Astronauts, Anxiety and the Trip to Mars

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Mark George

Well, I got very interested in the disease of depression. And as a resident, we had patients here at MUSC who were so depressed they couldn't eat, they actually couldn't move. It's a thing called catatonia. And then we could do a thing called electroconvulsive therapy or ECT, where a little bit of electricity over three or four weeks, 12 sessions can take someone like that, and then they're back and they're totally back.

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Mark George

And unlike other brain diseases where you've had a stroke or Parkinson's, where you can't really get back to the same level of function, they were often back absolutely. As well as before. And I said, What the heck is this disease that kind of takes over your body and your brain? So that was the pain point that I saw, that these there were these patients and this disease that we really didn't understand where it was in the brain, what it was It's almost like an infection.

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Mark George

You take an antibiotic and you're back on your game.

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Kevin Smith

This is the innovatively speaking podcast brought to you by the Medical University of South Carolina. It's a place where we dove into the origin of the next big things the who, the why, the how, of ideas that are changing what's possible here at the Medical University of South Carolina, I'm Kevin Smith here in the MUSC podcast studio with my co-host, Dr. Jesse Goodwin.

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Kevin Smith

Good morning, Jesse.

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Jesse Goodwin

Good morning, Kevin.

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Kevin Smith

Tell me a little bit about our guest today. This seems like an exciting one to me.

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Jesse Goodwin

This is. Our guest today is Dr. Mark George and I'll and I'll share that. Dr. Mark George is one of the faculty on campus that I think whose reputation actually precedes him. And so I had an opportunity to travel to Israel on behalf of MUSC years ago as part of a delegation. And while I was there, I actually met with some companies who were asking me if I had ever met Mark.

00;01;47;27 - 00;02;11;15

Jesse Goodwin

And actually at that time I had not. But that was my first introduction to Mark. And all of the really fascinating work that Mark is doing in the field of brain function and stimulation. And so it is probably the only time in my tenure here that I've been international only located with people asking me had I had a chance to meet to be considered a superstar on our campus.

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Jesse Goodwin

So I think that might be the best way to to sum up, Mark, is his reputation precedes him because he's extraordinary.

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Kevin Smith

Fantastic. Well, let's dove right in Dr Mark. George, welcome to the MUSC Podcast Studios.

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Mark George

Thank you. I'm absolutely pleased to be here.

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Jesse Goodwin

So, Mark, to kick us off can you tell us a little bit about the field of research that you do here at MUSC?

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Mark George

So I'm a native South Carolinian, born in Columbia, and I went to medical school here. I wanted to do international medicine and went to Haiti and realized that it was really not suited for me and came back and didn't know what to do. I've always been interested in the brain and behavior. And so in medicine there are two, two areas that deal with the brain, neurology and psychiatry.

00;03;04;26 - 00;03;23;29

Mark George

And I thought they were both good, but both incomplete. So I did residencies in both. And it doesn't didn't take long, still doesn't take very long when you're learning how to practice medicine about the brain, where you run up against where our knowledge stops. And it's just tradition. We just don't know, you know, the brain is the last frontier.

00;03;23;29 - 00;03;45;20

Mark George

And so I started and I... back then we were having new ways of imaging. The brain, I think called CT scans and PET scans. And so I got very interested and in taking pictures and the best place to take pictures was in London, England. And so I went there for a year to do a research fellowship. And then after that and I age in Bethesda.

00;03;45;20 - 00;04;09;15

Mark George

And so I started my career really as a brain scientist, clinical scientist, taking pictures. I was a photographer. And my my main question was what part of the brain is involved in emotion when I'm sad or angry or anxious, what's going on in there and are there specific spots? And if so, can we understand those? And then can we use that information to come up with new treatments?

00;04;09;15 - 00;04;32;10

Mark George

So it's a real simple question. And I just was very lucky to be clinically trained. And then at research spots where I could do some of the first really basic science and then one of those new technologies that I stumbled on turned out to be a a blockbuster treatment. So and yeah, so that's kind of a nutshell of what I do.

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Mark George

So brain imaging initially, but now more brain stimulation geared towards coming up with treatments.

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Jesse Goodwin

So I like on this podcast to talk a lot about pain points. So that's where we like to start each of these episodes because to me, innovation really at its heart is a creative solution to a pain point. And so as you're thinking about what attracted you to the field, can you speak a little bit about the pain points that you thought patients who were maybe exhibiting symptoms were experiencing, or what was the actual pain point that sort of drove you to be interested in advancing this field?

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Mark George

Well, I got very interested in the disease of depression, and as a resident, we had patients here at MUSC who were so depressed they couldn't eat, they actually couldn't move. It's a thing called catatonia. And then we could do a thing called Electroshock, Electroconvulsive Therapy or ECT, where a little bit of electricity over three or four weeks, 12 sessions can take someone like that, and then they're back and they're totally back.

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Mark George

And unlike other brain diseases, where you've had a stroke or Parkinson's, where you can't really get back to the same level of function, they were often back absolutely. As well as before. And I said, What the heck is this disease? That kind of takes over your body and your brain and it's there. And then with a little bit of stimulation in the right spots, you can bring people back so that was the pain point that I saw, that these there were these patients and this disease that we really didn't understand where it was in the brain, what it was.

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Mark George

It's almost like an infection. You take an antibiotic and you're back on your game. And that was the pain point that I, I said, well, you know, what is it? How do we reset with electricity?

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Jesse Goodwin

And so how did you parlay that into the transcranial approach that I think you're also pretty famous.

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Mark George

Yeah. So I was in London doing these studies where we'd put people in the scanner and get them terribly sad and see what parts of the brain turned on or off. And then we would do the same thing with depressed patients. So we were coming up with kind of a circuit of what parts of the brain were involved in mood regulation.

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Mark George

So that was my imaging work. And then one day in an elevator in London, I was there and nobody talks in an elevator in London, at least they didn't. It was just not proper. And this subject turned over turned to me, says, Hey, doc, you'll never believe what happened. This guy put a magnet on my head and made my thumb twitch.

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Mark George

And I said, Oh, really? And and then I said, What floor was that? And he said, eight. So we went down to the ground floor. He got off, I punched eight and I went up. I kind of poked my way around and sure enough, I walked into a lab of a guy who is now a great colleague and friend, but he had a TMS machine, a transcranial magnetic machine, where you could put an electromagnet on the surface of the brain and create a powerful magnetic field which would go into the brain and induce electricity to flow.

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Mark George

So they were actually electrically stimulating the brain non-invasively. And if you do that over the motor area, you can make your thumb twitch. And so he was doing that investigating motor system. If you have a weak thumb is that damage in the thumb or in your shoulder or in your neck or in your brain? So you could use it to investigate motor system.

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Mark George

And that's what they were doing. And I'll never forget, I just turned to him while he was doing that. I said, what would happen if you move that thing forward? And I pointed to the spot over them, over your eyes, where we were beginning to think that that was part of the mood regulation circuit. And he looked up at me, he says, I don't know, but why would you ever want to?

00;08;12;04 - 00;08;38;10

Mark George

And so that was when I came up with the idea that we might be able to stimulate that part of the brain, non-invasively and not causing a seizure. And that over time we might be able to rehab that circuit and get people on depressed. And it does. And so I spent 15, 20 years getting it on to market doing the discovery science.

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Mark George

And now it's a and just this weekend I was driving from Charleston up to up to the mountains and I went through Columbia and right there at that dysfunction junction of I-26 and everything, there's a huge billboard. Don't suffer from depression any more there's a a chain of TMS clinics. And I said, Wow, it's back to my hometown now.

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Jesse Goodwin

I think that's actually really truly fantastic. And I think as your science has really taken off and this has become accepted and, you know, it's FDA approved for depression now, does this approach the other types of indications that it could be used for has also expanded? So can you talk a little bit about the expanded use of TMS outside of depression?

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Jesse Goodwin

What else it's got potential for being studied for or used clinically for?

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Mark George

Yeah, well, the revolution is that we now understand the brain is there's all these circuits in different parts of the brain, two things. And instead of buttons, it's actually circuits things that are connected. And then the connection is actually what creates healthy behavior. And and so a lot of diseases are now being understood as diseases of circuits. And so Parkinson's disease, the tremor, I mean, it's a circuit that's wrong.

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Mark George

And in psychiatry, obsessive compulsive disorder, addictions, you name them, almost all of our major psychiatric disorders are we're now and unraveling the circuits. And so whenever we have a circuit that seems pretty good we can use TMS non-invasively to go in and push and pull and then say, how would we do this to come up with a new treatment?

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Mark George

And in the last couple of years, we've gotten FDA approval for OCD. We've gotten FDA approval for smoking cessation. We're close to getting it for pain and for post-traumatic stress disorder. So it's it's just discovery science in a nice way where we're taking imaging knowledge and then using this new tool coming up with therapies. There are some brain diseases where we don't really understand the circuits.

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Mark George

Still, the schizophrenia are like that. Maybe autism is like that. And so those we're not able to get at with TMS yet because we really just don't know where to put it. We don't know the circuit yet, but it's an exciting time where almost, you know, every couple of months there's a new announcement and these things are out there helping people.

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Jesse Goodwin

Yeah, I think it's extremely exciting just to see how the field is sort of blossoming and taking off. And the sky's somewhat the limit in terms of, as you said, once we can unravel these brain circuitry is what we're going to be able to to treat using this approach. So with that, can you describe a little bit about what that treatment paradigm actually looks like for these patients that come in with any one of these disorders?

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Jesse Goodwin

What does a TMS treatment look like when they come in?

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Mark George

Well, this is a great question because this is all about innovation, and it's I can tell you how we started and how I made some educated guesses that were good enough to get it approved. But we're really not the final answer. And I knew they weren't the final answer then. But so when I started, we would do a session so we'd sit in a chair.

00;11;48;21 - 00;12;08;03

Mark George

minutes, and we'd give maybe: 3000

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Mark George

And weekends were off just because I couldn't come in and do all the treatments all the time. And, and we started with just two or three weeks of treatment and then we realized that wasn't sufficient time. We ended up doing six weeks and that was what we locked end to get FDA approval and the frequency of stimulation was ten hurt.

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Mark George

what got FDA approved back in: 2008

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Mark George

One is our pattern of stimulation cost data bursting and it sounds like this, it goes back to say where did that come from? Well that's the noise that if you stick a wire into the hippocampus and listen to human nerve cells talking to each other that's how nerve cells communicate. And so not me. Somebody else said, Wow, if that's how the brain talks, why don't we talk back to it in its own language?

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Mark George

And so that's called data bursting. And it seems to be a much more efficient way to use TMS to change brain activity. And so with that, we're able to do we're a lot more efficient so now you can do theta bursting, which as opposed to 20 minutes a session can be only 5 minutes a session. And then so people said, wow, people have driven 2 hours to come for the five minute session.

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Mark George

What if we did multiple sessions in a day? And so one of my students here who's now out at Stanford just recently published a exciting study where you bring people in and you do ten treatments a day for five days straight, and that's it. And he got 90% remission with that new protocol. And that was published and is likely to get FDA approval in the next month or so.

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Mark George

So people are reevaluating how we do it. The old pattern of once a day with weekends off for six weeks was a big time commitment, especially if you lived far from a TMS chair now with just one week, everybody can take a week off for vacation. And so the idea of going somewhere, taking a week off and getting your depression dealt with is really exciting in terms of opening up new possibilities for patients.

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Kevin Smith

And these treatments are permanently put in remission.

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Mark George

Oh, that's the thing. We don't talk about cures yet with depression. What we do is if you do one of these paradigms and you've got depression and you've tried and failed other medicines, it's about a rule of thirds, one third of people will get remission. That is their depression. Symptoms are totally gone, at least temporarily. Another third won't get remission.

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Mark George

They'll still have some depression symptoms, but their symptoms are at least cut in half. And then unfortunately in one third, it doesn't work. Now, how long do you go afterwards? Again, another rule of thirds. One third of people who get well with TMS never need TMS again. They may still need talking therapy, occasionally medicines, but we strengthen their brain so that their depression is easier to deal with.

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Mark George

Another third will need a treatment within two years. But the good news is they just come back. They do the same thing again and always works again, and then they may go another two years or forever. Some people will relapse within a couple of months. And so then they also re respond when we bring them back. But then we start talking about doing maintenance treatment where we do a treatment a week treatment every other week.

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Mark George

And we've got several patients over at the VA where I practice, where we just do a treatment every whatever there we kind of accordian out how long it can go before they need a maintenance treatment and that people doing that for years and doing well.

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Kevin Smith

And you said strengthen the brain. Is it actually strengthening the circuits, building them up?

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Mark George

What's happening that's where the neuroscience is so interesting. And the answer is we are strengthening the brain. And so what does that mean, the brain strings? Well, you're talking about connections between different nerve cells in that circuit. And you can measure that either by looking at the cells themselves or the white matter that surrounds a neuron. And is there more white matter or is the brain bigger?

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Mark George

And TMS actually makes those circuits bigger. What we really think is happening is how a nerve cell communicates with another nerve cells. They have these little buttons that connect, and those are called synapses. And you can count the number of synapses and those actually increased with TMS and that circuit that's functioning. So so we are actually the hypothesis that I had way back then.

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Mark George

You know, if you did that, could you get people could you strengthen that circuit? It's true. We are doing that by actually causing and this is what the brain does. Naturally, when I'm learning a new thing, that circuit that embodies the new knowledge actually has more synapses that connect and allow me to do that behavior. So yeah, it does that.

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Mark George

So one of the exciting new innovations is, well, what is the what's the actual mechanism by which synapses form? And are there medicines that we could give with TMS that might boost that? And sure enough, another former student, Josh Brown, who's now up at Brown University, is doing that. He's giving a medicine that we know either promotes or blocks synaptic plasticity and shows that TMS with the growth, the fertilizer, that does exactly that, it's a lot more powerful.

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Mark George

And if you block it, TMS doesn't work. So we're starting to understand not only the mechanism, but the adjunctive pharmacology. And the reason that's important is I said a third of people, it doesn't work. And so you might want to actually give those people this kind of medication that would boost it.

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Jesse Goodwin

So with that latter sort of approach, Mark, where you might be able to give a boost with some pharmacotherapy, would that have a role in a potential treatment for things like Alzheimer's, where you're starting to see some changes in the Senate to synapses of the brain and perhaps stave off some of those side effects? Have you started to look at that or are people looking at that?

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Mark George

So in terms of TMS for Alzheimer's, that's been a little bit disappointing. A lot of patients with Alzheimer's are depressed and sometimes depression is one of the first symptoms of Alzheimer's. And I always say that we we have a hammer called TMS and the nail is depression and we can treat depression, whatever it is and wherever it occurs.

00;18;42;25 - 00;19;04;07

Mark George

So we can treat the depression of Alzheimer's. And often people's cognition will improve and they'll get back but we really haven't figured out a way of using TMS to fundamentally get at the memory and the long term changes in the brain. There's a lot of research on about doing that and what you're talking about, how we actually combine it with with pharmacology might be the answer.

00;19;04;07 - 00;19;20;01

Mark George

But right now, that's one of the areas that it's just harder than the luck that I had with depression. And I think it's solvable and will be a treatment. We just have to find that circuit and then the pattern of stimulation and then potentially the adjunctive pharmacology to make it work.

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Jesse Goodwin

So Mark, I recently saw a picture of you and some colleagues in a space flight simulator, so you know, thinking of this is space is the next frontier. Can you describe, you know, what the goal for that particular study was and what you were doing in a space flight simulator? All wearing interesting looking head gadgets?

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Mark George

Yeah, this was a real bit of fun. So I've been so blessed in my career with amazing colleagues and the amazing colleague here is Dr. Donna Roberts, who is a NASA engineer who came to medical school, I think in her freshman year. She knocked on my door and she's been working ever since. And then, you know, she became a radiologist but has always been interested in space and has been taking pictures of astronauts before and after they come back from floating.

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Mark George

But she and I have been trying to get NASA interested in using brain stimulation as a way to undo the effects of weightlessness. And then also the idea that when we go to Mars, I think we're going to be able to solve all the payload issues and communications, all the technology stuff you can solve. But the big unknown is actually the human factor of depression.

00;20;35;29 - 00;20;59;13

Mark George

And the crew and NASA now understands that you can't just choose the right stuff. There's no person who won't get depressed and you can't select the few chosen individuals. That's just not possible. So how are you going to treat the depression that will occur on Mars? Well, you could send up a whole bunch of Prozac, but not everybody responds to Prozac and it goes bad after a year.

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Mark George

So you'd have to send up a whole bunch of five or six different medicines. They'd all be bad after a year. You'd have to send a second payload what if that payload failed? So solving it with what is the bioavailability of pills and weightlessness. So pills are complicated but if they have a solar panel and electricity they have, they can have TMS.

00;21;20;16 - 00;21;47;13

Mark George

So they've been very interested in whether you could use TMS on spaceships or in Mars to treat the depression that we know will occur and other brain diseases that that might. And so one of the first questions is can you do TMS when someone's floating? And so we wrote a grant to ask that question and it got funded and we went down and got on what's affectionately known as the Vomit Comet which is this plane where you go up.

00;21;47;19 - 00;22;10;11

Mark George

It's just a regular plane, a big cargo plane, but it goes up and you fly in parabolas where you're going along you go up. And then as you tip over and fall, you're floating. So you have 30 seconds of weightlessness. And then they do that over and over about 2 hours. So you get up over that time, you know, 20 minutes of weightlessness time.

00;22;10;11 - 00;22;33;06

Mark George

And so we proposed to do TMS actually going back to that first time I saw the thumb twitch do that exactly. While you're floating and to see whether the amount of electricity needed would change when you're floating versus when you're sitting on the tarmac or back to the tarmac. And sure enough, it takes about ten, 15% less electricity to stimulate your brain when you're floating.

00;22;34;03 - 00;22;54;01

Mark George

And we're not sure we think maybe the brain kind of rises up and gets a little closer to the coil when you're floating. That's probably that's our major explanation. But we showed that you can do it and and that there are some changes in and physiology that you need to know. And so hopefully we'll be able to do more like that.

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Mark George

And at some point when we're on Mars, there'll be a TMS device there.

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Jesse Goodwin

So think about how different the outcome for the Martian movie would have been if only Mark Watney was armed with TMS, including his botany skills. Right.

00;23;07;19 - 00;23;26;23

Mark George

Well, he didn't get he got a little depressed, but he was able to work through it in that movie. But you can imagine it going the other way where he just got catatonic and gave up. Yeah. Or psychotic and gave up. And that's unfortunately not not an uncommon outcome in situations like that. So yeah, you don't want to have that possibility, right?

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Mark George

Yeah.

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Jesse Goodwin

So, Mark, to your best, it sounds like you're the field of study is really just taking off and going and all of these fantastic directions. But science is science. And so what are still the current stumbling blocks that you grapple with or that keeps you up at night? That you're thinking about, how am I going to solve that tomorrow in the lab?

00;23;46;27 - 00;24;16;14

Mark George

Well, the thing that I worry about the most is not the technology. Oh, my gosh, there's so much there and it just gets discovered and it's there. The rate limiting step for how well and quickly these things will translate into patients really is what I call translate all neuroscientists. So people who can do the discovery trials where you have an idea and it's a good idea, but how do you really tested in people with a disease and then figure out whether it's working or not?

00;24;16;14 - 00;24;38;13

Mark George

And that's it takes a complicated skill set because you have to be be kind of clinically trained and you also have to understand the science and you have to be able to put those things together. And often that's done in teams and that's great, but everybody in the team needs to be a translational kind of a discovery scientist, and that's the rate limiting step that I see there.

00;24;38;13 - 00;25;05;07

Mark George

Not that many people. It's a little bit easier, better, higher paying different approach to just treat patients. And, and then if you just do science and discovery science, the technology that's almost easier and what I worry about is do we have enough of these translational neuroscientists who are going to be able to do the very hard work? And looking back, you see all the successes.

00;25;05;07 - 00;25;25;24

Mark George

I could spend a lot of time about all the failed trials. And it's discouraging when when that happens. And so my worry is that we don't have enough translational neuroscientists who can can move these things through. And that's why I'm so blessed to be here at MUSC and a place that allows us to do that and promotes and grows the next generation.

00;25;25;24 - 00;25;52;11

Mark George

So that's my worry. I don't think that technology is going to be a problem, and I think these will become even more common in our world. How fast they get adopted is really that issue of how many people do we have to do the work. I'm grateful for all the patients who partner with us. Everything that we've talked about here involve not just me as a scientist, but as somebody taking a risk saying, Oh yeah, OK, that sounds a little crazy, but I'll work with you and I'm always grateful for those people.

00;25;52;20 - 00;26;13;19

Jesse Goodwin

Well, this has been an absolutely wonderful conversation, and I learn so much every time I talk to you about just all of the amazing things that you've accomplished over the course of your career and where the field is still, to me, the next frontier, no pun intended. And so thank you for your time and thank you for joining us here in the podcast studio.

00;26;13;21 - 00;26;14;25

Mark George

You're welcome. Thank you.

00;26;17;14 - 00;26;38;10

Kevin Smith

You've been listening to the Innovatively Speaking Podcast with the Medical University of South Carolina. If you enjoyed this episode and would like to support the show, leave a rating and review to hear more innovative ideas and to share your own. Subscribe to the show or visit us on our web page. Web Dot MUSC Dot edu slash innovation.

00;26;38;17 - 00;26;41;13

Kevin Smith

And remember, don't hesitate to innovate.