>> GOOD MORNING, EVERYONE. WELL, GOOD MORNING, ALL OF YOU NEWSMAKERS. NICE TO SEE YOU THIS MORNING. SOME OF US LOOKING AT THE CLIPS THIS MORNING RECOGNIZING THAT THEY MADE A LOT OF INTERESTING COMMENTS AND GOT A LOT OF ATTENTION IN THE TOPICS WE TALKED ABOUT YESTERDAY WHICH WERE PROFOUNDLY INTERESTING AND IMPORTANT AND YOUR INPUT ADVISING US ON ALL OF THOSE IS DEEPLY APPRECIATED. IT WAS GREAT HAVING A LITTLE CHANCE FOR SOME DOWNTIME LAST EVENING. DIANE AND I WERE DELIGHTED TO HAVE YOU IN OUR MIDST. MY ONLY REGRET -- ANNE CHURCHLAND IS A CLASSICAL PIANIST, THERE'S A LITTLE MARKER HERE THAT NEXT TIME THERE WILL NEED TO BE SOME ADVANTAGE TAKEN OF THAT. SO THIS MORNING, WE HAVE ALSO INTERESTING AND IMPORTANT TOPICS, I WON'T GO THROUGH THE AGENDA, I BRIEFLY TALKED ABOUT IT YESTERDAY, BUT GLAD WE HAVE PRETTY MUCH FULL APPEARANCE HERE OF OUR GROUP AND I'M GOING TO TURN IT OVER TO LARRY TO TALK ABOUT A COUPLE OF BEGINNING TOPICS AND THEN WE'LL GET TO THE BRAIN WORKING GROUP. LARRY. >> OKAY. THANK YOU, AND GOOD MORNING, EVERYBODY. IT'S ALWAYS GOOD TO SEE NEW MEMBERS COMING BACK FOR THE SECOND DAY. THAT'S A VERY GOOD SIGN. AND FRANCIS, THANK YOU AND DIANE FOR JUST A LOVELY, LOVELY EVENING. SO THIS IS THE PART THAT EVERYBODY WAITS FOR, THE NEW MEMBERS. THAT IS THE APPROVAL OF AWARDS, OKAY, IT'S ONE OF THE HIGHLIGHTS OF THE MEETING. IF YOU TURN TO TAB 15, THIS IS A LIST OF AWARDS THAT THE ACD REVIEWS FOR US. AS A REMINDER, FEDERAL LAW PROHIBITS FEDERAL EMPLOYEES FOR RECEIVING ADDITIONAL MONEY DURING THE PERFORMANCE OF THEIR JOBS, AND SO THESE AWARDS ARE PRE-SCREENED BY DRS. LIFTON AND GRIFFITH WHO SERVE AS THE SUBCOMMITTEE IN THIS CASE, AND THESE ARE DEEMED ELIGIBLE BY THE NIH ETHICS OFFICE AS WELL, SO THERE'S MULTIPLE LAYERS HERE OF REVIEW. RICK, I DON'T KNOW IF YOU'RE ON THE PHONE, I KNOW LINDA IS HERE BECAUSE I SEE HER, BUT ARE YOU ON THE PHONE, RICK? I GUESS NOT. LINDA, I DON'T KNOW IF YOU HAVE ANY COMMENTS TO MAKE? >> IT'S WONDERFUL TO SEE ALL THESE AWARDS GOING TO PEOPLE AT NIH. IT'S A FUN SUBCOMMITTEE TO BE ON. >> IT IS INDEED. SO WHAT I DO NEED FROM THE GROUP IS IF THERE ARE ANY QUESTIONS, GENERAL QUESTIONS, AND IF NOT, THEN I DO NEED A FORMAL MOTION FOR APPROVAL. >> I MOVE THAT WE APPROVE. >> SECOND. >> THANK YOU. ALL IN FAVOR? -- RUNS THE ETHICS OFFICE. I'M HOLLI IS THE BRAINS BEHIND ALL OF THIS, I'M JUST THE PRETTY SIGNATURE THAT YOU CAN'T READ AT THE BOTTOM OF YOUR FORM. AND ALSO WITH US THIS MORNING IS CLAIRE HARRIS, WHO'S THE ACTING DIRECTOR OF THE OFFICE OF THE FEDERAL ADVISORY COMMITTEE POLICY, SO THIS IS, AGAIN, THE TWO FOLKS WHO HELP BRING ON BOARD ALL OF YOU IN YOUR CAPACITY AS SPECIAL GOVERNMENT EMPLOYEES. DON'T BLAME THEM FOR ANYTHING, IT'S ALL MY FAULT, BUT THEY'RE THE ONES WHO ACTUALLY MAKE IT WORK, AND SO THEY WOULD LIKE TO SPEAK TO YOU THIS MORNING ABOUT USING AN ELECTRONIC SYSTEM, IMAGINE THAT, TO HELP YOU ONBOARD A SPECIAL GOVERNMENT EMPLOYEE. >> THANKS, LARRY. HI, GOOD MORNING. I'M HOLLI BECKERMAN JAFFE,. WE WORK WITH CLAIRE AND THE COMMITTEE MANAGEMENT STAFF TO BRING YOU ON TO GET YOUR APPOINTMENTS AS SPECIAL GOVERNMENT EMPLOYEES. SO AS YOU RECALL, WE ASKED YOU TO PILOT THE ELECTRONIC FILING SYSTEM, THE NIH ETHICS ENTERPRISE SYSTEM TO FILE YOUR DISCLOSURE REPORT, THE FORM 450. WE APPRECIATE VERY MUCH THOSE WHO PARTICIPATED IN THE PILOT, GOT A LOT OF INFORMATION, CLAIRE IS GOING TO TALK MORE ABOUT THAT, AND NOW THAT THE PILOT IS OVER, STARTING IN JANUARY, ALL THOUSAND SL SGEs AT THE NIH WILL START ENTERING THEIR DISCLOSURE REPORTS. SO FOR THOSE WHO ALREADY DID IT, YOU'LL BE ABLE TO JUST WORK OFF OF YOUR CURRENT ELECTRONIC FORM AND FOR THE REST OF YOU, WE'RE GOING TO ASK YOU TO NOW USE THE SYSTEM TO FILE YOUR REPORTS AND YOU'LL GET A LOT OF TRAINING AND INFORMATION ON THAT. SO THE BENEFITS OF NEES, JUST TO LET YOU KNOW, IS THERE IS THIS PRE-POPULATION FUNCTION, YOU FILE ONCE, YOU GO BACK THE NEXT TIME, SAY NEW REPORT, AND ALL YOUR INFORMATION WILL BE TRANSPORTED INTO THE NEW FORM, AND FROM WHAT I CAN SEE, NONE OF YOU ARE DAY TRADERS SO THERE SHOULDN'T BE HUGE CHANGES FROM ONE FORM TO THE OTHER, SO YOU DO THE HEAVY LIFT THE FIRST TIME AND AFTER THAT, IT YOU SHOULD BE PRETTY SIMPLE AND PRETTY QUICK. THE OTHER GOOD THING IS THAT FOR THOSE WHO ARE ON MULTIPLE COMMITTEES, YOU WILL ONLY HAVE TO FILE ONE SET OF FORMS. WE'VE CALLED THIS POLICY KIND OF FIRST IN TIME SO FOR EXAMPLE, IF YOU WERE APPOINTED TO THE ACD IN 2016 AND THEN YOU WERE APPOINTED TO A BSC MAYBE IN 2017, THE ACD WAS YOUR FIRST APPOINTMENT, THAT'S GOING TO BE YOUR PRIMARY COMMITTEE SO YOU'LL FILE THROUGH THE ACD AND YOU WON'T HAVE TO FILE A SEPARATE SET OF FORMS TO THE BSC BECAUSE IT'S AN ELECTRONIC SYSTEM, THE OTHER COMMITTEE CAN JUST GET INTO THE SYSTEM AND DO THE REPORTS AND HANDLE IT THAT WAY. SO IT WILL BE LESS OVERALL FOR EVERYBODY ONCE WE GET THE REPORTS INTO THE SYSTEM. LAST, ANOTHER GOOD THING I THINK ABOUT THE SYSTEM IS YOU CAN JUST UPLOAD BROKERAGE STATEMENTS IF YOU WANT. YOU WILL BE DISCLOSING MORE BUT IT IS A CONFIDENTIAL SYSTEM. IT HAS SIGNIFICANT FIREWALLS WHICH I THINK SOME OF YOU EXPERIENCED, SO IT'S VERY HARD TO GET INTO, IT'S A VERY SAFE SYSTEM. WE'VE THIS FOR MORE THAN 15 YEARS, WE'VE NEVER HAD A BREACH. SHOULDN'T SAY THAT OUT LOUD. SO AGAIN WE CAN TALK TO YOU ABOUT THIS, BUT IF YOU OPT TO DO A LITTLE MORE OVERDISCLOSING, IT WILL CUT DOWN A LOT ON YOUR TYPING. NOW CLAIRE CAN TALK ABOUT THE PILOT. >> GOOD MORNING. SO THE WAY WE LOG IN TO THE SYSTEM IS USING YOUR ECOMMONS ACCOUNT. SO THOSE THAT TESTED, IT WAS VERY MUCH APPRECIATED, WE LEARNED A LOT ABOUT LOGGING IN WITH YOUR ECOMMONS AND I IDENTIFIED A LOT OF DIFFERENT ISSUES AND SCENARIOS THAT WE NOW HAVE RESOLUTIONS TO. SOME DON'T HAVE ECOMMONS ACCOUNT, A VERY SMALL PERCENTAGE OF SGEs DON'T BUT WE HAVE SOME THAT HAVE MULTIPLE OR INACTIVE ACCOUNTS OR MORE THAN ONE ACCOUNT. SO THANK YOU FOR TESTING BECAUSE THAT WAS, YOU KNOW, VERY BENEFICIAL TO MAKING THE LOG-ON EXPERIENCE IN THE FUTURE VERY FAST AND VERY QUICK. WE WILL HAVE A QUICK REFERENCE GUIDE THAT WE'LL SHARE WITH COMMITTEE MANAGEMENT STAFF TO HELP THROUGH, YOU KNOW, ANY ADDITIONAL ISSUES THAT COULD BE ENCOUNTERED. WE ALSO REDUCED THE NUMBER OF DATA POINTS FROM 6 TO 1, THAT ARE USED TO ACCESS NEES SO WE HOPE THAT WILL ENSURE LESS TROUBLESHOOTING ISSUES AND HELP IDENTIFY ADDITIONAL LOG-IN ISSUES QUICKLY. AND IN TERMS OF THE NEES SYSTEM, WE REALIZE THERE ARE ENHANCEMENTS THAT CAN BE DONE THERE. SO THE FIRST IS WHEN YOU LOG IN TO NEES, YOU SEE YOUR PERSONAL INFORMATION, SOME MAY NOT BE CORRECT BECAUSE WE'RE PULLING FROM YOUR ECOMMONS ACCOUNT, AND SO WE HAVE A PROCESS NOW IN PLACE WHERE YOU WILL CONTACT COMMITTEE MANAGEMENT AND WE'LL PUT THOSE INSTRUCTIONS TOGETHER TO MAKE ANY RECOMMENDED CHANGES TO YOUR PERSONAL INFORMATION AND THAT WILL TAKE ABOUT 24 HOURS TO REFRESH TO WHERE YOU CAN THEN GET BACK INTO THE SYSTEM. BUT WE ALSO FEEL THAT THERE COULD BE FASTER REPORTING AND WE CAN GIVE YOU PROMPTS, WE CAN GIVE YOU -- IF YOU ENTER AN ASSET, YOU KNOW, WHAT IS THE ASSET, WE CAN PROMPT FOR THAT, WE CAN PROMPT FOR DATES FOR ONE-TIME HONORARIA, AND WE REALLY FEEL LIKE IF WE ADD THESE ADDITIONAL PROMPTS, IT WILL MINIMIZE THE TIME THAT WE CONTACT YOU, THE NUMBER OF TIMES, AND THE NUMBER OF QUESTIONS THAT YOU RECEIVE. SO OUR GOAL IS FOR A MORE TIMELY ACD APPOINTMENT. SO THIS IS SOME OF THE FEEDBACK WE RECEIVED, BUT WE WOULD LIKE ANY ADDITIONAL FEEDBACK OR COMMENTS THAT YOU MAY HAVE. >> I KNOW THAT JOSE AND BRENDAN USED THE SYSTEM, SO HAVE AT IT, THE GOOD, THE BAD, THE UGLY. >> I WAS VERY HAPPY TO ENTER THE 21ST CENTURY. [LAUGHTER] >> I THINK ONCE THE LOG-IN ISSUES WERE OVERCOME, THEN IT WAS QUITE EASY. I THINK THE FACT THAT THERE'S NOW ONE SYSTEM FOR MULTIPLE COMMITTEES SAVES AN ENORMOUS AMOUNT OF TIME. EVEN THOUGH YOU MIGHT BE ON MULTIPLE COMMITTEES BECAUSE THE TIME OF ACTIVATION IS DIFFERENT, YOU'RE ALWAYS UP TATING, SO YOU'RE BASICALLY UPDATING TWICE A YEAR SO THAT'S VERY HELPFUL. I GUESS ONE QUESTION IS A GENERAL QUESTION NOT SPECIFIC TO NEES BUT SINCE YOU'RE HERE, MEAFN US GIVE ZILLIONS OF TALKS AND YOU GET A $200 HONORARIUM. YOU REQUEST THE EXACT DATES FOR ALL OF THOSE. I'M WONDERING WHETHER THAT'S ALL THAT IMPORTANT, AS LONG AS YOU HAVE THE YEAR RIGHT. >> THANK YOU. SO ONE THING, AND WE'LL GO ON THIS STARTING IN JANUARY, THE REPORTING THRESHOLD FOR EARNED INCOME HAS ACTUALLY IKED UP TO 1,000. SO THAT MAY REMOVE SOME OF THE REPORTING BURDEN. AND THE REASON WHY WE'RE ASKING FOR THE DATE, IT'S REALLY WHETHER OR NOT -- IT'S A FUTURE DATE. IF IT'S PAST, SO WHEN YOU SAY HON HONORARIUM INCOME, IF YOU GIVE US THE MONTH AND THE YEAR, THAT WOULD BE SUFFICIENT. THERE'S A ONE-YEAR COOLING OFF THAT WE NEED TO TRACK, SO THAT'S THE ONLY THING. AGAIN, THERE'S A COMMENT BOX, AND IT'S CONFIDENTIAL, SO PLEASE USE THAT BOX AS MUCH AS POSSIBLE TO GIVE DATES, TIME FRAMES, WHETHER OR NOT IT PAYS IF YOU HAVE AN OUTSIDE POSITION, SO YOU CAN SAY NO COMPENSATION OR COMPENSATED, THAT WOULD BE REALLY HELPFUL SO THAT WILL CUT DOWN ON A LOT OF OUR QUESTIONS. AS CLAIRE SAID, WE'RE GOING TO ADD THESE PROMPTS IN THE SYSTEM BECAUSE AS MOST OF YOU ARE ACADEMICS, THERE'S JUST CERTAIN THINGS LIKE ON RARE YUM FOR TALKS, TIA CREF ACCOUNTS, THERE'S STUFF THAT'S VERY COMMON THAT WE SEE OVER AND OAF AGAIN SO WE'RE GOING TO TAILOR NEES TO ACADEMICS AND MAKE THIS A LOT EASIER AND HOPEFULLY STREAMLINED AND MORE INTUITIVE FOR YOU. >> A VERY SIMILAR QUESTION TO BRENDAN'S. IT'S NOT SO MUCH THE TALKS, BUT ALSO YOU ASKED FOR EXACT MONTH AND YEAR OF WHEN WE MIGHT HAVE DISCONTINUED OUR SERVICE ON CERTAIN BOARDS AND THINGS LIKE THAT. SOME OF THESE WERE, YOU KNOW, A COUPLE YEARS AGO AND I HAVE NO IDEA SOMETIMES -- I KNOW THE YEAR, BUT WHETHER IT WAS JULY, AUGUST, SEPTEMBER, MARCH, I HAVE NO IDEA. >> SO THE REVIEWER GUIDE TELLS US WE SHOULD ASSUME YOU ALL ARE INTELLIGENT PEOPLE WHO CAN READ THE INSTRUCTIONS AND IF YOU GIVE US THE DATE FROM THE BEST OF YOUR RECOLLECTION AND I HAVE NO REASON IT TO DOUBT IT AND I WON'T, IT'S GOOD. JUST FILL IN THE BOX FOR ME. >> SO, WITH THAT GUIDANCE -- >> I'M THINKING LIKE, WOW, A LOT OF WITNESSES. PROBABLY NOT THE BEST MOVE BUT ALL RIGHT. >> THIS IS BEING VIDEOCAST, ALL YOUR COLLEAGUES HEARD THIS. >> THE RIGHT. BUT OKAY, THANK YOU BOTH VERY MUCH. WE REALLY APPRECIATE IT. >> ALL RIGHT. THANK YOU FOR THOSE OPENING ITEMS. NOW WE'RE GOING TO TURN TO A VERY IMPORTANT DISCUSSION ABOUT WHERE WE ARE WITH THE BRAIN INITIATIVE. AND I BELIEVE DR. JIM EBERWEIM MIGHT BE JOINING US BY PHONE. JIM, ARE YOU THERE? >> YES, I AM, FRANCIS, THANK YOU. >> TERRIFIC. LET ME PAINT A PICTURE HERE AND THEN I'M GOING TO ASK OUR CO-CHAIRS OF THIS WORKING GROUP, CATHERINE DULAC AND JOHN MAUNSELL, TO WALK US THROUGH THE STATUS OF THIS VERY IMPORTANT EFFORT TO COME UP WITH WHAT WE MIGHT CALL BRAIN 2.0 AS FAR AS THE STRATEGY FOR THIS REMARKABLE PROJECT. THE BRAIN INITIATIVE WAS FIRST ANNOUNCED IN 2013 WITH A VERY AUDACIOUS GOAL, NOTHING LESS THAN SOLVING THE MYSTERY OF THE HUMAN BRAIN, PARTICULARLY FOCUSING ON HOW THE CIRCUITS IN THE HUMAN BRAIN DO WHAT THEY DO IN REALTIME. OBVIOUSLY WITH 86 BILLION ESTIMATED NEURONS BETWEEN YOUR EARS WITH EACH OF THOSE HAVING PERHAPS A THOUSAND CONNECTIONS A PIECE, THIS IS AN INCREDIBLY COMPLEX STRUCTURE, I'VE BEEN FOND OF SAYING THE MOST COMPLEX STRUCTURE IN THE KNOWN UNIVERSE, I MAY BE EVENTUALLY PROVEN WRONG BUT RIGHT NOW I CHALLENGE ANYBODY TO COME UP WITH SOMETHING THAT HAS MORE COMPLEXITY THAN THAT. AND OF COURSE AN INCREDIBLY IMPORTANT STRUCTURE TO UNDERSTAND, BOTH JUST FROM BASIC UNDERSTANDING OF WHAT IT MEANS TO BE HUMAN, BUT ALSO ALL THE IMPLICATIONS THAT THIS WILL HAVE FOR TRYING TO UNDERSTAND DISORDERS OF THE BRAIN, EVERYTHING FROM AUTISM AND SCHIZOPHRENIA TO ALZHEIMER'S DISEASE, EPILEPSY, DEPRESSION AND SO ON. SO WE WANTED TO, AS THIS WAS ANNOUNCED, TO HAVE A CLEAR PATHWAY AND A SET OF MILESTONES AND GOALS AND SO WE PUT TOGETHER BACK THEN THE FIRST BRAIN INITIATIVE WORKING GROUP OF THE ACD, ALL OF THIS COMING OUT OF THIS VERY COMMITTEE, AND THAT FIRST GROUP WAS A TEAM OF EXTERNAL EXPERTS LED BY DRS. CORY BARGAINMAN AND BILL NEWSOME. CORY WAS A MEMBER OF THE ACD AT THE TIME. THEY HELD A SEQUENCE OF PUBLIC WORKSHOPS AROUND THE COUNTRY, I THINK WORKED INCREDIBLY HARD OVER THE COURSE OF A YEAR, FRANKLY FACING ALSO SOME RESISTANCE FROM SOME IN THE NEUROSCIENCE COMMUNITY WHO WEREN'T QUITE SURE WHETHER THIS WAS GOING TO BE A GOOD THING, AND I THINK GENERATED A LOT OF EXCITEMENT ABOUT WHAT THIS COULD LOOK LIKE. AND THAT LED, THEN, TO THE BRAIN 2025 REPORT, WHICH IS VERY MUCH UP ON THE WEB FOR PEOPLE WHO WANT TO SEE WHAT IT SAID. IT WAS THE STRATEGIC PLAN FOR THE FIRST 10 YEARS OF THIS INITIATIVE AND IT WAS SUPPOSED TO BE A 10-YEAR INITIATIVE SO THAT'S PRETTY BOLD. IN ANY AREA OF SCIENCE THAT'S MOVING QUICKLY TO TRY TO PROJECT WHAT'S GOING TO HAPPEN OVER A DECADE IS A REAL STRETCH, AND SO WE ALWAYS KNEW THAT THIS WOULD BE A GREAT STARTING POINT BUT IT WOULD PROBABLY NEED A RE-THINK AND A REFRESH, AND THAT'S WHERE WE'RE GOING TO TALK ABOUT THIS MORNING. BUT LET ME JUST TELL YOU, IN THE COURSE OF THE FIRST FOUR YEARS OF THIS, IN THE FIRST YEAR, OCTOBER 2014, WE FUNDED PROJECTS ADDING UP TO JUST 46 MILLIONED, JUST GETTING STARTED ON THIS RAMP-UP, BUT THE SUPPORT HAS BEEN INCREASING OVER THE YEARS AND WAS STRONGLY ENCOURAGED BY THE CONGRESS IN THE 21ST CENTURY CURES BILL WHERE THE BRAIN INITIATIVE IS ONE OF THE FOUR THINGS THAT THEY FOCUSED ON. NOW THROUGH FY18, WE HAVE FUNDED OVER 500 INVESTIGATORS WITH A CUMULATIVE FUNDING TOTAL OF ALMOST $1 BILLION. SO THIS IS A PRETTY BIG PROJECT, A PRETTY BIG DEAL. IT'S BEEN WONDERFUL TO SEE THE WAY IN WHICH THIS HAS RECRUITED NEW IDEAS AND NEW INVESTIGATORS INTO THE FIELD, PARTICULARLY ENGINEERS. REMARKABLE FREQUENCY OF THE MOST RECENT ROUND OF GRANT APPLICATIONS THAT PIs HAVE BEEN ENGINEERS, AND THAT'S CRITICAL, OF COURSE, FOR WHAT WE'RE TRYING TO DO IN TERMS OF TECHNOLOGY DEVELOPMENT AND APPLICATION TO UNDERSTAND HOW THESE CIRCUITS ACTUALLY WORK. I WANT TO TAKE A MOMENT AND ACKNOWLEDGE THE WORK OF OVER 100 FOLKS ACROSS 10 INSTITUTES AT NIH WHO HAVE WORKED CAREFULLY TO PUT TOGETHER THIS REMARKABLE INTERDISCIPLINARY PROGRAM AND THE HUNDREDS OF INVESTIGATORS IN NEUROSCIENCE AND PHYSICS AND CHEMISTRY AND COMPUTER SCIENCE AND ENGINEERING THAT HAVE RESPONDED TO THIS CALL, AND CATALYZED DEVELOPMENT OF TRULY REMARKABLE PROGRESS. AND I THINK WE HAVE CREATED A COMMUNITY ALSO BY THE REGULAR GATHERINGS OF THE GRANTEES, MANY OF WHOM DIDN'T KNOW EACH OTHER BEFORE HAVING THIS OPPORTUNITY TO COME TOGETHER, AND SO THIS HAS MADE IT POSSIBLE TO MOVE THIS PROJECT FORWARD IN MANY WAYS FASTER THAN I MIGHT HAVE IMAGINED IT COULD BE. WE'VE SCENERY MARKABLE PROGRESS, TO TAKE A CELL CENSUS IN THE BRAIN, OBVIOUSLY A LOT OF THE WORK IS BEING DONE IN MODEL ORGANISMS WHERE IT'S POSSIBLE TO DO INTERVENTIONS THAT WOULD NOT BE ACCEPTABLE IN HUMANS BUT WE ARE INCREASINGLY LEARNING A LOT ABOUT THE HUMAN CIRCUITS AS WELL THROUGH NEW TECHNOLOGIES. SO GIVEN, GERNTION THE RAPID PROGRESS OF THE INITIATIVE, THE EVOLVING NEUROSCIENCE LANDSCAPE, THE SURGE OF FUNDING PROMISED THROUGH THE 21ST CENTURY CURES ACT, WE FELT IT WAS VERY TIMELY TO RECRUIT A NEW WORK OHING GROUP 2.0 TO PROVIDE SCIENTIFIC FEEDBACK ON HOW BEST TO ACCOMPLISH THE AMBITIOUS VISION FOR BRAIN OVER THE SECOND HALF OF THIS INITIATIVE. WE WERE FORTUNATE TO RECRUIT CATHERINE DULAC AND JOHN MAUNSELL TO LEAD THIS GROUP OF EXPERTS AND HAPPY THAT ANNE CHURCHLAND AS PART OF THE ACD IS ALSO A SIGNIFICANT MEMBER OF THIS EFFORT. THE GOAL TODAY IS FOR THEM TO PROVIDE AN INTERIM UPDATE OF THEIR REVIEW THUS FAR. THEY ARE DEEP INTO THIS WITH THE GOAL OF HAVING A FINAL PRODUCT FOR THIS ACD GROUP TO LOOK AT IN JUNE. THERE IS A LOT OF INPUT THAT IS BEING OBTAINED BY COMMUNITY WORKSHOPS, TOWN HALLS, MEETINGS AT SFN, REQUEST FOR INFORMATION. ANOTHER IMPORTANT PART OF THIS EFFORT THIS TIME IS A NEUROETHICS SUBGROUP RECOGNIZING THAT SOME OF THE TECHNOLOGIES WE'RE TALKING ABOUT, INCLUDING THE DEVELOPMENT OF BRAIN ORGANOIDS, DO RAISE INTERESTING AND IMPORTANT QUESTIONS THAT OUGHT NOT TO BE LEFT FOR SOME FUTURE TIME, AND WE HAVE THIS SUBGROUP WHICH IS CO-CHAIRED BY JIM EBERWINE WHO'S ON THE PHONE AND JEFF KAHN, AND THAT GROUP IS INTEGRATED WITH THE BROADER GROUP BECAUSE IT HAS MEMBERS FROM THE WORKING GROUP ON THIS SUBGROUP AND WE'LL INCORPORATE THEIR FINDINGS THEN IN THE FINAL REPORT OF BRAIN 2.0 AS WELL AS TO DEVELOP A NEUROETHICS ROAD MAP FOR THE BRAIN INITIATIVE. SO THIS IS ALL ABOUT INTEGRATION, PUTTING TOGETHER TECHNOLOGY, THE CLINICAL APPLICATIONS, THE BASIC SCIENCE, NEUROETHICS, ALL OF THAT FOLDING TOGETHER AND YOU'RE GOING TO HEAR WHERE THIS STANDS AS OUR TWO CO-CHAIRS BRING TO YOU THEIR PRELIMINARY FINDINGS CONSIDERING YOUR INPUT AND WANT TO HEAR ABOUT THAT, THIS WILL PROBABLY BE A DISCUSSION THOUGH AT THE HIGH LEVEL FINDINGS. I DOUBT WE'LL EITHER HAVE THE EXPERTISE OR TIME TO DIG DEEPLY INTO SOME OF THE DETAILS, AND THERE ARE MANY DETAILT, BUT THEN THEY WILL, THIS WORKING GROUP, DRAFT A REPORT IN SPRING OF 2019 MADE AVAILABLE FOR PUBLIC INPUT, WHICH WILL THEN BE HAPPENING DURING THE COURSE OF THE NEXT FEW MONTHS AND THEN A FINAL REPORT BASED ON THAT PUBLIC INPUT SHOULD BE READY FOR PRESENTATION HERE IN JUNE OF NEXT YEAR. SO THAT'S A LOT OF WORK, BUT IT VERY MUCH DESERVES IT GIVEN THE SIGNIFICANCE OF THIS, AND SO WITHOUT FURTHER ADO, I'D LIKE TO INVITE CATHERINE AND JOHN TO COME AND WALK US THROUGH FROM CELLS TO CIRCUITS TOWARD CURES. WHERE ARE WE. AND DEEP THANKS TO YOU BOTH BECAUSE I IMAGINE A LOT OF OTHER THINGS YOU WOULD HAVE BEEN DOING THIS YEAR, YOU'RE THE NOT DOING BECAUSE YOU'RE DOING THIS, AND WE REALLY APPRECIATE THAT. PLEASE PROCEED. >> THANK YOU, FRANCIS, FOR THE INTRODUCTION. JOHN AND I ARE REALLY DELIGHTED TO GIVE YOU AN INTERIM REPORT ON WHAT WE -- ON THE WORK OF -- WORKING GROUP BRAIN 2.0. WE ARE EAGER TO GET FEEDBACK FROM YOU. WE ALSO -- YOU KNOW, WE'RE KIND OF SURPRISED BY THE AMOUNT OF WORK THAT THESE ENTAIL, BUT ON THE OTHER HAND, WE ALSO WERE ASTONISHED BY THE SCIENCE WE HEARD AND I HOPE WE'LL BE ABLE TO CONVEY ON THE SCIENCE THAT HAS OCCURRED AND FUTURE PROJECT THAT WE CAN ENVISION. SO WE'VE ENTITLED OUR REPORT FROM CELLS TO CIRCUITS, TOWARDS CURES. SO AS FRANCIS MENTIONED, IN 2014, THE GROUP PROVIDEED/CAME UP WITH THIS VISIONARY ROAD MAP THAT THEY CALL BRAIN 2025, THAT IS MEANT TO HELP ORGANIZE NIH FUNDED INITIATIVE TOWARDS UNDERSTANDING THE BRAIN. OBVIOUSLY THIS IS A VISIONARY GOAL THAT HAD A NUMBER OF PRIORITY THAT WERE PROVIDED, AND ALL OF THESE ORGANIZE AROUND A PRINCIPLE OF UNDERSTANDING CIRCUITS, NEURAL ASSEMBLIES IN THE BRAIN. SO THE CHALLENGE IS TO MAP THE CIRCUITS OF THE BRAIN, MEASURE THE FLUCTUATING PATTERNS OF ELECTRICAL AND CHEMICAL ACTIVITY FLOWING WITHIN THOSE CIRCUITS AND UNDERSTAND HOW THEIR INTERPLAY CREATES A UNIQUE COGNITIVE AND BEHAVIORAL CAPABILITIES. SO THE PRINCIPLE OF TRYING TO UNDERSTAND CIRCUITS WAS BASED ON THE PREMISE THAT A CIRCUIT WILL REALLY PROVIDE THE MOST REVOLUTIONARY DISCOVERIES AND IN TURN, PROVIDE NEW IDEAS FOR CURE OF NEUROPSYCHIATRIC DISORDER. SO WE WILL SUMMARIZE OUR CHARGE AND PROCESS. SO OUR CHARGE HAS MULTIPLE ASPECTS. ONE IS A REVIEW OF WHAT HAS BEEN DONE IN THE BRAIN INITIATIVE SO FAR, WHAT ARE THE ACTIVITIES, WHAT IS THE PROGRESS, WHAT WERE THE RFA THAT WERE LAUNCHED, THE TYPE OF GRANTS THAT WERE PROVIDED, THE PUBLICATION AND DISCOVERIES THAT CAME OUT OF THIS, AND HOW MUCH THEY FIT WITH THE INITIAL BRAIN 2025 DOCUMENTS. OBVIOUSLY SCIENCE HAS MOVED ON, SOMETIME FASTER OR IN DIFFERENT WAYS THAN ANTICIPATED, SO THE 10-YEAR PLAN THAT IS PROVIDED IN THE BRAIN 2025 SUDDENLY HAS TO BE TUNED UP AND THAT IS MUCH A PART OF OUR DISCUSSION TO REFINE SOME OF THE SPECIFIC GOALS BASED ON THIS EVOLVING SCIENTIFIC LANDSCAPE, AND PART OF THIS HAS BEEN TO IDENTIFY NEW OPPORTUNITIES FOR RESEARCH AND TECHNOLOGY DEVELOPMENT. AND WE HAVE VERY LIVELY DISCUSSION, A LOT OF IDEAS ON THESE NEW OPPORTUNITIES, AND IN INTERESTING WAYS, MANY OF THESE NEW OPPORTUNITIES CAN ACTUALLY BE GROUPED INTO LARGER TRANSFORMATIVE PROJECTS. WE USE SOMETIMES THE TERM MOONSHOT, BUT I THINK THE IDEA IS MORE THAT SOME OF THESE TRANSFORMATIVE PROJECTS WILL BE EXTREMELY HARD TO -- SOME OF THESE TRANSFORMATIVE GOALS WILL BE EXTREMELY HARD TO REACH, INVOLVE LARGE -- TEAMS WITH PEOPLE WITH VARIOUS SPER EXPERTISE BUT REALLY WILL HAVE THE POWER OF TRANSFORMING WHAT WE UNDERSTAND ABOUT BRAIN FUNCTION. SO THESE AS YOU YOU WILL SEE ARE VERY MUCH INTO DISCUSSION RIGHT NOW, AND WE'D LOVE TO HAVE YOUR FEEDBACK ON THIS. AND THEN FINALLY, REALLY IMPORTANT PART A OF OUR TASK IS ALSO TO CONSIDER MORE THE SOCIOLOGY OF BRAIN SCIENCE, THE TYPE OF SCIENTISTS THAT WE WANT TO TRAIN TO EMPOWER AND DIVERSIFY IN ORDER TO MAKE THE BRAIN COMMUNITY A REALLY INTERESTING AND SUPERB SCIENTIFIC COMMUNITY. SO HERE IS OUR GROUP. OUR GROUP IS VERY DIVERSE IN ITS SCIENTIFIC EXPERTISE. WE HAVE PEOPLE WHO ARE EXPERT IN MORE MOLECULAR, CELLULAR AND GENETIC APPROACHES MAINLY IN THE MOUSE, SO THIS IS THE CASE OF MYSELF, DAVID ANDERSON FROM CALTECH, KAFUL DZIRASA FROM DUKE DUKE, WE HAVE NEUROSCIENTISTS MORE INTERESTED SYSTEMS LEVEL, MANY OF THEM IN PRIMATES SUCH AS MY CO-CHAIR, JOHN MAUNSELL, KRISHNA SHENOY, PEOPLE INTERESTED IN NEUROSCIENCE SUCH AS BRUCE ROSEN, KRISHNA, TIM DENISON, SOME TBIELDERS, AND THEN FINALLY WE ALSO HAVE EXPERTISE, MORE CLINICAL EXPERTISE WITH SOME PRACTITIONER MDs D. SO AGAIN, A WHOLE RANGE OF EXPERTISE, VERY DIVERSE, AND WE ALSO HAVE SOME EX-OFFICIO MEMBERS REPRESENTING VARIOUS FUNDING AGENCYIES, AND FINALLY, WE ARE REALLY EXTREMELY THANKFUL TO THE SUPPORT AND HELP OF SAM WHITE, NINA HSU AND ALISON DAVIS WHO REALLY MADE OUR WORK POSSIBLE. IN PARALLEL TO THIS GROUP IS A WORKING SUBGROUP MORE FOCUSED ON THE IMPLICATION, NEUROETHICAL IMPLICATION OF THE BRAIN INITIATIVE, AND I THINK THIS IS VERY TIMELY, AS THE BRAIN INITIATIVE WILL MOVE MORE AND MORE INTO APPLICATIONS RELATED TO -- OR SCIENCE RELATED TO HUMAN NEUROSCIENCE. THE GROUP IS HEADED BY JIM EBERWINE WHO IS ON THE PHONE AND MIGHT BE ABLE TO ANSWER QUESTIONS LATER ON, AND JEFF KAHN, AND IMPORTANTLY, THERE ARE THREE MEMBERS OF OUR WORKING GROUP, ADRIAN FAIRHALL, CHRISTINE GRADY AND ELIZABETH HILLMAN. THESE TWO SUBGROUP WORKING GROUPS HAVE BEEN WORKING IN PARALLEL WITH SLIGHTLY SHIFTED START DATE. WE STARTED LAST APRIL, AND HAD A SET OF CONFERENCE CALLS, WEBEX, FOLLOWED BY THREE WORKSHOPS, A TOWN HALL AT SFN, SOCIETY FOR NEUROSCIENCE ANNUAL MEETING, THE UPDATE NOW, THE NEUROETHICS SUBGROUP STARTED IN JULY, ALSO GOES INTO WEBEX DISCUSSION, AND WE'LL ALSO HAVE A PUBLIC WORKSHOP AND WORKSHOPS LATER ON. AS FRANCIS MENTIONED, WE HOPE TO HAVE A FINAL REPORT IN JUNE, AND IN THE MEANTIME, I HAVE AN INTERIM REPORT SOMETIME IN LATE WINTER/EARLY SPRING, AND WE WILL ALSO HAVE A GENERAL TOWN HALL AT THE BRAIN INVESTIGATOR MEETINGS LATER ON. THE NEUROETHICS SUBGROUP HAS BEEN WORKING VERY HARD ALREADY, HAS A NUMBER OF WEBEX DISCUSSIONS WHERE THEY WERE ABLE TO REVIEW THE BRAIN 25 DOCUMENT AND TRIED TO -- TO THESE WHAT ARE THE AREAS OF NEUROETHICAL CONCERN, AND THEY HAVE ALREADY STARTED TO DISCUSS CASE STUDIES, ENROLL SOME OUTSIDE EXPERTS AND DEVELOP A FRAMEWORK FOR WRITING THE FINAL REPORT. NEXT WILL BE CONTINUOUS DELIBERATION, WORKSHOP, PUBLIC WORKSHOP AT THE NIH, AND THE FINAL PRODUCT THAT WE ANTICIPATE IS BOTH CONSIDERATION, NEUROETHICAL CONSIDERATION TO BE INTEGRATED ON OUR OWN WORKING GROUP REPORT AS WELL AS A STANDALONE DOCUMENT THAT WOULD FOCUS ON NEUROETHICAL ISSUES. SO ON OUR SIDE, WE HAD A VERY INTENSE SCHEDULE WITH EIGHT WORKING GROUP MEETING ON WEBEX THAT ENABLED US TO REVIEW THE BRAIN 1.0 PROGRESS. WE LOOKED IN DEPTH AT THE BRAIN 2025 PRIORITY AREAS AND RECOMMENDATION AND TRIED TO SEE HOW MUCH OF A FIT WERE THE RFA THAT HAS BEEN LAUNCHED SO FAR, THE TYPE OF GRANTS THAT WERE AWARDED AND THEN THE OUTCOME OF THESE GRANTS THEMSELVES. THIS WAS DONE BY SUBGROUPS IN OUR WORKING GROUP, WITH EXPERT IN THE VARIOUS TOPICS. ANOTHER CONSIDERATION -- SET OF CONSIDERATIONS WAS WHAT ARE THE NEW TOPICS, WHAT ARE THE AREAS THAT NEED A LITTLE BIT OF REFRESHER AND ADDITIONAL EXPERTISE THAT WE WOULD INVITE IN THE WORKSHOPS. AND SO WE HAD THREE PUBLIC WORKSHOPS THAT I HAVE TO SAY SCIENTIFICALLY WERE JUST A BLAST WE REALLY HEARD FROM A WHOLE RANGE OF NEUROSCIENTISTS -- JUNIOR FACULTY, I HAVE TO SAY JUNIOR FACULTY WAS ON AVERAGE SPECTACULAR. JUST THE VISION THAT WE HAD WHICH IS EXTRAORDINARY, ENTHUSIASTIC AND SCIENTIFICALLY REALLY EXTREMELY INTERESTING, SO WE DECIDED TO GROUP OUR WORKSHOP INTO THREE THEMES. ONE IS HUMAN NEUROSCIENCE, WE WANT TO HEAR, WE WANT TO HEAR FROM NEUROSURGEON AS WELL AS A WHOLE RANGE OF SCIENTISTS DOING& IMAGING OR RECORDING OR ANALYSIS OF THE HUMAN BRAIN, WHAT'S NEW, WHAT ARE THE BOTTLENECKS, AND HOW TO THINK ABOUT HUMAN NEUROSCIENCE NEXT. IN THE SECOND WORKSHOP, WE MORE GENERALLY LOOKED AT EMERGE BE OPPORTUNITIES FROM A TOOL DEVELOPMENT, TECHNOLOGICAL DEVELOPMENT, AS WELL AS SCIENTIFIC STANDPOINT, AND THEN FINALLY, I THINK ONE REALLY IMPORTANT COMPONENT OF THE BRAIN INITIATIVE IS REALLY TO REACH A SET OF MODELS ON HOW THE BRAIN WORKS THAT TAKE INTO ACCOUNT THE VARIOUS SCALE OF EXPERIMENTATION IN THE BRAIN AND SO OUR THIRD WORKSHOP WAS ENTITLED -- WE HAD A LIVELY TOWN HALL AND REQUEST FOR INFORMATION, HERE ARE THE WORKSHOPS, AGAIN, FOR HUMAN NEUROSCIENCE, WE HAD SOME NEUROSURGEON INVITED A REALLY IMPORTANT TOPIC IS HOW DO WE MOVE THE SCIENCE THAT IS CURRENTLY DONE IN SMALL BRAINS INTO THANK YOU HUGH MAN NEUROSCIENCE. THE SECOND WORKSHOP ON EMERGING OPPORTUNITIES HAD A REALLY IMPORTANT DISCUSSION ON HOW TO DEVELOP AND DISSEMINATE NEW TECHNOLOGY, A TOPIC THAT WAS NEW TO ME BUT I UNDERSTAND THERE ARE SERIOUS BOTTLENECKS HERE THAT WE HAVE TO DISCUSS A LITTLE FURTHER LATER ON. WE DISCUSS ABOUT NEW METHODS TO CIRCUIT ANALYSIS ON THE PLEAK MOLECULAR AND CELLULAR LEVEL, AND FINALLY CIRCUIT ACTIVITY INTO BEHAVIOR. THERE'S NOT BEEN A LOT OF EMPHASIS DONE SO FAR INTO BEHAVIORAL ANALYSIS AND THERE ARE NEW TOOLS THAT ENABLE, I THINK, TO PERFORM BETTER MORE IN DEPTH ANALYSIS OF THE CIRCUIT TO BEHAVIOR BRIDGE. THEN THE FINAL WORKSHOP, FROM EXPERIMENTS TO THEORY AND BACK, WONDERFUL PRESENTATIONS OF TELLING US HOW TO UNDERSTAND BRAIN FUNCTION AS A MODELING, BUT WE ALSO HAD OTHER INTERESTING DISCUSSION ON DATA TOOLS AND DATA MANAGEMENT, IN PART LED BY ANNE HERE AND THAT WAS REALLY AN EXTREMELY INTERESTING SESSION. AND THEN AS THE BRAIN INITIATIVE IS TAKING OFF, THEIR ASSEMBLY OF SCIENTISTS IN TEAMS THAT HAVE REALLY PROVIDED SIGNIFICANT INSIGHT TO THE PROGRESS OF THE BRAIN INITIATIVE, AND WE HAD THE DISCUSSION THAT WAS FIRST ENTITLED "BIG TEAM VERSUS INDIVIDUAL LAB SCIENCE," HOW MUCH SHOULD GIVEN TO TEAMS VERSUS INDIVIDUAL LABS. OUR CONCLUSION WAS ACTUALLY IT'S BIG TEAM AND INDIVIDUAL LAB SCIENCE, POT ARE BOTH ARE EXTREMELY IMPORTANT AND SHOULD BE MANAGED ACCORDINGLY. IN TERMS OF THE REQUEST FOR INFORMATION, WE RECEIVED 69 SET OF INPUT RECEIVED FROM JULY TO NOVEMBER. WE WILL KEEP COLLECTING RESPONSES THROUGH MARCH 2019. INTERESTINGLY, THE RECOMMENDATION AND COMMENTS FIT EXTREMELY WELL WITH THE WORKING GROUP RECOMMENDATION AND COMMENTS. ONE IS ADVANCING HUMAN NEUROSCIENCE, ANOTHER ONE WAS AN EXTENSION TO NON-NEURONAL CELLS AND THEN AGAIN THIS DEEP CONCERN OVER THE CURRENT STATE OF DATA SHARING SUPPORT FOR TOOL DEVELOPMENT AND DISSEMINATION, THEORY AND TRAINING, ALL THEMES THAT YOU WILL SEE OUR GROUP HAD IDENTIFIED. SO WHAT WE WOULD LIKE NOW IS REALLY TO GIVE A MORE SYSTEMATIC ASSESSMENT OF THE VARIOUS PRIORITY AREAS THAT WERE LINED UP IN THE BRAIN 2025. OVERALL, IF WE LOOK AT WHAT HAS HAPPENED IN THE BRAIN INITIATIVE FROM 2014 TO 2018, WE WERE, IN SHORT VERSION, EXTREMELY IMPRESSED. WE THINK THAT NOT ONLY THE CURRENT BRAIN INITIATIVE BY THE NIH IS VERY FAITHFUL TO THE DOCUMENT, INITIAL DOCUMENT BRAIN 2025, THE VARIOUS PRIORITY AREAS, THE VARIOUS RECOMMENDATION, WE ALSO ARE EXTREMELY IMPRESSED BY HOW WELL CRAFTED AND HOW STRATEGIC THE EXECUTION WAS, AND THESE BEING DONE IN EXTREMELY SHORT TIME FRAME, WHICH IS REALLY THE FIRST RFA REALLY ROLLED OUT IMMEDIATELY AFTER THE REPORT, AND AGAIN, WERE DONE IN AP EXTREMELY STRATEGIC MANNER BY THE NIH PROGRAM STAFF. AS A RESULT, WE THINK THAT THE CURRENT STATE OF THE BRAIN INITIATIVE HAS NOT ONLY LARGELY FULFILLING THE FIVE-YEAR PLAN, THE INITIAL FIVE-YEAR PLAN, BUT IN MANY CASES, ACTUALLY SURPASSED THIS INITIAL VISION, AND SO THIS IS WONDERFUL FOR US TO SEE WILL THIS VERY FAST PROGRESS AND REALLY EXTREMELY INTERESTING SCIENCE BEING DONE BUT ALSO GIVE US THE OPPORTUNITY TO THINK AHEAD, YOU KNOW, WHAT ARE GOING TO BE THE NEXT FIVE OR 10 YEARS IDEAS THAT WILL COME UP. AND SO WE WILL PROVIDE TO YOU SOME EXAMPLE OF OPPORTUNITIES FOR REFINEMENT AND ENHANCEMENT, AND WE EXPECT OUR FINAL DOCUMENT TO HAVE NOT ONLY MANY MORE OF THESE RECOMMENDATIONS BUT ALSO ORDERED IN CLEAR PRIORITY AREAS. SO HERE ARE THE SEVEN PRIORITY AREAS THAT WERE NICELY DESCRIBED AND PROVIDED IN THE BRAIN 2025 DOCUMENT. THE FIRST ONE WAS DISCOVERING DIVERSITY, THE IDEA THAT ONE CANNOT UNDERSTAND THE BRAIN IF WE DON'T UNDERSTAND THE PARTS, THE ULTIMATE PARTS OF THE BRAIN WHICH ARE THE CELL TYPES, AND THE BRAIN IS THE MOST COMPLEX ORGAN OF THE BODY, NOT ONLY IN CELLULAR TERMS BUT IN MOLECULAR TERMS. AND SO THERE'S A LOT OF DISCOVERY TO BE MADE HERE. THE SECOND ONE WAS TO MAP THE CIRCUIT AT MULTIPLE SCALES FROM THE MOST INFRASTRUCTURAL TO THE WHOLE BRAIN MAP, BRAIN IN ACTION, MONITORING NEURAL ACTIVITY, UNDERSTANDING CAUSALITY IN THE BRAIN, HOW DO WE RELATE NEURONAL ACTIVITY TO CHANGING STATES OR CHANGING BEHAVIOR, UNDERSTANDING FUNDAMENTAL PRINCIPLES TO BE ABLE TO ACHIEVE MODELS OF BRAIN FUNCTION AND PREDICT HOW CIRCUIT FUNCTION CAN LEAD TO BEHAVIORAL CHANGES. ADVANCING HUMAN NEUROSCIENCE, AND THEN SOME INTEGRATIVE APPROACHES FROM THE BRAIN INITIATIVE TO UNDERSTANDING GLOBALLY THE BRAIN. SO LET ME GO OVER THE DETAIL OF THE FIRST TWO PRIORITY AREAS AND JOHN WILL FOLLOW UP ON ALL THE OTHER FOUR OR FIVE. SO DISCOVERING CELL DIVERSE I WE THINK THAT THE PROGRESS HAS BEEN JUST ASTONISHING. THIS IS DUE TO BOTH THIS EXTREMELY STRATEGIC EFFORT FROM THE NIH STANDPOINT AND RIGHT AT THE LAUNCH OF THE BRAIN INITIATIVE, WHERE BREAKTHROUGH, TECHNOLOGICAL BREAKTHROUGH IN HARD TO STUDY INDIVIDUALS. SO THE BRAIN INITIATIVE HAS LAUNCHED SOME -- THE BICCN, THE BRAIN INITIATIVE CELL CENSUS NETWORK, AIMED AT IDENTIFYING CELL DIVERSITY IN THE MOUSE BRAIN, AS WELL AS IN PART IN THE PRIMATE AND THE HUMAN BRAIN, AND THESE LED TO ALREADY THE IDENTIFICATION OF CELL TYPES OR WHAT WE THINK AS CELL TYPES THAT STILL NEED TO BE DEFINED, NOT ONLY IN MANY BRAIN REGIONS, BUT ALSO VERY IN DEPTH AWILLAL CYST. SO THE INITIAL BRAIN 2025 DOCUMENT ANTICIPATED THAT WITHIN FIVE YEARS WOULD BE AN IDENTIFICATION OF CELL TYPES IN RETINA AND MAYBE ONE OR TWO BRAIN AREAS. WE'RE IN A STAGE WHERE WITHIN,& YOU KNOW, A COUPLE OF YEARS, THE ENTIRE CELL DIVERSITY OF THE MOUSE BRAIN WILL BE UNCOVERED. THIS IS DUE TO TECHNOLOGICAL ADVANCES SUCH AS SEQUENCING THAT ENABLES THE SEQUENCING OF HUNDREDS OF THOUSANDS OF CELLS THAT WAS NOT AVAILABLE BEFORE AS WELL AS BREAK THROUGH IN THE ANALYSIS OF THIS LARGE DATASET USING MACHINE LEARNING TOOLS THAT REALLY ENABLE TO MAKE SENSE OF THIS GINORMOUS DATASET. THE SO IN TERMS OF CELL TYPES, WE ARE REACHING VERY SOON COMPLETION OF THE IDENTIFICATION OF CELL TYPES ACROSS THE MOUSE BRAIN AND IN ADDITION TO THE DIVERSITY IS REALLY TWO, I THINK, EXTREMELY INTERETING ASPECT OF CELL DIVERSITY THAT HAS COME ABOUT. ONE IS THE ABILITY TO SEE CELL DIVERSITY IN SIGH IN SITU. SO HERE IS AN EXAMPLE, SHAMELESSLY, WORK FROM MY LAB, WHERE WE'RE ABLE TO IDENTIFY DIFFERENT CELL TYPES REPRESENTED IN VARIOUS COLORS IN TISSUE SECTION. THIS IS PARTICULARLY IMPORTANT FOR THE BRAIN BECAUSE THE BRAIN HAS VERY SPECIFIC STRUCTURE, LAMBAL LAMINAL STRUCTURE, THE PARTICULAR AREAS OF THE BRAIN DO MA MATTER IN TRYING TO UNDERSTAND THEIR FUNCTION. ALL SORT OF IN SITU-BASED TRANSCRIPTOMICS THAT ARE EMERGING, AND THIS IS A WONDERFUL DEVELOPMENT. MOREOVER, ONE IS NOW ABLE TO LOOK AT THE EPIGENOME, SO THE CHROMATIN ACCESSIBILITY, OF INDIVIDUAL CELLS. JASON WAS ONE OF THE PIONEERS IN EVEN BEING ABLE TO LOOK IN THE SAME TEST TUBE, BOTH TRANSCRIPTOME AND EPIGENOME, AND I THINK THESE ARE ALSO EXTREMELY INTERESTING FINDING THAT WILL ENABLE TO UNDERSTAND HOW THE CELLULAR -- THE CELLULAR ORGANIZATION OF THE BRAIN. SO THIS AGAIN HAS WAY EXCEEDED THE EXPECTATION EVEN LONG TERM EXPECTATION OF THE INITIAL DOCUMENT, AND SO THE NEXT STEP ARE VERY EXCITING, WE CAN NOW DIG INTO THE HUMAN BRAIN OR LARGER BRAIN, AND ESTABLISH SOME COMPARISON OF CELL TYPES THAT DO EXIST IN THE BIG BRAIN THAT DON'T EXIST IN THE SMALL BRAIN, AND HOW THESE CELL TYPES OVERALL COMPARE WITH EACH OTHER. ONE ASPECT OF CELL DIVERSITY THAT IS LAGGING BEHIND A LITTLE BIT ARE -- YOU KNOW, YOU WANT NOT ONLY TO IDENTIFY THE CELL TYPES WITH YOU YOU WANT TO BE ABLE TO ACCESS CELL TYPES FOR MANIPULATION, AND THESE WILL RELY ON A NUMBER OF GENETIC TOOLS AS WELL AS NON-GENETIC TOOLS. THE NON-GENETIC TOOLS ARE PARTICULARLY IMPORTANT IF WE WANT TO USE THE CELL TYPE INFORMATION INTO -- FOR INTERVENTION IN THE HUMAN BRAIN. AND SO IN PARTICULAR, YOU KNOW, WE ARE VERY INTERESTED IN EXPANDING PROTEIN BASE TO ANTIBODIES OR OTHER TYPE OF TOOLS THAT COULD BE USED ACROSS DIFFERENT SPECIES INCLUDING PRIMATES AND HUMAN, AND THAT MIGHT BE THE BASIS FOR INTERVENTION, THERAPEUTIC INTERVENTION. THE PROTEINS AND NOT THE TRANSCRIPT ARE THE PLAYERS, THEY ALSO HAVE MULTIPLE VARIANTS OF THE SITE OF MUTATION AND CAUSE OF DISEASE, SO WE THINK THIS IS IS A REALLY IMPORTANT AREA. FINALLY, WE DON'T KNOW WHAT NEURONAL CELL TYPE -- WE DON'T KNOW WHAT A CELL TYPE IS IN THE BRAIN. WE KNOW ABOUT CLUSTERS AND WE HAVE MANY CLUSTERS, HUGE DIVERSITY, AND WE HOPE THAT USING AN ASSESSMENT AT THE MOLECULAR, THE CELLULAR, THE CONNECTIVITY LEVEL, THE MORPHOLOGY, THE ELECTRICAL RECORDING, OPTICAL RECORDING, WE CAN COME TO AN AGREEMENT ON THE DEFINITION OF CELL TYPES AND THEN ACCESS THE CELL TYPE, MODEL THEIR FUNCTION AND TRY TO UNDERSTAND HOW TO PARTICIPATE AS A WHOLE TO BRAIN FUNCTION, AS WELL AS TO POSSIBLE PATHOLOGY. WE KNOW THAT IN NEURODEGENERATIVE DISEASE SUCH AS. ALS, PARKINSON'S, SPECIFIC CELL TYPES ARE AFFECTED BUT IT'S NOT CLEAR YET THAT NEUROPSYCHIATRIC DISEASES HAVE A BASIS IN MISFUNCTION IN SPECIFIC CELL TYPE. IF WE'RE ABLE TO DEMONSTRATE THIS AT LEAST FOR SOME NEUROPSYCHIATRIC DISEASES, THAT COULD LEAD TO IDEAS FOR POTENTIAL CURE. MAP AT MULTIPLE SCALES. SO HERE THE SCALES ARE FROM THE ULTRA STRUCTURAL TO THE MESOSCALE FROM ONE BRAIN AREA TO THE OTHER TO THE ENTIRE BRAIN, A MACRO SCALE. WE THINK THEY ARE GOOD PROGRESS HERE. HERE THEY HAVE BEEN EXTREMELY INTERESTING ADVANCES, TECHNOLOGICAL ADVANCES DURING THE BRAIN -- NEW BRAIN CLEARING TECHNIQUES THAT ARE COMPATIBLE WITH MAPPING AS WELL AS MOLECULAR IDENTIFICATION, SERIAL EM, X-RAY TOMOGRAPHY, MACHINE LEARNING TOOLS APPLIED TO LARGE SCALE ANALYSES HAVE BEEN IMPLEMENTED MORE LARGELY, AND THEN THERE HAS BEEN EXTREMELY INTERESTING PUBLICATION AND EFFORT ON LARGE SCALE RECONSTRUCTION OF SINGLE CELL CONNECTIVITY. SOME AT THE MY MICROSCOPY LEVEL, BUT SOME AT THE E.M. LEVEL, FOR EXAMPLE, HERE, THIS EXAMPLE HERE IS THE CONNECTOME OF THE MYELINATED AXE AXOME IN THE ZEBRAFISH LARVA AND WHERE OVER 2,000AXOM, PROJECTION TOMORROW WERE DELINE ATED, THESE REALLY CAME OUT OF THE PROGRESS IN SERIAL E.M. AND SEGMENTATION AND REALLY GIVES THE HOPE THAT LARGER BRAIN NOW CAN BE STUDIED IN THEIR ENTIRETY USING THIS ULTRA STRUCTURAL CONSTRUCTION. NOW THERE ARE A LOT OF MISSING PARTS FOR MAPPING. AT THE MESOSCALE MAPPING, WE PROGRESS. THERE HAS BEEN PROGRESS IN MR THE I BUT ONE MRI BUT ONE WONDERS WHETHER ONE WILL REACH A LIMIT IN THE RESOLUTION OF THAT METHOD. ONE MIGHT WANT TO THINK ABOUT NEW CREATIVE METHODS THAT MAY BE OPTICAL OR CHEMICAL-BASED SUCH AS PET. HUMAN MAPPING HAS BEEN HAPPENING AT THE STRUCTURAL LEVEL AND INDIRECTLY AT THE FUNCTIONAL LEVEL AND BEING ABLE TO LINK THOSE TWO COMPONENTS USING FOCAL STIMULATION, FOR EXAMPLE, IS SOMETHING THAT IS ABSOLUTELY NECESSARY AT THIS POINT, AND THEN FINALLY, WE HAVE ALL THESE EFFORTS OF THE DIFFERENT SCALE, NANOSCALE, MESOSCALE, MACRO SCALE. WE HOPE AT EACH SCALE, THERE WILL BE PROGRESS IN REDUCING THE COST AND I CREASING THE THROUGHPUT OF EACH OF THE SCALES AS WELL AS CREATIVE NEW PARADIGM TO LINK THOSE VARIOUS SCALES AND INTEGRATE ALL OF THESE WITH A THEORETICAL FRAMEWORK OH. AND ON THIS, I LEAVE IT NOW TO JOHN. >> THANK YOU, CATHERINE. I'LL CONTINUE BY TAKING UP THE THIRD TOPIC WHICH IS THE BRAIN IN ACTION. THE GOAL HERE IS JUST TO REALLY ADVANCE UNDERSTANDING THROUGH MONITORING WHAT INDIVIDUAL NEURONS AND CIRCUITS ARE DOING IN SPECIFIC BEHAVIORS. HERE THE PROGRESS HAS ALSO BEEN EXTREMELY GOOD. WE CAN NOW RECORD SIMULTANEOUSLY FROM HUNDREDS OF NEURONS USING OPTICAL METHODS OR THOUSANDS SIMULTANEOUSLY USING ELECTROPHYSIOLOGICAL METHODS AND THIS IMAGE ON THE RIGHT IS JUST A SNIPPET OF THE DATA THAT WERE COLLECTED FROM A FEW HUNDRED ELECTRODES IN THE CEREBRAL CORTEX OF AN AWAKE MOUSE. OTHER METHODS LIKE WIDE FIELD IMAGING MAKES IT POSSIBLE NOT ONLY TO LOOK IN ON AN INDIVIDUAL CIRCUIT BUT ACTUALLY MONITORED, WIDELY SEPARATED CIRCUITS SIMULTANEOUSLY TO SEE WHAT THEIR INTERACTIONS ARE AND HOW THOSE CHANGE BEHAVIORS INVOLVE. DEEP STRUCTURES HAVE BEEN A CHALLENGE FOR OPTICAL METHODS, BUT THESE MICRO END SCO PEE TECHNIQUES HAVE BEEN WELL REFINED SO IT'S NOW POSSIBLE TO DO DETAILED IMAGES OF CIRCUITS DEEP IN THE BRAIN, SO THEY'RE GETTING THE ATTENTION THAT THEY WEREN'T GETTING BEFORE. THERE'S ALSO BEEN IMPROVEMENTS ON HUMAN IMAGING AS WELL, FMRI, FUNCTIONAL IMAGING FOR THE HUMAN BRAIN, BOTH SPATIAL AND TEMPORAL RESOLUTION HAS IMPROVED DRAMATICALLY, PARTICULARLY SPATIAL RESOLUTION IS APPROACHING VOXELS OF ABOUT A HALF MILLIMETER OR SO, SO VOLUMES OF 125 NANOLITERS INVOLVING TENS OF THOUSANDS OF NEURONS ONLY. SO WE REALLY ARE GETTING DOWN TO A SCALE WHERE IMAGE ACTIVITY OF THE HUMAN BRAIN AT REALLY FINE RESOLUTION, THAT'S HELPING A LOT. OTHER IMAGING TECHNIQUES FOR HUMANS GIVE LESS SPATIAL RESOLUTION, SO FUNCTIONAL NEAR-INFRARED IMAGING, SO THAT ALLOWS BEHAVIORAL STUDIES THAT JUST AREN'T POSSIBLE IN FMRI. THERE ARE MANY OPPORTUNITIES THAT WE SEE FOR CONTINUED PROGRESS HERE, TOPICS THAT WE WOULD LIKE TO SEE EMPHASIZED. MULTIMODAL TOOLS ARE LIKELY TO BE IMPORTANT. SO COMBINING FUNCTIONAL IMAGING WITH ELECTRICAL RECORDING OF ACTIVITY WHICH WE GIVE MORTEM PORL PRECISION AND SOMETHING THAT HAPPENS BUT NOT ON A LARGE SCALE IS LIKELY WITH THE SORT OF COMPLEMENTARY VIEWS WILL BE VERY IMPORTANT. WE'VE DISCUSSED THE CHEMICAL CONNECTOME, CONNECTOME IS ALMOST ALWAYS DESCRIBED IN TERMS OF STRUCTURAL CONNECTIVITY, BUT WE ALSO NEED TO CONSIDER THE DIMENSION OF NEUROMODULATION SIGNALING MOLECULES WHICH ACTUALLY ARE KEY TO MODIFYING HOW THE CONNECTIONS ACT AND SO THIS IS ALTERNATE DIMENSION THAT NEEDS TO COME INTO PLAY IN THE NEAR FUTURE IN TERMS OF UNDERSTANDING THE CONNECTIVITY OF THESE CIRCUIS THAT MEDIATE THE BEHAVIORS WE'RE LOOKING AT. WE WANT TO SEE MORE DEEP BRAIN IMAGING. WE TEND TO FOCUS ON THE SURFACE AREAS ESPECIALLY WITH OPTICAL TECHNIQUES BUT DEEP BRAIN STRUCTURES ARE JUST AS IMPORTANT AND DOING THAT IN BEHAVING ANIMALS IN MULTIPLE AREAS IS LIKELY TO PROVE TO BE VERY IMPORTANT. WE'RE EXCITED ABOUT THE DEVELOPMENT OF LONG TERM RECORDINGS. THEE ARE NOW ADVANCES ON POLYMER-BASED SEMICONDUCTORS THAT ARE BEING USED TO DEVELOP ELECTRODES THAT COULD BE STAPLED IN BRAINS FOR PERIODS OF YEARS RATHER THAN DAYS OR WEEKS AND THAT'S GOING TO GIVE US INSIGHT IN ADAPTABILITY OVER THE LONGER TERMS. AND WE WOULD SAY THAT IT'S IMPORTANT TO STUDY COMPLEX MORE NATURAL SORTS OF BEHAVIORS. THERE'S A DEFINITE REDUCTIONIST APPROACH TO STUDYING BEHAVIORS WHICH HAS ACTUALLY SERVED US VERY WELL, BUT IT'S A FACT THAT WE WILL NEVER OBSERVE ALL OF THE ACTIVITY IN THE BRAIN AND WHAT IT IS CAPABLE OF WHEN WE CONFINE OURSELVES TO THE SIMPLEST SORTS OF BEHAVIORS. WITH ADVANCES IN A.I. FOR MONITORING, VIDEO MONITORING OF BEHAVIORS, IT'S POSSIBLE TO INSTRUMENT ANIMALS AND HUMAN SUBJECTS TO MONITOR THEIR ACTIVITY WITH HIGH PRECISION SO THAT WE CAN INTERPRET ACTIVITY DURING COMPLEX BEHAVIORS. FINALLY, THERE ARE NEW SORT OF INTEGRATED APPROACH TO HUMAN AND PRIMATE THE NEUROIMAGING THAT WE WOULD LIKE TO SEE EMPHASIZED. IN GENERAL, THE TECHNIQUES IN PRIMATES, HUMAN OR NON-HUMAN, ARE LESS WELL DEVELOPED AND THAT'S I THINK SIMPLY A CONSEQUENCE IN MANY CASES OF THE SMALL NUMBER OF SUBJECTS THAT ARE AVAILABLE FOR DEVELOPING AND REFINING AND EXPANDING TECHNIQUES BUT SOMETHING WE NEED TO CONTINUE TO EMPHASIZE. SO ACTION IS ONE DIMENSION THAT THE BRAIN INITIATIVE IS LOOKING AT. ANOTHER IS ACTUALLY PERTURBATION, SORT OF MODIFYING THE ACTIVITY IN THE NERVOUS SYSTEM AND IT'S CAST HERE AS DEMONSTRATING CAUSALITY. THOSE PERTURBATIONS ARE THE WAYS WE TEST HYPOTHESES ABOUT HOW CIRCUITS WORK, AND PROGRESS HERE HAS ALSO BEEN VERY GOOD. OPT GENETICS HAS BEEN A STAPLE IN NEUROSCIENCE FOR A DECADE, IT ALLOWS THE PERTURBATION OF GENETICALLY DEFINED POPULATIONS OF NEURONS WITH DEVELOPMENTS GOING ON IN THE BRAIN INITIATIVE NOW, IT'S GOING UP TO THE NEXT LEVEL WHERE IT'S BECOMING POSSIBLE TO PICK AND CHOOSE WHICH INDIVIDUAL CELLS IN A CIRCUIT SHOULD BE PERTURBED, USING TWO PHOTON STIMULATION COMBINED WITH HOLOGRAPHIC METHODS, IT'S POSSIBLE TO ACTUALLY LIMIT THE LIGHT STIMULATION TO A SUBSET OF AT THIS POINT UP TO 100 NEURONS IN PATTERNS THAT CAN CHANGE ON A TIME SCALE THAT'S ACTUALLY APPROACHING THE BEHAVIORALLY RELEVANT TIME SCALE FOR NEURAL CIRCUITS. SO THIS FIGURE HERE JUST SHOWS AN EXAMPLE OF ONE CELL BEING MONITORED WHILE ACTUALLY -- ACTUALLY STIMULATED WHILE BEING MONITORED WITH AN ELECTRICAL RECORDING DURING HOLOGRAPHIC STIMULATION. THIS SORT OF APPROACH MAKES IT POSSIBLE TO ASK A LOT OF QUESTIONS THAT ARE JUST NOT GOING TO BE APPROACHABLE IN OTHER WAYS SO THIS DEVELOPMENT IS VERY EXCITING. ALSO BY MODIFYING ENGINEERING, IT'S BEEN POSSIBLE TO SHIFT THE ACTION SPECTRA SO THAT WITH RED SHIFTED CALCIUM INDICATORS AND BLUE SHIFTED OPSONS, IT'S NOW POSSIBLE TO DO SIMULTANEOUS ACTIVITY RECORDING AND ACTIVITY PERTURBATION IN THE SAME FIELD OF VIEW IN EFFECTIVELY AN ALL-OPTICAL EXPERIMENT INVOLVING ACTIVITY. WE'RE CLOSE TO BEING ABLE TO DO REAL CLOSED LOOP PERTURBATIONS WHERE INDIVIDUAL CELLS SELECTED BEFOREHAND WITHIN A CIRCUIT WILL BE MODIFIED BASED ON THE BEHAVIORS THAT AN ANIMAL GENERATES IN ORDER TO CLAMP ACTIVITY AND SEE WHAT THE EFFECTS OF THAT MIGHT BE OR TO ADJUST THE ACTIVITY IN A CIRCUIT CIRCUIT. THAT'S A TECHNICAL CHALLENGE, BUT IT'S WITHIN REACH, AND IT'S THE SORT OF EFFORTS THAT THE BRAIN INITIATIVE REALLY SHOULD BE SUPPORTING IF WE WANT TO TRY TO UNDERSTAND HOW THE BRAIN WORKS. THERE ARE OTHER SORT OF BOLD APPROACHES, NANOPARTICLE BASED, NONINVASIVE ACTIVATION, THE IDEA THAT WE MIGHT BE ABLE TO DELIVER TO SPECIFICALLY GENETICALLY DEFINED CELLS, PARTICULAR AGENTS THAT WOULD ALLOW MODULATION OF THOSE CELLS' ACTIVITY USING EXTERNALLY APPLIED MAGNETIC FIELDS IS SOMETHING THAT REALLY NEEDS MORE ATTENTION AND MORE WORK. AND ONCE AGAIN IN THIS AREA AS WELL, WE NEED TO FOCUS ON GETTING THESE TOOLS AND METHODS INTO NON-HUMAN PRIMATES SO WE HAVE A MODEL THAT'S CLOSE TO HUMAN AND POTENTIALLY APPLICATIONS IN HUMANS. THE FIFTH AREA, IDENTIFYING FUNDAMENTAL PRINCIPLES, REALLY CONCERNS THE THEORY OF BRAIN FUNCTION AND ALSO THE SORT OF MATHEMATICAL APPROACHES THAT ARE USED TO ANALYZE THESE VERY COMPLEX DATASETS. HERE THE PROGRESS HAS ALSO BEEN GOOD AND I WOULD SAY ONE OF THE IMPORTANT ASPECTS OF THIS IS THE REVOLUTIONARY CHANGES THAT HAVE HAPPENED IN DEEP LEARNING METHODS AND ARTIFICIAL NEURAL NETWORKS, SO WE NOW HAVE THEORISTS AND MODELERS WHO ARE SIMULATING PROCESSES LIKE THE ENFORCEMENT OF LEARNING, BAYESIAN INFERENCE, DECISION-MAKING IN THESE NET YO WORKS AND ESTABLISHING THE TYPES OF PRINCIPLES USED IN COMPUTING THOSE PROCESSES IN A DISTRIBUTED NEURAL-LIKE NETWORK. DATA PROCESSING HAS ALSO BEEN ADVANCING IN LEAPS AND BOUNDS, DIMENSIONALITY REDUCTION IS JUST ONE EXAMPLE BUT AN IMPORTANT ONE, WHICH SORT OF AIMS TO TAKE THE ACTIVITY OF HUGE POPULATIONS OF CELLS, DIFFICULT TO IPT PRET THE BUT REDUCE IT DOWN TO THE SPECIFIC COMPONENTS THAT ARE MOST CLOSELY RELATED TO AND MOST IMPORTANT FOR DETERMINING THE PERCEPTUAL REPORTS OR THE BEHAVIORAL ACTIONS THAT COME OUT FROM THE SUBJECTS THAT ARE USING THAT NEURAL ACTIVITY. IN TERMS OF OPPORTUNITIES, WE ACTUALLY LIST AT THE TOP THAT THIS AREA HAS FAR TO GO. THAT'S ACTUALLY UNFAIR, I'D SAY ALL THESE AREAS HAVE FAR TO GO TO THE EXTENT WE DON'T UNDERSTAND THE BRAIN YET, BUT IN OUR DISCUSSIONS OF THEORY, IT SORT OF SHINES A GLARING LIGHT ON THE FACT OF THE MATTER BEING THAT WE REALLY DON'T HAVE DEFINITIVE THEORIES OF ANY REASONABLY INTEGRATED BRAIN FUNCTION, AND SO WE FOCUS IN THESE DISCUSSIONS ON HOW CAN WE BRING MORE THEORY. THERE'S PLENTY OF THEORY GOING ON A THE LEVEL OF VERY SMALL CIRCUITS, THERE'S PLENTY OF THEORIES GOING ON IN TERMS OF CHARACTERIZING BEHAVIORS, BUT WE HAVE REALLY SPENT SOME ENERGY TRYING TO TALK ABOUT HOW WE CAN HELP DEVELOP THESE THEORIES AT THE LEVELS OF INTEGRATION THAT LIE BETWEEN THE LOWER LEVELS AND HIGHER LEVELS, WHICH IS REALLY LIKELY IT TO BE OUR BIGGEST HOLD IN UNDERSTANDING. SO BRIDGING THESE MICRO SCIELS TO THE MICRO SCALES AND COMING UP WITH METHODS FOR DEVELOPING NEW THEORIES IS SOMETHING WE'RE FOCUSING ON IN OUR ONGOING DISCUSSIONS. STATISTICAL ANALYTICAL MODELS BASED ON CONNECTIVITY MAPS ARE LIKELY TO BE VERY IMPORTANT. WE'RE GETTING A TON OF DATA ABOUT THE CONNECTIONS THAT EXIST IN THE BRAINS, THE CONNECTIONS ARE THE BASIS FOR THE COMPUTATIONS THAT OCCUR IN THE BRAINS AND WE NEED BETTER AND MORE RICHER DEEPER MODELS TO TRY AND UNDERSTAND WHAT ARE THE PRINCIPLES BY WHICH THE BRAIN COMPUTES WHICH ARE UTTERLY UNLIKE THE PRINCIPLES BY WHICH YOUR SMARTPHONE COMPUTES. AND A FURTHER UNDERSTANDING OF CIRCUIT PLASTICITY IS LIKELY TO BE IMPORTANT BECAUSE MOST OF THE HIGHER FUNCTIONS WE TALK ABOUT IN THE BRAIN COME ABOUT THROUGH EXPERIENCE. SO KNOWING THE LEARNING RULES THAT THE BRAIN RELIES ON TO DEVELOP THOSE CAPABILITIES IS GOING TO ESSENTIALLY BE CRITICAL FOR UNDERSTANDING WHAT'S GOING ON. ADVANCING HUMAN NEUROSCIENCE ACTUALLY SORT OF OVERLAYS MANY OF THE TOPICS THAT WE'VE ALREADY DISCUSSED, I'VE ALREADY MENTIONED THERE HAVE BEEN GREAT ADVANCES IN FUNCTIONAL IMAGING AND OTHER NONINVASIVE METHOD. THERE HAS BEEN REAL PROGRESS HERE IN TERMS OF CLOSED LOOP STIMULATION METHODS. SO TECHNOLOGIES ARE NOW BEING DEVELOPED, FOR EXAMPLE, IN TREATING PARKINSON'S, IT'S NOW POSSIBLE AT LEAST ON AN EXPERIMENTAL LEVEL TO IMPLANT ENTIRELY SELF-CONTAINED DEVICES WHICH MONITOR ACTIVITY OF THE CIRCUITS WHICH THEY'RE GOING TO STIMULATE, PROCESS THOSE SIGNALS AND USE THAT INFORMATION TO ADJUST THE STIMULATION IT TO ACHIEVE THERAPEUTIC LEVELS OF SUPPORT WITH FAR LESS STIMULATION THAN YOU WOULD NEED IN A SYSTEM THAT DIDN'T HAVE MONITORING OF THE ACTIVITY OF THE CIRCUIT. THIS HAS BEEN A CASE WHERE THERE'S LOTS OF OPPORTUNITY FOR PUBLIC-PRIVATE PARTNERSHIPS AND THE IDEA OF DEVELOPING THOSE SORTS OF RELATIONSHIPS IS SOMETHING THAT'S COME UP FREQUENTLY IN OUR DISCUSSIONS. IN TERMS OF HUMAN NEUROSCIENCE, WE NEED CONTINUED WORK ON NONINVASIVE TOOLS TO INTERROGATE AND MODULATE ACTIVITY. WE HOPE, AS CATHERINE MENTIONED, THAT THIS PROGRESS IN LEAPS AND BOUNDS ON CELL IDENTITY COMING FROM THE CELL CIRCUITS CAN BE TRANSLATED OVER TO HUMAN NEUROSCIENCE AND WE CAN BEGIN NOW TO USE THAT IN WAYS THAT REALLY APPLY TO THE HUMAN CONDITIO. IN OUR DISCUSSION, WE HAVE, I THINK, RECOGNIZED THAT THERE'S FAR MORE LIVING HUMAN BRAIN TISSUE AND FAR MORE OPPORTUNITIES FOR RECORDING IN HUMAN BRAINS AND NEUROSCIENTISTS ARE TAKING ADVANTAGE. I DON'T THINK THAT THERE ARE ANY REAL STRUCTURAL BARRIERS TO PREVENT THOSE SPAIRNLTS BUT I THINK THIS IS AN AREA WHERE NEUROETHICS LOOMS LARGE IN TERMS OF THE TYPES OF EXPERIMENTS WE'RE THINKING OF AND TALKING ABOUT AND IT'S OUR HOPE THAT IN COORDINATION WITH THE NEUROETHICS SUBGROUP, THAT WE COULD COME UP WITH PRINCIPLES AND GUIDELINES THAT MAY ACTUALLY MAKE IT CLEARER AND MORE OBVIOUS WHICH EXPERIMENTS REALLY ARE APPROPRIATE AND ENCOURAGE MORE WORK ON HUMAN SUBJECTS. ORGANOIDS CAME UP BRIEFLY IN AN EARLIER MENTION. I WILL SAY WE'VE DISCUSSED THEM. THERE'S SOME ENTHUSIASM FOR TAKING THIS APPROACH, IT OBVIOUSLY OFFERS A LOT OF ADVANTAGES, BUT THERE'S SOME SKEPTICISM ON THE WORKING GROUP ABOUT THE EXTENT TO WHICH ORGANOIDS WILL REALLY RECAPITULATE THE GENETIC EXPRESSION AND PRECISE CIRCUITRY THAT WE NEED TO STUDY TO UNDERSTAND HOW THE BRAIN WORKS. THE LAST PRIORITY AREA IS SORT OF BRINGING BRAIN INITIATIVE TO THE BRAIN, AND HERE WE'VE INCLUDED ALL THE SUBJECTS THAT WE THINK ARE RATHER OVERARCHING TOPICS WHICH REALLY CONCERN ALL ASPECTS OF THE BRAIN INITIATIVE AND WHAT'S BEEN GOING ON. THERE ARE SEVERAL OF THEM. ONE IS WHAT WE'VE CALLED THE SOCIOLOGY OF SCIENCE AND IT COVERS A NUMBER OF TOP INNINGS. ONE OF THEM IS EMPHASIS IN THE BRAIN INITIATIVE ABOUT CREATING MULTIDISCIPLINARY TEAMS OF INVESTIGATORS, SO MOST NEUROSCIENTISTS, I THINK, HAVE COME TO THE FIELD THROUGH BUY OL OR MEDICINE AND ONE OF THE THINGS EMPHASIZED IN BRAIN 2025 IS THE NEED IT TO BRING IF IN THEORISTS, CHEMICAL SCIENTISTS, ENGINEERS, DATA SCIENTISTS, COMPUTER SCIENTISTS, AND THAT'S ACTUALLY BEEN HAPPENING TO A VERY IMPRESSIVE EXTENT, BUT IT'S SOMETHING THAT WE REALLY WANT TO BUILD ON MORE, AND IN PARTICULAR, WE'VE HAD DISCUSSIONS ABOUT YOUNG CAREER SCIENTISTS AND HOW WE BRING THEM INTO THESE PROJECTS AND RETAIN THEM IN THESE PROJECTS, AND PART OF THIS IS THE FACT OF THE MATTER THAT A COMPUTER SCIENTIST OR A DATA SCIENTIST CAN BE MUCH MORE HIGHLY COMPENSATED IN THE INDUSTRIAL SECTOR BUT IT'S ALSO NOT CLEAR WHAT CAREER PATH EXISTS FOR A COMPUTER SCIENTIST IN NEUROSCIENCE IF THEY REALLY WANT TO COMMIT THEMSELVES TO TAKING THIS ON. SO WE'RE DISCUSSING HOW WE MIGHT BE ABLE TO IMPROVE THAT SITUATION, AND NEW MODELS OF COLLABORATION THAT MIGHT BE BROUGHT TO BEAR ON THIS PARTICULAR TYPE TOPIC. I'LL ALSO SAY WE'VE LOOKED AT DIVERSITY IN THE BRAIN NICHE INITIATIVE ACROSS ALL LEVELS AND IT'S STRUCK US AS DISAPPOINTING PARTICULARLY AT THE LEVEL OF TRAINEES, SO THAT IS SOMETHING WE'RE GOING TO BE MENTIONING IN OUR REPORT AND DISCUSSING FURTHER IN OUR WORKSHOP MEETINGS. DATA SHARING IN STANDARDS REMAINS A BIG PROBLEM FOR THE BRAIN INITIATIVE, IN PART BECAUSE THESE DATASETS ARE VERY BIG, VERY COMPLEX AND VERY IDIOSYNCRATIC. THEY'RE DIVERSE APPROACHES AND THEY DON'T LEND THEMSELVES TO A SINGLE STRUCTURE OR SINGLE SORT OF FORMULATION. THERE HAVE BEEN GOOD EFFORTS MADE IN THE BRAIN INITIATIVE TO DATE IN TRYING TO ENCOURAGE ACTUALLY GRASS ROOTS EFFORTS TO DEVELOP THE SORTSZ OF -- WE NEED, BUT AT THE VERY LEAST, WE NEED TO ESTABLISH CORE PRINCIPLES, PRACTICES FOR DATA STANDARDS MANAGEMENT AND SHARING, SO THAT WE CAN ENFORCE SOME EFFORT TO GET THIS DATA OUT TO WHERE IT WILL GET THE MOST USE. AND SORT OF PROMOTING STANDARDIZED DATA ARCHITECTURES ACROSS BRAIN AND NEUROSCIENCE, I THINK IS GOING TO BE ONE OF THE MESSAGES THAT WE WILL BE PUTTING ACROSS STRONGLY. OBVIOUSLY THIS HAS TO BE DONE WITH REAL AWARENESS OF THE VARYING EFFECTIVE HALF-LIVES OF USEFULNESS OF DIFFERENT DATA TYPES AND THE REAL COSTS THAT GO INTO ANNOTATION AND CURATION OF DATA AND REAL DECISIONS ABOUT WHICH DATA NEED TO BE PROMOTED BUT IT'S QUITE CLEAR TO US THAT THERE'S SOME VERY VALUABLE PERMANENT DATA HERE THAT NEEDS TO GET INTO WELL-DEFINED DATA REPOSITORIES WITH TOOLS TO ALLOW THE BROADER COMMUNITY READY ACCESS. TECHNOLOGY TRAINING AND DISSEMINATION IS RELATED IN SOME WAYS. WE WON'T HAVE -- A FRACTION OF THE IMPACT IF THE TOOLS STAY IN THE LABS THAT DEVELOP THEM, AND YET GETTING IT OUT TO OTHER LABS IS NOT AS SIMPLE AS PUBLISHING A PAPER OR SORT OF MONITORING A TECHNIQUE OR EVEN SENDING A POSTDOC TO VISIT FOR A FEW DAYS. MANY OF THESE ARE VERY ELABORATE, DIFFICULT, COMPLICATED TECHNOLOGYIES, AND THEY REALLY REQUIRE SOME TECHNICAL SUPPORT AND ASSISTANCE IN TERMS OF GETTING THEM UP AND RUNNING SO WE HAVE A WHOLE GAMUT TO RELATIVELY STRAIGHTFORWARD THINGS TO THINGS THAT PERHAPS SHOULD BE COMMERCIALIZED BUT THEY JUST CAN'T BE BECAUSE THERE WILL NEVER BE A MARKET LARGE ENOUGH TO MAKE THAT EFFORT PROFITABILITY AND WE THINK IT'S CRITICAL THAT THAT GET ADDRESSED AND WE HAVE SOME MECHANISM FOR HELPING TO BRING THESE TECHNOLOGIES OUT THE TO A LEVEL WHERE LABS CAN PICK THEM UP AND USE THEM IN THEIR OWN EXPERIMENTS AND WE'VE DISCUSSED A LOT OF APPROACHES, I'LL SAY ONE OF THEM INVOLVES NIH ESTABLISHING A SORT OF TRANSLATION -- TECH TRANSLATION COUNCIL TO WORK IN PARALLEL WITH SCIENCE COUNCILS TO TRY AND MAKE INFORMED DECISIONS ABOUT HOW THIS DISSEMINATION PROCESS SHOULD BE SUPPORTED FOR VARIOUS OPPORTUNITIES THAT COME ALONG. THE BRAIN 2025 DOCUMENT TALKED ABOUT ACCOUNTABILITY TO THE PUBLIC. IN OUR DISCUSSIONS, WE'VE THOUGHT ABOUT HOW IMPORTANT IT IS TO ACTUALLY MAKE THE PUBLIC AWARE OF WHAT'S GOING ON AND HELP INFORM THEM ABOUT THE IMPORTANT WORK THAT'S COMING OUT AND THE LIKELY LONG TERM CONSEQUENCES FOR HUMAN HEALTH. WE'VE DISCUSSED A NUMBER OF POSSIBILITIES IN THIS AREA. ONE SUGGESTION WAS A MOUSE PROJECT THAT WOULD ACTUALLY HAVE HIGH SCHOOL STUDENTS COLLECTING GENETIC AND BEHAVIORAL DATA FOR MICE AND ADDING IT TO A CENTRAL REPOSITORY WHICH WOULD SORT OF BE EVERGROWING AND WHERE THEY COULD ACTUALLY EXPLORE THOSE DATA AND USE IT IN PROJECTS. ANOTHER WAS THE YTD OF JUST ENGAGING WITH WELL ESTABLISHED SORT OF PUBLIC ADVOCACY GROUPS SUCH AS THE ASSOCIATION FOR SCIENCE TECHNOLOGY CENTERS, SPEAKING DIRECTLY TO THE PUBLIC ABOUT WHAT THE BRAIN INITIATIVE IS AND WHAT ITS PROSPECTS ARE. ONE OF THE MAIN POINTS WE'VE BEEN DISCUSSING HEE THIS IS ACTUALLY MORE HEADING INTO THE LAST SECTION OF THIS, IS JUST THAT ALTHOUGH PROBABLY OUR FIRST ORDER RECOMMENDATION WILL BE TO CONTINUE AS WE'RE DOING NOW, WITH SOME TUNEUPS, EXTENSIONS, REFINEMENTS, ONE AREA WHERE WE THINK THERE MIGHT BE REAL ARGUMENT FOR MAKING A CHANGE TO THE BRAIN INITIATIVE IS TO EMBRACE MORE GENEROUSLY LARGE TRANSFORMATIVE PROJECTS THAT ARE LIKELY TO BRING LARGE DATASETS OF REAL SIGNIFICANCE TO THE COMMUNITY, AND HERE I WOULD JUST POINT TO THE CELL CENSUS AS AN EXAMPLE OF ONE OF THOSE SORTS OF PROJECTS WHERE IT'S A MAJOR INVESTMENT, TENS OR HUNDREDS OF MILLIONS OF DOLLARS, BUT IT IS ACTUALLY GOING TO CHANGE THE WAY THAT THE BRAIN INITIATIVE MOVES FORWARD, AND TO THE EXTENT THAT OPPORTUNITIES LIKE THAT WILL ARISE, WE THINK THAT THE BRAIN INITIATIVE SHOULD BE VERY OPPORTUNISTIC ABOUT TAKING THEM UP AND USING THEM, NOT TO ELIMINATE THE SMALLER PROJECTS WHICH ARE ACTUALLY SORT OF THE HEART OF THE BRAIN INITIATIVE, BUT THERE'S REAL OPPORTUNITY HERE, AND WE LISTED A FEW JUST TO GIVE EXAMPLES, NOT TO IMPLY THAT THESE ARE THE CORRECT ONES OR THAT THESE ARE THE HIGHEST PRIORITIES OR THAT THEY'RE IN ANY PARTICULAR ORDER, BUT THE CELL CENSUS HAS GIVEN US WONDERFUL INSIGHTS ABOUT THE DIVERSITY, A SORT OF PARTS LIST OF THE BRAIN AT THE CELLULAR LEVEL, BUT IT'S OBSERVATIONAL. WE CAN'T USE THOSE TO PERTURB THE SYSTEM AND EXPLORE THE SYSTEM. SO THE NOTION ABOUT GETTING EXPERIMENTAL ACCESS TO A SUBSET OF THOSE CELLS, DOZENS, MAYBE A HUNDRED, WHERE WE COULD ACTUALLY START TO PERTURB THAISH THEIR ACTIVITY AND STUDY WHAT THEIR CONTRIBUTION IS IN A BEHAVIORAL SENSE WOULD REALLY MAKE A DIFFERENCE. AND THERE ARE TECHNIQUES THAT ARE WITHIN REACH THAT WOULD MAKE THAT POSSIBLE, BUT NOT EASILY. ANOTHER IDEA WOULD BE JUST TO GET A COMPREHENSIVE MAPPING AT EM OR AT THE LIGHT LEVEL EVEN OF AN ENTIRE MAMMALIAN BRAIN. HAVING THAT SORT OF RICH FAR REACHING DATASET WOULD BE TREMENDOUSLY INFORMATIVE. THE FACT OF THE MATTER IS, NEUROSCIENCE, WE TEND TO FOCUS ON SMALL PARTS OF FAMILIAR STRUCTURES LIKE CEREBRAL CORTEX, HIPPOCAMPUS, CEREBELLUM, AND WE REALLY DON'T KNOW WHAT WE AREN'T LOOKING AT DOWN IN THE DEEPER STRUCTURES WHICH ARE ABSOLUTELY INVOLVED IN ALL OF THESE BEHAVIORS WE CARE ABOUT, THEY'RE PHYLOGENETICALLY ANCIENT, BUT A KEY IT TO BEHAVIOR, AND THEY DON'T GET MUCH ATTENTION. AND JUST HAVING THE MAPPING OF WHO'S INVOLVED, WHO'S CONNECTED TO WHOM AND HOW MUCH IN A QUANTITATIVE WHICH I THINK COULD REALLY INFORM US ABOUT WHAT WE HAVE BEEN OVERLOOKING. NOT TO MENTION THAT DATASET WOULD BE A FANTASTIC RESOURCE TO MODELERS. BASICALLY COMPLETELY STAR OFFED FOR THAT STARVED FOR THAT TYPE OF INFORMATION. IT IS IN REACH FOR A BRAIN THE SIZE OF A MOUSE SO THAT'S SOMETHING THAT COULD BE SERIOUSLY CONSIDERED. ALSO ACHIEVING A CIRCUIT LEVEL UNDERSTANDING AND INTERVENTIONS FOR A VULNERABLE CIRCUIT SUCH AS THOSE INVOLVED IN HUMAN PSYCHIATRIC DISORDERS WOULD POTENTIALLY BE A VERY GOOD TEST CASE TO HAVE MANY OF THE ELEMENTS, THE MAIN STRUCTS IN A CIRCUIT THAT ARE INVOLVED IN A PARTICULAR CLASS OF BEHAVIORS THOROUGHLY STUDIED AND WORKED OUT IN DETAIL COULD ACTUALLY HELP JUMP START UNDERSTANDING ON CIRCUIT FUNCTION AND WOULD WREELY HIGHLIGHT THE RELEVANCE IN THE BRAIN INITIATIVE TO HUMAN HEALTH. FINALLY, IN TERMS OF GETTING DATE TA OUT THERE, GETTING THE STANDARDS INVOLVED, IT MAY BE THAT THE CORRECT APPROACH OR THE ONLY REALLY PRACTICAL APPROACH WOULD BE A MAJOR COMMITMENT IN TERMS OF GETTING THAT -- SOME SORT OF ORGANIZATION TO SUPPORT THAT EFFORT. IF THAT'S WHAT IT TAKES, IT'S WELL WORTHWHILE. SO IN SUMMARY, I JUST WILL GO THROUGH A LIST TO REMIND YOU OF SOME OF THE HIGHLIGHTS WE'VE MENTIONED IN THE COURSE OF THE PRESENTATION. THE CELL CENSUS WE JUST CONSIDER A HOME RUN, THAT REALLY HAS PAID OFF IN AN ENORMOUS WAY, WE THINK THAT'S GOING TO MAKE REAL DIFFERENCE TO OUR UNDERSTANDING. BRINGING CELL AND CIRCUIT BASED SCALES TO HUMAN NEUROSCIENCE IS SOMETHING OBVIOUSLY THAT NEEDS TO HAVE CONTINUED ATTENTION. BRAIN 2025 IMAGINED A SORT OF SHIFT FROM TECHNOLOGY DEVELOPMENT TO DISCOVERY SCIENCE IS HOW THEY PUT IT IN THE SECOND FIVE YEARS, WE THINK THAT'S CORRECT BUT I THINK IT WOULD BE A SERIOUS MISTAKE TO SHUT DOWN TECHNOLOGY DEVELOPMENT. BRAIN 2025, NEVER SAID THAT, I THINK THEY WOULD ALSO BE HORRIFIED -- CONTINUE TO BE SUPPORTED GOING FORWARD. WE HAVE TO BRIDGE THESE SCALES, WE'VE GOT TO GET SOME MORE THEORY IN THERE, EXPLOIT NATURAL BEHAVIORS, WE NEED TO TRY AND MAKE PROGRESS ON WHAT LIES AT THE HEART OF THE BRAIN INITIATIVE. UNDERSTANDING HOW THOSE CIRCUITS ACTUALLY CREATE BEHAVIORS. AND THEN IMPROVING DISSEMINATION OF NEW TECHNOLOGIES, DATA SHARING, IMPROVING DIVERSITY AND RECRUITMENT AND RETENTION OF SCIENTISTS FROM THE DISCIPLINES, BRINGING THE PUBLIC ON BOARD AND THESE OPPORTUNITIES FOR TRANSFORMATIVE PROJECTS. THAT, WE'D LIKE TO THANK YOU FOR THIS OPPORTUNITY TO GIVE YOU AN OVERVIEW. >> JOHN AND CATHERINE, THANK YOU FOR THE AN INSPIRING OVERVIEW OF THE KINDS OF THINGS YOUR GROUP HAS BEEN LABORING WITH TO TRY IT TO IMAGINE HOW WE CAN TURN THIS INTO A TRULY TRANSFORMATIVE FLAGSHIP PROJECT, WHICH IT IS MOST DEFINITELY. LET ME FIRST ASK ANNE CHURCHLAND IF YOU HAVE COMMENTS, GIVEN WITH YOUR ROLE ON THIS GROUP, THEN I'LL CALL ABOUT JIM EBERWINE WHO'S ON THE PHONE TO SAY SOMETHING ABOUT THE KNEW OWE ETHICS GROUP. >> I HAVE ONLY ONE COMMENT TO ADD, ONE THING THAT BOTH JOHN AND CATHERINE HIGHLIGHTED WAS THE NEED FOR IMPROVEMENTS IN DATA MANAGEMENT AND DATA ARCHITECTURE AND I WONDER WHETHER THAT'S AN AREA WHERE THE BRAIN INITIATIVE MIGHT KIND OF PARTNER OR GAIN INSIGHT FROM SOME OF THE OTHER GROUPS AT THE NIH. I KNOW DATA MANAGEMENT, DATA ARCHITECTURE IS A PRIORITY FOR A LOT OF GROUPS AND WONDER IF WE MIGHT BE ABLE TO LEARN FROM EACH OTHER IN THAT AREA. >> I REALLY APPRECIATE YOUR RAISING THAT BECAUSE I WAS A LITTLE CONCERNED THAT WE HADN'T MADE THAT LINKAGE AS TIGHTLY AS WE NEED TO, THE TIME IS NOW TO SEE HOW TO MANAGE THOSE INTERFACES. I THINK I MENTIONED YESTERDAY OUR EFFORT IT TO RECRUIT THIS CHIEF DATA STRATEGIST, WE HAVE A DATA SCIENCE STRATEGIC PLAN, BUT BRAIN OUGHT TO BE VERY MUCH FRONT SEAND TER IN TERMS OF THE LARGE REALLY COMPLEX PROJECTS WHERE THESE KINDS OF INTD ACTIONS ARE GOING TO BE HELPFUL. WHEN WE TALK AT THE END OF TODAY'S MEETING ABOUT AN ARTIFICIAL INTELLIGENCE WORKING GROUP, I THINK THERE ALSO WILL BE REALLY IMPORTANT ISSUES THERE ABOUT HOW TO BE SURE WE'RE RECRUITING AND RETAINING TRAINING THE RIGHT KINDS OF MINDS TO DEAL WITH THIS REMARKABLE DATASET ABOUT THE MOUSE AND THE HUMAN BRAIN TO TRY TO LEARN WHAT WE CAN FROM IT ABOUT HOW IT ALL WORKS. SO I'M GLAD YOU BROUGHT IT UP. LARRY, YOU WANT TO SAY ANYTHING ABOUT THAT? >> I ONLY WILL SAY WE DO HAVE SOME ONGOING EFFORTS TO BOTH MOVE AND CURATE AND PUT INTO SOME SORT OF METADATA STRUCTURE EXISTING UNIQUE DATASETS THAT WE ALREADY HAVE. I HOPE IT'S EASIER IF YOU START AT THE BEGINNING RATHER THAN DO RETROFIT. I'M LOOKING AT DAVID, WHO MAYBE WILL NOD HIS HEAD YES -- THANK YOU -- SO THE TIME MIGHT BE VERY RIPE TO ENSURE THAT -- I KNOW WALTER IS HERE SOMEWHERE, SO THE TIME MIGHT BE VERY RIPE TO ENSURE [OF OFF MIC] [OFF MIC] >> JIM EBERWINE, CAN YOU TELL US A LITTLE BIT ABOUT WHERE THE NEUROETHICS WORKING GROUP IS AND HOW IT ALL FITS TOGETHER? >> SURE. THANK YOU, FRANCIS. I WANT TO THANK CATHERINE AND JOHN FOR A VERY NICE LUCID PRESENTATION OF WHAT THEY'VE BEEN DOING, AND FOR HELPING TO ACTUALLY INTEGRATE OUR EFFORTS INTO THEIR LARGER EFFORTS. THAT'S REALLY ONE OF THE KEY THINGS FOR OUR NEUROETHICS SUBGROUP IS, WE REALLY WANT TO TRY TO ENSURE THAT NEUROETHICS IS GRAINTED PER VASIVELY THROUGHOUT THE REPORT AND THINKING ABOUT THE SCIENCE AND AS THE BRAIN PROJECT MOVES FORWARD. OF COURSE IT WAS MENTIONED IN THE ORIGINAL RORL, BUT NOW REPORT, BUT AS WE MOVE MORE AND MORE INTO WORKING WITH HUMAN TISSUES AND HUMAN SUBJECTS, IT BECOMES EVEN MORE IMPERATIVE TO START TO THINK ABOUT THE ETHICAL CONSIDERATIONS OF THE APPLICATION OF PARTICULAR TECHNIQUES, USING PARTICULAR TYPES OF APPROACHES TO TRY TO UNDERSTAND CIRCUITRY, AND TO POTENTIALLY AT SOME POINT HOPEFULLY DEVELOP INTERVENTION STRATEGIES SO THAT -- THE NEUROETHICAL CONSIDERATIONS. I DID WANT TO HIGHLIGHT, AGAIN I THINK JOHN MENTIONED ABOUT NON-HUMAN PRIMATES. CERTAINLY ONE OF THE -- OF OUR NEUROETHICS SUBGROUP IS NOT ONLY TO LOOK THROUGH AND EXAMINE ASPECTS OF THE BRAIN INITIATIVE WITH RESPECT TO HUMANS BUT ALSO NON-HUMAN PRIMATES, AND MY CO-CHAIR, JEFF KAHN, HAS BEEN INTIMATELY INVOLVED IN ASPECTS OF THAT THROUGH THE NATIONAL ACADEMIES AS WELL. SO OUR WORKING GROUP IS COMPOSED OF PHILOSOPHERS, NEUROETHICISTS, SCIENTISTS, WE HAVE A SURGEON, WE HAVE ANOTHER CLINICIAN, SO WE'RE TRYING TO APPROACH THIS FROM A VERY BROAD GENERAL PERSPECTIVE. THE DISCUSSIONS HAVE BEEN FUN AND FAR REACHING. I THINK WE HOPEFULLY WILL COME UP WITH SOME HELPFUL AND INTERESTING OPPORTUNITIES THAT BRAIN INITIATIVE INVESTIGATORS WILL BE ABLE TO AVAIL THEMSELVES IN THINKING ABOUT THEIR SCIENCE AS THEY MOVE IT FORWARD. >> GREAT, THANKS. WE ALL LOOK FORWARD TO SEEING WHERE YOU ALL GO WITH THIS, AND IT'S GREAT TO HAVE THIS INTEGRATED INTO THE WHOLE ENTERPRISE AND NOT AS AN AFTER THOUGHT. SO WE'LL OPEN THIS UP TO ACD MEMBERS, LINDA, JOSE, BRENDAN. >> SO APP AND OTHERS, AGAIN, CONGRATULATIONS ON A WONDERFUL REPORT. VERY ILLUMINATING. AS YOU THINK ABOUT DATA SCIENCE IN PARTICULAR, I AM CURIOUS IF YOU'RE THINKING ABOUT -- THERE'S OFTEN AT NIH, YOU GET DATA AND YOU HAVE BIOLOGISTS AND CLINICIANS AND SOMEHOW MORE DATA THERE'S A ROLE FOR BRINGING MECHANISM INTO LOOK BEING AT HETEROGENEOUS DATASETS. YOU HAD A BEAUTIFUL TITLE FOR THIS, BRINGING MOLECULES UP TO SYSTEMS ESSENTIALLY, OFTEN COMPUTER SCIENTISTS WITH DATA AREN'T AS FAMILIAR ON HOW TO INTEGRATE, FOR EXAMPLE, BIOPHYSICAL AND BIOCHEMICAL MECHANISMS ACROSS MULTIPLE LENGTH AND TIME SCALES. THERE WAS, FOR A WHILE, A MULTI-SCALE MODELING INITIATIVE AT NIH THAT HAS GONE BY, BUT I WOULD URGE YOU TO RE-THINK BRINGING IN MULTI-SCALE MODELING TO BRING IN THE KIND OF PEOPLE WHO WOULD THINK ABOUT MECHANISM BECAUSE AS A COMPUTER SCIENTIST, IT'S HARD TO GRAPPLE WITH A LOT OF DATASETS AND BIOLOGISTS, SH YOU NEED PEOPLE WHO KNOW SOMETHING ABOUT HOW TO PULL MULTIFACETED KIND OF PHENOMENA TOGETHER. AND THAT'S -- WE STARTED A NEW DEPARTMENT AT MIT SPECIFICALLY TO BRIDGE THAT GAP BETWEEN PEOPLE WHO KNOW A.I. AND DO ALGORITHMS AND CAN THINK ABOUT HOW DO WE HANDLE ALL THESE DATA, AND ED BOYDEN IS ACTUALLY A MEMBER OF OUR DEPARTMENT, HE BUILDS TOOLS, ENGINEERS AND BUILDS TOOLS WITH THE PROBES AND SO ON, BUT THERE'S ALSO ENGINEERS WHO HELP BRIDGE THE GAP BETWEEN DATA AND THE BIOLOGISTS AND THE TOOLMAKERS TO REALLY SAY, WE'VE GOT TO BRING SOME INSIGHT AND MECHANISM AND HYPOTHESIS GENERATION AROUND THE SYSTEMS LEVEL THINKING. AND I CANNOT MAKE THAT PLEA STRONGLY ENOUGH AND UNDERSCORE IT STRONGLY ENOUGH, AND IT PARTICULARLY COMES IN ALSO WITH YOU'RE GOING TO GET ALL THIS FABULOUS DATA THEN THAT SETS A FOUNDATION TO LOOK AT PATHOLOGY. SO WE OFTEN GO DOWN RABBIT HOLES PURSUING -- IS IT TAU, PROTEIN, CELL TIMERS, THERE COULD BE OTHER MECHANISMS THAT MIGHT REASON VEALED BY AN AGNOSTIC APPROACH FROM FOLKS WHO UNDERSTAND INTEGRATION OF BIOCHEMICAL AND BIOPHYSICAL MODELS AND ARE NOT TIED UP TO A PARTICULAR PATHWAY. SO I REALLY URGE US TO THINK THAT. FINAL LACI, INTEGRATION OF MECHANICS, BRAIN TISSUE WITH BIOCHEMISTRY IS BECOMING INCREASINGLY IMPORTANT AND RECOGNIZED, SO A PLEA FOR FOSTERING THAT INTERFACE BECAUSE IT HASN'T BEEN PARTICULARLY STRONG AT NIH IN TERMS OF PROGRAMS. EXOWP >> THIS HAS BEEN VERY MUCH ON OUR RADAR SCREEN, AND IT'S ACTUALLY REALLY INTERESTING TO SEE HOW THE CELL CENSUS HAS THIS ENORMOUS CELL DIVERSITY. THERE ARE 120 TYPE OF CORTICAL CELLS AND HOW DO YOU INTEGRATE THESE INTO MOUSE? AND MANY THEORISTS OF BRAIN FUNCTION USE ONE INHIBITORY NEURON AND ONE -- NEURONS AND THAT'S THEIR MODEL OF SPECIFIC CIRCUIT, AND I THINK, YOU KNOW, THE DATA NOW ARE FLOURISHING AND EXACTLY AS YOU MENTIONED, I THINK THE INTEGRATION OF THIS BIOCHEMICAL, BIOPHYSICAL CELLULAR UP TO LARGER SCALE DATA IS ABSOLUTELY NECESSARY. >> JOSE. >> SO I WANT TO ECHO MY THANKS TO CATHERINE AND JOHN AND ANNE FOR YOUR WORK ON THIS, IT'S IF AN AMAZING OPPORTUNITY, WITH THAT COMES THE RESPONSIBILITY AND I'M GLAD TO SEE THAT IT'S IN GOOD HANDS. SO AS A FORMER NEUROSCIENTIST, I'M VERY EXCITED ABOUT THE PROJECT. AS A CURRENT HUMAN GENETICIST, I COULDN'T BUT NOTICE MAYBE THE ABSENCE OR MAYBE IT'S NOT MENTIONED AND IT'S THERE SOMEWHERE OF THE EMERGING HUMAN GENOMIC DATASETS AND INFORMING A LOT OF YOUR ACTIVITY. SO WHEN IT COMES TO THE GENETICS ARE RARE, NEURODEVELOPMENTAL DISORDERS IN CHILDREN OR THE GENOMICS OF EPILEPSY OR NEURODEGENERATIVE DISEASE, ALZHEIMER'S AND PARKS SONS PARKINSON, ON RISK TAKING, NUTRITIONAL CHOICES, A NUMBER OF THINGS, YOU WOULD IMAGINE BRINGING IN THOSE DATASETS, SCHIZOPHRENIA, COULD REALLY INFORM A LOT OF THESE AREAS. YOU KNOW, WHETHER IT'S THE MAPS, THE CELL TYPES, OF COURSE HUMAN NEUROSCIENCE, EVEN CAUSALITY BY SMART USE OF MAN DALIAN -- SO AT LEAST ON THE FINAL REPORT, I WOULD LIKE TO SEE A LITTLE MORE OF HOW ALL OF THIS IS BEING BROUGHT IN TO INFORM IF IT'S NOT ALREADY PRESENT. >> THANK YOU AS WELL FOR A GREAT PRESENTATION AND REPORT. I WAS GOING TO MAKE A SIMILAR POINT TO JOSE'S, BUT I'LL EMPHASIZE OR AT LEAST ASK YOU ABOUT YOUR THOUGHTS ABOUT TRANSLATION. I KNOW THIS IS A VERY INTENSE DISCOVERY INITIATIVE, THERE'S NO QUESTION ABOUT THAT, BUT I WONDER IF YOU'RE THINKING ABOUT SORT OF THE TRANSLATIONAL PATHWAYS FOR THAT DISCOVERY WORK THAT YOU'RE DOING AND FOR EXAMPLE, IF SOME OF THE NETWORKS THAT YOU ARE DEFINING MAY BE AMENABLE TO DRUG TARGET DISCOVERY, AND YOU ALREADY MENTIONED THAT THERE'S SOME PUBLIC-PRIVATE PARTNERSHIPS THAT YOU'RE PURSUING BUT NOT NECESSARILY IN THAT AREA, I'M JUST WONDERING IF IT'S TOO EARLY IN YOUR MIND TO THINK ABOUT A TRANSLATIONAL STRATEGY OR CERTAINLY FOR PUBLIC HEALTH AND BENEFIT, AND WHAT THE NIH STAND FOR. >> WE HAVE DISCUSSED THIS A LOT, AND THE BRAIN INITIATIVE AS LAID OUT IN BRAIN 2025 WAS VERY DECIDEDLY FOCUSED ON BASIC UNDERSTANDING, AND I DON'T KNOW IF YOU'RE FAMILIAR WITH THAT DOCUMENT, BUT IT REALLY WENT ON A CAREFUL EXPLANATION ABOUT WHY AT THAT POINT IT MADE SENSE IN TRYING TO UNDERSTAND THE FUNCTION OF THE THE HUMAN BRAIN, WITH THE HOPE THAT THAT WOULD GREATLY ACCELERATE THE APPLICATIONS IN THE CLINIC. SO IT DIDN'T OUTRIGHT EXCLUDE TRANSLATIONAL STUDIES BUT IT REALLY SAID THAT THE EFFORT REALLY SHOULD BE FOCUSED ON UNDERSTANDING THE BASIC FUNCTION OF THE BRAIN. WITH HAVE HAD DISCUSSIONSWE HAVE HAD DISCU SSIONS ON WHETHER WE SHOULD MODIFY THAT. THERE ARE DIFFERENT VIEWS ON THE WORKING GROUP, ALL OF THEM WILL BE REFLECTED IN OUR FINAL DOCUMENT, BUT I THINK THE NOTION THAT WE WOULD WANT TO CHANGE THE COURSE OF BRAIN IN SUCH A MAJOR WAY IS UNLIKELY, NOT LIKELY TO SAY THAT THIS SHOULD NOW FOCUS, INSTEAD THE THOUGHT IS, BRAIN IS PROVIDING THE BASIC UNDERSTANDING WHICH THE BULK OF THE REMAINING NEUROSCIENCE OF NIH CAN TAKE UP AND USE AND PUT INTO TRANSLATIONAL APPLICATIONS. >> SO I ACTUALLY WANT THE TO PURSUE THIS COURSE OF DISCUSSION A LITTLE MORE. IN FACT, WHEN WALTER PRESENTED AN UPDATE NE LAST ACD MEETING, SOME OF THIS WAS TOUCH THE ON. I ACTUALLY THINK IT WOULDN'T BE DISSIDENT, IT WOULD BE CONS DENT IN TERMS OF THESE TWO THEMES. THERE'S NO QUESTION THE BRAIN INITIATIVE HAS BEEN SPECTACULARLY SUCCESSFUL IN TERMS OF THE FOUNDATIONAL PHENOTYPING AT EXQUISITE WRES REST LEUTION, ONE COULD ARGUE IT'S ACHIEVED AN ORDER OF MAGNITUDE OR EVEN TWO THAN ANY OTHER SYSTEM IN THE BODY, BUT AT THE SAME TIME, I THINK IN TERMS OF THAT SAME PHENOTYPING WHEN APPLIED TO DISEASE, AND PERHAPS SELECT GROUPS OF DISEASE, CAN SIMILARLY INFORM THE BASIC SCIENCE. I THINK THERE'S NO QUESTION, YOU KNOW, RARE DISEASES HAS SHOWN THAT. NOT SO MUCH AS A TRANSLATIONAL EXERCISE, YOU CAN ARGUE FINDING THE PERTURBATION IN A RARE DISEASE MAY OR MAY NOT BE CLIPICALLY RELEVANT AT THAT BE CLINICALLY RELEVANT AT THAT MOMENT IN TIME. SO I WOULD SAY THAT NOT NECESSARILY CLINICAL TRANSLATION BUT STUDYING THE RIGHT PHENOTYPES AND APPLYING EXACTLY WHAT YOU'RE DOING, QUANTITATIVE PHENOTYPING AT MUCH HIGHER RESOLUTION IN THOSE SITUATIONS ALLUDES TO ALSO WHAT YOUR THIRD OR FOURTH TRANSFORMATIVE POINT IS, SO I THINK IT'S COMPLETELY CONSISTENT WITH THE ORIGINAL PLAN. ALSO, I THINK IT WOULD THEN ADDRESS THIS WHOLE ISSUE OF EXPANDING ALL THE PRINCIPLES OR AREAS TO HUMAN NEUROSCIENCE, BECAUSE BASICALLY THAT'S WHAT THAT WOULD BE. AND SIMILARLY, I WOULD SAY US A ALSO TOUCHED ON, IT WOULD BE THE BEST STRATEGY, I THINK EVEN BETTER THAN GOING TO SOME OF THE GROUPS THAT YOU PROPOSE IN TERMS OF ENGAGING THE PUBLIC. WHAT MORE POWERFUL THAN ENGAGING THE PUBLIC IN SAYING THAT THE BRAIN INITIATIVE HAS USED THE STUDY OF SOME SPECIFIC NEUROPSYCHIATRIC DISEASE TO INFORM, YOU KNOW, BASIC PRINCIPLES OF NEUROSCIENCE. >> YOU KNOW, A SIGNIFICANT PORTION OF THE NEUROSCIENTISTS WERE FUNDED BY THE BRAIN INITIATIVE WORK ON MODEL OF DISEASE IN VARIOUS MODEL SYSTEMS. AND IN TERMS OF TOOL DEVELOPMENT, THERE ARE A LOT OF TOOL DEVELOPMENT THAT HAS BEEN DONE ALSO IN THE MOUSE OR IN PRIMATES WITH THE GOAL OF ADAPTING THESE TWO HUMAN NEUROPSYCHIATRY DISEASES. SO WE HAVE ALL OF THIS IN MIND VERY MUCH. >> I MEANT TO REALLY FOCUS ON SPECIFIC PERHAPS RARE NEUROPSYCHIATRIC PHENOTYPES, SORT OF WHAT YOU WERE ALLUDING TO AS A STRATEGY. IN HUMANS. NOT NECESSARILY IN ANIMAL MODELS. >> THE STUDY OF HUMAN DISORDERS IS DEFINITELY PART OF BRAIN 2025. THERE'S LIGHT OF INSIGHTS A LOT OF INSIGHT S THAT WILL COME FROM THAT. IT WAS MORTGAGE NOTION OF FOCUSING ON CREATING THE A CURE AT THIS TIME FOR THIS DISEASE, THAT WAS THE THING WE THOUGHT PROBABLY DOESN'T BELONG IN BRAIN. >> I AGREE WITH THAT. >> WALTER HAS JOINED US AT THE TABLE, THAT'S GOOD. WALTER? >> I JUST WANTED TO GET INTO THIS THEME HERE, SO THE WAY WE THINK ABOUT IT IS THAT THE BRAIN INITIATIVE IS BUILDING THIS FOUNDATIONAL KNOWLEDGE AND THEN THESE NEW TOOLS, AND ALL THE NEUROSCIENCE ICs SALIVATING NOW ABOUT MOVING THOSE TOOLS INTO THEIR PARTICULAR DISEASES, AND THAT'S HAPPENING. SO IF YOU LOOK AT HOW PEOPLE ARE LOOKING AT PSYCHIATRIC DISEASES, THE PAPERS THAT ARE COMING OUT ARE, YOU KNOW, LOOKING AT HOW THE CIRCUITS ARE AFFECTED BY A MUTATION THAT LEADS TO AUTISM. SO ALREADY, IT'S COMPLETELY CHANGED HOW WE DO THE -- UNDERSTAND CIRCUITS AND DISEASE. I THINK IT POINTS OUT THAT THE OTHER THING THAT WE'VE BEEN GRAPPLING WITH IS THAT THE BRAIN INITIATIVE IS THE CORE, BUT THEN THERE ARE THESE TREMENDOUS CONSEQUENCES THAT COME OUT OF BRAIN INITIATIVE, AND HOW DO WE BETTER ORGANIZE OH NIEZ ORGANIZE THOSE IN AND THE DISEASE AREA IS I THINK A PERFECT OPPORTUNITY. SO YOU HEARD YESTERDAY WE'RE IN THE PAIN SYSTEM PROJECTS, WE HAVE BRAIN INITIATIVE TOOLS THAT WE WANT PEOPLE TO ADDRESS TO DEVELOP TECHNOLOGIES TO ALLEVIATE PAIN. SO THAT'S ONE EXAMPLE. BUT YOU COULD THINK OF A THOUSAND. I THINK ALL THE INSTITUTES ARE ALSO DOING THIS. SO WHEN WE THINK ABOUT IT, WE THINK OF THE BRAIN INITIATIVE AS BEING DISEASE-AGNOSTIC, BUT USING DISEASE MODELS LIKE EPILEPSY OR PARKINSON'S OR OCD, WE HAVE PROJECTS WHERE WE'RE RECORDING FROM PEOPLE'S BRAINS ACTUALLY, BUT THEN THE NEUROSCIENTISTS ARE WORKING TO TAKE THOSE AND FOCUS THEM ON DISEASES. SO IT'S REALLY -- A REALLY IMPORTANT PART OF THE BRAIN INITIATIVE AND WHAT DO WE CALL IT, MAYBE WE SHOULD ALL CALL IT BRAIN INITIATIVE. >> JUST BUILDING A BILL LITTLE BIT MORE ON THIS THEME, YOU DID MENTION IN THE ADVANCING NEUROSCIENCE THIS IDEA OF CLOSED śLOOP DEEP STIMULATION, PARKINSONISM. IS THERE APPROPRIATELY WITHIN THE -- TO LOOK BEYOND THAT, SAY, TO EFFECT OF DISEASES OR THE EFFECT OF DEEP BRAIN STIMULATION OR IN HEALTH -- IN OTHER WORDS, HUMAN EXPERIMENTATION IF YOU LIKE IN THE SENSE OF WHERE A SPINOFF MIGHT BE THERAPEUTIC BUT YOU'RE ACTUALLY LEARNING VERY MUCH THOSE CIRCUITS. >> SO THIS WAS VERY MUCH DISCUSSED DURING OUR WORKSHOP ON HUMAN NEUROSCIENCE. WE HAD BOTH NEUROSURGEONS AS WELL AS MODELERS THAT EXPLAINED TO US HOW FROM THE RECORDING OF PATIENTS MAINLY WITH EPILEPSY, ACTUALLY MUCH MORE COULD BE LEARNED RELATED TO NEUROPSYCHIATRIC DISEASES, AMONG PEOPLE WITH EPILEPSY, A NUMBER OF THEM HAVE DEPRESSION, FOR EXAMPLE, SO A VERY LARGE INSIGHT CAN BE OBTAINED OUT OF THIS, AND THIS CLOSED LOOP STIMULATION, THE ABILITY TO MODEL FUNCTION OF THE BRAIN DURING NEUROPSYCHIATRIC DISEASE, FOR EXAMPLE, THIS IS VERY MUCH BEING DONE IN THE GOAL OF THE BRAIN. >> CATHERINE AND JOHN LET ME ASK, I'M REALLY PLEASED WITH YOUR INCORPORATION WITH YOUR INCORPORATION OF THESE TRANSFORMATIVE PROJECTS BECAUSE I THINK THAT CAN BE SOMETHING THAT INSPIRES PEOPLE TO GO EVEN FURTHER THAN THEY THOUGHT THEY COULD, AND INCLUDING THAT LIST AND I HOPE THAT LIST CAN GROW AND EXPAND OVER THE COURSE OF THE NEXT FEW MONTHS, NOT THE THAT THEY'RE NECESSARILY ALL GOING TO BE ACHIEVABLE, BUT THEY'RE STRETCH GOALS THAT CAN POTENTIALLY BRING THE FIELD EVEN FURTHER ALONG THAN THEY MIGHT OTHERWISE HAVE GONE. CERTAINLY ONE OF THOSE BEING A COMPREHENSIVE UNDERSTANDING OF THE MOUSE BRAIN IS EXCITING TO CONTEMPLATE WHAT THAT WOULD LOOK LIKE. I WAS LOOKING TO SEE SORT OF WHAT YOU WOULD SEE AS THE COMPREHENSIVE UNDERSTANDING OF THE HUMAN BRAIN IN 2025, SINCE THAT, AFTER ALL, WAS THE MOTIVATOR FOR THIS WHOLE ENTERPRISE. I GUESS IN THAT REGARD IT'S PRETTY HARD TO SEE FORWARD HOW WE PARTICULARLY WITH A BRAIN THAT WE ARE SOMEWHAT IMPEDED IN TERMS OF BEING ABLE IT TO DO INTERVENTIONS THAT ARE SIMPLY NOT GOING TO BE ACCEPTABLE, HOW FAR CAN WE GO. BUT MAYBE THE REAL THING I'M WONDERING IS, IN TERMS OF HOW WE GET AS FAR AS WE CAN IN THAT SPACE, IS IT TIME TO CONTEMPLATE PULLING TOGETHER NOT SORT OF A COLLECTION OF REALLY BRIGHT SCIENTISTS WHO ARE GETTING R01 GRANTS OUT OF THE BRAIN INITIATIVE, BUT TO HAVE MORE OF A FOCUSED MANHATTAN PROJECT KIND OF ATTITUDE TOWARDS THE HUMAN BRAIN AND SEEING HOW FAR WE COULD TAKE THAT IN THE NEXT FIVE YEARS. YOU PROBABLY WILL RECOGNIZE I'M COMING OUT OF THIS MAIN MAIB FROM A SORT OF HUMAN GENOME PROJECT PERSPECTIVE WHERE FOR THE FIRST FIVE YEARS OF THAT ENTERPRISE, IT WAS A LOT OF INDIVIDUAL INVESTIGATORS DOING THEIR THING, DEVELOPING A LOT OF TECHNOLOGIES, BUT AT SOME POINT IT BECAME NECESSARY TO SAY WE HAVE TO HAVE A PROGRAM THAT HAS MILESTONES, AN ORGANIZED STRUCTURE AND ALL THE NECESSARY TECHNOLOGIES AND SKILLS TOGETHER TO TRY TO MAKE A REAL PROGRAM HAPPEN THAT MIGHT NOT HAPPEN JUST ONITY OWN. IS THERE ANYTHING THAT RESONATES THERE ABOUT WHERE WE NEED TO GO IN THE SECOND HALF OF THIS 10-YEAR EFFORT? >> SO IT'S INTERESTING, THE COMPARISON WITH THE GENOME PROJECT, BECAUSE YOU CAN VIEW THE NANOSTRUCTURE OF A MAMMALIAN BRAIN AS THE EQUIVALENT. WE HAD DISCUSSION SHOULD WE TAKE THE STRUCTURE OF ONE PARTICULAR BRAIN REGION AND LOOK ACROSS SPECIES FROM THE MOUSE, THE NON-HUMAN PRIMATE AND HUMAN AND COMPARE, AND THAT WOULD BE THE EQUIVALENT OF, LET'S SAY, SEQUENCING ONE PARTICULAR CHROMOSOME IN THE MOUSE, HUMAN AND PRIMATE, OR HAVE A COMPREHENSIVE GENOME EXPWEENSING OF ALL THE GENOME IN ONE SPEE SPEES SHEES AND IN PARALLEL TO, LET'S SAY, THE NANOSTRUCTURE OF THE MOUSE BRAIN, CLEARLY SCIENTISTS WILL ALSO LOOK AT OTHER BRAINS AND SEE THE SIMILARITY AND DIFFERENCES. THE NANOSTRUCTURE OF THE MOUSE BRAIN, I THINK IS OUT OF REACH, BUT STARTING BY SMALLER BRAIN, I THINK IS VERY MUCH THE CASE. ORGANIZING THE ENTIRE BRAIN AROUND ONE MAN MANHATTAN PROJECT DOESN'T SEEM VERY APPEALING TO ME. JOHN MIGHT AVE A DIFFERENT OPINION. BECAUSE BRAIN FUNCTION HAS SO MANY DIMENSIONS AND THAT WOULD OBLIGE YOU TO PICK ONE OF FEW DIMENSIONS OUT OF THE EXTRAORDINARY DIVERSITY OF SCALES AND DIMENSIONS THAT ARE BEING NOW CURRENTLY INVESTIGATED INDIVIDUAL LABS. IT WOULD BE A VERY RISKY BET. I THINK YOU REALLY -- I WOULD SUGGEST TO MORE TAKE ADVANTAGE OF THE CREATIVITY OF ALL THE VARIOUS LABORATORIES, THE INDIVIDUAL INVESTIGATORS, TOGETHER WITH THIS TEAM THAT HAVE DEVELOPED AT THE INSTITUTE OR THE INTERNATIONAL BRAIN LAB IN WHICH ANNE PARTICIPATES, AND REALLY TAKING ADVANTAGE OF THIS DIVERSITY. BUT JOHN? >> I THINK I WOULD ECHO CATHERINE'S VIEW THAT IT'S TOO RISKY TO TAKE THAT ON. WITH THE HUMAN GENOME, YOU KNEW WHAT THE END POINT WAS. WHEN I CONSIDER WHAT THAT MANHATTAN PROJECT WOULD BE, I FEEL LIKE THAT WOULD BE AN INTENSE EFFORT ON THESE INTERMEDIATE LEVELS OF ORGANIZATION TO GET YOU FROM THE LEVEL OF SMALL MICRO CIRCUITS UP TO A MODERATELY COMPLEX BEHAVIOR, BECAUSE AT THE SYNAPTIC LEVEL, WE DON'T HAVE ALL WE NEED TO KNOW ABOUT SYNAPTIC FUNCTION, BUT WE'VE GOT THE CONCEPTS. I GET THE CONCEPTS TO UNDERGRADUATES EVERY YEAR, AND THEY MAY NOT BE COMPLETELY ACCURATE, BUT THEY UNDERSTAND THAT, AND THAT BEHAVIOR. WE KNOW ENOUGH ABOUT COLOR VISION, MAYBE THERE'S MORE TO LEARN, PROBABLY NOT, BUT WE UNDERSTAND THOSE CONCEPTS. WE LACK THOSE FUNDAMENTAL THEORIES TO TELL YOU HOW YOU CAN GET A PER SEPTEMBER OUT OF 100 MILLION NEWER NEURONS. WE DON'T REALLY KNOW HOW FAR OFF WE ARE ON THAT ONE, I SUSPECT IT'S THE FACT THAT THE BRAIN IS DOING COMPUTATIONS WE DON'T UNDERSTAND, COMPUTER SCIENTISTS HAVEN'T DREAMT. THEY'RE ENGINEERS, SO THEY'RE USED TO PUTTING TOGETHER WORKING PARTS INTO DOING NEW THINGS. WE'RE NOT ENGINEERS, BUT WE NEED TO GET TOGETHER WITH LIKE A RANGE OF PEOPLE, COMPUTER SCIENTISTS, PEOPLE WHO HANDLE DATA, KEM KISSES, LINK WISES PROBABLY, PEOPLE WHO CAN TELL WHAT IT SAYS. WHEN WE SAY THIS CELL MEANS THERE'S A VERTICAL BAR ON THE RETINA, WHAT DOES "MEAN" MEAN TO THE BRAIN? SO THERE'S A WHOLE LEVEL OF UNDERSTANDING THERE THAT WILL BREAK OPEN UNDERSTANDING ACROSS THE WHOLE BRAIN ONCE WE GET THERE BUT WHO ARE THE RIGHT PEOPLE FOR HOW LONG, AND WOULD IT EVER WORK, AND I JUST THINK THE RISKS ARE A LITTLE HIGH NOW THAT I JUST COULDN'T SANCTION IT AS SOMETHING THAT I WOULD RECOMMEND INVESTING A LARGE AMOUNT OF MONEY. >> I VERY MUCH HEAR. YOU DO SAY IN YOUR TRANSFORMATIVE PROJECTS THAT ONE COULD BE ACHIEVING CIRCUIT LEVEL UNDERSTANDING THAT MIGHT HAVE SIGNIFICANT CONSEQUENCES FOR NEUROPSYCHIATRIC INTD PRE TAITION OF DISEASE. SO WHAT KIND OF CIRCUITS DID YOU HAVE IN MIND WHEN YOU PUT DOWN THAT VULNERABLE CIRCUIT DESCRIPTION? >> HERE I REPRESENT OUR WORKING GROUP. OUR WORKING GROUP IS VERY KEEN ON THE IDEA OF APPROACHING SOME SORT OF PSYCHIATRIC DISORDER, PERHAPS. PERHAPS SCHIZOPHRENIA, AND TRYING TO UNDERSTAND IT NOT JUST FROM SORT OF BEHAVIORAL LEVEL OR TRANSMITTER LEVEL BUT TO TRY AND ADDRESS THE THEORIES THAT EXIST ABOUT THE INVOLVEMENT OF PREFRONTAL CORTEX AND CONNECTIONS AND CIRCUIT PROBLEMS THAT NOBODY HAS REALLY EVER HAD ANY DATA FOR TO SEE IF YOU COULD ENGAGE IN MONITORING A WHOLE HOST OF STRUCTURES THAT SHOULD BE ENGAGED IN THIS KIND OF PROCESS AND GET SOME INSIGHT IN THAT DIRECTION. I THINK IT'S ALSO HIGHLY RISKY SORT OF UNDERTAKING, BUT THAT ONE, I THINK MIGHT ACTUALLY -- WILL PROVIDE INSIGHTS, IT'S JUST NOT CLEAR WHETHER THERE WILL BE STRONG INSIGHTS ABOUT SCHIZOPHRENIA. >> IF I COULD JUST BUILD ON WHAT JOHN WAS SAYING, AN EXAMPLE OF PERHAPS A VULNERABLE CIRCUIT MIGHT BE THOSE ALTERED IN POST-TRAUMATIC STRESS SYNDROME, SO THAT WOULD BE A SITUATION WHERE THE SAME SINCE REINPUT IN A TYPICAL HUMAN WOULD CAUSE MAYBE NO RESPONSE OR A SMAR STARTLE RESPONSE, WHEREAS SOMEONE SU SUFFERING FROM PTSD WOULD HAVE A STARTLE RESPONSE. WE HAVE THE POTENTIAL TO COMPLETELY UNDERSTAND THAT CIRCUIT BECAUSE WE CAN MANIPULATE THE INPUTS TO THE KEY NEURONS, WE CAN MANIPULATE THE NEURONS THEMSELVES, THEIR OUTPUTS, WE CAN UNDERSTAND THE WHOLE PATHWAY AND THEN FIGURE OUT WHAT'S GONE WRONG IN THE ANIMALS THAT ARE HAVING THE ABNORMAL RESPONSE TO A SENSORY STIMULUS. THAT'S SOMETHING THAT ULTIMATELY WE WANT TO UNDERSTAND IN HUMANS, THAT'S THE GOAL, BUT WE DON'T HAVE THE TOOLS TO TAKE THAT CIRCUIT APART RIGHT NOW IN THE HUMAN IN THE WAY THAT WE DO IN AN ANIMAL MODEL. I THINK THAT'S THE EXAMPLE OF THE KIND OF CIRCUIT THAT YOUR WORKING GROUP HAD IDENTIFIED. >> WHAT WILL WE KNOW ABOUT MEMORY IN 2025? >> I THINK WE MIGHT REACH AN UNDERSTANDING OF PLASTICITY AT DIFFERENT SCALES, WHICH IS SOMETHING THAT WE REALLY DO NOT UNDERSTAND AT THIS POINT, FROM THE NANOSTRUCTURE, THE SYNAPTIC LEVEL, TO THE CONNECTIVITY LEVEL, TO WHAT'S HAPPENING ACROSS THE BRAIN AND MULTIPLE BRAIN REGION. AND AN OVERARCHING THEORY. I THINK THAT MIGHT BE CONSIDERABLE AS A GOAL. >> THAT WOULD BE PRETTY PROFOUND. >> I WOULD JUST ADD, YOU KNOW, MEMORY IN THE HUMAN BRAIN IS NOT LIKE MEMORY IN YOUR COMPUTE E IT'S NOT ALL STASHED AWAY SOMEWHERE IN RAM, WHAT MAKES THE BRAIN DIFFERENT IS THE MEMORY IS IN THE CIRCUITS THEMSELVES, AND SO WE WILL KNOW A LOT ABOUT MEMORY WHEN WE UNDERSTAND HOW THOSE CIRCUITS COMPUTE. SO I THINK MEMORY IS GOING TO BE A LITTLE DIFFERENT THAN MOST PEOPLE IMAGINE. >> AND IT'S ALSO A VULNERABLE CIRCUIT AS MOST OF US RECOGNIZE YEAR BY YEAR. OTHER COMMENTS. JAY? >> MAYBE PICKING UP ON FRANCIS' FIRST COMMENT, SO THE TRANSFORMATIVE PROJECT THAT STRUCK ME AS QUITE INTERESTING WAS THE MAPPING OF THE MOUSE BRAIN FROM -- WITH LIGHT MICROSCOPY TO EM. SO THAT'S LIKE A FIVE-YEAR KIND OF GOAL IS ONE QUESTION? AND TWO IS KIND OF WHATS -- THERE'S ALSO ECHOES OF THINGS OF HOW MAP THAT WAS RECENTLY LAUNCHED, COMMON FUND INITIATIVE, AND I WAS CURIOUS ABOUT HOW YOU STRUCTURALLY KIND OF VIEW THAT. IS THAT A HUMAN GENOME PROJECT-TYPE INITIATIVE OR IS THAT SOMETHING THAT COULD BE TAKEN ON BY ONE LAB OR WHAT SCALE DOES THAT HAPPEN AT? >> SO A COMPLETE EXHAUSTIVE EM RECONSTRUCTION OF A MOUSE BRAIN IS WITHIN REACH IN FIVE YEARS. IT'S A MATTER OF MONEY AND MANAGEMENT IF YOU WANT TO DO THAT. I THINK THERE ARE LOTS OF GOOD REASONS WHY YOU MIGHT WANT TO DO THAT. THERE'S EXPENSE IN TERMS OF THE NUMBER OF SCANNING ELECTRON MICROSCOPES YOU WOULD NEED TO DO IT. YOU WOULD HAVE TO PARTNER WITH POTENTIALLY DEPARTMENT OF ENERGY TO GET SUPER COMPUTER TIME IN ORDER TO DO THE SEGMENTATION AND RECONSTRUCTION, BUT IT COULD BE DONE. PROBABLY THE BIGGEST ISSUE IS YOU'RE NOW TALKING ABOUT SOMETHING APPROACHING AN EXOBYTE OF DATA. THAT ALSO CAN BE HANDLED, BUT NOW ACCESSING THAT DATA AND GETTING THE INFORMATION YOU WANT TO GET OUT, IT WOULD BE NOT THE A MANHATTAN PROJECT, STATEN STATEN ISLAND SORT OF PROJECT, BUT I WOULD SAY IT IS DOABLE IF THERE'S EXCITEMENT AND JUSTIFICATION FOR A PROJECT OF THAT SCOPE. BUT I WOULD POINT OUT SOME OF THE OTHERS ARE ON THAT SCALE AS WELL IN TERMS OF THE AMOUNT OF EFFORT THAT WOULD BE NEEDED. >> I THINK IT WOULD BE A MULTI-LAB PROJECT, IT WOULD ALSO ENTAIL MOLECULAR IDENTIFICATION AS WELL, IT WOULD NOT BE ONLY PURELY STRUCTURAL, I THINK WE NEED IDENTIFICATION OF SYNAPSES, BUT I THINK IT WOULD PERMEATE ABSOLUTELY THE ENTIRE BRAIN INITIATIVE FROM NOW ON. >> JEFF, LAST QUESTION. >> JUST A COMMENT, I WANT AD TO SAY THAT I REALLY LIKE YOUR IDEA OF THE HIGH SCHOOL PROJECT THAT YOU MENTIONED IN TERMS OF FOR PUBLIC OUTREACH. I THINK IT NOT ONLY PROVIDES AN OPPORTUNITY AS BEST AS I UNDERSTAND HOW YOU DESCRIBED IT FOR POTENTIALLY GATHERING DATA IN SORT OF A CROWD SOURCED WAY, BUT ALSO TO REALLY PRIME THE PIPELINE POTENTIALLY FOR THE NEXT GENERATION OF NEUROSCIENTISTS, SO I REALLY APPLAUD THAT. >> THANK YOU VERY MUCH, CATHERINE AND JOHN. IT'S VERY EXCITING TO SEE HOW FAR YOU'VE ALREADY COME WITH THIS INTERIM REPORT. GLAD TO KNOW THERE'S GOING TO BE ADDITIONAL INPUTS AND DISCUSSIONS AND WE LOOK FORWARD TO HEARING IN JUNE HOW THIS HAS ALL EMERGED AND THE ACD WILL WANT TO SPEND A GOOD CHUNK OF OUR TIME IN JUNE ON DEBATING THIS AND DISCUSSING THIS BECAUSE THIS IS AN INCREDIBLY IMPORTANT FLAGSHIP PROJECT. THANKS, JIM, BY JOINING US BY PHONE. REALLY APPRECIATE WHAT YOU'RE DOING WITH THE NEUROETHICS PART OF THIS. OKAY. >> THANK YOU. >> WE'RE NOT SCHEDULE THE TO TAKE A BREAK BUT I SENSE THAT PEOPLE ARE FEELING A LITTLE UNCOMFORTABLE SO MAYBE WE'LL TAKE A 5 MINUTE BREAK JUST TO STRETCH YOUR LEGS OR WHATEVER AND THEN WE'LL COME BACK AND HEAR ABOUT THE DOWN SYNDROME INITIATIVE CALLED INCLUDE. WE ARE COMING BACK TO ORDER AND COMING DOWN THE HOME STRETCH BUT WE DO HAVE TWO MORE IMPORTANT THINGS TO PRESENT TO YOU IN THE ACD. AND THIS NEXT ONE IS ABOUT A PROJECT CALLED INCLUDE, WHICH STANDS FOR INVESTIGATION OF CO-OCCURRING CONDITIONS ACROSS THE LIFESPAN TO UNDERSTAND DOWN SYNDROME. THAT IS QUITE A STRETCH AS FAR AS AN ACRONYM BUT WE'RE GOING TO GO WITH IT BECAUSE WE LIKE THE WORD INCLUDE. LARRY IS GOING TO WALK YOU THROUGH THIS. ARE DIANA BIANCHI AND GARY GIBBONS SON THE PHONE? >> DIANA IS HERE FROM NEW YORK CITY. ARE >> GREAT. GARY, ARE YOU THERE? I THINK WE'RE EXPECTING HIM BUT MAYBE HE'S JUST A FEW MINUTES COMING -- >> HOPEFULLY -- WE'RE PINGING HIM AND HOPEFULLY HE'LL BE ABLE IT TO JOIN US. SO THANK YOU AND GOOD MORNING, EVERYBODY. SO THE TRY IT. I JUST GOT THE PRIVILEGE TO PRESENT THIS TO YOU BECAUSE NEITHER DIANA NOR GARY ARE HERE IN PERSON. THE FIRST SLIDE I'M GOING TO SHOW IS THE MOST IMPORTANT SLIDE OF THE PRESENTATION. IT WILL TELL YOU EVERYTHING YOU NEED TO KNOW ABOUT THIS PROJECT. EVERYTHING ELSE IS JUST DETAIL. SO PLEASE LISTEN CAREFULLY, AND PAY ATTENTION TO THIS FIRST SLIDE. >> ON A DEEPLY PERSONAL NOTE, I CANNOT TELL YOU HOW MUCH IT MEANS TO ME THAT MY CHROMOSOME MIGHT LEAD TO THE ANSWER TO ALZHEIMER'S. IT'S ONE THING THAT THIS -- ONE DAY STEAL MY MEMORIES, MY VERY LIFE FROM ME. THIS IS VERY HARD FOR ME TO SAY. BUT IT HAS ALREADY BEGUN TO STEAL MY MOM FROM ME. PLEASE, THINK ABOUT ALL THOSE PEOPLE YOU LOVE THE WAY I LOVE MY MOM. HELP US MAKE THIS DIFFERENCE. NOT FOR ME AND MY MOM, THEN FOR YOU AND THE ONES YOU LOVE. FUND THIS RESEARCH. >> SO I CAN'T DO BETTER THAN THAT. RIGHT? MR. STEVENS' TESTIMONY BEFORE THE HOUSE APPROPRIATIONS COMMITTEE I THINK SAID IT ALL. AND NOW I'LL GO THROUGH. SO DETAILS. I THINK MANY OF YOU KNOW THAT 6,000 INFANTS ARE BORN EACH YEAR WITH DOWN SYNDROME, AND BECAUSE OF ADVANCES IN OUR BETTER UNDERSTANDING, THE LIFESPAN FOR INDIVIDUALS WITH DOWN SYNDROME HAS DOUBLEED OVER THE PAST 25 YEARS SO IT IS NOW UNCOMMON TO SEE INDIVIDUALS, TO INTERACT WITH INDIVIDUALS IN THEIR 50s -- >> WE'RE CHECKING, GARY GIBBONS, DID YOU JUST JOIN US? GARY? >> SO IN 2018, THERE WAS LEGISLATION PROVIDED TO THE NIH TO DEVELOP A NEW TRANS-NIH INITIATIVE TO STUDY WITH THE YIELD OF AIMING SCIENTIFIC DISCOVERIES IT TO IMPROVE THE HEALTH AND NEURODEVELOPMENT OF INDIVIDUALS WITH DOWN SYNDROME AND TYPICAL INDIVIDUALS AT RISK FOR THIS WHOLE RANGE OF DISEASES AND CONDITIONS BECAUSE AS MR. STEPHENS' REMARKS IMPLIED, PEOPLE ARE DOWN SYNDROME ARE AT GREATER RISK FOR AN ALZHEIMER'S DISEASE-LIKE OUTCOME, BUT THEY ALSO ARE AT RISK FOR THESE OTHER CONDITIONS, BUT PARADOXICALLY THEY ARE ALSO PROTECTED FROM A NUMBER OF CANCERS AND FROM CERTAIN FORMS OF HEART DISEASE, AND SO MR. STEPHENS AND HIS FOLKS FROM THE DOWN SYNDROME COMMUNITY APPRECIATE THAT THEY HAVE THIS UNIQUE DOUBLE BENEFIT IN A SENSE IN THAT BY UNDERSTANDING DOWN SYNDROME, WE MAY BE ABLE TO HELP THEM WITH THE VARIOUS DISEASES AND CONDITIONS THAT THEY FACE, BUT WE MAY ALSO BE ABLE TO HELP OTHERS IF WE UNDERSTAND WHY THEY ARE RESILIENT IT TO OTHER DISEASES AND CONDITIONS. NOW THE NIH RESEARCH PLAN ON DOWN SYNDROME WAS UPDATE THE IN 2014. THE PRIORITY AREAS ARE ARTICULATED ON THE SLIDE SO I DON'T WANT TO LEAVE ANYBODY WITH THE IMPRESSION THAT UNTIL NOW WE HAVEN'T INVESTED IN DOWN SYNDROME RESEARCH, INDEED WE HAVE, AND IN MANY WAYS DIRECTIONSLY AMONG THESE FIVE PRIORITY AREAS. AND THERE HAVE BEEN A NUMBER OF RESOURCES FOR INDIVIDUALS WITH DOWN SYNDROME, SO BACK IN 2013, THE CHILD HEALTH INSTITUTE DID, IN FACT, LAUNCH DC CONNECT -- DS-CONNECT, WHICH IS A RESOURCE THAT CONNECTS PEOPLE WITH DOWN SYNDROME AND THEIR FAMILIES TO VARIOUS RESOURCES THAT THEY CAN USE TO HELP IMPROVE THE LIVES OF THEMSELVES OR THEIR LOVED ONE. OH OF COURSE THERE HAVE BEEN EXTENSIVE PARTNERSHIPS. NIH INSTITUTES AND CENTERS, THE SELF ADVOCATES AND THEN THE MANY ORGANIZATIONS THAT ARE LISTED HERE, AND THEY WERE CONVENED IN JULY AND NOVEMBER TO SPECIFICALLY ENGAGE IN THE INCLUDE PROJECT. SO JUST TO GIVE YOU A TIMELINE OF WHAT WE DID IN FISCAL YEAR '18, WE ESTABLISHED AN INCLUDE STEERING COMMITTEE. THIS IS VERY BOTTOM-UP. WE MAKE A CALL TO THE INSTITUTES AND CENTERS AND -- LOOK, WE HAVE THIS POTENTIAL OPPORTUNITY, WHO WOULD BEST REPRESENT THE UNIQUE EQUITIES THAT YOUR INSTITUTE OR CENTER HAVE THAT COULD BE BROUGHT TO BEAR ON THESE ISSUES. WE DEVELOPED A WORKING GROUP WHICH REPRESENTED SOME 13 NIH INSTITUTES. IN JUNE -- JUNE 20TH, THE PROJECT WAS FORMALLY ANNOUNCED BY CONGRESSIONAL OFFICES. WE CREATED A RESEARCH PLAN AND RELEASED FUNDING NOTICES IN COORDINATION WITH THAT. THIS WAS ON A RAPID PACE BECAUSE OF THE TIME IN THE FISCAL YEAR THAT THIS WAS POSITIONED, AND INDEED BY THE END OF THE FISCAL YEAR, THE VERY END OF THE FISCAL YEAR, WE WERE ABLE TO MAKE AWARDS AND IN NOVEMBER, A WORKSHOP WAS HELD AND WE ACTUALLY TOOK ADVANTAGE OF A WORKSHOP THAT HAD ALREADY BEEN SCHEDULED FOR ALZHEIME'S DISEASE AND ADD ADDITIONAL TIME SO THAT ALZHEIMER'S DISEASE CLINICAL TRIALS AND DOWN SYNDROME COULD BE DISCUSSED WITH THE PARTICIPANTS. SO AGAIN TO GIVE YOU A SENSE OF THE FUNDING, THE BASE FUNDING, IF YOU WILL, WAS BY 2017, ABOUT $35 MILLION ACROSS THE AGENCY, WITH THE ADDITION OF INCLUDE FUNDING, WE WERE ABLE TO GET THAT UP TO ROUGHLY 59 MILLION, AND OUR CHARGE GIVEN TO US BY FRANCIS WAS BASICALLY "LEAVE NO STONE UNTURNED." BECAUSE OF WHERE THINGS STARTED DURING THE FISCAL YEAR, OUR APPROACH WAS TO ACTIVELY SOLICIT A SUPPLEMENTS FOR THE FIRST YEAR, AND WITH THE NOTION THAT WE WOULD EXPAND EXISTING PROJECTS THAT WERE STUDYING DOWN SYNDROME OR, AS AN EQUALLY IMPORTANT OPTION, TO AMEND OR AUGMENT AN EXISTING PROJECT TO ADD A DOWN SYNDROME COMPONENT, BE IT BIOLOGICAL SAMPLES OR TRIAL PARTICIPANTS. WE THOUGHT THAT THAT LATTER STRATEGY WAS PARTICULARLY IMPORTANT BECAUSE IT BROUGHT A FRESH PERSPECTIVE TO THE DOWN SYNDROME RESEARCH COMMUNITY, AND IT ALSO BEGINS TO ADDRESS THE NEED TO INCLUDE, HENCE THE ACRONYM, INDIVIDUALS WITH DOWN SYNDROME INTO ONGOING CLINICAL RESEARCH BECAUSE AS YOU MIGHT IMAGINE, WHAT WORKS FOR SOMEONE WITHOUT DOWN SYNDROME MAY NOT WORK FOR SOMEBODY WITH DOWN SYNDROME. MAYBE IT WILL WORK BETTER. AND EITHER POSSIBILITY, OF COURSE, IS IMPORTANT TO LEARN. SO THE INCLUDE RESEARCH PLAN IS NOW LISTED ON A WEBSITE WHICH CAN NOW BE INTERROGATED, AND THE LINK IS SHOWN HERE. SO LET ME JUST BRIEFLY SKETCH THE RESEARCH PLAN FOR YOU. IT'S IN THE FORM OF THREE COMPONENTS THAT ARE INTERRELATED, OF COURSE. FIRST TARGETED HIGH RISK HIGH REWARD BASIC SCIENCE STUDIES ON CHROMOSOME 21 FOR OBVIOUS REASONS, SECONDLY, TO BUILD A LARGE COHORT OF INDIVIDUAL WITH DOWN SYNDROME TO ALLOW FOR AND AFFORD A COMPREHENSIVE BIOMARKER BIOMARKER, AND TO INCLUDE INDIVIDUALS WITH DOWN SYNDROME IN ONGOING AND FUTURE CLINICAL TRIALS. WE THINK THESE THREE COMPLEMENTARY APPROACHES REALLY DO COVER SIGNIFICANT PART OF THE NEEDED WORK. SO IN 2018, WE WERE ABLE TO SUPPORT SOME 49 AWARDS. IT WOUND UP THAT 14 NIH INSTITUTES PARTICIPATED, THE ACTUAL TITLES OF THE PROJECTS ARE LISTED AND YOU CAN INTERROGATE THE WEBSITE FOR THE SPECIFICS. INCLUDED IN THE AWARDS WAS AN A EXPECTATION OF FREE DATA SHARING, SO WE'RE BEGINNING TO BUILD THAT NASCENT COMMUNITY TO ENSURE MAXIMUM VALUE OUT OF EVERYTHING THAT COMES OUT OF THIS. AND SO JUST TO JUST GIVE YOU A BRIEF SENSE OF WHAT THE EMERGENT AREAS ARE AS A RESULT OF THIS, TO EXAMINE THE ROLES OF MULTIPLE GENES ON CHROMOSOME 21 SIMULTANEOUSLY, TO LOOK AT WHAT CHROMOSOME SILENCING IS ALL ABOUT, EVALUATE EPIGENETIC METABOLOMICS TRANSCRYPTOMIBG PROFILING IN BOTH PO DELL KORG NISMS AS WELL AS INDUCED PLURIPOTENT STEM CELLS AND TO BEGIN TO MAKE THE USE OF SOME BRAIN ORGANOIDS, JUST FAST FORWARD TO THE COMMENTS OF THE PREVIOUS DISCUSSION, AND THEN TRY TO DEVELOP NOVEL MODEL SYSTEMS INCLUDING A MOLECULAR A ATLAS FOR CARDIAC TISSUES BECAUSE OF THE PREVALENCE OF CERTAIN FORMS OF HEART DEFECT. IN ALL OF THIS, THERE WAS AN EMPHASIS ON STUDIES THAT CAN INFORM THE OTHER TWO COMPONENTS SO WE KEEP THIS AS COHESIVE AS POSSIBLE WITH THE ULTIMATE GOAL OF UPPING THE POTENTIAL FOR CLINICAL TRANSLATION. SO THESE ARE JUST A FEW EXAMPLES OF THE ACTUAL PROPOSALS. I WON'T READ THROUGH THESE, BUT I THINK JUST BY PERUSING THE TITLE, YOU GET A SENSE OF WHAT THE TYPE OF WORK WAS INCLUDED. AGAIN JUST TO CONTINUE WITH SOME OF THOSE TITLES. SO COMPONENT TWO, HERE WE'RE TRYING TO ASSEMBLE LARGE COHORTS FOR THE SORT OF PAN OMICS APPROACH AND BIOMARKER STUDIES, AND WE WERE ABLE TO TAKE REALLY A VERY GOOD ADVANTAGE OF A NUMBER OF EXTANT COHORTS AND SOME OF THEM ARE LISTED HERE, INCLUDING THE GA BREE ELLA MILLER/KIDS FIRST STUDIES, TWO OF THEM, THE ALZHEIMER'S BIOMARKERS CONSORTIUM, THE EUNICE KENNEDY SHRIVER INTELLECTUAL AND DEVELOPMENTAL DISABILITIES RESEARCH CENTER AT AT VANDERBILT, AND CLINICAL EVALUATION OF PULMONARY HYPERTENSION IN DOWN SYNDROME, WHICH WOULD EX- EXPAND -- IT'S A PEDIATRIC COHORT THAT WOULD EXPAND TO DOWN SYNDROME. SO AGAIN, IN IN COULDING ALL OF THIS, THE EMPHASIS WAS TO BUILD COHORTS THAT EXPAND ACROSS THE LIFESPAN TO ADDRESS KEY HEALTH AND QUALITY OF LIFE ISSUES. WE WERE FORTUNATE TO BE ABLE TO STITCH MANY OF THESE TOGETHER FOR THIS PURPOSE. NOW, AGAIN, COMPONENT THREE IS THE EMPHASIS ON BUILDING CLINICAL RESEARCH RESOURCES TO ACHIEVE FULL INCLUSION OF INDIVIDUALS WITH DOWN SYNDROME NOW AND IN THE FUTURE IN CLINICAL TRIALS. THE RATIONALE IS OUTLINED HERE. THERE'S EXTREMELY LIMITED MEDICATION TRIALS IN DOWN SYNDROME, THEY'VE BEEN UNDERPOWERED, THEY LACK EFFICACY, AND SIMPLY PUT, WE NEED TO UNDERSTAND HOW COMMONLY USED MEDICATIONS AFFECT PEOPLE WITH DOWN SYNDROME AND WE NEED TO DEVELOP APPROPRIATE CLINICAL MEASURES. FOR INDIVIDUALS WITH DOWN SYNDROME. THIS WORKSHOP, ALZHEIMER'S DISEASE AS YOU MIGHT IMAGINE AGAIN LINKING BACK TO MR. STEPHANES' CONCEPTS, ALZHEIMER'S DISEASE IS A MAJOR CONCERN AMONG MEMBERS OF THIS COMMUNITY. THIS MEETING WAS HELD COORDINATED BY NICHD AND NIA. BOTH ADVOCACY COMMUNITIES PARTICIPATED. IT WAS PRETTY POWERFUL TO GET THESE TWO GROUPS TOGETHER. AND OF COURSE INVESTIGATORS ENGAGE IN CLINICAL STUDIES AND COHORT STUDIES FOR EITHER AND/OR BOTH GROUPS WERE PRESENT AND ACTIVELY ENGAGED IN THE CONVERSATION. SO THESE ARE JUST A FEW EXAMPLES OF HOW THIS IS GOING FORWARD. AND AGAIN, YOU CAN READ THEM QUICKLY THAN I CAN SAY THEM, BUT IT JUST DOES GIVE YOU A SENSE OF THE TYPES OF THINGS THAT WE'RE TRYING TO ACCOMPLISH, BOTH WITHIN ALZHEIMER'S DISEASE AND SO, FOR EXAMPLE, PETE TRICK PEDIATRIC TRIA L IN SLEEP APNEA, AT ALL LEVELS OF THE LIFESPAN. SO 2019 SUPPORT AND BEYOND, WE ARE WORKING FEVERISHLY, ALTHOUGH ANNA WOULD SAY NOT FEVERISHLY ENOUGH TO ME, PERSONALLY, BUT NOW WE'RE GOING TO DO THIS, TURN OUR ATTENTION TO IT, FOR THE FOAS TO BE RELEASED. WORKSHOPS ARE IN DEVELOPMENT FOR EARLY CALENDAR YEAR 2019 TO PLAN A VIRTUAL DOWN SYNDROME COHORT ACROSS THE LIFESPAN, AND THEN A STATE OF THE SCIENCE FOR MEANINGFUL CLINICAL TRIALS IN DOWN SYNDROME. SO AGAIN, THOSE OF YOU WHO ARE INTERESTED OR IF YOU HAVE COLLEAGUES WHO ARE INTERESTED, WE WOULD CERTAINLY ASK YOU TO DRAW THEIR ATTENTION OR DRAW YOUR ATTENTION TO THE WEBSITE AND INTERROGATE IT OFTEN BECAUSE AS ADDITIONAL INFORMATION IS AVAILABLE, OF COURSE WE UPDATE THAT. SO THIS IS GROUP OF AMAZING PEOPLE FROM ACROSS NIH WHO HAVE BEEN DOING ALL THE HARD WORK, AND AGAIN, GREAT THANKS TO ANNA WHO IS HERE, AND DRS. BIANCHI AND GIBBONS, AND WITH THAT, I'M GOING TO TURN IT TO THE GROUP, AND DIANA AND GARY, IF HE'S ON THE PHONE, HAVE PROMISED TO FIELD ALL THE QUESTIONS. SO I'LL GO BACK TO MY PLACE NOW. >> JUST CHECKING AGAIN WHETHER GARY GIBBONS WAS ABLE TO CALL IN. >> YEAH, I'M ON, FRANCIS. >> GREAT. AND DIANA, ARE YOU STILL THERE? UH-OH. I HEARD -- THAT WAS ONE OF THOSE MOMENTS WHERE SHE REACHED FOR THE MUTE BUTTON AND HIT THE OTHER ONE? I'VE DONE THAT A LOT. SO PRESUMABLY DIANA WILL BE BACK SHORTLY. MEANWHILE GARY WILL ANSWER ALL THE QUESTIONS. DO YOU ALL HAVE THINGS YOU WOULD LIKE TO DISCUSS HERE? >> DID YOU HEAR THAT, GARY? YOU'RE IT. >> THE PLANES AND TRAINS ARE CALLING. >> OH, NO, IT WAS A PERFECTLY CLEAR PRESENTATION. >> THAT COULD BE TOO. AS YOU ARE FAMOUS FOR JOSE. >> I HAVE A SISTER WITH DOWN SYNDROME AND I'M SO EXCITE THE TO SEE THIS HAPPEN, IT'S REALLY VERY MOVING. FROM POINT OF VIEW OF -- >> HI, SORRY. I WAS ON, I GOT CUT OFF FOR SOME REASON. >> OKAY, GLAD YOU'RE BACK. WE'RE JUST STARTING THE DISCUSSION, DIANA. JOSE HAS GOT THE FLOOR. >> I SAW YOU HAD -- WITH THE OTHER ORGANIZATIONS THAT HAVE BEEN SORT OF INVOLVED. WHAT IS THE EXTENT OF THEIR ENGAGEMENT INCLUDING SELF ADVOCATES ON THE STEERING OF AT LEAST THE PUBLIC PROJECTION OF THE INITIATIVE? >> DIANA, WOULD YOU LIKE TO FIELD THAT AND THEN MAYBE GARY WOULD HAVE SOMETHING TO ADD AS WELL? >> SURE. SO THE MULTIPLE ORGANIZATIONS HAVE ACTUALLY BEEN INVOLVED VIA THE DOWN SYNDROME CONSORTIUM FOR MANY YEARS. THERE ARE MEMBERS OF NICHD AND OTHER INSTITUTES WHO PRESENT RESEARCH THAT'S GOING ON IN DOWN SYNDROME TO THESE ORGANIZATIONS AT VARIOUS SCIENTIFIC MEETINGS THROUGHOUT THE YEAR. SO THESE ORGANIZATIONS HAVE BEEN CONTINUOUSLY UPDATED WITH REGARD TO THE PLANS AND THE PROGRESS FOR THE INCLUDE PROJECT. >> AND THE ROLE OF SELF ADVOCATES? >> INCLUDING SELF ADVOCATES. >> WE MET WITH A GROUP OF SELF ADVOCATES TO REALLY DISCUSS THE PROJECTS AND, YOU KNOW, THEIR PERSPECTIVE IS SO CRUCIAL TO ALL OF THIS, AND I WOULD SAY THAT IT'S A DIMENSION THAT OCCASIONALLY YOU WANT TO OVERLOOK THE PERSON IN THE ROOM WHO'S AFFLICTED, SO I WOULD SAY THEY HAVE BEEN FRONT AND CENTER, AND UNBELIEVABLY SUPPORTIVE. I MEAN -- >> AND WE'VE ALSO LEARNED FROM, I WOULD SAY, NOT SO GREAT EXAMPLE THAT HAVE PRECEDED US. SO FOR EXAMPLE, SOME OF THE CLINICAL TRIALS THAT HAVE BEEN PERFORMED BY INDUSTRY, WE'VE HEARD FROM ADVOCATES AND THEIR FAMILIES THAT THESE TRIALS WERE SHUT DOWN AND FAMILIES FOUND OUT ABOUT THIS BY FACEBOOK OR OTHER SOCIAL MEDIA. I MEAN, THERE WAS NO DIRECT CONTACT BETWEEN THE PRINCIPAL INVESTIGATORS AND SUBJECTS ENROLLED IN THIS VERY IMPORTANT RESEARCH, SO THAT IS SOMETHING THAT WE WILL DEFINITELY NOT THE DO, AND WE WILL CERTAINLY ENCOURAGE OUR GRANTEES TO KEEP THESE THINGS IN MIND. >> BRENDAN. >> HI, DIANA. THIS IS BRENDAN. IT'S AN OPERATIONAL QUESTION. YESTERDAY I GAVE AN INTERIM REPORT FROM THE HRHR WORK GROUP, AND I NOTICED THAT THE FIRST PHASE OF THE PROGRAM IS FOCUSED ON HIGH RISK, HIGH REWARD. I WAS WONDERING, FIRST MAYBE WHAT WAS THE MECHANISM OF REVIEW? ONE OF THE SORT OF INTERIM RIMTIONS FROM THE WORK GROOM WAS PERHAPS THE PROGRAM CLEARLY WORKS SO WHETHER ONE WOULD ACTUALLY RECOMMEND EXTENDING THE FORMAT, THE REVIEW MECHANISM, THE FORMATS OF THE APPLICATIONS TO OTHER PROGRAMS WITHIN NIH, AND I WAS WONDERING WHETHER YOU IT CONSIDERED THAT AS A STRATEGY. >> YEAH, SO -- GO AHEAD. >> NO, PLEASE, GO AHEAD. >> NO, I THINK THE USE OF THE TERM HIGH RISK/HIGH REWARD, REALLY WHAT WE HAD IN MIND WITH THE AIM ONE, THE AIMS ARE ALL GOING ON IN PARALLEL. IT'S NOT LIKE ONE LEADS TO TWO WHICH LEADS TO THREE. BUT WITH AIM ONE, WE WERE LOOKING AT THINGS THAT WERE LIKELY TO TRANSLATE TO CLINICAL STUDIES WITHIN THE NEXT FIVE YEARS. WE DID HEAR FROM THE COMMUNITY THAT THEY REALLY WANTED RESEARCH THAT WOULD IMPROVE THE OVERALL QUALITY OF LIFE FOR PEOPLE WITH DOWN SYNDROME. SO ACTUALLY IN THE MIX OF THE SUPPLEMENTS THAT WE FOUNDED IN FISCAL YEAR '18, WE INCLUDED THINGS LIKE IMPROVING EYEGLASS PRESCRIPTIONS, RESEARCH LOOKING AT HOW YOU EVALUATE THE EFFICACY OF EYEGLASS PRESCRIPTIONS FOR PEOPLE WHO HAVE DOWN SYNDROME. SO THERE WERE SOME THINGS THAT WERE VERY PRACTICAL LIKE THAT AS WELL AS MORE BASIC SCIENCE RESEARCH. AND PLEASE CORRECT ME, LARRY, BUT MY UNDERSTANDING IS THAT THE FOAs WERE DISCUSSED YESTERDAY OR EARLIER THIS WEEK, AND THE SPECIFIC MECHANISMS HAVE NOT YET BEEN WORKED OUT FOR EVALUATING THE PROPOSAL IN FISCAL YEAR '19, BUT MAYBE THAT'S A GOOD SEGUE TO LARRY. >> THANKS, DIANA. SO FISCAL YEAR '18, BECAUSE OF WHERE WE WERE IN THE FISCAL YEAR YEAR, WE WERE REALLY LIMITED WITH SUPPLEMENTS. BUT AS DIANA CORRECTLY REPORTS, THE FOA POSSIBILITIES ARE HAVE NOW BEEN DISCUSSED AND AS PART OF IT, CAN WE FIND THE VERY BEST MECHANISM, GET THE TYPE OF RESULT THAT WE'RE LOOKING FOR, AND US A RIGHTLY POINT OUT UNDER PARTICULARLY THE BASIC SCIENCE GROUP, THERE MIGHT BE SOME LESSONS LEARNED AS YOU WELL KNOW HAVING CO-CHAIRED THIS HR/HR GROUP, THAT WE COULD APPLY TO THE EFFORTS IN THIS TOPIC. AND SO THAT WILL BE SOMETHING WE'LL LOOK AT FOR SURE. >> ROY. >> YOU KNOW, SOME OF THESE MEMBERS OF THE DOWN SYNDROME CONSORTIUM FUND A LOT OF RESEARCH THEMSELVES LIKE THE GLOBAL DOWN SYNDROME. HAS THERE BEEN ANY ATTEMPT TO COORDINATE WITH ANY OF THIS TO MAKE SURE THAT THE RESEARCH THAT'S BEING DONE IS COMPLEMENTARY AND ADDITIVE AS OPPOSED TO DUPLICATIVE? >> DIANA, I'LL ASK THAT YOU START. >> OKAY. SO GLOBAL HAVE BEEN INCREDIBLE ADVOCATES ON BEHALF OF PEOPLE WITH DOWN SYNDROME. IF YOU LOOK AT OUR HOUSE APPROPRIATIONS TESTIMONY IN APRIL, YOU CAN BEHIND MY BACK ARE TH PEOPLE FROM GLOBAL. THEY'RE VERY PRESENT ON CAPITOL HILL, AND WE'VE ALSO HAD THEM LITERALLY IN THE ROOM WITH US AS WE'VE DISCUSSED PLANS THAT INCLUDE NIH, SO SPECIFICALLY IN& THE OFFICE OF THE DIRECTOR'S CONFERENCE ROOM, WE HAD A MEETING WITH GLOBAL ON HOW WE CAN COORDINATE OUR EFFORTS. IT'S A LITTLE BIT COMPLICATED BECAUSE SOME OF THE PEOPLE THAT THEY SUPPORT ARE ALSO APPLYING FOR FEDERAL FUNDING, SO WE WANT TO WORK WITH THEM BUT WE ALSO HAVE TO BE AWARE OF CONFLICT OF INTEREST ISSUES. >> JUST TO ADD, BECAUSE THE VARIOUS STAKEHOLDER GROUPS AND ADVOCACY GROUPS, PROFESSIONAL GROUPS ARE SO ENGAGED IN THIS, THERE IS AN UNUSUALLY HIGH LEVEL OF CONVERSATION GOING ON. I THINK WE WILL BE ABLE TO MAXIMIZE THE VARIOUS RESOURCES THAT ARE BEING BROUGHT TO BEAR. >> I WOULD ALSO ADD THAT EVEN THOUGH THERE'S NONE OF THE ORGANIZATIONS REPRESENTED HERE IN TERMS OF THOSE THAT FUND US IN THE RESEARCH, VERY FEW WITH NOT A WHOLE LOT OF MONEY, GLOBAL MAY BE THE EXCEPTION. THE LE JEUNE FOUNDATION HAS SOME MONEY, BUT OTHERS HAVE NO MONEY TO FUND RESEARCH. >> I WAS THINKING OF GLOBAL SPECIFICALLY. I USED TO BE ON THEIR BOARD AND I KNOW THEM VERY WELL. >> I THINK IT'S IMPORTANT TO RECOGNIZE THAT THERE ARE 300 THOWN THOU PEOPLE IN 300,000 PEOPLE IN THE UNITED STATES WITH DOWN SYNDROME SO THIS IS A SIGNIFICANT POPULATION OF PEOPLE WHO HAVE HEALTH NEEDS THAT WE NEED TO ADDRESS, AND THE REAL BRILLIANCE OF THIS PROJECT, I THINK, IS THAT IT REALLY WAS MR. STEVENS WHO DROVE HOME THE POINT THAT WE CANNOT ONLY IMPROVE HIS HEALTH BUT WE CAN LEARN FROM THE UNUSUAL ASPECTS OF DOWN SYNDROME TO IMPROVE THE HEALTH OF ALL PEOPLE. AND THAT'S REALLY THE OVERALL GOAL OF THE PROJECT. >> DO YOU HAVE ANY SENSE OF THE REPRESENTATION OF DOWN SYNDROME IN THE ALL-OF-US RESEARCH PROGRAM AND WHETHER THERE' AN OPPORTUNITY THERE GIVEN THE KINDS OF DEEP MOLECULAR AS WELL AS PHENOTYPIC INFORMATION THAT ARE BEING COLLECTED TO LEVERAGE THAT? >> SO AS FAR AS I KNOW, THERE ISN'T A SPECIFIC CALLOUT FOR DOWN SYNDROME, BUT BECAUSE PEOPLE WITH INTELLECTUAL AND DEVELOPMENTAL DISABILITIES ARE VERY MUCH INCLUDED IN THE NICHD PORTFOLIO, WE HAVE BEEN ADVOCATING WITH REGARD IT TO ALL-OF-US FOR INCLUSION OF PEOPLE WITH INTELLECTUAL DISABILITIES THE AS WELL AS PREGNANT WOMEN AND CHILDREN. SO THEY'RE VERY MUCH ON OUR MIND BUT WE HAVEN'T SPECIFICALLY SEPARATED DOWN SYNDROME AS A POPULATION. >> AND AS YOU KNOW, JEFF, IT IS A LONGITUDINAL COHORT STUDY THAT AIMS TO TRY TO BE MOSTLY REPRESENTATIVE OF THE POPULATION, WE'VE TRIED NOT TO HAVE SPECIFIC AREAS OF SPECIFIC DISEASE CALLOUTS, ALTHOUGH THERE'S A POSSIBILITY THERE FOR ADDING THOSE AS SORT OF EXTRA SORT OF SPOKES TO THE HUB, BUT CERTAINLY JUST GIVING THE POPULATION PARTICULARS, IF YOU HAVE A MILLION PEOPLE AND YOU'RE DOING A GOOD JOB OF RECRUITING PEOPLE FROM ALL BACKGROUND, INCLUDING THOSE WITH DISABILITIES, WE SHOULD HAVE QUITE A NUMBER. >> I WAS GOING TO SAY THAT THE ENTRY INTO THE STUDY IS EQUALLY EASY FOR PEOPLE, AND I WOULD SAY PEOPLE WITH INTELLECTUAL DISABILITIES, BECAUSE OF THE EXTRA CONSENT OR ASSENT THAT NEEDS TO TAKE PLACE OR SO ON, IT'S DIFFICULT, AND THE A REAL DANGER DAING IF NOTHING IS DONE, THERE WILL BE AN UNDERREPRESENTATION. >> I CAN ASSURE YOU THE LEADERSHIP OF THE ALL-OF-US PROGRAM IS DEEPLY CONCERNED ABOUT NOT MAKING THE MISTAKE OF MAKE MISTING DISABLED INDIVIDUALS BECAUSE IT WILL BE MORE COMPLICATED. YOU'RE RIGHT, IT WILL BE BUT THAT'S A BIG DISCUSSION AND AN OUTREACH THAT'S ALREADY BEGUN. I CAN'T TELL YOU OF THE FIRST 150,000 THAT HAVE ALREADY BEEN ENROLLED, HOW SUCCESSFUL THEY HAVE BEEN, BUT I CAN FIND OUT. >> THE OTHER THING I WOULD SAY IS, IN THE FUNDING DECISION, BECAUSE WE HAD MANY MORE PROJECTS TO CONSIDER FUNDING THAN WE HAD MONEY FOR, WE DID PRIORITIZE SOME BIG TICKET ITEMS THAT WOULD RESULT IN, FOR EXAMPLE, SEQUENCING RESOURCES AND SEQUENCING DATA FLOORNLG COHORTS THAT WERE LOOKING AT DOWN SYNDROME AND CONGENITAL HEART DISEASE FOR EXAMPLE OR DOWN SYNDROME AND TUMORS. THOSE RESOURCES WILL BE MADE PUBLICLY AVAILABLE FOR ALL. >> SO MAYBE GARY SINCE SOME OF THOSE COHORTS COME FROM THE WORLD OF NHLBI, MAYBE IF YOU CAN JUST ELABORATE A BIT ON THAT BECAUSE I THINK JEFF'S CONCERNS ARE, YOU KNOW, GOOD ONES, BUT MAYBE YOU CAN SPEAK TO THOSE. >> SURE, LARRY. I APPRECIATE JEFF'S COMMENTS. THINK ONE OF THE THINGS AT LEAST I'VE GLEANED FROM THIS PROCESS IS THE CONNECTIVITY ACROSS NIH, LET ALONE SOME OF THE OTHER STAKEHOLDERS, THAT HAVE DIFFERENT DEEPLY PHENOTYPED COHORTS. I THINK ONE OF OUR GREATEST OPPORTUNITIES THAT THIS GIVES US IMPETUS ON IS TO ACTUALLY CREATE GREATER CONNECTIVITY AND COHERENCE TO THE NIH ENTERPRISE WIDE EFFORTS TOFEE TYPE ANDPHENOTYPE AND HARMONIZE DATASETS THAT ARE OFTEN SILOED AMONGST CARDIOVASCULAR TYPES OR PEDIATRIC VERSUS ADULT, AND REALLY CREATE THAT KIND OF CONNECTIVITY AND SYNTHESIS OF COHORTS. SO I THINK THAT WOULD CERTAINLY COMPLEMENT AN ALL-OF-US STRATEGY, BUT I THINK THE OPPORTUNITY HERE IS TO GET MUCH DEEPER PHENOTYPING AND BROADEN OUT FOR THIS SYNDROME THAT HAS SO MANY ELEMENTS. THAT'S, I THINK, THE GREAT OPPORTUNITY. >> THANKS, GARY. THANK ALL OF YOU FOR INPUT. I WANTED YOU TO KNOW ABOUT THIS PROGRAM BECAUSE IT'S COMING UP QUITE QUICKLY AND I THINK HAS A VERY COMPELLING MOTIVATION BEHIND IT. WE'LL KEEP YOU POSTED. THE LAST ITEM ON OUR ACD AGENDA FOR THIS MEETING IS TO HEAR ABOUT A NEW WORKING GROUP BECAUSE WE DIDN'T HAVE ENOUGH, AND WE HAD TO HAVE MORE GETTING GENERATED, AND ONCE AGAIN, LARRY TABAK, WHO SEEMS IT TO LIFT MOST OF THE HEAVY ITEMS AROUND HERE, IS GOING TO TELL YOU ABOUT A PLAN TO PUT TOGETHER A WORKING GROUP ON ARTIFICIAL INTELLIGENCE AND ITS APPLICATIONS TO BIOMEDICINE. >> WELL, YOU MIGHT WONDER HOW I GOT TAPPED FOR THIS SO I'M GOING TO SHARE WITH YOU THE REASONS WHY. I'M AT A POINT IN MY CAREER NOW WHERE NOW PEOPLE WANT TO KNOW ABOUT MY CAREER PATH AND HOW I GOT TO WHERE I AM AND ALL THIS KIND OF STUFF. I GUESS I'M SUPPOSED TO BE PHILOSOPHICAL AND I TELL EVERYBODY, BECAUSE I'M USUALLY SPEAKING TO REALLY, REALLY SMART YOUNG PEOPLE, WHO ARE ALWAYS ACCUSTOMED TO BEING THE SMARTEST PERSON IN THE ROOM. I TELL THEM LOOK, YOU DON'T HAVE TO BE THE SMARTEST PERSON IN THE ROOM TO SUCCEED GOING FORWARD. YOU JUST HAVE TO BE ALWAYS IN A ROOM WITH SMART PEOPLE. OKAY. WELL HERE IT IS. THIS IS THE GROUP, OKAY, THAT UNDERSCORES THIS. BY WAY OF BACKGROUND, ACTUALLY WE DON'T EVEN NEED TO DO THE BACKGROUND BECAUSE IN THE LAST TWO DAYS, ARTIFICIAL INTELLIGENCE, DEEP LEARNING, MACHINE LEARNING HAS BEEN MENTIONED LIKE ABOUT A HUNDRED 50 TIMES. BUT OKAY. AND INSTEAD OF GOING THROUGH THIS LOVELY PICK TOE GRAPH, SOME OF YOU, NOT ALL, MOST OF YOU ARE NOT OLD ENOUGH TO REMEMBER THE MOVIE "THE GRADUATE." BUT THERE'S THIS FAMOUSSCENE IN THAT MOVIE SOMEBODY ASKED DUSTIN HOFFMAN, WHAT'S THE GREATEST NEW THING IN THE FUTURE, AND OF COURSE THE ANSWER IS "PLASTICS." OKAY. WELL, THE NEW ANSWER IS "A.I.." AND THAT BRINGS US TO PRESENT DAY. AND I DON'T THINK ANYBODY HERE NEEDS TO BE CONVINCED OF THAT. BUT IT IS, I THINK, ABSOLUTELY TRUE THAT BIOMEDICAL RESEARCH IS ALREADY BEING REVOLUTIONIZEED BY THESE APPROACHES, AND AS WE HURDLE FORWARD, IT'S ONLY GOING TO ACCELERATE. AND WE'VE GOT TO BE BETTER PREPARED TO DEAL WITH THIS. THIS IS WHERE FRANCIS AND OTHERS WERE PROUDLY SHOW THEIR DEVICES THAT THEY WEAR. I DON'T KNOW HOW MANY OF YOU WEAR THESE FIT BITS OR OTHER DEVICES OF THIS TYPE, WE GENERAL THIS DATA. ACTUALLY THIS TELLS ME HOW MANY STEPS I WALK EVERY DAY AND HOW MANY FLIGHTS OF STAIRS I WALK, AND HOW MANY I SHOULD BE WALKING THAT I'M NOT AND SO FORTH. WELL, HOW DO WE DEAL WITH ALL OF THIS? AND HOW DO WE MAKE BEST USE OF ALL OF THIS? BECAUSE EVERY ONE OF THESE POTENTIAL INPUTS IN THE SO-CALLED WEARABLE TECHNOLOGY SPACE COULD BE INVALUABLE. YOU KNOW, GOING FORWARD. SO I GUESS IT'S NOW ABOUT NINE YEARS AGO, I HAD A CHANCE TO SPEAK TO THE PROVOSTS OF VARIOUS COMPONENTS OF THE UNIVERSITY OF CALIFORNIA SYSTEM, AND I WAS SORT OF ASKED TO BLUE SKY ABOUT THE FUTURE, NOT QUITE A DECADE AGO. AND I TALKED ABOUT BIG DATA. BECAUSE IT SOUNDED GOOD, RIGHT? SO I TALKED ABOUT BIG DATA. THEY ALL CHUCKLED, THEY ACTUALLY LAUGHED. I WAS VERY UNNERVED ABOUT THIS. UNTIL THEY EXPLAINED THEY WERE ALL IN ASTRONOMY OR ASTROPHYSICS. TO THEM, BIOMEDICINE HAS NOTHING RELATED TO BIG DATA RELATIVE TO THEIR DISCIPLINES. THAT WAS NINE YEARS AGO. IF YOU FAST FORWARD TODAY, WE'RE DOUBLING THE AMOUNT OF BIOLOGICAL DATA EVERY 10 MONTHS, AND OF COURSE IT COMES IN ALL FLAVORS AS YOU MIGHT IMAGINE. IMAGING, PHENOTYPIC ANALYSIS, EXPOSOME, HEALTH, BEHAVIORAL, ANYTHING THAT YOU CAN THINK OF, IT IS JUST CONTINUING TO POUR FORTH. AND AS YOU HEARD A LITTLE BIT THE IN THE PREVIOUS DISCUSSION OF THE BRAIN INITIATIVE, HOWEVER NASCENT IT IS, TREMENDOUS AMOUNTS OF INFORMATION, HOW DO WE BEST ORGANIZE IT, HOW DO WE MAKE SURE THAT WE KNOW WHERE IT IS, DO WE HAVE THE TOOLS TO INTERROGATE IT, AND DO WE HAVE ENOUGH PEOPLE WHO HAVE THE REQUISITE TRAINING TO BE ABLE TO MAKE THE MAXIMAL BENEFIT. AND SO RIGHT NOW WE REALLY NEED TO IMPORT AS MANY TALL TALENTED PEOPLE WHO ARE FACILE IN THESE APPROACHES TO OUR PROBLEMS IN BIOLOGICAL SCIENCES, BUT GOING FORWARD, WE NEED TO THINK LONG AND HARD ABOUT IS THAT THE BEST MODEL, CAN WE COMPLEMENT IT WITH TRAINING SOME PEOPLE WHO ARE ALSO, YOU KNOW, COGNIZANT OF BIOLOGY. THE OPPORTUNITIES ARE ENDLESS AND YOU COULD THINK OF 20 MORE, I MEAN, WE'VE JUST LISTED A FEW HERE. SO LIT ME JUST GIVE YOU LET ME JUST GIVE Y OU A SENSE OF DATA SCIENCE AT NIH. SO OUR CENTER FOR INFORMATION TECHNOLOGY SUPPORTS 100 GIGABIT NETWORK. WE MOVE 4 PETABYTES OF DATA EVERY DAY. WE HAVE MANY, MANY DATASETS, SO FOR EXAMPLE, WE'VE GOT 15 PET PETABYTES OF GENOMIC SEQUENCE DATA, THE LARGEST DATASETS ARE LISTED ON THE RIGHT HERE, AND THESE WILL JUST KEEP GROWING. AND SO I THINK EVERYBODY WOULD AGREE EVEN ASTROPHYSICISTS THAT BIG DATA HAS ARRIVED IN BIOLOGICAL SCIENCES. IF ANY OF YOU THINK THAT YOU ARE NOT ENGAGED IN USING ARTIFICIAL INTELLIGENCE DURING YOUR NORMAL LIFE, THINK AGAIN. BECAUSE IF YOU DO ANY OF THESE THINGS, INCLUDING FIGURING OUT HOW TO GET HOME FROM FRANCIS' HOME LAST NIGHT, THANK YOU, WAZE, THERE ARE ALL THESE DIFFERENT APPROACHES. AND SOMEBODY WAS TELLING ME YESTERDAY THAT THEIR DOT THING SPEAKS TO THEIR TOWER THING. IT'S A LITTLE SCARY, BUT THAT -- YOU KNOW, WHICH IS GOOD. SO ANYWAY, IT'S UBIQUITOUS AND WE NEED TO FIGURE OUT BETTER WAYS OF UNDERSTANDING AND TAKING ADVANTAGE OF THESE POWERFUL, POWERFUL TOOLS. SO THIS IS HERE FOR ME, YOU ALL KNOW THIS STUFF, BUT I NEED THIS AS A CRUTCH. SO THE LARGE FIELD OF ARTIFICIAL INTELLIGENCE DESCRIBES PROGRAMS THAT CAN EITHER SENSE OR REASON, ACT OR ADAPT, SUPER ORDINATE TO THAT IS MACHINE LEARNING WHERE YOU HAVE ALGORITHMS THAT HAVE PERFORMANCE IMPROVEMENT AS THEY'RE EXPOSED TO MORE DATA, AND THEN THERE'S THE SUBSET OF MACHINE LEARNING CALLED DEEP LEARNING IN WHICH MULTI-LAYERED NEURAL NETWORKS LEARN FROM JUST VAST AMOUNTS OF DATA. AND AGAIN, ALL OF THESE THINGS, EACH AND EVERY ONE OF THESE, ARE IMPORTANT FOR BIOMEDICAL RESEARCH TO EMBRACE, UNDERSTAND BETTER AND TAKE ADVANTAGE OF BETTER. SO HOW IS IT BEING USED NOW? THERE ARE A MYRIAD OF CLINICAL APPLICATIONS ALREADY BEING USEED, SO PATHOLOGY DIAGNOSIS, IT'S QUITE REMARKABLE HOW TALENTED THESE VARIOUS ALGORITHMS HAVE BECOME. DERMATOLOGICAL EXAMINATION OF LESIONS, OPHTHALMOLOGY. ROYAL WILL TELL USROY WILL TELL US WHERE W E ARE. RADIOLOGISTS, I DON'T KNOW IF THEY'RE AN ENDANGERED SPECIES NOW, BUT THE PROGRAMS ARE NOW BEING USEED ARE QUITE REMARKABLE, TREATMENT OPTIONS LIKE CANCER ARE BEING CONVOLUTED BY THESE APPROACHES, ROBOTIC SURGERIES, AND THEN, OF COURSE, ELECTRONIC HEALTH RECORDS NEED SOME HELP IN NATURAL LANGUAGE PROCESSING APPARENTLY IS ONE WAY THAT THIS IS BEING ACCOMPLISHED, AND THEN, OF COURSE, IN THE AREA THAT I'M A LITTLE MORE COMFORTABLE WITH TERMS OF BASIC SCIENCE, ALL SORTS OF IMAGE ANALYTICS, CRYO-EM, YOU KNOW, WHICH IS REVOLUTIONIZING STRUCTURAL BIOLOGY, CON FOCAL MICROSCOPY, WHICH IS NOT A AT ALL LIKE THE CONFOCAL MICROSCOPY I KNEW WHEN I WAS IN ACADEMIA, SOPHISTICATION IS SPECTACULAR. WE HEARD SO MUCH ABOUT THE BRAIN INITIATIVES PREVIOUSLY. WE HAVE, SIGNATURE AROUND THE TABLE, PEOPLE WHO CAN TELL US MUCH ABOUT GENOMICS, SO I WON'T EVEN TRY. THE MICROBIOME WHICH, BY THE WAY, DENTISTS KNEW ABOUT A LONG, LONG TIME AGO, A GUY TALKED ABOUT PLAQUE ON TEETH, BUT THAT'S JUST AN ASIDE. BUT OBVIOUSLY, THESE TECHNOLOGIES HAVE REALLY REVOLUTIONIZED HOW WE CAN LOOK AND ANALYZE THESE THINGS AND EPIGENOMICS AS WELL AND BEYOND. I'M JUST LISTING THINGS THAT ARE OBVIOUS. WE WERE VERY FORTUNATE TO HAVE A WORKSHOP HERE. JESS WHO IS HERE HELPED ENORMOUSLY WITH SETTING THIS UP TO REALLY INVITE MANY TALENTED EXPERTS ARE IN THIS SPACE TO NIH. THE WORK SHOP -- IT'S TOO BAD WE COULDN'T SELL TICKETS BECAUSE WE ACTUALLY COULD HAVE FUNDED A LOT OF RESEARCH IF THEY WOULD ALLOW US TO DO THAT, BUT WE'RE NOT ALLOWED TO DO THAT. BUT THIS THING SOLD OUT IN THE SENSE OF BEING SUBSCRIBED OF 10 MINUTES -- >> LIKE A YOUTUBE CONVERT. >> THERE YOU GO. SO IT WAS REALLY QUITE REMARKABLE. SO WE'VE GOT THIS WORKING GROUP, AND AGAIN, WITH THE EXCEPTION OF MYSELF, EACH AND EVERY ONE OF THE PEOPLE ON THIS WORKING GROUP ARE REAL LEADERS IN VARIOUS ASPECTS OF THIS. AND AS YOU WILL SEE JUST LOOKING AT IT, THER ARE MANY PEOPLE FROM INDUSTRY BECAUSE THERE'S SO MUCH TALENT THERE THAT WE NEED TO TAKE ADVANTAGE OF, THERE ARE ALSO INDIVIDUALS FROM ACADEMIA, AND I HOPE YOU WILL SEE THAT WE ARE FOLLOWING OUR APPROACH TO HAVING PEOPLE AT ALL STAGES OF THEIR CAREER, BECAUSE WE HAVE SOME YOUNGER FOLKS ON THE GROUP WHO ARE EARLIER IN THEIR CAREER WHO ARE BREATHTAKINGLY ACCOMPLISHED. IT'S JUST REMARKABLE, WHEN YOU READ WHAT SOME OF THESE FOLKS HAVE BEEN ABLE TO DO SO FAR. AND THEN NO ONE QUITE LOOKS LIKE ME BUT THERE ARE SOME PEOPLE WHO ARE A LITTLE BIT MORE SENIOR. SO WE'RESO REALLY LOOKING FORWARD TO WORKING WITH THIS GROUP. WE STILL HAVE TO ADD SOME FOLKS WITH EXPERTISE IN ETHICS. THERE WAS A BIG ISSUE AND WE HAVE SOME OUTSTANDING INVITATION BUT HAVEN'T QUITE CONNECTED YET, SO THE MEMBERSHIP STILL NEEDS TO BE FINALIZED HERE. SO THE CHARGE, MAYBE WE NEED TO MODIFY THIS ALREADY, ARE THERE OPPORTUNITIES, LET'S SAY WHAT ARE THE OPPORTUNITIES ACROSS NIH EFFORT IN A.I., HOW COULD THESE EFFORTS REACH BROADLY ACROSS BIOMEDICAL TOPICS AND HAVE POSITIVE EFFECTS AMONG MANY DIVERSE FIELDS. THIS IS AN IMPORTANT ONE AND ACTUALLY IT WAS MASSAGED BY THE PREVIOUS TALK IN THE BRAIN INITIATIVE, HOW CAN WE BEST BUILD BRIDGES BETWEEN A COMPUTER SCIENCE COMMUNITY AND THE BIOMEDICAL COMMUNITY, AND I KNOW SOME OF YOU, LINDA, PERHAPS PARTICULARLY, BUT OTHERS, WILL HAVE IDEAS ABOUT THAT SPECIFICALLY. WHAT CAN WE DO TO FACILITATE TRAINING THAT MARRIES UP BIOMEDICAL WITH COMPUTER SCIENCE. CLEARLY YOU NEED EXPERTISE IN BOTH PLACES BUT CAREERS MAY NOT LOOK LIKE TRADITIONAL TENURE TRACT POSITIONS THAT FOLLOW THIS SORT OF PATHWAY FROM PH.D. TO POSTDOC TO FACULTY, BECAUSE MANY EXPERTS IN THIS SPACE DON'T NEED PH.D.s, THEY CERTAINLY DON'T NEED POSTDOCS, SOME MAY ARGUE THEY MAY NOT EVEN NEED FACULTY POSITIONS BECAUSE OF THE NATURE AND FLUIDITY OF THIS INTELLECTUAL PACE, BUT WE'VE GOT TO GET OUR ARMS AROUND IT TO MAKE SURE THE RIGHT PEOPLE IN THE RIGHT PLACE HELPING US OVERALL. FINALLY ETHICAL CONSIDERATIONS AS RELATES TO BIOMEDICAL RESEARCH USE, TO SUGGEST HOW NIH CAN BUILD THESE CONSIDERATIONS INTO ARTIFICIAL INTELLIGENCE RELATED PROGRAMS AND ACTIVITY. SO THE TIMELINE, SO I GET TO DO THE BEGINNING AND THEN MY CO-CHAIR WILL GET TO DO ALL THE REST, WHICH INCLUDES INTERIM RECOMMENDATIONS AT THE JUNE MEETING, FINAL RECOMMENDATIONS BASICALLY A YEAR FROM NOW, BUT YOU ONE WOULD ANTICIPATE THAT THE GROUP WILL REMAIN AND CONVENE INTERMITTENTLY AS REQUIRED BECAUSE THIS IS SUCH A RAPIDLY EVOLVING SPACE THAT QUN NOT IMAGINE SAYING OKAY, WE'VE GOT IT ALL FIGURED OUT NOW, THANK YOU. SO TO BE CONTINUED FOR SURE. SO WITH THAT, I WILL TURN IT OVER TO FRANCIS TO LEAD THE DISCUSSION. >> THANKS, LARRY. DAVID, YOU WANT TO MAKE COMMENTS IN YOUR ROLE AS CO-CHAIR ABOUT THIS CHALLENGE? >> JUST A MINUTE, LARRY. THANK YOU FOR SETTING THIS UP. I'M EXCITED ABOUT MEETING THE PEOPLE I HAVEN'T YET MET ON THE WORKING GROUP AND THE ONES THAT I HAVE. I THINK THAT THE ONE OBSERVATION IS THAT -- AND THIS CAME UP IN VARIOUS CONVERSATIONS OVER THE LAST TWO DAYS IS CREATIVITY OFTEN HAPPENS ON BOUNDARIES AND INTERIT TITLE INTERTITLE ZONES. I THINK ONE OF THE MOST IMPORTANT THINGS WE WILL BE ABLE TO DO AS A WORKING GROUP IS HOW TO NURTURE THOSE BOUNDARIES, INCLUDING INTERPRETERS, THE TRAINING, THE DEVELOPMENT YOU TALKED ABOUT, INCLUDING WHAT ARE THE MISSING SKILL SETS THAT YOU CAN'T JUST TAKE AN ARTIFICIAL INTELLIGENCE EXPERT AND A BIOLOGIST AND SAY, HEY, HAVE COFFEE TOGETHER, RIGHT? THERE'S MORE NEEDED. AND I THINK THAT'S ONE OF THE AREAS THAT I EXPECT WILL BE FRUITFUL IN OUR WORK. >> COMMENTS FROM ACD MEMBERS? JEFF. >> I WANTED TO ASK YOU ABOUT HOW THIS FITS WITH THE NLM, HAVING SERVED ON THE BLUE RIBBON PANEL WHERE OUR ROLE WAS IT TO REALLY EXAMINE THE INTRAMURAL PROGRAM BUT IT WAS VERY CLEAR THAT THE VIEW OF THE PANEL WAS THAT THE NLM SHOULD BE SORT OF THE HUB OF DATA SCIENCE FOR NIH. SO NOT SEEING ANY NLM REPRESENTATION ON THIS COMMITTEE, I'M JUST WONDERING HOW TO AVOID SOME DUPLICATIVE EFFORT OR POTENTIALLY A SILO EMERGING. >> THANK YOU FOR RAISING THAT, JEFF. SO AS I THINK YOU KNOW, AND FRANCIS MENTIONED IT YESTERDAY, WE NOW HAVE A STRATEGIC PLAN FOR DATA SCIENCE IN THE BOOK. NLM IS DEEPLY INVESTED IN THE DEVELOPMENT OF THAT STRATEGIC PLAN AND ULTIMATELY ITS IMPLEMENTATION. SO THEY WILL CERTAINLY INFORM AND WILL LEARN FROM AS WE ALL WILL FROM THESE EFFORTS, SO THEY'RE BOTH GOING TO CONTRIBUTE AS WELL AS GAIN. AND OBVIOUSLY WHEN WE TALK ABOUT DATASETS, AS YOU WELL KNOW, SEVERAL OF THEM ARE HOUSED IN NCBI, WHICH IS PART OF NLM, SO NO, I THINK THERE THEY WILL BE FULLY INTEGRATE THE INTO THIS, AS WILL THE GENOME INSTITUTE, AS WILL THE NCI, AS WILL THE ALL-OF-US PROGRAM. IF MEAN, AGAIN, I THINK EVEN SINCE THE PREPARATION OF THAT ACD WORKING GROUP REPORT ON NLM AND ITS FUTURE, THE PROGRESS IN THIS SPACE HAS BECOME SO DRAMATIC THAT WE NEED TO THINK A BIT MORE BROADLY ABOUT IT THAN JUST ANY ONE IN PARTICULAR INSTITUTE OR CENTER. BUT I DO TAKE YOUR POINT. WE HAVE TO AVOID DUPLICATION, EVERYTHING THAT'S GOT TO BE INTEGRATED AND ENHANCED BECAUSE WE CAN'T AFFORD THE DUPLICATION, WE CAN'T AFFORD THAT. >> I HAD A QUESTION ABOUT THE DATA STORAGE THAT YOU MENTIONED EARLIER IN YOUR TALK AND YOU MENTIONED A BUNCH OF NIH INITIATIVES THAT WE'RE STORING THERE, THE BRAIN INITIATIVE WAS ON THERE. DOES THAT MEAN ANYONE WHO'S A BRAIN INITIATIVE GRANT CAN PUT DATA ON THAT SERVER AND HOW MUCH DOES IT COST? THIS WAS SOMETHING WE TALKED A LOT ABOUT AT THE BRAIN INITIATIVE GROUP THAT WE WEREN'T SURE WHETHER THAT EXISTED. >> YEAH, SO WE HAVE SOMETHING CALLED A STRISE INITIATIVE THAT WAS NEGOTIATED WITH SEVERAL CLOUD VENDORS, THERE ARE ADDITIONAL DISCUSSIONS WITH OTHERS BECAUSE WE DID NOT WANT THESE DISCUSSIONS TO BE WITH A SINGLE VENDOR. WE WANTED TO ENGAGE MULTIPLE PLAT PLATFORMS IF YOU WILL, AND WE ARE NOW WORKING THROUGH ENGAGEMENT OF HOW BEST TO USE THE RELATIONSHIPS THAT WE HAVE CREATED. INITIALLY IT WILL BE RELATED TO DATASETS THAT WE HAVE HERE ALREADY AT NIH, BUT AT SOME POINT, THE GOAL IS TO BE ABLE TO EXPAND THIS OUT INTO THE EXTRAMURAL SPACE. NO DOUBT LOOKING AT HIGH VALUE, EXTREMELY LARGE ASSETS, NOT THE STUFF THAT YOU PUT ON AN EXCEL FILE BUT, YOU KNOW, THE LARGE ASSETS. THE OTHER THING ABOUT THIS SET OF RELATIONSHIPS THAT WE'VE CREATED WITH SEVERAL VENDORS SO FAR IS THEY WILL HELP US WITH TRAINING AND IT WILL NOT BE TRAINING JUST RELATED TO NIH STAFF ONLY BECAUSE THIS TYPE OF TRAINING LENDS ITSELF TO SO CALLED DISTANCE LEARNING OR LEARNING INTERACTIVELY ON A COMPUTER, WE CAN EXTEND THIS -- IT'S GOING TO TAKE A LITTLE TIME TO GET THERE, BUT WE WILL BE ABLE IT TO EXTEND THIS OUTWARD TO THE EXTRAMURAL COMMUNITY AS WELL, AND SO ONE COULD ENVISION, YOU KNOW, STUDENTS OR POSTDOCS AND SO FORTH WHO ARE VERY SENIOR PROFESSORS ACTUALLY LEARNING HOW ALL THIS WORKS, GREW MATERIALS THAT ARE MADE AVAILABLE BY TRUE EXPERTS, YOU KNOW, WITHIN THESE COMPANIES. SO WE ARE WORKING THROUGH THE DETAILS OF HOW BEST TO TAKE ADVANTAGE OF THESE RELATIONSHIP RELATIONSHIPS, INCLUDING HIGH VALUE ASSET DATASETS IN THE EXTRAMURAL COMMUNITY. >> I REALLY APPRECIATE YOUR RAISING THE DATA QUESTION AGAIN ABOUT BRAIN BECAUSE I DO THINK WE ARE GOING TO NEED TO MAKE PLANS FAIRLY QUICKLY ABOUT HOW BEST TO BRING TOGETHER OUR DATA SCIENCE ENTERPRISE AND BRAIN INITIATIVE, THE AMOUNT OF POTENTIAL THERE AND THE AMOUNT OF PAIN AND SUFFERING IF WE DON'T DO IT RIGHT IS GOING TO BE VERY SIGNIFICANT. AND I GUESS AS OUR BRAIN 2.0 PEOPLE ARE CONTEMPLATING WHERE TO GO FORWARD, AND YOU'RE A GOOD VOICE ON THERE, I THINK WE NEED PROBABLY TO INCREASE THE INVESTMENTS WITHIN THAT PROJECT FOR THE DATA ASPECTS OR WE WILL REALLY BE DROWNING. THANK YOU. WELL, WE HAVE ARRIVED EXACTLY AT THE CLOSING REMARKS AND ADJOURN TIME. THE CLOSING REMARKS ARE GOING TO BE VERY BRIEF, BUT LET ME JUST THANK ALL OF YOU FOR YOUR WONDERFUL INSIGHTS OVER THE KORGS OF OVER THE COURSE OF THE LAST DAY AND HALF AND ALSO REMIND YOU, YOU DON'T NEED TO TAKE YOUR BRIEFING BOOKS WITH YOU, IF YOU'D LIKE US TO SEND THEM TO YOU, WE CAN DO THAT, BUT IF YOU WANT TO TAKE THEM, YOU CAN DO THAT TOO. I PARTICULARLY WANT TO THANK THE STAFF SUPPORT FOR ALL OF THE THINGS THAT IT TAKES TO PUT THIS TOGETHER, AND THAT INCLUDES GRETCHEN WOOD, WHO'S NORMALLY HERE IN THE ROOM AS A MAJOR PART OF THE PLAN AND WAS THIS TIME TOO, BUT IS ENGAGED IN A FAMILY MEDICAL CIRCUMSTANCE AND WAS NOT ABLE TO BE HERE YESTERDAY AND TODAY, BUT ALSO CYNDI, NICOLE WHO YOU HAVE CITED A COUPLE OF TIMES FOR THE AMAZING THINGS SHE'S DONE FOR SOME OF THE PRESENTATIONS IN THE WORKING GROUPS. JESS IS RIGHT BEHIND ME, AND ANNA, WHO YOU HEARD BEING ACKNOWLEDGED EARLIER. AND ESPECIALLY, I WANT TO ACKNOWLEDGE LARRY TABAK FOR THE REMARKABLE THINGS THAT HE HAS DONE TO PUT THIS PARTICULAR MEETING TOGETHER AND EVERYTHING ELSE THAT HE JUGGLES, AND ALSO TO SAY THERE'S A SPECIAL DAY COMING UP TOMORROW, WHICH HAPPENS TO BE HIS BIRTHDAY. SO I THINK WE OUGHT TO SING, DON'T YOU? * HAPPY BIRTHDAY TO YOU HAPPY BIRTHDAY TO YOU * * HAPPY BIRTHDAY DEAR LARRY * HAPPY BIRTHDAY TO YOU SEE YOU ALL JUNE 13TH AND 14TH. WE'RE ADJOURNED!