Search for tag: "funding"

Interviewer: This year, the White House has proposed to cut the national budget for Science and Technology Research by up to 20%. We'll talk about what that could mean to science and the scientists, up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking to Dr. Bryan Jones, an investigator at the Moran Eye Center at the University of Utah. Dr. Jones, are you worried?

Dr. Jones: I'm terrified actually.

Interviewer: Yeah.

Dr. Jones: We've gone through a period of almost two decades of benign neglect in science which is fine for most scientists. We sort of want to be left alone, want to be allowed to do our work. The problem is benign neglect has sort of caught up with us, and we're at the point now where science is dramatically underfunded. And the prospect of another 20% cut to the budget will be devastating to science and careers.

Interviewer: So this is still hypothetical. We'll have to see what comes down the line. But what could that mean for you in your research?

Dr. Jones: The problem is, if the 20% budget cut goes into effect at the National Institute of Health, NIH will likely award no new awards next year. They will all have to service their existing obligations. And this means the research that we do into blinding disease will be delayed or will, in a worst case scenario, never happen.

Interviewer: And, of course, this would go beyond impacting your research theoretically. It would have really broad implications.

Dr. Jones: What a lot of people don't realize is how limited the funding is for a lot of labs. So I was at Google last year talking with a gentleman named Rob Cook from Pixar. Rob is famous for developing the RenderMan software package. And we were talking about where science grants come from. And so he asked me to sort of explain to him how a science grant came about and what kind of money we were talking about and explain to him that the basic sort of unit of research funding is the RO1 mechanism. And for a modular RO1 grant, that's about $250,000 a year.

And he looked at me and he says, "Okay, so the $250,000 is for your salary, right?" And I said, "No. It's for my salary and for post-doctoral salary, and graduate students salary and undergraduates, and technicians, and annual costs and lab materials, and equipment, and computers, and everything required to run the grant for a year." And he looked incredulous. And he furrowed his brow and he says, "But the $250,000 is for your salary, right?"

And I said, "Well, yeah, and everything else that we just talked about." And he couldn't believe it. He slapped his hand on the table and he said, "That's impossible. How do you get biomedical work done on margins that thin?"

Interviewer: Yeah, budgets for internet and technology are way, way higher.

Dr. Jones: Yeah, yeah. So Facebook employees are making $140,000, $150,000 just right out of college. So people don't realize that the amount of time spent training, learning highly skilled technologies, to push technology forward at the bleeding edge takes years. And we don't actually make that much money doing it. So any sort of budget cut already is actually devastating.

Interviewer: Well, and I wonder if that hones in on part of the problem, that science and scientific research is really a black box to a lot of people. And I think maybe some people don't really understand that if you invest in something today, you're not going to get any answer tomorrow, it takes time.

Dr. Jones: Right, right. So the classic case here in Utah is Dr. Mario Capecchi, our noble laureate here at the University of Utah. Dr. Capecchi started working back in the '70s and '80s on this transgenic technology. This ability to take a gene from one organism and insert it to another organism. And he reasoned that he knew a little bit about the chemistry of DNA and he thought it should be possible to take a human gene and insert it into a mouse.

And he got a lot of pushback at the time, but it turned out that fundamental technology has become a cornerstone of biomedical research and has changed the world forever. And at the time, he had no concept of where that was going to go. And only with the passage of decades would we realize how valuable that technology has actually become. Science has a way of doing this. We have to invest in sort of the basics. We have to invest in things that seem a little wacky or seem a little far-out before we actually understand what the value of these things is.

Interviewer: When it comes to the budget though, I wonder if it's kind of like choosing your favorite child? If you're investing more in science, does that mean you're taking away money from the arts or something else? How can you even make those decisions or justify them?

Dr. Jones: Reality is the amount of money that we spend on defense in this country is larger than most other nations on the planet combined. So if you look at the F35 program, which is our joint strike fighter program, that program is estimated to cost of about $1.35 trillion over the life in that program. That amount of money would fund the National Institute of Health, the program that the department, the agency that does all the Alzheimer's, all the diabetes, all the heart disease, all the blindness research, all the epilepsy research, all the cancer research in this country. That amount of money would fund the National Institutes of Health for 27 years. Fundamentally, an entire generation of bioscientists.

And if we want to fund all the rest of the science in this country, the National Institute of Health and the National Science Foundation, the National Aeronautics and Space Administration, that amount of money would fund all of those agencies for 22 years.

So literally, an entire generation of scientists and engineers in this country could be educated and allowed to do their jobs for the cost of a single weapons system. I just don't think it's a valid argument to say that there's not enough money to fund the arts and the sciences. We could literally double the National Institute of Health Budget for very little effort.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.

Interviewer: Stepping out of the Ivory Tower and into the arms of the patient community. Up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Gabrielle Kardon, Associate Professor of Human Genetics at the University of Utah. Dr. Kardon you were in Washington D.C. last week, what were you doing there?

Dr. Kardon: The purpose of the whole trip to D.C. was to go with these families who are all affected by congenital diaphragmatic hernias. So this is a common birth defect that affects about 1 in 3,000 children, and to rally support from the House and Senate for increased funding for NIH, in particular for birth defects and CDH.

Interviewer: Could you have imagined doing this a year ago?

Dr. Kardon: Well maybe a year ago, but five years ago I wouldn't have. What we were able to find is that the connective tissue, which is basically the matrix that's surrounding the muscle and hooking the muscle to the tendon was regulating everything about development of the diaphragm's muscle. It controlled normal development, and that actually mutations in the connective tissue were the cause of this very common birth defect.

At first it was it's just a really interesting scientific questions and then over the years as we started to make progress and we realized that actually maybe we could gain some serious insights, then I was very interested in connecting with the families. In part just because you get interested in it and you want to know really what is the situation if you have CDH. And then in part because it turns out the family members have lots of information that they don't realize that they have that gives you incredible insight into the birth defect.

Interviewer: Is it fair to say that this intersection with this disease has totally refocused, at least part of your lab?

Dr. Kardon: Yes. I had always worked on limb development and limb defects, but now more than half the lab is working on the diaphragm.

Interviewer: You have mentioned that they have information that has helped you. What kind of information?

Dr. Kardon: So for instance, I was talking to parents in D.C. and there were at least two parents who were talking about CDH babies in which also in that baby was not only this diaphragmatic hernia, but they had a cleft palate. And it turns out that there are developmental processes that are very strongly linked between the two and so to see them repeatedly in the same patient gives you some insight into the science behind it, so that was something that was really interesting.

Interviewer: Do you think that you've been able to give something back to them? Do you talk to them about your science and do they understand it?

Dr. Kardon: Right. Actually, I think there's one way that was sort of surprising that I think maybe had the most impact on them. There's an enormous variability in the single diagnosis and for the families that's really hard. So it is really hard to be the parent of a child who dies and meet up and see a parent of a kid who also has the same defect, but looks completely normal. And I think that's very difficult, I think it's difficult to be a cohesive group when there's such different outcomes.

So I think the thing that I could contribute to that conversation is to tell them that there are good genetic reasons as to why there's such variability and in fact this is one of the real scientific conundrums about the defect is that there are many ways to get a hernia. And in part some of those ways to get it involves this de novo mutations that arise in the kids and when and where those mutations arise really affects the outcome. And so that when as a parent, as a pregnant mother, you're diagnosed at 20 weeks with the CDH, you have absolutely no idea what's going to happen when your baby is born.

Interviewer: So it's not their fault.

Dr. Kardon: It's not their fault and it's very different from let's say, people who have Duchenne muscular dystrophy, where they're all pretty... there's some uniformity to the disease. There's a pretty general progression. There is not any uniformity in CDH, which makes it really difficult.

Interviewer: Do you think they take comfort? Some people have taken comfort in knowing that?

Dr. Kardon: I don't know, it's hard to know. This is my first sort of serious interaction with patients... sorry, with parents of patients and with patients, and some of the parents it was pretty raw. There were parents who were at this meeting who have lost their baby only a month ago. So they're in a tough place.

Interviewer: Yeah. Obviously this turned into kind of an emotional investment, as well as a time investment. I don't know, what does that mean for you?

Dr. Kardon: I don't know. I make a pretty serious commitment to do the science, and that commitment means that I'm taking time away from my family, and so I would hope that what I'm doing should be something that's important and makes an impact on someone. And so it's helpful to see who that would make a difference to. And I really am still a basic scientist. But it's kind of hard when you're working in this direction and you can see that there are hints that you may be able to do something in terms of therapy and it feels like it's a challenge, it's kind of this puzzle, "Why wouldn't you do it?" We could actually do some clinical trials using mice, now wouldn't that be really interesting?

Interviewer: Is there anything that you can think of that you want to make sure to get across?

Dr. Kardon: I guess the one thing it's really that scientists sometimes shy away from interacting with the patients of the families and it seems a shame, it seems like you can learn so much from them. They have an enormous amount of knowledge that they don't even realize that they have about the disease. It's just buried in them, funny little observations that they have made. And you come in there with a completely different set of eyes and talk to them, and they'll say something and you'll go, "Wait, wait, say that again. What is it? What happened here?" And you learn a huge amount from them, so I think it's really worth while.

Announcer: Interesting, informative, and all in the name of better health. This is the Scope Health Science's Radio.

Interviewer: Many diabetics experience dangerous fluctuations in blood sugar levels but the problem is compounded and what they don't even know it's happening. Dr. Simon Fisher explains his research to combat hypoglycemia unawareness work supported by the JDRF.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Simon Fisher Co-Director of the Diabetes and Metabolism Center at The University of Utah. Dr. Fisher before we get into the research I wanted to talk about the role of non-profit organizations. Your work is funded by the JDRF and I think we're becoming more familiar with other visible campaigns such as the ALS Ice Bucket Challenge. It seems that these organizations are becoming more prominent these days.

Dr. Fisher: As you know the National Institute of Health, our Federal Government, is under a lot of financial restraint and they're very selective of giving out money, and money's tight all around, so the actual rates of funding from the National Institute of Health has not grown in the pace that research is. So there's an incredibly important role and we rely on agencies to fund our research. So the JDRF focuses on Type I Diabetes based research. Everyone has their own interest, personal connections to family members who may have this disease, and I guess we're talking about diabetes, and it's very important for them to feel that they're doing something that is leading towards you know better treatments or a cure, and every agency has their own agenda so to speak that allows them to put money where they think it needs to go.

Interviewer: Your most recent grant from JDRF is supporting your research investigating complications associated with diabetes. So it stems from this paradoxical observation that diabetes causes high blood sugar levels but one of the major problems of diabetes is hypoglycemia, or low blood sugar, how does that happen?

Dr. Fisher: Because we're treating diabetes better and better and getting more and more aggressive and trying to get blood sugar down to normal or even below normal levels the incidence of hypoglycemia, that's low blood sugar, has now eclipsed that of high blood sugars in terms of hospital admissions. People are coming in now because we're treating them more and more aggressively. These low blood sugar reactions can be mild, I mean they happen every day, or every other day for people who have tightly controlled blood sugars.
The problem is as it happens more and more they run the risk of having neurological problems. Again, what happens is your ability to defend against this low blood sugar becomes impaired over time your brain runs almost exclusively on blood sugar so as your blood sugar drops your brain starts having problems functioning, sadly. You get, it can be as mild as a confused, a little disoriented, but it can cause people to pass out if your blood sugar gets low enough. It can cause people to have seizures if your blood sugars get low enough and a recent study we published shows that low blood sugar actually is fatal. If your blood sugar is low enough for long enough people die.

Interviewer: Wow. Now normally people know when they're becoming hypoglycemic, right? There are different warning signs that the body give you?

Dr. Fisher: Right so you can imagine as your blood sugar gets low and your brain stops functioning it's a flight or fight stress response. Your brain activates your adrenaline, your epinephrine, your norepinephrine, other hormones in your body help bring your blood sugar back up. What I'm studying in our laboratory is hypoglycemia unawareness. What happens is your body doesn't get these traditional warning signs, you don't get hungry. For example, you don't go, "Gee my blood sugar is low," and go get something to eat, go grab a glass of orange juice, etcetera
Nocturnal, that is night time; low blood sugar is particularly dangerous. People with diabetes and hypoglycemia unawareness don't wake up in the middle of the night. This leads to the unfortunate "dead in bed" syndrome, which is as horrible as it sounds.

Interviewer: Well obviously it's a very serious problem and your approach is to study it in an animal model.

Dr. Fisher: Right, that's the novel part about our research, is we've now created an animal model to investigate hypoglycemia unawareness. So the trick for many, many years is how do you get an animal model to respond hypoglycemia unawareness? In humans it's easy you say, "Do you recognize that your blood sugar is low?" And we lower their blood sugar and they say, "Yeah I feel horrible," and I go, "Okay you're aware of hypoglycemia."
For people with long standing diabetes if we lower their blood sugar into a low level and they say, "No I don't feel anything at all." They're by definition hypoglycemia unaware. You can't ask a rat...

Interviewer: No I guess not.

Dr. Fisher: ...if they're, how they're feeling. So what we've done is we've modeled this by saying, "What is going to help somebody if their blood sugar is low?" Basically they need to go and get food. So what we're doing is we're measuring how much food our rat takes when his blood sugar is low, and in our model now what we've done is we make the rats who are currently hypoglycemic, similar to patients that take insulin every day, and if their blood sugar gets you know low one day or the next day they're at high risk for hypoglycemia unawareness the next day and that's what happens in our rats.

Interviewer: So the rats who get food are aware, at least subconsciously aware of their hypoglycemic condition. The rats that don't eat are hypoglycemic unaware.

Dr. Fisher: Right, and so what the JDRF has, the goal of their research is to say, "Well what we can do to make people more aware?" So essentially what we're doing is a drug screen. We're giving many different kinds of drugs that act in the central nervous system to these rats, these rats that we've made hypoglycemia unaware, and then we're seeing which drug is really going to make them say, "Oh geez I feel horrible I've got to go eat," and any drug that can help them decide to go eat is a drug which is enhancing hypoglycemia awareness.

Interviewer: Now I noticed in your drug screen that you're screening through drugs that are already FDA approved for other conditions. Is there reason that you're taking that route instead of screening through new compounds for example?

Dr. Fisher: There are several reasons. One is, technically it's easier. These drugs are all FDA approved so we can just pull them off the shelf and you know throw them into rats and see if they work. Secondly, from a practical point of view if we want to get something to a patient as quick as possible if we find drugs that really show clear promise in rats we can jump immediately to clinical trials because these drugs are already FDA approved, we can accelerate the pace of research and get it into people sooner rather than later.

Interviewer: And what do you think is a realistic time frame of going through the screen and getting a drug to clinical trials.

Dr. Fisher: So obviously these studies need to be done in rats first then we'd probably do it in a large animal model then we could relatively quickly move into a human model. So that's why, again I'm trying to take my clinical experience and seeing people suffer out there with severe low blood sugars that were admitted to the hospital, they were driving their car, they passed out because their blood sugar was so low they crashed, they took away their license, and as a Diabetologist I want to get them back and functional and living a normal life. What I'm hoping is that my study will have a translational aspect so I can get drugs into humans that might benefit them so that they can live full, meaningful, and productive lives.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.

I think the regulatory agencies can use their platform to help inspire science and development of new tools that will provide better, safer, more effective, higher quality products, which is really what we're trying to do in terms of getting good therapies to patients.

The major barrier to entry in the market is the cost and the time that it takes to bring a discovery that's made in the laboratory actually to the clinic.

On average, right now, to bring a new drug to the market, it's probably somewhere between one and two billion dollars. If you've made a $2 billion investment in a new product, what do you have to price it at in order to get your return on investment?

If we were to try to support cures for all the orphaned diseases, it would consume the entire U.S. GDP. Clearly, we need to do a better job in driving down development costs so that we can drive down what these products are listed at in order to not completely break the healthcare system.

All of these different trends that are happening in the industry, the kind of merger and acquisition, the loss of capital, the direction that science is driving toward smaller markets, all of this is really converging to a point where this industry is under significant stress.

I think one of the things we need to do is think about establishing a national infrastructure for clinical trials. The other thing we need to think about is how we design smarter, I'll call them leaner, less expensive clinical trials that allow us to get just as much information about a therapy out of a much smaller trial.

We spend little to no effort on actually taking what knowledge we have, in terms of real world performance and things that we know about in prior studies, and integrating it back, or reverse engineering into the discovery or to the next generation product development.

Probably, most importantly, we don't include the patient and the consumer perspective. What are their opinions? What are their experiences, which are going to be critically important.

I think the academic medical centers are the drivers, or the engines of discovery and innovation, in terms of bringing basic fundamental mechanisms of knowledge of disease forward.

I think what academic medical centers could do, that might improve the situation, is take those findings a little bit further down that path of product development.

One of the problems, of course, is that they're not funded to do so. So the NIH isn't really funding product development, and that's something that I think, that the FDA is trying to change through its Regulatory Science Initiative, but it may necessitate other types of partnerships between academic institutions and private industries.

What we have to confront in our own nation is: Do we have a national commitment to funding research to improve health?

Well, imagine if we have a population that's not healthy, that doesn't have access to the best care that science underpinned. Imagine that absent science we have no idea what works best for whom, in what context, and why.

So how can we confront those challenges? The power of science brings an evidence base to that that really separates it from unguarded or unfounded opinion. So once we have the power of science, we can think about health in terms of improving the health of an individual patient but also of that patient's family, of the community, and the population, many of whom are vulnerable. And I think once we talk about reframing that for innovation as to improving health through all of those, then some of our other challenges may fall away.