Scientist Stories: Nancy Hopkins, Genetics of Cancer & Development

It's a very great pleasure to introduce Nancy Hopkins today. Nancy came to the biology department in the early '70s. She was one of the first assistant professors that was hired when Salvador Luria started the new biology cancer center. So we were both hired the same year, and we've been colleagues for a very long time. During that time, I've seen Nancy develop a really remarkable scientific career. And she's going to tell you about that. But another area of her activities has had a very great impact. And that's what I'd like to tell you about. In the 1990s, there were 17 women on the School of Science tenured faculty. That actually counted 2 women whose primary appointment was in engineering. But they had secondary appointments. Just to give you an idea of scale, there were 199 men on the tenured faculty in the School of Science. And I don't think they had to count secondary appointments. So we all loved our jobs, but we had some concerns. And one was the size of the women faculty. There were very few women being hired and even fewer being tenured. We ran as fast as we could and almost kept in the same place. And our other concern was that we weren't running on a level playing field. So— I think this mic only does that. I think I have to yell. So anyway, we were concerned that we weren't running on a level playing field. And Nancy suggested that we do a study. Now, there have been oodles of this sort of study. And my bet is that very few of them had as unstatistical a set of subjects as the 17 women we had. And those studies had been made and published and forgotten. But Nancy led a study that had a very different outcome. And that's what I want to tell you about. The Dean of Science at that point was Bob Birgeneau. And he agreed to appoint a committee to do the study. So he appointed one woman from each faculty in the School of Science, except of course math, because it didn't have any women. So he appointed a man from math. And he also appointed two other men from other departments. And that turned out to be a very good thing, because they were wise in the ways of MIT administration. And there hadn't been any woman in MIT administration to become wise in those ways. So the committee went to work. Nancy chaired it. And it really worked. It collected data. It had access to all the MIT data. It collected its own. So it did salaries. It did space. It did honors. It did teaching. Everything you could think of. And it also— did in-depth interviews with the 17 women, and I think any other woman that would agree to talk to them, or men. Anyway, they wrote a report, and they sent the report to Dean Burgenau and President Vest. And the amazing thing was that something happened. The administration paid attention and started answering their concerns. And so they corrected inequities in salary, in space. They even corrected some of the inequities of retirees who were paid less than they should have because they'd been paid less than they should have before. They set up other committees in the other schools to do the same thing. They started appointing women to administrative positions. They established the Faculty Council on the Council on Faculty Diversity, which was co-chaired by the provost, and Nancy was the other co-chair. And this had a lot of advantages. It put her on the academic council, which was the committee that reviewed salary and promotion. And this was the first time a woman had reviewed that sort of thing. There were other things, I'm sure. Anyway, it was a very satisfactory conclusion. And we all thought, hmm. And then not long after, it got even better. I woke one morning with my clock radio saying, MIT admits discrimination of women faculty. And I lay there thinking, have I woken up yet? And realized, as the story went on, as the faculty newsletter had published a report on the report. And this had been picked up by the national news. It made the front page of The Globe. It made the front page of The New York Times. And I was going down to a meeting at Cold Spring Harbor that afternoon. When I got off the limo from the airport, women from all over the world came rushing up to say, what's going on at MIT? And it got better. And the Ford Foundation approached MIT with the offer to give them money if they would replicate some of this in other schools. President Vest set up a meeting with presidents of 8 other major universities— Harvard, Princeton, Stanford, Berkeley, Michigan. They brought— the presidents came with other representatives. They had a meeting discussing this and it led to other meetings of what came to be called the MIT Nine. So Nancy gave, I forget how many lectures, how many places to academic groups, to business groups, to who knows how many groups. She got a slew of awards ranging from the Girl Scouts to the Lady Steelworkers of America and everybody in between. So it did have a terrific impact and continues to. In the meantime, her science has gone on terrifically, and it's been awarded with election to the National Academy of Sciences and the Institute of Medicine. And she's going to tell you about that. Nancy, nice to have you here.

Wow. Well, life passes before your eyes. Mary Lou, thank you so much. I should say that before I came to MIT, I was a graduate student at Harvard. And one day I was in the library— every department used to have a library then, of course. You had to have all the journals come in and be in the library that everybody had access to. And one day I picked up a journal and I read a paper by this person named Mary Lou Pardue. And it was about this amazing technique that she had invented that people said was impossible, but it wasn't because it worked. And I just thought, whoa. I can still remember standing there with my jaw dropping thinking, that's unbelievable. So she became one of my scientific heroines, heroes, and has remained so for all of the years since. And I really didn't know her until we got to work together on the issue that she described. And I got to the point where I valued her judgment so much I never dared to make a single decision without first consulting her. And I frequently still do. So thank you for being a wonderful colleague all these years and an inspiration. To me. Mandana, I have to say a word about you. This series, I'm sure some of you have been to other ones of them, but it's a wonderful idea in a way, except I think it's a wonderful idea when it's somebody else who's speaking. I found that I myself personally didn't want to speak. I wanted to hear my other colleagues speak. But this person is without doubt the most persistent person I think I've come across. I'm a bulldog. I've never seen anything like it. So she pursued me to the point Well, I realized pretty soon— and I kept saying no, no, no— I was going to have to either start to avoid her in the halls or I was going to have to give this talk. And I decided it was better to give the talk because I really like to talk to her. So here I am. So why does one want to resist this? And I think there are several reasons, many reasons. I think that scientists look forward. They're people who like to look forward. I don't like to look back. Second of all, I have a terrible memory. I really can't hardly remember anything. And so I have some notes and some slides to dog my poor old brain. And the other thing is, maybe this is not right, we'll see by the end, we'll see what you say, but I think I really had an amazingly interesting life and I'm enormously grateful. The older you get, certain things happen to you, watch out, I'm warning you. You start to be really grateful for the things that happened to you that were wonderful. And I am. And I realize I'm very privileged and really very interesting, but I don't I think to tell the story of your life in a way that other people can understand it requires that you be almost a novelist, a poet, some other kind of person. And you don't want to tell a story and not have people understand it because it's so important. You want them to really understand it. And it's a hard thing to do. So I think for that reason, probably, I resisted. But she got me in the end. So here I am. So now I thought about what I wanted to say. And of course, there's a lot to say because I've been in this I've been in this field for 48 years. And I think part of the reason for these talks was people want to have a kind of record of two things. One is how do people become scientists? What determines why you become a scientist? And then why do different people's careers take the particular path in science that they actually do take? So I'm going to talk about those two things. And in terms of how I became a scientist, I have the world's simplest story on how I became a scientist. My entire life scientific career was determined in the space of one hour. One. One hour. I was 19 years old. And I was a junior in college at Radcliffe College, which for those of you— some of you may never have heard of Radcliffe College. You look very young. Yeah, Radcliffe College was the female division of Harvard. Harvard was not yet co-ed. And there was a separate college that attended all the same classes, but had a separate dormitory and a separate name. Boys not allowed in the dormitory except for 1 hour on Sundays. Anyway, so it was 1963. I was a junior and so forth. Now, I have to say, before that one transformative hour that was to determine my entire life, at college, I was not a great college student. And I was very sad to say that Harvard had a great education to offer. I did not take full advantage of it. So to those of you who still have the opportunity to take full advantage of your classes, please do so. In fact, when I retire, I may go back and go to college all over again. Then in sophomore year, late sort of sophomore year, well, I didn't even know what to major in, honestly. I was floating about. I'd gotten to college. I wanted to major in math. They said, are you joking? You couldn't possibly major in math. You're so far behind everybody else that you'll never catch up. I'd gone to an all-girls school People didn't believe girls liked math, didn't want to learn math. So I couldn't do that. So what was I going to major in? I wasn't sure. So I floated around. Really what I got interested in when I got to college was actually, I got to tell you, boys. Having been to an all-girls school, suddenly away from home, it was a very restrictive generation, you know. There I was and there were all these boys. I met a very nice one the first year. Liked his friends. We went to football games. There was drinking wine from wineskins, going to Paris in the summer. Man, it was great. And so that's kind of what I majored in the first couple of years. But then in sophomore years, I fell into this kind of malaise. And I don't know whether it was the realization that this would end one day. You couldn't just go on like this forever. But you had to actually do something in your life. And I had needed a major. And I'd taken all the basic science courses in chemistry, math, physics, so I could major in pretty much any one of those sciences, I thought, you know, maybe this sort of malaise I'm having— it was this question that afflicted people then. I don't even know if it afflicts young people today. What is the meaning of life? Do people still have this problem? You do. Oh, good. OK, well then you can relate to this. It was a sort of existentialism was popular then. We read Camus. We lounged about. What was the meaning of it all? And I was, I think, quite— for a while, lounging about, wondering about what was the meaning of life and, you know, what would you do with your life. And, you know, your fate in my generation was ultimately to marry, have children, and do that. But in the meantime, you had a window of opportunity where you could do anything. And I decided, well, maybe I should go to medical school and save people's lives. That would be a good way to deal with this question of what is the meaning of life. And also because when I was a child, 8 or 9 years old, my mother had had cancer. And in that generation, which was in the early '50s, the word cancer was so terrifying that you never told a soul. Nobody knew. In fact, my mother wasn't going to tell her family or her children. But she started to cry all the time. And so we realized this was so uncharacteristic. So it turned out she had cancer. And nobody else was told. But it was so terrifying. And that left a very lasting impression. So I thought, well, one thing you could do is maybe you could help treat people, make the world a better place. I should say the kind of cancer she had could never have killed anybody. I mean, it was completely non-dangerous. But just the word alone was that scary and so little known about it. So I thought, OK, well, I'll major— maybe I'll major in biology. I'll give that a shot. So in the spring of my junior year, I signed up for a course called Bio 2 at Harvard. And it had 4 modules, each taught by a different professor. And the first module was on physiology. So we had a man named Castle. I thought he was ancient. He was probably about 40. He was 50 maybe. And I thought he was about 900 years old. And he was talking about physiology. And it was terrific. He talked about the kidney and how that works and the heart, how that— different organs, how they work. I took careful notes. I learned it all. I thought it might be helpful in medical school. And it was really remarkable. But I thought, you know, how— but where do these things come from? How do you make something that's that amazing? This, you know, it was just delivered to you as the truth. And the next module, I thought, well, maybe, you know, we'll get to the bottom of what the explanation of all this amazing stuff is. Because the next module was supposed to be about genetics. And I had a vague idea what that was. And the person who was supposed to lecture in that section was Jim Watson. And I knew who he was because I had read in the Crimson that earlier in that year, he had won a Nobel Prize for discovering the structure of DNA. Now, I scarcely knew what a Nobel Prize was. And I certainly didn't know what DNA was. Hadn't been taught in my high school. And anyway, it said in also— so I looked him up in the confidential guide, the undergraduate confi guide. And it said that he was— some students liked him, but he had a tendency to drop his voice at the end of the sentence and turn and address the blackboard head-on. So if you really wanted to know what he was talking about, you better get to class early and sit in the front. So that's what I did. So I thought, you know, maybe this person's going to come and explain how this biology works, and this will be very interesting. So I got there very early, and I took my seat in the the aisle on the second seat at 2 Divinity Avenue. And I waited for Jim Watson to come in. So that hour changed my life. But before I tell you what happened, let me just tell you, back up a little bit, because I know people like to know a little bit more about where people come from than that. So I'll just give you a few minutes of what led up to— how did I happen to end up getting to Harvard in the first place. So I grew up in New York City. And my father had come from New Hampshire. And he had planned to stay there forever and be a lawyer like his father and his father before him and his father before him and his father before him. I don't know when they came to America. They were just always here. My mother, on the other hand, had her family come to the United States from England. And when they met, my mother somehow got my father to give up that plan and move to New York. So he did. And he worked as a librarian at the New York Public Library. My mother, my mother was a very interesting person. I adored her, and she was an extremely driven person. And I think what drove her honestly was fear, I have to say. She had wanted to be a painter, but she gave it up because she realized that this was not a good occupation if you chose to eat. If you preferred to eat, you would need to be— so she became a teacher of art. But she understood— I think she was driven by sort of immigrant mentality, the desire to fit in. And I think she was also marked for life by living through the Great Depression. She really never got over it. So she had this notion that life was precarious. You could lose everything. The richest people in the world could become poor overnight. And that everybody, men and women, had to be able to earn a living. And that the route to being able to earn a good living was, well, to be highly educated. So women and men had to be educated because you never knew what was going to happen. And of course, for women, you could also marry an educated person. That was the alternative. So those were your two choices. In any case, she understood that in America— she read the newspaper, she figured out, okay, you got to go to Harvard. Okay, so how do you go to Harvard? Well, you're going to go to Harvard. It was good in those days to go to a private school because they had a higher acceptance rate to Ivy League colleges than public schools did. So she decided, well, my family wasn't rich enough to send us to a private school in New York City. It was very expensive. But if you did well on these entry tests, you might be able to get a scholarship. So she brought home some IQ tests to test me and my sister and determine what sort of material she was working with. So we had these IQ tests and she decided it was worth the investment to let us go to a school called Spence. And Spence was a small private girls' school in Manhattan, 22 East 91st Street. And it was a fabulous, fabulous place. My family was absolutely not poor. Believe me, not poor. We had everything anybody could want. However, it's likely, probably true that I probably was the poorest person in the school. This was a school for the children of millionaires, and the girls who went there were preparing to be debutantes and to be the social leaders of Manhattan. And so we wore white gloves to school and we learned how to curtsy because some of these people seriously were likely to be presented at court, and you needed to be able to curtsy when you met the Queen, so we learned how to do that. But what was remarkable about it was that the level of education was fantastic. In the humanities, it was as good as I think there ever has been, that I know about, and to this day. The sciences were very weak. What they taught was terrific, but there wasn't much of it because most debutantes really weren't thought to need a whole lot of mathematics. Anyway, it was a wonderful school and I loved my students. I email still with my classmates from first grade. We meet periodically. It was a lifetime bonding. I should say it had one other, I think, wonderful effect, and that was these people were extremely wealthy. So at the end of the day, there would be a line of limousines outside the school with a chauffeur. Each little child would get out, walk to a car, get in. The car would drive off. The next one would get in. The car would drive off. My mother would be waiting in the Chevrolet. I'd get in and drive. But I learned that great wealth was not something that I wanted to aspire to in my life. Everybody wanted to come to our house because we had a wonderful family and they had lots of governesses and lots of money and lots of things. But it wasn't the route to happiness. So there we are. Anyway, my mother's plan worked. And my sister and I both went to Spence. And we both applied on early decision to Radcliffe. And we both got in. And we both went to Radcliffe. And we actually roomed together. Plan A. Anyway, that's how I ended up in that room at 2 Divinity Avenue and waiting for Dr. Watson. So in he comes. You know, this is what I mean about how can you explain something like that? How can you explain an event like this, really? I do remember it was the most beautiful spring day, like— well, not today. But it was this time of year, sort of, and the trees were all out. Beautiful. And I walked in, and I can only say that it was— I think some people, I have heard many people say that, you know, they drive across the Golden Gate Bridge and they get religion as they're driving across the bridge. Suddenly they're struck by the truth. Well, that's what happened to me in that hour. I went in one person, I came out a different person. Jim came in And I can't remember specifically what he was saying. 1963 was the year the genetic code was being cracked. Can you believe it's possible that you actually can see a living person who was alive the year the genetic code was being cracked? But that's what it was. And he would come to class. He would have talked on the telephone with the people who were decoding, breaking the code. And he would come in with little scraps of paper with the codon assignments and give you the latest codon assignment. There was no question as I sat there. I thought, you know, it wasn't just— this is life. He's telling us what life is. This is the secret of how all life works. And for me, for some reason— it's hard to explain these things— but deeply emotionally, it was not just the secret of life, but the answer of life. So this big amorphous question, what's the meaning of life? Well, this was it. That was totally it. And I really do think that in a funny way for scientists— well, I have friends who are religious. Not too many, but some. None who are scientists, I should add. Maybe they don't tell me. But I don't have any. However, I have friends who are. And when they describe how religion has affected their lives, I can say that discovering molecular biology had that kind of effect on my life. It has provided a sense of why anything matters to the extent that we can understand, you know, well, you know, you wouldn't be doing this either if it didn't have the same effect on you, I suspect. Anyway, that's what it was. The other thing that happened in that hour of which is, and that's why it's so hard to remember what he must have said, but in some way he conveyed that what biological organisms were was in their genes. And so I said, whoa, if everything's in the genes, everything's written there somehow, this is also going to explain cancer. Hey. And you know, the other thing that had bothered me a lot in my period of angst and existential angst was the world. I was bothered by the world. I think in my generation, if you grew up in my generation, Not only were we afraid of cancer, but the big thing that had affected the lives of people in my generation was war. It was really either you lived through World War II and were directly affected by it, or you were indirectly affected by it, but nobody escaped having their life shaped by it, I think. Then we went into— there was the atomic bomb and there was the Cold War. These had terrifying impact on you as a child. I think part of science also was an escape. Escape from an incomprehensible world for many people. But I thought, you know, listening to this, you know, everything's in the genes. Even the way people behave is in their genes somehow. So maybe someday, even by understanding DNA, you'll understand why the world is the way it is. So for a young person, it provided everything. It was the answer to everything that was bothering me. I said, gotta, gotta do it, gotta have it, gotta be with it. Whoa, this is taking longer than I thought. I've got to speed up. OK. So I say, here's Jim Watson. I think the way he— I honestly can't remember that well. But I think that's kind of the way he looked in 1963. And so I wanted to work in his lab. I didn't really want to work. I didn't know what that meant. I just had to be near the science. I just had to get as close to it as I could. So I went to his office at the Harvard Biolabs and asked if I could work in his lab. And this is a picture of Jim's office. And I just happened to find this one. I wish I had a better picture. But I think this must have been when he won the Nobel Prize. And he's probably talking— that probably is what a reporter looked like in 1962. It's not the way they look today. But anyway, he had a little lab next to his office. And he took undergraduates into his lab who could work there. And I was fortunate to be one of them. So I worked in the lab next to Jim's office for the next year and a half. And in that year— and this is the part I thought about— there's no way that I can describe what that experience was like for a 19-, 20-year-old person to have discovered molecular biology. And of course, not only had Jim given me science, given me this extraordinary gift of molecular biology, but here was a whole world I had not imagined. First of all, Jim worked Saturday nights. I mean, I had no idea adults worked Saturday nights. I knew people worked hard. I never heard of such a thing, of somebody sitting at their desk on a Saturday night by themselves doing work. But what was extraordinary about him was Jim— many of you, some of you know him. How many people know him? I know Bob, you know him. Chris knows him. Mary Lou and Graham. Young people have met him. You may have missed his best years. He was so extraordinary. I can't put it into words really. He had such an imagination. He created a world, the world according to Jim. And he drew— if you were drawn into his world, you became part of the Jim Watson world. And you were a lucky person. Because in that world, it didn't matter if you were an undergraduate student, whether you were a Nobel Prize-winning person, whether you're a professor or a graduate student. If you're part of Jim's world, you're all on one level. And the whole point of the thing was science. He was science in some funny way. But he was also sort of remarkably youthful. Well, of course, he was only 35. So I guess that is pretty youthful. But he seemed— I didn't really realize how young 35 could be. He was very young. And he loved to have parties. And he had parties at his house. And everybody would come, all age groups. He loved to come to our parties. He was always asking, inviting himself to our parties. He wanted to come to my parties, my roommate's parties, my husband's parties, my boyfriend's parties. And we did lots of things. We went to the movies. It's hard to imagine a faculty member engaging so much with undergraduate students, with graduate students. I don't know. It was an extraordinary thing. And I just could not— I followed him around because I was waiting for that latest bit of gossip from the telephone, some new fact of molecular biology to fall. And you knew that very likely somebody would make discovery. They happened so fast. And they were so profound. And your whole world would turn upside down. You'd understand the world differently. And that person would win a Nobel Prize and on to the next. So it was an amazing experience. Anyway, in senior year, I— I happened to hear a lecture by, I guess, Francois Jacob. And he was talking about the operon hypothesis. And so by then, we pretty much had the code. We had the central dogma. And I thought the next big thing is we got to understand how gene expression is controlled. And along comes Francois Jacob with the operon hypothesis. I got very excited about that and said, repressa. I became completely obsessed with— the repressor. Had to isolate this protein called the repressor and see if Jacob-Monod were right. Well, my time at Harvard was ending. And you had to go to graduate school. And they had a sort of rule. You shouldn't go to graduate school in the place where you come from. So what to do? And in fact, I'm not sure I would have gone to graduate school. If I'd had my choice, I would have just stayed there and been a technician. Because I didn't really care about getting a PhD. I just cared about being near the science I loved. Jim said, you've got to go to graduate school. So you're going to Yale. So off I went to Yale. Well, I get to Yale. And I said, OK, who's trying to isolate the repressor here? And he looked at me and said, the repressor? That's a very hard problem. I said, yes, but it's very important. It's the problem. Got to work on that problem. And I couldn't find anybody who was working on the repressor. I left there. What department were you in? I can't remember. I might have tried several. I looked all over the campus for somebody working on the Oppressor. I thought it would be— it's a long story.

In those days they kept changing anyway.

They kept changing. I mean, they stayed in one and it kept changing. I don't know. Anyway, I couldn't find anyone who was doing it. Meanwhile, back at Harvard I had met a a young person who was a TA, I think, in one of the classes I'd taken. His name was Mark Tashney. And Mark Tashney was really smart. So I thought, well, Mark Tashney is really smart. He's really ambitious. That guy is certainly going to isolate the repressor. I'm sure he wouldn't consider working on any other problem. So I wrote to him from Yale, and I said, I said, what are you doing? He said, I'm trying to isolate the repressor. I said, I knew it. So I said, how's it going? He said, oh, well, it's a very hard problem. So I said, do you have any openings in your lab for technicians? And he said, yeah, sure. So I left Yale and came back to Harvard to help Mark isolate the repressor. And it was a really hard problem. But it was the other great scientific experience I had. So the first one was being around Jim and learning what science as a whole was like and being drawn into this extraordinary world of molecular biology. And the second incredible experience I had was working side by side with Mark Ptashne while he isolated the lambda phage repressor. So we had a tiny— not tiny— a small lab. And we were side by side at the bench. And this person was intense. Really intense. And it was a very, very hard— technically hard experiment to do. And he'd had a great idea of how to do it, but to actually carry it out was really hard. But working together, it really was a two-person experiment. And we became like one person. And that was how I learned how to do science. So I'd fallen in love with science, and now I learned how to actually do science. So he was a great teacher. And of course, because it meant so much to him also that this work— so if you didn't do the controls, boy, you only made that mistake once. You didn't go back again. Again without all the proper controls. And so we isolated— Mark isolated— we isolated isotopically labeled repressor. So then the big question, scientific question, was did it bind specifically to DNA and therefore control gene expression as had been predicted by Jacob-Monod? And this isn't the first experiment, actually. It's a slightly later one. But that experiment I can, of course, still remember very vividly doing. The critical experiment. It was such a technically hard experiment. Anyway, we got the label repressor. We had the DNA. What you did is you mix them together, and then you ran it down a sucrose gradient. And you poked a hole in the bottom of the tube, and you collected drops. And then you ran them over a thing, and you filtered it, and you washed them, and you individually took them. And then you took them to a scintillation counter upstairs and ran up, left them there to quiet down. And then you let them count for 5 minutes each, and so forth. And Mark had gone off to a seminar, and I was doing the experiment. And the thing was in the counter. And I'd run upstairs every 10 minutes and plot the next point. And there it was. And when he came back after the talk, I had the result on the graph. And there was the repressor binding to DNA. And we raced down the hall. And we showed it to Guido Guidotti. And we raced down the hall. And there was Jim Watson and Wally Gilbert just leaving. And we said, look at this. Look at this. And they saw it. And it was pretty exciting. So that was how we figured out that they were right, Jacob-Monod. The repressor did bind to DNA. And so then I was having a wonderful time. But I realized that, wow, this science is pretty intense. And there'd been a lot of competition over the repressor. And people would call Mark up all the time and sort of needle him. And I could see this was a rough business. And I kind of wondered, boy, I don't know if I'd be tough enough to be a scientist like these guys. But I sure loved it. Around that time, Jim Watson came in one day and he said, OK, that's it. You're going to graduate school. I said, oh, well, OK, if you insist. So next day I was in graduate school. So I went to Harvard. And I— he was much more casual, I think, in those days. So I had a good project. And by then, as I say, I really understood it. And I showed that there were operators on either side. I got mutants from Jacob-Monod and showed that there were operators on either side and that the repressor bound to them and that virulence and so forth, the whole thing. And so it was a wonderful, wonderful experience. So then that came to an end. And the question was what to do next. So my plan in life had been to indulge in science to the maximum as early as I could so that I could prepare for my next phase of life, which was a bit like the guillotine falling. It's a terrible way to describe having children, but that's how I felt about it. I was married by then. And I felt that it was inevitable that I would have to give up the science and move with my husband to wherever he got an academic job. He was in English. And he was on the faculty at Harvard as a junior faculty member, which meant he would not get tenure. That was almost an automatic. Thing. And so we knew he would have to move. And— but what happened was that I thought, well, I don't know when he'll move. So I'll just go on. What would be the next logical step? And I must say, I was still thinking about cancer from that first hour listening to Jim Watson. When were we going to be able to approach cancer as molecular biologists? Well, when I started in graduate school, in school or as an undergraduate, that same hour that I heard Jim Watson when the genetic code was being cracked, the possibility that you could actually understand phage lambda did not seem possible. And yet here it was just a few years later, and now we understood lambda, which had been chaos. I mean, incomprehensible mess. And now we had the repressor. It bound DNA to operons. It was all straight. So you saw how quickly an understanding had come out of this absolute morass. And I thought, you know, we now know how to study viruses really well with molecular genetics, molecular biology. So maybe it's possible that you could apply the same thinking and methodology and ideas to tumor viruses because it was already well known that viruses could cause cancer in animals. So I thought, well, I'll get my dream. I'll get my dream. I'll get to work on cancer even if I only do it for a year or two and then I give up science. At least I'll have done it and so completed the dream. So I took a postdoc officially with Jim Watson in Cold Spring Harbor and went and learned how to grow tissue culture cells and work with SV40. And then my husband decided he didn't want to be married anymore. So that took care of the problem. I didn't have that problem anymore. Off he went. And there I was, and free to do as I pleased. I decided to stay on. And so the question at that time was— well, first of all, I should say that when I left the phage field, which was a wonderful field, to go into cancer, many people— you actually didn't talk about it with many people. I didn't even know that Jim was planning to do it when I first decided to do it. And I certainly didn't talk to Mark about it. People in the phage field thought— in the bacterial world— kind of thought that working on animal cells was a selling out, that it was a lost cause. You could never do serious science with those things. And cancer was the sort of graveyard of careers. So if you went into cancer, they'd never hear from you again. You'd never do good science, and goodbye. So I thought, that's OK. I'm not going to be here anyway. So what difference does it make? At the time I decided I was going to do it, it didn't really matter to me. I'll just go do it. The big question— well, there were two questions. One was, here were these viruses that had a very small number of genes. And so you could imagine, as I say, that you might be able to find the genes in those viruses that made them able to cause cancer in animals. And the other question of the time was, are viruses the main cause of cancer in people? And there were two theories. Some people thought viruses probably caused most cancers. And some people thought, no, it's probably mutations in some kind of genetic alteration. So there was really two issues. And I think many of us were influenced by this discovery. This was another moment that I had that was like the moment of reading Mary-Lou's paper. I one day picked up a magazine instantly and there was the discovery of reverse transcriptase by David Baltimore and Howard Temin. And that was just mind-blowing at the time. It just blew us away. It blew me away. I must say, I was at Cold Spring Harbor and I said to Barbara McClintock, And you probably know who she is. I said to her, is this the most amazing thing? The central dogma isn't just one way, it goes backwards. It's amazing. Barbara said, oh, ho-hum, you know, she said. Of course Lamarck was right. Just ponder that one for a while. Barbara always had something profoundly interesting and different to say. She wasn't as impressed as I was. But I was tremendously impressed by this. It was so intellectually remarkable. And this class of viruses that had reverse transcriptase were the kind that caused cancer in animals at such a high frequency. So it seemed like a good thing to work on. And that story is very complicated. But around this time, as I was thinking about this, out of the blue came a phone call from MIT asking me if I'd be interested in a job in the new cancer center that they were founding and a similar call from Harvard. So as you know, well, I was pretty visible because of the work I'd done with Mark. But of course, it was also an era when universities were required to hire women, frankly. So I was hired because they had to find somebody. And I was standing there with all the right training, working on the right topic. And they didn't know that I had been planning to quit science. But so they called up. And so that was how that happened. And off I went. And I should say that the story of the tumor viruses is well known. And it was a wonderful era in cancer virus work. And I should say that there are these two questions. How do the viruses cause cancer? And do viruses actually cause human cancer? The question of whether viruses cause human cancer was not actually worked on by any of us. Really. It came out of a different set of people doing something different. How the viruses themselves— some of them could cause cancer— was what molecular biologists worked on. And I actually ended up working on mouse leukemia viruses that cause leukemia in mice. And I studied— there were viruses that had many different degrees of oncogenicity. And they caused different kinds of cancer. Different in how cancer-causing they were. And I ended up doing genetic analysis of this. And what we really were studying, it turned out, how leukemogenic they were was dependent upon how well they grew and tissue-specific aspects. And so we ended up studying that. And it turned out there were many factors that could. And some of the most interesting ones were— and unexpected ones— were was finding that the capsid proteins inside the virus could determine host range. And that there was something called— that later came to be called an enhancer. The transcriptional signals had the kind of tissue specificity at the time. Anyway, around this time, by now in the field, oncogenes had been discovered. And the field was moving towards that. And I was becoming disheartened by the cancer field. And I decided I was going to make another switch. A long story and time's running out. And so I'm going to just go on and say that I decided that if cancer could be cured by finding drugs that inhibit oncogenes, other people could do it. I didn't have to do it. Genes had been discovered and people could look for drugs. And if they could inhibit oncogenes, well, cancer would soon be cured. If that wasn't the answer, well, it wasn't the answer. So off I went thinking, well, what would I do? And I should say that— In addition to realizing I was not really working on cancer so much, I was working on virology. That was fine, but it wasn't what I wanted to do. This was where I really ran into the wall that Mary-Lou talked about. I found the field was a real problem for women. And so I thought, well, I'll pick a field that's not got the problem. And I thought about that a lot when I decided what else I wanted to do. And I thought about when I'd made the transition into cancer, this realization that suddenly it was possible to work on cancer. So you went from not even being able to imagine it to actually being able to do it productively. Was it conceivable that you could do the same thing now for behavior? Was it possible you could do the genetics of behavior, which is the other topic I'd been— from my first hour in science, wanted to work on. So I decided that I would go and invest— oh, I should say that these were wonderful collaborators I had in the virus field, Wally Rowe and Janet Hotley. So I thought, well, I'd like to see— maybe you could do genetics of behavior. Forward genetic screens. And I didn't want to work on mice, so I thought— or humans. So I decided that maybe you could do zebrafish. And I learned that there was this amazing woman, Janie Nusslein-Volhard, whom I didn't know but who I'd heard of. And I figured she had to be a genius. I mean, I'd read some of her papers too, and I could not believe it. And so this is Janie the way she looked when I went to do a sabbatical in her lab on the left. And I guess this is how she looks now. And I couldn't decide which picture to use, so I put them both. So off I go to Tubing in Germany for a sabbatical with Janusz Nusslein to see whether or not you could do the forward genetics of behavior in zebrafish. I'm there about a week, and it's clear the answer is no. Don't even think about it. It's so ridiculous. No, you couldn't do the genetics. And if I tried to do that, well, I'd certainly be out of science many years ago. However, what happened in that week was first of all, I loved Tubing and I loved Janni. I loved the lab. And I loved the zebrafish. I was seduced by the absolute beauty of the zebrafish embryo. Watch out. Watch it. Somebody hands you a plate of embryos and says, look at this. Be careful, because that's what happened to me. Janni said, just look at this. And I watched it for 24 hours. And there developing right in front of your eyes was this magnificent thing, this little fish. And I could look at it and I thought I could just visualize lax Z patterns in that fish and thought, boy, if you had the technology in this, boy, you could really do the genetics of early development. So you can't do behavior, but you could do that. And so that's what we did. And we isolated lots of genes. And it was a great success due to much good fortune and frankly being at MIT. And then at the end of it, 20 years later, some of the mutations we isolated turned out to predispose fish to cancer. And so back to square one. So here I am 48 years later. And I'm going to just take 2 minutes and then— because I'd like to hear some chat. This is a conversation. So I'm not hearing anything back yet. So I want to hear something back. So I want to reflect on this. Well, as I said, when I started, I wanted to work in cancer. You could not imagine doing so at molecular level. Here we are today. At that time, I knew one day you could do it, but I thought it was 200 years away. Instead, it's only— it's less than 4— it's half a century. OK. So where are we, in fact, today? And I should say that about 2 and a half years ago, I actually had cancer. And this has been one of the most interesting scientific experiences of my life. I have to say. I don't recommend it. But if you happen to have it, it's fascinating. It really is. And so it's caused me to really look at this question of what happened through this whole period of time when I was moving along as I did, the molecular biologists were moving as they did, the cancer field was moving as it did. What really happened to the cancer field? And I have to say, when you— at least my experience is having gone through it, is very different than how I looked on it before I went through it. And my experience, the way I see it now is that this whole undertaking that we did collectively in various ways has been an unbelievable success. It's just astonishing how successful. I don't know if the war on cancer, but the whole endeavor of molecular biology is applied to disease, certainly into cancer in particular, in particular. So what do I mean by that? Well, first of all, I started— I went to some meetings. And the first thing you see when you look at the big picture of cancer, you find that one of the things that have really made an impact on this disease, one is that we know now that if you look worldwide at cancer, 30% of cancer is caused by smoking. OK, well, you may not think that's a wonderful thing. But honestly, 30%, that's a lot. Of things that could be prevented. The next thing, which is really remarkable, and which unfortunately I didn't get to work on, but which was taking place, 20% of cancer deaths are caused by viruses. So it wasn't the viruses we worked on. It wasn't the ones that really led to so many of the advances in understanding cancer genes initially. But a significant fraction of cancers are preventable. And vaccines have been developed to these and are in progress. And so we should soon see worldwide a very significant impact of those vaccines on cancer. And then there are other factors that are even more— that are more amorphous. I think those two things are really very, very definite. There are amorphous things like obesity and something in the diet and the lifestyle that's been hard to pin down. Perhaps hard to deal with, but that people think certainly is responsible for another 20%. Then you come to our prevention methods, screening methods. And if you talk to a doctor, my doctor at MIT— I've mentioned this before to many of you— but he says they almost don't see fatal colon cancer at MIT because the screening is so effective that— and this is a population of people that get screened and has excellent medical care, so they don't And finally, so this is in itself amazing. OK? So if you could eliminate, say, 50% to 60% of cancer just by some kind of World Health Organization kind of program, that's incredible. Meanwhile, this amazing science— I mean, imagine living through this from the breaking of the genetic code to where we are today in one lifetime. Yesterday, I went to see my oncologist. You go every few months for a checkup. I said, this man is so excited, he could barely deal with my particular case. All he wants to do is talk oncogenes. He wants to talk about genes. But he said what he sees in the— what he is seeing in clinical trials and in patients when you treat people with these drugs is so extraordinary that he says he just believes that in the next— in this decade, with personalized— with the ability to type individual cancers, he said cancer will be a disease of many, many orphan diseases. And they'll be typed. And then there'll be drugs for each one. And he already has patients that have had previously lethal cancers who have lived for 15 years. Gleevec is the most spectacular one. But there are others that are coming along that are equally able to beat back. And so it really is tremendously exciting. And I think that this new building with the fusion of the sciences the engineers that MIT has is really a brilliant thing. Because when you go and actually get treated, you realize how many of these things have had to come together to make these treatments work. And I'm a person who probably would be dead if it hadn't been for these things. And you see the actual impact of the science that we've all done and the technology that's been done. And you see what's coming. And honestly, you have to be very grateful to be part of this. Occupation. So thank you very much. That's my comments.

Thank you, Nancy. That was a wonderful view of the life of a scientist and why we all want to do it. I'll let you handle the questions.

Okay, thanks, Mary Lou. Lisa? Did any of your other Spence friends or Were there other people you knew there going into science, or were you unique? I think I may have been the first person to major in science in the college and came out of there. I went back this year to see what was going on because I hear from them. And I have my friends that I see. But I went back to— they asked me to go and talk, actually, to teachers of independent schools in New York, schools like Spence. It was a wonderful experience. I went back to Chapin, which is another one like it. And they think they've— well, they've made such huge progress, they kind of think they've solved it. I was slightly shocked by what I found. And people— I was shocked. And I suspect it isn't just what goes on in these fabulous private schools. But if you went and looked at some other schools, you'd be really shocked. What I discovered is science is not treated equally to the humanities in these schools. The teachers themselves said they have to fight constantly with the humanities to get enough time for science to be taught properly because it does take more time and hours. It's improved, but it certainly hasn't gotten where it needs to be. There was a young woman there who had gone to Chapin and been a star student. She went to college. She had the same problem that she found that she wasn't prepared when she got to college. I went to a big public high school in New York and it was marvelous science teaching. And that was true throughout, I think, in many public schools in New York City. So it's kind of interesting that the social factor, the socioeconomic factor, seems to have tilted the private schools one direction. I think they've probably tilted. I think they have tilted, don't you? I don't know. I don't know the data for who, I don't know the data.

But was your public school co-ed? Yeah. It was Bronx High School of Science.

But women went, I mean Maxine Singer went to the same school and a couple of other people. Right. Well, I think, you know, even in our era, I mean, that Bronx High School of Science, Stuyvesant, there were a couple of these schools, one on Long Island that Terry Grodzicka went to But yeah, they did have great science. But there weren't many. Hi, Chip. Hi.

If you were a kid starting out, what would you work on now?

Oh, by the way, speaking of behavior, I'm reminded when I think about my views of how genetics of behavior was going to play out. I remember going to a seminar here— no, it was a symposium. And Seymour Benzer was there. And so Seymour and I had gone there because we were interested in studying consciousness. And this symposium was about receptor molecules. And Benzer said, well, your chance of studying consciousness by studying receptors is about the same as understanding the cell by studying the atom. And I think that— so that whole idea was wrong. And I think actually the work that that Mary Lou and I and Lisa and others did on women in science was probably much better science about behavior than I could have ever learned by doing the genetics of some kind of whatever, particularly in zebrafish. Anyway, so I got to work on behavior by a totally different route. But if I was going to do something today, you know what I'd do? Well, there's different things. If you're young or you're old. Were you asking for a young person or an old person? You said young person. Oh, try them both. Try them both. OK. For an old person, I would like to see— this cancer thing solved. It needs a different level of solution right now. And this is what this— it needs a whole new kind of medicine almost. And a whole new kind of fusion of kinds of people and research and ways of doing things. I think that's really interesting. And how could you do that on a worldwide basis even? I mean, it's just a really interesting problem. It's every kind of problem— money and access. All kinds of stuff. As a young person, well, you know, the brain, I have to say, and I want to talk to you afterwards. I have a question for you about the brain. Did you go to— yeah, I was— I think the brain— I'd given up on the brain, but I've decided to give them another chance. I think that— I think, wow, I think you're finally really making amazing progress. We're going to understand the brain. Then what are we going to do? Wow. Chris?

Thinking back on how the whole Women in Science Committee sort of process unfolded and the dean taking rapid action, do you think that— I mean, the reason it was on the front page of the New York Times is because other universities probably had similar inklings. That there was discrimination, systematic discrimination, but didn't really do anything about it. So why MIT? Is it because of you, because of Bob Birgeneau, in other words, particular personalities that happened to be here? Or is it because of something about the way MIT is organized? Sort of maybe a more objective institution and maybe more able to deal with kind of objective data in a way. I don't know, I'm just curious to know.

It's a great question. And I think, I mean, there was certainly an extraordinary set of circumstances came together at MIT. One was the solid, the bond between the women that formed. I mean, we were a group. And that was a critically important thing. But I really believe it's a reflection of a great institution. I really do. I think that MIT has had remarkable leadership, actually. And I think what you see is— I think institutions were very afraid of this issue because they were afraid of lawsuits. And I don't really know what went on behind the scenes, obviously. But I think that Bob Brejnow and Chuck Vest were just two really outstanding administrators. I think that they understood this issue in the sense of its importance to the future of universities. And I think they thought they'd understood it. And somebody came along and presented them with evidence that none of us had understood it. And they got it, so to speak. And they believed in it. And I think they just did the right thing. I think they took a chance and decided to do the right thing. I do think other universities certainly had the opportunity. Everybody was just— they suppressed it. They really did. So I think the other part of it honestly was Lottie Bailyn because she was the chair of the faculty and she knew about the things that women had done and she was talking to the president. She understood it at a different level. She understood it as a a social science person who has also worked with companies on issues of women and where diversity is essential. So she knew a lot about this issue. And she was presenting it to the president and the deans. And I think that had a huge impact as well. And but so many things came together. There's another thing about the women in science. I mean, working with those people was absolutely a high point in my life. I think they're amazing people. I've never met such a group of people. You couldn't meet a more amazing group of people. And I think there had been a kind of tradition at MIT of women supporting other women. And when I first went around, I was asked— I've been asked— I lost track. After 700, I stopped counting how many talks I've been asked to give on this topic. I mean, hundreds and hundreds and hundreds. But you'd go and people would say, but how did you get the women to work together? I said, "What do you mean?" I mean, you know, they supported each other. So I think it was many things, but in the end, if President Vest hadn't supported it, it wouldn't have happened. So I guess— and he has always said, after I joined the administration, people said one reason that they, of course, agreed to it wasn't just the data in the report, it was the quality of those women. And if you look at their accomplishments today as a group of people. They are extraordinary. I mean, so they knew that people like that serious just don't complain. They just don't sit around complaining. They have better things to do. So they were just good people. But that is what a great institution is, right? It's doing the right thing. And I sort of have a— I sat on Academic Council. I got to see how presidents— I knew I could never do that job. I wouldn't sleep at night. They have to make the right decisions. It's a really hard job. I think that's what distinguishes a very great institution is they get people in those jobs who can do that. They're not always right, but here they've been right a lot of the time.

[Speaker:JOSHUA_ELKINGTON] You described several instances in your career when very accomplished individuals told you, "This can't be done. It's a very difficult problem.

Don't try to pursue it." How do you know when to take that advice to heart and when to— I love that question. When I was going to go into cancer, I was so driven to do it. And I thought, what do I have to lose? The time is short. When I went into the zebrafish, I remember going to see Maury Fox. And I asked him exactly the same question you just asked me. Because I was less sure. And there was much more to lose, really. And it wasn't clear you'd ever get funded or the project could ever conceivably work. It was, again, to know that you can develop methanol. You never know. And he made a great comment, which I love. It doesn't help answer the question in a way. But he said, well, the people who made the right decision are here at MIT. So maybe the answer is, you know, you take risk. And if it works, good. And if it doesn't work, you go somewhere else and try again. Maybe. I mean, I think I learned this from watching colleagues at MIT. I think taking risk is essential in science. And so how much risk? And so being able to fail and being, again, in an institution that allows you to fail is a big part of success, probably. It probably also accounts for some of the great success of people we see here at MIT. We like to think we're all geniuses. But honestly, you bring smart people to MIT and they tend to do well. Because there's depth of support and resources and people. So you have more leeway to fail, perhaps. But I think it's the critical question, really, isn't it? How do you know when your judgment's right? And somebody taught— when I was young, people used to say, because if you do anything really important, nobody will ever think it was the right thing to do. Of course, by definition, if it's really ahead of its Next time people won't recognize it. They'll always tell you it's wrong. So you've got to have that inner confidence and belief driving you along. But when do you know not to go down that road? When I saw those fish, the idea that you could figure out what they were thinking about just wasn't going to happen. Yeah, that's a good question. Nancy, you mentioned the competition within the lambda community. When you were working on repressors. Now there was work going on in lac repressors at the same time. So was there much communication between the— Do you not know this story? Not really? Oh, that was an extraordinary story. And I thought, yeah. Well, there wasn't just one person at Harvard trying to isolate the repressor. There were two. Molly Gilbert was trying to isolate, with Benno Muller-Hill, the lac repressor while Mark Tashney was isolating the lambda repressor. Presser. Mark revered Wally, really. I mean, he just thought Wally was a total genius. They talked all the time. Mark accepted that Wally was going to beat him to the first step. Then Mark kind of beat Wally on the second step and things got a little dicey. Jim said, I'm never going to allow two people to work on the same thing at the same building again ever. But who invented competition in science? And this is the sort of question I still have. I mean, the world according to Jim, I bought it hook, line, and sinker. I couldn't imagine being part of it and being in such a competitive thing really at the time when I was young. But on the other hand, it was so exciting. And I just thought, well, that's the way science is. It's a very competitive race. But is it always like that? Some people say that's what moves science forward. I'm just wondering whether that is really the case. Right. What's the answer? What's the answer? You know, I don't know the answer. I think in a company, if you want to really move— and that's why I think this cans of problems. So if you want to really move this problem forward, you know, it's collaboration that's going to move it forward fast. So I think there are times when you need independent people doing their thing and allowed to go off and do that really hard thing that nobody thinks makes sense. You know, like Gleevec, the whole development of Gleevec is in a way such a story, don't you think? I don't know. And then you need times when you know what to do and now you've got to all get together and just do it because you really know what to do. So what's the point of competing, it doesn't make sense. But I think Mark and Wally, they benefited from each other. And, well, yeah, Wally was at Mark's 70th birthday party. They're still friends. As was Jim, as was Matt Mithelson.

I happened to sit in on a bikini keynote panel for the Brains, Minds, and Machines symposium. And one of the keynote speakers, Dr. Sidney Brenner, he mentioned that a question that he was intrigued with was how did genes evolve if only the description of the instructions can change and not behavior directly. So I was wondering what might be your comments on the latest research regarding that area.

I'm not sure I follow what you mean. And I didn't hear his talk. I heard it was terrific, but I didn't hear it myself. And I'm not sure what he meant. Was he—

he was talking about evolution of genes in terms of the way they only are allowed to encode instructions, and they themselves, the behavior mechanism of them, of the genes, do not change directly.

Oh.

These are genes that control behavior he's talking about?

Um, I think so.

That's a good question. That's a complicated question. I think that's a— maybe we should talk one-on-one about that because people, it's now overtime. But thank you all very much for your time.