Dr. Dennis Drayna — Part 2: Genetics of Stuttering and Communication Disorders

>> So do people who are maybe deaf or use sign language, do they also stutter?

>> This has been controversial. There are people who claim to see something that looks like blocks in sign language. So, people whose fluency, that is the ability to string together words into sentences and sentences into paragraphs, somehow seems to be impaired. And it's been suggested that people who use sign language have repurposed parts of their brain that are used by other people, normal hearing people, for speech. Okay? So, there's some overlaps in the mechanisms used for sign language by the deaf, overlap with the mechanisms used for speech by the hearing. Okay? But it's a little anecdotal because it's uncommon, right? It hasn't been the subject of large placebo-controlled, double-blind prospective studies, the kind of big difficult studies that are typically used in the world of clinical medicine to characterize diseases and response to diseases or response to drugs. So, it's a little anecdotal. It's sort of like the evidence on stuttering in foreign languages. So, sometimes people who speak a second language stutter just as much in the second language as they do in the first language, but sometimes they don't. Sometimes they don't.

>> I wonder why.

>> Well, there is a theory about this. I'm not sure how much I subscribe to the theory. But there is a theory that things that distract you from your speech can improve fluency among those who stutter. Okay? So, if you take a person who stutters and do something surprising — if you startle them — they can often be immediately thereafter perfectly fluent. Even relatively severe stutterers. Or I've heard it said — and I don't know if it's a fair thing to say — but I've heard it said that one feature that's in common with a lot of stuttering therapies is that they force the person to think about something else when they speak. And that maybe that contributes to the increase in fluency from the therapy, right? So that may be what's going on in the people whose fluency improves when they speak a second language. Short answer is we don't quite know yet.

>> Sure, yeah. Are there any common myths that you hear about stuttering that are just not true, that a lot of people might believe?

>> It's a long list, and it's a very unfortunate list. I think the most common myth is that if you just tell a person who stutters to relax that that will allow them to be fluent. As a general rule, people who stutter don't find that helpful. They just don't. I think some of the myths about stuttering are incredibly damaging. The myth that there's something wrong with the people—I mean intellectually wrong with them, or psychologically wrong with them, or, even worse, psychiatrically wrong with them: that this is some sort of, something akin to a mental illness—there's no evidence that any of this is true. And it's obviously very damaging to people who stutter.

>> Yeah, I think you said almost everyone who stutters has almost no other issues that are detectible?

>> The vast majority of the people who have the common form of stuttering don't have anything else wrong with them. They just, they don't. My favorite example: Bill Walton, NBA's most valuable player from the Portland Trailblazers, back several years, back I think in the 1980s. Bill Walton has a severe stutter. And anybody who's the NBA's most valuable player clearly doesn't have other motor problems. [Laughs] So, and there are plenty of intellectually brilliant people who've had a severe stutter. Plenty of people in all walks of life, in all aspects of professional success have a stutter. James Earl Jones. Now you might expect someone like that, who's so reliant on that incredible voice that he has, right? The voice that we all, I wish I had. He has a stutter, but he's able to control it. John Stossel has a stutter. I can hear it because I'm used to seeing, you know, I'm used to subtle cases. But it hasn't prevented him from being a major figure in, you know, television news for decades. But lots of people have had a stutter that hasn't really affected their career success. Winston Churchill, Marilyn Monroe, it's a very long list of very accomplished people. So, I think the myth that there's something like mentally wrong with people who stutter is pervasive and damaging and just a myth. It's just not true.

>> Yeah. How did you originally get interested in stuttering? Research for stuttering?

>> Well that was a combination of factors. First of all, big family history. My uncle stuttered, actually quite significantly until he got to college, interestingly enough. My brother stuttered through his whole life, my older brother. I have twin boys. They both stuttered when they were young. Although very different presentations, very different. One was kind of the classic presentation. And one was kind of an unusual variation, didn't start stuttering until he was a little older.

>> Are they identical twins?

>> No, they're fraternal twins. They're fraternal twins. So there was a family history. And I, that sort of intrigued me. I've[CB([1] never felt I had a fluency problem. But the family history was interesting. But I think there were several things. First of all, it's an unmet need. It's, yeah. It's, it's surprisingly common. And it's inadequately treated. It is. I think the third thing is the scientific challenge. It, it has many puzzling clinical features to it. It, it clearly is something very specific because it, it's like a motor problem, okay? Yet these people don't have general motor problems. So it seems to me that there's a part probably of the brain that's uniquely dedicated to speech. And uniquely affected by whatever this problem is, okay? I think it's a part of the brain we might not even realize exists yet. But there's something special in some unique part of the brain. And we think it's unique because there's no other symptoms in these people, right? So it was a scientific challenge. And then finally the fact that I thought there was something I could do about it. At the time, the evidence that there were genetic factors that were involved was kind of sparse. The way geneticists determine nature versus nurture, genetic versus environment. Is with usually twin studies and adoption studies. And I looked at the old twin studies. And they looked very intriguing to me. So in that sense it was a little bit of a bet. And in fact, that bet turned out to be the correct one. Because in the first five years I was at the NIH, many more twin studies came out. And then the evidence was overwhelming. I mean enormous studies. Thirteen thousand pairs of twins. And evidence for, for very high values for what we call heritability which is a, it's a statistical construct, heritability. But what it, what it really means is the amount of a trait that is due to genetics. Versus environment or other things like random factors, you know, what we call stochastic factors. So the heritability of stuttering turns out to be really high. And so that meant the genetic approaches could likely be fruitful. So it was a combination of those factors. It was really an unmet need. A fascinating scientific problem that I felt maybe there was something I could do about it.

>> Yeah, it sounds like a very interesting challenge.

>> It was. I think to be honest, when, when we started, I think there would have been. There were no shortage of people. Not to be critical here, but there were, there were no shortage of people who thought this idea was nuts, frankly. Because it wasn't widely recognized that stuttering was highly familial 20 years ago. Most people weren't aware of the, of the strongly, the strong genetic evidence here. And if you went to the stuttering community, this was let's just say not well accepted. It was not. In general, most people in the stuttering community at that time focused on the social factors. You know, people would come to me and say. "Well, I know what causes stuttering. Stuttering's caused by anxiety."

>> Maybe as a way to be hopeful that they could overcome it.

>> Well, maybe, yes. But I think it's also true that it's well known that anxiety will, will make fluency worse. You, as I like to say, you can take a mild stutterer and turn them into a moderate to severe stutterer by just asking them to stand up in front of 500 people and give a speech, right? So there's some fundamental connection with emotional factors and stuttering that we don't understand yet. And that frankly was another scientific aspect that attracted me to this. We have no idea what this could be. But we think that this, this is telling us something. I think this is telling us something about what I call the phylogenetic origins of speech. Where does speech come from? There's lots of vocal communication out there in the animal world. As, as I've heard people say. That while, while speech and language as we know it may be unique to humans. It is based on genes that are not unique to humans, right? And if you look at vocal communication in the animal world, a lot of it has to do with anxiety. You, when something is frightening, you hear it, right? Lots of vocalization comes in response to a threat in the animal world. And so I think that might be the origins of the connection between anxiety and severity in stuttering.

>> Interesting. Yeah, because it's kind of an involuntary response to something.

>> It's completely involuntary. One of my favorite examples is go to an amusement park, right? And stand next to the roller coaster. Just stand there. And the roller coaster starts up, you know the initial incline. Clink, clink, clink, clink, clink.

>> You feel the tension building.

>> And as it goes over the top for the first big drop, every person on that roller coaster vocalizes, right? [Laughs] Voluntarily or otherwise. So there's, there's something fundamental here that we think will be an interesting. An interesting aspect of basic neuroscience.

>> I imagine not. But have any, any animals ever been identified to stutter in the natural world?

>> So there are a group of very talented people who study birdsong. And the reason they study birdsong is because there are some birds, not actually that many, but some. That share an unusual feature of their vocalization with humans. Which is they learn it. The vast majority of animal vocalization is kind of innate, and it's preprogrammed. It's like a dog barking, right? It's, but some species of birds learn their song, okay? And so this has become heavily studied. Lots of talented people working on it. And they, there are birds that have various problems. Brain lesions or various things where their song becomes disrupted. In a way that sounds kind of reminiscent of human stuttering. The problem is the, the bird brain is very different from the human brain. They, they don't really, there are big parts of the human brain like the cerebral cortex that birds don't really even have. So it's a little early to tell. One of the problems is there's no genetics in birds like there is in mice. You can't manipulate them to be kind of whatever you want. Like you can a mouse. So I think there might be some hope for, for birds, birdsong research in stuttering or other speech problems. But I, I think it's still a little ways off. From, from where we are today.

>> And what's, do you know roughly? What's the prevalence of stut--stuttering in the general population?

>> So the standard figure for this is one percent worldwide. I'm not sure. This seems slightly high to me. It seems slightly high. And part of it is, is that actually it's not such a simple statistic. And the reason why is because of the way the disorder develops. It's actually very common in real young children, right? So almost all stuttering develops in young children. At a particular time in the development of their speech. It's actually called developmental stuttering because it arises at such a characteristic time. Not when they first begin to talk. But often as their speech begins to get more complex. And then all of a sudden stuttering comes out. And this might be at age three or four. Something like that. So this developmental stuttering is, may be in as many as five percent of kids have this. The good news is that the great majority of them just outgrow it. So maybe 80%, they just recover. Either with the help of some speech therapy or just spontaneously, okay? My kids recovered completely spontaneously. They just, they just grew out of it. And so what's left is called persistent developmental stuttering. And that's the real problem, right? Because a lot of people who had it as young kids, they were so young, they don't even remember they ever had it. So it's, when it first appears, it's hair-raising for those of us parents who have been through it. But in the end, it, it turns out to not be a problem. The problem is the stuttering that doesn't resolve. What's called persistent developmental stuttering. So that's what we work on, okay?

A lot of those are very mild cases. So I think it’s something that you and I as nonprofessionals, speech/language pathologists could recognize. Maybe it's not quite one percent. Maybe it's half a percent. But that's, okay an amateur's, an amateur's guess here. But it's nonetheless, it's millions of people in the United States. And many millions worldwide. And it's, it's remarkable in that it occurs in every language. Every language that's ever been studied has people who stutter.

>> Wow. So it sounds like you figured out how to, for lack of a better term, mimic stuttering in mice. So that'll probably take up a lot of your time going forward. You've got a lot of avenues to pursue with that mouse model. What's, so what's coming up next for you? You already sort of mentioned you're writing papers furiously on what you're looking at now. But what are some of your goals for the next maybe one to five years?

>> Well, let's see. We have a lot more genes that we know exist. We even, because of family studies we've done. We've done lots of family studies over the years. We even know where these genes are. There's one on chromosome three. There's one on chromosome 14. There's one that we found in Brazil that's on chromosome ten. There's one on 16. So we're, rapidly chasing these down. As what are hopefully the low-hanging fruit to find the next collection of genes. Whatever these are going to tell us. I think it's likely that they may be something new and different than what we've seen with the genes thus far. The analogy I, I like to have is from my colleagues. In our institute who study deafness. A large fraction of deafness is due to simple genetic factors. There are something like 150 known deafness genes.

>> Wow.

>> Right, yeah, it's a lot. So it's hard to imagine that there might not be a lot of genes that cause stuttering in the end. There's 150 that cause deafness? But, but we'll have to see.

>> Yeah. What are some of the precautions or approvals, or what do you do to ensure that the animals used in research have, are treated as well as can possibly be?

>> Well, I think the United…, I'm sorry, I think the NIH has been and still is, certainly is, a leader in issues related to animal research. To just give you an idea of the attention that's given to this here. Every single mouse in our studies, and it's a lot. It's, by the time you do all the breeding and engineer all these lines of mice with all these mutations. It's thousands of mice. Every single one of them is accounted for in advance. In our animal research protocol. And every single one of them has to be justified before it is ever born. So there are no extra animals in our research studies. And a main focus of any research protocol here at the NIH, interestingly, is what can be done, in fact, without using animals? That's one of the first things you have to address. When you propose to use animals. Is what could be done without them? Okay? So that gives you some idea of the priorities around here. But not only that. Every single adverse event, you know mice don't live that long. So if you have special mice and you want to keep them alive for you know a couple of years. They're getting to be pretty geriatric mice at this point. And they become susceptible to all sorts of normal problems of aging. So you lose animals just for all sorts of reasons at a low level. Every single one of them has to be accounted for. And you have, you have to be able to describe what happened to the mouse. And whether you think the mouse died based on some aspect of your research procedures, right? Or some complication of your research procedures. So I maintain a human research study protocol, and a mouse research study protocol. And I would say that the protections for the living subjects in both of them are just about equal. So the NIH looks at research animals as a very precious resource. That we have been entrusted with their welfare. There are some things that just, research would just be enormously retarded or set back if we didn't have a way to look at it in an animal. It, you, there are things you just, you can't do in humans. You can't do, not just for ethical reasons in humans. But you just physically can't do in a human. Humans don't, they don't have all the genetic tools. And all the reagents and resources that have been developed for laboratory animals. So I would say that the, that, that it's. It's really been, I think, a great, I think it's been not only a great benefit to our research. But we've been entrusted with, with a lot of responsibility in the care and the welfare of our, of our research animals. So if you want to do animal research. The idea that somehow these animals are mistreated, I think is, is not a full characterization of the situation. It's just really not the case. The veterinary staff here are amazingly skilled. And they are, they are on the lookout for their animals. And I can't tell you the number of times a member of the veterinary staff has appeared in my office doorway to bring something to my attention that needed my attention. With regard to welfare of my animals. So I'm glad we have them. I've learned an enormous amount from our, from our veterinary and animal care staff here. And it's, it's, it's been really a unique and incredibly valuable opportunity. To be able to do it.

>> Yeah, and I guess you couldn't, you also couldn't have people living here for years from birth until, until they become adults and grow old. That's just impossible to do any type of research like that in people. Whereas mice just live for a couple years, naturally, or a few years.

>> There are many advantages. To, to different animals. The, the majority of the animals, the great majority of the animals here at the NIH are mice. And yes, they, they are born quickly. They develop quickly. And they grow old quickly. So that all saves valuable time in our studies. Yeah.

>> And so how many people are on your team?

>> So my team currently sits at five. It fluctuates. We, we have a lot of interest from trainees. Summer research experience at the NIH is coveted by lots of people. And we do try and accommodate summer trainees, so the number goes up. Often in the summer, I'll have maybe eight or ten. People in my lab, yeah.

>> So a few summer trainees, three or four?

>> Exactly, I, but personally. I, I am not in favor of a really large laboratory. I have found that when I get more than about eight people in my lab, I stop seeing the original data. And if I can't see the original data, I don't want to do this job.

>> Meaning because you don't have time to see all of the data that's produced?

>> Your administrative and other management responsibilities. You just, you just aren't able to see it. And so you know, the real excitement of this business is really. If you sort of take off all the layers and get down to the, to the bottom of it. The real excitement of this business is seeing and analyzing the data. Because that's where new things are discovered. And so that's why I don't like to keep my lab group any larger than I need to.

>> And what do you look for people who apply to join your team?

>> Well it's a list of things. It's a number of things. We like people who are self-motivated. We like people who are coming to us because they're interested in doing research. Not because someone tells them that they think they should go to medical school, right? And that doing an internship at NIH would help them accomplish that goal. We have plenty of people who want to go to medical school. And have. Almost all of them have ended up being primarily research in their professional activities rather than clinical. But of course, the NIH is the perfect place to find out whether you might be more interested in clinical things or basic laboratory things. We look for people who are not only self-motivated. But people who have a work ethic that sort of understands the excitement of what we do. People who, who realize when they're sequencing a person's DNA. Some human subject's DNA. That for instance they're looking into that person's genetic makeup maybe for the first time, right? And maybe finding something important. Right? And as opposed to, for instance, someone who would like to put another line on their CV. And would maybe have more, less focused interest in what we do. So we rarely, in my lab, we rarely advertise for postdocs and students. We like to hire people who approach us.

>> Showed some motivation.

>> Showed some motivation. Showed some, the ability to not only motivation, but the ability to just go do something when there's not an established protocol for doing it. Right? Just walk into my office and give us, give me the sales pitch, right? Those people tend to work out very well. And we're fortunate at the NIH in that there are many, many mechanisms for bringing trainees in. The NIH has an incredible array, it's almost no matter what level of education, you know, beyond a high school education, what level of education or what setting they're in, the NIH has an appointment mechanism that can be used for that person. And that's very unusual.

>> One thing I'm wondering about is, what has been the most difficult part of being a scientist in your career? Or maybe another way to approach it is what are common mistakes that you see people make? I'm kind of curious about your thoughts on that.

>> I think one of the most difficult parts about being a scientist. Especially for young investigators. Is to balance feasibility with impact. So, it's easy to think of enormously impactful projects or discoveries, right? Most of those tend to be very hard to accomplish, right? On the other hand, it's very easy to accomplish simple things, right? We all know how to do something simple in our field, most of them though tend to be lower impact. So, there's the constant, in some places there's a constant motivation to try and do the simple, easy things, right? So, you can get lots of papers and things like that. But the problem there is that you do that at the risk of tackling something hard that's going to have an enormous impact. So, you have to be able to find something that's going to have an big impact that's realistically doable. And finding that balance I think is the most difficult thing. It really helps if you, you know, have the ability to think broadly and to bring in techniques and intellectual approaches from widely disparate fields of science to bring to bear on your problem. So that's why I encourage people to think broadly and to get broad experience. Go to seminars in things that aren't so much your field, because you'll hear things that might allow you to make that magic connection that will allow you to do something highly impactful that's very doable, just by bringing two things together that normally no one thought of as bringing together.

>> Yeah.

>> So that's a tough one. Science is, it's not an easy business. It takes an internally motivated person. Because lots of things don't work. [Laughter] And it can be very discouraging to be slugging away. Especially with something new. When it's just one difficulty after another after another. But if you surround yourself with good people. And you surround yourself with ample resources. You can, you can plug away and actually break through those barriers. And so I encourage people to not let themselves get easily discouraged. Science is tolerant of a fair amount of failure. Probably much more so than in a lot of other enterprises. And that's because we don't know where it's going to lead us, you know. There are, we go up a lot of alleys that turn out to be blind alleys. And in science, that's okay. You can back out and try the next alley. But you have to have an, an attitude that, that is okay, you know? It's, it's and you need to be brutally self-critical. You can't do experiments in science unless you have a cherished hypothesis. A great idea, and it's your idea, right? But you have to be prepared to destroy your own idea. Because unless you really, truly try and fail. Right? You're not going down the right path. Right?

>> So, you do research in areas other than stuttering, I believe, and one of them is looking at how variation in genes linked to taste affect tobacco use. What have you learned so far in that area?

>> Yeah, well I should say taste is an example of, taste is an example of serendipity in science. I had the great pleasure of working when I first came. With Dr. James Battey who was then an investigator in our institute. And had not yet arisen to scientific director. And then subsequently institute director, from which he has just retired. So Jim, Dr. Battey, a very inspirational and talented person. Real, a real joy to work for. We're sitting around a meeting and he, he worked on cell signaling. And he noticed there was a lot of activity excitement in the cell signaling that he was an expert in. In the field of taste perception. So this is sweet, sour, bitter, salty, right? Those tastes. Not much was known about them at the time. And it was beginning to look like sweet and bitter taste were the kinds of things. These what are called G-protein coupled receptors. That are a famous class of molecules. And what Jim Battey worked on and so he sort of threw out a bunch of provocative questions. One of which at the time was well none of these molecules has been shown to actually function as a real-live taste receptor in some living organism. And I, I said, well wait a second. There's an extremely famous human trait. It's used as a, a teaching example in junior high school or high school. I did it in high school. My kids did it in junior high. But it's your ability to taste this really bitter substance. And about three-quarters of the world's population can taste it. And about one-quarter of the world's population can't taste it at all. It's tasteless to them. And it's inherited more or less as a simple genetic trait. And I happened to be working on a great big project. A general human genetics project at the time. And I said we can just add this into that big project. The genetics of this difference in taste. Because we know it's genetic. And that is a bitter receptor. We know, you know there you go. And so that's how I got into it, and we did find that gene. And it is an unusual bitter receptor and turned into a pretty big story. But, but where that led to was the recognition that there's a lot of differences in how people perceive what they taste that's based on their genes. Okay? And in particular, we got interested in menthol taste. Because. There's this very large difference. It's considered to be a major public health problem in menthol cigarettes. So flavorings in tobacco were all outlawed about 10 or 11 years ago by the FDA. With the exception of menthol which was grandfathered in and allowed to remain as a flavoring in tobacco. Especially cigarettes, okay? The problem with menthol is that it's predominantly, overwhelmingly used by African Americans. And it represents in some sense a racial disparity. An important racial, racial health disparity in America. And many prominent leaders in the African American community have begun to put their foot down. And say this, this is no longer okay, right? We feel this targets the African American community. And we don't, we don't think this should be allowed. And we think the FDA should regulate this. So we, we initially thought there was a very simple possible explanation. Which is that most of the world's genetic variation is in Africans.

>> Oh, wow.

>> Yeah, the vast, 90% of all the genetic differences in humans are only in Africans. Yeah, a way I like to think about this is you think of this so-called out-of-Africa hypothesis. And the way I think about it is, is known to not be true, but I find it helpful. If you think about it. Just about a few people got out of Africa, and they promptly spread to cover out, occupy the whole rest of the world. And we are almost clones of each other. Compared to Africans, one to each other. Okay? So there are lots and lots of different forms of the menthol receptor. It's known what gene codes for the menthol receptor. It's a really interesting story. And Africans have lots of different forms. That don't exist in non-African populations. And so we thought, oh. Well we'll just look at this African menthol receptor and see if that accounts for the use of menthol cigarettes by African Americans. Turns out it's not true.

>> Oh yeah? [Laughter]

>> It's not true.

>> You gave it a shot.

>> Oh yeah,. [DS([2] [CB([3] It was funded by the Food and Drug Administration. Another example of what's great about working at the NIH. You're allowed to get grants from outside institutions. So the Food and Drug Administration gave us a lot of funding. To actually pursue this. And it was kind of right up our alley. So and we did. We found, we found a surprising result. We got one hit, one gene in the genome seems to explain a big part of this and it's a complete surprise. It's a gene that was known. All the human genes are known since the human genome project found them all. But what this one did was not very well known. So we're working really hard on figuring out what this gene does. But one thing is clear is that it doesn't have anything to do with taste.

>> Okay.

>> It has, probably has something to do with what's called nociception, perception of noxious stimuli. So we're working hard on it. And we're hopeful that the information we find can be helpful to the Food and Drug Administration. To help regulate, regulate such things in tobacco. Which is really their authority to do. And I think to be perfectly honest. I think any cigarette smoking is generally not so good. And the more things that, the more knowledge we have that allow us to understand what lead people to smoke. And what lead people to keep smoking. The more, the more weapons we'll have to help wisely regulate tobacco use.

>> You also teach at the University of Maryland? What, what do you do there?

>> I have an adjunct full professor appointment in­­­ the Department of Neuroscience and Cognitive Science, and I teach in their translational neuroscience course every year. And it's fun. I'm hopeful that we can recruit a very really good student who's looking for a PhD project. Haven't been successful yet. But it's always fun to be able to interact with students. And give them, in addition to give a purely scientific lecture in some aspect of neuroscience. I work mostly in, I work a lot in sensory neuroscience. And in this communication disorders business. Which is not so well understood. It's a kind of unique little area. But it, it gives, it also gives the students a chance to learn about the pursuit of science in a setting outside the university. It gives them another, another perspective on, on academic research.

>> Cool. And I think I've got two more questions in mind, but feel free to add anything else. But are there any other aspects of your research that we didn't talk about at all, or that we didn't cover as much as you'd like to? Or that, that the world should really know about what you're working on? Or maybe that's not the way to put it. But that you find most interesting that I didn't catch?

>> I, I think we've touched on all the things that were on my list. Most of the things, other things on my list are generic things to say about the NIH. Because I think, I think, I think I've been a particularly good fit with the NIH. I've worked for a number of years in academia. I've worked for a number of years in industry. I've worked for a number of years here. And so I have kind of a broad perspective. And yeah, there's, there really is no place for the, no place like the NIH. And I think a lot of people misunderstand. That part of the reason we're a little different here is because we're more direct stewards of the taxpayer's dollar. We're federal employees, and we need to operate under the principles of transparency and accountability that other organizations don't need to operate under. And if you naturally believe in the greatness of the mission of the NIH, and I do, then you see that these aspects are what really help the NIH do its job, in spite of the fact that they seem burdensome sometimes to people who work here, and sometimes to people who are on the outside looking into the Intramural Research Program. So, we are different here, but we're different for good reasons. And I personally find the safeguards and the principles of doing research at the NIH to be one of the great benefits of pursuing things in this particular arena, in this particular place. [DS([4] [CB([5] Not to mention a huge number of colleagues who are somehow predisposed to be interested in the same things we are interested in is really, it's almost impossible to duplicate. You just, you, you couldn't do this anywhere else. You just couldn't. As I, as I once said to a group of assembled NIH scientific directors who. There's a little bit of jargon here. Most NIH research funding is done through the extramural program. And the flagship mechanism is something called the RO1 research grant. And those grants are given out after scientific review by peer review by study section. And then subsequent review by each institute's council, right? We don't operate under, under those, under those oversights. We operate under the oversight of the intramural program administration. And as, as I said, to do the work we've done on stuttering. We would have gotten our first RO1 grant. But I don't think we would have ever gotten another one. Because it's just too, it's too speculative. And it's, it's too improbable. I mean who, who would have thought that you could find genes that cause stuttering? And who would have thought you could put these mutations into a mouse? And get, get a mouse with a vocalization disorder? And that you could use that vocalization disorder to find the cells and the molecules that they're, actually underlie this disorder. I mean, it, it was just, it was just too speculative, I think.

>> Yeah, seems too risky for a grant. But here they kind of bet on you. And then they, they review you after you do your research.

>> Right. Right. I think that's, that's absolutely correct. The extramural system is completely forward-looking. And the intramural system is a mix of backward-looking, what you have done. And forward looking, what you're proposing to do. And to have the, the elasticity in what you do. And in the, the control of what you do is kind of unique to the NIH. They, they bet on people. [DS([6] [CB([7] And they find people who just have this automatic ability to make the most of what they're given. And I think, you know I'm surrounded by the people with so much talent and so much education who could command so much more compensation. Somewhere outside of government service. And I think if, if the average person understood this. They would realize that the taxpayers are getting an enormous bargain in the NIH. It's, it's really, I think the shared mission of this place. To understand and then improve the nation's health. That really does guide what people do here.

And I for one am proud and grateful to be a part of it.

>> Yeah, it's really cool that there's so many people here like you who are not necessarily working for money. But you're working to solve problems and help people. You even did that in your, in your previous life in industry. Apparently you, you found a cure for something that you can't make money from. And then figured you'd do that full time. [Laughter]

>> Yeah, the NIH is. It's, it's a system that--. So I travel a great deal. Because human geneticists here pursuing rare and unusual families in all sorts of exotic places. You're in Cameroon. You're in Pakistan. You're in Brazil. You're, you know I'm finding families, you know all sorts of places. And you get exposed. Of course you deal with academic colleagues and researchers in lots of places. And you come to the conclusion that the NIH system, it's hard to imagine it working very well anywhere else. Because I think the values of the institution are so pervasive here. And the, the mechanism is such. It's unique to America. It's, it's, it's really complete meritocracy. And it's stable funding. For people with a long-term track record of accomplishment. And who want to do something that just couldn't be done anywhere else.

>> Yeah, I feel very lucky too. Because I don't, I can't think of anywhere else where I could have thousands of scientists I could talk to and make videos about. And do podcasts like this. So…

>> We're always glad to help spread the good word about the NIH, because it deserves it, because it's a good place doing really good things.

>> What was the most memorable moment you had in the lab?

>> Well thanks for asking that question, because it really I think goes to the heart of the scientific enterprise. And when I think about this question, I can come up with a few examples. But I want to say something about those examples collectively that I think is maybe the most important thing, which is when you're working on something hard, it takes a long time. And it can be intellectually challenging, because you have to be brutally honest with yourself, right, and your hypotheses and your data. But when you finally find something, and you have found something important, and this has happened to me, I think for most people, this is a rare event. You get a handful of these in your career, if you're lucky. There'll be one every five to ten years. But when you find it, and you finally see the data in front of you, when you realize you've done everything, and the case is airtight, and it really is true, you know you've discovered something important, and at that moment, you're the only person in the world who knows it. And that is a pleasure that is, it's almost indescribable. Because for just that little time, it's you realize that you're there. And you realize what an effect it's going to have. But at the moment, you have this incredible sort of internal sense that you just don't get in any other enterprise. So, I've had a number of exciting moments, and some of them very colorful. The first stuttering gene we found, my postdoc, Chang Su Kang, a very talented postdoc from Korea, came into my office on a Thursday evening. He just was, he was such a hard worker, very talented. And he came in. He said, "I've been working on this for three years." He DNA-sequenced 86 genes by hand. I mean, it was just a heroic effort. He said, "My kids are getting older. It's time for them to go to school, and I'm going to have to move back to Korea. I know we haven't found the gene. And I want to apologize for this. But I just, I can't, you know, I can't do it anymore." And I said, "Well, look. No one has worked harder than you. And I will write you the very best letters that I can possibly write. And I'll call everyone I know to try and get you the best possible job I can get you. And he said okay. So that was Thursday night. Friday morning, he came in, and he said, "Do you have a second to look at something?" And he had actually found it. He had found the first stuttering gene. So, we came within a millimeter of losing him! [Laughter]

>> Yeah, that's incredible.

>> And but in the result, it was the featured article in the New England Journal with a commentary, accompanied by a commentary. That also got commentary in Science, Nature, and Cell. The most prominent scientific journals. And the Journal of American Medical Association. And it was picked up by the Associated Press and written up in 755 newspapers around the world.

>> Wow! That's a big story!

>> Right! So yeah, coming in Friday morning and taking a look at that data and seeing it, and I looked at him. I said, "I think you do have it." It was, you know, it was a remarkable moment. Especially because we were on the cusp of losing him! But yeah, that was one of several.

>> But I guess he didn't need your letters anymore, because he discovered something.

>> He didn't need any letters.

>> I'm sure he still appreciated them though.

>> He didn’t need any letters. Now he's a very successful faculty member at a good university in Korea.

>> Very cool.

>> Oh, it was extremely cool.

>> Well, Dr. Drayna. I really appreciate your time. This has been very, very interesting. And it's great that there's people like you working on these big, just challenging problems that, you know, trying to figure out how to treat conditions like stuttering. So, I'm glad that there are people like you working on it. And I wish you luck in making the rest of your future discoveries.

>> Well, thank you very much. And thank you for really this wonderful opportunity to talk about our work.

>> My pleasure!