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Human Migration, Malaria & Modernization in the Pacific: DNA Studies — Transcript

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0:01from the Library of Congress in
0:03Washington,
0:21DC. My name is Ray Grafala. I don't know
0:24how many uh staffers we have here and
0:26how many outsiders. So, uh, permit me to
0:30introduce myself. Um, I head the Library
0:33of Congress Asian-American Association.
0:36This is one of our, uh, first, uh,
0:39programs. I'm told that, uh, our guest
0:42speaker, Dr. Lum, has been here before.
0:46Have you? Yes, he has been here before
0:48about I think about six years before I
0:51was even alive in the Library of
0:53Congress. So, I welcome him thoroughly.
0:56Um, I welcome all of you for coming
0:58today. Uh, I guess it's too early for
1:01lunch and when you leave, lunch is
1:03almost halfway uh at the cafeteria. So,
1:06without further ado, may I introduce the
1:08vice president of the LCA who will
1:11introduce Dr. Lum Kamoko.
1:17Thank you so much for coming. Um, I'm
1:19Tomoko Stein. I'm research specialist at
1:22science, technology, and business
1:23division. This is a co-sponsored event
1:26of the LCAA, AsianAmerican Association
1:29and uh library science and technology
1:31and business division. Um so it's my
1:35pleasure to uh welcome back the
1:38professor. uh he came for the our Asian
1:41Pacific um heritage months uh 7 years
1:44ago and uh this this is the second time
1:48but the huge data accumulated over the
1:51time and I hope you can enjoy that you
1:54know the all the stories he is going to
1:57tell us um professor lamb did a
2:00bachelor's degree at baker and uh at
2:03that time uh the so many leading
2:06molecular evolutionist were air and he
2:10studied under them and then he did a PhD
2:12at the University of Hawaii under um
2:15Rebecca K who is you must some of you
2:19might know about the mitochondria eve
2:21she's well known for that scientist
2:24science work and um he is um professor
2:29at banton currently Sunni Banton and uh
2:33he's a anthropologist molecular
2:35anthropologist so study anthropology in
2:38the molecular level and uh but he covers
2:41many different subject including ancient
2:43DNA. So we will have a a lot of
2:46interesting stories here. So um without
2:50further ado, please welcome with me the
2:53professor lam.
2:55[Applause]
2:59Uh thank you Tomoko for inviting me back
3:01here again. Um is this okay? Can you
3:03hear me? Everybody hear me? Okay. So,
3:06um, I'm going to be telling you a lot of
3:09little things that fit together. It's
3:10all about the Pacific. It's a, uh, kind
3:13of an overview of the things I've been
3:14doing for the last 20 years. Uh, I
3:16started, uh, looking at at at Pacific
3:18migration as a graduate student back in
3:201989 in University of Hawaii. And since
3:23then, I' I've kind of expanded from just
3:25looking at how people got to uh,
3:27different islands in the Pacific to uh,
3:29looking at at malaria and infectious
3:31disease in the Pacific. and then uh
3:34looking at commensal organisms, how
3:35different things got out there, how
3:36mosquitoes got out there that then
3:38transmitted the malaria. And then more
3:40recently, I've been looking at and
3:41focusing on modernization and how uh
3:44changing cultures changed the health of
3:46people in different areas. Um and then
3:49most recently, I'm I'm I'm starting to
3:50get into some work on the microbiome and
3:52and I'll close with that. So, I'm going
3:54to give you kind of a whirlwind tour of
3:56some of the things I've been doing um
3:58with with my graduate students and and
4:00other students uh from Bingmpington
4:02University. Um and uh I guess I'll start
4:06by telling you a little bit about the
4:08what my laboratory does. My laboratory
4:10is the laboratory of evolutionary
4:11anthropology and health. And the basic
4:13idea is that uh humans evolved in Africa
4:18and then over the last 80,000 years or
4:20so um spread out all over the world and
4:24from one population that was in one
4:26place they're now just we're now
4:28distributed all over the world and over
4:30that period of time we've adapted in
4:32different ways to those different
4:34environments. Um in the middle of the
4:36the the slide you can see um for example
4:39skin color and how skin color has
4:41changed and we now have have different
4:44arrays of skin colors but we also have
4:45different body types and a lot of these
4:47have environmental uh influences. Why
4:50are some people dark? Why are some
4:52people tall and skinny? Why are some
4:53people more round? And a lot of this has
4:55to do with environmental selection and
4:57and uh different processes. Um this map
5:01I'm showing you over in the middle of
5:02the slide is looking at uh BMI um your
5:06ratio how how kind of round you are
5:08versus how tall you are and how that
5:10changes as you move away from the
5:12equator north and south. And this has to
5:14do with heat conservation. But in the
5:16same way our bodies and our skin color
5:18has changed, so has our immune function.
5:20As we've gone to different environments,
5:22we're we're influenced by different
5:24types of diseases and those diseases
5:26influence our immune systems
5:27differentially. And we've also um um had
5:31different ways to sustain ourselves. We
5:33have different types of of uh uh food
5:35gathering and food production. Different
5:37populations evolved uh agriculture in
5:40their societies and different
5:42populations were still hunter gatherers
5:43until very recently. So our bodies have
5:45responded not only to climates and
5:47environments but diseases and also
5:49diets. And and that's that's part of the
5:52story, but the the recent story is all
5:54about modernization and how in the last
5:56500 years, all of these diverse
5:58populations that got very different,
6:00started as as a a uniform population,
6:03moved all over the world, got very
6:04different in very many different ways
6:07are now increasingly coming together.
6:09And we're finding ourselves people from
6:11all over the world with different
6:13susceptibilities to diseases, different
6:15propensities for for succeeding in
6:17different environments and different uh
6:20cultural adaptations are increasingly
6:22finding themselves together and bringing
6:24all of those things together. Beliefs,
6:26behaviors, cultures, diseases, diets,
6:29all coming together, especially in in
6:31our modern cities um like Washington DC.
6:35But the other thing that's happening in
6:36modernization is that we're living in
6:38larger groups than we ever lived in
6:40before. And so that our our the very
6:42societies and the way that our societies
6:44work are also changing. Um if you're off
6:47on a small island like like I was a
6:50month ago and you walk around and you
6:52see someone, the first thing you do is
6:53you try to figure out how you're related
6:54to that person or who you know. You
6:57don't do that in Washington DC or New
6:59York City. There are just too many
7:01people. You can't know everyone that you
7:03run into. the Dunar number the the
7:05number of of humans that we can actually
7:07know has been estimated to be something
7:09like 150 or 200 and you bump into more
7:12than that on your way to work. So we
7:14can't physically intellectually
7:15emotionally know all the people that we
7:18see regardless of how many Facebook
7:20friends you have. So part of the the
7:23modernization is changing the way that
7:25our societies work. changing the way
7:27that we have access to foods or you know
7:29I have TV dinners down here with things
7:30that we call foods that may or may not
7:33be good for us. Um and also these
7:36diseases I have some condoms here to
7:38show to to infer AIDS and HIV and
7:41different diseases. It could be SARS any
7:43of these things that that are are
7:45pandemics that are moving around. So we
7:47started off as a a uniform population.
7:49We move all over the world. we adapt to
7:52all these different places, become very
7:54different in very different ways, and
7:56now we're all coming back together. And
7:58these, I think, are are kind of the
8:00scenarios that are important right now
8:01for human
8:03health. Um, specifically, most of the
8:06research that I I do is is focused on
8:08the Pacific. Um, how people settled the
8:11the various islands of the Pacific, how
8:14they then became adapted to those local
8:16environments. Um, often this meant that
8:18that as you move farther and farther out
8:21into the Pacific, there is less and less
8:23raw materials already there. So to
8:25succeed, you have to bring your own
8:26plants and animals with you. As you move
8:28out farther and farther though, you
8:30start avoiding some of these different
8:32diseases that that are are common in the
8:34tropics. So your whole disease profile
8:37changes, your food profile changes. Um,
8:40so you have to bring things with you.
8:41One of the things that that you bring
8:42with you are things like pigs um
8:45inadvertently out to Vanowatu which I'll
8:47be talking to you about um at length
8:49during this talk. The nofles mosquito
8:52also came and this is the the the vector
8:54for malaria. Um malaria then sets up
8:58these gradients of selection on
8:59different environments that then affect
9:01the humans. Secondarily, more recently
9:04uh we've evol uh developed different
9:05kinds of medicines to combat malaria. uh
9:08the parasites have have secondarily
9:10become immune or resistant to these
9:12different medicines in different ways in
9:14different places. So I'll tell you a
9:16little bit about that. Um and then I
9:18I'll close by talking about
9:19modernization and the effects of chronic
9:21disease. I show a little cruise boat
9:22here. One of the islands that I work on
9:24in Vanuatu and Nichum uh where my
9:26colleague Ko eradicated malaria in 1991.
9:29They've been having increasing number of
9:31cruise boats. Um they just signed a a
9:33contract with Royal Caribbean. Next year
9:35they're going to have 70 cruise boats.
9:37This year they had about 50. So they're
9:39already getting about one a week.
9:41They're going to get more than that. Now
9:42this is a island with a population of
9:44about 800 residents. These cruise boats
9:47dump 1500 2,000 tourists out a day. And
9:51this is is is a a good source of of hard
9:54currency, but it is also changing their
9:56cultures. It's changing what they do in
9:59terms of their daily activities, what
10:00they eat, and what resources they have.
10:03And that's having an effect on their
10:04their health. All right. So that's kind
10:06of an overview of what I'll be talking
10:08about within this context of of um
10:10dispersal and and uh diversification and
10:14modernization. All right. So I'll give
10:16you I'll start by giving you an overview
10:18of how people got to the Pacific. Um the
10:22earliest people reach uh the things that
10:24we call the Pacific Islands uh New
10:25Guinea up here and and Solomon Islands,
10:28Bismar's uh about 40 to 60,000 years
10:30ago. At that time uh in the plyosene um
10:34the sea levels were a lot lower. So you
10:36could walk out from Asia all the way out
10:38almost to Borneo
10:41um and and look across at Sulowesi. Uh
10:44meanwhile New Guinea was attached to
10:46Australia which was attached to
10:48Tasmania. So you have these these superc
10:50continents at that time. This Sunda
10:52Peninsula was was larger than the Indian
10:55subcontinent. This is now broken up into
10:57what is now Indonesia and the
10:59Philippines. All right. So people get
11:00over there when when the the the
11:02voyaging distances across the uh the
11:04seas were a lot smaller but it's still a
11:06major biogeographical barrier wala. So
11:09you have placental mammals mainly in
11:11Asia and then you have uh marsupial
11:13mammals mainly in Australia and New
11:14Guinea area. Um so you get a drop off of
11:17of biodiversity and changes there. Um,
11:20so humans are getting uh out to New
11:21Guinea and Australia back in the plea
11:24scene. And then there's this recent
11:26expansion off into remote Oceanania
11:29fairly recently within the last 3,00
11:313,500 years. Uh, another group of people
11:34um settled all of these these very
11:36remote islands. So, there's two major
11:38waves of these human settlement of the
11:41Pacific. Um, and this is this is very
11:44easy to tell archaeologically because
11:46the second group of people, um, we refer
11:49to them as the Lepita cultural complex
11:51or the Leita people. They made this
11:53amazingly intricate pottery. Um, and
11:56it's it's
11:57identical uh, in in its forms, not just
12:00it its form, but its decorations across
12:02large distances within a few hundred
12:04years. So, it's very clear that this is
12:05one group of people uh, traveling these
12:07distances. They also had a number of of
12:10uh animals of Asian origin. The pig, the
12:12dog, the chicken, the rat, and
12:14inadvertently the anophles mosquito that
12:16they bring with them. Um so these are
12:18the the big things that you find
12:20throughout the Pacific in Polynesia
12:22everywhere. And these are of Asian
12:23origin. They also brought a number of
12:25different tree crops and things that
12:27were domesticated in in New Guinea and
12:29Solomon's. Um, and we can also look at
12:32the languages of of people that that are
12:34currently within the Pacific. And you
12:37see that that all of these people that
12:38are associated with the the the
12:40holysine, the recent expansion, speak a
12:43very closely related uh group of
12:44languages, Aronesian languages that are
12:47related to languages in Taiwan and
12:49interestingly all the way out to
12:50Madagascar. So before the European
12:52expansion, uh the Aranesian language
12:55family was the most uh dispersed
12:57language uh family in the world over
12:59halfway around the world. Um
13:01particularly on islands in the Pacific
13:03because these are also the people that
13:04invented the outrigger canoe um and also
13:08Starlight navigation. And so I don't
13:10know if anybody's a sailing fan. I just
13:12came from San Francisco the other day
13:13and I was watching some of the America's
13:15Cup and they have these new uh winged uh
13:19boats, but they're still catamarans. So,
13:22$500 million of design later, these
13:25boats still look like Polynesian double
13:26hold canoes. Um so, there's still not a
13:29better boat out there than the ones that
13:31these guys were using to get all the way
13:32from Easter Island um and onto
13:35Madagascar on the other side of the
13:36dispersal.
13:38Um, some of my early work, my
13:40dissertation work was looking at
13:41mitochondrial DNA, these maternal
13:43lineages, and looking at at what
13:45maternal lineages were on different
13:47islands and trying to infer where people
13:48came from. One of the things that uh I I
13:52discovered was that um of the uh the two
13:57groups, the possible source populations,
14:00Southeast Asia and and Australia and New
14:02Guinea are very different. They have
14:03mutually exclusive groups of of
14:05mitochondrial lineages represented by
14:07these colors. Um the people in Polynesia
14:10are predominantly Southeast Asian in
14:12their origin of their lineages. Um but
14:14they do have about 5 to 10% of lineages
14:17that look like they came from New Guinea
14:18on the way. Um you have these islands in
14:21Micronesia, particularly in western
14:22Micronesia. Here I'm showing you the
14:24Marianas, which look like they were
14:25settled directly from Southeast Asia.
14:28Whereas you have these these islands
14:29like Vanuatu where the languages are
14:32very similar to the languages in
14:33Polynesia. They're settled at the same
14:36time as Tonga and and Samoa and Fiji and
14:39yet most of their maternal lineages look
14:41like they came from New Guinea. And I've
14:42argued in in a number of publications
14:44that I think this is post settlement
14:46gene flow and there's a lot of people
14:48moving back and forth and this is one
14:50reason why the Anophles mosquito makes
14:51it out there. And Vonowatu is the last
14:53malarious island archipelago in in the
14:56Pacific. So in some ways there's a
14:58correlation between language and
15:00genetics um and biology and in other
15:03areas there's a a discontinuity there
15:05and the patterns don't quite mix which
15:07which says that there's something
15:08interesting going on there in in
15:09prehistory and vanuatu is one of these
15:12places. Um the languages don't match the
15:14genetics per
15:16se. Um we also did some studies where we
15:19looked at u uh genetic diversity as you
15:22move out from the presumed source in
15:24Southeast Asia and New Guinea. As you
15:26move out farther and farther, one thing
15:27we notice is that the amount of genetic
15:29diversity decreases. And this is has
15:32more recently been shown to be true
15:33across the world. If you start in in uh
15:36Africa and you move outward, you see a
15:38decrease in genetic diversity. This has
15:40also been shown in terms of languages.
15:43Uh not words per se, but if you look at
15:45the number of sounds in a language, the
15:48South African languages, the the click
15:50languages have the most sounds per
15:52language. And as you move away from that
15:55uh you get less and less consonants in
15:58your language. And you see the same
15:59pattern in in the Pacific where if you
16:01look just at Austronesian languages
16:03these very closely related languages
16:04associated with the second diaspora as
16:07you move from let's say uh somewhere
16:09here in the western Pacific out to
16:11Hawaii you just lose uh consonants even
16:14from Tonga and Samoa in in in uh western
16:17Polynesia to Hawaii you lose about five
16:19or six different consonants. So things
16:21get simplified. You lose things easier
16:24than you generate diversity both in
16:26languages and genetics. Um so we showed
16:28that that you know you see this decrease
16:30in in genetic diversity as you move out
16:31into the Pacific. And if you incorporate
16:33different kinds of patterns that we
16:35think we know based on archaeology or
16:37language then the correlation between
16:39the loss of genetic diversity actually
16:42increases. Um now I'll tell you a little
16:45story about the pigs. Um, this was kind
16:47of a fun side project that started when
16:49we were doing malaria surveys and we we
16:52we heard that there were these these um
16:55very odd uh pseudoh hermaphroditic pigs
16:58out in Vanuatu. Actually, my my
16:59colleague Ralph Gerudo came in and said,
17:01"Do you know anything about these pigs?"
17:03And I said, "No." He says, "You work in
17:05Vanuatu, don't you?" And I said, "Yes."
17:06He says, "These are really crazy pigs.
17:08Why don't you check them out?" So, the
17:10next time I went out there, I did just
17:12that. I was out uh collecting mosquitoes
17:14for another study that I'll tell you
17:16about shortly and uh we started
17:18collecting samples from these pseudo
17:20hermaphroditic pigs. So what's the deal
17:22with these things? Well, it turns out
17:24that pigs are very very important in the
17:26Pacific partly because you have
17:28agriculture but you don't have food
17:30storage. It's the tropics. Most of your
17:32carbohydrates are roots and they don't
17:35preserve very well. So you can't get
17:37graineries with thousands of lifetimes
17:39of food just sitting there. things rot
17:41in the Pacific, especially starchy
17:43roots. So, the way that you can you can
17:45preserve food or accumulate wealth is
17:47through animals. And if you have lots of
17:49pigs, then that is lifetimes of wealth.
17:52Um, and this is true throughout the
17:53Pacific, but it reaches its most uh uh
17:56important aspect in Vanuatu where pigs
17:59are actually modified biologically for
18:02uh social reasons. And one of the things
18:05that they do in the northern islands of
18:07Vanuatu is that they will um remove the
18:10upper canines of the pigs. And pigs have
18:13indeterminate growth uh canines kind of
18:15like rats. They gnaw. They constantly
18:17sharpen their front teeth. Well, pigs
18:19have the same thing with their tusks. So
18:20if you remove the upper canines, what
18:23happens is the lower ones will do a
18:25complete circle in about 6 to seven
18:27years and two circles in about 11 or 12
18:30years. And it they look very beautiful.
18:33They're not so good for the pig because
18:35these things come up and they puncture
18:36the cheek and they sometimes if they do
18:38it really straight, they actually
18:40puncture the jaw coming back down. These
18:42pigs are are not happy and you have to
18:45kind of hand feed them. They're hard to
18:47raise. But if you're in Vanuatu,
18:49northern Vanuatu, and you can grow these
18:51pigs with the tusks, then you can trade
18:53them to your friends who want to take
18:55chiefly ranks and they can kill them
18:57ritually and take chiefly ranks. So
19:00tuskers are very important. The curled
19:02pig's tusk. These modified uh uh tusks
19:05are very important. They're so important
19:07that when Vanuatu got its independence,
19:09they put the tusk on the flag. Um it's
19:12also on the national beer. Tusker.
19:14There's two national beers that are
19:15tusker. One is from Kenya and that's an
19:18elephant tusk. The other one is in
19:19Vanatu and it's a pig's tusk. All right.
19:21So here's some examples. This is a
19:23wedding where they're killing a bunch of
19:24pigs here. Um here's the pig jaws in
19:29Jimmy Stevens. Um he he led a failed
19:32coup after independence, tried to take
19:33the northern islands and and separate
19:35and have them still remain under French
19:37control. That's a different story. If
19:39you want to hear about that, I can tell
19:40you about that. Um but uh uh pigs are
19:43very important. This is a pig killing
19:44club from Umbre. Now, if you want to
19:47take the highest ranks though in
19:48northern Vanuatu, you not only have to
19:50kill a bunch of pigs and a bunch of
19:51tusker pigs, but you have to kill
19:54narave. And narave are these special
19:57pseudohermaphroditic pigs. These are
19:59pigs that have um a as yet undescribed
20:03genetic mutation that results in them
20:05not having differentiation of their
20:07their external sexual genitalia. So
20:09these are are male pigs, chromosomally
20:11male pigs without a penis and uh without
20:15external testes. Well, sometimes they'll
20:17have one, sometimes they don't have any,
20:19sometimes they'll be inside of their
20:20body. So they produce testosterone, but
20:23they have nothing to do with it. And
20:25these are honory pigs. And you can't
20:27castrate them like other tuskers to calm
20:29them down because they their their their
20:31testes are inside their bodies. So these
20:33are really tough to grow and maintain.
20:36Uh they're sterile. They don't have a
20:37penis. So they have to be produced
20:39through their mothers and sisters,
20:42right? Uh so you have to you have to uh
20:45get these tusker pseudohormaphroditic
20:48tuskers from your friends if you want to
20:49take the highest chiefly rankings. So
20:51these are are still important and we
20:53wanted to take a look at this question
20:54in terms of these these ideas of of
20:56modernization and globalization. Um
20:59globally in the 1850s or so European and
21:02and Asian pigs were bred together to to
21:05build the the fast growing pig that is
21:07common now the global uh domesticated
21:10industrial pig and these pigs have been
21:12distributed all over the world. And so
21:14one of the questions were these pigs in
21:16Vanuatu, to what extent are they the
21:18original pigs that got out into the
21:19Pacific, and to what extent are they uh
21:22have they been interbred with these
21:24these global Tabescuits? So we we uh got
21:27DNA samples from 16 of these Nav
21:29Tuskers, these pseudo hermaphroditic
21:32pigs. Um we got nine samples from this
21:34other interesting pig in Vanuatu. In the
21:36southern islands, they have hairless
21:38pigs called capia. And these are also
21:40high maintenance because they get
21:42sunburned. So you have to baby these
21:43pigs. Um so you have two genetic
21:46mutations. Two highmaintenance pigs used
21:48for social reasons. This is the ochre
21:50face painting of a chief on this copia.
21:52So these are very important pigs.
21:54They're traded for uh turtles and humans
21:56and other high status things and they
21:59use for chiefly purposes. We got a bunch
22:01of those guys. We got a bunch of control
22:03pigs. Pigs just wandering around. Pigs
22:05that were um stuck in little bags on
22:08airplanes. Uh pigs being carried to
22:10feast. We just pulled hair samples off
22:12some of these pigs to get controls from
22:14the same
22:15islands. Then we sequenced their DNA and
22:17what we found is that the nurave almost
22:19all of all of the naravves and almost
22:22all of the controls from the same
22:23islands where they keep narab are the
22:25original Pacific pigs. Whereas the capia
22:28these these hairless pigs a lot of them
22:30most of them are are global
22:32domesticates. And when we think about
22:33this at the genetic level this makes
22:35sense because copias are bald pigs. You
22:38can breed them with anything and then
22:39just select out the
22:41bald babies from the litter. Whereas
22:44these these these narave you have to
22:47breed them from the mothers and the
22:49sisters of previous narave. And we're
22:52looking at a maternal inherited marker.
22:54So the maternal line is passed through.
22:57Everything passes through the maternal
22:58line. And so the mitochondrial DNA of
23:00the of these pigs is maintained. Plus
23:03these things are so valuable they don't
23:04want to interbreed them with with any
23:05other pigs. All right. So that's our
23:07little story for the the narave. When we
23:10look more globally, we found that these
23:12Pacific pigs that we were looking at in
23:14Vanuatu are very closely related to the
23:16Hawaiian and the French Polynesian, the
23:17New Guinea ones and the ones in
23:19Indonesia. Interestingly, nobody had
23:21seen this, but there was we found this
23:23paper and there's some Vietnamese wild
23:25boores and one of them also had this
23:27sequence. So we think that these guys
23:28are coming out of Southeast Asia, maybe
23:30not Vietnam, but somewhere in this area
23:32and relatively quickly they they change
23:35their morphology and get them down to a
23:37small size that can fit on a boat and be
23:39taken to all these different islands in
23:40the Pacific. But the same lineages that
23:42we have in Vanuatu are still found in
23:44these Vietnamese wild boores
23:46here. Okay, now I'm going to switch
23:48gears away from these these these funky
23:50domestic animals and tell you a little
23:52bit about the mosquitoes that transmit
23:53malaria. Um what we knew before was that
23:57there were um there's about
24:01um 12 different cryptic species at the
24:04genetic level for the anophles
24:06punctilotus group. Traditionally there
24:08were there were known as three different
24:09species based on their probosus
24:11morphology. But once people started
24:12sequencing their DNA it turned out that
24:14there were about a dozen of these
24:15things. Um there might be a few more now
24:18or a few less. This is always slightly
24:20changing. But each of these different um
24:22species had different environmental
24:24adaptations. Some live on the coast and
24:26are very salt tolerant. Uh some are
24:28living in the mountains, some were
24:29living in different environments. Uh in
24:31Vanuatu, it was reported that there was
24:33only one. This kind of makes sense
24:34because people have only been in Vanuatu
24:37for about 3,000 years, whereas the
24:38Solomons in and New Guinea and
24:40Australia, they've been for, you know,
24:41since the pleasy. So we saw that there
24:44was a difference in the number of
24:46species based on the the time of human
24:48habitation. Uh, but we also knew that
24:49Vanuatu was very rugged. There's, um, 80
24:52inhabited islands. Some are small, some
24:53are big. So, we went out there just to
24:55see what the genetic diversity of these
24:57guys look like, if there was really only
24:58one, and and how they were related. Um,
25:01so this was kind of the M's project of
25:02one of my students, Dana, and we went
25:04out. This is some of the data we've
25:06analyzed. We've still got another couple
25:07thousand mosquitoes sitting in my my
25:09lab, undescribed yet, but this is from
25:12about a thousand mosquitoes from five
25:15different islands. And what we see is
25:17that um there's one main lineage that's
25:20found on all the islands. This what I'm
25:22showing you here on on this side is is a
25:24network diagram. So each of these are
25:26genetic sequences. Each circle is a
25:28genetic sequence. The size of the circle
25:30represents how many individuals in our
25:31data set had that sequence. And the
25:33length of the bars, they're all just one
25:35mutation away. So what you see is that
25:37there's a lot of mosquitoes that are
25:38identical and they're found on all
25:40islands. The different colors are the
25:41different islands. And then you have a
25:44lot of of island specific mosquito
25:46lineages which suggest that one group of
25:48mosquitoes came in, it went to all the
25:49islands and then the island the
25:51mosquitoes don't move back and forth
25:53between the islands. So you you generate
25:54a lot of island specific lineages. Um
25:58which was interesting for us from a a
26:00malaria control perspective because that
26:01means that that the mosquitoes aren't
26:03really moving back and forth. It's the
26:04people that we got to worry about, not
26:06the mosquitoes. Um we do have another
26:08lineage is what we're calling this group
26:09two which which looks like it it's a a
26:11bit different and it's only in the
26:13north. So it looks like there was one
26:15main introduction of Nafles mosquitoes
26:17into Vanuatu and then maybe a second
26:19introduction into the northern
26:21islands. U when we started looking at
26:23the diversity of these mosquitoes and
26:24different islands we get really good
26:26correlations with with island size. So
26:28the number of lineages we find per
26:30island, the diversity of those lineages
26:32are are pretty well correlated with the
26:34size of the island and also the number
26:36of languages that the people speak. So
26:38the the same kind of area size uh uh uh
26:42parameters are affecting both the the
26:44diversity and also the human cultural
26:46diversity. Human population size is is
26:48pretty much correlated except for this
26:50island Tana where there's a lot of
26:51people on one small island but they
26:53don't speak very many languages. Um
26:55that's another story about Tana. All
26:57right. Um, so then we had we had data
26:59from from mosquitoes. We had previously
27:01looked at uh data from humans and the
27:04malaria parasites themselves. And what
27:06we found there was that the malaria
27:08parasites only moved around when the
27:10human uh also looked like they moved
27:12around where there was human gene flow
27:14shown here by this connection between
27:16the purple lines between Malakula and
27:18Pentagos where humans were going back
27:20and forth. The parasite the malar
27:21parasite also went back and forth. We
27:24added the mosquitoes to that and what we
27:26we got a good correlation too. The the
27:29places where there were shared lineages
27:31were also the places where humans were
27:33moving back and forth. So what we think
27:35is is the key to this is controlling
27:37human movement. If you control human
27:39movement, you control the movement of
27:40mosquitoes and you control the movement
27:42of parasites.
27:44Um, the next little bit I'll tell you
27:47about is a little bit about uh um the
27:51way that humans have responded to
27:53malaria. And this is uh I just showed
27:55you some work that that Dana had done
27:57for her master's degree. This is some of
27:58the work that she did for her PhD which
28:00she just defended in in the fall. And
28:02what she wanted to do is she wanted to
28:04look at the ways that different humans
28:07on different islands responded to
28:09malaria. Um so she looked at uh a total
28:12of 23 populations over 1,200 uh
28:16different samples uh individuals from
28:18those different islands and she screened
28:20a number of different uh genes. We have
28:23um uh Southeast Asian occytosis which is
28:26a a mutation that helps you resist
28:29malaria but it's not a very good one. uh
28:32I say it's not a very good one because
28:33it it really distorts the shape of the
28:36red blood cell and to this date no one
28:38has ever been found with two copies of
28:40this gene. So and when you have
28:43populations with a high frequencies of
28:45hetererozygot you have a higher
28:46frequency of stillborn children. So the
28:49implication is that if you inherit two
28:51copies of this gene then you're not even
28:53born you're you're still born. Um so
28:55this is is a way to avoid malaria but
28:58not a very good one. a very costly
29:00mutation to avoid malaria. We also look
29:03at this garbage negativity al um and
29:06this is also resist malaria. Um CR1 also
29:11resists malaria. And then we looked at
29:13this TNF alpha promoter. So TNF alpha is
29:16um part of the the immune response and
29:19it's a general fever response. So if you
29:22have this promoter, it upregulates your
29:25ability to cause a fever. But in a
29:27malarious environment, it also leads to
29:29a higher susceptibility of cerebral
29:31malaria. So we had three resistant alals
29:34and one susceptibility
29:36alf of these things are working the way
29:38we think then we should see different
29:40patterns in those you know where the
29:42susceptibility ones are high resistance
29:44should be low and vice versa. We have
29:46different different alals with opposite
29:48selections on them. And then because
29:50like I told you the people in the
29:52Pacific especially in Vanuatu are
29:54composite between these two different
29:55gene pools. Part of the the main group
29:57of people are coming in in the plyosene
29:59near oceanic people. And then you also
30:01have this second movement of people in
30:03from Southeast Asia. Both malarious
30:05environments but different gene pools
30:07that are are uh developing over long
30:09periods of time. So instead of focusing
30:10on on any of these single uh locus uh
30:14alals that are single locus what we did
30:16was we we sum these all together to get
30:18what we're calling a malari resistant
30:19genotype score. So for example as I said
30:23you can only get one of these um SOAs.
30:27So you can get a plus one or you're at
30:28zero for for that locus. Uh gerbitch
30:31there's homozygote so you can go from
30:32zero to plus one to plus two. Uh same
30:35with CR1 0 plus1 plus two. TNF alpha you
30:38can be at zero minus1 minus2. So you can
30:41either have go from minus2 to a plus
30:44seven in terms of your malaria
30:47resistance uh plus five sorry plus five
30:50to minus2 a range of seven. And so we
30:53get this score that sums up all these
30:55different genetic inherited ways that
30:57you combat malaria. Um because the idea
31:00is that uh any population has a certain
31:03number of alals in it and you can pick
31:06and choose the the evolution can tweak
31:08any of those and it's not one or the
31:10other. It's kind of a composite of those
31:11and that's your your uh immune response
31:14to these different diseases. We also
31:16looked at a number of UNL STRs just to
31:18look at the genome and to see whether or
31:20not that has the same pattern. Hopefully
31:22it doesn't have the same pattern. If it
31:24does, then what we're really looking at
31:25is population history and not disease
31:27selection. And then we looked at a
31:29number of things that are involved with
31:30u um Anophles mosquito habitat quality.
31:33What the latitude is, what the altitude
31:35is, what the longitude is. As you go up
31:37a mountain, it gets colder and drier. So
31:39the mosquitoes don't live as well. Um as
31:41you go south away from the equator in
31:44the Pacific, it gets colder, it gets
31:45drier. So lowlands in the tropics right
31:48near the equator have the highest level
31:50of malaria. As you move away from that
31:52and up mountains, then you get less
31:53malaria. So we have gradients of
31:54selection and differential gradients.
31:56Um, and then because we're we're pulling
31:58these malaria parasites out of human
32:01serum samples, we can actually um look
32:04to see what the frequency of people in
32:06each of these population at the time of
32:08sampling had malaria. So that's our our
32:10point prevalence of malaria. So we have
32:11a a guesstimate of how much the malaria
32:14selection was by just looking at how
32:15many people had malaria in that
32:16population. And then we also looked at
32:18language and and geographic distances.
32:21I'll tell you a little bit about this
32:22first part of the data set which is just
32:24on New Guinea. a few Aronesian
32:26populations, the these people that came
32:28later, a lot of these populations that
32:30speak uh Papuan languages that have been
32:32there presumably since the pleaosene
32:34across these gradients of of uh
32:37altitude. What we see for these these uh
32:39those those different genes that I
32:40showed you um what I'm showing you here
32:42on the the um on this axis is the the
32:46level of malaria, the point prevalence
32:47of malaria. And as that increases, the
32:50frequency of the resistant ALC CR1
32:53increases. um the frequency of the
32:56gerbic negativity al increases the
32:58frequency of this TNF alpha that's a
33:01susceptibility one goes down so those
33:03three work the way we would expect them
33:04to the only one that doesn't respond
33:06very well is is this Southeast Asian
33:09ovaltosis that's kind of flat but again
33:11this is the the the alil that's not so
33:13good this is the expensive one the one
33:15that you don't really want anyway and if
33:17you only have that it's fine but if you
33:19have a choice to to select for any other
33:21alil to resist malaria those the better
33:23ones So um it kind of made sense when we
33:26start adding all these things up and
33:27summing them up we get a much better
33:29correlation even than the ones we see.
33:31So these ones have 73 uh this
33:34is 088 when we add them together into
33:37our our uh um our malaria resistant
33:41genotype score the correlations come up
33:43a little bit. So we think this is a good
33:45method. Um, the only other thing I'll
33:46I'll tell you about her data when we
33:48look at all 23 of those populations and
33:51we just focus on this malaria resistant
33:53genotype score, what we see is that the
33:55people on the coasts and some of these
33:57islands on the coast that have a lot of
33:59malaria have on average almost two
34:02different alals that resist malaria. And
34:04then as we go up these mountains into
34:06the highlands of New Guinea or go to
34:08these Polynesian outliers where there is
34:09no malaria, people often have uh less
34:13than one or almost one susceptible alil.
34:16So across these these gradients of
34:18selection within a very region, a small
34:21region, we have big differences in the
34:23selection on these different alals. And
34:25I this is it will be important in about
34:28three or four minutes. But just kind of
34:30think about that highlands and small
34:32islands versus coastal uh malaria
34:34selection because what I'm going to tell
34:36you next about is um drug resistance to
34:39malaria. And so this is a an NIH funded
34:42project that I um we're just wrapping up
34:44and it was to look at the evolution of
34:46chloricquin resistance in malaria
34:47parasites in uh the Pacific. The general
34:50history of this is that
34:53um after World War II uh chloricquin
34:57became very important. It was actually
35:00discovered by the Germans during World
35:02War II but for some reason it was
35:05claimed to be ineffective for malaria.
35:08And there is um there is an argument
35:12that uh Himmler controlled all the
35:15revenues from these pharmaceutical
35:17companies and the scientists just didn't
35:19want to give him the rights to this. So
35:21they they lowballed the effectiveness of
35:23this drug. In any case, uh after the
35:25war, the US independently discovered it
35:27and then the Germans rediscovered it and
35:29chloricquin became the most important
35:31antimmalarial. But within about a a less
35:35than a decade, we started to see um
35:37resistance appear in Southeast Asia and
35:40simultaneously in in South America. Um
35:43and then uh in the 70s it appeared in in
35:48the Pacific um and also in Africa. Now
35:51this is kind of interesting because the
35:53most malarious uh areas are actually in
35:56Africa. So resistance doesn't appear
35:59where there's the most malaria. actually
36:00appears where there's the least malaria.
36:02So, this is kind of interesting and and
36:04this will tie into my my story on the
36:06Pacific. Um it wasn't until about a
36:09dozen years ago that we actually knew
36:11what the molecular basis for this
36:13resistance to chloricquin by the
36:14parasite was. Um uh David Fidok uh at
36:18Colombia discovered uh through a series
36:20of very elegant experiments discovered
36:23uh that there is one single amino acid
36:25in one gene that is is is has been shown
36:28to be correlated 100% correlated around
36:31the world with resistance to coopin. So
36:34it's one amino acid change. But it's
36:36it's a little bit more complex than that
36:38because there's no parasites that have
36:40ever been found today that have only
36:43that one mutation. All the resistant
36:45parasites have a suite of eight to 10
36:47different mutations including that one
36:49and different regions of the world have
36:51different sets of these complex
36:52hletypes. So there was a big debate um
36:55over the last five or six years of how
36:57these these complex suites of mutations
36:58evolve. Does that magic K76T appear
37:02first and then you need these helper
37:03mutations to to make that genotype more
37:06fit or do you get these kind of uh
37:09tolerant mutations and then K76 comes as
37:12the kind of the the lynch pin of all of
37:14that and ties everything together and
37:15pushes that parasite over the edge. So
37:17what we wanted to do was to actually
37:19look at this process in real time by
37:22exploring a series of samples u from the
37:25Pacific that had been collected in the
37:271950s60s7s and 80s that span this time
37:30of the evolution of drug resistance
37:31within the Pacific and just sit there
37:33and watch mutations accumulate. So
37:35that's what I'll show you now. Um we we
37:38just published some of this in in plots
37:40earlier this year. I'm going to show you
37:42decade by decade and region by region.
37:44So, in the the lower right of all these
37:46these slides is kind of a color-coded
37:48region of where these samples are coming
37:50from. We've got some from the the North
37:53Coast. We've got some from the
37:54Highlands. We got some from the South
37:56Coast in these early 5960 period. Um,
37:59all of them are susceptible to uh
38:01chloricquin. Um, there's a few mutations
38:03out here, but not very many, not very
38:05interesting. None of these magic K76T
38:07guys appearing yet. These are the same
38:09network diagrams, by the way. So each of
38:11these different circles is a different
38:13uh DNA sequence and the size of the
38:15circle represents how many individuals
38:17in that that decade have those
38:19mutations. 6265 same thing we have
38:22samples from now from Fawatu from these
38:25different coastal highland populations.
38:27They're almost all these susceptible
38:28guys. These guys right here are probably
38:30susceptible too. You see a few amino
38:32acid changes but nothing so interesting
38:35till we get to the late 60s and early
38:3770s and then we get all this diversity
38:39coming out. we get diversity. We start
38:41getting K76T, this magic resistance guys
38:45popping out here. But what I want you to
38:47notice on this is almost all of these
38:49mutations are yellow. So they're coming
38:51out of one population. And it's not like
38:54the yellow guys are are more than a
38:55third of the total data, but they're
38:57they're like 90% of all the interesting
38:59mutations coming out. And the yellow
39:01guys are from these very small islands
39:03in
39:04Wanowatu 79. We've got this nice
39:07highland population for this decade.
39:08this we don't have any from the islands
39:10but we start seeing all these really
39:12bizarre interesting fully formed fully
39:15resistant genotypes appearing in the
39:16highlands of New Guinea but not in the
39:18coast
39:19again our last sample from the late 70s
39:21and 80s we have both the small islands
39:25and the highlands they all have these
39:26resistant guys some of them are
39:27identical but these are on opposite
39:29sides of the Pacific in between are the
39:31lowlands where we still don't have any
39:32resistant parasites
39:35um so this is a summary of all the
39:36mutations and all the interesting ones
39:38are the vast vast majority of the
39:39interesting ones I hope you can see are
39:40yellow and red. And so, uh, as I told
39:44you a few minutes ago, when we look at
39:46the human beings from these same
39:47populations, the yellow and the red guys
39:50are the guys that have very few, uh,
39:52inherited resistance to the parasites.
39:54They have the the least functioning
39:55immune systems, inherited immune systems
39:57to resist malaria. You and I, if we go
40:00to a malarious country, there's three
40:02things that that can help us with
40:03malaria. One is our inherited genetics.
40:05The other one is what we've developed um
40:08during our lifetime. How many times our
40:10immune systems have been exposed to
40:11malaria. And the third thing now is
40:13pharmaceuticals. So really the
40:15pharmaceuticals are being helped out by
40:17our inherited genetics and our
40:19experience with with the disease. What
40:21we see is that the guys the parasites
40:23that evolve resistance the earliest are
40:26the ones that are in the bodies of the
40:27people that had the fewest inherited
40:29mutations to help them out. So basically
40:32those are the human bodies that are like
40:33the baby pool. they can figure out, they
40:35can explore this mutational space and
40:37tweak their genes in different ways and
40:40still survive because the immune systems
40:41of those human beings are weaker. And
40:43once they develop this this complex
40:45hletype, then they can invade into the
40:47lowlands where the people that have high
40:49inherited resistance uh live and they
40:52can then invade those areas and they do
40:54this very rapidly. If you go to these
40:56areas now or even five years after our
40:59sampling dates in the early 90s, almost
41:01every parasite is resistant.
41:03But five years before that, there were
41:05no resistant parasites in the lowland.
41:07They were only in the highlands and
41:08small islands. And and nobody would have
41:11known this if that we didn't have this
41:13amazing series of collections that that
41:15predated and and bounded that time of
41:18disease resistance. So when we put the
41:20human genetics together with the
41:22parasite genetics, we can actually see
41:24what the selective uh uh forces were
41:27that encouraged the evolution of drug
41:29resistance in these
41:31parasites. Okay. Now I'm going to switch
41:33gears again and talk a little bit about
41:35chronic disease. Um, and I'll tell you a
41:38little bit about my favorite archipelago
41:40in the world, Vanuatu. This is the most
41:42interesting place I think to do research
41:44because it has currently about 240,000
41:48people on 60 inhabited islands and they
41:50have over a 100 indigenous languages. So
41:52it's the most culturally linguistically
41:54diverse place on the planet. Um, some of
41:57these islands, the larger ones like Sto
41:58and Malakula, have over 20 languages on
42:01them each. So this is really
42:03interesting. Most
42:04archipelos at some point in prehistory
42:07there's some kind of cultural
42:09homogenization either initially where
42:11only one group of people founded that
42:13island or something happens and and the
42:15island is homogeneized. Not this place.
42:17There's so many different languages and
42:18cultures and uh throughout uh prehistory
42:21they're trading things. They're in
42:22contact with each other. They're trading
42:24sculptures uh carving forms, poems, sand
42:28drawings, the rights to do different
42:29things. And they're doing this while
42:31maintaining cultural diversity. And so
42:33in some ways, I think this is a really
42:35neat model for globalization. How can
42:37you be in contact with people without
42:39losing your cultural identity and be
42:41functional? All right. Um, currently
42:43about 25% of the the population is
42:45urban, which means you either live in
42:47Port Villa on on a fate or in Luganville
42:50on Sto. Um but there's the majority of
42:53the people are still uh rural and
42:55there's big gradients in development and
42:58that's why uh we're working there. We
43:00want to know what happens when you start
43:02controlling malaria and then chronic
43:05disease starts coming up with
43:06modernization. To give you a feel of of
43:08some of these differences um these are
43:10the five islands that we worked on last
43:12summer. Um in 2007 we worked on three of
43:14these. Um this last summer I was on the
43:17same three again that are a subset of
43:19these. I was on Umbai. Um, Ambai has
43:22very little infrastructure. They still
43:23have malaria. Um, it's very rural. Um,
43:27and and most of it is is is very
43:30uh hard to get around. No running water.
43:33Uh, no electricity except for generators
43:36in some small areas. Um, we also have an
43:39island, Nuna, which is on the back side
43:41of the main island, and it doesn't have
43:43very much infrastructure. It still has
43:45malaria. In a lot of ways, it's like
43:47except the US just built this wonderful
43:49road and you can get from the back side
43:50of Afate uh over to uh the capital of
43:53Port Villa in about an hour. And in Port
43:56Villa, you're on a power grid. You have
43:57Wi-Fi, you have supermarkets, you can
44:00buy uh they had a dual French and
44:02British colonialism. So, you can go into
44:04one of these French grocery stores and
44:05get 30 kinds of cheeses and and five
44:08kinds of pate and 50 kinds of wine. You
44:10can get anything you want in in Port
44:12Villa. Um we also work in on a niche.
44:16This is an island uh where my uh
44:18colleague I mentioned uh eradicated
44:19malaria in 1991 and they've been getting
44:22increasing tourism. They've got this
44:24little atole uh where they they make all
44:27the the tourists stay and they've built
44:29this this complex now that now has like
44:31six flush toilets. There's only one
44:33flush toilet on the main island, but
44:34there's six for the tourists. And
44:36there's these big markets where they'll
44:37braid the tourist hair and they'll sell
44:39them little knickknacks or take them out
44:40game fishing. And so every time the
44:43tourist boat comes in, and now next year
44:45it's going to be 70 70 times a year,
44:48they drop anchor and they pay the
44:49village association
44:51$5,000. And then they go off and they
44:55they spend another maybe $5,000 on on
44:57the hair braiding knickknacks and then
44:59they spend another $10,000 on the
45:01fishing tours uh and other things. So
45:04every time one of these these cruise
45:05boats come in, they get like $20,000 of
45:07hard currency. So this place has been
45:09changing really rapidly. Uh, in 2007
45:11there were three generators on the
45:12island. 2011 there were 29 generators on
45:16the island. This last summer I was there
45:18a month ago and everybody's switching to
45:20solar. Um, and and it everything is just
45:24leaps and bounds. Everybody has cell
45:26phones now. They never had cell phones
45:27in 2007. Even now, this last summer,
45:30little kids, five, sixy old kids have
45:32cell phones. They don't they don't work
45:34as cell phones. They work as little
45:36iPods or something. They play games on
45:37them because their parents when they get
45:38new cell phones they give their kids
45:40their old ones. So these kids are
45:42running around playing games and taking
45:43pictures. Um and then we also went to
45:46Futuna, this this Polynesian outlier
45:48island and and this is interesting
45:49because it's just a a small rock
45:51sticking out of the the ocean and it's
45:53so rugged um that they've never had
45:55malaria because they don't have any
45:56standing water. The water just kind of
45:58runs right down. So this is a population
46:00with no infrastructure but no malaria.
46:02So these are the kind of the five
46:03islands that we've been looking at in
46:05terms of modernization. Uh no
46:06infrastructure in malaria. Uh no infra
46:09uh no direct infrastructure in malaria
46:12but access to the main capital. Um
46:14increasing tourism, no malaria. Uh no
46:18malaria, low infrastructure and uh no
46:20malaria and lots of
46:22infrastructure. This is some preliminary
46:24data from last year. What you see this
46:26is the obesity rate. And when you go
46:28from no infrastructure and malaria,
46:30there's only about 7% um obesity. Same
46:34with Futuna, the rugged one without
46:35malaria. You go to the one with
46:37increasing tourism, it's up to 14%. You
46:39go to the backside of a fate, it's up to
46:4122%. When you go to the town, it's 34%.
46:44It's like the US. So the the rate even
46:47within this small archipelago where
46:48there's only 240,000 people, you're
46:50seeing the gradients from from
46:52subsistence agriculture and and very
46:54healthy people in terms of chronic
46:55disease to situations that are not
46:58unlike Australia or Europe or the United
47:00States. And when we did a survey, one of
47:02my graduate students is really
47:03interested in internet addiction. So we
47:05wanted to look at technology acquisition
47:07and usage. Um I'll just have you focus
47:10on this one line. Um has 40 last year
47:13now I haven't looked at the data from
47:15this year but at that time there were
47:1642% of the people the adults had had
47:18cell phones in Futuna there was 21 a
47:21nitro there's 65 Nuna 78. Aat had 81%.
47:26So again this is like the US 81% of the
47:28people have cell phones. The interesting
47:30thing, Futuna didn't even have a cell
47:31tower last year and 21% of the people
47:33had cell
47:34phones and they were either using them
47:36as iPods or you know these are the
47:38people that were moving back and forth
47:40and they spent a lot of time on other
47:42islands so they they had cell phones but
47:4421% when they don't even have cell tower
47:46was high but all of these other things
47:47are are correlated with that. So, the
47:49more time you s spend sitting around on
47:52your computer and not going out growing
47:54your food, the more time you spend
47:55eating storebought food are correlated
47:57with these these obesity
47:58rates. Um, this is just same data except
48:01for splitting it up into males and
48:03females, young adults and and older
48:05adults. Uh, this red line right here is
48:08overweight, a BMI of 25. And you notice
48:12that most of the young men are fairly
48:13fit, but the older men as you get more
48:16and more infrastructure start moving
48:17into the the on average into the
48:19overweight category. And females is is
48:22exaggerated. Um this this solid line
48:25right here is the obesity rate. Again,
48:27younger women are in general more fit
48:29than the older women, but by the time
48:30you get out to a fate where they have
48:32the power grid and everything else, the
48:34average woman, older woman is obese. So
48:37these are very big differences uh
48:39between men and women and one thing that
48:41we know happens um with modernization
48:44and the increase of chronic disease is a
48:47a reduction of the age of menarchy. So
48:49if we look over the last 150 years in
48:51Europe and America where we have this
48:52data um back in 1860 the average woman
48:56in in Europe and America is getting
48:57their first period somewhere around 15
48:5916 years old and now it's down to 12 and
49:01a half and this happens over 150 years
49:04and part of this has to do with
49:05energetics. the the body has so much
49:07energy it starts telling them that
49:09they're they're it's time to reproduce,
49:11right? So, their bodies are maturing
49:13faster than their minds are in the
49:15developing world. This is this is our
49:17data from last summer. We asked all the
49:19the the women in our survey when you had
49:21your first period and this is broken
49:23down by age groups. So, the oldest women
49:25they had their first period around 15 16
49:28then it drops down to around 15 and then
49:30the youngest class is down to 13 and a
49:32half. So within a few maybe one
49:35generation, we're seeing the changes
49:37that happened over 150 years in Europe
49:41and America happening in Vanuatu due to
49:44modernization. They're getting so much
49:46energy. And this is you put the cell
49:48phones together with the the the age of
49:50menarchy and this is a big problem
49:52because now the teenage pregnancy rate
49:54is going up and also the the rate of
49:57sexually transmitted infections is going
49:59up because all these young people and we
50:01have a we have a technology generation
50:03gap in this country. Young kids are are
50:05much more um uh competent at using these
50:09devices than older people but more so in
50:11Vanuatu. A lot of these older people,
50:13they're they're barely literate. Whereas
50:14the young kids, they they pick up these
50:16cell phones and they're making dates in
50:17the bush and not telling their parents
50:19where they're going. And you know,
50:20they're forming all these networks with
50:22with maybe some good consequences. But
50:24in in in what I'm seeing in the sexually
50:26transmitted infections, there's also
50:28some a dark side of this. And um this is
50:31this is an increasing problem.
50:34Um, getting back to this idea that that
50:37the males are somehow uh showing less uh
50:40chronic disease or obesity than the
50:42females, I started thinking about this
50:43and and I've been working in Vonowatu
50:45now for 12 years. And one of the things
50:47that I know that the males are doing
50:48that the females aren't doing is um
50:51drinking the ritual drug cava almost
50:54every night. And cava is um uh is a
50:58root. You take it out fresh, you clean
51:00it up, you grind it up. In in the
51:02northern islands, you take a piece of
51:04coral and you araid it and you you
51:06strain it and you drink it. Um, in the
51:08southern islands, you actually chew it
51:10up and spit it out and then take that
51:12and mix it with water and you drink
51:13that. And um, what it does is it it's a
51:17a postnaptic neuroinhibitor. It makes
51:19your body really loose and it's a muscle
51:22relaxant. Um, if you drink a lot of it,
51:24you lose control of your body and it's
51:26very hard to walk, very easy to fall
51:28down, but your mind is still kind of
51:30lucid. You get sensitive to light and
51:32sound. U, but it makes you very calm.
51:35And it's probably why Vanuatu has one of
51:37the lowest crime rates in the Pacific
51:40because most young males are sedated
51:42every night of the year. And if you
51:44sedate all your young males, crime
51:46somehow goes down.
51:48Um so but the other thing it does is it
51:50also is an appetite suppressant and it's
51:53actually marketed uh well was marketed
51:55around the world as a an herbal um
51:59herbal Valium uh relaxant anti-anxiety
52:02compound um until there was a a few
52:04cases of liver failure a few years ago
52:06and we can go into that later but um but
52:09it it it uh kind of suppresses your
52:11appetite. It's been marketed in Japan as
52:12a diet pill. Um so when you drink cava
52:15you don't really eat much. So I was
52:17thinking maybe this has something to do
52:18with this difference between males and
52:19females. So last year we went out and we
52:21asked people how many people were
52:22drinking cava and how often they're
52:24drinking cava. And what we found is yes
52:27almost all the males over 70% of the the
52:30males in most islands are drinking cava
52:32almost every night five or six times a
52:34week whereas the females not so much.
52:37One island by the the older women drink
52:39a lot of cava. Um I went back this year
52:41and I actually asked them how many how
52:43much cava they're drinking each time
52:44they drink cava. And the women on Umbi
52:46are drinking a lot of cava almost every
52:48night just like the guys in most
52:49islands. The women in Umbai are also the
52:51thinnest ones. So there's something
52:53about taking an appetite suppressant
52:55every night and and maintaining your
52:58weight. And this this now can be a a
53:01problem with modernization because the
53:03other thing that vonatu does as it plugs
53:05into the rest of the world is it's part
53:07of this Pacific music reae Caribbean
53:10reae culture. And uh this is uh uh
53:14Ocean, this son of a missionary from
53:16California who grew up in New Guinea and
53:18now spends half his time in New Guinea
53:20and Hawaii and he's one of the biggest
53:21music stars in in the Pacific hanging
53:23out with Ziggy Marley. Um this is a
53:26Vanuatu flag. This is a a reggae band
53:28from Vanuatu and they've replaced uh the
53:30pigs tus with a marijuana leaf. Um these
53:34are different reggae bands. This is one
53:35of my uh survey assistants with his dog
53:38Ganja on on a nightm and so we also
53:42asked the guys do you smoke ganja and on
53:45every island the young men said yes
53:47about five to 15 um on one island uh
53:50almost 30% of the guys young guys on on
53:53Nichim are are smoking ganja. So there's
53:56now there's a kind of a switch from cava
53:58to ganja and if you go from an appetite
54:00suppressant to something that
54:02creates munchies then maybe that
54:04protective effect uh from ganja is going
54:06to go down. All right so the last from
54:09cava is going to go down. The last thing
54:10I want to tell you is what I did this
54:12summer. Um we were wondering about how
54:14chronic disease is affected by diet.
54:16Eating fish, eating fruit bats, pigs,
54:19octopus, lobsters, uh sharks. um as
54:23those diets change to a more modern
54:25diet, what is happening to your
54:26microbiome? This this one to two liters
54:28of bacteria that live in your your uh
54:30intestines and is fed by all the things
54:32that you don't digest. And so what I did
54:35was I collected from three of these
54:36islands on uh a niche and and uh Ericore
54:41um saliva samples and also tooth swabs
54:43to take a look at what are the bacteria
54:45living in people's mouths and how that
54:47is u correlated with their diets. We we
54:50took dietary recalls which we also have
54:52from
54:532007201 and we're going to compare the
54:55the microbiome data to their diet data
54:58and their chronic disease diet. And uh
55:00maybe next time I come I'll have
55:01something to tell you about that. And uh
55:03I'll finish by just acknowledging all
55:05the people that we've been working with
55:06in Vanuatu. um uh my graduate students
55:09and my my uh colleague Ralph Gerudo and
55:12my lab manager Rita and all the people
55:15in Vanuatu who help us out when we're
55:17there and my colleague Chuck Whites from
55:18Temple University and funding from NIH
55:21Winter Grant and Bingmpington
55:22University. And with that um I'll take
55:24any questions you might have.
55:28[Applause]
55:32With the spread of Could you repeat?
55:35Okay. With the spread of mosquitoes,
55:38yes, from island to island or from
55:40continent to continent. Um, is it the
55:43same with the spread of cockroaches?
55:49Cockroaches and mosquitoes. Um,
55:52is it the eggs that that I'm I I don't
55:56think so. I mosquitoes are Oh, sorry.
55:59The spread of mosquitoes. How is that
56:01similar to the spread of cockroaches?
56:02Cockroaches have dry eggs that can last
56:04for a long time. Whereas the mosquitoes,
56:06we think what's happening is they're
56:08actually being distributed in water. So
56:10I found them in the bottoms of canoes
56:12and the one that gets all the way out to
56:14Vanoatu is the salt tolerant one. And
56:16this one can live in brackish water and
56:17also in seawater and still develop
56:19normally. So we think that the
56:21prehistoric transmission was in in
56:23boats. Um recently since World War II,
56:25Guam has something like seven introduced
56:27mosquito species probably due to World
56:30War II. So, I think the mosquitoes is
56:32more moving around wet things either
56:35moving around like um uh live plants or
56:39the other big one is there's a a trade
56:41in used tires and rain gets in these
56:42tires and they're really good breeding
56:44spaces for for mosquitoes. Um but most
56:47of the anophles they don't do so well in
56:50non fresh running water. So, it has to
56:52be pretty rapid. So, they don't transmit
56:55through boats or they don't they don't
56:57get out to places very easily. And
56:59that's why maybe Vanoatu is the last
57:01place. It never gets down to New
57:02Calonia. It never gets down to Fiji.
57:04Those distances are a little bit longer.
57:07Um to get down to New Calonia, you have
57:08to go through these upraised coral reef
57:10islands without much fresh
57:12water. But I think it's a a very
57:15different process. But you know, Hawaii
57:17now has has a lot of mosquitoes and that
57:20was historically from I think a
57:21Portuguese or a Spanish ship dumped out
57:23their water and they had mosquito larvae
57:25in there. So if you were in Hawaii 150
57:28years ago, there were no mosquitoes and
57:29that would have been really nice.
57:31Y just a quick
57:35question. Second, just a point of
57:37information, your slide about diet
57:40and changing. Yep.
57:44Back in the ancient
57:49days, we used to simply correlate that
57:52with body fat.
57:55fatty fat relative to muscle and it
57:58carried explained huge variety of
58:01factors why South African bushman
58:08usually age was like 17
58:16and you could go to things as recent as
58:18the Olympics and look at all these girls
58:20doing these incredible gymnastics and
58:22many of them don't straight until Right.
58:24So it was a nice cut and dried
58:26explanation. You introduced another term
58:27for that matter energetics. I'm
58:29wondering what is the difference? What
58:31has changed since 20 years? Nothing.
58:34It's body fat and energy usage. Oh,
58:36sorry. It Yeah. age of menarchy and how
58:39that affects how that's correlated with
58:41just body fat or exercise. And I that's
58:43what I'm talking about. You know, your
58:45energy in versus your energy out. Um,
58:48yeah, if you're you're a female athlete
58:49and you have less than I think 7% body
58:52fat, then you you stop menrating. Um,
58:55and so I think that's that's what's
58:57driving this that people start becoming
58:58more sedentary. They're they're not
59:01going to their gardens, they're not
59:02growing their own food. Uh, they're also
59:05going to stores and buying more energy
59:07dense food. So less activity, more
59:10energy. Um, and so the the age of
59:13metarchy is dropping. And so we in our
59:16other uh surveys in 2007 and 2011, we
59:19also looked at activity, we looked at
59:21diet, we looked at material possessions.
59:24Um so we're we're trying to look at all
59:26those different variables to try to
59:28figure out what are the most important
59:29ones because
59:31uh chronic disease is the biggest
59:33expense for for our healthcare in the
59:35United States, but vanatu doesn't have
59:37any money. You know, if they if they go
59:39down that same path, then they're in
59:41they're in big trouble. So, if we can
59:43figure out ways to do education and
59:45prevention before it it's it gets worse,
59:49then we're ahead of the game. But if we
59:51don't, then maybe the game is over
59:54because there's there's already 25% of
59:55the population that is in this state.
59:5875% are still okay.
1:00:03Uh you mentioned the human bile which
1:00:06seems to be a hot research topic the
1:00:07last few years and
1:00:10um
1:00:12apparently you digestion is through the
1:00:16billion small intestines but apparently
1:00:19uh the biome that
1:00:23digest material is ordinarily this fiber
1:00:26in our large intestines. People are
1:00:28talking about absorption of those. Maybe
1:00:30we need some of that. But tell me
1:00:33something about that about the about the
1:00:36u the human the biome digesting and to
1:00:40what extent it's absorbed by the human
1:00:42body. Well, I sorry. So she's asking
1:00:46about the microbiome and digestion small
1:00:49versus large intestine. These things
1:00:50that we used to think about as just
1:00:52fiber that were somehow good as a just a
1:00:55physical movement of things through your
1:00:57intestine are now thought to be actually
1:00:59feeding a diverse uh community of
1:01:02organisms. So I guess the idea is my
1:01:05idea my understanding is that you have
1:01:07this ecosystem within you and you're
1:01:09feeding that ecosystem in in addition to
1:01:11feeding yourself. So, if you only eat
1:01:13very easily digestible things um that
1:01:16you digest, then you're starving off
1:01:18this this vast array of things that
1:01:20could potentially be inside of your your
1:01:22intestine. And those are the things that
1:01:23we presumably evolved with. And so, if
1:01:27you're going around and only feeding
1:01:28yourself and and being selfish in a way
1:01:30and not feeding these other things, then
1:01:33you're you're going without half your
1:01:34digestive system. And so uh they're
1:01:38associated with a lower diversity of
1:01:39these these organisms are things like
1:01:41irritable bowel syndrome, potentially
1:01:43Crohn's disease. A lot of these
1:01:44autoimmune functions of the intestine
1:01:46are are are uh maybe influenced by a
1:01:50lack of these diverse organisms that we
1:01:52evolved with. And so that's why we're
1:01:55we're we have this nice gradient. We
1:01:57already know something about the rates
1:01:58of chronic disease. We already know
1:01:59something we think about their diets.
1:02:02Um, and so we'd like to see how the
1:02:04microbiome diversity correlates with
1:02:06those things. The other interesting
1:02:08thing that I I didn't really mention,
1:02:09but I I touched on is the other thing is
1:02:11that in the southern parts of the
1:02:12island, these guys are chewing cava and
1:02:14spitting it out, and then everybody sits
1:02:15around and drinks that. So, you're also
1:02:17sharing your microbiomes with each other
1:02:19as you drink cava. So, one of the things
1:02:21that we did as a group um when we went
1:02:23out there was we we did sampled our
1:02:26microbiome before we left the US. Well,
1:02:28two of us left the US, two of us left
1:02:29Japan. And then once we got there, we
1:02:32sampled it again. Then we went down to
1:02:33the southern islands and drank cava that
1:02:35people had chewed and we sampled it
1:02:36again. Then we went to the northern part
1:02:38uh where they ground cava and we sampled
1:02:41it again. So what is the effect of cava
1:02:43on your microbiome? What is the effect
1:02:44of drinking cava that somebody else has
1:02:46chewed on your microbiome? How long do
1:02:48does it take to be in another
1:02:50environment being exposed to these
1:02:51different uh organisms that are not
1:02:53potentially washed off? You know, these
1:02:55we're not going to a supermarket where
1:02:57things are, you know, sterilized
1:02:58somehow. These are, you know, things
1:03:00picked off of a a tree and kind of
1:03:02washed in a river and then you eat them.
1:03:04So you're you're getting a lot of things
1:03:05from the environment in these different
1:03:07areas and and so one aspect of this is
1:03:09traveler's diarrhea. Is traveler's
1:03:11diarrhea just coming into a new place
1:03:13and finding an equilibrium with what
1:03:15around you and what you have, right? So
1:03:17how quickly can these things kind of
1:03:19change and how flexible are they?
1:03:20because everybody's born with nothing
1:03:22and then you get something when you're
1:03:23breastfeeding or your early age and some
1:03:25of the studies have shown that all
1:03:27breastfeeding babies around the world
1:03:29have the same things in their gut. It's
1:03:31only when they they start weaning and
1:03:33getting these region specific diets that
1:03:35the diversity of those things
1:03:36change. But how fast does it change in
1:03:39somebody with an already established
1:03:41microbiome? How resistant is that to
1:03:43change? Do you have to just go to some
1:03:45place and eat local foods or do you have
1:03:47to um physically take in someone's
1:03:50saliva by whatever means to to to change
1:03:54your microbiome?
1:03:57So we we kind of did that as a a side
1:03:59project. We monitored our own
1:04:00microbiomes as we did these things. Did
1:04:03you take antibiotics or do you want
1:04:05mention the researchers got diarrhea?
1:04:09Uh I I didn't take any like
1:04:14If there is no other questions, uh,
1:04:16please join me to thank Professor L
1:04:19again. Thank you for coming. This has
1:04:22been a presentation of the Library of
1:04:24Congress. Visit us at loc.gov.

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