Published 1 December 2022 by Hanna Kurlanda-Witek

Nobel Prize in Physiology/Medicine 2022: Cavemen Relatives

Sequencing DNA, but of a Neanderthale bone, is in the focus of the 2022 Nobel Prize in Physiology/Medicine. Photo/Credit: KariHoglund/iStockphoto

The recipient of the 2022 Nobel Prize in Physiology or Medicine is Svante Pääbo, a Swedish geneticist and professor at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. Pääbo’s research forged an entirely new field in evolutionary biology − paleogenomics, or the analysis and reconstruction of ancient genomes. The milestones of Pääbo’s career so far have been the sequencing of DNA from a Neanderthal bone in 1997 and publishing the first version of the Neanderthal genome in 2010.

Mummy DNA

As a boy, Pääbo became interested in archaeology, frequently scouring the forests outside his hometown of Stockholm, looking for pot shards from the Stone Age. His mother encouraged his interests and the two travelled to Egypt three times, where they visited the pyramids and marveled at ancient treasures. Studying Egyptology was a natural choice for Pääbo, but he soon became disillusioned with his studies, which often involved deciphering hieroglyphics, and switched to medicine, as advised by his father, the Nobel Laureate Sune Bergström.  

Yet Pääbo never quite forgot about archaeology. While studying for a PhD on adenoviruses, and without letting his PhD advisor know, he sought the help of his former Egyptology professor to conduct experiments on isolating DNA from Egyptian mummy tissues. The experiments worked and resulted in a cover story in Nature in 1985.

Ancient Animals

Soon afterwards, Pääbo received a letter from the evolutionary molecular biologist Allan Wilson of the University of California, Berkeley. As this was before the age of Google, Wilson didn’t know that Pääbo was a graduate student and asked if he could spend a sabbatical in Pääbo’s lab. When Pääbo wrote to Wilson to explain, he was offered a postdoc position at Berkeley, where he attempted to analyse a sample from a 7,000-year-old human brain. He soon found that contamination of ancient tissues with DNA from modern humans or bacteria was a major setback and meticulous controls were necessary. Pääbo then resorted to isolating DNA from extinct animals, such as mammoths, and this helped him refine the techniques he was to use later on.

A Little Bit of Genetic Material

Once back in Europe in 1990, Pääbo became a professor at the University of Munich. He was contacted by the Rheinisches Landesmuseum in Bonn, which possesses the first Neanderthal bones ever identified, and was asked if he could try and extract DNA from the fossils. Thus began the long process of trying to isolate Neanderthal DNA from a piece of skull discovered in a German quarry in 1856. It was the early 1990s; the Human Genome Project had already been launched, but it was one thing to sequence DNA from living organisms and yet another to sequence DNA from a 40,000-year-old piece of bone. Pääbo thought the project had a 5% chance of success.

“Mr. N”, a life-size figure reconstructed on basis of human fossils that were found. Photo/Credit: 2021 Neanderthal Museum · Holger Neumann

Eventually, Pääbo and his team isolated the first DNA sequences from a Neanderthal’s mitochondrial DNA. The results were published in Cell in 1997, and this is the accomplishment Pääbo is most proud of: “We had a little bit of the genetic material of that individual, and that was emotionally quite a strong thing.”

Neanderthals lived in Europe and Asia from about 400,000 years ago and became extinct around 40,000 years ago. There were various theories about where Neanderthals fit in the history of humans; were they our direct ancestors or a genetically unique species? The Cell study determined that Neanderthals and Homo sapiens, or modern humans, were distinct groups of hominins, which had separated around 500,000 years ago. At that point it was still unclear whether Homo sapiens and Neanderthals had ever co-existed and whether there was any gene flow between the hominin species.

First Hurdles: Not Enough Bones

Nearly a decade later, Pääbo initiated the Neanderthal Genome Project. At first, the group encountered difficulties with finding enough Neanderthal bones, and even when that was successful, in finding extractable and uncontaminated genetic material. About 80% of the DNA sequenced for the project was of microbial origin. Despite these significant obstacles, the first Neanderthal genome sequence was published in 2010, and with it the astounding discovery that modern-day Europeans and Asians share up to 4% of their genetic makeup with Neanderthals. It was also estimated that humans and Neanderthals had a common ancestor about 800,000 years ago.

Now that a Neanderthal genome was available, it could be compared to other genomes. In 2008, a fragment of a finger bone and a tooth were found in a cave in the Altai Mountains in Siberia. Pääbo and his group wondered whether it could be Neanderthal in origin, although Neanderthal bones had never been found that far east. Experiments demonstrated that the bones belonged to a unique, previously unrecognised hominin, which was named Denisova, after the cave where the fossils were found. Interestingly, the Denisovans also interbred with Homo sapiens; today’s South East Asians have up to 6% of their DNA in common with Denisovans.

A recent article published after the Nobel Prize announcement shed yet more light on the Denisova findings; the Denisova cave was occupied by both Neanderthals and Denisovans. Bones from a group of eleven Neanderthals, some closely related, were found in the Chagyrskaya cave, located around 100 km away from the Denisova cave. Genetic data can tell us how we are related to these extinct hominins, but it can also provide clues as to what their social structure looked like.

Extinct Forefathers

When asked by Nobel Media’s Adam Smith about the importance of these discoveries, Pääbo replied that they show us how closely related we really are with ancient hominins. “It’s the realisation that quite recently, maybe 1400 generations ago or so, there were other forms of humans around and they mixed with our ancestors and have contributed to us today.” Pääbo added that he sometimes wonders what the world would be like if Neanderthals had survived until today. Would there be racism against them or would we see our place in the living world differently, as just one form of human amongst others?

Hanna Kurlanda-Witek

Hanna Kurlanda-Witek is a science writer and environmental consultant, based in Warsaw, Poland. She has a PhD in geosciences from the University of Edinburgh, where she spent a lot of time in the lab. As someone familiar with both worlds of research and industry, she enjoys simplifying science communication across the divide.