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00:00:55 I know you were born in New York in 1913,

00:00:58 and perhaps you could tell me a little bit about

00:01:00 growing up in New York, about your family,

00:01:02 about some of your early education.

00:01:05 Well, my mother and father were both immigrants from Russia,

00:01:09 and I lived in the Bronx as a child.

00:01:13 I started school when I was five and a half,

00:01:17 and it rushed me through because it was just after World War I,

00:01:21 and the schools were very crowded,

00:01:23 and so I skipped many times.

00:01:27 And so by the time I graduated from high school,

00:01:30 I was only 14.

00:01:32 My father encouraged all this.

00:01:34 He thought the faster I got through school, the better.

00:01:37 And he was very much interested in my education,

00:01:41 and he had the greatest respect for scholarship and so on,

00:01:46 and he was very supportive of my wanting to study

00:01:51 and go to college and so on.

00:01:55 We lived first in an Irish Catholic neighborhood

00:01:59 where we were definitely a minority,

00:02:01 and I was made very aware of this.

00:02:04 But later we lived in a cooperative community

00:02:08 that was entirely Jewish,

00:02:10 which was also a very strange and unusual environment.

00:02:14 It was a very exciting time to grow up in New York City as a teenager

00:02:18 because in the 30s there was all sorts of experimental theater and so on,

00:02:22 and I was exposed to a great deal of that kind of thing.

00:02:29 For example, I belonged to a dance group,

00:02:31 semi-professionally, I may add.

00:02:34 We actually performed with a professional group.

00:02:37 So I had all kinds of really very exciting and rich cultural life as a teenager,

00:02:46 and I'm very glad that I grew up in New York City at that particular period in history.

00:02:53 And while I was still in grade school,

00:02:56 I had a friend whose father was in the cosmetic business.

00:03:02 He had beauty salons, and he also sold cosmetics that he manufactured himself.

00:03:07 And he encouraged both of us to become chemists.

00:03:10 He said it was a wonderful field in cosmetic chemistry for women.

00:03:16 So the seed was planted when I was about 12 years old.

00:03:23 In high school I had a very good chemistry teacher,

00:03:26 and in fact I took two years of chemistry in high school.

00:03:29 I doubt whether that's still available in the high schools of New York today.

00:03:33 But in any case, at that time there was an introductory course and a more advanced course,

00:03:39 and I took both of them.

00:03:42 When I got to college I was so excited about everything that I was studying

00:03:47 that I wasn't at all sure that I wanted to major in chemistry

00:03:51 after the first half of my freshman year.

00:03:57 But then I thought about it, and with the arrogance of youth,

00:04:00 I decided I could learn other things like the humanities and the social sciences myself,

00:04:05 but science I really had to study.

00:04:09 And so I did become a chemistry major at college.

00:04:12 I should tell you that even at 14, which is when I entered college,

00:04:18 I was really very much interested in abstract thought and so on,

00:04:23 and physics appealed to me too.

00:04:26 But at Hunter College at that time there was no physics major.

00:04:30 Girls weren't supposed to be that interested in physics,

00:04:33 and so there was no possibility.

00:04:35 I took it as a minor, which is all one could do.

00:04:38 But I was attracted, even in chemistry, to the more physical side of it

00:04:44 because I felt that's where you learned all about the principles of the subject.

00:04:49 And so I knew by the time I finished college

00:04:54 that if I pursued any area, it would be physics and chemistry.

00:04:58 Of course, I graduated in 1931, which was in the depth of the Depression,

00:05:05 and it was very hard to get jobs anyhow.

00:05:08 So entering Columbia was not a problem.

00:05:12 Did you consider other graduate schools?

00:05:14 Oh, yes. I applied to many graduate schools.

00:05:17 In my ignorance, I even applied to Princeton.

00:05:19 I didn't realize.

00:05:20 I knew that undergraduates were all male,

00:05:22 but I didn't realize that even the graduate school didn't admit women, which it didn't.

00:05:26 They wrote me a polite letter telling me that.

00:05:29 But nowhere, in spite of the fact that I was Phi Beta Kappa

00:05:34 and had graduated with excellent grades in chemistry,

00:05:38 no school that I wrote to, and I wrote to at least 20,

00:05:42 offered me a scholarship of any kind.

00:05:45 And I could go to Columbia and live at home

00:05:48 so that I at least didn't have to pay for room and board,

00:05:51 and so that's what determined my going to Columbia.

00:05:54 Okay. And actually, you couldn't be supported at Columbia either?

00:05:59 Oh, no. No, no.

00:06:00 At Columbia, either you got a scholarship, and there were none,

00:06:05 which I figured, for example, there was a scholarship for a young woman

00:06:10 who came from Ohio whose parents had been missionaries in China or something of that sort.

00:06:15 Obviously, there were no scholarships for young Jewish girls from the Bronx.

00:06:20 But there were assistantships where the students were lab instructors.

00:06:29 They didn't give those to women either.

00:06:32 Columbia College was, after all, a male college,

00:06:36 and they told me that they had had bad experience in World War I with women,

00:06:42 and so they had no women teaching in Columbia College.

00:06:46 So I couldn't get an assistantship either.

00:06:49 In a year at that time, you could get a master's degree.

00:06:53 There was no requirement for any research work.

00:06:56 If you had done well in your courses, that's all there was to it.

00:06:59 They handed you a master's degree.

00:07:01 If you hadn't done well, you had to take an examination.

00:07:04 And I apparently did well enough that I didn't have to take an examination,

00:07:08 and I got a master's degree.

00:07:10 I was very disappointed that you never got into a laboratory except in coursework.

00:07:14 You didn't get into a research laboratory.

00:07:17 And I had gone to grad school thinking that I was going to do research.

00:07:21 And when I got to Columbia, I found that one couldn't do research

00:07:24 until one had passed the qualifying examination.

00:07:27 And that usually took at least a year and a half of coursework

00:07:31 before you could take the qualifying exam.

00:07:34 So in that first year, I had no opportunity to do research in the chemistry department.

00:07:42 What is it that enamored you about a life in research?

00:07:45 You had done no research as an undergraduate.

00:07:47 I know, but I was very curious, intellectually curious, I think.

00:07:52 And I was very excited at the idea of finding out new things.

00:07:56 I must admit I had a much more romantic notion of what research was like

00:08:01 than I have today when I know how much of it is just tedious and routine.

00:08:07 It's only the moments when everything falls together that are as exciting.

00:08:13 I had the notion that something exciting happened every day,

00:08:16 but I was naive enough to believe that.

00:08:19 But I really thought it would be wonderful to find out something new.

00:08:24 And so that's why I was so anxious to do research.

00:08:30 After two years, you returned to Columbia.

00:08:34 Well, first I thought perhaps I took a leave of absence.

00:08:38 I didn't actually quit because I had thought of a problem

00:08:41 that I thought was suitable for a Ph.D. in chemical engineering.

00:08:45 And this had to do with the evaporation of the injected fuel,

00:08:51 which comes out in a spray of drops.

00:08:53 And it's very important, the rate of evaporation.

00:08:55 I had figured out how to do this thing.

00:08:58 So I thought, well, I'll try to get into the graduate program in chemical engineering.

00:09:03 And I went to see the head of the chemical engineering department.

00:09:07 They had no women students at that time, and they didn't inform me.

00:09:12 They didn't plan to start with me, so that was that.

00:09:15 So I went back to the chemistry department and dropped that idea.

00:09:19 And I decided that I wanted to work with Harold Urey.

00:09:24 He had been one of my professors in the course that I took that first year in thermodynamics.

00:09:32 In fact, I took two courses with him.

00:09:34 One in thermodynamics and one in molecular spectroscopy.

00:09:37 And I was so impressed with him that I thought he was the man that I wanted to work with.

00:09:43 I should tell you that the attitude in Urey's laboratory was

00:09:47 whatever you had to do for your experiments, you learned how to do.

00:09:51 And this stood me in good stead in later years.

00:09:55 Not everyone is trained that way.

00:09:58 In those days, there were many things you couldn't buy, and you had to make them.

00:10:03 For example, one of my fellow graduate students was studying the separation lithium 6 and 7.

00:10:10 And he not only built a column two stories high in the stairwell of the building,

00:10:17 he had to have a mass spectrometer, a different kind, that worked with solids for his analysis.

00:10:24 And he went down to the Bureau of Standards and worked for a while with someone who had one.

00:10:29 Then he came back and he built one.

00:10:31 And that was sort of accepted.

00:10:33 I mean, that's the way you worked.

00:10:35 And so from that point of view, I think I had an excellent training.

00:10:39 No matter what the problem was, you found out, you went to the literature,

00:10:43 you found out how it was done, and you did it.

00:10:46 And sometimes you had to invent your own.

00:10:49 When I finished my thesis work, I couldn't get a job.

00:10:56 The notices would go up on the bulletin board, Mr. So-and-so from whatever company

00:11:01 will interview all prospective PhDs of this year, male, Christian.

00:11:06 I was out on both counts, and I never got an interview.

00:11:11 So Uri was so upset that he couldn't get me a job that he offered me a postdoc,

00:11:16 and he asked me what I would like to do.

00:11:19 Well, I had gone to the library and looked up a book on organic mechanisms,

00:11:24 and I picked out about ten reactions that could be studied for a mechanism using O-18,

00:11:33 finding out bond cleavage and exchanges and so on.

00:11:37 And so I rattled these off to him, and he stood there amazed.

00:11:41 He said, you're the first PhD student I've ever had who has any idea when they get through.

00:11:46 So I said, yes, it does tend to make one rather sterile, doesn't it?

00:11:52 But then I was offered another job.

00:11:55 I was offered a job by Divigno.

00:12:00 I got this job, and I talked it over with Uri.

00:12:03 We both decided it would be a good idea for me to take it.

00:12:06 For one thing, biochemistry was a field that was much friendlier to women.

00:12:11 Besides, what they were doing, what Schoenheim and Rittenberg were doing,

00:12:15 was really very exciting.

00:12:16 It was really opening up new business.

00:12:19 And I knew that I was told that Divigno was really a first-class biochemist,

00:12:25 and so I thought this was quite an opportunity to get into a field that was just beginning.

00:12:30 In fact, this is what I often tell young women who want to know

00:12:35 what they should do to have careers in science.

00:12:38 And I always tell them to have a skill that is fairly unique in some area that is just beginning,

00:12:44 and they will then have a much better chance of getting a job,

00:12:48 because that's how I got mine.

00:12:53 So you took the job with Divigno, and you went to Washington.

00:12:57 Yes, he was at George Washington University in the medical school.

00:13:02 And tell me a little bit about his laboratory and some of your work.

00:13:07 He was interested in amino acid metabolism, in particular sulfur amino acids,

00:13:12 cysteine and methionine.

00:13:16 And his first problem that he was interested in was the conversion of homocysteine,

00:13:26 which he had synthesized, labeled with deuterium in the alpha and beta positions,

00:13:34 how it got to methionine and how it got to cysteine.

00:13:38 And so then Divigno looked at the diets.

00:13:41 Now the amino acids were exactly the same, but the vitamin supplements were different.

00:13:46 Divigno had used all the pure vitamins that he could find,

00:13:50 but Rose had used, for his vitamin B complex, he'd used Tiki-Tiki,

00:13:56 which are rice polishings which have all the vitamin B vitamins in them.

00:14:03 And Divigno looked at that and he said,

00:14:06 choline, transmethylation from N-methyl to S-methyl.

00:14:11 And I thought that was amazing, to make that connection.

00:14:15 First of all, he knew that this Tiki-Tiki had choline,

00:14:18 and he was a chemist, so he knew that choline was an N-methyl compound.

00:14:23 And he immediately thought of the possibility of transfer to homocysteine.

00:14:28 So, they added choline to the diet of these rats and they grew happily.

00:14:32 And that's how transmethylation was discovered, and of course went on.

00:14:37 I then worked for the next six or seven years on transmethylation

00:14:42 with labeled methionine, labeled choline, and so on.

00:14:47 So that was really a very remarkable discovery.

00:14:52 After a year with Divigno's group you were married,

00:14:56 and then, while you were still working with Divigno, you had a couple of children.

00:15:02 How did you manage the double life of being an active researcher

00:15:10 and a married woman and a mother?

00:15:15 The way to do it, as I've always told other young women,

00:15:18 in this I think I resemble, in one respect, I resemble a man's mental outlook.

00:15:25 I compartmentalize. When I'm at the lab, I don't think about my home.

00:15:29 When I'm at home, I don't think about the lab.

00:15:31 At least that was so when my children were young.

00:15:35 When they got older and didn't need me, sometimes these things overlapped a bit.

00:15:39 But that's how I managed.

00:15:41 Otherwise, you get emotionally so stressed that you can't work.

00:15:46 And that's how I did it.

00:15:48 So how did he help you get a position in St. Louis?

00:15:52 Of course, the obvious place to go to in St. Louis was Corey's department at Washington University.

00:15:59 Corey had just become the chairman of biochemistry,

00:16:01 and of course was a very well-known biochemist.

00:16:05 And Corey was coming to New York to give a Harvey lecture.

00:16:10 And so Divigno invited him to lunch and introduced me to him

00:16:18 and introduced me as his right-hand woman that I'd worked for him the past eight years.

00:16:25 And I really was humiliated when Corey said,

00:16:30 Where have you been these eight years?

00:16:32 And then I realized that I was a complete unknown,

00:16:35 in spite of the fact that by this time I had published more than ten papers with Divigno, of course.

00:16:41 Divigno was always the first author.

00:16:44 And I had really contributed considerably to this work, but I was unknown.

00:16:50 But then Corey took you on.

00:16:52 Yes, well, Corey had a talk with me and asked me what I wanted to do if I came there.

00:16:57 And I suggested two problems.

00:16:59 One was this O18 problem of introducing it into enzymatic reactions

00:17:05 to find out what bond was cleaved and so on, which was not known at that time.

00:17:10 And the other problem I suggested was investigating the isotope effect

00:17:15 and kinetics of enzymatic reactions by using deuterium and tritium.

00:17:21 So he didn't say anything, and he listened, and eventually he offered me a job.

00:17:27 I hadn't come there to continue the kind of position I'd had at Divigno's lab.

00:17:34 I wanted to do independent research.

00:17:36 I felt eight and a half years was enough of an apprenticeship.

00:17:40 And they were very wise people, and after six weeks they really understood that I meant it,

00:17:45 and they left me alone.

00:17:47 And Corey asked me again what I wanted to do when I outlined the two problems.

00:17:52 He said that he preferred that I work on the O18 problem, and that was fine with me

00:17:56 because I really thought that was a more clear-cut kind of experimental thing to do

00:18:03 than the isotope effect on kinetics.

00:18:08 Though that, too, is important for mechanism.

00:18:10 The other is more direct. The O18 thing would be easier and more direct.

00:18:15 In the early 1950s, you began to do work in another type of spectroscopy,

00:18:20 paramagnetic resonance.

00:18:22 And in the late 1950s, you were using nuclear magnetic resonance.

00:18:26 Essentially, you were almost a pioneer in both of these areas in the way you used them.

00:18:32 And also in their use.

00:18:34 Can you tell me a little bit about your work with...

00:18:40 Well, I was at that time interested in enzymes that transferred phosphoryl groups.

00:18:48 And all those enzymes require a divalent metal ion for activity.

00:18:54 And the usual, normal one is magnesium.

00:18:59 But they all work with manganese as well.

00:19:02 And manganese is paramagnetic.

00:19:04 Now, I had been interested in paramagnetism way back in about 1940.

00:19:09 I was very much influenced by Pauling's papers on hemoglobin,

00:19:13 where he investigated the iron in hemoglobin by their magnetic susceptibility.

00:19:19 And Washington University, in their physics and chemistry departments,

00:19:24 chemistry and physics, were quite centers of magnetic resonance.

00:19:28 George Paik was there.

00:19:30 And they had excellent electron paramagnetic resonance instruments, home-made.

00:19:37 At that time, they were non-commercially available.

00:19:40 And so I got the idea of investigating the structure of the enzyme complexes,

00:19:49 enzyme substrate complexes, by using manganese instead of magnesium and the enzymes.

00:19:58 And so I started working with EPR in collaboration with a physicist.

00:20:08 That's how I got interested.

00:20:10 Now, I suppose one of the reasons I knew about all this

00:20:13 is that my husband was in the physics department.

00:20:16 But also, I had a background in physical chemistry.

00:20:19 And I'd always been interested in magnetochemistry, as a matter of fact.

00:20:23 And so it was natural that I should go into this field.

00:20:30 And how about your introduction to NMR?

00:20:33 Oh, yes.

00:20:34 Now, NMR, I also knew about because of the activities in the physics and chemistry departments.

00:20:40 Sam Weisman in the chemistry department did both EPR and NMR.

00:20:44 And I found out that if you could distinguish the different protons in a hydrocarbon by NMR,

00:20:50 I thought, well, one should be able to distinguish the three phosphorous atoms of ATP.

00:20:56 And wouldn't it be nice to find out what happens to them when a metal ion binds?

00:21:01 And wouldn't it be nice to find out what happens when they bind to an enzyme?

00:21:05 Okay, but you need a special probe for doing phosphorous.

00:21:08 Yes, sure.

00:21:09 Okay.

00:21:10 Those were available already.

00:21:12 There was a pre-made instrument in the chemistry department, but it could only do protons.

00:21:17 And it was very unstable.

00:21:20 They could only work at night.

00:21:22 And it was not very sensitive either.

00:21:28 And just about that time, Varian started selling NMR instruments.

00:21:38 It was in 1955, 1956, something like that.

00:21:44 They started selling 60 megahertz instruments, 60 megahertz of protons.

00:21:49 And I got this idea in 1955, actually, when I was on sabbatical.

00:21:56 And when I got back in 1956, I wrote to Varian and told him I wanted to look at phosphorous

00:22:01 and would it be possible.

00:22:03 And he wrote back a very enthusiastic letter saying, sure, come right out, we'll do it.

00:22:09 Well, at that time, I had three young children and I didn't have household help that I felt I could leave my children with for a week or two.

00:22:17 So I decided to put it on the back burner and do other things, which I did, until I had a better opportunity to go out there.

00:22:27 Well, that opportunity arose in 1958 when my husband was invited to Stanford as a visiting professor for the summer quarter.

00:22:37 So I got the protons done about the first week I was there, but I didn't get the phosphorous done until about five weeks later.

00:22:42 But the exciting thing was I discovered I had a problem, that indeed I did see the three phosphorous of ATP.

00:22:51 And it was different with magnesium. And when I added manganese, I knocked out the phosphorous signals altogether by the paramagnetic effect.

00:23:01 In 1960, only two years after you received this faculty appointment, you moved with your husband to the University of Pennsylvania.

00:23:12 Your years at Penn were certainly your most prolific.

00:23:16 I think you have over 100 papers from Penn, and I assume that was also personally your most rewarding period in terms of your work.

00:23:25 Well, I don't know. I still am very fond of my years at Washington University. It was quite a different thing.

00:23:32 At Washington University, I worked entirely by myself.

00:23:36 When I came to Penn, the situation was very different.

00:23:41 I had postdocs and lots of them. I say lots of them. I never wanted more than about four people in my lab, anyhow.

00:23:51 And then I had an electronics engineer working for me and a full-time technician, a chemical technician.

00:24:01 So, of course, I became more prolific because I had more people working with me.

00:24:08 And I was very fortunate. I got very good postdocs.

00:24:13 And I was also very fortunate at Penn that after I'd been there about two, three years, I've forgotten the exact date, maybe three, four years,

00:24:26 I was awarded a career investigatorship of the American Heart Association.

00:24:31 And that was something you couldn't apply for. You had to be nominated.

00:24:36 There were only 11 in the country. I think I was the 12th.

00:24:41 Needless to say, I was the only woman. And that was a wonderful plumb.

00:24:47 Tell me a little bit about the work at Penn.

00:24:50 By the time you left St. Louis, you'd already started your work on ATP.

00:24:56 And what were your objectives?

00:24:59 Well, I knew that the manganese affected the proton relaxation time of water.

00:25:07 And I also knew that it depended on how many waters there were in the first coordination sphere.

00:25:13 And I thought I could find out how many waters there were in the first coordination sphere of manganese ATP

00:25:19 by studying the proton relaxation rate of water as affected by the paramagnetic manganese.

00:25:27 First without any ATP and then with ATP.

00:25:30 And that I could figure out from that how many waters there were.

00:25:34 So I was really interested in how the metal was bound to ATP,

00:25:39 why it was required in the catalytic process and so on.

00:25:43 And I started by trying to find out what the structure was.

00:25:46 I then decided that the thing to do was to study the proton relaxation rate of water.

00:25:51 And you don't need a fancy NMR for that.

00:25:53 And my initial work was done.

00:25:55 There was an EPR at Penn.

00:25:58 I used the magnet on the EPR instrument, which, of course, is a very low field magnet.

00:26:03 And that's why I happened to work at 25 megahertz rather than 60, which the NMR instruments had.

00:26:09 Again, it was one of those lucky accidents.

00:26:16 What do you think is sort of the future for chemistry and biochemistry?

00:26:23 Well, it's very interesting.

00:26:24 When I started working in biochemistry, no chemist would even think of touching an enzyme.

00:26:33 And now most of the enzymology that's done is done in chemistry departments rather than biochemistry departments.

00:26:43 I thought back in 1937 when I got my Ph.D. that biochemistry was a great field for chemists.

00:26:52 But in the last 10 years or so, lots of other chemists have gotten this idea.

00:26:57 And there is a lot of what used to be biochemistry now done in chemistry departments.

00:27:03 And I think biochemistry departments are going more and more into molecular biology

00:27:10 and genetic approaches rather than the purely chemical approaches that used to be used.

00:27:16 Not that there aren't plenty of people who do use them and plenty of problems where they have to be used.

00:27:24 But the emphasis is elsewhere.

00:27:29 In particular, I think the future, even in enzyme studies, which used to be mostly on mechanism

00:27:36 and still are to a certain extent, is now on regulation.

00:27:41 Regulation of enzymatic activity, regulation of physiological processes, and so on.

00:27:48 And I think that that is the direction.

00:27:51 Regulation of gene expression, regulation of metabolic pathways,

00:27:56 all that kind of thing of regulation is the area that is being pursued now and will continue to be.

00:28:05 What advice do you have for young people who might be considering a career in science today?

00:28:11 Well, I think, in a way, this is a good time to have a career in science.

00:28:18 There are very great disadvantages now.

00:28:21 I hear all the young people talking about the difficulty of getting grants.

00:28:25 On the other hand, one reads everywhere that there's going to be a terrific shortage of scientists,

00:28:33 both for industry and for academia, in the next ten years.

00:28:37 So it looks good if you're starting now.

00:28:41 You will be assured of a position, it seems to me.

00:28:45 So that even if there are some lean years right now,

00:28:50 I think that the future looks very rosy for anyone who's going in for science as far as getting a job is concerned.

00:28:57 As far as the problems that are available,

00:29:00 I think this is really a fantastic period to be in the biochemistry and molecular biology area

00:29:08 because what with all the genetic engineering and so on,

00:29:13 even using it as a tool in entomology,

00:29:16 it turns out to be very useful and promises to give results that we never even dreamed of.

00:29:23 So I think this is a very exciting period to go into research in this area.

00:29:29 I wonder if, unless you have something more to add, I really appreciate this.

00:29:34 Thank you very much.

00:29:35 Okay.