Announcement of 2022 Nobel Prize in Physiology or Medicine Transcript

Anna Wedell: (00:00)
… answered by analysis of ancient bones and artifacts alone. Questions such as how we and our extinct relatives are related to each other, and, importantly, what makes us different. DNA technology offered a new way of addressing these intriguing questions. DNA holds the code of life. Gradual changes to this code, mutations, form the basis of evolution, and these mutations remain in our DNA as traces from our ancestors. Our cells contain DNA in two different compartments. The long nuclear DNA carries the overwhelming majority of our genes, but the small mitochondrial DNA is present in thousands of more copies and therefore easier to study.

Svante Pääbo was from an early age fascinated by ancient human history. While using DNA technology for his doctoral studies in immunology, he also attempted as a side project to use these modern tools for studies of ancient human remains. He soon realized that this is extremely challenging, since ancient DNA is damaged by chemical modifications. It is also fragmented and present in extremely low amounts together with contamination from microorganisms and present day humans. Svante Pääbo therefore embarked on a long series of rigorous technological developments that lasted over three decades. He performed much of this work on extinct animal species, but his goal was a seemingly impossible task. He aimed for our closest relative, the Neanderthal, that went extinct around 30,000 years ago.

After setting new experimental standards in this challenging area, Pääbo first set out to retrieve and analyze Neanderthal mitochondrial DNA. He obtained a bone from the Neanderthal type specimen that had been discovered in 1856. From a small piece of this bone, he managed to extract and sequence mitochondrial DNA. He compared his new sequence to present day humans and to chimps, and found that the new sequence was different from both of them.

This was an important milestone. Pääbo had proved that it is possible to retrieve and sequence DNA from 40,000 year old bones. Mitochondrial DNA, however, contains very limited information and Pääbo’s goal was to sequence the three billion base pair Neanderthal nuclear genome, which would allow in-depth analysis and comparisons across multiple genomic regions. The human reference genome had been sequenced in a huge international collaborative effort, and the chimpanzee reference genome sequence was also available. Sequencing the nuclear genome of an extinct hominine, however, seemed impossible.

Pääbo embarked on his bold plan and for this, he needed more bone. Thanks to his strong international networks, he managed to obtain three bone specimens from Vindija cave in Croatia, together with additional material from Germany, Russia, and Spain. All along, he refined and optimized his experimental procedures. By skillful use of new high throughput sequencing technologies and by bringing together a large international group of collaborators for advanced computational analysis, Pääbo finally achieved the impossible, seeing an assembly of the Neanderthal genome. For the first time, important questions on our relationship with the Neanderthal could be addressed. The time of divergence could now be determined to around 800,000 years ago.

Pääbo and his team also surprisingly found that gene flow had occurred from Neanderthals to Homo sapiens, demonstrating that they had children together during periods of coexistence. Importantly, comparisons could now also be made to search for differences between Neanderthals and Homo sapiens, differences that may underline features that are unique to all humans living today.

Pääbo’s team also retrieved DNA from a minute finger bone found in the Denisova cave in the Altai Mountains in Southern Siberia. Again, they started by analyzing mitochondrial DNA and to their surprise, the sequence was different from both present day humans and from Neanderthals. Pääbo had discovered a completely new hominine entirely by analyzing and comparing genome sequences. This was a sensational discovery. The new hominine was given the name Denisova. Pääbo’s team next analyzed the nuclear Denisova genome sequence enabling important investigations. Neanderthals and Denisovans were shown to be sister groups, diverging from each other around 600,000 years ago.

They further found evidence of gene flow from Denisova into Melanesian Homo sapiens, indicating that mixing had occurred. Svante Pääbo’s groundbreaking discoveries have provided important new knowledge regarding our evolutionary history. Neanderthals and Denisovans lived in different parts of Europe and Asia for hundreds of thousands of years and adapted to these environments while Homo sapiens evolved and lived in Africa. By mixing with them after migrating out of Africa, Homo sapiens picked up sequences that improved their chances to survive in their new environments.

We now know that present day humans in Europe and Asia can carry one to 2% of Neanderthal sequences and that Asian and Southeast Asian populations carry an additional, up to 6%, Denisovan sequences. Examples include a gene variant that improves living at high altitude in Tibetans and sequences that affect how our immune system response to different infections. No extinct hominine DNA has yet been sequenced from Africa, since conditions for preserving archaic DNA are poor in tropical climates. Thanks to new advanced computational methods, it has still been possible to find indications of gene flow from as yet unknown archaic hominines into Homo sapiens on the African continent.

Through his persistent and innovative work, this year’s Nobel Laureate established a new scientific discipline, paleogenomics. This area is now expanding dramatically. After the discoveries cited here, Pääbo went on to generate genome sequences from many additional Neanderthal and Denisova individuals. In parallel, genome sequences from ancient Homo sapiens have also accumulated from different time points and different geographic locations by research groups around the world. By using Svante Pääbo’s archaic genome sequences for comparative studies, important lessons are being learned regarding our evolutionary history, including how we spread across our planets. Svante Pääbo’s groundbreaking discoveries allow us to address one of the most fundamental questions of all; what makes us unique? Like us, Neanderthals had big brains, they lived in groups and they used tools, but these changed very little during hundreds of thousands of years until the Neanderthals, for unclear reasons, disappeared.

Homo sapiens on the other hand, rapidly developed complex cultures, figurative art and advanced innovations. They crossed open waters and they spread to all parts of our planet. The basis for this dramatic development must lie in genetic changes that occurred after we separated from Neanderthals and Denisovans not so long ago. By providing genome sequences from our closest extinct relatives, Svante Pääbo has provided a novel, much more recent reference point for studies of who we are and where we came from. Thanks to his seminal discoveries, genetic variants that are shared among all now living humans, but absent in Neanderthals and Denisovans have been identified. The list of such genetic variants is not very long. Understanding their functional implications is a focus of intense research by Svante Pääbo, but also by other scientists. Thank you.

Speaker 2: (09:59)
Thank you, Anna. So we will now open up for questions and to our help, we have Gunilla Karlsson Hedestam, who is a professor at the Karolinska Institutet and a member of the Nobel Committee. Nils-Göran Larsson, also professor at the institute and chair of the committee, and Professor Anna Wedell, who you just heard. So please, yes. Microphone is coming.

David Keaton: (10:46)
David Keaton from the Associated Press. I understand you have been able to contact this year’s winner. Can you tell us a little bit about his reaction when he heard that he won this prize and what he maybe or what you believe this award can mean for future developments in this area?

Speaker 2: (11:06)
Yes, I did reach him on the phone. This year. He was situated in [inaudible 00:11:15], so he was not in bed, so it was easy to reach him. He was overwhelmed, he was speechless, very happy and asked if he could tell anyone and asked if he could tell his wife. I said that was okay. Yeah, he was incredibly thrilled about this award. I think I’ll pass on the question about what this prize might mean. I’ll give it to Gunilla here. Could you respond to that?

Gunilla Karlsson Hedestam: (11:52)
Yes. I think as we learn more and more about the genomes of current humans from different parts of the world, it’s very, very important and useful to have these reference points, which tell us when we diverged from these earlier human forms. That tells us both what’s unique to us, to all Homo sapiens living in the world today, but also it tells us something about these gene regions that were passed on to some of the people living today from the extinct hominine. So there are a lot of implications both in terms of understanding our evolution and with the potential medical implications and basic understanding of our physiology.

David Keaton: (12:30)
Could you elaborates on the potential medical implications, please?

Yeah. In regards to what makes us uniquely human, I think that a big area of interest is of course how we evolve to become this sort of social creature that we are in terms of collaborating in large social groups and doing this very sort of … these innovations that are very specific for Homo sapiens. That has to do with brain function, of course, and other interesting aspects to study are these genes that were inherited from the extinct hominines and they relate to many physiological functions. They relate to our immune response, as we heard, also how we survive on high altitude. Many sort of interesting examples that are just being elucidated now.

Speaker 2: (13:25)
Here we have one, yes.

Speaker 5: (13:31)
In his research, Svante Pääbo has used a lot of methods that have been developed by other scientists. What would you say is his specific contribution for which he’s receiving the prize today?

Speaker 2: (13:46)
Nils-Göran, could you respond to that?

Nils-Göran Larsson: (13:50)
So his big contribution, which has been very decisive for these prizes, that he has really developed methods to analyze and recover ancient DNA. So DNA in old bones get very degraded and also chemically damaged. On top of that, you have a heavy contamination with DNA from bacteria and contemporary humans who have handled this specimens. So he has used existing technology as this has evolved and implemented his own methods to refine the analysis of ancient DNA. So this is, of course, very important.

Speaker 5: (14:36)
Could you be even more specific where he’s not refining but actually finding something really new?

Yeah, I mean, I think it was certainly considered to be impossible to recover DNA from 40,000 years old bones and you may also remember that was a lot of erroneous papers actually describing recovery of DNA from dinosaurs and old insects in amber and so forth. He really has worked very, very stringently with clean rooms. He has demanded or required that experiments should be reproducible in independent laboratories, and he’s also devised bioinformatic and chemical tricks to be able to analyze ancient DNA.

Speaker 2: (15:38)
We have any other question here? [inaudible 00:15:58].

Speaker 7: (16:09)
[inaudible 00:16:09], TV 4. I think it’s interesting these differences in the genome when it comes to medical issues. I wonder if you could be a little bit more specific when it comes to this immune response. I’ve heard that those genes carry some disadvantage when it comes to immune response and maybe some other diseases as well.

Yeah, so the sequences that we have picked up during evolution that had conferred an advantage, many of those sequences are related to immune function, but they can work in different directions. Of course, today, the effects they have on us today are not immediately translatable to what it used to be prehistorically because there were different microorganisms. So they give us a general information on sequences that are important for immune function. But there are also specific examples, like for instance COVID 19. There are sequences that confer a risk of severe disease and others that confer slightly less risk. In some cases, the exact sequences aren’t precisely known, but there are indications. But there are sequences working in both directions and there are several different examples.

Speaker 2: (17:31)
I know there are many who wants to get to the interviews after this press conference, but I’ll still ask if there is anyone else. Here is a question. One more question here.

Speaker 8: (17:54)
Thank you. I’m [inaudible 00:17:56] from Chinese Nordic Times and my first question is now that the Neanderthal has been intermarried with Homo sapiens, but why Homo sapiens has been survival and Neanderthal has become distinct?

Speaker 2: (18:11)
Why Homo sapiens have survived and why the Neanderthals …

Speaker 8: (18:14)
Yes.

Speaker 2: (18:15)
I think we do not know the answer exactly, but I think a little bit the key is that we now have a handle on that. Anyone want to elaborate? Gunilla?

I think there are several theories about that. One is that human sapiens basically develop very large population sizes, so the Neanderthals were sort of assimilated into Homo sapiens, so that is certainly a possibility.

Speaker 8: (18:42)
Is that related to the genes, that Asian genes probably, and [inaudible 00:18:50]?

I didn’t hear the question. I’m sorry.

Speaker 8: (18:51)
That’s related to the Asian genes because the genes, they’re toxic?

Speaker 2: (18:55)
I think we can’t say that. As what’s said here, I mean, most likely there were cognitive differences. I mean, it’s very hard to speculate what those cognitive differences were, but we know that there were differences in behavior, in the group size form, the cultures that were much more collaborative in Homo sapiens and creation of figurative art, for example. That didn’t seem to happen in Neanderthal populations. I think it’s hard at this point to say more exactly what those differences are, but what we can say that they must exist and thanks to Svante Pääbo’s work, they have now been mapped and identified and are open for studies. There are already studies out that are speculating on gene differences, that are genes that are present in us, all living humans, but are different in these populations.

Speaker 8: (20:04)
Yes, thank you. The second question is I think many people may be curious about that MRI technology. I think it has been influenced a lot during this pandemic, but why this year is not recognized for Nobel Prize?

Speaker 2: (20:22)
That is a very good question that I’m not going to answer. We only talk about people who are getting the Nobel Prize and not about those who are not received them or not received them yet.

Speaker 8: (20:36)
Yes, thanks.

Speaker 2: (20:39)
Okay. Is there one more question or should we … Yes, here is one more question.

Speaker 9: (20:51)
There was one paper that Pääbo published early about a mummy from a museum in Germany where he described the DNA, and if I understand it right, that data was contaminated and it’s no longer valid. Do you have any comment on that and what do you think about it?

Speaker 2: (21:10)
Nils-Goran.

I think that’s correct. He himself says that this is not correct because you cannot get that long DNA fragments after the thousands of years, so this also led him to develop procedures to be able to recover ancient DNA.

Speaker 2: (21:34)
Okay. I don’t see any waving hands, so I think we will conclude here and then we’ll meet a few of you outside here. Thank you very much.

Announcement of 2022 Nobel Prize in Physiology or Medicine Transcript

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