Svante Pääbo: "When we published the Neanderthal genome, women wrote to me telling me their husbands were Neanderthals."

BarcelonaAs a young man, he was passionate about Ancient Egypt, and his insatiable curiosity about the past eventually made him one of the fathers of paleogenetics, a discipline that studies human evolution through ancient DNA preserved in fossils. Biologist and geneticist Svante Pääbo (Stockholm, 1955) won the 2022 Nobel Prize in Medicine for having deciphered the genome of Neanderthals, a species extinct 30,000 years ago, a milestone that opened the door to research into the foundations of our genetic makeup. The researcher at the Max Planck Institute for Evolutionary Biology is in Barcelona this Monday to receive the fifth European Hypatia Science Prize, awarded by Barcelona City Council and the BCN Knowledge Hub of the European Academy.

Is there anything unique about modern humans compared to Neanderthals?

— Well, in a way, this is one of the reasons we're so interested in the Neanderthal genome: looking for things that all living humans have in common. So, genetic changes that we all share. If you like, you could say we're looking for the "genetic recipe" for being a modern human. The million-dollar question is which of those changes might be important. We've spent the last few years studying a number of changes that may have to do with how the brain develops or functions, but unfortunately, we still don't fully understand them. I mean, there are things you can observe, like how modern humans became much more numerous than other forms, that they disappeared, and that culture and technology began to change very rapidly. Understanding some of these aspects is a dream come true.

You're one of the driving forces behind paleogenetics. I imagine it was difficult to read and extract information from ancient genomes.

— That was more than 35 years ago. To put it mildly, we've had many small improvements based on the technology that emerged in genomics, as we've adapted it to address the special problems of ancient DNA, which is material that reaches us in a degraded state, in short pieces, with chemical modifications and suffering from contamination. Overcoming all of this is one of the many things that must be dealt with.

When did you think it might be interesting to study ancient genetic material?

— As a teenager, I wanted to be an archaeologist, particularly an Egyptologist, but I think I had too romantic an idea, and when I started studying, it wasn't what I had in mind, and I ended up studying medicine and a PhD in molecular genetics. But then I learned there were hundreds of thousands of mummies in museums, and I wondered if we could see if they contained preserved DNA. That is, to be able to study evolution over time—not just current genomes to indirectly infer what happened in the past, but also going back in time. And not just with humans, but with animals and plants, pathogens, viruses, and bacteria.

And why the Neanderthals? What made you think they could be such a great source of information?

— They are the closest evolutionary relative of all living creatures. They are our closest extinct relatives. Therefore, if we want to define ourselves as a species group, biologically or genetically, we should really compare ourselves to them.

Can we love how similar we are to them?

— We're generally very curious, but we have a limited number of changes in our genome—approximately 30,000. Knowing all this is important because we can debate. I mean, in a sense, I'd say what we do is driven by curiosity. It's not so different from digging in a cave to see who lived there or what stone tools they made. The difference is that we dig in our genome to try to figure out what happened genetically in the past.

What do Denisovans mean for human evolution?

— They are a species of Eastern Neanderthals. They are somewhat related to the Neanderthals and were probably more numerous than them, and they also had a more interesting and complex history. There were subgroups. Just as Neanderthals contributed to the genetic roots of everyone who had ancestors outside of sub-Saharan Africa, in the East, the genetic contribution of the Denisovans is added.

And do we still have any genetic relationship with Denisovans as with Neanderthals?

— Some of the genetic variants we've obtained from Denisovans and Neanderthals are important. Some have been known for a long time, and now we know where they come from, such as the high-altitude adaptation in Tibet. But we're still learning about them, especially what their genetic contributions are.

Are there any "negative" examples?

— During the pandemic, we participated in a large international consortium to search for genetic variants to determine the extent to which some people were severely ill with COVID. Some risk factors were known—male sex, older age, diabetes, etc.—but they weren't enough to truly explain the difference, and it was clear that something else had to be genetically changing. In the summer of 2020, we observed a region of chromosome 3 that would have a major influence: a risk variant originating in Neanderthals. In healthy people over 60, this change almost tripled the risk of dying from coronavirus.

Have you studied why?

— This region has been carefully analyzed, but unfortunately, it's very complex. There are at least three genes that allow for plausible hypotheses and ideas, but we don't fully understand them. Meanwhile, we've found other, even protective regions that come from Neanderthals. But the effect is much, much smaller. Similar attempts are also being made to understand MPOX or Ebola.

He recounts in his book that when he published the article on the Neanderthal genome he received curious emails.

— When we published the Neanderthal genome in 2010 and announced that the contribution persisted in the current population, we started receiving many emails and letters, mostly from women, saying their husbands were Neanderthals. There were no men writing and saying the same about their wives. It was astonishing to see the kind of popular cultural perceptions of Neanderthals—as robust, insensitive, and brutal beings.

Are you concerned that some science-based information about genetics could be distorted to promote racist messages?

— There's always a risk that some political groups will want to misuse or distort science, and it's very difficult for that not to happen if they deliberately want to do so. Researchers can present findings in ways that are somewhat more difficult to distort. I mean, one thing we've learned by studying genetic variation in the current population is that there are no genetic factors that are absolutely fixed between geographic groups of humans. Nothing is absolutely rooted in Africa or Europe—that is, everyone in Africa has one variant and everyone in Europe has another. It's all a matter of frequency differences. How we treat each other in terms of racism is really a political and social question. I don't think there's a scientific answer.

Has your life changed with the Nobel Prize?

— A little. I've really had to learn to say no, and it's sad. I get a lot of nice invitations to speak to students here and there, and five years ago I would have said yes without fail. But I can't travel all the time. I have a 12-year-old daughter at home. This is probably the biggest change.

Ideology is threatening science. Are you worried about what Donald Trump is promoting?

— It's a little scary, not just in the United States, but around the world, because this country is a very strong player in the scientific community. We don't know how it will end. In a way, we're lucky to be in Europe, where things like this don't happen. For the moment.