Animal Genes and Human Health with Vincent Lynch

As a kid, all Vincent Lynch wanted to do was hang out by the river near his home, fishing and crabbing and playing in the muck. School, by contrast, was a bore. Then he discovered biology—and never looked back. Today, as an evolutionary biologist at the University at Buffalo, Lynch studies the genomic history of animals both living and extinct to understand everything from why elephants don’t get cancer to why women go into labor. In this episode of Driven to Discover, Lynch talks to host Tom Dinki about what it means to run a “curiosity-driven” lab, why resurrecting extinct species is a bad idea, and how analyzing animal genes could help humans lead longer, healthier lives.

Credits: 
 
Host: Tom Dinki
Guest: Vincent Lynch
Writer/Producer: Laura Silverman
Production and editing by UB Video Production Group 

Coming on Feb. 4: Continuing the conversation on social determinants, host Ellen Goldbaum sits down with Leonard Egede, chair of UB’s Department of Medicine and a nationally recognized expert on health equity. Egede is known for developing innovative interventions to tackle health disparities, including, his newest effort, using AI to address hospital closures in redlined neighborhoods.

Transcript

Tom Dinki: He may not have had a word for it back then, but Vincent Lynch has been fascinated by biology since childhood.

Vincent Lynch: I grew up along the Hudson River, playing in the swamps, trying to catch fish and crabs, and I was always amazed by how weird and different all the different animals looked.

Tom Dinki: Today, as an associate professor of evolutionary biology at the University at Buffalo, Lynch explores how animals came to look the way they do by studying the genetic histories of species living and extinct. And in doing so, he hopes to better understand human health. Among his many research projects, he's used Neanderthal DNA to better understand how humans stay pregnant, searched the gorilla genome for clues about infertility in men, and studied large, long-lived animals to learn their secret to beating cancer. 

Welcome to "Driven to Discover" a University at Buffalo podcast that explores what inspires today's innovators. My name is Tom Dinki, and on this episode I'll be talking to Dr. Lynch about the many ways evolutionary biology can help us understand our planet and ourselves, and perhaps even provide the keys to longer and healthier lives. 

Dr. Lynch, thanks for joining us. Can you tell us more about why you enjoyed nature as a kid, and how did you realize it could be something you could study later?

Vincent Lynch: I always remember just always wanting to be outside when I was a kid, and I grew up in a particular place downstate where we had access to the Hudson River. Basically, I grew up five minutes from the river, and I was always out there fishing and crabbing with my grandfather or just playing in the muck, trying to catch strange animals. Meanwhile, in school I was incredibly bored. Nothing could keep my attention, and I wasn't a particularly good student, probably because I was really bored. But then I started taking biology classes and I found a way to connect, you know, an academic discipline, biology, to the world outside. That was what really interested me.

Tom Dinki: You come from a military family and were a first-generation college student. So what did you think your career options were?

Vincent Lynch: Well, when you grow up on bases surrounded by people in the military, you naturally think, because you see them as your role models, that, okay, this is what I'm going to do. So that was the plan until I started applying to colleges. I had even gone so far as to get letters of recommendation from my senators so I could apply to the service academies. But as I started applying, I realized I don't like people telling me what to do, and if they tell me what to do, they better well tell me exactly why it is I have to do it. And that's probably not a good fit for the military where you’re just supposed to take an order and listen to someone. 

So I knew that, okay, that wasn't an option. So I would go to college. I loved biology, I figured I could major in biology, but I really didn't know what you could do with that major. I thought you either became a medical doctor or a nurse, or you became a biology teacher. So I had started taking biology with the intent of probably becoming a medical doctor. Then I transferred to U Albany and did a research project in a lab with a PI who I sort of really love. We still text each other and call each other. And then, in that lab, I realized that there were all these people around me who were doing research as their job. There were graduate students and postdocs and my biology mentor, Caro-Beth Stewart, she only taught two classes. For the rest of the time she was doing research. And that sort of opened the world to me, that, I realized that I could do that as my profession.

Tom Dinki: I think we all think we know what evolution is, but how would you define it? And can you also tell us what exactly an evolutionary biologist does?

Vincent Lynch: It's actually pretty simple. Evolution is just change in species through time. They can change the way they look, or they can change the kinds of animals that they interact with, and they can change the places that they live. And that's all evolution. If something is heritable, you can get it from your parent, then evolution can work on it. So that's pretty, pretty basic. 

What evolutionary biologists do can vary a whole lot. They can study species and want to know where species come from. They can study adaptations and try to understand how it is that animals are very well adapted to the environments in which they live. Or they can be like me and try to understand why animals look the way they look, why they're patterned the way they are, why they have certain morphologies that other animals maybe don't.

Tom Dinki: My favorite animals at the zoo are always the apes. I love looking for all the similarities between them and us and imagining what our common ancestor was like. But you actually get most excited seeing related species that look very different from each other, right?

Vincent Lynch: Yeah, so, for example, birds evolved from dinosaurs. Dinosaurs really didn't go extinct at the end of the Cretaceous, they just evolved into birds. Most dinosaurs, many dinosaurs, actually had feathers. So, for example, T. rex had feathers. So if you think about what the smallest birds are, like the hummingbird, it's amazing that its, one of its closest relatives, are one of the biggest animals on the planet, like Brontosaurus or like T. rex. You can see it just fluttering through the air. That just always provides me with, like, a better understanding of how evolution can dramatically change the way species look.

Tom Dinki: Is it a bit humbling to be an evolutionary biologist? We like to think of humans as pretty special, but your field kind of finds the opposite.

Vincent Lynch: It is very humbling to be an evolutionary biologist. For example, depending on how you count, humans have been around for about 6 million years. That's when our lineage diverged from chimpanzee. And in the vast span of sort of evolutionary geological time, that represents less than one-tenth of 1% of the history of life. So we're really newcomers on the scene and we're actually not all that special. Six million years isn't a long time to evolve something entirely new. Basically everything that humans have, other animals have, which is also incredibly humbling.

Tom Dinki: And for the vast majority, I mean virtually all species, it will end in extinction.

Vincent Lynch: Yeah, so for a while, biologists didn't think that extinction was possible because they were strongly influenced by theology and the idea that God wouldn't make a species that would go extinct, because that would somehow show that he hadn't planned for the future (and it's always a he, because that's the way it worked). Or that he wouldn't design a species intentionally to go extinct. So we discovered extinction and then realized that almost everything that ever lived has gone extinct and probably will go extinct.

Tom Dinki: Your two main research focuses here at UB relate to pregnancy and cancer. Let's start with pregnancy. Some people may be pretty surprised to hear that human pregnancy is still rather mysterious. What are the unanswered questions that you're trying to answer?

Vincent Lynch: It's actually pretty amazing and kind of disturbing that if you were to pick any animal, any mammal anyway, I can probably tell you why it is that that species goes into labor and delivery at the end of its pregnancy. And that's because there's a special hormone called progesterone. And when it's high, you stay pregnant, and when its levels fall, you give birth. And in humans, the progesterone levels never fall. They just keep going up and up and up. So we don't know the signal that initiates labor and delivery in humans. And it's this very basic aspect of biology that you think that we would understand. We understand so much about human anatomy and physiology, but this very basic thing, we still don't have a clue.

Tom Dinki: You've also looked at infertility in males. You actually were able to recently identify over a hundred new candidate genes for human male infertility by studying gorilla genes.

Vincent Lynch: Male infertility is actually relatively common, but it's incredibly difficult to study because why an individual male is infertile is probably a unique genetic mutation to that male, which makes the tools that we have available in genetics not particularly useful for discovering what that mutation is. So again, we can look to other species to try to figure out what's going on. 

A good model for this actually is gorillas. They have an unusual social structure. They have a single male that has a harem of females, and he's basically the only one that mates with that harem of females, which reduces the competition between males. So in mammals, males can compete with each other with their big bodies. Think about, like, two deer going head to head. They can compete with each other by being pretty, basically trying to show off to the females. And they can also compete with each other through their sperm. So if a male has faster sperm than another male, chances are that that male sperm is gonna fertilize the egg. 

Gorillas don't do any of the sperm competition stuff. They basically only use their big bodies for competition. If you were to give them, for example, a sperm count test, they would be considered infertile. They produce very few sperm. The sperm that they do produce are abnormal, and they don't swim very fast. And gorillas seem to still be able to reproduce. So what we did was compare gorilla genomes to the genomes of other species of primates and try to identify genes that have weird patterns of molecular evolution. Those kinds of patterns associated with selection not acting on them very strongly. And we identified a couple hundred of those, and when we look at their molecular functions, they're almost all involved in something to do with the biology of the testes or the biology of sperm. This gives us some clue to think that maybe they're also related to human infertility.

Tom Dinki: Let's turn to your research on cancer. You've investigated why some of the animals that should have the highest risk of cancer actually rarely get it.

Vincent Lynch: Yeah, there's this theoretical prediction that the bigger an organism is and the longer it lives, the higher probability it has of developing cancer. The first person to recognize this was Sir Richard Peto and now it's called Peto's paradox. And the idea is actually pretty simple. Cancer is the result of an accumulation of mutations that cause a cell to hyperproliferate. If an animal has many more cells than another animal, that's just more cells in which that mutation can occur. And if an animal lives a really long time, that's a long time for those mutations to occur. So this is why we generally think of cancer as a disease of old age. We get cancer when we're old and have accumulated those mutations. 

But then if you look out in the world, there are things like whales that have billions and billions more cells than humans. And there are these things like Greenland sharks, which we don't know actually how long they live, but we think they can live at least 500 years. So why doesn't every Greenland shark have cancer? Why doesn't every whale have cancer? We want to know the evolutionary explanation for the pattern that we expect there to be lots of cancer but there isn't a lot of cancer. Evolutionary biologists love these kinds of paradoxes.

Tom Dinki: Have you found any answers or at least any partial answers yet?

Vincent Lynch: Yeah, well we think we've identified some. There's probably lots of reasons that they don't get cancer. Some is probably environmental. They just live in an environment with not a lot of carcinogen, for example. Humans don't live in particularly good environments. We sort of build houses and sit around a lot. That's not the way we evolved. Those kinds of things can predispose us to cancer. 

But we've also identified genetic differences between species that protect them from cancer. There's this special gene called p53. It's commonly called the master tumor suppressor, and it does exactly what its name sounds. When a cell acquires the kinds of mutations that give rise to cancer, p53 is activated and it causes the cell to kill itself. And we found that species like elephants, which live a long time and are very large-bodied, have 20 copies of p53, while nearly every other animal has only a single copy. So we think that some of the genetic changes that give rise to cancer resistance are just getting more of these genes that protect the cell from turning into cancer.

Tom Dinki: You describe your lab as a curiosity-driven lab. Can you tell us what that means?

Vincent Lynch: An evolutionary biologist is interested in a process, the process of evolution, more so than a system, more so than an individual species. This gives rise to us having a kind of intellectual ADD. Everything is interesting because everything evolves. It makes it really hard to focus. So in my lab we've studied why animals don't get cancer, why women go into labor, why species like bats can live for as long as they do. We've studied  Neanderthals, we've studied woolly mammoths. Basically a student can come to me and say, I really think this thing is interesting, and we can find a way to study it because we can turn that question into an evolutionary question.

Tom Dinki: Speaking of woolly mammoths, you've done work resurrecting their genes to learn more about why they went extinct. But there's actually a company out there that's trying to revive the species and reintroduce them to the wild. What do you think about these kind of "de-extinction" efforts?

Vincent Lynch: Oh, they're just stupid, for lots and lots of reasons. What they're saying is that they're gonna de-extinct a mammoth, that makes it seem like they're gonna do the "Jurassic Park" thing and bring back an extinct species. But they're not bringing back an extinct species. They're taking an Asian elephant and using genetic engineering to make it look like a woolly mammoth. So for example, we identified when we did our study of the woolly mammoth genome, some genetic changes that we think are associated with having long fur and having curly fur. So what Colossal is proposing is taking those genetic changes that we identified in woolly mammoth, introducing them into Asian elephants and making shaggy Asian elephants. But that's not a woolly mammoth; that's a shaggy Asian elephant, right? How many genetic changes do you have to swap between woolly mammoths and Asian elephants before you really make that thing a woolly mammoth? If you're a good evolutionary biologist, and I think I'm a good evolutionary biologist, you know that that's not possible. 

The rationale that they're using is that the absence of woolly mammoths from the Arctic has increased the melting of permafrost. Melting permafrost releases carbon dioxide into the environment. Therefore, if we put woolly mammoths, or Asian elephants that look like woolly mammoths, back into the Arctic, that will prevent the permafrost from melting, which will prevent the release of carbon dioxide, which will prevent greenhouse gas emissions and improve the outcome for global warming. That's a whole lot of steps to get from introducing genetic changes in an Asian elephant to preventing global warming. 

And I can't imagine the number of Asian elephants that look like woolly mammoths that you'd have to put in the Arctic in order for that to work. It can't be more than 10, it can't be a hundred, can't be a thousand. We're talking about millions. I just don't see that working. And even if it did work, there's probably all kinds of unintended consequences for doing that kind of thing. Putting an Asian elephant that looks like a woolly mammoth in the Arctic isn't restoring something that was there to the way it used to be. It's introducing an exotic invasive species into an environment that it's never lived in before. We know the consequences of that.

Clip from "Jurassic Park": Your scientists were so preoccupied with whether or not they could, they didn't stop to think if they should.

Tom Dinki: So in other words, listen to "Jurassic Park."

Vincent Lynch: Listen to "Jurassic Park" and listen to me when I tell you it's silly.

Tom Dinki: So you don't want to bring back extinct species. Can you talk more about what you do hope to accomplish with your research?

Vincent Lynch: I just want to understand how biology works better. So, like, it's very basic. Animals look different. Why do they look different? I want to know that answer. Animals behave different. I want to know why animals behave differently. Animals have different physiology. I want to know why they have different physiology. 

But more practically, I recognize that what we're studying can have implications for human health and disease. If we understand why it is that women go into labor, then maybe we can develop an intervention that prevents them from going into labor early. If we understand why some animals are cancer-resistant, maybe we can develop more effective treatment and prevention strategies using that information. While my lab's not gonna be the one doing that, because that's biomedical research and I'm an evolutionary biologist, I hope the things that we discover can feed into those kinds of studies and eventually give rise to something that improves human health.

Tom Dinki: So much of your field looks to the past, but do you ever find yourself wondering what the next step of evolution looks like? Human or otherwise?

Vincent Lynch: Yeah, you can't help but daydream, we do it all the time. And actually one of the first books on evolution, called the "Vestiges of the [Natural] History of Creation"—came out before Darwin had proposed an evolutionary theory— doesn't just stop in the 1850s. It proposes that humans will continue to evolve and it imagines what that future evolution was like. So there's a long history in evolutionary biology of trying to run the tape into the future to predict or explore or just, you know, be fascinated about what might evolve.

Tom Dinki:  And it's not necessarily even a guaranteed thing that we'll evolve, you know, towards a more advanced society. It could even go backwards, right?

Vincent Lynch: Lots of species have seemed to regress in their evolutionary history. So things like cave fish have lost their eyes because you don't need eyes in a cave. So there's no guarantee that we're not gonna go extinct, number one, because almost everything goes extinct, and that whatever our future is like, it's a sci-fi one out of the pages of a futuristic novel.

Tom Dinki: Dr. Lynch, thanks so much for joining us.

Vincent Lynch: Thank you for having me. It's always fun to talk science.