Okay, hello. It's my real great pleasure to welcome you to the first international Steenbach Symposium. I'd like to just take a couple minutes to talk to you about the origins of this lecture series, starting with Harry Steenbach. So, Harry Steenbach was a Wisconsin native. He was born in Calumet, Wisconsin in 1886. He went to the University of Wisconsin-Madison. He got a bachelor's degree here in agricultural chemistry, a master's degree, and a PhD, all from this university in agricultural chemistry. He was recognized by his professor colleagues as being an outstanding prospect and was immediately hired into the faculty. When he began work in an environment where people were discovering vitamins at a university where the first experiments with rats were being carried out. And it was so in this environment, Professor Steenbach made a simple but really astounding discovery. That irradiation of the food fed to a rat suffering from vitamin D deficiency. It was not known that it was vitamin D at the time. The irradiation of the food, not the rat, cured the disease. This set the stage for a series of discoveries that extend clear to our time. Professor Steenbach was a very practical man and realized both the immense importance of this discovery for health and disease, but also the commercial potential. Some of you know this part of the story. Professor Steenbach sought to patent this discovery and did receive that patent and attempted to assign it to the university. That was an unusual event for academics at that time and the university declined that assignment of the patent. And so Professor Steenbach formed an organization called War for the Wisconsin Alumni Research Foundation with some of his friends and assigned that patent to war. Shortly after that, the Quaker Oats Company licensed that patent and paid $2 million. At that time, it was a very large sum of money. And I mentioned as I look through some of the history, Professor Steenbach's annual salary when he started here was $720 a year, eight and 10 installments. So he had basically a C basis appointment. So as we walk about this campus, we can see many, many examples of how this partnership and inspiration of Professor Steenbach to start war has enriched this campus. It's spread everywhere as you look. Now, as is true now, inventors who have a patent that receives royalties to war get a personal share of that income. That was true when Professor Steenbach was here. And so Professor Steenbach returned that income, his personal income to the university in many, many ways. This lectureship is one of those. And so we have this to recognize his generosity and to honor that thought and contribution to the university. I'd like to now pass the microphone to Professor Asim Ansari who will introduce our guest of honor for this first international Steenbach lecture. Thank you, Brian. Today's speaker, of course, needs no introduction. His work in identifying the Neanderthal genome is well known in 2009, I believe. They announced the full draft of the Neanderthal genome. 2010, the Denisovan genome. And that really captured the imagination. He has woven together many strands of intellectual pursuit that engage us all in the deepest abiding mystery. We want to understand where we come from of human origin. He's going to talk to you about that today. It brings together archeologists, anthropologists, molecular biologists. You could have seen the sort of people that requested to meet with him. It spans the entire campus. And he's done it in a way that is understandable to each one of these disciplines, people who follow each one of these disciplines. And today he's going to tell us what he has used, innovated, and applied from a variety of different disciplines to understand the genome. Tomorrow is a second talk at the historical society where he'll give us a sense of a more public view, an understanding of the genome. I want to also point out that he comes here today from San Francisco for having given out the Breakthrough Awards. These are the new awards that have been launched just like the International Steam Box. He's the inaugural speaker. He handed out yesterday Breakthrough Awards at San Francisco. And he received one last year. And before that, he was in Tokyo receiving yet another award. And before that, he was in Leipzig where he's the director of the Max Planck Evolutionary Anthropology... Yeah, let me get this right because it's got exactly... Molecular Anthropology Institute at Leipzig, Germany. Now, I mention this because a friend of mine just decided to give up her Howard Hughes to move to Munich as a member of the Max Planck. She tells me that being a director of the Max Planck is a beautiful thing. Those are her words. So if you give up a Howard Hughes to move there, you can imagine. And with that, he has brought together a collection of amazing scientists. And before that, he was... Let me see. He was listed as the most influential scientist, 100 most influential scientists by Time Magazine. He's won the Gottfried Libnitz Prize, one of the highest awards from the German Academy. He's a member of various academies, national academies of the US and Sweden, Helsinki, Finland, Croatia, Japan, Russia. I can just go on. Members of the Academy of all these scientific agencies. Before that, he was a professor at Munich and a postdoc at Berkeley. And while he was in transition, his first paper that caught the collective imagination of scientists across was sequencing them, amplifying, and sequencing the Mamed DNA, Egyptian mummies in 87 in nature. And since then, it's just been a trailblazing to the force and has defined this field and is perhaps going to help us nucleate the molecular archaeology group here at Wisconsin. And with that, let me hand it over to Professor Pebo. Welcome him to Wisconsin. Okay, thank you very much for this very generous introduction. Please tell me if the loudspeakers work or not. They do work. Okay, good. So I should just start by sort of saying that I feel very honored and happy to be here finally to give the very first, as I understand, Steenbock lecture. It's an amazing place that I've heard a lot about and it's wonderful to finally be here. So what I then wanted to do is to begin with a bit about how we retrieved the Neanderthal genome, what we may learn about interactions between Neanderthals and modern humans from studying the genomes and then for the second half of the talk, then more volume. Talk about what we might learn about human origins in the sense of sort of functional adaptations in humans that are there in modern humans and not seen in the Neanderthals. So that would be the second half. But I just want to start with sort of reminding you sort of what you all know that our genome is like 3 billion base pairs and that we have a difference about every 1200, 1400 nucleotides or so when we compare to human genomes. So it means we have in the order of 3 million differences or so between genomes. So we have a lot of information with which we can potentially reconstruct human history. So if we now do that in a very bird-sized view, we just look on the variation among present-day humans. What you also know is that what we then find is that most of the variation is found in Africa. If we take the entire world outside Africa, the amount of variation there is less and not only that, most haplotypes or sequences out here have close relatives inside Africa. But there is a component of the genetic variation in Africa that doesn't have any close relatives outside Africa. So the interpretation of that is then that modern humans the direct ancestors of everyone today evolve in Africa, accumulate variation there and a part of that variation go out and colonize the rest of the world. And with genetic tricks by looking at sort of the extent of linkage disequilibrium and haplotypes out here, you can approximately estimate when that happened and it's sort of less than 100,000 years ago or so. So that's sort of the genetic evidence for this recent African origin of modern humans. But if you like, there is then a problem of that with that and that is that 100,000 years ago there had of course been other forms of humans there for a very long time. And most well known are then the ones we have in Eurasia, particularly the Neanderthals in western Eurasia and other less well known groups in eastern Eurasia. So as you also know I think Neanderthals are then this robust forms of humans. They appear in a fossil record depending a bit on how you define a Neanderthal now between three, 400,000 years ago. They exist in western Eurasia until about 40,000 years ago when they become extinct, generally in connection with that modern humans appear in an area. So you may then ask why should we be so interested in Neanderthals? And I think there is to me one big reason for it if you like and that is that they are the closest evolutionary relative to all present day humans. So if we should sort of define ourselves as a group it's really them that we should compare ourselves to. So in some sense they sort of define us as a group. There are other reasons too to be interested. They were here quite recently just 3,000 generations ago or so there were Neanderthals in western Eurasia so you can ask how are they related to us what happened when we met and so on. And this last question then what happened when we met has been debated a lot in paleontology. So essentially there is one extreme opinion that says modern humans come out of Africa meet Neanderthals and replace them with no mixing whatsoever meaning there would be 0% contribution from Neanderthals to present day Europeans. Another extreme view that no one really holds I think is saying Neanderthals are the direct ancestors of Europeans. They would be direct continuity but you can imagine anything in between here. So we got the chance to test this with molecular means then in the 90s when we got sort of access to the first Neanderthal fossil not just any Neanderthal but the Neanderthal from Neanderthals to say that was found in 1856 and was really the first time I realized there were other forms of humans around before present day people. So a sample from the upper arm there at the time we needed quite a lot of material to do this kind of work and we could profit from already like 20 years almost of experience in how you work with ancient DNA that you're very scared of contaminations you dress up in funny clothing and work in special lab and do a lot of stuff. And at that time with the technology one had the polymerase chain reaction you needed to focus on some certain part of the genome you're interested in so we focused on the mitochondrial genome simply for the fact that there are many copies per cell so it's a bigger chance that some fragments will survive we focused on a particular variable part of the mitochondrial genome and then determined that an estimated phallogenetic tree for the mitochondrial genome. And what we found was rather surprisingly to us at the time the Neanderthal mitochondrial genome go quite far back to common ancestor shared with modern humans about half a million years whereas all present-day mitochondria go back just between a hundred and two hundred thousand years and there have been a lot of humans tens of thousands of humans studied by now and it's very clear there's no present-day human that runs around with a mitochondrial genome from an Neanderthal. So in this scheme of things then is sort of total replacement. But it's of course also true that the mitochondrial genome is a very tiny part of our genome inherited as one unit so it's a big element of stochasticity and it's only inherited from mothers to offspring so any woman that has only male offspring for example her mitochondria will become extinct. So it gives a very limited view of our history that the real picture isn't a nuclear genome and it was again sort of technology that came around and made it possible to start studying the nuclear genomes and that was high throughput sequencing that came around in the beginning of this millennium. So instead of then focusing on some certain part of the genome you could just start doing an extract of the DNA and sequence all the DNA that's there in this fossil make your own little database compare it to the nuclear genome other of humans and others and sort of start working with this. Ooh, it got dark. That's okay. Perhaps it's good with dark. People can sleep. So the first place then where this worked for Neanderthals was the site in Croatia, in southern Europe and this bone, this fragment of the bone here around 40,000 years old and the first thing you will then notice if you sequence DNA from this is that it's indeed very short fragments. It's degraded 50, 60 base pairs hardly anything above 200. Let's see. The other thing that you will notice is that only a tiny part of the total DNA is coming from the Neanderthal and the vast majority is from bacteria fungi that have lived in the fossil when it was deposited in the ground. So our very best Neanderthal bones at the time had like 3, 4%. That's exciting. Now it's good, isn't it? No. No? Wow. Wow. Lecture. I'm sorry. Yeah, that's fine. Can we take away this thing at least? How do we get that to work? We do right. Lecture. I don't want to turn that light off. Yeah. Lecture. Now I hit the lecture. That's it. Lecture. Lecture capture. This is very exciting. We do dim. I like that. Ha! Ha! Okay. Let's see. Interesting. So we were then, this was about 2005 or so and we were very lucky then to get funded for five years to really work when we sort of could show that it would be a chance to reconstruct the Neanderthal genome. We could get money to sort of improve our method for extracting DNA from such bones, turning them into a library that you can feed into these machines in a more effective way. So we got a lot better in doing that. In the process, we also learned a lot of other things. For example, that if you now look in the sequence of these fragments and map them to the human genome, you will find a striking thing that you have a lot of apparent C to T substitutions and that they are particularly towards the ends of the molecules. And that turns out to be due to the amination of cytosine residues. So you lose this amino group, you get uracil. And of course, the uracil is read by DNA polymerases as a T when you replicate these molecules. And that happens particularly towards the end of the molecules where you have single-stranded overhangs that are more sensitive to the amination. So we also looked through many, many sites and bones. Finally, the focus of three neanderthals from three different individuals at that site in Croatia sequenced a bit over a billion DNA fragments, most of them then of bacterial origin from those bones, and then designed computer programs to map these short fragments to the human genome taking into account that you have this apparent C to T substitutions that particularly accumulate towards the ends of the molecules. So we then did that and sequenced about 3 billion bases from the human genome. So on average, each position had been seen once, but that then means that we had covered with one or more fragments a little over half of the genome. But we could then for the first time begin to ask questions. And one of the questions we were interested in was and this. What happened when one met? Was there interbreeding or not? When modern humans came to Europe and met neanderthals. And we addressed that in many ways, but the most obvious direct one is sort of this, saying that if there had been interbreeding, we would expect Europeans today to share more genetic variance with neanderthals than people in Africa today, because there never been neanderthals in Africa. So there's no reason to assume any special relationship between Africans and neanderthals. So it's just this idea, if there is no contribution here, then the neanderthal is just as far from people in Europe as from people in Africa. If there is a contribution, then on average, the neanderthal will be closer to Europeans than to Africans. So we had a neanderthal genome. We went and sequenced five genomes from around the world, Europe, two in Africa, China, Papua New Guinea, and did a very simple test first. Simply saying, if we now compare two present-day genomes and to test this idea, we take two Africans, find places where they differ, and then we have the neanderthal genome. And we can just see how often does the neanderthal match this African or that African. And that should be 50-50, right? Since we don't expect neanderthals to have contributed more to one African than the other, since they've never been there. And indeed, that's the case. We found, statistically speaking, 50-50. But when we then looked at the European individual and one African individual, to my surprise actually at the time, we found significantly more matching to the European individual than the African individual. Even more surprising was that we went to China versus Africa. We again find more matching to the Chinese individual, although most people would say there had never been neanderthals in China. And Papua New Guinea, where everyone would agree there had never been neanderthals, we also find more matching. So the sort of idea that came out of that was then to say that, well, when modern humans come out of Africa, they're probably passed by the Middle East. We know there were neanderthals there. So if these early modern humans that then went on to become the ancestors of everyone outside Africa mixed with the neanderthals, they would sort of carry with them this neanderthal contribution out into the world, also to regions where there had not been neanderthals to the extent that somewhere 1-2% of your DNA, if your roots are outside Africa, will come from neanderthals. So we've then gone on and worked, particularly with archaeologists in Russia, particularly at a site in southern Siberia on the border to Mongolia and China, the Nisava Cave, this beautiful site, where they in 2010 found this toe phalanx, which turned out to come from a neanderthal. By that time, we had then designed a new way to doing DNA libraries. That's much more sensitive than the ones we had before. So other methods rely on having the double-stranded DNA, manipulating the ends so you can ligate on adapters here, amplify and sequence your thing. This new development then relied on separating the two strands. You have single DNA strands. You do single strand ligation here, immobilize your fragment on a surface, and then synthesize the other strands. Each strand in a double-stranded molecule have two chances to make it into the library, so to say. And that turned out to be a big breakthrough for making really sensitive libraries. Often you have chemical modifications that affect only one of the strands, so that's lost, but you don't lose the whole molecule. You can get the other strand then. So we could go from then having just a little over half of the genome covered to covering this from now a single individual actually 50 times on average over, so we have a 50x neanderthal genome. So you can then begin to do much more things. You can, for example, walk over the genome and look for heterozygosity in windows. And one striking thing that we saw immediately was that there were huge segments in this genome without any variation at all, big regions of homozygosity. So this, of course, indicated that the parents of this individual must have been closely related. So you can then estimate the relationships that these parents must have had. So they could have been either of these four scenarios. They could have been half siblings. They could have been grandfather and granddaughter. They could have been, don't even ask me what double first cousins are, but sort of something went on in the cave there anyway. So it will be very interesting in the future to see if this is sort of typical of neanderthals or not, or this is sort of only at this site. I should say we now have a second high-caverage genome from Croatia, and at least this closely related is the parents are not there. So this is sort of not totally typical. You can then also, in present-day people, say, example one chromosome here, go over the chromosomes and identify with greater accuracy than it could before segments that come from neanderthals. And indeed, it's sort of one to 2% of the genome, just quantitatively to give people a feeling for this. But it's, of course, a case that that sort of, in total amount of DNA, it sort of represents as if you would have one neanderthal ancestor, six generations back. But of course that would be distributed in large chunks. This is in small chunks, thanks to recombination. You can also then ask how much remains today of the neanderthal genome in present-day people. You can sort of go from person to person and puzzle together longer segments like this. And it's a bit unclear, but in the order of, say, 40%, maybe 50% of the neanderthal genome still then exists in people today. And there are more interesting things that people, that they find there in this site in Russia. In 2008, they were very skilled, I must say, to realize that this little fragment might come from a hominin and it turns out to be a part of the last phalanx of a child, the fragment of the last phalanx of a child. If you want to know if there are archaeologists here, I should probably not say anything. I should say that, at least. I mean, there is a tendency in Western archaeology, I think, to talk down about Russian archaeology and say they excavate like we did 30 years ago. They just want to find the big things. Not really scientific excavations, but it was very skilled of them to realize that this might be a hominin bone, I think. So we actually were able to sequence a good genome from this little bone too and were very surprised to find that it was not a neanderthal, not a modern human, but something else, something that goes back a long way to common ancestor shared with neanderthals. So if the deepest population split among human populations today is in the order of 100,000 years, this is about four times deeper. And as always with these things, this depends on what mutation rates in humans you believe in and things like that, but this ratio of 4 to 1 will sort of remain. So we debated a lot about what to call these things and decided they are called the Denisovans, just as neanderthals are named after the first site they were found. These are named after the Denisovac cave. You can ask, have they interbred with modern humans? And yes, they have. And you find contribution particularly out in populations in the Pacific, a bit in mainland Asia and nothing in western Eurasia. And up in Papua New Guinea, for example, up to 5% of the genomes of present-day people then come from these Denisovans. And that's on top of the neanderthal contributions, so to say. You can look at heterosagosity, begin to look at that. In present-day people you see Africans and more heterosagosity than present-day people. And the neanderthals and Denisovans then have even less, about a third or so of the heterosagosity that you find in Europeans, for example. And you can then look for contributions from these extinct forms to present-day humans, but also in other directions. So there is this contribution then from neanderthals into the ancestors of all non-Africans. But what you find is that Asians actually have slightly more neanderthal DNA than people in Europe. So there is rather good evidence that there is later contribution to the ancestors of Asians that add on a little bit on that. There is also in the other direction contribution from neanderthals into Denisovans of a few percent. And there is a contribution from Denisovans then to Asians, mainland Asians, and a much bigger contribution to people in Oceania. And quite interesting, there is a sort of old component in the Denisovan genome that is not there in the neanderthal genome. So there is a contribution from something else into Denisovans that separated more than a million years or so ago from the human lineage. It's very tempting to say this is homo erectus in Asia or something like that, but we don't know what it is, of course. And it's even more complicated than that. There is now also some evidence that there might be info that they've gone on in the other direction from really early modern humans into neanderthals. And I just want to give you a feeling for the evidence for this. So if you sort of go in windows across the genome and look for windows where you have sort of one archaic group, say, neanderthals falling way back in the tree much further than the other archaic than the Denisovans or vice versa. So this is regions where not neanderthals and Denisovans have a common ancestor, but one of them go much further back. Then you will see that there is an excess of these deep lineages in Denisovans. This is this indication of this very archaic, very early diverged contribution into the Denisovan genome. But if you now go in the other direction and look for places where one archaic individual falls in with present-day Africans and there are other archaic falls outside, sort of having young haplotypes, if you like, in the archaic group that is similar to some people in Africa today, then there's an excess of that in neanderthals. So the interpretation of this is then that yes, there is this contribution from this early diverged thing into Denisovans, but there seems to also be a contribution from really early, more than 100,000 years ago, modern humans into neanderthals. And it's quite interesting what that is if there is some sort of early out-of-Africa population that is then not ancestral to present-day people outside Africa, but that mixed with neanderthals. And I think in the future one will probably learn more about that if that is true. But so one message of this is then that we have always mixed as humans also with these other forms of humans and at least to some extent. And we have a recent indication of that. That is a fact from this site in Romania where one has found this mandible that looks like a modern human mandible. It's 40,000 years old. So it's among the earliest modern humans we know of outside in Europe, outside the Middle East. And when we studied the genome of this individual we were then very interested to ask since this person lived when neanderthals were around had it already mixed with neanderthals or not. So this is a number of other modern humans on one chromosome, colored lines indicate there are fragments coming from neanderthals. So the question is, do we see any such contribution in this individual? And indeed we do. And a lot more actually than in present day humans. And in fact where it's black here or sort of areas where we have no information. So there is really this case that more than half of this chromosome is solidly of neanderthal origin. Across the genome there are then seven such regions. So this again suggests there is a neanderthal ancestor here quite recently in a family tree. So with this sort of size and number of fragments we can sort of say that six, five or four generations back there was a neanderthal ancestor to this individual. There is sort of almost caught someone in the act of mixing. So we then know that when modern humans come out there is this sort of early mixing, ancestors of Asians and so on but there is then also mixing locally in Europe. So very clearly then we have rejected this total replacement idea. There is a contribution from other groups but it is rather minor. It's certainly below 10%. I doubt one will find anything more than that in present day people. The vast majority of our genetic variation still comes out of Africa. So to sort of not lose track of that we sort of like to call this model say leaky replacement or so. The big picture is replacement out of Africa but there is some contribution from these other groups. So we can then ask does this matter? Does this mean anything? Is there any functional consequences of this contribution from neanderthals? So you can say go over the genome, whole genome of Europeans or Asians and find places, generally these contributions from neanderthals are a few percent but there are some regions where 60, 70, 80% of people carry something from neanderthals. So it seems to have been positively selected and you can ask overall what group of genes are in such regions and that turns out to be keratins. So structural proteins in skin and hair. So we don't know what that is but we will probably learn in the future then of some sort of functional aspects of skin or hair that comes to Asians and Europeans from neanderthals. There are also other things. There was a group that found this gene variant, the variant of a liquid transporter which is associated with risk for type 2 diabetes. And this risk allele is prevalent particularly in Asia and Native Americans and if you make a tree you then see that the risk allele is closely related to present day risk alleles and not to the preposterous alleles. So you may then ask why would something that causes disease type 2 diabetes come over from the neanderthals and rise to high frequency. And I think there is at least the speculation that this must then have been of advantage in the past and it's sort of possible that that advantage could be survival in starvation. That those alleles that sort of give us type 2 diabetes today when we eat too much during our whole life may have been an advantage in the past. It may be some neanderthal adaptation to starvation. Denisovans also contributed something, yes they have. So in Tibet populations live at very high altitude where there is little oxygen in the air. It was already known that an important genetic adaptation for that was in a gene called EPAS1 that has to do with being able to take up a lot of oxygen without getting very many red blood cells per volume in your blood. The lead frequency of this variant is very high in Tibet, very rare at other places. And Rasmus Nielsen's group at Berkeley showed that this variant of EPAS1 comes over into the ancestors of Tibetans from Denisovans actually. So it's fascinating that it may not be that we would have had so large populations on the high plateau in Tibet if it wasn't for this contribution from Denisovans. There's many things coming out now sort of with sort of functional consequences of this variance. One thing is a cluster of toll-like receptors, receptors that have a function in innate immunity that actually come over both from Neanderthals and Denisovans into present-day people. If you look at people that are homozygous for these Neanderthal variants they express more of these toll-like receptors. And if you look at association studies with phenotypes for this, these variants from these two groups are then associated with increased resistance to helicobacter pylori infections. So if you don't have an ulcer, you may perhaps thank Neanderthals for that. But these same variants are then associated with increased sort of risk for allergic problems. You may blame them if you have allergies. So there are quite a few things. This is just a review that came out a few weeks ago of things that seems positively selected in the human genome that have come from Neanderthals. So several of these things are involved in immunity and actually also in skin and pigmentation. And quite a few things are not known what they've done. So there is a sort of this view emerging then that these modern humans come out of Africa, meet these other groups that have lived for hundreds of thousands of years in the environment in Eurasia that may have evolved sort of some advantageous variance there and they then transmit to modern humans and they then increase in frequency. So this is something you might call adaptive radiation or so. But it's still the case of course that most variants we find in present day people from Neanderthals that have some function are simply associations with risk for disease or being protective alleles. So many things such as hypercoagulation, many skin diseases but also things like depression or so that comes up now. So finally then what I wanted to also discuss was in a sense what was not contributed by Neanderthals to modern humans. So you can go over the whole genome in Europe in red, Asia in green, look at the frequency of things coming from Neanderthals and then ask are the regions where we would statistically expect Neanderthals to have contributed but we find nothing. It's like we select against the contribution and there are indeed such regions and we are so interested in them because we sort of imagine that it might be then the genetic background for sort of functions unique to modern humans that hide here. So things changed after we separated from Neanderthals and became prevalent among present day humans. And we are so interested in them because there are of course some things that are sort of behaviors or things that seem unique to modern humans. It's after all true that if you compare modern humans to Neanderthals, Denisovans, all other forms of now extinct humans that existed. It's only modern humans that start developing technology, it changed really rapidly and become regionalized in the world. Only modern humans start doing figurative art that really depict something we can recognize. It's almost like political correctness today to sort of find as an archaeology some Neanderthal art but I'm sometimes a bit sort of saying that it looks like very modern art to me because you cannot see what it sort of depicts sort of things that really show something that counts with modern humans. And of course only modern humans start becoming really numerous millions of people and spread across open water and colonized entire world, come to Americas, come to Australia. So the idea is then that looking at things that are there in everybody today no matter where we live on the planet but not in Neanderthals would be interesting. So we can make this catalog now because we have the Neanderthal genome and it's not a very long list. So it's an order of 30,000 changes in the genome. So whereas two genomes between people today differ at sort of three million differences, if we make the requirement that everyone should share something today but the Neanderthals differ then it's just 30,000 changes. You can look through them in an afternoon in a computer. The problem is of course that you don't really know what you look at, what it means. And I think that is where there will be a lot of interesting things for the next five or 10 years. So we have to give you a feeling for how we begin to scratch the surface of this. We can think about these 96, there are only 96 amino acid changes fixed in humans and ancestral chimp-like in the Neanderthals. And they fall then in 87 proteins and you can then ask which ones of this would be important and we have a bias from what I said about modern humans that we think it should have to do with cognition or brain function in some form. So you can then ask for example in the developing brain by looking in the Allen brain atlas, is there some region of the developing brain where these proteins are over expressed, more expressed than as a control the genes that have silent changes that are ascertained in the same way, fixed in all humans, ancestral in Neanderthals but doesn't change amino acid changes. So the only region is then in the subventricular, matricular zone of the epithelium where neurons are born in the developing brain. And this now is a weak effect. It relies on very small numbers. In total 87 genes, right, this is like six genes that are expressed there, but very surprisingly to me three of them are involved in the spindle and the kinetic core so the machinery that pull chromosomes apart in mitosis. So we speculated when we saw this saying maybe this has to do with how stem cells divide and the geometry in which they divide determines how many neurons you form perhaps also what type of neurons. This was just speculation, but I sort of want to hint that one can now start studying this functionally and this comes from work with induced pluripotent stem cells that as you know you can differentiate into different types of cells, different types of neurons for example, but also into organoids like three dimensional structures that sort of mimic developing tissues. So you can make brain organoids, little bubbles in tissue culture where you sort of have this sort of same architecture with epithelium. So a group in our lab has sort of done sort of studied and compared between fetal developing brain and organoid brain and shown that this sort of patterns and gene expression in single cells here are very similar. We also can now do from chimpanzees, stem cells, chimpanzee brain organoids and compare now brain organoids from chimps and humans. In general they are very similar, but you do find some interesting differences and one of them actually involves precisely these cells that go through mitosis in the apical part of the epithelium here. So if you look by time-lapse photography on how the cells now, the chromosomes line up in this metaphase plate and the chromosomes are then put apart, you will find if you compare the chimpanzees to the humans that this period phase is longer in the humans than in the chimpanzees. And that turns out to be specific to these stem cells that form neurons in other mitosis that we look at between chimps and humans. We don't see this difference. So now it's sort of very tempting to say maybe it has something to do with these amino acid changes that affected the proteins in the mitotic spindle and kinetochore. So the next thing we want to do is then to introduce these changes into stem cells and make organoids now ancestralized for these proteins or to say and see if we see any effect of this. So this sort of, I think, where this field will be going in the future, one direction will be to ancestralize stem cells and study in vitro cells and organoids. The other approach will actually be to do the same thing in the mouse and we try to do the same thing for these proteins in the mouse. For the last two, three minutes, I just want to illustrate one other such project, the gene that we work on since 10 years now to indicate that mouse models or suggested mouse models may also be useful for human-specific traits. And this gene was found by Tony Monaco's group in Oxford in a famous family where a severe language and speech problem segregates over three generations. So they were able to identify the gene. It's a gene called Foxp2 encoding a transcription factor. And interestingly, the encoded protein is very conservative among mammals but has two amino acid changes in humans that's not there in apes and other mammals. So we were, of course, very interested then when we started getting the Neanderthal and Denisovan genomes, what were the states at these positions? So these are the two positions in the gene. So when we then get the Neanderthal and get the Denisovan, what we found was that they were identical to present-day people. So these changes clearly happened here before we separated from Neanderthals. They are still interesting, but whatever we find about them is shared with Neanderthals. And as I said, this protein is very conservative all the way to the mouse. It has only one other change that's hopefully very conservative there. So what you can do is humanize the mice. So you change the genome of the mouse to carry these human-specific changes. So you then end up with a mouse that essentially makes a human protein from its Foxp2 gene. And this idea is this should have something to do with speech and language. You try to speak to the mouse, and it doesn't answer. Probably it sort of lifespan is too short to really acquire fully human language. But you at least have a sort of model where you can then start looking at this. So for example, you can find that in the humanized mice when you compare to their littermates, neurons in some parts of the brain make longer dendritic trees, bigger dendritic trees. And this is then seen particularly in parts of the brain that are part of these corticobasal ganglion circuits that have to do with motor learning. So this stimulated the graduate student and the laboratory finished, Kristianne Schreiweis, to go to MIT and work with Ann Graybill, went there with these humanized mice to study motor learning in the mice. And then they do experiments like this where the mouse has to go in a maze and find something it really likes, which is chocolate milk. And you give it a cue, say a light or a signal saying it should go to the left to find this. And you can then train the mouse to sort of follow this cue. And there's no difference for the humanized and wild type mice in how quickly they learn this. But it then comes a time, if you always give the signal, say to go to the left, where you can take away the cue. And the mouse sort of internalized this. I just go to the left and I get my chocolate milk. And that switch comes in seven to eight days in the humanized mice and their siblings that are wild type take 11 to 12 days to sort of figure this out. So there is a clear difference in sort of how fast you sort of do proceduralize something like this. So I'm not a neurobiologist, but the neurobiologist sort of explained this to me by saying this is a model for sort of motor learning in humans. For example, when you learn to bicycle, when you start to learn to bike as a kid, you're really bad at it, right? You think about what you do and it's very complicated. And if I tip to the left, I should stare to the left actually to compensate that. But then comes the time and you can't really make it clear for yourself when you stop thinking about what you do. And the moment you stop thinking about what you do, you get really good at biking. And this goes together then with a switch in activity from the middle part of the striatum to the lateral part of the striatum. One of these parts where we see this bigger dendritic trees. So that may stimulate us to go back to the mouse and look for long-term depression. So sort of a model for learning and memory where you give a high-frequency stimulation and measure how much less excitability you get after that in these neurons. And in the lateral part, we see this effect much more pronounced in the humanized mice than in the wild-type littermates. Whereas in the medial part of the striatum then we don't see any such effect. If there is an effect, it's even in the opposite direction. So this matches then with the idea that it would be a stronger switch to a lateral part to automation of this motor behavior. So you then at least have a hypothesis suggesting that these human-specific amino acid changes may have something affect these corticobasal ganglion circuits to make for faster automation, if you like, or motor coordination tasks. And it's of course very stimulating or sort of tempting to speculate that the sort of most sophisticated motor learning, motor coordination I should say that we do as humans is articulation. We need millisecond control between vocal cords, lips, tongue to produce articulate speech. No other primate can do that to that extent and it actually takes two, three years for us as kids to learn this. So it may well be then that this has something to do with that. So I think that sort of very, very optimistic that one may actually be able to use a mouse as a model also for some human-specific traits. We might be able to humanize and neanderthalize if you like, pathways in the mouse or organelles even in the mouse in the future. And I think that's sort of where I think this sort of field of sort of modern human origins is going that we now have the neanderthal genome. We can determine what happened earlier on the human lineage and what happened very recently. And the next challenge is now also to try to understand this functionally, which will be a lot of work, but it will involve, I think, stem cells that you manipulate and also then mice that you humanize. So with that then, I should say, many more people that have been involved in this than I can mention. Many paleontologists, archaeologists, many people in the lab. I mentioned one person in particular, Mathias Meyer, who developed this highly sensitive, single-stranded method for making libraries. Without this invention, we would not have high-caverage genomes of neanderthals and denisovans today. I should also mention Jesse Daveney, who is now here and thus ancient DNA at this famous university. And there are a lot of people also involved in this functional, in population genetics work, interpretation of this, I should say. I mentioned particularly Janne Kelsen, Keif Rufler, who sort of coordinate all this bioinformatics and David Reich at the Broad and Harvard, and Montes Latkin for population genetic work. Functional work, many people are also involved. I mentioned particularly the single cell genomics group in our institute, Barbara Troitlein. And Jiland Hotner's group for the sort of mouse brain development work that we do with them. And with that, I then thank you for your attention. We do questions, right? So we can pass the bike around, or perhaps you could repeat the question. We also will limit the questions. There's a reception after this in the neighboring building in the atrium, the latest glass building on the other side of the oak. It's Hecht Deluca Laboratories. So you go until six. So if you have questions, reserve them. I didn't get your question right now. With that, let's start. Can we turn the lights on? No, we do that. Lecture, let's... You can wake up now, questions. Please. So the question is, 40,000 years ago, the Neanderthals were already mixing with humans? Yes, they had mixed. Some Neanderthals had mixed with humans at that time. Yes, so well, those Neanderthals that we have studied, also 40,000 years ago, they have not mixed with Neanderthals or their ancestors yet. I think that mixing happened in the Middle East somewhere. It didn't have in Siberia or in Europe where we studied this. But we also have older Neanderthals, yes, that are more than 60,000 years old. But we have not yet... We would actually be very interested in finding a Neanderthal where we found gene flow in the other direction more recently. And we have not found that yet. Ah, yes. So when did the Neanderthal ancestors leave Africa? We don't quite know that, but the ancestors of... The common ancestor of the Nisimans and Neanderthals presumably lived in Africa and came out. There is something called Homo heidelbergensis that the paleontologists recognize that are seen both in Africa and outside Africa. That's probably the ancestor of these people. We have... The oldest DNA we now have from hominins is around 430,000 years old in Spain. And that's already... It's early, but it's only Neanderthal lineage. So by 430,000 years ago, the ancestors of Neanderthals were already in Europe, so to say. But it's probably a bit before half a million years ago or something like that. Yes, the question is, was it primarily males who contributed? So Monteslatkin has sort of... We have been very tempted to claim that. But Monteslatkin had simulations on the reasonable population sizes and things that this could happen just stochastically. You could lose the mitochondrial DNA just by chance. There is another expectation. If it was primarily or only males, we would expect less contribution on the X chromosome, right? Because the males would only contribute an X chromosome to half their kids, to their daughters. And in fact, we see less contribution on X. So then we were again very excited and said, yes, it's indeed so that modern human females found Neanderthal men attractive. But then we have found this sort of negative selection in other parts of the genome, in the autosomes. We see this sort of deserts. So then we got very scared and said, well, it could be that you also have selection on the X for this. So we sort of don't dare really claim that it is like that. But if I should bet on something, yes, it was the men that were attractive. Do you see a similar appetite as that? Yes, so it's a good question. It's of course, what about the mouse background? So we have not done that. We should probably do that. I mean, I would perhaps then more go and do it in a marmoset or something like that, where you would have more vocalization, more human-like things. There is actually a group at Keio University in Japan that is putting in these things in the marmosets. So we will know in a year or two. We have not seen anything that's fixed. The question is, do we see anything in European donations that's fixed that come from Neanderthals? And I'm now thinking, do we have some kind of ascertainment bias in that we wouldn't really discover it immediately. But I think we should have seen it because the way we identify these things are looking for things outside Africa. That's not in Africa, but that is Neanderthal, similar to Neanderthals. They should have popped up. There are things that are 80, 85 percent. Yeah. Shall we do that first? The question is, do ex-chromosomal depletion suggest that hybrids will less fit? I think yes, probably. There's another thing that I didn't mention if we just say in these deserts where we seem to select against Neanderthal contribution, the genes in those regions, where are they expressed in the body? And the only sort of significant thing there is testicles, male urnite. So that sort of suggests that yes, it may be a whole day in cirrhubal that when closely related population species mix, it's often the heterogenetic sex that has problems. And that applies then for some of these things on ex-chromosome, too. So yes. It may well be that one mixed both sexes, but it's actually the male offspring had problems. Yeah. So you have this mixing between Neanderthals and modern humans in Asia and Middle East. But back at Africa, apparently, there's multiple hominid groups involving at the same time. And presumably, there's some mixing there and maybe some of the genetic diversity in modern Africans is due to that. Is there anyone looking at that and trying to put together some of that evolution that's happened in Africa? Yes. So the question is what about Africa? Is there contribution from other groups in Africa to modern humans, archaic groups? And yes, absolutely. I think that may very well happen. We don't have any really old genomes from Africa. We have now one genome from Ethiopia that I think is 3,000 years old or something like that. There are some other things coming in the literature that is in the Holocene, all of them. But I think the situation is also a bit more complex in Africa because outside Africa, we have these sort of Neanderthals and these other forms, and there's a period of separation, and then one meets again. So we can sort of really detect it. In Africa, there were probably different forms of humans, perhaps more continuously in contact with each other. So it might be a bit harder to figure out, but it may well be exactly as you say that the bigger variation in Africa is also due to. So I've been tempting to say only Africans are the fully modern human population. Everyone else has this primitive thing from these other groups, but I would think that that exists also in Africa in the end of the day, when one has looked. Perhaps you can stop here and head over to the reception and get some food as well.


Hello thank you for tuning in to Y254TV as we will be talking about politics. Where we can discuss politics, and what is a virus, how does it exist, you can keep on talking about it, as we are making conversation. Join the conversation by sending in comments to all social media platforms on Facebook and Instagram and also Twitter to us in comments on our reactions, Kwa miho kwa yung cha menda wa expek Kindaatsi ya raide terumia za poza kpentamia kwa menda yung mahena. Mada niya wakama niya, kwa menda kiya sakut게 hafu wajakia. Kwa menda kiya sakutya hafu wajaka na hama kwenia. Bada niya kwa mombefoka kama manda waka menda kwa menda kwa menda. Kufu ya. Na gafu na menda yung mahena? K natomiast hvali na yung mahena? Ngoek wajakia hia menda rado wa matisa. Bahwaja, kwa menda kwa menda kwa meni. Pungi, KUya, heneha medini yung mahena. Kendi, politikul, analist, jende, konvazisyon. My name is Dereva Hillary. Good morning. Ladies, how are you? It's a pleasure to have you here. Pleasure to be here too. It has been a trend. Bitris, I will have you here after maybe a week or two. Glad you are back. And now we are speaking the head of state to be addressing the nation later in the day, maybe from 11 o'clock state hours. We should expect he will address the nation. And we have so many expectations from the speech. What you will be telling the nation, we want the decision of movement to end. We want the curfew to end. But if the numbers keep on speaking like it has been seen, are our counties ready to handle in case of a large surge? Bitris. I think counties are not ready. No, they are gearing up towards that. Now that we are all locked down, all of us. Nobody is flying out or in. And only Baba we had that he flew out. But for normal average Kenyans, there is no going to outside countries. So I think now counties are feeling the effect that they really need to style up. But the healthcare sector is still deplorable. It still has a long, long way to go because a place like Siaya County, they only had five ICU beds. So you can imagine if the beds, if there is a high spike of this corona and you need more people to be in ICU. Though the treatment and management of COVID varies, there are some medics of the opinion that ICU is not really necessary. So most likely the people who go to ICU are those with other underlying complications, but generally mechanical ventilation in the treatment of COVID is not one of the regimen that is actually being used. But be as it may, we have Kenyans with other underlying ailments because you may be having chronic illness like diabetes or hypertension or what is it called? Cancer kinds of patients. All these people have been hindered one way or another in accessing treatment. So because this chronic illness kind of patients, you can imagine where have they been accessing treatment and care. Some people are scheduled to have surgical operations maybe in India or abroad. Now they are confined in this country since March you can imagine. So you can imagine if it was an urgent operation. So how aggressive is the condition that has made this patient be? So what will happen is that now counties have to style up. We have to now trust our local medics and healthcare workers. If we've trained them badly in our institutions, that is what we are going to get. If they have picked, that is what you are going to get. I think this is the time everything is now being laid bare naked. It's exposing every sector from education sector, healthcare sector, governance sector, church sector. This COVID has really exposed so many institutions. So if you produced half baked doctors, if you produced half baked nurses, if you produced half baked pharmacist, now we are now facing the music. So now running away you are going to go to UK for further treatment. So if you've been eating money to what is it called, to set up institutions, now the rabba is meeting the road literally. So you'll have to now be answerable to the populace how come there are no supporting machines, right? How come there are no well established departments within the healthcare institutions? So did you even stock up for drugs? Or are you still waiting to import last minute? It's very, very crucial. It shows even the preparedness because this is kind of a disaster. So disaster preparedness, how well cushioned for such disasters, right? So we really need to... I am glad COVID happened. I cannot regret that this situation did not happen. I am glad it happened. Why? Because it's exposing the debt that has been there from all the way, not only in government based on corruption, but also in our institutions. The learning institutions, the higher learning institutions all the way to the hospital setup, the business setup, everybody is getting exposed. So I think now the conversations we should be heading forward is to stop the blame game and we start now sitting back and asking ourselves can we now depend on ourselves? Now we put strategies in place on where we can depend on ourselves. We have today, for example, I hear like the EU is now opening but they have said Kenyans cannot go to the EU because they feel quote and quote we did not handle maybe COVID properly or places like Tanzania, they have been bad from accessing countries in the EU. So that tells you most of the things we have to style up our institutions we have to style up our healthcare sector we have to style up allies if we don't do that, I believe now the dispensations that we are entering in we are going to experience more pandemics I guarantee you, I always tell people I'm not a prophet but after this pandemic there will be another pandemic because global warming things are just cropping up right left and center so it is asked to now sit down and ask ourselves are we well prepared intellectually because preparedness is not just having equipment but can those people operate those equipment we are having a discussion whereby it's true right now counties are running to set up ICU Muranga was setting up ICU departments but then the question is do you have ICU nurses trained? it's okay, it's good to have a building and have equipment but are the doctors trained to treat people in ICU do we have enough ICU nurses do we have enough clinical pharmacists to deal with in the ICU we have to look at that capacity because it's one thing to have roads but will people be using the roads to drive their maize or is it because their cars that are going to use the roads so we really need to look at it holistically it's not just to dump ICU beds in the hospital facilities or just create a building and their beds there but do we have the right infrastructure infrastructure is not only equipment but also the right personnel and now even the institutions will now be not cushioned but they will have to be very ready even now engaging more training of such kind of personnel because right now next time we may actually be having our own healthcare personnel actually doing the treatment that people are actually soliciting outside the country so it's also upon the institution now to style up and now fully equip our healthcare workers so that we can fully trust because I always say every time actually I would like to hear in Kenya's comments I think you have so many ideas on this we will get there now can you tell me do you think the counties are ready to handle because according to the council of governors only a few counties are have gotten to the target of the 100 beds as directed by the president that is Mombasa is leading with around 400 do you think the counties are now ready to handle COVID-19 in case the decision of movement from Nairobi to Machinani considering Nairobi has the highest numbers I don't think counties are ready but I also think that you are going through this COVID thing from reverse we are going we are going about it from behind we are first looking at do counties have ICU beds do counties have beds for admitting us do you have isolation units but you see what you are looking at is the worst case in Nairobi can the counties can our country take care of us the first thing you are supposed to think about is our country is not prepared actually no country was prepared for COVID so the first thing you are supposed to look at it's not whether the counties are prepared is what can we do to make sure that we don't overwhelm the resources that we have just a few days after the minister of health said people could be treated from home and now we have issues of the 300 beds how many people will be treated from the health facilities how many people will be treated from home but the question will still stand if anything can the counties including even Nairobi itself can the counties match the numbers that will have spiked at the time no not just the counties Kenyata it's Kenyata hospital none of these hospitals can can manage COVID if the numbers go higher than what we have right now you have to know that right now the ICU units that we have they already have the maximum capacity not that before COVID we had enough ICU beds remember now people have not even been going to hospitals that I have an underlying condition I don't go to hospitals because I'm afraid if I go there I might get COVID from there so as Kenyans let us first stop looking at whether the counties are prepared let us do our role in first making sure that we don't overwhelm what we already have what can we do to make sure that we don't get the numbers higher we as individuals let's stop looking at counties let's stop looking at the government let's stop looking at Kenya is anyone prepared for COVID no so what can we do to make sure that the numbers don't go above the 300 again COVID I think we needed COVID in Kenya I am saying this from a good place as a patriotic Kenyan but we needed COVID in this country for us to wake up for us to start having the uncomfortable conversations that we are having right now our healthcare system has been going down and let us in the issue of us having qualified personnel yes we have qualified personnel remember these people who go to India for treatment our MPs who go to UK for treatment they go to public hospitals and are they diagnosed before they go to India remember they don't just wake up and we said in India you first have to be diagnosed who diagnoses them Kenyan doctors so if we equipped the Kenyan doctors with the facilities that are in India for treatment of cancers and everything else these doctors can handle all these things so as we are talking about COVID let us not be short-sighted and talk about COVID alone counties like Moranga started they were building something Machako is converted a stadium into a COVID isolation center which is very temporary it's not like COVID and we may let it sit down we already had these problems before COVID so these temporary measures that the counties are taking if we are actually at the counties my county is going to go take the stadium put a tent on it buy beds and put beds at the stadiums what happens after the COVID is over they take back the beds beginning when we were there we go back to the same healthcare system that we had we want the counties to have more permanent solutions and not just for COVID but for everything else when you need dialysis I don't have to come to Nairobi for dialysis when I need a surgery the counties were even what is it called, caesarean they can't perform caesarean in district hospitals you have to be to be referred to another hospital so these are the conversations that we need to have manufacturing before COVID we used to imports Kenyan made now we used to import right now we used to import so we were pushed to a corner where we now had to think out of the box and start producing our own PPEs we had caught on industry what happened to it, it died a natural death so these are the conversations that we are now supposed to start having manufacturing we need to be independent as a country we need to be in a place where because COVID is not going anywhere that's the sad reality and countries will not comfortably export stuff to other countries because every country is holding for its citizens so when it comes to things like masks see it is soon to transfer masks come out to the import so we have to think about that the beds our joakali people by they are very creative they do these things there is a course in KMTC what is it called I am forgetting the engineering course in KMTC Biomedical Engineering Biomedical Engineering we have people who have learned these things but have not been utilizing them because everything we have been importing everything this country that only exports flowers everything else including needles the only thing we export is flowers that's why it was so easy to give flowers to other countries because now we are not exporting flowers anymore coffee is going down tea is going down so right now we have to think about our food security about our health security about our manufacturing which was all in the big four and we had all forgotten about the big four until COVID came and told us you remember that housing you are talking about that is what we need right now you guys are being chased by landlords but imagine if we had a national government housing system it means that right now we will not be worrying about trend you will make the president smile if he is watching knowing his agenda was okay but the critics were against it but it was overtaken by politics and corruption brings me to the point of the high dependency where Kenya has been because do you think COVID-19 both of you have alluded that it has opened our eyes it has made us to be naked as now we can see all the data all the spots do you think we are now at the ICU or what happens to us from the high dependency now we are manufacturing our own PPEs masks and everything but also there are sectors that have stalled where do you think we are as a nation I think we are heading towards an economic crisis trust me we are heading because we never cushioned ourselves from the word go we were ill prepared and the other thing is it's true we will introduce manufacturing in the country but where is the excellence there is a reason why people still prefer even right now the masks that are imported and the ones that are made local why the quality of what is being manufactured you know we need first of all we need first of all we need to insist again from our institutions we need to instill excellence we have to start from that point there is a reason why you've said that most of the MPs by the time they go to India they are diagnosed by doctors but there have been a lot of misdiagnoses why because most of these doctors have not been given study leave to go and study these cancers in extensive right so most of the doctors you realize misdiagnosed only when he went outside when it was able to get proper diagnosis the same thing with Bob Colimo so what we are saying is it's not that our doctors are not intelligent or our nurses or our pharmacist are not intelligent enough the only thing is exposure so where are we still insist again right now the economy is bad that we just feel it's going to go deeper downwards actually unless we unless we have critical conversation among ourselves and the government since the what is it the gravity of the of the situation how grif the situation is I am telling it is not going to be business as usual and before people come back to what is it called come back to to I don't say come back to their senses or come back to that norm that was there before Covid it will take quite some time in another station or saying about an economic recession not only in Kenya but in other countries they are feeling there is going to be an economic recession where the whole world will actually feel it so we need to stop playing around and saying we are okay we are good to me as a to manufacturing here no no no no I don't think that is going to to really work so what we need to do I can see the president is getting a lot of donations from world bank from IMF I think we really really need to utilize these resources properly let's utilize them very very well otherwise what I feel is that we will get all this funding but when when all is said and done we will have nothing to sure of it you see there is nothing to sure of it number 2 we are doing a lot of viraka things you know I hate the viraka kind of doing of stuff because we take a kiraka reo na keshitara ruka and we have very short memory in terms of our leaders aki aki yo kiraka now everybody is okay people will not be okay so I think we need to start from the grassroots and what is the grassroots our institutions the president is true he had a very good agenda very good manifesto even when they were campaigning 2013 and even 2017 I was telling another time if they implemented the laptop project those kids would be now at home enjoying e-learning comfortable the kids are now in class 8 they would be really enjoying e-learning and even in our high schools right now so I usually say they had very good manifesto they had very good development plan for the country but not the problem and now alisema kusema na kutenda there is no agenda so I think right now let's go to the grassroots and a country is as strong as its institutions so whoever is corrupt wacha arudisha pesaya uma mebi apu tutapata pesaki dogo yakufanya 1 2 3 4 whoever has been doing illegal businesses let them be put to justice because the justice system number 2 because the institution already is corrupt the justice system in itself is already corrupt it's not even giving justice it's not even doing the correct thing on time what is happening it records down to other institutions that's why I keep insisting you'll have half baked doctors you'll have half baked nurses you'll have half baked engineers such that even manufacturing a very simple thing like a mask it is not to par excellence like the way you want one imported and I believe Kenyans have the brain and the capability of actually doing something we are among one of the smartest people in Africa we have a very good labour force but now we need to instill the excellence the culture of excellence the culture of proper running of institutions that is what we need to instill in our people so that the culture changes even if I'm half baked I'll still get a top position we need to shift from that and it's very evident even in the leaders we choose we choose half baked leaders we choose leaders who are not excellence a simple thing like a road small roads you can see there is no excellence in it until a Chinese has to come on board and yet we have civil engineers we have we have structural engineers but they cannot build the same roads that we are proud of but when you give a Kenyan to build the same road they don't reach to par excellence until a Chinese come in and then you're like you cannot notice the difference it's because Kenyans love the shortcut exactly so we need to instill a culture of excellence and once we kill that root of of Medioka I would call it Mediokristi because even the type of leaders you'll produce are going to be Medioka so you'll have a Medioka nurse you'll have a Medioka doctor you'll have a Medioka teacher you'll have a Medioka engineer so it will be replicated all over and this is the thing we cannot start killing the fruits and you have not dealt with the root system we have to go deep into the root system in terms whereby you'll head an institution based on merit but even if you are given on merit and you have very good papers but how well were you grilled to have actually earned that some people went the back door and scored others went the back doors and were able to acquire degrees and you still got that portfolio but now when it comes to actually result oriented so funny enough I'm a result oriented person when it comes not to the result itself it is not to the quality to the excellence we are very smart people but the problem is the smart people are very corrupt no the problem they don't do things to the excellence that you want they don't construct the roads that you want that the Chinese can construct here I'm supposed to use 15 tons of gravel let me use 5 because it's a culture yes that's what I'm saying it's not a training it's because you are well trained but then again you are corrupt that I'm thinking as a doctor I have to prescribe this medicine to you but instead of me making the hospital procure the medicine I will tell you but then you have a clinic see after this prescription just go to my clinic yes the selfishness agreed all that that is why we have public institutions and and very bad and very bad public schools all right actually on the same thing she has been mentioning of the excellence we are having a problem now the president is being turned between reopening the economy or letting things remain as they are we also have the other problem of the resumption of schools with this children go back to school how is the testing Professor Mogwe says they will ensure all the teachers will be tested and before we even began we asked will the kids be tested but even so do we see the education that we had from the physical class to online back to now physical again what will be happening to these children mentally in terms of education are we ready for reopening I don't think health status we are not ready but our economy is suffering so it's either people will die from covid or die from hunger the president has to choose between those two and when you look at it our country had not gone into a lockdown we were still a little free to move just that even before covid we also had this problems that we have are pre-existing apart from schools everything else has almost remained constant that this covid the government has been leaving because the government has been leaving because then you are left as you are to go back to work that is the same way the government has been leaving that it pays wages does that but it didn't have extra funds for cushioning in case of a pandemic or in case of an emergency so if right now we say that the government reopens and helps the business people get back to their feet is it even realistic can our government do that can our government afford to cushion our business people I don't think it can but for that in terms of the education education sector was already at the AE remember the government had said 100% transition kibaki came with the free primary education prior so we already have kids who have done a class 8 but not transitioning to high school was where there was a bit of a gap so it reached a point the government introduced a policy of 100% transition that whoever does class 8 transition or everybody transitions to high school so that at least the populace will have at least literate people with at least an all level kind of a certificate now the problem was one you've gone to a school let's say like limuru girls high school which I am a PTA member the school initially was a free stream now you have insisted for it to have 100% transition that means for it to have 100% transition it has to be a 7 stream so where does the school get for classes from and already the infrastructure itself it's ilia 1900 or 1920 they are about so government was not even finding these institutions to be able to set up infrastructures parents were the ones going back maybe to their pockets public participation to train and ensure a harambe way of doing things to ensure institutions are being set up so now when you now want us to go implementing covid measures do we even have the infrastructures in the first place in our institutions even the teachers strike exactly so first of all even before we look at the teachers let's just look at the building where these children are going to go the dormitories hakuna, dining hall hamuna classes, bados, schools have not been able to transition fully 100% and even if they have transition 100% kids are squeezed in classrooms you find a classroom of 60 students a class that was initially to host 30 to 40 students to bring the 1.5 meter so do you see where the challenges where will there be this space for the kids to actually utilize up to that point now when you say now you are going to test the children themselves how many kids do we have in this country already we have a challenge of even testing people even in Nairobi only so now all the students to be tested is it possible number 2 to test all the teachers now as she said if the interval is 14 days how often will you be repeating among the same children now don't only focus on high school we have the primary school and we have the kindergartens are you looking at all because that's the whole education and then we have the university students so why already there is already a challenge of infrastructure let's agree on that that cannot be able to put the potentials of COVID I think we are going through about COVID in a very short-sighted manner for example when we say we test teachers that means that when children are reporting back to school they have to go back to school with a certificate showing that they had been tested but for how long, how viable is that certificate I can be tested today 21 days from now I can have COVID because you will be moving actually because I will be moving around and interacting what COVID has brought to us is we have to change our settings right now instead of us having the conversation it's about going back to school which is not realistic according to me it's not realistic for us to have a class a class that used to have 80 students now tell them that you have to observe social distancing of 15 students per class how many classes does that school even have it already had the problems of infrastructure even before COVID which we are supposed to be having right now it's supposed to be realistic and tenable like these students cannot go back to school that's the reality of it can we now look at how these children can continue learning under the circumstances that we have how can we enable these children in our rural areas to go through the same I left my son at home he was on an online class how can that child who is back at home in Oshago have the same advantage with this child in Nairobi who has a tablet who has internet settings and who has a teacher who is engaging him in a zoom class so now we are supposed to think about bringing these other children who don't have this advantage bring them at the same level of advantage with the children at the private sector I think the minister for education is going about this in the wrong way let's be realistic let's now start thinking about how to engage these children on online classes until we have a more permanent solution until we can live with covid maybe get the herd immunity then we can all go back to school but as at now how will we engage these students they've been at home since March they can be home back in December that's how the pregnancy needs are going higher they are idle we need to find something for them these are young minds that we need to start engaging right now you can't keep a child who is five years who is around ten years you can't keep him at home from March to December actually one of the suggestions the task force that's for education because parents were engaged actually on how the strategy for kids to go back to school and one of the strategies was kids not to go back to their initial schools like before for example you could be in Nyeri kid was called to Alliance high school so they have to travel you come from Turkana and maybe a kid is operating from a school in Nairobi so now they were suggesting they look at schools within the county but do those counties even have those schools that's what you say they look at the counties first the first suggestion was to look at the counties the schools that they have and how many students can be contained because remember right now you cannot start putting internet into Turkana right now actually you can you cannot start giving laptops right now to a student maybe even in their own homestead there is no steamer so first you have to start installing the steamer in those deep rural areas accessibility, right now there are rains all over and floodings and everything so how are people now even going to access even such things the things that are there are actually very critical to the point now we have to agree or disagree whereby if we are going to set infrastructure and I still go back again to my poetry of institutions so first the schools, how many do you have what is the population in that county based on the number of schools that we have do we have kids boarding or doing this calling you know you have to look at it so that you can say there is now going to be a schedule for every lesson can the kids be staying at home with their parents because also remember now the food and all those other things but I also think there is a consideration of the region if I am in this region this is Nairobi CBD we have only one school which is primary but has the population that can handle that only then we have another one in say Westlands there is no school in Westlands there is no school in Kasarani Nairobi how will they now start merging and how will they live if not boarding we are thinking as if this country is very rich when we start saying about building infrastructure and doing this TSA teachers are actually receiving salaries since March in health we have community health workers who go home to home when HIV was very prevalent they used to go from house to house I mean serving ARVs why can't we do the same with the teachers these teachers what are they doing they are receiving salaries from TSA they should be doing something yes why can't we just have community engagement of students like get a data of all the teachers in this in this world how many teachers do we have in this world okay you will be teaching class on students go home to home give an assignment to these students what have the teachers been doing from March up to now what will the teachers be doing from March up to December why can't we engage the teachers to do community outreach to the students at home the teachers enough how have they been operating no you see when you have a classroom of 80 students it's not a classroom situation I'm just saying if it's a classroom of 80 students and there is one teacher one teacher is reaching to 80 students at once community health workers the population of patients is different from a population of students you see remember a sick person you could have a population of 100 people and maybe 10 are sick the rest are held in so the 10 and you have community health workers it's able to but now when you talk about students in Ipase these are not sick people so in one class where one teacher was teaching 80 students now you want to tell that one teacher to go to 80 people it's not possible it is actually possible let's do this this country that are not used for example what do you do with our chiefs camp apart from having those public marazas why can't we have a schedule at the chiefs camp for this village tell the villagers there is a schedule at the chiefs camp tomorrow on Monday the class 1 teacher will be there she will be giving assignments to class 1 students if you have a class 1 student in your home please let her come to the community take away I end up in Mualimuampati assignment go back with it bring it next Monday at least you have these students being engaged weekly it doesn't have to be online we don't have to be to use internet let us use the resources we have right now because when we say about building classes of 15 students per class surely it's not it's not possible for now it goes for 500,000 years national government rates it may be 1 million per class apart from that later we ziote we don't want our audience to react to the same questions what they feel about the homeschooling which will be now the community the teachers now going to to the homes and teaching or giving assignments that you could send your comments to all our social media platforms on Facebook and Twitter and Instagram as well tell us what do you take what should be your opinion when we say teachers should be going home door to door teaching students because actually the online is favouring only those that are able to have the tablets or the laptops or have the TV set for them that are watching the TVs but someone far flung in the villages are not able to access that and actually I'm sure most of the people most of the students are now engaged in the shambas they are not learning so what's your idea tell us what you feel about that I wanted to say maybe the only way out if she says the outage thing and I am boring a leaf from the healthcare sector where I have more experience in is where we reintroduce untrained teachers we have people who maybe did in university by the machics actually our university students are at home exactly that's what I'm saying in Kenya we had an exposure untrained teachers they can be given a small stipend by the government to be able to do now the outreaches and do the homeschooling settings where the kids can still be in their homes and you can have actually when Uru is saying this is the right opportunity this is the right opportunity for actually Uru engaging we have very bright university students who have been jobless for a very long time they can use their intellect being a medic myself it's very easy to go teach biology to these students as an untrained teacher and engage these students and it's much cheaper it's cheaper than us building a class of 1 million for now because it is not sustainable for now we can do it actually it's a very good suggestion I hope Uru is watching us you should have been in the committee to come up with these ideas Uru is watching us to I hope even Magoha is watching us actually we can engage untrained teachers they are not really employed by TSC but they can be quote and quote community community education TSC teachers have been earning a salary for what then maybe a TSC teacher can coordinate the untrained teachers then they are dispersed to the community one untrained teacher can be told this homestead it's Uru who is going to ensure that the students are engaged at least make sure that the students are engaged at least 3 times a week you are not asking for so much instead of them being free from March to December then taking them back to school again in January we shall not have students to take back to school children in their teenage will all be pregnant and we shall be here talking about children being raped but most of them were not raped it's because they had nothing to do and then we shall be here but then let me tell you the results of COVID shall be felt 20 years from now when these students were in class 1 are now grown ups who have responsibilities this is a child who was kept free for 1 year a whole year at around the age of 13 years tell me what is happening to that child's mind it's a mind that has become has become idle there's nothing going in children nowadays don't even read books they don't even read story books so what is going into this child's mind this is the best time the earliest time for you to mold that child's mind adakama wanafunzwa kitu moja peke adakama wanafunzwa cleanliness or hygiene but these children need to be engaged in something until December I should stop in what she is saying because COVID is so health related if they introduce the entrenched teachers we can now combine with the community health worker just to ensure that even in those homestead and in villages the entrenched teacher accompanied by a community health worker ensuring COVID measures are being taken into place people are observing hygiene in a way it can help flatten it can actually help flatten the cabinet essence because apart from community health worker teaching these villagers or I would say citizens on how to carry out hygiene practices then it can also promote other things that we know this COVID you fight it with your immunity I was seeing the Ministry of Health website pages they were telling people how to eat properly this is the right time to engage now the community health workers the public health people to engage I should say every sector is intersectoral education sector cannot be independent on its own health care sector cannot be independent on its own this is what I preach always let's have departments that are intersectoral let's not have an independent kind of governorship where each department is always independent on its own this is a very good example bringing the community health worker bringing the entrenched teachers they are able to go into the communities they are being told by Uwuru the teenagers to not be getting pregnant under their watch this is the right time this is the right time because when you have an entrenched teacher you have a community health worker engaging these students telling them the dangers of unprotective sex they are also teaching them about HIV AIDS and STIs while they are engaging these students this is the right time actually to implement what is it called community participation it's part of actually community development so your Pesa World Bank has given to the government I think this is the high time Uwuru should engage the youth because there are so many youths who are very much unemployed and would actually benefit in flattening the curve and also ensuring now our young people are actually engaged in terms of education you see Hillary also that should be the last comment and after the break we will be talking about the politics that comment we have a lot of resources in this country in this country that had never utilized for example we also have agricultural field officers these are people now that we can bring together right now and start teaching children we don't have to teach these children algebra, long divisions multiplication it's not just COVID it has taken us to factory settings this is a time now to engage children in life skills wacha kama wa limu hawatoshi we engage even the agricultural field office in that place between 10 years or 16 years today we are teaching them how to plant skumawiki wacha watoto wa toke nyumba ni na skills during this COVID time but we can start saying but then we can start saying we need the children what do they learn in school that they cannot learn at home you know every place every place you are is a classroom I say every day you learn something new so we can have a classroom anywhere, everywhere it doesn't have to have desks and books they don't even have to use textbooks that's the problem let them come and community health officer they may come across a COVID patient let them know what to look out for we don't have to have this TV advertisement every time about what to look out for imagine if a 5 year old knows what to look out for COVID yes it helps us it helps us to know if this 5 year old knows that if you have a breathing problem what you are supposed to do to this person who has a problem the emergency response yes the emergency response the first aid agriculture teach them everything it doesn't have to be what was in the curriculum so the agriculture extension officer the community health workers that now in the villages atuna internet atuna data but we have these people in the villages we don't have them in Nairobi do you have agricultural officers in Nairobi county we don't have them we don't have them we don't have them we don't have them that's a good point we will be taking a very short break and when we come back we will look at the politics that was the response to COVID-19 in terms of education whether we will be resuming schools what needs to be done what is possible to be done right now or what is not possible send us your comments on what you feel about the home teaching the untrained teachers going around teaching our students back in school we are saying CBC we take a very short break to not go too far the at 7.30 pm the buzz Y254 gives you a 360 view of what's happening in the entertainment scene


Dear students, in this topic we shall discuss what are sensory modalities and various types of receptors which receive these sensory modalities. Dear students, the sensory modalities are the types of sensory information that we can distinguish or perceive. They are commonly known as senses. Receptors may be external or internal depending on the source of stimulus. The sensory modalities are perceived through specific receptors. These receptors are located in sense organs or they are scattered in various parts of the body. Dear students, first we shall discuss the external sensory modalities. There are five major external sensory modalities of humans which we call senses, five major senses, that is, sense of vision, sense of hearing, sense of touch, sense of taste and sense of smell. The sense of vision is perceived through eyes. These eyes have photoreceptors. Sense of hearing is perceived through ears which have mechanoreceptors. Sense of touch is perceived through skin which has misnourished carpacels. Sense of taste is perceived through taste buds in the tongue which have gastatory receptors. The sense of smell is perceived through nasal cavity that has olfactory receptors. Dear students, now we shall discuss the internal sensory modalities. The internal sensory modalities are perceived through intraceptive receptors. These intraceptive receptors respond to the stimuli or signals from within the body. We shall take few examples or types of intraceptive receptors. The first example is of vestibular system. The receptors of vestibular system respond and monitor orientation of the body. Body's direction and angles and balance are receptors in the vestibular system to monitor. Thermoreceptors are second type. Thermoreceptors are scattered on the skin. They keep track of thermal changes or thermal state of the body. Chemoreceptors which detect chemical changes in the body. Another type of intraceptive receptors is the proprioceptors. These proprioceptors are located in the movable joints. They monitor the position of muscles and joints. Then another type is nociceptors, which are distributed evenly in the skin and deeper parts of the body. They perceive the sensation of pain. To perceive the sensation of pressure, there are pasenian carpacels which are situated deep in the skin. The intraceptive receptors and these sensations are very important because they communicate information to the brain about the internal conditions of the body through the pathways which are not brought into consciousness. They play a crucial role in providing information to the brain about the state of the body and its position in space. Just imagine that we walk using our joints and muscles and they are being used in balance. Just imagine that if we have to give orders to our joints, bones, and muscles to think about which angle we are going to go, whether we are straight or not, then the walk becomes so difficult. Non-human animals have sensory modalities. In addition to such modalities that we have discussed and are present in men, special modalities have distance thermoreception, electroreception, and magnoreception. The distance thermoreception is the detection of heat energy emitted from a distance. It is perceived through special pit organs which are found in some snakes. Snakes use this sense to detect their prey from a distance due to temperature difference. Mammals and other animals have a different body temperature of a few degree centigrade, and snakes perceive this difference from a distance because of their pit organs. Mammal detection is the detection of low-frequency electric signals. This sense is found in some electric fishes and they use this sense to communicate with one another in murky waters. Dear students, In order to perceive the magnetic field of the earth, birds have special magno-receptors which provide sense of direction during the navigation of the sky. These receptors are usually found in migratory birds.


To measure your students, and I was thinking for a student, for somebody who is a beginner in subtitling or digital translation in general, it can perhaps seem a bit overwhelming to think about all these skills that you need to master. And perhaps getting certified is a way to test yourself and see if you have already achieved all these goals. Or it can be also a sort of a goal to strive for. Why do you think there is a need for certification in subtitling? Because obviously, setting up a certification system takes lots and lots of work, right? So why did you decide that it's worth it and that there is this need for certification? I think that this is a question that was in the air for a while. And I think it came to mind when we started thinking about action research, the areas of research that we cared about that could have an impact on people, some kind of benefit. This was during the pandemic, so it was a special period there. And so if we look back at the long list of skills required to be an expert in subtitling, I think that the truth is that if there is no external body out there to test, assess, and certify in an objective way that an individual can perform a job at the highest standards, there is no way for us to know if somebody is an expert, right? Being an expert is not a feeling. It's not a way you care yourself. It's not how popular you are on social media or how many followers you have, right? It's not about that. You need to prove it. So I think that in the realm of translation, at least in the UK, which is where I live and operate, banished such as, you know, the Tartar Institute of Linguists or the Institute of Interpreters and Translators, they offer prestigious qualifications for translators, not operating in the ABT field, of course. And those certified translators are experts for sure that we know it. In the ABT field, we are very fine, far behind in this sense, until now. I think that we have been lucky to have the support of some language service providers that I think believed in this vision. And I think we are in the process of trying to align subtitling as a profession to translation and trying to make this profession officially acknowledged. I think this is the sense of the ABT Pro certification. We can see that the certification is very much present in many disciplines, including translation in general. And it is actually a bit straighter than it has been missing in the area of subtitling for so many years. So it's high time that we have a certification for subtitling.