Dr. Justin Mott on How Medical Research Gets Funded

Transcribed automatically and lightly edited.
Michael Lyon: [00:00:00] This is Heartbeat, conversations about medical science, research, and the discoveries that touch our lives in collaboration with the University of Nebraska Medical Center. I'm Michael Lyon. My guest today is Dr. Justin Mott, an associate professor in the Department of Biochemistry and Molecular Biology at the University of Nebraska Medical Center.Dr. Mott heads a research program to use innovative models and techniques for the study of liver cancer. Welcome.
Justin Mott: Thank you.
Michael Lyon: Great to have you here. We're talking about research funding 101 today, how medical research gets funded.When people hear that a research project received a grant, what does that actually mean? How is medical research typically funded in the United States?
Justin Mott: Receiving a grant means that you have put together a proposal, a request for funding that was compelling to the scientific reviewers, that addresses an important problem, and was clear enough [00:07:00] that there would be something that came from it that would benefit medicine, science, potential people.
Michael Lyon: So it started with a question then?
Justin Mott: Yes. In somebody's mind, and in order to investigate that further, they're looking for the funding for that.
Michael Lyon: And that comes from several different sources, doesn't it? A combination of federal agencies, National Institutes of Health, state governments, private foundations, universities, industry partners.Would you explain what sort of different roles these funding sources have?
Justin Mott: So this is one of the things I love about being in Nebraska is all of those funding sources come together here. Mm-hmm. Um, that's not always the case. You don't always have the kind of community engagement and philanthropy that I've seen. So the, the question really is who can benefit from the research? And when it's hard to answer that, when the research is very early on before we know what disease this might treat or even what process this can help [00:08:00] with, we don't have a target audience that's available to sort of fund the research. We don't know that this is gonna be medically important. We don't know that this is going to potentially have a technology impact. And so early on, this really has to come from a, a broader funding source such as the federal government. Presumably because they are interested in supporting fundamental scientific discovery where foundations, for example, might focus on specific diseases or populations.
Michael Lyon: Right. And then of course there is industry, driven not just by the need for research, but by the outcome for patients and also for their bottom line. Industry, though, looks at studies typically aimed at, what, developing drugs, diagnostics, devices, those kind of things?
Justin Mott: Yeah, the diagnostics, preventing disease, treating disease, even modifying disease, these potentially have commercial [00:09:00] value. So your companies are going to get involved. When there's a need to shift from, okay, we have satisfied the curiosity, and we have a good indication of how this can work, we have enough evidence that it will work, but it still needs, it still needs somebody really to back it and to push it forward, and this is where industry comes in. They can bring their vast resources, but also their experience in knowing where drugs might have difficulty or fail, and they want to get to that point very early. If it's going to fail, they want it to fail as soon as possible, because if it doesn't, then that means that it is, it's something that they can carry forward. They don't want to spend years on it and then have it fail, whereas a basic scientist might not be thinking in that way. The basic scientist is thinking, "Okay, I want to find out how this is working, and if it's this drug, if it's this target, that's open, but I'm not tied to one of those."
Michael Lyon: What's the role of [00:10:00] universities in this? Where does their funding come in?
Justin Mott: So the university, the main role is probably to concentrate the researchers, to concentrate the intellectual environment that allows for the curiosity and then the innovations. They're funding, they're supporting the scientists, the administrative staff, all of the support team that we couldn't work without. And so working within a university, you don't have that particular motive of, this is the disease we want to treat. They want to see that we are innovating. They want to see that we are teaching. They want to see that we're providing medical care for those who see patients. UNMC obviously has these goals internally, and the faculty can satisfy those. One of those goals is innovation, and the university doesn't say, "You have to innovate in this area." They say, "We want some scholarly output. We want you to be creative, and we want you to solve problems that maybe we don't know about yet."
Michael Lyon: And is the university where some or most of the seed funding comes [00:11:00] from?
Justin Mott: The university receives money from most of the sources, but they don't tend to generate that money. At UNMC, we have our clinical partner, and they can generate some of that funding that can help with those seed projects. But when I apply to the NIH for a grant, it's not actually me applying, it's the institution because the institution has that agreement with the NIH. We're gonna follow these rules. We're gonna make sure all of these things are in place. It's beyond me, and so I can't s- say, "Yes, this is all in place exactly as it needs to be." I need that institutional background. And so the institution provides not only a, an intellectual place where I can be pushed forward by my colleagues, where I can get students who can do the actual work, but it also provides that reassurance to the funding sources, "This is gonna be done well, and we're going to oversee this and make sure that it's handled appropriately."
Michael Lyon: I'd like to talk to you about the process, about how a [00:12:00] scientist goes about securing funding for a research project, and I wonder whether you could tie that to some of your work at UNMC. Yeah. What does it look like from start to finish, or what did it look like in your case? Yeah, I'd like to break this up a little bit if I can.
Justin Mott: The first thing I wanna talk about is funding individuals and then funding a research idea. And the reason I separate these is 'cause they're quite different from a philosophy. Funding an individual is actually not generally the way that most of our research works. We don't pick somebody and say, "Okay, you have, you have funds and resources available.Go do something well." The university makes that decision, but the funding source does not And the funding source tends to say, "What's the project? What are you starting with? What's the background information? Is this a good rationale? What do you hope to get out of it at the end?" But at a training institution, I think a lot about our trainees, and so funding the individual, especially early in their career, [00:13:00] lets them have ownership of the science that they do, lets them really internalize that they are a scientist, a research scientist. If they've got funding of their own, that's a big step toward their future success and independence. This generally comes in the form of fellowships, so it might be an external fellowship from the American Heart Association, from the Rheumatology Research Foundation. There's a NASA Nebraska grant that's available for medically significant space flight type concerns, or it might be coming from the federal government. There are individual fellowships available, and these are supporting the training and the development of that scientist.
Michael Lyon: Can we go back a little bit to the process? We've determined that research starts with a question. Can you give us an example of what sort of a question in one of these processes you really wanted to find the answer to? And then what was your process [00:14:00] after that? Did you look at existing research, develop a study design, and then did that ultimately involve a whole team?
Justin Mott: It always involves the whole team. We never do science alone. We're dependent on each other, and so this image of a scientist in their white coat standing alone in a room, that might happen, but that's not what's driving the project forward. It's that team that's driving it. So we became interested in a fairly rare type of liver cancer called cholangiocarcinoma. This is the lining of the bile ducts as they come out of the liver. If these develop into a cancer, it can be quite aggressive. In fact, most patients die within about a year or two of diagnosis, and we don't have a lot of great treatment options. So this has been a project that my lab has worked on for a long time, trying to understand how can we make it easier for chemotherapy or easier for the body to kill off the tumor cells. And I would say with [00:15:00] every research project, it comes from an observation, and that observation, you have to be ready for it. In this case, I happened to be teaching a little bit about how, how bile is made and how bile flows, and it involved a growth factor that comes to the liver. And once I'd learned a little bit more about that, that it was regulating the bile flow, I also knew that growth factor regulated how cells live and die. So if we could interrupt that, we might make these cells more sensitive to cell death, and in fact, we were able to show that. So it comes from being ready to ask a question and then reading what others have done so that you know what's available, what not to do. Sometimes there's information out there that takes your great idea and says, "Nope, it's either already been done or someone tried and it didn't work." But if that's not the case, if there's an open area, if there's a gap there, we can use that creativity and sort of dive in.
Michael Lyon: Research funding is highly [00:16:00] competitive. I know that many excellent proposals are sub- are submitted, but I understand only a fraction actually receive funding. What's your biggest challenge in trying to se- secure support for your work?
Justin Mott: Yeah, as you say, the competition is very high. Somewhere between 10 and 20% of grant proposals get funded, and these are competing with really excellent proposals from other labs, from other groups. The biggest challenge, I would say, is the communication component. It is making the case that this is feasible, and this will have an outcome that's worthwhile, but it's not obvious. We haven't already worked this out. You wanna be innovative because we want the next medication, we want the next treatment, we want the next way of diagnosing something. But if you're too innovative, there's no support for the idea. Nobody has gone into [00:17:00] that area, then we don't know if this will work, and that looks risky. If you are too safe, then it looks too obvious. And so communicating that there's enough safety within this idea, and by safety, I mean enough of a chance that this will work to help with this disease, but not so much that it's obvious that, yeah, e- everybody could do this. And we have the expertise in my group, in the students or the background that we've got. That's the communication that we have to provide, and our colleagues are doing the same thing, and they are making a fantastic case for their project. And so the competition makes us better, but it makes it harder. We have to spend more and more time trying to secure funding. So the funding decisions require choices on the part of the funders or the funding agencies. They decide which projects are worthy of investment.
Michael Lyon: My question to you is, [00:18:00] how then does funding influence the direction of scientific discovery? Does the availability of funding shape which questions get asked and which don't?
Justin Mott: This is a great question. So funding has, has a number of effects. It can really promote an idea or a group or an individual, and I talked about that a little bit with, with fellowship funding. It can shift a field when there's enough support for new ideas or for varied ideas. One of those might stand out, and it wouldn't have been tried if there hadn't been that kind of support. So the funding has that effect on ideas. Where it really comes down to is it has an effect on people. The funding, what does it go to? Most of it goes to salaries, and for salaries, I mean for staff, for people who are hired by the lab, but also for trainees, and these trainees are our future scientists. So even as that funding is for this project, the people who are working on it very often [00:19:00] are developing their own expertise so they can ask the future question that has never occurred to me. So there's a future payoff or a future return within the funding that is, I think, somewhat hidden. But I would say most of the majority of the dollars that come are creating jobs. They are allowing a lab to hire somebody to help ask that question, and usually multiple people. Some very important breakthroughs have come from basic research, but no obvious immediate application.
Michael Lyon: And forgive me, I will ask you this question, but maybe this is better answered by somebody from a funding organization, which is how do those organizations balance support for long-term discovery with the demand for practical near-term results?
I think this is a great question. I'm part of that decision-making because I help review other grants, and it comes down to the scientific community. The reviewers are drawn from the people [00:20:00] asking the questions. And might sounds a little self-reinforcing, but ultimately, if we're conflicted, if we are in competition with another group and working on the same project, we're not gonna be reviewing those proposals. But if they're close enough that I can understand what they're up to, I can be a reviewer, and I can help to make that decision. What's too basic? And I don't know if I can answer that in a general way. In the individual proposal, I can do so. So I want to give the example of hepatitis C if I can. This is a disease that, when I was born, didn't have a name, and today we have a cure for more than 95% of patients. It didn't have a name. We didn't know what the virus was that was causing the trouble. It was called non-A, non-B hepatitis. It looked like a virus. We had hepatitis A virus, we had hepatitis B virus, and this one was different from both of those. It's an interesting name. It's not this, and it's not that. Yes. It's something else. [00:21:00] And that's all they had to begin with. Research funding to identify what was the virus, how can we detect it, that led to the naming of it, hepatitis C. The basic biology of the virus at the time was a curiosity. We didn't have any antiviral medications, so there was no obvious medical route. But there was funding to say, "How does this virus get from an RNA that it brings into the body to being able to reproduce itself, cause liver injury, and then infect the next patient?"Hmm. And funding of that curiosity for decades led to the point where in, I think about 2014 or so, the first clinical trials were being done on anti-hep C on these highly active anti-hep C therapies. And like I say, we, we can cure it in almost everyone that, that comes in with an active infection now.
Michael Lyon: Let's move on from that particular question about funding affecting what [00:22:00] breakthroughs are made to a great extent and talk about how that sort of funding, those funding decisions ultimately affect public policy, healthcare, and the treatments that become available to patients. What's your feeling on how much research funding has to do with that?
Justin Mott: There's a step in between that I don't understand very well, and that's the commercialization process. So what becomes available is different from what is investigated at the start, and what becomes available has business implications. Is this something that's marketable? Do we have a large patient population? Imagine, if you will, a rare disease. It affects a few hundred or maybe a few thousand people in the US each year. If the medication for that only has this small potential target population, how do we get that to those patients so we can help them with their health, we can help them with their condition, improve their life if we're [00:23:00] dependent on funding, on, on commercialization funding? And here again, the, the federal government has a role because they created a process for rare drug development. They said, "We're gonna build in some incentives because the business model doesn't consider something like this." And so there's added protections for intellectual property, for example, that makes this business decision more viable and more appealing and, and makes it accessible then to our patients who really need this.
Michael Lyon: If there's one thing, and you've touched on a lot of these things, I think, today, but if there's one thing you wish the public better understood about how medical research is funded, what would that be?
Justin Mott: I think I would go back to this is funding people in their career, it's funding them in their training, but it ultimately it's funding people who have come into this career because they value service to others, they value curiosity and creativity, and they want to be a [00:24:00] problem solver in a way that makes a difference. And so these young scientists that we get to work with are just so fantastic. They are such excellent people. They care about each other. They care about others. They care about people they've never met, and that's why they're doing the research. They're also doing it because they're very curious. They can't satisfy that itch without being able to ask a new question.
Michael Lyon: I've been talking with Dr. Justin Mott from UNMC about how medical research gets funded. I'm Michael Lyon, and this is Heartbeat.