Steve: Welcome to Manifold. Corey, this week we’ve got a real treat. Our guest today is John Hawks, a professor at the University of Wisconsin. He is my favorite perhaps — or definitely one of my favorite — “bone-diggin’ologists” in the whole world. And John is actually a triple threat, he’s a very rare talent: he participates on the physical anthropology side of things, actually finding new fossils, new bones, new sites to dig in; he’s got the chops to really understand the computational genomics around ancient DNA, how to derive knowledge from really complicated archaic DNA sequences; and third, he’s really a great public speaker. He’s become kind of one of the best-known people in this field for communicating to the public. So really excited to have John as a guest. Welcome to our show.

John: Brilliant, thanks for having me.

Steve: I’ve been aware of John for many years reading his blog, but also I think we have some scientific collaborators in common, so some of the people he’s worked with in the past or people that I’ve known. So I want to start with your sort of scientific biography, maybe talking about what you were thinking when you were a grad student, what you did for your PhD, and then after that where you went for your postdoctoral research.

John: Sure, absolutely. You know, I got into anthropology as an undergraduate at Kansas State and I Iearned my bones from a forensic anthropologist, his name was Mike Finnegan. He was the forensic anthropologist for the state of Kansas, great guy, and I was teaching for him because at Kansas State we had undergraduates teaching laboratories. So it was a great way for me to get into the field. I was not thinking anthropology at all when I really started this. I was an English major and I was interested in anthropology, but I didn’t really know what that would be as a career. When I went to graduate school I went to Michigan. I was a student with Milford Wolpoff, and he was very famous for his participation in the modern human origins debate. He was a big supporter of the idea of multi-regional evolution, that modern humans had ancestry from populations that lived in Africa and other parts of the world, and that was a really exciting scientific debate at that time. And so I was really privileged to be able to do some research on Neanderthals, on other kinds of fossils to try to address this issue of human origins. But this was also the late ’90s, when genetics was becoming a bigger and bigger source of evidence about human relationships, human origins; and genetics at that time was clearly a growth industry. Finding fossils — some of the really premier people in in the field were saying look, we found all the fossils that we’re gonna find and you might as well close up shop because all of the fossil fields are becoming exhausted. And so I moved into genetics, went to work on a postdoc with Henry Harpending at the University of Utah — great human geneticist, great anthropologist — and started working on genetics and population size, and the way that we could talk about ancient population sizes and demography by looking at DNA sequences from today’s people. This was really well before we had useful information from ancient DNA. And we did some work on natural selection in humans, we tried to look at ways that population growth would affect the pattern of natural selection, and then did some theoretical work on the way that you might expect to find genes from Neanderthals and other ancient populations, what they would look like and what kinds of things you would get. And so that was what I was up to in my early career.

Steve: Henry passed away a few years ago, and I knew him, and I always thought he was not only a fine human being but also just a very, very sharp intellect, and the things he had worked on in various areas over the years were just really impressive. And when I found later that he had done actual field work in Africa and lived in the, I guess they would say in the bush or whatever, with some various tribes, I was just further impressed. Maybe you could just share maybe one good anecdote about something that happened with you and Henry when you were his postdoc?

John: You know, Henry, I think he was at Penn State for many years, and when he went to Utah he went with a budget, he was a member of the National Academy and, you know, he was always a theoretician. Henry was always concerned with trying to figure out what you could do with data, and really pioneered some of the early applications of principal components analysis to genetics, to gene frequencies, he thought very deeply about demography and what you could say from hunter-gatherer demographies about ancient humans. And when I went to work with him I really feel like he hired me to have somebody to come down to his office and shake him up once in a while [laughs], like, you know, he had been one of the big Out of Africa proponents, because his genetic work had really focused on population growth and dispersal and the idea that we could look at mitochondrial genetics and look at this Out of Africa event. And so for him to hire me, I’d come from this big multi-regional school, I really believed that he just wanted me to poke him once in a while. [laughs] And so I did, you know, it was a lot of fun. We’d have some new paper come out, and I’d go down, and he’d say “Now, doesn’t this finally convince you that you were wrong all along?” I said “Well, Henry, there’s a problem, and here’s what it is.” And by god he would usually walk away and think about it for a while and then come back and say “Damn it Hawks!” [laughs] You know, it was that kind of relationship, it was really neat.

Steve: That hits one of our themes here on our podcast, which is that you always want to hear the strongest arguments against your views, and it sounded like Henry wanted you there to do some of that for him. I think for our audience maybe who aren’t so familiar with this field, multi-regionalism was the idea that humans could have evolved sort of separately in different places on earth, whereas Out of Africa was that modern humans first arose in Africa and then spread to the rest of the globe. And that was a very controversial topic, I guess going back into the ’80s, is that correct?

John: Yeah, there were basically three views, and one of them was that you had Neanderthals and Homo erectus and some African populations, but we had very little fossil evidence about them, and they might have progressed separately and evolved into modern humans separately from each other. That point of view was called polygenism, and by the 1980s nobody believed this. It was really debunked in the 1960s. But that idea sort of hung on, because it’s always easier to try to reject an idea that has these really clear boundaries. The Out of Africa idea was that the African ancestors of modern humans were the real important ones, and they spread throughout the world sometime within the last 100,000 years and extinguished Neanderthals and potentially homo erectus and whatever other populations there were. So you had this one source population that spread throughout the world recently in our evolutionary history and got rid of all the others that were there without any interaction. And then the multi-regional point of view was that all of these were connected in some sort of network all the way back into prehistory, so Africa might have been really important, but Neanderthals were also important, and they’re all sort of connected and all, you know… The extent to which they’re different is driven by distance and not by replacement. It was really tough to convincingly come up with evidence that absolutely rejected one of those, you know, that was really the challenge that we had from the fossil record was, you’re looking at this stuff and it’s like, well, some people say these look similar and some people think these look different, and how do you quantify that and how do you establish what differences and, right, it always came down to these real detailed sort of things that you could argue about.

Corey: It’s actually unclear to me a little bit how they’re so different. Is it different time scales that are at issue, so we’re talking about in the regional hypothesis there are thought to be human populations there going back three to four hundred thousand years? Or only there are human populations there are a million years before? Was there clear — there must have been clear time lines attached to each of these theories, because it’s just hard to get them precise less you’re saying, you know, this group was there at this point in time or not. Was it all that clear, was it equally — it seems like it’s a little vague. How clear were these theories, how clear are they now?

John: The thing is that if I’m sketching out a picture of what our evolutionary history looks like, the big picture today it’s gonna be somewhat different from twenty thirty years ago. And so and I didn’t want to introduce wrong information now, but I can say that twenty, thirty years ago, fifty years ago even, our ideas were so dominated by Neanderthals, because Neanderthals were a fossil population that lived in Europe from hundreds of thousands of years ago up until about 30,000 years ago, and they don’t live in Europe now. And so both, all of these theories were really formulated when the Neanderthals were the major source of evidence about fossil humans, and the question is, are they us or not? And if they’re not us, what happened to them, right, why are they gone? And if they are us, why don’t we look like them? What is the mechanism of evolution that caused later Europeans to look so different from the Neanderthals? So that was the framework in which these developed, and it was very end-oriented. It was really about what happened to these people that lived 40,000-50,000 years ago, and in the absence of real evidence about who else there was. The way that the world has changed in the last twenty, thirty years as we know some more things about who else there was. Some of this has come in from the rich genetic record that’s accumulated, and some of it’s come in from new fossil discoveries, and while we haven’t filled in every last place — in fact, I would say we’ve only really just begun to fill in the details of these things — nonetheless it’s, we can, we have the luxury today of not being so focused on Neanderthals.

Steve: I seem to recall, Corey, when I was a kid growing up and reading about this stuff, that there was a very strong multi-regionalist hypothesis was literally that modern humans, like East Asians and Europeans and Africans, could have actually evolved separately from different archaic ancestors. And that would be the really strong kind of multi-regionals, like you got modern humans in different places but through different mechanisms and different lineages, as opposed to the first moderns appearing in Africa and then spreading out across… So those are very different hypotheses.

Corey: Well, even the multi-regional hypothesis — presumably humans are the same species, right — if you’ve got them evolving to modern form in different regions, at some point in time they had a common lineage, so it seems to depend upon the time frame.

Steve: So you could just draw different diagrams with different time scales for when the different divergences happened and things like that, I suppose.

Corey: Does that sound right, John?

John: Yeah. To put this into real chronological perspective, more than two million years ago we have found no evidence for any kind of hominins anywhere other than Sub-Saharan Africa. Before that we know our origins are African, but all of those hominins that lived at that time were fundamentally ape-like: they walked upright like we do, but they had small brains, they were, maybe some of them initial tool users —we have some stone tools that go back that far — but they didn’t have body shapes like modern humans do, they didn’t seem to be super well adapted for walking long distances or maintaining large home ranges. They were apes that walked upright. After two million years ago two things happened: one is, we see the first evidence of members of our genis homo, that have human-like body shapes and seem to have larger home ranges. They’ve got a little bit bigger brains than their ancestors did, and they seem to be more sophisticated in that sense. They seem like food-sharing, hunter-gatherer looking subsistence pattern, and they show up outside of Africa — we first find them in the Republic of Georgia, but we have early evidence of tools that are about two million years old in China, there are hominins in Java before one and a half million years ago — and so it’s clear that there’s this dispersal that happened with very primitive early members of our genis. The Out of Africa / multi-regional debate was about what happened after that point, and whether these early colonists were the ancestors of today’s people at all, or whether they were replaced by successive waves of migration from Africa, and the most recent of those waves was seen as — probably was — the most important, the largest, and that all happened within the last 100,000 years. So you’re looking at this difference between, maybe human variation becomes established one-and-a-half, two million years ago, or — and then after that point there’s evolution so that we become modern humans everywhere — or modern humans are a recent product, they evolved in one place, Africa, and after that point they dispersed and replaced all these other people, so all of these other primitive hominins were just gone, because modern humans which evolved in Africa were superior, they replaced them.

Steve: I guess the, you know the statement is we sort of know the answer to this question now, that based on the DNA similarity of all modern humans around the earth and the evidence for a very tight bottleneck that they may have passed through really does suggest the latter scenario that he’s describing, which is that modernity first manifested in a local region in Africa, and then those people spread throughout the world and largely eliminated — maybe mated with but largely eliminated — the archaic species that were already established in Europe and Asia and other places. And I think that, am I correct in saying that’s a pretty strong consensus view now?

John: Yeah, it’s very clear that a major population increase began among African peoples sometime before 100,000 years ago, and that growth caused their descendants to spread throughout the world. Today your DNA and my DNA and the DNA of everybody in the world comes 95 to 90% from that initial African population, and what’s at issue today is, how much difference did the 5% that we got from other places make? Is that important, is it significant, does it signify that these different ancient groups were different species from us or the same species? So there’s those questions which remain unresolved. There’s also the question of what happened in Africa before. Was this a Africa-wide population, was it some very small group? Was there a displacement within Africa before the dispersal of these people, right, what was that process? And that’s right now a really exciting scientific topic.

Corey: Do we know, John, what happened about 100,000 years ago to cause the population to increase so much and to want to disperse out of Africa?

John: No clue. No clue at all. I mean you say well, you know, people have ideas about this, right. Maybe modern humans evolved language at that time, they became fully linguistic, and so that gave them tremendous advantages in symbolism and in social relationships and in technology: they became smarter, they were more inventive. We do see changes in the archaeological record that indicate that they’re making more symbolic objects and they are maintaining larger social networks, and they do become somewhat more inventive and so there’s a, you know, maybe that’s a feedback: maybe that’s the process, it’s fundamentally cognitive. Other people say ah, cognition, what — That depends on population size, it depends on culture environments, you know, you can’t look at these ancient people and say that they were impoverished genetically or cognitively because they clearly had smaller populations — unless, you know, there’s less ideas that emerge in smaller populations, etc. etc. So I’d say, while we focus on some things, we really don’t know what the key changes were that caused this population transition to happen.

Corey: You must be very familiar with the work of linguists trying to trace the origins of language and looking at linguistic diversity in trying to find languages that appear, have common elements, might be common ancestors. How does that work line up with the current work that you’re doing on human origins? Is there a pretty nice map between the language origin map and human origin map?

John: They both converge into the past. In that sense, there is an alignment, in that we know that all of today’s languages come from common ancestors that were originally diversifed, and we know that today’s genetics come from populations that diversified. what’s not clear is whether there is a timeline that connects them. And once linguistic reconstruction, you know, reconstructing ancestral languages — so English and German and Greek and Italian they all go back to early Indo-European, right ,and that’s a common ancestral language that gave rise to lots and lots of descendant languages — that kind of reconstruction in linguistics goes back quite accurately to that level of ancestry, which is 6,000-8,000 years ago. Beyond that, establishing clear connections between languages becomes more and more difficult. While it looks like you can create some larger level groups, tying those groups into ancestral population origins on the scale of 30,000-50,000 years is controversial, and so it’s not clear whether we can get those way-back points from language. It is clear that language is diversified that came from common ancestors, and genetics did as well. In recent times those genetic connections aligned with the linguistic connections in in lots of ways, but there are mismatches also, there are populations that pick up languages from others that they were not strongly genetically connected to.

Steve: So I wanted to ask you about our evolution in understanding about the situation of Neanderthals vis-à vis moderns and how it evolved, I would say roughly in the last ten or fifteen years? So about a dozen years ago I think or ten years ago Henry Harpending and Greg Cochran published a book called The 10,000 Year Explosion, which was mainly about recent evolution I guess in modern humans, but they also mentioned in the book — I think it was in the book — they strongly hypothesized that Neanderthals and humans had interbred. I seem to recall that as being a pretty minority view. So if you just randomly selected some physical anthropologists and asked some hey, did humans and Neanderthals interbreed or did we just wipe them out without interbreeding and maybe we’re not even the same species in some sense? people mostly thought the answer was no, we didn’t interbreed with them. But now the genetic information firmly establishes that we did, and you can go on 23andMe and look up your Neanderthal, some estimate of your Neanderthal DNA fraction. So can you talk about how it felt, I mean what, how your views evolved and how the community’s views evolved during that roughly ten- or fifteen-year period?

John: Yeah, I think that, you know, I came into this thinking that Neanderthals contributed to human populations a good deal. You know, if you asked me twenty years ago what did I think the proportion of Neanderthal ancestry in living Europeans was, I would have said well, you know, it could be 10 or 15%, and I viewed that as being a significant contribution. We now know that the actual level is about 2 or 3 % and so it’s not an order of magnitude less than I was thinking, but it is a lot less. If you asked some other anthropologists at that time they might have said, you know, zero, you know, they never interbred; or if they did inter breed, right, I think the most common answer you would get from somebody like Chris Stringer, for instance, who was really, you know, very Out of Africa focused, very Out of Africa oriented, he would say you know, I would never deny that interbreeding could have happened, but we know that it was not important, we know that it did not have an evolutionary impact that mattered to the development of later Europeans.

Corey: Why would he make such a strong statement, and on the basis of what?

John: [laughs] Well, largely on the basis of looking at a major population transition that happened. Neanderthals were the only hominin occupants of Europe, as far as we knew, before 45,000 years ago, and after 30,000 years ago we see nothing that is a Neanderthal and only people that we identify as modern human, and they differ by a number of traits. That population of modern humans did have some low frequency traits that we otherwise see in Neanderthals, right, so those of us who thought that there was a contribution, we had a reason for thinking it. You find these traits and it’s like, you know, things like the shape of the foramen on the inside surface of your jawbone — the part of your jawbone that connects with your skull, the mandibular ramus — the inside part has a hole in it, and that hole has a different shape in some Neanderthals than it does in most modern humans. But the few modern humans that look Neanderthal-like are all European, they’re much more likely to be Europeans 30,000 years ago. So you look at that kind of evidence and say okay, there’s some evidence of interbreeding. Stringer knew that evidence. He’s just an example, right, a lot of people would have the same point of view, look at that evidence and say yeah, and the fact that it becomes less and less common shows you that whatever interaction there was clearly was not adaptive, it clearly went away, and so that’s the sort of thing that they’re thinking. Explaining that kind of transition, right, how is it that you end up with nobody in the world who looks like a Neanderthal today? It must have been really disadvantageous to look like a Neanderthal.

Corey: Do we know that that is in fact true, that people today, no one looks like a Neanderthal? I had a, my advisor at Columbia insisted that he was at least half Neanderthal.

John: A lot of people say this, right, and I get letters from people — and they’re always women [laughs] — who are, like, I want to find out if there some way my husband can participate in your research, because he has hair on his back, and he has a really sloping forehead, and I think he is more Neanderthal than anybody else. That is the popular stereotype of what Neanderthals were like, right. We have no idea whether Neanderthals had hair on their back right, it’s not like there’s a fossil that tells us that, oh yeah, ape then, you know. No, it’s people’s stereotypes. if you think of the person that you know who has the most prominent brow ridge, I guarantee you that looks nothing like a Neanderthal brow ridge. And the reason why is that Neanderthals have a brow that is arched over both of their eye orbits and thick on the outside, as thick as it is on the, in the middle, right, and if you saw somebody like that with a groove between their brow ridge and the rest of their forehead, I’d say okay, that’s exciting right, that’s something that you don’t see every day. But in fact when you look at the details of traits like that, they just aren’t around anymore.

Steve: But I thought even at the level of like, the shape of their rib cage or torso, there were just huge differences between what Neanderthals looked like and what moderns looked like. Is it, am I wrong about that?

John: Well there are some differences. I would say [laughs] those differences have a way of being exaggerated, right, because we’re comparing a particular group of Neanderthals that we know about — mostly from southern France and mostly from the end of their existence — with living people’s skeletal collections who are mostly indigent and poor, and mostly collected in the early 20th century from people who didn’t eat very much.

Steve: Hmm, I see.

John: [laughs] And so while there are differences, you know, in average stature in the, you know, the barrel-shapeness of the ribs and that sort of thing, these are differences that actually overlap a good amount.

Steve: I see. So, but the question I was trying to get at is that, okay, so the situation was unsettled before the DNA results came in, but then the DNA results came in, and were they just quickly accepted and people gave up cherished, long-held, long-defended beliefs in the face of better data and technology, or was it a kind of battle with some people going to their graves not accepting it? What, just sociologically in terms of the history of science, how does…

John: To simplify a little bit, right, anthropologists understand numbers [laughs] and yet we have different understandings of numbers. [laughs] So some people look at, oh we’ve got 3% Neanderthal, oh my god we’ve proven at last that we have Neanderthal ancestors, we were right all along! And other people say yeah, we’re 3% Neanderthal, god, that’s nothing, we’ve proven that Neanderthals made no difference to us, we were right all along! [laughs] And say you got, the same data have provoked…

Steve: Okay.

John: …you know, totally opposite reactions.

Steve: Yeah, nobody pinned with a published prediction of zero that, yeah, like the offspring would be infertile, for example, like…

John: When Svante, when Svante Pääbo who was, his research team first got a Neanderthal genome data and they provided the first estimate of, you know, maybe this is 1 to 4% Neanderthal ancestry in recent people, he started talking about this as “leaky replacement.” Okay. It’s mostly replacement. The Africans spread throughout the world, their DNA replaced the DNA that was there before, but there was some kind of mistake in the process that, oh, the Neanderthals put in a little bit, right. And I think there’s a tendency to look at small percentages and say yeah that’s, okay sure, it shows that it’s there, but it doesn’t establish that there’s any evolutionary importance to this.

Corey: What’s clear is we’re not actually talking about the functions of these genes, we’re simply talking about the percentages. There’s no discussion it comes down to what it does.

John: Yeah, and in fact, it is totally… People were totally incapable of looking at the functions of anything at the time that the DNA sequences were derived, because they had no mechanism to identify particular genes that were coming from this introgression, and so the only data that they had was the Sesame Street kind of data. You can see with, between two people, one who lives in Sub-Saharan Africa and one who lives in anywhere outside of Africa, that one outside of Africa had a little more Neanderthal. That was the comparison. But some Neanderthal resemblances in anybody’s genome today, including Sub-Saharan Africans, come from ancient diverse genes that we inherited from our common ancestors with Neanderthals. That’s called incomplete lineage sorting and it, we have incomplete lineage sorting with chimps, right. There are genes for which some people resemble the chimpanzees and other people don’t. So the fact that you have some similarity doesn’t reflect necessarily genetic input for any particular gene.

Corey: So it seems that what you need to actually have genetic input is to show a diversification of genes into Neanderthals, and then a reunification of those genes through interbreeding. Is there any schematics that exist…

John: Right. So what you have to show is that you have a haplotype, a long section of chromosome where variations are linked together, that existed within Neanderthals and today has come into modern humans, and it’s the difference across a section of chromosome that tells us that this came into our population recently, as opposed to having been retained in the modern human population for hundreds of thousands of years. And we do have that evidence now. It is possible to look at regions of the genome where today somebody carries a haplotype that is never found in Sub-Saharan Africans and that is found in Neanderthal genetics. And we know a lot of these now. Some of them are much more common than they should be, right. While the average Neanderthal input for people outside of Africa is 2 or 3%, there are genes where, outside of Africa, 40 or 50% of people have the Neanderthal variation, and those are genes where we look at it very closely and say ah, this does something super useful, this must be advantageous in some way.

Corey: Do we happen to know what any of these genes does?

John: Some of these genes are HLA genes, where we have alleles that have come into human populations — HLA is human leukocyte antigen, and these are immune system genes. They control some of the antigens that are displayed on the surfaces of blood cells, and that is an immune defense from pathogens and sometimes cancers and that sort of thing.

Steve: I think it’s also claimed, although I don’t know exactly how strong this evidence is, that some of the Tibetan altitude adaptation actually may have been due to introgression from Denisovans, which are a kind of Neanderthal. I don’t know if there’s consensus on whether that’s true or not.

John: Yeah so this gene EPAS1, which has a variation, an allele that’s very common in Tibetan and Nepalese and Himalaya living peoples, that allele came from a Denisovan-like population, so it came from one of these archaic groups. There are other immune system genes besides HLA, where today people have a Neanderthal variant that’s much more common. There are metabolic genes. The most common genetic correlate of type 2 diabetes in Mexico today is a gene that came from Native American Mexican populations that was a Neanderthal-derived gene. So we know quite a number of these now. It is not yet the case that we know what all of them do, and that’s actually nothing to do with Neanderthals: it comes from the fact that we don’t know what genes do…

Steve: Yeah.

John: [laughs] … and it’s a limit on human genetic information as opposed to understanding particularly the Neanderthal contribution.

Steve: So when the first Neanderthal paper, DNA papers came out, I think the consensus view was that okay, the Neanderthals had already been in Eurasia when the first modern humans came out of Africa — perhaps in a Middle Eastern region, that’s where the intermixing perhaps happened — and there was, I think, a definite view that we were likely to find more DNA fraction from Neanderthals in Europeans, and less in East Asians. But I think the current result is actually the opposite of that, and so could you comment on that?

John: Yeah, Chinese people have systematically about a half percent more Neanderthal than Europeans. And that’s counterintuitive: the Neanderthals did not live in China. [laughs] And it’s not just Chinese — East Asian generally, and I don’t believe that that’s true of South Asian, I think it’s more Eastern than South Asia. And so what’s going on with that? It appears that what’s going on is that the differences in different populations today of Neanderthal ancestry are coming from multiple mixture events with Neanderthals, potentially different Neanderthal populations. Europeans who were of the Upper Paleolithic time period, who followed the Neanderthals, also had a higher fraction in some cases. We’ve got a European ancient human skeleton that has something like 8-10% Neanderthal.

Steve: How ancient?

John: About 45,000 years old.

Steve: Okay.

John: And this is from Romania.

Steve: Yeah.

John: So there were individuals that had a higher fraction, and the fact that those individuals have not contributed that higher fraction to later people is in part due to the fact that today’s Europeans are not the Europeans of 30,000 years ago. Today’s Europeans have come in through repeated waves of immigration with early farming, with steppe pastoralists who have come in, with Bronze Age peoples, and so today’s Europeans have got more Near Eastern in them than they have Upper Paleolithic European by quite a lot.

Steve: So in that last few sentences you sort of brought in some more recent history of human migration and evolution, and so I wanted you maybe to describe for our viewers the current landscape of work on archaic human DNA and fossil records. My impression is that so, for example, David Reich at Harvard, he specializes in maybe the last 10,000 or so years of developments, whereas Svante Pääbo who you mentioned earlier, he’s looking more further in the past, like hundreds of thousands of years. Maybe you can just give us an overview of what people are working on and how the field is evolving.

John: Sure. Ancient DNA is preserved in bones of all kinds of eras, right, and not only hominin bones, obviously, you know, other kinds of animals, and it’s a similar technological process that you go through for any bone. Different preservation contexts present somewhat different challenges. The oldest hominin bones that we have ancient DNA from are 450,000 years old. They’re from a site in Spain called Sima de los Huesos, and the DNA in those bones is broken up into very small fragments. By the time you get down to 20 or 30 base pair fragments, it becomes fairly difficult to retrieve that DNA and compare it with modern human DNA to reconstruct sequence. Even though all ancient DNA is broken up into fragments, by the time you get down to like 20 or 25 base pairs it’s like, wow, the information’s truly gone, it becomes just vastly more time-consuming and difficult to reconstruct. And that causes some specialization between laboratories in terms of what time periods they’re optimized to look at. Other laboratories who are doing ancient DNA have specialized on the DNA of various animal lineages, so you have David Reich’s lab, which is studying lots and lots of Neolithic and later human specimens, is also studying elephants, you know, so you’ve got this sort of looking at particular groups to pursue scientific questions. What’s going on now with it, what are the frontiers? The exciting stuff that’s emerged in the last year or two has to do with finding, in a much more systematic sense, bone fragments that are eligible for sequencing. Denisova Cave, which is this exciting place, it’s in Siberia, in the low Altai Mountains, and it’s got evidence of ancient Neanderthals and ancient members of this other population, the Denisovans, and they, we now know, alternated in this cave — Denisovans there before 200,000 years ago, Neanderthals coming in for some period of time, Denisovans coming back — and we’ve got a hybrid individual who had a Denisovan father and a Neanderthal mother, right. How does all this happen, right, how do we know all this? We know all of it because today people are systematically sampling cave sediments and retrieving DNA signatures out of them from the hominins, so you’ve got hominin DNA inside of the sediments in the cave, not in bones, just in the sediments. You’ve got a team of people led by Katerina Douka at the Max Planck [Institute] for the Science of Human History, who are systematically going through every bone fragment at the site that is unidentified — which is mostly red deer and horse and other kinds of, right, faunal bone fragments — and doing collagen sequencing from them, because they have a method for collagen fingerprinting. So you do this for thousands and thousands of bones, and out of this process they find four or five hominin bones. And then with bone fragments that you, that an anthropologist cannot identify, right, and say oh, here’s a hominin, and they take it and get DNA out of it. This is where the hybrid came from, here’s DNA and it’s half Neanderthal and half Denisovan. Wait a minute! What do you mean, half Neanderthal and half Denisovan? And they reconstruct this like, No seriously, one Denisovan chromosome, one Neanderthal chromosome: this is somebody who had a mother and a father who were two different populations, species, something like that, right. So the retrieval systematic search for ancient bones, where DNA is the major target, has become a big thing, and I expect that to be, you know, sort of worldwide in the near future, because the promise of this systematic search is so great. That being said, there’s also people focused on these historical questions, you know, where do the Indo-Europeans come from, how were early farmers connected to anybody else, what kinds of adaptations were changing in early farmers, right? And those sorts of studies are being pursued by lots of different teams of people.

Corey: John, I just have a question about the environment in these caves. Is it frozen, is it just, is it 70 degrees Fahrenheit? Under what circumstances does ancient DNA survive for 20,000 years?

John: It’s a spectacular question, right, because we don’t fully know. We know that cold is better, and Denisova Cave has this tremendous preservation in part because the average temperature year-round is 5° Celsius in the cave. You walk into the cave and it’s like walking into a walk-in refrigerator. That’s one aspect, that cold, right. A cave has the average temperature of the outside environment over, you know, the year, and so in areas where I work in Africa, the caves are much warmer. The cave where we work is 19° year-round and that is much less beneficial for long-term preservation of biomolecules. So cold makes a difference — dry makes a difference, drier is better — but beyond that it’s also chemistry.

Corey: Are you finding DNA in the cave you’re working in Africa, are you just, are you finding proteins, are you finding… What kind of biomolecules are you finding preserved in that kind of environment?

John: So we have attempted to get DNA from our bones and today’s technology cannot get whatever there is there, we’ve made no progress with it. We do think that it’s likely that we’ll have protein preservation in teeth. The proteins in teeth, because they’re bound up in the enamel and dentin matrix, which is harder and a little more protective, they have a longer duration, and folks have been successful getting protein sequence out of some of these specimens that are 1.8, 2 million years old. So I think there’s a good chance that we’ll have protein preservation. That’s a vastly smaller source of information than DNA. You said yeah, there’s lots of proteins, but actually very few of them are expressed in bone and teeth, and so you’re only looking at very particular amino acid sequences — which is sometimes, you know, gives you really interesting information, but it’s not a genome, you know, so…

Corey: Sounds like, John, we’re looking at kind of a difference in, across the world, right? If it’s far north enough, we’re getting information about DNA but further south we’re not. Is there a line you could draw, say the DNA line across the globe, or above that, you’re getting…?

Steve: Depends on technology.

Corey: But current technology?

John: Yeah, it’s… If you look at sites before 30,000 years ago, they are nearly all — I think all, actually — above a line that runs from Spain to northern China, and so — and in southern Africa we have nothing that old. In Africa generally the oldest sequences that we have are about 20,000 years old. That’s probably not a preservation limit, that’s the limit of what has been investigated and what people are willing to invest today’s technology to do. That willingness comes on two sides, right. One of them is based on somebody — there’s always DNA people who will try, but the fact is that the best DNA people sort of know where their limits are and know it’s worth trying; and there’s also a forward look to it, right, what might be at the very edge of possible today is probably going to be easy the ten years from now, and don’t destroy something now if 10 years from now it’s gonna be with, easily within our reach. So people are very, I think most people are very thoughtful about when to try something. And the other side of this obviously is the museum institutional side, right: these bones have curators who are responsible for them as world heritage objects, and we don’t destroy things willy-nilly, you know, we think very carefully about whether examining something is going to be justified in terms of the science it produces, whether today’s techniques are the best or whether we should really let the technology develop. So Africa sampling is complicated for that reason. We know that it’s at the edge in many cases and the edge is exciting to be at, but also not the place to take your most valuable specimens and destroy them.

Steve: So let me switch gears a little bit, and I want to talk a little bit about what I call the David Reich controversy. And so David Reich is a leading figure in this field, I think focusing— correct me if I’m wrong — at least recently more on the sort of last 10,000 years than way back, probably deserves, I guess, credit for sort of really working out the waves of Indo-European settlement that people modern-day Europe. I think it was about a year ago he wrote an editorial in the New York Times which caused a huge kerfuffle [John laughs] and, you know, I do some work on the genomic prediction of human height, and so we now kind of in a way have almost solved that problem. If you look at northern European populations, they tend on average to have more of the plus alleles for height, and southern European populations have more of the minus allele. And so there is actually a genetic contribution to a group difference. The group difference in height is, between northern and southern Europe, is about a standard deviation. And so this seems to have been — this is a little bit more speculative — but it seems to have arisen in the last 10,000 years or so, so it’s a relatively recent, perhaps natural-selection-driven group difference on a complex trait. And Reich wrote an editorial warning people that — and he, I think he’s actually published on this topic as well — he warned people that we should get ready in some sense to discover more genetically driven group differences between populations that could have arisen relatively recently. Now, he took a huge amount of blowback for this. I think there was a huge petition signed by many people — I don’t know if you signed it or you know people who signed it — so many genomicists signed a petition against his editorial. And then much more recently in a way there may be two David Reich controversies: so there was that one, and then recently there was a big New York Times Magazine perhaps hit piece, but anyway negative profile in some sense of David Reich, which also then got into some of his research practices having to do with treatment of maybe DNA obtained from indigenous peoples and things like this. So I would just like to get your overall opinion of everything that I’ve just discussed.

John: [laughs]Well it’s a big topic, right — I mean, the fact is that we’re really privileged to have information about the most intimate details, at least in biological terms, of ancient people who cannot tell us what their wishes are. And I have for a long time studied Neanderthals and have always felt like, you know, by trying to understand their biology, by trying to understand their lives, I am bringing them back into the present in some way, right, I’m restoring in some sense their heritage that has been lost because they’re not with us, right, they’re extinct; and I’ve always thought about the work that I do that way, you know, in the sympathetic kind of vein. I want to understand past people in part because it helps us to understand ourselves and the diversity that’s in the world, and the way that that diversity emerged, it’s important to be scientifically accurate about it, because a lot of people think about diversity in racial terms that fundamentally is not scientific. And so I think about things that way. Part of that practice when you get to remains that are clearly more connected to some living people [than] others, right —, as you have with Native American remains in the United States, as you have with Native American remains throughout the Americas, as you have with Khoisan-affiliated remains in southern Africa, Polynesia, and affiliated remains in Polynesia — you know, there’s lots of areas of the world where you’re studying bones that may or may not have living descendants, right, you may not be looking at the ancestors, but you’re clearly looking at cousins of theirs that are closer to them than you. And my attitude in that situation is, in those situations you have to be communicating with, and making a role for, the people in your research who are more directly connected than you are to them. One thing that I didn’t like about David’s book is that he sort of takes this attitude of, you know, what business is of these other people who are descendants or relatives to say anything about these individuals who lived in the past, right, what right do they have? And I look at that and I’m like, that’s sort of tragic, you know. It’s tragic a) because if we actually incorporate people into this research we have the potential of building something really positive and getting people onto the same page, right: our science has to be built by involving people and not by saying hey, we’re doing science over here and guess what we’re gonna tell you about your ancestors next, you know, I don’t get people who have that kind of attitude. But also that the number of ancient bones that we have in the world is limited. There are not going to be thousands and thousands of new ancient skeletons that are unearthed by archaeologists. We don’t do work like that anymore. This is a, fundamentally a limited resource. You say well, you know, but you’re making new discoveries all the time. It’s our goal to leave our new discoveries in the ground as much as we can, because we recognize that when we dig a site we’re actually losing evidence, and our choices about what to dig are shaped upon a trade-off between building science and building evidence today, and retaining something for future scientists who are gonna have much better techniques than we have now. And when I look at a laboratory that is just sampling thousands and thousands of bones, I know that that constitutes a very high fraction of the bones that there are; and the bones that there are, there’s not gonna be twice as many in the future, right, the bones that there are, are sort of what we have.

Steve: You’re saying in a sense these, maybe his lab and maybe some other labs have become so dominant that they’re getting their hands on all the best samples, and they’re maybe processing them in a way that’s irreversible, that leaves, you know, some future developments unable then to use those bones, and that is a sort of major criticism, maybe, of what’s going on right now. Is that a fair summary?

John: I think so. You know, my attitude toward this is, I want to see us make the responsible choices so that tomorrow’s scientists do not look at us and say: How could they have done this? And one thing that you do is, you maximize the value for building science of everything that you destroy.

Steve: Yep.

John: That to me is like the prime directive.

Steve: It’s a difficult optimization because it involves future progress in technology, right.

John: And the pressures that are on you in the moment…

Steve: Yes.

John: …right, I’ve got to get that new nature paper, and the nature reviewers say that my sample is too small; and I know that I can build up my sample by destroying twice as many inner ears, [laughs]and so, you know, I have to do what I have to do, because they tell me that I have to do it.

Steve: Right.

John: And what we need, I think, is an effective… This has all developed without a real conversation among scientists of many fields saying: Hey, where is this going, guys? When I read that David Reich’s lab had sequenced something like 3,000 or 5,000 bones, I said wait a minute, how did this happen? you know, and I follow the field [laughs] right; so the fact that this has really emerged, it’s burgeoned, I know that many archaeologists, bio-archaeologists, people who study ancient remains have been approached and thought, you know, if I do this my name’s gonna be on a nature paper; or if I don’t do this maybe I’m not gonna have another chance because they’re interested in my sample today but, you know, next week they might… You know, there’s a lot of people who are trying to optimize things. Very few of them are thinking about optimizing what science looks like 40 years from now.

Corey: Is anyone having that discussion kind of on a broader scale?

John: There are discussions that are happening. I am involved in a few of them with people who are geneticists, who are interested in optimizing or improving the interactions that folks have with indigenous societies, indigenous peoples, and increasing consultations, you know; I’m involved in lots of conversations about optimizing genetic information versus other kinds of biomolecule information.

Corey: But also the love of the whole field right? Are people actually having discussion — I don’t know what the organization of physical anthropology is called — but is there a policy discussion about these very issues saying look, you know we’re basically, we have to carry out research now we don’t want to mortgage the future of our field for our current interests. It’s a little like the global-warming debate except it’s actually in some sense much more severe because…

Steve: We can’t even organize ourselves to stop getting gouged by Elsevier on journal subscriptions, and you’re asking us to coordinate, you know…

John: There’s reality that… and there’s also reality to the fact that these conversations, right — You say, what’s the association of physical anthropologists and I say, well, the American Association of Physical Anthropologists, and that’s the problem: it’s American, and the problem is global, and while those of us who are in the American association — it’s the largest, without question, association in the world — can have that conversation, the fact is that the people who are crucially important to that conversation are not American researchers who are coming into other countries and doing research as guests. They’re people like me who are engaged year-round in the countries where we work, and the people who are in the countries and responsible for the remains, right, and that’s a much broader group but also more difficult group, because they’re more pressed by the need to have impact come from your collections, more pressed by the lack of funding for the work that they do, and so more inclined to bring in large-money collaborators, you know, there’s a… It’s very difficult, and I don’t know that — I don’t know, right, I think we do, all of us do what we can. That’s where it has to go.

Steve: I think we’re running out of time. We have a whole set of other things that we want to talk about, so, you can come back?

John: Yeah sure, of course.

Steve: Okay, awesome. So thanks a lot, it’s been really fantastic. So we don’t want to keep you from your class, and I don’t want to get beat up by the Provost, so…

John: [laughs] All right, that sounds great.

Steve: …I guess we’ll just stop now.