David Rose

Phillips:

Today is July 8, 2023. I'm at the ACA meeting in Baltimore and speaking today with Dr. David Rose. Thank you, David, for being here today and doing this.

Rose:

My pleasure.

Phillips:

As I mentioned a moment ago, start at the very beginning. Tell me a little bit about where you were born, what your parents did, your family life growing up.

Rose:

Okay, sure. I was born in Buffalo, New York, actually not far from where I live now. [Laugh] And my father was a very distinguished MD/PhD. His specialty was autoimmunity. We moved around a bit. I lived in Buffalo right through high school pretty much and went to the local public schools there, and then moved to the Detroit area, where my father was at Wayne State University for a few years. And during most of that time, I was in university. And then, subsequent to that, my parents moved here, to Baltimore, actually. My father was at Johns Hopkins for many years. He was chair of the Department of Immunology and Infectious Diseases in the School of Medicine here and did his final few years of research here.

Phillips:

And in Buffalo, I assume he was at SUNY?

Rose:

He was at SUNY Buffalo, yeah. He, as I said, was an MD/PhD. He never formally practiced, but he did a fair amount of consulting on patients. Obviously, I grew up in an academic research environment. I sort of knew what it was like to have that sort of a career. Although it's a different area of research from mine, I was still surrounded by university and part of university life.

Phillips:

What did your mother do?

Rose:

My mother was–well, she's trained as a nurse. She's still alive. She's trained as a nurse originally and worked, much of the time that we were in school, as a school nurse in the local elementary schools. I wouldn't say she had, like, a formal career apart from that, just basically supporting a lot of what my father did in many ways. But yeah, she did work as a nurse for a while.

Phillips:

Growing up in this scientific and medical environment, was science something you had an early interest in?

Rose:

I guess so. I'm not one of these people who was driven since I was 10 years old to do something specific. Just sort of everything fell into place. But since that was a world that I was familiar with, it sort of made sense to go in that direction.

Phillips:

I understand that when you started your undergraduate, you were a biophysics major?

Rose:

Yes. So I went to the University of Pennsylvania, Philadelphia. I started out actually as a physics major the first couple of years, and that was interesting, but I felt I wanted to get more into the–I wouldn't call it application, but more into the real world, I guess you could say. [Laugh] Partly influenced by my father, I guess, or at least subconsciously. Pennsylvania, at the time, was one of the few schools that had a biophysics major, which was basically just a general science major, in a way. It combined with the physics that I had already done for my first two years with chemistry and biology, which I did mostly in the final two years.

Phillips:

Had you started out planning on an academic career path?

Rose:

No. Not in the formal way. It was a little bit of a default, I guess you could almost say. But I had thought about med school, for example, as another alternative. But the pieces fell into place to pursue a research-based career, so I just followed that path.

Phillips:

Was there anything in particular that led you to that over medicine?

Rose:

Yeah, some of it was summer jobs. While I was an undergrad, I had summer research positions. These were mostly in the Detroit area, so first at Henry Ford Hospital in Detroit, working in a clinical testing lab. Actually, I think I had one even when I was in high school in Buffalo. And then, subsequently, working in a lab close to the area that I ended up doing my research in. And in fact, this was at Wayne State. My supervisor I worked for, I ended up going back to his lab to do a post-doc after I'd done my PhD. His name's Gregory Petsko. He's a quite well-known structural biologist.

Phillips:

By the time you were wrapping up your undergraduate, you'd done a couple years of physics, switching to the biology track, sort of defaulting into this research pathway. When you were looking at graduate schools then, did you have any sort of research agenda in mind already?

Rose:

No, I didn't know anything about crystallography, never heard of it. Didn't know much about protein structures apart from very basic undergraduate knowledge. At Penn, they had an opportunity to apply for funding to do graduate work abroad. A little bit like a Rhodes Scholarship, but at the university level rather than the international level. And so, I applied for that. I didn't actually get it. [Laugh] But I decided to go ahead anyway. It was influenced largely by the fact that my father religiously went on sabbatical every seven years to a different country. When I was, I think, 2 or 3, we were in Paris for a year. Then, when I was 10 or 12, we went to Switzerland for a year. And then, the final one that I was on, when I was in high school, so I was 17-ish, was at Oxford. He was working at the university there. And I went to the local high school. Every one of these sabbaticals, they would send us to school –so in Switzerland, I went to the local school. It wasn't a special American school or anything like that. So that was useful, not just learning about the cultures, living in different places, but also in that case, learning the languages as well.

Phillips:

In Switzerland, was there an English-language school that you went to?

Rose:

There was, but I didn't go to it. I went to the local French school. At that point, I spoke French very well. Haven't used it that much since, despite living in Canada. I've used it a bit. I'm sure it would come back if I had the opportunity. And then, at Oxford, I went to a school called Magdalen College School, which was what we would call a public school. It was sort of a mix. It was associated with one of the Oxford Colleges, but it was also a general school. It wasn't really what we would call a private school. I was familiar with Oxford from just two or three years earlier. And then, when this opportunity to go abroad came up, that was where I was looking to go. I didn't know who to work for. [Laugh] But consulting with, again, this same supervisor I did the summer job with, his supervisor was named David Phillips, so I contacted him, and he was willing to take me on as a graduate student. He very much liked having American graduate students. He had a whole series of them.

Phillips:

What year was this that you went over there?

Rose:

Would've been '77. I graduated from Penn in '77, so it would've been that fall.

Phillips:

Once you were over in England, was there a project in the lab that you just were attached to off the start? Or were you able to create a project?

Rose:

It was a new project. I didn't make it up myself, it was conceived by my supervisor and the collaborator who was working with us on it. And there were people in the lab who helped me with the technical aspects of it because I'd never done any crystallography before. It was still a new area. It was basically protein crystallography. It was pretty much invented in the UK, or at least certainly came to maturation in the UK. You've probably talked to some people in your series who were involved in that. Many of them, I met. Max Perutz, Dorothy Hodgkin, and a whole series of people who were there. Towards the tail end of their careers, but still, I was able to meet them. It was a very inspiring place to be. And it existed in North America, but was still relatively new.

Phillips:

What proteins were you working on?

Rose:

My main project was on a fragment of an antibody. We called it the Fv fragment. It's sort of the tip of the antibody that binds to its target antigen. Tried to get crystals of that, obviously. The only way of doing structures at the time was binding heavy atoms to the structures. Again, you've probably interviewed people who developed these sorts of techniques. It was very time-consuming. It was hard enough just to get crystals, and then very time-consuming to try to get the structure. And I got part of the way to the structure. But it wasn't like these days, where you have to have a whole series of structures and a whole biological story. In those days, even just getting most of the way towards a structure was enough to get a PhD.

Phillips:

And how long were you there?

Rose:

Three and a half, four years. Something like that.

Phillips:

I'm less familiar with how the PhD programs work over there. Did you have any teaching responsibilities or anything?

Rose:

No formal requirements for teaching and no formal courses. So it was all based on research. Having said that, I did take some courses. A crystallography course and some biochemistry courses at the university. But those were basically what we would call auditing. They weren't formal courses as part of the program. But I didn't do any teaching formally. I did a little bit of supervising of undergraduates or more junior students who might've been just getting started.

Phillips:

And this project you were working on, were you the only graduate student working on it?

Rose:

Yeah.

Phillips:

Okay. So small team.

Rose:

Yeah, I don't think he had a big group. I'm trying to remember how many. Maybe six or seven grad students at the time, and then some senior people. One particular person who specialized in growing crystals, so he was key, obviously. In those days, well, it still is sort of a magic art. And this one guy had knack for getting crystals.

Phillips:

After three and a half years, you made significant progress towards this. But when you were looking for post-docs at that point, were you planning to continue the same project or something similar? Or were you looking further afield?

Rose:

I'm trying to remember exactly how I made the decision to go where I went, but again, it was partly because I had worked with Petsko before as a summer student, I guess. And he was also part of the David Phillips lineage or school, I guess you would say, and again, one of the earlier proponents of crystallography in North America. At that point, he had moved to MIT. And I guess we kept in touch, and when I was finishing up, I made my way to his lab, basically.

Phillips:

And what was he specifically working on at that point?

Rose:

Again, it was antibody-based. We were working with a group at Mass General Hospital, I think, at the time. Antibodies to small molecules, how they bound specifically to them, doing structures of those. The lab itself was mostly an enzymology lab. Most of the work was on enzymes, which was what Petsko's history was. This was a little bit of a different venture than most of the lab.

Phillips:

And just out of curiosity, you're working on antibody stuff with Mass General, was this NIH-funded?

Rose:

I assume he was NIH-funded. I don't actually know where his main grants were from at the time. But I think that's normal.

Phillips:

And so, you would've been on that same grant.

Rose:

Yeah, so he would've been paying me off of his research grants. I didn't have an independent scholarship or anything like that.

Phillips:

As a post-doc in his lab, were you collaborating with him on that same antibody project?

Rose:

No, it was a different antibody project. But at the time, I was the only post-doc. I think I was Petsko's second post-doc. He was still a new assistant professor, or maybe one step up the ladder. And he had four or five grad students, I guess. And so, one of my main responsibilities was maintaining the lab. [Laugh] The instrumentation in the lab, showing students how to use various tools–and that's the best way to learn how to do things is to show other people how to do it.

Phillips:

You had mentioned, obviously, that this was a more mature field in the UK than it was in the US, certainly in the 70s, at least. When you came back to MIT, what was the state of the field of protein crystallography in the US?

Rose:

It was growing. Many of the people doing it had come from the UK, done their training in the UK or were British and came across to North America. But the ACA, I think, existed at that time, and they had meetings, and there were enough people. Of course, it's more than just macromolecular crystallography. But there were more and more people doing crystallography. Gordon Conferences existed at that time, so there was enough of a community to have meetings. I don't know what the number of groups were, but it was certainly growing quickly at that time. It was still a fairly specialized tool. More recently, I wouldn't say anybody can do crystal structures, but it's become much more, I guess, automated in a way, or at least there's much more of a facility available. Whereas when I started, we had to write our own programs. Obviously, collecting data was much more involved than it is now and took much longer than it is now. Even the computational resources were much more primitive.

Phillips:

And did you do the crystallographic imaging in house at MIT? Or did you travel to Brookhaven or someplace else with a more powerful beamline?

Rose:

They didn't exist at that time. [Laugh] But they were just getting started. So it was only for very special things that you would travel. We had a single counter. I don't know if that means anything to you, but rather than doing an image photographic plate, or nowadays, an electronic detector, we had a counter that counted one spot at a time. Imagine, you have to get tens of thousands of spots to get a structure. So it was pretty time-consuming.

Phillips:

You were a post-doc at MIT for a couple years?

Rose:

When did I move? I would've gone there around the end of '80, I guess. I think for three and a half to four years. '84-ish, I guess. And I moved up to Canada at that point.

Phillips:

I'm curious what the job field looked like when you were applying. Were there faculty positions?

Rose:

It was growing, but it was a little bit of an interesting story. I was familiar with Canada, obviously, having grown up in Buffalo. We'd go across the border all the time to southern Ontario. And we happened to have a student in the lab whose name was Rob Campbell, who was from Kingston, Ontario. And at the time, of course, there was no internet or whatever, so advertising was done just by sending letters out, basically. And Greg Petsko had received a letter from the government lab in Ottawa, the National Research Council in Ottawa, saying, "We're looking for somebody with experience in protein crystallography." They had a very strong crystallography group, but they hadn't been working on proteins at that point. "If anyone in your lab is interested, please apply." He put this letter on Rob's desk because Rob was Canadian and figured maybe Rob would like to go back to Canada. And I was just walking by, and I happened to notice this. "That sounds interesting. I've been to Canada. I kind of like it up there. Maybe this would be a nice next step for me." It wasn't pre-planned or anything like that, it just sort of–a lot of my career has been like that. It just sort of happened.

Phillips:

Serendipitous.

Rose:

Yeah. At that point, it was what was called a research associate position, which was essentially a post-doc in the government system. And then, it led to the scientific staff ladder, if you want to call it that. After I don't remember how many years, I actually became a staff scientist, basically. I worked my way up that ladder.

Phillips:

And as a government research associate, this was, I assume, not a soft-money position.

Rose:

Yeah, this was government-funded. I didn't have to apply for grants or anything, although there were some pots of money available that you could apply for. But yeah, the core of the research was supported internally.

Phillips:

What degree of freedom did you have to dictate your own research agenda at that point?

Rose:

It was pretty free at that point. They didn't really have a predetermined project for me to work on or anything like that. They were just, at that point, starting to develop linkages with industry and that sort of thing. But it didn't really affect what we were working on. When I went up there, I started working on areas that other people in the Institute were working on, what the department, basically, were working on. I didn't bring in something completely new.

Phillips:

Were you still doing antibody work?

Rose:

Yeah, I was still doing some antibody work at that point.

Phillips:

Going from an academic environment in graduate school, post-doc, and everything, to a national research lab…

Rose:

It wasn't that different. Obviously, it wasn't a university, so we didn't have a lot of students. We had a few, and we had summer students. But the atmosphere was quite academic. I would say there were fewer people around because it was basically the scientists, technicians, and maybe the odd student or whatever, whereas at university, you have students in all the time, courses, things going on. There were close affiliations with the University of Ottawa. My first teaching experience was doing courses at University of Ottawa.

Phillips:

Did you have an appointment there, or was it just adjuncting?

Rose:

It was an adjunct appointment, yeah. It was basically just to get the experience. It was optional. You didn't have to do it.

Phillips:

How did you find teaching?

Rose:

A little bit scary. But I liked the concept of explaining things to people. I'm less comfortable doing big lectures. I've sort of developed a necessity to have to do it as my career's gone on. But I do like sort of the more small group or even one-to-one. Maybe comes from my Oxford background, where things were more tutorial style, where you worked with small groups of people. But yeah, I enjoy that part of it very much.

Phillips:

Can you tell me a bit about how your research progressed at the lab in Ottawa?

Rose:

It was interesting. Again, there was one other person there who had been working on proteins but hadn't really been trained. A lot of the research I did was bringing the technique up to where it needed to be. Some of that was getting equipment in. A lot of it was computer work, so getting in the programs as they started to develop across the world. They refined the programs. At that time, one of the big things was what's called solvent flattening, which was a major concept that was brought in during that period. So I remember spending a long time getting that program working. And then, obviously, doing the actual structure work. That was, again, fairly new on computer graphics. So getting that operational and getting used to using that. I remember spending time doing that. Yeah, so it was a very fun time in a way because the technique was sort of developing as my research career was.

Phillips:

And you mentioned that there was at least a little bit of industry connection with the lab. Were any pharmaceuticals or biotech companies paying attention to what you were doing?

Rose:

At that time, I was not involved in that at all. It was something that was relatively new. Right now, at this point, it's pretty much required, I think, for any project at the NRC, to be connected probably to the private sector, or at least to some outside organization. At that time, it was sort of like Bell Labs. It was in a structured environment, but it was still very open.

Phillips:

From your perspective, that sort of shift from the basic free, into something that now sort of requires more applied or practical, was that more of a cultural shift in the lab or an administrative policy decision?

Rose:

It was more an administrative policy, I would say. That was sort of my first experience working in the glyco field or glycobiology field. A lot of what they were doing was related to that, and that was a real strength in the Institute. And that was something that was very applicable to developing vaccines or other certain products based on glycans and carbohydrates. It wasn't an unnatural connection to make, but it was a cultural shift, to some extent.

Phillips:

What were those collaborations? Was the NRC lab working with staff scientists in these industries? Or was it more the industries contracting out to the lab?

Rose:

Yeah, it was more of what you just described. Yeah, you'd have a project that would be supported by a company. There were some projects that were probably more collaborative that I wasn't really involved in.

Phillips:

Again, looking at the field as it's growing, were industry positions growing as well? Was that a career option that was available?

Rose:

I think so. Yeah, I think so. I didn't go that route, but yeah. But that is where I had my first venture into a slightly more administrative position. Not long before I left, I became head of the–Protein Crystallography group. And again, it was mostly staff scientists, so there weren't a lot of students or anything around. Being head just basically meant you were the person who the director general went to with information, or questions, or whatever.

Phillips:

Were you still able to get some actual research in while you were a department head?

Rose:

Oh, yeah. It was not a big administrative job, it was just the first taste of doing that side of things, which developed as my career went on.

Phillips:

What prompted you to start thinking about looking at academic…

Rose:

Not a headhunter, but somebody from Toronto, where I ended up working. I don't even remember how he came across me, [Laugh] but somehow heard I was there. And I guess they were also looking to expand their protein structural work at this particular institute, which at the time was called the Ontario Cancer Institute.

Phillips:

It was affiliated with the University of Toronto?

Rose:

Yeah, it was a research arm of Princess Margaret Hospital, which is the largest cancer hospital in Canada. In Toronto, anyway, and I think in several cities throughout Canada, and maybe in the US as well, large hospitals have research departments, basically, attached to them.

Phillips:

Right. St. Jude's.

Rose:

Yeah. It was very much that model. The Princess Margaret was the big cancer hospital. Another was Sick Children's Hospital had a big research institute, Mount Sinai Hospital, etc. And each of these research institutes was autonomous. They were operated by the hospital, but they had academic appointments at the University of Toronto faculty of medicine.

Phillips:

Oh, interesting. Faculty of medicine, not biology or…

Rose:

Right. There was an academic department that was based in the institute. It's a very unusual model. It was a graduate only program. It was called the Department of Medical Biophysics, sort of a meaningless name that was meant to cover all the types of research that have to do with cancer, biology, basically. But it was a University of Toronto department, but based off-site.

Phillips:

You were able to set up your lab? Did you have students?

Rose:

Yeah. My first grad students and post-doc. And my lab was there in that hospital research arm. It moved as I was there to a new building. Then, it moved a second time to another new building in the time that I was there.

Phillips:

Did you port over what you were working on at the NRC?

Rose:

No, it was completely different. Well, it's a little bit of an interesting story. Before all that happened, I had been working in Ottawa, and I remember quite clearly–there are a lot of things I don't remember clearly, but I remember this particular thing clearly. We had moved within Ottawa to a new NRC building. Our stuff was mostly in the basement. All the crystallography stuff was down there. And I was in there, and the phone rang. Of course, at that time, there was minimal email. Everything was either phone or written down. The phone rang, and someone said, "It's for you, David," so I went and picked it up. And on the other end of the phone, the voice said, "My name is Michael Smith." I don't know if you know who Michael Smith was, he was a Nobel laureate from the University of British Columbia in Vancouver who got the award for site-directed mutagenesis, basically.

So he was involved in starting up what came to be called a Network of Centres of Excellence. It was a government-funded program that was meant to bring what they're calling Centres of Excellence, or universities, or clusters of universities together into a national network. And I don't know how many were funded, maybe three or four that were funded in the first round, one of which was called the Protein Engineering Network of Centres of Excellence, PENCE. At that point, I had not really done a lot of work outside of antibodies, but their interest was anything to do with protein engineering. And so, at that time, I hooked up with a group that was working on enzymes that work on carbohydrates, and this is where my career switched into that whole field of structural glycobiology. They were interested in doing structure work and then engineering these to change their characteristics or whatever it was.

And that was with application in mind, but it was still basic science. It was still structural biology. So this guy named Victor Ling from Toronto came to recruit me in Ottawa. [Laugh] And actually drove all the way from Toronto to Ottawa and convinced me to move. Because at that point, I had no intention of moving. I was going to spend my career in the government. So there was no predetermined thing I was going to work on in Toronto, but he just wanted to get–the OCI, the Ontario Cancer Institute, wanted to get into that field. And he was sort of heading what came to be called, I guess, a structural group. He was a molecular biologist, basically. Because of this connection with PENCE, I had started working on these enzymes that metabolize carbohydrates or are active against carbohydrates. Carbohydrate-active enzymes, we call them, or CAZys.

When I was in Toronto, I met, actually as part of the recruitment group, a gentleman called Jeremy Carver. And Jeremy's main work at that time was on a protein called Golgi alpha-mannosidase II. This was a protein involved in the glycosylation pathway in human cells. All of our cells are covered with carbohydrates like M&Ms, basically. There's a whole series of enzymes that build these up in various ways, and cut them down, and build them back up, and cut them back down.

And so, alpha-mannosidase II is one of the keystones, if you like, of that pathway. And Jeremy was interested in it because he's a biochemist and molecular biologist, and he had a compound that was very good at inhibiting this that he wanted to develop into a commercial product as an anti-cancer agent, basically. He was not at The Princess Margaret, he was at the university proper. But I hooked up with him through PENCE. This wasn't the only project I was working on, but this was a major one. This developed into a major project in Toronto. And so, we were able to do that structure, which turned out to be a very large, complicated structure. And many, many inhibitor complexes, and substrate analogue complexes, and that sort of thing. So that's how I sort of shifted into that whole area, which then went right through the rest of my career.

Phillips:

And when you were starting in looking at the glycobiology and the carbohydrate metabolism, were you also looking at specifically human cells? Or were you looking at more basic enzymes in bacteria?

Rose:

Well, the alpha-mannosidase II was a fly.

Phillips:

Drosophila?

Rose:

Yeah. But it was obviously closely related to the human one, but behaved much better in the lab. So we used it as our model. But yeah, that was the Drosophila one. I worked on other human enzymes that were related but that was the most successful one, for sure.

Phillips:

And my background is in the history of evolutionary biology, so anything to do with Drosophila always–did you have your own Drosophila lab?

Rose:

No. It was all done in recombinant cell culture.

Phillips:

How did that group at Toronto develop over time?

Rose:

Well, it was driven by grad students, basically. When I was hired, at more or less the same time, there were two, actually, people who were hired as NMR spectroscopists because NMR was also developing at that time. They are both still at Princess Margaret and doing extremely well. The structural group, if you like, also included a senior scientist there named Peter Ottensmeyer, who was one of the earliest proponents of what is now cryoelectron microscopy. Peter was ahead of his time in many ways. He was an electron microscopist trying to develop ways of looking at macromolecules, proteins, using electron microscopy, trying to develop cryo techniques, and then trying to develop the software to process the images, that sort of thing. So that was basically the core of the structural biology group when I started, and then it expanded with a couple of more people more on the protein crystallography side at about the time we moved to the new hospital building, which is still in downtown Toronto. They call it Hospital Row. University Avenue in downtown Toronto.

Phillips:

I've been to most of the major cities in Canada, but I've never made it to Toronto. [Laugh]

Rose:

Well, you should come there sometime. It's interesting, it's a very condensed set of hospitals with the new Princess Margaret there right next to Mount Sinai Hospital, which is a big, more general hospital. And then, across the street is Hospital for Sick Children, and then Toronto General Hospital. And they're all basically across the road from the main University of Toronto campus. So it was a really nice geographical setup down there to have everything so close together. The original Princess Margaret, where I started, was about a mile away from campus.

Phillips:

While you were at Toronto, you had a faculty appointment there, did you also do any undergraduate teaching?

Rose:

A little bit. It wasn't required at all, but again, I wanted to get experience in that area. It was mostly upper level, fourth-year. Most of the time I was there, three of us did a course on structural biology. I did the crystallography section, one of the NMR people did the NMR section, and then Peter Ottensmeyer, who I mentioned before, did the electron microscopy section. And then, we were all gradually replaced as we moved on or new people came in. I think that course still exists, I'm not sure.

Phillips:

How long did you end up staying at Toronto?

Rose:

Most of my career, actually. It was almost 20 years. I think it was about 19 years, during which we moved a second time to a new building called the MaRS Building, MaRS Complex. It's an acronym for Medical and Related Sciences, I think. And that also had a core of incubator startup companies, and financial companies, and that sort of thing. And that has since expanded quite a bit. There's now two towers and a place in between. Basically, across the other side of University Avenue from the main Princess Margaret Hospital. And now, I think all of the Princess Margaret research, or at least basic research, is in that tower. Also, while I was there, there was a major initiative in what became known as structural genomics. The Structural Genomics Consortium, which was a private-public sector collaboration, started out during that time in the same location. And one of those initial people who was hired as an NMRspectroscopist, her name is Cheryl Arrowsmith, became the Toronto co-director of that, along with Aled Edwards.

Phillips:

Do you remember some of the major industry entities or other academic entities that were involved in that work?

Rose:

I wasn't really involved in it that much. But I think a lot of the major pharmaceutical companies. And then, they were supported by the federal government and probably the province of Ontario as well. Yeah, it's a very interesting–in fact, there's a session at this meeting on structure genomics.

Phillips:

Yeah, I'm going to have to see if I can sit in on that.

Rose:

one of the speakers is from that Toronto group.

Phillips:

What ended up leading you to go from Toronto to Waterloo?

Rose:

I wouldn't say it was planned, but it was a progression that probably existed in my brain. [Laugh] I'd started my career in the government lab, and then I moved to the research institute, which is not strictly academic because it's tied to the cancer umbrella in this particular case, but it was certainly not commercial-based or industry-based either. Again, there were collaborations. And so, while I was at Princess Margaret and in the Department of Medical Biophysics, I became more and more involved in the administration of the academic side. So much of the time, probably about half of the time I was there, I was what was then called the graduate coordinator. Basically, the graduate chair of the department.

Since it was a graduate department, it was not the chair, but pretty much in charge of a lot of the academics that go on in the department. And that was a huge department at the time. We had over 200 grad students. Not just at Princess Margaret, but also there were some at Sunnybrook Hospital in Toronto, some at Sick Kids, and a couple even on the main campus who were part of that department. So there was a lot of coordination of geography and a lot of establish of processes for exams, defenses, supervisor relationships, all sorts of things that graduate students go through. And with 200-plus grad students and, I don't know, 75 or 80 professors, it was a pretty big handful.

And it was interesting because it was a University of Toronto department, but none of these people, with the exception of maybe a couple, were actually hired by the university. We were all paid by our research institute, our hospital. So it was very much a dual loyalty, if you want to call it that, [Laugh] where you had to abide by the rules of the university, but you were employed by this other organization. I really enjoyed it. It was a great time. There's always going to be things that come up, but overall, I enjoyed it. But it was much more complicated than just being in a department. [Laugh] But anyway, while I was there as the graduate coordinator–I, in fact, had just finished my term as graduate coordinator. We got a new department chair who came in, who passed away very suddenly, unexpectedly.

So I spent the last two years as the chair. We could call it the interim chair because it wasn't part of a search process or anything. I was basically the chair of the department. So that got me interested more and more into the academic administration side of things. At that time, our kids had grown, and left home, and gone to university themselves. So we were thinking, "It's time to downsize." We had this big house out in the suburbs. What were we going to do? We were going to stay in Toronto and try and maybe move closer to the city, or were we going to maybe look somewhere else? At the same time, the University of Waterloo was advertising for a department chair of their biology department.

And I don't remember how I happened to notice this ad. I don't think I was actively searching, but somehow, I heard about it and applied, and I was fortunate enough that they hired me. And so, that meant that the third and the final stage of my career was in a core academic university. The main part of the job was to be the department chair. Obviously, my research program continued, but at a lower level. So that's how I ended up at Waterloo. I spent two four-year terms as department chair. And then, the last four or five years since then, just as a regular professor.

Phillips:

What was it like going from overseeing this massive and fairly specialized program to a much smaller but also general biology program?

Rose:

That's a very good way of putting it. It was very different. [Laugh] Being in a core university, there was a different culture, different way of looking at things. And Waterloo is quite an unusual university. It's very entrepreneurial, which is something that I was not and still am not really. I was sometimes pushing against the current, to some extent, in terms of being a basic biologist, or not really biologist, basically, molecular structural person, working in this environment. It didn't require but very much promoted entrepreneurial work by everyone, even students. There was a very big undergraduate program for students to start up companies. There's a huge co-op program where students would go off and work, usually in the private sector, but sometimes at universities, or even research institutes, three or four times during their program. So it was very much an emphasis on work experience as well as the academics. And as a department chair at a university department, unlike at Toronto, I was actually overseeing personnel. I was doing the annual reviews of all the professors and the staff. It was really managing the professionals as well as students.

Phillips:

Was there a lot of tension between wanting to promote and protect basic research with this entrepreneurial sort of culture?

Rose:

Not really. I don't think so. It's not that they didn't welcome basic research, it's just that the culture of the university is entrepreneurial, I would say. There's basic research that goes on there, some of it quite good. But it has very much this flavor of, "What is this good for? Or how can this be commercialized or applied in some way?" And some of it comes from the engineering background. There's very strong engineering in that school. A lot of the computer science programs are developed there. The Blackberry was invented there, for example. That's the sort of thing that they're best known for. I wouldn't say it was discouraged. Maybe basic research might not have been promoted as much as some other areas. But there was no antagonism or difficulty in doing it, as long as you can get funding, basically. You could do pretty much what you wanted.

The bigger, if you want to call it tension, probably came from the different aspects of biology, which you alluded to before. Because it's a biology department, I was almost the only molecular structure person there. We had plant biologists, we had environmental, a big water biology group. These are all still very much strengths of the department. Biochemistry was not a separate department, it was a joint program with chemistry, biology and chemistry, and most of the biochemists were in the chemistry department at that time. In fact, still are, I would say. So when they hired me into the department, I think there was a fair amount of butting heads or whatever between those arms of the department.

And one of the things I tried to do during my term was to promote the convergence of biology, especially with genomics becoming bigger and bigger and the fact that microbiologists, and the fish biologists, and the plant biologists all had this common sort of genomic approach, which has become much more pervasive now, I think. And I think that helped to some extent to at least get people on the same page, speak in the same language. So that was a really interesting challenge when I was there.

Phillips:

That sort of repeats a similar thing that happened 80 or so years earlier when genetics–after the modern synthesis, and all of the disparate biology departments that were fighting were sort of unified in that sense. Just out of curiosity, do you remember not necessarily which people or personalities were clashing, but which fields?

Rose:

Yeah, certainly the aquatic biologists and the more evolution-based or ecologists, I guess you would call them, were somewhat on a different page from the microbiologists and those few of us who were actually working on structure, more molecular biology. If I had to make a division, that would be it. And then, during the time I was there, part of this convergence approach, I guess, also was the whole computational side, which was just developing. And Waterloo being Waterloo, was a very big thing there anyway. So a lot of what I tried to do was to make connections with other departments. Biology had almost been in a silo, to some extent, at least outside of the science faculty.

So I tried to make connections with the computer science people, with the health science people, and even the engineering. We worked with engineering to set up a biomedical engineering program. I tried to bring the department out. And this was actually something that was told to me when I was being recruited by the powers that be, deans and presidents, that, "If you're going to come here, you really need to try to get biology more integrated into the university and bring it out of its shell." And so, I spent a fair amount of effort trying to do that.

Phillips:

Those two four-year terms, what date range was that?

Rose:

They coincide almost exactly with Barack Obama's presidency. '09 to…

Phillips:

'16-ish?

Rose:

Yeah.

Phillips:

And your own research over those years, were you still doing glyco?

Rose:

Yeah, still working on structural glycobiology. I had pretty much finished all the mannosidase stuff at that time. The main person who was working on that project for me in Toronto didn't move with me, so he stayed in Toronto, and I moved over to another lab and am still working at another lab. At that time, I had already started working on a different set of carbohydrate-active enzymes, but ones that were involved in starch digestion, so more of a nutritional disease, if you want to call it that, genetic disease related to inability to digest starch and sucrose, which are major components of pretty much everything we eat. [Laugh] Including things like baby food, baby formula. It's relatively rare, fortunately, but the people who have it have it very severely and have developmental issues in terms of nutrition.

Phillips:

That's very impactful research.

Rose:

Yeah. It's two enzymes, but each enzyme has two enzymatic units, so you could almost think of it as four enzymes, two of them connected. And we were able to get structures of a couple of those and model the structures of others that are related structurally, even though they have somewhat different specificities. So yeah, basically the last 10 to 12 years of my career were focused on that. It was a really interesting collaboration between myself as a structural biologist, a synthetic chemist, and a pediatric gastroenterologist, who was one of the people who really uncovered these enzymes and identified their importance. And a food scientist, another enzymologist. It was a very diverse and international group from Mexico, to Germany, to the US and Canada.

Phillips:

Did this lead directly to therapeutics?

Rose:

To some extent. There was a company involved who was developing compounds to treat these patients, basically by giving them an enzyme replacement type of therapy. We did a lot of work, especially in collaboration with the synthetic chemist I mentioned, developing inhibitors. They're not really inhibitors, they're more regulators, I guess you could say, so togglers of activity, to be able to turn it on and off at will, basically. Part of the motivation, in addition to this nutritional problem, was that this was potentially a way of controlling glucose levels. So if you could regulate the activity of these enzymes, you could dial up or down the free glucose level for diabetic patients.

Phillips:

Right, that would be fantastic.

Rose:

Yeah. I wasn't really involved that much in the commercial side of it. I don't think any of them actually developed into commercial products, but there is a commercial product that is this enzyme replacement, I guess you could call it that, that some of these patients can tolerate to help them digest starch.

Phillips:

I guess now, we're getting close to the present. Looking back at the last few years, post your term as chair, especially the last couple of years, one of the things that I try to ask people about, because it's important in looking at all these different settings, and departments, and such, how did COVID start…

Rose:

My lab was actually quite small at that point. I still had a couple of students going during the COVID years, and they just had to–we made up a little project that was COVID-related, which let us keep the lab operating. Because it had to be identified as a required…

Phillips:

Right, and were you doing some sort of viral protein imaging?

Rose:

Well, I've got to remember what it was now. We were working with a company on a different project, and they were developing a way of making antibodies using plants. Real plants, not cells, but tobacco-related plants as a way of making large amounts of protein. So we dreamt up a story with them on COVID antibodies, basically. [Laugh] We didn't actually do much with it except keep the lab open. So they learned to work within the rules the university set up. You couldn't have more than a certain number of people in at the same time, so you had to have schedules and that sort of thing. And then, the hardest part was not being able to have group meetings and that sort of thing, at least not face-to-face. But we adjusted and kept going. I think the bigger effect of COVID on me was because that was the time I was president of the ACA.

Phillips:

Before that, as far as teaching at Waterloo…

Rose:

Yeah, so teaching all went online. The course that I taught when I was there, my main course, was a fourth-year course on glycobiology. One of the very few that existed at the time. There may not even be that many now. I did it with a colleague who actually ended up at the University of Alberta. And so, he spent a couple of years where he actually came to Waterloo, and we co-taught it at Waterloo. Then, he wanted to do it locally as well. So we were one of the very first proponents of Zoom. We used Zoom 10 years before anybody had heard of it as a teaching tool and lectured to each other's students for this joint course. Anyway, so it just so happened that I knew I was retiring at that point or would be retiring in the next three years, so I did the last round of that course before COVID, fortunately.

Just before COVID, the fall term. And then, I'd filled in for a professor who was on sabbatical in an online course that had actually already been developed, so I didn't have to do any development, so that was nice. But it was a big course, over 400 students. So that was all online during COVID. And that was a microbiology course. And as part of that course, I did some short videos on COVID. The course was developed before anyone had even heard of COVID. But it did sort of 5- or 10-minute since it fit in very nicely with the theme of the course. So that was nice. And then, I did a little bit of writing, if you want to call it that, on the structural biology contribution to the response to COVID or whatever.

Phillips:

Tell me about your tenure.

Rose:

Well, it started out great. [Laugh] The first meeting was at the end of 2019 in Buffalo, as it turned out, which is only a couple of hours from where I live. And then, of course, everything hit the fan. And so, I was originally vice president and then did my year as president during the COVID period. And yeah, we had to figure out what we were going to do. Everybody thought originally, "A couple of weeks, we'll be back up again." This was obviously early in 2020, when we were just learning about what was going on. We were supposed to have our meeting in San Diego in August. Hemming and hawing, "What do we do?" "Well, by August, everything will be fine. No problem at all." Then, as it got further on, we said, "Oh, we're going to have to make a decision about this."

More and more organizations were going virtual at that time. So obviously, we eventually had to pull the plug. A lot of the issue was negotiating with the hotels because they didn't want to lose the business. But at the same time, they realized what was happening, and they didn't want to get in bad books or anything. So we have an excellent executive officer in the ACA, and she was able to minimize the damage, basically, with the San Diego hotel. And we had a very successful virtual meeting, one of the most profitable meetings we've ever had, obviously. [Laugh] There were relatively few expenses, apart from the Zoom licenses and that sort of thing.

I wouldn't say I enjoyed it as much as a face-to-face meeting, but it was the best we could do, and it brought in some people who had not been able to attend meetings because either financially or for personal reasons, couldn't travel. At least for a couple of years, we had expanded our membership database to include people like that. And I think hopefully, some of them remained on board as we've gone back. And then, the subsequent meeting to that one when I was president was supposed to be here in Baltimore. And that's why we're here now. So as part of the discussion with the hotel that year, we made a decision fairly early on that we were going to go virtual. So we had to negotiate with the hotels. "What can we do?"

So we said, "Okay, well, we won't penalize you if you come back here for your next meeting that's not scheduled." So that's why we're here now. And we're very happy to be here. It's a great location. A lot of the stress during that period was just making sure the organization didn't go under financially because of all the penalties and that sort of thing. And at the same time, learning how to run a virtual meeting. And all the discussions about hybrid and stuff, which I think have sort of faded a bit. I certainly feel that hybrid is the worst of both worlds, in a way.

So I don't think we would do a hybrid meeting, but we certainly are interested in potentially doing virtual meetings in years where there's an international crystallography meeting. There happens to be one this year, but because we had to have the ACA here in Baltimore this year, we went face-to-face. But in the future, potentially when there's international meetings, we might do those virtually and encourage people to go to the international meeting. But we'll see.

Phillips:

Were there any particular administrative challenges or anything beyond just the annual meetings?

Rose:

Well, obviously, over Zoom. We didn't meet face-to-face, which we normally had done. I don't think so. The organization's main task is organizing the meeting, so that was really where most of the effort went, I think. I guess the other thing that affected the conference to some extent was that we put on sessions on COVID, on structural biology and COVID and contributions to the pandemic. Or to addressing the pandemic, I should say. But yeah, understanding how the enzymes work. We had a fairly major transaction session on COVID. So that was a big success. [Laugh] So I guess if you want to look for silver lining, maybe that's one. And we learned how to do virtual meetings. Even though they're not as good, at least you could do something virtually. Which does have the advantage, as I said, of bringing in people who might not normally attend. So yeah, there were some silver linings that we were able to pluck out of it.

Phillips:

I guess that, again, brings us to the 2023 Baltimore meeting, the present day. I was wondering if you have any thoughts or reflections on your career as a whole, the culture of the field, anything?

Rose:

Yeah, it's interesting. It's been a great time to be doing this sort of work because I was fortunate with the timing that I was involved in the field as it developed. The challenge to that, of course, is that as the field developed, things changed quite a bit. New techniques came on board, NMR, cryo EM, cryo ET, all these other fancy names that are cropping up now. And now, of course, we have computational approaches like AlphaFold that are coming in. And so, crystallography has, to some extent, lost a bit of its luster, or at least a bit of its visibility maybe as being the workhorse technique of structural biology. I think it still is. And I remember when NMR came in relatively early in my career, people said, "Oh, that's the end of crystallography. No one's going to bother with crystals anymore." But we're still here. So yeah, that's been a really interesting aspect to the career, I think. And then, I wouldn't say switching fields, but getting interested initially in antibodies, which is a little bit of an extension of my father's work on autoimmunity.

And then, getting more into the sort of structural glycobiology field, and then first cancer, and then the food science area. And then, the big thing is all the collaborations. It's always been collaborative and getting to meet people, very interesting people, and working in different areas. And I think that's how science progresses. I think it's relatively unusual, in current days, for an individual to be working in isolation and coming up with anything major. Maybe that's the way it worked back in Darwin's day or whatever, but it's evolved since then, I guess. [Laugh] And science is now much more complex and involves a lot of different techniques.

Phillips:

Certainly looking at author lists on papers over time, you go from one, to two, to five, to…

Rose:

Exactly. You can't be an expert in everything. And you wouldn't necessarily want to be. I think part of the joy of this type of work is reaching in different directions and growing yourself in different directions. And then, especially with the ACA, one reason I keep coming even though I'm retired is interacting with the next generation, the other people. I'm really interested in mentoring. I've gotten to know some of the people who are two or three generations behind me reasonably well from year to year, and catch up with them every year, and ask how they're doing. And sometimes, we even communicate a little bit outside of the meeting, just if they want to bounce something off somebody who's been around a little bit. That's sort of the area that I really look forward to trying to continue for a while.

Phillips:

Yeah, absolutely. Well, thank you. This has been a fantastic interview.

Rose:

That was great.

[End]