I was born in 1955 in Malaysia, actually, in Penang, which is a small island. I left Malaysia when I was four years old.
 My father [Stanley V. "Bill" Adams] was with the British government, and he actually had most of his career out there. He was there for, I think, thirty-two years. So I was born there because that's where my parents were.
 At the age of four we all left. He retired, basically. He was a lot older. He was in his fifties, I think, when I was born. So he retired, moved to England. We all moved there with him and set up a whole new life in England.
 To Dorset, the southwest of England, a small town called Sherborne.
 No. Well, by American standards maybe it's on the ocean. It's about thirty miles inland.
 He actually was with the British government. He worked for the city council. He was the treasurer and secretary of the council and very involved in sort of running the town there, George Town, on the island.
 Actually he had amazingly little education. He was born in a coal mining town in England and left school, I think, maybe at the age of sixteen or something like this and lied about his age and got a job in Malaysia with the government and from then moved up and did extremely well. He was really famous over there by the time he was done with the whole experience. So his formal education was very, very minor, really.
 His father actually was a dog breeder, so I don't know exactly who were the miners. I don't think his father was a miner, but it was a coal mining town in the Midlands of England.
 Cheslyn Hay. It's in the Midlands of England.
 Yeah, yeah. He never talked that much about things, so I don't know that much about them. And they were dead by the time I was born, his parents.
 Yes. Let's see. After World War II, she went out to Malaysia as part of the volunteer women's corps [Women's Volunteer Service] to look after the troops. She met him while she was there for that time. Actually, it's a very funny story. My father and my mother sat down for dinner total strangers and they got up engaged. I've never heard of a faster engagement than that. [laughter] So I guess they were both in the mood.
 Quite a lot younger. She was, I think, thirty-three when she met him. He was probably forty-seven, forty-eight, something like that.
 Yeah.
 No, she also left school. I think she left at the age of eighteen. She actually went into photography and worked in studios in London. During the war she was involved in touching up negatives as part of the war effort to block out crucial buildings and things. Then I guess after the war was when she started traveling, for she went to Italy and then on to Malaysia.
 She grew up in Surrey, a small place called Hindhead.
 Her mother was a nurse and her father was a bank manager.
 Yeah, much more, because they were still alive when I was young. I actually knew them both a little bit.
 Hobbies-- My father loved cricket and golf. He taught us how to play bridge--very badly, I might say. He was a really quiet man. He was always very interested in our well- being, more so than, I think, pursuing his own activities. My mother loved photography. She was always very interested in having a big family, so she had six of us, in fact, even though she didn't begin until she was thirty-five. Let's see, hobbies. What did she have for hobbies? When she was younger she loved traveling.
 He was always called Bill, but his real name is Stanley Vernon Adams. My mother, her name is Dorothea Christina Margaret Adams. She was a Duggan.
 I actually don't know their names.
 Dora was her mother, and-- Ooh. Can't believe I can't remember his name. Bertie, I think, was her father. [laughter]
 Yeah. [laughter]
 Probably. I honestly don't know.
 Duggan.
 Yeah.
 I'm third.
 Jeremy [Adams]. Actually there were six of us. Then my father had two others by a previous marriage, but I don't know them at all. I haven't met them since I was about five. So of my full sibs, Jeremy is the oldest. He's just three years older than me. There were six of us within eight years, very closely jammed together. He's now selling wine in France, which I always find very amusing: an Englishman selling wine to the French. [laughter]
 He did, actually, though by a very circuitous route. Ultimately he ended up going to university to study textiles, but he never used his degree. After that he decided to go to France to pick grapes and never came back. He just stayed there. But he ultimately ended up selling wine instead of picking grapes.
 Is Nick, Nicholas [Adams]. He's just a little older than me. He buys houses and does them up. He's very artistic at doing up houses, even though he really doesn't have formal training in it either. But he hires a band of men who work with him in construction, and then he does them up and rents them out or sells them and makes a living that way.
 Yeah, yeah. So he's in England.
 That's Timothy [Adams]. He left school at the age of sixteen, and he started off working in a bank and did that for quite a while and then became a stockbroker, and decided he hated it after a certain number of years and decided to retire. It's a bit mysterious to me how he managed to do that, but he's younger than me and now he seems to be retired. Now he lives in the country with his wife and two kids and goes for nice walks along the country lanes and plays golf. It's all very mysterious, but it seems to work. [laughter] He seems happy.
 Is David [Adams]. He also left school early. He left at the age of sixteen--he hated it--and went off to London. We grew up in a very small town, so what people did when they left was to move to a big city, go to London. And he went up there. He became a croupier in the casinos in London--it's a very different kind of activity as well--but also hated it. So he did that for a long time, maybe ten years or something. But he's very artistic and became obsessed, really, with making videos. He started off by making videos of weddings and this sort of thing. He spent a lot of money on equipment, and he's really extremely good at it. I've seen things he's edited, and it's really beautiful, what he does. So now he actually left the croupier business to try to make a go of this video thing. He's struggling with it, but I really hope he continues, because I think he's much happier doing it, even though financially it's tough.
 Yeah, and then the last one is Rosemary [Adams], Rose. She's my sister. She also left school very young. She left at the age of sixteen, and through a failed engagement she actually ended up becoming a single parent at the age of eighteen or so. I mean, she's terrific, really. She struggled a lot with poverty and so on bringing up this child but has done really very well, because while he was growing up, she decided to go back and take courses. She educated herself all through courses at home and ultimately talked her way into a university, even though she had none of the previous qualifications that you normally need to get there. She got her degree and did great. Then she took a qualification [exam] for teaching but failed to get a job in England. It's almost impossible to get a job in anything, let alone teaching. So at this point, she's not looking for a job in teaching anymore.
She's very artistic and has gone through a number of different creative trends or activities. At the moment she's very involved in theater groups with kids. I think she's actually become sort of like a community leader. She lives in a very small village, and she gets all these kids from all the surrounding villages mobilized to work in theater groups. Initially it started off that she would pick a play and, you know, audition them and put on the whole production, and they all loved it. But it evolved to the point where the kids themselves started directing it. They started auditioning each other, choosing their own play, and then most recently they actually wrote their own play. So they do the whole thing now, from writing the play onwards. It's been extremely successful. It's incredible what she does. Unfortunately, this is all sort of volunteer work too, so she also lives in great poverty. But she's a good example of somebody who's very happy with very little material stuff.
 I think my parents had a very hands-off approach to our growing up, actually. Partly my father, I think, was very withdrawn, although he was always there. He always went out to work and brought the food home and did all the cooking and all this sort of stuff, but he never played an extremely active part in disciplining us or even advising us or anything. My mother, I think, for quite a while in my childhood, wasn't very active in our upbringing, either. She actually had a nervous breakdown fairly early on. So the six of us kind of muddled around, [laughter] just kind of ran wild, I think, for quite a long time.
 Yeah, she did. She went through a lot of psychotherapy. I don't really remember when it all finished, but probably by the time I was eighteen or something like this she had become very, very much recovered. She had a poor childhood. And now she's very happy. She lives a very happy, independent life.
 No.
 Hindhead was where she grew up.
 Sherborne was where we first went. But a lot of the time we lived in places that were even smaller than Sherborne. I actually don't know the population of Sherborne. But at one point we lived in a village with a population of sixty, of whom eight were us. [laughter]
 Blackford. This is actually a fourteenth-century cottage that we lived in that my mother-- I mean, so this is her artistic side, too. She bought this house for something like £500 back in the early sixties and wanted to do it up, to restore it. She did that for two different cottages. One of them my sister now lives in. It's an old thirteenth-century chapel, in fact, that one. This other one that's a fourteenth-century cottage-- My brother who I told you retired, he's now living in it with his family.
 Some of the time we took buses--we actually moved from village to village within this general area--depending on where we were living at different times. Sometimes there were school buses that would bus us in. This one place where the population was sixty, Blackford, we used to drive in. My father was such an atrocious driver. Actually, that was the reason I learned to drive, because we had a greater chance of making it to school intact. [laughter]
 Yeah. They weren't that small, but the school probably had a population of something like 250, which I guess is small. It's not as small as some schools.
 Yes.
 There were different ones. They had this awful system in England of "Eleven Plus"--I don't know if you've heard of it--where you take a test when you're eleven years old and it decides your entire future. So at the age of eleven all of us took the Eleven Plus. The first three of us passed the Eleven Plus and so went to grammar schools, which are very good schools. Oh, no. The first four of us passed them. The next two didn't, and, I mean, it's not for any reason to do with brain power. It was just random, if you ask me. So they ended up going to a very bad school, I think. Basically they're sort of technical schools. It's very difficult to dig yourself out of that into a route in which you end up going to university, which is even more amazing that my sister was able to do it ultimately, since she'd gone to one of those schools. She ended up getting a degree through studying at home on her own and so on. So I think I went to a very good school, that I was lucky just because of the stupid exam at the age of eleven.
 When I first went to school-- This was after we moved to England. Soon after that I went to what's in England called a private school, and I guess it's a private school here, too. That was for probably five years. I went to that [Newell House School] till the age of ten or so. Then I ended up switching to the public school, which was also the elementary school that you go to till the age of eleven. So for my last year, or maybe my last two years, I went to that school [ Sherborne County Primary].
I think both of the teachers that I had at that school were actually very good. The last one I think of in terms of having at least some influence on my career, because I think he was very good at making sure that people passed the Eleven Plus. So the one thing I remember about him was helping me to understand the sorts of questions that they ask in the Eleven Plus. This is a very mechanistic kind of thing. In terms of philosophically there wasn't much value to any of it, but it actually did help in passing them, I think, because there's certain ways of answering those questions that he actually taught me.
More meaningful teachers, I have to say, were mostly negative influences. So my biology teacher was really atrocious. [laughter] It's amazing to me to think that I actually ended up in biology. She was my teacher [at Lord Digby's School] from the age of eleven to eighteen, as far as I remember. She would basically just dictate notes to us. That was our biology, so there was no excitement or nothing interesting about it at all.
I loved chemistry. That was actually what I went off to university to do first. I think a lot of why I liked it was because I liked the chemistry teacher a lot. He was fun, and chemistry was interesting to me. My other teachers--
Although I say it was a good school, I think my teachers were actually pretty bad, so I'm not quite sure why I said it was a good school. [laughert] The P.E. teacher I liked a lot. I think she had a major influence because I actually almost went to P.E. college to learn how to teach physical education. I actually got accepted there and, until six weeks before I went there, I was planning to go there.
 Yeah, yeah.
 Field hockey was a very big one for me, and actually I still do a little bit of it. I did a lot in college. Tennis I loved, gymnastics, running, stuff like that. Probably, field hockey was the biggest one for me.
 Then or now?
 You know, I think my family being so big and the six of us getting along so well, actually, meant that a lot of what we did very much revolved around the family activities. We spent a huge amount of time just playing together. We had tremendous numbers of different games that we'd play inside or outside, and we were almost like a self-sufficient unit It's really amazing to look back on it. And we all learned to play bridge together, like I said earlier. And reading, music. Music was a big thing for me, actually. I took piano and violin lessons from the age of about eight and did fairly well, at least in piano, but unfortunately dropped it when I went to college. I've always loved camping and that sort of stuff. When we were kids we used to go on camping trips a lot.
 England and Ireland, actually, which ultimately then led to me going to college in Ireland. We used to go on camping trips for six, eight weeks at a time in Ireland. I loved Ireland. There was a chance to go there for college, so I chose it.
 Oh! [laughter] I'm embarrassed to say that when I was really young I loved reading Enid Blyton. I don't know if you know Enid Blyton; Americans don't know her as well as the English do. But we were always told never to tell anyone we read Enid Blyton. [laughter] At the Eleven Plus age if we had interviews, "Don't tell them you read Enid Blyton." But I have to say I loved Enid Blyton. She wrote about adventure stories of kids, boarding school activities, and stuff like this. Very low quality, I think. [laughter]
 Well, I did a lot of jobs growing up to get money. One of the things about my family was that although in Malaysia we lived a very wealthy lifestyle--my father had done very well in the colonial system, you know; we had servants and the whole thing--when we went to England, the whole-- It was like from riches to rags. We went into really a pretty great state of poverty later on. So all of us worked from a fairly young age to get pocket money, since we never got any from our parents. From early on I started doing jobs like washing dishes in hotels and waitress and barmaid and all these things. The sorts of jobs that were available were very limited, because it was a very small community. Things like research were totally out of the question. I must have worked in twenty different types of restaurants, ranging from roadside cafés to highfalutin hotels, country clubs, and things. But I also worked in a factory, which I absolutely hated.
 This was packing baby food into boxes, and I remember being so bored. This was at the age of eighteen. I remember my particular job was to watch the food cartons coming off the conveyor belt, and I was supposed to pick off the ones that were not packed correctly. I was so bored that I couldn’t even be bothered to pick off the bad ones when they came by. [laughter] So I just sat there like a zombie for hours at a time. That was really bad. That was enough to make me realize I didn't want a job like that.
 Yeah. Yeah, I had a lot of good school friends. We just enjoyed hanging out together and so on.
 Almost all the time I was growing up I thought I wanted to go to medical school. I wanted to be a doctor I think this is also a part of the British system of education. At the age of sixteen they make you specialize, and you choose three topics that you do for A level. That's the end of any sort of openness. You get very focused very early, which I think overall I'm not in favor of. But I wanted to go to medical school, so it was fine. I did chemistry, physics, and biology for A level. But the headmistress had this idea that I wasn't going to succeed in medical school. I think the way they write letters--they wrote letters with our university applications--had a big impact on whether or not we went. So I actually got rejected from all medical schools at the age of eighteen. [laughter] The way you do it is not like the U.S. You apply for medical school at the age of eighteen and that's what you go to university to do. I was rejected from all of them, and I'm sure it must have been because of the headmistress's letter, because there was nothing in my record that suggested I was so bad.
 Yeah, yeah. You do O levels, which is two years before A levels. I got ten on those, which is a good number to get. I think she felt I wasn't serious, because at that point, for my final year in high school, the family actually moved into a trailer. I told you we went through these poverty stages and things. At one point we actually were in transit between houses, and we lived in this trailer, which of course had no electricity. She couldn't imagine how I was going to get homework done, and she used to complain to me. She'd say, "You're going to have to tell your parents. Do something about this. You're in your final year of high school. You have to get a better working situation." Of course, what could I do? But I did fine. My A levels were fine. I could and should have gone to medical school. So that was kind of stupid. But anyway, meanwhile I decided, "Well, I'll go and teach physical education.” So I went off on that track. Six weeks before I was supposed to do that, I got my A level results. In fact, that was what happened. I did really well in chemistry and physics. I felt very sad that I was never going to do these subjects ever again, because I had loved them. So it was on the basis of that that I had decided to go to university instead and actually study chemistry. I called up one of the places that I applied to medical school for [University of Dublin Trinity College]--this place is in Ireland--and I said, "Will you consider me for your science program?" I told them what these A levels were. They said, "Oh, yes." They more or less accepted me over the telephone. Six weeks later I went off to Ireland, to university.
 I accepted it. I think it was uncomfortable, because part of what happened was we lived in a huge house which was too expensive for what we could afford. It had eight bedrooms and it was-- I don't know why my parents ever bought this thing. We couldn't heat it, so it was really cold. We'd go down to the kitchen in the morning and it was forty-two degrees--we had a little thermometer there--and your feet would be so cold you’d have to wear things on your feet. Otherwise, you’d have to end up running across the hallway so your feet didn't go numb. [laughter]
Actually, we didn't even have enough food most of the time. But we had animals like goats and ducks and things. I remember my father used to go down to the greengrocer's and also to the bakery and ask for food for these animals, for the goats and the ducks. The bakery gave us food for the ducks and the greengrocer gave us food for the goats. He'd come up with these huge stacks of stuff. Then my mother would sit at the table sorting it: that for the goats and that for us. We'd have these tremendous soups out of discarded brussels sprouts and things. [laughter]
 I think for my mother it was very scary. I don't know what my father felt about it. He's not alive now, which is unfortunate. I'd love to talk to him about it. I mean, he just sort of accepted things the way they were and just kept going. He always would say, "Oh well, we must do what we can." I think part of his perspective was that he actually had been interned during the World War II in a Japanese prisoner of war camp. So any time things were bad, he'd say, "Well, it's not as bad as it was in camp." For three years he was actually in Changi jail in Singapore. If you read what he wrote about that, you understand why he said, "Things are not as bad as they were then."
 Well, later on he went blind. And my mother, in trying to get him mobilized to do something other than just sitting there, actually persuaded him to start writing his memoirs. So he wrote a whole thing on being a Japanese prisoner of war, which was very interesting, because he had never really wanted to talk about it. It was pretty factual rather than any sort of emotional thing. But it was interesting, all the same, because he talked about how bad it really was.
 Yeah, yeah.
 Right.
 Okay. We'd camped there a lot of years for the summers, actually while my mother was doing psychotherapy a lot. The psychotherapist who I think helped her most was in Ireland. We would go there for the summers so she could have big blocks of time to work with him. We'd go for eight weeks at a time. I loved it. We got to know a lot of people, family friends, during that time. Then the idea of going to Ireland for college was very appealing, because I knew people there, I loved Dublin, I loved Ireland, you know, and I could just imagine going to Trinity. So that was why I just felt free to call that day and see what the story was.
 Well, I started off that way, but it became clear to me after my first semester that chemistry was not going to be the thing for me because there was a huge amount of math and I wasn't prepared for the math at all. The way it works over there is you get on a track and there's no turning back. So after the first semester, if I hadn't changed at that time, I wouldn't have been able to change from chemistry. I would have been stuck in chemistry. So I could see that I wasn't going to make it in chemistry. So I flipped into biology, which was still a possibility at that point. Then it was only later that I realized how much I enjoyed genetics in particular.
 Exactly.
 Well, it was partly bail out but also partly-- As part of the chemistry course I think I'd had a bit of biology that first semester. I can't actually remember. But I think for some reason I was starting to like it. Most definitely it was a bail out, to be totally honest.
 Actually, no. It was fascinating. I had great biology teachers at the university. There was one guy, I remember from an early course, who talked to us about the evolution of life, basically, from the most simple organisms up to mammals. I was absolutely fascinated by this. I thought it was fantastic. Then we had a bunch of other classes that I found very interesting. When we got into genetics I really loved it, and I thought, "This is the only thing that's important at all."
 Well, I mean I guess because it's-- DNA is the basis of life and mutations make for such powerful changes. I'm not sure. I can't totally remember why it seemed so important. But for the last two years of the undergraduate degree we had to specialize again into some subset of biology, and the genetics department was the one that I wanted to go to. There was no second choice for me. It was genetics or nothing. So I was lucky that they took me, because the classes are very small at that point. They take something like ten students per department. Only ten of us could go into genetics even though there'd been, I don't know, a couple of hundred or so before that.
 Trinity-- There's a picture of it on my door, in fact, because they had a reunion at Christmas that I went to. Trinity College is actually the third of three Trinity Colleges: Cambridge, Oxford, and Dublin. So it runs very similarly to those two. I think that was the reason I was actually able to go to it, because it was the only university outside the U.K. that I could get a grant to go to. I think it's because of that connection with Trinity College: Dublin, Cambridge, and Oxford. So—
 To tell you the truth, I don't really understand how they're connected, but they're considered a threesome. Trinity College: Cambridge, Dublin, and Oxford. I don't know what ties them together. I never thought about it till this second, actually. [laughter]
 All of it.
 This is one good thing about-- At least it was. I think it's probably changed now. The British system of education gives a grant to everybody who wants to go to university. Or did give a grant. The grant pays enough to live on. It pays your fees, your housing, everything. At a pretty low level, but enough so you don't come out with loans.
 Yeah.
 When I first went I lived in what we call "digs," which is with a family. I just moved in with a family who kept students. They would give us bed, breakfast, and evening meal. They took care of us. So I lived with them for two years, and then I lived in a hall of residence--which I guess is a dorm over here--for a year. Then finally, in my last year I lived on campus in what they call rooms, which is like an apartment that two students would share right on campus.
 Play field hockey. I was very fond of field hockey in college. These were probably my best years for hockey. I was part of the university team, and we'd travel a lot and we did very well. We won tournaments, and one time we went to Belgium and played in a tournament there, which we also won. So field hockey was a big part of my life there.
 Yeah. [laughter] I was a forward. I was right wing most of the time.
 Yeah. When I first started playing field hockey, as an eleven-year-old, I was actually the goalkeeper. For two or three years I would stand back there watching what was going on. Then one day I said, "I've had enough of this. I want to play right wing." They put me up there, and I guess I was great. I got goals and it was like they couldn't believe the goalkeeper could play like this. But I think I'd been watching for so long, I kind of knew how the game should be played.
 From then onwards I was a forward.
 Yeah, I was fast.
 I was fast and enthusiastic, and I guess I had a bit of skill. There's stickwork involved with twizzling the ball around to get out of the way. I could do a bit of this.
 I always went back home. I got some more of these amazing jobs. [laughter] One summer I sold ice creams on an ice cream van for seven weeks and was so good at it the guy actually offered me a partnership in the ice cream business.
 In college?
 I had a lot of good friends in college I don't know what you want me to say about them.
 Well, I had a boyfriend at the time called Ed [Edwin Carey] who-- We split up, actually, because I wanted to come to the U.S. to be in science. That was the closest I came to that type of scenario. I started getting driven in science during college.
 What happened was we used to have these labs that I always hated, I couldn't stand. Most the time we used to spend discussing how to get out of it: who was going to go for coffee while who stayed behind to look after the experiments. It never actually occurred to me until the summer of my third year there that I actually even liked science or research.
What happened was I was given a fellowship to come to the United States to work in a research lab in [University of] Michigan. This was John [R.] Pringle's lab. It was an amazing experience for me. I thought I was coming to the U.S. to just basically see the U.S. and take a vacation and then go back to Ireland and sort of piddle on. [laughter] But when I came over I just totally fell in love with science. I worked like nothing I've ever experienced before or probably since. I mean literally sixteen, twenty hours a day the whole summer. I was just like an animal. I was obsessed with it. I would be dreaming about the experiments. It just took over.
So by the end of the summer it was perfectly obvious to me that this was what I should be doing for a career.
I talked with John Pringle, who is the guy I'd worked with that summer, about the possibility of going back for graduate school to his lab, and he said, "Yeah, sure." [laughter] So I decided that summer that's what I was going to do. I was going to go back there and do a Ph.D. in his lab. It was really that that first turned me on to science.
 Yeah, it was really luck.
 Yeah. Actually, I think I was better prepared because we focused so much, right? From the age of sixteen I told you we just did chemistry, physics, and biology. In college I just basically did biology with a bit of chemistry and physics. In my last two years I did nothing but genetics. So I knew a lot of stuff compared with my American fellow students, who I think were much more broadly trained. In the end, I think they do better, because they catch up in these fields because that's what they're doing. They also have all the background stuff that I never had. That's why I prefer the American system. But when I started I was at an advantage. In fact, I took my prelims [preliminary examinations] my first semester there, which normally people didn't do for another year.
I could already see that I had more information in my head then than I was going to have a year later, so I should take advantage and take the prelims without even studying, which I did. And I passed them. It got me out of an exam later on.
 There's an Irish American Foundation which supported this program. So every summer they would pay for two or three students in the genetics department to come over to the U.S. for the summer to work in a research lab. Actually, at this reunion that I just went to, I spoke with David McConnell, who's now head of the [genetics] department and who I knew back then. He still is pushing this program, and he saidthat 75 percent of the students in their department go on and do Ph.D.'s. He thinks a lot of it has to do with this Irish American Foundation.
 No, all over the U.S. So it's contacts that people there have with people over here. Actually, I think there's a good chance that students will start coming here to [University of] Arizonanow, because he said, "Can you take students?" And I said, "Yeah. Even if I can't right now, other people in the department can," and so on.
 Well, actually, John Pringle was just starting his lab. I was very lucky, because he was able to take time to show me the most basic things like pipetting and really, really basic things. I felt that I really learned from a master how to do science that first summer. I really learned a lot from him. Yeah, I don't know if in practical terms I was much further behind than anyone else.
The following year, when I went back to Ireland, I had to do a research project, which I must say I hated. I think I must be very fickle in terms of what situations suit me, because although I was working on yeast again when I went back, I really hated it. Part of it, I think, was the difficulty of working in Ireland, because the resources are so limited. Just to get things autoclaved was a major operation. Cover slips, I remember, we used to recycle. Here, you know, we just toss them out. Over there we'd wash them, and we'd stick them in these little plasticine things to let them dry. I found all this very frustrating. Another thing that I was doing in my project was looking for mutants that I'd then have to go and pick out under the microscope with a toothpick. This was like taking some elephant foot or something and hoping to pick up something tiny with it. So I got very frustrated, I think, by that whole business.
 No. [laughter] I was very focused on going back to that one lab. So I applied for graduate school there. I might have applied for graduate school in a very half-hearted way to Dalhousie [University]. It was just because I knew there was somebody working on yeast there, but I was never enthusiastic about it, and I'm not sure I actually even did the formal applications. So if I hadn't got accepted in Michigan, I don't know what I would have done. I mean, it would have been dire.
 Yeah, and that itself was a whole other experience. There were a group of us, now, among my classmates that wanted to come to graduate school in the U.S. We all knew we had to take this GRE. We had never even seen a GRE. We had no idea what it was. I remember we figured out it was on some far side of Dublin some day. So, you know, the night before we were up drinking beer and discussing where we were going to go for this thing. The next morning we kind of roll in. We have absolutely no idea what to expect, and I did extremely badly in it. I don't know how the others all did, but I remember in the verbal part of it I got 22 percentile or something, which makes me sound as though I'm from some far corner of the earth or something. [laughter] But somehow they accepted me anyway. The trouble was I didn't even realize it was a speed test. I think it was like the end was up, and I was still halfway through the thing.
I think another part is--something that people always talk about with the GRE--there' s a definite cultural component to it. It's actually fairly hard to read that stuff, because none of it do you just understand immediately. You know, it's talking about baseball or something. You don't know anything about baseball. It's amazing how that's true.
 I loved it. I loved it. Ann Arbor was wonderful. I lived in a house for international students, and I made immediate friends. You know, every evening we'd eat dinner together. It was tremendous. I really loved it. It never occurred to me that I was going to end up living here, I have to say. After I realized I wanted to come back for graduate school, I got very cold feet about the idea of moving so far from home. The only way I was able to get myself over here to come to graduate school was to say, "I'll just do it for a couple of years. I'll just do a master's [degree], in fact, and then I'll go back." But it never works like that.
 Yeah, but by then I was starting to make friends. Then your life starts to shift. I mean, I still loved that lab the way I had that first summer. If I'd gone back I don't know what I would have done.
 Well, partly, but I think I actually don't belong anywhere now. I think I don't belong in England. I love going back to England, and I love being with my family. I can't imagine how it is that I've organized my life so now I live so far from them. But on the other hand, I honestly don't know if I could live there. At the same time, over here I don't really feel that I belong here, either. I definitely don't feel American. I constantly am thinking about going back. In reality I don't know if I ever will.
 No, no.
 Yeah.
 I don't vote anywhere. I don't vote there and I don't vote here. [laughter]
 That's sort of true. But I don't know. I mean, that is definitely true that science sort of unifies the whole world or something. I guess the way I think about it right now is that I don't actually belong anywhere, but maybe it doesn't matter, because I can perhaps pick different things from different places. All I need is a base. So the way I think about it right now is Arizona is my base. It's a job that I love, but I have all these other aspects in my life that I also love. By definition I cannot have all of them at once, anyway, no matter where I live, so I might as well live here and sort of pick these other things.
 Yeah. We had to take classes. Let's see. One of the requirements was to take a language, because I didn't have anything officially that said I'd taken any foreign language in college--which I hadn't, because we specialized so early. I decided to take French even though I was already pretty fluent in French because I'd had a lot in high school and did very well in French. And, you know, England's so close to France. You spend a lot of time going back and forth. I took French mostly because it was very easy just because I already could speak it. [laughter] So that was fun.
I didn't have to take that many required courses. Since I already knew exactly what lab I wanted to work in I had no interest in doing rotations and managed to talk my way out of them. So I did no rotations. I think that was it. I did my prelim at a very abnormal time, so I didn't have to worry about that, either.
 Yeah, right.
 Yeah, though I mean, looking back, if I think about undergraduates now that I have in the lab, they only have to have some spark and some-- You don't have to be a superstar to agree to take them on as a graduate student, I think. But I think we had a very good interaction, and so I don't think there was any reason why he shouldn't have wanted to take me.
 Yeah. I think he'd probably been there a couple of years when I started graduate school.
 Yeah.
 I think he was an undergraduate and a graduate student in Harvard [University]. Then he did a postdoc in Switzerland and also one with Lee [Leland H.] Hartwell in Seattle [University of Washington]. I think, actually, the order of those two were flipped. Yeah.
 He was wonderful. I really liked every aspect of working with him. There were frustrating sides to him—that I'll tell you about in a second--but he was a very good friend to me. I felt incredibly supported by him. I think he thought of himself as in loco parentis to me, being so far from home. He was probably the first person I really saw acting in science. He's very highly ethical. He works very, very precisely. He has a very high standard. So I think I learned a lot about those sorts of things from him but also a lot about how to be generous in science. These kind of things I also learned from him: not to be competitive with people. It's not worth it. I'm sure he had more impact on my scientific life than anyone else in science.
 Yeah. I mean, I had two. I would say I've had two excellent ones. So he was one during my graduate time. But he's the one, I think, that really got me into science in the first place.
 [laughter] No, he didn't yell at people. He's got a terrific brain. He's a very, very smart guy and very interested in science. We were in a very general biology department, which was also, I think, another reason I loved graduate school. So we'd have these very wide-ranging seminars, and he would always ask questions, even on things totally unrelated to anything that any of us did. Very good questions. He's deeply interested in science and very, very focused on it.
I think, as a student, one thing that was hard was that he was so conscientious that I think it had two results. One was that he was actually very difficult to talk to, because he would lock himself in his office for hours. It was very, very hard to find times when he would talk to you, because he was always sort of frantically doing something. Because he did everything so carefully that everything took up a huge amount of time. That was frustrating, that I couldn't always talk to him.
I think that the other thing that's frustrating with him is it's very difficult to publish with him, because everything has to be so perfect, even down to the last bit of grammar, that writing a paper is really a major operation. I think his lab ends up publishing much less than it really should, given how much science actually is done there. And to someone in his lab that's frustrating. But I would say that that's really the biggest negative that I experienced working in his lab. I regarded it as an excellent experience.
 Yeah, and I used to babysit for his kids.
 None that I can really place like that.
 It was a nice-- I mean, I had a lot of good friends in the lab. So it was a very wonderful place for me to be. I enjoyed it.
 Well, when I first went there I actually went back to this international house that I'd first lived in that summer. So for the first year--or maybe it would be less than a year--I lived there. Again, it was a wonderful thing, because it was just full of international students and very, very social. It was a great way to start to meet people. For example, I ate dinner every night for months and months with a bunch of Indians. That was really great.
Actually, these apartments had four people per two-bedroom apartment, so I had a roommate who drove me completely crazy. [laughter] I decided to move out of there because of it, and actually I moved into the lab, which is something John Pringle never knew about at the time. I don't know if he knows even now that I did that. I decided to save money. Part of it was I also didn't have enough money, because I wanted to send money back home. I told you about this poverty thing. So I was sending some money home, and it just seemed like a waste of money to spend money on this apartment.
I moved into the lab instead. I used to keep all my clothes in petri dish boxes high up on shelves so nobody knew I was in there. I'd roll out a mat that I had behind someone's desk in the lab. I think I slept there for about three or four months. At the same time I was also working in a fraternity sweeping floors in exchange for food. The whole problem of living in the lab wasn't really a very big problem, because I just had all my food at this fraternity each day. In exchange for it I just swept floors for half an hour or something. I used to go to the gym to shower. But then after that I moved into a proper living situation, which was great.
 Well, John Pringle always went home by eleven o'clock at night. I'm sure I never slept before he left. [laughter] I slept in a room across from the main lab. Actually, I can't remember how I organized all this to be. I think most people in that lab actually left by eleven, so it wasn't—
 Yeah, I had a sleeping bag on a camping mat that I just rolled out. I used to keep it in a filing cabinet drawer or something so no one knew.
 [laughter] John always thought it was very odd that every time I'd babysit or something I'd want to be taken back to the lab, because he'd never end up taking me home. He thought it was very odd.
 [laughter] He might know about it by now. I forget.
 The reason it's valuable in terms of-- I guess there's a sort of indirect route and a direct route. I think indirectly the way I see basic research is that you don't know where the big, major, important breakthroughs are going to come from. By that I just mean the ones that are most relevant to mankind. So there has to be this background of progress being made by this machine of science. I feel that I'm just part of that and with no particular goal of solving anything really major. I think you just have to have a certain number of people providing the background bulk of science so that one or two areas can emerge. So there's that.
I think more directly you can make a strong case that yeast actually is a very valuable model system because, of course, all the genes, processes in yeast are found in humans and all other kind of organisms. Learning about yeast is very, very easy compared with learning about the cells of humans or something else. There are already lots of very good examples of how studying something in yeast has actually helped us to understand something like cancer in humans. Actually, in this very department, Ted Weinert works on a gene that he found just through studying yeast, and it turns out to be a gene that's very important in humans in cancer.
 This is the ATM gene for a certain type of cancer called AT [ataxia telangiectasia]. And I think there are going to be more and more examples of that. Again, you go into it kind of blindly. It's kind of luck, really, which genes really happen to turn out to be human disease genes. But at the same time I think it's important to really understand something well--the way you can yeast--to be able to understand humans.
 Right. Actually, I started in science round about at the beginning of it, so I don't think I had a good appreciation of what it was like before that. I remember, actually, in Trinity going into the library one day and seeing this big poster--they were advertising something in one of the journals--saying "Genes are split!" So it was the first time that there'd been the observation of introns. But that was in my final year in college. Already, at that point, recombinant DNA technology was very much a part of science, I think, though I have to say that my entire graduate career didn't consist of any recombinant DNA methods at all. All my graduate work was without any recombinant DNA methodology.
 Actually what I was doing was a lot of microscopy, also genetics, and just sort of basic physiological analysis of yeast cells. I was one of the few people in the lab who was not doing any recombinant DNA stuff, and they used to make fun of me, just lightheartedly, because I didn't know any DNA stuff.
 No, I mean—
 Yeah. I was interested in what I was doing, and it didn't require-- I thought at one point I was going to have to learn how to do that stuff, and sure enough I did as a postdoc. But I didn't mind not doing it as a graduate student.
 That's a very complicated question. I think he's basically right, and I think he's been right all the way through. It becomes an interesting question now, because at this point the yeast genome is on the verge of being sequenced throughout. So in some ways molecular biology is sort of what's going to happen next. The way I see yeast, it's gone through this era in which everybody has been cloning, sequencing, doing just a whole series of experiments that have been very laid out and very obvious for everybody. Now with the genome having been sequenced, it raises the question about where the whole thing is going to go to next. I think actually that what Kevin was talking about there still applies, that actually there's going to be no substitute still for the mutational analysis. [tape recorder off]
 Yeah. I think some of things that make yeast great still are so. I think yeast is going to go into a very interesting era now because all this molecular stuff has taken a lot of man-hours, person-hours, and it's kind of mindless. It's very obvious all the time what you have to do. People have just kind of plowed through it for years. That's really coming to an end. I think now is going to be the time when it's going to take really thoughtful science. So in some ways we're going to kind of go back full loop, I think, to where we were: that those sorts of experiments that were really thoughtful, less obvious ones are going to have to be the ones that make progress again.
 I don't know. To me it's hard to imagine a time when it was ever surprising. It's so much a part of the way I think about it now. I guess it must have been back then, but it's hard for me to remember that.
 I mean, I remem-- Actin is one thing I work on. Actin is about 90 percent identical between yeast and chickens. Probably about that time-- It was actually a bit before that that they knew about that. You know, it's surprising that things are that identical, I think. I guess I'm not sure exactly what they were so surprised by at that point, whether it was that degree of similarity or what.
 Yeah. That was absolutely true. I think it's actually a major reason why I stay in yeast. I love the yeast field. I think it's exactly like that. People really try hard not to compete with each other. There may be pockets of it within a field, but I think it's a very, very nice field to be in. In thinking about why that would be, I think part of it is probably, again, the people who started the field were very interested in that. Gerry Fink, for example, I think had a lot to do with that. All those guys at the beginning, I think, were very instrumental in making it that way. I think now the yeast field is very proud of it being that way, and people try really hard to maintain it.
 But you know what? I think in yeast, in genetics-- this is something I've actually chatted about with one of my colleagues here--because there's basically an infinite supply of different mutants and things, you don't get stuck working on one thing. There are always other mutants, other ways of looking at it. Because yeast is a whole organism and you can look at so many different things in it and the interrelationships of all the different processes and so on, I think that the competition isn't nearly as bad as in some other things. Certainly in my field I would say all of us communicate totally freely with all our stuff. If we find something that I know is of interest to somebody else, I would much rather send it to them than even think about competing. I'd much rather say, "Here. We found this. Why don't you go--?" I think other people do the same thing. I think there's enough room in it that there's not an issue.
 I don't think so, no. For me I think it's very important to be in a cooperative kind of situation. I feel I have a tremendous number of really good friends in the yeast field. Part of what I love is going to the yeast meetings each year and seeing these people and exchanging ideas. You just build up the contacts, so every year it just becomes a bigger and bigger social group.
 Well, I don’t know. I think some of being successful is doing what you do well. If you identify a niche and you just do well in there, you don't have to be shutting out other people. So I'm not sure that competition is so essential in this field.
 When I first went over for that summer, my project was to look for mutants of yeast that initiate division at an abnormal size and, in particular, at a small size. This was an idea that came from work with another yeast, Schizosaccharomyces pombe, a lot of which was done by Paul Nurse, who of course is still very well-known in the field. My first summer I was really looking for mutants that made small cells.
When I went back as a graduate student, that wasn't what I worked on at all. Partly I'd become very frustrated by the project when I went back to Ireland and continued to work on it there. I told you I didn't enjoy that experience. So when I came back to the U.S. I then picked up a whole different line of work. Actually, I started off with several different sorts of projects and just went in whichever direction worked best.
 Let's see. One of the projects I was working on was actually looking for cell cycle mutants that made abnormally shaped cells, because I was interested in the process by which cell shape is generated normally. So we looked for mutants that were defective in that process. The other side of my dissertation was asking whether the cytoskeleton is important for generation of the cell shape. Very little was known about the cytoskeleton's roles at that point. I think that side of the project is actually what really became my dissertation. That was the most important part of my thesis.
Some of that involved working out a way of visualizing cytoskeletal elements in yeast through immunofluorescence methods. This has had some impact in yeast in general just because now everyone likes to use immunofluorescence. So the same methods that we worked on then are now used. But at the same time it also allowed us to learn about what the cytoskeleton is actually doing in yeast.
 It's just a way of visualizing a certain protein that you're interested in. Basically, the process is to-- If you're interested in, say, actin, you make antibodies against actin in rabbits by injecting the actin into rabbits. You have antibodies against actin. You can take them out of rabbits, then, by bleeding blood from the rabbits, purifying the antibodies. Then if you tag them with a fluorescent tag, then if you now put these antibodies into a cell-- whether it's yeast or anything else--you can see where the protein is in cells.
So this had been done in all different cell types but never in yeast. One of the things I wanted to do early on was to figure out a way of visualizing things in yeast.
 Yeah. And then you used fluorescence microscopy to look at where these proteins are. Just by seeing where the proteins are you can learn quite a lot about what they're actually doing.
 Fluorescence microscopy is where you're looking at a fluorescent image. It's fluorescent because of the fluorochrome that you have associated with the antibodies. It's like regular microscopy, but you're just looking by fluorescence instead of by light.
 Yeah, basically. People thought that with yeast it was going to be very difficult to do it because yeast has a cell wall and also because yeast is very small. So a lot of people thought it wasn't worth trying, but in my state of great ignorance I thought it was. Actually, it wasn't that hard to modify those methods. We could see amazingly well both actin and tubulin when we did this for yeast.
 Uh-huh.
 Barbara Sloat was sort of a senior research scientist in John Pringle's lab. She's the one who initiated the field of morphogenesis, I think, really, in John Pringle's lab by studying a mutant that was defective in forming buds and just grew sort of uniformly. I was very interested in her work, and I think that that was what first made me want to work on that side of the lab, that project in the lab. So although I really didn't work that much with her subsequently--she left the lab, I don't know, a couple years later or something--she definitely had an impact on me choosing that field.
Then as part of my thesis proposal I said that I wanted to work out immunofluorescence methods, and I proposed to use antitubulin antibodies that John Kilmartin had already generated. The reasons I wanted to do it was because we knew where tubulin was already, so it would be easy to see if the method was working. I remember getting very frustrated with John Pringle, because I wanted him to write a letter to Kilmartin to ask him for antibodies. And I told you he was always procrastinating. This letter never got written. I got very frustrated.
And I was going to [the Marine Biological Laboratory at] Woods Hole one summer to work with Bob [Robert D.] Goldman, who had antibodies against intermediate filament proteins. Another thing I was interested in doing was actually looking for intermediate filaments in yeast. This was just a different project. Goldman had agreed that if I went to Woods Hole that summer that I could just use his antibodies and check by Western blots for cross-reaction in yeast. But when I went to Woods Hole, it turned out that John Kilmartin was there teaching the course. So immediately I dropped the intermediate filament project and said, "I want to work with Kilmartin to work out immunofluorescence." I just worked with Kilmartin for those two weeks, using his antibodies to develop the immunofluorescence method. By the end of two weeks we'd worked it out. So that's all I actually ever worked with him. He went back to England after that, and I went back to Michigan. Each of us did things with the method, and that was how we ended up publishing together.
 When we first were doing immunofluorescence we did it with tubulin. It was just really beautiful, because microtubules in yeast form the mitotic spindle. That's part of the nuclear division apparatus. And also the cytoplasmic microtubules that go from the nucleus into the cytoplasm-- It was really tremendous because we could actually see both of these. By electron microscopy, which is what had been used before, the cytoplasmic microtubles were always very, very difficult to see because you were just looking at individual sections. Immunofluorescence was great because it just allowed you to see--in most of the cells--how extensive the cytoplasmic microtubules were. It was just really beautiful. [laughter]
 No. It was just surprising to me that it worked so well. It was just beautiful. Then, using these methods, we were able to look at actin, whose distribution we really had known almost nothing about before. Kilmartin actually worked with the antiactin antibodies. At the same time I had been working with another fluorochrome which was a fluorescent-labeled phallotoxin, which is a mushroom toxin that binds specifically to actin and gives very similar patterns to antiactin antibodies. That was really new because we didn't know where actin was, and it was exciting to see that.
 Well, no. Before that I did have years of frustration, because in waiting to get Kilmartin's antibodies, I'd been working with some antiactin antibodies from chicken or somewhere. I'd seen these patterns of dots in yeast cells, and I had absolutely no idea if this bore any relation to reality.
I got extremely frustrated by it, actually. I used to work on a fluorescence microscope in the department in the medical school, which was a ten-minute bike ride away. So I'd have to prepare myself, as in bike over there with these samples. By the end of it I felt like throwing the microscope out the window. [laughter] It made me very frustrated for months and months. It was sort of non-reproducible and—
I think, looking back, probably what I was looking at at that point was artifactual, in fact, because I think it's very easy to see dots by immunofluorescence for just sort of random reasons. But fortunately I had the sense to think that there was a good chance it was an artifact. Later when we had more confidence that the immunofluorescence method was actually working and we saw similar things with phalloidin, then the whole thing actually became much more meaningful. What was meaningful later was that Kilmartin had generated anti-yeast-actin antibodies. So we were no longer dealing with anti-chicken-actin antibodies. I don't know for sure, but I doubt if those chicken antibodies were actually working against yeast actin. It probably was an artifact. Whereas Kilmartin had antibodies that really recognized yeast actin.
The other thing that was very frustrating early on was getting the thing on film. These fluorochromes would fade [snaps fingers] almost instantaneously under the microscope. I'd see something and then it would be gone. I couldn't even take photos of it to show people what I was seeing.
I guess two things happened. One was that [Theodor] Wieland, I think his name is, developed a better fluorochrome for phalloidin. It was a rhodamine-labeled phalloidin instead of NBD [nitrobenzoxadiazol] phallicidin, which had been used before. This rhodamine- labeled phalloidin was terrific because it didn't fade anything like as fast. So that was one really wonderful thing.
The second thing was that somebody else developed an anti-fading mounting medium with phenylene diamine in it. I just happened to find this thing one day in going through Current Contents. I was very excited by it, and so I tried it and it was great. It suddenly made it possible to take photos, you know, get the thing on film. Up until then I'd been fiddling around with-- There was a guy [John Langmore] in the biophysics department [at University of Michigan] who let me use a laser beam and God knows what to try to get photos. It drove me really crazy. After I got back from Woods Hole things were much, much better.
 I think the frustrating part of it probably was in my second, third year or something. Probably in my third year--about then I should think--I went to Woods Hole. Things then got much better.
 Yeah, but until very recently I've actually also really thought a lot about going to medical school. Just very recently I've put it out of my head completely, but I think I've always had this yearning, actually, to have more of a "people" kind of job. Science really makes you very focused on what you're doing and makes you not even want to talk to people while you're working. I really hate to talk to people when I'm working. But it's very opposite to how I actually am, because I really much prefer to interact with people. I mean, my greatest joys in science are really through interacting with other people and doing collaborative things and so on. I always felt that I wanted to do something more relevant that was really helping people more.
But I think I've recently come to realize, first of all, that ten years in medical school is not realistic at this point in terms of what I want to do. But secondly, I think being in academics there are lots of different ways you can have this job. I don't even know what way I'll end up dealing with this job, but I feel that you have tremendous freedom to pursue whatever things you want. I can probably organize this job to have as much people contact as I want. I don't know. That's the way I think about it right now.
 Yeah.
 No. [laughter] Actually, that was one thing I was certain I did not want to be. All the time I was in graduate school I just loved it and I couldn't imagine where I was going to go next, because I knew I did not want to run a lab. So then the time came to do a postdoc and I thought, "Okay, being a postdoc's probably just the same kind of thing. I'll just be a postdoc, and I'll enjoy doing that, and then I'll cross that bridge later about what to do." I loved being a postdoc, again. It was also a wonderful experience for me. But then the ugly time was coming in which I couldn't go on being a postdoc. At least that's the way it seemed. Actually, I think that's one really sad thing about science: that there are not positions for people like that who do not want to run a lab, who are very talented at the bench, love being at the bench. I think there are a lot of scientists out there and they should be a great resource. I would love to have people like this in my lab now, right? I think the funding agencies should think about setting up money for people to go on supporting people like that. They're well-trained. They're very good at what they're doing.
 Yeah, she was.
 After she left she was really interested in women-in-science programs and things. Right now she's actually teaching in Michigan, so she's not really still in science. She teaches in a residential college. She got very involved in this women-in-science program and so on. So she didn't really stay in it the way I think I would have liked [her] to have.
 Well, at this point I decided that I really wanted to go back to England. I decided, "If I'm ever going to go back to England, this is the time to do it. Otherwise, that's it." Actually, [John V.] Kilmartin I wrote to, to ask him if I could do a postdoc. I was very excited about the idea, because he worked on spindle pole bodies, which are microtubule- organizing centers, and they were a total black box. I thought the whole thing was fascinating. I was very excited about the kind of approaches that can be used. I wrote what I thought was a great letter. I'd love to look at it now, go back. I think it was a great letter. It described what I wanted to do as a postdoc and-- At any rate, he wrote back to me after about a month and said, "Sorry, no room."
I was incredibly disappointed. It was like when I first went to-- When I first went to everywhere, actually. I always only applied to one place. When I went to [University of] Dublin I just applied to Dublin, ultimately. When I went to [University of] Michigan, I just applied to Michigan. For my postdoc I just applied to Kilmartin, and then suddenly he couldn't take me. I had no idea what I was going to do. Then I went into this kind of frantic mode looking for random postdocs in England. It was very chaotic.
I found some yeast person. Actually, she [Jean Beggs] happened to be advertising in Nature for a postdoc. I thought, "Fine, this will do; I'm getting back to England." But I had a very bad feeling about it. I wasn't interested in it. The day she wrote to me and said, "Yes, you can come," I had this really bad sinking feeling in my belly that this was not what I wanted to do. Then I thought, "Oh, well, I'll apply for money or something." I thought there was another way out of it. Oh, I think she was waiting to see if she got money, and I was hoping that she wasn't going to get money so then I wouldn't have to go. But no. She wrote to me and said, "Yeah, I've got money." Then again my heart sank and I felt committed.
 Yeah.
 Probably it was because the previous summer I think I had been over there for a meeting in Edinburgh and I had met some of the people in the lab, and I just didn't have a good feeling about it. I wasn't particularly interested in the field. I wasn't particularly energized by the people I spoke to. I felt like I had had a great career so far. I'd really enjoyed it. I just felt it all sliding away. But I went out of a sense of obligation.
But actually, six weeks before I went, I went to a meeting--or maybe even less that six weeks--in Colorado. I think it was a Keystone meeting. And I already had the idea that at this meeting I was going to line up a second postdoc in case the thing didn't work out. So I went to this meeting and David Botstein was there. I think it must have been someone from his lab who gave a talk. I'd always been impressed by people from his lab; they always gave beautiful talks. Right after this talk I said, "Okay, that's it, I'm going to go ask David." I hadn't decided who I was going to talk to, but after that talk I said, "I'm going to go ask David." So I went up to him-- It's funny, because he said, "Oh, Alison, I want to talk to you." I never found out why he wanted to talk to me. I was just a graduate student, I didn't even know he knew me. But I started my thing. I said, "David, I wanted to talk to you about the possibility of doing a postdoc with you." He said, "Great, great, great. Walk with me while I go get a cigarette." [laughter] We went to buy cigarettes and by the end of the conversation he agreed to it that I'd go for a second postdoc.
This really helped a lot when I went to Scotland. He understood exactly. I had been totally honest. I said, "I'm not happy about this thing. I don't know how it's going to work out. I want to come back to a second postdoc with you. I don't know when." And he was great. He was very supportive. I went to Scotland and it didn't work out. That's a whole other story. I don't think we can do that in two minutes.
 Well, actually he knew about me because of immunofluorescence, because his lab was also interested in actin and tubulin. They had mutants. They were approaching what actin and tubulin were doing for mutants. I'd been doing it through looking at the localization of the protein. I think he was impressed with the immunofluorescence, probably.
 No, but I'd talked to other people in his lab. Actually, he might have known that I was interested in doing a postdoc with him, because for a lot of the meeting I had been whining to people who had been in his lab about how I wanted to talk to him and I didn't know if I had the courage and I thought I wasn't good enough. All these people kept saying, "Oh, go talk to him." I have a feeling that perhaps one or two of them had said to him that he should talk to me about it. That's probably what happened.
 Actually, my eldest brother [Jeremy Adams] did graduate in textile management. My youngest sister [Rosemary Adams] also graduated from [University of] Bath. She transferred. She started off with the Open University and then the qualifications she had achieved through that enabled her to go to a regular university.
 Yeah.
 I was the only one who went on the straight and narrow.
 I probably was the only one who didn't have the courage to do anything else. I mean, in the case of the younger ones they had a disadvantage because of this Eleven Plus problem. So it was a very tricky route for them to get anywhere else. My second eldest brother [Nicholas Adams] went to university and dropped out of it. He finished after about a year or two. He was the only other one who went to university straight from school. I don't know why.
 No, we all played together and had different friendships at different stages with different ones of us.
 Actually, I didn't think things were off-limits so much, but I always assumed that I would get married and have kids and just do the traditional standard kind of thing. In the schools I think we had extremely poor career counseling, in which they would suggest that we could be air hostesses or secretaries or nurses and that was sort of the extent of it. So I think we weren't really very well encouraged. As for Ph.D.'s, I'd never even heard of the word, I don't think.
 Right. So doctor was by far the most professional thing that was an option that I knew of at that stage.
 Right, right.
 No. I don't know, I just always liked the idea of helping people.
 Yeah, I think I was very frustrated just by more lack of organization type of issues, you know--that to actually do an experiment we first had to wash dishes and then go and autoclave them; they weren't just there. So I don't think it's so much an issue of the money. Actually, I think low-budget science is really very possible. I think there's a huge amount of data and information at the moment that's been generated. People don't have the time to go read the literature, so they don't even know what's out there. I think if everybody stopped doing experiments for a few years, we'd probably make a lot of important discoveries just through reading and putting different ideas together.
I also think in places like England, where money is limited, people spend more time thinking about what they're doing rather than bashing on through large volumes of stuff in the hopes that something will come out of it. So I don't think it's so bad to have less money. I think it's very bad to have no money.
 Yeah, I think that's unusual. I think it's very good when people do that. It would really help people to be creative if we all felt we had more time to actually go do things like that.
 Yeah. You're rushing from one thing to another--one committee, one grant, one teaching type of thing to another.
 The cytoskeleton is a system of fibrous elements that run through the cell. They're made up of different types of proteins. A lot of different roles have been ascribed to them, varying from roles in motility--moving things around inside the cells--to roles in maintaining structure of cells and so on.
 Yeah.
 It gives you clues. So for example—
 --if a protein is in the nucleus, there's a good chance that it’s doing something to do with nuclear functions rather than something to do with secretion out in the world of vesicles and so on. It's a pretty standard thing in cell biology to learn about where your protein is if you're interested in learning about what it's trying to do.
 Yeah.
 Tubulin-- We already knew where it was by electron microscopy studies that had been done by other people. It's found in microtubules that are both inside the nucleus and outside the nucleus. Actin-- We didn't know where they were. So by looking by immunofluorescence and these other fluorescence methods with phalloidin, we found where it's localized, and we found specifically that it's concentrated in regions where the cell is growing, making us think that actin is involved in helping cells to grow in particular regions.
 Let's see. It's like a big topic. I arrived there and-- I mean, part of the difficulty perhaps was that I'd been already in the United States for six or seven years. There's always some level of culture shock when you shift countries like that, even though U.S. to Britain isn't such a huge thing as, say, U.S. to India would be. But still you always miss things about the place you come from.
I wasn't particularly interested in the project but I was hoping that I would become interested in it. I think the trouble with the lab for me was that people in general were not cooperative and friendly, particularly towards each other. Everyone was their own little island and in a competitive type of mode, which I never like. I really hate it when there's a lot of bitching about each other going on. So usually I just kind of drop out. Actually, for the first time in my life people thought that I was a very quiet sort of person in that lab. [laughter] It very quickly became clear to me that I wasn't really going to be very happy there. In fact, something that perhaps was more of an excuse than anything else was that I had the chance to observe very closely a case of fraudulent science. I used this as an excuse, or at least part of an excuse, to leave. After three months, I told the person whose lab it was [Jean Beggs] that I wanted to leave. She managed to talk me into staying, but after seven months I actually left anyway. It's hard to--
 Yeah. I was actually the person who uncovered it, which was not a particularly nice thing to have to do when you first arrive in a lab. I had arrived there to pick up a project from a graduate student who was going to soon be graduating. His project had actually been to look for mutants defective in splicing, which is the removal of introns from genes. He'd supposedly identified some nice-looking mutants and characterized them. They looked very good. But it was always a problem trying to see his data. I always wanted to understand exactly what he had done, because I was supposed to be picking up his project. He never really had organized notes or anything, so it was difficult.
Then at some point I started to get the feeling that actually it wasn't all quite kosher. I don't actually remember what the experiment was, but I set up an experiment that would tell me definitively one way or another whether the thing was fraudulent. I remember arriving on a Monday morning, looking at these plates, and realizing that the whole thing was completely made up. At that point I decided I was leaving the lab. That was after three months. As I said, I think it was perhaps as much an excuse as anything, because, you know, you can live with that. You just change projects or do something different.
But the head of the lab-- I mean, to her credit she was very good at listening to me, believing me, and she took action. Something like a year later he was actually thrown out and everyone-- I think he admitted to it and then he was thrown out of science. Fortunately nothing had been published, so there was no long-term damage from that. Because I was very unhappy there anyway--I just felt I was wasting my career being there--I decided to leave.
 Yeah.
 Not really. My heart wasn't in it at all. So I went through a very major lull. I did absolute minimal work while I was there. I've never worked so poorly in my life.
 Well, Edinburgh's a beautiful city. It was kind of fun living in a city like Edinburgh for a while. The scientific buildings were on the outskirts of Edinburgh, so every day I'd go running through the woods and things. One thing that was really great was several people in the department were also interested in these sort of things, so there was a whole group of us that would go exercising together. Probably I was fitter at this point in my life than any other time because I wasn't interested in my science at all.
 Yeah. Actually, I remember calling John [R.] Pringle and saying, "John, I'm really unhappy. What am I going to do?" and just whining and whining. He said, "Look. Just get out. Just do something." I also called David Botstein and said that I wanted to come soon. He was great. He said, "Yes. Come any time you want." So that's what I did.
 [laughter] He is a character.
 Well, he's wonderful. When I was in his lab, I'd go to meetings and people would say to me, "How can you stand to work with him? He's so aggressive and obnoxious. I couldn't see what they were talking about at all, because in the lab he was just wonderful. He was very, very supportive of everyone in the lab. He never, ever put us down. We could be as stupid as we had to be, and he would always answer things seriously and very, very nicely with a lot of support. I found him tremendously interesting.
He'd talk to us on all sorts of different subjects with great authority. He had a lot of knowledge about a lot of different types of things. We had this cookie room where David had somehow managed to set up a fund by which we could all buy cookies every afternoon, so we'd have some tea and cookies. David would come in there sometimes and talk to us, because David loves to talk. I guess some of us liked to listen. We'd have this phenomenon whereby we said, "David's holding court." Everybody would be listening and David would be talking.
But I really loved working with him. He was terrific. And he had a great lab. He had a lot of really good people in it. So even though we didn't see much of David, we had a lot of very interesting interactions. I could learn a lot from the other people in the lab. David himself would always make incisive comments at critical moments.
 We actually had tea and cookies ourselves every day. David didn't always come down to it. Often he was out of town or something. But sometimes he'd come in, and then he'd hold court, as we said.
 Yeah. Towards the end of my time in his lab, he moved to Genentech. So for a while he was on two coasts. He had his MIT [Massachusetts Institute of Technology] lab and also his Genentech lab. Most of us stayed in MIT for that year, and then most of us shipped out to Genentech. I mean, it's to David's credit, I think, that probably ten people at least from his lab--I don't know, maybe ten people--moved out. And we set up a lab there in Genentech. Then, of course, David moved on again later. And at that point I know a few people moved on again.
 Yeah, so I spent almost a year there.
 Uh-huh. So initially I was at MIT with David. Then when he shifted to Genentech, I went as a postdoc with him to Genentech.
 Yeah, yeah. I think we were basically baggage. It was sort of part of the deal. They got David, but he got to take us. So we continued to work on our own things. I think we were of very little interest to Genentech, probably. Just as baggage.
 It was a lot of money. Yes. I mean, it was terrific. I was actually a Burroughs Wellcome [Fund] fellow. The way the Life Sciences [Research Foundation] is set up-- Don [Donald D.] Brown is to be really thanked massively for it. It's money from industries. They give you a stipend but also a large amount of equipment money that you can then take on with you to wherever you go. So I bought a computer and a microscope, a very good microscope. It's really a nice fellowship to have.
 Where did I live? First of all, I lived on Beacon Hill in Boston in an apartment. I actually jumped around a lot. Then I moved to Jamaica Plain, lived in a house there. Then I moved--where did I go?--to North Cambridge, which is probably the closest one.
 Yeah, I remember it.
 I had a very good time in Boston altogether. The lab itself was a very fun place to be. There were a lot of us that got on extremely well in the lab. We'd often go out for dinner together and then go back together to work in the lab in the evening. So it was a very good social environment intermingled with the lab experience.
But in addition, I also had a very, very good group of friends outside of it who I'd met through, again, an international thing. This was, actually, a European club in this particular case that was very active in having meetings on interesting things. I made a lot of very good friends through this European club. We'd do things together like go hiking and skiing and stuff--play music together.
 Oh, absolutely. I thought it was fantastic. But I also loved graduate school. To me the two were very similar. Both were good experiences. You know, after your first year or two in graduate school you don't have requirements there either. You just have to get something done, which is also what you have to do as a postdoc. Yeah, it's a great time. I wouldn't mind being a postdoc for the rest of my life.
 Yeah. Somebody needs to fund people in that position. If it was NIH, they'd need to allocate money to those types of positions.
 Yeah. I don't know how interested universities are. Especially in the current climate, the universities seem to be much more interested in teaching.
 Yeah, I took a new approach. Whereas I'd been looking at where the actin is in cells, David's lab had been very involved in getting mutants of actin to ask what goes wrong when you don't have good actin in the cells. It was a very genetic kind of approach. So I picked up in that sort of genetics. My particular project was to look for actin-binding proteins through genetic methods, and in particular through a suppressor analysis, which is a way of looking for interacting proteins through compensating mutations.
 The idea is if you have two proteins that interact with each other in the cell, if you make a mutation in the gene for one of them, that the complex between the two proteins might be defective now because the two proteins fail to interact. You might be able to restore the function of this complex by a compensating mutation in the gene for the interacting protein. It's sort of a lock-and-key type of phenomenon.
Through those sorts of suppressors, then you can identify actin-binding proteins, or proteins that are interacting with actin. So that was the approach I took, and happily it led to an actin-binding protein that I still work on.
 This protein we called Sac6, which is the yeast equivalent of a vertebrate protein called fimbrin.
 I did solid genetics for probably about a year. I think at the end of the year, I'd identified Sac6 and I had very good genetic evidence that it would be an interacting protein. Probably it was another year before we showed that actually it is a bona fide actin-binding protein. Because when you do these sorts of suppressor studies there's a lot of garbage you can get, and so you always wonder whether you're really dealing with what you think you've got.
It was actually very nice, because there was a postdoc in the lab at the same time called David [G.] Drubin who was looking for actin-binding proteins biochemically. It turned out that one of the proteins he found biochemically was the same as this protein I found genetically. David Botstein, when we called him and told him about it, said, "Oh, it's the 'golden spike.'" He was very excited, because this was sort of what-- The whole thing he'd had as his goal was that we'd find such a thing.
 Yeah. He called it the "golden spike" because we'd come in from both directions-- from the genetics and the biochemistry--and we'd arrived at the same thing. I had to be told what the golden spike was, because with my English background I didn't know. [laughter]
 Yeah. What I was just talking about was when two proteins interact with each other and have to have that interaction to function. Another genetic phenomenon is when you delete an actin-binding protein--or any other protein--and find that the cell is still viable, so it can get by without that protein at all. So then the question is, how does it do that? I guess the basic thing is that there is redundancy in function so that there are other proteins in the cell that can compensate for the lack of that protein. So we've also done some work to look at redundancies of proteins in cells.
 Yeah, right. So we found that Sac6 after about a year. Probably about a year later- -I don't really remember, but sometime in there--we found that it was the same thing as David Drubin's actin-binding protein.
 Then we talked about how to proceed. There are always issues when there are two postdocs in the lab about-- Because both of you are trying to develop a project to take on with you to an independent position. So the question was how to split it, since now we were working on the same thing. I have to say David was really wonderful about it. He was extremely generous in giving me as much of the project as I wanted. He had other actin- binding proteins from his column, which I think helped him to give away the whole thing. For me it was harder, because Sac6 was actually the only one that I was working on at that point. He was more generous than I was. In the long run it's been-- We have a very nice collaboration still. It's continued.
 David worked on the bench right opposite me. Throughout my postdoc time we were great friends. We would chat away. We had different scientific backgrounds, and it was always interesting to exchange ideas and perspectives with him.
 Yeah, he was very much a biochemist, and I was very much a geneticist. It's interesting that now he actually does a lot of genetics now, and we now do a lot of biochemistry. So we've sort of almost switched positions temporarily, though I think at heart he's still more of a biochemist than I am.
 He had been a graduate student with Marc [W.] Kirschner in UCSF [University of California, San Francisco]. Now David's at UC [University of California] Berkeley, and I still regard him as a great friend. In science we have really terrific collaborations.
 Yeah, on and off. So any time that our paths cross we collaborate. This is what I was talking to you about yesterday. Rather than competing-- I don't like to get into competitive situations. And with him it's terrific. We just collaborate whenever we come across a similar thing.
 Paul Matsudaira, the reason I got involved with him was because he works on the human version of Sac6.
 Yes, fimbrin. So I wanted to do an experiment in which we asked whether the human gene will work in yeast. There were different isoforms of this human protein. Paul had one of them. Two of the others came from John Leavitt [at the Research Institute, Palo Alto Medical Foundation] in California. So I got the genes from all these different people and tried all of them in yeast. That was how Paul and I ended up collaborating.
 Yeah, so we found that two out of the three isoforms of human fimbrin can compensate for the yeast fimbrin, which really I think is remarkable in terms of conservation of function.
 Well, they're about 43 percent identical in amino acid sequence. But functionally they're very, very similar. They're not identical, because there are slight differences that we can detect in terms of how the cells grow with the yeast versus the human one. But they're very similar and close enough that one can substitute for the other.
 Yeah, though a lot of the time you have amino acids that are conserved, so they look similar in their biochemical properties, but they are different just because they're not the same amino acid. There's an issue of conservation of 43 percent are identical, but then maybe another 20 percent that are similar and probably have the same properties. Also, people say that once you reach about 40 percent identity in amino acid sequences-- The three- dimensional structures of proteins are very, very similar. So once you've folded up these proteins into their complex structures, they probably actually look very similar.
 Yeah. I had a lot of friends at MIT--mostly women, I must say--who I used to talk a lot about it with, because none of us it seemed wanted to go on and run labs. We constantly debated this whole issue of what we were all going to do and whether it was feasible to stay as postdocs or what. I think through discussion we actually came to the conclusion that so long as you go into the position in the way in which you want to do it, then it would be an okay job.
You know, there's a view of academics, especially of untenured professors, that they work like maniacs and they're forced to do all sorts of different things because they're under all this pressure of tenure and all this. I think these discussions led me to really develop a very strong philosophy that I was going to do it exactly the way I wanted to do it. If it wasn't good enough for tenure, I didn't want tenure, anyway. I wanted only to do this job if I could do it the way I wanted to do it. I think that helped me tremendously when I came here, because I had that attitude. It totally took off the pressure, because I didn't mind if I didn't get tenure. As a result, I've been pretty happy, more or less, doing what I want.
 Well, we loved science. I think we all enjoyed our projects. I think when you do something you want to do it well, because otherwise it's pointless.
 We enjoyed being at the bench doing the experiments ourselves. None of these PIs that I had were still at the bench. They were all administrators, they'd been teaching, they dealt with problems at the lab. I saw no relationship between that and what I was actually doing as a postdoc.
 Yeah, I think that's really true. The only thing we're trained to do is science. We're not even trained to teach people how to do science. The whole thing kind of happens by osmosis. But you start to realize that in the initial stages-- I mean, osmosis is a very slow process. Students need to pick things up faster than the natural way of just observation really allows. So I found it very frustrating that I didn't actually know how I do science to communicate with people what you have to do. I still don't know how I do science, really. I guess I'm learning a little bit about how to tell people how to do it. But since nobody every actually told me how to do it, I don't know how to tell other people how to do it. That's frustrating.
Same thing with teaching. No one ever teaches you how to teach. You're just doing it. Fortunately, when I first started teaching, there was one person in particular whose teaching I really admired: Marty [Martinez J.] Hewlett, who's in this department. I taught with him. He's an excellent teacher. The students love him. I think just watching how he did it really helped me a lot to get started.
And then the whole process of running a lab. Because I'm pretty good with people in general, I thought, "Oh, this won't be so hard." But I found it very difficult. I don't know how to sort out people's problems with each other. So there are all sorts of issues that I don't think we're trained for at all.
 I think both of them had a very hands-off approach. I think when there were problems, neither of them really liked to deal with them, which I totally understand. I don't think I learned from them how to deal with lab problems.
 Not really either. Yeah, that's a whole other thing which I still think I'm still learning how to do. I have almost no idea how to do it. When you first write your first grant-- I think at that point I'd only ever read in my life two grants, right--one from John Pringle I remember reading and one from David Drubin, because he set up a lab a year before me. So those were the two grants I'd read before I had to go out and write my own. That's it. I mean, I guess prior to that I'd written a postdoc fellowship application which was a two- or five- page thing for the life sciences, for example. But again, that's a different sort of process, I think.
 Yeah, somehow I got funded. I mean, I think it was more out of sympathy than anything else, [laughter] because if I go back now and look at the grant it looks atrocious to me. I can't believe anybody would have funded it.
 It's up for renewal right now, so we'll see how we do.
 Yeah, I think I had five offers altogether. I’d gone on this massive interviewing effort which was totally exhausting. In the end for me it came down to a question of McGill [University] versus Arizona. Those were my two top choices. The reason I chose Arizona-- Actually, it was interesting the way I chose it. The day before, I remember being at Genentech in the cafeteria and sitting outside--and it was very hot and sunny--and thinking, "Oh, no, I can't go to Arizona. I can't bear to be in heat like this. I'll go to McGill." I remember leaving the cafeteria and saying, "Okay, I'll go to McGill."
I walked into David Botstein--met him in the hallway--and he goes, "So, Alison, what are you going to do?" I said, "I'm going to go to McGill." He looked at me and said, "Nope. Nope. Don't do that. Go to Arizona." [laughter] He said, "Look, there are a bunch of things that are important. One is, you know, how good the science is, how good the students are, how good the department head is." He said, "Go to Arizona" and "There are two things that you should do. One is, you should hire a maid. When you go live somewhere you need to have your house looking nice." He probably could tell from the way my lab bench was that my house probably wasn't very nice most of the time. He said, "Hire a maid."
"The second thing you need to do if you go to Arizona is--because you're obviously worried that there's not going to be enough cultural activity there--you need to just skim $10,000 a year off the top of your salary and put it aside for traveling. So if you feel like going to San Francisco for a good meal, go to San Francisco. If you feel like going to New York for an evening for an opera, go to New York." Although I've never done this, it was a very liberating concept that you could just pick up and go somewhere for an evening or a weekend as you wanted.
So this had a really major influence on me, this conversation, because the next day I called Arizona and told them I was taking the job there.
 It's a wonderful department. The question of whether to go to Arizona or McGill really was a question of whether my priority was going to be science or fun. Because Montreal, to me, seemed like a wonderful place to live, but I could tell from being here that this was going to be a really nice department to work in. There were obviously good people. It was a department where there were a lot of people with interests similar to my own. It was a young department, so I could really imagine getting started in a place like this. It wasn't too intimidating to me. They were trying to hire two other yeast geneticists at the same time who I think really had a major impact on me coming here too because I could imagine starting off with these other two, and it really helped a lot.
 Yeah. Both of them came.
 Roy [R.] Parker and Ted Weinert both came at the same time. The three of us were instantly friends, great colleagues. Actually, in the first year this building [Life Sciences South] wasn't ready. So the three of us shared a lab. We chose to do that rather than have our labs scattered around the old building. It was terrific. It was like being postdocs together. We'd all go into work together. None of us had anybody working with us at that time. We'd order stuff together and talk about how to run labs and how to hire people and all these things. So this was a really, really nice way to start as an assistant professor. We had a very good transition. All of us have remained great friends and colleagues still.
 I started in February of '90.
 Well, it was temporary space, because everyone knew we were moving into this building. There were three labs there, but only two of them were near each other. The third one was off on another floor. We decided we'd rather all just work together and share a space since we didn't need huge labs at that point. So that's what we did.
 Yeah, less than a year.
 Yeah. And now we all have labs. There are actually four yeast labs. Carol [L.] Dieckmann also has one. All four yeast labs are on this same floor. So it's a very nice community for us to work in.
 Yeah. The department gave us a start-up.
 Yeah, they gave us a good start-up. I can't actually remember the details of it. It's hard to remember what they gave us, but they gave us a whole bunch of money and equipment and technician support and God knows what. Yeah, they were very fair to us, very good to us.
 Yeah. So bit by bit it all built--
 Well, the first person I recruited I fired. I took a student early on who hadn't been able to find a lab, and I thought, "Oh, that's okay. I'll work with him." But I couldn't work with him either, and so after a while I told him it wasn't going to work out. That was kind of an unfortunate way to begin.
Then I think soon after that I managed to get a very good technician, Sharon [M.] Brower, who fortunately was in a long-term situation here, I think, because she's married to somebody else in the department. She's a terrific person to work with. She's a great technician. Right now she's on sabbatical in Australia. She's great. She's a very good person to have in a lab--she's very good technically, she's a very good influence in her personal-ity on the lab, and so on.
 Right.
 Yeah. The department-- I think they have a very wide range, so we have some excellent students, as good here as you get anywhere. We also have some terrible students, though I think the number of students that are bad is going down, because I think there's a definite move to take in fewer students rather than take in a certain number. So this year our class was probably half the size of what it is normally, and I think the average student is now better. There are good students. There have always been excellent students. I've been lucky in having good students.
I'm also pretty fussy. I think the way labs end up with students-- My view is that everyone, basically, has a different way of running a lab--different personalities, different amount of involvements. I think part of what's helped me to relax in this job is realizing that that's okay, and there are different students who have different needs and want to be in different types of labs. It's okay for us all to be different. Basically it's just a selection process where you end up with a student that suits your style.
For example, I run my lab in a very hands-off way. The students have to be extremely independent to survive in my lab. They have to be able to design their own experiments a lot and be very self-motivated. I don't take anybody who doesn't look as if they're going to be like that at all.
Students, I think, who want more involvement obviously have no interest in coming to my lab, either. So it works both ways.
 Probably it's because I don't enjoy day-to-day contact of telling them what went wrong in that gel or-- I don't like troubleshooting the whole time. I don't mind for bigger scientific issues, but I want them to be able to sort out things themselves.
 Absolutely.
 Yeah. I mean, ultimately, I think they do succeed. They might take longer to succeed because of this route. But at the same time I'm the way I am and I just don't think I could do this job if I had to go in every day and see what everybody was doing and figure out all the problems and so on.
 This is one thing that's very discouraging to me, is I've done very little bench work for at least two years now. I really want to get back into it, because that's the thing I think that gives me the most joy. So one thing I have to do is to figure how to get back into that mode. Next year I'm going on sabbatical, and I'm hoping that by being in the lab again for several months I'll establish a routine again that I'll make a major effort not to break when I come back.
 No, I'm going to go away on sabbatical.
 Yeah. I'm going to go to London [Imperial Cancer Research Fund] to work with Paul Nurse, who I mentioned earlier. I'm going to do that probably for six months. Then actually what I'd like to do, if I can arrange it, is to go to India and teach for a couple of months somewhere in India.
 Yeah. I've always had a great interest in Third World countries. This last January I actually taught a course in Puerto Rico, which I really enjoyed. I enjoyed the students tremendously. I don't know. I mean, I'm not sure where the boundary is between what I just enjoy doing and what I think is useful, too. I think there's some value to helping Third World countries, but I'm not sure how much help this kind of thing is.
 They have some. I think it's tough. I think it's more of a lower-technology kind of science, probably more similar to the type of thing we had in Ireland in terms of recycling cover slips and lacking some of the major pieces of equipment that you have over here and so on.
 Well, there's a fellow in the department here called Mani Ramaswami. He's from India. He knows people in India that I could very easily establish this through. I've already met one of them when she came to visit him. I'm actually communicating with her over E- mail about how to actually do this. She's very enthusiastic about the idea of me going, giving a course in yeastgenetics or something in India. That's the general idea.
 That may be true. Maybe. But I'm not sure that all of us have to be Nobel laureates to be in science. I think all of us bring different things to science and society and we should just pick and choose the things that we're good at or that interest us. I also think that's true at the level of a department--that some people are great teachers, some people are interested in this committee or that committee, and people should do what they're interested in or good at. Because between us probably together we actually cover it all.
 Yeah. I definitely agree with all that. I think that's really true. As far as my lab floundering-- As I said, my lab is very independent. They have to be, just because of the way I run it all the time. I don't think it's going to be a major problem for them if I go away for a reasonable amount of time, because, you know, there's E-mail. They are independent. I don't tell them what to do day-by-day. When I was a graduate student, John Pringle went off on sabbatical. I don't think we saw him for many months at a time, and it was no problem. Sometimes I find when I go away that people have actually been more productive in my absence than they are when I'm here. So I don't worry about that aspect of it.
I also don't really know what my role in science is, so I'm still trying to experience different types of aspects of it.
 Well, I think there are lots of different ways of doing science. I guess I don't really know which way I want to do science yet, basically. I don't really know what I want to work on for the next twenty years, which direction my research is going to go in. It's hard to say. I don't have a clear view of myself now, any more than I did when I was a postdoc. I didn't have a clear view of what my life as a PI was going to be. It's kind of involved in something that I'm recently happy with, but at the same time I don't know that this is how I'm going to remain.
 One thing it means is that if I don't want to be on committees I don't let people force me to. I feel very free to say no. I think a lot of people when they're starting don't feel that freedom to say no to this and that. One thing is that this department is very supportive, so they don't put a lot of pressure on us the way I know some departments do, particularly on assistant professors. An example is, I was invited to teach the Cold Spring Harbor [Laboratory] yeast course, which is a three- or four-week time commitment every year. I wanted to do it. My department supported me. But even if they hadn't, I think I still would have done it with this attitude that I want to do it the way I want to do it. I want to pick the things that are important to me. Those are the kind of things I mean.
 Very valuable. It's a very interesting experience. I've done it now twice. It's a very intense course. It's three weeks, seven days a week. You start at nine in the morning and you go on till you drop at night, basically. We have a half-day off during the entire three weeks. So it's like being on a retreat. You're constantly immersed in yeast genetics and yeast biology and so on. I find when I go that I always come back with a new perspective. It's very, very refreshing to me, even though it's also very exhausting.
 Yeah, and I think we have different seminar speakers every day. Somebody from the yeast field comes and speaks every day. You just end up with this feeling that yeast is tremendous, that you can do anything that you want in yeast. Because you have such a barrage of information, you put together different ideas that you perhaps wouldn't normally connect, just because it's all so concentrated. So both times I've done it I've found it extremely valuable, so far.
 Yeah.
 Uh-huh.
 There are also three instructors: there are three of us who are there the whole time and teach the whole thing as well. I've learned a tremendous amount just from listening to those other guys. So even though I myself only teach a third of the time, all of us are in the class the whole time. I learn from them and I learn from the seminar speakers who come in. Even though I vaguely know what they do, the details of what they do are always interesting to hear. Then the students themselves are an interesting collection of students. It's just very, very concentrated science for three weeks.
 Currently they're Dan [Daniel E.] Gottschling from the University of Chicago and Chris [A.] Kaiser from MIT. When I first started, Susan Michaelis and Aaron [ P.] Mitchell were teaching it, but they've since retired from it.
 Yeah. When they ask us to do it, they want us to do it for five years or something in that range, so for now I plan to continue it.
 Yeah, I actually enjoy teaching. I wouldn't want to do it as a full-time operation, but I find it refreshing. This Cold Spring Harbor course is one example. The thing in Puerto Rico also was a very good teaching experience for me. It was just one week, but it was really neat to be among a completely different type of student. They were very excited and interested in what was going on.
 That was actually in Cayey [University College], which is about an hour from San Juan. There were students who were selected on the basis there of how well they'd done, so it was a very good collection of students that we had.
 They were undergraduates, senior-level undergraduates.
 Currently I'm teaching two courses. I teach cell biology to both graduate students and undergraduates. My teaching load is about fourteen hours of each of those courses. I don't know if that's considered heavy or not. To me it doesn't seem that bad. It takes up probably two months in a very full-time way because I jam it all together.
Again, I've learned a tremendous amount from teaching. To prepare lectures for graduate students, you can't fail to learn new information. Every year you update it. And it gets very familiar, but also it's new. Even the undergraduate course I've learned from, because you're teaching much more broadly than areas you normally think about. So I've learnt a lot about different fields that I wouldn't normally think a lot about. I think perhaps some of it comes back to what I said yesterday about science tending to take you away from people. And I think probably what I like about teaching is the contact with the students.
 I like it. It was quite a major shock for me because it's so dry. I've never lived anywhere where there's no water. But at the same time, the outdoors are really great here. There are mountains all around Tucson; there's great hiking and biking and all these things. People in Tucson tend to be very outdoors oriented. So that side of it I've really grown to love here.
The cultural stuff isn't so bad. There are actually some very good series of music and ballet and different things here that I go to. I have series tickets for certain things. It's fine. And I still maintain this attitude that I can always leave for a weekend if I want, although I almost never do that. It's something to know.
 I bought a house in the Tucson mountains, so this is about seven or eight miles west of campus. It's very, very beautiful, beautiful desert. I like to bike in and out from there, so I get to see the desert on a regular basis.
 I usually come in about six thirty or seven in the morning, and then work till probably five thirty or so, six in the evening. That's my standard Monday-through-Friday routine. Then on the weekends I work some amount, depending on how much I have to do.
 Not a lot. Sometimes I do, but I'm usually pretty wiped out by then.
 I walk the dogs. I like to read, listen to music.
 Last year I read a lot of Primo Levi. I don't know if you've ever read anything of his. He's Italian, a Jew, and has a very, very interesting view on life. He was also a chemist, previously, so some of what he writes is about his scientific life. He was sort of the person I read, person of the year, last year. I read all sorts of different things--biographies and all sorts of things.
 Let's see. When I first came here, it was very much continuing with what I had been working on as a postdoc. There were a bunch of things finishing up those sort of postdoc studies. I mean, I guess it's all been related, as perhaps you might expect. But one thing that was interesting was that we became more involved in biochemistry than I ever would have expected, since I'm not a biochemist. Partly this was because I got a postdoc [Jerry E. Honts] to come to the lab very early on who was a biochemist by training, and so was already pretty good at purifying proteins. I also had a graduate student called Tanya [M.] Sandrock, who was interested in purifying the Sac6 protein biochemically and with amazingly little input from me worked out a beautiful purification scheme for doing it. Between her and postdoc Jerry Honts, they actually managed to really get biochemistry up and running in a very professional way in the lab.
That was really terrific and it allowed us to start to look at the biochemical basis of the interaction between actin and Sac6 protein. Prior to that it had all been a genetic type of analysis. That together with sequence analysis of the various mutations led us to understand a lot about how actin and Sac6 interact normally and also in the situation in which you have actin mutations that are then being suppressed by Sac6 mutations. The basis of that suppression is at the biochemical level.
We're sort of taking that a step further at this point in collaboration with the biochemist here, Bill [William R.] Montfort, in trying to crystallize the Sac6 protein, because we'd really like to understand how actin and Sac6 interact at the three-dimensional level. In order to do that, we need to have a crystal structure of Sac6. This is a collaboration that's ongoing with Bill Montfort. It's sort of in the works at the moment.
 No. As you say, you can't be sure. It's a risky business. But Bill's a good and experienced crystallographer, and we have pretty pure protein as a result of this purification scheme that Tanya worked out. So we're going to try it. We have ideas about trying just single domains of the protein, breaking it up into small pieces in the hopes that those pieces would crystallize better. We're just going to try a bunch of different things and see what works.
 Once you have crystals then Bill's lab has to take over, because they're the only ones who know how to solve the structure. So then they apply x-ray crystallography methods to the analysis of the structure, so that you end up with a view of the protein in three dimensions and you can see where all the atoms are.
 Yeah, I think so. I hope so. [laughter] We'll see.
 No. I'd have to do something major like take a sabbatical in it, I think, to really learn it. It's more a matter of us giving them protein. At one point, Jerry Honts--who was my first postdoc I told you about--was working in Bill's lab. So it was a perfect collaboration, because he'd already worked in my lab. He went and worked in Bill's lab. And so he was sort of the intermediary in the process.
 Well, the Sac6 protein, the human homologues of it were first called plastin, but they also are fimbrins. It turns out that the plastins were first identified on the basis of differential expression in normal versus tumor cells. So there's some issue with the expression of different fimbrins in cancer cells versus normal cells that's interesting and may have something to do with what's going on in cancer cells. Though how direct it is is a whole other question altogether.
One thing we could do through studying yeast--and actually we're doing this in collaboration with Paul Matsudaira--is to learn about what are the differences between these different fimbrins using yeast as an assay. Since the human fimbrins will work in yeast, we can then fool around with the human ones, see what changes we can make to interfere with the function, and then assay them in yeast. For example, there's one isoform that doesn't work. We can learn about the differences between the ones that do work and the ones that don't work in yeast through this type of analysis.
 Well, for several years in a low-key sort of way. I think we published a paper in '95 showing that the human fimbrins work in yeast [A.E.M. Adams et al., 1995. Isoform- specific complementation of the yeast sac6 null mutation by human fimbrin. Molecular and Cellular Biology, 15:69-75]. Since then the postdoc [Wenyan Shen] in Paul Matsudaira's lab picked up the analysis and has studied the differences between the different isoforms by assaying them in yeast. It's an ongoing collaboration, though it's a back-burner kind of project.
 Actually, it's always interesting to hear that. The one thing the yeast doesn't do that is associated with the cytoskeleton is move the entire cell. It doesn't locomote. For example, Dictyostelium, which is a slime mold, moves by some sort of amoeboid activity, and that's an actin-based movement. Yeast doesn't do that.
But on the other hand, yeast does everything inside the cell that a normal cell will do. A lot of these intracellular processes use actin. So we can study all those things that happen inside cells and that are intrinsic to a single cell in terms of what actin's doing. It's true we can't study locomotion, but on the other hand locomotion is only one thing that actin is involved in. I don't think it's a problem, because I think we're a long way from understanding what's happening inside the cell--you know, how actin is involved in any of these things that are going on inside cells. I mean, I agree--to study everything you have to choose other cell types too.
 The idea is that if you get rid of a protein in a cell and the cell is still fine without it, then there must be something else that's able to function in its place. Otherwise, that protein is just not important, and why would the cell continue to make it?
There are different ways you can learn about what these redundant functions are, and yeast is terrific for applying genetics to this problem, because you can do two different types of things. You can either make a cross between mutants that are defective in the protein you're interested in and guess about which other proteins might have redundant functions and make double mutants lacking both of those and see if they now drop dead. The other thing you can do is to do a genetic screen for mutations in genes that you don't know anything about to ask what mutations now are lethal in combination with the mutation of interest.
So what we've mostly done was the first type of analysis, where we made guesses about what genes would have redundant functions with the sac6 gene. And we made combinations of mutations that lacked mutants. It lacked both gene products. That was what led us to this paper, "Unexpected combinations in which we found that mutants lacking both fimbrin and capping protein, which are two actin-binding proteins that have different types of functions, are lethal.
It was interesting, because when we first set out in it we thought that the sorts of things we'd find would be proteins that have similar functions. Fimbrin is an actin filament cros slinking protein; we thought that other proteins that have actin filament crosslinking activity would be the ones whose functions would be redundant with the Sac6 protein. But it turned out that we found, say, capping protein mutations were synthetically lethal with sac6 mutants or mutations. This was surprising, because capping protein doesn't have actin filament crosslinking activity and fimbrin doesn't have capping protein activity. So those two functions don't seem to be redundant in terms of what they actually do at the molecular basis. The way we think about it is that in sort of a coarser way these two proteins do have redundant functions. For example, perhaps both of them stabilize actin filaments but in very different ways: one by crosslinking filaments, the other by capping the ends and preventing depolymerization.
 The trouble is that in the yeast field everybody works with different strains. By this I mean they're not identical genetically to each other. So they are all Saccharomyces cerevisiae. They all mate with each other, you know, and you can generate progeny from these crosses. But because they're not identical, if you make a mutation in one strain, it may have a slightly different phenotype from a mutation in another strain. And that might be because of the background effects of the two different strains. So there may be random mutations that exist in one strain that don't exist in the other strain backgrounds. Different people use different strains because some strains are good for what they're interested in, and other strains are good for what somebody else is interested in.
For example, there are strains that are excellent for sporulation. So if you're interested in studying sporulation you work with those strains. But the vast majority in the yeast field doesn't work with those because they don't care, for the most part, how well sporulation works. They'd rather work with something they consider more of a standard strain. So this introduces variability into the strains across labs.
 Oh. People talk about strain backgrounds. Some of the classic ones are the S288C backgrounds and the A364a backgrounds and this sporulation one is the SK1 background. But there are a whole bunch of different ones, and it's not entirely clear how they're all related to each other. Some of them are closer than others. But because of this, when you make crosses between different people's strains, you're not dealing with identical genetic backgrounds. So when you look at segregation of markers coming out of crosses, there can be genetic background effects based on which mutations are segregating how. The best way around it, if you're dealing with nonisogenetic strains like this, is to look at a lot of different segregants, for example, and see that they all basically behave the same way when they carry a particular mutation that you're interested in.
 Well, what people do a lot now is have lab strains that within their lab are considered isogenic. They're identical genotypically except for any one gene that they're studying. So within any one lab, strains may be very much isogenic. But then the problem is when you start crossing between labs, because not everyone has the same idea about what strain they want to use, you introduce nonisogenicity into it. You can get around it by-- There are very easy ways of making gene disruptions in yeast. So if you get from somebody a plasmid that allows you to disrupt the gene that they've been studying, you can disrupt it in your own genetic background and then compare it directly with what you've been looking at.
 Yeast has one really great thing about it, and that is that you can freeze it. All our different strains we freeze at minus seventy degrees, and they stay viable for years, probably decades. Which means that anytime you want to use them, you can just take them from the freezer, thaw out a little bit of them, grow them up, and then you have these strains that haven't undergone any sort of change. Because one of the things you worry about if you don't freeze things is that as they sit around they'll gather mutations, especially if they start off being a little bit sick. There's a selective advantage in accumulating mutations that will suppress some of these problems.
 Because a lot of what we do is working with mutants that are defective in one process or another. That makes them sick.
 If, for example, you have a mutation that interferes with secretion or the cytoskeleton or something, it's an interesting mutation to you, because you can study that process and see exactly where the block is and so on. But the problem is, because it's defective in secretion or the cytoskeleton or whatever, it's not a happy yeast cell.
The way we get around this is to use conditional mutations, which means that they're worse at one temperature than at another. The problem is that even at the permissive temperature where they're supposed to be healthy they're often still slightly sick. So if you just leave things sitting around in a condition in which they're growing, random mutations that occur will get selected for if they allow the cells to grow better, even at that temperature. That's the basic problem. But as we can freeze them away, we can freeze away even very sick strains and get them out of the freezer in some shape that at least resembles how they went in there.
 Oh, we just throw it away whenever we want. We just grow up a few milliliters of culture or grow them up on a plate. You know, we throw away masses and masses of plates all the time. We're constantly testing things and scoring phenotype or whatever and then throwing it away.
 I guess usually it depends on how unhappy the particular strain is that you're working with. I personally tend to work with them for about two to four weeks before I'd go back to the freezer and get out a fresh batch, to minimize these problems.
 [laughter] Not as if they're people or anything like that. I am very fond of working with yeast. I really enjoy the process. I love all the manipulations that we do with them, the basic genetic manipulations. I like working with an organism where so much is known, because you can think about all the different things that happen inside the cell. You can think about your process in that context. So I do like that aspect of it.
 Well, any time you have a mutant, say, and you think there's a difference in the way something looks inside the mutant versus the normal wild type, to be really sure that you're not just focusing on some little difference that's not really representative-- The easiest way to do it is to do these double-blind experiments, in which somebody labels the tubes and then you see if you can tell the difference between them. If routinely and consistently the mutant looks different--you can tell which one it is versus the wild type--then that's good evidence. I mean, we do these sort of experiments with all sorts of microscopy, whether we're looking at actin filaments that are just individual filaments or actin filaments that are bundled into bigger arrays of actin filaments. It just really helps you not to be subjective.
 Yeah, it actually had a major impact because-- I mean, for anybody who's been working on actin there have been all these different observations about which proteins bind where on the surface. Because actin has so many different functions, many of which are believed to occur via actin-binding proteins, it's nice to know where on the surface different proteins bind so you can start to understand which ones are competing with each other if they bind at the same site, and issues like that. Ken [Kenneth F.] Wertman with David Botstein had generated a large number of yeast actin mutations that they had predicted would be on the surface of actin and should be scattered, hopefully, all over the surface of actin. When the crystal structure came out they were able to map these different mutations on the surface and found that indeed they had made mutations all over the surface of actin.
This actually provided a tremendously useful resource for us and everybody in the yeast actinfield because now we had mutations that identified potentially different activities of actin through their interactions with different proteins. So we could start to interpret a whole load of different things in light of these mutants. The crystal structure really helps, because it crystallizes a lot of information that people have into a form that they can actually make sense of.
 The introduction of recombinant DNA technology was definitely major. But as I said before, that happened sort of at the beginning, so I was only slightly aware of how much difference that was making. But I was aware that people were cloning and sequencing like crazy at that phase. That was in the late seventies.
Oh, God. I don't know if I can answer that off the top of my head. I have to think about it.
 Actually, I just wrote a grant renewal, which was a very interesting and useful process for me. This was for my NIH grant. Of course, it really made me think about what way we want to go for the next five years or so. I found it very interesting, because for one thing, it made me change direction a little bit. Part of this also came from the Cold Spring Harbor course that I spoke about before. Being at Cold Spring Harbor last year made me think a lot about phenotypes of mutants and that we have a huge number of mutants in the actin cytoskeleton. It made me realize that what we should do is really go back and work with existing mutants and see what we can learn from things that already exist. In writing my grant, I in a short amount of time read a large amount of stuff, which I guess is the normal way of doing it. But it helped me to synthesize things and put ideas together about what actin might actually be doing in a way that I hadn't thought about before.
So we're going to go off in a slightly different direction in thinking about what actin is doing in yeast. It's slightly different in that in the past we've always thought about actin's role as being in the generation of polarized growth. What I'm interested in is whether it has other roles in addition to this and what these roles actually might be.
 Yeah. It's still very much a cytoskeletal issue. What I've actually become interested in is what the role of the cytoskeleton is in endocytosis. Howard Riezman has shown that actin is required for endocytosis in the yeast. The question is, what is endocytosis required for in yeast? And why is the cytoskeleton required for that process? I think a lot of observations of the mutants can actually be explained by the role of actin in endocytosis rather than the role for it in polarized growth, which is how I think most of us have been thinking about it.
 Mostly through an analysis of all the different mutants and analyzing endocytosis and its roles during different modes of growth. So for example, one of the things I'm interested in is what actin is doing during meiosis in sporulation. This is a whole phase in the yeast life cycle that's very, very little studied by the yeast community in general. I've come to appreciate how little cell biology actually is known during this phase.
But one thing that's clear is that mutants defective in the cytoskeleton are defective in sporulation. I always thought that it would be perhaps because they were defective in processes similar to those that occur during mitotic growth, as in laying down new walls around developing spores and so on. But it turns out that actin actually is required much earlier in sporulation than that, at a time which we don't really understand what its role could possibly be. One possibility is that actually it has a role in endocytosis during this time. But again, we don't know anything about what endocytosis is doing during sporulation, if it's even involved during sporulation. This is the sort of direction that we're going off in.
 Right. We're actually looking at existing mutants, a large collection of them, and asking if we can explain or understand why they’re defective in, say, sporulation. That's just one example of using a phenotype that we see to learn about what the role of actin normally is during sporulation. We really have very, very little idea as a starting point, which is nice, because it means that the whole field is sort of wide open. It's really a neat puzzle to think about it and to think about how to actually approach the problem.
 Well, I think there's enough space in science that just because people are not working on it doesn't mean that it's not interesting or it's the wrong direction. As I said, people don't know anything about, really, the cell biology of sporulation. All that's really known is issues of regulation, of whether or not the cell chooses to go into the meiotic program, and also of course things like DNA repair, recombinations that occur during sporulation. So of the cytoplasmic events almost nothing is known, and I think that's just because people haven't studied it. I find it exciting because I think it's a wide-open field that we can probably learn a lot about. I think it's not necessarily just going to give us information about sporulation. I think we may learn a lot about the cytoskeleton in other situations also as a result of studying this.
 Not really. I totally agree that you don't know where things are going to go. You can't predict where the breakthroughs are going to come from. I think basic research is extremely important as a resource from which things will spring.
I have no particular aspirations as to where this will go. I'm not sure that this is always how I'll be in science. Perhaps this refers a little bit to what I was saying earlier. I think it's possible that at some point I want to study something that I can see is more related to, say, human behavior or something. I think human genetics is going to be very interesting in the next few years. I think questions about how neural networks are set up and what's involved in behavior are very interesting, and I can imagine one day getting into that.
 No, I mean just in general. Just a question of how the human brain works, what's involved in development of neural connections. So that's the behavior side of it. And then human disease genes, how those lead to diseases such as schizophrenia, for example, not to mention all the other nonbehavioral things like cancer. So I think all those things are going to be very interesting in the next few years.
 Right. Things like mapping of human genes, disease loci, and so on, is as close as you really get to human genetics, because obviously you can't set up crosses or anything like that. So you're working, at the moment, probably at the level of identifying genes involved in different things.
 I think so, yeah. The way I would probably do it would be through a sabbatical. Obviously, I can't do it this time. But in the future, probably the thing to do would be to go on a sabbatical, set up collaborations, and go to meetings where those people are.
 Just with somebody who's working on whichever aspect of it that at that time I choose to work on.
 I feel so. This is one of the things that I think about academics, that you can really do whatever you want to do. I think that's one of the great things about it. At some point if I decide that's what I want to do--maybe I'm very naive--I feel pretty confident that I could make a switch to something very different. I mean, I've seen people make switches during sabbaticals. Perhaps not quite so drastic a switch, but nevertheless, they have made switches. And I don't see any reason why it can't be done.
 I'm just very interested in the idea of what shapes behavior of humans. Obviously there's a genetic component to that. But in addition, the question of how our experiences at a physiological level really shape what we become and how much plasticity there is in how we behave and how that relates then to the physiological basis of the neural connections and so on.
 Oh, absolutely, yeah. Yes. It's a different level of question, I think. Yeast is great for understanding what happens at the single-cell level. I think the sorts of things I'm talking about right now are actually at a bigger level, where you're talking about interactions of lots of cells with each other and how much of that is programmed by the genes and how much is environmental and so on.
 Again, this will have to be something I have to think about. It's hard for me to think of it straight off the top of my head.
 I don't actually think so. When we do journal clubs in our department, for example, I always like to do things-- For example, I gave a journal club once on color vision in humans and what color blindness is all about. I think the molecular basis of that is fascinating. It's amazing how reductionist you can get in explaining what's involved in color vision. So those are the sorts of things that I like to give journal clubs on, things where people can really relate to it and have sort of general interest.
 There are a lot of people whose science I respect. It's very hard to pick out anyone like that.
 I don't think any yeast people have ever won the Nobel Prize as far as I know. I think we're due for some.
 I think the cell cycle people are good candidates. So Lee [Leland H.] Hartwell would be one. Paul Nurse would be another. More recently in the cell cycle field there are checkpoints that I think are extremely important. I spoke about it yesterday in terms of my colleague Ted Weinert's work. He, actually, is somebody who was there right at the beginning of checkpoints. I think it's conceivable that those people-- He did it with Lee Hartwell, first identified checkpoints and established the idea and so on. So again, among the cell cycle field, I think those people would be one group. Marc [W.] Kirschner is somebody else who is in the cell cycle field.
Actually, I think David Botstein has potential for getting a Nobel Prize, but not for his yeast work, more for the RFLP [restriction fragment length polymorphisms]. The idea of using RFLPs as markers in the human genome. Then if he did, he'd get it with a bunch of other people. But he's somebody in the yeast field.
 Is it?
 I have no idea. I didn't know people write letters like that.
 Really?
 I give them--at least I hope--a sense of what's important. I think it's very easy when you're starting in science to go so haywire in a lot of different directions and not really know what are important things worth following up. I think that actually is a very difficult thing for anybody to know. I think as a mentor it's important to be open-minded enough to think that they actually may be following something--even if you don't think it's important-- that may be important, because I think a lot of useful things actually come from those sorts of directions. Perhaps one of the things that's worthwhile is just imposing standards. So helping them to understand what a good experiment actually is and that incomplete data or data without controls really are of not much value. I think I have fairly high expectations in terms of how the experiments should look. Hopefully, that's helpful to them.
 We have lab parties at some sort of frequency. Probably the better ones are the ones where we actually go out into the desert and have picnics and everyone brings their dogs and things and we play softball and this kind of stuff.
 There's about seven or eight people. It fluctuates a bit. Often we do it with other labs; other yeast labs will join together and do things. We do lab lunches sometimes and stuff like this.
 I always try to encourage them to have more than one thing going at a time, because I think you never know whether something's going to work or not. I think it's important to have multiple things going. Then I think it's also important to know when it's time to drop something. I guess I feel that I do have some role in that, that I say, "Okay, I think this is enough. It's really time to focus on that," or something. I've definitely done that with at least two of the students. Probably all my students, actually, I can think of situations in which I've done that.
 Yeah.
 Yeah. I mean, I may not always be right. I think a lot of how I do science is by gut, actually. I really think that when I was doing science myself, I had gut feelings that are very hard to explain in any sort of rational way. I think part of the difficulty for me being a mentor is that I still do it this way, that I start to get bad feelings about what they're doing. It's very hard for me to really explain to them why they should drop it, other than the fact I have a bad feeling in my gut. [laughter] Maybe they're learning to put up with this style of explanation.
 With more or less degrees of resistance. Ultimately, I think that they did agree. Sometimes they agreed immediately and they were glad that I was saying it or something. There are varying degrees of it. I have a student who I told I thought she should switch projects, and she basically agreed, and she picked up the second project that I thought she should start. But she's actually kept the other project going on a back burner, which I'm very glad to see. It's nice to see them take the initiative to do that. I don't necessarily want them to agree with me. If they feel strongly enough that they don't want to drop something or they want to keep going in some direction, that's fine. I guess mostly I want to just know that I did the best I could to steer them in some direction that I thought was useful.
 I really don't remember much of that, actually. With John Pringle I remember very little of that. I had a lot of things going when I was with him. With David Botstein I started a whole bunch of different things. I think it was becoming clear to me which was the most important, which was the Sac6 thing. I remember after about a year talking to him about all these different things. His conclusion at the end of this meeting-- He wrote it down: "Sac6, crank!" His conclusion was that that was the direction to go in. But I think I'd already decided that myself, anyway. So I'm not sure that any of them ever really steered me, but it's possible that I've just forgotten it because I didn't end up going any further that way.
 Yeah, to some extent.
 Yeah, I think it's absolutely true. I think there's one thing that can be done within the funding levels that exist. I mean, obviously one thing is to fight and to get increased funding levels. But given the funding levels that exist, I think one thing that the scientists can do is to make a more equal payout. I think a huge amount of money goes to some labs. I don't know; I have absolutely no idea of the statistics on this. But I think some labs get enormous sums of money, and I cannot believe that the last $100,000 that some of these labs get is better off going to those labs than it would be going to some of the young people who are getting nothing. So I think there should be caps on how much any one lab can get that's reasonable. I don't think it should be $1 million even. I think it should be a lot less, because I think there are a lot of really good young scientists who are not getting funded and getting discouraged and not going to continue and so on. That's one thing I think.
 Absolutely. But I think a lot of people pick on Howard Hughes. I think in reality Howard Hughes is just one of these things. I think a lot of people are getting $500,000 or more from NIH, $800,000. I don't know what they get. So I think Howard Hughes is just one of many. The combined amounts of money should really be examined very carefully.
 I mean, that's fine if they can be persuaded to give it. [laughter] They are also pretty limited, I think, in their funds these days.
 I only accept postdocs who bring their own money with them. It's too much anxiety for me to have to support everybody off my own NIH grants. So I always tell them when they first write to me that they'd have to get their own money if they wanted to come. That's, in fact, how the postdocs have all come to me. The same thing, actually to some extent, goes for the students. The students have been fairly well supported by various fellowships, both nationally and locally, that have really allowed me to free up the grant for just standard things--technician support and so on.
 That would be nice. But in conversations with people like the dean [Eugene H. Levy] of this university [University of Arizona], it's very clear that issues of teaching are really of a major priority. I find it very hard to imagine that the university is ever going to fund research. There's already enough ideas out in the general public's mind that the students are actually funding research. I think that would just cause hell for the university to start paying technician salaries.
 Yeah. I mean, I don't think he agrees with it, but he tells us about it. So definitely what I'm talking about is the public's perception of what a university is here for. I don't think they care a huge amount, at least in a state university like ours, about the research.
 Actually, the classes I teach-- I teach a huge undergraduate cell biology class with 250 students, and there is no lab associated with that. Part of the problem is that labs are actually very expensive to run. Again, with limited university resources, there's a limit to what you can do without.
 I think that happens to an extent. I don't think it's possible at the level of salaries, or at least not in a very major way. But I think it's possible in terms of supplies that you have some sort of reciprocal sharing that goes back and forth to cover each other's losses in terms of poverty. But I'm not sure that it's possible to do it in a very big way, just in terms of legalities.
 Yeah. I mean, all we have to do is to continue to write for other grants. The question is, how many years do you go on doing that with no funding? Hopefully it won't come to that, and at the most I'll miss one or--absolute worst--two funding cycles. But even those would be pretty dire in terms of maintaining a lab.
 Right. Well, nine months of my salary is secure.
 Right.
 Right.
 Sure. But it's clear that some of them should fall by the wayside, right? There's a big range in terms of abilities, and only the best ones should really go on into full-scale academic positions. But I think there are a lot of students who want to be teachers at small colleges, for example, and they have to go through the same system of doing a Ph.D. and then doing a postdoc, even though in reality I think that research experience doesn't really mean so much when you go to a small college ultimately.
I think one of the issues is there are actually a lot of different types of careers that the graduate students probably end up doing. I think the problem is that in general in academics we train them for an academic position. Only a small minority probably go on and actually do something like that. Again, I don't know the numbers. But I think an interesting question is, what do we actually train them for? Should we alter the way in which we train them?
I think the same thing also goes for the undergraduates, because I think that it' s no longer the case that undergraduates are here for an elite kind of training. It's sort of the baseline thing now. Fifty percent or so of people in this country go to university. I think the bachelor's degree has taken the place of what a high school education used to be. I think in some ways it's like remedial high school. So the question that again arises is, what are we actually teaching these undergraduates to do? Because I think perhaps some of them are here in a sort of trade school capacity and obviously learning nothing of any trade.
 I think I only really got a glimpse. I wasn't really part of the company. I didn't know people in the company very much. We were very much a sort of island in the middle of this company. So I don't really have a good sense for it at all. It didn't make me want to stay there or be in industry, but I'm not sure that's really meaningful. I know a lot of people in industry enjoy it tremendously.
 Yeah. I have friends who are very happy in industry.
 I guess so. I mean some of them run pretty major operations.
 Yeah.
 I think he was only there for two years altogether.
 I never totally understood what the whole reasoning was behind leaving. My own opinion is that he basically missed academics. When he was at MIT [Massachusetts Institute of Technology] it was very obvious he loved interacting with the students, and I never was able to imagine what he was going to do without those sorts of interactions. So the job at Stanford [University] seemed like a perfect thing for him to go back into.
 It's pretty basic. I can't think of a direct way in which companies would be interested in it.
 Oh, yeah. There's a company in Tucson called Selectide, where one of David Botstein's former postdocs is now doing very well, Ken [Kenneth F.] Wertman. I mentioned him before. He's now there. I think he's doing pretty well.
 Yeah, once in a while.
 Uh-huh.
 Oh, all sorts of different ones. I've reviewed for Genetics fairly regularly, MCB [Molecular and Cellular Biology], MBC [Molecular Biology of the Cell], JCB [Journal of Cell Biology], occasionally Nucleic Acids Research, all sorts of different things.
 Reasonably. It takes a fair amount of time. It depends how busy I am with other things.
 Yeah, I try to be.
 I think a lot of papers you can find holes in it. It depends how aggressive you get about it. I think in a journal club kind of format where the idea is to rip things apart you can get into a sort of "hound" mentality with things. I think in general a lot of good science is published. There's a range of journals with different standards, I would say, in terms of what gets accepted. You sort of factor that in when you read a paper you know what journal it's out of.
 Yeah. David Botstein always said to us, "Is it new? Is it true?" That was the criterion by which we should accept a paper. So that's what I usually try to apply when I read papers.
 I also read Science, Nature, Cell. Those are the hotshot, trendy things.
 No, I like to read broadly. Again, it depends on what else I'm doing, how much time I have. Unfortunately, it seems that journal reading is sort of the thing that most easily goes, so it's very easy to get behind in the literature.
 I have to say it's been fairly straightforward. I don't think I've had anything out of the ordinary happen. I haven't been involved in massive arguments with anybody about it.
 I sent something to Nature once, maybe a couple of things to Nature, that weren't accepted. But I think with Science, Nature, and Cell, it's just a crapshoot. That never bothers me if things don't get accepted there. But the good workhorse journals like Genetics, Journal of Cell Biology--those are the two major ones that I like to publish in--I think things have always been accepted when I sent them there.
 Occasionally somebody will say something useful. I haven't obtained massive insight through those, I don't think, but it does vary.
 The meetings I go most often to are the yeast meetings. I'm not sure they're the ones that are really best for me to go to, but they're the ones that I enjoy, largely because I know a huge number of people at them. It's very easy to exchange ideas and just chat with people.
 There are two different types of yeast meetings: The Cold Spring Harbor [Laboratory] cell biology yeast meeting, which I enjoy a lot. That's every two years. And then on the off year there's a general yeast meeting which I go to occasionally, not so often.
 It might be the Genetics Society of America. I actually don't know, I'm embarrassed to say. I think it might be.
 They're probably four or five days I think, yeah. They're usually pretty exhausting.
 My grant usually does. That's how I usually do it.
 Well, I think there are different types of science that are done. I think there is some molecular biology that's mindless, where you're just cloning and sequencing a whole bunch of different things. As I told you with the yeast work, I think it's gone through a fairly mindless phase in which everybody had to clone, sequence, disrupt their genes, and make antibodies. That was just sort of a sequence that people went through without any thought, because those were the tools that we all needed. I think molecular biology has a component of that. Obviously it's not all like that, by any means.
 Yes, except molecular biology in yeast, which is the thing I know best, is really a fast way of learning a lot about what you're interested in. And probably there is no good alternative to it. But it's a lot of labor, and again, it's fairly mindless in terms of thinking about the biology. So I think a lot of people can do science without really thinking a lot about what's being done. I think now with the genome project coming to an end--this genome project in terms of the sequence--it's going to really cut back on that sort of mindless activity. People are really going to have to think more, which is good. I think genetics itself is always terrific because people end up thinking a lot about what they see.
 No. That actually just uses a fluorescent probe, which is not radioactive.
 Sure, we've used radioactivity.
 I like to minimize it. I actually don't like radioactivity at all. I think more and more methods are being developed to really cut back on the amount of radioactivity that has to be used in molecular biology. There are all sorts of probes now that use nonradioactive materials. I think those are becoming increasingly used.
 Yeah, but some of them decay very rapidly. So like 32P has a half-life of only two weeks or something like that. So it's not that long until there are no essential side effects.
 I don't know. [laughter] The University comes and picks them up and takes them away. I don't know what they do with them.
 Oh, they're very strict about making sure we don't have food in the labs. Actually, people here are very good about it. You often see them standing in the hallway eating or drinking. Coffee cups are probably the thing that most often creep into the labs. But I think food, as far as I've seen, really is actually kept out of the labs.
 I think it's stricter than it used to be. I think when I was a graduate student we used to eat in the lab all the time.
 Well, chemicals are also something you really have to worry about. You know, we use a lot of nasty things--ethidium bromide, chemicals for electron microscopy, and so on. We try to do things in the hood to minimize any sort of impact in the lab. It's something I'm definitely concerned about. I don't at all like the idea of a hazardous work environment. I like to be able to walk through the lab and feel that it's clean.
 I guess there's a desire for high security. That's what that means. In the past there have been problems of people wandering around stealing things out of offices or something like that. I think to help with that they've put up this notice to tell people to go register at least to discourage people a bit.
 Yeah. Jeremy Rifkin, was it?
 We always seem to have somebody controversial at the Pew meeting.
 Yeah. I mean, I think on that particular subject it is an issue. The capacity for what we can do is really getting pretty advanced. I'm not sure society's figured out how far we want to go, who's going to agree to what, or anything about it, you know. So issues of course of changing the germ line of people are very, very serious issues--by gene therapy or whatever. I don't think there are definite policies--as far as I know--of exactly where we're going with it. So I think they are things that have to be thought about. I don't think it's a reason to stop learning about science, making progress, and understanding things.
 Probably, if I thought that the child was going to have problems in life as a result of being really petite, if that's what we're talking about. I mean, I assume we're not talking about 5'7" versus 6'2" or something. We're talking about something more drastic, I imagine.
 I always worry. I mean, I always worry about effects of any sort of medications. I always assume that things have not actually been checked out as much as you'd like them to have been, in terms of long-term problems and so on. I would probably look into it pretty carefully before I actually made a decision about it.
 Already the cosmetic industry uses science in various forms, right? Just chemical applications for whatever--as you said, breast implants and things. Is that something that we shouldn't be doing? What are the appropriate uses of science? I think it's not an easy question to answer.
 I can't say I ever have. I think the biggest problems are actually more internal things. I don't think anybody has ever limited what I can do because I'm a woman. I think more it's my own expectations based on the way I grew up and all this sort of thing. That's the problem.
 Yeah. I think a lot of women in science, me included, feel that we're not good enough to be in it. I think this is something that comes from the way we grew up. For some reason women end up with these kind of feelings more than men do. So I think those, then, lead to limitations.
 Well, I'm not sure that we reach as high, sometimes, as we might. Sometimes when you just reach even though you don't think you're capable, you actually do succeed. I think that's a potential problem.
 Probably being aware of it is one thing.
 No, I think it was just as individuals. We all ended up with those same feelings about not knowing what we were doing. I must say I was very struck by the fact that there were so many women at a place like MIT who had so many doubts the way I did.
 Probably most of them are male, actually. I have some good female coworkers here at the university. But probably most people I actually collaborate with are men. You know, I have good women friends in science across the country also.
 Yeah. But it's a two-edged sword. On the one hand, people are trying to help you, because what your CV looks like does actually have some impact. So if you say, "I did this" or "I did that," people pay attention to that. But on the other hand, you end up doing a lot of things, I think, on committees as a woman. And perhaps a disproportionate number, I think, because there are fewer women around to do things. Or perhaps they refuse more often, too. There is a constant barrage of stuff.
 That's true. I do say no fairly frequently.
 That's right, yeah. I think so long as women realize that they can say no, then it's probably good that they get asked, because then they have the choice.
 I would find it very hard to make a generalization about that. I don't have strong feelings about it.
 It's hard to know how much of me is me as a woman and how much is me as me. [laughter] I run my lab in a certain way and I don't know which component is which.
 I don't think so. I think I'm aware with all of them of lack of confidence and things like this, so I try to work with them on that.
 Through different things. For example, if they're worried about giving talks or stuff like this I talk to them about the fact that everybody, I think, is always nervous about giving talks; it's a question of how well you cover it up, and it gets easier and easier. I actually used to be terrible. I refused to give talks for my entire graduate career. Obviously at some point I had to start doing it. Now I probably have gone to the extreme where I'm probably less nervous than most people in giving talks. You know, I talk to them about those sorts of things.
Also, I think this comes back a little bit to the hands-off approach that I have with the lab, that they take really major responsibility for their own projects. I think that that is good, because it make them realize that they can, that they're in charge, that they know how to design experiments. So I think that actually builds their confidence. They don't have to feel they have to keep coming to me to ask me how to do something.
 Yeah, but I don't think he wanted to fight with me about it. I was really adamantly opposed to giving talks. I think he probably didn't have the energy to make me.
 Let's see. I probably gave my first talk at a national meeting when I was in David Botstein's lab, so that was probably two or three years into my postdoc there. I think that was one of the first talks I ever really gave.
 No. I think that by that point I decided I really had to. So I never even verbalized that I was so afraid of it.
 Oh, yeah. I actually go overboard and don't at all accept them saying they don't want to give talks. That's how I react to it.
 No, she's got a master's degree. But she also is very independent, which is something that I really like about working with her. I guess she's probably become that way as a result of working with me. As I said, it's sort of a process of natural selection in my lab. But in the paper in which she's first author she did almost all the work, the bench work, herself. She also put a lot of thought into it. As I said, she turned out to be really pretty independent. I have no problems giving her first authorship in that.
 I've always said to her that she should feel totally capable of doing it. She just doesn't want to. I guess she doubts her abilities, but I've told her many times she's as good as anybody else.
 I'm not married and I don't have a family, so I'm not sure if I've sacrificed it or not. They just haven't happened, so it's hard for me to say. I haven't knowingly sacrificed them, but I think it's possible that being in science you reduce your chances of it, obviously. Actually, that's not true. Most people succeed in having a family, so they aren't experiencing reduction in chances of it.
 Yeah. One of my graduate students [Tanya M. Sandrock] just had a baby, a female graduate student.
 No. She just came to me and told me she was pregnant. I said, "Congratulations." I think here a fair number of people have families. I have a number of friends on the faculty, women and men, who have kids and so on. So I don't think there's any lack of role models, really.
 Right. Because I don't have children it's hard for me to see how hard it is.
 Yeah. Already in science I feel that I don't do anything well because already you're stretched too thin between teaching and doing science and talking to people. Everything you seem to be rushing through, which is sad, because part of what our training is, is really to do something very well. So when we first are trained as scientists we're taught to think very, very carefully about what we're doing and all this. Then suddenly we're in this position of not having enough time to do anything properly. You're just sort of rushing through everything. I'm sure with a family it's infinitely worse.
 We have a tremendous departmental office staff who really are great at supporting us. They keep total track of what's going on with the budgets and things. When the time comes for renewing grants, we can just hand them pages and pages of that sort of stuff that has to be filled out, and they do it for us. All we really have to do is sign things at the end and write the scientific stuff. We have an excellent support staff here.
 Oh, yeah. I think it's minimal for us here. It's very, very good.
 No, it's subdivided. There are many departments. I'm in the Department of Molecular and Cell Biology. But there's [the Department of] Biochemistry, [the Department of] Ecology and Evolutionary Biology, all sorts of different things.
 I think there are fourteen or fifteen primary faculty and twenty-odd faculty with joint appointments from other departments.
 They did. I actually don't know the history of the whole thing. But it was definitely before my time.
 I have a feeling our department does pretty well, which is probably why I don't know much about it. I have a feeling if we weren't doing well I'd probably know more.
 Yeah.
 We've grown enormously in the last few years. When I was hired, there were three of us that I told you about who were hired at the same time. Let's see, I don't know, four or five other faculty have been hired since us. There are eight or so of us that came in the last six years. I think now it's really going to slow down. That will probably be the end of expansion for a bit.
 I assume. I honestly don't know. [laughter] That's how well they take care of our affairs for us. I don't even know these things.
 Yeah. Maybe it's something I should think about. The department in general is very, very cooperative and doesn't fight for resources very much at all among themselves. We have a common dishwashing facility that we all feed into, and it's just split even between all the labs. Everyone just sort of supports everyone else, more or less.
 Yeah.
 I think it's 48 or something like that.
 But then the department gets a whole bunch of that back. They're constantly telling us how much they-- I never remember the numbers, but we get some back in the department. The department spends it on supporting people during dry spells of grants and things like that. So it's good.
 I don't know if this is really answering your question at all, but I totally believe in the whole evolutionary type of concept. As far as the universe goes, in some ways it's kind of a depressed view of it that I have, because I feel that really what happens on this planet is of absolutely no consequence in any sort of time in the universe. This planet's going to come and go. You know, we have these wonderful things on this planet, but it's all going to be short-lived anyway. In my most depressed moments it makes me think that nothing is worth doing at all, even the science. What is the point of trying to improve conditions around the world or trying to solve diseases? Overpopulation, of course, is a tremendous problem, but in the end that's going to take care of itself through starvation and disease. It would be nice if we could prevent it. I feel that it's all kind of hopeless, I'm sorry to say. It seems that momentum is so tremendous in terms of destroying this planet that it's going to happen without any sort of intervention being possible.
 Slightly. We used to go to church and get bored. Right at the moment I'm not religious at all. Then I was only sort of marginally religious.
 Well, I don't know. Actually, I think it's a problem for me at the moment. You know, only recently have I really been thinking about what I really want to do beyond what I'm doing right now. Sometimes it's very hard to get motivated to do anything other than just keep going with what I'm doing, because that's the path of least resistance. Because it's very easy to think, "Well, nothing in the end actually makes a difference anyway." I mean, it's a terrible attitude and I hope I lose it before too long. [laughter]
 Oh, definitely. I think it's both. I think there's variation. They're just sort of stochastic based on low concentrations of regulatory proteins or something like this. So there are general ways in which things are done, but there's also a lot of room for variation.
 Ah, that's a hard one.
 I actually don't know. I don't know what I'd like to do. This is part of what I was saying to you the other day when I was saying I'm not sure what my role is in science. I don't really know what I want my contribution to be.
 I think having to deal with conflicts among people. I find it extremely frustrating when people won't cooperate with each other, won't be forgiving with mistakes that others have made, and stuff like this.
 Yeah, you know, whoever, whatever.
 I'm sorry to say I forgot to think about it.
 I can't think of anything right now.
 Thank you. I've enjoyed it.