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Interview Off the Beaten Path: An Interview with Spencer Wells Jane Gitschier

pencer Wells has this geneticist’s Spencer Wells: Well, it was kind of dream job. He transits the globe, roundabout. I had done my PhD at S collecting DNA samples, Harvard, and like many geneticists in building collaborations, and the late ’80s and early ’90s, I was orchestrating what may be the most working on a model organism, and in extensive and fascinating project on this case, because my advisor was human origins yet, sponsored by one of [Richard] Lewontin, it was Drosophila. the most respected institutions in the I did basic molecular evolution stuff, US—The National Geographic Society. trying to detect selection in protein There, Wells holds the oxymoronically coding regions for an enzyme that was named post of ‘‘Explorer-in- important for flight. I looked at Residence’’ and runs the Genographic variation across species and within Project (www.nationalgeographic.com/ species and did detailed statistical genographic), whose mission is to analysis. I found no evidence of collect and genotype the Y and selection, but lots of evidence of mitochondrial chromosomes from population structure. And at the end of people the world over in order to track the day I wasn’t terribly interested in male and female lineages, respectively, the population structure of fruit flies, and thereby infer migratory patterns but I had always been interested in throughout human history. human history. doi:10.1371/journal.pgen.0030044.g001 I was curious to learn how someone So I wanted to apply those methods Spencer Wells so young (he started working with to humans, and the technology in National Geographic when he was only genetics was getting to the point where 1996—how did you make those 33) could plunge into a project of this you could start to study human connections? magnitude. The answer is that Wells is a population genetics, because back in man of many facets, vision, and energy. the ’80s it had been quite difficult. The SW: Good question. We knew next to And he has a knack for creating the human genome was so big and you had nothing about , which is opportunity. to clone everything. With PCR it got a why it was so fascinating. I sent off Happily, I had less difficulty pinning lot easier. letters to the US Embassies in all of the him down than I had anticipated. He Lewontin said, ‘‘You’ve got to work ‘‘stans’’—the newly independent suggested getting together at the with Luca Cavalli-Sforza,’’ out at stans—Kazakhstan, Turkmenistan, American Society of Human Genetics Stanford. When I got to Stanford, one Tajikistan, Uzbekistan, and Kyrgyzstan. meeting in New Orleans, where he was of the first things that Luca said to me I asked the US Embassies if they could scheduled to give a talk. We held our was that I needed to get out into the suggest any local scientists who might interview at the open-air Cafe´du field and meet some of the people that I be interested in working with me on Monde in the old French Quarter, was thinking of studying. Not only do collecting local samples and doing a where we were embraced by a warm we need the samples, but it’s also DNA study. breeze and the cacophony of traffic, important to hear their stories and to Most of the embassies came back and tourists, and two busking saxophonists. get to know them—to become an Our conversation ranged over two cups anthropologist, in effect. of cafe´ au lait; six continents; and a JG: Did Luca encourage everyone to do medley of ‘‘The Pink Panther,’’ ‘‘As Citation: Gitschier J (2007) Off the beaten path: An that? interview with Spencer Wells. PLoS Genet 3(3): e44. Time Goes By,’’ and two rounds of doi:10.1371/journal.pgen.0030044

‘‘Somewhere Over the Rainbow.’’ SW: He did. I had always been Copyright: Ó 2007 Jane Gitschier. This is an open- Picture, if you will, an Indiana Jones fascinated by Central Asia and I put access article distributed under the terms of the type, passionately delving into ancient together my first short expedition there Creative Commons Attribution License, which permits unrestricted use, distribution, and mysteries, but in Wells’s case, for the summer of 1996. I spent five reproduction in any medium, provided the original sunburned, hatless, and minus the weeks in Uzbekistan, Kyrgyzstan, and author and source are credited. whip. Kazakhstan collecting samples. Jane Gitschier is with the Department of Medicine and Pediatrics at the University of California San Jane Gitschier: Let’s talk about your JG: Wait a second. Just hopping on a Francisco, San Francisco, California, of transition from academia to adventure. plane and going to Uzbekistan in America. E-mail: [email protected]

PLoS Genetics | www.plosgenetics.org0341 March 2007 | Volume 3 | Issue 3 | e44 said, ‘‘No, we can’t help, we don’t know at the time. He said, ‘‘Nobody has I was just in Tajikistan a week and a anybody who would be interested in pictures of this part of the world. I’d half ago, and we were sampling all over this.’’ love to come with you if you wouldn’t the southern part of the country and But the University of Tashkent, the mind—I have nothing to do this asking people to name their capital of Uzbekistan, relayed it to the summer.’’ grandparents and great-grandparents Academy of Sciences. And eventually, So I said, ‘‘Yeah, sure, sounds like and so on. I could do that back to Ruslan Ruzibakiev, the director of the fun.’’ So the two of us set off to Central maybe to my great-grandparents. These Institute of Immunology, happened Asia knowing very little about it, people can do it back six, seven, eight upon it. He thought it sounded speaking very little Russian. generations. They’ve always lived in the fascinating, so he wrote back to me. JG: Is Russian the language of all those same place and beyond that they know That was the start of a great countries? even more about their history, but not relationship. necessarily their names. SW: It’s the lingua franca because all JG: What exactly did you suggest to So they have a sense, a clear idea of those countries were part of the Soviet him? where they came from, that something Union. is passed from generation that ties SW: I told him that we know very little When we got off the plane, Ruslan them to their ancestors. You explain to about this very important region of the picked us up with other members of the them that that thing is DNA and that it world. If you look at Eurasia, and you Institute. We went to his office—it was will tell us not only about the people think about people coming out of 8 o’clock in the morning—he gave us they can name but also people beyond Africa and populating the planet, this shots of vodka and said, ‘‘We have two that that they can’t name, and also region must have played a very variants: first variant is we rest today people on the other side of the world— important role—certainly the and work tomorrow, and the second me, people you’ve never met in Africa populating of Asia, but potentially the variant is work today. I think we’ll take or southeast Asia, and so on. populating of the Americas as well, and the second variant.’’ People tend to get really excited possibly India. But the very little we did So I was making buffers in the lab about that, I find. Generally we get a know about it suggested that it was and getting ready for the first part of very positive response. They want to unusual. It wasn’t just a mix of East and our expedition out of the capital two know more. They say, ‘‘I’ll give you the West. There might be a unique hours later. sample, but make sure you get the indigenous group of people who always JG: Who drew the blood? This always information back to me, and tell me lived there. seems like a daunting logistical what it’s all about.’’ I told him about the new DNA problem to me. markers, microsatellites, and SNPs, and JG: Do you get back to them? this thing called the Y chromosome we SW: I drew some of the blood, but we SW: Yes, but not necessarily every were working on at Stanford and how mostly worked with local phlebotomists, single person individually. Sometimes it’s starting to reveal some interesting nurses, and so on. I was taught by one of we do a press interview and it will be patterns. What if we collected samples the nurses there. broadcast into an area that we’ve and did some studies to try to figure JG: Did you have consent forms for all worked in, and we’ll talk about the out how these people fit into the world these people? group and what their DNA samples pattern? And he said, ‘‘Yeah, sounds have told us. amazing. I can set up all the details SW: We did. We mostly took oral locally. You deal with all the other consent but we did have people sign in JG: So you came back to Stanford with logistical stuff, getting yourself over most cases. We tried very hard to these bloods. Had you extracted DNA here and funding it, but I know the explain what the project was all about. as you were collecting? people we need to contact.’’ JG: This is a good point for me to ask SW: We made a white cell lysate into a JG: How much later after you had you about something called your high SDS, high Tris buffer, so they were corresponded did you take off? ‘‘blood speech.’’ stable in field conditions and didn’t have to be refrigerated for weeks or SW: That’s a term we used in Journey of SW: He got back to me early in 1996, even months. and by the summer, after a stack of Man when we were filming it. [Journey of faxes, I went. Man is also the title of Wells’s expertly JG: How did you get them all through written book on the use of DNA to customs? JG: How did you fund it? track human origins. His new book on SW: It turns out there are no SW: the is called Deep That was funded with money from regulations about the import of DNA Ancestry.] my Sloan Foundation post-doctoral in the United States. DNA samples can Most people are interested in their fellowship. They give you $8,000 for be received from anywhere. They can’t reagents and supplies, and I used about history, and indigenous people, who be sent out of China or out of India, $5,000 to get over there and bring all are the ones who give us the clearest there are very strict controls, but in the equipment. glimpse of their genetic history, are terms of importing DNA, if it’s particularly interested, because in JG: You went by yourself? noninfectious, absolutely. many cases it is all they have—what SW: I went with a photographer, Mark they cling on to—their sense of JG: Now we’re back at Stanford Read, an English friend of my girlfriend identity. sometime into 1997.

PLoS Genetics | www.plosgenetics.org0342 March 2007 | Volume 3 | Issue 3 | e44 SW: And it’s clear that we’re seeing JG: Oh, God. Why did you do that? do the html, upload it, often at four in some interesting stuff in the samples, the morning before we had to leave at SW: Because I liked the challenge of it. but we can’t make a lot of sense of it six a.m. Then I slept on the road. It was because we’ve got this one little dot on JG: Yeah, but how many thousands of really fun. We had a digital camera and the [geographic] map with a huge area extra miles is it? we posted sounds with RealAudio from around it that hasn’t been sampled. So SW: It was also because I liked the idea people singing in cathedrals in Georgia, what we needed to do was increase the of seeing the transition from Europe to counting to ten in Lezgi—whatever. sample size from the surrounding Asia, and because we were going to JG: So you went around Central Asia, regions. start sampling in the Caucuses and the giving the blood speech, collecting JG: And this informed your thinking in flights would have been very expensive, blood, engaging people. Six months is a going back to Central Asia in 1998. Tell trying to hop between all these long time! countries and hiring local cars and all me about it. SW: of that. It made more sense to have a Toward the end, we had two SW: That we should do it as a huge trip. car once we got there, and it was just a graduate students from Oxford—Matt And we should do it with a media question of getting it there. And it Webster and Tatiana Zerjal—and they component. turns out it’s a pretty quick drive. If you spent two to three weeks with us out in the field to experience it collecting JG: Why did you feel that way? went straight through it would take you five days to get to the Georgian border. samples themselves. I think they had a SW: Because it’s interesting! It’s fun to good time and learned a lot. That forms tell people about these things. The JG: OK, you are planning this trip. the core of what Tatiana did for her Internet was just becoming big then. SW: I decided to leave Luca’s lab to do thesis on Genghis Khan [i.e., evidence The BBC had just launched their new this trip. It’s hard to convince anybody, for a common Mongol Y chromosome Web site, which was quite big in the even Luca, to pay you for six months spread throughout Asia]. UK, where Mark Read was based. He while you’re out in the field. And I JG: Was there any point during this at knew somebody there who was didn’t know where I was going to end which you felt despair? ‘‘Oh my god interested in covering the trip. It was up afterwards. why am I doing this?’’ also in part to help attract the funding for it, because a six-month overland JG: So who actually funded it? SW: Absolutely. A lot of fieldwork is expedition is expensive, and you need a SW: Luca’s NIH grant did pay for the incredibly boring. A lot of time is spent vehicle. Vacutainers and the reagents. waiting for permissions, sitting in So we approached Land Rover, and I had applied for grants from various meetings, waiting for people to show they were very interested in this and organizations and the anthropology up. Or you blow into town on a gave us a brand new Discovery. Virgin funding groups would say, ‘‘You’re Saturday afternoon in one of the Atlantic agreed to fly all the equipment doing genetics, you should be able to ugliest places in the world and you have and us over to the UK, where we were get NIH funding for this,’’ and the NIH a day and half to waste. going to start the trip, for free. comes back and says, ‘‘We don’t want to JG: So what did you do? JG: Just for people like me who might do human diversity or human origins research.’’ And that’s part of the reason SW: You read or talked. But I did want to try this kind of approach, how question what the hell I was doing out did you pull this off? we’re funding Genographic the way we’re funding it [partially through here. I didn’t have a job lined up for SW: You write a letter. public involvement, below]. when I returned. Later, a possibility presented itself to JG: To whom? JG: I know the frustration. Who else work with at Oxford. SW: To a contact. For Land Rover, it was on the trip? So the samples moved to Walter’s lab. was through a family friend, who knew SW: Nat Pearson, who had been an And post-docs started coming through. someone on the board. The letter gets undergraduate at Stanford and was Then things started to get really into the right hands. In the case of starting grad school at the University of exciting scientifically. We had a huge Virgin Atlantic, it was just writing out Chicago that fall. Mark Read. The number of samples. In addition to the of the blue to their marketing or public journalist Darius Bazeran, who left us ones we collected on the trips, our relations department. Just selling in , and then Ruslan Ruzibakiev collaborators continued to collect, so people on a sexy idea. The Web site, I met us in Georgia. we ended up with over 2,000 samples think, did play a role in getting the and amazing Y chromosome markers JG: Was the journalist posting the funding. It provides a place for the that Peter Underhill and Peter Oefner things on the Web? person who gave you the equipment to discovered. The combination was be seen. And it was a new idea at the SW: He posted stuff for the BBC. The incredible. Every experiment we ran time. Not a lot of people were doing day we left, the BBC had a big story on was exciting and new. You’re getting live expeditions on the Internet. the front page about ‘‘Groundbreaking these results and they start to make US/Uzbek team leaves for Central sense. Piecing together migratory JG: Does Virgin Atlantic fly to the Asia.’’ patterns. As we started to publish stans? We did the posts [http://popgen.well. papers, the popular press picks up on it SW: No, we started in London and ox.ac.uk/eurasia] ourselves—I would because the Y chromosome is such a drove. write one, then I would edit everything, great tool for telling these stories and

PLoS Genetics | www.plosgenetics.org0343 March 2007 | Volume 3 | Issue 3 | e44 because it actually reveals migratory database created by IBM. They supplied We’ve gotten some fascinating results routes and ties in with historical the server, which is sitting in the and a lot of e-mails. For example, a figures, in the case of Genghis Khan basement of National Geographic. Hungarian woman wrote in and said, and so on. They have given everybody laptops ‘‘You’ve got to redo my test. You told Eventually I was contacted by a film with biometric [i.e., fingerprint] me I’m native American or Siberian, production company in London that recognition so that only the PIs can and I know my ancestors came from was working on a film about human access to the database. We are working Hungary—I can tell you the village they variation. Are we all the same, or are we closely with their computational were living in in the sixteenth century.’’ different—the whole race issue. They team on analyzing the data. So The Hungarian language, Magyar, is interviewed me and the producer said, some of our first publications, which actually related to languages spoken in ‘‘This stuff is absolutely amazing,’’ and are starting to go into the journals now, Siberia, and this is one of the first cases suggested, ‘‘We should do a film just on are coming through that group. where we’ve actually seen Siberian what you guys are doing,’’ and that JG: Are you at liberty to say what these lineages showing up in the Hungarian became . are about? population. They are there at very low Then, people at National Geographic frequency. We now through this wanted to have a meeting with me SW: We are expanding the survey of project have over 350 people who are because Journey of Man was going to be whole mitochondria genomes in Africa. of Hungarian descent and we see these one of their big television specials. That We’ve doubled the size of that database [Siberian] lineages at four to five was the genesis of the Genographic and it’s revealing interesting percent on both male and female sides. Project. We developed it over the mitochondrial patterns. That effort has course of the next couple of years, been spearheaded by Doron Behar in JG: What kind of information do organized the funding, and it is now Haifa. people give you when they sign on to launched. People tend to ignore what went on this project? within Africa. There is this inherent bias JG: For our readership—the goal of the SW: It is totally anonymous. We don’t in European and Asian scientists that Genographic Project is to . . . actually know which number goes into ‘‘ ’’ we’ve done Africa and then things got which kit. You get a randomly SW: To use DNA as a tool to answer interesting when we [humans] left, but generated alpha-numeric code and that that basic human question—where do of course there was still a lot going on is the only way you can access your we all come from. within Africa. We’re looking at routes results on the Web site. When you log people might have taken out of Africa JG: And the way you are going to do on, the first thing that pops up is a sign and back migration into Africa. that is . . . that says, ‘‘please help us with the Information that is coming out, in part, project by telling us more about SW: Is by studying genetic markers from an expedition I organized in 2005 yourself and donating your from people from around the world, to the Tibesti mountains in , up information to the database.’’ So we ask focusing particularly on indigenous on the Libyan border. groups because they retain that people their sex, their birth date, zip JG: There is also the public geographic context in which the code, language of their parents, origin participation component of the project genetic patterns originated to a greater of their earliest known male ancestor, [https://www3.nationalgeographic.com/ extent than people like me—I’ve got and so on. So it provides a little bit of genographic/participate.html]. How ancestors from all over northern anthropological context. many people have sent in their 100 Europe and I live on the eastern JG: I’d like to do it myself. bucks and their cheek swab [for DNA seaboard of north America. analysis]? SW: Well, we can send you a kit. JG: And you’re doing this via SW: Around 165,000. It’s been a great Public participation has raised collaborations with people all over the response. around sixteen million gross. The net world. proceeds are around four million. This JG: What is the reaction from people SW: We have ten regional centers is a nonprofit endeavor, and we’re when they get their ancestral focusing on sampling extant plowing that money back into the information? populations. One center is devoted to project, with half going to the field ancient DNA, which is a very important SW: It runs the gamut from people who research and the other half going to the component of it. write to tell us how amazing the project ‘‘legacy’’ fund to fund projects by is and how they’ve learned what it is to indigenous groups. For example, a JG: Does National Geographic support be human to people who say ‘‘I already project on language preservation, or to these people directly? knew I was Western European, you fund a Middle Eastern women’s SW: Yes, we essentially give them multi- didn’t tell me anything new.’’ But cooperative to resurrect a particular year grants. They are contracts, and mostly people are very positive about type of traditional embroidery work. there are deliverables. it. I think it is really tapping into We’re giving our first grants before the something, certainly in North end of the year. They are typically JG: So these centers do the fieldwork, America—this desire to learn more around $25,000 each. It’s a way to give make the DNA, and do the genotyping, about where we came from. We are a something back to the indigenous and then? nation of immigrants, so it’s not too people whose way of life is endangered SW: The data are sent to a central surprising. in some places.

PLoS Genetics | www.plosgenetics.org0344 March 2007 | Volume 3 | Issue 3 | e44 JG: Shifting gears, I’m interested in the biology in college, at the University of skins and we were in thick down general question of how people end up Texas at Austin. coats—that really gives you pause! doing what they’re doing. As a child, My father is a lawyer, a tax attorney. I People have lived like this for tens of what was your thinking? was never tempted to follow his thousands of years. SW: I wanted to be a historian or a footsteps. But he comes from a military I’m very, very lucky that I have the writer when I was very young. family. His father, whom he never knew opportunities that I do, to travel because he died in World War II, around the world and meet people and JG: Why? graduated top of his class from West hear their stories and see their way of SW: I was fascinated by history. It was Point and was apparently a wild man life. It makes me very sad to see that just this idea that there were people out in the field. I think maybe I got those ways of life are dying. who lived in a different way in a some of my love of danger and going to different time. And you could imagine strange places from him. JG: The Genographic Project is a model for doing things outside of a university yourself, through reading a book, being JG: Give me an example or two. there with them—like time travel. setting, for getting the public actively I wasn’t that interested in science as a SW: Everything is interesting in its own involved in a real-time scientific kid. I collected rocks and insects just way. Spending time with the Chukchi enterprise, and to help fund it. I think like any other kid, but in terms of a reindeer herders, where one morning it’s fantastic. 8 career, I wasn’t that excited till my in Siberia it got down to À70 C. I had SW: The only advice I would give to mother went back to graduate school to never experienced cold like that—dry get her Ph.D. in Biology and I started ice levels almost. It takes you out of young scientists is to think outside the hanging out in the lab with her and yourself. You think that life is all about box. Don’t just do what your advisor discovered that science was really fun certain things, but something like that did. Don’t just do what the other and cool. It’s not just about geeky guys causes you to sit up and think there graduate students are doing. If you in white lab coats, it’s about solving are some pretty extreme, amazing have interests that seem a little bit puzzles on a daily basis. things in the world. And the fact that flaky, off the beaten path, that’s I decided I wanted to combine the we were there filming people who were probably a good thing—especially if two in some way. I studied molecular living in a traditional way in animal they are passions. &

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