Dr. Hermann Haller: MDI Biological Laboratory

Today I have with me Dr. Herman Hollerer, who is the president of the MDI Biological Laboratory and also a professor. And also a lot of very interesting things, including a nephrologist. I mean, you have a list of attributes, Dr. Holler, that's a mile long plus very impressive. So thank you for coming in today. I know you're a busy, busy person. Well, thank you for having me on the show. I'm looking forward to this. It's not that long really. I'm a kidney doctor, I'm a nephrologist. I got my training in Germany. I'm German. And then I spent some time as a postdoc at Yale, went back to Germany, worked in different institutions for the last 20 years. I was chairman of the Department of Nephrology and Transplantation, which was or is the largest transportation unit in Germany. And at the same time I spent doing basic research at Mount Deserter Island Biological Laboratory for the last 25 years. And now I'm president here. I still have a lab in Germany, but I'm not chairman anymore. But this covers basically what I am. I am kidney doctor, interested in basic mechanisms of the kidney and blood vessels. And then trying to translate this into the biomedical arena. Use zebra fish embryos to analyze the molecular mechanisms to determine how embryonic kidneys become connected to the aorta and whole body circulation. I mean that's actually very interesting. So you're working at a fairly micro level as you're doing this work? We have here, originally the lab is 125 years old and originally we were doing marine animals. So we were doing Dogfish from French Prince Bay and we were looking into other animal species. But now we are working with species you can genetically alter. It's important we have on the same island, the Jackson Laboratory, most people know about at M-D-I-B-L, at the Biolab, we are using the SPR fish. We are using exot, we are using a roundworm called sea elegance. We are using other fish and they all share that we can genetically order them and thereby we can use them as tools to understand. And in our case, we want to understand the vascularization of kidneys. So we want to make new kidneys from stem cells and we are interested in the problem, how to put the blood vessels into these kidneys so that we can transplant newly made kidneys, organoids into humans. How far are you along this journey? I mean, are you close to getting to a place where you're going to be able to use this basic science research in humans? We are. Difficult question, but very important question. We all understand that this is an international effort. So the US has a consortium at NIH called regenerating a kidney, and we are part of that internationally in the Netherlands, in Denmark, they have formed large consortia in order to get there within the next five years. So that's the goal. I perhaps will give us more than that, but within the next 10 years we'll be able to generate an organ and then put it into patients and the origin will be the patient's own cells. So for people who are not medical, what are we seeing as far as kidney disease and the incidence of kidney disease in the United States, but also around the world? Very very important question. Thank you very much. Because a lot of people when they think about causes of chronic disease, everybody thinks about the heart and the heart is very important. But next to the heart it's chronic kidney disease, which is the most important disease, crippling disease in the us. And on a personal level, we can save the life of a patient with chronic kidney disease by putting the patient on dialysis, which is cumbersome, which is three times per week you survive. But the quality of life is not that high despite all our efforts or we transplant now the cost both for transplantation and dialysis for chronic kidney disease, this is where most of the money in the nation is spent on. So this is why the NIH and there are federal programs feverishly looking for a solution both for a medical problem, which is of importance. We have because diabetes and hypertension are the causes for chronic kidney disease. You can imagine the numbers are staggering out there of patients with chronic kidney disease. Even a lot of patients they don't know about that and their doctors don't know about that. And the problems we have with dialysis and transportation to keep up with the problem. In the work I do as a medical doctor, I'm a family doctor, but I work with our nephrologist at our institution. And in one of our recent conversations across our service lines, we talked about the fact that we aren't even screening patients as effectively as we really should be as early as we really should be because it hasn't been as much of a focus as it should be until relatively recently. Yes. And so our point, I've been lecturing for the last 30 years around the globe on how to screen patients and tumor remarks about that. It's relatively easy as you know, we just have to know is there protein in the urine because that's the earliest sign of chronic kidney disease. So actually we and our patients should know about do I actually have protein in the urine? And then in addition to that, it's a relatively easy measurement of the function of the kidney measuring serum creatinine or TFR. But we are not doing this on a regular level. And this is one of the problems because, and now it becomes very important. Over the last three years we have developed new ways to treat chronic kidney disease. There are now medications out there where we can actually perhaps not completely stop the progression, but we can slow the progression of chronic kidney disease. So now it becomes really important that everybody knows about proteinuria. So you should know about your blood pressure and you should know whether you have protein in the urine. It's so interesting to be talking to somebody who is a nephrologist or a kidney specialist who is also doing research because that isn't always the case. Many people who are clinical doctors, that is their focus. They focus on treating patients. But to have somebody like you who is really trying to have both sides actually do basic science research and have it be applicable to the patients that you're caring for, that's probably representing quite a bit of work on your part. Because either one of those paths, they require time and effort and expertise. Yes, you need a good structure both in your personal life but also from the hospital side. The hospital has to provide you with protected time. If you are only with patients as we all know, you'll be overwhelmed because there are too many patients to be taken care of. So you have to structure how much clinical duties you have and how much time you have for research. So at the moment, because I have no clinical duties running the ESSA biological laboratory, I'm not privileged. I miss my patients in a way, as you can imagine. But on the other hand, now we can fully concentrate on solving such a small but very important problem of how to get blood vessels into a newly formed kidney. I know you've described your work at the MDI Biological laboratories. What other types of things are your scientists doing? We are interested in two areas. We are interested in regeneration and we are interested in aging. So we do basic research and then hopefully we translate this research into the clinical areas. So we work on regeneration in not only the kidney, but also muscle regeneration of skeletal muscle, which is a clinical problem. When you get older you lose muscle. And so we are trying to regenerate that. We look into the regeneration of limbs. So we have animal models where you can actually take off the limb. We just cut it off and then it regrows within a couple of weeks and we are studying these mechanisms and try to understand why this happens. And in zebra fish, we also work on the regeneration of full kidneys. So not only the blood vessel problem, and so this is what the others are doing. And then we have two models for eating. One is a fish from Africa, and these fish, they are from the tropical world and they have to live a full life within eight months and then they die. So they age within six months. And we are using these animals to understand mechanisms of aging and how to prevent that. And we have a small roundworm, sea elegance, and this is also an aging model. So we are using these animals and I think we are all aware of that, that aging and regeneration are two sides of the same coin. I mean if we can stop aging, then regeneration becomes possible. And the other way around. One of the things that I found most interesting in reading about your laboratory is the collaboration that you have with other institutions. Well you've described around the world, but certainly within the state of Maine there is a lot of research that's being done within the state of Maine and your laboratory is collaborating with lots of the people who are doing this research. This has changed a lot. We have always been a very international place for a very long time. So lots of people coming in, but to be honest, within state of Maine we were not that well connected. But now this has really changed over the last couple of years. We have a very strong collaboration with the University of Maine. So we have now NIH grants together. We obviously collaborate with the Jackson lab because we are on the same island, but we have also reached out. We have collaborations with the colleges, a very important collaboration with Kobe College where the students come two times per year to train with us and we go to Waterville and lecture. And last, not least, with the new RO institute in Portland and the main medical research center and the hospital, we are now collaborating and we are trying to find grounds. And my first collaboration with Portland was 12 years ago and it was very small and we just published one paper together, but now we're working together on different areas and drawing to use these connection to grow a biomedical workforce in Why is it important to grow this biomedical workforce in Maine? What is it about this particular state or this particular area that makes that work important? We have different research institutions and the research in Maine is quite active. It's small, but we get support, federal support and also support within the state. So we have to connect. Collaboration is really a necessity for a state like Maine and to exchange ideas, which is an effort. I mean, driving to Portland from Bar Harbor is five hours, and so you have to do this. Zoom helps, but also to define then projects to concentrate on what we want to achieve. And especially when you work together with hospitals translational research, which questions are we asking and how relevant are they to clinical practice? And then you were asking about why is it important for Maine? We want to have more biotechnology in Maine and especially, and it's not only Maine, it's also New Hampshire. We have for instance, for regeneration, a large center in New Hampshire, and we are collaborating with them also, but we want to have more biotechnology in the state in order to get them here, they need support. And this is a more political problem, but they also have to find the right people. So they need trained people. So we have to train people in Maine. We have to attract people and train them here so that they want to stay. So when we have a biotech company coming or a large pharmaceutical company and they ask the question, can we actually recruit the people we need for the child? This is what we want to do, this is where we can help. This is where we can on a very international level, educate young people so that we have the workforce necessary to change the biomedical situation in the state. So when I was going through my training, I did some basic science research with the main medical center research institute, and then my son subsequently came along and he did research before he went to medical school with another one of the Maine Institutes. Is this something that you're seeing more and more is that people who go to school who are students in Maine are actually staying within Maine to affiliate themselves with institutions like the MDI biological laboratory. We have a long standing summer program where we had what you described with the main medical research center. Young people when they stay with us for six or eight weeks working on an independent research project, then you learn what biomedical research is and then you can make an educated decision for yourself. I mean either you like it and that's great. And then we are here, you can come back to M-D-I-B-L or we help you to connect to other institutions or you had a wonderful experience of a summer doing biomedical research and you are very clear, no, I want to do English literature or I want to go into business. That was great. Wonderful. Thank you very much. And this is what we are helping young people to make an educated decision about their own life. As you're talking about what is arguably more of a scientific field, many of us, well, it is a scientific field. Many of us look at science as being perhaps more linear and maybe people don't realize that this is actually a very creative field. There are a lot of unknowns, there are a lot of things that people are investigating. And so I'm wondering how do you encourage people to be creative as they're approaching science and the projects that they're working on? Oh yes, that's a very good question. And I may talk about my own experience. I mean, you mentioned that there are different aspects of my career and one is before I went into medicine, I was actually an art historian. So art and art history is really very important to me. And I'm from Germany, and as a German professor, I am entitled to teach everything. I can teach medicine, but I can also teach art history. So we have now also a program where I actually use art to educate us more about science or the other way around. I mean you just mentioned we all have more or less the impression that we know science, we know the problem, and then we are solving the problem, then we go to the next problem and so on. And this is not how science works. I mean we go from one small problem, then we go sideways. And it has also to do with the structure of research. We have scientists, but we have also technicians and we have to work together. So there is a lot to learn from the artwork. A painter is useless without somebody preparing the paint. And some painters can do this themselves, and some scientists, they don't need technicians. But so this is a very interesting area to learn how new techniques develop and how you work together as a team. And you can look back in history and you find out that in the 19th century when science started and art was there, that there is a lot of overlap. And it's very interesting. We know some example paintings in medical schools. Philadelphia will have American Society of Nephrology meeting in a couple of weeks down there and they have the cross clinic and other famous paintings there. So this is just one example, but I was also interested in teaching about paintings where you have a disease on the painting. So my most famous patient is Mona Lisa and our famous painting, Italian Renaissance, most people know the painting, but when you look very carefully, you'll find signs of hypercholesterolemia. And I'm not just making this up, it's very clear that the painter painted that. And then you can make educated guesses about where does the hypocholesterolemia come from. You look into the patient history of her and find out that she died at the age of 72. So she has definitely not a genetic cause of hypocholesterolemia. So the question is then acquired hypocholesterolemia, and then all of a sudden you come up with the possibility that she has a renal disease with puffy fingers and a little bit of edema plus the hypocholesterolemia. This I think is also something where we use that and it makes life more interesting. It makes our work more interesting and it opens up new words to the scientists. So this is something we are also developing at M-D-I-B-L. So it's basic research. We want to translate this into the biomedical world and at our small institution we also want to have this connection to the humanities and art. How do you communicate the work that your institution is doing to the community at large? You've described how you collaborate with other institutions across the world, around the world, but how do you help people understand somebody who's not in bioscience, who's not in the medical field, somebody who's just living in Maine, maybe lives down the road from MDI biological labs. How do you help them understand the importance of the work you're doing? Well, on a local level, we have science coffees where we want to translate our research into for everybody so that you understand what we're doing. We will have a science coffee in Portland in two weeks. We have a project together with the Biglow lab trying to find new substances in and how we do that. So we'll talk about that. So we have 60, sometimes 80 or a hundred people attending these. Although that's on a small scale. We do also have lectures which are open to the public. We are now on air together with you talking a little bit and explaining what we are doing. So this is, we try to engage the community. We have environmental programs also where we have access to high schools and we talk to students. So we are very active with programs and outreach is an important part. However, you always can do more. So running a show where we explain our research in more lay terms or to explain the Nobel Prize, which were handed out two days ago. In lay terms, that's also something we are interested in. It seems like the importance of translating the research is something that hasn't always existed. I know that in talking to people from the Jackson lab maybe 10 years ago, this was very important to them then. But when I was in medical school, there was often a divide between the people who were doing the clinical work and the researchers. At what point did we finally realize we all need to get together and understand what each other is doing? Yeah, I mean it's not an easy problem. I still do journal clubs for medical doctors every week on a very early Tuesday morning, both for Germany and for doctors here. And we are all busy during the day as, I mean, we are taking care of patients. So to carve out half an hour for a journal club is not easy. So it has to be worthwhile. I mean, you have to translate the research into something which makes it valuable for you to attend something like a Turner Club or to go to a more general lecture. So it's a challenge. One has to, as I said, translation is a key word for that. But we also, and we have strong support from other major institutions. You also have to see that an education, basic research helps you as a medical doctor. So we have courses together with Harvard up here and a very interesting course where we teach the fellows in internal medicine together with our Harvard colleagues to understand the physiology of disease. Because then when you do rounds and you have talked about it and you have a better understanding where this historically comes from, then you can explain to the patient what this disease is all about. But you have first, you have to make the effort yourself to understand in more lay terms. And there are lots of problems. We are all specialists, so we actually are very proud that we are specialists. So to break down your knowledge into more common language is something which is highly appreciated by the public, but not so much appreciated by our more specialist colleagues. Yes, and it is an interesting conundrum because you have different audiences and you have to be able to speak to all of them. You have to be able to speak to your specialist colleagues, to your primary care colleagues, to other professionals, to patients. So it sounds like you're always trying to need to use a different language almost when you're talking about the work you do. Yes, that's true. And you have to reflect on that. I mean, for me, it helps that I'm German, but I'm from a farmer's background. So I'm the first one doing medicine and research and I'm somewhere up there now, but I still have my feet on the crop. I know that the MDI biological laboratories are 125 years old, so we've clearly come a long way in 125 years. Where do you think that your organization will be 125 years from now? Yeah, that's a very good question. I can't look into the future for 125 years, but for the next 20 years or so, we are a small institution on the outskirts of the living world. I'm looking here at the infringement bay at the moment. So we will stay small. We want to stay focused. So at the moment, we are 10 research groups. I want to grow us to around 15 groups, and we're in close contact with NIH about that. The goal is to do stellar research. So each research group will be around 10, 12 people. So altogether we'll have a 150, 170 people doing research here. We need the message for that. And we have built new microscopes and we are focusing on bioinformatics. We're working with the RU Institute talking about collaborations in the state of Maine. So it'll be focused, stellar, basic research. And then we have added these two wings, so to speak. One is translation into the biomedical field, and the other is arts and humanities. So this is how I see the future of M-D-I-B-L, and I'm very optimistic that we get there. We are getting more support. We have been, my staff always said, we are the best kept secret in the state of Maine. We are still small, but it's not that much of a secret anymore. And Dr. Holler, I do appreciate the time that you've been speaking with me today. I certainly have learned a lot about a broad variety of topics, so I thank you for teaching me. Well, thank you very much. It was a pleasure. I like doing this. And you gave us the opportunity to spread the word and to talk about M-D-I-B-L, which is my most favorite subject before. I'm Dr. Lisa Lyle. You have been listening to or watching Radio Maine today. I've been speaking with Dr. Herman Holler, who is a professor and also the president of the MDI biological labs. And as I said, I certainly do encourage you to go and learn more about this wonderful organization and maybe Dr. Holler, you and I will have a chance to perhaps meet in the future in person. I'm looking forward to that as doctors who try to be specialists that at the same time to communicate about medicine and research. I'm looking forward to that. Absolutely. Thank you very much.