's when it's doing everything. Well, let's say as according to plan. But sometimes things don't go according to plan. And that's where we talk about mutations. And I always have to say this when I bring up the word mutations, a lot of people have a very negative view of mutation. The reality is mutations are both good and bad, and sometimes they're just they don't do anything. Let's talk a little bit about mutations and evolution because actually, those mistakes were important.

Brandon:

Oh, I mean, it's like a lot like life, right? I think to make any discovery of anything you want to meet a new friend, you can identify a new recipe that you like. It's oftentimes because you didn't have what you needed it. You tried something else, but you put some applesauce in your pasta by mistake and all of a sudden you got a special new recipe. And I think biology works the same way. 

Mutations, the vast majority of them do nothing. We think they don't actually bother anything. When you get one of these kinds of changes in your DNA, for example, we don't notice them at all. Mutations are happening all the time in our bodies, and we don't notice them because they don't have an effect. But a small fraction of mutations can do one of two things. They can cause problems, right? They can cause errors, or occasionally they can actually do something like we talked about with this apple pie. You know, with this pasta. They could actually do something good. And those are a very small fraction of them. So, this is why studying mutations is so critical is they're responsible for a lot of problems. 

So, for example, genetic disease is caused by mutations in DNA that is then transcribed into RNA that often gives you proteins. So, you might have heard of sickle cell anemia, for example, which is a disease caused by a mutation in hemoglobin [found in blood]. Right. A very important protein. But sometimes evolution works because it identifies a novelty, a mutation that allows you to do something different or better, right? Or allows you to kind of survive a condition that's very, very challenging. So, we shouldn't look at mutations as all negative. It's just kind of a change. And depending on where you are and what context you're in the world you're in and where you're occupied, it can be good or bad, right?

Dr. Biology:

And when you talk about mutations, they have to have some kind of final form that actually is still functional. And the reason I bring that up is you're introduced - we're at a lecture at a major university with a roomful of scientists and you introduce a word game. I had not played this game. I have to admit it was really interesting because it's you know; it's called the Ladder game or some people might know it as doublets or word links. 

And what was interesting about that is it really made it clear that you could make changes in this game. But they have to be changes with meaning. So, let's talk a little bit about this word game and mutations and how this becomes so important when we're doing our science and we're looking at how biology works.

Brandon:

Yeah, I mean, I think there's many important lessons in this word game. I first read it from one of my scientific heroes in evolution who used this word game to describe how evolution happens little bit by a little bit. And that's important for a bunch of reasons. This was a fancy, smart mathematician, a biologist named John Maynard Smith, and instead of using fancy mathematics, he used this word game to explain a critical concept.

And so I borrowed that as a way to talk about my science. You never want to talk about it any more complicated than you have to. Sometimes, you know, you have to actually use the math because you're talking to mathematicians. So, you try to make a particular point. And if you talk about RNA, sometimes you have to talk about kind of, you know, you know, individual atoms depending on who you're talking to, but not even sometimes you can actually describe things in basic terms. So, what he said was this you take the game word ladder where the idea is you start with a word and let's just say word w-o-r-d, right. 

And the goal of the game is to take this word and go to another word, changing one letter at a time. So, you have w-o-r-d and I want to change that to g-e-n-e and gene. Now, those are different words. The question is, how do I get from one of these words to the other changing one letter at a time? And what he said is and this is the way evolution actually works, how mutations work is you can identify steps that gets you from word to gene. One letter at a time. Where all the words in between make sense. So, for example, we can go from word to wore, change that D to E to wore to gore. Right? g-o-r-e, gore to gone g-o-n-e. And then you flip that o to an e, you get g-e-n-e. 

And those are mutations that do that. And like I said, just like with some mutations, some mutations you're talking about word w-o-r-d, maybe the first mutation is, I don't know, you know, gord and you know, in American English, right? That's not really a word we use. Not really. You know, maybe sometimes, but like, not really. You know, that's not like a common word, g-o-r-d. That'd be a mutation that gives us a mistake. Doesn't help us either. Doesn't help us or even maybe harms us. Right. 

So, there's a lot of mutations that aren't helpful, but sometimes you find that w-o-r-d to wore, and that now makes sense that next word makes sense. And so evolution works by moving step to step such that each of those individual words make sense. And those mutations mean genes that makes sense are RNAs that make sense and proteins that make sense. And using an algorithm like that, using a tool like that works like the word game evolution could come up with all kinds of new solutions for problems.

Dr. Biology:

Right. And I'll actually leave the audience with one to play with. They can start with cells. Right. And try to end up with human.

Brandon:

Oooh...

Dr. Biology:

Okay, how many? Not going to give an answer here. You guys can try it out.

Brandon:

That’s a good one.

Dr. Biology:

Okay. That makes a lot of sense. So, if you have a mutation that doesn't do anything, fine. But most importantly is you need to have something that doesn't basically cause enough harm that the cell can no longer function. So, I mean, basically, we're talking about back to the words. The words had to have some meaning. They have to still work. I love that. 

So, you're a storyteller. And I suspect that in the world of evolution because that's where you, your view on the world comes from that perspective. But you're a storyteller. Are there some unexpected plot twists that you have seen past, present, or future phases of evolution? Let's talk a little about those unexpected twists.

Brandon:

Mm hmm. Mm hmm. Yeah. I think the great thing about evolution as a science and I think the challenge of evolution of a science is that there are rules that govern the way things evolve. Right. We understand, like I just told you about the word game, right? There are things that we can understand about what the rules are, how mutations happen, what the rate of mutations is, for example. And we can describe evolution and populations of things. So, we have a lot of fancy and smart rules and tools to understand [how] evolution works. But the beauty of it is that it's nothing but surprise. 

I can't tell you for sure what's going to happen with a given species of bird. There's a lot of things that I have to learn and understand about the world in order to be able to make a prediction, right? So, evolution is full of surprises and, you know, there's an old analogy, right? Like they say that if you replayed the tape of life is and you started it over again, you would get a completely different set of solutions. Maybe we may not be here, or we would look completely different. And that's what makes evolution so exciting. 

It's a story of surprise and kind of like drama and excitement. And so, I think it's full of it. I think we see it everywhere. We think about even serious things like COVID-19 pandemic, for example, right? Which, you know, was such a serious, serious thing and a lot of other diseases. And being able to understand, for example, how those populations went from Beta to Delta to Omicron, I think Omicron in particular was a very, very surprising one because Omicron acquired all of these different mutations that did not exist in the Beta strain or the Delta strain or the original strain 

And that was very, very surprising to us. And I think we're still trying to understand how that happened. And we do have some ideas about going back to HIV. Right. Which, you know, of course, was a major, major problem. Part of what made our understanding of HIV so important from an evolutionary perspective is not only the origin of it, which was a big, big mystery. Where it came from is related to a virus SIV. Right. Simian immunodeficiency virus. 

But the reason why we've been able to treat HIV effectively is because we identified combinations of drugs that actually make it very difficult for HIV to evolve. So, by understanding evolution, we now can engineer drugs to prevent resistance, and that's helped a lot of people live a lot of healthy and happy lives. And I think it's a triumph of this kind of science. So, I think that's the beauty of evolution, is there's so much surprise in it. It's all these glorious things. It's responsible for the diversity of life and all the beauty and the plants that we see and the beauty in the animal species that we see. 

But it's also responsible for a lot of the problems that we're having. And even though it's surprising, there's a lot of things that are hard to predict, there's still rules that we can learn that can help us understand it, to help treat disease and perhaps even understanding how we'll respond to things like climate change.

Dr. Biology:

Climate change. How is evolution going to have an impact on climate change?

Brandon:

Yeah, So I mean, I think climate change describes a whole host of global changes that are going to happen in a lot of different places. So, it won't look like one thing in one place. But for example, you take the, you know, the term global warming. Let's just say in some setting you're going to have higher average temperatures than you would have. Right. We now know because of the way the world works, because of warm places, the types of adaptations that organisms have to have in order to be successful in warm climates. 

We know how cells evolve. We know how bird feeding evolves. We know how diets evolve in high temperatures versus cold temperatures. We know that. And so, we can begin to think about, okay, so maybe now we'll see more adaptations. So, for example, in a hot climate organisms have to retain water. Water is scarce in a lot of places, right? And the hotter it is, you risk losing your water. So, we could actually make the prediction now that, okay, we're going to have species that adapt by retaining more water. Another thing we can predict is things like, okay, well, this is an issue for disease, right? Because mosquitoes only live in certain climates typically. And, you know, they're pretty adaptable and we see them in many parts of the world. But if you see the climate associated with mosquito temperature, we see that expanding. 

Well, then we can expect to see mosquito-borne illnesses potentially in more settings. And so now we're going to need a new generation of insect experts, not just people in the tropics, but people who are in other parts of the world. So, now we can respond by saying, you know what? We need more young people to get interested in insects and to learn how insects evolve and learn how mosquitoes evolve and why they feed on certain species, etc. So, we can actually see that as a thing to think about. So, thinking about processes that change globally allows us on the scientific side and the public health side to be able to prepare for how we can help us.

Dr. Biology:

Interesting enough about mosquitoes. We had Sylvie Huijben on the podcast, and the title of that episode is The World's Deadliest Animal. Most people don't know that it is the mosquito, so there's a lot to that story. We'll put the link in as usual. Okay. During your lecture, one of the things that you emphasized, and I think this is really important for all scientists and especially all the young scientists because you were talking about context. Let's just talk a little bit about context and why that becomes so important in the world of science.

Brandon:

Yeah, I mean, I think context includes all of the settings, environments, things you're experiencing, the world that you're in. And one of my fascinations and obsessions scientifically is how that changes scientific phenomena. So, for example, one of the things that we've learned about the world and one of the reasons why we admire people like Isaac Newton is they came up with rules. Right. Like fundamental rules of motion. And that's what makes him such a genius, is that he was able to distill down all of this world into a bunch of simple rules that describe the way the world works. 

The problem is you take those rules and we think they apply everywhere the same way in terms of physics they do. But even those rules in terms of motion, for example, can be influenced by friction, for example, or depending on how far away you are from the earth. Right. You know, the gravitational pull is slightly, slightly different. And that can kind of meaningful impacts the way objects move on Earth. And so, what I'm saying is, even for the most basic and fundamental rules on earth, you have to know something more about where you are. Right. 

So, now let's move on to something like biology. Right. When we talk about genetics and I have, you know, genes that are associated with me being tall or risk for disease or having eyes of a certain color, it's not unlike the physics laws. Some of those things are really, really important. They tell you a lot of information about the way a biological organism will work, and I think that's why it's important to understand genetics. But the more and more we learn about biology, it's you have to understand more than just that information. You have to understand where that organism was raised, how it was raised when its diet was right. 

These other things that have an influence on the way the genes are working. And in my view, this is the hidden dimension that we haven't focused on enough in fields like biology. And I think once we learn to appreciate these things, like what's friction in biology, how is that influencing the biological laws of motion? I think we'll understand a lot more about who we are as people and the way the biological world works.

Dr. Biology:

Especially today, because we're talking about going to Mars, Right? All right. You just mentioned gravity. Well, that's what our cells what everything is used to is gravity on Earth. You're out in space. You have no gravity. Context has changed exactly what's going to happen? 

Brandon:

Exactly. No, this is a good question. There's you know, there is space medicine, there is astrobiology there are fields that actually specifically ask the question of, well, how does a microorganism or organism, a microorganism like human beings, what actually happens to bone density and stuff like that in microgravity? And this is a good question because that is not the environment or context in which Homo sapiens, have ever had to experience. And it certainly isn't one where Homo sapiens evolved. 

And so, this is a completely different environment. In fact, one of the main things we're worried about when it comes to space travel, we've always been worried about space travel isn't so much like the physical or muscular things, it's actually the psychological influences. 

So, for example, like I don't know about you all, but being by yourself, you know, I like being myself at times. But even if you're introverted, who wants to be up in outer space for six and ten and 12 months and two years with nobody or with the same person in one small area, relatively speaking? That's actually a stressor on us psychologically, and that's a different context. And so the more we understand these dimensions, I think the better off will be for predicting disease, for being able to treat disease, for being able to go to outer space, for being able to understand climate change. I mean, there's a host of problems on Earth that being able to understand context and environment will help us.

Dr. Biology:

 That is so true… and suspect a pretty good hint for some future scientists or at least some future science careers. 

Now I was doing some research on you, in preparation for our conversation today – And I found out that you are a history buff.

Brandon:

Yes.

Dr. Biology:

Is there a part of history you really love? I know science [history].

Brandon:

Yeah, yeah, yeah. I do love history. I think it just allows us to think a lot about who we are and where we've gone. And I think it allows us to think about the future. And I think for me, yeah, the history of science and ideas, obviously, because that's the practice. But for me, yeah, I mean, it's African-American history. I think African-American history is it is American history. It's that you can't really understand America without the history of African and other groups. 

But this is the one that I've studied the most. And I think it's just such a great experience of triumph and perseverance and creativity. And in fact, a lot of the creativity that I apply in my basic science I got from studying the Harlem Renaissance, and I got that from studying the birth of jazz and the birth of hip hop and these kind of, you know, creative movements in the African-American community. I actually embraced that in my science now. So, I think that's the great thing about history. You can kind of borrow things and ideas and you can animate them in your life in ways that, you know, might be surprising.

Dr. Biology:

Right? So learn from history, but don't have it dictate to your future.

Brandon:

That's exactly right. I think you borrow things from it, and I think you certainly learn the mistakes that were made as well. But the idea is building a future. So, I'm a futurist, ultimately. I want to build an exciting and healthy and happy future for people. And I think history gives me the tools to help get there.

Dr. Biology:

Yeah, Great. Okay. Okay. So, you're a fan of RNA. You're a fan of evolution. You're a storyteller. I'm going to shift to a place where I ask all my guests three questions. So, you ready?

Brandon:

Let's do it.

Dr. Biology:

When did you first know you wanted to be a scientist?

Brandon:

Well, you know, I think for me, there's a moment that I can use, but it really is a series of conversations and experiences with my mother. I think my mother is the biggest influence on who I am. I consider myself to be like a carbon copy of her in many ways. But I think fortunately I have many more opportunities than she had, and I think I became a scientist because she would have been one. Could she have done it in her day. 

And I think from around the house she was putting New York Times science articles on the refrigerator when I was a child, and she was telling us, Look at this discovery here. Look at this discovery here. She had us watching science fiction when I was a young person. Right. But I remember when I ran outside, we lived in a low-income housing unit in New York City, and there was a dead mouse on the ground. And I was six years old. And I walked up to the mouse, and I just picked it up in my hand and like brought it to my face and looked at it. And she says that's the moment. 

She says you were so inquisitive was the word she used. And who knows? I was probably just being a silly little six-year-old being a six-year-old, and that's what six-year-olds do. They do little silly stuff like that. But I think she encoded that as this is a person who wants to understand the way the world works. And I carried that one with me for my whole life. And so that's like the moment that I can focus on where I learned that being a scientist is a thing. And I think through her influence, I've always carried this as my lifelong dream.

Dr. Biology:

Aahh. Well, so now I'm going to be what I say a bit on the evil side because I'm taking it all away. You don't get to be a scientist. I know you're a writer and a storyteller, so I'm going to take that away.

Brandon:

All right.

Dr. Biology:

I want you to think about if you weren't in this space now, what would you be or what would you do?

Brandon:

So if I couldn't be a scientist or writer or storyteller, all those are off the board. So, I'll give a cheat answer and then I'll give you a not cheat answer. And I think the cheating answer is my mother was a schoolteacher, okay? And I think that's about as far as people went in her demographic in that day. You know, there weren't a lot of women scientists and they certainly weren't a lot of African-American scientists, and she taught.

But through that, I saw a lot of her goodness, she did a lot of good for people. And she reached and connected with people and she was able to leverage her love of ideas. And I think that's very much a part of why. So, I could see myself teaching young people and helping young people. So, that's, you know, I said that's probably my answer, but it's a little bit cheating because I'm borrowing for my mother.

I think otherwise I get personal joy out of doing good for people who are in need. I think that's just fun to do that, and I try to do that as much as I can in my profession. So, I look at fields, professions like social work, for example, where people, you know, they help keep families together, that you're having a hard time and they, you know, provide people with needs and people who are struggling with disability or illness or other challenges, particularly young people, you know, I know social workers that dedicate their life to just keeping households together and they do it successfully.

Brandon:

I look at that craft and I have a lot of admiration for them. And I think I would also find very, very meaningful.

Dr. Biology:

Yeah, a bit of the RNA of the human roles or jobs, right?

Brandon:

Oh, it's a great analogy. Absolutely. 

Dr. Biology:

The unsung heroes, right? 

Brandon:

Absolutely!

Dr. Biology:

You bring up this point about going out and helping people. I also noticed in your lecture you flipped something, something really important. And I haven't seen this before. I've seen people, some scientists just say there are a lot of people behind the scenes, but they don't really bring it upfront. So, for those that don't go to scientific lectures, which isn't on everybody's schedule, you come in, you meet the audience, you give your talk. At the end of the talk, you give a list of the people that made you successful because science is a team sport, I would call it. Right? 

So, it's interesting. It's always left to the end. You didn't do that. You start off with gratitude, but I think it kind of leads into my last question. And the last question is what advice would you have for someone who wants to be a scientist, especially the ones that don't think they have a chance of being a scientist? What would you say to them?

Brandon:

Yeah, So I think on one end, a lot of the things that you've heard about, you know, learning science are true. Do your studies and working hard and doing your homework. And I think that's important because science is challenging and requires that you understand a lot of technical things. And so, your math I'm working English, I'm working and writing so that part's true. Okay? And I really recommend that to young people. 

I think what you don't learn, and I think part of what you're asking me, these other set of tools and things that have made one successful. I appreciate that you notice how I thanked people upfront because what I learned from my mother, it's something that I've kind of activated in my career, and that is being a gracious and decent and thankful person is the most powerful tool we have in science. That's how you get students to care. That's how you get your mentors to care. That's how you get people wanting to work with you. It's being excited about your work in the world, being grateful of the people that have helped you, and paying that forward by being good to other people. Those are my secret weapons in science. 

I feel like those end up being as important as any equations or any mathematical method or any experiment is how do you build a community of people in science? And that's the fun part. Science and in medicine and engineering and all these fields that I've participated in, all of them, it's the community of friends and colleagues that I've built that's the most fun. And that's only because I've tried to exude positive energy and gratitude and generosity wherever I could. So, that's the secret weapon. It's not a not a long time ago. It's not decades ago was individual people making discoveries. Science doesn't work that way anymore. If you can't get a group of people to help you or believe in you, you're not going to succeed in earlier, you learn that I think the more successful you're going to be.

Dr. Biology:

Well, Brandon, I want to thank you so much for sitting down with me on Ask A Biologist. It's been a pleasure.

Brandon:

Dr. Biology, a pleasure. Thank you for the invitation. This was a blast.

Dr. Biology:

You have been listening to Ask A Biologist, and my guest has been Brandon Ogbunu, a professor at Yale University and a computational biologist who spends his time researching ecology and evolutionary biology. And when he's not doing that, he's big into storytelling. And you can imagine parts of those stories have to do with evolution. But he has other tales to tell. Will be sure to give you some links in the notes on the podcast. 

The Ask A Biologist podcast is produced on the campus of Arizona State University and is recorded in the Grassroots Studio housed in the School of Life Sciences, which is an academic unit of The College of Liberal Arts and Sciences. And remember, even though our program is not broadcast live, you can still send us your questions about biology using our companion website. The address is askabiologist.asu.edu or you can just use your favorite search engine to search for Ask A Biologist. As always, I'm Dr. Biology and I hope you're staying safe and healthy.