Neuroscience is a relatively young field, and in recent decades, astonishing advances have been made in how we understand the brain. New ways of looking at what goes on inside our heads are key to this understanding. Join Kojo for a look at a new Brain Atlas, and find out how technology is helping identify and understand the way genes shape who we are.

Guests

  • Thomas Hyde, M.D., Ph. D. Chief Operating Officer, Lieber Institute for Brain Development
  • Allan Jones, Ph. D. CEO, Allen Institute for Brain Science
  • Ketema Paul, Ph. D. Assistant Professor, Department of Neurobiology, Morehouse School of Medicine

Transcript

  • 12:19:10

    MR. KOJO NNAMDIWelcome back. Your brain makes you who you are. It shapes your personality, retains your memories and controls your movements. In fact, 82 percent of your genes express themselves in your brain. Just how our brains work is still something of a puzzle, but new technology can help us put the pieces together. The hope is to develop new treatments for diseases like schizophrenia or Parkinson's.

  • 12:19:32

    MR. KOJO NNAMDIA new brain atlas recently made its debut at the Seattle-based Allen Institute for Brain Science. And with the ability to see inside our heads comes greater understanding of what makes us, well, us. Here to shed some light on the technology behind neuroscience is Thomas Hyde. He's a neuroscientist. He formerly worked for the National Institute of Mental Health.

  • 12:19:53

    MR. KOJO NNAMDIHe's currently the chief operating officer for the Lieber Institute, a nonprofit research center in Bethesda, Md. Tom Hyde, thank you for joining us.

  • 12:20:01

    DR. THOMAS HYDEThank you. It's a pleasure to be here.

  • 12:20:02

    NNAMDIAnd joining us from the studios of KUOW in Seattle, Wash., is Allan Jones. He is the CEO of the Allen Institute for Brain Science. Allan Jones, thank you for joining us.

  • 12:20:13

    DR. ALLAN JONESThank you. Great to be here.

  • 12:20:14

    NNAMDII'll start with you, Allan. The Allen Institute's brain atlas goes in to very precise detail, enabling researchers to see exactly where in the brain certain genes are turned on. What does it mean for a gene to be turned on in the brain? And how does seeing this help researchers?

  • 12:20:32

    JONESWell, the -- I think most people understand that genes drive much of what we do. They drive the underlying biochemistry of ourselves, of the tissues in our body, and so when we're creating out atlases, we're creating a mapping framework in which we take traditional maps, which people might see, for example, on an MR. If you go get an MRI, you get a very detailed map of your brain from the outside.

  • 12:20:59

    JONESWe're actually taking post-mortem brains and going in into that tissue and looking at where every gene in our genomes is turned on at various places -- about 1,000 regions in the brain -- and ultimately extracting that information and putting it out on the Web for free.

  • 12:21:21

    NNAMDITom Hyde, how does this compare with an MRI or a CAT scan? They're frequently used to look at the brain. How does a brain atlas provide different or better data?

  • 12:21:30

    HYDEWell, the MRI or CAT scan will give you anatomical data. And it will give you a structural picture of the brain, and it will show up pathological lesions that you see in the brain, like tumors or strokes. What this brain atlas does is it takes ostensibly normal brain tissue and maps it at a very fine level at a -- but at more the sub-cellular molecular level of the brain. So we're looking actually at gene expression in this atlas at a very fine level, almost at the cellular level there.

  • 12:22:07

    HYDESo the type of information you're getting from these radiological studies, like an MRI or a CAT scan of the brain, would be like looking at the structure and blue print of the physical nature of a building. Whereas when you get into this brain atlas, you're actually looking at the biochemical nature of the brain, which is much more of the fine architectural elements, so to speak.

  • 12:22:30

    NNAMDIAllan Jones, anything you'd like to add to that?

  • 12:22:33

    JONESI think that was a great description.

  • 12:22:37

    NNAMDIWell, in that case, I'd like to ask our audience to join this conversation. What would you like to know about how we see into the brain? Call us at 800-433-8850. Send us a tweet, @kojoshow, or email to kojo@wamu.org. Tom Hyde, during your time at the National Institute of Mental Health, you helped to assemble brain banks. And it's kind of a delicate process. What are the key steps to establishing a medical collection of brains which can later be examined?

  • 12:23:04

    HYDEWell, in the company of Daniel Weinberger and Joel Kleinman, for the past, now, 17 years, we have been very intimately involved in the collection of post-mortem human brains for scientific research. And we -- Joel Kleinman actually started this effort nearly 30 years ago. It involves working very closely with Washington, D.C. and Northern Virginia Medical Examiner's Office.

  • 12:23:29

    HYDEAnd by working with the staff at the offices, we identified potential donors on the basis of their medical history and the condition of the individual at the time that the decedent arrives at the medical examiner's office. We then contact the next of kin and get informed consent for donation for research. And I'm pleased to say that we've collected probably about 1,300 brains in that way in the past 15 to 16 years.

  • 12:23:57

    NNAMDILet's go to the telephones. We'll start with Gary in Washington, D.C. Gary, you're on the air. Go ahead, please.

  • 12:24:03

    GARYGood afternoon. I want to -- I'm interested in this from a more pure point of view because there seems to be a presumption that brain creates humanity, that our person-ness (sic) is created by the brain and is not pre-existent. So what are the limitations of brain mapping, even under the best case scenarios, even if we were able to completely do what we want to do in describing the brain and its activities if the brain is not what creates our person, but through -- but our soul or our consciousness or through some other device and the interaction with the brain that our activities come about?

  • 12:24:56

    NNAMDIOkay. I will let Allan Jones deal with the neuroscience aspect of that. I, of course, will deal with the philosophical aspects of it. No. Allan Jones, go ahead, please.

  • 12:25:06

    JONESGreat. I'm glad you'll deal with the philosophical aspects of it. I think, you know, any of these techniques that we're doing, certainly, the ones that we're using right now have limitations in that they're a static measurement in a post-mortem individual. And, obviously, when you want to get down to the level of inquiry that we want to get down to, down to the individual molecules -- the genes that are turned on -- it does require us to go post-mortem.

  • 12:25:32

    JONESThe techniques that are currently available to do these sorts of things in a living individual are things like functional mapping, functional MR. And there's great progress being made in those fields in terms of being able to map information in a living human as they're thinking about something. But the resolution is very poor. The resolution might be a millimeter and in that millimeter, there are millions, if not, you know, hundreds of millions of cells that are all doing individual computations, et cetera.

  • 12:26:02

    JONESSo we are a very, very long way off from really truly understanding how the brain does very complicated things, like, it takes information and stores it and retrieves it and thought and concepts, like consciousness, are well downstream of our understanding with current technologies. But what we're doing today is really starting to get, I think, a handle on those underlying molecular events.

  • 12:26:31

    NNAMDIGary, thank you very much for your call. Tom Hyde, in addition to all of the imaging technology, you have what are called microarrays, which transcribe RNA, a genetic code, much like DNA. How do you researchers use these microarrays?

  • 12:26:46

    HYDEWell, we are really on the cusp of a revolution in all of medicine, but particularly in neuroscience and the studies of brain and behaviors. We have these, what we call, high-throughput systems, where we can -- from a single brain sample, using these microarray -- look at the expression patterns of thousand and thousands of genes simultaneously. But there's other technologies that are now on the horizon beyond microarrays that are even finer in their use.

  • 12:27:15

    HYDESo, for example, we can take something called laser capture microscopy, where you take a very thin slice of tissue and actually dissect out individual nerve cells, extract the RNA from that nerve cell, amplify it and put it either on an array or something called RNA seek. And in an individual nerve cell, we can actually find out what its expression patterns are of RNA. And, of course, RNA is one of the codes that builds proteins. And proteins are what make cells work.

  • 12:27:43

    NNAMDIWhen you talk about brain diseases, most people probably think about epilepsy, Alzheimer's. But what about problems like addiction or depression? How should we understand the way biology plays a role for that kind of problem, Allan Jones?

  • 12:27:59

    JONESWell, I think that's a great question. You can expand your list to a huge number of different disorders and things, like obesity or other eating disorders. You named addiction, depression. All of these things are driven by the underlying biochemical events that are going on in our brain, so one of the things that we're trying to do with this particular resource is to bridge those worlds of the brain in areas of disease with the underlying genes.

  • 12:28:35

    JONESNow, there are great studies that are out there, and you'll see more and more of this come about over time. Of course, these have been going on for years, people studying large populations and saying, uh huh, we found the genes responsible or contributing to this particular indication, be it depression, whatever. Now, for the first time, we've been able to link those genes now into the place in which those genes are turned on in the brain and having their activity.

  • 12:29:03

    JONESIt's the first set of clues that are going to help researchers, who are studying any number of different diseases, to be able to come in and dial in and say, aha, look at this particular system, look at this particular structure that is affected.

  • 12:29:20

    NNAMDISpeaking of the impact that our genes can have on brain diseases, we also want to take a look at the impact genes can have on sleep and wakefulness. Joining us now by telephone is Ketema Paul. He's a professor of neurobiology at the Morehouse School of Medicine, where he has the lab focusing on the study of the genes, molecules and hormones that influence sleep and wakefulness.

  • 12:29:46

    NNAMDIFull disclosure here, Ketema Paul is also my son. He joins us by telephone from Atlanta. Ketema, thank you for joining us.

  • 12:29:52

    PROF. KETEMA PAULHi, Dad. Thanks for having me today.

  • 12:29:53

    NNAMDIHow should we understand the role biology plays for sleep and wakefulness and the genes?

  • 12:30:02

    PAULThat's actually interesting. Sleep is a behavior for which much of the neurobiology and a lot of the role that genes play still remain to be determined. In my lab, we focus on the ability to recover from sleep deprivation. And the big picture of that is how that contributes to predispositions for disease and general morbidity.

  • 12:30:27

    PAULSo for a project such as the Brain Atlas, it allows us to get information about genes and how they're normally expressed in humans, and then asks very direct questions about how sleep-wake states may regulate those genes and, in turn, how those genes may regulate the risks for sleep-wake disorders.

  • 12:30:48

    NNAMDITom Hyde, neuroscience is, well, relatively a young field. It's my understanding that, back when brains were first collected to study mental illness, it was kind of a novelty. Why?

  • 12:30:59

    HYDEWell, I think that, first of all, the study of mental illness has gone through permutations over the years and started out as an offshoot of neurology, actually. And to the turn of the 19th century, they were actually studying human brains. And then environmental influences superseded the interest in natural brain structure and function. And it's only been in the past 20 to 30 years that people have refocused in neuropsychiatric diseases and behavioral diseases on the biological bases.

  • 12:31:29

    HYDEAnd if you're going to study the biological bases of behavior, you're going to study the tissue that mediates that behavior, and that's the brain. I just want to mention one other point that came up. We don't want to forget about the fact that environment plays a very important role and interfacing with the biology of all of these diseases, and so that we will want to study the history of each individual when we study their brain tissue in order to understand the intersection between genetic risk and environmental influences in producing a pathological state.

  • 12:32:04

    HYDEOne other point, when we have a post-mortem human brain, it's a snapshot. It's an individual. There's a large amount of genetic variation between individuals, and that's why the Allen Brain Atlas is a great reference tool. But when we study diseases, we're going to have to study very large cohorts of individuals, lots of brains. And that's why these high-throughput platforms, of which the Allen Brain Institute, I'm happy to say, has pioneered, are vitally important in gaining that type of information.

  • 12:32:30

    NNAMDIAllan Jones, at what point did technology really begin to exist to help scientists examine living brains? How has that changed how brain diseases are treated?

  • 12:32:41

    JONESWell, the living brain studies, those are done with imaging. And imaging has been around, what, probably 15, 20 years, if not longer. The functional imaging world -- this is where you put an individual into a machine. They're actually breathing a little radioactive tracer sometimes to look at various places of the brain that light up. Those kinds of technologies -- probably around for 15 years or so.

  • 12:33:12

    JONESAnd those have really shed a tremendous amount of light on how the brain is functionally organized in terms of how we compartmentalize information within our brains, what different systems turn on in response to various things that we do. The technologies that we've been talking about today, that we've taken to do the atlas that we've done is microarrays, for example. We just talked about those. Those are about 10 years old or so.

  • 12:33:49

    JONESThat technology -- the newer technologies, like RNA-based sequencing, are probably only a couple of years old now. So technology moves forward very quickly. One of the things that we do frequently, as part of the Allen Institute suite of tools, is a lot image data that's actually microscopy, where we take individual photographs through a microscope, stitch all those together in a very large format.

  • 12:34:19

    JONESAnd those sorts of technologies -- the microscope has been for hundreds of years. But the ability to take a digital photo, stitch it together and then put it on the Internet for anybody to come grab and use is actually quite new. Also, the ability to store the massive amounts of data. So with all of the projects at the Allen Institute, we've generated over a petabyte of information, of data, that we try to make available it in some way to the larger science community.

  • 12:34:49

    JONESAnd, again, those sorts of things have really been enabled not so much by science technology, but by other forms of technology, you know, high-speed Internet, those sorts of things.

  • 12:34:58

    NNAMDIIn case you're just joining us, it's a Tech Tuesday conversation on technology and neuroscience with Allan Jones. He is CEO of the Allen Institute for Brain Science. He joins us from Seattle, Wash. Tom Hyde is a neuroscientist. He formerly worked for the National Institute of Mental Health. He's currently the chief operating officer for the Lieber Institute, a nonprofit research center in Bethesda, Md.

  • 12:35:20

    NNAMDIAnd Ketema Paul is a professor of neurobiology at Morehouse School of Medicine, where he heads the lab focusing on the study of the genes, molecules and hormones that influence sleep and wakefulness. We're taking your calls at 800-433-8850. Do you have questions about brain diseases and how they can be seen at the genetic level?

  • 12:35:40

    NNAMDI800-433-8850 is the number to call, or you can go to our website, kojoshow.org. Ask a question or make a comment there. Tom Hyde, the brains mapped out so far are, for the most part, male. Why is that?

  • 12:35:54

    HYDEIt's a very interesting phenomena. We got most of our brain tissue from the medical examiners' offices of Northern Virginia and Washington, D.C., and there is a male preponderance of individuals who end up in medical examiners' offices because they either of dying a sudden death from an accident. Males are more prone to accidents than females. Or they are sometimes victims of violent crime.

  • 12:36:17

    HYDEAnd males are more prone to be involved in violent crime than females. So we do end up with a slight male -- well, a significant male predominance in the cases that we access. But we do get enough females that we can balance out our studies quite nicely.

  • 12:36:31

    NNAMDIOn a genetic level, are there notable differences between male and female brains?

  • 12:36:37

    HYDEThere are fewer than you might think, but there are some significant ones. Obviously, females have two X chromosomes. A male have an X and a Y chromosome. So to the extent of the Y chromosome yields different genetic products or RNAs than the X chromosomes, you're going to see some differences. Barbara Lipska and Carlo Colantuoni, at my group at the National Institute of Mental Health, are currently studying those differences.

  • 12:37:02

    HYDENow, some of those differences are on the Y chromosome versus the X chromosome. But some of those differences are what we call autosomal chromosomes, those non-sex related chromosomes. And those are really quite interesting, but it's a relatively small number of genes. But that is something of great interest to all of us.

  • 12:37:20

    NNAMDICan we now reassure all the members -- the female members of our listening audience that all males actually have brains?

  • 12:37:27

    HYDEThey do, but they don't use them as much as females, unfortunately.

  • 12:37:31

    NNAMDIMost people would think, Allan Jones, that your brain makes you who you are, makes you unique. So the idea of a normal brain is kind of disquieting. How do you define a normal brain?

  • 12:37:45

    JONESWell, it's a great question and one that we've had lots of debate on. What we're trying to do is have a fairly broad definition of what normal is. This is something where no, at least, recent history of anything that would be diagnosable as a psychiatric disease. We want to make sure that -- so we do, for example, a pretty significant toxicology workup to be able to understand if the individual had a history of, for example, drug abuse that wasn't known.

  • 12:38:16

    JONESSo, broadly defined, we're taking an age range between 20 and 60 and filtering through those criteria of known neuropsychiatric disease for being normal. But, beyond that, there is certainly not any personality test or any other sorts of things that we're applying to say whether or not an individual is normal.

  • 12:38:41

    NNAMDIThe Allen Institute also has a mouse brain atlas. And, Ketema, I know that you use mice in your research. Why is the mouse brain so important to understanding the human brain?

  • 12:38:52

    PAULFor two reasons. The one is because the mouse is a mammal. And any research done on mammalian brains tend to be informative to the degree that the genes or the proteins that you're studying are similar, are conserved across species. But another more important reason is the mouse has become kind of the pre-eminent mammalian model for genetic research. And the reason that that is, is because the mouse genome was cloned before most of the other mammals.

  • 12:39:18

    PAULSo because we have such detailed information on mice -- and it's a lot easier to do experiments and ask specific questions about genes in the mouse model. For instance, I study sleep. And I can look at the ability of sleep deprivation to increase or decrease how a gene works or gene expression in the brain much more easily in the mouse than I can in other models. But I did have a question for the other guests, if I may.

  • 12:39:43

    NNAMDIYeah.

  • 12:39:43

    PAULAnd it's right on the subject that you're asking me. Obviously, one of the potential benefits for the research I do, I look at gene expression in a test tube or a gene expression in an animal model, such as a transgenic mouse. One of the obvious potential benefits is the ability to go to this brain atlas and see if I find something cool in what I'm doing, if there is a similar expression profile in the brains that are on the atlas.

  • 12:40:08

    PAULOr if I introduce a mutation into a gene, and it works differently, can I go to the brain atlas and see how it should be working in humans? Can either of the panelists speak to those benefits, please?

  • 12:40:19

    NNAMDIAllan Jones?

  • 12:40:20

    JONESSure. I'd be happy to. I mean, this is -- the Allen Institute actually started its projects about eight years ago, kicking off with a mouse because of all the great reasons that Ketema just mentioned in terms of the benefits as a model system of study, and the fact that we could be very, very systematic about it, all of the issues that we've talked about related to human with a variability in human populations, the fact that, you know, you're going to get what you get when you get post-mortem tissue, so you can have much more experimental control.

  • 12:40:54

    JONESAnd then we could do it very, very systematically, which is what we did and in 2006, released our mouse brain atlas. We've subsequently added a developmental component for that, so we've looked at gene expression as it's changing across development, which we think is very important. And a number of researchers have found very valuable.

  • 12:41:14

    JONESAnd, now, we're finally into looking at the human, again, with all of its limitations. But then the way we've created our resource -- and, again, researchers come in and use these for free -- they can bounce back and forth between the human and the mouse. And we've created sort of links and other things that people can go very quickly back and forth to look at the mouse data, to look at the human data.

  • 12:41:39

    JONESAnd as we continue to add more and more human data, I think the ability for the mouse researchers, who are always, you know, the reason we study the mouse is not really to understand the mouse, but to better understand human disease. It's a great model. And so we're always doing that relevance check and going back from the mouse and looking at what's in human.

  • 12:42:02

    NNAMDIAnd...

  • 12:42:02

    PAULAnd I noticed that you also had the -- you're working the guy at SRI International, so you have pretty detailed information on gene expression in sleep-deprived mice on that website. So that has potentially made me an advocate of your site.

  • 12:42:16

    JONESGreat.

  • 12:42:18

    NNAMDIAnd with that, we're going to take a short break. When we come back, we will continue our conversation. But before we go, Tom Hyde, one of the reasons we study the brains of mice is because our brains are, well, a little larger than theirs.

  • 12:42:29

    HYDEYes. A mouse brain is probably about the size of a large almond or a small walnut. The human brain is about the size of a good size cantaloupe. And so it's much, much bigger, much, much more complex. There are areas of the brain that are quite similar between the two species, some of the more primitive or visceral controlling parts of the brain. But when you get into the consciousness, thinking parts of the brain, the problem-solving parts of the brain, they're proportionally much, much larger. The cortical regions of the brain are much larger in the human than they are in the mouse.

  • 12:43:03

    NNAMDIGot to take a short break. When we come back, we'll continue this Tech Tuesday conversation on technology and neuroscience. If you have already called, stay on the line. We'd love to get to your call. Still a couple of lines open, so you can call 800-433-8850. Are you concerned about the genetic basis of a particular brain disease? You can also go to our website kojoshow.org or send us a tweet @kojoshow. I'm Kojo Nnamdi.

  • 12:45:18

    NNAMDIIt's Tech Tuesday. We're talking technology and neuroscience with Ketema Paul. He's a professor of neurobiology at Morehouse School of Medicine. He heads the lab, focusing on the study of the genes, molecules and hormones that influence sleep and wakefulness. He joins us by telephone from Atlanta. Joining us from the studios of KUOW in Seattle, Wash., is Allan Jones. He is the CEO of the Allen Institute for Brain Science.

  • 12:45:41

    NNAMDIAnd Thomas Hyde joins us in our Washington studio. He is a neuroscientist who formerly worked for the National Institute of Mental Health. He is currently the chief operating officer for the Lieber Institute, a nonprofit research center in Bethesda, Md. And, gentlemen, we have a lot of calls. I'll start with Ann in Lorton, Va. Ann, you're on the air. Go ahead, please.

  • 12:46:02

    ANNYes, Kojo. Thanks for taking my call.

  • 12:46:04

    NNAMDIYou're welcome.

  • 12:46:04

    ANNI would like to know how the technology of brain mapping can relate to treatment of diseases or disorders like ADHD and Asperger syndrome in terms of possibly biofeedback technology.

  • 12:46:21

    NNAMDIAllan Jones?

  • 12:46:23

    JONESWell, it's a great question in terms of how do these current technologies help researchers today. And, I think, for something like biofeedback, there are technologies that are used right now for brain mapping in a living individual, which is what you're talking about, for something like biofeedback. Unfortunately, usually, to get the level of resolution of a map, you have to get into this machine.

  • 12:46:53

    JONESYou have to sit very still. And so it's not really very conducive to immediate feedback such as biofeedback might give. So I'm not quite sure that the deep structural mapping would be the way to go. There are probably things and probably people out there -- I'm not aware of them -- who are doing things probably more driven by EEG, for example. But EEG tends to be a little bit of a black box in terms of what those signals actually mean.

  • 12:47:24

    NNAMDICare to add anything to that, Tom Hyde?

  • 12:47:26

    HYDEWell, as a clinician, as well as a researcher, biofeedback, of course, has been used for a long time in order to treat a lot of behavioral disorders. And I would differ probably a little bit with Allan. I think, actually, the FMRI and the magnetoencephalography, which is an electrophysiological measure of brain waves, can be used in a research setting to look at the effects of biofeedback on a variety of brain functions, under a variety of experimental conditions.

  • 12:47:52

    HYDESo I wouldn't be surprised that there -- if there aren't studies ongoing, as we speak, to look at the direct effects of biofeedback, certainly, on a variety of behavioral disorders. With respect to autism or Asperger syndrome and ADD or ADHD, I think you would probably have to search on the Web or go to the nih.gov website and see what types of studies are actually ongoing.

  • 12:48:17

    NNAMDIOkay. Thank you very much for your call, Ann. We move on now to Muya (sp?) in Bethesda, Md. Muya, you're on the air. Go ahead, please.

  • 12:48:26

    MUYAHi. My name is Muya. And I've always been healthy, no medical problems. And I'm not a violent husband. I've never been busted into a fight all my life, and I'm 60 years old. But, last year, something strange started happening. When I sleep at nighttime, I would dream. And when I'm dreaming, I will get violent. I kick and punch my wife. I punched her three times. And she wakes up screaming and don't know what's going on.

  • 12:48:51

    MUYAAnd I don't know why I'm doing it. I've never (unintelligible) my wife, and we don't know what's going on. Can anybody help me to understand what's going on, please?

  • 12:49:01

    NNAMDIKetema Paul, you're studying sleep and wakefulness. Can you tell Muya anything about why he, as a non-violent person, seems to be having dreams in which he gets violent?

  • 12:49:11

    PAULWell, there are two disorders of which I'm aware, that his description of his symptoms would fit. One is REM behavioral disorder, and that's a disorder that, when you reach rapid eye movement sleep, which is a stage of sleep, you'll experience involuntary limb movements. Some of them can be pretty vigorous.

  • 12:49:30

    PAULAnd the other one would be restless legs syndrome, which is another disorder of limb movements during sleep. However, his description seems pretty intense. So the best advice I would have is to go see -- I'm not a clinician myself. So the best advice I would have is try to see a sleep doctor or a sleep clinician as soon as possible. I'm sure that they would have answers for you.

  • 12:49:53

    NNAMDIMuya, thank you very much for your call, and, Ketema, thank you for that advice. How does something like the way your brain controls sleep affects other body systems? And how does this relate to our genes?

  • 12:50:05

    PAULOh, well, it's interesting. So the way the brain controls sleep is reciprocal for the way that the brain controls the body. So when you're sleeping, if you're in the state of non-rapid eye movement sleep, you have a sustained muscle tone, where if you're in the state of REM sleep, which is where most of your dreaming occurs, your muscle tone should be relatively limp. So if you have, say, a disorder in which you are experiencing muscle tone during REM sleep, it can cause some of the symptoms that the caller has described.

  • 12:50:35

    PAULInterestingly enough, we don't -- we know so little about how genes control sleep itself. We know how it controls the timing of sleep, but we don't know, for instance, which genes are responsible primarily for some of the mechanisms in which I described.

  • 12:50:50

    PAULSo learning more about how genes can regulate -- learning more about how genes change during sleep/wake states, and the ability to study gene expression in different -- what we call vigilant state sleep, non-REM and REM sleep -- can lead to an increase of understanding about how some of these disorders may be related to genetic anomalies, mutations or what we call polymorphisms, the different ways of gene expressions in different people, depending on your heterogeneity.

  • 12:51:16

    NNAMDITom Hyde, just how much difference is there on a biological level between any two people's brains?

  • 12:51:22

    HYDENot as much as you think, but quite a bit. So if you look at people's brains, actually the program that builds the structure of the brain is remarkably resilient despite all the genetic differences between people. They all have a very, very similar structure. But there are polymorphisms that affect more of the molecular and chemical constitution of the brain. There are some polymorphisms in -- or genetic abnormalities that will affect the actual structure of the brain.

  • 12:51:48

    HYDEBut most of the differences are at the very fine molecular level, and that's what we're starting to tease out with tools like the Allen Brain Atlas, with transgenic mice work that your son is doing and the types of work that we've been doing at NIH and now at the Lieber Institute, where we're looking at the impact on -- of genetic variation on the molecular pathology or the molecular constituency of the human brain.

  • 12:52:11

    NNAMDIAllan Jones, science is often more competitive than many people realize. So what's the advantage of making resources like a Brain Atlas available for free?

  • 12:52:21

    JONESGreat question. I think in order to enable lots of different people to make progress quickly, this is one of the reasons that Paul Allen has invested in the Allen Institute for Brain Science to...

  • 12:52:37

    NNAMDIBecause he's a guy with a background in computers, right?

  • 12:52:40

    JONESRight. But, again, I think, you know, there really should be more efforts like this that put data out there. We're all trying to solve incredibly hard problems, especially as it relates to the brain.

  • 12:52:52

    JONESAnd even though there's competition and there's -- competition is often good, I think sharing is even better in terms of getting maximum value from these kinds of resources where people can share and leverage what others have learned and move forward quickly. 'Cause at the end of the day, what we're all doing is trying to move forward as quickly as possible to the kinds of things that people really care about. Let's actually get better diagnosis and treatment of disease, and, to do that, working together and sharing the information broadly is a great way.

  • 12:53:31

    NNAMDIPaul Allen is one of the co-founders of Microsoft. His mother had Alzheimer's, and in a "60 Minutes" interview, he said, quoting here, "Once you see the horrific effect of brain disease at a personal level, it's a tremendous spur to move even faster." We move on now to Leo in Tampa, Fla. Leo, you're on the air. Go ahead, please.

  • 12:53:51

    LEOYes. Thank you guys for coming on. I love your research. Years ago, when Ted Bundy was doing his thing throughout the nation -- they found out who he was -- I started thinking, is there a genetic or just -- when I say genetic, I don't mean passed from parent to parent, but a breakdown in the DNA somewhere -- a genetic mutation for him? Or was it maybe neurological? And if that is the case -- there seems to be (unintelligible)

  • 12:54:21

    LEOWhat implications does it have for us in the court system? Is a person then -- maybe is not guilty because there's something that they cannot control? Or is it possible...

  • 12:54:32

    NNAMDILet me have -- we're running out of time, so allow me to have Tom Hyde offer a response.

  • 12:54:36

    HYDEWell, now you're getting to the confluence of philosophy and the concept of free will and the determinative nature of genetic variation. There are certainly genetic predispositions toward certain types of behavior, including illegal behavior. There are people who tend to be more aggressive than other people. There's also the confluence of environmental influences. You can't discount the environment of an individual in determining how their personality is structured and how their behavior unfolds.

  • 12:55:05

    HYDEWill we ever be at a time where we can predict faithfully that an individual will become a criminal or a violent individual? Probably not in my lifetime. That's science fiction right now. But, yes, there are individuals that have genetic risk factors. But genetic risk is not wholly determinative.

  • 12:55:26

    NNAMDILeo, thank you very much for your call. Allan, there's an interesting similarity in the way you can talk about genetic brain data and the way you talk about computer data. One description of the Human Brain Atlas says that the institute can produce over a terabyte of data per day. What is the goal for the Human Brain Atlas in terms of the amount of information gathered?

  • 12:55:48

    JONESIt's a great question. Right now, what we're doing is continuing to gather. We have two whole brains' worth of data. That is equivalent to about 100 million data points on these gene expression measurements. We'd like to target around 10 -- 10 brains in total -- which will take that number up to five times that, so 500 million data points. But that's just the start. And as Tom had mentioned earlier, it's a great normal base line. And even 10 brains would be wonderful.

  • 12:56:26

    JONESBut in order to study disease, you're going to have to do many, many more to build up statistical confidence in the measurements that you're taking, et cetera. So I think, you know, it's just the start of these kinds of mapping. It's a great base line mapping. And then the future is ahead for the more detailed studies around disease.

  • 12:56:47

    NNAMDITom, what projects are being worked on at the Lieber Institute?

  • 12:56:50

    HYDEWell, you know, the Lieber Institute is on the medical campus of Hopkins in Baltimore, although at times we're operating out of some offices here in Bethesda and Chevy Chase.

  • 12:56:58

    HYDEWe are also doing high-throughput studies. So we're currently, in conjunction with the National Institute of Mental Health, studying 1,000 individuals with a high throughput form of analysis called RNA sequencing in conjunction with DNA methylation, in conjunction with demographic information on about 350 normal people, spanning the lifespan, plus about 200 patients with schizophrenia, a cohort of bipolar patients, autism.

  • 12:57:26

    HYDEThis will eventually be a public database as well. We are studying one region of the brain called the dorsolateral prefrontal cortex, which is sort of the thinking, reasoning part of the brain. And the Lieber Institute will be putting out huge amounts of data as well, and we're going to be relying on a lot of the tools from the Allen Brain Institute in order to analyze that data.

  • 12:57:47

    NNAMDIThomas Hyde is a neuroscientist who formerly worked with the National Institute of Mental Health. He's currently the chief operating officer for the Lieber Institute, a nonprofit research center in Bethesda, Md. Thank you for joining us.

  • 12:57:57

    HYDEThank you. It's a pleasure to be here.

  • 12:57:58

    NNAMDIAllan Jones is the CEO of the Allen Institute for Brain Science. Allan, thank you for joining us.

  • 12:58:03

    JONESThank you.

  • 12:58:04

    NNAMDIAnd Ketema Paul is a professor of neurobiology at Morehouse School of Medicine, where he heads the lab focusing on the study of genes, molecules and hormones that influence sleep and wakefulness. He is also my son, the one who can fall asleep at the drop of a pen, and so, I guess, he should be researching sleep. Ketema, thank you so much for joining us and for staying awake during the whole broadcast.

  • 12:58:25

    PAULThanks, dad.

  • 12:58:27

    NNAMDIThank you all for listening. I'm Kojo Nnamdi.

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