What is our approach to drug discovery?
Dr. Dennis Selkoe
So one of the things that I am most excited about that the center has pioneered really among academic medical centers around the world, is direct access to drug discovery. What do I mean by that? Big pharma does drug discovery every day, but they need to have a very strong economic incentive to do that of course and the shareholders in those companies need to be rewarded in our system. Here, at the Harvard NeuroDiscovery Center, we take that profit motive out of the picture and we can work on diseases that are sometimes called orphan diseases like Huntington’s like Lou Gehrig’s disease and frankly even Parkinson's although it’s quite common has elements of being an orphan disease still. We don’t have a breakthrough drug that will treat all Parkinson’s. The drug discovery center allows academic scientists like myself to go physically to a very well outfitted plant in Cambridge, right across the river from where we are now and get the experience of people who worked at companies like Merck or DuPont or Sepracor or other companies like that who actually know how to discover drugs which we academic scientists have very little experience with.
Dr. Adrian Ivinson
So when we looked around our community, frankly, we didn’t see what we needed so what we did was we went out to the biotechnology industry and the pharmaceutical industry and we hired some really terrific people from industry and we said, what we’re looking for here is the best of both worlds. We want the imagination, the flexibility. And the fact we don’t have to concentrate on profit, we want to take that from academia, from the university and the hospital setting, but we want to balance it with that real clear focus and efficiency that will come from the commercial sector. This idea that when you’ve identified a problem, when you’ve set your sites on a particular target, you really can be focused and go straight for that target. So we wanted the best of both worlds and that’s what we built into the drug discovery laboratory here within the center
So that’s a group of 14 people, full time people. They’re not individually looking to create their own labs or to build up their own groups. They’re working as a team and it’s I think probably unique in the US. We don’t know of another drug discovery center set up like this.
Why now?
Dr. Dennis Selkoe
So we are standing on the shoulders of giants in the science community and we can see much farther than we ever did and the discoveries are coming fast and furious. That’s why a collaborative center is needed right now. We want to build on the momentum and we want to solve problems that are devastating to the human population. Why do we need to do this now? Because we’re all getting gray hair and the fact is that so many of the terrible; diseases we study are related to time on the planet. How long has a person been there? So we want to treat diseases of middle and late life with the best knowledge of how the brain works and we have those two elements now. We have a population that has a great medical need and we have hot science that is falling all over itself making new discoveries.
Dr. Joseph Martin
Well I think it’s important to recognize the burden of disease created by these conditions. It’s estimated that as our population ages and in the case of Alzheimer’s disease we go from what is now estimated to be 4.5, four and a half million people effected to as many as 10 or 15 million affected within the next 20 to 30 years. The burden of disease here is in the multiple hundreds of billions of dollars of expense for the care of the patient and for the families who have to divert resources to take care of their loved ones. So all of this places great priority on our finding solutions that can be applied to the disease burden of our society and to the families whose lives are so interrupted and in many cases destroyed by these conditions.
How do we fund our work?
Dr. Adrian Ivinson
So the funding for the center is really quite unusual. Most of our colleagues get most of their money from the federal government or from state government funding and we get important and critical funds from these sources as well. But the majority of our funding, about 70 percent at the moment comes from individuals and foundations who have recognized that we are trying to do something a little different, that we are pushing our necks out there and that we are trying to change the model. These are individuals who have looked at us, have compared us, have done their due diligence and have decided this is a place worth putting their dollars.
Dr. Joseph Martin
And we work together planning the most efficient and effective way to use the resources that we’ve been able to put together. And I think it’s important to recognize that the resources that we have identified are applied almost entirely back into the research mission. Our administrative costs are very low. We’re efficient in the way we manage the structure of research and we’re able to put almost every dollar back into where it belongs which is trying to work with our patients and our doctors in solving these problems.
Dr. Dennis Selkoe
To do cutting edge biomedical research is very expensive. The tools are expensive. We spent a lot of our money on salaries for very gifted people who actually don’t get individually paid that much. They could get more money if they were in industry or purely in private practice. So the costs are high and the way that we fund that is that we first try to find the informed donor who is really upset and concerned about at brain degenerative disease or maybe more or than one and who wants to see his or her dollars used efficiently and effectively without unnecessary competition and overhead. That’s what we do well.
Why invest in us?
Dr. Joseph Martin
I think we put together a collaborative effort with the best people who are committed to alleviating human suffering from disease and the people who we have working with us in the Center both within the Harvard Medical school and it’s hospital Access and those we collaborate with around the world, all are dedicated to the notion that science and discovery, NeuroDiscovery, will lead us to answers that our patients will benefit from in the short term rather than the long term.
Dr. Dennis Selkoe
The reason that we think we’re just the right recipient of philanthropic donations is because we work together and we can use the money wisely and directly to further the research of a number of scientists simultaneously. So rather then asking the informed donor to put their money into one basket only, one egg into one basket, we have many eggs in one basket, we have many shots on goal for therapeutic advances. We think the reason this works the best is number 1, we like to say that we’re among get smartest centers around the world in doing this kind of work and we work in a rarefied and spectacular atmosphere intellectually, but number 2, we apply almost every penny of a dollar directly to research so we’re lean and mean in terms of our structure, our overhead.
Dr. Adrian Ivinson
What you should consider in making that decision, I want to spend my money wisely, what do you actually mean? Do you mean you want to make progress towards developing ways of treating patients? Do you mean you want to do it efficiently? Do you mean that you have a particular interest and a focus on certain diseases? Now if the answer to that is yes, I’m interested in neurodegenerative diseases—One or more of them; yes, I like the idea of not having to select an individual group but supporting a community who really work well together and yes, I like the idea of pushing research through to the point where it has implications for patients where it starts pushing towards new treatments, new diagnostic tools. If that’s your answer, then I think we have a good story to tell you. And I think that’s probably the most significant point for many donors is, it will be a very efficient, targeted focused use of your funds.
What is a neurodegenerative disease?
Dr. Dennis Selkoe
So the hallmark of neuro-degeneration in humans is this gradual, inexorable loss of certain brain cells, not all brain cells so in one disease, memory cells go out—that would be Alzheimer’s—in another disease, cells important for the smoothness of movement go out, that would be Parkinson’s. In another disease, cells that allow the muscles to move properly would go out and that’s ALS. So the common theme is selective breakdown of cells before their time, before they’re supposed to die out.
Dr. Joseph Martin
We think the mechanisms by which these diseases cause those losses of neurons are common mechanisms which when looked at together will give clues that we wouldn’t find if we were isolated and separating them one from the other.
How close are we to effective therapies?
Dr. Adrian Ivinson
It’s such an important question. It’s one we get a great deal for good reason. I mean, I think the first thing to say is none of us can really predict in the short term or in the medium term when new treatments, when cures, when preventative treatments are going to come through. It’s just too complicated to make that kind of very specific prediction. However, I think if you go into this community and you ask people who’ve been working on this part of biomedical research for a couple of decades or a decade or more, you are going to hear a common theme and that is: that over the last 10 to 15 years, we have learned a significant amount of cause behind these diseases. We’ve learned what causes them at a very basic level. We’ve learned some terrific basic biology that seems to underlie these diseases and once you have that basic understanding you suddenly have the capacity to look ahead and say Okay, how do I take advantage of that, how do I translate that basic discovery into something that really will work for a patient in five or 10 years
Dr. Joseph Martin
Basic science that lies behind the work that our researchers are doing has led us to understanding the mechanisms of these disorders. Some of them are genetic. When you find mutational in a gene, it helps you understand what the actual process by which the disease leads to the symptoms and the deterioration that the patient experiences. These brought together give us clues about points in the process that we can take on for therapeutic targets and that’s all happened since 1995 I would say.
Dr. Dennis Selkoe
So Alzheimer’s’ in many ways is sort of a flagship disease for efforts that this center is making. It’s very common, it’s devastating, It’s enormously expensive, but just in the last 7 years, since the Harvard NeuroDiscovery Center began, we have the advent of a number of clinical trials that believe it to not have reached phase 3, the final phase of clinical testing and so there is a real hope that in the year 2008 hopefully certainly by 2009, there will be some trial results announced. So in Alzheimer’s, in Parkinson’s, in MS in particular, the therapeutic opportunities are right in front of us and in some cases have already been delivered. So it’s not just a matter of hopeless brain diseases.
What's unique about the Harvard NeuroDiscovery Center?
Dr. Joseph Martin
The idea was to bring together investigators from different fields, who are working toward understanding the nature of these conditions and to help them work together in collaborative mode so that they can learn new things from each other. The whole point of this is to take this kind of work in a translational way, which means to move from ideas that tell us about the mechanisms of the disorders to actual therapies that would become treatments for the patients who have them.
Dr. Dennis Selkoe
So what I think the Harvard NeuroDiscovery Center does best is to bring scientists, physicians out of their silos and get them to talk about common problems and common opportunities.
Dr. Adrian Ivinson
Everyone these days in biomedical research is talking in about collaboration. It’s become a real buzzword. We wanted to take it a step further and we wanted to say, how do you put together a program where you actually identify the challenges and the problems through a collaborative effort and then you assemble the right groups to take on that challenge through a collaborative effort and then you actually implement and do the science and do the work collaboratively.
Who is on our team?
Dr. Adrian Ivinson
So we have over 600 members and they come from a whole variety of places and backgrounds and skill sets. So we have investigators from all the major teaching hospitals in Boston. We have them from Harvard University and the Medical school. We also have another ring of collaborators from beyond the Harvard System.
Dr. Dennis Selkoe
So the center is really quite a large organization. I would venture to say that it may be the largest concentration of brain scientists really working together anywhere in the world. The essence of this center is cooperation and collaboration and we haven’t had enough of that in science. I hear donors sometimes say, you know, I don’t know if to give to you or to give to another university in another school here or overseas. And the answer is here, we have a community that actually doesn’t just collaborate among many, many gifted Harvard Medical School affiliated scientists, 600 and growing, but to many other institutions. We have wonderful agreements with 15 or 20 other groups around the country, around the worlds and we are very much a collaborative fraternity.
Dr. Joseph Martin
It’s more than just us. It’s important to recognize that our collaborations in these conditions reach allover the world. We have collaborations locally with MIT, with the other universities in the area. We have collaborations with Cambridge University in England, with the UCSF in California, and so our work is not just local. It is taking advantage of the world of science out there that allows these discoveries to bring the most promise to the work we’re doing together.
What progress have we made?
Dr. Adrian Ivinson
We’re in a better position today than we ever have been in terms of making a serious impact on these diseases. We can’t tell you precisely when that will be, but we know that every day, every week, every month, every year, we’re making progress and that leaves me very optimistic.
Dr. Joseph Martin
We’ve been able to identify for each of these disorders key metabolic steps that we think may explain why nerve cells deteriorate and die and cause of symptoms. We have a laboratory of drug discovery, which has taken clues from these specific mechanisms of deterioration or degeneration, and are applying tests with known drugs and some that are from panels of drugs that have not been widely used yet in patients, and are testing them in what we call biological models of disease.
Dr. Dennis Selkoe
So in the area I know the most about, Alzheimer’s, the progress has been enormous and I’d like to attribute some of that progress in my own research to what the Harvard NeuroDiscovery Center has provided for us. Tremendous core facilities to do things that individuals, scientific labs like mine wouldn’t be able to afford to do, or have the wherewithal to do. So the reason, that I feel that we can boldly predict that some of these diseases will gradually ease off, is because in the example of Alzheimer’s we are where we need to be. We are in the advanced stages of clinical trials.
What are the priorities of the Harvard NeuroDiscovery Center?
Dr. Joseph Martin
The Harvard NeuroDiscovery Center has a first priority to bring together people to collaborate around research that will direct us toward cures for the neurological disorders that we associate with degenerative changes in the brain. Alzheimer’s disease, Parkinson’s disease, ALS, or Lou Gehrig’s disease, multiple sclerosis, and other conditions like that.
Dr. Adrian Ivinson
The idea was I guess threefold. One is, we’re going to focus on these diseases. There’s a big need for these diseases, these neurodegenerative diseases. Secondly, we’re going to do it in a very collaborative and open way. Unfortunately, that’s not the typical pattern in academia so there was a real challenge there. And then finally, this idea of translation––take basic discoveries and move them towards the stage where they’ll be useful for a patient. So that translational emphasis, that collaborative emphasis, and that focus on disease. That’s just a terrific opportunity for all of us.
Dr. Dennis Selkoe
I think what‘s unique about the Harvard NeuroDiscovery Center is that it takes scientists out of their silos. A silo is the appropriate word for how we live our lives, we scientists, and I’m one of them. And that is, we focus on these little molecules or particular abnormalities and it’s hard for us to connect to each other the Center really challenges us and helps us connect in many different ways.
Is there reason for hope?
Dr. Joseph Martin
If you had asked me that 15 years ago, I would’ve said, I’m not sure. Today, I think there is, and the reason for that is that the basic science that lies behind the work that our researchers are doing has led us to understanding the mechanisms of these disorders. And today every condition that we are working on shows promise for the development of new strategies that are based upon scientific facts that we simply didn’t have 15 or 20 years ago.
Dr. Dennis Selkoe
So the reason I am hopeful is because we know a huge amount. The Center here at Harvard has helped us create that knowledge in a very dramatic way. And we’re applying that in clinical trials. Indeed, the center actually helps sponsor clinical trials.
Dr. Adrian Ivinson
You know 15, 20 years ago, we were scrambling around in the dark. We’re not in the dark anymore, we don’t have all the lights on, but we’ve got enough light shining on this problem that there is a great deal of hope. Now, in biomedical research, luck always comes in. You know, Mother Nature’s tricky and it’s a fool who tries to predict how she’ll behave, but having said that, there’s a great deal of hope in this community.
