What Dinosaurs Can Teach Us About Science and Medicine

HELEN: Welcome to Talking About Blood. I’m Helen Osborne, host of this podcast series and a member of the advisory board for The Blood Project. I also produce and host another podcast series, and that’s about health communication called Health Literacy Out Loud. Today’s guest is Mary Higby Schweitzer, who has had a lifelong fascination with dinosaurs starting when she was just five years old. Life took a few twists and turns before Mary realized her goal of becoming a paleontologist. Her many accomplishments include researching the world’s first sample of still soft dinosaur tissue. She, on this project and other projects, has collaborated with other disciplines who were not normally a part of dinosaur research. Now retired, Mary has held many academic appointments, including being a full professor in the Department of Biological Sciences at North Carolina State University. Mary, welcome to Talking About Blood.

MARY: Thanks for having me.

HELEN: Paleontology, dinosaurs, I’m so intrigued by this, and I’m sure that our listeners are too. But let’s, as the saying goes, let’s start at the very beginning. Please explain to all of us, what is a paleontologist?

MARY: Well, paleo means old, and ologist is the study of. I study old life.

HELEN: Okay.

MARY: I’m also a paleobiologist, which might be a little easier to understand.

HELEN: Well, tell us what that is.

MARY: I study the biology of extinct organisms.

HELEN: So extinct organisms, we’re talking how old?

MARY: The last dinosaur walked our planet, as best as we can tell, well, the last, let me clarify, the last non-avian dinosaur walked the planet about 65, 66 million years ago. But the reason I clarify is because by all indications of how we classify animals, birds are a type of dinosaur, just like a chihuahua is a type of dog. So they are the same thing, and dinosaurs didn’t go extinct, they’re still around in your backyard.

HELEN: Birds and dinos, a little tiny, like little wren or hummingbird is the same thing as like this enormous T-Rex that I can see it, the bones I can see in the museum. They’re like related, they’re cousins or something?

MARY: Yep, they sure are.

HELEN: Fascinating. We need to know more. So you’re a paleobiologist, looking really at the science of this. So these extinct, incredibly old critters, what are we learning? Tell us more.

MARY: So I think what you’re asking is why on earth should we study dinosaurs?

HELEN: Well, that’s, yes, well said, Mary.

MARY: We’re never going to interact with them, we’re never going to have them as pets, so do they really have any value? And I would argue absolutely yes. Dinosaurs were better than humans and still are better than humans in just about every way that we can measure. And so I think that we can learn an awful lot from these organisms.

HELEN: How can we learn a lot? How are they better than we are?

MARY: Everybody hears that our world is warming because we are putting excess CO2 in the atmosphere all through.

HELEN: Okay.

MARY: But dinosaurs came to be when CO2 levels in their atmosphere were 10 times higher than they are now.

HELEN: Wow.

MARY: And they were very happy. And the whole reign of the dinosaurs saw higher CO2 levels than we’ve ever seen as humans. And they did just fine. And so how they did just fine is a really good question and one that we should probably understand.

HELEN: Well, you said they did just fine, but they’re not here anymore.

MARY: They were around a lot longer than humans.

HELEN: Okay.

MARY: Humans in our current form have only been around a couple hundred thousand years. And so dinosaurs, you know, they lived a very, very long time and were very successful. They lived on just about every continent. Granted, the world was a little bit different back then. And again, there are almost two times as many species of living birds as there are of living mammals. So I think dinosaurs are kind of still leading the pack.

HELEN: Well, this is all about blood. This is Talking about Blood. And you did some soft tissue research. And what’s the connection? I mean, do dinosaurs, birds have blood just like we have blood? Is that our common link?

MARY: Well, they did have blood just like we have blood and just like birds have blood. But their blood was different and again, a lot more efficient than our blood. The best we can tell. We haven’t done the kind of studies on dinosaur bone to see if they have blood that I would love to see done. But if you use modern birds as an example, they’re a lot more efficient at downloading oxygen, which is why they can fly around way up high and dive under the ocean and everything in between. And they did it by using a different allosteric effector. So what that is, it’s a helper molecule.

HELEN: OK.

MARY: Hemoglobin loves oxygen so much that it won’t release it once it’s found without a helper molecule. The helper molecule in birds is more efficient than that of mammals. And in fact, the reason it is, is because it is called inositol pentaphosphate, whereas we use bisphosphoglycerate. Inositol pentaphosphate is often used in sports for doping because it gives more oxygen to your tissues. So why do birds have it naturally and humans use something less efficient?

HELEN: Yes, tell us more. Yeah, it’s an excellent question. And I don’t even expect me to pronounce those words you just did. But answer the question that you find so fascinating and you think hematologists might too.

MARY: Well, I think that is one way of looking at physiology for sure. But we can learn an awful lot more. Again, how did their lungs function in a high CO2 world to get them the oxygen that they needed?

HELEN: Right.

MARY: Dinosaurs were very active animals from what we can tell. And they also crossed barriers that no mammal has ever done. We do not have today a living, breathing 80-ton herbivore.

HELEN: 80 tons?

MARY: So what did they do different than mammals? And I think that’s a really important question, especially going forward with the changing world.

HELEN: So 80-ton mammals eating just plants, just plants who could adapt to the environment. What are some of the either questions you’re asking about modern medicine and science? Or what are the lessons you would want scientists and medicine folks to know?

MARY: Well, getting back to the big, massive, long necked plant eating dinosaurs, they started out in an egg. And eggs are constrained by physics. They can only be so big or they don’t function. And so you get an 80-ton, maybe as long as 100-foot long dinosaur from an 18 inch embryo in about 20 years, 20 to 30 years, as best as we can estimate from there, looking at their bones.

HELEN: Wait, 20 years from the time that they produce the egg until it hatches?

MARY: No, no, no. From the time it hatches until they reach full size.

HELEN: OK, 20 years.

MARY: Yeah, so they roughly 20 to 30 years to go from an 18 inch embryo to a 70 or 80 foot dinosaur. And we don’t have any, even hummingbirds don’t have that high of a metabolic rate. And then you complicate that by looking at their heads, which were tiny, 5% of their body. You would look ridiculous if your head was 5% of your body. But they did. And then they had, to complicate matters further, weakly rooted teeth and very weak jaws. And their mouth was probably with an opening from about your elbow to your wrist.

HELEN: Tiny, tiny.

MARY: And they had a 40 foot neck. How are they going to get enough plant material through that mouth and down that neck to sustain that metabolism?

HELEN: Right.

MARY: So you have three options. The plants were maybe much more nutritive than they are now.

HELEN: All right.

MARY: Or dinosaurs possessed an enzyme, a digestive enzyme, that allowed them to get more nutrients out of the plants. Or dinosaurs had a gut microbiome that was much, much, much more efficient than any animal we have today. Or, most likely, a combination of those factors. But each one of those things is a molecular question. So if we can get at the molecular makeup of dinosaurs and figure out how they did that, that might be a way of helping us to plant agricultural crops and then do it more efficiently.

HELEN: Oh, this is absolutely fascinating. But how does one do research? I know you said you’ve done it in collaboration with people who are not necessarily doing the same work as you. How can scientists learn from critters that are not walking around the planet anymore?

MARY: By looking at their molecules. And it doesn’t necessarily have to be DNA, although DNA would be the target goal, obviously, if you’ve ever seen Jurassic Park. But if they have proteins, a digestive enzyme is a protein. We know that proteins can last longer than DNA. And we’ve been able to obtain fragments of protein and sequence that data. And again, this is not my area, so I work with people who do, on a regular basis, the methods that I want have done to get the information out of my dinosaurs. So I’ve worked with people who are world-renowned for doing protein sequencing. And I’ve worked with people who are really, really good at probing these molecules for, eventually, for function. So I use their methods.

HELEN: So that’s their methods, is they’re in a laboratory, they’re looking at a microscope. What is your role in this as a paleontologist? Are you the one who poses the questions? Are you the one who looks historically at this? What’s that collaboration like when your skill sets are complementary but not the same?

MARY: Well, a lot of them overlap. So I am a microscopist. I look at dinosaur tissues through the microscope. And we use multiple different kinds. So we use transmitted light microscopy, which is basically your standard, you know, high school microscope. We use transmission electron microscopy, which requires that you slice your dinosaur tissues to a maximum of about 90 nanometers… very, very, very thin sections. And then you pass electrons through those tissues. Or I do scanning electron microscopy, which gives a three-dimensional look with higher resolution than the light microscope. And we’ve recently added micro-CT as a way of looking at three dimensions. So we do that in our lab, as well as paleoimmunology, using immunological methods on these tissues to localize protein epitopes. So we look at blood vessels, for example. And we know how they’re made. In all modern vertebrates that have blood vessels, which is all of them, we know their vessel structure. And we know the proteins that make up the vessels. So we have endothelial cells on the inside, next to the lumen. And those are joined together with proteins that form a tight junction and underlain by a basement membrane. We know the proteins that go into all of those things. So when we recover a dinosaur, and we recover their still soft vessels, we test those vessels to see if they have the same proteins, using antibodies in different ways.

HELEN: OK, well, I have all these images here of you doing this. And you’re talking about these huge critters that were 66 million years ago and gigantic. And you’re talking about up-to-date, the most latest technology at a teeny, teeny, tiny level. What contrasts in there. You also talked about recovering the soft tissue of a dinosaur. They’re not around anymore. How would you get that soft tissue?

MARY: Well, that’s a really good example of why we can use these in medicine. So when bone is forming in any vertebrate, especially in the bone, the vessels come in and invade the pre-existing cartilage in an embryo and help to lay down bone tissue itself. And part of the reason it does that, vessels come first, is because vessels express a protein on their exterior surface that really binds bone mineral strongly. Now the problem is, if you flip that around, you get atherosclerosis or plaque buildup inside the vessels. It basically turns into bone inside your vessels. But if that same epitope is expressed on the outside of dinosaurs’ vessels, maybe we can figure out a new way, thinking outside of the box, to treat plaque deposits.

HELEN: Well I’m still kind of hung up on this. I have this image of you with your hat on, going out there in the wild somewhere, like Jurassic Park, like digging around in the ground. Is that how you get these vessels? Is that how you get the samples?

MARY: We get the bones, absolutely. So one of my, well several of my colleagues, send me bones from their excavation sites, and I go out and collect myself. And then once we get the bones there, it’s like any studying modern bone. If you want to look at bone microstructure, you want to get rid of the mineral. Because the mineral blocks your ability to see through the bone. So you take bone and you demineralize it using acid, and then you can embed it and section it and use your microscope. And that’s just what we do, and we came by it kind of accidentally. I was not expecting to see any tissues remaining. Most people don’t like it when you dissolve their dinosaurs, because they don’t have anything left. But we were looking for something in particular that had nothing to do with soft tissues. And so we were trying to etch the mineral away from the bone without losing structure, and we let it go a little bit longer than we should have. And there was stuff left. Nobody predicted that. And certainly not me. And the stuff that was left included what looked like collagen matrix, what looked like blood vessels and bone cells. And again, we weren’t looking for this. So my hypothesis is that when those blood vessels and soft tissue become complexed with mineral, when the bones are forming, it protects the soft tissues. And the soft tissues protect the bone. So we actually can see bone microstructure that looks exactly like yours. And that bone microstructure, that mineral in bone, gloms on to the organics so tightly that they can’t break down. And we see both.

HELEN: Fascinating.

MARY: It was scary, actually.

HELEN: Was it scary? What were you scared of?

MARY: Well, going against conventional wisdom is really hard for a pathologically shy person. And I was not expecting any of this. And so, I mean, we basically sat on the data for about a year before we tried to publish it because I knew it was going to cause a firestorm, and it did.

HELEN: It did?

MARY: Yeah. And, you know, when we had all our data, when we repeated it like 17 times, when we were sure that we could do it over and over and over, we published it. And life has never been the same since. And it didn’t help that some of this stuff was coming out about the same time as Jurassic Park, so… That was not intended.

HELEN: Bill Aird, the head of the Blood Project, introduced me to you because he had read some of your work, and he had some similar kinds of interests. How would a practicing hematologist have heard about this research? You said your life was never the same after this. Put this in context of modern medicine. What happened?

MARY: Well, I’d really like a modern hematologist to have a go at these blood vessels because they know far more than me. And I, you know, if I could get a couple of them on board and say, yeah, that meets all our criteria for a blood vessel, that would be awesome because they know more than I do.

HELEN: Well, maybe you’ll get somebody who’s listening to this podcast.

MARY: Maybe we will. But, you know, I mean, if you want to do a small experiment with your kids in your kitchen, take a chicken bone and put it in a jar of vinegar for about two weeks. And then take it out, and you will be able to tie the chicken bone in a knot.

HELEN: Huh, because it’s so soft.

MARY: Because it’s removed all the mineral. And that’s basically the same thing we did in the lab. We didn’t use vinegar and chicken, but, you know, we basically took these chunks of dinosaur bone and put them in a mild acid and changed the acid every day or every other day until we could see at the bottom of the petri dish, there was a lot of things that shouldn’t be there. Now the question is just what can we learn from all that stuff?

HELEN: Well, that’s where I want to take this conversation now. I want to tell you about the listeners to this podcast. They might be practicing hematologists or seasoned physicians of some level of practice. They might be people newer in their science or medical careers, or also people like me who are just fascinated in learning new things about blood. What would you like to tell all of us about that at all those different levels from your journey from wanting to be a paleontologist when you were five to now retired and all your lessons learned? What can we learn from this?

MARY: Well, it’s like I tell my students, there are two things that do not belong in a scientist’s vocabulary: the word believe and the word never. And all my life I’ve heard, well, you’re never going to get proteins out of dinosaur bone. You’re never going to see these structures. You’re never gonna. And the problem that we have is when you use those words in science, you shut off the doors to investigation. Who’s going to give you money to study the molecular makeup of dinosaur bone when everybody says you’ll never get it? You can’t do it. And so I think every discipline of science in the 21st century that we live in, every discipline, those fundamental founding sentences that make up that discipline need to be retested every single, well, every five years anyway, with new technology. Because the technology, we’re like four generations down from when I started this. And they’re more sensitive, they’re more accurate, they can inform better. Look at what we’ve done just with DNA. We’ve gone from PCR to next-gen sequencing to single-cell sequencing. None of that was even remotely possible when we started in our dinosaur studies. So never say never.

HELEN: What would you use instead? Would you use maybe or would you do let’s see?

MARY: I would say go test it.

HELEN: Go test it. Okay.

MARY: Go test it and find out for yourself. And the other thing that I would say from my own experience is that if you have a dream and if you have a passion that you cannot let go of, you’re never too old to pursue it. Keep trying. I mean, I was, what, 36, 37 when I started grad school. So you’re never too old. Now I’m too old, but…

HELEN: Well maybe for going digging around getting those bones, but whatever. I love your messages. The science is fascinating. You took your lifelong passion. You’ve made our understanding of the world so much better. And I love your messages of follow your passion. That goes for anyone at any level of wherever we are. And if you think something might be out there, go test it. Mary, thank you so much for sharing your experiences and your inquisitiveness and your passion with all of us on Talking About Blood.

MARY: Thanks.

HELEN: As we just heard from Mary Higby Schweitzer, it’s important to follow our passion, to never say never, and keep learning. That’s what Talking About Blood is all about. To learn more about The Blood Project and explore its many resources for professionals and trainees and patients, go to thebloodproject.com. I invite you to also listen to my other podcast series that is about health communication, and that’s at healthliteracyoutloud.com. Please help spread the word about this podcast series and The Blood Project. Thank you for listening. Until next time, I’m Helen Osborne.n.