Jenny Glusker

JennyGluskerOctNewsletterDr. Jenny Glusker is a professor emeritus at Fox Chase Cancer Center in Philadelphia. One of her primary interests is chemicals that cause cancer and how they work. She also investigates enzyme mechanisms involved in growth and how the enzymes control these mechanisms. She has co-authored textbooks on crystallography, a method that is used to determine molecular structures. She has been a Sigma Xi member since 1956.

An Interview with Dr. Jenny Glusker


Hello, this is Heather Thorstensen, I am the manager of communications with Sigma Xi, The Scientific Research Society. Today I’m talking with Dr. Jenny Glusker. Dr. Glusker is a professor emeritus at the Fox Chase Cancer Center in Philadelphia, Pennsylvania. She is Sigma Xi’s 2014 winner of the William Procter Prize for Scientific Achievement. Since 1950, the Procter Prize has been awarded annually to a scientist who has made an outstanding contribution to scientific research and has demonstrated an ability to communicate the significance of this research to scientists in other disciplines. She will accept her award at Sigma Xi’s Annual Meeting, November 7, in Glendale, Arizona. Dr. Glusker, thank you for joining me on this call.

My first question is about your work having to do with your start at Oxford and you were working in the lab with Dorothy Hodgkin. Can you talk a little bit about your working experience with her? She went on to win the Nobel Prize.

I was very lucky to be able to work with her. I had gone as an undergraduate to Oxford to study chemistry and Dorothy Hodgkin was my tutor who helped me get through the three years of college and then one year of research where I did some spectroscopy. But I wanted to continue and do graduate work and I decided that I would really like to work with her. I always found her to be a very friendly and helpful and knowledgeable person, and I thought I would learn a lot, which I did. So I went to work in her lab. I knew nothing of crystallography. I remember the excitement of getting my first x ray diffraction picture, which is how we work with crystals to get [molecular] structures. And she was at that time working on vitamin B12 and I was able to help with the determination of a structure of a compound that had all the unknown parts of the molecule, chemical formula and a molecule with more than a hundred non-hydrogen atoms and quite a very complicated molecule that we all need to survive. It’s used as a cure for pernicious anemia. You have to take vitamin B12, usually by injection and that will kill pernicious anemia, which used to be a nasty disease but now pretty much taken care of.

She was a very good scientist, anxious to find out the actual results. Very helpful. Critical at times, but she could do it so that you were anxious to do the right thing. I had a very pleasant two years working with her and we got the structure and she allowed me to be the first person to announce the actual results in a meeting and I thought that was very nice of her. And I could meet a lot of the other famous people in that area of science. This year is the International Year of Crystallography so it’s a hundred years since the first crystal structure has been determined. So we are now celebrating that this year.

Can you explain, for people who many not know, how crystallography is used in your field?

What you do is you have to grow a nice, little crystal but quite a small crystal, a few millimeters in size, much smaller than an inch in each dimension. You grow this little crystal and you shoot an x ray beam at it, a little, fine x ray beam. You have the x rays go down a hollow tube to make sure you get a very fine beam. When it hits the crystal—the crystal is made up of multiple little building blocks, each the same, that contain molecules that you’re interested in—so as the x ray is scattered from the molecules in the crystal, you will get an x ray diffraction pattern. If you’re not used to what the word “diffraction” means, you can see it for example if you look through a drape—a curtain—in a hotel room and you look into the distance, you can see a few spots around the original…if you’re looking at street light at night, you will see little dots around the edge and that is what we try to analyze and see if we can find out what molecular structure gives those extra dots on the diffraction pattern.

And then you went to Caltech [California Institute of Technology] and you were working on a peptide. Can you talk a little bit about what that was?

Well I finished my degree but I had met the man I was going to marry who was a Rhodes Scholar so I went to the United States—I was originally English—so I wanted to go and study in America for a while. Dorothy Hodgkin arranged for me to get a position working in the lab of Linus Pauling and Robert Corey, who were then interested in what proteins look like. And Linus Pauling had just won the Nobel Prize for his work in chemistry. So I went from one wonderful teacher who won a Nobel Prize to another wonderful teacher who won a Nobel Prize. So, as you can imagine, I was extremely lucky and I had a very nice year working there. It wasn’t long enough to do a tremendous amount of work but I learned a lot about the field. And then I was married so we were both looking for a job and I wanted to do research. And that’s when I came to Philadelphia and my husband came, too.

And that’s where you started work at Fox Chase and you were working there on enzyme mechanisms. Can you talk a little bit about what that was?

At Fox Chase Cancer Center, the main interest was growth and what makes things grow and what makes things stop growing. And you could see why this would be important in the study of cancer. So anything to do with growth was being studied in those years. This was the middle 1950s, so it was quite a long time ago. And there was a crystallographer there who was very famous because he worked out one of the most important ways of analyzing the diffraction pattern and getting a crystal structure. So again, I wanted to work with him. And I worked with him for 10 years until he died and then I continued the lab. So we were [particularly interested in] molecules that are involved in life cycles and how you get energy to work and so on. And so we were interested in quite simple molecules but how they were converted one to the other. And it was still before anyone had determined the structure of an enzyme. So we were looking at it from the point of view of the molecule that the enzyme worked on. Enzymes are very important in life because they work and make chemical reactions go better so that we can have energy to work, we can breathe…all that kind of thing and so on. So I was studying enzymes in the Krebs cycle, which is one of the cycles that you would learn about if you were studying biochemistry. And in so doing I eventually was able to gather up the data that we had and make a suggestion as to how one molecule got converted to another and I’m still interested to find out how we can get evidence to really prove that particular suggestion. I have been working since then on other enzymes.

And you’ve also worked a lot on compounds that prevent cancer and those that cause cancer as well.

Yes, yes. Well of course the structure of DNA is very interesting because it’s got a backbone, which is a helix. And most people when you talk to them about DNA, even if they’re not biologists, they will usually take their fingers and draw a little helix in the air for you, so they all know that DNA has a helical structure. What the helical structure is, it makes the base pairs…they pack in a very specific way and they are flat but sometimes if another flat molecule comes along, it might insert itself between two of those bases, sort of stretch the helix just a little bit. So I was interested in what the relationship was between the structures of some of the molecules that prevent cancer or are used in treatment of cancer, mostly flat molecules or fairly flat molecules and if they had any indication of how they might fit in the helix, for example by having a little bit of them that’s not completely flat. And so the kind of chemicals that you get in cigarette smoke and soot and industrial waste and so on—in the air so inhalation, or taking it in by mouth, will give you problems. So it was quite interesting. The molecules involved were molecules like benzopyrene.

And then, your recent work: Can you talk a little bit about the stuff that you’ve been working on lately?

I retired a while ago, but I’m still working in collaboration with people at Los Alamos National Lab and Oak Ridge National Lab who are now working on neutron diffraction. And neutron diffraction is interesting because it can give you different information about atomic arrangements than x ray diffraction gives you. X rays, of course, are waves; neutrons are little particles but they work in rather the same way. The radiation is scattered, [and the results] depend on whether you shoot x rays or neutrons at them. So you can get a lot more information on what hydrogen atoms are doing in enzyme reactions and so I’ve been working with the people there, just sort of helping in some of the analysis to figure out more in detail about how enzymes might work because now we know exactly where to find hydrogen atoms, instead of having to make a guess. Hydrogen is the lightest element and so it’s hard to diffract x rays at all, you can almost neglect the hydrogen atoms in a protein structure, or they’re hard to find anyway. Only if you have very, very good data are you able to get good information on them. But they scatter quite heavily with neutrons so you can get a lot more information.

And then the other thing that I’ve been doing lately also is trying to figure out what various metals do in enzymes and looking at all the…hundreds of thousands of crystal structures have now been done, looking to see how the metal might bind oxygen and nitrogen and sulfur atoms around it, as it would in a protein and then get some information about how calcium might behave slightly differently from magnesium, behave very differently from copper or zinc. That has been a great interest of mine, just analyzing all the structures that are done which have the particular atom, a heavy particular metal atom in them.

What would you say your goal is to figuring out how these metals bind to molecules?

The goal is to be able to characterize what kind of binding a given metal has. Because you might say, well I won’t use this metal and this enzyme uses a particular metal but if I change the metal I might get a different result. The reaction might not work but it might still bind in a place where the normal atom would bind. A lot of enzymes like to bind magnesium and you might find that, well for example, we do know that manganese will also bind where magnesium binds but what happens if there is no magnesium available but you give it some rare metal, rhodium, or something? What will it do with that—Because maybe that’s also another line that might lead to some new medical discoveries of reactivity of metals in various systems.

Something that inspired your love of chemistry when you were younger was your chemistry set, which probably had chemicals in it that kids today might not be able to get a hold of. Do you think that this has any kind of effect on kids’ ability to get excited about science?

Well, when I was young, first of all I did have a chemistry set which I loved and I was able to get all kinds of chemicals, mainly because my father was a doctor and he would help find them. But I also learned to be very careful how I used them. A lot of my friends also had chemistry sets so we would have sort of competitions, you know. Who could make a bright green solution? Who can make a purple solution? Or, how can you do something in the garden that makes it explode a little and it was a lot of fun. But we did learn to be very careful. And then, I had a very, very good chemistry teacher so that helped, too. A lot of people tell me that they really didn’t enjoy chemistry in school and I think part of that may be that you got to be rather careful what you do with chemicals. You know, you can’t mix them indiscriminately. If you want to smell them, to see if you made another horrible odor, you might be inhaling something that’s quite dangerous. So you really need to have some kind of supervision.

I’m not quite sure but growing crystals, all students love. And you can learn to grow very interesting crystals. And it’s possible to grow for certain chemicals with different colors of the same kind of arrangement of atoms. You can grow a crystal for example of an alum with a purple interior, nice crystal growth, and then you grow it in a solution that doesn’t have any color to it so you’ve got a very interesting-looking crystal. Once young people start to do that—in my lab anyway, they have greatly enjoyed doing that. And then we can teach them to try and find out the structure by doing a diffraction experiment. But of course until they’re 18 years old, they can’t do anything with x rays. Because that’s state law, where I live it’s state law, and should be. So we have to take the photographs for the diffraction photographs for them and then teach them to analyze them. So then they learn to use computers as well as learning some chemistry. So we do have some quite excited students from time to time.

I once was asked to talk to a group of high school students who were visiting Fox Chase Cancer Center and they said “you have five minutes to explain the whole science to these students,” which is quite a difficult thing to think about. So I took in to where the students were, I took a model of DNA and I took the crystal structure of bits of DNA and I was able to show them what the relationship was between the actual molecular structure and the diffraction pattern. So yes, you can teach that.

And you had mentioned when we had talked about your chemistry set that your chemistry teacher was very inspiring to you, she was a female teacher and of course Dorothy Hodgkin was a woman and a professional researcher. And I wondered how important having those mentors was for you as a professional female researcher yourself.

I went to school in England in the public education system, as here, you know. I didn’t go to a private school or anything. So in those days, you went to a girl’s school or you went to a boy’s school. So most of my teachers in school were women, except for a few cases where the woman were called for war work and a man came and substituted for them, if you can believe that but that did happen. And I had Dorothy Hodgkin as a teacher but before that, I worked in infrared spectroscopy for a man and I worked at Caltech for two men and then I worked in Fox Chase for 10 years for a man. I have tried both and to be honest with you I was more interested in what they could teach, rather than if they were men or women and I was pretty lucky that they were all nice people. We got along well.

Working for someone like Dorothy Hodgkin, I learned a lot about how to manage a family and research and that was a great help and we did remain friends through all of her life. She had three children and managed to raise them. They’re all very helpful members of the community. It’s kind of inspirational for all of us who worked with her because I hoped I could do that [work in science and raise a family] because my mother had to give up her job when she got married and I think she really missed it.

I think in having to think about my career at this point, which I haven’t done much before, I was very lucky in who I worked for. I hope anyone who is reading this or thinking about it is as lucky.

And you also had experiences with doing a lot of really detailed work with big computers and doing computations to get the three-dimensional map, to get three dimensions on your electron density maps when you were working out the structures of these molecules. What do you think you could have accomplished if you had the technology of today back then?

Oh, it takes my breath away. I mean, the first electron-density map that I calculated took me six months and I worked day and night and I had a whole room to myself with a machine that could only add. You had to fool it. We used IBM cards and we had to fool it to subtract. We had to make sure we didn’t lose cards. And we painted the cards so that we could tell exactly what kind of a function we were adding. Now the whole thing could be done in seconds if not less time than that, so quickly. So I would’ve been able to spend more time looking at a lot more structures. But on the other hand, because it was such hard work, one did also have time to think a lot in depth about particular things one was working on. But yes, science moves much more quickly now. And of course people are working with the larger and larger structures. You know, large groups of enzymes, you can do the structure now. And consider diffraction patterns where there are millions of spots because in the old days, you had to look at each spot and make an estimate of how intense it was. Now the computer will do that. So yes, we are learning a lot more about biological systems and it’s very exciting and wonderful but in the early days we had to learn how to do all these analyses and what works and what didn’t work, and that was what led to the programs and now we have these very fast moving computers. Everyone has their own computer nowadays. You always hope that things will get better as time goes on so this is a case where it really has. And x ray detection is better because of traveling on airlines, they had to have better ways to detecting without giving you too much x rays when you’re going through some of these detection systems. But the computation, what programs like Google can do, to give you information is just wonderful, instead of having to go to the library and look everything up and not be sure where to find it. [Now, using search programs] you can type in a few words that describe what you want and you can find, if it’s chemistry, a system you’re interested in. If it’s done, a crystal structure on it. If so, what it is and you can actually produce on your terminal a picture of the molecule, thanks to the people who have collected all the data and made that possible.

I wonder what’s more rewarding for you, if it’s understanding molecular structures of a protein and getting very specific and detailed, down to that level. Or, if it’s the bigger picture of you’re working at a cancer center and the research that you’re doing is making progress against cancer.

To tell you the truth, I think both of those are important. One keeps all of that in mind, and how it might be helped. But when you start working on a project, you really have to carry it through and find out what the answer is and that does take time. You can’t tackle all the problems that there are. You just have to decide to tackle one area of it and then when you finish finding out how that works, you can go on to another. In other words, you’ve chosen a specific problem to work on that will give information that will help what your organization is trying to find out about, in my case, what to do about cancer. You just have to make sure that you continue with your project and really find the answer and not try and dabble into too many different aspects at one time.