>> From the Library of Congress in Washington D.C. [ Pause ] >> My name is Reme Grefalda, I don't know how many staffs we have here and how many outsiders so permit me to introduce myself. I had Library of Congress Asian-American Association. This is one of our first programs. I'm told that our guest speaker Dr. Lum has been here before, have you? >> Yes. >> He has been here before about-- I think about six years before I was even alive in the Library of Congress. So I welcome him thoroughly. I welcome all of you for coming today. I guess it's too early for lunch and when you leave, lunch is almost halfway at the cafeteria. So without further ado, may I introduce the Vice President of the LCAAA who will introduce Dr. Lum. Tomoko? >> Thank you so much for coming. I'm Tomoko Steen. I'm a research specialist at Science Technology and Business Division. This is a co-sponsored event of the LCAAA, Asian-American Association, and Library Science and Technology and Business Division. So it's my pleasure to welcome back Professor Lum. He came for the-- our Asian Pacific Heritage month, seven years ago. And this is the second time but a huge data accumulated over the time and well, we hope you can enjoy that, you know, all the stories he is going to tell us. Professor Lum did a Bachelor's Degree at Berkeley [phonetic]. And at that time, there are [inaudible] molecular revolutionists were there and he studied under them. And then he did PhD at University of Hawaii and, Rebecca Cann, who is-- you must-- some of you might know about the Mitochondrial Eve. She is well known for that scientist-- science work. And he is professor at Binghamton currently, SUNY Binghamton, and he's an anthropologist-- the molecular anthropologist. So study anthropology in the molecular level and-- but he covers many different subject including ancient DNA. So we will have a lot of interesting stories here. So without further ado, please welcome with me Professor Lum. [ Applause ] >> Thank you, Tomoko, for inviting me back here again. Is this okay? Can you here me? Okay, so I'm going to be telling a lot of little things that fit together. It's all about the Pacific. It's kind of an overview of the things I've been doing for the last 20 years. I started looking at Pacific migration as a graduate student back in 1989 in the University of Hawaii. And since then, I've kind of expanded from just looking at how people got to different islands in the Pacific to looking at malaria, an infectious disease in the Pacific. And then looking at commensal organisms, how different things got out there, how mosquitoes got out there that then transmitted the malaria. And then more recently, I've been looking at and focusing on modernization and how changing cultures change the health of people in different areas. And then most recently, I'm starting to get into some work on the microbiome and I'll close with that. So I'm going to give you kind of a whirlwind tour of some of the things I've been doing with my graduate students and other students from Binghamton University. And I guess I'll start by telling you a little bit about what my laboratory does. My laboratory is the Laboratory of Evolutionary Anthropology and Health and the basic idea is that humans evolved in Africa and then over the last 80,000 years or so, spread out all over the world. And from one population that was in one place, they're now-- we're now distributed all over the world. And over that period of time, we've adapted in different ways to these different environments. In the middle of the slide, you can see, for example, skin color and how skin color has changed and we now have different arrays of skin colors but we also have different body types and lot of these have environmental influences. Why are some people dark? Why are some people tall and skinny? Why are some people more round? And a lot of this has to do with environmental selection and different processes. This map I'm showing you over in the middle of the slide is looking at BMI, the ratio, how kind of round you are versus how tall you are, and how that changes as you move away from the equator, north and south, and this has to do with heat conservation. But in the same way, our bodies and our skin color has change so has our immune function. As we've gone to different environments, we're influenced by different types of diseases and those diseases influence our immune systems differentially. And we've also had different ways to sustain ourselves. We have different types of food gathering and food production. Different populations evolved agriculture in their societies and different populations will still hunt or gathers until very recently. So our bodies have responded not only to climates and environments but diseases and also diets. And that's part of the story but the recent story is all about modernization and how in the last 500 years, all these diverse populations, they got very different, started as uniformed population, moved all over the world, got very different in very-- in many different ways are now increasingly coming together. And we're finding ourselves people from all over the world with different susceptibilities to the diseases, different propensities for our succeeding and different environments. And different culture adaptations are increasingly finding themselves together, and bringing all those things together, beliefs, behaviors, cultures, diseases, diets, all coming together especially in our modern cities like Washington D.C. But the other thing that's happening in modernization is that we're living in larger groups than we ever lived in before. And so that our-- the various societies and the way that our societies work are also changing. If you're off on a small island like I was a month ago and you walk around and you see someone, the first thing you do is you try to figure out how you're related to that person or who you know. You don't do that in Washington D.C. or New York City, there are just too many people. You can't know every one that you run into. The Dunbar number, the number of humans that we can actually know has been estimated to be something like a 150 or 200, and you bumped into more than that on your way to work. So we can't physically, intellectually, emotionally know all the people that we see regardless of how many Facebook friends you have. So part of that modernization is changing the way that our societies work, changing the way that we have access to foods or, you know, I have TV dinners down here, things that we call foods that may or may not be good for us. And also these diseases, I have some condoms here to show for AIDS and HIV and different diseases. It could be SARS, any of these things that are pandemics and are moving around. So we started off as a uniformed population, we moved all over the world, we adapt to all these different places, becoming very different in very different ways, and now, we're all coming back together. And these I think are kind of the scenarios that are important right now for human health. Specifically, most of the research that I do is focused on the Pacific. How people settled the various island of the Pacific? How they then become adapted to those local environments. Often this meant that as you move farther and farther out into the Pacific, there is less and less raw materials already there. So to succeed, you have to bring your own plants and animals with you. As you move out farther and farther though, you start avoiding some of these different diseases that are common in the tropics, so your whole disease profile changes, your food profile changes. So you have to bring things with you. One of the things that you bring with you are things like pigs inadvertently out to Vanuatu, which I'll be talking to about at length during this talk. The Anopheles mosquito also came and this is the vector for malaria. Malaria then sets up these gradients of selection on different environments that then affect the humans. Secondarily, more recently, we've developed different kinds of medicines to combat malaria. The parasites have secondarily become immune or resistant to these different medicines in different ways, in different places. So I'll tell you a little bit about that. And then I'll close by talking about modernization and effects of chronic disease. I show a little cruise boat here. One of the islands that I worked on Vanuatu and team, where my colleague, Akira Kaneko, eradicated malaria in 1991, they've been having increasing number of cruise boats. They just signed in a contract with Royal Caribbean. Next year, they're going to have 70 cruise boats. This year, they had about 50. So they're already getting about one a week, they're going to get more than that now. This is an island with a population of about 800 residents. These cruise boats dumped 1500, 2000 tourist out a day. And this is a good source of hard currency but it's also changing their cultures. It's changing what they do in terms of their daily activities, what they eat and what resources they have and that's having an affect on their health. All right, so that's kind of an overview of what I'll be talking about within this context of dispersal and diversification and modernization. All right, so I'll give you-- I'll start by giving you an overview of how people got to the Pacific. The earliest people reach the things that we call the Pacific Islands, New Guinea up here and Solomon Islands, Bismarck about forty to sixty thousands years ago at that time in the Pleistocene, the sea levels were a lot lower. So you could walk out from Asia all the way out almost to Borneo and look across at Sulawesi. Meanwhile, New Guinea was attached to Australia which was attached to Tasmania. So you have these super continents at that time. They assumed the Peninsula was larger than the Indian subcontinent. This is now broken up into what is now Indonesia and the Philippines. All right, so people get over there when the voyaging distances across, the seas were a lot smaller that it's still a major biogeographical barrier [inaudible]. So you have placental mammals mainly in Asia and then you have marsupial mammals mainly on Australia and New Guinea area. So you got a drop off of biodiversity and changes there. So humans are getting out to New Guinea and Australia back in the Pleistocene. And then there's this recent expansion off into remote Oceania with fairly recently within the last 3000, 3500 years. Another group of people set on all of these very remote islands. So there's two major waves of these human settlement at the Pacific. And this is very easy to tell archeologically, because the second group of people, we refer to them as the Lapita Cultural Complex, they're the Lapita people. They made this amazingly intricate pottery and it's identical and in its forms, not just its form but its decorations across large distances within a few hundred years. So it's very clear that this is one group of people traveling these distances. They also had a number of animals of Asian origin, the pig, the dog, the chicken, the rat and inadvertently, the Anopheles mosquito that they bring with them. So these are the big things that you find throughout the Pacific and Polynesia, everywhere and these are of Asian origin. They also brought a number of different tree crops and things that were domesticated in New Guinea and in Solomon. And we can also look at the languages of people that are currently within the Pacific and you see that all of these of people that are associated with the whole scene, the recent expansion speak a very closely related group of languages, Austronesian languages that are related to languages in Taiwan and interestingly, all the way out to Madagascar. So the before the European expansion, the Austronesian language family was the most dispersed language family in the world, over half way around the world, particularly on islands in the Pacific because these are also the people that invented the outrigger canoe, and also a starlight navigation. And so I don't know if anybody is a sailing fan, I just come from San Francisco the other day and I was watching some of the Americas cup and they have these new winged boats but they're still catamarans. So 500 million dollars of design later, these boats still look like Polynesian double hulled canoes. So there's still not a better boat out there than the ones at these guys were using to get all the way from Easter Island and onto Madagascar on the other side of the dispersal. So my early work, my dissertation work was looking at mitochondrial DNA, these maternal lineages and looking at what maternal lineages were in different islands and trying to infer where people came from. One of the things that I've discovered was that of the two groups, the possible source populations, Southeast Asia and Australia, New Guinea are very different, they are mutually exclusive groups of mitochondrial lineages represented by these color. The people in Polynesia are predominantly Southeast Asian in their origin of their lineages. But they do have about five to ten percent of lineages that look like they came from New Guinea on the way. You have these islands in Micronesia particularly in Western, Micronesia. Here, I'm showing you the Marianas which looked like they were settled directly from Southeast Asia whereas you have these islands like Vanuatu, where the languages are very similar to languages in Polynesia. They're settled at the same time as Tonga and Samoa and Fiji and yet most of their maternal lineages look like they came from New Guinea. And I've argued in a number of publications that I think this is post sediment gene flow and there's a lot of people moving back and forth. And this one reason why the Anopheles mosquito makes it out there and Vanuatu is the last malaria's island archipelago in the Pacific. So in some ways, there's a correlation between language and genetics and biology and in other areas, there's a discontinuity there and the patterns don't quite mix, which was-- says that there's something interesting going on there in prehistory, and Vanuatu is one of these places. The languages don't match the genetics per se. We also did some studies where we looked at genetic diversity as you moved out from the presumed source in Southeast Asia and New Guinea. As you move out farther and farther, one thing we notice is that the amount of genetic diversity decreases. And this is-- as more recently been shown to be true across the world if you start in Africa and you move outward. You see a decrease in genetic diversity. This is also been shown in terms of languages, not words per se, but if you look at the number of sounds in a language, the South African languages, the click languages have the most sounds per language. And as you move away from that, you get less and less consonants in your language. And you see the same pattern in the Pacific where if you look just at Austronesian languages, these very closely related languages associated with the second diaspora, as you moved from let's say somewhere here in the Western Pacific out to Hawaii, you just lose all consonants. But even from Tonga and Samoa in Western Polynesia to Hawaii, you lose about five or six different consonants. So things get simplified. You lose things easier than you generate diversity, both in languages and genetics. So we show that-- you know, you see this decrease in genetic diversity as you move out into the Pacific and if you incorporate different kinds of patterns that we think we know based on archeology or language then the correlation between the lost of genetic diversity actually increases. Now, I'll tell you a little story about the pigs. And this was kind of a fun side project that started when we were doing malaria's surveys and we heard that there are these very odd pseudohermaphroditic pigs out in Vanuatu. Actually, my colleague Ralph Garruto come in and said, "Do you know anything about these pigs?" And I said, "No." He says, "You work in Vanuatu, don't you?" and I said, "Yes." He says, "These are really crazy pigs, why don't you check them out?" So the next time I went out there, I did just that. I was out collecting mosquitoes for another study that I'll tell you about shortly. And we started collecting samples from these pseudohermaphroditic pigs. So what's the deal with these things? Well, it turns out that pigs are very, very important in the Pacific, partly because you have agriculture but you don't have food storage. It's the tropics, most of your carbohydrates are roots and they don't preserve very well. So you can't get granaries with thousands of life times of food just sitting there. Things rot in the Pacific especially start to roots. So the way that you can preserve food or accumulate wealth is through animals, and if you have lots of pigs and that is a life times of wealth. And this is true throughout the Pacific but it reaches its most important aspect in Vanuatu, where pigs are actually modified biologically for social reasons. And one of the things that they do in the northern islands of Vanuatu is that they will remove the upper canines of the pigs and pigs have indeterminant growth. Canines kind of like rats, they gnaw, and they constantly sharpen their front teeth. Well, pigs have the same thing with their tusks. So if you remove the upper canines, what happens is the lower ones will do a complete circle in about six to seven years and two circles in about 11 or 12 years. And if they look very beautiful, they're not so good for the pig cause these things come up and they puncture the cheek and they sometimes if they do it really straight, they actually puncture the jaw coming back down. These pigs are not happy and you have to kind of hand feed them, they're hard to raise. But if you're in Vanuatu-- Northern Vanuatu and you can grow these pigs with the tusks then you can trade them to your friends who want to take chiefly ranks and they can kill them ritually and take chiefly ranks. So tuskers are very important, the curled pigs tusk, this modified tuskers are very important. They're so important that when Vanuatu got its independence, they put the tusk on the flag. It's also on the national beer, Tusker. There's two national beers that there are tusker, and one is from Kenya and that's an elephant tusk. The other one is in Vanuatu and it's a pig tusk. All right, so here are some examples. This is a wedding, where they're killing a bunch of pigs here. Here's the pig jaws and Jimmy Stevens, he led a failed coo after independence tried to take the northern islands and separate and have them still remain under French control. That's a different story. If you want to hear about that, I can tell you about that. But pigs are very important. This is a pig killing club from Ambrym. Now, if you want to take the highest ranks though in Northern Vanuatu, you not only have to kill a bunch of pigs and a bunch of tusker pigs but you have to kill Narave. And Narave are the special pseudohermaphroditic pigs. These are pigs that have as yet undescribed genetic mutation that results in them not having differentiation of their external sexual genitalia. So these are male pigs, chromosomally male pigs without a penis and without external testis. Well, sometimes they'll have one, sometimes they don't have any, sometimes they'll be inside of their body. So they produce testosterone but they have nothing to do with it and these are ornery pigs. And you can't castrate them like other tuskers to calm them down because they-- their testis are inside their bodies. So these are really tough to grow and maintain. They're sterile, they don't have a penis. So they have to be produced through their mothers and sisters, right? So you have to get this tusker-- pseudohermaphroditic tuskers from your friends if you want to take the highest chiefly ranks. So these are still important and we wanted to take a look at this question in terms of these ideas of modernization and globalization. Globally, in 1850s or so, European and Asian pigs were bred together to build the fast growing pig that is common now, the global domesticated industrial pig. And these pigs have been distributed all over the world. And so one of the questions were, these pigs in Vanuatu, to what extent are they, the original pigs that got out into the Pacific, and to what extent are they-- have they been interbred with this global domesticates? So we've got DNA samples from 16 of these Narave tuskers, these pseudohermaphroditic pigs. We got nine samples from this other interesting pig in Vanuatu. In the southern islands, they have hairless pigs called Kapia. And these are also high maintenance because they got sun burned. So you have to baby these pigs. So you have two genetic mutations, two high maintenance pigs use for social reasons. This is the oaker phase pinning of a chief on this Kapia. So these are very important pigs. They are traded for turtles and humans and other high status things and they're use for chiefly purposes. We got a bunch of those guys. We got a bunch of controlled pigs, pigs just wondering around, pigs that were stuck in little bags on airplanes, pigs being carried to feast, we just pulled hair samples off some of these pigs to get controls from the same islands then we sequence their DNA. And what we found is that the Narave is almost-- all of the Naraves, and almost all of the controls from the same islands where they keep Naraves are the original Pacific pigs. Whereas the Kapia, these hairless pigs, a lot of them-- most of them are global domesticates. And when we think about this at the genetic level, this makes sense because Kapia's are bald pigs. You can breed them with anything and then just select out the bald babies from the litter. Whereas this Narave, you have to breed them from their mothers and the sisters of previous Narave. And we're looking at maternal inherited marker. So the maternal line is past through, everything passes through the maternal line and so the mitochondrial DNA of these pigs is maintained. Plus these things are so valuable, they don't want to interbreed with any other pigs, right? All right. So that's our little story for the Narave. When we look more globally, we found that these Pacific pigs that we were looking at in Vanuatu are very closely related to Hawaiian and the French Polynesian and New Guinea ones and the ones in Indonesia. Interestingly, nobody had seen this but there was-- we found this paper and there are some Vietnamese wild boars and one of them also had this sequence. So we think that these guys are coming out of Southeast Asia, maybe not Vietnam but somewhere in this area and relatively quickly, they changed their morphology and get them down to a small size that can fit on a boat and be taken to all of these different islands in Pacific. But the same lineages that we have in Vanuatu are still found in these Vietnamese wild boars here. Okay. Then I'm going to switch gears away from these funky domestic animals and tell you a little about the mosquitoes that transmit malaria. What we knew before was that there were-- has about 12 different cryptic species at the genetic level for the Anopheles punctulatus group. Traditionally, they were-- they're known as three different species based on their proboscis morphology but once people started sequencing their DNA, it turned out that there about a dozen of these things. There might be a few more now, a few less, this is all slightly changing but each of these different species had different environmental adaptation. Some live on the coast in a very salt tolerant, some are living in the mountains, some are living in different environments. In Vanuatu, it was reported that there's only one. This kind of make sense because people have only been in Vanuatu for about 3,000 years, whereas the Solomon's and New Guinea and Australia, they been for, you know, since the Pleistocene. So we saw that there was a difference in the number of species based on the time of human habitation. But we also knew that Vanuatu is very rugged. There's 80 inhabited islands, 0some are small, some are big, so we went out there just to see what the genetic diversity of these guys look like if there was really only one and how they're related. So this was kind of the master's project with one of students Deni [phonetic], and we went out-- this is some of the data we've analyzed, we've still got another couple of thousand mosquitoes sitting on my lab, undescribed yet. But this is from about a thousand mosquitoes from five different islands. And what we see is that, there's one main lineage that's found on all the islands. This-- what I'm showing you here on this slide is a network diagram. So each of these are genetic sequences, each circles have genetic sequence, the size of the circle represents how many individuals are in our data set had that sequence and the length of the bars, they're all are just one mutation away. So you see this that there's a lot of mosquitoes that are identical and they're found on all islands, the different colors or the different islands. And then you have a lot of island specific mosquito lineages, which suggest that one group of mosquitoes came in, it went to all the islands and then the island-- the mosquitoes don't move back and forth between the islands so you generate a lot of island specific lineages, which was interesting for us from a malaria control perspective 'cause that means that the mosquitoes aren't really moving back and forth. It's the people that we got to worry about not the mosquitoes. We do have another lineage where we're calling this group two which looks like it is a bit different and it's only on the north. So it looks like there was one main introduction of Anopheles mosquitoes in Vanuatu and then maybe a second introduction into the northern islands. When we started looking at the diversity of these mosquitoes in different islands, we get really good correlations with island size. So the number of lineages we find per island, the diversity of those lineages are pretty well correlated with the size of the island and also the number of languages that the people speak. So the same kind of area, size, parameters are effecting both the Anopheles diversity and also the human cultural diversity. Human population sizes is pretty much correlated except for this island Tanna, where there's a lot of people on one small island, but they don't speak very many languages. That's another story about Tanna. All right, so then we had data from mosquitoes, we had previously looked at data from humans and the malaria parasites themselves. And what we found there was that the malaria parasites only moved around when the human also look like they moved around. Where there was human gene flow shown here by this connection between the purple lines, between Malekula and Pentecost, where humans were going back and forth, the parasite-- the malaria parasite also went back and forth. We added the mosquitoes to that and what-- we got a good correlation too. The places where there were shared lineages were also the places where humans were moving back and forth. So what we think is-- the key to this is controlling human movement. If you control human movement, you control the movement of mosquitoes and you control the movement of parasites. The next little bit I'll tell you about is a little bit about the way that humans have responded to malaria. And this is-- I just showed you some work that Deni had done for her master's degree, this is some of the work that she did for her PhD which she just defended in the fall. And what she wanted to do was she wanted to look at the ways, the different humans on different islands responded to malaria. So she looked at a total of 23 populations over 1,200 different samples, individuals from those different islands. And she screened a number of different genes. We have Southeast Asian ovalocytosis which is a mutation that helps you resist malaria, but it's not a very good one. I say it's not a very good one because it really distorts the shape of the red blood cell and to this state, no one has ever been found with two copies of this gene. So-- and when you have populations with a high frequencies of heterozygotes, you have a higher frequency of stillborn children. So the implication is that if you inherit two copies of this gene, then you're not even born, you're stillborn. So this is a way to avoid malaria but not a very good one, a very costly mutation to avoid malaria. We also look at this Gerbich negatively allele and this also resist malaria. CR1 also resist malaria. And then we looked at this TNF-alpha promoter. So TNF-alpha is part of the immune response and it's a general fever response. So if you have this promoter, it up-- regulates your ability to cause a fever but in a malaria's environment, it also leads to a higher susceptibility of cerebral malaria. So we had three resistant alleles and one susceptibility allele, then hopefully if all of these things are working the way we think then we should see different patterns on those. You know, where the susceptibility once are high, resistant should be low and vice versa. We have different alleles with opposite selections on them. And then, because like I told you, the people in the Pacific especially in Vanuatu are composite between these two different gene pools, part of the main group of people are coming in the Pleistocene, near Oceanic people, and then you also have the second movement of people in from South East Asia, both malaria's environments but different gene pools that are developing over long periods of time. So instead of focusing on any of the single locus or alleles that are single locus, what we did was we sum this altogether to get what we're calling a malaria resistant genotype score. So for example, well as I said, you can only get one of these SOAs so you can get a plus one or you add zero for that locus. Gerbich, those homozygotes, so you can go from zero to plus one to plus two. Same with CR1, zero, plus one. TNF-alpha, you can be at zero minus one, minus two. So you can either have go from minus two to a plus seven in terms of your malaria resistance-- or plus five, sorry. Plus five to minus two, a range of seven. And so we get the score that sums up all this different genetic inherited ways that you combat malaria. Because the idea is that, any population has certain numbers of alleles in it and you can pick and choose the evolution can tweak any of those and it's not one of the others, it's kind of a composite of those and that's your immune response to these different diseases. We also looked at a number of unlink STRs just to look at the genome and to see whether or not that has the same pattern. Hopefully, it doesn't have the same pattern. If it does then what we are really looking at is population history and not disease selection. And then we looked at a number of things that are involved with Anopheles mosquito habitat quality, what the latitude is, what the altitude is, what the longitude is. As you go up a mountain, it gets colder and drier, so the mosquitoes don't live as well. As you go south away from the equator in the Pacific, it gets colder, it gets drier, so lowlands in the tropics right there in the equator have the highest level of malaria. As you move away from that and up the mountains then you get less malaria. So we have gradients of selection and differential gradients. And then because we're pulling this malaria parasite out of human serum samples, we can actually look to see what the frequency of the people in each of this population at the time of sampling had malaria. So that's our point prevalence of malaria. So we have a guess estimated how much the malaria selection was by just looking at how many people have malaria in that population. And then we also looked at language and geographic distances. I'll tell you a little bit about this first part of the data set which is just on New Guinea, a few Austronesian populations and then these people to came later, a lot of these populations that speak Papuan languages that have been there presumably since the Pleistocene across these gradients of altitude. What we see for these-- those different genes that I showed you, what I'm showing you here on the-- on these axis is the level of malaria, the point prevalence of malaria and as that increases, the frequency of the resistant allele CR1 increases, the frequency of the Gerbich negativity allele increases, they frequency of this TNF-alpha, that's the susceptibility one goes down. So those three worked the way we would expect them to. The only one that doesn't respond very well is this Southeast Asian ovalocytosis, that's the kind of flat. But again, this is the allele that's not so good. This is the expensive one and the one that you don't really want any way. And if you only have that, it's fine. But if you have a choice to select for any other allele to resist malaria, those are the better ones. So it kind of makes sense when we start adding all these things up and summing them up, we get a much better correlation even in the ones we see. So these ones have 0.73, this is 0.88. When we add them together into our malaria resistant genotypes score, the correlations come up a little bit. So we think this is a good method. The only other thing I'll tell you about her data when we look at all 23 of those populations and we just focus on this malaria resistant genotype score, what we see is that the people on the coasts and some of these islands on the coast, they have a lot of malaria, have on average almost two different alleles that resist malaria. And then as we go up these mountains into the highlands of New Guinea or go to these Polynesian allies where there is no malaria, people often have less than one or almost one susceptible allele. So across these gradients of selection within the various region, a small region, we have big differences in the selection on these different alleles. And this is-- it will be important in about in three or four minutes, so just kind of think about that. Highlands and small islands versus coastal malaria selection, 'cause what I'm going to tell you next about is drug resistance to malaria. And so this is an NIH funded project that we're just wrapping up and it was to look at the evolution of chloroquine and a resistance in malaria parasites in the Pacific. The general history of this is that after World War II chloroquine became very important. It was actually discovered by the Germans during World War I, but for some reason, it was claimed to be ineffective for malaria. And there is an argument that Himmler controlled all the revenues from these pharmaceutical companies and the scientists just didn't want to get him the rights to this. So they low-ball the effectiveness of this drug. In any case, after the war, the US independently discovered it and then the Germans rediscovered it and chloroquine became the most important antimalarial. But within about less than a decade, we started to see resistance appear in Southeast Asia and simultaneously, in South America. And then in the '70s, it appeared in the Pacific and also in Africa. Now, this is kind of interesting because the most malaria areas are actually in Africa. So resistance doesn't appear where there's the most malaria, it actually appears where there is the least malaria. So this is kind of interesting and this will tie into my story on the Pacific. It wasn't until about a dozen years ago that we actually knew what the molecular basis for this resistance to chloroquine by the parasite was. David Fidock at Columbia discovered though a series of very elegant experiments discovered that there is one single amino acid in one gene that is-- that's been shown to be correlated, a hundred percent correlated around the world with resistance to chloroquine, so it's one amino acid change. But it's a little bit more complex in that because there is no parasites that have ever been found today that have only that one mutation. All the resistant of parasites have a swift of eight to ten different mutations including that one. And different regions of the world have different sets of these complex haplotypes. So there is a big debate over the last five or six years of how these complex swifts in mutations evolve. Does that magic case 7060 appeared first, and then you need these helper mutations to make that genotype more fit? Or do you get these kind of tolerant mutations and then case 76 comes as the-- kind of the linchpin of all that entice everything together and pushes that parasite over the edge. So what we wanted to do is to actually look at this process in a real time by exploring a series of samples from the Pacific that had been collected in the 1950s, '60s, '70s and '80s that spend this time of the evolution of drug resistance within the Pacific and just sit their and watch mutations accumulate. So that's what I'll show you now. We just published some of these in PLOS [phonetic] earlier this year. I'm going to show you decade by decade and region by region. So in the lower right of all these slides is kind of color coded region of where these samples were coming from. We've got some from the north coast, we've got some from the highlands, we got some from the south coast in this early '59, '60 period. All of them were susceptible to chloroquine. There's a few mutations out here but not very many, not very interesting, none of these magic case 7060 guys appearing yet. These are the same network diagrams by the way. So each of these different circles is a different DNA sequence and the size of the circle represents how many individuals in that decade have those mutations. '62, '65, the same thing, we have samples from now from Vanuatu, from these different coastal highland populations, they're almost all the susceptible guys. These guys right here are probably susceptible too. You see a few amino acid changes but nothing so interesting. 'Till we get to the late '60s and early '70s and then we get all of this diversity coming out. We get diversity, we start getting case 7060, this magic resistance guys popping out here. But what-- I want you to notice on this is almost all of these mutations are yellow, so the coming out of the one population and it's not like the yellow guys are more than a third of the total data but there are like 90 percent of all of the interesting mutations coming out. And the yellow guys are from these very small islands in Vanuatu. In '79, we got this nice highland population and for this decade, we just-- we don't have any from the islands but we start seeing all these really bizarre interesting fully formed, fully resistant genotypes appearing in the highlands of New Guinea but not in the coast again. Our last sample from the late '70s and early '80s, we have both the small islands and the highlands, they all have these resistant guys. Some of them are identical but these are on opposite sides of the pacific in between of the lowlands where we still don't have any resistant parasites. So this is the summary of all the mutations and all of the interesting ones or the vast majority of the interesting ones, I hope you can see here yellow and red. And so, as I told you a few minutes ago, when we look at the human beings from the same populations, the yellow and the red guys are the guys that have very few inherited resistance to the parasites. They have the least functioning immune systems-- inherited immune systems to resist the malaria. You and I, if we go to a malaria's country, there's three things that can help us with malaria. One is our inherited genetics. The other one is what we've developed during our lifetime, how many times our immune systems have been exposed to malaria? And the third thing now is pharmaceuticals. So really, the pharmaceuticals are being held back by our inherited genetics and our experience with the disease. What we see is that the guys, the parasites that evolved resistance the earliest are the ones that are in the bodies of the people that had the fewest inherited mutations to help them out. So basically, those are the human bodies that are like the baby boom. They can figure out, they can explore this mutational space and tweak their genes in different ways and still survive because the immune systems of those human beings are weaker. And once they develop this complex haplotype, then they can invade into the lowlands where the people that have high inherited resistance live and they can then invade those areas, and they do this very rapidly. If you go this areas now or even five years after our sampling dates in the early '90s, almost every parasite is resistant. But five years before that, there were no resistant parasites in the lowland. They're only in the highlands and small islands. And nobody would have known this if we didn't have this amazing series of collections that predated and bounded that time of disease resistance. So when we put the human genetics together with the parasite genetics, we can actually see what the selective forces were that encourage the evolution of drug resistance in this parasites. Okay, now I'm going to switch gears again and talk a little bit about chronic disease, then I'll tell you a little bit about my favorite archipelago in the world, Vanuatu. This is the most interesting place I think to do research because it has currently about 240,000 people on 60 inhabited islands and they have over a hundred indigenous languages. So it's the most culturally, linguistically diverse place on the planet. Some of these islands, the larger ones like Santo and Malekula, have over 20 languages on them each. So this is really interesting. Most archipelagos at some point in prehistory, there is some kind of cultural homogenization either initially where only one group of people founded that island or something happens in and the island is homogenize, not this place. There's so many different languages and cultures and throughout prehistory, they're trading things, they're in contact with each other, they're trading sculptures, carving forms, poems, sand drawings, the rights to do different things and they're doing this while maintaining cultural diversity. And so in some ways, I think this is really neat model for globalization. How can you be in contact with people without losing your cultural identity and be functional? All right, currently about 25 percent of the population is urban which means you either live in Port Vila, on Efate or in Luganville, on Santo. But there's-- the majority of the people are still rural and there's big gradients in development. And that's we're working there, we want to know what happens when you start controlling malaria and then chronic disease starts coming up with modernization. To give you a feel at some of these differences, these are the five islands that we work on last summer. In 2007, we worked on three of these. This last summer I was on the same three again that are subset of this. I was on Ambae. Ambae has a very little infrastructure. They still have malaria. It's very rural and most of it is very hard to get around, no running water, no electricity except for generators in some small areas. We also have an Island Nuna, which is on the back side of the main island, and it doesn't have very much infrastructures. It still has malaria and a lot ways, it's like Ambae except that US just built this wonderful road and you can get from the backside of Efate over to the capital of Port Vila in about an hour. And in Port Vila, you are in a powered grid, you have WiFi, you have supermarkets, you can buy-- you'd had a dual French and British colonialism. So you can go into one of this French grocery stores and get 30 kinds of cheeses and five kinds of patty, 50 kinds of wine, you can get anything you want in Port Vila. We also work in Aneityum, this is an island where my colleague I've mentioned eradicated malaria in 1991, and they've been getting increasing tourism. They've got this little atoll where they make all the tourist stay and they built this complex now. That now it has like six flash toilets. Here's only one flash toilet on the main island but there's six for the tourist. And there's these big markets where they'll braid the tourist hair and they'll sell in little nick-nacks or take him out in game fishing. And so every time the tourist boat comes and now, next year is going to be 70 times a year, they drop anchor and they pay the village association 5,000 dollars. And then they go off and they spend another maybe 5,000 dollars on the hair braiding nick-nacks and then they spend another 10,000 dollars on the fishing tourist and other things. So every time one of this cruise boats come in, they collect 20,000 dollars of hard currency. So this place has been changing really rapidly. In 2007, there were three generators on the island. 2011, there were 29 generators on the island. This last summer, I was there a month ago and everybody is switches in to solar. And everything is just leaps and bounce, everybody has cellphones now. They never had cellphones in 2007. Even now, this last summer, little kids, five, six-year-old kids have cellphones. They don't work as cellphones, they work as little iPads or something. They play games on them because their parents when they get new cellphones, they give their kids their old ones. So these kids are running around playing games and taking pictures. And then we also went to Futuna, this Polynesian out wire island, and this is interesting because it's just a small rock sticking out of the ocean and it's so rugged that they've never had malaria 'cause they don't have any standing water, the water just kind of runs right down. So this is the population with no infrastructure but no malaria. So these are the kind of the five islands that we've been looking at in terms of modernization. No infrastructure and malaria-- no direct infrastructure and malaria but access to the main capital, increasing tourism, no malaria. No malaria, low infrastructure, and no malaria and lots of infrastructure. This is a preliminary data from last year. What you see, this is the obesity rate, and when you go from no infrastructure and malaria, there's only about seven percent obesity, same with Futuna, the rugged one without malaria. You go to the one with increasing tourism, it's up to 14 percent. You go to the backside of Efate, it's up to 22 percent. When you go to the town, it's 34 percent, it's like the US. So the rate, even within the small archipelago where there's only 240,000 people, you're seeing the gradients from subsistence agricultural and very healthy people in terms of chronic disease to situations that are not, unlike Australia or Europe or United States. And when we did a survey, one of my graduate students is really interested in internet addictions. So we want to look at technology acquisition and the usage. Just have you focus on this one line, Ambae has 40 last year. Now, I haven't look at the data from this year, but at that time there were 42 percent of the people, the adults had cellphones in Ambae. Futuna, there is 21. Aneityum, there's 65. Nuna 78, Efate had 81 percent. So again, this is what the US, 81 percent of the people have cellphones. The interesting thing, Futuna didn't have a cell tower last year, and 21 percent of the people had cellphones. [Laughter] And they are either using them as iPads or, you know, these are the people that were moving back and forth, and they spend a lot of time on another island, so they had cellphones. But 21 percent when they don't even have cell towers, but all of these other things are correlated with that. So the more time you spend sitting around on your computer, and not going out growing your food, the more time you spend eating stored dense food are correlated with these obesity rates. This is just same data except for splitting it up into males and females, young adults and older adults. This red line right here is overweight, a BMI of 25, and you notice that most of the young men are fairly fit. But the older men as you get more and more infrastructure sect moving into on average into the overweight category, and female is exaggerated. This solid one right here is the obesity rate. Again, younger women are in general more fit than the older women but by the time you get out to Efate, where they have their powered grid and everything else, the average woman, older woman is obese. So these are very big differences between men and women, and one thing that we know happens with modernization and the increase of chronic disease is reduction of the age menarche. So if we look over the last 150 year in Europe and America where we have this data, back in 1860 the average women in Europe and America is getting their first period some around 15, 16 years old. And now it's down to 12 and a half, and this happens over 150 years. And part of this has to do it with energetics. The body has so much energy that starts telling them that they're-- its time to reproduce. All right, so their bodies matured faster than their minds are in the developing world. This is our data from last summer, we asked all the women in our survey, when you had your first period, and this is broken down by age groups. So the oldest women, they had their first period around 15, 16, then it drops down to about 15, and then the youngest classes down to 13 and a half. So within few, maybe one generation, we're seeing that changes that happened over 150 years in Europe and America happening in Vanuatu due to modernization, and they're getting so much energy. And this is-- you put the cellphones together with the age of menarche, and this is a big problem because now, that teenage pregnancy rate is going up, and also the rate of sexually transmitted infection is going up because all these young people. And that we have a technology in generation gap in this country. Young kids are much more competent at using these devices than older people. But more so in Vanuatu, a lot of these older people they're barely literate, whereas the young kids, they pick up these cellphones and they're making dates in the bush and not telling their parents where they're going, and where they're forming all these networks with maybe some good consequences. But in-- what I'm saying in the sexually transmitted infections, there's also a dark side of this, and this is an increasing problem. Getting back to this idea that the males are somehow showing less chronic disease or obesity than the females, I started thinking about this, and I've been working in Vanuatu now for 12 years, and one of the things that I know that the males are doing that the females aren't doing is drinking their ritual drug kava almost every night. And kava is a root, you take it out fresh, you clean it up, you grind it up. In the northern islands, you take a piece of coral, and you braid it, and then you strain it, and you drink it. In the southern islands, you actually chew it up, and spit it out, and then take that and mix it water, and you drink that. And what it does is it's a postsynaptic neuron inhibitor. It makes your body really loose, and it's a muscle relaxant. If you drink a lot of it, you lose control of your body, and its very hard to walk, very easy to fall down, but your mind is to kind of lucid, you get sensitive to light and sound, but it makes you very calm. And it's probably why Vanuatu has to one of the lowest crime rates in the Pacific because most young males are sedated every night of the year. And if you sedate all your young males, crime somehow goes down. So-- but the other thing it does is it also it's an appetite suppressant, and it's actually marketed-- well, it's marketed around the world as an herbal Valium relaxant, antianxiety compound. Until there was a few cases of liver failure a few years ago, and we can go unto that later. But it kind of suppresses your appetite. It's been marketed in Japan as a diet pill. So when you drink kava, you don't really eat much. So I was thinking maybe this has something do to with this difference between makes and females. So last year we went out, we asked people, how many people where drinking kava, and how often they're drinking kava. And what we found is yes, almost all the males over 70 percent of the males in most islands are drinking kava almost every night, five or six times a week, whereas the females not so much. One island in Ambae, the older women drink a lot of kava. I went back this year and actually asked them how many-- how much kava they're drinking each time they kava, and the women in Ambae are drinking a lot of kava, almost every night just like the guys in most islands. The women in Ambae are also the thinnest ones. So there's something about taken an appetite suppressant every night and maintaining your weight. And this now can be a problem with modernization because the other thing that Vanuatu does as it plugs in to the rest of the world is part of this Pacific music reggae, Caribbean reggae culture. And this is O-Shen, son of a missionary from California who grew up in New Guinea and now spends half of his time in New Guinea and Hawaii, and he's one of the biggest music stars in the pacific hanging out with Ziggy Marley. This is a Vanuatu flag and this is a reggae band from Vanuatu, and they've replaced the pigs tusk with a marijuana leaf. These are different reggae bands. This is one of my survey assistance with his dog, Ganja, on Aneityum. And so we also asked the guys, do you smoke ganja? And on every island, the young men said yes, 5 to 15. On one island, almost 30 percent of the guys-- these young guys on Aneityum are smoking ganja. So there's-- now, there's kind of a switch from kava to ganja and if you go from an appetite suppressant to something that creates munchies, then maybe that protective effect from ganja is going to go down. All right, so the last from kava is going to down. The last thing I want to tell you is that, what I did this summer, we're wondering about how chronic diseases affected by diet, eating fish, eating fruit bats, pigs, octopus, lobsters, sharks. As those diet exchange to more modern diet, what has happened to you microbiome, this one to two litters of bacteria that live in your intestines and it's fed by all the things that you don't digest. And so what I did was I collected from three of these islands, Ambae, Aneityum, and [inaudible], saliva samples and also tooth swabs to take a look at what are the bacteria living in people's mouth, and how that is correlated with their diets. We took dietary recalls, which we also have from 2007, 2011, and we're going compare the microbiome data to their diet data and their chronic disease diet, and maybe next time I come, I'll have something to tell you about that. And I'll finish by just acknowledging all the people that we've been working with in Vanuatu. My graduate students and my colleague Ralph Garruto, and my lab manager Rita, and all of the people in Vanuatu who helped us out when we're there, and my colleague Chuck Whites [phonetic] from Temple University, and funding from NIH [inaudible] grant, and Binghamton University. And with, that I'll take any questions you might have. [ Applause ] >> With the spread-- >> Could you repeat the questions? >> Okay. >> With the spread of mosquitoes-- >> Yes. >> -- from island to island or from continent to continent, is it the same with the spread of cockroaches? >> Cockroaches and mosquitoes. >> Isn't the eggs of the-- >> I'm-- I don't think so, mosquitoes-- oh sorry. The spread of mosquitoes, how is that similar to spread of cockroaches? Cockroaches have dry eggs that can last for a long time whereas the mosquitoes, we think what's happening is they're actually being distributed in the water. So I found them in the bottoms of canoes, and the one that gets all the way up to Vanuatu is the salt tolerant one, and this one can live in brackish water, and also in seawater, and still develop normally. So we think that the prehistoric transmission was in boats. Recently, since World War II, Guam has something like seven introduced mosquitoes species probably due to World War II. So I think the mosquitoes is more moving around wet things, either moving around like live plants or the other big one is there's a trade in used tires, and rain gets in these tires, and they're really good breathing spaces for mosquitoes. But most of the Anopheles, they don't do so well in non-fresh running water, so it has to be pretty rapid, so they don't transmit through boats or they don't get out to places very easily. And that's why maybe Vanuatu is the last place that never gets down to New Caledonia, it never gets down to Fiji, those distances are a little bit longer. To get down to New Caledonia, you have to go through this upraised coral rift, islands without much fresh water, but I think it's a very different process. But, you know, Hawaii now has a lot of mosquitoes and that was historically from I think the Portuguese or Spanish ship dump out their water, and they had mosquito larvae in there. So if you were in Hawaii 150 years ago, there were no mosquitoes, and that would have been really nice. [Inaudible Remark] >> Just a point of information, your slide about diet, change in age of menarche. >> Yup. [ Inaudible Remark ] >> Right. >> So it was a nice cut and dry explanation. You introduced another term, they're [inaudible] very energize. What forms the difference? What has changed 40 years ago, just this course? >> Nothing, its body fat and energy usage. Oh sorry, yeah, age of menarche and how that affects, how is that correlated with just body fat or exercise, and that's what I'm talking about this. You know, your energy inverses your energy out. Yeah, if you're female athlete, and you have less than I think seven percent body fat then you start menstruating. And so, I think that was driving this that people start becoming more sedentary. They're not going to their gardens, they're not growing their own food, and they're also going to stores, and buying more energy dense foods, so less activity, more energy, and so the age of menarche is dropping. And so we've-- you know, other surveys in 2007 and 2011, we also looked at activity, we had looked at diet, we looked at material possessions. So we're trying to look at all those different variables to try to figure out what are the most important ones, because chronic disease is the biggest expense for our healthcare in the United States, but Vanuatu doesn't have any money. You know, if they go down that same path, then they are in big trouble. So if we can figure out ways to do education and prevention before it gets worst, then we're ahead of the game. But if we don't, then maybe the game is over, because there's already 25 percent of the population that is in the state. Okay? >> You mentioned human bile which seems to be a hot research topic for the last few years, and apparently, [inaudible] is what digestion is through the billion small intestines but apparently, the bile that digest materials ordinary blood [inaudible] in our large intestines. People are talking about absorption of those, maybe we need some of that. So tell me something about that, about the bile digesting to what extends it's absorbed in our human body? >> Well, sorry, so she's asking about the microbiome and digestion, small versus large intestines, these things that we used to think about it just fiber that were somehow good as just physical movement of things through your intestine are now thought to be actually feeding a diverse community of organisms. So I guess the idea is my idea-- my understanding is that you have this ecosystem within you, and you're feeding that ecosystem in addition to feeding yourself. So if you only eat very easily digestible things that you digest, then you're starving off this vast array of things that could potentially be inside of your intestine. And those are things that we presumably evolve with. And so if you're going around and only feeding yourself, and being selfish you migth, and feeding these other things, then you're going to without half your digestive system. And so they're associated with the lower diversity of these organisms are things like irritable bowel syndrome, potentially Crohn's disease, a lot of these autoimmune functions of the intestine are maybe influenced by a lack of these diverse organisms that we evolve with. And so that's why were-- we have this nice gradient, we already know something about the rates of chronic disease, we already know something we think about their diets, and so we like to see how the microbiome diversity correlates with those things. The other interesting thing that I didn't really mention but I touched on this, the other thing is in the southern parts of island, these guys are chewing kava, spitting it out, and then everybody sits around and drinks it, so you're also sharing your microbiomes with each other as you drink kava. So one of the things that we did as a group, when we out there was we did-- sampled our microbiome before we left the US, well two of us left the US, two of us left Japan, and then once we got there, we sampled again then we went down to southern islands, and drink kava, the people had chewed, and we sampled it again. And we went to the northern part where they ground cava, and we sampled it so again. So what is the effect of kava on your microbiome? What is the effect of drinking kava that somebody else has chewed on your microbiome? How long do you-- does it take to be in another environment being exposed to thwaw different organisms that are not potentially washed off? Tou know, you're not going to supermarket where things are, you know, sterilized somehow. These are, you know, things picked off of a tree and kind of wash in a river and then you eat them. So you're getting a lot of things from the environment in these different areas, and so one aspect of this traveler's diarrhea. This traveler's diarrhea just coming into a new place and finding an equilibrium with what around you and what you have. All right, so how quickly can these things kind of change and how flexible are they? Because everybody is born with nothing, and then you get something when you're breastfeeding or your early age, and some of studies have shown that all breastfeeding babies around the world have the same things in their gut. It's only when they start weaning and getting these regions specific diets that the diversity of those things changed. But how fast does it change in so many within already established microbiome? How resistant is that to change? Do you have to just go to some place and eat local foods, or do you have to physically taken someone saliva by whatever means So we kind of did that as a side project. We monitored our own microbiomes as we did these things. >> Did you take antibiotics 'cause you mentioned the research in diarrhea? >> I didn't take any. >> If there's no there questions, please join me to thank Professor Lum again. Thank you for coming. [Applause] >> This has been a presentation of the Library