SAPIENS host Chip Colwell speaks with evolutionary geneticist Hugo Zeberg about his surprising discovery of a connection between Neanderthal DNA and a greater risk for severe COVID-19. Zeberg is also a researcher at the Karolinska Institutet in Sweden and the Max Planck Institute for Evolutionary Anthropology in Germany.
Read the paper in Nature Zeberg co-authored announcing the discovery: “The Major Genetic Risk Factor for Severe COVID-19 Is Inherited From Neanderthals.”
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Chip Colwell: As an archaeologist, I’ve often had the chance to work on large scientific teams. In fact, my dissertation research many, many years ago was based out of a nonprofit with other researchers and involved a deep collaboration with the Zuni, Hopi, O’odham, and Apache tribes. And today I’m helping to lead a project that has six co–principal investigators and nearly 50 contributors across the United States and Canada.
But while collaborations are often helpful to achieve scientific goals, they can be all the more vital when scientists are working to address a public health crisis like a global pandemic. The need for scientific collaboration has become especially clear this year, as demonstrated by the public release of the SARS-CoV-2 genome to the rapid development of possible vaccines by international teams.
This year saw another scientific collaboration lead to another fascinating scientific discovery—a surprise that links the pandemic to humanity’s evolutionary roots.
Hugo Zeberg: Sometimes science is that you have a hypothesis and you work for years, and it’s just a series of failures. And this was just, I just fell over it.
Chip: Meet Hugo Zeberg. He’s a Swedish evolutionary geneticist, a medical doctor, and a researcher with the Max Planck Institute for Evolutionary Anthropology. He recently co-authored a study published in Nature showing that people with a certain piece of DNA that puts them at a higher risk of developing severe COVID-19 symptoms was inherited from Neanderthals. Hugo, welcome to the show.
Hugo: Thank you so much. Nice to be here.
Chip: So, let me see if I understand this correctly. We learned early on in the pandemic that different people have very different reactions to the virus. For some, it’s a mild cough and fever. For some, it seems like there are no symptoms at all. And then for others, it can escalate to full respiratory failure. And your discovery indicates that part of the reason why some people have the most severe reactions is because they carry this piece of Neanderthal DNA. Is that right?
Hugo: Yes, that’s correct. Carrying one copy of this variant, you are 100 percent more likely to get severely ill. And if you carry two variants, probably even more—by some estimates, three times more. It’s a striking fact, but that is true, yes.
Chip: You know, I think part of the reason this connection between COVID and Neanderthals is so surprising is that someone made it in the first place. Was this something that you were looking for for some reason, or what’s the story here?
Hugo: Yeah, so it all started with me actually working in the clinic, in the ER, with these patients, and I decided to genotype them to check the genetic variants of these patients getting severely ill with COVID-19. But I realized that I cannot do this alone. And then I found an international collaborative effort with people genotyping, checking the gene variants of people getting severely ill with COVID-19. And then, since a couple of years back, I worked with a Neanderthal genome, and I just one day decided to check: What are the genetic variants that get to severely ill COVID-19, and do they look like the Neanderthal genome? And strikingly, the most important risk factor is almost identical to the Neanderthal genome.
Chip: You say it almost matter-of-factly, but it’s such a stunning discovery. Can you share with us that moment when you must, maybe, you saw on your computer screen, or what was it?
Hugo: I saw on my computer screen just the overlap. And I was totally falling off my chair. And my collaborator Svante Pääbo, he was at his cottage in southern Sweden, in a small town. And I texted him and said, “This is a Neanderthal variant.” And then I actually flew down to his cottage, and we wrote the first version of the manuscript in a matter of days. And then on Saturday, The New York Times had a big piece on our preprints, which was, of course, surrealistic.
Chip: That’s an amazingly rapid scientific process. That doesn’t always happen that way. Often, it’s quite the opposite. Many years of hard labor, right?
Hugo: Yeah, yes. Yes. Hypotheses that fail and blood, sweat, and tears. And this was the opposite.
Chip: And then just to step back for a moment for maybe listeners that aren’t familiar with the science, what is the genetic relationship between Neanderthals and Homo sapiens?
Hugo: OK, so Neanderthals are, in a way, our cousins, and they left Africa before us, so they were the first Europeans and the first Asians, and they lived there for some hundreds of thousands of years. And then we, modern humans, left Africa some hundred thousand years ago—it’s a little bit debated. And then on the route out, on the exodus route, the route out of Africa, we met Neanderthals, and we got children together with them. So, people with ancestry outside Africa carry around 1, 2 percent of Neanderthal DNA still living in them today.
Chip: All right. Well, let’s step back into the question about the relationship between COVID and Neanderthals, and, you know, I don’t want to get overly technical, but can you just help us understand a little bit further, a little bit more in-depth, what exactly are we saying here in terms of, you know, I’m envisioning this triangle. You know, you have the Neanderthal genome, the Homo sapiens genome, and then the virus’ genome. And so, what exactly is the relationship between those three points?
Hugo: First, we need to understand that when we say that we carry 2 percent of Neanderthal DNA, what does that mean? So, the first offspring of someone, say, that had a Neanderthal mother and a modern human father, then they would carry one chromosome from the father and one chromosome from the mother, of each of our chromosomes. But then you have a phenomenon called recombination, that this chromosome gets chunked up into smaller and smaller pieces. We find stretches of DNA that are all from Neanderthals. So, this variant that is 50,000 base pairs, DNA consists of base pairs, so 50,000 base pairs that are from Neanderthals. It’s a small piece on, in this case, chromosome three. And then, as you say, of course, there’s also, to make it even more complicated, there’s a genome in the virus itself. But that is not what I study. I study the host genetics, the genetics of the patient, you know.
Chip: You said a minute ago that when you made this discovery you nearly fell out of your chair, which is a pretty hilarious picture to have. But it makes me wonder. For someone like yourself who is intimately familiar with Neanderthal DNA, did your discovery have implications for other areas of health science research? Can you share with us what you might know about that?
Hugo: We, I mean, as I said, it was a little bit of a wild shot, to be honest. But we do know that there are variants from Neanderthals related to the immune system that have risen to a high frequency. So, we know that there are, the immune system is somewhat different. And that’s not so surprising, perhaps. If you separate groups of people, they adapt their immune system to their local environment. One prominent example is, of course, what happened to Native Americans when Columbus first got there. A lot of people died from measles, for instance.
Chip: So, can you tell us a bit more about this particular piece of Neanderthal DNA? Where did it come from? Do we know what populations tend to have more carriers?
Hugo: Yeah, so that’s something striking that it’s quite unevenly spread. In some regions of the world, it’s very common. So, as I said, it’s 50,000 base pairs and 1-in-6 with European ancestry. And that would also be people in the Americas with European ancestry.
Chip: So, 1-in-6 people in this population carries the variant of Neanderthal DNA?
Hugo: Indeed.
Chip: OK, mm-hmm.
Hugo: And then in South Asia, it’s 50 percent. And that’s surprisingly high for being a Neanderthal variant. We typically find this variant in 1, 2 percent, not 50 percent. And then it’s totally gone, on the other hand, in East Asia.
Chip: Hmm.
Hugo: So, this kind of points to some selection in the past. Probably, it has been beneficial in South Asia, and some previous pandemic or infection wiped the variant out of East Asia.
Chip: OK. So, in other words, early modern Homo sapiens probably all carried this variant. And then over the tens of thousands of years, because of diseases and the movement of people, in some populations, it remains prominent. But then in other populations, it dissipates to the point of not even being visible today?
Hugo: Yes, yes, indeed. So, that’s exactly how it is. When modern humans left Africa, they probably encountered Neanderthals quite early. So, all people with ancestry outside Africa carry Neanderthal gene variants. So, it probably was there in these early settlers of Eurasia. And then it has, the frequencies are now different in different populations.
Chip: And do we know to what degree genetics does play a role in our body’s response to the COVID-19 virus? In other words, and I’m sure there are many factors, like, I’ve heard about viral load, for example, how much of the virus you’re actually exposed to, I’m sure, preexisting health conditions, right? I mean, there’s a kind of an array of factors that I’d imagine, not being a physician, but I can imagine, you know, would lead to how the body’s reacting to the virus. So, is genetics, do we know is that playing a major role, or is it kind of a minor backstory to what’s happening?
Hugo: Yeah, so, one can interpret this genetic risk in terms of age, and it’s approximately as being 10 years older. So, if you are 50 years and carrying this variant, you have the risk of a 60 year old, something like that.
Chip: OK, that’s a helpful way of putting it. Yeah.
Hugo: Yes. I mean, it is a substantial increase. It is.
Chip: Yeah. I wouldn’t want to add 10 years to my life, especially when facing down a deadly virus.
Hugo: No, no. But still, someone who’s 20 years old and carrying this variant is still not in the risk group. But if you’re 70, then your risk is increased.
Chip: So, this really is much more than a curiosity. There are serious implications here.
Hugo: Yes, I mean, the evolutionary origin that is from Neanderthals is perhaps more of a curiosity, but we and a lot of others are trying to understand this piece of Neanderthal DNA and that this might also be, open up for future treatments if you can understand how this variant makes you so sick. So, it is very clinical in that sense. And I think it’s striking that you can, it started with archaeology and went into genetics and ancient DNA and now it’s connected to the current pandemic. Science is full of surprises.
Chip: [laughing] It is. And, you know, it seems to me that part of the story here, too, is about the scientific work itself and the intersection of these different fields, as well as this discovery arising from an international collaboration. And so, I wonder if you could tell us a bit more about how your work through this kind of collaboration is unfolding and how you see scientists working together today and maybe even in a post-COVID world.
Hugo: So, this, I mean, this pandemic has been terrible, but it has brought out a lot of the best out of some scientists, at least. And it’s really striking how we collaborate. We sit down in Zoom meetings, digital meetings. I have weekly meetings with a lot of scientists all over the world, which I never met outside my laptop. And we need power, statistical powers. We need a lot of patients to figure these things out. So, then I’m bringing in clinical data, genetic data from patients in Sweden. Some are bringing [data] from Canada, from the U.S., from Latin America, from all over Europe, from Asia. And we’re all collaborating in a very nice way. And that’s really striking and very beautiful and nice to see.
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Chip: Hi again, Jen, how are you doing?
Jen Shannon: Yeah, I’m doing pretty good, and I really enjoyed your conversation with Hugo, especially because usually it’s sort of like you don’t even know what you have until you’ve crunched a year of data and then you’re like, oh, there’s a blip on the graph.
Chip: Yeah, yeah, it was totally amazing, totally amazing. And, you know, it does make me think about how we decided to make a kind of left turn with this season, right? When the pandemic hit. That wasn’t our plan. Of course, it wasn’t the world’s plan. But nonetheless, we decided to like, let’s just go all in on trying to address the crisis that’s facing so many people around the world because of the COVID pandemic. And, you know, it really strikes me that back in the spring when we made this decision, we knew, or we thought we knew, that the pandemic was going to be bad. But now, at least in the United States and in many other places around the world, I mean, it’s even worse than we feared.
Jen: Yeah. And to add to the mix, we had, you know, the summer protests and a lot of unprecedented election politics in the U.S., and it’s felt kind of dizzying to try to comprehend all of this and then to cover it all. And we couldn’t cover it all, but hopefully, we added some important ideas to the conversation.
Chip: Yeah, I feel like we did. And looking back on the season, for you, what are some of the big takeaways?
Jen: Well, I guess some of it is how the pandemic feels like déjà vu but also something totally new.
Chip: Yeah, I definitely see that and a lot of these days, for me, déjà vu is the denominator. Maybe it’s just because I’m stuck in the house, you know, day after day. But nonetheless, I feel like also in the podcast, we’ve touched on so many issues that in some ways seem brand new but actually are a throwback. So, the question, for example, of whether or not pandemics are good for the environment; the origins of the quarantine that actually stretch back hundreds of years ago to Venice, Italy; the conversation we had with Agustín Fuentes about how we are biosocial beings, how we are the combination of biology and culture all at once. And that, actually, has been fundamental to humanity’s evolution over millions of years.
Jen: Yeah, and there were also connections back to previous episodes that I thought were really interesting, like a return visit to the preppers.
Chip: Oh, yeah. We called that one, right?
Jen: Yeah. But also, this unexpected connection to Neandertals. Sorry, Neanderthals.
Chip: And what’s also really fascinating and important, and we touch on this in Hugo’s interview, is that these vaccines are appearing because of these incredible international collaborations among scientists. And yes, there have been, of course, you know, networks of scientists for a long time, but with new technologies and then this unprecedented need on a global scale, you know, we’re seeing brand new ways of science unfolding.
Jen: Yeah, and I have to say, you know, I’m the kind of person who looks for the positive in difficult times, and that’s one of them, this idea that science might work differently or better moving forward as a result of creating these models and networks because of the pandemic. And I guess that’s kind of one of my big takeaways from all of this, is just, people adjusted and changed so quickly in just a few weeks. You know, I was driving home and I passed a restaurant that I had gone to a lot, and it had been closed for two weeks, and then it had a sign out front that said: We are open again for delivery. And it just, I started, honestly, I started crying because it was like, everything was so up in the air, and all the way down to restaurants changing so dramatically and quickly to try to respond to the moment. You know, in cultural anthropology, we always say that, you know, the way things are, it’s not a natural order of things. Things are the way they are because we made them this way, and we can unmake them and create something different, if we want to. And now we can point to what happened during the pandemic and really show that that’s the truth. All these systems changed: education, health care, government. And so that’s kind of the thing that I’m taking away from the pandemic is that societies can fundamentally shift. It doesn’t have to be temporary or reactive, though. It can be intentional. And I hope that’s what comes next.
Chip: Yeah. I love your optimism, and most days I want to share it.
Jen: I can’t help myself. I know. [laughing]
Chip: Yeah, because we can change. But will we choose to change? I guess that’s for all of us to figure out together in these moments as we struggle through the pandemic and what comes after.
Jen: Yeah.
Chip: And well, Jen, one thing I know we’re both really optimistic about is next season, right? Season 4, it awaits. You know, it’s going to be a different season and a big story that we’re looking to tell, so definitely stay tuned, dear listeners.
Jen: Well, I have to say that I really appreciate the opportunity to work through the pandemic with you, Chip, this season, and I appreciate all of our listeners for listening alongside as we try to make sense of it all.
Chip: Same here, Jen, thank you so much for your time. And I just always really enjoy learning along with you. And it’s been quite a ride this year. And the podcast goes along with that.
Jen: And a big thank you to all of our guests who took time to talk with us this season.
Chip: Oh, my gosh, that’s huge because I mean, just like us, you know, you’re in your attic. I’m in my daughter’s bedroom, and we had our guests, you know, scattered all over the globe, trying to have a studio experience with dogs barking and phones going off and kids running around. So, definitely, a big thank you to everyone who participated in this podcast and including House of Pod and our amazing colleagues and partners there, Paul Karolyi and the rest of the team.
Jen: Yes. Thank you so much, everyone.
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Chip: This episode of SAPIENS was produced by Paul Karolyi; mixed, audio edited, and sound designed by Jason Paton; and hosted by me, Chip Colwell.
Jen: And me, Jen Shannon. SAPIENS is produced by House of Pod, with contributions from Executive Producer Cat Jaffee.
Jen: SAPIENS is an editorially independent magazine funded by the Wenner-Gren Foundation and published in partnership with the University of Chicago Press. Thanks to Danilyn Rutherford, Maugha Kenny, and all the staff at the Wenner-Gren Foundation and SAPIENS.org.
Chip: SAPIENS is part of the American Anthropological Association Podcast Library.
Jen: Until next time, be well, fellow sapiens.
