: Good morning Professor Saunders. I'd like to start out by talking a little bit about where you went to school, where you grew up, your background basically.
Aleister Saunders: I grew up in Pittsburgh, and like many Pennsylvania residents I went to Penn State to do my undergraduate work. And, like many Penn Staters, my first course was Biology 101 with 1200 students in an auditorium. But, I had a great teacher, and that first semester he said something about cells communicating through small chemical compounds and I thought, "That's amazing;" and I got involved in research there. I was a bio-chemistry major at PSU, and then I went to graduate school at the University of North Carolina because I'd done a good amount of undergraduate research. Then, I went to UFC at Chapel Hill and got my Ph.D. in biochemistry. After that, I was in a very basic science lab. It wasn't really applied to anything; it was like, "If we can solve these problems maybe 50 years down the line, we can utilize this for better human health." It was science fiction sort of stuff. I did a post-doc, which is quite common in my field. In fact, I did two post-docs. I did those at Boston and at Harvard medical school. One was in functional genomics and the other was in Alzheimer's' genetics. That was nice for me because I was able to understand the disease, not from a clinical aspect but more from a molecular aspect. That's what I get excited about, and that's what I do here. We do research on Alzheimer's disease, on genetics and biochemistry. We're trying to understand what genes are involved in giving rise to the disease, and if you can understand that, you might be able to understand potential avenues for therapeutics. That's how I got here. I'm here, more specifically, because my wife is from Philadelphia. I love Boston, but we had two small children at the time and wanted to be in Philadelphia. Having been at Harvard, I was pretty sure I didn't want to be at Penn or schools like that. The other thing I knew was that when I was in graduate school I had an amazing Ph.D. mentor. In fact, I still talk to him regularly about everything. In fact, I really want to be able to do two things: I want to teach undergraduate and graduate students, and I want to do research. There aren't too many places you can do that: First class research, as well as have a real teaching job where you're actually in the classroom regularly. Then, if you add on the further restriction of it being in Philadelphia, it makes the options even smaller. So I basically applied for a job with Drexel, and it's been a perfect fit so far.
: I see. Can you tell me about the courses you teach at Drexel?
AS: I teach a large sophomore introductory course, The Principles of Molecular Biology. In addition, I teach a senior-level elective, The Biology of Aging, because the biggest risk factor of Alzheimer's disease is age. That's been a really fun course for me. I also teach a graduate-level course called the Molecular Mechanisms of Neurodegeneration. Alzheimer's disease is a neurodegenerative disease, so you can see the obvious reason why I'm teaching that. I'm teaching another graduate course called Readings and Biochemistry Cellular Molecular Biology, and that's a graduate course for first-year students to give them a survey of our field.
: From the sounds of it, most of the courses you teach also tie in with your research. Is that unusual?
AS: That's a good question. They don't all tie in to my research. The sophomore-level class is sort of a basis of what we do. It's a really nice introductory course and was my favorite course as an undergrad. The fact that I get to teach this course that I found to be so fascinating is really a great experience for me. Otherwise, I'd say two out of the five courses can directly relate to what I do: The aging course and the molecular mechanisms neurodegeneration course. That's basically what we do, and they're very literature-based and detailed. The biology of aging course has been really fun for me because the first time I taught it, I had a student in the course who ended up working for me for a year after she graduated. She stayed at Drexel and worked in the lab. In the course, she had to give a presentation based on a paper and literature, and she did something on aging. When we hired her, we took that whole idea from the unrelated biological system she wrote about, and we said, "Let's put it with Alzheimer's disease." She's only been gone for two years now, but this project has really blossomed into something really wonderful and really enjoyable; and that's all because of that course and having wonderful and interested students to propose these great ideas.
: Can you tell me a little bit more about this research you and the students have been involved with?
AS: First, we don't work with patients; we are interested in working with cells and taking a step up towards organs like the brain. Most importantly, there are no drugs for Alzheimer's disease. If you get it, it's a death sentence; and it's a slow death sentence. It just gets worse and worse with time. There're no drugs, and there aren't any on the horizon. So, in our field, we think we can develop a drug; we're just not sure what we should be aiming for. Our research is to try to identify targets that drugs may be targeted against – molecules that make the disease happen. We're trying to find key steps in the disease's pathogenesis, and we do that in a number of different ways. One way is hypothesis-based. We know a good amount about the biology, the molecular and cellular biology of the disease, so we can look at the literature and the charts and say, "We know this is what happens with Alzheimer's disease." There's sort of this black box of molecules that interact with other molecules, and at the end of that box you've got disease. We know some of these connections, but we don't know how it all interconnects to make a functioning machine that dysfunctionally releases things. We have insight into some clusters, and those clusters may not be completely defined, so what we can say is, "We know something about this, so if we can manipulate this cluster, this protein, this gene, what happens to the disease? Does it get worse? Does it get better? Does it have no affect?" So, we make a hypothesis about a specific protein in human cells that might be involved in the disease. That's one way to do it.
The other way we do it is to admit, "We really don't have any idea what's going on," which is not really true, but it's not really wrong either; it's just so complex. We have a parts list of what's in our cells, but we don't know how they connect. It's like having an in-depth present. Kids' toys have a parts list, and you have to put it together. Imagine if there was no diagram showing you how to put the toy together, it was just a list. That's sort of what we have right now. That interaction of how you put a cell together is coming, but it's far away, and that's just for a normal, let alone a diseased, cell. So, one approach we're taking is saying, "We don't really understand what these things are, but here's a list. Let's not make any assumptions and just test all of them. Do any of these things affect our outcome, which is disease?" We have laboratory reagents that allow us to basically turn any gene off. That's unique. That's through a process called "RNA interference." We've even developed a multi-campus center to facilitate these sorts of studies. We wrote a grant with 24 other investigators from across Drexel, and that was funded by the state. What we have now are these reagents that we're using for our own work, but we distribute them across Drexel so others can also take advantage of this technology because I couldn't afford these reagent by myself, and neither could my neighbor, but together we can. We have ways to manipulate molecules themselves. We're doing this from the hypothesis-driven way. You know, "We don't know – let's just try it all." But, like I said, we don't look at people directly, we're looking at cells. We're looking at the production of a specific protein that has been quite robustly proven the cause of the disease. In biology, we call the outward appearance of an organism a phenotype. We can take that down a level and talk about a cell's phenotype – the shape, or it's expressing this protein etc. We're looking at a very specific phenotype for our cell model, and that's the production of this protein. What we've been able to do is to have this protein light up. We've got this unofficial system that when this bad protein is produced, it lights up. Instead of having to spend a lot of time, energy and money to detect these proteins, or use animal models, we can detect it very easily. So we strip the disease to the basics, and we can look at it in the light. So, we have our hypothesis; we have our screen; we can turn things off and on; and we look at what happens with this light. We think the production of this light is really the basis of the disease. If we can learn how to manipulate that, that's called a drug. That's where we are. It's basic, yet applied. We're also gearing up to get an animal model of the disease up and going through a transgenic mouse. Mice have been given human genes, and they recapitulate the neuropathological features of the human disease. We obviously want to use the stripped down model because we can do it quickly and inexpensively, but these animal models take months to years to get. But that's the obvious next step. And that's, in broad terms, what we do.
: You said your end goal is to find a drug for the disease. Do you, as a researcher, play a role in creating the drug, or does your role end after you find the drug's target?
AS: No, we wouldn't produce the drug. What we would probably do is identify the target. See, we've got these screens, and there's this gene. If you can turn this off, you can possibly prevent or delay Alzheimer's disease. Then, you could say to a drug company, "Try to turn this off." Drug companies are very good at doing that. The drugs for HIV are just a classic example of that. They got a target, the AIDS protease. Drug companies are very good at making protease inhibitors, which is this cocktail of drugs, some of which are protease inhibitors, so that's what they do very well and can spend millions of dollars to do. What I do is sort of that lower-level, "What should we be shooting for? What should we try to shut off to make a drug?"
: The research you're doing at Drexel with Alzheimer's disease, is it completely new for you, or is it a continuation of the research you started at Harvard?
AS: Yes, both. I came up with the idea while I was at Harvard, and I wrote a grant while I was there to fund it, which was funded just as I was leaving. So when I came here, I basically re-started that on my own. The grant that I had gotten was an internal Harvard grant, so I couldn't take that money with me. So, I had to reapply for the grant, and I did that; and I got an NIH grant to basically redo what I'd been doing. It is an idea that had its genesis at Harvard, and the genesis of that idea was involved with my interactions and my advisor and the environment there, and it wouldn't have happened if I hadn't been there. But what we thought we'd be doing there and what we're actually doing to make it happen is completely different because it's been really tough to do. As I tell my beginning graduate students, 90% of what we do doesn't work. One of the things you need to know about being a scientist, at least a life scientist, is you have to have really thick skin. You have to be able to get up in the morning after having a failure or failures and say, "Look, I've had these failures, but I want to do it again; and I want to do this experiment again in a more informed way knowing what hasn't worked before and try to make this work." So we're always just going from one technical issue to another to try to get something to work, and that's very frustrating. But, when you get through it and you get a result and the system is working, it's overwhelming. It's such a challenging process.
: You mentioned writing the grant at Harvard and then bringing this research to Drexel. Would you say you're a pioneer in your field?
AS: I can say that no one else is doing what we're doing.
: With that in mind, do you have researchers coming to you to get involved with this research and your project? Or, being that you work for a university, are the other researchers involved with your project internal – students and other professors, for example?
AS: Most definitely. The students are the hands-on people. I am the person who manages them. I don't have the time, unfortunately, to be in the lab all the time. That's their job, and they're doing a very good job. It's been wonderful to see because we're trying something no one has tried before. It's taken us two and half years, almost three years now, and it's finally starting to work. We're not even talking about results. We're talking about our experimental system being online; and that's very satisfying. I think our results will come quickly. I think the majority of the work is just trying to get the system up and running. The actual experiments will take very little work compared to what we've done beforehand. With this research, we're hoping to understand this sort of cloud of molecules and interactions that happen within cells, healthy and Alzheimer's diseased cells, to lead to new research. We're hoping to help define this cloud of interactions of proteins that go wrong in Alzheimer's disease.
: Do you expect to have some sort of drug for Alzheimer's disease within the next 10 or 20 years?
AS: I think there will be drugs within the next 10 to 15 years. I don't think they'll cure people. I think these drugs will delay the progression of the disease. The real key here is, right now, Alzheimer's is a disease of neuronal death. So, the neurons in your brain die, and once they're dead, they're dead. Right now, we don't have a way to have cells come in and replace them. That's why the stem cell debate is so crucial to Alzheimer's disease. It has huge potential to reverse some of those lost cells. Right now, there's no way - once you've lost them, you've lost them, and you're not getting smarter. The idea is, if you can delay the progression of Alzheimer's, keep people at a steady state, they're going to live and probably die of something else. Everyone dies, and most people die of heart attacks; so what's a better way to die? People need to figure that out. But Alzheimer's is such a slow, insidious decline, and what it does to families and friends is just heart wrenching.
: With all this research in progress, have you written any books or do you yourself write the reports on your research?
AS: We write papers. Currently, I'm right in between the stuff at Harvard that's finished, so I have a bunch of papers from that, and those have just ended, and we're just now writing our own little papers for my own lab. So now we have our own results, and we're coming back and writing those first papers. It's a very exciting time for us, but it's also a little scary for us to stand on our two feet in our field.
: Since the students play such a large role in the actual research, do they also have a role in writing these papers?
AS: It's between myself and the students, initially the students. They give it a first draft, and we talk about it: What does it mean, how can we make it better? Then I get my hands on it after they've done it, and we iterate back and forth. Then, we distribute to colleagues, asking if it makes sense. It's a slow process, but it's a teaching process as well. Students really learn how to write, and they learn what it means to make a cogent argument scientifically in literature.
: Your research on Alzheimer's disease seems like it could have some relevance in other medical practices and research. With that in mind, has Drexel's merger with Hahnemann had any affect on your research?
AS: I wouldn't have come here if it weren't for the merger with the medical school. That's been huge for me. I have a number of colleagues that I interact with, write grants with, because I'm in a medically related field. I will say that I haven't met anyone else in the Alzheimer's research field in an undergraduate campus. All my colleagues are in medical schools. I guess I'm not in the place I should be, but I'm in the place I want to be because I think students yearn for these applied research questions.
: I guess this is a cheesy question, but are there any "best kept" secrets about the biology program here at Drexel or even about your own research?
AS: I think the undergraduates in our major get a very comprehensive education in modern biology as well as a very practical one. Practical because we really have a lot of lab classes, more than other places. If you couple that with students who do co-ops, I think that's a really powerful combination. Plus, I still collaborate with my Harvard lab, so I go up there about every three months and interact, and we do projects together. I actually send students up there as well. My first graduate student who got his master's now has a job there, and I sent an undergraduate up there this past summer to do some experiments of mine that I didn't finish. I hope to repeat that this coming summer to continue some work that we started. So, I have an ongoing and active collaboration with my post-doc laboratory. It's really good for the students and I don't want to say this, but I want to say this, my post-doc mentor is one of the top five people in the world in Alzheimer's research. So, not only are they at Harvard, but they're with this guy who is one of the top researchers in the world. The feedback I've gotten from the people up there is that the students are excellent, very hard-working. I have colleagues up there asking me to send them co-op students as well, and I'm trying to make matches up there. I've got two of those potential matches happening right now. That's why I'm doing what I do. I love helping and mentoring students in that way and helping to guide them through this tough profession of how do we do this career-wise? The career path for a life scientist is long, and it's challenging to get through that. You need guidance along the way, and not everyone has that guidance. I had excellent guidance and I need to repay those mentors by doing the same for other students.
: Since this field of biology and life sciences can be so difficult to plow through and even penetrate, do you have any advice for incoming students or current students, about how to survive in this field and, before that, at this university?
AS: It's all about getting experience. The nice thing about Drexel is you can get experience built into your education, and that's very powerful. In addition you can get experience while you're here on campus through research with professors. Those professors can give you the best "recommendations" because they see you on the whole. They're the person who sits in your class, they watch you do research. That's the advice I would give students.