What do Neanderthals have to do with medicine? More than enough, it turns out, to earn Svante Pääbo Monday’s Nobel Prize in medicine for sequencing the Neanderthal genome. It may sound more like a feat worthy of an anthropology prize, but scientists are already using Neanderthal DNA to make important medical findings, and they expect many more to come.
For example, in 2020 Pääbo and Hugo Zeberg found that having a specific Neanderthal gene variant may double the risk of dying from Covid-19. That gene is present in about 50% of people in south Asia and about 16% of Europeans. They later found another Neanderthal gene variant with a possible protective effect against Covid-19. It shows up in about half of people outside Africa.
Pääbo’s work on Neanderthal DNA has led to a whole new field of studying ancient DNA, and in 2010 brought the world a shocking discovery that violated what every schoolchild knew about Neanderthals being a dead-end branch of the family tree. Neanderthals were our ancestors’ lovers, or spouses, or maybe rape victims. One way or another, they interbred for thousands of years and passed their genes all the way through to today’s humans.
That genetic legacy has influenced modern humans’ risk for type 2 diabetes, Crohn’s disease, lupus and even smoking behavior. What might look like a curiosity has provided a new window into human physiology and health.
“Some of the most fundamental and deepest questions about human biology can be addressed directly from this information from Neanderthals,” said Richard E. Green, a biomolecular engineer who worked with Pääbo to decode the genome from ancient bones.
Some of the Neanderthal genes that people continue to carry have negative effects on health, and some have beneficial effects — or some combination whose overall balance depends on environmental factors such as which diseases pose the biggest threat. One archaic gene helped Tibetans adapt to living at high altitude.
More recent work by geneticist David Reich at Harvard used bones from ancient humans in our lineage to show that they carried many more genes from Neanderthal interbreeding than people do today, suggesting many of these genes had a deleterious effect. Of the genes that remain, scientists are still sorting out how they affect skin, hair and susceptibility to disease.
“This interbreeding was a profound experiment of nature,” said Reich. “The legacy in that mixture lives on in people today — it injected huge amounts of genetic material into the modern human population that hadn’t been there before.”
Pääbo’s lab is now doing exciting research on the genes that make our brains different from Neanderthals’ — and different from any other species on Earth, said Mary-Claire King, a genetics professor at the University of Washington. She’s known for the discovery of the first breast cancer gene and for her 1975 discovery that the DNA of humans and chimpanzees is 99% identical.
Comparing our DNA to that of other species has helped us understand what the various human genes do. With Pääbo’s work, she said, we have another, much closer species for reference. Modern humans diverged from chimpanzee ancestors around 7 million years ago, and from Neanderthal ancestors around 400,000 years ago. We and Neanderthals are genetically 99.8% identical through our shared ancestry, and through intermixing that started about 60,000 years ago.
King told me that finding what’s unique about the genes governing modern humans’ brain structure and development could shed light on the roots of brain disorders and mental illness — a mystery she’s currently working to unravel. And it could help us understand why the human mind is so creative and good at problem solving.
Pääbo’s work unlocked more than the genes of Neanderthals — it unlocked ways to get DNA from other ancient remains. When I was writing about evolution in the early 2000s, scientists were intrigued by his quest to sequence Neanderthal DNA, but thought this delicate molecule would be too degraded after tens of thousands of years to provide much information.
Green said Pääbo was one of the rare scientists willing to take a massive risk by embarking on a project that was very likely to fail. “He envisioned technologies that had not yet been invented that might overcome his limitations,” said Green. People advised Green as a young researcher to stay away from ancient DNA, saying such work would go nowhere.
Because Pääbo persisted, we also now know about a previously unknown branch of the human family, called Denisovans. Pääbo discovered our new relatives after sequencing DNA from a finger bone found in Siberia.
Harvard’s Reich said it’s now understood that all humans on Earth are mixed up with different archaic species — the Neanderthal, the Denisovans, and in Africa, groups whose bones didn’t fossilize but whose genes left their mark. We have a different understanding of our past than we did just a decade ago, and the implications are just beginning to be understood.
“These are really early days and I think it will take another decade to really figure out the full extent of the Neanderthal legacy on human genetics,” said Green. It may not sound like typical biomedical research, but the recognition the Nobel brings to this field is richly deserved.