Svante Pääbo's path to Nobel Prize began in Uppsala

Svante Pääbo as a doctoral student in the lab in the 1980s. Karin Sege-Peterson, at that time a postdoc, is pictured in the foreground talking to doctoral student Ann-Christin Arvidsson.

Photograph: Erik Bongcam-Rudloff

Svante Pääbo, this year's Nobel laureate in Physiology or Medicine, created a completely new field of research when he succeeded in mapping the DNA of the Neanderthals, thus contributing to completely new knowledge of human evolution. His research career began at Uppsala University with studies in Egyptology and a doctoral thesis on adenoviruses.

Svante Pääbo began his doctoral studies in the early 1980s. One of his doctoral colleagues was Lena Claesson-Welsh, who today is a professor at the Department of Immunology, Genetics and Pathology. She remembers that time happily.

"We were a very cohesive group. It was a time of technological revolution in the life sciences due to the introduction of molecular biology. This was absolutely essential in terms of what Svante wanted to do. We all had the feeling that we were leading the way and were satisfied that our research mattered and that we were doing something new and important," Claesson-Welsh remembers.

She got to know Pääbo well because they shared an office, and she remembers him as a person with a sense of humour and who was extremely dedicated to his research.

Trying to extract DNA from a mummy

But the future Nobel laureate not only devoted his days to his thesis, he also launched a side project that would become the starting point for the research career that would make him world-famous. It all started with Pääbo trying to extract DNA from a several-thousand-year-old mummy.

"There was some kind of adventure associated with how he got hold of this mummy. To test how he could extract DNA from destroyed tissues, he put pieces of meat in our heating cabinet and it didn't smell good," Claesson-Welsh remembers.

"Everyone had respect for him; there was something different and exciting about Svante and his mummy experiment. We followed it with excitement and interest, but did not understand what it might lead to. We thought extracting DNA from mummies would be very difficult," she recalls.

Contamination a major problem

Pääbo actually did find DNA remains in the mummy, however, and the results had a major impact when the study was published in Nature, which even had it adorn the cover. Later, however, he realised that the DNA sequences he had found did not come from the mummy, but probably from himself. This helped him understand that contamination was a major problem when dealing with this kind of material and that he needed to develop methods to sift out the irrelevant DNA.

Pääbo received his doctorate in 1986 for his dissertation on how a protein in an adenovirus can change the immune system. His main goal, however, remained attempting to find out more about humans that were thousands of years old through their DNA. This eventually led him to the University of California at Berkeley.

"I met him for the first time when we did a postdoc in the same lab in Berkeley together with a professor named Alan Wilson, who worked on evolutionary biology and molecular methods. So we overlapped during our time there, and he also worked on essentially the same issues as now: how do you access the DNA in archaeological samples," says Ulf Gyllensten, Professor at the Department of Immunology, Genetics and Pathology.

Their paths diverged in 1990 when Gyllensten took a professorial post at Uppsala University.

"The idea was that Svante would come too, but he got a better opportunity in Germany," recalls Gyllensten.

DNA from Neanderthals

After a few years in Munich, Pääbo received an offer in 1997 to build up and become director of the Max Planck Institute for Evolutionary Anthropology in Leipzig. It was there that he would do his ground-breaking work in extracting DNA from extinct human species such as the Neanderthals.

"I have kept in touch with Svante, and we also had a research collaboration and publication around the year 2000 in Nature on human evolution specifically. At that time it was not about fossil samples, but blood samples from living people. We did a study of the entire mitochondrial genome of humans from different parts of the world and were able to reconstruct the human evolutionary tree. It was a very fun study," adds Gyllensten.

In 2003, Pääbo returned to Uppsala University as a visiting professor at the Department of Immunology, Genetics and Pathology, where Gyllensten was then head of department.

"He came every year to give a lecture and sit down with our researchers and discuss research projects. It was packed every time when he came, as his lectures are always highly appreciated. People came from far and wide to listen to him," recalls Gyllensten.

Lost hair in a criminal investigation

One of the research projects in which Pääbo was involved was carried out by Gyllensten's doctoral student, Marie Allen.

"The study we carried out together analysed mitochondrial DNA from lost hair. We conducted analyses as part of a criminal investigation concerning the Götabanken robbery (1990), in which the robbers made off with over SEK 930 million. It turned into a collaboration on how to use the methods that worked on mummies on newer material for criminal investigations," explains Marie Allen, who is now a Professor of Forensic Genetics leading her own research team at the Department of Immunology, Genetics and Pathology.

As the method was so new, Gyllensten had to testify as an expert during the trial.

This was the first time that mitochondrial DNA was used in Swedish law, but it has been followed by many more cases that we have then analysed," notes Allen.

She describes the collaboration with Svante as very rewarding.

"It was both fun and stimulating. He's always so engaged in research, be it his own or that of others," she says.

Extracting ancient DNA in Uppsala

Uppsala University was relatively early in setting up its own lab to extract ancient DNA. There, Mattias Jakobsson's research team works to find new answers about human evolution. He had long been convinced that Pääbo would one day be awarded a Nobel Prize.

"He created this field of paleogenomics in research, so there's now a field that has been established for quite some time. But a Nobel Prize makes it very clear that this is a broad and important discipline within evolutionary research," notes Jakobsson, Professor of Genetics at the Department of Organismal Biology.

Technological developments have progressed rapidly, and one area of application in which researchers are now interested is the possibility of extracting DNA from material other than skeletons, such as soil samples from an ancient settlement.

"This allows us to find out if humans, Neanderthals or some other group lived there. So far, we are at the level where it is possible to differentiate between groups in that way, but we are not quite at the level of individuals yet," explains Jakobsson.

Åsa Malmberg