 Hello, hi Ty. What an absolute pleasure it is here to welcome you. We have a fabulous program planned. You are in for a real treat. My name is Heather Young. I am the very proud Vice President of Communications and Public Relations at OIST, the Okinawa Institute of Science and Technology. And I'm also your emcee this afternoon at this public lecture by 2022 Nobel Prize winner and OIST adjunct professor, Svante Pabo. So please, turn off your phones so that we may have your undivided attention for the next two hours. First, we will be privileged to hear from the Governor of Okinawa, then the President of OIST, and as she will introduce Professor Pabo. And then we will hear from our guest of honor. After that, we will conclude with a question and answer period. And this is your chance to ask a nobelist about what inspires him or where his research is heading from here. We have planned an afternoon of learning and illumination. But let's start off by expressing our appreciation. Thank you very much to our co-sponsors, the Okinawa Perfectural Government, and the Council for the Promotion of OIST. And to our supporters, the Okinawa Perfectural Board of Education, Ona Village, and the Ona Board of Education. Thank you. We are very fortunate to have here with us Governor Denny Tamaki. Governor Tamaki has been representing the people of Okinawa in his current role since 2018. Prior to that, he was a member of the Okinawa City Council, and he also represented Okinawa's third district in Japan's House of Representatives. Please welcome Governor Tamaki. Hello, everyone. First of all, I would like to congratulate Dr. Tsubante Pabo for 2022 Nobel Prize for Physiology or Medicine. Please give him big applause. Thank you. At this Nobel Prize Season Public Lecture, we would like to say a few words. As you know, OIST was established with the purpose of sustainable promotion of Okinawa and the development of science and technology of the world. It's been 10 years, and with its international and interdisciplinary structure, it has done researches about COVID or quantum technology, as well as genome reading of the Muzukusi Weed, which is the specialty of Okinawa. And with OIST's genome data, Dr. Pabo has been researching Neanderthals and denisovans and compares them with the current human being. In Okinawa, Minato-Gawa-Mem bones from a totalithic age was found, and I heard that genetic contribution of archaic people on the modern people affects the symptom of coronavirus. So I look forward to Dr. Pabo's research. Today, we have many children from Okinawa, and the first Nobel laureate from the research institution in Okinawa encourages children of Okinawa. And we are blessed to have the opportunity to hear directly from the researchers. And we would like to take advantage of this to encourage Okinawan children to be leaders in future. I am the chair of council for promotion of OIST, and the council is committed to introduce OIST researches to the general public. I am looking forward to see more research results, and also I am committed to support the researches at OIST. And I hope to see great research results. And I wish the best for the researchers at OIST as well as Dr. Pabo. Thank you very much, Governor Okinama Demitamaki. Thank you Governor Tomeki. Thank you and your colleagues for your ongoing support of OIST. I know that the governor has to make a quick exit to his next engagement. We're very grateful that he was joining us. Next, we will hear from Karen Markides, the president and CEO of OIST. Like Professor Pabo, President Markides hails from Sweden. An analytical chemist by training, she brings with her decades of experience in researching, educating, and leading at world class universities on three continents, including time at Stanford, Brigham Young University, Chalmers University, Uppsala University, and the American University of Armenia. We are so pleased she joined OIST earlier this year to lead us into the future. Furthermore, we are delighted to have her here today to introduce our guest of honor. President Markides, welcome. First, I want to thank Governor Tomeki for coming here and show his interest for science, and now also for you, ladies and gentlemen. What you will hear about here today is amazing. It's mind-blowing, but it's still logic. Professor Svante Pabo or Svante, as we say in Sweden, has opened a secret box for humankind to the understanding of our knowledge blocks and thereby explaining the main reason why we are reaching in different ways to medicine and environment, while we humans are still so similar in so many ways. In Japan and at OIST, we are so proud and enthusiastic that Svante decided to join OIST in May 2020 as an adjunct professor leading the Human Evolutionary Genomics Unit. Svante and his research unit fit perfectly in the research culture that OIST stands for. The fact that Svante received his doctorate from Uppsala University, my home university, makes me also personally extra proud. This curiosity-driven research culture that we have at OIST are becoming more and more important for the characteristics of universities in this century. Allow me to take this opportunity to express how grateful we are to the government of Japan and the Okinawa prefecture government for their ongoing support of OIST, which enable us to fund curiosity-driven research where Svante is an excellent representative. We are at a crossroad where we can see that bold, basic research plays an increasingly important role in society and is existential for the development of a sustainable future. Many of you know that Svante has developed techniques and approaches that allow DNA sequences from archaeological and paleological remains to be determined. For this he received numerous awards, including the 2020 Japan Prize and the 2022 Nobel Prize in Physiology or Medicine. Over the course of his career, Svante has pioneered methods in extracting and sequencing DNA from ancient bones, resulting in several key discoveries that have rewritten what we know about human evolution and mobility patterns over the Earth's surface. His successful decoding of the Neanderthal genome led to the finding that modern humans still contain traces of Neanderthal DNA, unmistakable evidence that Homo sapiens and Neanderthals coexisted and interbred tens of thousands of years ago. He also identified an entirely new species of extinct humans, the Nisovans. Svante's curiosity had taken his research even further to identify variants of genes that are found only within modern humans. The research is aiming to see if these differences have resulted in functional changes or, in other words, how genetic variants that are unique to modern humans needs to be considered for our well-being and our health. For Svante, it all started at a very young age when he became curious about Egyptology and his interest was stayed with him through research of the DNA of Egyptian mummies as a doctoral student and later depending his knowledge of molecular biology methods. He focused on molecular genetics and managed to overcome numerous difficulties studying these ancient samples to unlock the secrets of genetic differences between Neanderthals and the Homo sapiens. We now know that 40,000 years after the last member of Neanderthal walked on the earth, their traces continue to live in our DNA and Svante has given us a new scientific discipline, the discipline of paleogenomics. So it is with great honor that I introduce our speaker, Professor Svante Pebo. Please join me to give him a very warm welcome. Well, Governor Tamaki, president, ladies and gentlemen, dear friends, what I then wanted to want to do here is begin by just reminding you a little bit about things that I think most of you are well aware of and that is that our genetic material, our DNA is stored in every cell in our bodies on the chromosomes that we have inherited from our mothers and fathers and it is stored there in the form of this famous double helical molecule, the DNA, and the information, the genetic information is there twice, so to say. It's encoded in the sequence of these four letters or nucleotides, abbreviated AT, CNG, and it occurs on each of the two strands of the DNA and that is important because when a cell will divide, those two strands are taken apart and new strands are synthesized with the old strands as templates and this is a particular interest to us in our germ line when the cells that will form a new individual are formed and this process where the DNA molecule is duplicated is a very accurate one but nothing is of course perfect in nature. So sometimes an error is made, the wrong letter is built in and if that is not repaired before the DNA molecule replicates again, then that results in a mutation and we can see the result of such mutations when we compare DNA sequences between individuals today, for example between two individuals in this room. What you will then find is that approximately every thousand such letters differ between two individuals or between the two chromosomes that you inherited from your mother and from your father and since these mutations and happen in every generation as a function of time, if you compare ourselves to a chimpanzee for example we will find more differences on average one every hundred letters so about ten times more and we can then reconstruct the history of a piece of DNA or our whole genomes by using these mutations and we gently depict that history in the form of these trees and in this case it's very simple of course the two DNA molecules into humans go back to a common ancestor here and much further back about ten times further back if they're a common ancestor shared also with the chimpanzee and as you will also know our genome is rather big over three billion such letters so there is a lot of information there that is supposed to throw the chromosomes yes about three billion such letters so there is around three million differences between any two genomes that we can use to reconstruct our history our and if you do that if you start out just by looking at the genetic variation worldwide among humans a surprising finding is that most of the variation exists in Africa and the entire variation outside Africa all over the world outside Africa is less than that although there are of course many fewer people living in Africa than outside Africa and the reason for that is then that there is a component of the variation in Africa that doesn't exist outside and the interpretation of that is that modern humans the ancestors of everyone alive alive on the planet today emerged in Africa lived there and accumulated genetic variation there through these mutations and part of that variation then went out of Africa and colonized the rest of the world and with genetic tricks we can also figure out when that emigration out of Africa happened and it's quite recently in evolutionary terms less than 100,000 years ago or so but an interesting thing then is that when modern humans left Africa say between 50 and 100,000 years ago they were not alone on the planet there were other forms of humans around that already existed there most famously in western Eurasia Neanderthals and in eastern Eurasia in China for example other forms of humans that we know less about but begin to learn a little bit about now so Neanderthals on the left here were these robust forms of humans that then emerged in Europe and western Asia about 500 600,000 years ago and live there until modern humans to the right appear on the scene whoops I should let me see until modern humans to the right there appear on the scene and the last Neanderthals died somewhere around 40,000 years ago and our group is then since 25 years or so almost obsessed with Neanderthals to study them and you may then ask why we should be interested in a form of humans that are not here anymore and I think there are at least two reasons for that one is that the Neanderthals are the closest relatives or present-day people no matter where we live on the planet so if we want to define ourselves from a genetic or biological perspective as a group or as a species if you like it's the Neanderthals we should compare ourselves to and say in what ways are we similar to them in what ways are we different from them another interesting thing is of course that they were here rather recently just 40,000 years ago maybe 14 1500 generations ago they were around met our ancestors and the question is what happened then how did one interact with each other but if we now want to address this with genetic means we need to retrieve then DNA from bones and skeletons that are at least 40,000 years old and that work then goes back to the early 80s when we started looking at not Neanderthals but ancient Egyptian mummies which are two three or four thousand years old for example this mummy here that's 2,300 years old a mummy of a child from Egypt if one looks in the skin of this one in a microscope you will see structures here that look like cell nuclei where the DNA would be preserved and you can also I should not touch that thing you can also stain those cell nuclei with dyes that shows that DNA is there so back at the time I got very enthusiastic extracted the DNA from these samples replicated it in the bacteria and showed that there were fragments of human DNA in there and published that to great fanfare at the time but what then happened over the next couple of years was that I came to realize that those DNA sequences were sure for sure not from the ancient mummy they were probably from myself or from a museum curator or an archaeologist because what I had not realized was how sensitive all this was for contamination from tiny amounts of present day DNA on dust particles for example in a room so if we compare above here the DNA from a present day person from a blood sample for example to the DNA below that you would extract from such an ancient mummy there are a number of differences here you can note one is no I will not touch that thing and one is that there's a lot less DNA there at least is sort of in the order of a hundred thousand a million fold less or so the DNA is also degraded to a much smaller size small little fragments that are chemically modified and they're a present in a large excess of DNA from microorganisms from bacteria and fungi that have colonized the bones over tenths of thousands of years and that leads to a number of technical problems but one is that even tiny amounts and a present day DNA that may land in your experiments from a dust particle for example may totally overwhelm the results here and wouldn't even be noticed if you study present day DNA so over the years we worked a lot and overcoming lots of these technical problems working in clean room conditions for example to prevent contamination we worked a lot of extinct animals because it's much easier to then recognize contamination from humans so ground sloths in America mammoths from Alaska or Siberia but we were really interested in Neanderthals so in the early 90s when the techniques had gotten better we started coming back to the question about Neanderthals and at the time there were at least two ideas around how Neanderthals are related to present day people so one of them to the left here suggested modern humans appear in Africa come out of Africa to Europe and Asia where Neanderthals and other forms live and replace them with no mixture whatsoever so that means that a person say living in Europe today would have no special relationship to Neanderthals at all another idea is that these modern humans come mix with Neanderthals here and with other groups in Asia so a European person would be sort of slightly more related to Neanderthals than to people who live today in Africa for example and you could imagine all kinds of gradations between this going from the left no replay no contribution at all to that Neanderthals are the direct ancestors of Europeans which some people also thought so we were very happy then in the early 90s when we got access to the first Neanderthal remains and that's not any Neanderthal remains it was the remains that gave their names to this group of humans that were found in 1856 in Neanderthal in Germany so sample from the upper arm here and we focused on a part of the genome that was particularly easy to retrieve because it's present in many many copies per cell which is the mitochondrial genome that we inherit from our mothers and pass on to the next generations always on the mother's side so we focused on a particular variable part on that part of the genome cambers only studying short pieces overlapping pieces putting together a longer stretch of DNA and we could then estimate how it is related to the mitochondrial genomes of present-day people and depicting that in such a tree so you will then find that the mitochondrial genomes of all people today no matter where you are on the planet have a common ancestor something like a hundred thousand hundred and fifty thousand years ago and much further back is there a common ancestor shared also with the Neanderthals about half a million years or a bit more ago so this then showed that the Neanderthal mitochondrial DNA was very different from present people so in this scheme of things it was total replacement there is no person today who walks around on this planet with a Neanderthal mitochondrial DNA but it was also very clear that the mitochondrial genome is just a tiny part of our history tiny part of the genome and reflects only the female side of history the big picture contributed that both our mothers or fathers is in a nuclear genome so the chance to address that came about 10 years later in the beginning of this millennium with new DNA sequencing techniques that allow you to sequence many many pieces of DNA quite inexpensively and efficiently we've worked on all steps in this process in how you extract such old DNA from the bones how you modify it to a form that you can sequence and create a little database and then compare that with the human genome that became available we also did a lot looked at a lot of different archaeological sites to find the best preserved bones focused on one site in southern Europe where we found used three bones from Neanderthals that we extracted the DNA from and processed it sequenced a lot of DNA fragments and then mapped them to the human genome here taking chemical modifications that present in them into account so by 2010 then we had the first overview of the Neanderthal genome where we had seen a little over half of it at least once among our DNA fragments so we could then begin to to ask questions and one question we were interested in was this question what happened when modern humans met Neanderthals and as we indicated if one would have mixed if modern humans would have mixed with Neanderthals in Europe for example then that would mean that Europeans today would share more genetic variants with Neanderthals than people today in Africa where there has never been any Neanderthals so to address this we put together a big consortium actually of population geneticists that helped us analyze this and we went out and sequenced five individuals from different parts of the world one person from Europe two from Africa one from China and one from Papua New Guinea and did some very simple comparisons so one comparison we did was simply to say if we compare two individuals and let's start with the two Africans first to illustrate this we can compare these two genomes and find all the positions where they differ from each other and then we take the Neanderthal genome and say how often does the Neanderthal match the variant this African or that African and it should be 50-50 right because there's no reason to assume that Neanderthals contributed more DNA to one African than another African individual and indeed that's the case statistically speaking there is no difference but when they then did the same comparison between a French individual in Europe and an African individual to my big surprise we found more matching to the European individuals suggesting that there could have been a contribution there more surprising even was that when we did this one person from East Asia from China we again saw more matching although Neanderthals are not believed to have been in China hmm and even more surprising than in Papua New Guinea where there for sure has never been a Neanderthals it was the same situation so the idea that came out of that was that when modern humans left Africa they met Neanderthals probably for the first time in the Middle East where we know there were Neanderthals and if these and if these early modern humans that then became the ancestors of the rest of the people outside Africa mixed with Neanderthals they could sort of carry with them this Neanderthal contribution out to the rest of the world and the result of that would be that people outside sub-Saharan Africa today have something like one or two percent of the DNA come from Neanderthals what has since happened is that we have gotten much better Neanderthal genomes we have particularly from the site in southern Siberia the Nisra cave for example from this part of the sort of toe bone of a Neanderthal using new techniques we have developed we have now gone from having this a bit half of the Neanderthal genome to covering the entire Neanderthal genome entire part to which we can map these short things to be seen every position many many times over and have a quality as high as from a genome from a present day person and we have three such Neanderthal genomes of high quality and become can start comparing them to present-day people for example looking on one chromosome here one line is one present-day person I don't know why this wants to disappear and in red we have indicated segments of some tens of thousands of such genetic letters that are identical or almost identical to the Neanderthal genome and you will see that different people here different lines carry different fragments of the Neanderthal genome so you can then and that adds up to something like one or two percent per individual but what you can do is jump from person to person for example in this room and see how much of the Neanderthal genome can I puzzle together in present-day people that's indicated in blue down there and that ends up being something like 40 or 50 percent of the Neanderthal genome still exists in people alive today so at that site in southern Siberia the Nistava cave they discovered something that was also extremely interesting a tiny little bone that turned out to come from the tiny pinky of a child from which we could also determine a good DNA sequence and we were very surprised to find that that was not a Neanderthal it was not a modern human but something else here that went quite far back to a common ancestor 400 000 years ago or so shared with the Neanderthals these are distant relatives of Neanderthals that existed there in southern Siberia we called them the Nisavans and we could then ask have they also contributed to present-day people and indeed they have we find no contribution in Europe but wherever we look in Asia we find a small but substantial contribution of 0.2 0.3 percent of the DNA and in Melanesha in Papua New Guinea for example up to five percent of the genomes of people there come from these the Nisavans and not only that you can look in more detail on this contribution of the Nisavans this is in a study by a group at Princeton that have used our genomes and looked on in people in Papua New Guinea today on this axis what how many fragments are there that are similar to the Neanderthal genome identity would be here and you find these fragments there that come from Neanderthals on the other axis it's the Nisavans and you find these fragments here that are quite distant actually more distant than the Neanderthal fragments from the Neanderthal genome here but if you then look for example in Japan you find this contribution from Neanderthals you find that the Nisavan contribution that's quite distant from our genome but you find an additional contribution there that is very close to our genome so this then suggests that at least two different hello two different than Nisavan populations that were quite distinct from each other contributed to the people in East Asia and China and in Japan so if I should now summarize for you what we think we know about the origin of modern humans from Neanderthals and the Nisavans from Stalin genomes Neanderthals and the Nisavans have some common ancestor in Africa that leave Africa well over half a million years ago they evolve in western Eurasia to what we call Neanderthals and in eastern Eurasia then to what we call the Nisavans the border between these groups probably shifted over the millennia we know that at some point at that the Nisava cave there were Neanderthals at other point there were the Nisavans there and then modern humans appear in Africa two three hundred thousand years ago begin to leave Africa seriously after hundred thousand years ago mix early on with Neanderthals continue to spread and mix several times with Neanderthals and in the east they mix with the Nisavans also several times and they then continues to spread out to other parts of the world where no human forms have been before to Australia the Americas and so on and these earlier forms of humans disappear but then live on a little bit in present-day people in these contributions you may then ask if Africans are fundamentally different in not having a contribution from earlier forms of humans I don't think so but we are not ready to answer that conclusively because we have no genomes from other forms of humans in Africa yet modern humans obviously appeared somewhere in Africa spread across the continent and if one spread mixed with other forms outside Africa one probably did it also inside Africa so problem when we find that the same things have gone on in Africa and interesting things that's now going on is that we find very direct evidence of this mixture with Neanderthals when we go back to very early modern humans and so far this has only been done in Europe for example the first case was in Romania where Cavers in 2010 found a mandible that looked like a modern human mandible it's dated to 40 000 years ago so it's a very early modern human and we were then very interested to look if this individual had mixed already or its ancestors had mixed with Neanderthals and on the chromosomes here we marked in blue segments that are similar or identical to Neanderthal genome and you see there are huge huge segments there sometimes almost half of the chromosome and such big segments of course indicate that in the family tree of this individual there was a Neanderthal and we can then show that six five or four generations ago this individual had a Neanderthal in her family tree and if we look in Bulgaria a site that we recently studied everyone finds technology that's typical of these early modern humans there the earliest modern humans are 45 000 years ago among the very earliest modern humans we have in Europe 10 000 years later there are other modern humans living at that site and if you look at three individuals deep down there that are 45 000 years ago all of them have Neanderthal relatives in their family tree 10 000 years later the people there look very much like people today no close family relationship to Neanderthals so the picture that is emerging is that when we begin to look at the very earliest modern humans that come out of Africa almost all of them have close family ties to Neanderthals so a picture that I think is emerging is that the very first modern humans mixed often with Neanderthals and it may be that the story why Neanderthals and the Nisimans disappear is not that one killed them all or so but simply that they were absorbed into larger modern human populations that came and there are some indications from archaeology that group size in modern humans were bigger than in Neanderthals and the Nisimans but what I then wanted to do before we end here is discuss with you what we can now do when we have genomes from our closest evolutionary relatives we can compare that genomes to people today and to our closest living relatives the apes and when we find the Neanderthal changes that we share for example with Neanderthals but that's not there in the apes these are then changes that happen on the common lineage to Neanderthals and present-day people when we find something that's present only in the Neanderthals and where we look like the apes these are changes that happen in the Neanderthal ancestors and spread to all of them and when we find things that are unique to modern humans and not in the Neanderthals that happen in our ancestors so I will begin a bit with two examples of this Neanderthal variants there and this is work that was done by Hugo Seberg who is a postdoc in Stockholm and with us and a guest scientist here at OIST and he's particularly interested in ion channels so proteins that sit in the cell membrane and let ions go through the membrane when they are stimulated and he noticed that this protein had three amino acid changes in it in all Neanderthals bed sequence which is unusual that is more than any other protein actually we have looked at this is also a very interesting protein since it sits in the peripheral nerve endings and initiate the sense of pain when we hurt ourselves so we expressed this protein the Neanderthal form modern human form in human cells and stimulated it and you could then see that for a certain stimulation here the red Neanderthal version lets through more ions through the cell membrane as if it was more sensitive than the modern one and we could show that that is not due to that it opens more rapidly but that it remains open for a longer time before it's inactivated in him after stimulation we could also show that that effect is just due to two of these amino acid changes and the third one seems to be irrelevant and what we then did which surprised us was we thought this was specific to Neanderthals and was not present in present-day people but when we looked in the UK Biobank which is a big big project in the United Kingdom where they have more than 400 000 people that have answered questionnaires about their lives we have the medical record and genetic information from everybody so we can then look for these Neanderthal variants if they exist today in present-day people and indeed it turned out that some people in the UK 0.4 percent of the population so very few but some did do carry this Neanderthal version so it has come over from Neanderthals when they met modern humans and exist in some people today so we could then look in the questionnaires that these people had answered and there were 19 questions there that had to do with pain all kinds of pain back pain stomach ache headaches what have you and see how often they report that they experience pain in their lives first of all for me it was the first time I could play with such big population data so big interest was just what does pain correlate with in our lives in general and rather sadly when you get older the biggest correlation is with increasing age the older you are the more pain you have and it's trivial the older you are the more medical issues you have but more relevantly than carriers of this Neanderthal variants here reported significantly more pain in their lives and if we relate that to that age effect I mentioned then it is as if you were if you carry this Neanderthal version it is as if you were eight or nine years older in terms of how much pain you report so it seems indeed that carriers of this is more are more sensitive to pain now that doesn't mean that we can conclude that the Neanderthals experience more pain in our lives because as you all know a pain sensation is very much modulated in spinal cord and particularly in the brain depending on our mood and our attitudes sort of our sense of pain is very different however it is interesting that people who today have one copy of this on one of our chromosomes do report more pain in their lives this was present in all the Neanderthals so they had all inherited from their mothers and fathers and had it on both their chromosomes so they had at least the ability to be more sensitive than people are today so maybe we need to modify our view of Neanderthals as these insensitive brutish individuals maybe they're actually almost too sensitive when modern humans appear now the other example I want to mention concerns a hormone that many of you have heard about I think progesterone it has many functions in the body but is primarily produced by the ovary after ovulation and prepares the uterus for a possible pregnancy and we are interested in the receptor there for the progesterone and it was already known that it was a variant of this receptor that exists in the population it has this distribution worldwide where it is absent in Africa and occur outside Africa at some frequencies and variants that are like that turns out to almost always come from Neanderthals so they're absent in Africa present outside Africa and this variant was known to be associated with preterm birth so having premature babies which is of course a risk for the baby so it seemed that this Neanderthal version of this variant would be a bad thing to carry because it would put the babies at risk but something that one can now begin to do is to follow the frequency over time of such variant in the population and we can do that because we begin to have thousands of modern human skeletons of different ages we will have genome information particularly in Europe we have something like 15 000 skeletons now varying in age from 10 15 000 years ago up to present day so we can see how the frequency of such a variant has changed over time so I made a little movie here that starts 15 000 years ago and carriers of this variant are black little dots and non-carriers are gray dots and red are just the Neanderthal and the Nisovan genomes so if we now move forward in time here you will that is a pity let me see come come come let's see let's try it again we move forward in time and you will see around 7 000 years ago carriers of this become very much more frequent this almost explodes in frequency and that seems to make no sense right something that's bad and puts your baby at risk why would it increase in frequency so we could go back to the UK Biobank and ask how carriers and in this case you're actually asked the question the other way around to ask a question the modern non-Neanderthal variant of this receptor what does it associate with in the UK population and then we find that it's associated with an increased risk of bleeding early in pregnancy with increased risk of miscarriages and it's negatively associated with number of full siblings that you have from the sisters and actually also brothers so it seems that the modern variant is actually increased the risk of having miscarriages during pregnancy so the story here seems to be that the Neanderthal variant is indeed associated with premature births but it is also protective against miscarriages and results in more live births so it's probably a trade-off where this Neanderthal version of the progesterone receptor saves pregnancies that would otherwise result in miscarriages and the price you pay is that some of those babies are born early and we begin to understand why that is too because if we look at how much of this receptor you express when you have the Neanderthal version you express more of it you have more of the receptor in the uterus for example sort of suggesting that you could have more of a progesterone effect and over the past few years it has indeed been four different studies now where one has given progesterone to women who have experienced multiple miscarriages before and you can substantially increase the number of live births compatible with this idea that more progesterone effect either by having more of the hormone or more of the receptor will result in more live births and this is sort of a pattern many genetic variants of medical importance turns out to come from Neanderthals just as an example there are two enzymes that are expressed in your liver and have to do with how you metabolize drugs they come clearly from Neanderthals they are very close to the Neanderthal genome and for example then if you eat ibuprofen against the pains you have a much better effect if you have carried the Neanderthal version because the half life in the blood of the ibuprofen is much longer if you take warfarin to protect against blood clots then if you have the Neanderthal version you need to take a lower dose because you have it's metabolized slower and it's a bigger risk for bleeding complications another example of this is from the pandemic of the corona pandemic where as you know some people that get infected get very sick and even die but most people who get infected have very few symptoms or very mild symptoms we know what the risk factor is to get some of the risk factors old age male sex and so on but all those risk factors are not enough to explain why one person gets very very sick and another person has hardly any symptoms at all so there was early on in the pandemic already an international consortium formed to look for genetic factors in the people who get infected influencing how sick they get and we were peripherally involved in that with some patients from Leipzig where we are situated and when the first results came in then we were very surprised to see that there was a one big risk factor for this located on chromosome 3 there and when we then looked at the DNA in that sequence we were totally shocked to find that those risk variants there were closely related particularly to one of our Neanderthal genomes and the protective variants were modern if you like so this risk factor on chromosome 3 has come over from Neanderthals to modern humans and exists in some people today and this for being a genetic risk factor this is a big one if you were hospitalized early on in Europe in the pandemic with severe covid you and were not the carrier of this Neanderthal variant you had a seven percent risk of requiring artificial ventilation or even dying and your risk if you were a carrier and had this variant was about twice that 13 or 14 percent so of course there is a much interest in functionally what is in this region unfortunately this region is very complex there are several genes in it that are influenced in their expression by variants in here so they are not yet possible to explain how this have these consequences if you could do that we could also hope to develop better treatments for severe covid but it's also very interesting to see the distribution across the world of this risk variant as any Neanderthal variant is absent in Africa and present outside Africa we can estimate how many extra deaths we had so far in the pandemic due to this Neanderthal contribution and it's for sure one million probably more than one and a half million extra deaths due to the Neanderthal contribution to the genomes of many of us but you can also notice here strikingly that this variant is absent in East Asia so it's absent in Japan absent in China but it's present at the substantial frequency something like 50 percent of carriers in South Asia so it's somehow very clear that this has been selected in the past it has been bad in East Asia and they've been eliminated there we don't know why it's tempting to speculate it could be epidemics or coronaviruses for example in the past in the history of humans in these regions it has clearly had good effects to carry this in South Asia again we don't know why but it's clear that this region must have many functions particularly in interactions with infectious diseases and we're beginning to learn a bit about that so Hugo then noticed that if you look in the vicinity on the chromosome here one million base pairs down from this region there is a famous gene there ccr5 that is a core receptor for the virus hiv virus that gives you aids to which the virus binds on the cell surface when it will penetrate the cell and if we look at carriers of the Neanderthal risk variant for covid they actually express less of this of this ccr5 on their cell surfaces so they have less of this receptor for hiv and indeed if we look at the risk of getting infected by hiv if you're exposed to it that risk is reduced if you're a carrier of risk Neanderthal version so the story is that this Neanderthal variant on chromosome 3 it increases your risk for severe covid but it decreases it decreases your risk of hiv infection so it has good effects if you're exposed to hiv bad effects if you're exposed to covid so it's at least a double-edged sword but we know that other factors that selected against it for example in east asia that couldn't have been hiv or coronavirus right so it's at least a sort of a multi-edge sword and that's a general message i think that genetic variants are almost never only good or only bad it depends on the environment and in this case to which pathogens you're exposed so just before leaving Neanderthals i should say that they didn't only have a bad effect in the pandemic now when we have much bigger cohorts of patients one begins to find other variants on other chromosomes that also influence how sick you get on chromosome 12 of there there is a variant that comes from Neanderthals and that is protective against severe covid in that case we know the mechanism there is a sort of genes there that induce a enzyme that degrades double stranded RNA the sort of form of genetic material in the coronavirus and it's also protective against other coronavirus is coronavirus one but unfortunately the effect is much smaller so whereas the risk factor on chromosome three doubles or even triples your risk of becoming severely ill this is just a 20 percent reduction of the risk so before we end then i want to just mention that what we are also particularly interested now are these changes specific to modern humans that Karin mentioned in the beginning too so these are then changes that happen on the human lineage and is present in everybody or almost everybody on the planet today but they happen after we separated from Neanderthals and Neanderthals look like the apes or other mammals there and why are we so interested in these changes well we think that among them may hide some variants that are important for functioning as a modern human and modern humans are very special compared to Neanderthals, Denisovans all other forms of humans that have existed i think because with modern humans technology starts changing very rapidly we notice that for example if you look at stone tools on Neanderthals they look the same all over their distribution from Central Asia to Western Europe and modern humans come technology starts changing so rapidly so it becomes easy to distinguish stone tools from Southern Europe or Western Europe or Asia for example what also comes with modern humans is figurative art art that really depicts something that we immediately recognize as humans when we look at it and as I already hinted modern humans become much more numerous they probably live in larger human groups we can even see that genetically because they have more genetic variation in the groups and they spread across the whole planet they sail out on oceans where you don't see land on the other side they come to places like Okinawa where other forms of humans had never been they come to the Americas Australia Madagascar and so on so a dream is that some of the sort of genetic scaffold or foundation you need to absorb modern human culture fully may be due to changes here that we could study and those changes are not very many when we require that it should be present in everybody today and not in the Neanderthals it's around 30 000 changes all over the genome and much fewer if we focus on things that we think have functions amino acid changes in certain proteins we changes that change whole genes are regulated and since we think that modern humans are special in terms of behavior and cognition maybe we are particularly interested in things that influence the development of the brain or the function of the brain and that is sort of things that we try to address at the oyster at the moment in the little group I have there and also in Germany at the Max Planck Institute in Leipzig where we also are and with that I then hope that I convinced you that it is interesting to have the genomes of our closest evolutionary relatives because we can focus on these changes that make modern humans special we can look at things that may Neanderthals special and look on their contribution to people today what we also very much want to do is to study the Nissevan variants in the same way and their contribution in Asia for example in this country and we then do that by using large data banks we have genetic information and biological information from many people but we also modify presently cells from present day people back to the ancestral state or even use animal models to address these things and with that I then thank you for your attention thank you wow professor thank you I have a feeling that you have inspired as many questions as you have answered and now it's time for those questions so please make your way to the standing microphones we have one at the front stage right another one on the first platform right there stage left and one in the center at the top you see folks waving there if you have a mobility challenge and would like to ask a question just give me a wave and we'll get you a microphone but first a few house rules if you're asking in Japanese please take your receiver with you so that you can hear the answer please keep your question to just one so that as many people as possible have the opportunity please keep them on topic so go ahead now please don't be shy well folks are moving around I'll go ahead with my first question Sontet it's been a year since you got the call what has the last year been like what have you learned what has been unexpected no no I would say that that what I have had to do is adapt to saying no to very many invitations and suggestions there was actually a joke in Stockholm when we got the prize a year ago that they would give us something called a Nobel a bell that says no in all languages if we pull it so it's a Nobel it makes us that much more grateful that you're that you're here today and then may I ask what drew you to OIST and to Okinawa other than the warm weather and the even warmer people I was very privileged to be here I think six or seven years ago and get an honorary degree at OIST and then I discovered what an amazing place it is to work it's a very unique university I think that is composed of very many very good groups and it's a very flat structure where everybody has ability to interact with each other and for us now when we're interested in neurobiology for example I'm not a neurobiology system amazing place to be because it's very collegial and interactive and one can get a lot of input wonderful thank you okay so let's you and I put our earpieces on we just press on should be on the right channel already okay let's go to the audience we'll we'll start right here what's your name and your question please my name is Michael Turelli and I have a question about integrations the bits of the Neanderthal genome in modern humans on X chromosomes versus autosomes I think there's a very strong prediction that the X integrations will be much smaller much lower frequency is that true that's cool because it is lower yes so you make that prediction if you say that they're primarily male Neanderthals that contributed because they will contribute an X chromosome only to their daughter and the Y chromosome to their son so they would have less contribution on the X than females would but more specifically because of so-called Dubjansky-Muller incompatibilities thank you yes that said though I'm not ready to sort of there are other reasons also why one has large segments of the genome lacking Neanderthal contribution there's something called deserts of Neanderthal contribution we find regions on the autosomes also where this statistically would expect Neanderthal contribution but we don't see it so I want to leave it a little open to that might be more selection against Neanderthal versions on the X particularly then because in males you have only one X chromosome so things are exposed more to selection there but yeah okay thank you okay do we have someone down here yeah go ahead hello good afternoon I teach history at high school I read a book by Brian Sykes and I'm interested in common ancestors so what do you think about the future of this common ancestor research when I would say the book that you refer to by the book that you refer to by Brian Sykes it's about mitochondrial DNA I think and of course as I indicated here that is sort of a limited view of our inheritance it's a female side and it's just one instantiation so to say the bigger picture is in the nuclear genome I think that that's where certainly the future lies in this research and I think it's important to convey the idea that to the next generation that the variation around the planet is very very we are very mixed with each other there were never sort of pure populations one idea is about pure population then then we have mixed with each other that is not true there were variations from the beginning and when we look in the human genome for example all over the genome if we sort of say subs are in Africans versus the rest of the world so the biggest difference in frequency we have there is still true that there is not a single thing that is an absolute difference in a sense hundred percent have it here zero percent have it there there are things that differ drastically in frequency but these are frequency differences always so these are the sort of things that I think is very important to convey as a teacher to the next generation say excellent thank you okay folks please don't be shy okay let's go up to the top do we have someone with that microphone a few more questions yes okay I think we have someone here oh a good night first thank you so much for your inspiring research and your presentation today professor Pablo my name is Ekamaya I'm studying marine molecular ecology on the horsescrap at the University of Lucas so I'm from Indonesia actually so we're a tiny species of the homogeneous homoflorensis that still exists until nowadays so that's interesting also regarding your presentation you mentioned the data on genetic characteristics of netherland and denifonus they spread from Africa throughout the Southeast Asia so my question first is how do you see the study of if you compare your study recently with the homonines in Indonesia that's contributing to the broader narrative for the narrative I mean for the human evolution and then particularly in terms of migration of pattern and the emergence of modern humans so the question is how we would see homofloresiensis in sort of this that is very interesting question I think that's one of the most interesting so homofloresiensis is on the island of Flores there is this short-statured homonines one has found with very small brains that lived there quite recently I think the last date is something like 30 000 years ago or so so they disappeared sometime when modern when neanderthals and denifonus disappeared now they are very interesting I think because they have features that paleoanthropologists say suggest that they are an earlier divergence on the homonine lineage than neanderthals and denifonus and so we are actually working together with people in Indonesia now unfortunately there has not been excavations for three years because of COVID and next year there will be excavations again on Flores and we will then have one student there to take samples when the bones come out of the ground so far we have not been able to retrieve anything from the samples we've gotten from homofloresiensis but from animals bones in the same layer stegodons actually this is a little bit secret because it's not published yet but from stegodons in the same layer we are actually able to get DNA now that is easier because it's an animal to distinguish contamination from real thing and so on but I'm hopeful that that may happen in my lifetime actually that we will get homofloresiensis and then we might be able to date things on the homonine lineage sort of more accurately so Leslie my question I would appreciate any advice you can like offer to young researchers like me now that how to maintain motivation to like our research actually I often get that question and I don't really have any advice if I would say anything I would say follow your interest do what you really think is interesting and important because at least you have a good time while you're doing it then and then if you're lucky it turns out to be something that results in something that others appreciate and is useful sometimes I even tell my students you know if you are in science and have studied you're smart enough to earn much more money if you go to banking or business but so the only reason to really do it is that you enjoy it all right thank you so much thank you okay let's go to the front here well my son wanted to ask you uh he's five years old and dr pabo when you were five years old I heard that you are interested in the egyptology so in your childhood what made you interested in what kind of subject what kind of thing you were you interested in when I was five years old I was interested more in in fire trucks things like that I think later on I did become interested in archaeology and were digging in the ground in where I live to look for ancient things and I was lucky that my mom took me to Egypt when I was 14 years old and that made a big impression and maybe think I want to study ancient things but then as often happens I think when I studied it at the university I got less impressed I had two romantic idea what it would be like and didn't know what to do and studied medicine and molecular biology but then sort of brought the things together again right so it's also okay to change what you're interested in over life thank you thank you okay do we have anyone on the top yes go ahead there we go yes hello I'm Katie Tyra I live in Urazoe so my question is as people are more mobile and more people intermarry and move around the world has there been difficulties kind of pinpointing ancestry and DNA like for instance you're talking about the sun and the Yoruba people and people might marry into the tribe and stuff so like maybe 30 years from now it might be more difficult to get a sample of like a Yoruba person or a sun person well in some sense yes but I would not worry about it in some sense we're interested in what is really there and something we do see is that there has been gene flow almost always even you know with Neanderthals that were truly a bit different as we learn more and more about this we even find that there has been gene flow from modern humans into Neanderthals that go back to 300 000 years ago migration sort of out of Africa to Neanderthals etc so I think you sort of we should take it as it is out there in the world simply okay thank you okay let's go on my left please your name in question please my name is Akami Men thank you very much for very inspiring talk and science is difficult for me and I was wondering if I could ask your talk but the talk was actually related to ourselves our body so it was really good my question is that you probably had many difficulties in your research but what was the biggest challenge difficulty and how did you overcome and continue during your research oh I don't know I think I think that I have been very lucky I don't experience it as I have had very many challenges or I mean yes I have been very lucky that I've been in organizations and at universities that have allowed me to follow this rather crazy idea of going back in time and try to follow evolution over time of course I've been occasions such as when I published at first Egyptian Mami sequences and then realized that there could not really be true that is sort of a setback you're of course always more happy if you find out that you made something wrong so you can correct yourself rather than other people correcting you that feels much better but in a way I think I have been very very lucky you sort of you have this long-term goal you often don't succeed in what reaching that directly but our small progress sort of steps forward that you then continue to follow but isn't it maybe part of it of how you see those challenges you call them setbacks that you see them as just that a setback so not necessarily a problem but just how then you're going to get to the next to the next road the biggest challenge in science is probably to know when something you try to do is impossible so you should abort it and stop that is sort of yes but yes that's not an easy question to answer in some general sense all right okay thank you okay down here thank you very much good afternoon my name is ryo Tanaka my question is that when you lose do you ever lose your focus on your research when that happens what do you do to bring back your focus those focus particularly say when other things happen in your life that distract you I think probably you should then take a break for a week or two and do something totally different and come back to it because if you really try and try and try you probably just get stiff and don't make any progress I would take a break it would be my own advice I think thank you okay do you have some at the top please go ahead my name is Sophia the ancient people like ourselves the color of skin and the colors of the eye were they different from what we have in modern human so there's often a great interest there's in skin color and eye color so the truth about much of genomics is that we are actually very bad to just look at the genome and infer how people looked or what they did in many cases we are very bad at it looking at the genome of a person today I think we are just in order of 70 80 percent accurate in sort of predicting the skin color if we then go to Neanderthals that were really a bit different we're sort of even worse probably at that so if we're interested in the skin color of Neanderthals the truth is we don't know we know variants that have come over from Neanderthals to us that are variants both associated with lighter skin and darker skin so perhaps they varied in skin color just like like we do it is interesting one has a better accuracy in modern humans and these early hunter-gatherers modern humans that came into Europe 30 40 000 years ago and spread they were actually with great sort of probability dark skinned and had blue eyes so sort of a strange combination that we don't see today as that is probably everything I know about that yeah thank you okay on my left please go ahead hello I'm Lea Picard I'm a postdoc in Yamamoto Unity Noist so I have a bunch of questions I will not ask all of them because a lot of people are interested thank you I was wondering if there were add-mix choose between other like ancient human species like deniesovans and Neanderthals and the second part of this question would be also what's the assimilation of Neanderthals within the modern human species like something that we observe in other species like with another closely related species with larger populations so so yes the more we study this the more we see that they have all mixed with each other in deniesova cave we have actually found one individual who's the first generation offspring of a Neanderthal mother and a deniesovan father so that is sort of we've been lucky to totally hit someone like that yes there is also as I said the evidence of gene flow in the other direction from modern humans into Neanderthals we have much less evidence of that but I think part of that is really ascertainment because we then need to find Neanderthals that are so late so their ancestors have seen modern humans and that's of course very small percent of all the Neanderthal finds you find whereas the other way around we can study anybody today and see the evidence of this right and the other question was if there is sort of assimilation yeah is that like a common aversionary yeah yes I think as I hinted I think the more we now of I'm now a bit challenged eight or nine modern humans that are so old that they lived at the time when Neanderthals were around out of those at least five of them have close Neanderthal relatives in their family tree so I would sort of think that big part of the story is the sort of assimilation where modern humans come or a bigger populations and sort of incorporate Neanderthals and denismans does that exist in like other animal species or the mammals yes I do think that more even using the same methods at David Reich and others developed for the Neanderthal genome people find more and more admixture between everything from butterflies to mammals too thank you very much thank you okay let's down let's go down here go ahead Good afternoon my name is Sowa Atama we have not any DNA from Inato Gawa man yet but he for sure has it because he's a modern human and he will look pretty much like you and me in terms of one or two percent we hope in the next year or so to be able to get some DNA from some old remains on Okinawa maybe not Minato Gawa man but maybe something else then I can answer the question better so he'll have to come back okay thank you okay do we have someone at the top thank you very much for a very interesting lecture I'm a university student and my name is Genki Togawa I'm also internship student at OIST first I'd like to make sure that the African people from Africa spread all over the world but those the group well so after people spread all around the world then the group from Africa followed is that correct sort of modern humans come out of Africa and eventually then yes differentiate a bit in different parts of the world and mix with these earlier groups there has of course been later migrations both in and out of Africa also back into Africa we find a little bit of Neanderthal variants in Africa but they always sit in sort of longer segments that come from Europe so due to back migration but so there has been migrations also subsequently of course good does that was that the right question and answer combo I don't quite know if I understood just vaguely yes I understood so genisobans are identified as a different new type of human and I thought genisobans could mix with Neanderthal so when how different are genisobans like the when we estimate the time of divergence based on the differences in DNA sequences between the groups they differed about 400,000 years ago from Neanderthals now that's really dependent on many things such as what we think about mutation rates or so but if we say that the divergence between modern humans and the ancestor of Neanderthal menisomes like 500,000 years so this is sort of far back so that means that they over made long time did not have that much gene flow between them even if it did occur as I said they are in denisobacca we do find evidence of it we also find some evidence actually that denisobans are mixed with something else that's more deeply diverged that Neanderthals did not mix with there's a small contribution from something there who knows what it is homorectus or something in asia okay thank you okay let's go down here hi there my name is a little wehara my question is that when you received the noble prize how did you feel really I was totally surprised and that's not just I say that because I thought I have gotten other very nice prices a Japan price for example but I thought that sort of what we do doesn't really fit into what they give noble prices for so I thought when they called me in the morning and said they want to give this to me there was clearly someone from Sweden who called and spoke Swedish to me so I thought it was a joke I thought it was some friend of mine who pretended to call from Stockholm and say this so for like half a minute I was saying oh yeah yeah tell me more tell me more and then I realized that it was actually true so I'm still very surprised actually and as fun to can you tell us what happened I saw on instagram there was a pool incident yes we have this tradition in our institute in Germany that when my finish once phd one gets thrown into the pond so I guess my students thought I had passed exam now so they threw me into the pond yes wonderful okay back here go ahead my name is Kobayashi doctor people thank you very much for your interesting talk my question is as I heard your talk the gene coming from Neanderthal sometimes susceptible for to pain and there's a risk to get infected by a corona virus and get severe and there's also a risk of our Ali are diverse of a baby which is a sad image I think that's a disadvantageous to survive I wonder how come such genes the negative which might work negatively are survived today and we all have this gene and will it continue to be in us to the the futures in future generations as well I think that almost all variants are a bit like this corona risk variant that they have both good and bad effects and that may even change over time you know this variant that increase the risk of dying in the corona pandemic where we're almost in a sense and see selection going on because you're twice as likely to die if you have it we know that in South Asia it has reached 55 percent and it's zero percent in East Asia cities clearly had some positive effects probably due to other epidemics in the past so I think for and say the the progesterone receptor thing there yes it results in more premature births but it also results in less miscarriages so it is almost always a case of things have both bad and good effects and that it may have been different in the past if we go back a few thousand years things that are today we say are negative maybe positive in the past and maybe can positive again so I think with the exception of some you know variants that singly cause very bad diseases that kill you in a young age that is clearly bad but otherwise I think this should really give us pause for thinking about you know thinking that we can tell what is good and bad in the genetics of people okay thank you hi what's your name and what's your question hello my name is Aina what's your question Aina did you forget question do you want to go ahead mom well what we study is sort of this genetic material that came from mama and papa and approximately equal amounts and made up you and that then makes for making hearts and livers and all the other things you have inside your body that's a nice very good thank you thank you thank you thank you okay back here on my left go ahead eto pebo sensei good afternoon doctor pebo my name is show asato i work for the okina perfectural government thank you very much for the lecture with a nice okinawan shirt my question is that there must be many different type of human like including neandil tall how many different kinds were there so I don't think there is a room in the genetic variation of people today for example in Asia to have any big contribution from something else but we know there were other forms around that we discussed in in Indonesia there is hobbits the home of fluorescence is that clearly was there recently and was quite different but if they have contributed to present day people we don't know we find this contribution from the nissan's all over asia and also native americans that then come from asia and so on so I think if we're talking about what forms of humans were there when modern humans appeared so sort of in the last 100 000 years there are not that many forms outside africa at least there are the hobbits there is probably something else could be something else but not anything that contributed a large part of our variation today in africa there are clearly other forms of humans around also and it's a more complicated picture problem thank you okay stay true go ahead hello my name is Amelia and my question is you said that you were interested in this kind of archaeology paleontology since you were a young age and I'm also very interested in the sciences but whenever I try to learn about the more modern stuff that's been going on the more technical and like complicated stuff I find that a lot of the science journals they're full of this technical jargon and I get frustrated because I can't read the graphs and I can't read the sentences sometimes so how would you recommend like aspiring scientists or even non-scientists people who aren't up to date with that kind of jargon how do you recommend that we keep abreast with the new innovations and the new publications of these kind of modern sciences well I would of course say that find good teachers and at the university you will learn to sort of I hope you have universities here that allow you to combine very different things I think I was very fortunate that I could study Egyptology and medicine and molecular biology in many parts of the world now it gets very focused you say you should become an engineer and you should just study this and this subject you become an archaeologist and you start this and this and it's often in the combination of things as you say that new things appear it's even so that you know sometimes say if you just say I'm going to cure cancer there are tens of thousands of very smart scientists that try to cure cancer out there so it's very hard to sort of really make a contribution if you combine something that's hardly anyone combines like there's molecular biology and archaeology you don't even have to be so smart to contribute something because you have a unique combination the combining things can be a good thing okay thank you okay thank you okay let's go up at the top please my name is Nakajima so part of DNA of us come from nandil tar but how about nandil tards is there any DNA in nandil tards that came from us from the modern human really good question that has interested us a lot so for a few years we were not able to find any evidence of DNA in nandil tards from modern humans but in the end we have now been able to find evidence that somewhere two three hundred thousand years ago there were some gene flow out of Africa from ancestors to modern humans to neanderthals and we can detect that because that's affected neanderthals that lived you know outside Africa but close to Africa whereas we don't see that in the denissivants which are far away from Africa and were not affected by that so we have this contribution in neanderthals and not in denissivants and we've even found some specific genes that have come over there from ancestors to modern humans into neanderthals and then back to modern humans again when they again mix with neanderthals sort of back and forth so indeed just as you say there is evidence or going in both ways thank you thank you thank you I'm Shimabukuro from Okinawa City I have two questions when you take sample of DNA you are taking it from bones like the pinky any parts of I'm wondering the bones that the DNAs can be extracted from any parts of the bones of the body are there parts that you it is easier for you to take DNA from like tooth for example in principle you could take it from any part of the body in practice it turns out that some part of the skeleton preserved DNA better the best one is actually the inner ear something called the petros bone where where the the sort of where you the inner ear is located because it's a very compact bone it doesn't have little channels through it where the water can percolate through and things like that so ideally the inner ear teeth are also often quite good actually the dentin in the teeth not the enamel and the good thing I could mention is that we also nowadays can take very small samples four or five milligrams of material so tiny tiny amounts okay quick follow it kind of difficult question to ask the I'm wondering why neanderthals are extinct what do you think is the reason for the extinction so why neanderthals disappeared is in a way the a million dollar question I think that it has to do with modern humans and modern human behavior because not only neanderthals disappear you know the home of fluorescence is in Indonesia the nissan ones disappear all other forms of humans also in Africa disappear now it may not only be that modern humans were more aggressive and killed everybody it could really be there is some evidence as I said that the popular group size of modern humans were bigger than neanderthals it may simply be that one assimilated they mixed in and were diluted very simple calculation if you're two percent of the DNA comes from neanderthals if there were 50 times more modern humans than neanderthals that would be two percent right of our genome now I don't think it's that simple it must have been more complex than that but in principle the sort of bigger group size then the next question is of course why do modern humans have a bigger group size that behave quite differently also colonize across open waters and so on it's something social and sociality maybe sometimes I say it may not be that modern humans individually are smarter than neanderthals or something like that but it may be something with sociality that we are more into big group size politics lying to each other impressing each other maybe things like that going on the governor is not here so we can say things about politics thank you on that note we do need to wrap up for folks still standing please make your way back to your seats I do have a quick housekeeping or a couple of notes please be sure to return your responder please drop them off on your way out also we have a survey through this qr code in the back of your program once you leave when you get home please be sure to fill that out for us and let me pose the last question so what are you most excited about for the future either in your lab or in science generally I would really say understanding some aspects of what sets modern humans apart we will not understand that fully but understanding some aspect of it that would be a dream okay it's a big possibilities thank you professor pavo so much for choosing oist in okinawa to host your lab we are so proud to call you one of our own and thank you again to our co-sponsors the okinawa perfectural government and the council for the promotion of oist as well thank you to our supporters the okinawa perfectural board of education own a village and the own a board of education and to all of you thank you so much for joining us this afternoon thank you for being fans of professor pavo fans of fans of oist and and fans of science and if you haven't already been to oist you are invited to come and see us and say hello and beautiful ono son but until then thank you for attending this public lecture by spent to pavo 2022 Nobel prize winner and adjunct professor at oist