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Courtesy of Helen Berman, credit unknown.
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Interview of Helen Berman by David Zierler on April 28, 2020,Niels Bohr Library & Archives, American Institute of Physics,College Park, MD USA,www.aip.org/history-programs/niels-bohr-library/oral-histories/44399
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In this interview, David Zierler, Oral Historian for AIP, interviews Helen Berman, Professor Emerita at Rutgers, where she remains affiliated with the Proteomic Center and the Institute for Quantitative Medicine. Berman recounts her childhood in Brooklyn, her early adventures in science working in a lab at Barnard College, and she expounds on how Martin Buber’s “I-Thou” concept, which she learned as an undergraduate, continues to shape her thinking today. Berman explains her early interests and talents in crystallography, which she learned from Barbara Low of Columbia. Berman describes her decision to pursue her graduate degree at the University of Pittsburgh, where she worked with George Jeffrey and where she completed her dissertation on carbohydrate crystallography. She explains the sequence of events leading to her career at the Fox Chase Cancer Center in Philadelphia where she researched nucleic acids, and how a personal health scare led her to make a significant personal and career shift. Berman describes her early involvement with the Protein Data Bank at Brookhaven Lab and her vision to harness computational power to grow the PDB into a massive collaborative effort and the rise of structural bioinformatics. In the last portion of the interview, Berman describes her decisions to move to California, and her recent foray into documentaries that focus on human health issues HIV and diabetes, which stem from her broader interest in improving the way that scientists interface with the broader public.
This is David Zierler, oral historian for the American Institute of Physics. It is April 28, 2020. I’m delighted to be here with Dr. Helen Berman virtually because of social distancing and coronavirus. Dr. Berman, thank you so much for joining me today.
Thank you. I enjoy being here.
Okay. So let’s start with your title and your institutional affiliation.
I’m Professor Emerita at Rutgers University in New Jersey. I’m affiliated with the Department of Chemistry and Chemical Biology, and I’m also a part of the Proteomic Center and the Institute for Quantitative Biomedicine.
Also at Rutgers?
At Rutgers. Now in my retired status, I’m an adjunct professor at the University of Southern California in the Department of Biological Sciences.
And are you currently teaching virtually there now?
I am not teaching. I’m working on a project with the film school at USC.
Oh, wow. Well, we’ll get to that later in the interview. So for now, let’s start right at the beginning. Tell me about your birthplace and your family background and your early childhood.
I was born in 1943 in Chicago. My father was in the Army. He was a surgeon, and they were trying to get from New Mexico to Brooklyn, which is where my mother felt was the only place I could be. She didn't make it, and so I was born in Chicago.
What is the New Mexico connection?
My father was in the Army. He was associated with the veteran’s hospital. I have no idea what he was doing in New Mexico. I know he had been in Tucson, Arizona. But they spent the war years somewhere in the Southwest, and then after I was born they went to North Carolina. When the war was over, we were in North Carolina and I remember people screaming in the streets. I remember that very clearly. When the war was over, they moved permanently back to Brooklyn where my mother’s family lived, and I lived in a neighborhood called Borough Park. They bought a house and I remember marching down the street to the house. Well, my father had taught us how to march, and I remember marching hup, 2, 3, 4, hup, 2, 3, 4 into that house, and that was the house I was raised in.
Mm-hmm [yes]. Were you Jewishly connected growing up? Was your family observant at all?
Well, yes and no. According to my grandparents, no, because my parents belonged to a conservative temple. My grandparents were Orthodox and many of my relatives were Orthodox. My uncle was a cantor. It was a very big family. My mother’s family had nine brothers and sisters, and they were all raised in basically the Orthodox tradition. So when my parents decided to be conservative, that was a step away from where the rest of the family was.
Did you go to public school?
Did you go to religious school?
No. I went to PS 103, which was a public school a few blocks from us in Borough Park. Then I went to Montauk Junior High School and then to New Utrecht High School. They were all public schools. New Utrecht was kind of a rough place to be, and when I asked my parents, “Why are you sending me here?” they said it was very important that I learn how to live with people and not be set aside. I’m sure he had enough money to have us live in a different way, but they chose to live this way, and that actually has had a big effect on my way of thinking.
Where did he work as a surgeon when you were growing up?
He was a professor at NYU Medical School, and that’s where he also got his medical degree when he was quite young. He also had an appointment at Maimonides Hospital, which is a big hospital in Borough Park.
When did you start exhibiting an aptitude in the sciences?
I think I always wanted to be a scientist. I think my parents wanted me to be a physician because that’s what we were supposed to do.
Sure. [Chuckles] Right.
Again, my rebellion was to be a scientist. In 1957 when Sputnik happened, a lot of money was put into science education by the NSF, and so there were these programs all over the place where you could learn how to work in a lab. So when I was 15 I went to one at Yeshiva University, and the head of it was a great rabbi /physiologist named Moses Tendler. Moses taught us in the morning. We learned physiology, and then we were sent around to different labs in the city. So you have to remember I commuted from Borough Park to 181st Street by train because that’s what we did.
(You know, we walked ten miles in the snow.) It’s not like that now! [Laughing] So I went to Yeshiva, took the physiology course. Then I wound up in a lab at Barnard College at Columbia, and I worked in a lab studying active transport. My job was to fetch the rats from the animal colony, which was on the roof of one of the buildings at Barnard, remove kidneys from the rat, slice the kidneys and then study active transport of the kidney slices. The professor who was head of the lab was a woman named Ingrith Deyrup, who was a zoologist and eventually wound up going to University of Washington, but when I knew her, she was at Barnard. She strongly encouraged me to apply to Barnard although I was supposed to go to Brooklyn College. That’s where my parents felt I should be.
Now to turn back the clock just a few years, you mentioned you wanted to be a scientist from at least the age of 15. So I’m curious if you can remember, as a 15-year-old, what did that mean to you? What did it mean to be a scientist?
I have no idea. It just meant that I was going to understand things about science. I mean, I lived in a household where there was talk about medicine all the time. My father graduated from college when he was 19. He went to NYU, and he was not allowed to go to medical school because he was underage at that time. So he went and got a master’s, and I believe it was in physiology and I believe he was studying with somebody who studied kidneys, which is very interesting because then I wound up in this lab studying kidneys. I had no choice about which lab I was going to be in; that’s where Moses put us. So I think it was just in the household that that’s what I was supposed to do. But he always said I should get an MD and then I could do science, and I always felt, “No. If I’m going to do science, I’m going to do it for real.”
So I worked in the lab and I had to basically euthanize these animals and I didn't like that at all. So that made me decide that I wanted to be a physical scientist rather than a zoologist. Ingrith convinced me to apply to Barnard and I did, and I went to Barnard as an undergraduate.
Did you ever consider schools outside of New York? Was that within the realm of possibility.
I considered it, in that era in my community, young women were supposed to stay at home until they got married. I did apply to other schools, but one of the schools had a quota. I got into another school that didn't have a quota, but I never got to the place of deciding I wanted to go there. When I got into Barnard, I accepted that offer and then I went to Barnard and I commuted. It was the New York way of life, right? That’s what everybody did. I had to take three trains, and the one was the IRT train which went to Columbia, City College, and Manhattan College. There’s a particular car that you would be in that would let you at the staircase of those colleges, so all the Columbia kids would be in this one car and we couldn't sit. We had our arms around the pole reading. Everybody was doing it, so it didn't seem like such a terrible thing to me. It was fine.
What was your stop in Brooklyn?
50th Street and New Utrecht Avenue.
And that was what, the R?
It was called the West End line.
The West End line, okay.
I think it’s called the B train now.
It goes above ground.
And goes to Coney Island. So that same train also took me to New Utrecht High School.
Okay. My mom grew up on East 3rd between I and J, so I’m familiar with the territory.
Oh, that’s the fancy part.
So she probably went to Erasmus, right? She probably went to Erasmus High School.
Yeah. What kind of science classes did you take in high school?
Just the usual stuff: biology, chemistry, physics. I think I can remember my chemistry teacher’s name was Mr. Safran. I can remember that.
When you got to Barnard, how long before you declared a major?
I don't know, but I knew I was going to be a chemistry major from the day I got there. I make decisions very rapidly, too rapidly, but that’s what I decided to do. The philosophy at Barnard was that you should have a full liberal arts education and that we did not and they did not want us to get the American Chemical Society credentials because they said we could do that some other time. So I took religion, philosophy, music, architecture. I took the full chemistry load, but then I took all these other courses. I think it was very, very important in my career development. I took a course in modern religion where we learned about, you know, all the modern religions, and one of the things I learned about, which I should have known but didn't understand, is Martin Buber. Martin Buber is “I-Thou, here and now,” and that is the basis of my thought processes to this minute. That kept me anchored. But then we had lectures from people from all these seminaries in the Columbia area, so we had Ursula Niebuhr, who was the wife of the great philosopher, scholar Reinhold Niebuhr. So we had all of these things which basically rooted us in the cultures that we were in. By taking all those courses, I actually understood the world around me, which had a lot to do with what I wound up doing eventually.
What was it about Buber that spoke to you so deeply?
“I-Thou, here and now.” I don't believe in God in a conventional way. When somebody asks me about what God is, I say, “God is physics.” It’s very spiritual because if I look around me and I don't understand everything around me—no scientist understands everything around them- and that gives me the sense of awe about the universe. The idea that there is some force out there that I can try to understand and defines how I do my science. “I-Thou, here and now,” meaning whatever work I’m going to do on Earth, I have to do it now because there’s no afterlife for me. That’s how I believe.
Mm-hmm [yes]. So the awe might suggest… You might accept the idea that there might be a creator of the universe without that creator necessarily being involved in human affairs?
I don't think of it in any kind of a human way. I think of it as all the laws of nature around us. I continue to evolve in my religious thought because being raised the way that I was, I couldn't not, but I’ve had to adapt it to the way I think in other ways, and that’s what I’ve done. I still go to a synagogue now, but it’s a little bit of an interesting place, as only Los Angeles can have very interesting ways of doing things! [Laughing]
It’s a long way from Borough Park, I’m sure. [Laughs]
A very long way, although the Chabad here is very active, much more active than in New York. It’s really interesting.
Sure! Well, it’s more outreach opportunities, I’m sure.
So let’s get back to your education. Did you have a senior thesis at Barnard?
Yes! So what happened to me at Barnard was after my sophomore year, this physics teacher of mine named Daniel Greenberg asked whether I wanted a summer job at Columbia Medical School, and I said if he could make that happen, that would be great. He got me a job in the lab of someone named Barbara Low, who was in the biochemistry department at the medical school, and she was a crystallographer. She would have been 100 this year; she died last year. Barbara accepted me in the lab, and I learned crystallography from her. I was 19 when I learned crystallography . I loved the way she treated me, in that she gave me a real job. I had to do real science. She had an expectation of me which I later realized was way more than she should have. I had to do things that were very challenging, but I did it because she asked me to do it and I thought, “Well, that’s the way you do it.” So I just learned what I had to learn. I did my senior thesis in crystallography.
Now Helen, I just want to interrupt there. When you said that you learned crystallography, does that mean that you also learned the underlying physics of crystallography like diffraction and that kind of thing? Or you learned it in an application sense?
Both. Barbara got her degree from Dorothy Hodgkin, and she believed in the Oxford tutorial method. So every week she would get the kids into her office and she would teach us about diffraction or about symmetry or whatever. We would have these didactic lessons that we would have to learn. It was very, very hard for me. I mean, to learn all that was really, really hard.
But again, she did it and she did it as a tutorial. Then she had us in the lab. I mean in the lab, every day I had to go in the cold room, pick a crystal out of these crystallization dishes, put the crystal in a capillary, and then take diffraction pictures and characterize the crystal and say whether or not it was likely to have any differences that would indicate that there was perhaps isomorphous replacement. I did not know any different from what she expected me to do, so I did that every day.
Did you take physics classes to supplement this, or it was all informal learning? It was all in her office.
It was all just tutorials. I had one physics class with Daniel, and I learned from Barbara. She gave us stuff to read and I read it. Then I decided that’s what I wanted to do. I’d be a crystallographer, So she was very happy about that and she thought then I would come to Columbia and be her student. But I needed to get out of New York City for a whole bunch of reasons. When I graduated from Barnard, I went to the University of Pittsburgh where there was a crystallographer who headed up a program that eventually became a department of crystallography. I went there and at the time, I did not understand what I now understand, which is that it might have been better to go to Columbia in terms of issues having to do with pedigree and all that. But I didn't care about that because I was the kid from a home that said, “You go to public school.”
Was Columbia the place to be for crystallography?
Not particularly. I mean the crystallography was a very young field back then, and really the place to learn crystallography would have been England.
But I got accepted in a few places around the country. I think the only reason I would have gone to Columbia was because Barbara really wanted me to be her student.
Your interest in human health issues, was that part of the matrix at this point, or it was really only about the science of crystallography that fascinated you?
At the time, it was about the science of crystallography. Much later it became combining that with health. That became a big issue. But at that time, I was just fascinated by the science. I loved it. I just loved everything about crystallography and I still do. So if I would say what is my heart and soul, in terms of science it’s crystallography. [Chuckles] So I took the trek to Pittsburgh. I remember before I went, thinking about that that must be like on the other end of the world. You know, leaving New York was a really big deal.
But I did and I went there. I was a very good student, and I finished my Ph D degree in less than three years.
Now when the department became the Department of Crystallography, had that happened during your time there?
Where did it come from? What department did it come from mostly?
No department. My professor was English. His name was George Allen Jeffrey, and he did not believe that courses were important. He believed that doing the practical science was important because that’s how an English graduate education is. So we took courses wherever we had to take courses to learn what we had to learn. So I had to take a pretty tough course in the basics of crystallography. We had to read the book by James which was like this thick and it was really, really tough. We had to really learn the basics. He was not going to allow us to just do crystallography.
When you say “us,” how big was the graduate cohort?
I don't know how big the graduate cohort was, but the lab was very big. It had people from all over the world. It was at that time a mecca for crystallography. It had people from Australia and England and Germany and Switzerland. We learned by the apprentice method; I barely saw my advisor. Basically I got some problems to work on and I just worked on them. So the particular area that I was doing at that time was carbohydrate crystallography, and I studied that. I wrote five papers in peer-reviewed journals, and my first paper was in Science.
What was it on? Do you remember?
Yes. It was on the anomeric effect and it was about how the conformation of sugars will affect the valance geometry of the bonds and angles. So the holy grail for most people is that—and even to this day that there’s this sort of ideal carbon-carbon single bond length in an ideal carbon-oxygen ideal, and that’s what people believe. But it turns out that depending on the position of the hydroxyls in the sugars, you’ll get a different bond length because there’s actually a resonance effect. So that’s what I discovered by doing some of the structures that I did. With small molecules you could really get very, very high quality structures with very detailed bond lengths and angles. So that’s what I did. Then there was a theoretical physicist, named Pople and Pople took all of that work and then he did a lot of calculations for several years on trying to understand this anomeric effect.
Then it seemed like a minor point back then, but fast forward to now. When you do large molecule structures, you have these dictionaries of the geometries that it could fit in because at that resolution, you can't really see distinct atoms. There is evidence that depending on the conformation, you're going to get different valance geometries, so the dictionaries really need to contain that. To this day, people are hassling and arguing about how to make those dictionaries. I’ll say, “No, no. You have to take into account the anomeric effect.”
Jeffrey’s own research—how integrated was that with the kinds of things that you were doing?
His big interest were carbohydrates and clathrate hydrates, which were these water structures that formed around hydrophobic groups. So if you have like a methyl group and then have a water cage around it; you basically have a cage. So he had a group that worked on that and did the earliest structures of these clathrate hydrates, so that’s how we know what they look like. His big thing were clathrate hydrates and carbohydrates.
The other big thing that he was interested in, which had a huge influence on me, was the idea that you don't look at just one structure. You look at many structures and you try to get patterns and you try to understand the principles. He was really into categorizing structures and figuring out what I later wound up doing-how you make databases of all this information so that people can learn new things.
He was really into the systematics, and he had a very strong influence on me—not by saying it, but by doing it.
What was his style as a mentor? Was he pretty hands-on with your research?
He was involved?
He basically would occasionally ask me how I’m doing, and then he would tell me, “I think it’s time to write up”. He would very heavily edit everything I did. He also understood my psychology absolutely perfectly because I remember coming into to see him one day and saying, “I’ve been working on this-and-this structure for a certain number of months and I’m not getting anywhere and I think I don't want to work on it anymore.” He said, “Well, okay. That’s the first time you’ve ever failed.” I was 24 years old and I was so angry when he said that. I went back to my little desk and I just worked maybe another two or three months and I finally figured out how to solve the structure. He knew what he was doing. He understood what motivated me.
Did you ever think about going to Oxford as a post-doc?
No. I did not. I’m not sure how much I want to talk to you about the wiring in my psychology, but the answer is no.
I did actually eventually marry somebody from Oxford, which I think is kind of interesting in itself. [Laughs]
What was your dissertation on?
Carbohydrates. It was on carbohydrate crystallography. There were five structures that I did and then I analyzed them. I also had something about the anomeric effect. But again, Jeff’s style was you had to have the papers published, and then basically that was your thesis.
That’s your thesis.
What other fields were represented on your committee?
Peptide synthesis. Klaus Hofmann was the one I remember the most. The rest were other professors in the department. He was not in the department.
So after you defended, you decided you wanted to stay on at Pittsburgh as a post-doc.
I didn't really want to stay on, but I had to for personal reasons, so I did. During my qualifier for my PhD, we had to do a proposal of research that we wouldn't actually do, but it had to be in the style of an NIH proposal. So at that point, I was very interested in peptide chemistry and peptide conformation. Of course, I was very aware of the new protein structures that were coming out. So I made a proposal to study the crystal structures of the known proteins and figure out what the sequence conformation relationships were, and then figure out whether there were patterns that defined, say, what a helix should be or a loop should be or whatever. That’s what I wanted. Then I said to then synthesize model peptides and then do those structures to see whether they would conform. Of course, that could never have happened because if the peptide is too short, you're not going to get the same structure as when it’s wrapped up in a protein, and Hofmann said, “This couldn't possibly work,” and he’s right.
On the other hand, it formed the basis of my interest in looking at sequence structure relationships and finding out a way to get that information, and the only way you could do that was to make a data bank that would have everything in it. So that idea came in 1966, and I began going around talking to people about forming a protein data bank from--I don't think there were more than five structures, okay, but we needed to have all that information. So that all came from my PhD environment.
Now to get back to an earlier comment you made, at a certain point later on you did connect crystallography with interest in human health issues, so I wonder in graduate school when you more closely put those two together.
Well, I obviously did that when I was thinking about these protein structures, okay, but it didn't really happen until I went to the Fox Chase Cancer Center in Philadelphia, where I became a research associate, I was surrounded by biology and medicine and cancer, and so there it became more and more clear that I needed to connect my work to medicine.
So in graduate school you never latched onto a particular health condition that you thought crystallography--
It wasn’t like that.
No. No. It was completely, totally intellectual and totally chemical and crystallographic. That was my interest.
How did the opportunity at Fox Chase come about?
[Chuckles] Well, I was married at the time and my husband was moving to Philadelphia, so I had to go to Philadelphia. I went to an interview in two places, one at Princeton and one at Fox Chase. In Princeton, I interviewed with somebody named Bob Langridge, who then became a pioneer in computer graphics and visualization. I really liked him and I really would have loved to work for him. I drove up to Princeton from Philadelphia and when I got there—this was 1969. When I arrived, before we started the interview I said, “Could you tell me where the ladies room is?” This is in the chemistry building at Princeton. Bob said, “We don't have one.”
You know, I can confirm that that’s… This is amazing. This is the second time I heard that very comment today. I interviewed this morning Bruno Coppi from MIT. He was at Princeton for a while, and he said that same exact comment about when his wife was with him at an event, that literally there were no women’s bathrooms. So if I didn't believe it the first time, I believe it now! [Laughs]
So Bob’s assistant said, “Well, this is how it works.” So she takes me to the men’s room. She said, “I stand out here and guard the door.” [Laughter] That was so traumatic to me, okay, the idea that I’d be in a place that was so hostile towards women that they didn't even have a ladies room in the chemistry department? That told me a lot, okay.
Yeah, yeah, and obviously it’s not about it just being 1969. I mean you didn't experience this in Pittsburgh, it doesn't sound like.
Oh, no. No. They had lots of ladies rooms in Pittsburgh. [Laughs]
So besides Philadelphia being a limiting factor, up until that point, did you give much thought to whether you wanted to enter into a faculty appointment or if you wanted to be in more a research environment?
This has to do with some level of confidence that I did not have. So when I first came to Philadelphia into my position in Jenny Glusker’s lab, it never at that time occurred to me that I could ever be a faculty member, okay? That was not in my head. And Barbara would be calling me on the phone saying she had a position lined up for me in some fancy place in New York and she said, “You’ll get this job. All you have to do is show up,” and I said, “Oh, no. I can't do that,” because that had to do, again, a lot with the way in which I was raised, okay? It took many years before I had the confidence that I now have and understand that I could have done that, but I couldn't back then.
So I went to work in Jenny’s lab. That was in 1969, and I was kind of a rebellious, somewhat hippie kind of young woman. I started working with people that I had met at MIT who were actually doing the same kind of computer graphics that Bob had done at MIT. They seemed more interesting to me, and I wound up sort of hanging out in Alex Rich’s lab at MIT. My colleagues were Joel Sussman who was a student at MIT working at Columbia and Sung-Hou Kim at MIT. Sung-Hou had been a student in Jeff’s lab. Ned Seeman, who was also from the Pitt lab was a post doc at Columbia. So the Pitt lab had Sung-Hou Kim, who became a very distinguished structural biologist; Ned Seeman, who invented nanotechnology, DNA nanosystems—I mean he’s incredible—and then Sundaralingam, who was a big guy in nucleic acids. So we were all in the lab approximately around the same time, and that had a huge influence on us.
I wound up working with Ned and Joel and Sung-Hou, and I was not spending my time in Jenny’s lab. Jenny being the way Jenny is, she just kind of accepted that. I have no idea what she thought. At some point, many years later when I invited her to teach a class at Rutgers, I apologized for my behavior because I said, “How could I do that to you?” and she just said, “Well, that’s how it is.” You know, she’s… [Laughs] She’s chill. But anyhow, I wound up working with those guys and we worked on the crystal structure of a dinucleoside phosphate, which was at that time a very big deal.
Why was it a big deal? What were the ideas?
It was the first structure of a piece of nucleic acid that had all the necessary components, and from that structure we really learned a huge amount about nucleic acid conformation. I worked with them on that, and we wrote a paper with just the four of us. We didn't put our mentors on the paper. That’s how outrageous we were.
[Laughs] Because your mentors really weren't involved, you thought why include them if they didn't really do much of the work?
Yeah. Right, but that’s terrible! I mean that’s a terrible thing to do, but that’s what we did.
Terrible—it’s just bad manners?
Well, it’s probably inappropriate. If we didn't have these guys, we wouldn't have done this work.
Okay. Interesting. Okay.
It’s just really ridiculous, what we did.
Did that come back to bite you in the end, not putting your advisors, your mentors on the…?
No, no. That paper was done in 1971 You know, it was a different era. People were fighting about all kinds of things back then, so this was just small potatoes. Then another colleague from England named Stephen Neidle contacted me whether or not he could work with me and do a sabbatical with me. That was 1976. By that time I was a faculty member at Fox Chase, so I got a position there, a real position. We worked on that structure, and again, that was a piece of RNA complex with a drug that binds to RNA. Little by little I was getting involved in things that are much more biological and much more medical than what I had been doing before.
Helen, at this point did you connect the relatively narrow world you were operating in to larger issues that were responsive to Fox Chase’s mission, or were you not thinking along…? In other words--
Fox Chase had a philosophy which I really liked, and I think it’s very important. Its philosophy at that time was basic research was the key to medicine, and if we didn't do basic research or we didn't understand the fundamentals, then we couldn't understand the bigger picture.
Is that understood to mean basic research as it contributes to understanding cancer or beyond cancer?
Well, in Fox Chase they were interested in cancer. It was a very, very strongly intellectual environment back then where they really believed that you should just try to understand your science the best you could and it would all come together somehow.
Right. Right. So I guess my question is you were not defining research problems, or you were not handed research projects on the basis that it was all definitely related to some sort of cancer research.
It was just learn the science and see where it goes.
We were very strongly encouraged to think that way, and at that time, in that era we all did. That was the golden era of Fox Chase. For example, in 1976 Barry Blumberg won the Nobel Prize in medicine for his work on Australia antigen and hepatitis B.
I knew Barry very, very well. We were really good friends. He actually was another person who had a strong influence on what I wound up eventually doing. He believed that you collect all the data and then the discoveries will come. So in his case, what he was doing was collecting blood samples from all over the world, having absolutely no idea what he was looking for—absolutely no idea, okay? Then eventually he discovered something. He was the one who taught me about databases, relational databases, how you put all the data in, and then you could do a data exploration and something will come out of it.
So that’s how he operated. Another person who was at Fox Chase at the same time I was, an older person (same age as Barry), was Ernie Rose. Ernie Rose was an enzymologist who basically studied the most fundamental aspects of enzymes. Just absolutely fundamental. That’s all he cared about. He read and he thought and he did all that stuff. Eventually he worked on ubiquitin and he got the Nobel Prize for that. Then he had a post-doc named Judith Klinman who again worked on some very fundamental biology and enzymology, and she eventually wound up in the National Academy and at Berkeley. Shirley Tilghman was there. Shirley was one of the early molecular biologists doing molecular genetics. She did brilliant work and wound up going to Princeton and setting up a whole program there and then became the president of Princeton. So this little place just basically said, “You do whatever science you think is important and it will all work out,” and that was the philosophy I believed in.
So obviously the executive leadership, they were scientists. These were not businesspeople.
No. Well, I mean the director at the time, the first director that I dealt with, was a guy named Tim Talbot. He was a physician, but he knew how to just get things done. He called me in once when I didn't have tenure and he said, “I want you to write a grant to the NIH or somewhere to get us a computer,” because we didn't have computers, and I said, “Is that a threat?” He said, “Yes.” [Laughter] So I wrote the grant and we got the grant and then we built this whole program in computation.
The leader after that was a really brilliant, brilliant guy named Al Knudson with an MD-PhD, and he had this idea called the two-hit hypothesis that you have to have the right combination of environment and genetics in order to get cancer. He had studied retinoblastoma and was very well-regarded for his work. He was very supportive of me and my ideas. I could go in and talk to him about almost anything- he was also a very inspirational guy and very supportive. So the environment was like a cocoon! You know, they fed us. They gave us tea every day. All of the administrative stuff was taken care of by other people. All we had to do was our science.
It was so fantastic.
That sounds better than a faculty job, actually!
Then when each of us eventually left and went to other places, we were in a state of shock.
…they don't give you a secretary who will proofread your paper for you, okay, which is what we had! [Laughs] It was a very supportive environment.
Now as you moved up the ranks at Fox Chase, did you remain close to the labs and the science the whole time?
Or did you get to a point where you were managing other scientists?
During that period, I had been involved in a behind-the-scenes thing to develop the Protein Data Bank at Brookhaven, in the early ’70s. Then I had a small lab, with a few people where we did crystal structures. Then I got involved in setting up the research computer facilities and I did that.
Then somewhere in the middle of all that I got cancer. I continued to work at Fox Chase, I had a very complicated feeling about my cancer. I didn't like having cancer, obviously, but I also felt kind of very oppressed by being in a cancer center with everybody involved in cancer. The place where I was being treated was just one door over from where I was working. So I’d come in in the morning, go get my treatment, and then come back to my office just on the other side.
So May 4, 1988, I said to my husband at the time, “If I get through my next checkup okay, I’ve got to leave Fox Chase. I have to do something else,” and so I got through my checkup. My reasoning was that… One reason to stay at Fox Chase during that period was I was afraid I was going to die, and how could I go to a new job if I was going to die? Then when I had this epiphany, I said, “Well, actually, if I die, I’ll be dead and so I won't know what happens, so who cares? If I live, I want to live a different life.” So I got through the checkup fine. I basically made a couple of phone calls and I took the job at Rutgers because again, I needed to be somewhere near Philadelphia. We moved to someplace sort of halfway in between. I lived there for a long time. I went to Rutgers, and that’s when everything kind of came together. I decided that I wanted to do something really big. I was tired of doing something little.
Helen, when you say “little,” what was little about what you were doing at Fox Chase?
Well, I had a small lab and I was very much in the Fox Chase way of doing things, which is small and intense. But I was ready for more. I was ready for more interaction. I was ready for a bigger world. So I went to Rutgers and that was pretty big. Of course, there were zero support services for me. I decided first I wanted to tackle the whole database issue, so I decided to make a database of nucleic acid structures since my research at that point was in nucleic acids. I learned how to make this database. Again, it came from a combination of Barry Blumberg’s influence and my thesis advisor’s influence . Then I realized that that database could be the basis for something much bigger and I could really make the PDB this way. The PDB was at Brookhaven and being run by my colleagues at Brookhaven, and so first I tried to work with them to make it happen. They weren't ready for what it is that I wanted to do. [Chuckles]
What were you articulating? When you were thinking really big, what did really big mean in the way--
Instead of a sort of passive archive, I wanted to have a searchable database with resources where people could learn about molecular science, where they could do structure comparison, where they could do sequence structure—the things that I said I wanted to do when I was 24 years old, okay?
Were computer programs and computational power up to the job for what you wanted and what you envisioned at that point, or were you--
I think so. I thought we could do it, and in fact, they were because we did it. So first I worked with Brookhaven because I had very good colleagues at Brookhaven who I liked very much. I just didn't think they were doing it the right way. So at first I tried to work from behind and help make it happen. That again comes from this upbringing, okay? Just stay in the kitchen and it will be okay. Then at some point I broke out of that mold and I said, “If I know how to do this, stop being so passive. Just do it.”
So I applied when there was a call for proposals. I failed. Then I applied again and succeeded. I formed a consortium of several groups, and we won the competition. Then all of a sudden I could no longer work from behind. I had to lead something big and I had to make it work. There were a lot of people who were saying that I wouldn't be able to make this work because it was not something I knew how to do, they thought. It was a very, very challenging time for me. We worked together and we eventually built what I wanted it to be. It became kind of the gold standard for data resources, I think.
I did that from the year 1998 and then in 2014, I’d identified someone who I thought could handle the project and do it and he came on board. Then a year later, I stepped down and just became a regular professor.
Now in terms of building the database, in terms of your dreams of what the database could accomplish, what beyond that were your goals? What did you hope the database would do?
Well, I thought if we had the data in the right way and if we made it accessible in the right way, we could do structure prediction. It would help design drugs. It could make us understand sequence-structure relationships, make us understand biophysics, make us understand cell biology. I mean there’s all kinds of things that we believe we could do if we had all the data in some coherent way. Now I’m not saying it’s there yet, but it’s pretty far advanced as a data resource.
So a similar question as I asked before. It sounds like still you're not motivated by looking at a particular ailment or illness or syndrome.
You're still looking at the basic science and then it’s going to lead where it’s going to lead.
Basically I believe that my skillsets and my interests are an enabler for science, so I want to be able to do something that’s well beyond what my own head can do. So if I can make a data resource that people can use that will help them understand biophysics, biochemistry, cell biology, help them understand disease, then I’ve accomplished something.
Now you're strategically located in central New Jersey in terms of the pharmaceutical industry. I wonder, thinking about drug design, if you ever had any interactions with people in pharmaceuticals.
Yes, of course. I know that they use the database all the time for helping to design drugs. One of the big stories in the case of the PDB was the story of HIV/AIDS. In 1982, when it looked like there was going to be an AIDS epidemic, various letters and stuff were written. Somebody called from the NIH and said, “We have this epidemic about to happen. If the NIH is going to support structural biology related to HIV, we have to be certain that all the data are available. How can we be sure that will happen?” So it was a call to arms and there were many people involved in this call to arms.
So who were your main collaborators on this?
Many different committees were set up find out what it means to make the data available. What data do they want available and then guidelines were produced to make that happen, and the whole culture of the field changed dramatically. In the case of HIV, people understood that all those data had to be out there, and even the pharma companies put data out publicly. That’s exactly what’s happening now with COVID. All the structures that are coming into the PDB, they’re being released now before publication, because it’s so important. It’s a public health crisis just like HIV was a public health crisis. So that was a a big policy issue that had to be resolved for a public health reason. That’s the way I think, in an indirect way, the PDB is so important, and it’s going to be super important now.
In terms of who helped build the database- before I became in charge, the structures were all in a flat file format, with not enough information, not enough metadata. In the early ’90s before we took over, I was involved in a project called the Crystallographic Information File project. It was headed up by the IUCr, and I was on a committee to figure out how to define the data in a more computer-readable way. So we did that and then when I was not with the PDB yet, and I was doing the nucleic acid database, we used that format to make a relational database for the nucleic acids. We used that as a test to see if it would allow us to really ask questions and compare structures and so on. So that work was done.
There was a committee that was headed up by Paula Fitzgerald, who at the time was at Merck, and she did this as a volunteer effort at night. She used to come down to Rutgers from Merck and we’d work. The computer architect for it was a guy named John Westbrook, who is still with the PDB at Rutgers, and he helped design this new format for biological structure. Then when we took over the PDB, we put the whole PDB into that format. . There were people that we brought onto the project at Rutgers, and then we worked with a group at UCSD headed up by Phil Bourne, who also was involved in this thing. The database has changed but the basic format of the data is the mmCIF format which allows us to really make databases.
Now in the way that you tell it, it seems so self-evident why the database is important, and so that begs the question why you and why then? Why had something like this not existed even before computers, in the sense that it represented collaboration and transparency, right?
Why would something that so obviously needed to exist, why would it not have existed much longer before you thought of this idea?
I don't know. Several people have asked me that question, like, “How did you know that we had to do this?” So remember when we started doing it, there were about five or six structures.
So who cares about five or six structures? Nobody knew that this was going to explode, but I felt it would.
So in the early days, what were some of the feedback mechanisms that gave you the confidence or the conviction or whatever to know that you had really hit upon something and that it was working?
I didn't know.
No. I just believed in it.
So when did you start knowing?
Well, I mean I always knew for me it was important. It took a long time for other people to think it was important, but now I see the numbers. I see how many people access the data, , how much the data is used, how many papers have they written about the data and different kinds of analyses, so it’s obvious now.
So when did that transition happen where you say it’s obvious now and it was only important to you then, roughly speaking? When did that transition happen? Like 5 years ago, 15 years ago?
No, I can't really answer. It was sometime in the last 15 years that I began to see, that so many people were accessing the data.
Mm-hmm [yes]. Now beyond traffic, what other analytics are there available possibly so that you know that collaboration and discovery is happening and pushing science forward as a result of the database—so people coming together and looking at these things because of the database—or that’s really hard to determine?
Well, there’s a whole new field that came as a result of the PDB which is called structural bioinformatics. We wrote a paper when we first took over the PDB, and the paper was published in 2000. That was the paper that we ask people to cite whenever they use the database, It’s been cited about 20,000 times.
So then what we did is an analysis. Who is citing this paper and why were they citing it? First of all, very few people who deposit the data cite that paper, but people who use the data cite that paper. So we started to look at where the papers they were writing were. What areas of science were they in? We discovered they were in structural bioinformatics, computational biology, statistics, several medicine-related papers. The majority of people who cite that paper are in the general biological area, but then there are people who are not and they’re using the data to learn how to handle data,. So that paper has been cited more than 20,000 times. Very few of the people who cite the paper are crystallographers and structural biologists.
Oh, that reminds me. I wanted to ask you during these later years at Rutgers, how close did you remain with crystallography?
Well, I didn't give up. I came to Rutgers in 1989, and I kept my lab going till about 2002. When I took over the PDB in the year 1998, I felt that I could still run my lab, and about four years later I said, “No, I can't do this anymore. It’s a full-time job running the PDB,” and that’s really important to realize that it’s a full-time job. If you want to make it really important, you can't be a caretaker. You really have to do it.
But in running the PDB as a full-time job, are you working in your capacity as a scientist or are you more managing data and understanding the science?
I don't know how to describe it. When I was doing this work, I had to make decisions about what would be the most important things that we needed to do to enable science, so I had to make those decisions with the group. People would ask questions. They would send an irate email about something. That email was often forwarded to me and then I would try to understand what the question they were asking is, then try to figure out if there was a problem with the system we have or only their one little problem. So in order to do that, I would have to actually understand the science because they would say, “This-and-this structure has this and this,” or “Those people are idiots,”
I could be very much in the weeds during those discussions, and I think that was very important. In general, I’m the canary in a coalmine. I tend to see one small problem and then say, “Hmm. This could be a sign that we have a much bigger problem,” okay, and then try to analyze it. So I had to know my crystallography to do that.
Were you keeping up with teaching still at this point or no?
Yes. I taught the whole time; I always taught.
Yeah, yeah. And then from 2011 to 2013 when you had these short-term directorships, was that part of the… You were Director of the Center for Integrative…
That’s another story. When the PDB first came to Rutgers, we had very inadequate space, and it really annoyed me, okay? So I said, “Look. The PDB is too important to be in a trailer.”
[Chuckles] Is that really where it was? It was in a trailer?
Yeah, it was in a trailer. I had a meeting in the early 2000’s. I don't know if you know Jonathan King. He’s a biophysicist at MIT. Jonathan came to a meeting that we had. He walks into the trailer, and he’s a big, tall guy, you know, and he’s also from Brooklyn. He walks in and he says, “Hmm! Does Rutgers realize what it has to lose?” [Laughter] I laughed. He said, “Why are you allowing this?” I said, “Just the way it is.”
So anyhow, I went on this campaign. I didn't really care about the trailer or any of that. That wasn’t that important, but what was important is that we needed to be in an intellectual department. The PDB had to be fed and nurtured in an intellectual environment, so starting in about 2000, I began to say, “Look, we need to have a center that would have all the layers that the PDB represents from the experimental things to the PDB itself to all the analytical and computational work that people do. It should be an example of what you can do with the PDB.” I wanted to have that kind of a center.
I had to do a lot of lobbying, and eventually the university decided that we would have the center. The name I gave it was the Center for Integrative Proteomics Research. We got a building that is just beautiful. On the ground floor there was like proteomics and cryo-EM, and then on the first floor is the PDB. Then the second and third floor was a mixture of computational experimental labs doing different kinds of biophysics and biochemistry that were related in some way to structure. So that’s what we built, and it was opened in 2011. I also believed that we needed to have a very strong seminar program where we brought people from all over the place to talk about their science, and so that’s what we did. We formed that center.
Then when Stephen Burley took over—he’s the head of the PDB—he renamed it the Institute for Quantitative Biomedicine, but it’s basically the same building and he’s recruited some new people. One of the things that I thought was really important was to place the PDB in a good intellectual environment.
Mm-hmm [yes]. Then when did you become emeritus at Rutgers?
I think I began that process in 2016.
Mm-hmm [yes], but from then your intention was to maintain a relationship with Rutgers and teach and still be involved at the database?
Yeah., only in an advisory capacity,?
The person who took over would have to define it in his way, not my way.
Mm-hmm [yes], mm-hmm [yes]. And the decision to move to California—were there teaching opportunities here that you were specifically attracted to, or did you just want to retire to California and you still wanted to teach?
My reasons for coming to California were purely personal. I have a son and a grandson. It’s my only child, and I never expected to see my son get married and have children because you remember the story of when I had cancer in 1982. That was pretty bad and since that time learned I was BRCA1 positive. I had the mutation, so I’m like a time bomb. The only good thing about being BRCA1 positive is that it allows you to have a certain point of view about the COVID virus. [Laughs] I mean I’ve learned to live with catastrophic illness, okay?
I really wanted to be with them for a whole lot of reasons, and so when I retired, I decided I would move close to them but not with them. I’m about a mile and a half away from them., I wanted to find a new thing to do that would utilize my talents and my interests. So one of the things that I felt very strongly about is that I got tired of people not understanding about what structure is. So actually the COVID thing is really interesting because every day people see that virus and the structure.
Now Helen, when you say people not understanding, do you mean your peers or the broader public or both?
I think people don't really get it, okay? We live in a genomic era. People think they understand DNA but they don't really understand why three-dimensional structure should be that important. I’ve heard this articulated many times; I’m used to it. I think it’s interesting. With COVID, there is absolutely no question about the fact that we’ve got to understand what these spikes are doing and then how to prevent the spikes from penetrating the cells. We have to understand about the membrane. We have to understand about what’s inside and what the RNA is doing. I’ve heard enough on TV and I’m kind of happy that people actually are trying. I mean they don't understand it, but at least structure is figuring very prominently in this. I know with the PDB, Stephen has told me that they’re getting a lot of structures in that are all related, and that’s going to be key to developing a therapeutic.
Not only a vaccine, but a therapeutic also?
Yes. I think the therapeutic will probably come before the vaccine because there’s enough we know about RNA-type viruses… I think it’s possible. We have a lot of knowledge that we didn't use to have, so I think it’s possible.
Are you talking to people about this now? Are you involved in coronavirus research at all or you're just sort of watching from the sidelines?
Before I had the meeting with you, I listened to a seminar about how scientists can communicate about COVID if we’re not ourselves COVID experts. One of the things they said in the seminar was that scientists are very mindful about not trying to explain things that they don't fully understand.
And so they were trying to sort of tell us about how we might be able to help in explaining things to people. So anyhow, when I came out here, I knew that being the way I am, I couldn't be passive. Various people encouraged me to talk to people in the film school here, and USC has a really spectacular film school. I went over there and I talked to various people. That’s a long story, but eventually, we built a little team and decided to make a documentary on HIV prevention. We made the documentary--
What’s it called?
Target Zero. You can get it online at TargetZerofilm.org. If you have access to ProQuest, you can get it for free. If you don't have access to ProQuest, then I think it costs $2.99 to see.
So we made this video. There are three stories of people who either have HIV or are afraid of getting HIV The first two stories are prevention of transmission to a baby, an unborn baby, and the third is about prevention in adults. These are real people that were filmed in real clinics in Los Angeles, and then we made a series of animations to explain how the drugs work and what the medicines actually do. So it was a combination of documentary and animation.
I don't know how much it’s been seen, but it’s been seen. We’ve had a couple of screenings, and I have to teach a class at Rutgers on May 18 using this film.
The film is supposed to teach people about how the drugs work, and it also is supposed to teach medical students about how to interact with patients where you have to tell them bad news, or you have to motivate them to behave in certain ways. The film is 57 minutes long. By my film friends’ standards, they say it’s successful. By my standards, I’m not happy because I’d like to have it used more, and I’m still working on projects to make that happen.
My second film that I’m working on now is basically about diabetes. This one is a virtual reality thing, which is much harder than a documentary. We had to create these characters that would be “empathetic.” These are the words they use in the film industry. And we did. We just finished the build on that and we have to figure out how to get that viewed. I want to use that in an educational setting. I’m doing a syllabus now for a course that will show how insulin is packaged and released in the pancreatic beta cell. I am using some of the footage from that film. That’s what I’m doing now. It’s not unrelated to what I did before, but it’s closer to trying to get people to understand the molecular basis of medicine.
You moved to LA and now you're working in film. [Chuckles]
That’s right. I’m very adaptable.
Well, Helen, I want to ask some sort of broader questions now that we’ve brought the narrative up to the present, and the first one is… You know, certainly we don't need to go through all of the many, many honors that you have received, but I wonder if any particularly stand out as a matter of personal pride or evidence of professional accomplishment or recognition among your peers. Are there any from earlier on or later that really jump out at you as being particularly special to you?
Becoming a member of the American Academy of Arts and Sciences was very important to me because that really is a blend of what I do. I got in the same year as Tom Hanks and Barack Obama, so that was nice.
Cool! [Laughs] Now in terms of your long career in service, basically in scientific service on various advisory boards and committees and things like that, are there any guiding principles that you have brought to all of those panels and advisory boards that sort of are informed from basic ways about the way that you see science and how it should be applied, how it should be supported, how it should be communicated? Do you have any sort of overarching principles that you bring to all of those positions?
I’m not sure I can answer your question, okay? I’m not sure I can answer. I think community-based things are very important to me, so I’ve been very good at being on any panel or anything having to do with data because I think people who are doing what is basically community service are not often appreciated as much as they might be.
Aside from that, I mean if somebody can tell a good story about what they’re doing and I can understand it [laughs]…because I think one of the things that I’ve noticed is that not very many people write well, and writing is key to being able to get your science across and have people understand it, and it really annoys me when people try to snow me by writing in not necessarily the most articulate ways. So that bothers me a lot.
It’s very obvious that you care deeply about the way that scientists interface with the broader public.
So I wonder if you could communicate or convey your feelings about this very peculiar moment that we’re in right now where there are crowds of people saying, “Fire Fauci!” just as one example, and where that might come from.
We’ve done an absolutely miserable job of communicating science. As scientists, I think we have not done what we should have done to communicate science.
So what is that? What is the do-over game plan?
Well, you have to explain things clearly, okay, and you have to make it accessible. There are enough people out there—I feel very strongly about this—who believe that if they write in very convoluted ways, and not tell all the details of what they’re thinking or what they’re doing, that that makes them look very smart. I don't like that. So that’s why I like Anthony Fauci, because he tells you what’s going on to the best of his knowledge. He’s an honest straight shooter, as was Richard Feynman. Notice that they all have the same thing in common. They all have New York accents. I’m making a joke, but-- [Laughs]
You didn't have to say it. I got it. I got it. [Laughter]
But I think that’s really, really, really important and people don't get it. So I think in this sort of last stage of my career, if I can figure out how to do this… It’s really hard to do. It’s really hard to do.
But it’s possible. You think it’s possible.
I think it’s possible. As I said, before I talked to you, I attended a webinar about science communication. My daughter-in-law is a science writer and she spends all day long trying to explain complicated things, and I think we need to have much more of that. The scientists have got to get out of this thing that “Well, nobody could possibly understand me, so therefore I’m not going to try.” I think that’s very bad, so I feel very strongly, really strongly about that. So I’ve done a lot of things in my career which are not popular and I know it. I mean I’ve heard people say, “Film? You're doing film? What, are you kidding?” and I say, “Well, people like to look at film. Maybe I can teach that way,” so I think it’s important.
I want to ask you a question within the context of the ACA and your very strong identity as a crystallographer. The context, of course, is that the ACA is one of AIP’s most valued member societies, right? We connected through Virginia, and so the question is sort of beyond your personal career, but as a representative of crystallography over the course of your long career and very broadly based, what do you see as the basic contribution of crystallography in the second half of the 20th century, and where is it headed in the future?
One of the issues that has come up repeatedly in science in general is the issue of reproducibility. How do you know whether something is right or wrong? Crystallographers, from day one, have always been very strong about having very high standards and very strict standards as to how data are represented, how data are archived. I mean that has always been the case. So whereas people sort of fussed around about the exact correct way of representing a macromolecular structure, at least we are representing it. At least we’re producing it. We’re making it available. So the way crystallographers in general have done things to small molecules, big molecules, powder, whatever, has always been to make their data…produce their data in such a way that somebody could actually reproduce the experiment. Maybe some of the things they do are not exactly perfect, could be done better, but compared to other fields… So then what happens to crystallographers is they get into trouble. Well, it must be very easy because you can reproduce your results. So it must be too easy to do, or something like that. [Laughs]
I mean I ran into that when I was on study sections You know, just turn a crank and you get the answer, but that’s not true. I think that crystallography has really led the world in this whole issue of standards, reproducibility, very high standards for how to do the science. So we get involved in these little petty fights about detail. So then other people in other fields will say, “Well, we can't do it that way,” but you can! They could take the time to do it that way. I mean my attraction to crystallography initially was, frankly, totally aesthetic, you know? It’s a beautiful science.
I think many of us who became crystallographers were attracted by that beauty.
I probably then relate to my later interest, my current interest in the art/science interface. I’ve been involved in one way or another. Most crystallographers are very interested in art/science and how that works. They just are. So I think that it’s funny that you have something that’s both aesthetically very pleasing and at the same time very exacting. I think the crystallographers have led in that. They’ve also led in the whole thing of community involvement. The field has always been one where people have to work together.
And it’s been a very supportive community. My mother died in 1994, and I remember writing a piece which I hope I saved about my father and my mother. My father was a scholar and a scientist and a physician, and my mother was a community activist, and I’m a hybrid of those people. I took that value system from both of them. So my mother set up these storefront centers for mental and community health in Borough Park. People could come there and get help. She got some kind of an award from Mayor Koch for doing that, and that was really great. She did that all as a volunteer, and so that’s what I’m doing now. I’m a volunteer. I’m a retiree, but I really want to do something new and different that will help other people. I think that that’s a value system that’s consistent with the value systems in crystallography because there are a lot of political activists in crystallography who spoke their minds very strongly about various things—for example, Linus Pauling and Dorothy Hodgkin, J. D. Bernal. People at least my age had to be very influenced by that. I don't know if it’s the same now, but in my age group that was really important.
And looking forward, I mean with advances in microscopy and things like that, what does crystallography have to offer in the future?
So crystallography still is the gold standard. I work with electron microscopists right now, and their goal is to be as good as crystallography, you know? So that’s okay. This reminds me of when I worked in the cancer center and people said, “Well, what are we going to do if they find a cure for cancer?” We’re going to say, “Hooray!”
So if electron microscopists can get results that are as good as what we can get in crystallography, that’s great.
Yeah. Are you surprised that it hasn’t happened yet?
Well, it’s happening very fast, and I’m working very closely with people on that.
But are advances in crystallography… I mean advances in microscopy are… I mean, they can be exponential because that’s a matter of technology, right?
But if the thing you're working with is a crystal, is crystallography in some way static in terms of what it can do, or are there still always ways that crystallography can push the ball forward also?
Oh, crystallography has advanced enormously since, say, my day when you had to have a crystal that you could see. Now you can work with crystals that you can't even see. Now it’s standard to grow crystals robotically. Well, you couldn't do that. It used to be some kind of voodoo thing that we did. So the technology in crystallography went through a huge advance in the early 2000s. In structural genomics all these robotic methods were done or created to do high-throughput crystallography. I remember people worrying that if we do it high-throughput, the quality will not be as good, and it turned out the quality was better. So in crystallography, I think there have been huge advances and there will continue to be huge advances. If at a certain point the quality of the electron microscopy is such that it can take over crystallography, I don't think anybody will be upset.
Mm-hmm [yes]. Well, Helen, I think for my last question I want to ask something that’s a little forward-looking, you know, looking into the future, and that is given your ongoing and deep involvement in so many areas—you know, teaching, film, remaining involved in some level in the database—what are the things that you really want to accomplish personally?
Of all the things I want to do, I want to really get it so that people are comfortable with structure. I would like these outreach efforts that I am trying to do, I would like to make it so that…
And again, “people,” you mean the broader public.
And fellow…and your peers. Right.
Yeah, and my peers. Yeah.
So what is… I mean if it’s true for both the broader public and fellow scientists, what is it about structure and why is it so important to understand it?
I don't see how we’re going to develop drugs to cure terrible diseases if we don't understand what’s interacting with what. You could do it as a shotgun way and not pay any attention. I think that would be very hard. So some form of rational design is required. If you want to say that we don't really have to know how things work as long as they work, I suppose that’s okay, but I don't think it’s okay. I think we have to understand why they work so when they break we can fix them.
Are you optimistic that structure can be understood and that great things will happen as a result?
I’m not as optimistic as I’d like to be, but I mean ironically, as I said, every time I see a picture of the COVID virus, I think, “Well, at least somebody thinks that it’s worth showing what it looks like.” We don't actually know for sure that’s what it looks like, but we think we know.
That must be the case because you could look at 20 different recreations of a coronavirus and they all look different.
Well, it depends on the representation. That’s a whole other issue about how you represent structure.
Right. Well, Helen, it’s been an absolute delight speaking with you today. I really want to thank you for our time together.