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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. Bryan Jones, an investigator at the Moran Eye Center at the University of Utah. Now anyone who sees you knows that you carry a camera around with you wherever you go.

Dr. Jones: I do.

Interviewer: And I suspect your love for photography might have come before you delved into science.

Dr. Jones: It did, yeah.

Interviewer: I'm wondering if that passion for photography and how maybe we see the world or how the camera sees the world sort of influenced what type of research you're doing now?

Dr. Jones: I came to photography initially in college. My first major was film studies. And I spent a lot of time with a Leica M6 camera and a Canon 1D camera that my parents had. And I fell in love with photography. I've had the privilege of knowing a couple of friends who have retinitis pigmentosa. One of my friends is an army veteran, and I've watched him go blind. So for me, the ability to do photography and to share what I see is a constant reminder of why the work we do is so important.

Interviewer: And what are you looking at these days? What's driving your research?

Dr. Jones: So our lab has two main focus areas. The first is understanding how the retina is wired. So the retina is this piece of gauzy tissue at the back of your eye that is an extension of the brain. And this brain tissue at the back of the eye is sort of a layer cake-like structure with 7,200 neurons or more in our human eyes. And it captures light, photons of light and then computes all the parameters required for vision. Captures contrast and luminance and edges and movement. And calculates all these parameters and sends that information on to others and brain and cortex and sub-cortex for higher processing.

People have been studying the retina for about 150 years, and we still don't know precisely how all those 7,200 or more neurons are wired. And that's the first mission of our lab is to try and pull apart that wiring and identify all the neurons and figure out how they are precisely wired together. That's a field called connectomics.

The second main mission of our lab is to understand how that structure and how the neuron identity and how the wiring is altered in diseases like retinitis pigmentosa and age-related macular degeneration that steal vision from us.

Interviewer: So you're looking at circuitry itself?

Dr. Jones: Yes, ma'am.

Interviewer: And how are you doing that?

Dr. Jones: So there are two new approaches that have been pioneered. The first one that was pioneered by Dr. Robert Mark here at the University of Utah called computation molecular phenotyping. We basically use antibodies to serially label tissues and pull out smaller molecule fingerprints that uniquely identify populations of neurons. And then we insert those data into electron microscopy datasets.

So we basically take the retina and section it very thin. Each section is thinner than the wavelength of light. There are about 90 nanometers. And then we section in the case of the mouse retina that we recently finished, about 1,490 nanometer sections, and then we reconstructed those 1,400 sections into a digital layer cake and create a volume and then we go in by hand and trace neurons all the way through the dataset along with all their connections, their synapses and their gap junctions.

Interviewer: So the hope is to create like a three dimensional representation?

Dr. Jones: Yeah. A three dimensional representation that we then extract out circuit topologies. So it turns out the circuit topologies are far more complex than we thought they were. And so we're now having to develop new software that can allow us to visualize how complex some of these topologies are. The circuit topologies are things that give us excitation and inhibition and ultimately end up tuning response profiles in retina.

Interviewer: You know, if you think about circuitry in how most of us think about circuitry, I mean, if you look at the circuitry like in a computer or in the electronic system of a car, I mean, it doesn't exactly tell you how it works. Or does it?

Dr. Jones: So there was a pretty famous paper that came out a few months ago where they took a standard computer integrated circuit chip and they took it apart digitally and they tried to predict how it would work. And it turns out they didn't have a whole lot of information. It didn't function the way it should have functioned. Or at least their models, their predictive models that they thought how it would behave, it didn't actually behave the way the chip actually did.

So while the circuitry is what we're after and the circuitry in any neural system is sort of the substrate that gives us a basic performance profile and ultimately makes us who we are, there is still a lot we don't know. And so for us the connectomics framework, the circuitry framework we're trying to obtain is only the basic starting point.

It is a framework and on that framework we have to hang physiology, we have to hang physics and we have to put molecular biology and we have to put genetics into it. And so for us it's only the very beginning of understanding how neural systems are wired. Even though the science community has been studying the retina for 150 years. In a lot of ways, we are still right at the very beginning.

Interviewer: So it's kind of new frontier. Something that hasn't really been done this way before.

Dr. Jones: Yeah, exactly.

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

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.