In Our Time - The Evolution of Teeth

Episode Date: April 11, 2019

Melvyn Bragg and guests discuss theories about the origins of teeth in vertebrates, and what we can learn from sharks in particular and their ancestors. Great white sharks can produce up to 100,000 teeth in their lifetimes. For humans, it is closer to a mere 50 and most of those have to last from childhood. Looking back half a billion years, though, the ancestors of sharks and humans had no teeth in their mouths at all, nor jaws. They were armoured fish, sucking in their food. The theory is that either their tooth-like scales began to appear in mouths as teeth, or some of their taste buds became harder. If we knew more about that, and why sharks can regenerate their teeth, then we might learn how humans could grow new teeth in later lives. With Gareth Fraser Assistant Professor in Biology at the University of FloridaZerina Johanson Merit Researcher in the Department of Earth Sciences at the Natural History Museumand Philip Donoghue Professor of Palaeobiology at the University of BristolProducer: Simon Tillotson

BBC Sounds, music, radio, podcasts. Thanks for downloading this episode of In Our Time. There's a reading list to go with it on our website, and you can get news about our programs if you follow us on Twitter at BBC In Our Time. I hope you enjoy the programs. Hello, great white sharks can produce about 100,000 new teeth throughout their lifetime. For humans, it's closer to a mere 50, and most of those have to last from childhood. Looking back half a billion years, though, the ancestors of sharks and humans had no teeth.

in their mouths at all, nor jaws. There were armoured fish sucking in their food. At some point, either their almond scales seeded teeth or their taste buds did. And if we knew more about that and why sharks can regenerate their teeth, then we might learn how to grow new teeth ourselves in our later lives. With me to discuss the evolution of teeth. I've Phil Donahue, Professor of Pellio Biology at the University of Bristol. Zerina Johansson, Merritt Researcher, in the Department of Earth Sciences at the

Natural History Museum, and Gareth Fraser, assistant professor in biology at the University of Florida. Gareth Fraser, can you tell us what is a tooth? Is there an agreed definition? There is a sort of agreed definition, and it's a simple one, I think. So a tooth itself is a highly mineralised unit within the mouth. It's hypermineralized in terms of the enamel that coats the tooth.

It's underlying the enamel. has a dentine block, which is surrounded by a core pulp cavity, and the pulp really contains the nerves and the blood supply that's important during development. There's a fourth tissue that's involved in the attachment of that tooth. We call it a bone of attachment if we're thinking about fishes, but in mammals it's a cementum, which is that sort of structure that sits between the tooth and the jaw itself, the bone of the jaw.

So it sounds like a very simple structure with four different layers, but in actual fact it's a very complex. What makes it complex? It's complex in terms of the development of the unit, although there are two main cell types that go towards making the tooth. Those cell types differentiate into many different cells in order to secrete some of the hard tissues or the minerals that become hard tissues in the tooth.

But there are some 400 or so genes that are involved in the actual production of that tooth, and many more around the supporting tissues of the tooth itself. So it's actually a very complicated sort of concert of interactions between genes, cells and tissues that go towards making a tooth. In terms of the other organs in the body, is it one of them more complicated? No, not at all. But it's a really good question because actually the tooth is seen as a sort of a model organ. Because actually a lot of the genes that are involved in making a tooth are also involved in making lots of different organs within the body, whether it's the brain, the eye or the liver or other elements of the skeleton.

So lots of these genes are sort of turned on in lots of different parts of the body. So yeah, so it's not the most complicated, but it's definitely not the simplest. You are interested, I might say, from reading your notes, obsessed by sharks. In what way does sharks teeth singular? So sharks are an incredibly important group of organisms. For me, they're important because they contain a number of characters that are quite interesting for me as an evolutionary biologist. Not only do they have teeth in their mouth,

but they also have teeth in their skin. And so we're really trying to sort of figure out what it is about sharks that allows them to develop these strange tooth-like structures. But one of the most important things about sharks for me is that the teeth in the mouth of sharks and all fishes actually are almost identical, I mean almost identical to the teeth that we have.

And the genes that make those teeth are almost equivalent across the board. So we're looking at a unit, a tooth within a shark that's incredibly conserved in the way it's made, which is great news for us, because that means we can learn a lot about sharks and how they make their teeth,

and at some point that information can be useful for humans and human health. You're talking about skin, and what way are teeth on the skins, like the teeth in the mouths? So structurally, they're almost equivalent. So we call them skin teeth, but they're not true teeth

because true teeth are sort of defined by the location within the mouth. But in the skin, they're still made from enamel or enamel-like covering, covering a core of dentine surrounded by a pulp cavity. So essentially, structurally, they're the same thing.

So, you know, why sharks make them the skin is a really good question. And this sort of lends itself to the evolution of these structures and the origins of these structures. So we can answer some questions about the origins of teeth looking at sharks. So did teeth evolve in the skin

of some of these ancient fishes? Or do they evolve in the mouth, like the teeth in our mouths? Why the frequency, this incredible frequency, and then the numbers involved in the number of teeth they have throughout their lifetime? Yeah, a great question.

So we don't really know. I mean, so there are also sort of guesses and sort of ideas about why the sharks make so many teeth. It absolutely played in to the idea that they have now become incredible predators, Apex predators, and the fact that they can renew their teeth in some species every two weeks, that means that they're always active and always predatory.

But yeah, The amount of teeth they produce is quite startling. And so you did mention the opening of the show that Great Whites can potentially make up to 100,000 teeth in its lifetime. And we think that's actually quite a sort of common standpoint in sharks that they can make between 50 and 100,000 teeth in a lifetime, which is incredible, really. And the rate at which they make those teeth is pretty impressive too.

So every 10 days or two weeks, some species make a new set of teeth. But, yeah, why they do that is a great question. And so that's something that we're sort of looking at in terms of what it is about the genes that enables them to turn that system to make a rapid development of these new teeth. Thank you. Zerina Johansson. Can you tell us about the fossils of fish and why are they relevant to the study of teeth?

Well, Gareth hinted at that answer when he was talking about we're interested in the evolution of teeth and evolution of scales in the skin. But fossils are important because they tell us about the evolutionary history of animals, like sharks and like a variety of other animals. So when you're talking about teeth and the evolution of jaws, we need to be thinking about a group of animals known as the vertebrates. So they have a backbone like we all do, for example. And the history of vertebrates goes back, I think, as you said, close to 500 million years.

And so if we think about the vertebrates, we can separate them into jawed vertebrates, which are normally the vertebrates that have teeth, and the jawless, vertebrates. So jawless vertebrates today include like the lampreys and the hagfish, but there's a whole range of fossil jawless vertebrates as well. So one of the things we're interested in is investigating whether some of these jawless vertebrates may have had any type of precursors to teeth that we see in jawed vertebrates. And also because we are able to look at fossils and look at the evolution of jaws and teeth, we're able to see whether jaws evolved first. and then teeth later, because you might think that in terms of an evolutionary advantage for vertebrates,

it might be, well, again, advantageous to evolve jaws at the same time as teeth. But in fact, if we look at a group of jawed vertebrates known as the placoderms, it looks like their jaws evolved first and then teeth evolved later. Are teeth particularly prominent in fossil remains? Yes, absolutely. So normally what fossilizes in animals are the heart. tissues. So bone, for example, is mineralized. It's a mineralized part of the skeleton. Sharks mineralize their skeletons in slightly different ways. But teeth and scales, as Gareth was saying,

are covered in this heart tissue called enamel or enameloid, and scales as well. And also, because sharks produce teeth through their lifetime, they're incredibly rich in the fossil record. They're preserved very well. So a lot of our early history of sharks is known primarily from teeth and from scales. Are teeth always found with jaws in the fossil record? No, they don't actually. So again, what we know from placoderms, which is this unusual group of fossil vertebrates,

a fossil fish, is that what we think of as the most primitive jawed vertebrates, these placoderms have jaws, but they are bare. They don't appear to have structures that are teeth in the same way, well, true teeth, in the same way that we have teeth. teeth in sharks and other bony fishes.

So looking at these placoderms, we see jaws first, and teeth seem to have evolved in the mouth later. Phil Donahue, how do teeth develop from the early stages? So initially, the earliest vertebrates that have teeth are the placoderms, and they just have structures, cone-like structures, which are comprised almost exclusively of dentine with bone cells that bind them onto a bony jaw surface. And then in more advanced vertebrates like sharks and some early bony fishes, they have a hypermineralized layer called anameloid, which is like enamel, which coats the upper

surface and is a more wear-resistant tissue. And then later within vertebrate evolution, we have a structure more like, that resembles more our own teeth that has a cap of true enamel that encloses the tooth itself. Can you look back more than 500 million years ago and tell us about the world without teeth? So within vertebrates at least, a world without teeth would have been jawless vertebrates, which had an extensively developed mineralised skeleton in the form of a body armour, which has these tooth-like structures coating its outer surface, but they didn't appear to have had teeth inside their mouths, and indeed they didn't have jaws. They made a living simply by slurping,

mud and trying to find nutrients within that mud. When teeth appeared hundreds of millions of years ago was this related to fish scales which have been mentioned but could you develop that a bit? Okay so within the fossil record and if we

put the fossils and the living species into a genealogy of life what we can see is that the most primitive vertebrates that have tooth-like structures those tooth-like structures only occur in the form of an external body armour. There are no tooth-like structures inside the mouth. It's only when we have true jaws that we have structures

that Gareth, according to his definition, would accept it as true teeth. But there are some other dead fish in between that have tooth-like structures associated with their pharynx, fossil groups, but they didn't have jaws. What those tooth-like structures were doing, nobody really knows. Have you any idea what provoked or promoted the development of teeth? Well, I think once you have jaws, you know, if you want to capture prey and... So jaws came before teeth?

Well, jaws and teeth seem to have come at more or less the same time. Yes, by the evolutionary history. And so jaws without teeth aren't particularly useful necessarily because, you know, the primitive function for teeth could simply be retaining prey that's being captured by the jaws and preventing it from being released. So have you any idea how jaws and teeth came into existence and why? So I would argue that effectively teeth evolve first. They are modifications of the developmental units that make up scales

and that they were co-opted to performing a tooth function once jaws first evolved. But how jaws came about, I don't think anybody really knows. But have you any guess as to why the scales turn into teeth? I mean, you must be one of the people best able to make an educated guess. Well, so scales and teeth develop in much the same way. I see. And the traditional hypothesis is that scales which were on the outside of the mouth, once jaws first evolved, were co-opted to performing a tooth function.

They were there, and they were adapted to retain prey. So teeth come from scales. That's the outside-inside theory, isn't it? Yeah, the outside-in is the traditional hypothesis that's, as old as evolutionary theory itself. But Garrett, isn't there an inside-outside theory? There is. It's like the eggs, isn't it?

So there is an inside-out theory, and that's actually a little misleading in terms of the way the term was coined, or the name was coined. So what they, so, so to... We've heard Phil's theory. Could you just give us your opinion? Right, so it's actually my PhD advisor,

Moyer Smith, and a colleague of hers, Mike Coates, who's at Chicago, came up with this idea that teeth may have evolved in the pharynx of these jawless fishes. And we know that they did possess denticles, as Phil said, within the pharynx. We just don't really know what the sort of status of those denticles were and how they may have transitioned into teeth if they did. So the theory actually came from a group of fossils called thylodonts that actually had these sort of connected denticles

that seemed to show a whirl, almost like a developmental series of teeth, like you might have in the jaws of shard. sharks, but in the back of the pharynx of these georishers. And so it's these sort of fossils that gave both Moyer Smith and Mike Coates the idea that possibly teeth may have evolved in these very early vertebrates in the pharynx and not in the skin. And so this then sort of developed this debate, which is, you know, which came first, teeth in the mouth or the oral pharynx, which is the sort of the mouth and the sort of the internal cavity where the gills are or in the skin. And so the traditional theory, like Phil says,

is that scales evolved first or, you know, these scale-like structures evolved, and then they sort of translocated, or at least the cells that were competent to make those scales, translocated into the mouth, timed perfectly well with the evolution of jaws to become teeth. Sorry. Oh, sorry. After you have finished, please. And so, yeah, and sort of translocated into teeth. Whereas the inside-out theory actually doesn't really make any real connection between the teeth and the oropharynx and the skin.

it talks about these two structures of very separate developmental entity so teeth may have evolved inside the cavity and just worked their way more sort of anteriorly as jaws evolved but they're very separate from the skin themselves. Zarina, can you arbitrate or give us your view between these two?

Yes, well I've been a very close colleague of Moyas for quite some time and so yes, the group that Gareth referred to the thylodonts is very well. where you do find these tooth warls or in the gill arches in the pharyngeal region in the pharynx. And so it looked like, excuse me, that these were, they had a pattern for the addition of these teeth in this jawless vertebrate group. And there was another group called the conodons, which this was work that Moy had done a few years ago and fill as well. But it looks like they had similar

types of tissues in their dental apparatus that were comparable to what we see in teeth. But I'll get to that in a second, Phil. But these conodont apparatuses were located in the same region, associated with the gill arches behind the mouth. And they were organized in a way that looked like they were opposing feeding structures. So again, it appeared that conodonts, which were very primitive jawless vertebrates, fossils, had, again, some type of patterning that might have been transposed into the mouth to be related to teeth. But Phil's group had shown or has shown that these conodons, in fact, are quite derived within the group, and the thelodonts as well. So we might have two instances of this patterning, of this apparatus

and of this warrel within quite different groups, but they're so far separated and quite separated from the jawed vertebrates, that they may, in fact, have not much to do with the evolution of teeth at all. Do you want to take that up, Phil? Yeah, so I think Zarina's captured it quite well. So it appears on the balance of evidence that conodons and theodonts have independently, convergently evolved tooth-like structures, which I think, you know, says something about the evolutionary potential of tooth-like structures evolving, extending the competence to produce teeth-like structures. extending from the outside of the body

into the pharynx and into the mouth to perform tooth-like functions. So you're back on the outside inside, Siri? Yes. I think you've always been. That's where I've always been, that's I'm afraid. Well, to stay with you, Phil, why would some vertebrates regenerate their teeth

and others not? So most vertebrates, one way or another, do regenerate their teeth because teeth are basically tools that are used in food processing. And once they've worn out, then it's a bit limiting. You can't feed and maybe you won't live long enough to breed and you won't pass on your inability to regenerate teeth onto future generations. But lots of vertebrists have solved it in different ways.

Some of them simply carry on growing the same tooth to keep a pace with wear at the surface. Such as? So rabbits, for instance, and primitive shark-like. organisms like chimerids and lungfish as well do all do the same thing Rabbit? Can you just go between the rabbit? So rabbit incisors and some of their molars

they just continually grow them from the base. They never stop developing. And so the teeth themselves wear down very, very quickly. I mean, horse teeth do much the same as well. They just continually grow. They continually extend to keep a pace with wear. And then there are other groups which reinforce their teeth once they get worn down, they develop hypermineralised tissues,

wear-resistant tissues within the tooth structure itself. And then there are others that replace worn-out teeth but don't shed the worn tooth, and then others that shed that tooth and replace it with a pre-formed functional tooth. Is there any pattern to this? So that latter pattern of replacement, shedding and replacement, that's the most derived,

the most, if you like, advanced mode of replacement within vertebrate evolution. So trying to get to the root of this, if you'd like to use it. What do we know about the genes that make up the... Are the genes that make up these teeth? Are they exclusive to teeth? What's going on? So the genes that actually sort of are involved in the development

and regeneration of teeth, they're not exclusive to teeth. There are some proteins that are specific to the laying down of the mineral enamel, for example, during secretion of enamel there are a number of proteins that are involved, which are seemingly specific to that function. But during the development of teeth and regeneration of teeth,

the genes themselves are actually well used throughout the body during embryogenesis. So there is no tooth gene, per se. There are just a sort of a collection of genes that we call a gene network that function together in order to make a tooth. And it's the interaction of those genes

that's quite specific to teeth. What else do they make? These genes? These genes. Well, so the term is pliotropy, right? So these genes have functions in many different organs around the body, even sort of organising the axis of the body as well. So lots of these genes are involved in many, many different developmental processes.

And so it's just, it seems to be the right combination of genes that are key or essential to the production of a tooth. But we don't know why that is. We, I mean. You know it is, but not why it is. Yeah, I think that's what the research that at least I'm doing is sort of focus on it. I try to understand what it is about that sort of core network of genes that sort of offers something different to allow the formation of teeth.

So actually what we're doing right now is we're looking at sort of understanding all of the genes that are expressed during this process. Not only of the developing tooth, but also the regenerative nature of the cells that make new teeth. Serena, do you want you to come in? Well, I was just going to say one of the important differences between teeth and scales in the skin is that teeth can regenerate. So that's an important thing that you're investigating, Gareth, at the moment. It is, yeah.

And so the term regeneration is quite interesting because the skin is regenerative. So if you cut yourself, the skin will grow back. And that's the true sort of classic definition of regeneration. And so in sharks, if you cut their skin or you take a plug of tissue out of their skin, they'll grow the skin back relatively quickly. And then they'll also regrow those denticles, these skin teeth back as well. So there is a regenerative capacity that is sort of inbuilt within the skin,

but teeth do it slightly differently, right? So teeth have this sort of autonomous sort of cycle of regeneration where every one tooth is followed by a whole series of teeth sort of lining weight. And there's a little stem cell niche at the end of that battery of teeth that seems to be maintained and it continues to make teeth over and over again. But I was just going to interrupt. But one of the important things about this regeneration or in the same, scales, is it actually regeneration because

new scales will form, but they are deformed, they don't develop the similar type of scales. So it is very different from what happens with teeth. Can I say with you, Zerun, what difference would it have made to the early vertebrates when they discovered they had teeth? Well, again,

as an evolutionary advantage, teeth are very good because you can bite things, you can tear flesh, and then you can also break it down so that it's is processed and digested more quickly, and the nutrients from it much more quickly as well. But when the jaw vertebrates first evolved,

there seemed to be several features that evolved at that one particular time. So you get jaws and teeth. You get also in placoderms, you get the evolution of a movable head on the body armor, so a neck effectively, and then you get two sets of fins. So it looks like that jawed vertebrates, when they first evolved became more active

in terms of their locomotion, which would go together nicely with them, also being able to have jaws and teeth to attack and break down their food. In that sense, did it give them, let's call it, a sort of supremacy? Certainly an advantage, in evolutionary terms, I would say. How much of an advantage?

Well, they're now the most successful group of vertebrates living today. So, again, the jawless vertebrates that are alive today just include lampreys and hagfish. which are only known from a very few number of species. So is teeth that made the difference? One of the differences, sure. What's the other? Well, again, just this ability to, well, locomotion,

to be able to swim more quickly, to be able to capture prey. Moving your head on the rest of your body is also very advantageous because if you think about a fish raising its head and dropping its jaw at the same time, it creates a very big mouth so it can eat bigger prey items, but also as the jaws dropped, it creates suction as well.

So that whole mechanism is very, again, advantageous, functional for bringing food into the mouth of these jarred vertebrates. Phil, what about the animals that didn't get teeth, the nonvertebrates? What happens to them? So lots of invertebrates also have teeth or tooth-like structures. They've evolved independently, but in terms of their shape and their function, they're much the same, even though they're not supported necessarily by jaws. So close relatives of vertebrates, things like sea urchins,

they have teeth as part of their Aristotle's lantern. Aristotle's lantern? Yeah, so it's a complex jaw apparatus which sits just inside the test. In Aristotle's study, it comes from that. Yes, yeah. So it's a very complex mechanical apparatus for scraping away at subsist.

or eating prey. And in fact, some of the genes that are involved in the development of those so-called teeth are some of the same genes involved in tooth development invertebrates as well. But there are a whole host of different groups of invertebrates like the penis worms, the horsehair worms, the round worms, as well as lots of arthropods and cynthicephylans. All of them have tooth-like structures because they all want to grasp prey, which doesn't want to be eaten. When you say tooth-like, does it accord?

of the definition that we were given at the beginning of the program? No, they certainly don't have teeth that are made up of the same tissues. They're not made up of enamel or dentine. But in terms of their shape and in terms of their function, they are the same. And that's why they basically look the same. So they can be predators too?

Yes. So why did I say earlier that vertebrates got an advantage? And you all seem to agree? Well, vertebrates did get an advantage, but compared to what? Compared to their jawless and toothless relatives, which were making a living just by you know, swimming around in slurping mud up,

then I don't know, I think that the life of a jawed and toothed vertebrate is a better one. I hope they knew it at the time. Gareth, when so many other animals regenerate teeth in various ways, why are we stuck with a mere two lots? Great question. So in mammals it seems that we have reduced the number of teeth that we make because we're more sort of focused, I think, on forming teeth in a specific shape

for a specific function. So mammals have a relatively specialised diet, for the most part, and their teeth are made for function, right? So they're made for a specific diet. If you think about cows that chew a cud, and they sort of like to chew and grind grass down, they really need their molars to work together. This is called occlusion.

The fact that their molars are shaped perfectly to align with each other. It means that they can actually process that grass down to a cut and actually get all the nutrients out of it. If they didn't have those teeth aligning, then they wouldn't be able to generate the nutrients from the grass. What other variants are there? Oh, many.

Well, can you give us a few more? Well, just the teeth in our mouth, for example. We have incisors, we have canines, we have premolars and molars. They're all very different shapes because they all do slightly different things. So if you think about our incisors, our incisors are really there to sort of grasp the prey,

So to take whatever it is we're eating and pass it through to the back of our mouth where it can then be processed by our molars, right? So we're omnivorous. And so our molas are really good at chewing plant matter and also chewing meat. But there are some vertebrates, for example, cats that have molars that aren't like cows, they're more blade-like, and they're there to shear and to slice through meat and muscle. So we have a huge – I think mammals are incredible, that they have a huge diversity of dental form.

And, yeah, it's a very specific way. But I think mammals specifically have targeted occlusion as a really sort of important sort of mechanism. So if we did replace our teeth multiple times, the chances of our molars misaligning are quite high. And so some vertebrates wouldn't survive because if their molars don't align, then they can't generate the nutrients from their food.

Well, I was just thinking that we do have examples in sharks that show a similar type of. of differentiation of their teeth from the front to the back. And that's known as heterodonti. So the Port Jackson shark, for example, is heterodontus. And it has more of a grasping dentition at the front of the jaw. But then as you proceed back towards the jaw joint, there's more of a flat crushing dentition.

So, again, that's maybe not exclusive to mammals. Sharks are normally not so heterodont in terms of their dentition, but that does give one example where that happens. I think this is actually interesting because I think there should be a division between crushing, which is I think what you're discussing, and an occlusion that we see in mammals, the actual grinding of food. And so in sharks, even though they have these malaria form, these flattened back teeth, they're able to crush prey, hard prey like mollusks, for example,

and crack open that shell and maybe process that stuff, that food stuff to some extent. But that's, I think, slightly different from true occlusion that we see in mammals, where you have molars that come together perfectly. The shape of those molars are incredibly sort of intricate and multicuspid. So the development of those structures are, it's quite complicated. So if you replace the teeth that sharks will replace

multiple times during a lifetime, and we're thinking about those back teeth, they still can perform the function. But if you do the same and you try and replace the molars of a caro multiple times, the chances of those misaligning are quite high. So I think that's why mammals don't have really the capacity to regenerate multiple times.

And what's interesting about humans is that we probably need more teeth. So our lives are getting sort of longer. Our diets getting worse are more acidic. And so... What ways are diet getting worse? It's becoming very acidic, I think. I think, well, it depends on which group of humans we're talking about. But we're talking about the Western world.

I mean, you know, our diets are becoming more salty, more sugary. And so that sort of, that lends itself to an acidic diet. And so that's basically taken away some of the material, the minerals, within our teeth, and creating cavities and eventually we lose our teeth. So I think humans would like to have more teeth. I think if we live to 100, which is the way that things are going with medical science. By the time we're 40, we could do with another set of teeth, maybe 50. But absolutely, by the time we get into our 60s and 70s, we need new teeth.

And so the problem is that our dentition isn't really fit for purpose in that sense. So we need to figure out a way to make new teeth. like sharks. Phil, how near are we to figuring this out? Well, I think there are start-up companies already that are trying to grow teeth on a dish so that with the ideal of patients being able to have their own cells creating teeth in a dish that can be clinically implanted into their jaws.

Yeah, there are several groups also that have some sort of topical gels that you can sort of smooth over your own. enamel. And it helps to try and sort of, I guess the idea is that it tries to renew the enamel that you already have to try and reinforce the amount you have. So there are lots of labs and groups and private companies that are really trying to extend the life of our teeth that we have. And then there are lots of other labs and research groups that are trying to figure out ways in which to make new teeth, brand new teeth. And so the one thing about sharks that really intrigues me is the fact that they can make brand new teeth over and over again. Do you want

to take this up, Serena? Well, again, I'm not going to pass it over to Gareth, but his work is showing that taste buds in the mouth seem to be very important in tooth development and tooth regeneration. And when he first told me about this a few years ago, I was just really, I didn't really understand how that could be. And it was such an interesting idea that these two sort of of what seemed to be quite dissimilar structures were related in developmental terms. So maybe you can go into that a bit more, Gareth. Yeah. So what's interesting is that if we talk about the origins of teeth and the evolution of teeth, One of the things that I guess as penantologists or evolutionary biologists we're sort of keen to understand is what was before teeth.

What are the structures that came before? And so if you look at these jawless fishes, their mouths are probably lined with taste buds. And taste buds definitely evolved before teeth did. And so one of the things that we've been trying to think about is this link between taste buds in the jaw and how teeth may have taken over that space. And what's intriguing about taste buds is that they're incredibly regenerative. So I think in mammals, I think maybe 10% of the cells in a taste bud in mammals is to replace. every day. And so they're incredibly regenerative. The same genes are involved in the development of taste buds that they are in teeth. So we're actually starting to think about taste buds as

sort of almost like a forerunner for teeth. And so if you think about this inside out or outside in theory, when competence to make teeth made its way into the mouth, it probably interacted with those factors or genes that were involved in regeneration of taste buds. And that then may have allowed teeth to adopt that fate of regeneration. Phil, did Teeth appear only once on the evolutionary scale? Well, according to Garis' definition of a tooth, yes, but there are many types of teeth also within vertebrates. So Zerina has already mentioned the jawless vertebrates,

the hagfishes and the lampreys, and they actually have tooth-like structures, but they're made exclusively from keratin, so the same tissue that makes up our fingernails and toenails. and they are supported by a jaw-like apparatus, but it works from side to side rather than top-down. And some people have argued that maybe that foreshadows, you know, the development of a true tooth.

But then there are other more advanced groups like amphibians, so the tadpoles of frogs, they have a set of primitive teeth, but again, they are composed of keratin, they're not made of dentine and enamel in the way the teeth are classified. basically thought of. And then there are various extinct groups like there are some pelagic birds that survive for tens of millions of years that couldn't develop teeth because they had a caratinous beak and that precludes tooth development. So instead what they did was

to develop these huge bony projections that extended through the caratinous beak to perform a tooth-like function. There are many lineages that have solved the problem of wanting to retain prey or processed food in different ways without simply co-opting the existing tooth. Going forward from 450 million years ago, when did the teeth arrive at the point where it made a significant difference to the way that the animal kingdom, including mammals, of course, was developing? So I think almost instantly, we see, if we look at the, within the first tens of millions of years of jawed vertebrae evolution, we see a great diversity.

of tooth types, crushing denticians, shearing denticians, grasping denticians, showing that the feeding ecology of jawed vertebra, it's a dramatically increased from the simple deposit feeding modes of their jawless and toothless ancestors. So it really did have a very dramatic effect. And as we look at the rest of vertebrae evolution, we just see the emergence of these recurrent themes of of convergent tooth evolution to perform the same sort of tool functions of food processing and food capture. But I was just going to say what I find quite interesting is that, again, in the fossil record, if we look at the animals that are most closely related to sharks and bony fish,

some examples from Chinese fossils are showing that teeth are in fact absent. And if you go into the fossil history of sharks themselves, we see some groups, have teeth, but other ones have lost. So it seems to be quite a patchy patterning of whether you have teeth or not, for example, when you're looking at shark evolution. But in the introduction, I said something

like that once the teeth got underway, he gave those with teeth a supremacy. When did that, I just would like to know if you have any idea about what time did that make itself evident? Well, I think, again, as Phil said, when jaws first of all, we do have teeth appearing. But again, just the capacity to change teeth and change denticians, sometimes perhaps you lose them. Sometimes they're modified to be fused in the chimerids. I was a type of shark relatives that Phil mentioned. And I just feel it's really

interesting for my own research to be looking at how these different types of dentitions evolved and developed. But again, yes, when you first have jaws, and teeth, that's when they become important. I guess a big changeover was the end of the Devonian period about 350 million years ago, when this great diversity of armored jawless vertebrates that didn't have jaws, didn't have teeth, they basically went extinct.

And that is something that follows the dramatic diversification, both of lineages of jawed vertebrates, but also of feeding ecologies rooted into different dental functions. Did they go extinct because those with those with... teeth were making them extinct, or was it a coincidence? I think it's a coincidence because they weren't feeding in the same way. They weren't trying to capture the same prey. They weren't competing for resources in anything like the same way.

But nevertheless, you know, being a jawed vertebrate was a better deal than being an armoured jawless vertebrate. Gareth, are these things developed in the embryo, the modifications and such? They are, yeah. So, yes, so teeth develop in the embryo, but also modifications do occur in the embryo. So if we look at the embryo of fishes, the first dentition to develop in fishes may not be the same dentition it has when it emerges as a larva or as an adult. And so one of the things that we're sort of looking at is the change, not only in terms of the evolutionary change of teeth, but the developmental and the continued developmental change of teeth as well. So one of the fish groups that I study are pufferfish.

and puffer fish are really quite incredible because they, as embryos, they develop a normal set of teeth like any other fish, these sort of unicuspid conical teeth that lie in the jaws. But their second generation, so this is a result of regeneration there, their second generation teeth, start to make a beak,

much like a bird, right, but made of dentine and enamel. And so what I'm sort of really sort of keen to understand is the diversity of these structures and how they diversify not only among groups, but within groups during development. So looking at groups like puffer fish and other strange fishes to show the transition of teeth between embryonic teeth, larval teeth and then adult teeth.

And it's this process of regeneration that allows them to do something really quite different with their dentition. So puffer fish are only able to make a beak because they regenerate their teeth continuously like a shark. But instead of making brand new teeth every time, they just make these new bands of dentine, which have an enamel cap, and they sort of pack these together and stack them up into a beak. And so they're only able to make these beaks because of this, this propensity to regenerate the dentition. Zerino, in your area of research,

what is it you most want to learn about teeth? We've been looking at shark teeth and dentitions now for quite a few years, and we've been looking at various aspects of how sharks organize their teeth along the jaw to get the very precise patterning that you see in many, many sharks. But again, in this group known as the chimerids,

they just have a plate-like dentition. But if we look at the fossils of these chimerids, they have separate more shark-like teeth. So one thing that we're very interested in now is to learn how you go from this separate tooth-like, sorry, this separate tooth dentition that you have in sharks to being this fused plate-like dentition that you see in these chimerids. So again, like Gareth, just looking at how teeth change through evolution. Finally, Phil, what application would this have? what you've been talking about now to human health?

So we've already discussed the possibility of growing your own teeth or using topical substances to try and regenerate tissue layers on teeth. But the other aspect that's of importance with regard to teeth and tooth development is the fact that they serve as fantastic models for organogenesis, for simply organ development. Teeth are at the same time perhaps the simplest and the most complex of all organ systems. They're very simple because they develop simply as a consequence of bending a sheet of cells and the shape of the tooth is dependent on the way in which that sheet of cells is deformed.

But they're also amongst the most complex of organs because they result from an interaction between two different primary embryological tissue layers. One is the oral epithelium and then the other is a migratory population of stem-like cells that comes basically. from the midbrain and migrates to the position where teeth will develop. That's quite a complex system of getting all the right cells in the right place at the right time and getting them to communicate biochemically to get the tissue laced at a form, to make a tooth shape, and for all the cells to develop into the tissues that make a tooth. Well, thank you very much. Thank you very much for your Donoghue.

Zarina and Gareth Fraser. Next week, it's a mid-summer-night's dream, one of Shakespeare. most popular plays. Thank you very much for listening. And the In Our Time podcast gets some extra time now with a few minutes of bonus material from Melvin and his guests. We are looking at taste buds in a bit more detail. We're now starting to sequence cells that are more specifically taste-like versus those that are more tooth-like,

to see if there's any real comparisons between those cells. But yeah, looking at rays, potentially at some point looking at chimeras too. Oh, yeah, we should talk about that. That would be great. We'll talk about that now. Yeah, well, again, as I was saying, that in the fossil record, we have relatives of these chimerids that have separate shark-like teeth. They're added in the same way. They have similar shapes.

But then they also show within their dentition some degree of fusion. So what we're interested in at the moment is how does this fusion occur and how does that relate to the, again, chunky dental plate that you see in modern chimerids? Is there some sort of evolutionary and developmental process? So I would be interested to know if you know anything, and maybe also you feel about how teeth may fuse. Think of Helodus, for example. That's what I'm talking about. So we're looking at Helodus denticians,

and along the jaw, there are separate teeth, but at certain points in the jaw, it's pleoplax, it's this fused structure that you might know about. But it's the same species, and we're just interested in how you get that transition from separate teeth to fused teeth. And that's the transition we see within early shark evolution, right? So modern sharks have these families of teeth where all the teeth are lined and they all develop from the same pocket within the dental lamina.

They're all basically descendants of the same lineage of cells. But they're essentially separate from each other so that once they're done, they can be shed. The latest, the oldest tooth can be shed. But the ancestors didn't do that. The teeth were all fused together. They had a bony, curved plate. And these poor early sharks would have had a face full of rotten teeth. teeth basically hanging out the outside of their

jaw, yeah. So is that a precursor then to fusion to just retain the teeth and then fuse them later into more of a plate-like structure? Great question. I mean, there's a practical problem here and that is you can't always get embryos of these funky fish. No. Right? And so you know, I study a species of shark because you can get hold of those embryos relatively easily. They're not protected. They're not threatened in any way so they're easy to get hold of. But some of

these species like the chimerids, these are hard embryos to get They are. You can get them off of Australia. Yeah, right. So you can get them in some places like Australia. And the problem is that these fish or these sharks, shark relatives, they lay these eggs very deep in the water. So they're very hard to come across the embryos.

And even if you do come across them, you may come across a handful. And the sorts of numbers of embryos that we study mean that we can sort of understand processes across developmental times. You need quite a few embryos to do this study. So I think we're limited by the number of embryos we can get hold on. And we're definitely limited in terms of the number of the number of. number of species we can study because most of the species that we'd like to study, we can't find embryos for. Some of these fishes that I study, some of these puffer fish,

they're sort of open ocean breeders, so the males and females will basically lay their eggs and melt in the open ocean. They'll fertilize those gametes in open ocean, and then those embryos will just go and float around the ocean. So it's really difficult to go and get a bunch of embryos, right? So this is the problem, this is the sort of limitation to the developmental studies that we're doing. We need to be able to find embryos to do the stuff. study. If there's a great morphology of a specific species, that's wonderful, but you may not be able to get the embryos to do that study. So the thing I'd like to do, or get someone to do more, more likely, would be to learn not more about tooth development, but more about scale development.

So one of the key aspects of tooth development is this migratory population of cells. The neurocrest is intimately involved in the differentiation of all the component tissues and the interplay in terms of its biochemical conversation with the oral epithelium. But we don't really know whether that's the case with scale development. You know, in terms of the morphology of the development, the shape of the development of scales, it looks exactly the same as in teeth. And indeed, most of the genes that are involved,

they're all expressed in more or less the same way in tooth-in-scale development in beasties like sharks. But we don't know for sure whether Neurocrest has this role within scale development. And if it doesn't, then that could really be an important arbiter in this debate about where teeth came from or whether inside or outside of it. So the one thing I would add to this inside out, outside in debate, is that there have been a few studies recently that have shown that actually the endoderm, which lines the mouth and the sort of the posterior cavity of the mouth and pharynx and it also bleeds into the foregut. This is all endoderm. And actually endoderm is the tissue that outpockets rather than ectoderm inpocketing.

And so if we really think about the sort of developmental problem. processes that are occurring, it's more likely the endoderm is making its way out into the ectoderm than it is the end of the ectoderm moving into the mouth. So to make matters worse, I should add, just for completeness, that Gareth himself has come up with an inside and outside hypothesis. I'd like to see him explain it. There's a chance. Okay, I can explain it. I mean, so the idea that scales in the skin or teeth in the skin versus teeth in the mouth are very separate entities and they may have evolved around about the same sorts of time. But it's really, so my idea is that there really really isn't an answer to whether one came before the other, that they

both appeared because of this interaction between the cells and the gene networks. And so if you have the right cell type and the right gene network, you can make a tooth in the skin or the mouth, it doesn't really matter where. And so then it's sort of, you know, the question is, does it really matter what came first? But this has been for 150 years, you can't just solve it like that. This The argument has been very important. I think the thing... All the textbooks have to be remitridden. Well, so annoyingly, one of our last papers,

we sort of, we support the outside in theory because we're talking about the competence of the ectodermal cells that make these skin teeth, moving their way into the mouth and collaborating with the taste buzz to make these regenerative teeth. And so in my mind, that sort of works, actually. And so I'm sort of, I'm right on the fence, I think, right now.

I like the endodermian, the sort of the main component of true teeth, but I also like the idea of these competent cells making their way into the mouth, interacting with taste buds to allow this new wave of regeneration. Is the producer? Just everyone want you to your coffee? I think I'm okay.

I'm all right, actually. Thank you. In our time with Melvin Bragg is produced by Simon Tillotson. Oi, you, while you're here, ever listen to this, Richard? Forest, four, four, fire, an environmental thriller for BBC sales. I'm so sorry. Meat, Pan. For what I did.

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