Svante Pääbo: Driven by curiosity and fascination

Regarded as one of the founders of paleogenomics, Svante Pääbo’s seminal research into the sequencing of the Neanderthal genome has given us so much in terms of understanding the tree of life, and he was awarded the 2022 Nobel Prize in Physiology or Medicine. The Prize for Pääbo did not quite come out of the blue. Hugo Zeberg, Assistant professor at the Department of Neuroscience at Karolinska Institutet said that “He had gotten all the prizes he could possibly get except the Nobel Prize. He is already a scientific superstar.”

Hugo Zeberg, who worked with Pääbo on showing a major genetic risk factor for COVID-19 was inherited from the Neanderthals, thinks the Nobel recognition is great news for paleogenomics and well deserved for Pääbo.

“He has this ability to energise the room so people stay in the lab and just go on. He brings enthusiasm to a project, and you can see he is so interested in it, that people around him start to be interested.”

“He is an amazing colleague and collaborator. He has this ability to energize the room so people stay in the lab and just go on. He brings enthusiasm to a project, and you can see he is so interested in it, that people around him start to be interested,” Zeberg continued.

An early interest in Egyptology

This wonder and enthusiasm has been a characteristic of Svante Pääbo since he was young. Born in Stockholm in the 1950s, Pääbo developed an early interest in archaeology and Egyptology as a young teenager. He would go on to study Egyptology at Uppsala University, though found the subject was not what he expected. After two years he moved on to studying medicine, and though he enjoyed clinical medicine, would eventually move again, on to biological research.

In the 1980s Pääbo began his doctoral research on adenoviruses, but part of his mind was still focused on Egyptology. Curious as to whether DNA could be obtained from ancient Egyptian mummies, he secretly (worried that his PhD supervisor would not approve) worked to isolate DNA from samples obtained from a German museum.

The result of the research would be a paper titled Molecular Cloning of Ancient Egyptian mummy DNA, published originally in 1984 in a small East German journal, before being published again in Nature. The research caused quite a stir with the revelation that “These analyses show that substantial pieces of mummy DNA (3.4 kilobases) can be cloned and that the DNA fragments seem to contain little or no modifications introduced postmortem”.

A 7,000-year-old human brain

This paper caught the attention of evolutionary molecular biologist Allan Wilson at the University of California, Berkeley. Pääbo would move to California in 1987 to work with Wilson and together they would analyze the mitochondrial DNA (mtDNA) of a 7,000-year-old human brain.

One of the problems encountered at the time was contamination was a major issue in assessing ancient DNA (aDNA), there “is all sorts of damage in the DNA that can cause you to determine incorrect sequences, especially when you start from very few molecules, and there is also contamination from human DNA that is almost everywhere”, wrote Pääbo in 1987. Pääbo would go on to note that his sequences of mummy DNA may have been contaminated by modern DNA.

This admission may have dissuaded many to give up on sampling aDNA any further, with the technical limitations proving too difficult to overcome. Pääbo himself shifted his focus from human remains to animal remains for a short time, working on mammoths, cave bears, and the moa, a flightless bird found in New Zealand, closely related to the Australian emu.

What makes humans human

Svante Pääbo would end his time in California and move to the University of Munich in 1990 and refocus on ancient humans, particularly the Neanderthal. Speaking to Spektrum der Wissenschaft in 2008 he said ultimately he wanted to find out what makes humans human.

In 1993, working with colleagues he proposed a new method of aDNA extraction which would enable researchers to gain vastly superior results to previous attempts. The first neanderthal DNA sequences were published by Pääbo and his team in 1997.

Shortly after, he moved to Leipzig and founded the Max Planck Institute for Evolutionary Anthropology where he continues to work to this day. It is here where yet another major success of Pääbo’s already impressive career would unfold: the full neanderthal genome, published in 2010.

For someone that has spent so much of their career unearthing the secrets of neanderthals, some might wonder what else could we possibly learn, but Pääbo, writing in the New York Times says “our ‘genetic recipe’ is incomplete and will most likely always remain so.

Yet to find the biological basis for what made modern humans unique will arguably answer one of the most fundamental questions in our history”.

How much of a contribution neanderthals gave to humans might be unanswerable, but we do know that “Neanderthals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neanderthals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other”.

“These discoveries simply fit into Pääbo’s desire to know what makes humans special.”

The list of achievements in terms of our understanding of our ancestors doesn’t end with the Neanderthal genome. When the finger bone of an unidentified hominin was found in Siberia, it was Pääbo’s techniques that showed that it was neither Homo sapien nor Neanderthal, but a previously unknown hominin altogether, a Denisovan. There is now evidence that Neanderthals and Denisovans interbred, and interbred with early modern humans. In 2008 it was revealed (again by Pääbo) that the protein encoded in the FOXP2 gene in humans is identical in Neanderthals, which raises the possibility they could have had similar language capabilities to humans. These discoveries simply fit into Pääbo’s desire to know what makes humans special.

The father of the field

Those that have worked with Svante Pääbo readily credit him with being the father of field, but also how he “will be the first to say it’s not just his work. It’s a team of people,” said paleoanthropologist Chris Stringer of the Natural History Museum in London.

Indeed, on the question of the Nobel Prize, “Who else would you give it to?” asked Johannes Krausse, co-director of a new Max Planck Institute of History and the Sciences.

“The recognition our field gets with a Nobel Prize is great. I have been in this field for more than three decades, and have always thought that it has a lot to give to science.”

The recognition is also important for the field believed Anders Götherström, Professor of Molecular Archaeology of the Centre for Palaeogenetics at Stockholm University. “The recognition our field gets with a Nobel Prize is great. I have been in this field for more than three decades, and have always thought that it has a lot to give to science,” he said.

Those associated with the field all have immense respect for someone who has persevered to answer deep burning questions that we may all wish to know the answer to. His curiosity, drive, and fascination with his chosen subject is now getting the attention of those who may until recently may never have come across the term paleogenomics.