Nobel Prize in medicine awarded for research into the evolutionary history of humankind

A Swedish scientist won the 2022 Nobel Prize in medicine or physiology on Monday for his groundbreaking research into the evolutionary history of humankind.

Svante Pääbo, of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, accomplished something widely believed to be impossible: recovering and reading DNA from 40,000-year-old bones. By developing new techniques for working with ancient genetic material — which is often heavily degraded and contaminated by microorganisms — he led teams that sequenced the genome of the Neanderthal, and discovered a previously unknown hominin, Denisova. Pääbo unlocked scientists’ understanding of how genes from these extinct relatives have been passed down to present-day humans.

Thomas Perlmann, secretary of the Nobel Assembly and professor of molecular development biology at the Karolinska Institute, announced the award at a ceremony in Stockholm.

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Every year, the committee considers hundreds of nominations from former Nobel laureates, medical school deans, and other prominent scientists from various fields, including microbiology, immunology, oncology, and others. They’re looking for a discovery that has changed the way scientists think about a problem. And according to the criteria laid out in Alfred Nobel’s will, that paradigm-shifting discovery also has to have benefited humankind.

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

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His work also uncovered that modern-day humans are not totally genetically distinct, and in fact interbreeding took place between Homo sapiens, Neanderthals, and Denisovans that has left remnants of these species in our genomes today, including important immune genes for fighting off invading pathogens. By comparing ancient DNA with humans living today, scientists are now able to ask important questions about what makes us different from any other species, including our closest evolutionary relatives.

“I haven’t quite digested it yet,” Pääbo said at a press conference Monday. At first, he believed his lab members were playing an elaborate prank on him. But he soon realized the call from his hometown was real. “What really drives our work is curiosity,” he said. “Just as if you do an archaeological excavation to find out about the past, we sort of make excavations in the human genome.”

Pääbo was born in Stockholm in 1955, the secret extramarital son of Sune Bergström, who won the 1982 Nobel prize in medicine for discovering hormones called prostaglandins (Pääbo is the third parent-child pair to win a medicine Nobel). That made for a “pretty weird” childhood, he told The Guardian in 2014, only seeing his father on Saturdays.

But a vacation to Egypt with his mother, chemist Karin Pääbo, as a 13-year-old captured his imagination and set him on a path to study Egyptology and medicine as a student at Uppsala University. Even from a young age, he had a knack for thinking outside the box. As a Ph.D. student in immunology, he applied new genetics techniques to archaeological remains, showing for the first time that DNA in mummies could survive for thousands of years and later be cloned in the lab.

Two years later, in 1987, he moved to Berkeley, Calif., to continue to work on ancient DNA with the geneticist Allan Wilson, whose work on molecular clocks had redefined the evolutionary split between humans and chimpanzees. His interest in evolutionary biology stirred, Pääbo began to focus on Neanderthals, an ancient hominid species that lived in Europe 30,000 years ago.

In 1996, he was able to acquire a small piece of a humerus from a specimen found in Western Germany. Working in extremely sterile conditions developed at his own lab at the University of Munich, Pääbo’s team extracted and amplified mitochondrial DNA from the fossilized bone. The groundbreaking work earned him a spot at the head of a new research institute dedicated to evolutionary anthropology and genetics in Leipzig, where in 2008, he and his team succeeded in reconstructing a first version of the full Neanderthal genome.

Using these same techniques, two years later they reported the discovery of an entirely new ancient human species, the Denisovans, from a fossilized pinky finger found in a cave in southern Siberia. Their research also showed that modern humans living outside Africa have little bits of Neanderthal and Denisovan DNA stitched into their genomes, the result of long-ago interbreeding. Together, these findings upended previous understandings of early human evolutionary history.

“People forget how radical it was to think that one could sequence ancient DNA up to the level of genomes,” deputy director general of the European Molecular Biology Laboratory Ewan Birney said on Twitter, calling Pääbo’s prize “well deserved.”

But at least among some ancient DNA academics, there has been a bit of head-scratching over Pääbo’s solo selection. Since 2007, the Swede has been closely collaborating with Harvard Medical School geneticist David Reich, who was brought on to help interpret the early Neanderthal genome data. Since then, Reich’s lab has become a powerhouse in paleogenomics, sequencing the genomes of more than 16,000 ancient humans from around the globe.

Awarding just one medicine laureate in a given year isn’t unheard of — most recently, Yoshinori Ohsumi took home the prize in 2016 for his discoveries of the mechanisms of autophagy — but it’s not the norm. And pioneering scientists haven’t been selected by the Nobel committee before. In 2020, Feng Zhang of the Broad Institute was conspicuously left off the chemistry Nobel for CRISPR, which went to Jennifer Doudna of the University of California, Berkeley, and Emmanuelle Charpentier of the Max Planck Institute for Infection Biology, despite the Broad’s relentless campaign in patent courts and the court of public opinion to give Zhang credit for the discovery.

Reich, for his part though, doesn’t seem to harbor any sour feelings. He told the Associated Press Monday morning that he was “thrilled” the prize honored the field of ancient DNA and that Pääbo “was, more than anyone, the pioneer of this field.”

The reference genomes that Pääbo’s group created made it possible to ask probing questions about where certain traits found in modern-day human populations might have come from, often illuminating how aspects of brain, lung, and immune function are influenced by our ancient genetic inheritance.

For example, many Tibetans carry a version of the gene EPAS1 that comes from Denisovans, and confers an advantage for surviving at high altitude. A trio of genes that have been tied back to Neanderthals — known as TLR1, TLR6, and TLR10 — rally the body’s initial defenses against foreign bacteria (and can trigger allergies). One of the biggest genetic risk factors for severe Covid-19, Pääbo found, in a paper published in Nature in 2020, is a cluster of genes on chromosome 3, inherited from, you guessed it, Neanderthals.

It might seem a little bit strange to have a Neanderthal or Denisovan sequencing pioneer recognized for science’s top honor before the groups that gave us the first human genome (a serial contender in STAT’s Nobel Prize predictions). And while we won’t know for 50 years exactly how the committee made its decision, Perlmann told STAT that the importance of ancient DNA to human physiology has never been a question. It was just a matter of finally getting a compelling candidate.

“This prize does break new ground by recognizing ancient human evolution for the first time,” Perlmann said in an interview. “For us, this was a clear case where we felt we should go there.”

Pääbo will receive 10 million Swedish kronor, or about $895,000. His name is added to a list of medicine or physiology Nobel winners that now includes 213 men and 12 women.

And speaking of Nobel predictions, what about the mRNA technology behind Covid-19 vaccines not receiving the medicine prize this year?

“That is a very good question that I’m not going to answer,” Perlmann told reporters after announcing Pääbo as the 2022 laureate. “We only talk about people who get the Nobel Prize.”

This story has been updated with additional background on the laureate and winning research.

Source: STAT