Svante Pääbo, father of paleogenetics: ‘The reason for the Neanderthals’ extinction lies in how numerous we’ve become’

Geneticist Svante Pääbo demonstrated that DNA can be extracted from human fossils that are thousands of years old. His team was the first to sequence the complete genome of Neanderthals, our closest human relatives, and discovered that Homo Sapiens had sex and children with them. He also revealed the existence of a third, previously unknown human lineage, the Denisovans, thanks to genetic material extracted from a tiny bone of a girl who lived in a Siberian cave some 50,000 years ago.

Some physical features of modern Europeans and Asian people, as well as part of our genome, are inherited from those hominids, who disappeared some 40,000 years ago. The difference between a modern human and a Neanderthal is tiny at the genetic level, but Pääbo is convinced that these few changes hold the key to Sapiens’ exceptionality and, perhaps, the explanation for why we are the last human species left on the planet.

Pääbo, born in Sweden 70 years ago, recently visited Spain to participate in the 50th anniversary celebrations of the Severo Ochoa Center for Molecular Biology (CSIC-UAM). At the entrance to the modern building, located on the campus outside Madrid, the diploma awarded to Ochoa in 1955 for the Nobel Prize in Medicine is displayed. On it, Pääbo found the signature of his own father — Nobel laureate in Medicine Sune Bergström — who never publicly acknowledged him as his son.

Little Svante grew up with his mother, Karin Pääbo, a chemist of Estonian origin, in a “secret” family that Bergström secretly visited on Saturdays; a family he combined with his “official” family. In 2022, Pääbo — the founder of a whole new scientific field, paleogenetics — won the Nobel Prize in Medicine 40 years after his father. In this exclusive interview with EL PAÍS, the scientist speaks with equal ease about his family background and the new discoveries his team is pursuing at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

Question. Did your family history influence your career as a scientist?

Answer. Not much. If anything, it convinces me that Nobel Prize winners are not so special. In my case, I could never look up to my father. In his official family, my father had an adopted son with his wife. He and I met when my father was about to die. My relationship with my father was good, but distant. The big influence in my life was my mother. When you’re an only child with a single mother, as I am, you develop a very special relationship; you become a kind of adult companion who is consulted about everything.

Q. When you won the Nobel Prize in Medicine, did you feel vindicated?

A. I don’t think so. There may be some deeper psychological mechanism that I’m not aware of, but that’s for others to judge. I don’t have my father’s last name, and that’s been a very good thing, because I’ve never felt like I was starting out with an advantage.

Q. After reconstructing their genome, what is left to learn about other human species such as the Neanderthals?

A. By understanding their genome, we can do two things. The first is to study their population history, which has been a huge success. We’ve found evidence that they and the Denisovans mixed with modern humans, and now we know that there were different groups of Neanderthals, and that one replaced the other in the East. The other thing is to try to understand the function of their genome, their physiology, and how it differs from ours. That’s the next frontier.

Q. And what are the latest discoveries in this area?

A. We have a problem because if we analyze modern humans, we’re looking for genetic traits that we all share. So we have to use stem cells and edit their genome with CRISPR to generate organoids, or create Neanderthalized mice, for example. The other option is to look for traits typical of Neanderthals and Denisovans. There, we can find modern humans who retain those variants. This way, we can use modern humans as models and see how those genetic variants change them.

Q. Do any of these traits influence the physical appearance and mentality of modern humans?

A. Yes. Within the human lineage, we’ve discovered the role of the TKTL1 gene. We’ve seen that the modern human version reduces the enzyme’s effectiveness, which means that in our brain, we accumulate substrates of the enzyme. When we introduce this variant into mice, we see that they compete more efficiently for water when they’re thirsty than normal mice. It’s a genetic change that impacts behavior: competing more efficiently for a resource. We don’t know its effect on humans, but it’s a genetic change that changes behavior and, interestingly, only occurs in females.

Q. You have created mini-brains with that variant, and they also develop more neurons, what implications does that have?

A. It could be a gene that influences early brain development, but it’s very difficult to know. There are people who carry the ancestral variant of the gene and who are perfectly normal, as far as we know, although we haven’t studied them in detail. It’s a complicated problem that we encounter frequently in this field.

Q. You maintain that Neanderthals did not become extinct, but that we absorbed them.

A. We’ve found several Homo sapiens who, tens of thousands of years ago, had close Neanderthal relatives. This means that the first wave of Homo sapiens that left Africa and arrived in Europe happily mixed with Neanderthals. Then a second wave came and replaced them all, both Homo sapiens and Neanderthals. I don’t think they came and killed them all. If you think that these modern humans were about 50 times more numerous than Neanderthals, and that they mixed with them, this would give you roughly 2% Neanderthal genetics, which is exactly what humans outside of Africa have today. I don’t think it was that simple, but I do think we assimilated them.

Q. What role did technology play?

A. There was very rapid change and specialization on our side, while the Neanderthal technology was more constant over time. Arrowheads begin to appear associated with sapiens. The question is why the Neanderthals didn’t pick up this tool for distance killing. There’s also evidence that their groups were smaller, so their societies must have been different.

Q. Why were Homo sapiens more numerous?

A. That’s the big question. We could imagine that, for some reason, they lived a little bit longer than Neanderthals, or that they had one more child per family on average, which would cause an exponential difference. But we don’t know.

Q. Why do you think we are the only humans left?

A. For most of the time, this wasn’t the case; there were many human species alive at the same time. The fact that we’re alone is truly unique in the last 40,000 years. Not only did other humans disappear, but sapiens are also the most numerous human species that has ever existed. And I think the answer lies in us as a species, in our behavior and in how numerous we’ve become. Orangutans are about to become extinct in the wild. There’s no point analyzing their genome to try to explain why; it’s clearly due to us, because we hunt them and damage their habitat. It’s our behavior, so it’s really understanding our own behavior and genetics that will answer these questions.

Q. You say we inherit physical traits from Neanderthals. Are there people today who look more Neanderthal?

A. In fossils, being a Neanderthal is a combination of traits: more pronounced brow ridges, an occipital bun, an oblong cranium, a barrel-shaped thorax. The same applies to modern humans. I think we’ll soon discover that some of these traits came from Neanderthals and are still present in us, like that occipital bun.

Q. What Neanderthal heritage do you find most surprising?

A. When SARS-CoV-2 emerged, a virus that had never affected humans before, we analyzed why some people suffered severe illness and others didn’t. We discovered that a Neanderthal variant plays a huge role, because it makes you two to three times more likely to be severely ill or even die from COVID-19. Suddenly, we saw that a genetic variant from the time of the Neanderthals has a very important effect in present day people.[According to Pääbo’s studies, this variant could have caused an additional million deaths from COVID-19. On the other hand, the same variant reduces the risk of contracting the AIDS virus by 25%.]

Q. Are there similar effects in mental illness?

A. We still know very little. There are hundreds of variants associated with autism, and each one contributes a little to causing it. Some of them come from Neanderthals.

Q. Do you think it is possible to understand the minds of these extinct humans?

A.I doubt it. The mind is the result of many genetic variants plus your environment and upbringing. We’ll never have that. It’s impossible.

Q. Is it possible to recover the genome of any other human species?

A. Yes, from Homo floresiensis, [known as the Flores hobbit]. We believe that, although the climate isn’t ideal for preserving DNA, it will be possible to extract it from its fossils. We’re working very hard, and I think there’s hope of achieving it.

Q. What about Homo erectus or what Chinese scientists have dubbed “the dragon man”?

A. The key here is to find relatively recent fossils that we can confidently assign to those species. Morphology doesn’t tell us that, so we need to extract DNA or proteins. In the case of Homo longi, we’ve shown that at least the fossil skull from Harbin, China, was actually from a Denisovan. From the oldest fossils, more than a million years old, I don’t think it’s possible to recover DNA.

Q. Do you think it is possible to de-extinct species like the mammoth, or even Neanderthals themselves?

A. We’ll never bring an extinct species back to life. It’s sometimes said that we have a high-quality genome of the mammoth or the Neanderthal. But that’s only a qualified truth: we don’t know how the repetitive parts of the genome are organized. In reality, we only have accurate access to about two-thirds of the genome — the single-copy parts. But for the rest, we only have a statistical estimate of how many repeats there were, and those regions are also functionally important.

First, we don’t have a complete genome to recreate. Second, we also don’t have the technology to introduce the hundreds of thousands of genetic changes needed. What you’re really doing is recreating individual traits: for example, taking a wolf and making it white because the dire wolf was thought to be that way, or making it bigger. You’re not even introducing the original mutations from dire wolves, but rather others that give it a similar appearance. In the same way, you can make an elephant have hair, with some mutation taken perhaps from a mammoth or maybe another animal. But that won’t be a mammoth: it’ll be an elephant masquerading as a mammoth.

And honestly, I don’t know what the purpose of that is. The worst thing is that none of this has been published in a scientific journal. And for humans, there’s a whole set of additional ethical problems, like editing germ cells. Perhaps in the future, when it’s proven safe, it might be allowed to cure some horrible, incurable disease; but it should never be pursued out of simple scientific curiosity.

Sign up for our weekly newsletter to get more English-language news coverage from EL PAÍS USA Edition