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Nobel awarded to Swedish scientist who deciphered the Neanderthal genome

Oct. 3, 2022 Updated Mon., Oct. 3, 2022 at 4:47 p.m.

By Carolyn Y. Johnson Washington Post

The Nobel Prize in medicine was awarded Monday to Svante Pääbo, a Swedish geneticist whose work on ancient DNA helped change our understanding of human origins.

Pääbo, an evolutionary geneticist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, led groundbreaking work to sequence the genome of long-extinct Neanderthals from 40,000-year-old bone fragments. It was a “seemingly impossible task,” said Anna Wedell, a member of the Nobel committee.

The work was transformative, showing that Neanderthals mixed with prehistoric humans after they migrated out of Africa, and the vestiges of those interactions live on in the genomes of many present-day people. Pääbo’s efforts laid the foundation of a new field of science that uses ancient DNA as a new stream of information to probe human evolution.

Pääbo, 67, learned he had won the prize in a midmorning phone call from the Nobel committee shortly before he was set to depart to pick up his daughter from an overnight stay with her nanny, he said in a recorded interview posted by the Nobel website. When he saw the call was from Sweden, he suspected that it was someone calling about the upkeep of his small summer house there - perhaps a broken lawn mower.

“He was overwhelmed. He was speechless, very happy,” said Thomas Perlmann, secretary of the Nobel Assembly. “He was incredibly thrilled about this award.”

As a young scientist, Pääbo focused on understanding how adenoviruses interacted with the immune system. But he had long been intrigued by human origins, and he worked on isolating DNA from Egyptian mummies as a side project.

At the time, the ancient DNA field was “kind of a joke,” full of incredible claims that would turn out to be incorrect as scientists tried to recover DNA from dinosaurs, said John Hawks, an anthropologist at the University of Wisconsin at Madison.

“It was Svante who came along and made this into a science,” Hawks said.

For decades, Pääbo chipped away at the difficult task of analyzing ancient DNA, devising ways to overcome the technical challenges of working with samples that degrade and change chemically over time and are easily contaminated. He worked largely on DNA from extinct animals, but always with the goal of bringing the techniques he was developing to modern humans’ extinct, big-brained relatives, Neanderthals.

Once he had developed those methods, he brought together a large consortium of scientists and built the relationships necessary to obtain the ancient bone fragments needed to take on the monumental task of trying to decipher the genome of Neanderthals.

That work disrupted the prevailing view of human origins. Homo sapiens originated in Africa about 300,000 years ago, but they emerged into a world filled with other hominid species - and mixed with them as they migrated.

“Until quite recently, 1,400 generations or so ago, there were other forms of humans around - and they mixed with our ancestors and have contributed to us today. The last 40,000 years is quite unique in human history, in that we are the only form of humans around,” Pääbo said in the Nobel interview Monday. “Until that time, there were almost always other types of humans that existed.”

Pääbo and colleagues showed that long-extinct Neanderthals live on in our DNA. As modern humans migrated outside of Africa, they mixed with Neanderthals. Those ancient genes live on, making up about 1 to 2 percent of the genomes of non-African people today. From a finger bone found in a cave in the Altai Mountains in Russia, he discovered a new species of early hominid, the Denisovans.

This genetic inheritance is relevant for understanding aspects of modern human health. A version of a gene that gives people an advantage at high altitude that is common among people living in Tibet has Denisovan origins. Some genes that influence how present-day people’s immune systems respond to infections are inherited from Neanderthals.

During the pandemic, Pääbo found that a genetic risk factor associated with severe cases of covid-19 was passed down from Neanderthals, carried by about half of people in South Asia and about 1 in 6 people in Europe.

“These are profound things that happened to human biology, and we need to know about it - it is an important part of the inheritance,” said David Reich, a geneticist at Harvard Medical School. “It’s changed our biology and the history of everybody. We all know we are all mixed.”

Reich said the prize was a thrilling recognition for a scientist he considers a close friend and collaborator - and for a burgeoning field of science that has transformed science’s view of the human species.

Reich was a key part of the consortium that helped determine that Neanderthals had mixed with humans, and said that when he joined the project, he - like many in the field - expected not to find evidence of mixing between Neanderthals and humans.

“When we saw the first evidence that it had occurred … it was surprising and unexpected, and I thought it was likely to be an error of our analysis - and I spent a lot of time trying to make it go away,” Reich said.

Ultimately, multiple lines of evidence supported the conclusion.

Before Pääbo’s contributions, scientists were limited to studying ancient bones and artifacts to understand human ancestors. His work has established a new field of science, paleogenomics, which uses ancient DNA analysis to probe questions about prehistoric life.

While Pääbo’s scientific work has been transformative, some wondered whether it would win a Nobel, often considered science’s highest honor, because it wasn’t an obvious fit with the traditional categories. In science, Nobels are awarded to medicine or physiology, physics and chemistry.

Hawks, however, argues that understanding human ancestry and evolution is a direct view into understanding deep questions about health and disease. Ancient DNA gave scientists entry to aspects about ancient humans and their relatives that would otherwise be inaccessible.

“This isn’t just a strange thing about our evolution that we’re learning - it’s relevant to our health,” Hawks said. “It matters because our ancestry is what is affecting our health, and when you uncover the genes that we inherited from these distant ancestors that matter to our health, you’re going to open a new window into understanding human disease.”

Forty years earlier, Pääbo’s father, biochemist Sune Bergström, shared a Nobel Prize with two other scientists. Pääbo revealed that he was the “secret extramarital son” of Bergström in his biography, “Neanderthal Man: In Search of Lost Genomes.” He said Monday that he wished he could share the news with his mother.

“The biggest influence in life was my mother, with whom I grew up,” Pääbo said. “It makes me a bit sad she can’t experience this day.”

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