Ancient DNA solves the mystery of who made a set of stone tools

Shamini Bundell

Welcome back to the Nature Podcast, this time: the ancient mystery of which hominin left stone tools in Northern Europe…

Nick Petrić Howe

…and why human brain cells grow so slowly. I’m Nick Petrić Howe.

Shamini Bundell

And I’m Shamini Bundell.

Shamini Bundell

Before modern humans — Homo sapiens — ruled the Earth, the picture looked very different. Many species of hominin occupied different regions of the globe, each with histories of their own, and picking apart this complex evolutionary history is a puzzle which palaeontologists and archaeologists have been working on for well over a century. Sometimes that involves archaeology — artefacts like stone tools, dwellings, paintings. Sometimes it involves palaeontology — the remains of the hominins themselves. But often it involves both — linking archaeological findings to palaeontological ones. And that is the subject of our next story. The search to work out who, or what made a particular set of European stone tools, what archaeologists sometimes refer to as assemblages. Was it Neanderthals? Or was it Homo sapiens? Reporter Geoff Marsh spoke with Palaeoanthropologist Jean-Jacques Hublin who you’ll hear from now.

Jean-Jaques Hublin

Today, there is only one species of human on Earth. And that looks to us like the normal situation — it’s not. For millions of years before, there were several species of hominins, or humans. And we think that probably the most important event in the last million years or so is the fact that one of these species replaced all the others.

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So, what we’re addressing is this event — is the fact that humans coming from Africa through the near East, moved into the higher latitudes and replaced or partially absorbed, all the archaic hominins that were living in Eurasia.

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My name is Jean-Jacques Hublin, I’m a palaeoanthropologist, so I work on human evolution. Currently a professor at the College du France, Paris, and I'm a former director of the Department of Human evolution at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

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Geoff Marsh

So specifically, then the story we’re talking about today is in Europe. And Neanderthals they’d been there for hundreds of thousands of years. Is that right?

Jean-Jacques Hublin

Yeah, we think the divergence between Africa and Eurasia in terms of hominid evolution started at least 600,000 years ago. And this is long evolution in western Eurasia of is very peculiar type of hominins — the Neanderthals. And for long time period, we have been considering that yeah, there was a sort of transition, and that Neanderthals themselves made a sort of cultural transition into what we call the Upper Palaeolithic before being replaced by Homo sapiens coming from elsewhere. The problem is that this took place, let’s say between 50,000 and 40,000 years ago, we don’t have such a rich fossil record for this time period.

Geoff Marsh

But what they do have a lot more of relative to human remains is archaeology. And in particular, different assemblages of stone tools with characteristic styles.

Jean-Jacques Hublin

And this is the very topic of our study, with one of these assemblages that we call the LRG that means Lincombian–Ranisian–Jerzmanowician, it’s a very cumbersome name, but this group of industries, is something that is present in north latitude of Europe, from say Poland to the British islands.

Geoff Marsh

So kind of like in a band, north of the Alps.

Jean-Jacques Hublin

Exactly. I would say even further north, it covers Poland, central Germany, the Netherlands, and Britain.

Geoff Marsh

And – and have I got this right then this particular style of stone tools looks to be a little bit, almost transitional.

Jean-Jacques Hublin

Yeah, because some of the features seem sometime to be inherited from the local Neanderthals, and others were clear innovations. And so the common wisdom was that very likely the LRG was made by Neanderthals, actually, and that Neanderthals themselves made a sort of cultural transition into what we call the Upper Palaeolithic before being replaced by Homo sapiens coming from elsewhere.

Most of these sites, unfortunately has been excavated in the late 19th century, or the first half of the 20th century in the very region where prehistoric archaeology developed first, which is Germany, France, UK. And so, most of these sites has being completely, I was going to say, devastated by archaeologists, but they don't exist anymore. So, I’ve been very lucky to put our hands on one of these sites. Ranis is the site that gave its name to the ‘R’ of LRG. And this site is peculiar, because it's a ancient cave that collapsed, there is a layer with blocks that are about the size of a car. And so that made the excavation very difficult in the 1930s, between 1930 to 1938, when the site was excavated, and so there are some parts of the of the site that were left by the archaeologist and somehow it was preserved for us.

And we had to cut through a huge block that was like six feet thick –

Geoff Marsh

– of rock? –

Jean-Jacques Hublin

– of rock, yeah of pure rock. To go into the layers where we find this LRG stone toolkit.

Geoff Marsh

So yeah, you’ve come back this time with more modern machinery but you also came with more modern molecular techniques as well, which allows you to link more confidently these different artefacts with humans or Neanderthals.

Jean-Jacques Hublin

Yeah that’s, I think is most interesting about the project. When you excavate sites like that, what you have to realise is that what you find mostly is small bits of bones. By sorting thousands of pieces, by chance, sometimes we could extract a piece of human and this has been working already in some other sites. And so by using this technique, we have been able to identify a series of piece of humans. And then, of course, we returned to the original collection that has been extracted from the site in the 1930s. And one of our colleagues found some extra human pieces that were morphologically humans. But after all this, we ended with thirteen pieces of human coming from this layer. So you know, we went from zero fossil hominins, from the LRG, to thirteen.

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Geoff Marsh

Did that kind of give you an answer then? Were they humans or Neanderthals?

Jean-Jacques Hublin

Absolutely. When we pass these samples to our colleagues, biogeneticists and they extracted mitochondrial DNA. First of all, they were very surprised because it turns out that the DNA is very well preserved in the site. And so immediately, what we found is that the mitochondrial DNA is not Neanderthals DNA it is Homo sapiens’ DNA.

Geoff Marsh

So, first of all, does that conclusively clear up then who is responsible for this style of stone tool, the LRJ? Is that–that sort of seems– it seems like that means Neanderthals had nothing to do with it?

Jean-Jacques Hublin

Well, if you have thirteen, or twelve, piece of modern Homo sapiens, associated with stone toolkit, I would say the most simple explanation is that this stone toolkit was made by modern Homo sapiens.

And now, the picture emerging is that probably most of these so-called transitional assemblages are not transitional. They are the assemblages made by these very first pioneer groups of sapiens moving into the higher latitudes of western Eurasia. These so-called transitional assemblages are not transitional at all, they are just something new. Moving into a, I would say, a technological landscape that is more primitive. And that’s the landscape of the stone tools of the Neanderthals of the middle Palaeolithic.

Geoff Marsh

And does that help you tell a story about how the Middle to Upper Palaeolithic transition, how that process occurred? Like, what do you think it was just a case of more advanced technology wiping the floor with the older technology?

Jean-Jacques Hublin

Well, I think, first of all, what we see is that the replacement took a long, long, long time because the oldest specimens of sapiens that we have in Ranis, they are older than 45,000. Actually, the LRG layer is more than 47,000 years old. And we know that in some parts of Europe, South of France, places like that, we still had Neanderthals 40,000 years ago. So it means that for several millennia, you had modern humans living in, in Belgium, in Germany, probably in the UK already. And you still had Neanderthals living in central France, in southwest France and in other parts of Southwest Europe. The second thing is that this first peopling, they are very small groups that move very far into the territory of the Neanderthals and they successfully settle in places which are not the most favourable. They basically settle at the periphery of the domain of the Neanderthals and they stay there for a long time. So if there was some kind of, I would say superiority of these groups, it was not overwhelming at all, because it took a long time before later waves of subjects moved into Europe. And – and I would say finish the job somehow of replacing the Neanderthals.

Shamini Bundell

That was Jean-Jacques Hublin from the College du France in Paris, and the piece was produced by Geoff Marsh. If you want to read more about Jean-Jacques’s work, they’ll be links in the show notes.

Nick Petrić Howe

Coming up, we’ll be hearing why human brain cells are just so slow … when it comes to growth. Right now though, it’s time for the Research Highlights, with Dan Fox.

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Dan Fox

Geologists might have finally got to the bottom of a long-standing question about how a mountain range got so high. Gravitational studies of the Sierra Nevada de Santa Marta mountain range in Colombia suggests that — unlike other tall mountains — these are not sitting on top of a thick root of crustal rocks. To understand why, researchers simulated how the crust beneath the mountains might have evolved. They found that while the range did once have a root, it slowly disappeared over time. That's because the rocks that made up the root were colder and denser than neighbouring rocks. Those dense rocks sank deeper into the earth, removing much the crust the lay beneath the mountains, leaving them standing tall – even without a root to support them. The team say that this could have happened as long as 56 million years ago, or as recently as within the last 2 million years. Dig deeper into that research in the Journal of Geophysical Research, Solid Earth.

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Wine flowed through all aspects of ancient Roman life. Now archaeologists have revealed how it might have looked, smelled and tasted. Ancient Romans fermented and aged wine in large, egg-shaped clay containers called dolia. To investigate how these vessels influenced their boozy contents, researchers compared Roman dolia with similar winemaking jars used in modern Georgia. The comparison suggest that the shape of the dolia, like that of the Georgian jars, encouraged heat-driven currents in the crushed grapes inside the vessel. These currents promoted uniform fermentation by mixing the jars’ contents. The grape solids that remained at the bottom of the jar after fermentation gave the wine and amber colour. Burial of the jars promoted the formation of compounds that give wine aromas of toasted bread, apples and walnuts, and the authors say the conditions provided by the clay also provided flavours of nuts and dried fruit. Uncork the rest of that research in Antiquity.

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Nick Petrić Howe

Finally on the show, it’s time for the Briefing Chat, where we discuss a couple of articles that have been highlighted in the Nature Briefing. Shamini, what have you got for us this time?

Shamini Bundell

Well, I’ve been chatting to the authors of a Nature paper, and using some of their pretty microscope images of neurons to make a film that's out on our YouTube channel, and it’s all about why certain neurons in our brains develop surprisingly, slowly, certainly compared to other cell types and definitely compared to the neurons in the brains of something like a mouse.

Nick Petrić Howe

How slow are we talking here? Is this days, weeks, months, years?

Shamini Bundell

So obviously, it varies. But yeah, months, can be years for some of these, and like the equivalent cells in a mouse, you know, might take weeks. So there's definitely something that's going on that is controlling that speed. And these authors were kind of wondering, okay, is this something to do with the environment that it’s in? Or is this something intrinsic in these cells? You know, the equivalent cells in a mouse and a human that makes these human neurons — in particular, the cerebral cortex cells — what makes them grow that slowly? How do they know? And what's kind of controlling that timeline?

Nick Petrić Howe

Mmm so, they wanted to see why they were growing so slowly. How did they go about it? Was this like growing these cells in a lab or something like that?

Shamini Bundell

Yeah so, this is growing cells in a dish. And it was kind of, sort of started off a huge task, because what they wanted to do was basically figure out all the different changes that were happening so that they could see if any of them looked like they were sort of a controlling or a sort of causal factor. And there's so much that obviously changes in the development of a sort of particular neuron, you've got the sort of cell growth itself where they’re growing kind of longer, they're growing different branches, they’re growing synapses connecting to other cells, they're becoming excitable, and then you get the electric signals sort of being able to pass through them.

If you sort of zoom in, they're all these metabolic changes, this transcription changes, the cytoskeleton is changing. So what they did was they started off making this big atlas, they grew cells for 100 days, which, again, for these cortical neurons, that's not to adulthood. But you know, there’s only– they had to cut off at some point and basically — this kind of study takes annoyingly ages, because human brain cells take ages to grow, that's kind of part of why they were interested — and they looked at all of these factors, and they kind of mapped out all these different changes. And then from all this data, they were kind of like, okay, what's–what's the sort of next interesting thing to look at? What can we see? What's a factor that's changing that sort of well-matched to the age? You know, so the changes kind of gradually as the cells age so that maybe you could even use it as a proxy for that kind of stage of maturation. And the thing that they sort of focused on — well ah ha, let’s look at this — were epigenetic changes. How much do you know about epigenetics?

Nick Petrić Howe

I know a little bit. So, these are sort of changes that can control the regulation of DNA, like how much of it is expressed or not expressed. And often, it's things like modifications to histones, the things that wrap DNA up, and that can control how much of the DNA is sort of unravelled, available to be eventually, sort of transcribed and then translated into proteins.

Shamini Bundell

Yeah exactly. So, it’s not the DNA itself that’s different, it’s this next level of regulation of how much the DNA is being expressed. And in this particular case, it's how much certain maturation related genes are being expressed. So that’s the sort of link with how fast the cells are growing. And there are these particular epigenetic changes that they found, which were, as you say, markers on the histone molecules that kind of support the DNA. And they found these epigenetic marks decreasing over time. So, this nice graph of just the epigenetics marks going down and the sort of maturation of the cells going up.

Nick Petrić Howe

So you’ve got these sorts of lines going up and going down in various directions. But is this sort of a correlative effect? Is this just happens to be something that happens as they age? Or is this actually having a causative effect? Is it stopping – is it stopping them growing so quickly?

Shamini Bundell

Well yeah, that was the next sort of thing that they had to test. Let’s do some experimental intervention and see what happens. So these epigenetic marks, they have genes which make them — essentially like the epigenetics also have genes associated with them as well as the genes that they're impacting, if that’s clear. So, what they did is they did some sort of knockout experiments, where they blocked certain epigenetic factors stopped these marks happening. And what they found was that their neurons, without certain of these marks were developing faster, suggesting that yes, there's a causal relationship between these epigenetic factors actually reducing transcription of the certain maturation genes and thus, slowing down maturation.

Nick Petrić Howe

And do they know why there is this sort of like braking effect on the development of neurons, like, why is it that they are growing so slowly?

Shamini Bundell

That's not something they looked into. And, you know, this is also I should say, you know, this is one thing that they've looked into, that seems to have a causal effect, there could be other factors as well. There are ideas about the sort of evolutionary history of the brain as to why it might be beneficial for humans to have developed these slow developing neurons, as well as our obviously slow-developing brains, compared to other animals. But that was very much out of the scope of this study. But the kind of more applied thing that they were thinking about is, if they know why the cells grow so slowly, they could potentially speed them up, which, like, as I said at the beginning, oh they had to wait a hundred days for an experiment, like –

Nick Petrić Howe

– annoying –

Shamini Bundell

– you can imagine that there are, yeah, scientists in labs around the world being like, oh I want some neurons I’m gonna have to wait for – wait for these ones to grow, oh, God I don’t have time for this. So if you can speed it up, you can get potentially more mature, maybe adult neurons, much quicker, much more efficiently for your research. And that's super relevant if you are studying diseases, which tend to impact older neurons or like adult brains. If you think about something like Parkinson's, for instance, you might need the older neurons to be able to do whatever your studies are doing.

So, this group were interested in not just kind of working out that sort of correlation, but also saying is there an intervention that we can do that would actually change the speed of cell development? And there was one in particular that they tested out, where rather than a sort of permanent gene knockout, they did a sort of temporary treatment, and actually did this treatment to the stem cells. So before the neurons were born from their respective neural progenitor cells, they did this temporary treatment, and that led to faster developing neurons.

Nick Petrić Howe

Ah that's super cool. Were the neurons relatively like, you know, I guess, normal, or were they a bit different compared to neurons that have been grown the sort of classic, slow route?

Shamini Bundell

Well, these are definitely neurons that are growing in a lab as opposed to a brain. So that's obviously really significant. They did try it out on as well as sort of neurons in a dish: organoids, so sort of like 3D cellular structures that sort of maybe slightly more closely mimic an actual brain. So just sort of make sure that, you know, there's still that same effect, although they haven't sort of like looked at, you know, compared it all to see what the differences might be. And another interesting thing that they mentioned, although they didn't go into it very much, was back to the sort of comparing this to mice thing, which is, there was an indication that this epigenetic barrier, they call it like a brake, like it's putting the brakes on the development. And then as that epigenetic barrier falls away, then you're kind of like lifting the brakes and the developments speeding up. So they found an indication that that same kind of mechanism might also exist in mice in the mice neurons, but perhaps at a lower level, so like a less of a braking effect, which could be why the mouse neurons develop faster. So it's the same thing but acting at different speeds.

Nick Petrić Howe

Well that’s super interesting and I'll be sharing that with some of my friends who I know grow neurons, because I imagine they'll be quite interested in getting them a bit faster. For my story this week, I've been reading about some gene therapies. And I've been reading about this in Science. And these are gene therapies that could actually allow deaf children to hear.

Shamini Bundell

Okay, and so take me back and explain what gene therapies actually are.

Nick Petrić Howe

So gene therapies are basically therapies that you can do on a person once they've been born. So this is not like modifying people before they've been born or anything like that. And basically, they aim to treat diseases that arise due to faulty genes. And they aim to replace those genes with genes that function as you might want them to. So for instance, in this case, they were looking at a particular gene that causes deafness in some people, which is the OTOF gene, and they were replacing faulty copies of this OTOF gene with functional ones that will produce the protein that's involved in allowing hair cells in ears to relay sounds.

Shamini Bundell

Okay, so this is a particular cause of deafness in children — a genetic cause — and a particular group of cells that they're targeting with this gene therapy.

Nick Petrić Howe

Yeah, that's right. So, what they do with this particular one is they use two viruses to carry parts of the gene to it, just because it's a massive gene. So, they had to package it between two viruses, the viruses will then go to these hair cells in the ear, they’ll inject the relevant DNA, and that will sort of replace, as it were, the faulty gene, and then they'll start producing the functional protein that will allow their hair cells to properly relay sounds. And this has been quite successful. So this article in Science is about a couple of different trials that have been done. So there was a press release from Eli Lilly & Co., where they've done this particular technique on a profoundly deaf boy in Morocco and now that boy can hear sounds. And there was also a small study that was reported on in the Lancet in China, where children can now verbally communicate after doing this therapy.

Shamini Bundell

And is this still at the sort of very experimental treatment type stage?

Nick Petrić Howe

Yeah, this is still very early days. So, there's a lot of things that we don't know about this, for instance, we don't know how long it will last. So, hair cells are interesting because hair cells don't divide. So, this could just last forever, it could just be that once you fix this particular gene, it stays fixed forever. But it could also be attacked by the sort of immune response and that sort of thing. So, we don't actually know how long it will last. So that will be one thing that we need to monitor. And also, this is for one particular kind of deafness and there are many different forms of deafness caused by genetics, that could be targeted by a similar approach. So, there's one that is sort of like the Holy Grail, which has the fun name of GJB2 and this can cause 30% of inherited deafness in some populations. So, to be able to tackle that would be able to help a lot of people who would like to be able to hear.

Shamini Bundell

So where are the researchers behind it what to go from here, then?

Nick Petrić Howe

Well, as I say, there's lots of different kinds of deafness that could be tackled. There's also adult deafness, which is a bit more of a difficult and intractable challenge that maybe researchers would like to tackle. But I think mostly researchers are just quite excited about this, because other than cochlear implants — which is a particular kind of prosthetic people can get, which can help them hear — there's been no real sort of successful therapy for deafness. So, this is the first of a new kind of therapy for deafness. And researchers are hoping because there's been these sort of small studies that have shown success, it will drive a lot more investment into this and there'll be a lot more interest in this field overall.

Shamini Bundell

Fascinating, and thanks, Nick. And that’s all we’ve got time for right now, but listeners if you want to read, or in my case, see more on those stories we’ve just been chatting about, we’ll put some links to them in the show notes. And also, as always, a link to where you can sign up to the Nature Briefing to get more of these kinds of stories.

Nick Petrić Howe

That’s all for now but keep an eye on your podcast feed for more later this week. We’ll have a roundtable on how cervical cancer may be tackled. In the meantime, you can keep in touch with us on X, we’re @NaturePodcast. Or you can send an email to podcast@nature.com. I’m Nick Petrić Howe…

Shamini Bundell

… and I'm Shamini Bundell. See you next time.