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Ancient DNA pioneer Svante Pääbo wins Nobel Prize in Physiology or Medicine

​​Svante Pääbo, a Swedish geneticist who has been a director at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany since 1997, has been awarded the Nobel Prize in Physiology or Medicine for discoveries related to the sequencing of ancient genomes, especially those from humans and extinct hominins such as Neanderthals and Denisovans. 

Pääbo played was a pioneer in the now-booming field of ancient DNA research, which is transforming our understanding of the past and has implications for future understanding of human biology.   

Pääbo was the first to successfully retrieve and sequence bits of ancient DNA from a Neanderthal in 1997. Then, after refining his methods to avoid contamination, his team sequenced a complete Neanderthal genome in 2009. His work has offered insights into the genetic evolution of modern humans, including a better understanding of disease risks. In 2020 he published evidence that people with Neanderthal ancestry had a higher likelihood of severe COVID-19 symptoms.

“Pääbo’s seminal research gave rise to an entirely new scientific discipline; paleogenomics,” the Nobel Assembly at Karolinska Institutet said in a press release today. “By revealing genetic differences that distinguish all living humans from extinct hominins, his discoveries provide the basis for exploring what makes us uniquely human.”

“He will be the first to say it’s not just his work. It’s a team of people,” says paleoanthropologist Chris Stringer of the Natural History Museum in London. “But he’s built a great team and they recovered the first bits of ancient DNA from an ancient human… That was the beginning of the story.” 

Christina Warinner, an ancient DNA researcher at Harvard University and the Max Planck Institute for Evolutionary Anthropology, adds that Pääbo’s own career evolved over time, in tandem with the research. “Once you have the sequences, you have to stand back and ask, ‘what does it mean?’ That means taking a new approach, using new technology, essentially learning a whole new field.” 

From early samples in the late 1990s that included just a few hundred nucleotides, Pääbo eventually isolated over 3 million base pairs, enabling him to analyze the Neanderthal contribution to modern human DNA. In 2010 he found that individuals in Europe and Asia today derive between 1% and 4% of their ancestry from Neanderthals. That shows that, as anatomically modern humans moved out of Africa beginning 100,000 or more years ago, they interbred with Neanderthals.

“I was one of the people who said, if [modern humans and Neanderthals did interbreed], it’s not significant,” Stringer says. “But in 2010, Svante and colleagues showed pretty convincingly that we had interbred with the Neanderthals, and that DNA is still active in our genomes. So it does have medical importance.”

In 2008, Pääbo and his team recovered DNA from a finger bone fragment in a Siberian cave that revealed a previously unknown ancestral human population, now known as Denisovans. Here, too, the genetic results offered insights into modern human populations, revealing that adaptations to living at high altitude found in modern Tibetan populations may be derived from distant Denisovan ancestors.

Pääbo’s interest in ancient DNA originated in a childhood fascination with ancient Egypt. As a student at Uppsala University, he shifted his focus from archaeology to medicine, following in the footsteps of his father Sune Bergström, a biochemist who won a Nobel Prize in Physiology or Medicine in 1982 for work on prostaglandins and related substances.

In a 1985 paper in Nature, Pääbo reported finding small amounts of DNA in the cells of Egyptian mummies. That early work was soon called into question due to the risk of contamination from modern DNA. Because the smallest speck of skin could introduce modern DNA to an ancient sample, Pääbo pushed to develop techniques to minimize contamination during sampling and to differentiate ancient proteins from modern ones.

“His Ph.D. work was on recovering DNA from mummies and it was pretty much a failure. He got nothing,” Stringer says. “Another kind of person might have said, ‘Well, I’m giving up, this is useless.’ But he didn’t. He kept going.”

In the late 1980s, Pääbo’s work got a boost from the development of polymerase chain reaction technology, which made it possible to replicate small fragments of DNA many times over. He reached out to museums in Germany to ask for Neanderthal bone samples, grinding small amounts into powder and sequencing the DNA that was contained inside.  

Published in Cell in 1997, the results were a watershed moment, showing that significant amounts of DNA could be recovered from bones 50,000 years old or more. The initial work relied on mitochondrial DNA, which is more plentiful in cells than DNA from the cell nucleus and therefore preserved in larger amounts. The results were enough to show that humans and Neandertals were two separate groups that diverged around 500,000 years ago. At first, this was interpreted as showing that the groups had not interbred—a conclusion upended by subsequent ancient DNA work. 

Also in 1997, Pääbo was named a founding director of the Max Planck Institute for Evolutionary Anthropology. In 2006, he launched an effort to sequence an entire Neanderthal genome. Fast-moving advances in DNA sequencing technology, along with new samples, helped Pääbo along: Within a few years, he and his team successfully sequenced over 4 billion base pairs. They published a draft Neanderthal genome in Science in 2010.

By scrutinizing DNA from ancient organisms, scientists have been able to gain insights into the subsequent evolution of new traits—and begun to understand why some populations, like the Neanderthal, failed to adapt to changing conditions and survive.

With reporting by Kai Kupferschmidt and Gretchen Vogel.

Source: Science Mag