Interview with Elizabeth Cavert and James Miller

James A. and Elizabeth Cavert Miller (#316) Transcript

LS: This is an interview with Elizabeth C. and James A. Miller of the University of Wisconsin McArdle Lab in the Department of Oncology. The interview is being done for the University of Wisconsin Archives Oral History Project. The date is November 11, 1985. We are talking in their office in McArdle Lab. I am Laura Smail. Which of you--do you have a pattern as to who begins?

JM: No. It makes no difference--I'll start. Do you want to go back to my family and my parents and so forth?

LS: I'm mainly interested in what influenced you as a child in terms of how your interests developed--so insofar as it's relevant, yes.

JM: Yes, well I was born in 1915--the fifth boy of a family of six boys, and my parents had only eighth grade education. My father eventually worked his way up 00:01:00to be general circulation manager of a Pittsburgh newspaper--and I think they were married in 1900 or 1899. As I said I was the fifth boy and when--I became interested I guess in science in 1920. I seemed to be the only boy of the six that really picked up on science.

LS: Do you know why?

JM: I'm not real sure, quite frankly, because this was when I was still in grade school you see. But I distinctly remember such happenings. I remember reading about the Scopes trial in the '20s, around 1925 or so, and I knew about 00:02:00evolution, and I even knew of the--later in the '20s--the early experiments on rockets by Goddard.

JM: I guess the one problem that affected me very greatly in my childhood was the occurrence of four deaths in my family in a period of not quite six years during the 1920s. That was very rough on me as well as the rest of my family. But in 1924 my oldest brother, who was twenty-four years old, died of lobar pneumonia. They couldn't control it in those days and he died very quickly. And 00:03:00then about two years later mother's sister, Aunt Rose, who had taken a special interest in raising me for some reason, also died of lobar pneumonia--they couldn't control it in those days and he died very quickly. And then about a year later we had another very traumatic death in my family. The youngest boy, who was three years younger than me, was killed behind our house. In Pittsburgh they have alleys and cars usually go one direction. He was playing in an excavation for a garage at the alley level and just ran out in the path of a car coming down--never saw it--and it just crushed his chest. The driver had to pick 00:04:00up the body--stopped quickly and picked the boy up. It wasn't his fault at all--neither of them saw the other, that's all, and carried it--I was some distance away--and the driver carried the boy--Harry was his name--up to the back of our house, and my mother was in the kitchen. She saw it all and she literally climbed out the window in her effort to get to the boy. Then a year later--two years later--my mother died of a cerebral hemorrhage. She was only 49 years old. So we had these four deaths in six years.

My father and mother were of different religions. They were married around 1900, 00:05:00as I said. He was a Methodist from a Protestant family and my mother was Catholic. They had both been born and raised in Pittsburgh and got married, much over the objection of father's mother. In fact, when the marriage took place she then stopped all contact with our family. So I never even saw my grandmother on that side and even grandfather only very rarely. There was just no contact between the two families. When they were married by a Catholic priest the priest insisted that any children be raised as Catholics, but my father insisted in return that they go to a public school. So I went to public school and have never regretted that. Now along with this, when you're a Catholic of that type 00:06:00you are forced to go to catechism to learn something about the religion and that always took place on Saturday afternoons--when we didn't want to go anywhere but to play and so forth. So that was a difficult subject. As I say I got into religion very early. These four deaths affected me greatly because at each of the first couple of deaths the pronouncement of the priest was that this was God's will and He needed this person in Heaven and so forth. I began to doubt that after the second death, and by the time of the very traumatic death of my mother I disbelieved it completely. Then I actually--at the age of 14--refused to have anything more to do with the Catholic Church, and I regarded the priest 00:07:00who was giving me these catechism lessons as ignorant. I have never gone back to any church, and literally I'm an agnostic--that's all. I don't think anyone knows the final answers or how to get through to them--I have just disregarded that. So I turned to science as the way of reaching at least truth about some matters. That greatly reinforced me inside.

And then in high school I happened to have a very good chemistry teacher--Dickerhoff was his name. He sort of took a liking to me and I had the free run of the chemistry laboratory. Already at home I had had a small workshop 00:08:00before going to high school--chemistry sets and the like. I wanted to become a chemist. The trouble was that I graduated in 1933 in the depths of the Depression from high school; our family was relatively poor and I--there was just no money to send anybody to college and that had never occurred before in our family anyhow. My first three brothers never finished high school. The custom in those years--in the 1910s, 1915s--was maybe you got a year or two of high school and then you went out and got a job and that's what they did so they never finished high school, but my brother Chuck, the next older before me, 00:09:00number four, he did finish high school,

LS: Did you want to go to college?

JM: Yes, very much so because I had heard a lot about graduate education--I mean college education--in chemistry when I was with this chemistry teacher in high school. Of course he had gone to college and gotten a bachelor's degree and so I wanted to do that too, but there was no money to do that.

JM: So from '33 to '35 I looked for work, but it was very hard to find. But through the intervention of the father of one of my friends--boyfriend--my 00:10:00age--he happened to be the manager of the welding division in one of the Bethlehem Steel mills down the river in Pittsburgh and he got me a job at the factory--welding. But that job lasted only a total of six months. When the job that we were doing was finished, they let everybody go. So I just got a small amount of work, but it helped quite a bit. And I started to go to night school at the University of Pittsburgh and got my mathematics off in those two years, so I did that. But then I was really rescued by one of the Roosevelt administration creatures--NYA--National Youth Administration. What that did was to pay me 35 cents an hour to work in a chemistry laboratory--filling reagent 00:11:00bottles, so I got to know the professor of chemistry that taught freshman chemistry. With the help of this WPA job and some money I borrowed against an insurance policy my parents had much earlier taken out on me--a life insurance policy--I was able to start day school at the University of Pittsburgh in 1935.

The chemistry professor that I worked for--this--my freshman year happened to share an office with another professor and this other professor was Charles King, a biochemist in the chemistry department. He was already famous because he 00:12:00was one of the persons that a few years earlier had crystallized the first vitamin--vitamin C--the first crystalline vitamin in the pure form. He had a lot of animals--relatively speaking--under all kinds of tests and he had these housed in an old World War I barracks behind the chemistry building. It just happened that he needed an animal room boy or man, so he hired me and I worked for him for the next three years till I finished the B.S. degree. I was taking the honors--we call it an honors course today--in chemistry; we called it a chemistry special course. I took only chemistry, math and physics--a little English and German--a couple years' of German. So I worked for him, and this was 00:13:00in the year before National Institutes of Health and the graduate work that Dr. King was--or am I talking too long?

LS: No, no.

JM: The work that Dr. King was carrying out with graduate students primarily was simply supported by what money the chemistry department could spare--this was a private university then--the University of Pittsburgh--and that was very little, quite frankly. But while I was with him--I think it was the second year I was working for him--he got some of the first money he had ever been able to get for post doctorate work. This came from a foundation that was supported by a 00:14:00department store in Pittsburgh--Boggs and Buhl--and with that money he was able to bring in three post doctorates. One came from Harvard, one came from the University of Louisiana, and then one came from the University of Wisconsin.

LS: Oh that's where the link is.

JM: This is where the link is and this fellow--his name is Max Schultze, Dr. Max Schultze. He's still living and retired in Albuquerque but he had just gotten his Ph.D. under Hart and Elvehjem in biochemistry; this was his first position with his Ph.D. And his story is much better--much more interesting than mine--because he was born in Switzerland in a farm family and at the age of 00:15:00eighteen he realized, because of their class distinctions there, he was never going to be able to get into a university. He was bright, so he emigrated to the United States by himself at the age of eighteen, and he ended up on a farm in northern Illinois. The farmer he worked for realized that this was a bright young college fellow and shouldn't be working on a farm. He ought to go up to Madison and go the University. So that's what he did--he came up here and worked his way through undergraduate courses and then finally became a graduate student under Hart and Elvehjem in biochemistry and got his degree.

LS: And where did he end up teaching?

JM: Well, he--after he was at the University of Pittsburgh for several years as a post doctorate--then he went onto the staff there in biochemistry; then soon 00:16:00moved to the University of Minnesota. He spent most of his graduate--his professional career at the University of Minnesota--became a professor of biochemistry and retired last--

LS: He was rather important in your life, wasn't he?

JM: Oh he was absolutely important because after I had worked--see I became his diener and servant until I graduated from Pittsburgh in 1939 in chemistry special. I wanted to go onto graduate work because by working with him I realized that you couldn't stop at the B.S. degree if you were going to get into real research. Fellowships weren't very available in those days but he finally 00:17:00got to me that Wisconsin had WARF scholarships available if you could qualify.

Well, I have to digress a bit. During high school, or grade school and high school, I liked science and I did very well in science but I did only so-so in all the other courses. I liked some aspects of English but many of them I didn't care for so I only got average grades. When I ended up in high school in '33 I had good grades in science but C's and D's in the other courses, and I realized how foolish I had been. There weren't many scholarships, but there were some, and I never qualified for anything, so I made up my mind that if I ever got to college I would do my best to get the very best grades. That's exactly what I 00:18:00did at the University of Pittsburgh; I became the top student in the course right from the beginning and somehow it carried all the way through, so when it came time to apply for graduate assistantships, I came here in '39 as a WARF scholar--.

LS: Let's find out what the equivalent is in Minnesota.

EM Well let me first add one thing. I think that though Jim's brothers were--none of them able to go to college and most of them didn't finish high school--they were very supportive of Jim's college work and actually helped him to go through--

JM: Our family fell apart after my mother's death. My father--a year or two had a so-called nervous breakdown and then he lost his job in the Depression--so 00:19:00that was a very devastating thing. But the four boys stuck together, and they had a tough time too. Chris was quite influential--my oldest brother--and he is an electrician--never finished high school as I mentioned--but he kept on trying to improve himself in electric information and that sort of thing. He certainly helped a lot in making me aware of some things while we were still living together. And then during my four years at the University of Pittsburgh I lived with these brothers, and none of them were married at that time. We all stayed 00:20:00together and some of them--Chuck, the next oldest brother--he actually didn't get a job in the Depression. He Painted houses occasionally and that sort of thing--anything to stay together, so I owe them an awful lot for helping me go to the University of Pittsburgh.

LS: Are they still living?

JM: Only one is living now, the other three--two of them died within the last decade.

EM: Yes, well I came from a more fortunate background in terms of opportunities. My father had a bachelor's degree from Union College and then a second Bachelor 00:21:00of Science from Cornell University at Ithaca, New York. And then he went from that to the University of Minnesota as an Ag Extension person. While he was doing that work he obtained his master's degree from the University of Minnesota in Ag Economics. And then in 1927 and '28 the whole family went back to Ithaca, New York, while he finished up his Ph.D. And he was an instructor and assistant professor at the University of Minnesota Department of Agricultural Economics and also in the Extension division. Then after he finished his Ph.D. he went back to the University of Minnesota, but within a few years was offered the position of Research Director for the 7th District of the Farm Credit 00:22:00Administration in St. Paul. And that was where he went and he stayed there until he retired in 1957. I came from a background of people who knew what research was.

LS: What about your mother?

EM: My mother, interestingly, had a bachelor's degree from Vassar College and then she went and took two years more at Columbia Teachers College and I presume, but I'm not sure, got a second bachelor's degree probably. And I am under the impression that this was a degree for teaching home economics, although I don't really know whether she was certified to teach or whether it was some other specialty. She never used that degree professionally but she certainly maintained active community interest which was based on that knowledge. Both of my parents were very active in community affairs. We always had many books and magazines in the house. In fact, one of my father's uncles 00:23:00had actually graduated from Princeton University many years before, and we used to visit there in the summers. They had a book--room set aside as a library; he was very literate in several languages. And we were brought up--my sister and my brother and me--all with the idea that of course we would be good students and of course we would go to college. It was just assumed--rather different from the background that Jim had.

EM: So my science education started in high school. We went to--lived in a small town of Anoka which was outside of Minneapolis-St. Paul, and it had a high school with classes of about 100 students per year. And I had a chemistry and physics teacher there by the name of James Waters who was--as I look back at 00:24:00it--must have been very young. He was doing graduate work at the University of Minnesota at the same time and later went on to become chairman of analytical chemistry at Ohio State University. He encouraged science interests--obviously was one who was motivated himself, and he ran a science club and, for people that were interested, he always had something extra you could do.

LS: I had two--we're about the same age--and I had two good science teachers too, I remember. But I didn't--I mean what made you decide to be interested in science?

EM: I --

LS: Do you know?

EM: I really don't know. But I was from the beginning always interested in science and always more interested in the chemical sciences than the biological sciences. In fact I had thought that I would become a chemical engineer and I 00:25:00have no feeling really where I got the idea of what a chemical engineer did, or if I really knew what a chemical engineer did. But my mother's college roommate married--the second wife--Dr. Gortner who was chairman of the Department of Biochemistry at the University of Minnesota. And so I am sure my mother went and consulted with him as to what she ought to do with this child who wanted to be a chemical engineer. And he thought a chemical engineer was--as a woman--not a very likely profession. So--but he persuaded me that biochemistry would be much better for a woman--at that stage of the game--and--

LS: This is, this is while you're still in high school.

EM: Well, as I finished high school and was beginning to look at the University of Minnesota. And so, he convinced me that chemistry was fine for a profession, 00:26:00but biochemistry was better than chem engineering. I think he was right, actually.

LS: Well what interested you about chemistry, can you remember?

EM: Well I was interested in how things went together, you know, the reactions that occurred--

JM: Did you have a chemistry set, too?

EM: Oh yes I had a chemistry set, too--and I think my mother was a little less grateful to us than Jim's mother, because he had a lab set up and I was always kind of encouraged to take it far back to the garage where, if something happened, it wouldn't be too much.

LS: Well, did you have to ask for it specially or--?

EM: I don't recall. I suspect I asked for it. But as a family friend, Dr. Gortner was the one I can remember. They used to visit us occasionally and I am sure he encouraged me some.

LS: And you did think of having a career?

EM: Well, at least as far as--yes I think I did. I don't really know that I had 00:27:00a really good solid knowledge of what one did as a professional chemist, you know, other than doing research--that was my interest. You see my father was on the University of Minnesota campus much of that time and we were--many of the family friends were from the faculty--so this was kind of a common thing. Anoka was close to the University of Minnesota so that there were many people around there who had gone to Minnesota. So anyway, after I graduated from high school, and as I said we were always encouraged that we'd better be doing as well as we could--I was the high school valedictorian--and so I went to the University of Minnesota.

LS: Did you consider going elsewhere, since your mother went to Vassar?

EM: No--well, I think she would have liked to see us go to Vassar, but as Jim 00:28:00says this was all during the Depression years and the University of Minnesota was close, and cheap, and good. And that was good enough reason for going there. And I had a sister who was already in college and a brother two years behind. So I think this was partly financial but also that they worked on the theory that the University of Minnesota was very good and you didn't have to--

LS: Did you have to work during college?

EM: No, I never worked during college. There weren't many opportunities for work at that time. Though it was Depression years, my father--and the University of Minnesota during that period actually had a third cut for all faculty. They did that rather than let the faculty go; they cut everybody by a third. And so though his salary didn't look high, I think he used to feel that he was one of the best paid people in the town that we lived in. He never felt that we ought 00:29:00to be competing for what jobs there were with the people who really needed them. And he was very generous to the family.

LS: I am going to turn the tape.

EM: So I followed Dr. Gortner's advice and enrolled at the University of Minnesota in 1937 in the Department of Biochemistry which is on the Agricultural campus, as it is here. I was one of five undergraduates in that program and it was largely a chemistry course. We took our general chemistry and organic and physical with the chemistry majors on the main campus, and at that time, interestingly, there was one woman on the faculty of the Department of Biochemistry whose name I can't remember. I had as an advisor, Dr. William 00:30:00Sandstrom, who was very good at devoting time to his students and trying to help them when he could. I was the only woman I know of on the Agricultural campus who wasn't in home economics. You see that was the campus of forestry, agriculture, and home economics, so all my friends essentially were home economists. And I did well. I got the Caleb Dorr scholarship and medal each year for the top woman student on the agricultural campus which then--I think each group--each class was about 500 students.

LS: Did you settle into any particular area at that time, or don't you in college?

EM: Well, there was a pretty fixed curriculum. We took a lot of chemistry, and 00:31:00then there was a series of courses in biochemistry that were taken by graduate students primarily, but whoever was also majoring as an undergraduate took most of those courses. So by the time I finished I had taken most of the graduate courses there were in that department except for the ones in cereal chemistry which were for specialists in that area.

LS: Have you ever compared your undergraduate science work?

EM: Well they were quite different, actually.

JM: They were quite different. As I mentioned, mine was primarily chemistry but some of the courses were industrial chemistry in Pittsburgh. They were iron and steel analysis--

LS: Oh, I see.

JM: Coal analysis, gas analysis, so I took all those courses. And then the final 00:32:00year I took a course in biochemistry. That was one of the early courses in biochemistry in those years. And King knew Elvehjem very well, so I heard about Elvehjem very early in my courses.

EM: I took the biochemistry courses and would have taken a course much more similar to his had I stuck to my idea of being a chem engineer. And in fact there was one woman in chem engineering, as I found out when I got there. I kind of thought maybe she had the right idea of sticking to her guns. But I am glad that--

LS: There was one here too, you know, Emily Hahn was here.

JM: Well I, of course, working for Dr. Schultze and Dr. King, I learned a lot about chemistry as an undergraduate, you see. I was taking care of hundreds of rats and mice and so I learned some practical things about animals and biology.

EM: By the time I had gotten started in biochemistry, I realized that really most of the people I knew in the department were graduate students. In fact I did a special topic--research problem my senior year, when I was in the graduate laboratory where these people were doing their master's and Ph.D. work so--and having my father with a Ph.D. I realized that if one was going to do anything more than be rather rudimentary in biochemistry, one had to have a graduate degree. So I began to think about doing graduate work. I went to my advisor, Dr. Sandstrom, and I went to Dr. Gortner, and they both agreed that this was what one should do. My parents certainly fully supported it, and so with Dr. 00:34:00Gortner's advice I applied to six places for graduate fellowships. And of those six I came out with three. One was a fellowship to go to Columbia and my mother, though she had been there for two years, or maybe because she'd been there for two years didn't really want me to go there. I think she was--felt it was too far from home, too large a city, and maybe too impersonal a place. And then I was offered a quarter time teaching assistantship at the University of Iowa, but like Jim I was offered a WARF fellowship here.

And there was only one problem with that fellowship--because I was a woman. Biochemistry was very reluctant to take a woman with a major in biochemistry, unless she also had a double major in home economics because they were really 00:35:00quite convinced that they couldn't place them when they finished. So I got a letter which offered me the fellowship and suggested this arrangement--personally from Dean Fred. So my mother drove me down and we had a meeting with Dean Fred and Dean Zuill from home economics and with Catherine Personius who was a foods major. They worked out an arrangement that I would take a double major--but primarily through home economics--and that they would find somebody in biochemistry who had a sufficiently close interest to help with that aspect of it.

LS: Did you mind?

EM: Well, I wasn't too enthusiastic in some ways, because I'd always been 00:36:00encouraged that home economics was the right field for a woman--my mother was a home economist, my sister was a home economist--and my father thoroughly thought that this was the thing. He always said that it was a good field where you could be productive and you could always use it if you got married. Very practical point of view. And I didn't feel I knew any home economics as a background to go into the field. But with some persuasion and the recognition that it really was a very good scholarship, much better than the others, I decided to give it a try. So I came down here in the fall of '41 and Catherine Personius was a remarkably good advisor. She went back to Ithaca (Cornell University) not too long after I finished my Ph.D. She was very understanding and tried very hard to give me a problem that would be related. So what we came up with was a problem 00:37:00on qualities of bread in terms of their biochemistry and so--and Marv Johnson was set up as my biochemistry professor. So about once a week or every second week I would go down to biochemistry to visit Marv Johnson. This was always the toughest time I had, because he always had a group of students around the lab. It was a big lab, and they were very curious about what this woman was doing with her bread.

LS: Nicely curious?

EM: Nicely curious, but they thought it was very funny. One of the things we were studying was tensile strength of bread so the question was how to test the strength at which it broke. Marv Johnson was an innovator and a very smart one, 00:38:00as you probably know, so he would dash out in the lab to look for this piece of equipment and that piece of equipment. So that was the way I started. I might just go onto say that I, of course, took biochemistry courses as well as home economics courses. So second semester I took the vitamins and metabolism course with Carl Baumann who taught it many times, and it just happened that Jim was teaching the blood and urine lab. So obviously we got acquainted as I took the lab. By that time the war had started and students were becoming less available in biochemistry and it was becoming apparent that very soon there would be relatively few, so he suggested to me that I talk to Carl Baumann, who was his 00:39:00major professor, and see if I couldn't persuade him to take me down there and on a primarily biochemical problem. I would keep the double major but from the other side. And so I suspect Jim did a lot of talking too to Carl Baumann but--

LS: Was he reluctant?

EM: I don't know how reluctant he was. He agreed, assuming I kept the double major. And so I moved down to biochemistry at the end of the first year and essentially became a biochemistry graduate student, although as I say I kept the double major and home economics affiliation through my Ph.D.

JM: When I came to the Department of Biochemistry in 1939 in the fall to start graduate work, the department had not assigned me to any particular major 00:40:00professor. I talked with Dr. Paul Phillips who sort of had that as one of his chores--i.e., to seek out major professors for new graduate students. He pointed out to me that the only ones available at that time were in Professor Steenbock's group and Professor Steenbock, at that time, had in his group Carl Baumann as an assistant professor, Dr. Carl Baumann. He retired just a few years ago.

LS: Yes, I've interviewed him.

JM: Right. And Carl had just recently returned from a postdoctoral fellowship in 00:41:00Germany and was getting started on various aspects of his research. In particular, he was helping Dr. Rusch, the first founder and first director of McArdle at the time, let's see that was 1939. Dr. Rusch had started doing cancer research several years earlier after he had gotten his M.D. at Wisconsin here, and after a year or two he realized he needed some biochemical help in what he was trying to do. He sought out help over in biochemistry and found that Carl Baumann had recently come back from Europe and was available to help him, particularly in aspects of diet. Carl Baumann was in his professional career 00:42:00essentially a biochemical nutritionist in many ways, And now that aspect of biochemistry is separated from biochemistry itself in the Department of Nutrition. And so I became a graduate student under Carl Baumann, and he was doing quite a bit of work at that time with Harold Rusch on aspects of the production of cancer by the then newly discovered chemical carcinogen. It was only in about the early 1930's that pure chemical carcinogens became available in crystalline pure form, and Carl and Harold were using these to produce tumors in mice and rats. Carl, in particular, and also Dr. Rusch were interested in how 00:43:00aspects of the diet affected the activity of these chemical carcinogens. So that's what I started on right away in the fall of '39.

LS: You said that that was the only place where there was space for graduate students?

JM: Yes, that was the--

LS: You mean Link's lab was full and--

JM: Apparently no one else seemed to want any new graduate students, but it was a possible--there was a possibility that I would work with Dr. Steenbock himself, but I'm glad that didn't turn out to be, frankly.

LS: You didn't know at the time--

JM: I had heard some things about him but after I'd been there a while I was very glad I wasn't working for him. And Carl's a very nice guy and--

LS: What about Elvehjem--you'd been hearing about him--

JM: Yes, I heard about him, but there was no space there either, to my knowledge. Paul pretty much pushed me toward Carl--and I was young and naive and I was interested in chemical carcinogens to some degree, because I'd heard about them in the senior course in biochemistry. We used the textbook that was written by Dr. Gortner, who was her advisor. He wrote a very good general biochemistry text, and Dr. King used that text in his course in biochemistry in my senior year at Pittsburgh. There was a couple of pages on the newly discovered chemical carcinogens. I remembered those, because I had the book and, so when I came 00:45:00here, here were two people, Carl and Harold, working on these compounds. During my undergraduate years I had favored of all the aspects of chemistry, organic chemistry. I became quite interested in organic chemistry--not as such but in relation to biochemistry because all biochemical compounds, essentially almost all, are organic compounds. Carl started me right away on the production of liver tumors in rats fed certain carcinogenic dyes, which had been discovered a few years earlier in Japan as being active carcinogenic compounds. We right away started to alter the diets--the levels of different components, fat level, protein level, vitamin level, and so forth. And right away we began to find some 00:46:00interesting aspects--that is, certain diets permitted much greater or much lower levels of tumor induction than other diets. It seemed like an interesting thing to study.

LS: How did you--in retrospect, what kind of a teacher was he?

JM: Well, Carl was a very good teacher. He was a good lecturer and in the laboratory he pretty much let you alone to find your own way, which is something we carried over into our own later career, but--

LS: You approve of that then?

JM: Oh yes. Sometimes it's better to make a mistake first and find out what really went wrong rather than just following the cookbook and having everything come out just like it should. He followed the path of having a frequent 00:47:00consultation with you on your research. You'd go in and talk to him and show him your results every week or even every few days, depending on what you were doing. But he let you work your things out yourself. He didn't stand behind you and. Do this, do that, and that sort of thing.

LS: Did any of the others do that?

JM: I think that was a common thing in biochemistry from what I could tell.

LS: Which?

JM: Other professors used that same--

LS: Of letting people on their own?

JM: Yes. Now Carl, as other professors did, had some more senior graduate students than I was at that time. Herb Jacobi was getting very close to his Ph.D. under Carl, so I learned from Herb Jacobi about how to do this or how to do that and so that--that's a very nice way to teach. In fact I think it's 00:48:00really the only effective way to do.

LS: Was it at all daunting going to graduate school or was it just a completely smooth transition?

JM: Well, no, it wasn't completely smooth. I recall feeling sort of out of sorts that whole semester. I didn't feel at home like I had at the University of Pittsburgh where I was not only an undergraduate student, but I was a helper in the lab so I knew all sorts of things--i.e., where I could get this or that. So it took me a semester to really start to fit into Carl's group. But it went very well and, of course, I had courses to take, so I was really only half-time in the laboratory.

LS: It would be nice if you could talk together about this or are your 00:49:00experiences too different?

JM: No, not too different.

LS: I'm wondering about courses you took, for instance with Elvejhem, with Steenbock--

JM: Well, Carl was actually giving a course, as Betty said, on vitamins and I eventually became his TA. In fact, at the end of the first year they decided not to keep me on the WARF fellowship but appoint me as a TA, a teaching assistantship, and as a result my salary went up from $600 to a $1000.

LS: Oh really?

JM: Just like--

LS: So that was--

JM: That was quite an advantage. So I became the teaching assistant that took 00:50:00care of the laboratory in the main biochemistry course that was taught by all of the top professors--Elvehjem, Steenbock, and so forth. That was the first semester. Then the second semester I TA'd with Carl for the blood and urine analysis course and there was a vitamin course also.

LS: They did this because you--you stood out or--?

JM: Well I don't know, I must have to some degree. I don't know quite why they needed one. I guess Carl thought I could do it, and I enjoyed it.

EM: Well I--Jim taught that for three years--had that TA assistant-ship--and 00:51:00then after he left I was--had that TAship for another two years. And my understanding when I was appointed TA was that they were supposed to have appointed somebody that had been associated with Steenbock. But they didn't have anybody in Steenbock's group--by that time his group was getting quite small. And so they went to Carl Baumann. He had started out with Steenbock, but then they sort of went their separate ways, so that might have had something to do with the fact that you were selected.

LS: Steenbock was busy working on his patent at that time.

EM: Yes I think that was his--we used to be interested to see him read the Wall Street Journal the first thing in the morning, because at that time the Wall Street Journal was a little esoteric to most biochemists.

JM: Sometimes we overheard him calling up his broker and ordering stocks. 00:52:00So--that wasn't very common but--

EM: That was while we were--the first two years that Jim was over there and the first summer that I was working with Carl, we were working in the general laboratory which was part of Steenbock's area. That was a laboratory which--in the then new part of the building--as I recall, had eight lab benches for individual students as well as side offices, one of which Harry Steenbock used. Then there were two lab offices one of which was for Quackenbush, who was another assistant professor, and the other one which was Carl Baumann's. By the fall of '42 it was decided that Carl Baumann would be better off if he was separated, and so we moved from that area down to the old station laboratories 00:53:00as the area was called. So then we didn't know anything more about what Steenbock was doing.

LS: Did you have any courses with Steenbock?

JM: Well, he taught part of the general biochemistry course and that's all.

EM: And he had a seminar.

JM: Yes.

LS: Did you take the seminar.

JM: Oh yes.

EM: That was the seminar--at that time--for all of Steenbock's people plus the associated ones with Quackenbush or Baumann.

JM: Yes, that could be intimidating at times because he ran the seminar and usually would start it or end it with kind of a monologue which could be on anything. I recall distinctly one on mother love. He was, as you know, a very poor farm boy and had had a very poor background and upbringing. But he had a very strict mother who taught him the way he should behave. When he then became 00:54:00an adult and so forth, he remembered those virtues and he lectured on some of them.

LS: Oh, I see it was actually a lecture telling you what you should do. It wasn't an essay.

EM: No, it was his opinion on how we should behave. Honor our mothers and fathers, and be sure that we paid attention to what they wanted us to do.

JM: He had very strong feelings on these subjects.

LS: And how did the students take this?

JM: Well, you--

EM: Sort of quietly.

JM: You took it in silence pretty much. He was a rather overbearing person at times and could get quite angry sometimes.

LS: Did it make you impatient?

EM: Probably.

JM: Probably. I just took it as part of it. I mean most of the time we talked science--people gave seminars. But Carl would sit right through all this too, 00:55:00you see. He'd heard this many times before, because he told us it wasn't anything new.

LS: I hadn't heard about any of this at all.

JM: But that was pretty common.

LS: And so there would be other things like this.

JM: Oh yes, sure.

EM: I can't remember the other subjects we used to listen to--

JM: Well, I think there was one on socialism as usual, that sort of thing.

EM: But mostly it was science but you remember these sorts of things--

JM: He would occasionally tell us little stories about other biochemists that he had known through his Ph.D. training--I mean he had been to Germany for his postdoctoral work--and we would hear stories about some of those famous old time chemists.

LS: So that was more interesting--

JM: Oh, yes that was more interesting. But he had his good points. And then as we knew him, he obviously mellowed in later years quite a bit. His to be future wife was of course Evelyn Van Donk, one of his assistants.

EM: And she was still an assistant, see, when we were there.

LS: So you got to know her.

EM: Oh yes.

JM: We got to know her very well very early.

LS: He gave parties occasionally--had they already started doing that?

JM: Yes he did give an occasional party.

EM: I never went to a party.

JM: Well, maybe you didn't.

EM: I was only up in that lab for three months because then we separated. Jim was there too.

JM: I was there earlier. For example I recall once he was going to give everybody a ride in his new motor boat on Lake Mendota here. And he did once. 00:57:00The only time I've been on a motor boat on that lake. But he was beginning to unbend a little I guess. So we learned about things like that.

LS: He was very restrictive of his lab and didn't let other graduate students--

EM: He was very rigid. One of my first experiences in that lab was going up there and, of course, Carl was introducing me and said "Here's your bench." I suspect I'd been assigned to Carl and then assigned to somebody-else, and Jim was somewhere up there. I needed to weigh something out, so Jim showed me the balance and where it was and whatever you needed to know. I was using it and Harry Steenbock came out of his office--"Who are you?" and I told him who I was. "Who told you you could use the balance?" I told him "Jim Miller", and Jim told 00:58:00me that was the wrong answer.

JM: That was the wrong answer.

EM: So I mean he was protective at that time.

JM: Oh yes.

LS: I heard, I forget which person told about needing a book and knowing--somebody saying well "Steenbock would have a copy of it" and going up there to look. He was very angry at him.

JM: Yeah, he could--I guess somehow he never seemed to...

LS: I think you better repeat that statement--you said that your dealings with him were pleasant--

EM: Yeah, dealings with him were generally pleasant and actually some years later I think we got to know him and Evelyn better personally. I recall being at 00:59:00a meeting in Chicago--probably the Federation meetings along probably in the "60s sometime--and having breakfast with him, and he was very charming then.

JM: Oh he could be very charming if he wished to be. No problem there. But when I started in biochemistry, I had already heard, of course, of some of these personalities like Steenbock and others. I soon became acquainted with these people, because when I first when into the building the secretary was trying to find some staff member for me to talk to.

EM: The first one as a graduate student.

JM: The first time I entered the building ever, and she couldn't find anybody until finally apparently Link was available. So she sent me down to a room and I 01:00:00entered and there was Link looking all for the world like a bronzed Greek God. He was clad only in shorts and sandals, and I don't know just what he was doing. But in his characteristic manner he greeted me and wanted to know where I came from and all that sort of thing--and what I was going to do here. But as you may recall, he was a very flamboyant character and he showed it right there.

LS: And what about him as a teacher?

JM: Well, he was a good teacher I think, but he used too many of the same jokes over and over. Because as a TA I kept hearing these things and he would give the same old thing. But the first time you heard them it was refreshing, because he 01:01:00was very different from Harry Steenbock who was rather dry, didn't talk very loud, and didn't have much expression in what he gave. But Karl Paul did.

Of course this was the time at which they had recently discovered dicoumarol. And so he would give illustrated lectures of how they collected the urine from these animals, how you had to wait around for it to come, and then when it did come they ran out of buckets to catch it. And all the problems that they ran into in trying to get enough of the urine of these animals that were fed this spoiled sweet clover and all that sort of thing. But he was an interesting character.

It soon became evident that Steenbock and Link did not like each other very much 01:02:00at all. I have the small distinction of being the only graduate student who witnessed the personal altercation of Link and Steenbock. This happened I think in about the second year I was there; I can't be more certain than that. But Steenbock had a post doctorate by the name of Forest Quackenbush. You may even know the name or have heard it--he got his degree with Link--I'm sorry, with Steenbock--and then went abroad to study in Holland under a famous biochemist there. Then he came back and Steenbock was having him conduct research on lipid fats, and it came time--the time came when Steenbock wanted to have Quackenbush 01:03:00promoted to the position of instructor. In those days you went in as instructor first and then assistant professor. Apparently this had come up in staff meeting, and Link violently opposed it. Now apparently the vote was taken and Quackenbush lost. And the--Link and Steenbock met shortly after this rather acrimonious staff meeting in the hall right outside the men's room. And who should be walking up the steps and coming toward the men's room--there I was. And when I saw them, they had been having some words and Link had Steenbock by 01:04:00the neck shaking him. Harry just stood there, stiff as a rod like he always did, and just sort of daring Link to do his worst. I was so embarrassed. I turned right around and walked away. What else can you do?

LS: Quite a dilemma.

JM: But Steenbock saw me. And later in the day he saw me in the hall and said "Did you see what that crazy man was doing to me?" And I said "Yes." I guess it was that week that he sent a letter to the Regents wanting Link to be suspended for this personal attack.

LS: I thought--that wasn't the time of the vitamin K?

JM: No, that was--

LS: That's later. Because that was pretty bad too I guess.

JM: Well, Link would sit out in front on the steps there--of the old part, on 01:05:00Henry Mall--in the sunlight and as people like myself would go by, he would say he was getting his vitamin D free. He was not going to pay Steenbock for that,

LS: I hadn't heard that.

JM: Yes, and then of course I didn't--wasn't--didn't actually hear it, but it was during that time that Elvehjem and Link had words in the hall. I think Link called Elvehjem two-faced.

LS: Do you know what was the occasion?

JM: I really don't know what the occasion was. But--

LS: But you thought Link was a good teacher.

JM: Yes, I--

EM: Yes, I was going to say I didn't really look at him as a very good lecturer. 01:06:00I mean--

JM: Well, I mean he was refreshing, but didactically I guess he wasn't as good as Steenbock. Steenbock could put you to sleep in no time. But not Link.

LS: You say neither --

EM: Neither one was a very good lecturer. Steenbock was much too dry and pedantic and Link was colorful but not organized.

EM: The much better lecturer at that time was Carl Baumann. He was a very well organized, straightforward lecturer.

JM: He took time to work on his lectures, I mean these other people, I think, came in with their old notes--and tried to speak from them.

EM: Marvin Johnson was at that time--

JM: Marv Johnson was a good lecturer because--

EM: He was also, you see, a relatively young professor at that time.

LS: And Elvehjem, was he--?

JM: Pretty dry.

EM: Elvehjem by that time had far too many things to do. He was head of the department, he had I think upwards of twenty people working with him. So he really didn't have very much time to sit down and prepare. He was reputed, at the time I was a graduate student, to take his manuscripts to church with him on Sunday and correct them as they were waiting for the service to start and so forth. I don't know whether he did or not, I never went--

JM: He had a peculiar habit in lecturing--Elvehjem did--and that is he would never look down or at the students. He looked up above them all the time--all the time. It was an odd thing to sit there and see him stare at the ceiling 01:08:00while he was talking or staring at the back of the room.

LS: So the three famous men of the department are in fact not particularly good teachers.

JM: Not in formal lectures.

LS: Oh, but you found them--did you have lab work with them?

JM: No, we didn't.

LS: No you wouldn't, would you?

JM: But again you see students under each of these people did very good things. They obviously learned something. It's true--when you have, as Elvejhem did, a whole series of people and you have senior graduate students teaching the next younger, the next younger, that's the way he did it.

EM: I think that the pre-eminence of that biochemistry department is reflected by the quality of the research that came out of it and the quality of the 01:09:00graduate students who were--came out of it, at least a large number of very good ones. And that probably didn't depend very much on the lectures that they received.

LS: So, that's really just by the way.

EM: Well you need the background. But you can get the background, if you're really motivated, from a pretty poor teacher as long as there are some good textbooks and some motivation to really learn it.

LS: I see.

EM: That may not be quite the same when you come to some of the areas in history or language. The quality of the lecture may be much more important because that's probably a much more major contact with the students, whereas in the biochemistry department the major contact that counted with the students was that which had to do with the research and--planning the research, doing the research, and writing about it afterwards--talking about it.

JM: I think another aspect in which these professors helped to teach in an important way, was in Journal Club.

LS: Oh, yes.

JM: Because when you had a subject that you were working on you were expected to know what was going on in that field a few years back and immediately. So that generally in these journal clubs when your time came you would give a recent paper and give it in such a way that people could tell just what was done, what was concluded and so forth. There the remarks of people like Elvejhem or Baumann or even Steenbock were important because they would point out flaws in reasoning, flaws in techniques, so you learned that way from them, you see. These formal lectures, as Betty says, are important; you've got to read them to get the necessary background, but--read the books--

LS: Excuse me, these are articles that graduate students have written, or that faculty have written?

JM: Well, they are what we call the primary literature. The papers that describe new things, new approaches. And many times those are written by the graduate students. And there's where you also learn from the professors. We learned a lot from Carl Baumann and that is in how to write your work up. It's not easy sometimes. And some students have an awful lot of trouble putting together a paper.

LS: Carl Bauman would go over what you had done?

JM: Right. He would tell you, as we do ourselves, put down--start a first draft on your work that you've just completed on this aspect--put it together. So you have to learn how to introduce your subject and how to tell--talk about or 01:12:00describe your methods and instruments and so forth. Then present your results and then you have to discuss the results in some way that is meaningful. Sometimes that's not easy. And I think Carl's--Carl is a good writer.

EM: Carl's a good writer. He spent a lot of time and so that this draft that we might have called--he probably called the first draft--but was really probably several times down--would come back--this crossed out, and something else written in, and this circled and put over here and totally changed, but that was his way of teaching. And it's actually a very effective way as we've learned. He spent much more time on the techniques of writing and producing finished manuscripts than did many of the staff. I think he was a much better writer himself. Just to clarify the question about the journal club that Jim was 01:13:00talking about--what happened was that individual graduate students were assigned time to give reports. For their reports they picked up one or two or three papers that had come out recently in some journal such as Journal of Biological Chemistry. They presented them as best they could, and then they were criticized in their presentations by the--

LS: Oh, I see; they were informing the people that were listening about what was--

EM: --the other graduate students and staff.

JM: Yes, right.

LS: --and so they had to master the ideas and be able to explain them. And this was a way of promulgating knowledge.

EM: Yes, yes.

LS: Yes, I see.

JM: And then of course there are national meetings--graduate students would give papers and that is a very important aspect in teaching too at the graduate level. It's not real easy to give work in ten or fifteen minutes that you've been doing for the last year or so and give it in a concise way, make 01:14:00appropriate tables and graphs, and get it all in ten minutes in a reasonably literate way. So there are many aspects of graduate teaching and lectures. In this particular case formal lectures are probably one of the least important. In a sense you learn by doing, by example. And that department, as you know, is a very famous department from way back and--going way back to Babcock and it really has produced over the years.

LS: Was it going into--onto a plateau in the 1940s?

JM: Oh no. The--see when we went in, you could say that work on vitamins was the cutting edge of biochemistry in those days. And this department under Hart and Elvejhem was one of the leading departments in the country in the isolation of new vitamins and their characterization. One of the objects, for example, was to--you could easily put together a crude diet that would suffice for the maintenance and reproduction of an animal, such as the rat. What they were trying to do in those days was to use purified carbohydrates, such as glucose or sucrose, and fat--certain kinds of fats, essential as well as nonessential fat, 01:16:00salt and necessary minerals. Then the so-called accessory food factors, which was the term used by Sir Frederick Gowland, a Britisher, in the very early days, long before 1940. And those accessory food factors turned out to be mainly vitamins, and it was Elvejhem's great accomplishment through his graduate students to discover the anti-pellagra factor, nicotinic acid, as well as several other vitamins. Then he got into the intestinal synthesis of vitamins as a source of vitamin factors. So it was far from plateauing in any intellectual aspects or research aspects, because it was just beginning to be fully 01:17:00appreciated when we started in biochemistry that the role of vitamins in biochemistry was to provide essential parts of certain enzymes in the cells. These enzymes couldn't function without these factors. A vitamin is simply an essential factor for life, for growth and maintenance reproduction, that they cannot--that the animal cannot make itself. It has to get it from some other source--plant source, bacterial source--that's how animals grew--I mean evolved through evolution. And man is a peculiar example and the guinea pig too and some other animals; thus, we can't make vitamin C so we have to get it in the diet. The rat doesn't need vitamin C because it makes its own vitamin C, you see. And 01:18:00so that this area was becoming very important. Carl Baumann was getting into this--the enzymatic composition of cells and how the cells depended on certain vitamins for certain cofactors that made an enzyme work.

EM: It might--you know, I hadn't thought about it though--but it might be that in retrospect you would say that the big burst of activity was in the '30s, and that by the mid '40s the nutritional aspect might have been beginning to plateau.

JM: Well, yes, if you're talking about nutrition, yes.

EM: And I'm trying to think--I'm not just sure, because I haven't thought about it much as to what the major activities of biochemistry were in, say, in the late '40s and in the '50s. It might be that--that it--

JM: Well,--

EM: I know recently the work is more at the cellular and subcellular level, and some of the work is in immunology and so forth. Whether if you looked at the records there's a period in there where it might have plateaued--

LS: I think somebody said that; that's where I got the idea and--

JM: The plateau would have to be only in nutrition because by the time we left the Department of Biochemistry, all the important vitamins had been found. So that phase was over. And now the phase that had been going at the same time but now became paramount was how each vitamin worked--

EM: Not much of that was done over there in biochemistry.

LS: Was that being done in the Enzyme Institute?

JM: Well, yes.

LS: What did you mean?

EM: I meant that that wasn't the activity that the biochemistry department 01:20:00picked up.

JM: Well, no it wasn't a real strong activity--it was done in other places.

EM: Now, who was it that was here in biochemistry and went down to Texas?

JM: Esmond Snell worked on how vitamin B6 and its analogues worked. But Elvehjem was doing something, I believe, on the role of vitamin B1 (thiamine) in carbohydrate metabolism but he didn't get very far. But then there has always been--and this goes way back--work in biochemistry on the role of minerals. It was Hart and Elvehjem really--in their work--that first studied this. It was obviously necessary to have iron to make hemoglobin, but they also discovered 01:21:00that you had to have a little copper. That was absolutely important, and they used very simple but decisive means of doing things. All you had to do to make a rat deficient in copper was to put him on a milk diet, and then take the milk and bubble hydrogen sulfide through it. This would transform all the copper into copper sulfide. When this happens the copper sulfide's not absorbable in the guts of the rat. So it becomes copper-deficient and becomes anemic. And all you have to do is give him a little bit of copper and show that he is no longer--has recovered from anemia. Or you could--if you had a diet that was active in curing 01:22:00anemia produced by hydrogen sulfide-treated milk, you could take that diet and incinerate it--ash it. You got rid of all the organic factors and it turned out the ash was active. That's how they did it and the ash turned out to have copper. The character of the biochemistry department has changed over the years.

LS: It was getting important new equipment I guess in the 1940s.

EM: I don't know, probably equipment became much more of an issue in the mid-1940s on.

JM: When we went over there--during our graduate work we had to often determine 01:23:00many things by their color and solution. And they had very primitive instruments in those days for determining the amount of color. Photoelectric colorimeters were just beginning to come in, and then very fancy spectrophotometers started to come in--and ultracentrifuges. You're right the equipment changed tremendously and it made many things much easier to do than you ever could. Now biochemistry has nuclear magnetic resonance machines, mass spectrometry, x-ray, crystallographic equipment and so forth and equipment you just couldn't conceive of. It was very important. [Recorder off]

LS: I'm just asking about the Enzyme Institute and whether you had anything to 01:24:00do with it, but you say you didn't--

JM: No we didn't.

LS: Even though your work involves enzymes.

JM: True. But there's all kinds of work all over the campus on enzymes--

LS: I see.

JM: And I had nothing to do with forming that institute.

LS: So you have no views on the--

JM: I think one of the reasons for that institute's being was what I said earlier--trying to find out how these vitamins work in making proteins act as enzymes. Not all enzymes have cofactors that are derived from vitamins, but many do. And I think it was apparent to some of the people like Elvehjem and Hart and others, I mean Potter and Elvehjem and others, that graduate students probably couldn't do all of the research necessary in that field and that it probably was 01:25:00time to have a kind of an institute where top people in enzyme chemistry would work. They worked mainly with post doctorates. In other words biochemistry is becoming more sophisticated, and it's just kept that up that all the time.

LS: Is there anything else to be said about the biochemistry department? I suppose you were pretty much divorced from it when you came over here.

JM: That's true, when we came over here we no longer had real intimate contact. We kept up our friendships and so forth with Carl Baumann, but we got into more chemical aspects of chemical carcinogenesis. He was using chemical 01:26:00carcinogenesis tools to produce tumors and studying the effects of diet and other factors on the tumor production by these agents. With my background in organic chemistry and working with these diets producing tumors in my graduate work, I gradually moved in the direction of trying to figure out how these carcinogens worked to produce tumors. Carl was somewhat interested in that, but not vitally so. As I tried to point out earlier, he let me go into that field and knew I was interested in it. So during my graduate work, and then with 01:27:00Betty, we started to work on just how these agents really bring about tumor formation.

LS: But we haven't found out how you got into this. Actually, I'm going to turn the tape off.

EM: How I got into the Cancer field?

LS: Yes, I found out how--

EM: Well, actually, this was a consequence primarily of having gone to start working in Carl Baumann's lab. When I started in Carl's lab, I started on, as every graduate student should, my own problems, which were very distinct from those of anybody else, including Jim in the lab. They were strictly nutritional problems. The first one was related to the--was a fallout of the studies that Jim and Carl and people over in this building--in McArdle--had been doing on 01:28:00diet and tumor formation with certain aminoazo dyes that caused liver tumors and so, and since they'd found that they could have effect which depended on the level of vitamin supplementation, we literally set out to find out how long you could keep an adult rat on a low level of vitamins and keep it alive.

LS: Did you think that up yourself or--?

EM: I'm sure that was given to me as a problem. Beginning problems they're almost always come out of the major professor.

LS: You were quite relieved to get out of the home economics?

EM: Well, I was--I had mixed feelings. I liked Catherine Personius very much. I liked May Reynolds a lot. And I had good contacts with both of them and I could see that they were productive people who were doing important research in their areas. But I didn't quite see how I was going to get into a field that really 01:29:00motivated me. And since my background was more biochemistry, it seemed to be the more logical area to go into. And so, in that sense, I was relieved to have found a home, because I had the feeling during that first year that after I got my master's degree I thought I would have to rethink things and figure out where I could go that would be more likely to yield the type of background that I was looking for. So it was a--I think--a real relief to find myself in a biochemistry department where after I got acquainted I felt more at home. Certainly not that first summer I didn't feel very at home.

LS: But they did accept you, did they?

EM: Oh, yes, and once I was taken in to the department, they had no difficulties with having women there as women. The difficulty was what they were going to do 01:30:00with them after they got finished their degree. But by the time I'd been in biochemistry a year, actually they began to set women on their own, because they realized that with the young men being drafted, if they didn't accept women, they weren't probably going to have many graduates. So by the second year I had company. And having been the only woman in biochemistry at Minnesota, it didn't bother me to be alone. I got along fine with that.

But anyway, after I finished, got started on the master's thesis, then we branched off into similar types of experiments with mice, and one of the early observations we made in that was that--there was the interesting difference in the ability of mice to survive on diets that were low in pyridoxine depending on the protein content of the diet. If you put them on the low protein content, 01:31:00they could get along with very little of this vitamin. If you put them on a high protein diet, they died quite rapidly if the levels of pyridoxine was low, and so, we began to investigate that and following up on some earlier data from the literature we studied the effect of tryptophan metabolism--tryptophan being the amino acid required for animals' growth and contained in most proteins. And that was the main bulk of my graduate work.

But at the same time, since the work was going on on the aminoazo dyes in terms of liver cancer in the laboratory, I began to pick up and did some studies on that with the graduate students. I had one paper with Carl on one particular 01:32:00aspect of that.

LS: Was this something you picked up on your own, or was this--?

EM: I suspect I probably picked it up in part talking to Jim and Carl and partly they said, "Well why don't you do it," you know. Who knows how it came about?

EM: And when Jim finished his PhD in 1943, he had a Finney-Howell fellowship to come to McArdle and at the same time, I stayed in biochemistry and--But he had some--or maybe I'm wrong, maybe you stayed in biochemistry one year.

JM: You know, I was one year in--

EM: You were one year in biochemistry as a postdoc. And during that time they did some analytical studies on the aminoazo dyes. And when at the end of that year it got time for him to move over to McArdle--Dr. Rusch had offered him a position--he hadn't completed those, and so one of the first ways we really got 01:33:00to working together was that, in order to get those studies completed, I would set up analyses during the day and then in the evening, he'd come over and we'd finish them up. And so that was the first collaborative work we did, and you can see it worked out all right, so we kept on doing it.

LS: And how did you feel about the invitation to come to McArdle?

JM: I was delighted, because in those days it was not easy to go somewhere to do postdoctoral work because of the war. I was exempted on the basis of supplying scientific knowledge, I guess. That was the basis of the deferment. But the university--I've forgotten the name of the lawyer that headed it for so many 01:34:00years, a very prominent labor lawyer--

EM: Feinsinger?

JM: Feinsinger.

LS: Okay, I was wondering about that. I didn't know he'd had anything to do with that.

JM: All of us traipsed up to Feinsinger's office to get our deferments certified because my draft board was back in Pittsburgh, so we had to contact the Pittsburgh draft board and get deferment that way.

LS: There wasn't any question of you going to Cold Spring Harbor or--?

JM: Oh no, nothing like that, but it was common in those days to go abroad for your postdoctoral work. Well, that was just impossible. And I know Hank Lardy solved it by going up to Toronto or wherever it was to work with a prominent carbohydrate chemist.

LS: Did you think of trying to do that?

JM: No, somehow I hadn't gotten around --

EM: You had a wife who was doing graduate work, for one thing. [laughs]

JM: By that time, of course, we were married, during our graduate work, and I 01:35:00just didn't entertain going, say, to Canada. There was no one there who was working on the field I was interested in, or for that matter, the rest of the United States didn't seem to have many people like that, frankly. I know Dr. Hart gave me a couple leads for possible jobs, but I just couldn't take too kindly to those--they didn't sound very interesting to me. They were strictly nutrition jobs.

And just one day, Harold Rusch came over and offered me to come over to McArdle and I was delighted, and took it immediately.

LS: Was this, you say it was a fellowship the first year?

EM: He was an instructor the first year, I think.

JM: I went in as an instructor.

LS: But was it likely to be permanent, did you know?

JM: I didn't know.

LS: But you thought of it as possibly just a year?

JM: See, Dr. Rusch started the department in 1940, and he'd of course wanted staff people to join the department and Van Potter was his first choice as a biochemist. Van had just come back from Europe, especially right after the war started. And as it turns out, I was number three. Harold, Van, and myself.

LS: Carl Baumann had been working at McArdle?

JM: Yes, Carl had, I guess, sort of a joint appointment in a way.

EM: He was paid in part by the Bowman fund, too.

JM: That's right, but his primary affiliation was biochemistry, of course.

LS: But from his point of view, he would have preferred to be at McArdle. At least, that was the impression I got.

JM: It's possible.

EM: We don't know.

LS: He had to take Steenbock's course one year, and to do that had to give up the work he was doing here. And I don't think he really was happy with that.

JM: I wonder if that was just about the time I came.

LS: Well then, as I understand it, then you took over the work that he'd been doing here.

EM: We certainly continued in the area he did, and I think he may have felt that by the time we were both working in that area, and with a somewhat different angle, that we may have more or less done--moved so that there was not as much 01:38:00productivity possible from his more nutritional aspect in time. I mean, the nutritional work was done, and he wasn't really supposed to do the chemical work.

LS: Well, was it possibly a way--because he perhaps wasn't appropriate for the kind of work to be done at McArdle--that--

JM: No, I don't think so.

EM: Well, he was still on the--he was still partly paid from the Bowman fund in the early 1950s. Not very much, but he was paid from it.

LS: But I mean you do say that he was--he was not in--he was on the--what happened, how--

JM: He was on the nutritional side much more than we were and--

EM: And he continued with some of that nutritional work--

JM: Oh yes, sure he did.

EM: --in the same area after I left he had a graduate student by the name of Howard Sauberlich who did studies in that area. I think he more or less let the 01:39:00nutritional aspects take him as far as they could and then--as one does in research--watched for other areas to move into.

LS: I think that what he didn't like was having--he spoke about this--was having graduate students instead of post docs. If you have graduate students you have to give them easier problems, and you don't get as much support from them for your own research. Being in a department, as against being in an institute--in a lab--is--

JM: Well of course even in those days we didn't have many post docs--that's a strange view, I think, but the department was very tiny. The old building, you know where that is, McArdle?

LS: McArdle--

EM: 426 North Charter.

JM: On North Charter. Now a six story building. All that's on it now is 426 01:40:00North Charter.

LS: Huh.

EM: When we built this building we moved the name with it.

JM: That building was built in 1940, and there were two views for the use of that building. One was the home for the Department of Radiology--which didn't have very good space at that time--and the second was for McArdle, that Harold had started. And so Harold had just the upper two floors of that four-story building, and radiology had the two lower floors and the basement for all the radiation work--anything that radiology did. And then two years later they put two more floors on top of this for a heart institute which never really developed very far.

LS: That's interesting--an unknown story.

JM: Yes, so when I went over there they were rattling around in those two upper floors. There were Harold and a couple of people that worked for him, no postdoctorals.

EM: And Fred Mohs.

JM: And Fred Mohs was in the lab.

LS: Oh, was he working there too?

JM: He had a lab there--he was working on surgery methods, and then Van Potter. And Van Potter had some graduate students and these were graduate students who got their degrees, so to speak, within other departments like physiology or pharmacology and so forth. And I think Harold did have maybe an M.D. or two.

EM: Roffo?

JM: Roffo, or no not Roffo.

EM: No the student came out of Roffo's--

JM: Yes. And, but I don't recall any other post doctorate at that time.

LS: Well, later on; I suppose he's talking about later on.

EM: I think he's probably talking about later on.

JM: Now Carl had a lab over there for a while, but he sort of gave it up after--

EM: Well I think it's the problem one has with split space--very difficult to work effectively in two places. And particularly if you're talking about lab work. You have a lab here and a lab there--I don't think that works very well. And the teaching and his graduate students would certainly keep him primarily in biochemistry so it would have been an effort to come over--. He came over very regularly for seminars.

JM: That's how we got acquainted with Harold. Harold and Carl--even before I came--had been having Journal Club.

LS: Yes, that's right. Harold Rusch describes that in his book.

JM: And that kept up all the time and for--even after we had come over to McArdle, Carl would come over for the Journal Club and--

EM: He's bring some of his students, he had a couple of students.

LS: But you didn't come over together? You came over--

JM: Separately. I came over in--I guess--'44, after I--at the end of '44. After I got my degree, Carl went to Europe on a mission for the Army for an investigation of the state of German science committee that he was part of, and it happened in a semester that he would normally give his lectures for the vitamin course. So I'd just finished my degree and I gave the lectures for that semester.

EM: Actually you came over here because that was '45 because I was over here. And he couldn't go till after '45.

JM: That's right, you're right, you're right.

LS: Well, it's just--this is such a fascinating side.

EM: It's a side that's easy to get off into.

LS: You were just saying that there was no place to go in the United States, and what--

EM: Because actually at that time Wisconsin was as far along as anybody in working with chemical carcinogens. There was some work going at the National Cancer Institute and some with other institutes. Though it wasn't doing much Wisconsin really was doing about as much as anybody. So he continued here with the--

LS: And this was due to Harold Rusch? Why had Carl Baumann gotten into chemical carcinogenesis?

JM: Well, because Harold Rusch started to do cancer research--see he got his degree--M.D.--I think in 1906. I'm sorry, 1936. And after a year internship he 01:45:00came back to the Department of Physiology--

LS: He's amply documented this.

JM: Yes, right.

LS: But I mean who got Carl Baumann started.

JM: Well, because he needed--he found he needed biochemistry--the expertise of somebody in biochemistry to help him, so that he got hold of Carl Baumann that way.

EM: And there was a nutritional aspect there too. The Germans--excuse me, the Japanese--showed the carcinogenicity of these amino azo dyes in 1933-34. Then the German investigators tried to reproduce it and didn't get tumors. But the Japanese continued to get tumors. So people like Carl looked at it and said well the Japanese--they're using such a poor diet and the Germans are trying to do it on a good diet--maybe there are dietary factors involved. So that's how he got 01:46:00into it.

JM: Yes, that's true.

LS: So that was quite a leap forward then, wasn't it?

JM: That's right, it really was. And as I said, during my graduate work I began moving my work more and more towards how the diet worked. Carl was not an organic chemist, but I had some organic chemistry behind me. I told Carl one time that I wanted to make a series of dyes which were related to the basic carcinogenic dye that we were using called dimethylaminoazobenzenes. I had been reading the Japanese literature on this and they had done a little bit on structure-activity relationships. Chemically it's possible to alter the structure a little. Benzene rings, a methyl group. If you had some organic 01:47:00chemistry you would know that this is--you could know what a hydroxyl group (microphone being moved--typist could not hear this part). But I told him I wanted to make three dyes related to the parent dimethylaminoazobenzene carcinogen we had been using by putting a methyl group ortho, meta, and para to the azo group. Chemically it's pretty simple to do, so I told him I wanted him to order for me the chemicals so I could do this. Well, he resisted--he didn't--he showed no great interest in it. But finally he broke down after my persistence and ordered them for me. They're just simple compounds that you can 01:48:00buy from Eastman Kodak and then simple amines with the methyl groups; you diatozie them and couple with dimethylaniline. So I made those three dyes and purified them and then I started to feed them to the rats. I was very lucky because two of the dyes turned out to be weaker carcinogens thant he parent compound, but the remaining one turned out to be several times more active than the parent dimethylaminoazobenzene, so I had discovered a more active carcinogen. And this became useful in the studies that he was doing, actually, because dimethylaminoazobenzene, the parent dye, is rather susceptible to the 01:49:00level of dietary riboflavin, one of the vitamins in the diet. A high level of riboflavin lowers the carcinogenicity. But this new, more active dye wasn't affected by the levels of riboflavin. So it was a new tool.

LS: And this was unexpected.

JM: Yes, quite unexpected. And once that occurred then he was interested in it. And then we were interested in the metabolism of the dye. The dye could produce--is it working?

LS: Well, try again.

JM: We were not only interested in altering the structure of the parent 01:50:00carcinogen, the dimethylaminoazobenzene in the animal when it was producing tumors--that is, there must be something that the dye is doing inside the animal to produce the tumor. For this we had to study what we call the metabolism--how the animal breaks it down, if he does. As it turned out, one other group in the country at the Sloan Kettering Institute--Memorial Institute--in New York had already fed dimethylaminoazobenzene to rats and taken the urine. They had shown that the rat was able to split its azo linkage, take off a methyl group, and put 01:51:00on a hydroxyl group on one of the rings--it had two rings. This was interesting, so I started to look for metabolites in the urine and in the liver. We discovered in the liver where the tumors were formed that the liver was able to take off the two methyl groups which are on the nitrogen of the dye--i.e., take them off one at a time to give a monomethyl dye and then an aminoazo dye. It was already known from some Japanese work that the compound without any methyl groups had very little activity in the rat, and I confirmed that. I also showed--I had synthesized the monomethyl dye--and showed that that was the same 01:52:00as what the animal was able to make from the dimethyl dye. At about the same time--I think you were getting into this--we showed that the monomethyl dye and the dimethyl dye had the same activity--

EM: Quantitatively the same.

JM: Quantitatively the same--and then--so that for some reason we needed the whole dye. We showed that the parts that the workers in New York had shown that some from the dye in the urine had no activity when we tested them by themselves. So we established that we needed the whole dye and at least one methyl group for the activity.

LS: How long a period is this going on?

JM: It was easily--

EM: From about '43 to '44-'45-'46--a period of three years or there abouts. 01:53:00These experiments--each one took something of the order of eight months to finish up.

JM: Chemical carcinogens don't produce tumors immediately in an animal. It requires a large fraction of the lifespan generally to produce tumors. And this was actually originally shown by Percival Pott in the chimney sweeps. The chimney sweeps got their main exposure to coal soot and so forth while they were 01:54:00small--small boys climbing up into the flues. Then they would become master chimney sweeps--young men who would then again indenture small boys to climb up. The tumors of the scrotum in the chimney sweeps occurred after puberty, so that it took a long time for this effect to show up. The master chimney sweeps, while they were still surrounded by soot, didn't get such close contact with it as the young boys did. These young boys were saturated with the soot--sort of a greasy soot--it saturated their clothes, they slept on bags of soot, and they just lived in soot. They rarely washed, you see.

LS: This has been written up somewhere, I'm sure.

JM: Yes, it has. We established quite early that it was likely that what we call the latent period in chemical carcinogenesis is long. In man it's a period of years. In a rat or mouse, which has a lifespan of two to three years, you measure it in one year or in months--many months. If you feed a high level of dye--high level of a carcinogen--you get your tumor sooner. But you don't get them overnight; it takes a while.

LS: What you've discovered has been written up in articles. I'd be interested to know, as you started working together, how you went about working together.

JM: Well, I guess--I think we collaborated in the sense that at least in those 01:56:00days Betty was more biologically competent and I was more chemically competent in terms of what we could do together. So that's how--that's sort of how--

EM: Yes, well when Jim came over to McArdle in '44, as he mentioned, he was an instructor. He became an assistant professor in '45. Then in '45 when I finished my Ph.D., Dr. Rusch indicated that he would be glad to have me come over too, if I was willing to apply for a postdoctoral fellowship.

LS: Both of you presumably had top records as graduate students and he wasn't taking you just because--

EM: I don't think he was taking me just because I was a wife. But of course I 01:57:00was handy, at least, and as Jim says the department was still small, so that he was looking for people. The number who had any training in this area in this country was certainly very small. So I think probably I had some advantages, but I also was looking for a position that was in Madison too, so it was particularly convenient for me. So I applied for a postdoctoral fellowship, and Harold was agreeable that we should work together if we wanted to. Jim and I had a lab which had three desks in it and lab benches, and that's where we started work together in McArdle.

LS: So you had worked together. Did you talk about considering not working together?

EM: Well I don't know really how much we considered it. I remember at one time--and it may have actually been when I became a permanent member of the staff, I'm not just sure--Harold asked me if I would rather have a lab of my own and I said I really didn't see any advantage to that, and he said "Well, if sometime you do, let me know and we'll arrange something." So--but we never needed to arrange anything.

LS: You're obviously not going to say if you ever regretted it.

EM: No, no we never regretted it, but we started out in a good size lab which had room for us. By that time we had one assistant who worked in the lab with us. We planned the research together, and we divided up the work and we wrote it 01:59:00up together, so it really was totally collaborative.

LS: What do you mean by wrote it up together?

EM: Well, one of us would write a draft. We still do this--one of us writes the draft, and the other one pulls it apart and marks it over and so forth. The net result may have been more of one person's effort than the other, but it's a reflection of both of our efforts.

LS: You take turns, or is it more on the particular project?

EM: Well, it all depends, and of course now more of our writing is with our graduate students, and they often do the first draft too. But it's still a collaborative activity and since we--our daughters used to say to us "Well, can't we have some other conversation at dinner?" We thought we had other 02:00:00conversations at dinner, but they thought at times we brought it all home. You don't stop at the time. So, I think we've really done--very tightly collaborative work ever since we finished our Ph.D.s.

LS: Were there--are there times when there are so many different directions that you might go into from what you're doing that it's a really painful decision as to which direction to take?

EM: Well, I think one always has to make decisions in research because you have to make decisions as to whether some area--line that you have been following may have lost some of its productiveness--at least for the moment--given the tools that are available. At the same time other opportunities are showing up which may have much more potential. You have to decide whether to drop some parts of 02:01:00one area that you're doing to pick up others. I think these are always decisions that are difficult ones, because one can't perceive well enough what's going to come out of the research to help discuss what is going to be. And I think, based on our own experience, some of the things that we were fortunate enough to see along the way have been as important as the ones that we thought we planned out well.

LS: Say that again.

EM: Well, as one's doing research with one goal in mind, if one is lucky something else comes up that isn't exactly what you're looking for. Quite likely a somewhat related observation, and one that you weren't looking for, may on occasion be more important that what you are looking for. So it's very difficult 02:02:00to predict in advance how productive--given your ideas and your techniques--any particular thing will be. But you do the best you can at thinking it through and then going ahead and trying.

JM: It's certainly particularly true in chemical carcinogenesis that you have to plan as carefully as you can because the experiments sometimes take so long. Nowadays some of our experiments take twelve months to eighteen months to complete, when we're using animals under tests with various compounds. You first of all have a bunch of experiments going for long periods of times starting at different times. Then you have a lot of regular laboratory work, analyses and 02:03:00preparations of compounds and so forth, that you have to do to get ready to test these things in animals. And as Betty said, I think the most important things that we have found we did not plan ahead. There was no way to plan these things ahead. It's just that we were doing things that we thought were worth doing. But then it turned out that in the process of carrying out those experiments, we discovered other things that Proved to be much more important than what we have started out to do.

JM: And then as the field developed, we were--we often felt very lonely in this field in the early years because there were so few people in the world doing similar experiments. So that there was just not much in the literature. But then as we published and a few others published, more and more people started to get 02:04:00into the field because they could see places that they could perhaps contribute.

LS: Has it reached a point--in a way it must be rather nice that the field isn't too big because then there isn't so much--

JM: Yes, well we felt that, but nowadays the literature is huge. As it is--

LS: How do you keep up with it?

JM: Well, you do your best. It's difficult to keep up, and that's not just chemical carcinogenesis; it's everything else, because studies in cancer research are really multi-disciplinary. It's made up of biology and chemistry and physics and all the subdivisions of biology--genetics, molecular genetics, now virology. And then in the chemical end you have organic chemistry and even 02:05:00inorganic chemistry now, and subspecialities. It's really a huge field and it's very difficult to keep up with the whole thing. We used to think we could keep up with the whole cross-section of both biology and chemistry as related to cancer research in our first decade of research, but we had to give up. We had to concentrate our attention on subdivisions after that--we couldn't begin to keep up with the literature.

LS: Does that bother you--are you afraid you'll miss something?

JM: Yes, it does bother you. But as you know, as a field develops then people like ourselves begin to write reviews on certain areas. And this helps you pick up a field more easily. And then we have publications such as what's called 02:06:00"Current Contents". You may not know this--but this is--instead of going to the library and going through a whole raft of journals every month or two to try to keep up--this is a bi--I guess it's a weekly magazine now--that reprints the table of contents of all of the journals. I think it covers some 2000 journals now in the life sciences. So you can quickly go to the important ones and at least see titles, and then you go to the primary journal.

LS: Is this on computer?

JM: Well, this is generated by a computer.

LS: How much interaction is there among members of McArdle Lab and how important 02:07:00is it?

EM: Well, I think we've been fortunate as a department in keeping quite close. The department started out small--we were fortunate in starting with it--and in the early years when we were all on two floors, the spontaneous meetings were very easy. One of my earliest recollections was the journal clubs where we actually often had only six or eight or ten people attending, but it was a very close group. Van Potter used to come in with his notebook at the end of the day to show us his newest results. He's a very enthusiastic person and he--we were right in the next lab--and he would run down to show us, so that we were very close on those. Along about 1960 or thereabouts, we started weekly regular staff 02:08:00meetings at which all the staff came and which were set out to be a combination of science and business. The objective was to keep the staff close, because by that time we were beginning to grow and we could see that in time we might have problems--people on different floors might not see each other regularly. So through the years we've continued to have an hour and a half that we set aside every Friday for staff meeting, and with a mix that is at least 50 percent science and 50 Percent business. And I think in a building this size that's been tremendously important.

LS: Does everybody come?

JM: Yes.

EM: Yes, we make a point. If somebody doesn't show up we know is present, we go talk to them.

LS: That's amazing.

EM: And you know some meetings are more interesting than others. But in the 02:09:00first place, just getting everybody in one room--if maybe we haven't seen them since last Friday--why then at least that's a lot better than if the meeting didn't occur. As people sit down, they say "Well you know, Rex, I just saw this" or "Jeff, I just saw that" or learned this. So those spontaneous conversations before the meeting ever starts are important and then by having every staff member give their research report in rotation--

LS: You do do that?

EM: We do do that, and in between we give what we call science reports--on weeks when there isn't a research report--that is an article that somebody picks up from the literature and reports on--something like a journal club. It helps us to keep acquainted with what the other people are interested in. In a relatively broad department this is, I think, extremely important.

LS: How closely connected are you?

EM: Well, basically the department has three overall groups of research--chemical carcinogenesis, which obviously Jim and I are in, and tumor biology, which covers the differences between normal and tumor cells and the reasons why they're different--differentiation versus growth. This brings in people, some of whom are not working very much on tumor cells but who are working on what differentiates--causes the cell to either differentiate or grow, since that's looked at as a primary problem in tumor growth. The third one is tumor virology and Dr. Temin is of course the leader of that group. And there 02:11:00are crosses between that. Some of the people in tumor virology obviously are also interested in tumor biology and the same with chemical carcinogenesis and tumor biology. And now there's much more interplay between chemical carcinogenesis and tumor virology. Many of the discussions that are now of great molecular detail, I'm not convinced I follow word for word, point for point, but I come out with much more information. We can ask questions, and so we do, I think, keep much better abreast than if we didn't have those meetings.

JM: The various professors who head up their research groups that fall into these three areas of chemical carcinogenesis, viral carcinogenesis, and tumor biology, themselves hold group meetings amongst themselves. There may be four or 02:12:00five professors with their graduate students and post doctorates who at least once a month get together and have a research report by one of the graduate students or one of the post doctorates. And then in addition to that, each little group--each individual professor's group like the group we have--we meet like as much--as often as we can--sometimes once a week, sometimes every two weeks. And our own students prepare talks on their research or some aspect of the literature. So that we have these different kinds of groups meeting frequently to try to distribute the information back and forth and get criticism.

LS: That's not a burden?

JM: No, no. Well it can--

EM: It's an important burden, yes.

JM: It's an important burden. And then, as you know, on a campus as active as this university is, you could spend all your time going to the lectures. You really could. Most people in this department try to attend biochemistry lectures, cell biology lectures, molecular biology lectures, and lectures all over the campus in subjects that are being studied in this building.

LS: You didn't have any dealings with the Enzyme Institute?

JM: No.

LS: Have you worked with people in biochemistry or genetics or molecular biology?

JM: No. In general we haven't.

EM: We had a little bit of collaborative work with Frank Strong at one time.

JM: Yes, very early one of our graduate students, actually a staff member--Gerald Mueller, Dr. Gerald Mueller--he's I guess our second graduate student from our group. He needed to prepare a certain coenzyme, which actually contains part of a vitamin--this was actually during his graduate work. He collaborated with Dr. Frank Strong and one of his graduate students in getting liver from the packing plant and working on it in large amounts in order to get out this very important cofactor. Well today you can buy it from a chemical company who makes it for this purpose--that sort of thing. But in those days you 02:15:00had to make your own or you didn't do it. Our work has been relatively specialized in terms of metabolism of foreign compounds--that's really the sort of work we've been doing and there hasn't been too much work of that sort on the campus. Right now, however, in pharmacology Dr. Jefcoate's doing--and several other people on the campus, even in Pharmacy, are doing studies on the metabolism of foreign compounds--drugs and so forth--that fit right in with the work we've been doing for several years.

EM: But--just in terms of collaborative work we also did some collaborative work with Phil Cohen and one of his students in the mid-'50s. And we had collaborative studies with both Henrik Hartmann and John Harmon in the 02:16:00Department of Pathology.

LS: Did you ever have anything to do with Joshua Lederberg?

JM: No. No we never--

LS: Do you feel isolated from the campus at all.

JM: No.

EM: No.

JM: No.

LS: Was it the other way around, or?

JM: No.

EM: Well, I--

LS: Of course this isn't a teaching department.

EM: No, no. But I think there is no feeling of isolation in this department. There is a lot of advantage to being a teaching department, but there are a lot of advantages of being a department that does not do much undergraduate teaching, because it--undergraduate teaching is both rewarding and time consuming. And as a graduate teaching department we have lots of contact with students and lots of contact with other faculty--for instance, through examining 02:17:00committees and seminars and that sort of thing--so there's no feeling of isolation. There's much more of an ability to pick and choose the things that you really want to do. I've always felt that we've had the best of all worlds here.

JM: We regard our having graduate students and teaching them how to do research as our main teaching function. But very early in this department--I think it started in 1948--we realized that with the increasing size of the department in terms of graduate students and professors--that we were graduating students who didn't know in a broad sense what cancer research was about. They knew their own little area. So we started giving a graduate course in oncology--experimental 02:18:00oncology--in 1948. It started out as a one credit course, eventually became split until recently into two two-credit courses--total of four credits--and covering viral carcinogenesis, chemical carcinogenesis and tumor biology again. Now it's been combined into a three-credit course that covers all three of those subjects for our graduate students and any graduate student on the campus that wants to attend, plus our post doctorates, many of whom attend. Because we have about fifty graduate students in this department.

LS: Oh, I see. And you each teach a section.

JM: Yes, yes in this three credit course. And then in addition for the last decade actually--it's more than that now I guess--started in 1970, almost 15 02:19:00years--I've been giving just a few lectures each year in a course called "Man, Chemicals, and Environment".

LS: What does it cover?

JM: Well, it covers actually all three colleges--Medical School, Ag School, and Pharmacy.

LS: Is that part of the Institute of Pharmacology?

JM: Yes, it's part of the Environmental Toxicology Center which actually came a little after the course. The course was started first. It was just an effort to provide undergraduates who were interested in some aspects of this. And we've had anywhere from 30 to 100 students each--it's generally given in the spring semester. I'm still teaching that--I give the--

LS: Even though you're retired?

JM: Well, it's minor. I don't feel retired. It's again a course given by 02:20:00professors all over the campus--Pharmacy and Ag School and Medical School. I just happen to give the first four lectures orienting in toxicology.

LS: One of the complaints in science departments has been that the research in the Medical School is not as good as it should be. It doesn't provide a basis of support. Has this affected--I mean what do you--?

EM: I think the exception may be--or the first exception--is McArdle.

LS: Oh yes, obviously--

EM: Well, we've looked at our position here as a very good one through its physical position because we're essentially next door to genetics and medical genetics which are very strong departments.

LS: Well, I was actually putting you on the side of the people who might suffer 02:21:00from the fact that there wasn't enough research going on in the Medical School.

EM: Yes, well I think that this is a--can be a difficulty. It's not been a difficulty to us or to most of the rest of the group, because the department is very much basic science. And so we get our stimulation more from genetics and medical genetics, biochemistry and molecular biology and that group than we do from the Medical School colleagues. Now, granted it might be an advantage if the medical research had been stronger and then--for instance, when Charlie Heidelberger was here doing basic chemotherapy, he did do some work with the clinical people. But if there had been more support in pharmacology, I don't know whether that would have provided a stronger base or not. So I think that 02:22:00anything--time--the stronger the base, the better things are going to be. But I don't think that we particularly saw the lack here because we had the support from medical genetics and genetics and biochemistry

JM: You see originally the graduate students in this department, as I mentioned earlier somewhere, were really based in other departments, like pharmacology or physiology and so forth in the Medical School in order to get their degrees. But they did their research over here. Well, eventually we began to feel that we really should be able to give a degree of our own. That came about in the--

EM: I think it was '48.

JM: Was it actually '48--about there--around 1950 or so. And then we laid out a 02:23:00curriculum. They took most of their courses in other departments, but we did give this course in experimental oncology. And now with the advent of molecular biology--the increasing interest in molecular biology in our staff--we give a number of shorter courses that are listed under oncology but involve many aspects of it.

LS: You mentioned Charles Heidelberger. He was somewhat of a difficult person, was he, as a colleague?

JM: Well, he was a very good researcher, a good lecturer, stimulating, but he 02:24:00was quite aggressive. And sometimes that aspect caused some irritation, but on the whole that's a rather small price to pay for somebody that can really make contributions like he did. He certainly was aggressive. He would frequently hire more people than he had the room for and then ask for more room and that sort of thing. He nevertheless was a very important member of the staff and we were really sorry to see him leave. Because he had been here--he came here just after his postdoctoral experience out on the West Coast and Dr. Rusch was important in 02:25:00selecting him. Dr. Rusch has had a real good eye for people. He's the one that selected Temin. Charlie was here--for what--twenty-eight years I think before he left for, frankly, a variety of reasons.

LS: I was just going to ask you, have you been able to recruit the people that you wanted to--have you been able to give them enough money to attract them.

EM: Yes, I think by-and-large we have. If somebody doesn't accept, one's never just sure what the mix of reasons are. I don't feel that overall that's been a major difficulty.

LS: You don't seem to have people leaving, or do you?

EM: No, we've had a fairly stable department. Actually, over the years in the early--in the '50s we had Schneider and Le Page leave, and in I think the next one that left was Charlie--well no, Nowinski left in between there. He was here for just a short period and was obviously one who wanted to go to a place where he had much more--a much larger group and much more power. No it's been a quite stable group.

LS: You must have had invitations to go elsewhere?

EM: We had some, probably fewer than might have been if it hadn't been apparent that they needed to find two positions instead of just one.

LS: But you wouldn't--you haven't been in the least handicapped by being in a small community, relatively?

EM: Well, in a small community this is actually a pretty good size department. 02:27:00Up until, say, ten years ago McArdle was one of the larger basic science--cancer research departments in the country. The influx of federal monies into cancer research has resulted in a great proliferation of such institutes so that we no longer are one of the really big ones. But I think we're still one of the good ones.

LS: McArdle isn't suffering for funding recently?

EM: No, we've so far been very fortunate. We've been able to keep our funds, I think, at a reasonable level. We are not growing, but we do not have room to grow in this building, and I think most of us feel that a group of seventeen staff is about as many as can keep really well acquainted with each other at one time.

JM: We still stay close to the laboratory--not getting cumbered by such a large 02:28:00research group that you're tied to a desk.

LS: You actually do deal with the animals, make slides?

JM: Oh, yes. Well, not so much slides.

EM: Well, we don't do the amount of actual hands-on work that we used to, but Jim is--particularly in the last few months since he retired--has gotten himself back in the lab quite actively and I've continued to do an appreciable amount of work--particularly in overseeing the animal work.

LS: Why did you go into--allow yourself to become an associate director?

EM: Well, I guess I did that for the following reason. As you know, Dr. Rusch decided that he wished to cap his career by starting a clinical institute. Most 02:29:00of us here at McArdle felt that, even if maybe he might feel that he could carry both the clinical institute and McArdle at the same time, we felt that we really wanted to have our own identity and to be separate. And so Dr. Rusch resigned as director in '72. The decision of the staff by vote was that Dr. Pitot should become the director, but at that time he was still acting dean. And in addition to that, by that time it was becoming evident that the grant applications and that sort of thing were beginning to proliferate. They've even proliferated more since that time. A job that at one time one person could do and still have time left for research--as Dr. Rusch handled it very well--was getting to the point 02:30:00where it would not be possible. So it was concluded by the staff that there should be both a director and an associate director to separate the load somewhat. Dr. Pitot was elected as chairman and appointed by the dean, subject to when he got--well appointed by himself--I don't know just how that works. Anyway he was elected chairman and agreed to do it, and he apparently thought some about who he would like to have work with him and asked me if I would do it. Jim and I discussed it some recognizing that it would reduce the amount of time I had for the lab work itself. But I guess between us we decided that maybe in--we just as soon have me try it and see if it was good for McArdle. So that's 02:31:00the reason.

LS: So you didn't mind?

EM: No, I enjoy a certain amount of administrative work.

JM: She's a much better administrator than I am.

EM: But I'll admit there are times when we're busy writing a grant or something that I would just as soon have the time for the lab. But overall I have hoped that I've contributed to the department as a whole and I enjoy some administrative work. I wouldn't want to do it full-time.

JM: Of course in 1952 I guess we started to have a family. So she went on half-time once that occurred. We had our first daughter in '52 and our second daughter in '55. So up 'til--when were you half-time?

EM: I don't know. I was half-time, then I was two-thirds time and then in '72 I was 80 percent time. When I talked to Dr. Pitot I said, "Well, if I'm going to be associate director, particularly acting director, I guess I might as well go full-time." And he said "Well I didn't even know you weren't full-time."

JM: I think she's put much more time in than the stated amount. That's usually the case, isn't it though.

LS: How did that--how did you feel about that? Nowadays people just go on working full-time.

EM: Yes, well I realize that. I wanted--I guess Jim and I both wanted to be able to have enough time with the children so that we felt--just as you do research--that you do a good job of raising your family. And there was the other side. Dr. Rusch was always very supportive of me, but he also, I think, had the 02:33:00feeling that if a woman has a job she should be doing it full-time too, just as much time--if she's full-time, she should be as full-time as a man. I don't think he was really convinced--I wasn't convinced--I could do it, so I said I would go half-time and then we would adjust it as need be. So I worked basically three days a week and then I had the other two days off and at the same time Dr. Rusch needed some help--he was editor of the Journal of Cancer Research and needed some help with that. So I agreed to take a quarter-time on that. So I did that part when I was home and I think he really felt that that was a desirable way of helping his problem in that respect, as well as having the time at home. 02:34:00But we had very good help. I was fortunate--we were fortunate--early we had a woman who came in three days a week and just stayed with the children. When she no longer could work with us, we were fortunate in obtaining a woman who had worked as a cleaning woman, but who had much more capability than that--who actually became sort of a second mother to our children and she worked for us twenty-five years, two or three days a week. It makes a very great--large difference. I think it must be very difficult to both maintain a full-time academic job where one is really expected to work more than forty hours a week and raise the children without at least some degree of help like that.

LS: You didn't consider both of you going on part-time--as nowadays again--I 02:35:00don't suppose you considered it.

EM: No I don't think that ever entered our minds.

JM: No, I don't think so.

EM: It was not the time. It was actually a very fortunate arrangement, because by working together, being on half-time was not nearly as restrictive as it would be if you had your own problem. Because if I wasn't there, Jim knew or he could call up or something and could talk with the students just as well as I could if I was there. Being at home, sometimes I could do some writing or something which might be difficult to get done at the lab. We were very fortunate.

JM: We were extremely fortunate in being able to work together starting so early. I suspect in many departments we would never be allowed.

LS: I also think very few people could manage it.

JM: We're, I guess, highly compatible. Great time.

JM: What we've noticed amongst our students, and I'm sure this applies to most graduate students today, the field of biochemistry--we're biochemists--and, of course, oncology--experimental oncology--is so huge and things move so quickly today that students really--the graduate students seem to end up knowing only what happened no later than five years ago--or maybe even less than that. So 02:37:00that they seem to not be familiar with basic findings in biochemistry as related to the people that did the work. So very frequently you will talk to them about a certain person's work ten years ago or farther back, and they're blank. They just don't know these people. They may know the finding in a basic form, but they don't know the people that did the work at all. This doesn't--and this includes Nobel Prize winners--they're just gone; they don't know them at all. In fact, they--

LS: They don't show up in articles that they're reading?

JM: That's right. That's right. The work is now sort of part of the knowledge in 02:38:00the field and the names that went with those findings--nobody seems to--these students don't know them, and they're not taught them either. They will say, "I've never heard of that person." And yet it will be some prominent person, probably more often than not got a Nobel Prize--that's a shame. So, as we've gotten older, of course, we've become more interested in the history of our subject. I think we always had a basic interest--knowledge of names in this field, but it's increased in recent years. In recent years we've summarized some of the history of this field in a few papers that we've written. And now that we're coming to the end of our career, we've written a couple of small reviews 02:39:00on our own work, trying to put it in perspective. So, it's a shame because I think the field, at least to us, comes more alive if you know what the--how the person did it and what problems he or she encountered in doing it and--

LS: Well you were tracing--just briefly earlier while you were on the phone--how your work actually related back--

JM: Yes. Things in those days--in the first part of this century and in the last century moved very slowly in science compared to today. It's just tremendously rapid today, because there are so many scientists now and they are so well supported--at least in this country as well as in many countries. Things move 02:40:00quickly. There are so many more ways of doing things--basic concepts that can be adopted and put into practice quickly. This wasn't true of science in the early part of this century and certainly not in the last century.

LS: What were the major discoveries that pushed your work along? DNA, I suppose.

JM: Yes, that was a very basic finding. We lived through that period. The basic Watson and Crick paper occurred in Nature in 1953 and--

LS: Was that directly important to you?

JM: Oh, yes, very clearly. Because in 1947 we made perhaps our first major discovery when we were working over here together. We discovered that these 02:41:00carcinogenic dyes in the liver became bound--attached to proteins in the liver. We started to study this finding because we immediately recognized maybe it had some important significance, and we found that the amount of this binding seemed to correlate directly with the carcinogenicity of the dye that we used. See, we had made these different dyes with different activities as carcinogens and the more active dyes bound more than the weaker dyes, so there was a connection. And we put forth at the time sort of what we call the protein deletion hypothesis. This was because when we waited for the time till the tumors appeared, we found 02:42:00no bound dye in the tumor. It was in the liver--the more or less normal liver around the tumor--but not in the tumor.

Then in collaborative work with Dr. Cohen in physiological chemistry and one of his graduate students, we found that the group of proteins in the normal liver that bound the dye were more or less missing in the tumor. So we put forth this protein deletion hypothesis. Well, it's only of historic interest now, but this at least brought up a close connection between important constituents of the liver cell--protein and the carcinogenic dye.

It was soon found that not only did the dyes bind to protein, but they bound to nucleic acids like DNA and RNA, which carry genetic information for making 02:43:00proteins. Proteins form most of the cell, in the form mainly of enzymes that carry out the metabolic processes in the cell that make it alive. So that was a finding that led to advance in the field, and many people started determining protein-bound carcinogens and nucleic acid-bound carcinogens. Then our next major finding, in a sense, was in the metabolism of the cells of the liver and other tissues of foreign compounds. We--I guess we were among the very first to--along with Gerry Mueller as a graduate student with us--to actually show 02:44:00that preparations made from the liver--you can break down liver cells to their so-called formed elements, like nuclei and mitochondria, things that you can see under the electron microscope as major complex bodies--under the light microscope too, in many cases. The proper combination of some of those components would metabolize the dye; others wouldn't. So we were sort of pioneers in that field.

And then with a graduate student, Alan Conney, a few years later in the '50s, we discovered that the enzymes in certain parts of the liver that metabolize these foreign compounds could be induced. That is, if you treated them either 02:45:00sometimes with the compound ahead of time--the whole animal--or you used some other foreign compounds, we found that then the level of these enzymes that would metabolize these foreign compounds would greatly increase quickly. This brought up a whole new subject of enzyme induction in the field of pharmacology and toxicology. And we just happened to be the first ones to find it. It was strictly an accidental finding, as was the protein-bound dye. That was an accident--we were doing something else when we discovered that. That was true of the enzyme induction.

And then the field was developing, so when we started the only carcinogens known were the carcinogenic hydrocarbons, carcinogenic dyes, one or two other odd compounds. But as time went on more and more chemical carcinogens were 02:46:00discovered, many by accident, some deliberately by just changing structure of known carcinogens. But the thing that began to interest us was that when you looked at the structure of all these carcinogens--all of which could convert normal cells to tumor cells--we couldn't find anything common about these structures--chemically speaking. There was just nothing common between the carcinogenic hydrocarbon and, say, a compound such as ethyl carbamate, even though you don't know what that is. There was just nothing chemically common and it looked like here we had these many classes of different carcinogens that had nothing common to them. And that puzzled us no end. We started studying again the metabolism, as closely as we could, of a couple of structures very 02:47:00thoroughly to see what went on in their metabolism. At first it appeared that every time we found a metabolite and tested it for carcinogenic activity, it didn't have any. Well this is an aspect of toxicology that is important, that is, drug inactivation. The body actually destroys the larger fraction of the dye or any drug that you give. And we kept looking, though, for a metabolite that would have activity as a carcinogen and we expected it to have more activity.

Well then we were lucky once again. We were carrying out a particular kind of study on a carcinogen, 2-acetylaminofluorene--that doesn't mean anything, that just gives it a name--and accidentally we discovered a metabolite of this that 02:48:00was more active than the compound we gave the animal. In other words, the animal had converted this carcinogen into something still more active. That really set the thing off, because that was the first example of what we call a proximate carcinogen.

LS: How did that show up?

JM: Well it was purely accidental in a sense. It's a little bit involved, but--

LS: But you thought--

EM: No, we were studying the urinary metabolites.

JM: We were studying the urinary metabolites, and we knew that this 2-acetylaminofluorene would produce liver tumors. We also knew that one of these enzyme inducers that we had discovered would inhibit the carcinogenic activity of this 2-acetylaminofluorene. So we set up two groups of animals, one getting the carcinogen alone and the other getting the carcinogen plus this inhibitor. 02:49:00And then we looked in the urine of the rats for the metabolites of this carcinogen--actually a series of hydroxy derivatives--all of which are inactive. We chased them down, that is we separated them on paper strips by a new technique called paper chromatography, and we estimated them by ultraviolet spectroscopy, absorption spectroscopy. We decided we would follow them every week, all the time up till they got tumors--looking for something different between these two groups, because we knew one group would get tumors and one wouldn't. We wanted to see what metabolite was different. Well, then we were extremely fortunate because after about a week of feeding the animals that got 02:50:00the carcinogen alone, we found a new spot that we were pretty sure was a new metabolite that no one had ever seen before. In the group that was being inhibited, we didn't see that spot, that came up later, but very weakly. So week by week the spot got bigger and bigger and bigger, and pretty soon we realized this was going to be possible to isolate. So we isolated it and then through chemistry we determined its structure, and it was a new metabolite. Because it showed up in the animals that--in the urine of the animals that were going to get tumors and did get tumors, we figured that thing probably is going to be more active. We'd been looking for something like that for a long time, so we then synthesized it in large enough amounts to test it by itself. And sure enough it was much more active as a carcinogen, not only in the liver but 02:51:00elsewhere, because it produced tumors in other sites. That happened to be the first example of a proximate carcinogen. Well, now the story is--today is that most chemical carcinogens have to be activated in vivo to form proximate or--and then finally the ultimate carcinogens. Because what we found was that this more active metabolite--when we tested it--it didn't bind to nucleic acid in the test tube. We thought it might--or to protein. But it would give more binding in vivo to proteins and nucleic acids. So we figured, well that's just the first step. There's a second step that's in the metabolism that's important. And we accidentally found that. It was just a series of accidents, because it turns out 02:52:00the body does one--the first step--it puts a hydroxy group on the nitrogen, then it does the second step. It just does it because there are enzymes there that do it. The second step produces something that is active and will bind nonenzymatically in the test tube to the nucleic acid or protein.

Tape 4, side 1

JM: And so this turned out to be, I guess, the first example of an ultimate carcinogen being derived--as we call it--from the parent carcinogen. So it turned out the majority of the chemical carcinogens we know have to be activated. And it turns out that the type of activity that they have is common 02:53:00to all carcinogens. That's what we had been looking for. So it's just that each of these different classes of structures that are carcinogens are activated in different ways, but the final active--the electronic form of the final active carcinogen in each class is the same. It's what we call an electrophile. That was our--kind of our last major discovery. Since then we've been expanding on this.

JM: We've really been very lucky over the years. The way you become lucky, I guess, is to keep your eyes and ears open and do many things. You've got to keep active. Even if some of them look kind of pedestrian, at least if they're worth doing, then you watch for things--that's all. We've been very lucky over the 02:54:00years. And that's true of almost every field in research--lots of things are found in the--they use that word "serendipity" when you're looking for one thing, you find something else--usually more important than what you're looking for. Some things can be done deliberately and that's what's characteristic today now of molecular biology. The basic theory and background in molecular biology is so precise now. At the molecular level you can on paper predict things that you ought to be able to do in animals and plants--and then go ahead and do them. It's an extremely powerful technique. You couldn't have done that with the 02:55:00chemical carcinogens we worked with. You have to have the good fortune to find some of these basic things and then from there you can start making predictions.

JM: And now you can predict from the work that we and others have done that, if a new compound shows up that has certain characteristics, you can come up and say that has a strong likelihood that it's going to be a carcinogen before you test it. And the chances are good that you're going to find it--it's not perfect. And then this general characteristic of the final active forms of 02:56:00chemical carcinogens makes it possible to use other techniques such as mutation, using bacteria. This isn't our work, but that now can detect compounds at very low levels that have the potential of being a carcinogen. It still doesn't prove that it will be a carcinogen, but the likelihood is very high if the compound that you're testing is mutagenic in these bacteria. So now it's getting even to the point with the recent discovery of oncogenes--these genetic sequences that are found in tumors and have analogues in normal cells--. The oncogene in the tumor--it's called a v-oncogene--is very, very close to the so-called 02:57:00oncogene--cellular oncogene in the normal cell. But there is only a very slight difference usually--it's a mutation in the DNA that this sequence contains. It turns out when chemical carcinogens bind covalently, as we first found, to proteins and then to nucleic acids, that actually the chemical carcinogen can actually cause the mutation that caused this cellular oncogene to become a viral oncogene--so-called--and cause the tumor. So it's getting down to the molecular level--but that's not our work.

JM: Things move all the time. So you've got to keep running to keep up with it, 02:58:00because there's so many people doing research, and research has become so much more--I guess in a term, productive--in terms of the time that it takes to make a finding and capitalize on it and move ahead. And of course you've heard the old story--what is it?--90 percent of all the scientists that ever lived are still living. Science only goes back 300 years--real honest-to-God experimental science. That's all. I mean there were smidgens before that, but the real idea of testing--looking for truth in the material world we live in by testing nature all the time against your ideas--by experimenting--that somehow took a long time 02:59:00to crystallize. It really started basically with Galileo. Before that the Greeks disdained doing anything with their hands. That was an artisan's work or something like that--a worker's--a laborer or something. They'd rather try to construct a theory of nature in their brain and expect it to be correct. That was a strange thing. I guess they weren't the only ones. I've been reading a little bit about Chinese science, because you know the Chinese--in their very long history--came across quite a few different things--some medicines, gunpowder, and so forth--but their top thinkers never considered trying to probe 03:00:00nature by experiments with their own hands.

EM: We have a lot more tools for doing it now.

JM: Yes, we do, but still in all it--

LS: [inaudible]

JM: Yes, somehow that never got across. That's so--what so impressed me about science in my formative years in the twenties and thirties. It gave answers that you could have some confidence in because it tested nature. You could worry about all you wanted about where you came from, what your purpose in life was, and what was going to happen in the so-called year after--and never come up with any answers except pure faith. That's all it's based on, there is nothing you 03:01:00can do about it. So I've grown up to the point where over the years I think you have to live with uncertainty on most aspects and I think to the large degree they're a waste of time to spend your precious time on. You can live a good life and in the service of man by almost ignoring them. That isn't to say that religion isn't good. It's done a lot of harm in many respects, but it nevertheless codifies conduct and, of course, that's taken out of the hands of religion to a large degree now, and thank God I live in this country. Well, I 03:02:00mean you have to have some basic idea of what your role in life is and the reasons for doing things--and science certainly can be misused along with anything.

LS: How important has it been to you that your work had to do with this disease--this dreaded disease?

JM: Well, I think that's given it a certain degree of urgency, so-to-speak, as much urgency as you can put into research, because research does go slowly sometimes and it seemed like it was a good reason to go into it because it--even when we started it it was becoming rather prominent as a disease and of course now it's--with all the great advances in science, nutrition, medicine, 03:03:00antibiotics and so forth--now public health, public hygiene--you have now an increasing length of lifespan. I mean--I was just reading some of this in a recent National Geographic with their photograph of the fossil face on it--this is history of early man--all their important findings. And most of the skeletons that they've found they've dated, and they know how long they lived--usually in the twenties. And then you realize at the turn of the century in this country the average lifespan, believe it or not, was in the forties. It's just amazing. Now it's up in the middle seventies.

LS: I'm going to my aunt's 106th birthday.

EM: I hope she's healthy. I mean that's the kind that counts.

JM: That's wonderful. So now by preventing and treating so many of the bacterial diseases and viral diseases, we now have diseases of old age and cancer is one.

LS: I was interviewing John Ferry in chemistry, in polymers and it had something to do with industrial--from my point of view it'd certainly be more interesting to be involved in the medical sciences.

JM: Well you see important polymers in cells are proteins and nucleic acids.

LS: Yes, I suppose so.

JM: They are the ones that can contain information, you see. The DNA contains information. That's what it is. It's the blueprint of the cell and in that huge 03:05:00long string of four different bases and different sequences--millions--molecular weight--millions of these bases is stored all the information needed to make that whole cell and control it. That's fascinating. And then you can speculate about how that came about.

LS: But you, yourself didn't get into this [inaudible]

JM: It proved to be an endpoint that was highly desirable--we were a long ways from it. But it's going to come, sooner or later. In the case of chemical carcinogenesis, an important aspect of this is that it gives a possibility of prevention of many types of cancer, as you learn more about the carcinogens in 03:06:00the environment and those that derive from habits such as smoking, excessive drinking, and so forth. Those aspects are quite good and plus the work of the cancer epidemiologists, who shouldn't be omitted, which has been brought about by their work in just the last, I would say, 30 to 40 years. They are--the study of the incidence of cancer at different tissue sites from country to country and in migrants going from one country to another. They come up with the conclusion that a high proportion--like anywhere from 60 to 90 percent, depending on the situation--of cancer that occurs in the human is somehow influenced by strong environment factors. Now what these are--diet surely is one, exposure to 03:07:00carcinogens--and carcinogens have been around long before man ever came on the scene, long before plants were making chemical carcinogens, long before man ever evolved and even some inorganic carcinogens were here before life evolved. So that the more we learn, the more may be able to prevent the occurrence of cancer, at least--or perhaps we may not--if man lives long enough. It may be a biological inevitability, but at least we ought to be able to postpone it by another couple of decades after the seventies.

EM: I think it's getting kind of beyond the purpose of the oral history.

LS: Is this a good point at which to stop?

EM: I think we are pretty well--

JM: Yes, sure.