SO I'D LIKE TO WELCOME EVERYONE
TO THE 167th MEETING ON THE
NATIONAL ADVISORY COUNCIL ON
ALCOHOL ABUSE AND ALCOHOLISM
OPEN SESSION.
I'LL CALL ON EACH COUNCIL MEMBER
AND THEN NIAAA SENIOR STAFF FOR
A ROLL CALL.
COUNCIL MEMBERS IT WOULD BE NICE
TO STATE YOUR RESEARCH,
INSTITUTE ORIENT -- OR
ENTERPRISE.
WE HAVE NEW PEOPLE WE'LL
INTRODUCE IN THE COURSE OF OUR
DIRECTOR'S REPORT SO THEY'D
PROBABLY LIKE TO HEAR WHERE YOUR
FROM.
STARTING WITH NANCY BARNETT.
>> I'M A PREVENTION IN THE
DEPARTMENT OF BEHAVIORAL AND
SOCIAL SCIENCES IN THE SCHOOL OF
PUBLIC HEALTH AT BROWN
UNIVERSITY
>> ANDREW CAMERON COULDN'T BE
WITH US TODAY.
>> I'M TINA CHAMERS A PROFESSOR
IN THE DEPARTMENT OF PEDIATRICS
AND SCHOOL OF PUBLIC HEALTH AT
THE UNIVERSITY OF PUBLIC HEALTH
SAN DIEGO.
>> NANCY GONZALEZ.
>> I AM A PROFESSOR OF
PSYCHOLOGY AND ALSO THE
EXECUTIVE VICE PRESIDENT AND
UNIVERSITY PROVOST AT UNIVERSITY
STATE UNIVERSITY.
-- ARIZONA STATE UNIVERSITY.
>> I'M A PROFESSOR IN THE
DEPARTMENT OF HEALTH CARE POLICY
AT HARVARD MEDICAL SCHOOL.
>> ANOTHER ZOOM RHONDA
JONES-WEBB.
>> I'M A PROFESSOR OF THE
DIVISION OF EPIDEMIOLOGY AND
COMMUNITY HEALTH, UNIVERSITY OF
MINNESOTA SCHOOL OF PUBLIC
HEALTH.
>> DAVID.
>> DAVID CARRIGAN FOR RESEARCH
IN NEUROLOGY AT INDIANA
UNIVERSITY AND DIRECTOR OF THE
ALCOHOL RESEARCH CENTER.
>> I'M FRANCES LEVIN AN
ADDICTION PSYCHIATRIST AND
PROFESSOR OF PSYCHIATRY AT THE
NEW YORK STATE PSYCHIATRIC
INSTITUTE AND COLUMBIA
UNIVERSITY AND CHIEF OF THE
DIVISION ON SUBSTANCE USE
DISORDERS.
>> THANKS.
>> MICHAEL LEWIS A PROFESSOR IN
THE DEPARTMENT OF PSYCHOLOGY
COLLEGE OF ARTS AND SCIENCES AT
HUNTER COLLEGE AND THE
UNIVERSITY OF NEW YORK.
>> DANE.
>> I'M DANE MAYFIELD A RESEARCH
PROFESSOR AT THE WAGNER CENTER
FOR ADDICTION RESEARCH
UNIVERSITY OF TEXAS AT AUSTIN.
>> KATY, YOU'RE ALWAYS LAST.
>> ALWAYS.
I'M KATIE WITKIEWITZ A PROFESSOR
OF PSYCHOLOGY AT THE UNIVERSITY
OF NEW MEXICO.
>> THANKS.
I'M NOW GOING TO GO THROUGH THE
NIAAA STAFF.
OBVIOUSLY I'M GEORGE KOOB THE
DIRECTOR OF NIAAA.
TRISH.
>> I'M THE DEPUTY DIRECTOR AT
NIAAA.
>> BOB.
>> BOB FREEMAN DEPUTY DIRECTOR
OF EPIDEMIOLOGY AND PREVENTION.
>> KATHY.
>> KATHY YOUNG THE DIRECTOR OF
THE DIVISION OF METABOLISM AND
HEALTH EFFECTS LOOKING AT THE
EFFECT OF ALCOHOL AND ORGAN
DAMAGE.
.
>> I'M GOING TO BRIDGETTE.
>> GOOD MORNING, EVERYONE.
I'M BRIDGET WILLIAMS-SIMMONS AT
NIAAA.
GOOD TO SEE YOU ALL.
>> LAURA, SINCE YOU'RE HERE.
>> THE CHIEF OF THE SCIENCE
POLICY BRANCH ALSO REPRESENTING
THING OFF OF SCIENCE POLICY AND
COMMUNICATION.
>> VICKY.
>> GOOD MORNING.
I'M VICKY BUCKLEY THE EXECUTIVE
OFFICER AND THE DEPUTY ETHICS
COUNCIL FOR NIAAA.
>> DAVID LEAVINGER FROM THE
DIVISION OF CLINICAL AND
BIOLOGICAL RESEARCH NIAAA.
>> ON ZOOM, DAVID.
>> SORRY.
I'M DAVID GOLDMAN CLINICAL
DIRECTOR.
THANK YOU, GEORGE.
>> AN TONIO.
>> GOOD MORNING.
ANTONIO NURONA THE DIRECTOR OF
NEUROSCIENCE AND BEHAVIOR.
>> I'M THE DIRECTOR OF THE
DIVISION OF TREATMENT AND
RECOVERY.
>> DAWN WAYMAN THE SCIENTIFIC
DIVERSITY OFFICER AT NIAAA.
>> I'M PHILIPPE MARMILLOT
EXECUTIVE.
>> I'LL DO THE DIRECTOR'S REPORT
AND THEN THE HUGHES AWARD.
>> SO EVERYTHING SOUND OKAY?
ARE WE GOOD?
>> THE FIRST THING I'M GOING TO
DO IS TALK ABOUT THE INSTITUTE
AND SOME NIH UPDATES.
UNFORTUNATELY WE'VE LOST AT
LEAST FOUR PEOPLE WE KNOW AT
NIAAA WHO HAD MAJOR CONTRIBUTION
TO THE FIELD AND/OR WERE PART OF
OUR EXTRAMURAL OR INTRAMURAL
PROGRAM.
I'VE KNOWN THREE OF THESE
PERSONALLY.
SO THEY'RE PRETTY BIG LOSSES
THIS YEAR.
GEORGE BREESE WAS THE JOHN R.
ANDREWS DISTINGUISHED PROFESSOR
AT THE NORTH CAROLINA SCHOOL OF
MEDICINE AND LED STUDIES ON THE
NEURO CHEMICAL AND BASIS OF
INCREASED STRESS FROM REPEATED
WITHDRAWAL FROM CHRONIC ALCOHOL
EXPOSURE.
PARTICULARLY SEMINOLE WITH US
HIS WORK IN STRESS RESPONSES IN
THE AMYGDALA AND THAT WAS
ASSOCIATED WITH REPEATED ALCOHOL
WITHDRAWALS AND SENSITIZATION
LIKE EFFECT.
AND HE ALSO MADE SCIENTIFIC
CONTRIBUTIONS IN UNDERSTANDING
THE ROLE OF NEUROIMMUNE
SIGNALLING IN ALCOHOL INDUCED
STRESS.
HE WAS WAY AHEAD OF HIS TIME.
IRREPRESSIBLE AND LOVED SCIENCE.
AND DR. MICZEK WAS A DIRECTOR OF
THE RESEARCH CENTER AT TUFT'S
UNIVERSITY.
HIS RESEARCH FOCUSSED ON PSYCHO
PHARMACOLOGIC AND BRAIN
MECHANISMS OF ANXIETY, SOCIAL
STRESS AND THE MISUSE OF ALCOHOL
AND OTHER SUBSTANCES.
AND LOOKED AT HOW THE
NEUROCIRCUITRY AND PRECLINICAL
MODELS AND HE WAS JUST AND
COUNTED ON GREAT INSIGHT.
HE RECEIVED A MORE IT AWARD FROM
US AND LEFT A LASTING ON THE
NEUROPSY PSPSY PSPSYCHO LOGY FI
ASKED QUESTIONS IN A DRAMATIC
WAY AND HE WAS VERY SUPPORTIVE
AFTERWARDS.
THOSE WHO KNOW HIM KNOW WHAT I'M
TALKING ABOUT.
DANIEL E RIO WAS A PHYSICIST IN
BRAIN PHYSIOLOGY AT NIAAA.
HE MADE IMPORTANT SCIENTIFIC
CONTRIBUTIONS IN NEUROIMAGING
AND DATA MODELS AND ANALYSES AND
HE TAUGHT COURSES IN APPLIED BIO
MEDICAL AT JOHNS HOPKINS SCHOOL
OF ENGINEERING.
I DID NOT KNOW HIM PERSONALLY
BUT I KNOW DAVID GOLDMAN DID AND
MANY PEOPLE IN OUR CLINICAL
CENTER.
WE WAS KNOWN AS A BRILLIANT KIND
AND PATIENT ININSTRUMENTER AND
MANY COMMITMENT TO TEACHING.
THEN THIS WAS IS BIG FOR THE
INSTITUTE BECAUSE KEN WARREN
RECENTLY PASSED AND WAS NIAAA
DEPUTY DIRECTOR IN 2008 AND
SER
SERVED AS THE NIAAA DIRECTOR AND
DID A YEOMAN'S JOB IN DIRECTING
THE INSTITUTE AND IT WAS A
TUMULTUOUS TIME FOR NIAAA.
HAD 41 YEARS OF FEDERAL SERVICE
AND RETIRED IN 2015 AFTER WHICH
HE CONTINUED TO SERVE AS A
SPECIAL ADVISER TO THE NIAAA
DIRECTOR, THAT'S ME, UNTIL 2018.
KEN WAS A FOREMOST RESEARCH
EXPERT ON FETAL ALCOHOL SPECTRUM
DISORDER AND WAS ON THE ADVISORY
ON ALCOHOL AND PREGNANCY IN 1977
AND HELPED LEAD THE FIRST
SURGEON GENERAL'S WARNING ON THE
ISSUE IN 1981.
I CAN'T TELL YOU HOW MUCH HE
CONTRIBUTED TO THE FETAL ALCOHOL
SPECTRUM DISORDER FIELD.
HE WAS BASICALLY THE FEDERAL
LEAD PERSON AND I THINK EVERYONE
IN THE FASD FIELD RECOGNIZES HOW
MUCH HE CONTRIBUTED.
AND THE LIFE TIME ACHIEVEMENT
AWARDS FROM THE RESEARCH SOCIETY
ON ALCOHOL FOR MANY THINGS I
JUST OUTLINED.
HE WAS KNOWN AS AN EXCEPTIONALLY
SMART, KIND AND GENTLE MAN AND
WAS A WONDERFUL MENTOR, FRIEND
AND COLLEAGUE TO ALMOST ALL OF
US AT THE INSTITUTE WHO
OVERLAPPED WIN KEN.
-- WITH KEN.
I'M SURE RSA WILL ALSO BE
HONORING SOME OF AS THE
INDIVIDUALS BUT I ALSO FEEL LIKE
WE SHOULD HONOR INDIVIDUALS THAT
HAVE COME THROUGH AND WORKED
WITH US.
NIAAA IS CLOSING OUT OUR HISTORY
OF OUR 2024 BUDGET AND RECEIVED
A 1.8 MILLION TRANSFER AND THE
FY2025 APPROPRIATION FOR NIH AND
NIAAA HAS NOT YET BEEN FINALIZED
AT THIS TIME AND DON'T HOLD YOUR
BREATH.
I'M NOT SAYING ANYMORE.
I AM GOING TO SAY AND VERY
PLEASED TO INTRODUCE AND I'D
LIKE ALICIA TO STAND UP SHE'S
BACK THERE SOMEWHERE.
SHE JOINED NIAAA THE FINANCIAL
MANAGEMENT BRANCH AS OUR NEW
BUDGET OFFICER.
HER CAREER WITH NIH SPANS MORE
THAN 19 YEARS IN MULTIPLE
INSTITUTES AND CENTERS.
SHE JOINED NIAAA AFTER SERVING
AS THE DEPUTY BUDGET OFFICER FOR
THE NATIONAL HUMAN GENOME
INSTITUTE.
PRIOR WAS DEPUTY BUDGET OFFICER
AT THE NATIONAL INSTITUTE OF
MENTAL HEALTH, BUDGET OFFICER AT
THE CENTER FOR SCIENTIFIC REVIEW
AND BUDGET ANALYST AT THE NIH
CLINICAL CENTER.
WE'RE LUCKY TO HAVE RECRUITED
HER.
SHE'S MOVED INTO THIS JOB SO
SEAMLESSLY THAT WE DIDN'T NOTICE
SHE WASN'T HERE.
VERY GRATEFUL TO HAVE YOU HERE.
WE HAVE A COLLABORATION WITH THE
NIDCD LAUNCHING THE SMELL AND
TASTE CENTER.
A NEW EFFORT TO IMPROVE THE
LIVES OF THOSE WITH SENSORY
DISORDERS AND IT WAS FORMED
THROUGH COLLABORATIONS TO EXPAND
WORK IN SMELL AND TASTE RESEARCH
AND THE NEED TO CAPTURE NORM
ATTENTION DURING THE COVID-19
PANDEMIC.
IT'S LED BY DR. JOSH LEVY AND
THE SECTION OF SENSORY SCIENCE
AND METABOLISM OUR OWN
DR. JOSEPH.
WE'RE PLEASED WITH THAT AND
REALLY PLEASED PAULE IS A MAJOR
PART BECAUSE SHE'S ONE OF THE
WORLD'S EXPERTS IN THIS AREA.
THE NIAAA DATA ARCHIVE WAS
ESTABLISHED IN 2019.
THE ARCHIVE IS HOUSED WITHIN THE
NATIONAL INSTITUTE OF MENTAL
HEALTH, DATA ARCHIVE.
AND IT PROVIDES A REPOSITORY FOR
DATA GENERATED THROUGH NIAAA
STUDIES IN HUMANS.
THE GROWING ARCHIVE CONTAINS
DATA FROM OVER 400 COLLECTIONS
REPRESENTING MORE THAN 55,000
RESEARCH PARTICIPANTS.
DATA SETS ARE NOW AVAILABLE FROM
THE NATIONAL CONSORTIUM ON
ALCOHOL AND NEURO DEVELOPMENT IN
ADOLESCENCE AND HUMAN STUDIES
THROUGH THE R21 MECHANISM.
EVERYONE ELSE IS ALSO INVOLVED
IN GETTING THEIR DATA IN THE
ARCHIVE OR WHAT WE FONDLY NOW
CALL THE NDA.
SO WHEN YOU HEAR ME TALK ABOUT
THE NDA, THAT'S WHAT WE'RE
TALKING ABOUT.
AND WE'RE KEEPING YOU POSTED ON
OTHER DATA SETS AS THEY BECOME
AVAILABLE TO INVESTIGATORS BUT I
HOPE IT WILL PROVE TO BE A
STIMULUS TO HYPOTHESIS
GENERATION AND ACTUAL RESEARCH.
WE ALSO HAVE SOME FUNDING
OPPORTUNITIES SPECIALIZED
ALCOHOL RESEARCH CENTERS AND
COMPREHENSIVE RESEARCH CENTERS
RFAs OUT THE OVER ALL PURPOSE OF
THE ALCOHOL RESEARCH PROGRAM IS
TO PROVIDE LEADERSHIP IN
CONDUCTING AND FOSTERING
INTERDISCIPLINARY COLLABORATIVE
RESEARCH ON A WIDE VARIETY OF
TOPICS RELEVANT TO THE NIAAA
MISSION.
THEY INCLUDE BUT NOT LIMITED TO
ETIOLOGY DIAGNOSIS, EPIDEMIOLOGY
AND PREVENTION OF ALCOHOL
MISUSE, ALCOHOL USE DISORDER AND
ALCOHOL RELATED AND ORGAN
DISEASES AS WELL AS RELATED BIO
MEDICAL AND PSYCHOSOCIAL AND
ECONOMIC CONSEQUENCES ACROSS THE
LIFE SPAN AND ACROSS RACIAL
ETHNIC GROUP AND OTHER HEALTH
DISPARITY POPULATIONS.
IF YOU ACTUAL REMEMBER FROM THE
CLOSED SESSION WE HAD
REPRESENTATION FROM ALMOST ALL
THESE AREAS IN THE GRANTS YOU
JUST APPROVED.
CENTERS ARE ALSO REGIONAL OR
NATIONAL RESOURCES THAT
CONTRIBUTE TO THE DEVELOPMENT OF
NEW RESEARCH METHODS,
TECHNOLOGIES AND APPROACHES THAT
SUSTAIN INNOVATIVE AND
GOAL-DIRECTED RESEARCH.
A PLAN FOR ENHANCING DIVERSE
PERSPECTIVES IS REQUIRED IN THIS
PROGRAM.
I'VE BEEN VERY SUPPORTIVE OF OUR
CENTER'S PROGRAM.
I CONSIDER IT AND HOPE THE
CRITICAL MASSES WILL EXPAND TO
CALL CENTERS AT LARGE AND THAT
HAS HAPPENED IN MANY CASES.
AND ONE OF THE REASONS I'M VERY
SUPPORTIVE OF OUR CENTER'S
PROGRAM.
AND WE'LL HAVE ISSUES AROUND THE
CENTER PROGRAM.
THE BUDGET HAS STAYED THE SAME
SINCE 1977.
SO YOU CAN UNDERSTAND WHAT THAT
MEANS.
INFLATION HAS NOT STAYED THE
SAME SINCE 1977.
AND THEN WE HAVE NEW ACTIONS AND
EFFORTS IN DIVERSITY, EQUITY AND
INCLUSION AND ACCESSIBILITY IN
ALCOHOL RESEARCH.
WE'RE PARTICIPATING INPLASM --
MAXIMIZING CAREER AWARDS KNOWN
AS THE K99, R00, INDEPENDENT
RESEARCH STUDIES WITH HUMANS
REQUIRE INDEPENDENT CLINICAL
TRIAL REQUIRED AND INDEPENDENT
CLINICAL TRIAL NOT ALLOWED.
THIS IS A REALLY SUCCESSFUL
PROGRAM AND WE CONTINUE TO BE
PART OF IT AND DAWN'S HELPING US
WITH MANY OF THESE ISSUES.
AND THEN OVER NIH INSTITUTES AND
CENTERS INCLUDING NIAAA WILL
HOST THE 2024 NIH DIVERSITY
SUPPLEMENT PROFESSIONAL
DEVELOPMENT AND NETWORKING
WORKSHOP SEPTEMBER 24 TO
SEPTEMBER 25, 2024.
THIS WILL BRING DIVERSITY
SUPPLEMENT SCHOLARS CONDUCTING
RESEARCH ON A VARIETY OF I.C.
MISSION AREAS TO RECEIVE
CRITICAL NIH RESOURCES AND
PARTICIPATE IN NETWORKING AND
PROFESSIONAL DEVELOPMENT
SESSIONS ON A NUMBER OF RESEARCH
AND CAREER RELATED TOPIC.
-- TOPICS.
SO WHAT'S AHEAD?
WE HAVE OUR ANNUAL FRONTIERS AND
ADDITION RESEARCH WHICH IS A
PRE-MEETING SYMPOSIUM WE DO WITH
THE NATIONAL INSTITUTE ON DRUG
ABUSE AS PART OF OUR
COLLABORATIVE RESEARCH ON
ADDICTIONS IN NIH HELD IN
CHICAGO THE FRIDAY BEFORE THE
SOCIETY FOR NEUROSCIENCE I THINK
OCTOBER 4 OR 5.
THE SCIENTIFIC SESSIONS THIS
YEAR ARE FASCINATING AND
INTERESTING.
PSYCHEDELIC PATHOGENS FOR THE
TREATMENT OF ALCOHOL AND
SUBSTANCE USE DISORDER.
THIS WILL CATCH EVERYONE'S
ATTENTION AN AGONIST FOR THE USE
OF AND HABENULA AS AN
ANTI-ADDICTIVE CIRCUIT FOR YOU
NEURO CIRCUIT AFICIONADOS.
I'LL BE THERE.
IT'S OCTOBER 4.
COMING SOON FROM OUR SCIENCE AND
WE HAVE THE NATIVE COMMUNITIES
ALCOHOL INTERVENTION REVIEW
NIAAA IS FACILITATING HEALTH
PROFESSIONALS IN IDENTIFYING
EFFECTIVE SCIENTIFICALLY
EVALUATED ALCOHOL INTERVENTIONS
FOR THEIR COMMUNITIES, NATIVE
AIR WILL PROVIDE INFORMATION ON
THE PREVENTION OF ALCOHOL MISUSE
AND TREATMENT OF DISORDER AND
TREATMENT OF ALCOHOL FETAL
SPECTRUM DISORDER AND A BIG
SHOUT OUT TO EVERYBODY WHO
WORKED ON THIS BUT JUDY AUROO
WAS THE LEAD INVESTIGATOR AND
HAS SUBSEQUENTLY RETIRED BUT I
THINK SHE'LL BE PLEASED TO SEE
WHEN WE LAUNCH THIS EFFORT.
THIS IS A FAIRLY NEW BUT CAME
OUT OF A LETTER OF INTENT TO
COLLABORATE WITH THE FRENCH
NATIONAL INSTITUTE OF HEALTH.
WE BROADENED IT TO INCLUDE AN
INTERNATIONAL EFFORT AND SO IT'S
A REQUEST FOR INFORMATION AND
HARMONIZATION OF THE U.S. AND
INTERNATIONAL ALCOHOL RESEARCH
METRICS.
THE DIVISION OF EPIDEMIOLOGY AND
PREVENTION RESEARCH HAS TAKEN
THE LEAD ON THIS ONE.
THERE ARE INTERNATIONAL
DIFFERENCES IN METHODS IN
ALCOHOL RESEARCH SUCH AS
STANDARD DRINK SIZE AND
DEFINITIONS OF BINGE DRINKING
AND OTHER HARMFUL ALCOHOL USE
AND MORBIDITY AND MORTALITY
INDICATORS.
THEY MAKE IT DIFFICULT TO
RESEARCH DATA ACROSS COUNTRIES
EVEN JUST GETTING INFORMATION ON
LIVER DISEASE CAUSED BY ALCOHOL
AND HOW MANY INDIVIDUALS DIE
FROM ALCOHOL AND AUTOMOBILE
ACCIDENTS ACROSS COUNTRIES IS A
CHALLENGE.
AND THE OVER ALL GOAL IS TO
ENHANCE THE RIGOR AND
GENERALIZABILITY OF ALCOHOL
RESEARCH FINDINGS ACROSS THE
WORLD.
SO THIS RFI WILL BE AVAILABLE
FOR COMMENT THIS FALL AND THEN
WE'LL SEE HOW WE CAN INNERVATE
THIS KIND OF EFFORT.
THE FRENCH NATIONAL INSTITUTE OF
HEALTH IS ALSO INTERESTED IN
INNERVATING IT FROM THEIR
PERSPECTIVE BUT WE HOPE OTHER
COUNTRIES WILL BECOME INVOLVED
AND WANT ON INTEGRATING THIS
WITH THE FOGARTY CENTER.
I'LL DO MY JOURNAL CLUB.
THESE ARE RESEARCH HIGHLIGHTS
THAT WERE SUGGESTED BY STAFF
FROM EACH OF OUR DIVISIONS.
FROM FETAL ALCOHOL DISORDER TO
INTERVENTION OF TREATMENT OF
ALCOHOL USE DISORDER AND ALCOHOL
ASSOCIATED LIVER DISEASE AND
FAIRLY QUICKLY.
THIS IS A STUDY BY DR. WANG.
IT WAS PUBLISHED IN MOLECULAR
PSYCHIATRY.
THE TITLE WAS REDUCTION OF
NEURAL BEHAVIORAL DEFICITS IN
FETAL ALCOHOL SPECTRUM DISORDER
AND APOE LIPO PROTEIN BINDS TO
RECEPTORS.
IN THE CENTRAL NERVOUS APOE ARE
AFFECTED BY INJURY AND HAS BEEN
IMPLICATED IN ALZHEIMER'S
DISEASE BECAUSE IT CAN INDUCE
EITHER BY ITS ACTIVATION OR
SUPPRESSION A BETA AND TAU
PROTEIN PATHOLOGY.
IN THIS STUDY THEY WERE LOOKING
AT PRENATAL ALCOHOL EXPOSURE.
IT'S QUITE INTRIGUING AND A HUGE
STUDY AND WON'T SHOW ALL THE
DATA BUT EXPANDED TO TWO SLIDES
ON THIS ONE.
IN MICE PRENATALLY EXPOSED TO
ALCOHOL THEY FOUND CHROMATIN
ACCESSIBILITY THROUGH THE LOCUS
GENE WAS DECREASED AND SO THERE
WAS A DECREASE IN EXPRESSION OF
APOE EG.
THAT RESULTED IN DECREASED
LEVELS OF APOE IN THE BRAIN AND
PERIPHERAL BLOOD.
AND THESE APOE LEVELS WERE
POSITIVELY CORRELATED WITH MOTOR
LEARNING AND ADMINISTRATION OF
AN APOE AGONIST.
IT'S A SMALL MOLECULE THAT GETS
IN THE BRAIN POST NATELY
INCREASED THE NUMBER OF APOE
MOTOR CELLS IN THE CORTEX AND
MITIGATED MOTOR ANXIETY AND
BEHAVIOR.
THE MOLECULE CONTAINS THE
RECEPTOR BINDING UNIT FOR THE
HUMAN APOE AND BINDS THE LOW
DENSITY LIPO PROTEIN RELATED
PROTEIN 1 BUT DOES NOT INCLUDE
THE LIPID BINDING DOMAIN SO IT'S
REALLY AN INTERESTING SERIES OF
STUDIES.
AND USING DATA FROM CHILDREN
PRENATALLY EXPOSED TO ALCOHOL
APOE LEVELS IN THE PERIPHERAL
BLOOD AND REDUCED WERE
ASSOCIATED WITH LOWER COGNITION
AND THE RIGHT FORECLOIGURE IS F
THOSE ON THE FASD PROGRAM DONE
IN UKRAINE BEFORE THE WAR,
OBVIOUSLY.
SO PRETTY COMPELLING
TRANSLATIONAL WORK FROM THE
RODENT TO THE HUMAN SUGGESTING
SOMETHING THAT INTERFACES WITH
ALZHEIMER'S DISEASE AND OTHER
PATHOLOGIES IN THE BRAIN ALSO
TRIGGERED BY FETAL ALCOHOL
SPECTRUM DISORDER.
WE LOOK FORWARD TO SEEING THIS
EVOLVE TO POSSIBLE TRANSLATIONAL
INTERVENTIONS.
AND THIS WORK WAS STARTED BY
INDIVIDUALS IN OUR INTRAMURAL
PROGRAM AND THERE WAS A PAPER IN
TRANSLATIONAL PSYCHIATRY INTO
IDENTIFYING SOME OF THE
UNDERLYING FACTORS OF THE
ADDICTIONS NEURAL CLINICAL
ASSESSMENT THAT HELPS CLASSIFY
INDIVIDUALS WITH AND WITHOUT
ALCOHOL USE DISORDER.
IN A PROSPECTIVE NEW SAMPLE
ACROSS THE SPECTRUM RESEARCHERS
TESTED AN ASSESSMENT BATTERY AND
STUDIED THE THREE DOMAINS OF THE
ADDITIONS NEURO CLINICAL
ASSESSMENT.
I THINK MOST ARE FAMILIAR BY NOW
AND AFFECTS EMOTIONALITY AND
EXECUTIVE FUNCTION AND
IDENTIFIED 10 FACTORS UNDER THE
DOMAINS.
OF THE 10 FACTORS, ALCOHOL
MOTIVATION INTERNALIZING AND
IMPULSIVITY AFFECTED INDIVIDUALS
AND SHOWN IN THE SLIDE.
IF YOU TAKE THE THREE DOMAINS,
EXECUTIVE FUNCTION AND LOOK AT
THE STANDARDIZED SCORE AND LOOK
AT THE SOLID BLACK LINES ARE THE
NON AUD AND THE GRAY BARS ARE
THE AUD FOR EXECUTIVE FUNCTION
THERE WERE A NUMBER OF THINGS
THAT CONTRIBUTED BUT IMPULSIVITY
AND SALIENCE IT WAS ALCOHOL
MOTIVATION A MAJOR DIFFERENCE
AGAIN AUD AND NON-AUD AND FOR
NEGATIVE EMOTIONALITY
INTERNALIZING SCORES WOULD MAKE
SENSE BUT ALSO PSYCHOLOGICAL
STRENGTH WHICH I THOUGHT WAS
INTERESTING.
SO THESE RESULTS REVEALED
ADDITIONAL DIMENSIONALITY TO THE
ANA DOMAINS BRINGING DIFFERENT
CONSTRUCTS TO A SINGLE COHESIVE
FRAMEWORK.
THIS PROVIDES OPPORTUNITIES FOR
THE ANA FRAMEWORK TO BE
INCORPORATED IN STUDY DESIGNS
INCLUDING FUNCTIONAL IMAGING OF
HUMANS.
SO MAYBE WE'LL BE ABLE TO
CONFIRM OR UNCONFIRM OR NOT
CONFIRM SOME OF THE CIRCUITRY
IDENTIFIED IN ANIMAL MODELS BY
LOOKING AT THESE SUB DOMAINS OF
DYSFUNCTION IN HUMAN INDIVIDUALS
WITH ALCOHOL USE DISORDER.
IT'S VERY EXCITING AND MOVING
FORWARD.
SOME ON COUNCIL WORKED IN THIS
AREA AND MADE CONTRIBUTIONS TO
THE DISCRIMINATIONS OF DIFFERENT
MOTIVATIONS FOR ALCOHOL SEEKING
AND I FLAGGED THE PAPER BECAUSE
IT ARGUES THE AFFECT OF ALCOHOL
MISUSE AND COLLEGE STUDENTS.
THE HYPOTHESIS IS NEGATIVE
AEFFECT MEDIATED THE
RELATIONSHIPS BETWEEN SEXUAL AND
GENERALIZED HARASSMENT AND
ALCOHOL MISUSE.
ABOUT 3,000 COLLEGE FRESHMEN IN
A COLLEGE IN THE MIDWEST FROM
EIGHT COLLEGES IN THE MIDWEST, I
MIGHT ADD, THOSE WHO EXPERIENCED
HARASSMENT REPORTED MORE
ALCOHOL-RELATED PROBLEMS THE
RAPI PROBLEMS MODEL THERE AND
THOSE ARE BETA SCORES LISTED.
AND YOU SEE IS THE SIGNIFICANCE
FOR HARASSMENT AT SCHOOL AND THE
INDEX ARE WHAT THE RPI ARE.
THE RAPI STANDS FOR AND THAT'S
THE FIRST COLUMN THERE AND I
WANT TO EMPHASIZE THAT AND THEY
ARE USED THE NEGATIVE
AFFECTIVITY ASSESSED WITH THE
POSITIVE AND NEGATIVE AFFECT
SCALE.
THE GENERALIZED HARASSMENT
MEASURED WITH THE QUESTIONNAIRE
AND SEXUAL HARASSMENT WITH A
MODIFIED 13I QUESTIONNAIRE.
USING ALL THE METRICS THEY
SHOWED THOSE WHO EXPERIENCED
HARASSMENT REPORTED MORE
ALCOHOL-RELATED PROBLEMS, HIGHER
LEVELS OF ALCOHOL, PROBLEMS
INCLUDED BINGE DRINKING AND
DRINKING TO INTOXICATION AND
INCREASING NEGATIVE AFFECT IN
THE TOP PANEL.
IT SUGGESTED NEGATIVE AFFECT MAY
BE A MEDIATED MECHANISM BETWEEN
EXPERIENCED HARASSMENT AND
SUBSEQUENT ALCOHOL MISUSE AND
RELATED PROBLEMS.
THE HARASSMENT NEEDS TO NEGATIVE
AFFECT.
THE NEGATIVE AFFECT IS A
MEDIATOR IN SETTING UP FOR
PROBLEMS WITH ALCOHOL DOWN THE
LINE.
IT'S AN INTERESTING WAY OF THE
NEGATIVE COMPONENT IN YOUNG
PEOPLE AND AN EARLY PART OF THE
TRAJECTORY TO ALCOHOL PROBLEMS.
AND SO I FLAG IT FOR THAT
REASON.
THIS PARTICULAR STUDY WAS AN
ALCOHOL POLICY STUDY.
IT'S REALLY INTRIGUING HOW THEY
DID THIS.
THE TITLE IS ALCOHOL POLICIES
PROVIDE INE OPPORTUNITY TO
REDUCE HOMICIDES IN THE UNITED
STATES.
TO UNDERSTAND HOW ALCOHOL
POLICIES INFLUENCE VIOLENCE
ACROSS THE UNITED STATES THE
STUDY USED A COMPOSITE MEASURE
OF STATE LEVEL ALCOHOL POLICIES
WHICH IS KNOWN AS THE ALCOHOL
POLICY SCALE AND DATA ON DEATHS
FROM 2002 TO 2019.
THE RESULTS SUGGESTED ALCOHOL
POLICY RESTRICTIVENESS IS
ASSOCIATED WITH FEWER TOTAL
HOMICIDES AND FIREARM HOMICIDES
IT LOOKS AT ALCOHOL RESTRICTIONS
FROM THE 25th TO 75th PERCENTILE
WOULD RESULT IN ALMOST 275
HOMICIDES THERE'S NO CLEAR
ASSOCIATION OF ALCOHOL POLICY
WITH SUICIDE.
THE LEFT HAND PANEL ACTUALLY
SHOWS THE DIFFERENCE IN ALCOHOL
POLICY AND TAKING THAT
INFORMATION AND APPLYING THAT TO
PREDICTED CHANGE IN DEATHS IN
2018 IF STATES IMPLEMENTED MORE
RESTRICTIVE POLICIES, WHAT YOU
CAN SEE IS A DRAMATIC REDUCTION
IN HOMICIDES AND IT'S SPECIFIC
TO HOMICIDE.
IT'S A FASCINATING STUDY AND
TALKS A WHILE TO GET YOUR HEAD
AROUND HOW THEY DID THIS AND
PRETTY COOL OBVIOUSLY OR I
WOULDN'T HAVE HIGHLIGHTED IT.
FINALLY I'LL END WITH
CONTRIBUTION FROM OUR COLLEAGUES
IN THE LIVER FIELD.
SOME OF OUR INTRAMURAL AND
EXTRAMURAL INVESTIGATORS.
AND HEAVY DRINKING IS DEFINED AS
FOUR OR MORE A DAY AND FIVE OR
MORE DRINKS PER WEEK FOR MEN.
AND WE'LL SEE IF IT CAN REDUCE
PROGRESSION OF LIVER DISEASE AND
IN 2001 NIAAA COMMISSIONED A
TASK FORCE WITH HEPATOLOGISTS
AND STATISTICIANS AND CLINICAL
TRIALIST -- I ALWAYS LIKE THAT
WORD, CLINICAL TRIALIST.
GOLDMAN, ARE YOU A CLINICAL
TRIALIST AND REGULATORY AGENCIES
TO DEVELOP RECOMMENDATIONS FOR
THE DESIGN AND CONDUCT OF
CLINICAL TRIALS TO EVALUATE THE
EFFECT OF ALCOHOL USE AND
TREATMENT TO REDUCE OR ELIMINATE
ALCOHOL USE IN PATIENTS FROM
ALD.
AND THE GROUP'S CONSENSUS IS TO
DO THE FOLLOWING.
I LISTED FIVE UP THERE AND THERE
WERE EXPERTS ON THE ALD RESEARCH
TEAM TO ENSURE ACCURATE
SELECTION OF MEASURES FOR
ALCOHOL USE AND AUD SYMPTOMS AND
AUD RELATED OUTCOMES.
MEASURE ALCOHOL CONSUMPTION
BEFORE AND CLINICAL TRIALS IN
ALL PATIENTS WITH LIVER DISEASE
WIN THE AFFECTS OF RIVER-RELATED
OUTCOME.
ASSESS CARDIO METABOLIC RISK
FACTOR AND TAILOR INCLUSION AND
EXCLUSION CRITERIA ACCORDING TO
THE STAGE OF LIVER DISEASE.
MONITOR AND ADJUDICATE ADVERSE
EVENTS BY A SEPARATE HE PATTIC
COMMITTEE WITH AN INDIVIDUAL AND
STUDY GROUP AND ADDRESS STIGMA
AND DEVELOP RECRUITMENT AND
GENERALIZABILITY OF THE
FINDINGS.
THAT ONE IS IMPORTANT AND OFTEN
GOES UNDER THE RADAR.
AND I'LL GO THROUGH THIS RIFF OF
A SLIDES.
I ASK YOU PLEASE DO THE SAME
WHENEVER YOU HAVE AN OPPORTUNITY
THEY GIVE YOU THREE EXTRA
MINUTES FOR YOUR TALK ON ALCOHOL
AND THROW THIS IN AT THE END.
NOBODY'S GOING TO NOTICE YOU
DIDN'T DO IT BUT THEY WILL
NOTICE IF YOU DO, DO IT.
NIAAA WEB SOURCE FOR SCHOOL,
MIDDLE SCHOOL INTERACTIVE
ACTIVITIES TO HELP REINFORCE KEY
MESSAGES ABOUT PEER PRESSURE AND
TOPICS RELATED TO UNDER AGE
DRINKING AND ONLINE RESOURCE FOR
TEENS HOW ALCOHOL AFFECTS YOUR
HEALTH AND WHERE TO GET HEALTH
FOR ALCOHOL-RELATED PROBLEMS.
YOU HEARD THIS BEFORE,
RETHINKING DRINKING.
EVERY PRESS INTERVIEW I DO I
RECOMMEND RETHINKING DRINKING AT
THE END.
COLLEGE AIM.
YOU KNOW ABOUT THAT ONE.
THE ALCOHOL TREATMENT NAVIGATOR.
ANOTHER ONE I PROBABLY USE AND I
KNOW WE BOTH USE RETHINKING
DRINKING THE NAVIGATOR IN EVERY
PRESS INTERVIEW WE DO.
WHETHER IT'S WRITTEN OR ORAL AND
WE PROBABLY AVERAGE ONE OR TWO
EVERY WEEK.
AND THIS IS THE ONLINE THAT
HELPS INDIVIDUALS UNDERSTAND AND
SEARCH TREATMENT OPTIONS
INCLUDING TELEHEALTH SERVICES
THAT INCLUDES A PORTAL TO ASSIST
HEALTH CARE PROVIDERS IN MAKING
REFERRALS TO THEIR PATIENTS,
DESCRIBES WHAT IS AN AUD.
IT DESCRIBES THE SPECTRUM OF
SYMPTOMS ASSOCIATED WITH AUD AND
SPECTRUM OF TREATMENTS FOR AUD.
THIS WAS SOMETHING THAT BEGAN
WITH BOB AND HE'S COMING UP NEXT
AND FINISHED BY ANOTHER TEAM AND
HAS BEEN A BIG SUCCESS.
WHEREVER I GO NOW AND WORK WITH
CLINICIANS THEY ALL -- I WAS
WITH A GROUP OF LOMA LINDA DOING
SPECIALIST TRAINING AND THEY
WERE WELL AWARE OF THE TREATMENT
NAVIGATOR AND USING IT ON A
REGULAR BASIS.
YOU GUYS DID GOOD.
AND THEN THERE'S THE HEALTH CARE
PROFESSIONAL RESOURCES.
THIS IS WHAT WE DID DURING THE
PANDEMIC.
THIS IS THE ONLINE EDUCATIONAL
RESOURCE THAT COVERS THE BASIC
FOR WHAT EVERY HEALTH CARE
PROFESSIONAL NEEDS TO KNOW ABOUT
ALCOHOL AND INCLUDING WAYS HOW
IT CAN IMPACT HEALTH AND PROVIDE
STRATEGIES FOR ALCOHOL SCREENING
AND INTERVENTION.
SO THESE ARE ALL ON OUR WEBSITE.
ALL YOU HAVE TO DO IS TYPE NIAAA
INTO ANY SEARCH ENGINE AND
YOU'LL GET THERE WITHIN ONE OR
TWO CLICKS.
SO CLICK AWAY AND URGE EVERYONE
ELSE TO CLICK AWAY, PLEASE.
AND NIAAA RECENTLY LAUNCHED THE
LINKEDIN PAGE TO ENGAGE
RESEARCHERS AND OTHER
PROFESSIONALS.
EACH INSTITUTE AT NIH IS ALLOWED
TO HAVE ONE OR TWO AS PART OF
THE ORGANIZATION.
YOU CAN HAVE YOUR OWN PERSONAL
LINKED IN PAGE.
SO THANKS A LOT.
I WANT NIAAA TO BE OUR SOURCE,
YOUR SOURCE FOR CREDIBLE
EVIDENCE-BASED INFORMATION ABOUT
ALCOHOL AND HEALTH.
THIS IS THE DRIVING FORCE OF THE
LAST COUPLE OF YEARS OF MY
EFFORTS AND I THINK YOU CAN SEE
FROM THE WAY I DO THESE RESEARCH
HIGHLIGHTS THERE'S THE BEGINNING
OF TRANSLATION NOW FROM
PRECLINICAL TO THE CLINICAL AND
EVEN IN THE SAME STUDY WHERE
PEOPLE ARE PUBLISHING IN PLACES
LIKE TRANSLATIONAL AND MOLECULAR
PSYCHIATRY PAPERS WHERE YOU HAVE
ANIMAL DATA, PRE CLINICAL DATA,
HUMAN DATA.
AND CROSS-TALK BETWEEN THE TWO.
SO I SEE PROGRESS.
IT TAKES A WHILE BUT I SEE
PROGRESS.
OKAY.
SO THE NEXT PART OF OUR COUNCIL
IS A PLEASURABLE ONE FOR ME.
SO BOB, DO YOU WANT TO COME UP?
WE'LL NOW PRESENT THE 2024
HAROLD HUGHES MEMORIAL AWARD.
THIS AWARD -- NOW SMILE, BOB.
THIS RECOGNIZES THE
CONTRIBUTIONS OF AN INDIVIDUAL
WHOSE WORK TRANSLATES TO
PRACTICE AND BUILDS BRIDGES
ACROSS ALCOHOL, PREVENTION,
TREATMENT AND POLICY MAKING
COMMUNITIES.
THE AWARD COMMEMORATES THE
LEGACY OF U.S. SENATOR HAROLD
HUGHES WHO SPEARHEADED REFORMS
TO IMPROVE ALCOHOL POLICY AND
SUPPORT ALCOHOL TREATMENT.
HE WAS A MAJOR FORCE IN NIAAA BY
THE LEGISLATION INTRODUCED IN
1970.
WE CELEBRATED OUR 50th
ANNIVERSARY TWO YEARS AGO.
HE ACKNOWLEDGED HIS OWN PERSONAL
JOURNEY AS A PERSON IN RECOVERY.
HE WAS AN OUTSPOKEN ADVOCATE
AGAINST STIGMA WHICH CAN ACT AS
A BARRIER TO TREATMENT.
TODAY I AM PLEASED TO ANNOUNCE
THIS YEAR'S HUGHES AWARD
RECIPIENT IS DR. ROBERT HUBENER.
YOU ONLY GET A CLAP WHEN YOU
JOIN AND LEAVE NIH.
HE SERVED AS A LONG TIME
COORDINATOR AND CHAMPION OF
ALCOHOL TREATMENT RESEARCH
DURING HIS CAREER AT NIAAA AND
AFTER HIS RETIREMENT FROM THE
FEDERAL GOVERNMENT.
IN A CAREER SPANNING NEARLY FOUR
DECADES INCLUDING 30 YEARS AT
NIAAA HE PLAYED A KEY ROLE IN
FOSTERING EFFORTS TO PROMOTE
EVIDENCE-BASED RESEARCH AND ITS
IMPLEMENTATION IN EVERYDAY
PRACTICE.
AFTER HIS REQUIREMENT HE SERVED
AS CHAIR OF THE FRIENDS OF NIAAA
FROM 2018 TO 2023 WHERE HE
BROUGHT HIS EXPERTISE TO BEAR
AND EXPERIENCE TO BEAR TO
ADVANCE ALCOHOL RESEARCH MORE
BROADLY.
BOB, ON BEHALF OF NIAAA, I'M
VERY PLEASED TO PRESENT YOU WITH
THE 2024 HUGHES AWARD.
CONGRATULATIONS.
AND THERE'S SUPPOSED TO BE A
PLOT SOMEWHERE.
THERE IT IS.
BOB DID AN OUTSTANDING JOB WITH
THE FRIENDS OF NIAAA AND THEY'VE
BECOME MORE ACTIVE AND MORE
BROADLY ENGAGED IN OUR SOCIETY.
I THINK IT'S REALLY BEEN A GREAT
CONTRIBUTION.
OKAY.
>> OKAY, EVERYONE.
SO WE'RE AT THE POINT FOR
COUNCIL DISCUSSION.
WE HAVE 12 MINUTES.
SO IF THERE'S ANYTHING YOU
WANTED TO BRING UP, MOST PLEASED
TO HEAR IT.
IF YOU HAVE QUESTIONS ON WHAT I
JUST TALKED ABOUT, PLEASED TO
HEAR IT.
WE'LL HAVE OTHER CHANCES FOR
DISCUSSION TODAY BUT WE HAVE A
FULL SCHEDULE THIS AFTERNOON AND
IT'S VERY EXCITING.
WE HAVE 27 MINUTES ACCORDING TO
THIS BUT I WOULDN'T MIND IF --
WELL, IF YOU WANT TO END EARLY
WE CAN BECAUSE THEN YOU CAN GET
LUNCH AND WHAT I'M TRYING TO
ARGUE IS WE'LL START PROMPTLY AT
1:15 AND JOHN NGAI WILL JOIN US
AND WE'LL HAVE OTHER TALKS THIS
AFTERNOON.
ANY THOUGHTS OR QUESTIONS,
ANYTHING WE'RE MISSING AT NIAAA.
IS THERE SOMETHING HAPPENING IN
THE WORLD WE DON'T KNOW ABOUT?
KATIE.
>> WELL, I WAS GOING TO TURN IT
OVER TO DANE.
WE HAD A GOOD CONVERSATION ON
THE RIDE OVER HERE ABOUT
THOUGHTS ABOUT POSTDOC TRAINING
LIMITS AND ALSO SALARIES AND
JUST THE DIFFICULT BALANCE OF
THAT.
DANE, I'LL TURN IT OVER TO YOU.
>> YES, THE THINGS YOU CAN DO IN
THE PRE-MEETING UBER RIDE.
SO EARLIER IN THE SUMMER I THINK
IN JULY NIAAA SENT OUT AN RFI
CONCERNING POSTDOCS AND HOW TO
IMPROVE THEIR EXPERIENCE AS
ACADEMIC RESEARCHERS OR CLINICAL
RESEARCHERS.
AFTER TALKING TO SEVERAL OF MY
POSTDOCS AND OTHERS AS WELL AS
OTHER INVESTIGATORS THIS IS A
FAIRLY COMPLICATED ISSUE.
ONE OF THE DIFFICULTIES FOR US
AS INVESTIGATORS IS LONGEVITY,
KEEPING POSTDOCS ENGAGED AND IN
THE LABS AND OFTEN THEY'RE
MOTIVATED TO LEAVE FOR INDUSTRY
OR OTHER THINGS.
SO THE RECOMMENDATIONS IN THE
RFI DEALT WITH TIME LINE OF
POSTDOC SERVICE AS WELL AS
CHANGING THE FOCUS TO MORE
INNOVATION OVER PRODUCTIVITY.
THOSE WERE A COUPLE DISCUSSION
POINTS BUT REALLY IN OUR
DISCUSSION HEADING OVER TO THE
MEETING AND IT MOSTLY REVOLVES
AROUND MONEY AND SALARY AND
RESEARCH FUNDS.
I'M WONDERING IF THERE'S BEEN
FEEDBACK AT NIAAA YET.
THIS HAS NOT BEEN OUT THAT LONG
SO YOU MAY NOT HAVE FEEDBACK AND
CURIOUS ON OTHER PEOPLE'S
THOUGHTS ON THIS.
>> I'M GOING TO ASK LAURA
LEONARDI AND BRIDGET ON ZOOM, DO
WE HAVE ANY FEEDBACK?
I DON'T KNOW OF ANY.
>> NO, THIS IS BEING HANDLED AT
THE NIH LEVEL.
I DON'T KNOW IF PHILIPPE MAY BE
MORE FAMILIAR WITH IT BUT WE
DON'T HAVE ANY IN IT.
>> NO, I DON'T HAVE ANY
FEEDBACK.
SORRY.
>> WHEN WE GET FEEDBACK WE'LL
COME BACK TO YOU BECAUSE THERE'S
A LOT OF BALLS IN THE AIR.
WE DID INCREASE THE SALARY OF
OUR INTRAMURAL POSTDOCTORAL
FELLOWS BUT THE POSTDOCTORAL
FELLOWS HAVE NOW JOINED A UNION
AND THERE'LL BE FURTHER
DISCUSSIONS IN THE PROGRAM.
I DON'T FROM FURTHER
INFORMATION.
DAVE, DO YOU WANT TO SAY MORE
AND THEN WE'LL COME TO
EXTRAMURAL.
>> WE DON'T REALLY KNOW ANYTHING
MORE WHAT THE IMPACT'S GOING TO
BE.
THEY HAVEN'T GOT THE NEGOTIATION
BACK YET.
WHEN THEY DO WE'LL SEE.
AND ONE OF THE IDEAS WAS TO
ACTUAL
ACTUALLY RESTRICT THE K99 TO THE
FIRST TWO YEARS THAT'S SERIOUS
AND ALL THE EMPHASIS ON FUTURE
PLANS, NOTHING ON PRODUCTIVITY.
THAT'S A SERIOUS CHANGE.
I ENCOURAGE YOU TO FIND THE LINK
AND TAKE THE SURVEY.
THERE'S THINGS IN THERE YOU MAY
AGREE OR DISAGREE WITH AND I
THINK THEY NEED IT HEAR WHAT
YOU'RE GOING TO SAY.
THEY'LL ALSO RESTRICT THE TIME A
PERSON CAN BE IN POSTDOC TO FIVE
YEARS.
THESE ARE THE IDEAS PUT FORWARD
AND HAVE RATIONALE FOR THEM.
YOU CAN SEE IF YOU AGREE.
>> THE REASON FOR THE FIRST IS
THEY FEEL PEOPLE ARE IN
POSTDOCTORAL POSITIONS TOO LONG.
THAT'S THE RATIONALE THEY SHOULD
BE MOVED TO ANOTHER POSITION OR
FIND A NEW POSITION.
THE RATIONALE FOR THE FIRST TWO
YEAR K99 AS I UNDERSTOOD IT WAS
TO TAKE THE EMPHASIS OFF
PRODUCTIVITY AND BIG PAPERS AND
PUT IT ON THE IDEAS AND THE
INNOVATION.
>> THE DOWN SIDE OF THAT
RECOMMENDATION IS THAT WE'RE
ALREADY AT NIAAA HAVING LESS AND
LESS INDIVIDUALS APPLY FOR A
POSTDOCTORAL FELLOWSHIP.
NOW MAYBE THAT COULD BE
REVISITED TOO.
I ACTUALLY HAD ONE OR TWO
INDIVIDUALS WHEN I WORKED AT
SCRIPPS AND THEY CAME TO MY LAB
WITH THEIR FELLOWSHIP IN HAND.
AND EVERYTHING MAY SHIFT
BACKWARDS.
BUT IF WE MOVE THE K99 TO THE
EARLIER YEARS NO ONE WILL BOTHER
DOING AN F32.
IS THAT A GREAT LOSS?
I THINK WE'LL HAVE TO LOOK AT
ALL THESE DIFFERENT THINGS.
THERE'S BEEN A TENDENCY TO USE
POSTDOCS AS SOPHISTICATED
TECHNICIANS.
I CAN USE OTHER DESCRIPTIONS BUT
LET YOU USE YOUR IMAGINATIONS.
BUT I'VE LOOKED AT POSTDOCS AS
MY RESPONSIBILITY AS A MENTOR.
I'M STILL A MENTOR.
TO MOVE THEM INTO A POSITION AND
FURTHER ALONG IN THEIR CAREER.
THAT'S THE GOAL TO MOVE THEM
ALONG IN THEIR INDEPENDENT
CAREER.
A POSTDOCS WENT TO WORK AND
SHE'S HAPPY AS A CLAM.
AND SHE MADE A MAJOR
CONTRIBUTION TO THE NEUROSCIENCE
OF ADDICTION AND IT WASN'T THE
ONLY BOOK SHE'S ENGAGED.
KATIE.
>> I WANT TO APPLAUD THE K99
AWARDS AND IT'S A GREAT
MECHANISM AND GLAD WE'RE
SUPPORTING THOSE AND GETTING THE
WORD OUT ON THAT MECHANISM.
I REALLY SEE THAT AS A NICE WAY
TO BRIDGE FOLKS TO INDEPENDENCE
WITH THAT MECHANISM SO THANK YOU
FOR THAT.
AND THANKS FOR YOUR LEADERSHIP
OF THAT.
>> I THINK WE HAD A STRAIGHT
LINE INCREASE IN THE NUMBER OF
TRAINING AWARDS IN MY TENURE?
>> I BELIEVE THAT'S CORRECT.
WE DO HAVE A FIGURE OUT.
I'LL GO FIND IT BUT YOU'RE
CORRECT.
THERE'S A LINEAR INCREASE.
IF THEY INCREASE MORE SALARIES
WE'LL HAVE TO COMMIT MORE TO
TRAINING.
I DON'T HAVE A PROBLEM WITH THAT
BUT MY BUDGET OFFICER MIGHT.
IT'S A QUESTION OF GETTING OUR
PRIORITIES STRAIGHT AND DECIDING
HOW TO SPEND OUR MONEY.
I'M VERY MUCH IN FAVOR OF THE
TRAINING PART MYSELF.
WE HAVE TO BALANCE IT WITH OTHER
RESPONSIBILITIES THAT ALSO NEED
HELP.
>> CAN I ADD TO WHAT DAVE SAID
ABOUT THE RFI, I WANT TO REMIND
EVERYONE IT CLOSES OCTOBER 23.
THERE'S STILL PLENTY OF TIME TO
RESPOND AND I PUT A LINK IN THE
CHAT FOR PEOPLE ON ZOOM.
>> THANK YOU, BRIDGET.
THAT'S VERY HELPFUL.
IT'S NOT CLOSED YET.
IF ANYBODY HAS IDEAS I'M HAPPY
TO ENTERTAIN THEM AND HAPPY TO
CONVEY THEM TO THE OTHER I.C.
DIRECTORS IF WE HAVE SOMETHING
UNIQUE WE THINK OTHER PEOPLE
SHOULD CONSIDER.
>> THERE'S MORE OF A QUESTION
ABOUT ONE OF THE REASONS WHY WE
MIGHT HAVE A SOMEWHAT LEAKY
PIPELINE WITH POSTDOCS THAT HAS
TO DO WITH HEALTH INSURANCE.
THERE'S BEEN LESS THAN ADEQUATE
COVERAGE FOR FAMILIES, FOR
EXAMPLE, IN THE T32.
SO I DON'T KNOW WHETHER THAT'S
CHANGED IN THE PAST FEW YEARS.
IT WAS A BIG DEAL.
IT'S A HARDSHIP FOR FAMILIES WHO
HAVE CHILDREN.
PLEASE CORRECT ME IF I'M
INFORMATION IS WRONG BUT I
BELIEVE IT JUST COVERS THE
INDIVIDUAL.
IT PROVIDES SINGLE COVERAGE BUT
NOT FAMILY.
>> YOU HAVE TO BALANCE HOW MUCH
YOU HAVE TO A LOT FOR INSURANCE
VERSUS OTHERS.
>> SO IT'S A SITE DECISION
INSTITUTIONS ARE HAVING TO MAKE
AND I BELIEVE AT BROWN THERE'S
BEEN RESOURCES PROVIDED TO THE
PROGRAM SO THERE WASN'T A
DISCREPANCY IN THE BENEFITS
PROVIDED BUT IT DOES THEN TAKE
MONEY FROM ELSEWHERE INCLUDING
THE RELATIVELY SMALL AMOUNT
THAT'S AVAILABLE FOR
COORDINATION.
>> AND THERE'S A LOT OF
VARIABILITY ACROSS T32s AND HOW
THEY HANDLE THIS.
SOME DON'T OFFER HEALTH
INSURANCE AT ALL.
WE DO AT OUR T32 BUT IT'S
LIMITED.
>> THANK YOU FOR CLARIFYING.
>> WE DO HAVE SOME FAMILY PLANS
BUT IT'S PRETTY LIMITED BECAUSE
THEY HAVE TO GO TO THE EXCHANGE.
>> SO IT FEELS LIKE IT'S A
RETIREMENT THE SITES HAVE TO
FIGURE OUT AND THAT WILL CREATE
INEQUITIES WITHIN T32 AT A
MINIMUM.
IS
>> DOES STAFF NOW HOW THEY ARE
ALLOCATED FOR INSURANCE?
ALICIA, DO YOU KNOW?
>> INDIVIDUAL T32s ARE PROVIDED
A STIPEND FOR CHILDCARE.
[OFF MIC]
>> THE HEALTH PART IS PART OF
TRAINING RELATED EXPENSES IS
LIKE AN OVER ALL AMOUNT THAT
INCLUDES HEALTH.
>> I'LL LOOK INTO IT AND FIND
OUT WHAT OTHER I.C.s ARE DOING
AND HOW THEY DEAL WITH THE T32s.
>> I FEEL THE NEED TO SAY AT
LEAST THAT PHYSICIAN TRAINING IS
VERY DIFFICULT AS A T32 AS A
MECHANISM.
I WAS READING ON MED SCAPE
BEFORE I SAID ANYTHING BUT IN 30
YEARS AS THE BEEN 4.4% OF THE
SCIENTISTS IN THE FIELD WERE
PHYSICIANS AND NOW IT'S AT 1.5%.
IT'S A MAJOR ISSUE.
I FOUND AS BEING A T32 DIRECTOR
OVER 20 YEARS AND OUR FELLOWSHIP
IS 30 IT'S BECOME HARDER AND
HARDER TO RECRUIT PHYSICIANS
INTO CLINICAL RESEARCH CAREERS.
I DON'T HAVE AN ANSWER FOR IT
BUT I WOULD LOVE IDEAS.
I HAVE NO CLEAR ANSWER FOR IT
BUT IT'S A HUGE ISSUE AND MOST
PANELS I'M ON I'M OFTEN THE ONLY
PHYSICIAN ON THE PANEL.
I THINK IT'S A HUGE PROBLEM A
LOT OF THE INTERVENTIONS IN
MEDICINE HAVE BEEN THROUGH
PHYSICIAN SCIENTISTS AND TO LOSE
THAT POPULATION I THINK IS
REALLY TRAGIC.
I DON'T KNOW HOW TO ADDRESS IT
BUT I HAVE A LOT OF OPINIONS
ABOUT IT.
>> I'M AFRAID IT'S GENERALIZED
TO ALL THE INSTITUTES IT'S BEEN
A STRUGGLE.
I DON'T KNOW THE ANSWER EITHER.
I DO THINK THE PROLIFERATION OF
ADDICTION MEDICINE FELLOWSHIPS
IS A GOOD THING GENERATING MORE
INTEREST FOR PHYSICIANS TO AT
LEAST BE COGNIZANT.
>> BETWEEN ADDICTION PSYCHIATRY
AND MEDICINE THERE'S OVER 100
FELLOWSHIPS MANY REMAINING HALF
FILLED SO HOW DO WE GET MORE
INTEREST AND WITH THE OPIOID
FACTOR MEDICAL STUDENTS ARE
CLAMORING FOR MORE TRAINING BUT
IT'S NOT NECESSARY TRAINING FOR
PEOPLE GOING INTO CLINICAL
RESEARCH BECAUSE AFTER ALL THEIR
STUDENT LOANS AND EVERYTHING
EVEN ONE YEAR OF FELLOWSHIP IT'S
HARD TO RECRUIT.
THEY DON'T SEE THE BENEFIT WHEN
THEY GO RIGHT INTO A FIELD.
THERE'S A LOT OF FACTORS BUT I
AGREE HAVING MORE FELLOWSHIPS IS
A GREAT THING.
>> YOU MENTIONED GOOD POINTS
ABOUT THE TRAINING.
WE'LL GET MORE INFORMATION FROM
WHAT WE DO AND WHAT OTHER
INSTITUTES DO.
WHEN THE INFORMATION COMES IN
FROM THE RFI IT SHOULD BE AN
EYE-OPENER.
I'LL BE CURIOUS TO SEE.
THERE'S A WHOLE GROUP OF PEOPLE
WHAT AND THE THE K99s TO GO
EARLIER NOT LATER TO SAVE THE
F32s.
>> I THINK I'M IN FAVOR OF THE
LATTER SAVING F32s.
I CAN SEE THE DRIVE FOR THE
INNOVATIVENESS.
AND I THINK WE'LL PROBABLY HAVE
A BRIEFING ON THIS AT OUR NEXT
COUNCIL, PHILIPPE, MAYBE WE
SHOULD DO SOMETHING ABOUT THIS
BUT I KNOW CSR IS CHANGING HOW
AUTHOR EVALUATING GRANTS AND
THAT'S KICKING IN IN 2025.
>> STARTING WITH THE DUE DATE OF
JANUARY 2025, THE CSR IS
IMPLEMENTING THE SIMPLIFIED
REVIEW FRAMEWORK FOR GRANT
APPLICATIONS.
IT'S A NEW WAY TO APPLY.
>> AND INNOVATIVENESS AND NOT SO
MUCH THE PRODUCTIVITY OF THE
APPLICANT AND NOT SO MUCH OF THE
APPLICANT OR MENTOR ARE GOING TO
BE HIGHLIGHTED.
SO IT'S GOING -- IT'S A BIT OF A
BIG SHIFT.
SO TUNE INTO CSR AS WELL.
ONE THING THAT CAME UP THIS
MORNING AT THE I.C. DIRECTOR'S
MEETING I THOUGHT WAS
FASCINATING WAS THERE'S A
PROGRAM INSTITUTED BY COSWOOD.
CAN YOU EXPLAIN THE ACRONYM?
>> IT'S THE CHIEF OFFICER FOR
SCIENTIFIC WORKFORCE DIVERSITY.
>> RIGHT.
SO THEY REACHED OUT TO A NUMBER
OF MINORITY-SERVING INSTITUTIONS
ACROSS THE UNITED STATES AND
START A PROGRAM OF MATCHING
INDIVIDUALS WHO WANT TO WRITE A
GRANT WOMAN A PROGRAM OFFICER AT
AN NIH INSTITUTE.
IT'S PRETTY COOL AND JUST GOT
OFF THE GROUND AS I UNDERSTAND
IT.
AND SOMEONE ASKED WELL WHAT
ABOUT HAVING MOCK STUDY SECTIONS
SO THEY CAN UNDERSTAND HOW
GRANTS ARE ACTUALLY REVIEWED.
AND NONI BURNS SAID THEY'RE
DEVELOPING A RESOURCE INDIVIDUAL
OF A MOCK STUDY SECTION AT CSR.
SO STAY TUNED TO CSR AS WELL
THERE'S CHANGES COMING IN THE
NEW YEAR.
>> I WOULD ALSO SAY ON THE
OFFICE OF EXTRAMURAL RESEARCH
WEBSITE THEY HAVE A NUMBER OF
RESOURCES AVAILABLE INCLUDING
MOCK STUDY SECTION REVIEWS AND
ONLINE CONFERENCES THEY'VE HAD
IN THE PAST THAT COULD BE
INCREDIBLY HELPFUL.
>> DO WE HAVE PLACES ON OUR
WEBSITE WHERE PEOPLE CAN FIND
THOSE AS WELL OR LINKS TO THEM?
>> SO, WE'RE ACTUALLY WORKING ON
REVITALIZING SOME AREAS ON OUR
WEBSITE INCLUDING THE MINORITY
HEALTH AND HEALTH DISPARITIES
PAGE.
THOSE RESOURCES WILL BE LINKED
THERE AND WE'RE ALSO LOOKING AT
AND THIS IS GOING TO PHILIPPE'S
OFFICE THE OFFICE OF EXTRAMURAL
ACTIVITIES AND LOOKING AT THE
GRANTS MANAGEMENT SECTION ON OUR
WEBSITE TO PROVIDE LINKS THERE
AS WELL.
>> THAT'S A BEE IN MY BONNET
RIGHT NOW.
THAT'S SOMETHING WE'LL START
WORKING ON NEXT YEAR.
I WANT TO SEE IF WE CAN MAKE
SURE OUR CENTERS HAVE A WEBSITE
AND THIS WEBSITE IS SOMEHOW
LINKED TO OUR NIAAA WEBSITE.
I'M NOT SURE -- I DON'T THINK
WE'VE EVER EXPLORED THIS AND
WE'RE NOT GOING TO BE ABLE TO DO
IT BEFORE THE END OF THE YEAR.
THIS HAS TO BE A FOR 2025.
THERE'S TOO MUCH GOING ON RIGHT
NOW.
>> SOME ARE LINKED THROUGH OUR
WEBSITE.
WE HAVE A WEB PAGE WITH JUST
CENTERS ON IT.
WE HAVE A HEAD START I GUESS YOU
COULD SAY ON THAT PROJECT.
>> THAT'S GOOD, BRIDGET.
I WANT TO SEE WHAT'S ON EACH
WEBSITE.
I HAVE TO DO THAT MYSELF AS
WELL.
ARE THERE COMMON ELEMENTS WE
WANT TO SEE ON EVERYBODY'S
WEBSITE.
OUR CENTERS SHOULD BE
AMBASSADORS LIKE YOU SHOULD BE
FOR THE ALCOHOL FIELD.
AND OUR CENTERS BECAUSE THE
BUDGET HASN'T CHANGED SINCE
1977, WHAT I HAVE CHANGED IS
EACH CENTER IS MORE FOCUSSED ON
A GIVEN DOMAIN OF ACTIVITY LIKE
MICROBIOME OR EPIGENETICS OR
TREATMENT.
I WANT TO SEE WE ALSO
COORDINATE -- THAT PEOPLE KNOW
THAT'S A TREATMENT ORIENTED
CENTER.
THAT'S WHERE CLINICAL STUDIES
ARE BEING DONE OR HUMAN LAB
STUDIES.
I DON'T KNOW WHETHER WE HAVE A
CENTER THAT DOES HUMAN LAB
STUDIES BUT ANYWAY.
OKAY.
>> ARE THERE ANY COMMENTS FROM
ANYONE ON ZOOM?
>> GOOD POINT, PHILIPPE.
ANYBODY ON ZOOM HAVE ANYTHING
THAT WE'VE MISSED?
WE'LL ALL BREAK FOR LUNCH EARLY.
SO I THINK WE'LL BREAK FOR LUX,
FOUR MINUTES EARLY AND YOU HAVE
A MAP AND KNOW WHERE TO GET
FOOD, RIGHT?
EVERYBODY HAS THE MAP?
IT'S A PLEASURE TO HAVE JOHN
NGAI ON COUNCIL TODAY AT NIAAA.
HE'S THE DIRECTOR OF THE BRAIN
RESEARCH THROUGH INNOVATIVE
NEURO TECHNOLOGIES HE EARNED HIS
BACHELOR'S DEGREE FROM POMONA
COLLEGE, CLAREMONT, CALIFORNIA
AND CAL TECH PASADENA AND WAS AT
THE COLLEGE OF PHYSICIANS AND
SURGEONS BEFORE STARTING IN A
FACULTY POSITION AT THE
UNIVERSITY OF CALIFORNIA,
BERKELEY.
OVER 27 YEARS AS A BERKELEY
FACULTY MEMBER, HE TRAINED 20
UNDERGRADUATE STUDENTS, 24
GRADUATE STUDENTS AND 15
POSTDOCTORAL FELLOWS.
IN ADDICTION TO TEACHING WELL
OVER 1,000 STUDENTS IN THE
CLASSROOM.
HIS WORK HAS LED TO SCIENTIFIC
ARTICLES IN THE MOST PRESTIGIOUS
JOURNALS AND 10 U.S. AND
INTERNATIONAL PATENTS.
HE RECEIVED MANY AWARDS FROM THE
SLOAN FOUNDATION, HUGH
CHARITABLE TRUST.
AS A FACULTY MEMBER HE SERVED AS
DIRECTOR OF BERKELEY'S GRADUATE
PROGRAM AND NEURAL SCIENCE
INSTITUTE AND PROVIDED EXTENSIVE
SERVICES ON COUNCIL SERVICES AND
STARING GROUP AND CO-CHAIR OF
THE BRAIN INITIATIVE CELL CENSUS
CONSORTIUM STEERING GROUP.
HE OVERSEES THE LONG-TERM
STRATEGY AND DAY TO DAY
OPERATIONS OF THE BRAIN
INITIATIVE AS IT STRIVES TO
REVOLUTIONIZE OUR UNDERSTANDING
OF BRAIN AND DISEASE.
HE'LL TELL US ABOUT THE BRAIN
INITIATIVE AND KIND OF OVERVIEW
OF ACCELERATING DISCOVERY
TOWARDS CURES.
I FIRST HEARD A VERSION OF THIS
TALK THAT SPAWNED MY INTEREST IN
HAVING US JOIN OUR COUNCIL WHEN
WE MET AT AN A TRANSLATIONAL
NEURAL SCIENCE MEETING AND GAVE
THE TALK TO A BROAD RANGE OF
INDIVIDUALS SO I'M HOPING IT
WILL BE A SIMILAR BROAD RANGE
TODAY.
IT'S ALL YOURS, JOHN.
THANK YOU FOR THE OPPORTUNITY TO
TELL YOU ABOUT THE BRAIN
INITIATIVE.
CAN YOU SEE THE PROPER SCREEN?
GEORGE TALKED ABOUT THE BRAIN
INITIATIVE TO ADVANCE THE
INNOVA
INNOVATIVE NEURAL TECHNOLOGIES
AND THERE'S THE REALITY THE
HUMAN BRAIN IS SO COMPLEX.
IT COMPRISES 86 TO A BILLION
NEURONS AND THEY MAKE TRILLIONS
OF CONNECTIONS THAT UNDER PIN
OUR ABILITY TO SENSE, MOVE, TO
HAVE EMOTION, TO BE CONSCIOUS
AND HAVE SPIRITUALITY AND
UNIQUELY DIFFERENT FROM EACH
OTHER.
THE REALITY IS WE DON'T YET HAVE
THE TOOLS TO UNDERSTAND HOW THIS
AMAZING ORGAN FUNCTIONS.
IF WE DON'T KNOW HOW IT
FUNCTIONS NORMALLY WE WON'T HAVE
A CHANCE OF UNDERSTANDING WHAT
GOES WRONG IN DISEASE AND DEVISE
CURES AND INTERVENTIONS FOR
FOLKS LIVING WITH DISORDERS OF
THE NERVOUS SYSTEM.
THAT'S IN A NUTSHELL THE
MOTIVATION BEHIND THE BRAIN
INITIATIVE.
THE BRAIN INITIATIVE SPANS 10 OF
THE 27 INSTITUTES AND CENTERS
AND BECAUSE WE'RE DISEASE
AGNOSTIC OUR GOAL IS TO CREATE
AND IMPLEMENT TOOLS IN A DISEASE
AGNOSTIC WAY IN SERVICE OF THE
MISSIONS FOR ALL THE BRAIN I.C.s
AND BEYOND OUR GOAL IS TO
DISSEMINATE AND DEMOCRATIZE
THESE RICHES FOR THE BENEFIT OF
ALL THE REALM OF BASIC DISCOVERY
AS WELL AS CLINICAL
APPLICATIONS.
SINCE STARTING WE FUNDED BY NOW
OVER 1600 AWARDS TO OVER 1700
P.I.s ACROSS THE COUNTRY AND
SUPPORT VARIOUS INTERNATIONAL
COLLABORATIONS.
IN THE UPPER RIGHT HAND CORNER I
SHOW THE KINDS OF JOURNALS FOLKS
HAVE BEEN PUBLISHING IN.
WHAT'S UNIQUE ABOUT BRAIN IS
THAT WE ARE LEVERAGING AND
BRINGING IN EXPERTISE FROM
MULTIPLE FIELDS OUTSIDE OF
BIOLOGY AND FOLKS FROM THE
PHYSICAL SIDE AND COMPUTATION TO
BRING TO BEAR NEW WAYS OF
THINKING HOW TO SOLVE THE
MYSTERIES OF THE MOST COMPLEX
ORGAN.
THE GROUP HAS BEEN WELL
PUBLISHED AND IF IT'S ON THE
LEADING EDGE I MAY WE WILL HAVE
BEEN FUNDED BY THE BRAIN
INITIATIVE.
I DON'T HAVE TIME TO GO THROUGH
THE ENTIRE PORTFOLIO BUT TO SAY
THE SCIENCE WE SUPPORT ON THE
LEFT IS THE PRIME SCIENTIFIC
AREAS.
THE FIRST BEING DEVELOPING NEW
TOOLS TO BETTER UNDERSTANDING
THE CELLS AND CIRCUITS THAT
UNDERPIN ALL THE BRAIN DOES.
THE SECOND WILL BE ON NEURAL
RECORDING AND UNDERSTANDING
FUNDAMENTALS AND A COOL PROGRAM
THAT APPLIES THESE NEW RECORDING
AND MODULATION TECHNOLOGIES IN
HUMANS AND FIRST IN HUMAN
CLINICAL TRIALS.
WE HAVE A VERY STRONG PROGRAM IN
NEURAL IMAGING ACROSS SCALES NOT
ONLY NON-INVASIVE NEURAL IMAGING
AND OTHER MODALS.
WE HAVE A SCHOOL SYSTEMS
PROGRAM.
THE PORTFOLIO SUPPORTS RESEARCH
IN HOUSE IT USES INNOVATIVE
APPROACHES AND ONE BRAIN-FUNDED
BRAMS -- PROGRAMS IS LEVERAGING
LARGER TEAMS TO COME TO BEAR ON
THE HIGHLY COMPLEX PROBLEMS AN
IN THE GRANT SESSIONS THESE ARE
MULTIINSTITUTION LARGE CONSORTIA
THAT REQUIRE THE DIRECTOR
INTEGRATION OF THEORY OF WHAT
THE SCIENCE IS PURSUING.
AND FINALLY OVERLAPPING IS THE
FUNDING IN HUMAN NEURAL SCIENCE
IT INCLUDES WHAT WE CALL OUR
RESEARCH OPPORTUNITIES IN HUMANS
PORTFOLIO.
THERE ARE PATIENTS WHO ARE
UNDERGOING TREATMENTS FOR OTHER
OPPORTUNITIES FOR PROBING
MECHANISMS OF SAY MEMORY,
STORAGE AND RETRIEVAL AND
SPATIAL NAVIGATION AND SO FORTH
WHILE UNDERGOING TREATMENT COULD
BE RECORDING AND THIS IS A HUGE
OPPORTUNITY WE'VE SET UP HERE
BUT ALSO RECOGNIZE THERE'S MANY
ETHICAL ISSUES AND EXCITING
PROGRAMS THERE.
THEN WE HAVE FOUR CROSS CUTTING
AREAS WITH DATA SCIENCE AND
INFORMATICS.
IMAGINE THE DELUGE OF DATA THAT
THE FIELD IN GENERAL ARE
CREATING AND IT'S IMPORTANT TO
THINK AHEAD ABOUT HOW BEST TO
LEVERAGE THAT AND RIGHT NOW
THERE'S A HUGE OPPORTUNITY BUT
RISKS WITH ARTIFICIAL
INTELLIGENCE AND WE'RE HOPING TO
EMBRACE THAT FULLY.
WE'RE COMMITTED TO ESTABLISHING
A GOOD PIPELINE TO ASSURE WE
HAVE A GOOD SOURCE OF NEXT
GENERATION LEADERS THAT WILL
TAKE OVER WHEN WE RIDE OFF IN
THE SUNSET.
WE HAVE A ROBUST TRAINING THERE
WITH A HEAVY FOCUS ON INCLUSION
AND EQUITY.
WE HAVE A NEURAL ETHICS PROGRAM
THAT FOCUSES ON NEURAL ETHICAL
ISSUES ASSOCIATED WITH THE WORK
WE'RE DOING AND DISSEMINATION
FOCUS TO MAKE SURE THE
TECHNOLOGIES AND RESOURCES
CREATED GET OUT FOR THE BENEFIT
OF ALL.
I WANT TO GO OVER THE BIG
PROJECTS LAYING DOWN THE FUTURE
FOR DISCOVERY ACCELERATING
TOWARDS CURES RATHER SOONER THAN
LATER.
IN 2022 WE LAUNCHED THE BRAIN
2.0 TRANSFORMATIVE PROJECT.
PROVIDING INFORMATION ABOUT
NEURAL CIRCUITS AND WAYS OF
INTERROGATING AND MODULATING
THEM TO TEST BETTER HYPOTHESES
ABOUT HOW NEURAL SECTOR
FUNCTIONS UNDER PIN DEVELOPMENT
AND DRIVE THEM TOWARDS NEURAL
CIRCUITRIES IN HUMANS AND
THERE'S THE BRAIN INITIATIVE
CELL ATLAS NETWORK TO MAP THE
BRAIN CELL TYPES ACROSS MULTIPLE
SPECIES WITH AN EMPHASIS ON THE
HUMAN BRAIN.
THE NEXT IS THE SO-CALLED PARTS
LIST AND NEXT IS THE WIRING
DIAGRAM.
THE TOOLS AND TECHNOLOGIES
NEEDED TO CREATE WHOLE BRAIN
WIRED DIAGRAMS IN THE MOUSE AND
SYNAPSE RESOLUTION IN BIG BRAINS
AND NON HUMAN PRIMATES TO GIVE
US THE LOGIC MUCH THE WIRING
BETWEEN THESE DIFFERENT
COMPONENTS.
BETWEEN THESE TWO PROJECTS THIS
WILL PROVIDE THE TRUTH FOR WHAT
A NEURAL CIRCUIT LOOKS LIKE AND
ASK BETTER QUESTIONS.
HERE I BRING IN THE
ARMAMENTARIUM FOR THE LARGE TOOL
KIT FOR ACCESSING THE IDENTIFIED
CELL TYPE AND CIRCUITS TO START
ASKING HOW DO THE CELL TYPES AND
CIRCUITS TO VARIOUS BEHAVIORAL
OUTPUTS ULTIMATELY WITH THE GOAL
OF STANDING UP PRECISION CIRCUIT
THERAPIES AND HOPEFULLY ONE DAY
PRECISION GENE THERAPIES.
LET ME GO START WITH THE BRAIN
INITIATIVE CELL CENSUS PROJECT.
THE GOAL IS TO CREATE ATLASES
AND CENSUSES OF WHOLE MAMMALIAN
BRAINS.
IT STARTED IN 2014 AT THE START
OF THE BRAIN INITIATIVE.
AS THE CELL CENSUS CONSORTIUM.
BACK AS A FACULTY MEMBER AT
BERKELEY I WAS PART OF THIS
GROUP AND 10 PILOT PROJECTS.
THE GOAL WAS TO DEVELOP AND
VALIDATE POTENTIALLY SCALABLE
TECHNOLOGIES THAT WOULD GIVE US
THESE COMPREHENSIVE CELL ATLASES
OF MAMMALIAN BRAINS.
THAT WAS QUICKLY SCALED TO THE
BRAIN INITIATIVE CELL CENSUS
NETWORK.
AGAIN, I WAS FORTUNATE TO BE
PART OF THIS GROUP BEFORE
JOINING NIH IN 2020.
HERE THE GOAL WAS TO REVOLUTION
I'D OUR ABILITY TO CLASSIFY CELL
TYPE ON THEIR MOLECULAR AND
PHYSIOLOGICAL PROPERTIES.
AND THE IDEA WAS TO CREATE A
COMPREHENSIVE CELL CENSUS OF THE
MOUSE BRAIN AND THE NEXT STEP IS
THE GENERATION OF COMPREHENSIVE
CELL ATLASES OF NON HUMAN
PRIMATE AND HUMAN BRAINS.
IN 2022 WE LAUNCHED THE BRAIN
INITIATIVE CELL ATLAS NETWORK.
I WANT TO TOUCH ON THE PROGRESS
WE'VE MADE SINCE THE INCEPTION.
THERE'S BEEN A NUMBER OF BIG
PAPER GROUPS PUBLISHED OVER THE
PAST YEARS STARTING IN 2021 THAT
BICCN PUT TOGETHER 27 ARTICLES
IN JOURNALS LOOKING AT THE
PRIMARY MOTOR CORTEX ACROSS
MULTIPLE MAMMALIAN SPECIES,
MICE, NON HUMAN PRIMATES AND
HUMANS CALLED THE MINI ATLAS
PROJECT AND ESTABLISHED OUR
ABILITY TO TACKLE WHOLE BRAINS.
THEN IN DECEMBER OF 2023 THE
GROUP PUBLISHED A SERIES OF 10
PAPERS IN NATURE, NINE OF WHICH
WERE BRAIN FUNDED DESCRIBING A
COMPREHENSIVE CELL ATLAS OF THE
ENTIRE MOUSE BRAIN.
IN THE FALL LAST YEAR THE GROUP
PUBLISHED SPECTACULAR PAPERS, 21
ARTICLES IN JOURNALS PROVIDING A
DRAFT HUMAN AND NON-HUMAN
PRIMATE BRAIN CELL ATLAS.
LET ME WALK THROUGH THIS WITH
YOU TO GIVE YOU A FEEL OF WHAT
WE HAVE AND WHAT FUTURE
OPPORTUNITIES ARE.
IN 2021 THE GROUP PUBLISHED A
MULTI-MODAL CENSUS OF PRIMARY
MOTOR CORTEX IN HUMANS, NONHUMAN
PRIMATES AN MICE.
THERE WAS SOCIAL ENGINEERING
THAT WENT ON TO ESTABLISH A
GROUP THAT COULD WORK TOGETHER
COMPRISING OVER 250 RESEARCHERS
SETTING THE STABLE FOR THE
LARGER ATLASES TO FOLLOW IN THE
COMING YEARS.
WE LEARNED ABOUT THE PRINCIPLES
UNDER THE CLASSIFICATION OF CELL
TYPE IN THE MAMMALIAN BRAIN IN
2021.
IN 2023 WE HAD THE WHOLE MOUSE
BRAIN CELL ATLAS.
THIS WAS INCREDIBLE.
IT WAS BREATHTAKING TO SEE THE
ANALYSIS.
IT WAS BASED ON AN ANALYSIS OF
OVER 32 MILLION CELLS ANALYZED
BY SINGLE CELL APPROACH THAT LED
TO THE IDENTIFICATION OF OVER
5,000 STATISTICALLY SQUISH
SQUISHABLE -- DISTINGUISHABLE
CELL TYPE, I'LL CALL LOOSELY AND
IDENTIFIED OTHER FEATURES
INCLUDING REGULATORY NETWORKS
GIVING RISE TO THE CELLS AND SO
FORTH.
IT'S GOING TO KEEP US BUSY MANY
YEARS TO COME.
FINALLY THE DRAFT ATLASES IN
BRAINS MAPPED THESE BIG BRAINS
WITH UNPRECEDENTED COMPLEXITY
ACROSS SPACE.
NOT ONLY HAVING MOLECULAR
INFORMATION BUT LOCATION
INFORMATION ABOUT THE CELLS IN
DIFFERENT NON HURMAN PRIMATE AND
HUMAN SPECIES TO UNDERSTAND THE
EVOLUTION AND SPECIALIZATION
BETWEEN US AND OUR CLOSEST NON
PRIMATE RELATIVES AS WELL AS
ACROSS DEVELOPMENT TIME AS WELL
AS AGING WHICH HAVE GREAT
BENEFIT FOR UNDERSTANDING NEURAL
DEVELOPMENT DISORDERS AND
DISORDERS OF AGING.
THIS PAVES THE WAY TO
UNDERSTANDING HUMAN BRAIN IN
HEALTH AND DISEASE AND ACTING ON
THE INFORMATION MOVING FORWARD.
THE GOAL OF THE THIRD PHASE OF
THE CELL CENSUS PROJECT IS TO
MOVE BEYOND GENERATING A TON OF
DATA ACROSS MANY MODALITIES TO
CREATE A NEW KNOWLEDGE BASE.
PEOPLE CAN USE THIS AS AN
ACTIONABLE RESOURCE.
IT'S ALREADY STARTING TO BE
ROLLED OUT INTO OUR BRAIN I.C.s.
FOR EXAMPLE THROUGH THE SCORCH
INITIATIVE, SINGLE CELL
INITIATIVE LAUNCHED BY THE
NATIONAL INSTITUTE ON DRUG ABUSE
TO LOOK AT THE CELLULAR CHANGES
THAT MIGHT HAPPEN IN MODELS OF
OPIOID ADDICTION INTERSECTS WITH
HIV INFECTION.
AS WELL AS THE NIDA NEXUS
LOOKING AT THE ENSEMBLES
ASSOCIATED WITH SUBSTANCE USE
DISORDER.
IN THE DEGENERATION SPACE THE
DIRECT OUTPUT OF THE VICCN WAS
USING RESOURCES TO STAND UP TO
SEATTLE ALZHEIMER'S DISEASE
BRAIN CELL ATLAS.
A GROUP BASED OUT OF SEATTLE
USING THE KNOW-HOW TO LOOK AT
THE HISTORY OF PROGRESSION OF
ALZHEIMER'S DISEASE IN A COHORT
OF PATIENTS AS IDENTIFIED
CHANGES OF THE DIFFERENT EARLY
AND LATE STAGES THAT PLAY SIGNAL
WHAT CELL TYPE AND GENE AND
REGULATORY PATHWAYS WE MAY THINK
TO TARGET THAT MIGHT LEAD TO
CURES AND PREVENTION AND NOT
JUST TREATMENTS THAT SLOW THE
DISEASE.
WE'RE EXCITED ABOUT SEEING THE
RESOURCES BEING ROLLED OUT MORE
BROADLY ACROSS THE NEUROSCIENCE
FIELD.
THE SECOND IS THE CONNEX
PROGRAM.
WE JUST RECENTLY FUNDED 11 BIG
PROJECTS SUPPORTING RESEARCH
TEAMS ACROSS 40 UNIVERSITIES
INCLUDING COLLABORATIONS.
THESE FOLKS WILL BE TASKED WITH
DEVELOPING AND IDENTIFYING AND
DEVELOPING SCALABLE TECHNOLOGIES
THAT CAN BE ROLLED OUT TO LOOK
AT ENTIRE BRAINS AT THESE
DIFFERENT LEVELS OF RESOLUTION,
SYNAPSE RESOLUTION IN MICE AND
AXON RESOLUTION IN HUMANS AND
NON HUMAN PRIMATES.
RIGHT NOW WE DON'T HAVE THE
TECHNOLOGIES TO SCALE UP AND
WE'VE ADOPTED THE APPROACH OF
THINKING BIG AND SCALING SMALL
AND FAST.
USING THE SUCCESS OF THE CELL
CENSUS PROJECT WE HOPE TO
DEVELOP HIGH RESOLUTION MAPS.
THEY'RE FOCUSSED ON DEVELOPING
COMPLIMENTARY METHODS COVERING
THREE CORE TECHNOLOGIES.
THE WORKHORSE IS
ELECTROMICROSCOPY AND THIS IS
WORK IN THE MICRONS PROJECT MANY
FOLKS HAVE GONE ON TO SUPPORT
HERE IN THE BRAIN CONNECTS
PROJECT.
THE NEXT IS TO USE MOLECULAR
TECHNIQUES TO GIVE GREATER
THROUGHPUT TO AUGMENT WHAT WE
LEARN IN THE E.M. STUDIES AND IN
BIG BRAIN LOOKING AT LARGER
REGIONS OF CONNECTIVITY AND NEED
OPTICAL TECHNIQUES TO GET TO THE
MICRON SCALE OF CONNECTOMIC
SCALE.
SINCE THE TIME WE CONCEIVED THE
PROJECT IN 2021, '22 TO NOW
WE'VE SEEN HUGE LEAPS IN THE
REALM OF SEGMENTATION AND WILL
GET THERE IN THE NEXT FIVE TO 10
YEARS.
WITH THE GROUND TRUTH
INFORMATION ABOUT THE CELL TYPES
AND CONNECTIVITY WE WANT TO
INTERROGATE AND MODULATE THESE
CIRCUITS.
THIS LEADS TO THE ARMAMENTARIUM
FOR PRE VISION BRAIN CELL ACCESS
AND HAVE DEVELOPMENT OF ACCESS
TOOLS THAT ARE BETTER AND BETTER
DELIVERY VECTORS AND GENE
REGULATORY ELEMENTS WE'RE
LEARNING ABOUT TO GET THESE PAY
LOADS INTO SPECIFIC CELL TYPES
WITH GREATER PRECISION.
OF COURSE THE PAY LOADS ARE
DEVELOPING BETTER ACTUATORS AND
HEMOGENETIC TOOLS AND GENE ET
TORS TO GET IN THERE AND MAKE
SURE THESE ARE MADE AVAILABLE TO
THE FOLKS IN THE FIELD.
THE PROJECTS ARE ALREADY QUITE
ACTIVE AND PRODUCTIVE.
THEY'RE CREATING GREAT TOOLS FOR
TARGETING BASED ON ENGINEERING
AND AAV AND IDENTIFYING GENE
REGULATORY AIL MANIES TO GET
GREATER SPECIFICITY.
WE'RE WORKING HARD TO MAKE SURE
THESE ARE AVAILABLE TO THE
BROADER RESEARCH COMMUNITY.
WE FUND DIFFERENT DISSEMINATION
CORES AROUND THE COUNTRY.
WE'VE PARTNERED WITH A SPECIAL
PAGE FOR BRAIN INITIATED
RESOURCES THERE WERE OVER 2900
ENTRIES YESTERDAY AND IT'S A
GREAT RESOURCE FOR FOLKS TO GET
THEIR HANDS ON THESE COOL TOOLS.
I WANT TO HIGHLIGHT THE TOOLS
GENERATED THAT YOU MIGHT
CONSIDER AS BEING RELEVANT FOR
THE MISSION FOR UNRAVELLING THE
CIRCUITS OF REWARD AND ADDICTION
AND SUBSTANCE USE DISORDERS
INCLUDING ALCOHOL ABUSE.
THIS IS FROM A MULTI-INSTITUTION
PROJECT THAT DEVELOPED WAVE
LENGTH SHIFTED SENSORS FOR
DOPAMINE NEUROTRANSMITTER AND
WHY'S THAT IMPORTANT?
WE WANT TO BE ABLE TO LOOK AT
NOT JUST DOPAMINE RELEASE AND
OTHER NEUROTRANSMITTER RELEASES
SO BEING ABLE TO CREATE AND
USING THESE SENSORS WITH
DIFFERENT WAVE LENGTHS ALLOWS
ONE TO GO IN AND LOOK AT
SPECIFIC CIRCUITS AND FROM THE
PERSPECTIVE OF NOT JUST DOPAMINE
RELEASE AND IN THE CASE OF
CHOLINE RELEASE AND COMBINING
THEM WITH OTHER SENSORS FOR
CELLULAR ACTIVITY.
IT'S JUST ONE OF MANY EXAMPLES
OF THE TOOLS THAT WILL ASSIST
RESEARCHERS LOOKING AT THESE
CIRCUITS OF REWARD AND ADDICTION
TO GENERATE BETTER MODELS THAT
HOPEFULLY CAN TRANSLATE TO
TREATING AND PREVENTION OF
ALCOHOL ABUSE.
OKAY.
WE'VE PUT TOGETHER THESE THREE
MUTUALLY REINFORCING PROJECTS.
THE FIRST TWO IS THE PARTS LIST
AND DIAGRAM TO GIVE THE GROUND
TRUTH INFORMATION ABOUT NEURAL
CIRCUITS AND THE THIRD THE
ARMAMENTARIUM PROJECT WILL GET
US INTO THE SPECIFIC CELLS AND
CIRCUITS TO START ASKING HOW
THEIR BEHAVIOR CAN CREATE BETTER
MODELS FOR HUMAN BRAIN DISORDERS
AND LEADING TO PRECISION CIRCUIT
THERAPIES PRECISION GENE
THERAPIES.
THESE ARE TRANSFORMATIVE
PROJECTS WE LAUNCHED THE BRAIN
BEHAVIOR OF SYNCHRONIZATION
METHOD AND TO DEVELOP APPROACH
TO QUANTIFY COMPLEX BEHAVIORS IN
HUMAN AND NON HUMAN MODELS AND
RECORDINGS OF BRAIN ACTIVITY.
THE GOAL IS TO USE THIS TO
INFORM CLOSED LOOP NEURAL
MODULATION THERAPIES FOR MENTAL
AND OTHER BEHAVIORAL DISORDERS.
AND DEVELOP MODELS SENSORS FOR
MEASURING BEHAVIOR AND VERY
IMPORTANTLY A WAY TO COORDINATE
ALL THE DATA COMING FROM THE
DIFFERENT STREAMS WHICH WILL
INCLUDE DEVELOPING BETTER
THEORETICAL MODELS AND
COMPUTATIONAL MODELS TO MAKE
SENSE OF THE DATA FROM THE
MULTIPLE MODALITIES.
WE'RE EXCITED ABOUT THAT.
IT'S JUST BEEN LAUNCHED.
WE HAVE DIFFERENT PROGRAMS THAT
ARE IN PROCESS WE'RE ABOUT TO
FOUND IF WE HAVEN'T ALREADY
FUNDED THE FIRST DATA IN A.I.
CENTER TO PLAY A CRITICAL ROLE.
OTHER BIG PROJECTS ALSO HAVE
THESE COORDINATION CENTERS THAT
ARE GOING TO MAXIMIZE THE
UTILITY OF THESE LARGE DATA SETS
AND WE'RE LOOKING FORWARD TO
GETTING INTO THE DEVELOPMENT OF
CUTTING EDGE SENSOR TECHNOLOGIES
AS PART OF THIS.
PLEASE STRAY TUNED FOR THAT.
.
THIS IS OUR APPROACH.
WE'RE LAYING DOWN THE FOUNDATION
FOR FUTURE CURES AND TO BRING
CURES CLOSER TO US.
IN THE MEANTIME IT'S IMPORTANT
TO HIGHLIGHT WHAT WE'RE DOING TO
HELP HUMANS RIGHT NOW.
I'M SURE YOU'RE ALL FAMILIAR
WITH DEEP BRAIN STIMULATION IT'S
BEEN AROUND OVER DECADES NOW TO
TREAT MOTOR SYMPTOMS ASSOCIATED
WITH PARKINSON'S DISEASE.
OVER THE LAST COUPLE YEARS WE'VE
SEEN AN EXPLOSION OF STUDIES
APPLYING THESE TECHNOLOGIES TO
MORE COMPLEX NEURAL PSYCHIATRIC
AND BEHAVIOR DISORDERS.
THESE ARE PAPERS FROM THE
LITERATURE.
IT'S OUT OF DATE BY NOW BUT
WE'RE NOW SEEING THE USE OF DBS
TO TREAT MAJOR DEPRESSIVE
DISORDER, POSTTRAUMATIC STRESS
DISORDER, OCD, RECOVERING MOTOR
FUNCTION AFTER STROKE AND WE'LL
SEE SOON THE USE OF DBS TO TREAT
CHRONIC PAIN AND MOOD DISORDERS.
IT'S STRIKING HOW QUICKLY THE
FIELD HAS EVOLVED.
IT'S BEEN AN EVOLUTION AND
ATTRIBUTE IT TO THREE MAIN
THINGS.
THE FIRST IS TO BETTER MAP
NEURAL CIRCUITS IN HUMANS AND WE
WILL KNOW WHERE WE WANT TO
STIMULATE.
THE SECOND IS THE DEVELOPMENT OF
BETTER AND BETTER RECORDING AND
MODULATION AND STIMULATION
TECHNOLOGIES AND ALL THE STUDIES
ARE DONE IN PARTNERSHIP WITH
DEVICE MANUFACTURERS.
THE THIRD IS THE IMPLEMENTATION
AND DEVELOPMENT OF BETTER AND
BETTER A.I. ALGORITHMS THAT CAN
READ OUT AS THE NEURAL SIGNALS
BEING RECORDED FROM INDIVIDUAL
PEOPLES BRAINS AND TO TURN THESE
INTO ACTIONABLE BIOMARKERS.
BASICALLY WE'RE SEEING THE
ABILITY TO READ OUT AND
INTERPRET BRAIN ACTIVITY AND TO
USE THESE AS BIOMARKERS AND USE
SIMULATION TO MOVE INDIVIDUALS
BACK TO BETTER SPACE AND IT'S
REMARKABLE.
WE'VE BEEN TALKING TO PATIENTS
WHO HAVE HAD THESE TREATMENTS
AND THE RESULTS ARE NIGHT AND
DAY.
ANOTHER ASPECT OF THE
TECHNOLOGICAL ARENA HERE BRAIN
HAS BEEN INVOLVED IN HAS ALSO
BEEN IN THE SO-CALLED BRAIN
COMPUTER INTERFACES TO RESTORE
FUNCTION FOR PEOPLE WHO FOR
EXAMPLE MIGHT HAVE LOST FUNCTION
BECAUSE OF STROKE OR INJURY OR
IN THE CASE OF DEGENERATIVE
DISEASE, ALS LOVING THE ABILITY
TO COMMUNICATE.
THERE'S BEEN EXCITING PAPERS
COMING OUT THAT HAVE SHOWN
AMAZING BRAIN COMPUTER
INTERFACES BRAIN TO SPEECH AND
BRAIN TO TECH AND THESE REQUIRE
A LOT OF TRAINING.
RESEARCHERS FIND WILLING SUBJECT
TO WORK WITH THIS AND IMPLANT
ELECTRODES AND GIVE A NEURAL
PROSTHESIS THAT'S IMPRESSIVE AND
THERE'S A CONSORTIA FUNDED BY
NIDDK WITH DEAFNESS AND
COMMUNICATION DISORDERS AND
BASED ON EARLIER WORK FUNDED BY
THE BRAIN INITIATIVE AND WANT TO
HIGHLIGHT THIS STUDY.
THIS WAS A PROJECT THE BRAIN
GATE CONSORTIUM BASED OUT OF
U.C. DAVIS NOW WITH A
45-YEAR-OLD MAN IN LATE STAGES
OF ALS NO LONGER ABLE TO
COMMUNICATE WITH HIS LOVED ONES
AND IMPLANTED ELECTRODES AND
DECODED THE SIGNALS COMING FROM
THE REGIONS OF THE BRAIN AS HE
TRIES TO ANNUNCIATE WORDS AND
PUT THIS THROUGH A SPEECH
SYNTHESIZER.
THE OTHER PART WHICH IS AMAZING
IS THEY HAVE RECORDINGS OF THIS
INDIVIDUAL BEFORE HE SUCCUMBED
TO THE PARALYSIS AND THEY CAN
PUSH THIS INFORMING THROUGH THE
SYNTHESIZER IN HIS OWN VOICE.
WHAT MAKES THIS REMARKABLE IS
IT'S LITERALLY PLUG AND PLAY.
WHEN THEY ARE IMPLANTED HIM WITH
THE ELECTRODES FOUR WEEKS AFTER
THE INITIAL IMPLANTATION WITHIN
HALF AN HOUR HE WAS ABLE TO PUT
OUT A 50 WORD VOCABULARY WITH
ABOUT 100% ACCURACY AND WITHIN
ANOTHER HOUR AND A HALF OF
TRAINING THEY WERE ABLE TO GET
HIM TO A 125,000 WORD VOCABULARY
WITH 90% ACCURACY AND LEVELED
OUT TO 97% ACCURACY.
THIS IS AS CLOSE AS WE CAN GET
TO PLUG AND PLAY.
WHAT THIS MEANS IS OUR ABILITY
TO ROLL THIS OUT TO MORE
PATIENTS IN NEED THE BARRIER HAS
BEEN LOWERED BY A SIGNIFICANT
AMOUNT.
I WANT TO SHOW TWO VIDEOS OF THE
RESEARCH SUBJECT AND WHAT IT DID
FOR HIM.
THE FIRST JUST SHOWS THE FIRST
TRAINING SESSION.
THE FIRST HALF HOUR TRAINING
SESSION.
THEY HAD TO STOP BECAUSE
EVERYBODY IN THE ROOM WAS
BROUGHT TO TEARS.
THE SECOND VIDEO IS MORE
EXTENSIVE AND YOU'LL LEHEAR WHA
YOU THINK IS A NARRATION OVER
BUT IT'S THE INDIVIDUAL SPEAKING
THROUGH HIS NEURAL PROSTHESIS.
IF YOU HAVE A HANDKERCHIEF
NEARBY IT'S AMAZING.
IF YOU CAN'T HEAR I'LL FIX MY
VIDEO.
>> IT TOOK WEEKS AND MONTHS TO
GET WORKING.
THE FIRST TIME WE TRIED TO USE
THE SYSTEM IT JUST WORKED.
6:
>> THE FIRST TIME HE TRIED TO
SPEAK.
HE STARTED CRYING.
I STARTED CRYING.
HIS FAMILY STARTED CRYING.
EVERYONE -- WE HAD TO PAUSE AND
STOP THE REST OF THAT BLOCK OF
EXPERIMENT TRIALS AND COMPOSED
THEMSELVES AND IT KEPT WORKING.
IT WAS REALLY SPECIAL.
PEOPLE WHO DO NOT HAVE THE
ABILITY TO COMMUNICATE WELL OR
QUICKLY ARE ISOLATED AND LONELY.
HAVING SOMETHING LIKE THIS GIVES
HOPE AND OPPORTUNITY TO BE
THEMSELVES.
>> IT WORKS WELL ENOUGH IT LETS
HIM JUST BE A PART OF SOCIETY
AND TALK.
>> I'M ABLE TO WORK FULL TIME
FOR CLIMATE ACTION AND ABLE TO
DO THAT WELL AND MORE
EFFICIENTLY WITH THIS DEVICE.
>> THE REASON IT'S SO
TRANSFORMATIVE IS IT PROVIDES
FOR HOPE WITH PEOPLE LIVING WITH
THESE DISEASES.
AS THEY ARE PHRASE THEIR DISEASE
BUT KNOW THEY'LL HAVE THE
ABILITY TO RETAIN COMMUNICATION.
>> THIS WAS TRULY THE STUFF OF
SCIENCE FICTION 10 YEARS AGO AND
AMAZING TO SEE THE PROGRESS
HERE.
I HAVE TO MAKE RAY CALL OUT TO
FOLKS LIKE HIM WHO ARE BRAVE
ENOUGH TO PARTICIPATE AS
PARTNERS IN CRITICAL RESEARCH
AND WE HAVE A LONG WAY TO GO TO
MAKE TECHNOLOGIES TRULY
ACCESSIBLE BUT THIS IS A VERY
IMPORTANT STEP AND WE'RE
GRATEFUL NOT ONLY TO THE
BRILLIANCE OF THE RESEARCH BUT
BRAVERY AND GENEROSITY OF THE
HUMANS WITH THESE CONDITIONS
WILLING TO WORK WITH US.
AND THIS BRINGS ME TO THE WINDOW
OF OPPORTUNITY WE HAVE IN
WORKING WITH HUMANS AS RESEARCH
PARTNERS TO BETTER UNDERSTAND
HOW THE BRAIN PROCESSES
INFORMATION.
THERE'S ROBUST OPPORTUNITIES IN
HUMAN AND NEED APPROACH THIS IN
A CAREFUL AND THOUGHTFUL WAY.
WE NEED TO TAKE THE ISSUE OF
WHAT WE BRING NEURAL ETHICS AND
THE SOCIETAL IMPACT OF WHAT WE
DO AND HAVE A NEUROSCIENCE
WORKING GROUP AND INFORMING THE
PROGRAM ON WHAT ARE THE
OPPORTUNITIES AND PITFALLS ARE
IN CONDUCTING SUCH RESEARCH AS
IT STARTS GETTING AND FURTHER
INTO PROBING THE HUMAN MIND AND
THOUGHT.
AND WE HAVE GUIDING PRINCIPLES
WITH NOT JUST SAFETY AND PRIVACY
BUT THE AGENCY AS WE START
ALTERING PEOPLE'S ABILITY TO
THINK AND HOW DOES IT AFFECT
THEIR DECISION MAKING AND WE
HAVE TO BE MINDFUL OF DATA
CONCERNS.
DATA PRIVACY IS A BIG ISSUE WITH
A.I. TECHNOLOGIES ESSENTIALLY
MAKING EVERYTHING OUT THERE
NON-PRIVATE IF WE'RE NOT CAREFUL
AND NAVIGATING THESE AREAS WILL
REQUIRE EDUCATION TO THE PUBLIC
AND ENGAGEMENT WITH THE PUBLIC
TO BETTER INFORM HOW WE'RE GOING
TO PURSUE TECHNOLOGIES FOR THE
BENEFIT OF ALL AND FOR
DEMOCRATIZING THESE FOR THE
BENEFIT OF ALL.
FINALLY, I WANT TO TOUCH ON THE
IMPORTANCE OF BUILDING A
STRONGER WORKFORCE BASED ON A
GROWING BODY OF LITERATURE THAT
TELLS US THAT TEAMS WITH DIVERSE
PERSPECTIVES TEND TO OUT PERFORM
TEAMS WITHOUT THEM IN TERMS OF
CREATIVITY AND INNOVATION AND
ULTIMATE OUTPUT.
WE PURSUED THIS IN AN
INTENTIONAL THOUGHTFUL WAY AND
ONE WE INTRODUCED IS THE PLAN
FOR ENHANCING DIVERSE
PERSPECTIVES AND REQUIRE THE AM
QUANTITY TO GIVE A SUMMARY OF
HOW THEY'RE GOING TO BETTER
LEVERAGE DIVERSE PERSPECTIVES IN
THEIR RESEARCH TEAM IN THE
INTEREST OF FURTHERING THEIR
SCIENCE AND THIS CAN BE CARRIED
OUT IN A NUMBER OF WAYS.
I'LL GIVE A FEW BULLET POINTS
HERE.
IT'S BEING ROLLED OUT GENERALLY
ACROSS NIH.
IT'S AN EXPERIMENT AT THIS PHASE
BUT MAKING US THINK ABOUT HOW WE
WANT TO BRING IN DIFFERENT KIND
OF EXPERTISE BASED ON NOT JUST
PROFESSIONAL EXPERIENCE BUT
LIVED EXPERIENCE, INSTITUTIONAL
DIVERSITY, GEOGRAPHIC DIVERSITY
IN THE MOST IMPACTFUL SCIENCE WE
CAN.
FINALLY I WANT TO TOUCH ABOUT
THE BUDGET AND WE'RE IN A PICKLE
TRACING BACK TO THE WAY WE
RECEIVE FUNDING WHICH IS A BIT
UNUSUAL.
SO BRAIN ENCOMPASSES 10
INSTITUTES AND CENTERS AND
RECEIVE ALLOCATIONS THROUGH EACH
OF THESE I.C.s AS PART OF WHAT
WE CALL THE BASE ALLOCATION.
IN FISCAL 22 WE RECEIVED FUNDS
AUTHORIZED BY THE 21st CENTURIES
CURES ACT GIVING VARYING AMOUNTS
TO THE PROGRAMS AND NIH ENDING
IN FY26.
SO THE UPS AND DOWNS HAS TO DO
WITH THE AVAILABILITY OF FUNDS.
IT CREATES SOME BUDGETING
CHALLENGE.
UP THROUGH FY23 WE ENJOYED A
ROBUST INCREASE FROM BASE
FUNDING AS WELL AS IN VARYING
AMOUNTS AND CURES FUNDING.
WHAT HAPPENED IN 2023 WE SAW
$152 MILLION TO 4$452 MILLION
AND WE GOT A NET INCREASE OF $60
MILLION THE BASE ALLOCATION DID
NOT GET RESTORED IN FY24
RESULTING IN A $278 MILLION OR
40% DROP IN FUNDING AND WAITING
ANXIOUSLY TO SEE WHAT HAPPENS
WITH THE FY25 BUDGET AND IN THE
ELECTION YEAR WE'RE NAVIGATING
THE IMPACT OF THIS SIGNIFICANT
CUT AND STAYING TRUE TO OUR
MISSION OF INNOVATIVE SCIENCE
DRIVING THE FIELD FORWARD.
WE WAR HOPING -- WERE HOPING TO
GET TO RECOVERY SOON BUT THIS IS
THE BEST WE CAN DO.
WE HAVE TWO PAGES WHERE PEOPLE
CAN LEARN MORE UPDATED AS THE
SITUATION EVOLVES.
SO FINALLY THIS IS JUST WHERE
YOU CAN GET MORE INFORMATION
FROM US.
WE HAVE A BRAIN BLOG THAT SHOOTS
OUT INFORMATION.
NOT TOO FREQUENTLY BUT IF YOU
WANT TO KNOW WHAT'S CURRENT YOU
CAN SUBSCRIBE.
I WANT TO DRAW YOUR ATTENTION TO
TWO UPCOMING EVENTS AT THE
SOCIETY FOR NEURAL SCIENCE IN
CHICAGO OUR PARTNERS ARE PUKT ON
OUR ANNUAL WHAT WE CALL OUR
TOOLS SOCIAL AND FOLKS COME IN
THAT ARE BRAIN FUNDED AND SHOW
WHAT THEY'RE DOING AND IT'S A
GREAT OPPORTUNITY FOR FOLKS TO
INTERACT AND FIND OUT WHAT FOLKS
HAVE IN TERMS OF COOL NEW TOOLS
AND RESOURCES.
AND IN NOVEMBER WE'LL BE HOSTING
BRAIN WORKSHOP FOCUSSING ON
INTERSECTION OF NEURAL SCIENCE
AND ARTIFICIAL INTELLIGENCE AND
HYBRID MEETING AND WILL BE IN
NACHER AUDITORIUM.
>> THANK YOU FOR A FABULOUS
PRESENTATION AND FOR SHOWING HOW
THE NEURAL INTERFACE IN ALS
PATIENTS WAS UNLOCKED.
VERY MOVING.
HE'S OUR CLINICAL DIRECTOR.
MY QUESTION IS WHEN WE WERE AT
THE TRANSLATIONAL NEURAL SCIENCE
THERE WAS INTEREST IN THE
POSSIBILITY OF BACK TRANSLATION.
WONDERING IF YOU COULD SPEAK TO
THE ISSUE OF WHEN SAY A GENE OR
GENE MUTATION IS DISCOVERED IN
HUMANS AND NOBODY KNOWS WHAT
THAT IS WHAT THE CELL CENSUS CAN
CONVEY TO ELUCIDATE THE
MECHANISM THERE.
>> GREAT QUESTION.
THERE'S WORK IN IDENTIFYING THE
GENE IN HUMANS AND TRANSLATING
TO BETTER MODELS.
THE COOL THING ABOUT THE CELL
CENSUS AND THIS WASN'T TO ME
OBVIOUS AT THE OUTSET BUT WHEN
WE WERE PUTTING TOGETHER THE
FIRST SET OF PAPERS FOR THE
PRIMARY MOTOR CORTEX.
WE THOUGHT WOULDN'T IT BE COOL
NOT JUST TO LOOK AT THE MOUSE
BUT ACROSS MULTIPLE SPECIES.
CONCERTED EFFORTS PUT TOGETHER
TO LOOK AT THE INFORMATION
COMING OUT OF THE CELL CENSUS
PROJECTS FOR MOUSE AND NON HUMAN
PRIMATES AND THEY'RE DIFFERENT
THAN MICE OR RHESUS MACAQUES AND
SEE HOW THEY EVOLVED.
THERE'S COMMONALITIES ACROSS ALL
MAMMALIAN SPECIES.
THE ORGANIZATION OF CELL TYPES
OR LET'S RESTRICT THE
CONVERSATION TO NEURONS IS
HIERARCHICAL.
IT'S A TREE.
YOU SEE VARIOUS GROUPS OF
NEURONS SHARED IN COMMON BUT AS
YOU GET DOWN TO THE BRANCHES AND
LEAVES YOU SEE SPECIALIZATIONS
BETWEEN SPECIES.
THIS IS WHERE YOU START SEEING
COOL DIFFERENCES NOT ONLY IN
TERMS OF THE PRESENCE OR ABSENCE
OR APPEARANCE OF NEW CELL TYPES
IN HUMANS VERSUS MICE BUT EVEN
WITHIN CELL TYPES YOU IDENTIFY
AS THE SAME BETWEEN SAY A MOUSE
AND HUMAN.
THE MARKER GENES YOU MIGHT USE
TO ACCESS THEM ARE DIFFERENT.
THE CRITICAL THING IS WHETHER
YOU HAVE IDENTIFIED A GENE OR
CELL TYPE IN AU MOUSE AND ASKED
WHETHER YOU CAN TRANSLATE THAT
TO HUMANS OR THE OTHER WAY
AROUND, IDENTIFIED SOMETHING IN
HUMANS AND ASK TO MODEL IT IN A
MODEL SYSTEM, WE NOW HAVE A
POWERFUL WAY OF SAYING OKAY, IS
THIS A TREE, IS THIS A STREET
LAMP WORTH LOOKING UNDER OR AM I
BARKING UP A TREE?
MIXING UP METAPHORS AND THE
THERE'S HARD WAY TO INFORMATION
WHY.
AND UNDERSTANDING WHY IN THE
PROFESSION IS WELL REPRESENTED
OR NOT IN A MODEL SYSTEM IS JUST
AS POWERFUL AS KNOWING WHETHER
TO DO IT.
IT'S AN EXCITING POSSIBILITY AND
GIVES US INSIGHT WE DIDN'T HAVE
BEFORE TO NOT ONLY PREVENT BUT
TO FOCUS EFFORTS ON WHERE IT
WILL COUNT.
>> THANK YOU FOR YOUR
PRESENTATION.
SO YOU DESCRIBED SOME OF THE
EVOLUTIONARY INFORMATION THROUGH
THE CELL ATLAS.
CAN YOU TOUCH ON THE DEVELOPMENT
SIDE AND WHAT IS HAPPENING
THERE.
THANK YOU SO MUCH.
>> WE HAVE A BIT OF WORK BEING
DONE IN HUMAN TISSUE AND SOME
DATA HAS BEEN PUBLISHED AS PART
OF THE FIRST ATLAS.
THAT'S A BIB PART OF THE PRIME
MINISTER.
THERE'S STILL THOUGH BI CCN
ENDED THERE'S PACKAGES AND ONE
IS DEVELOPMENT IN MICE.
AND LOOKING AT THE DEVELOPMENT
MORE INTENSELY.
PART WAS TO NOT GET SPREAD TOO
THIN.
WE DIDN'T WANT TO PULL THE WHOLE
HOUSE DOWN BECAUSE WE GOT OVER
AMBITIOUS BUT THOSE STUDIES ARE
COMING AND ARE IMPORTANT.
AS I'M SURE PEOPLE APPRECIATE
MANY OF THESE ARE LOOKING AT
THAT.
ON THE OTHER END OF THE LIFE
TIME SPECTRUM ARE THE ISSUES OF
DEGENERATION AND EFFECTS OF
AGING.
SO IN THE CURRENT ITERATION WE
ARE LOOKING ACROSS THE HUMAN
LIFE SPAN WHICH IS IMPORTANT BUT
IT'S ALSO IMPORTANT IT LOOK AT
DEVELOPMENT.
WHEN WE LOOK AT PROCESSES LIKE
ALZHEIMER'S WE DON'T KNOW WHERE
IT ALL STARTS.
IT COULD BE FROM THE DAY YOU'RE
BORN OR BEFORE.
IT WILL BE IMPORTANT TO HAVE
THIS ENTIRE CREW OF NOT JUST P56
BLACK 6 MOUSE BUT FOR HUMANS
ACROSS THE LIFE SPAN TO BETTER
MODELS DISEASES.
WE NEED TO START THINKING ABOUT
WHAT ARE GOING TO BE THE
INITIATIVES AND DRIVERS AND
TRIGGERS.
>> ONE QUESTION I DON'T KNOW IF
IT'S TOO POLITICAL TO ASK.
ONE STRENGTH OF THE BRAIN
INITIATIVE AND WE BENEFIT FROM
THE SUPPORT FOR LABORATORIES
ACROSS THE WORLD.
ARE THERE ANY PRESSURES TO
CHANGE THAT MODEL BECAUSE IT'S A
REALLY VALUABLE MODEL.
>> SO WE HAVE BEEN FUNDING AND
WE CONTINUE TO FUND THE
INTERNATIONAL COLLABORATIONS.
THERE ARE REQUIREMENTS THAT HAVE
TO BE MET.
NOT JUST BEYOND NIH AS AN AGENCY
ITSELF.
WE'RE TRYING TO BRING IN THE
BEST SCIENCE ACROSS THE WORLD.
IT INVOLVES SOME KIND OF
ADJUSTMENTS.
WE'RE ATTUNED AND SENSITIVE TO
THE GEOPOLITICAL CONDITIONS
UNDER WHICH WE WORK BUT OUR
BRAIN PROGRAM STAFF KNOW THE
FOLKS IN THE FIELD.
THE PROGRAM STAFF AT NIH IN
GENERAL ARE TERRIFIC.
I DON'T THINK PEOPLE APPRECIATE
HOW PLUGGED IN THEY ARE ARE WITH
WHAT'S GOING ON IN THE
SCIENTIFIC COMMUNITY AND HAVE A
GREAT NOSE FOR WHAT'S OUT THERE
AND WHAT WE CAN BRING IN AND
FRANKLY THERE'S GREAT
TECHNOLOGIES NOT ON U.S. SOIL
WE'D BE AT A HUGE DISADVANTAGE
IF WE DIDN'T BRING IN THESE S
AND IT'S A MATTER OF NAVIGATING
TO DO SO LEGALLY AND ETHICALLY
TO ADVANCE THE SCIENCE.
WE'RE DOING OUR BEST TO NAVIGATE
THAT AND WORKING WITHIN SOME
CONSTRAINTS AS EVERYBODY CAN
APPRECIATE.
THAT'S JUST THE NATURE OF THE
GAME.
>> HAS ANYBODY SPECULATED ON WHY
YOU NEED SO MANY CELL TYPES OF
NEURONS?
I ASSUME MOST MAY BE IN THE
CEREBRAL AND PREFRONTAL CORTEX.
>> I DON'T KNOW THE WHY BUT
INTERESTINGLY WHEN WE GOT
THROUGH THE WHOLE MOUSE BRAIN
ATLAS THE VAST MAJORITY OF CELL
TYPES ARE NOT IN THE CORTEX.
IF YOU THINK ABOUT THIS IT KIND
OF MAKES SENSE.
THE CORTEX IS A RELATIVELY NEW
INVENTION.
OR THE NEOCORTEX IS A RELATIVELY
NEW INVENTION, A.
AND B, I MIGHT THINK OF THIS
SIMPLISTICALLY AS A BASIC
STRUCTURE REPEATED OVER THE
SENSORY CORTEX AND TO SOME
DEGREE OVER MOTOR CORTEX AS
WELL.
WHEN I TALK TO WHAT I REFER TO
IS MORE WELL SCHOOLED NEURO
SCIENTISTS THEY'VE BEEN AROUND
LONGER AND SERVE ALL THESE
FUNCTIONS.
I THINK WHAT WE UNCOVERED IS
SOMETHING SOMETHING WERE NOT
SURPRISED BY AND PEOPLE STUDYING
THE NERVOUS SYSTEM MANY DECADES.
AS TO WHY YOU NEED SO MANY IT
REFLECTS THE DIFFERENT FUNCTION
THE DIVERSITY OF NEURONS ARE
CARRYING OUT AND THE CELL TYPE
VERSUS CELL STATE.
IT SPEAKS IT WHAT'S GOING TO BE
STABLY THERE AND RESISTANT TO
PERTURBATION.
IT GIVES A GREATER OPPORTUNITY
TO INFORMATION NOT JUST THE
FUNCTION OF THESE CELLS BUT WHY
THEY ARRIVE THERE.
I LOOK AT THE DATA THAT SAY
THEY'RE 5300 CELL TYPES IN THE
MOUSE AS 5300 HYPOTHESES WE CAN
TEST.
I'M NOT GOING TO TEST THEM ALL
BUT WE CAN GENERALIZE MORE
BROADLY.
IT'S A GREAT TIME TO LOOK AT
THESE THINGS TO KEEP US BUSY
MANY DECADES.
>> I THINK WE'LL STOP ON THE 53
HYPOTHESES WE'LL TEST.
>> 5300, GEORGE.
>> THIS MUCH VERY MUCH.
WE'LL HAVE TO MOVE ON BECAUSE OF
THE SCHEDULE AND WE CAN ACCESS
THE BRAIN RESOURCE AND IT'S A
GREAT INTRODUCTION TO SEE WHAT'S
THERE AND AVAILABLE AND OUR NEXT
SPEAKER JIM EBERWINE IS GOING TO
TALK ABOUT CELL TYPES IN MORE
DET
DETAIL.
ARE YOU ON?
>> I'LL INTRODUCE YOU AND LET
YOU ROCK AND ROLL AND MAYBE YOU
CAN ANSWER WHY WE NEED SO MANY
MODELS.
HE'S THE PROFESSOR OF SYSTEMS OF
PHARMACOLOGY AND TRANSLATIONAL
THERAPEUTICS AND CO-DIRECTOR OF
THE PENN PROGRAM IN SINGLE CELL
BIOLOGY.
HIS INTERESTS RESOLVE THE ROLE
OF VARIATION AND THE FUNCTIONING
OF SINGLE CELLS IN COMPLEX
NETWORKS AND DEVELOPED AMONG
OTHER METHODOLOGIES, SINGLE CELL
PCR AND mRNA PROTOCOL AND
TRANSCRIPTION.
THE TECHNIQUES ALLOWED HIM TO
SEQUENCE THE FIRST SINGLE CELL
TRANSCRIPTOME COINING THE PHRASE
EXPRESSION PROFILE TO DESCRIBE
HE RELATIVE ABUNDANCES OF SINGLE
CELL BIOLOGY AND THERE WERE THE
SEQUENCING OF THE SINGLE
MITOCHONDRIAL AND INTERACTING
WITH MMRP --
>> mRNA BINDING PROTEINS.
>> AND YEAH.
THE CHARACTERIZATION OF SINGLE
STRAND GENOMIC RNA STRUCTURES
AND THE IN VIVO ISOLATION OF
TRANSCRIPTOMES IN LIVE SPATIALLY
LOCALIZED CELLS AND
IDENTIFICATION OF THE COMPLEX
RNA LANDSCAPE OF NEURONAL
DENDRITES.
GIVEN THE NEED TO DEVELOP
TECHNOLOGIES THAT ADDRESS
QUESTIONS HE'S AN INVENTOR OVER
180 PATENTS.
HE ORGANIZED THE FIRST
INTERNATIONAL MEETING AT
LABORATORIES AND CORE ORGANIZED
THIS FOR SEVEN YEARS AND CREATED
SUMMER COURSES ADVANCED
TECHNIQUES IN SCIENCE AND
ADVANCED STUDIES ON SINGLE CELL
ANALYSES.
HE'S A MEMBER OF THE NIAAA
COUNCIL AND BOARD OF SCIENTIFIC
COUNSELORS FOR THE NATIONAL
INSTITUTE ON AGING.
HE'S CURRENTLY OUR NIAAA
REPRESENTATIVE ON THE NIH
MULTI-COUNCIL WORKING GROUP THAT
OVERSEES THE BRAIN INITIATIVE
AND AT THE MULTICOUNCIL WORKING
GROUP AND CO-CHAIRED THE NIH
ADVISORY COMMITTEE TO THE
DIRECTOR TO DEVELOP NEUROETHICS
ROAD MAP FOR THE BRAIN
INITIATIVE AND ONE OF THE
REASONS I WANTED JIM TO GIVE A
TALK THAT FOLLOWED JOHN GNAI'S
AWK.
HE RESOURCED A MERIT AWARD FROM
NIH AND THE SENIOR SCHOLAR
AWARD, DISTINGUISHED
INVESTIGATOR AWARDS THE
INNOVATION AND NEUROSCIENCE
AWARD, BRAIN RESEARCH FOUNDATION
SCIENCE INNOVATIONS AWARD AND
TWO NIH PIONEER AWARDS.
HE'S A MEMBER OF THE NATIONAL
ACADEMY OF INVENTORS AND THE
NATIONAL ACADEMY OF MEDICINE.
YOU'RE ABOUT TO GET A LECTURE
FROM ONE OF THE MOST
DISTINGUISHED MOLECULAR NEURAL
SCIENTISTS IN THE WORLD TODAY
AND HOPE EVERYBODY WILL ENJOY
IT.
IT'S ALL YOURS, JIM.
>> THANK YOU, GEORGE.
I APPRECIATE THE INTRODUCTION.
IT'S VERY KIND OF YOU.
CAN YOU SEE MY SCREEN?
>> YES.
>> THANK YOU.
>> THE OUTSET I'D LIKE TO THANK
JOHN FOR PRECEDING ME.
IT'S GREAT TO SEE THE PROGRESS
OF THE BRAIN INITIATIVE OVER THE
LAST DECADE WITH JOHN BEING THE
NEWEST DIRECTOR OF IT AND
AMAZING TO SEE THE PROGRESS.
I WANT TO COMPLEMENT NIAA THE
INTRAMURAL REPRESENTATIVE TO THE
MULTI-COUNCIL WORKING GROUP AND
HAS BEEN A GREAT AND ATTENDS ALL
THE MEETING AND NIAAA HAS A
GREAT REPRESENTATIVE ON THAT
COMMITTEE.
IN ADDITION IT'S BEEN FUN TO BE
ON THE COMMITTEE BECAUSE GEORGE
IS ALSO INVOLVED IN AND CURIOUS
ABOUT THE INITIATIVE AND HELPING
TO MOVE IT FORWARD AND IT'S BEEN
A PLEASURE TO WORK WITH HIM AND
OTHERS IN TERMS OF MOVING THE
BRAIN INITIATIVE FORWARD UNDER
JOHN'S TUTELAGE.
WHAT I THOUGHT I'D DO -- GEORGE
ASKED ME TO TALK ABOUT MY
SCIENCE AND NEURAL ETHICS DON'T
AND START WITH THE SCIENCE AND
PRESUME WILL TIME IN THE END I
HOPE TO GET TO THE NEURAL ETHICS
WORK AND GIVE A FLAVOR OF THINGS
IT'S INVOLVED WITH.
AND PROGRESS MADE IN TERMS OF
VOICE RECOGNITION AND ALL OF
THIS AND ANALYSIS OF CELL
FUNCTIONING THROUGH ORGANELLES
THE TITLE IS CHARACTERIZING
CELLS THAT MAYBE UP THE BRAIN
AND CELL FUNCTION THROUGH
SUBCELLULAR GENOMICS.
MANY CAN LOOK ALIKE
TRANSCRIPTOMICLY AND
MORPHOLOGICALLY AND FUNCTION IN
DISTINCT MANNERS.
SO WHAT MECHANISMS THAT UNDER
LIE THAT?
I'LL TRY TO MAKE ACATION FOR THE
PROPERTY OF CELL FUNCTIONING
COMES FROM THEIR INTRACELLULAR
STRUCTURES AND ORGANELLES.
THE ORGANELLES YOU'LL REMEMBER
FROM YOUR COLLEGE TEXTBOOKS
INCLUDE THE NUCLEUS, GOLGI AND
ERR AND CELL MEMBRANES AND
VARIOUS CELLULAR GRANULES.
WHEN THERE'S MUTATIONS OR
CHALLENGES THAT IMPACT THE
ORGANELLES THEY HAVE SPECIFIC
PHYSIOLOGICAL CONSEQUENCES.
AND TO UNDERSTAND HOW THE CELL
WORKS IT'S IMPORTANT TO
UNDERSTAND HOW THE ORGAN CELLS
WORK.
THEY INTERACT TOGETHER.
LYSOSOMES AND INTERACT WITH
MITOCHONDRIA AND THE ER AND MOVE
AROUND CELLS AND HUNDREDS OF
MITOCHONDRIA WITHIN AN
INDIVIDUAL CELL.
SOME AGGREGATE AROUND THE
NUCLEUS.
AND IT'S HOW THESE ORGANELLES
FUNCTION INDIVIDUALLY AND
TOGETHER TO CREATE THE EMERGING
PROPERTIES OF THIS CELL.
THE CELL IS MORE THAN THE SUM OF
ITS PARTS.
THIS IS IMPORTANT IN TERMS OF
ALCOHOL RESEARCH.
WE KNOW CHRONIC ALCOHOL WILL
IMPACT MITOCHONDRIA MORPHOLOGY
AND FUNCTION MORE MUTATIONS CAN
OCCUR WITH CHRONIC ALCOHOL
ABUSE.
IT'S METABOLIZED BY LYSOSOMES.
IT IMPACTS NUCLEAR STRUCTURE AND
STRESS GRANULE ANOTHER TYPE OF
ORGANELLE WITHIN THE CELL IS
IMPACTED AND MODIFIED BY ALCOHOL
ABUSE AND USE.
AND WAYS IT CAN IMPACT THE
STRUCTURES.
AS I MENTION THE ORGANELLES
THERE WILL BE MORE DISCOVERED
OVER THE NEXT FEW YEARS.
THESE ARE SOME OF THE ONES MOST
AS WE IDENTIFY MORE SUB CELLULAR
STRUCTURES.
THIS IS HOW THE CELL ORGANIZES
AND PROTEINS IN THE CELL IN
TERMS OF THE COHERENT MINI
MACHINES THAT EXIST WITHIN THE
CELL.
YOU'RE FAMILIAR WITH THE TYPES I
MENTIONED.
IN MY LAB WE'RE STUDYING SEVERAL
ORGANELLES AND HAVE A PROGRAM
CALLED THE VISTA PROGRAM WHERE
WE TRY TO UNDERSTAND THESE
ORGANELLES FROM THEIR GENOMICS
TO PROTEOMICS TO METABOLOMICS
AND FUNCTION.
DIFFERENT PROCEEDED AT VARIATION
DEGREES.
I'LL SHOW SOME WORK ON
MITOCHONDRIA AND SOME ON THE
NUCLEUS AND THINKING ABOUT
ORGANELLES, AND THERE'S BEEN A
HOST OF TYPE OF INITIATIVES IN
THE UNITED STATES AND AROUND THE
WORLD THERE'S BEEN WORK DONE IN
TERMS OF SINGLE CELL ANALYSIS
AND UNORGANELLES ARE SMALL, THEY
HAVE SMALL VOLUME.
YOU CAN HAVE ANYWHERE FROM ONE
TO MILLIONS OF LYSOSOMES AND THE
ORGANELLES ARE HETEROGENEOUS.
MOST THINK OF MITOCHONDRIA AS
THE POWERHOUSE AND THEY'RE ALL
THE SAME.
THEY'RE NOT.
THEY'RE FUNCTIONALLY DISTINCT.
I WON'T HAVE TIME TO SHOW MUCH
OF THE DATA BUT WE AND OTHERS
HAVE BEEN LOOKING AT INDIVIDUAL
MITOCHONDRIA CAN DIFFER WITHIN A
CELL.
ONE ISSUE TO STUDY THE OMICS OR
ANY ASPECT IS THE SIZE.
THE AVERAGE SIZE OF A NEURON IS
ABOUT 30 MICROONSS -- MICRON AN
WE NEED TO HAVE METHODOLOGIES
THAT GIVE US THIS TYPE OF
RESOLUTION TO QUANTITATIVELY
CELL THEM WITHIN CELLS AND LOOK
AT THEIR RESPONSIVENESS TO
ALCOHOL OR OTHER DRUGS.
AND THESE ORGAN CELLS CAN LOOK
DIFFERENT.
YOU HAVE MITOCHONDRIA OVER HERE
AND NEURONS AND ASTROCYTES AND
THE DEN DRDRITES OF THE CELL AN
MITOCHONDRIA ARE FUSED AND MANY
GO TOGETHER TO CREATE A LONGER
STRUCTURE.
THEY CAN LOOK DIFFERENT AND
FUNCTION DIFFERENTLY.
I'LL TRY TO SATISFACTION THE
COMPONENTS AND THIS WILL IMPACT
ALCOHOL RESEARCH YOU NEED THIS
RESOLUTION TO GO TO AN
UNDERSTANDING OF THE FUNCTION OF
THESE DRUGS WITHIN THE CELLS.
WHEN I SAY SPATIAL ANALYSIS WHAT
THAT MEANS IS WE WANT TO BE ABLE
TO LOOK AT THE CELLS, LOOK AT
THE STRUCTURES IN CELLS THAT ARE
CONNECTION WITH OTHER CELLS.
BASICALLY BRAIN SECTION OR SLICE
WHERE THE NEURON IS IN
OPPOSITION WITH WHAT IS TOUCHING
IT OR THE MICRO GLIIA BECAUSE IT
IMPACTS THE FUNCTION OF THE
CELL.
I'LL SHOW YOU ASPECTS OF HO YOU
WITH LOOK AT CHROMATIN WITHIN
THE CELLS.
FOR THOSE WHO PLAY NOT REMEMBER,
GENOME YOU CAN DNA IS PACKED IN
A CELL WITH A STRUCTURE OF
NUCLEOSOMES WITH DNA.
WHEN YOU HAVE TRANSCRIPTION OF A
GENE FROM THE DNA THE
NUCLEOSOMES ESSENTIALLY FALL
OFF.
THE DNA POLYMERASE AND OTHER
ENZYMES INVOLVED AND OTHERS ARE
INVOLVED IN RNA TRANSCRIPTION
BIND TO THE RNA AND TRANSCRIBE
IT INTO A MOLECULE.
THIS IS CALLED OPEN CHROMATIN
AND MANY STUDIED THIS IN
RESPONSE TO ETHANOL
MANIPULATION.
THERE'S THE BRAIN RESEARCH
EFFORTS THAT RELATED TO
CHROMATIN STRUCTURES ON ATAC SEQ
YOU NEED THE PROTONS AND EXCISED
FOR ANALYSIS.
IT'S AN DETAIL THAT MEANS YOU'RE
GOING TO SEE MUCH OF THE OPEN
CHROMATIN BUT NOT ALL OF IT
BECAUSE YOU NEED TWO OF THESE
EVENTS TO OCCUR TO BE ABLE TO
DETECT THE MATERIAL.
YOU STILL GET A LARGE AMOUNT OF
THE CHROMATIN BUT EACH APPROACH
HAVE PLUSES AND MINUSES.
AND YOU'LL SEE DISTINCTIONS
BETWEEN THE APPROACH.
WE WANTED TO SEE AS MUCH AS THE
MATERIAL IN SINGLE CELLS IN
THOSE IDENTIFIED.
WE DEVELOPED A PROCEDURE CALLED
CHECK SEQ.
YOU TAKE CELLS FIXED OR BRAIN
TISSUE SECTIONS FIXED AND USE
THE GLUING OF PROTEINS IN PLACE
AND QUERY IN A FIXED TISSUE
SECTION USING A SPECIAL OLICO
NUCLEOTIDE AND WHAT IS IMPORTANT
TO KNOW AND YOU CAN LOOK AT OUR
PAPER RECENTLY PUBLISHED IN
NATURE AND METHODS IS IT HAS A
BLOCKED SITE ON THE END OF.
WHEN THE DNA BINDS AS SHOWN HERE
OR HERE IT SITS ON THE DNA AND
INACTIVE.
WHEN YOU HIT THE CELL WITH LIGHT
THIS COMES OUT AND CAN ACT AS A
PRIMER FOR SYNTHESIS DIRECTLY IN
THE TISSUE SECTION.
BASICALLY YOU'RE COPYING THE
SINGLE STRANDED DNA INTO A COPY.
WHEN THAT HAPPENS, YOU CAN THEN
ANALYZE THE SINGLE STRANDED DNA
THROUGH SEQUENCING AND OTHER
PROCEDURES.
THE IMPORTANCE OF THIS BLOCKED
END IS THAT IT'S ACTIVATED BY
LIGHT.
WE CAN FOCUS OUR LASER ON AN
INDIVIDUAL CELL AND ACTIVATE
THIS INTERROGATOR IN THE ONE
CELLS.
THE OTHER CELLS WE WON'T SEE A
SIGNAL FROM AND SEE CHROMATIN
STRUCTURE AT HIGH COMPLEXITY
USING THIS APPROACH.
THE WE HAVE CO-INVENTORS AND
CO-OWNERS OF THE PATENT ON THE
PROCEDURE, LASERGEN AND AGILENT.
WE USED A CELL LINE CALLED K652
USED IN DEVELOPING MUCH OF THE
INFORMATION WE HAVE ABOUT THE
DNA REGULATORY ELEMENTS THAT ARE
DISPERSED THROUGHOUT THE GENOME.
AMONG THINGS I WANT TO HIGHLIGHT
IS THESE ARE K3562 CELLS WITH
OUR PRIMER SHOWN HERE AND IT'S A
FLUORESCENT PRIMER.
WHEN WE SHINE IT ON THE ONE CELL
THE PRIMER RAZE BEEN ACTIVATED
AND WIN THE TRANSCRIPTASE IT
WILL COPY THE SINGLE CELL DNA
INTO A DOUBLE STRANDED DNA SO
ONLY GETTING IT FROM ONE CELL.
WHEN WE COMPARE THE OPEN
CHROMATIN STATUS OF THE CELLS
WITH THEY WILL RNA MADE FROM
THOSE CELLS SO THE
TRANSCRIPTIONAL PRODUCT OF THE
OPEN CHROMATIN THERE'S A LARGE
OVERLAP IT'S LARGER THAN WITH
ATAC SEQ AND REASONS FOR THAT WE
CAN DISCUSS LATER IF YOU'RE
INTERESTED IN THE METHODOLOGY.
WHEN WE LOOK AT THE SINGLE CELL
DNA AND SOME WE CAN'T DETECT AND
DISCUSS THOSE MOMENTARILY.
THE GOAL IS LOOKING AT
INDIVIDUAL CELL WITH A VARIETY
OF PROCEDURES.
WE WANTED TO LOOK AT PROTEIN
EXPRESSION AND LOOK AT CELLS
EXPRESSING ANTIGEN.
THE PRESENCE OF AN RNA TELLS YOU
THE CELL HAS THE CAPACITY TO
MAKE THE PROTEIN BUT IT DOESN'T
MEAN IT'S MAKING THE PROGRESS AS
JOHN WAS TALKING ABOUT THE CELL
STATE AND FUNCTION AND YOU NEED
THE PROTEIN TO FUNCTION WITH THE
PROTEIN.
IT CAN HAVE FUNCTIONS OTHER THAN
TRANSLATION BUT GENERALLY THAT'S
WHAT YOU'RE INTERESTED IN.
THERE'S CONTROVERSY.
ASK WE STAINED CELL IN THE
HYPOTHALAMUS AND THIS IS THE ONE
CELL AND WE SHINE A LASER ON THE
ONE CELL WE ACTIVATED THE PRIMER
IN THE ONE INHIBITORY NEURON.
HOW TO WHEN WE DO THE CHECK SEQ
ANALYSIS WE LOOK AT THE
CHROMATIN ONLY IN THAT ONE
IDENTIFIED INHIBITORY NEURON.
WE'RE IN THE PROCESS OF
PUBLISHING MORE DATA.
THIS ALLOWS US TO GO TO SINGLE
CELL NUCLEUS AND LOOK IN
IDENTIFIED CELLS AT THE STATUS
OF THOSE CELLS.
HOW ETHANOL IMPACT IN CHROMATIN
WILL IMPACT THE AMOUNT OF GENES
TRANSCRIBED.
THIS IS ANOTHER AREA OF
RESEARCH.
I KNOW NIAAA HAS FUNDED A FEW
GRANTS IN THIS AREA BUT IT'S A
LARGE EFFORT NOW ON
UNDERSTANDING WHAT RNAs ARE
DOING AND THERE WAS A REPORT ON
SEQUENCING OF RNA FROM CELLS
FROM TISSUES AND THE GOAL WAS TO
STIMULATE RESEARCH IN THE AREA
OF TRANSCRIPTOMICS IT'S THE
ANALYSIS OF THE CHEMICAL RNA AND
EVERY CELL A CHEMICAL
MODIFICATION AND THEY'RE
INVOLVED IN RNA BIOLOGY.
THERE'S WORK IN UNDERSTANDING
WHAT THEY'RE DOING TO CELLULAR
FUNCTION.
I'LL DESCRIBE THE ON SURFACE
RNAs.
RNAs ARE NOT JUST THE RNAs WE
FIND IN THE TRANSCRIPTOME.
THERE'S OTHER BIOLOGY
ASSOCIATED.
ALL RNAs BIND WITHIN CELLS
WHETHER PROTEINS THAT ALLOW
TRANSLATION OF THE RNAs OR
WITHIN CELLS OR ASPECT OF RNA
BIOLOGY INCLUDING DEGRADATION.
THEY'RE CHEMICALLY MODIFIED IN
SOME WAY.
THEY CAN ASSUME STRUCTURES.
RNA WITH ONE STRUCTURE TO BE
TRANSLATED AND THE SAME RNA AND
DIFFERENT CODING MAY NOT BE
TRANSLATED AS EFFICIENTLY.
THESE GIVE RIDES TO DIFFERENT
BIOLOGIES AND THEY MODULATE CELL
FUNCTION.
THAT POSES A WHOLE HOST OF
QUESTIONS THAT ARE IMPORTANT
BEYOND THE KNOWLEDGE AN RNA IS
PRESENT IN THE CELL TO
UNDERSTAND WHAT THE CELLS ARE
DOING AND CHARACTERIZE THE CELLS
AND IN TERMED OF E
EPITRANSCRIPTOME MANY ARE
PROBABLY FAMILIAR WITH THE EPIC
GENOME AND MODIFIED TO THE
COPYING OF DNA INTO RNA.
YOU CAN ALSO MODIFY RNA THROUGH
CHEMICAL MODIFICATION.
FOR DNA MODIFICATION THERE'S
SEVEN AND HUNDREDS OF
MODIFICATIONS FOR RNA.
AND THEY CAN ALTER THE
TRANSLATION AND A HOST OF
BIOLOGIES.
THE NUCLEOTIDES ARE MODIFIED IN
THIS CASE AND AGAIN ETHANOL
IMPACTS THIS THE ACUTE
MODULATION OF RNA CAN BE
MODIFIED BY A HOST OF
PHARMACOLOGIC AGENTS AND THE
NATIONAL ACADEMIES REPORT MAKES
A CASE FOR STUDYING THIS IN
DETAIL.
THE RNA MODIFICATION REGULATED
BY MODIFICATIONS CALLED READERS,
WRITERS AND ERASERS.
EVERY CELL IS MODIFIED TO SOME
EXTENT AND WE HAVE ANY POSITION
AMPLIFICATION.
WE ATTACH SINGLE STRANDED DNA.
AND THERE'S AN ATTACHMENT AND
ENDS UP BEING AN RNA
INTERROGATOR.
I'LL SHOW HOW IT WORKS.
YOU HAVE AN RNA BINDING PROTEIN
OR ANTIBODY TO IT AND IT BIND TO
THE ANTIGEN AND BIND IT TO ANY
RNA AROUND IT.
WHEN THAT HAPPENS, YOU CAN ADD
AN ENZYME TO THE FIXED TISSUE
AND COPY IT AND THEN REME OF THE
ANTIBODY COMPLEX AND AMPLIFY THE
RNA FROM THE IDENTIFIED ANTIGENS
AND THAT'S THE DATA I'LL SHOW
NOW AND WE HAVE AN ANTIBODY IN
THIS CASE TO MODIFICATION CALLED
M6A.
WE HAVE OUR NUCLEOTIDE AND SEE
M6A IN THE FIXED CELLS AND THIS
ANTIBODY BINDS AND THE OLIGO
NUCLEOTIDE IS MODIFIED AND THEN
MAKE A COPY OF THE RNA AND WHEN
WE DO THAT WE CAN FIND 1200
mRNAs AND THERE'S A WAY OF DOING
THIS NOW AND WE CAN DO NOT JUST
M6A BUT ALSO FOUR MODIFICATIONS
AND DO THEM SIMULTANEOUSLY IN
THE SAME CELLS AND NOW TRY TO
UNDERSTAND NOT JUST THE PRESENCE
OF THE RNA BUT ASPECTS OF THE
REGULATION THROUGH THIS TYPE OF
MODIFICATION AND FOR THIS
TRANSCRIPTION FACTOR YOU CAN SEE
THERE'S AN END IN THE RNA IN THE
CODING REGION AND 6A IN THE
PRIME UTR AND DIFFERENT VERSIONS
WHERE THEY OCCUR IN THE RNA.
IT'S QUITE COMPLEX.
THESE ARE RED IN BY READERS.
FMRP A TRANSCRIPTION FACTOR HAS
BEEN IMPLICATED AND WHAT BINDS
TO THE RNA AND TRANSLATES THE
BINDING INTO SOME ASPECTS OF
FUNCTION.
TD343 AND THE TYPE OF DATA WE
CAN GENERATE FOR ABLE RNA
ASSOCIATED WITH HUNTINGTON'S
DISEASE AND YOU SEE THIS IN THE
FIVE PRIME END AND LOOKING THE
THE READER YOU SEE THE OVERLAP
BETWEEN THE READER AND THE
EPITRANSCRIPTOMIC MARK.
IT'S QUITE INTERESTING AND
LEADING US TO UNDERSTAND THE
SYMPHONY OF REGULATION WITHIN
RNAs.
NOW GOING TO ANOTHER AREA AND
THIS IS MITOCHONDRIAL FUNCTION
AND ETHANOL CHANGES IN
MORPHOLOGY OF MITOCHONDRIA AND
THE PROPENSITY OF MUTATIONS TO
OCCUR WITHIN MITOCHONDRIA.
WE KNOW THEY MOVE TO SYNAPSES IN
SYNAPTIC SIMULATION AND THERE'S
DIFFERENT REASONS AND WHAT WE
KNOW ABOUT MITOCHONDRIA IS YOU
CAN HAVE ONE TO 10 ORGANELLES
WITH DNA AND THIS IS THE
DOMINANT ONE OTHER THAN THE
NUCLEUS.
ONE OF THE THINGS WE WERE
INTERESTED IN IS MITOCHONDRIA
MUTATIONS OR HOW THIS VARIES
BETWEEN CELL TYPES AS A FUNCTION
OF DISEASE.
ARE THE MITOCHONDRIA AND HOW
DIFFERENT ARE THEY IN TERMS OF
GENOMIC IN THEIR MITOCHONDRIAL
DNA.
WE MANUALLY DISSECTED INDIVIDUAL
MITOCHONDRIA AND SEQUENCED THE
MITOCHONDRIA ALLOWING US TO
DETECT THE MITOCHONDRIA AND LOOK
FOR MUTATIONS.
IT'S SLOW THROUGHPUT BUT HIGH
RESOLUTION.
WE CAN SEE HOW THEY'RE
MAINTAINED AND THIS IS
PUBLISHED.
WE LOOKED AT SINGLE MITOCHONDRIA
FROM 83 NEURONS AN ASTROCYTES
FROM THE MOUSE WITH A HIGHER
THROUGHPUT APPROACH AND GET
INDIVIDUAL MITOCHONDRIA AND
SEQUENCE THE INDIVIDUAL
MITOCHONDRIA.
IN DOING THIS WE'VE BEEN ABLE TO
SHOW THAT NEURONS AND ASTROCYTES
HAVE DIFFERENT NUMBERS AND
VARIATION FOR THE SINGLE
NUCLEOTIDE VARIANTS SUGGESTING
THEY UNDER GO PURIFYING
SELECTION AND WE LOOK AT THE
REACTION TO INCLUDING ETHANOL.
THERE'S WORK THAT STILL NEEDS TO
BE DONE.
WE KNOW THESE THINGS NOW ARE
OCCURRING BECAUSE OF DIFFERENCES
IN CELL TYPE VARIATION.
RECENTLY WE PUBLISHED AND
WORKING HARD ON THIS TO A HIGH
THROUGHPUT APPROACH TAKING CELL
AND ENCAPSULATE IN HYDRO GELS A
FLUIDICS DEVICE AND HAVE
INDIVIDUAL MITOCHONDRIA AND
CELLS IN THE HYDRO GELS AND NOW
UP TO CLOSE TO A MILLION OF
THESE HYDROGEL BEADS WITH
INDIVIDUAL MITOCHONDRIA AND MOVE
THROUGH THE SEQUENCE.
THIS IS IN COLLABORATION WITH
THE ENGINEERING DEPARTMENT HERE
AT PENN.
WE NEED TO GO TO HIGHER
THROUGHPUT BECAUSE THE CELLS
HAVE HUNDREDS OF MITOCHONDRIA
AND WANT TO LOOK AT THE CELLS.
IT'S POSSIBLE.
WE'VE ADAPTED NANO CORE
SEQUENCING.
WE GET FULL LENGTH SEQUENCING IN
A SINGLE MIGHT KCON DRA --
MITOCHONDRIA AND THEY'RE
SEQUENCED AND LOOK AT THE
MUTATION LANDSCAPE ACROSS THE
CELLS.
THE NANO CORE HAVE GOTTEN BETTER
IN TERMS OF REDUCED ERROR RATE
AND PRODUCED A PROCEDURE TO
SELF-VALIDATE WHAT WE DETECT.
WHEN THIS IS PUBLISHED PEOPLE
WILL SEE HOW THAT'S DONE.
AND WE LOOKED AT AMEALIOR JATING
THE SYMPTOMOLOGY AND LOOKED AT
THE RNA THAT GAVE RIDES TO
MITOCHONDRIA AND THE NUCLEUS
MAKES HUNDREDS OF PROTEINS THAT
GO IN THE MITOCHONDRIA TO ALLOW
IT TO FUNCTION.
WE'RE LOOKING AT NUCLEUS
MITOCHONDRIA COMMUNICATION AND
CAN IDENTIFY PARTICULAR NUCLEAR
GENES THAT CORRELATE AND WE'RE
TRYING TO UNDERSTAND WHAT THAT
MEANS IN TERMS OF THE
COMMUNICATION AND WHAT THAT
MEANS IN TERMS OF CO-REGULATION
OF THE NUCLEUS AND MITOCHONDRIA.
THIS IS IN ITS INFANCY BUT HOW
WE'LL UNDERSTAND HOW THEY CREATE
THE PROPERTIES OF CELLS.
MY LAB AND OTHERS ARE TRYING TO
UNDERSTAND VARIOUS ASPECTS OF
BIOLOGY BY DETECT BEING
CHEMICALS AND THERE'S A HOST OF
THINGS I'D LIKE TO BE ABLE TO
TELL YOU ABOUT BUT WE HAVE
LIMITED TIME.
THESE ARE THE PEOPLE I'VE BEEN
FORTUNATE ENOUGH TO WORK IN
VARIOUS PARTS OF THE PROJECTS
AND OTHERS I HAVEN'T HAD A
CHANCE TO TALK TO YOU ABOUT.
SO THAT'S THE SCIENTIFIC
PRESENTATION.
GEORGE, I DON'T KNOW IF YOU'D
LIKE ME TO TALK ABOUT THE NEURAL
ETHICS GROUP OR IF I'VE RUN OUT
OF TIME.
IT'S UP TO YOU.
>> I'D LIKE TO ASK A FEW
QUESTIONS AND GET US BACK ON OUR
FULL SCHEDULE SO MAYBE WE COULD
INVITE YOU BACK TO DO THE NEURAL
ETHICS.
>> NO PROBLEM.
>> JOHN DIDN'T HAVE TIME TO GET
INTO NEURAL ETHICS EITHER AND
IT'S A BIG ISSUE.
YOU'LL BE ABLE TO TELL US.
I'M PARTICULARLY INTRIGUED BY
SOME OF THE ISSUES AROUND WHAT
DO YOU DO WHEN THE DEVICE WEARS
OUT AND THE PATIENT STILL HAS IT
IN THEM AND SOME ISSUES I
REMEMBER BEING RAISED.
MY QUESTION FOR YOU WOULD BE
THERE'S SO MANY HISTORIES THAT
WE DON'T KNOW IN THE ALCOHOL
FIELD.
ONE IS WE HAVE NO IDEA WHAT LOW
DOSES OF ALCOHOL REALLY DO.
DO YOU THINK THE APPROACH LIKE
WITH THE EPILEPSY CAN GIVE US
INSIGHT AND THE OTHER PART OF
THAT QUESTION IS ALSO IN CELLS
IN THE LIVER NOT JUST THE BRAIN,
WHY ARE SOME PEOPLE CAN DRINK
LIKE FISH AND THERE'S NO LIVER
DISEASE AND OTHERS HAVE A
VULNERABILITY TO LIVER DISEASE
JUST ABOVE THE MODERATE DRINKING
LEVELS OR SOMETHING OF THAT
NATURE.
>> THOSE ARE PHENOMENAL
QUESTIONS.
IN TERMS OF THE FIRST QUESTION
ABOUT IN TERMS OF ALCOHOL ABUSE
AND HOW IT IMPACT NUCLEUS
MITOCHONDRIAL FUNCTION I AGREE.
THAT WOULD BE A VERY IMPORTANT
TO LOOK AT.
PERHAPS EVEN MORE GERMANE IS THE
EPITRANSCRIPTOME.
IT'S DYNAMIC.
YOU CAN GET CHANGES FROM
PHARMACO LOGICALLY INDUCED IN 15
MINUTES SHORT OR LONG TERM.
MY GUESS IS LOW-DOSE ALCOHOL
WILL CHANGE THE TRANSCRIPTOMIC
STATUS OF CELLS AND CHANGE THE
TRANSLATIONAL STATE OF THE RNA
AND A WHOLE HOST OF BIOLOGIES.
I THINK THAT WOULD BE ONE ACUTE
WAY OF THESE DIFFERENT
CONCENTRATIONS OF ALCOHOL TO
IMPACT CELL BIOLOGY.
CERTAINLY THE OTHER IN TERMS OF
THE LIVER WITH SOME PEOPLE BEING
RESPONDING A CERTAIN WAYS TO
ALCOHOL ABUSE AND OTHERS NOT,
EVERY CELL IS DIFFERENT.
THEY LOOK ALIKE BUT THE
TRANSCRIPTOME IS DIFFERENT AND
THE MITOCHONDRIA COULD BE VERY
DIFFERENT.
THERE WILL BE DISTINCTIONS
GENERATED BY THESE ORGANELLES
WHETHER NUCLEAR DNA OR OTHER
FUNCTIONS AND CHARACTERIZATIONS
OF THE SINGLE CELL BIOLOGY AND
CHARACTERIZING OF THESE WITHIN
DIFFERENT CELLS.
THE LIVER IS A GREAT EXAMPLE.
YOU'RE RIGHT, MOST OF US THINK
OF LIVER CELLS AS BEING
RELATIVELY HOMOGENOUS AND WE'RE
ALWAYS TRYING TO COMBINE WHAT
WE'RE DOING GENOMICALLY TO
FUNCTION AND YOU CAN SEE WHAT'S
CAUSING THE FUNCTIONS.
>> THERE YOU GO, CATHY, ANOTHER
LEVEL OF ANALYSIS FOR PEOPLE WHO
SEND IN GRANTS.
I ALWAYS DOMINATE QUESTIONS
BECAUSE I'M SO CURIOUS BUT DOES
ANYONE HAVE QUESTIONS.
>> I THOUGHT IT WAS WONDERFUL
HOW YOU POINTED OUT HOW WE'RE
BEGINNING TO UNDERSTAND THE SUB
CELLULAR ORGANELLES.
NEW ONES ARE BEING DESCRIBED.
ALSO YOU MATE WANT TO IF YOU
COULD TOUCH ON PHASE SEPARATION
WITHIN CELLS AND ORGANELLE AND
IN PARTICULAR FOR NEURONS ON
WHAT WE'RE LEARNING ABOUT THE
PRIMARY CILIUM AND WHETHER
THERE'S LOCAL TRANSCRIPTION
THERE.
THANK YOU.
>> I ALWAYS GET GOOD THOUGHTFUL
QUESTIONS FROM YOU.
THANK YOU.
WE CAN ENVISION MITOCHONDRIA.
IT HAS A DOUBLE MEMBRANE LIKE
PLASMA AND WE HAVE RIBOSOMES
THOUGHT OF AS MEMORILESS
ORGANELLES.
THEY THERE'S ORGANIZED INTO
FUNCTIONAL UNITS.
AND SO I THINK THE TYPES ONE
GETS IN TERMS OF THE
DISTINCTIONED THEY'LL BE TONS OF
THEM AND PEOPLE TALK ABOUT
STRESS GRANULES.
WE ALREADY KNOW THERE'S AT
LATEST 15 SUB CLASS OF STRESS
GRANULES.
THERE'LL BE A REAL SPECIFICITY
TO ALL OF THAT THAT'S GOING TO
BE IMPORTANT.
IS SECOND QUESTION?
>> WAS ABOUT THE PRIMARY CILIUM?
>> THE PRIMARY CILIUM IS AN AREA
WHERE ON THE CELL YOU CAN START
IT GET PROTRUSIONS FROM THE
CELL.
THE BASE IS AN ORGANELLE TO GET
TRANSLATION OF RNAs.
WE'VE DONE THAT AND IDENTIFIED
ALL AT THE BASE OF THE CILIUM
AND WE'VE USED A TECHNIQUE AND
WE HAVEN'T SHOWN FUNCTIONALLY
BURT THERE'S SPECIFICITY IN
TARGETING OF THE MOLECULES.
>> WE'RE IN THE PROCESS OF
SUBMITTING A PAPER DOING SINGLE
CELL TRANSCRIPTOME IN THE SAME
CELL AND COMBINING PROCEDURES.
JONATHAN HAS BEEN INTERESTED IN
THE PROTEOME AS OTHERS HAVE.
WE JUST CAN'T DO IT TO THE LEVEL
OF MASS SPEC NOW.
THERE'S OTHER PROCEDURES THAT
ALLOW US TO LOOK AT
SUBPOPULATIONS OF PROTEINS AND
YOU CAN USE ANTIBODIES.
THE ANTIBODIES HAVE A WHOLE SET
OF PROBLEMS.
SOME ARE GOOD, SOME AREN'T.
YOU CAN LOOK AT THOSE USING A
VARIETY OF OTHER PROCEDURES.
WE ARE NOT ANYWHERE NEAR BEING
ABLE TO DO THE PROTEOME.
YOU CAN DO THE PEPTIDOME AND
THEY CAN BE CUT INTO SMALL
PEPTIDES AND MANY CAN BE
DETECTED MY MASS SPEC.
BUT BIO CHEMICALLY, WE REALLY
CAN'T DO THE PROTEOME YET.
PEOPLE ARE TRYING.
I THINK THE MOST WE'VE BEEN ABLE
TO LOOK AT THUS FAR IS ON THE
ORDER OF ABOUT 700 PROTEINS FOR
AN INDIVIDUAL CELL.
THE LATEST DATA I'VE SEEN.
IT'S MUCH LESS THAN THE
COMPLEXITY OF THE PROTEINS
PRESENT IN THE CELL AND THAT'S
WORSE THAN RNA BECAUSE THE
PROTEINS HAVE PHOSPHORYLATION
AND CHANGES IN FUNCTIONING.
WE UNFORTUNATELY HAVE A WAYS TO
GO.
>> WE'LL HAVE TO MOVE ON BECAUSE
OF OUR TIME SCHEDULE BUT I
WANTED JIM TO SPEAK BECAUSE HE'S
BEEN SUCH A GREAT SUPPORTER OF
NIAAA AND INTERACTION WITH THE
BRAIN PROGRAM.
I THINK ALL LISTENING IN ON ZOOM
KNOW HOW TO FIND THEM AND HE'D
BE HAPPY TO ANSWER QUESTIONS.
UNLESS ANOTHER COUNCIL MEMBER
HAS A QUESTION WE'LL MOVE ON.
>> YOU'VE KNOWN MICHAEL SINCE
BOTH OF US HAVE BEEN KNEE HIGH
TO A BULL FROG.
AND SOME OF YOU KNOW ABOUT OUR
HARRY JUNE AWARD WE DO WITH ACMP
FOR A TRAVEL FELLOWSHIP EVERY
YEAR AND HE WAS HARRY'S MENTOR.
HE PASSED TOO EARLY BUT WAS A
BRILLIANT YOUNG MAN DOING OUT OF
THE BOX THINGS.
MICHAEL TRAUAUGHT HIM HOW TO DO
THINGS.
HE'S A PROFESSOR AT HUNTER
COLLEGE AND CITY UNIVERSITY IN
NEW YORK BIO PSYCHOLOGY PROGRAM
AND BEHAVIORAL NEURAL SCIENTIST.
AND MICHAEL WILL TALK ABOUT GLP
1 OR ALLUDE TO IT AND WE'VE BEEN
DOING IN THAT RESEARCH AND
SHOWED THE OPIOID NEURO PEPTIDE
SYSTEMS PLAY AFFECT DEVELOPMENT
INDEPENDENCE AND LOOK AT WHO
WILL RELATED LEARNING AND
DEFICITS.
ANOTHER RESEARCH EFFORT IS TO
EXAMINE THE ROLE OF NEURAL
BEHAVIORAL SYSTEM THAT LOOK AT
THE RELATIONSHIP TO THE
DEVELOPMENT OF OBESITY AND BINGE
EATING AND ANOREXIA.
HE WAS FORMERLY AHEAD OF NEURAL
SCIENCE AND BIOLOGY DOCTORAL
PROGRAM AT CITY INVESTIGATION
UNIVERSITY OF NEW YORK AND HAS
BEEN A GREAT MENTOR OVER THE
YEARS.
AND HE'S ALWAYS BEEN A GREAT
COLLEAGUE FOR ME FOR SOUNDING
OFF IDEAS.
I HOPE THE FEELING IS MUTUAL.
BUT I THINK WE TALKED ABOUT
MOTIVATIONAL OUT OF THE BOX KIND
OF APPROACHES TO OUR SCIENCE.
I THINK THAT'S THE WAY I LOOK AT
MICHAEL.
HE'S WILLING TO DO THE OUT OF
THE BOX EXPERIMENTS AND NOT
FOLLOW THE REGULAR PATH.
I'M HOPEFUL HE'LL TELL US ABOUT
HIS WORK INTERACTION WITH
FEEDING BEHAVIOR.
IT'S ALL YOURS, MICHAEL.
>> THANK YOU, GEORGE FOR THE
KIND INTRODUCTION.
I'VE LEARNED A LOT IN THE LAST
COUPLE TALKS.
IT'S BEEN A VERY DIFFERENT
APPROACH TO GETTING AT ALCOHOL
PROBLEMS AND IT'S GOING BACK A
WAYS LOOKING AT HOW A NUMBER OF
US CAME TO DO ALCOHOL RESEARCH.
DOING ALCOHOL RESEARCH HAS BEEN
VERY DIFFICULT.
SOME MODELS WE'VE HAD TO WORK
WITH OVER TIME IN NEURAL
PHARMACOLOGY HAVE NOT EMBRACED
ALCOHOL ALL THAT WELL AND IT
HASN'T REALLY FIGHT INTO A LOT
OF THE MODELS.
THAT'S WHERE I'M COMING FROM IN
TERMED OF MY BACKGROUND.
THAT'S WHERE I MET HARRY JUNE
AND HE WAS IN THE SAME SITUATION
AND WE WERE STUDYING OTHER
THINGS BUT THERE WERE A VARIETY
OF RESEARCH WITH ALCOHOL.
I'LL TAKE YOU THROUGH HOW WE
CAME TO DO INTERESTING
EXPERIMENTS THAT HAD EMPHASIZED
BASIC AREAS IN BEHAVIORAL NEURAL
SCIENCE AND DEPARTMENTS AND
PROGRAMS I WAS IN LOOKING AT
MECHANISMS INVOLVED WITH FOOD
INTAKE, NUTRITION AND
REINFORCEMENT REALLY REWARD AND
REWARD SYMPTOMS.
I'M GOING TO TAKE YOU BACK TOE
LOOK AT SOME OF THOSE THINGS
RAND WHERE HARRY JUNE FIT IN AND
SOME OF THE NAMES GEORGE
MENTIONED EARLIER ABOUT KEN
WARREN AND A VARIETY OF OTHERS
NOT WITH US NOW.
I'M GOING TO BE TALKING ABOUT
ANOTHER PERSON WHO IS NOT WITH
US NOW AND THAT'S HARRY JUNE.
IT'S AN INTERESTING TOUR OF
TRYING TO UNDERSTAND HOW ALCOHOL
INTERACTS WITH OUR BASIC
SYSTEMS.
AND THINKING HOW TO TALK ABOUT
THESE DIFFERENT TOPICS I LOOKED
AT A VARIETY OF OTHER SPEAKERS
TO DISCUSS THEIR WORK.
WHAT CAME TO MIND WAS A RECENT
PRESENTATION BUT DAVID CARRIGAN
WHO GAVE AN INTERESTING
DISCUSSION OF HIS RESEARCH AT
INDIANA LOOKING AT REWARD AND
COMPETITIVE MECHANISMS AND HOW
THOSE MECHANISMS HAVE FIT IN
WITH MORE RECENT RESEARCH WITH
THE EXECUTIVE CENTERS OF THE
BRAIN.
THE DUALITY AND TALKING ABOUT
THEM AS MECHANISMS LIKE DOCTOR
DOLITTLE PUSH MY, PULL YOU WAY
OF APPROACHING THE DUALITIES
THAT EXIST IN UNDERSTANDING
REWARD AND UNDERSTANDING THE
REWARD SYSTEM.
WE'VE EMPHASIZED THE REWARD AND
DRIVE MECHANISMS VERSUS
INCENTIVE MECHANISMS.
THIS IS CLASSIC PSYCHOLOGY.
LOOKING AT THOSE KINDS OF
MECHANISMS TO TRY AND UNDERSTAND
ALCOHOL IT'S SOMETHING A LOT OF
US ENJOY.
IT'S ONE OF THOSE MYSTERIOUS
PHARMACOLOGIC AGENTS THAT'S VERY
UNIQUE.
DOES ANYONE KNOW WHY IN TERMS OF
NEURAL PHARMACOLOGY?
BECAUSE IT'S NOT ONLY A
PHARMACOLOGIC AGENT, IT'S A
FOOD.
IT'S A CALORICALLY DENSED FOOD
AND ALCOHOL IS INVOLVED WITH OUR
BEST OF LIFE SOME SOCIAL EVENTS
AND A WIDE VARIETY OF THINGS AND
IT'S A CHEMICAL THAT IS NOT VERY
COMPLEX.
I GAVE A TALK IN BORDEAUX ONE
TIME HAVING A DISCUSSION ABOUT
ALCOHOL AND ONE OF THE FAMOUS
PEOPLE IN THE ALCOHOL FIELD
TALKED ABOUT ALCOHOL AS BEING
ONE OF THESE INTERESTING SMALL
MOLECULES THAT GETS EVERYWHERE
AND MESSES UP EVERYTHING EXCEPT
HE DIDN'T SAY MESSES UP.
IT INDEED SEEMS TO BE THAT
COMPOUND.
THAT'S CAUSED A LAG IN OUR
UNDERSTANDING OF WHAT'S GOING
ON.
SOME THINGS I'LL TALK ABOUT HAVE
TO DO WITH OTHER PHARMACOLOGIC
AGENTS SUCH AS AMPHETAMINE AND
PSYCHOTICS AND USING METHODS IN
THAT AREA HAVE NOT BEEN ALL THAT
SUCCESSFUL.
THERE'S A MEMORIAM TO LARRY AND
IT'S APPEARED IN NATURE
PUBLICATIONS FROM THE RSA AND OF
COURSE HOWARD UNIVERSITY WHERE
HARRY WAS TRAINED AND ULTIMATELY
ENDED UP IN TERMS OF HIS CAREER.
I WANT TO TALK ABOUT HOW HARRY
AND I INTERACTED IN TERMS OF
DOING RESEARCH OVER THE YEARS.
HE WAS MY STUDENT PUT WENT ON TO
WORK AT OTHER LOCATIONS.
I JUST HEARD ABOUT SOME OTHERS.
OUR LOSS OF KEN WARREN ALSO
IMPORTANT PLAYING A ROLE IN SOME
OF THE RESEARCH I'M GOING TO
TALK ABOUT.
I'LL TALK ABOUT THOSE.
TO THE RESEARCH GOES TO
UNDERSTAND WHAT'S GOING ON WITH
REW
REWARD SYSTEMS IN THE BRAIN.
I BEGAN DOING RESEARCH THAT
FOCUSSED ON AN INTERESTING
DISCOVERY BY RESEARCHERS AT
McGILL UNIVERSITY AND THEY WERE
TRYING TO INFORMATION THE LIMBIC
SYSTEM AND DOING EXPERIMENTS.
OLDS WAS TRAINED IN CLINICAL
PSYCHOLOGY AT HARVARD AND PETER
MILNER HAD BEEN TRAINED AT
McGILL.
THEY HAD GOTTEN TOGETHER TO
START PROBING THE LIMBIC SYSTEM.
IT WAS SOMETHING INVOLVED WITH
EMOTIONAL BEHAVIOR AND WE HAD
MAYBE 30 OR 40 YEARS OF RESEARCH
IN THE LIMBIC SYSTEM.
THEY WERE MESSING AROUND IN THE
LAB TRYING TO SEE WHAT GOES ON
IF YOU STIMULATE VARIOUS AREAS
OF THE LIMBIC SYSTEM.
THIS IS A DIAGRAM I WAS GIVEN
AND THIS SHOWS THE INITIAL
EXPERIMENTS BETWEEN OLDS AND
MILNER LOOKING AT ACTIVITIES IN
THE LIMBIC SYSTEM AND SAW
BEHAVIORS THEY DIDN'T
UNDERSTAND.
THEY EXPECTED TO SEE STIMULUS
BEHAVIORS AND 340E6789
MOVEMENT THE ANIMAL WOULD ENGAGE
WITH AND OLDS RECOGNIZED THE
ANIMAL SEEMED TO BE GOING BACK
TO WHERE THEY GOT ELECTRICALLY
STIMULATED AND MAYBE WE WERE ON
TO SOMETHING RESEARCH HADN'T
GOTTEN AT.
MOST THE RESEARCH IN THE LIMBIC
SYSTEM YIELDED INFORMATION ABOUT
THE NEGATIVE EMOTIONS.
FEAR, AGGRESSION AND A WIDE
RANGE BUT VIRTUALLY NO STUDIES
UP THESE KINDS OF EXPERIMENT
WITH THE EXCEPTION OF HUMANS
THAT COULD BE INTERPRET ED AS
GETTING AT THE REWARD SYSTEM AND
MAYBE WE WERE TAPPING INTO
MOTIVATING BEHAVIOR.
HE SHIFT THE MODEL TO SOMETHING
MORE OBVIOUSLY CONDITIONING AND
GETTING AT REWARD FUNCTIONS.
HIS EXPERIMENT INVOLVED MOVING
THE SITUATION FROM THE OPEN
FIELD INTO THE CLASSIC SKINNER
BOX.
WHEN HE DID THAT HE WAS ABLE TO
DEMONST
DEMONSTRATE DISCREET RESPONSES
COULD HAVE CURRENT DELIVERS TO
SPECIFIC AREAS OF THE BRAIN.
HE SET ABOUT TRYING TO
UNDERSTAND THIS AND DID BRAIN
MAPPING EARLY ON AND DID A WIDE
VARIETY OF EXPERIMENTS USING
TECHNIQUES WHERE THE REWARD
FUNCTIONS WERE MORE OBVIOUS.
THE INDIVIDUAL ENGAGED UP
MOVEMENTS AND ELECTRICAL
STIMULATION AND THE ANIMALS
INCREASED THE RESPONSES.
AS THE LOOK VERY MUCH LIKE THE
CLASSIC AFFERENT CONDITIONING
SKINNER TALKED ABOUT.
HE DID RESEARCH IN THE AREA AND
BECAME FAMOUS FOR IT AND BECAME
A MEMBER OF THE NATIONAL
ACADEMIES AND A VARIETY OF
THING.
OLDS WORK WITH A NUMBER OF
PEOPLE AT HARVARD INCLUDING
SKINNER.
NOT SURE SKINNER WAS HIS MENTOR
BUT HE LEFT McGILL AND GOT AN
ACADEMIC POSITION AND STARTED
WORKING WITH THIS PERSON NAMED
DAVE MARGULES AND HE WAS HIS
MENTEE AND HE TURNED OUT TO BE A
VERY IMPORTANT PERSON IN THE
RESEARCH IN THIS AREA BECAUSE
THE TWO WORKED TOGETHER TO DO
RESEARCH SHOWING THE REWARD
SYSTEM OLDS FOUND WAS IN THE
MALTLY INVOLVED WITH FOOD
INTAKE.
AND HE PUBLISHED A PAPER LOOKING
AT IDENTICAL SITES IN THE BRAIN
THAT MEDIATE CELL STIMULATION.
THIS WAS PUBLISHED UP SCIENCE
AND BAG TO BACK WAS A MENTEE OF
A NOTED PHYSIO PSYCHOLOGIST AT
THE INVESTIGATION OF
PENNSYLVANIA.
THE RESEARCH WAS PUBLISHED
TOGETHER SHOWING THAT THAT
REWARD SYSTEM WAS INTIMATELY
INVOLVED WITH FOOD INTAKE.
THERE SEEMED TO BE SOMETHING
UNIQUE ABOUT THE SITES WHERE YOU
GET THE BEST RESPONDING FOR
BRAIN STIMULATION THAT INVOLVED
THE FEEDING SYSTEMS.
WHEN MARGULES MOVED ON TO AN
ACADEMIC POSITION HE HAD AN
INTEREST IN STUDENTS AND ONE WAS
ME AND HE WAS MY MENTOR.
I MOVED IN HIS LAB AND WE
STARTED DOING BRAIN RESEARCH AND
LEARN ABOUT BRAIN STIMULATION
REWARD AND HE SAID NO, WE'RE NOT
DO THAT.
HE SAID WE'RE GOING TO
UNDERSTAND THE MECHANISM
INVOLVED WITH CONTROLLING FOOD
INTAKE.
OUR FIRST PUBL CAKESES WERE
DOING FOOD INTAKE EXPERIMENTS.
HEAR WE HAVE THE FIRST
DISSERTATION WORK.
MY FIRST PUBLICATION WAS LOOKING
RAT HIPE -- HYPOTHALAMIC ROLE OF
FOOD INTAKE AND NOR EPINEPHRINE
AND CONTINUED DOING EXPERIMENTS
FOR SOME TIME.
EVENTUALLY I FINISHED WITH HIM
AND WE DID RESEARCH ON FOOD
INTAKE AND WITH S.
-- OPIOIDS IN PARTICULAR BEING
INVOLVED WITH FOOD INTAKE.
THIS LED TO A PUBLICATION THAT
LED ONCE I LEFT HIS LAB I WAS
WORKING AT ANOTHER INSTITUTION
TUFT'S UNIVERSITY AND WE WERE
DOING DIFFERENT EXPERIMENTS AND
I WAS DOING A SIMILAR STUDY WITH
A RAT BOTH GENETICALLY OBESE
ANIMALS AND LOOKING AT THE
EFFECTS OF MANIPULATING THE
OPIOID SYSTEM AND IT'S EFFECTS
ON THE BEHAVIOR IN THE ANIMALS.
WE CONTINUED THIS RELATIONSHIP
BETWEEN FOOD INTAKE AND REWARD
FOR SOME TIME.
AFTER MOVING WITH DAVE I MOVED
TO DOING RESEARCH AT TUFT'S
UNIVERSITY WHERE THERE WAS AN
INCREASED INTEREST IN MECHANISMS
INVOLVED WITH REWARD.
I BEGAN WORKING WITH OTHERS IN
THE FIELD AND IN THE OPEN FIELD
AND IT BECAME KNOWN AS DEEP
BRAIN STIMULATION AND THAT
BECAME THEIR PRIMARY FOCUS WHERE
ELECTRICAL STIMULATION OF BRAIN
AREAS ARE USED IN THERAPEUTIC
SITUATIONS.
THIS IS A RECENT ARTICLE LOOKING
AT DEEP BRAIN STIMULATION AND
DISCREET AREAS OF BRAIN AREAS IN
THE TREATMENT OF ALCOHOL RELATED
PROBLEMS.
IT'S BEEN AN ACCEPTED PARADIGM
AND ALLOWS US TO GET TO
IMPORTANT AREAS IN THE BRAIN
THAT ARE INVOLVED WITH
MOTIVATION AND REINFORCEMENT AND
I BEGAN DOING RESEARCH IN THIS
AREA.
WHAT ALSO DEVELOPED DURING THIS
PERIOD OF TIME I THOUGHT WE
COULD DO ELECTRICAL BRAIN
STIMULATION THAN OTHERS IN THE
AREA AND LOOKING AT SPECIFICALLY
AT AFFERENT CONDITIONING
PARADIGMS.
IN THIS RESEARCH I WAS WORKING
WITH TUFT'S UNIVERSITY AND
LOOKING AT RESPONSE RATES AND
WE'RE USING A FIXED RATIO
SCHEDULE OF REINFORCEMENT.
THIS IS THE KIND OF THING WHERE
AN EXPERIMENTAL ANIMAL OR HUMAN
SUBJECT ENGAGES IN SOME DISCREET
OPERANT AND GETS REINFORCEMENT
AND SOMETHING UNIQUE HAPPENS
WHEN THAT OCCURS.
WHEN A REPRESENTATION OCCURS YOU
GET AN INCREASE IN THE
CUMULATIVE RECORD.
WHEN YOU ARE WORKING ON A FIXED
SCHEDULE OF REINFORCEMENT IT'S
DIFFERENT FROM OTHER SCHEDULES
PARTICULARLY REINFORCEMENT WITH
BRAIN STIMULATION YOU GET A
PATTERN THAT LOOKS LIKE THIS.
HOWEVER IF YOU DECREASE THE
INTENTION -- INTENSITY AND ONLY
SO MANY RESPONSES AND HERE'S AN
FR40 FROM OTHER WORK.
WHEN YOU GET THE FIXED RATIO
REINFORCEMENT YOU GET THE
REINFORCEMENT PAUSE AND WE
THOUGHT THIS WAS AN INTERESTING
SITUATION THE POST REINFORCEMENT
PAUSE OCCURS WITH FOOD OR A WIDE
VARIETY OF STIMULI.
YOU GET POST REINFORCEMENT PAUSE
AND WHEN YOU GET TO SAY AN FR40
AND IT'S UNIQUE TO FIXED RATIO
SCHEDULE OF REINFORCEMENT.
SO RICK PHELPS AND I MY GRADUATE
STUDENT AT TUFTS LOOKED RAT THE
SHIFTS WHEN YOU HAD AN
EXPERIMENTAL ANIMAL ENGAGED IN
OPERENT BEHAVIOR FOR A
REINFORCEMENT USING A BIPHASIC
DILATION AND THIS OCCURS WHEN
YOU'RE ON A FIXED RATIO SCHEDULE
OF REINFORCEMENT.
THERE'S NO REINFORCEMENT
OCCURRING HERE.
AS YOU MAKE THE INNER RESPONSE
INTERVAL.
THE CURRENT INTENSITIES THAT CAN
BE DELIVERED HERE BEGIN TO
INCREASE.
WE FIND THE POST-REINFORCEMENT
PAUSE GETS SMALLER AND SMALLER.
WE USE THIS AS A WAY OF GETTING
AT THE THRESHOLD FOR ELECTRICAL
BRAIN STIMULATION.
AS WE INCREASE THE CURRENT
INTENSITY THE POST REINFORCEMENT
PAUSE GETS SMALLER AND SMALLER
AND THEN EVENTUALLY WHEN YOU GET
TO THE THRESHOLD FOR ELECTRICAL
STIMULATION, FOR EXAMPLE, HERE
THE FR CURRENT INTENSITY IS 65
AND YOU GET TO 40 THE POST
REINFORCEMENT PAUSE DISAPPEARS.
WHAT WE DEVELOPED WAS A BRAIN
STIMULATOR THAT COULD PRODUCE
THIS KIND OF OPERENT BEHAVIOR
WHERE THE ANIMAL WOULD LOOK TO
BAR PRESS AND IT'S REINFORCES
AND CONTINUES THROUGH THE
OPERENT SESSION WHEN THE FR IS
ABOVE THRESHOLD BUT AS YOU
INCREASE THE INTENSITY DURING
THE INNER RESPONSE INTERVAL THE
POST REINFORCEMENT PAUSE
DISAPPEARS.
WE USE IT AS A WAY OF MEASURING
THRESHOLD BY LOOKING AT THE
CURRENT INTENSITY THAT LEADS TO
THIS KIND OF SHIFT.
WE COULD DESIGN A STIMULATOR
THAT WOULD ALLOW US TO DO
VARIOUS DIFFICULT MATHEMATICAL
KIND OF ANALYSES AND USE IT TO
MEASURE THRESHOLD FOR ELECTRICAL
BRAIN STIMULATION.
EXPERIMENTAL ANIMALS AND THESE
ARE RATS IN THESE EXPERIMENTS
LEARN TO BAR PRESS ON THE FIXED
RATIO SCHEDULE.
AND THEN WE HAD A SEPARATE
CURRENT INTENSITY MECHANISM THAT
INCREASED THE INNER RESPONSE
INTERVAL UNTIL WE GOT TO A POINT
WHERE THE POST REINFORCEMENT
PAUSE DISAPPEARED.
THE COMPUTER AND SIMULATOR WOULD
ALLOW US TO ESTIMATE THE EXACT
CURRENT INTENSITY THAT YIELDED
REINFORCEMENT.
WE WERE USING THIS AS A WAY OF
SEPARATING OUT RESPONSE RATE
FROM REINFORCEMENT USING BOTH
REINFORCEMENT PAUSE.
NOW, I MOVED ON AND WE STARTED
BUILDING A LAB USING THIS KIND
OF MECHANISM.
AND I HAD A NEW STUDENT JOIN MY
LAB.
AND HARRY APPROACHED THE FIELD
FROM A CLINICAL PSYCHOLOGY
BACKGROUND AND JOINED MY LAB AND
BECAME INTERESTED IN OUR
RESEARCH IN THIS AREA.
HE STARTED WORKING ON FOOD
INTAKE EXPERIMENTS BUT QUICKLY
GOT INVOLVED WITH OTHER
REINFORCERS AND IN PARTICULAR
BRAIN STIMULATION REWARD.
SO WE BEGAN DOING EXPERIMENTS
LOOKING AT BRAIN STIMULATION
REWARD WITH A VARIETY OF DRUGS
STIMULANT DRUGS, DRUGS THAT
ENHANCE LOCAL MOTOR ACTIVITY AND
SERVED AS POSITIVE REINFORCE
MANIMREINFORCEMENT
IN ADDITION WORKED OUT WELL BUT
RESEARCH WITH ALCOHOL DID NOT.
THESE ARE THE BRAIN SITES WE
EXAMINED AND THE BRAIN SITE THAT
TURNS OUT TO BE BEST FOR
PRODUCING BRAIN STIMULATION
AWARD IS THIS SITE IN THE
HYPOTHALAMUS AND IT'S AN AREA
THAT PRODUCES THE HIGHEST RATES
OF BRAIN STIMULATION REWARD
LOCATED ALONG THE ASCENDING
FIBERS THROUGH DOPAMINE AREAS
AND WE SEE AN ELECTRODE THAT CAN
STIMULATE THE LATERAL
HYPOTHALAMUS AND SUPER IMPOSED
ON DOPAMINE PATHWAYS IN THE
BRAIN.
AND EXAMINED ELECTRICAL
STIMULATION BEYOND THE CELL
BODIES FOR THE DOPAMINE SYSTEM
AND LOOKED AT ELECTRICAL BRAIN
STIMULATION.
WE FOUND THAT WHEREAS ALCOHOL IS
A DEPRESSANT DRUG AND VERY
DIFFICULT TO LOOK AT OTHER THAN
IN TERMS OF OPERANT BEHAVIOR
OTHER THAN DEPRESSIVE BEHAVIORS,
WE WE LOOKED AT RESPONSE RATES
OR LOWERING THE THRESHOLD.
AND WE TRIED A VARIETY OF TIME
POINTS AND IT DOESN'T SEEM TO
WORK VERY WELL.
WHEN WE DID THE TYPICAL TEST IT
LOOKS LIKE THIS KIND OF OPERANT
RESPONSE AND WE TRIED A VARIETY
OF DOSES OF ALCOHOL.
THESE ARE IT CONTROL VALUES AND
INJECTION OF ALCOHOL WHEN WE
USED THE TIME AFTER
ADMINISTRATION 30 TO 60 MINUTES
WHICH IS WHAT WE USED FOR A
VARIETY OF OTHER DRUGS AND FOUND
NO EFFECT OF ALCOHOL.
I READ A PAPER BY A NOTED
RESEARC
RESEARCHER AND THEY SHOWED
RECORDINGS OF INDIVIDUALS TAKING
ALCOHOL BOTH ALCOHOLICS AND
NON-ALCOHOLICS IN HIS STUDY AND
FOUND THAT EEG RECORDINGS AFTER
THE ALCOHOL SHOWED STIMULANT
EFFECTS VERY SOON AFTER THE
ADMINISTRATION.
SO ALCOHOL LEVELS IN A VARIETY
OF CONCENTRATIONS PRODUCED AN
AROUSAL KIND OF EE G RECORDING
AND SAID THAT LATER ON THE EEG
RECORDING SHOWS MORE DEPRESSIVE
SIGNALS AND SO WE WENT BACK AND
LOOKED APT THE BLOOD ALCOHOL
CURVE AND WE FOUND THAT THERE
SEEMED TO BE VERY DIFFERENT KIND
OF BEHAVIORAL EFFECTS WHEN WE'RE
LOOKING AT THE S ENDING OF THE
BLOOD ALCOHOL CURVE AND THOSE
OCCURRING BACK OUT HERE.
SO AROUND 30 MINUTES THAT WAS
THE DESCENDING BLOOD ALCOHOL.
WE DECIDED WE'D LOOK AT THE
EFFECTS ON BRAIN STIMULATION AS
FAST AS WE COULD ADMINISTER
ALCOHOL AND SET THEM UP TO DO
ELECTRICAL BRAIN STIMULATION
REWARD STUDIES.
AND BEGAN FINDING POSITIVE
RESULTS.
HERE'S AN EXPERIMENT USING THE
SAME ANIMAL BUT GIVING ALCOHOL
BETWEEN FIVE AND 20 MINUTES WHEN
WE DID THE ELECTRICAL BRAIN
STIMULATION.
HERE'S THE THRESHOLD FOR
ELECTRICAL BRAIN STIMULATION
THAT YIELD A LOWERING OF THE
THRESHOLD.
THIS IS RESPONSE RATE HOW FAST
THE SUBJECT WAS BAR PRESSING AT
THE TIME.
LOW DOSES OF ALCOHOL SHOWED THIS
KIND OF EFFECT.
HOWEVER IF YOU WAITED THE 30
MINUTES AND AT A VARIETY OF
OTHER KINDS OF RESPONSES WE GOT
NO EFFECT.
THIS LED TO US LOOKING AT
ALCOHOL AND BRAIN STIMULATION
AWARD.
OTHERS HAD DIFFICULTY WITH THIS
EXPERIMENTATION.
WE HAD SOME INTERESTING
DISCUSSIONS ABOUT ALCOHOL AND WE
DID SOME EXPERIMENTS.
HE WAS NOT FINDING ALCOHOL IN
EVEN LOW DOSES TO ENHANCE BRAIN
STIMULATION AWARD USING A VERY
DIFFERENT SYSTEM THAN THE ONE I
WAS USING.
HE FOUND IF THE ANIMALS LEARNED
TO SELF-MINISTER ALCOHOL USE TO
THESE EFFECT BUT NOT WITH
ANIMALS NAIVE AND HAD LEARNED TO
SELF-ADMINISTER ALCOHOL.
SINCE THEN INCLUDING WORK WITH
LARRY JUNE AND INDIANA FOUND
ALCOHOL LOWERS REWARD THRESHOLDS
THOUGH THEY'RE IN THE USING
TECHNIQUES SIMILAR TO MINE.
THE EFFECTS IN TERMS OF
PRODUCING STRONG REINFORCING
EFFECTS DURING THE ASCENDING
BLOOD ALCOHOL CURVE STIMULATION
OVER HERE SEEMED TO HAVE THE
OPPOSITE EFFECT.
LOWERING THRESHOLD OR NO EFFECT
EVEN OF LOW DOSES WITH ALCOHOL.
SUBSEQUENT RESEARCH LOOKING AT
WHAT IS ASSOCIATED WITH THE
ASCENDING BLOOD ALCOHOL CURVE
AND ASSOCIATION WITH THE DES
DESCENDING REWARD AFFECTS WERE
ASSOCIATED.
SO WE CONTINUED WITH THIS
RESEARCH.
LARRY WORKED ON SOME OF THESE
EXPERIMENTS BUT HE HAD OTHER
AGENDAS AND BEGAN LOOKING AT
RESEARCH IN A VARIETY OF OTHER
AREAS.
HE GOT HIS DOCTORATE DOING BRAIN
STIMULATION EXPERIMENTS AND WAS
TRANS FIXED WORKING WITH THE
BENZODIAZEPINE SYSTEM AND
LOOKING AT EXPERIMENTAL ANIMALS
GIVEN ALCOHOL AND INTOXICATING
DOSES OF ALCOHOL ON THE COVER OF
SCIENCE.
IT CAME FROM THE LABS AT NIH AND
STEVE PAUL AND OTHERS.
HARRY BECAME TRANS FIXED BY THIS
BUT ALSO BECAME INTERESTED IN
OTHER RESEARCH HAVING TO DO WITH
THE GABA DIE AS PENE RESEARCH
AND CONTINUED RESEARCH GOING ON
TO WORK AT JOHNS HOPKINS WHERE
HE DID SOME VERY IMPORTANT WORK.
HARRY WAS NOT INTERESTED IN
GOING TO HOPKINS AND IT TOOK
CONVINCING.
OUR RELATIONSHIP TURNED OUT TO
BE COMPLICATED BUT PROFITABLE
FOR BOTH OF US.
WHEN LARRY WENT TO WORK AT
HOPKINS HE WORKED WITH A VARIETY
OF PEOPLE.
I WAS INVITED TO GIVE A TALK AT
THE BROWN BAG AT PRINCETON
UNIVERSITY IN THE LAB OF BART
HOGGEL AND FOUND ABOUT RESEARCH
WE HAD BEEN DOING AND BART
INTRODUCED ME TO DOING RESEARCH
WITH SOME OF THE NEURAL PEPTIDES
INVOLVED WITH FOOD INTAKE AND
NUTRITION AND REINFORCEMENT
EFFECTS.
I BEGAN DOING RESEARCH IN THIS
AREA.
WE HAD DONE EARLIER RESEARCH
LOOKING AT NPY IN TERMS OF
INCREASES IN FOOD INTAKE AND
REWARD AND WHEN WE BEGAN STUDIES
IN ALCOHOL IT DIDN'T PROVE
EFFECTIVE AND I BEGAN DOING
STUDIES LOOKING AT NEURAL
PEPTIDES THAT WERE REINFORCING
BUT ALSO INVOLVED WITH FOOD
INTAKE AND CARRYING ON RESEARCH
THAT WE HAD ORIGINALLY STARTED
AND THIS IS THE RESULTS OF SOME
EXPERIMENTS LOOKING AT GALLANIN.
IT'S AN INTERESTING COMPOUND.
AND GHRELIN THAT INCREASED FOOD
INTAKE AND A LAB STARTED WORK
WITH GALANIN AND WORKED WITH
ANOTHER LAB DOING RESEARCH AND
FOUND IT WAS INVOLVED WITH
INCREASING FOOD INTAKE BUT FOOD
INTAKE THAT INVOLVED FATTY
FOODS.
FAT RICH DIETS SEEMED TO BE
STIMULATED.
NPY DIDN'T WORK THERE BUT
GALLANIN DID AND BEGAN STUDIES
IN THAT AND NEURO TRANSMITTERS
AND REINFORCEMENT EXPERIMENTS
MAINEDD -- MAINTAINED IN MY LAB
AND WITH A LAB AT PRINCETON.
HERE WE SEE THIS IS COMING FROM
A LABORATORY AT ROCKEFELLER.
SHE WAS SHOWING THAT GALANIN
LEVELS IN THE BRAIN WENT UP WITH
HIGH FAT DIET.
AND YOU CAN SEE THIS EFFECT
HERE.
DIFFERENT EFFECTS WHERE HIGH FAT
DIETS WERE ADMINISTERED AND THE
SAMPLE WAS TAKEN.
SO WHAT HAPPENS AFTER ALCOHOL
ADMINISTRATION?
YOU MADE THIS CONNECTION BETWEEN
GALANIN AND EFFECTS OF ALCOHOL.
THERE SEEMS TO BE SOME SPECIAL
RELATIONSHIP THERE AND WE FOUND
CHRONIC ALCOHOL INJECTION OR CON
INCREASED GALANIN LEVELS AND
BEGINNING TO LOOK MORE
INTENSIVELY IN TERMS OF WHAT'S
GOING ON WITH GALANIN.
SO WE INJECTED IT AND LOOKED AT
VOLUNTARY ETHANOL INTAKE.
THIS IS A STUDY I DID WITH THESE
RESEARCHERS WHERE FIRST OFF WE
LOOKED AT THE THIRD VENTRICLE
AND INJECT ED GALANIN AND DIREC
INJECTION IN THE NUCLEUS AND
PRODUCE AN INCREASE IN ALCOHOL
CONSUMPTION.
WE SEE STARBUCKS OF GALANIN IN
THE BRAIN PRODUCED AN INCREASE
IN ETHANOL AND THESE ARE EFFECTS
ON WATER IN THE TWO-BOTTLE
CHOICE TEST WE SEE IN ALCOHOL.
THE EFFECT WAS STRONGEST DURING
THE DARK CYCLE.
THE LIGHT DARK CYCLE, ANIMAL
MEANTIME ON THE LIGHT/DARK CYCLE
AND WHERE HE CONTINUED TO PURSUE
THIS RESEARCH FOR A LONG PERIOD
OF TIME.
>> WE'RE RUNNING OUT OF TIME.
IT'S FASCINATING ON THE NEURAL
PEPTIDES AND BRAIN REWARD.
WE HAVE ABOUT FIVE MORE MINUTES.
>> OKAY.
THE RESEARCH CONTINUED.
I MOVED ON TO DOING RESEARCH
WITH OTHERS LOOKING AT THE LIVER
AND IT LED TO EXAMINING WHAT
HAPPENS WITH HIGH FAT DIETS.
THE CONNECTION BETWEEN FAT AND
ALCOHOL SEEMED TO BE
SUBSTANTIATED BY THE RESEARCH.
IT'S LED TO US BECOMING
INTERESTED IN NUTRITIONAL
FACTORS INVOLVED IN REGULATORY
SYSTEMS THAT GO ON BUT ALSO THE
EFFECTS OF CHRONIC ALCOHOL
CONCENTRATION IN MAINTAINING
NORMAL NUTRITION.
ONE OF THE THINGS -- I'M NOT
GOING TO BE ABLE TO TALK ABOUT
THIS IS MY CONCERN THAT IN THE
ONLY IS FAT IMPORTANT BUT IT'S
ALSO VERY MUCH INVOLVED WITH
ALCOHOLISM AND PATIENTS GIVEN
THE HANGING BAG EXPERIMENT.
I'LL SKIP TO MY DISCUSSION OF
HARRY JUNE WHO WORKED WITH ME
DURING MOST OF THESE EXPERIMENT.
WE REMAINED CLOSE STUDENT MENTOR
RELATIONSHIPS AS POSTDOCS AND HE
BECAME A PROFESSOR AN COLLEAGUE.
HE'S A BELOVED FRIEND AND HERE'S
A LIST OF PUBLICATIONS WE DID
OVER THE PERIOD OF TIME RIGHT UP
TO HIS PASSING.
THOUGH HE WENT OFF TO WORK AT
HOPKINS AND INDIANA UNIVERSITY
WE CONTINUED PUBLISHING AND
COMMUNICATING ABOUT OUR
RESEARCH.
ONE LAST STORY IS HARRY WANTED
TO TAKE A TEACHING JOB AFTER HE
GOT HIS Ph.D. AND HE WANTED A
SPORTS CAR.
HE WAS GOING TO TURN DOWN HIS
JOHNS HOPKINS OFFER AND BUY THIS
SPORTS CAR AND WE WENT BACK AND
FORM AND HE EVENTUALLY WENT TO
HOP KINDS AND ENDED UP GETTING
HIS SPORTS CAR.
I ASKED HIM ABOUT HOW COULD HE
POSSIBLY DO THE ELABORATE
STEERING AND SHIFTING OF GEARS
AS HE DID DRIVING THIS SPORTS
CAR AND HE SAID I GOT THE JOB
DONE AND THAT WAS HIS FINAL
STATEMENT AND THAT REALLY IS THE
THING THAT ONE SHOULD REMEMBER
ABOUT HARRY HE PERSEVERED TO THE
END AND ALWAYS GOT THE JOB DONE.
I WANT TO THANK ALL OF YOU WHO
HAVE RECOGNIZED HARRY AND IN
PARTICULAR GEORGE AND OTHER
MEMBERS OF NIAAA AND THOSE
INVOLVED GETTING THE ACMP
MEMORIAL FOR THE HARRY JUNE
TRAVEL AWARD AND GEORGE KOOB AND
I GAVE THE FIRST HARRY JUNE
AWARD IN 2016 AND HERE'S THE
PEOPLE WHO WON THE AWARD EVERY
SINCE AND THE WINNER FOR THIS
YEAR'S MEETING IN DECEMBER IS
MIGUEL.
HOPEFULLY THE NIAAA WILL
CONTINUE TO FUND THE HARRY JUNE
TRAVEL AWARD AND I THANK YOU.
>> THANK YOU FOR YOUR TALK TO
HARRY JUNE BECAUSE I DON'T
PEOPLE THINK THEY KNOW WHERE IT
CAME FROM AND IT WAS MOVING.
YOU DID A GREAT JOB.
I THINK AND WE'LL HEAR ABOUT THE
INTERACTION BETWEEN FEEDING AND
NUTRITION AND ALCOHOL USE
DISORDER.
WE'VE BEEN TALKING ABOUT AT
NIAAA.
MAYBE YOU CAN LEAD IN DISCUSSION
ONE OF THESE DAYS IN GLP1
AGONIST AND WHAT YOU THINK
BECAUSE I'D LOVE TO LEAR IT FROM
THE PERSPECTIVE OF YOUR WISDOM
HAVING SLOGGED THROUGH FIGURING
OUT HOW ALCOHOL COULD FACILITATE
ON THE ASCENDING LIMB OF THE
BLOOD ALCOHOL CURVE.
ANY QUICK QUESTIONS?
HOW DID HARRY COME TO YOUR LAB?
DID HE WALK IN YOUR DOOR?
THAT'S HOW MARCUS CAME TO MY
LAB.
>> HE WALKED IN THE DOOR BECAUSE
HE HEARD SOMETHING INTERESTING
WAS GOING ON AND HAD TALKING TO
OTHER STUDENTS.
MY DOCTORAL STUDENT SAID YOU
NEED TO PAY ATTENTION TO HARRY
JUNE AND HE TOOK MY COURSE AND
WROTE A 46 PAGE TERM PAPER WHICH
IS THE LONGEST I'VE EVER
RECEIVED.
I STARTED TAKING HIM AS SOMEONE
REALLY INTERESTED.
>> THANK YOU, MICHAEL.
PEOPLE CAN ASK QUESTIONS OR END
AN E-MAIL BECAUSE WE'LL RUN OUT
OF TIME.
I ENJOYED HEARING ABOUT THE OLD
DAYS AND STRUGGLES AND MET HIM
AT NEUROSCIENCE SYMPOSIUM AND
ELLIOT GAVE ME A PICTURE OF THE
NEUROSCIENCE.
I WAS A SCRIBE.
I COULD HARDLY SIGN MY NAME AND
GOT INVITED TO TAKE NOTES WITH
TONY PHILLIPS.
OKAY.
MOHAMMED -- SEE, YOU GOT ME
TALKING ABOUT THE OLD DAYS.
ALL RIGHT.
SO MOHAMMED WILL TALK ABOUT
CONCEPT CLEARANCE AND YOU HAVE
10 MINUTES ON THE NEURO BIOLOGY
ON ADOLESCENT DRINKING IN
ADULTHOOD AND WE CALL THE
INSTITUTE NADIA.
ALL YOURS.
>> THANK YOU.
GOOD AFTERNOON.
TODAY I'M GOING TO PRESENT A
RENEWAL CONCEPT CLEARANCE FOR
NEUROBIOLOGY IN ADOLESCENT
DRIRPGING IN ADULTHOOD.
TRAEDZ COMMON BETWEEN 19 AND 25
AND ACCORDING TO THE SAMHSA
SURVEY ALCOHOL CONSUMED IN THE
UNITED STATES IS BY 12 TO 13
YEARS OLD AND R57B9
AND SOME REPORTED TAKING SIPS OR
BINGE DRINKING.
I CAN LEAD TO DEVELOPMENT OF
ALCOHOL USE DISORDERS.
DATA FROM THE NATIONAL
CONSORTIUM ON ALCOHOL AND
NEURODEVELOPMENT HAS SHOWN THE
NEGATIVE EFFECT OF BINGE
DRINKING ON DEVELOPING BRAIN AS
THE GRAY MATTER VOLUME WHEN
MEASURED IN CLOSE PROXIMITY TO
BINGE DRINKING AND SHOWED CAUSAL
EFFECT.
IT WILL BE INTERESTING TO LOOK
AT GROWTH TRAJECTORIES MAY BE
REINSTATED WITH ALCOHOL
ABSTINENCE.
THE GOAL IS TO UNDERSTAND THE
BRAIN IMPAIRMENTS THAT PERSIST
OVER THE COURSE OF BRAIN
MODULATION ESPECIALLY FOCUSSING
ON THE MOLECULAR AND CIRCUIT
MECHANISMS AND UNDERLYING
BEHAVIORAL CHANGES.
IT WILL TRANSLATE THESE FINDINGS
IN THE CONTEXT OF HUMAN WHO
MISUSE ALCOHOL DURING ABSTINENCE
PERIODS.
TO SUPPORT RESEARCH ACROSS
DIFFERENT INSTITUTIONS IN ORDER
TO INVESTIGATE THE SEQUENCES OF
REPEATED ALCOHOL EXPOSURE ON
BRAIN MATURATION AND OTHER
OUTCOMES.
AND TO SUPPORT EXPERIMENTAL
STUDIES ON THE EFFECTS OF
CONTROL AND EXPOSURES.
AND THE INITIATIVE IS LIMITED TO
ANIMAL STUDIES ONLY.
AND BY THE NADIA THE
INVESTIGATORS RECOMMEND URs.
THE GOALS AND OBJECTIVES OF THE
PROPOSALS ARE TO UNDERSTAND
MECHANI
MECHANISTICALLY THE CELLULAR AND
NEURAL CIRCUITRY AND CHANGES IN
THE ADULT BRAIN WITH ALCOHOL
EXPOSURE AND SEX SPECIFIC
CHANGES.
AND IN TERMS OF EARLY VERSUS
LATE ALCOHOL EXPOSURE ON BRAIN
STRUCTURE AND FUNCTION.
>> I NEED TO FIND TRANSLATION
THAT LOOKS AT GENETIC
MODIFICATIONS AND BEHAVIORAL
TASK OR PHYSIOLOGICAL MEASURES
IN NEURAL DEVELOPMENT.
SO THE FUTURE DIRECTIONS ARE
INCLUDING BUT NOT LIMITED TO THE
TRANSITION OF SCIENTISTS
CONTRIBUTING AS CO-INVESTIGATOR
INTO LEADERSHIP ROLES AS P.I.s
AND INFRASTRUCTURE TO SUPPORT
ANALYSIS MEDIATION AND
ARTIFICIAL INTELLIGENCE MINING
LOOK FOR ALCOHOL EXPOSURE
EFFECTS AND PROMOTE TRANSLATION
THROUGH APPROPRIATE HYPOTHESES
AND PHENOTYPIC MEASURES IN
HUMANS AND SUPPORT
COLLABORATIONS AND PUBLICATIONS
WITH SCIENTISTS INVESTIGATING
ALCOHOL EXPOSURE EFFECT ON
DEVELOPMENT ON HUMANS.
ALCOHOL EXPOSURE ON PHENOTYPES
SUCH AS PAIN CONDITIONS AND
HYPERALGESIA AND SOCIAL
FUNCTIONING.
AND ALCOHOL EXPOSURE ARISING
FROM MICROFULLY -- MICRO GLIIA
AND TO INVESTIGATE THE MECHANISM
BASED DELINEATION OF TIME PERIOD
ASSOCIATED WITH INSULT AND
THERAPEUTIC TIME INDUCED AND
OBSERVED SEX EFFECTS OF ALCOHOL
EXPOSURE.
AND LOOKING AT CELLS THAT VARY
ACROSS BRAIN REGION IMPACTING
LARGE BRAIN NETWORK AND CAUSING
PSYCHO TARGETS.
AND FOSTER INTEGRATION AMONG
DIFFERENT PROJECTS OF THE NADIA
CONSORTIUM TO ESCALATE THE
RESEARCH FINDINGS TO HUMAN
CONDITIONS.
I'LL STOP HERE AND TAKE ANY
QUESTIONS OR COMMENTS.
THANK YOU.
>> THE VOTE OF COUNCIL IS TO
ENDORSE SO ONE MEMBER OF COUNCIL
CAN ENDORSE AND THAT WOULD BE
FINE.
MORE THAN ONE IS BETTER BUT IF
SOMEONE CAN ENDORSE THE CONCEPT.
>> THE FIRST THING WOULD BE ANY
QUESTIONS FOR MOE -- MOHAMMED.
THE SLIDES WERE CLEAR.
WOULD SOMEONE LIKE TO ENDORSE.
>> I MOVE TO ENDORSE.
>> THANK YOU.
LAURA KWAKO WILL TALK
INFRASTRUCTURE TO SUPPORT
ALCOHOL RELATED EDUCATIONAL
OUTREACH.
I BELIEVE THIS EVOLVED FROM
COUNCIL DISCUSSIONS.
>> THANK YOU, EVERYONE AND THANK
YOU MOHAMMED BECAUSE YOU SET THE
STAGE BEAUTIFULLY FOR THE
CONCEPT CLEARANCE I'LL BE
PRESENTING BUT THAT HIGHLIGHTS
NIAAA'S FOCUS ON YOUNG ADULT
DRINKING.
I'M LAURA KWAKO CHIEF OF THE
TRAINING HEALTH SERVICES AND
RECOVERY BRANCH HERE AT NIAAA.
I WOULD LIKE TO ACKNOWLEDGE MY
CO-CREATORS THUS FAR ON THIS
CONCEPT.
OUR DIRECTOR OF TREATMENT
RECOVERY AND OUR PROGRAM
DIRECTOR WITHIN MY BRANCH WITHIN
OUR DIVISION.
THIS WAS A TEAM EFFORT.
I'LL TALK ABOUT AN R52 EDUCATION
OUTREACH MECHANISM FOCUSSED ON
ALCOHOL EDUCATION AND OUTREACH
FOR YOUNG ADULTS.
SO MANY MAY NOT BE FAMILIAR WITH
THE R25 MECHANISM.
IT'S NOT UP WITH OF THE MOST
COMMONLY FUNDED AT NIH PUT WE'RE
FANS OF IT AT NIAAA AND IT
FOCUSES ON RESEARCH EDUCATION
AND PROVIDING RESEARCH EDUCATION
ACTIVITIES IN THE MISSION AREAS
OF THE VARIOUS INSTITUTES AND
CENTERS.
SO THE OVER ARCHING GOAL IS TO
REDUCE ALCOHOL CONSUMPTION AND
REDUCE EQUITY AMONG YOUNG ADULTS
WITH COMMUNITY BASED AND HIGHER
EDUCATION INFRASTRUCTURE.
AS YOU HEARD FROM THE PREVIOUS
PRESENTATION THERE ARE ENORMOUS
NEGATIVE SEQUENCES TO ALCOHOL
CONSUMPTION IN ADOLESCENCE AND
ADULTHOOD AND WE KNOW IT'S
COMMON TO DRINK HEAVILY AND IT'S
NORMALIZED IN A LOT OF SETTINGS
AND MANY HIGHER EDUCATION
SETTINGS AND COMMUNITY ONES AS
WELL.
YOU WANT TO TALK ABOUT A COMMENT
MADE AT THE LAST MEETING
AMBASSADORS GETTING THE WORD
OUT.
THAT SPARKED SOMETHING AND THANK
YOU FOR THAT.
WE LOOK FORWARD TO THAT.
THIS IS NO NOT A RE-ISSUE IS A
BRAND NEW AND WILL HAVE MULTIPLE
AREAS OF FOCUS.
IT'S A BROAD PROBLEM.
WE WANT TO CAST A WIDE NET IN
THINKING HOW TO APPROACH IT.
FOCUS ON COMMUNITY NEEDS
ASSESSMENT AND LANDSCAPE
ANALYSIS.
INFRASTRUCTURE FOR COORDINATED
IMPLEMENTATION OF AN EDUCATIONAL
OUTREACH PROGRAM FOCUSSED ON
ALCOHOL PREVENTION AND HARM
REDUCTION.
AND EVIDENCE-BASED HEALTH
RESOURCES AND DIGITAL OUTREACH.
USING SOME NOVEL APPROACHES TO
GET THE WORD OUT AND TO PROVIDE
INFORMATION TO PEOPLE.
AND PROGRAM EVALUATION OF HARM
AND RECRUIT AND TRAIN COHORTS OF
STUDENTS AND YOUNG PEOPLE TO
FACILITATE EDUCATIONAL OUTREACH.
WE'RE EXCITED ABOUT WHAT
PROGRAMS WE MIGHT SEE IN THIS
AREA AND COMMUNITY OUTREACH
SUSTAINABILITY.
SO IN COLLABORATION WITH
COMMUN
PARTNERS WE WANT SOMETHING
THAT'S ROBUST AND LAST AND
ENDURE IN COMMUNITIES AND
IDEALLY CREATE LASTING CHANGE
WHEN WE THINK HOW YOUNG PEOPLE
DRINK AND WHAT THEY KNOW ABOUT
ALCOHOL.
ELIGIBLE PARTICIPANTS.
IN AN R25 THE PARTICIPANTS ARE
THE TARGET OF THE OUTREACH
PROGRAM.
THESE ARE THE FOLKS WE'RE TRYING
TO REACH.
THAT INCLUDES YOUNG ADULTS
AFFILIATED WITH COMMUNITY
ORGANIZATIONS.
THESE ARE BROADLY DEFINED.
THESE ARE EXAMPLES NOT LIMITED
TO THE GROUPS BUT INDIVIDUALS
WHO RECEIVE SERVICES FROM HEALTH
CENTERS AND GOVERNMENT AGENCIES,
FAITH-BASED ORGANIZATIONS, EVEN
BIG BROTHERS AND BIG SISTERS AND
THERE'S A LOT OF ORGANIZATIONS
AND STUDENTS IN HIGHER EDUCATION
SETTINGS, PRIVATE, PUBLIC,
HBCUs, ETCETERA.
THIS MECHANISM WILL REQUIRE A
PLAN FOR ENHANCING DIVERSE
PERSPECTIVES.
YOU HEARD ABOUT THAT DURING JOHN
GNAI'S PRESENTATION AND RESEARCH
TEAM MUST BE DIVERSE IN
BACKGROUND AND QUESTIONS
INFORMED BY PATIENT AND FAMILY
PERSPECTIVES AND IN EVALUATION
DURING THE PEER REVIEW CRISIS.
THIS IS PART OF THE SCORABLE
CRITERIA.
IT'S A PRETTY ROBUST REVIEW
RECEIVED.
IN TERMS OF OUTCOME AND
JUSTIFICATION WE KNOW YOUNG
ADULTS IN THE U.S. DRINK WHO
WILL AT HIGH RATES INCLUDING
FREQUENT BINGE AND HEAVY
DRINKING AND WHAT WE CALL HIGH
INTENSITY DRINKING.
RATES OF HEAVY DRINKING HAVE
DECLINED OVER TIME.
BUT WE HAVEN'T YET SEEN THIS
DEEP DECLINE REALLY PERSISTS
PAST YOUNG ADULTHOOD
PARTICULARLY IN WOMEN.
WHILE RATES OF USE DRINKING ARE
GOING DOWN AS THEY GET OLDER,
WOMEN ARE DRINKING MORE THAN IS
GOOD FOR THEIR HEALTH AND THIS
IS SOMETHING WE WANT TO ADDRESS.
WE KNOW UNFORTUNATELY AND THIS
IS FAIRLY RECENT THAT WOMEN IN
THE YOUNG ADULT AGE GROUP ARE
MORE LIKELY TO BINGE DRINK THAN
MEN AND SUFFER ALCOHOL RELATED
HARM THAN MEN, PHYSIOLOGIC AND
WITH EXPOSURE TO PARTNER
VIOLENCE AND OTHER CONSEQUENCES.
DEVELOPING THIS KIND OF ALCOHOL
FOCUSSED EDUCATIONAL OUTREACH IN
COMMUNITY AND HIGHER EDUCATION
SETTINGS WILL OFFER A CHANCE TO
ADDRESS HEALTH EQUITY NEEDS AND
BY FOCUSSING ON THE
SUSTAINABILITY OF THE PROGRAMS
WE CAN INCREASE THE LIKELIHOOD
THEY'LL OFFER CONTINUED
BENEFITS.
THAT'S ALL I HAVE BY WAY OF
CONTENT BUT I OPEN IT UP TO YOUR
QUESTIONS AND COMMENTS.
>> IT SOUNDS GREAT.
I HAVE A BUNCH OF QUESTIONS.
I'M INVOLVED IN A SUPPORT SYSTEM
AND THE OPIOID RESPONSE NETWORK
AND WORK WITH A LOT OF
COMMUNITIES AND IT'S NATIONAL
SUPPORTED BY SAMHSA.
IT HAS TO BE A PROFESSIONAL
ORGANIZATION.
CAN THIS BE A PROFESSIONAL
ORGANIZATION OR AN INDIVIDUAL
P.I.
SOME HAVE COMMUNITY OUTREACH.
THE SECOND QUESTION IS SO MANY
KIDS, YOUNG ADULTS ARE USING
MARIJUANA AS WELL AS ALCOHOL.
IT'S INTERCHANGEABLE.
DO WE NEED TO FOCUS ON ALCOHOL
OR COULD IT BE COMORBID OTHER
DRUGS.
>> BECAUSE WE'RE NIAAA OUR
NOTICE OF FUND BEING OPPORTUNITY
FOCUS PRIMARILY ON ALCOHOL BUT
SOME CAN AND SHOULD INCLUDE
OTHER SUBSTANCES WHEN IT'S
RELEVANT.
WE CAN BUILD THAT LANGUAGE IN
WHEN WE'RE WRITING UP THE
FUNDING OPPORTUNITY.
>> OKAY.
SORRY, I'M TAKING SO MUCH TIME
BUT I'M EXCITED ABOUT THIS
BECAUSE I LIKE EDUCATION.
THIRD QUESTION IS I HAVE BEEN
INVOLVED WITH R25s TRAINING
INDIVIDUALS IN RESEARCH AND
PSYCHIATRY OR OTHER REPRESENTED
MINORITIES AND THIS SOUNDS LIKE
IT'S TRAINING THE TRAINERS.
IS PART OF THIS SO DEVELOP A
CURRICULUM OR TO TRAIN THEM?
ALSO MY OTHER QUESTION IS I'M
NOT AWARE OF BUT IT SOUND LIKE
YOU WANT A RESEARCH COMPONENT
AND I WASN'T AWARE OR MORE
DEMONSTRATION WHICH IS MORE LIKE
A SAMHSA THING WHERE YOU
DEMONSTRATE WHAT DOING AND SHOW
THE EXTENT OF WHAT YOU'RE DOING
BUT NOT PUTTING IN A RESEARCH
QUESTION TO TEST?
THOSE ARE MY QUESTIONS AND THEN
I'LL SHUT UP.
>> GREAT QUESTIONS.
R25s NEED TO INCLUDE A RESEARCH
COMPONENT DIFFERENT THAN AN R01
PUT ALL OF THESE REGARDLESS OF
THE FORM HAVE TO INCLUDE SOME
EVALUATION OF SUCCESS OF
WHATEVER THEY'RE PLANNING TO DO
AND THERE'S DIFFERENT THINGS WE
COULD PLAN TO DO.
WITH RESPECT TO THE TRAIN THE
TRAINERS QUESTION, THAT IS KIND
OF OUR GOAL.
THE IDEA THAT IF WE CAN EDUCATE
PEOPLE AND TRAIN THEM TO BE
AMBASSADORS OR THE TOPIC COULD
BE SUSTAINABLE.
WE DO SUPPORT OTHER R52
MECHANISMS.
WE HAVE THOSE FOR PRACTICING
HEALTH CARE PROFESSIONALS.
NOT SPECIFICALLY FOR RESEARCH
CAREERS BUT PEOPLE OUT IN
PRACTICE BUT MAY NOT BE AWARE OF
ALCOHOL OR KNOW MUCH ABOUT IT
AND WE HAVE R25s THAT SUPPORT
THAT.
THAT'S MORE THE MODEL OF WHAT
WE'RE TRYING TO DO.
>> THANK YOU.
>> I LOVE THE IDEA AND IT FITS
WITH WE HAVE EMPIRICALLY
SUPPORTED APPROACHES FOR YOUNG
ADULTS WE THEN CAN'T SEEM TO GET
TO STICK.
VEEP AS I SAY THAT, I'M THINKING
OF THE DIFFERENCES BETWEEN
COLLEGE STUDENTS AND WORK WITH
COLLEGE STUDENTS YOU CAN GET
ACCESS, THEY GET ENGAGED,
THEY'RE MOTIVATED AND THEY'LL DO
EVERYTHING FOR NOTHING.
RELATIVELY EASY, CAPTURE
POPULATION, EASY TO GET.
THERE'S BEEN MORE ATTENTION
LATELY TO NON-COLLEGE YOUNG
ADULTS.
MORE FOCUS ON THE HIGH RISK.
WE'RE SEEING ALCOHOL USE IN
NON-COLLEGE YOUNG ADULTS BEING
HIGHER THAN COLLEGE STUDENTS.
THEY'RE SO MUCH HARDER TO FIND.
THERE'S.
MOTIVATIONAL INTERVIEWS AND
THEY'RE HARD TO GET ENGAGED.
I KNOW AT LEAST HALF A DOZEN
PROJECTS ONGOING TRYING TO
ENGAGE NON-COLLEGE YOUNG ADULTS
AND HAVING A HARD TIME.
BECAUSE THEY'RE SO DISPERSE.
I HAVE A COUPLE THOUGHTS AND IT
WILL BE LIKE THE PROOF'S IN THE
PUDDING.
CAN YOU FIND A COMMUNITY OF
PEOPLE AT HIGH RISK BURT WHERE
DO YOU FIND THEM?
THEY'RE NOT GOING TO BE AT
CHURCH, MAYBE YOUTH PRIDE OR
PLACES WHERE AYOUNG ADULTS
GATHER.
THE ENGAGEMENT OF THE COMMUNITY
I APPRECIATE BECAUSE THEY HAVE
TO TELL YOU WHAT'S IMPORTANT TO
THEM AND BE A PART OF THE
SOLUTION AND BUILDING IT.
ONE OF THE THINGS MY COLLEAGUES
IS FOCUSSING ON IS HIGH RISK
OCCUPATIONS.
TRADES, TRADE SCHOOLS OR WE HAVE
ELECTRICIANS AND THEY'RE NEW
JOBS, CONSTRUCTION, HIGHER RISK
JOBS PEOPLE THAT DO NOT HAVE
COLLEGE EDUCATIONS ARE LIKELY TO
BE IN.
THAT'S ONE IDEA I HAVE AS A WAY
TO FACILITATE PEOPLE TO ENGAGE
WITH OUR DEPARTMENT AND ONE LAST
THOUGHT.
WHAT YOU'RE DESCRIBING IN
TRAINING THE TRAINER FITS THE
THEORY WHICH IS THE IDEA YOU CAN
TEACH PEOPLE WHAT TO DO AND DO
TO SUPPORT THEIR COMMUNITY AND
FRIENDS.
THERE'S SOMETHING THAT HAS
STANDING IN TERMS OF HOW TO
TRAIN OR BULLYING BUT NOT FOR
ALCOHOL AND NEED TO IMPROVE
SKILLS OF YOUNG PEOPLE IN THAT
BEHAVIOR.
THANK YOU.
>> I'M WE'RE RAPIDLY GETTING
TOWARD THE END OF OUR DAY.
I DO APPRECIATE THESE COMMENTS.
I'M SURE LAURA DOES AS WELL.
FEEL FREE TO SEND HER MORE
COMMENTS.
YOU'RE MOST WELCOME TO.
LOOKING AT PROFESSIONAL
ORGANIZATIONS IS PROBABLY ONE
WAY TO GET LEVERAGE.
WE'VE BEEN ASKED LIKE
FIREFIGHTERS THE WORLD HEALTH
ORGANIZATION TO DEAL WITH THE
WORKPLACE PROBLEM ASSOCIATED
WITH ALCOHOL.
WE NEED ENDORSEMENT.
WE GOT TWO.
YOU'RE GOOD.
NEXT IS BOB FREEMAN.
HE'S TAKING THE YEOMAN'S JOB OF
DOING TWO CONCEPT CLEARANCES AND
TALK ABOUT ALCOHOL-ACTIVATED
LOCKING SYSTEMS FOR FIRE RARMZ
AND FIRE RARM STOERNL AND
REPRESENTATION FOR ALL FOR SBIR
CONTRACT RESEARCH AND USING
COMMUNITY-BASED PARTS PRA TRY
RESEARCH TO OPTIMIZE ALCOHOL
SCREENING IN INTERVENTION IN
U.S. HEALTH DISPARITY AND SOCIO
ECONOMICALLY DISADVANTAGED
COMMUNITIES.
THE FIRST IDEA WAS A SIMPLE
REQUEST TO ADD THE TOPIC TO THE
SBIR, SMALL BUSINESS INNOVATION
AND RESEARCH CONTRACTS
SOLICITATION AND APPARENTLY IT
REQUIRED CLEARANCE SO THAT'S WHY
I'M HERE.
THE BACKGROUND AND THERE WERE
OVERLAPPING AREAS OF FIREARMS
AND SUICIDE AND DRINKING.
THEY CAUSED 45,000 DEATHS IN THE
U.S. OVER 2020 IN THE U.S. AND
HALF WERE SUICIDES.
AND FIREARM RELATED INJURIES ARE
THE LEADING CAUSE OF YOUTH 9 TO
18 AND SUICIDE RATES INCREASED
FROM 2001 AND 2021 RAND THE
SUICIDE RATE BY FIREARM
INCREASED AND RATES 15% AMONG
YOUNG ADULTS BETWEEN 2019 AND
2020.
THE ALCOHOL USE AND LEGAL
INTOXICATION PRIOR TO SUICIDE IS
AND ACUTE USE OF ALCOHOL
INCREASES SUICIDAL IDEATION
PRIOR TO AN ATTEMPT AND SO WHAT
WE'RE TALKING ABOUT IN THE
INITIATIVE IS TO DEVELOP ALCOHOL
ACTIVATED LOCKING SYSTEM FOR
FIREARMS AND/OR FIREARM STORAGE
UNITS.
THE ALCOHOL IS A KNOWN
DISINHIBITOR AND THERE'S
BENEFITS YOU WOULD THINK TO AN
ALCOHOL SENSOR DEVICE FOR AN
INDIVIDUAL WITH A DETECTABLE
ALCOHOL CONTENT LEVEL AMONG AN
ESTABLISHED LIMIT.
AND MIGHT EN LANCE THE SAFE
STORAGE OF FIREARMS BY BLOCKING
THE UNIT WHEN IT DETECT THE
ALCOHOL LEVEL IS OVER THE LIMIT.
OWNERS PREFER THEIR FIREARMS ARE
LOADED AND UNLOCKED AND THE
NUMBER ONE REASON IS THEY WANT
TO PROTECT THE HOME AND KEEP
THEM LOADED AND UNLOCKED AND
THERE'S BEEN SEVERAL SAFETY
TECHNOLOGIES.
THE DEVICES THAT ARE BEING
OUTLINED HERE ARE SOMETHING
ANALOGOUS TO THE DEVICES YOU
SOMETIMES REQUIRED WITH A DRUNK
DRIVING OFFENSE AND PREVENT THE
START OF A VEHICLE UNTIL A BLOOD
ALCOHOL TEST HAS BEEN TAKEN.
THE CALL FOR THE CONTRACT
PROPOSALS FOLS SEVERAL NIH AND
FEDERAL EFFORTS STIMULATING
RESEARCH ON THE PRODUCTION OF
VIOLENCE.
AND THEY PROVIDED $12.5 MILLION
AND THERE'S NOFOS FOR THE
BUILDING ON OUR EXISTING
VIOLENCE RESEARCH PORTFOLIO.
IN FACT THIS MORNING THEY
DISCUSSING THE PAPER ON ALCOHOL
CONTROL POLICIES AND HOMICIDE.
THERE WAS A STUDY THAT CAME OUT
OF THIS APPROPRIATION.
WE DON'T HAVE AS MANY FIREARMS
GRANTS AS SOME OF THE OTHER
INSTITUTES HOWEVER, THAT IS ONE
OF THEM WE HAVE FUNDED.
ALSO RECENTLY THE SURGEON
GENERAL DECLARED A NEW DIVISION
AND THE NATIONAL STRATEGY FOR
SUICIDE PREVENTION HAS A GOAL TO
REDUCE ACCESS TO LETHAL MEANS
AMONG PEOPLE AT RISK FOR
SUICIDE.
AND WE GENERATE CONTRACT
PROPOSALS FOR A DEVICE AND
PEOPLE UNDERSTAND THE LEVEL IS
INVOLVED WITH IMPAIRED DECISION
MAKING AND INJURIES AND SUCH
TECHNOLOGY CAN PROMOTE THE
STORAGE OF SAFE FIREARMS IN THE
HOME AND MAY HAVE AN IMPACT ON
THE EPIDEMIC OF ALCOHOL AND
FIREARM RELATED SUICIDE IN THE
U.S.
I'VE BEEN SCOURING THE INTERNET
LOOKING FOR EVIDENCE I THOUGHT
ABOUT THIS YEARS AND YEARS AGO.
TWO YEARS AGO I WAS ON A TEAM
ANNOUNCING THEY HAD DEVELOPED
SUCH A THING IN THEIR GARAGE OR
SOMETHING.
A YEAR AGO SOMEONE OUT OF THE
BLOOD CALLED ME AND SHE WAS IN A
SMALL SCHOOL AND THEY WERE
WORKING ON THIS CONCEPT AND
WANTED TO KNOW WHAT TO DO WITH
IT.
RECENTLY, IF YOU LOOK AT THE
INTERNET YOU'LL SEE A REAL
EXPLOSION OF INTEREST.
THESE ARE MOSTLY IN THE CATEGORY
OF SMART GUNS.
THEY USE FACIAL RECOGNITION AND
I'M NOT PULLING THAT BUT I DON'T
KNOW WHY YOU CAN'T INCLUDE THAT
SMART GUN WITH AN ALCOHOL
DEVICE.
I DON'T KNOW WHAT THE MARKET IS
FOR THIS SORT OF THING.
I KNOW LITTLE ABOUT SMALL
BUSINESS GRANTS.
I DID 25 YEARS AGO.
I WROTE A TEXTBOOK AND THAT WAS
MY LAST EXPERIENCE WITH THEM.
I KNOW BASED ON WHAT I'M SEEING
ON THE INTERNET THERE'S THE
LIKELIHOOD WE HAVE GREATER THAN
ONE APPLICATION FOR THIS.
I DON'T KNOW HOW MANY.
IF IT SAVES AT LEAST ONE LIFE
IT'S WORTH CONSIDERING.
I AM PROPOSING THIS.
I DON'T KNOW HOW YOU WANT IT
VOTE ON IT BUT AGAIN UNLESS YOU
WANT TO TAKE QUESTIONS HERE.
>> ANY QUESTIONS FOR BOB ON
THIS?
I AGREE WITH BOB WE DON'T KNOW
WHAT WE'RE GOING TO GET BUT WE
SHOULD TRY TO GET IT.
ENDORSED?
WE'RE DONE WITH THAT ONE.
BOB, YOU GOT TO THE ENDORSEMENT.
WE'LL SEE WHAT HAPPENS.
YOU NEVER KNOW.
SOMETIMES YOU END UP WITH A
HUNDRED APPLICATIONS.
THE NEXT ONE IS COMMUNITY BASED
PARTICIPATORY RESEARCH.
IT'S A SPECIAL KIND OF RESEARCH
WHERE THE P.I. IS EMBEDDED WITH
THE COMMUNITY AND WORKING WITH
THE COMMUNITY AND APPLICATION
AND DEVELOPING THE PROTOCOL AND
FORMING THE QUESTIONS.
YOU REQUIRE A SPECIAL REVIEW FOR
THIS KIND OF PROPOSAL.
WE'LL CALL IT APPLICATION THAT
USE PRINCIPLES AND METHODS OF
COMMUNITY-BASED PARTICIPATORY
RESEARCH AND TO OPTIMIZE ALCOHOL
SCREENING AND INTERVENTION IN
U.S. HEALTH DISPARITY AND SOCIO
ECONOMICALLY DISADVANTAGED
COMMUNITY BUILDING ON THE
BARBERSHOP MODEL SHOCK CAPACITY
TO REACH AFRICAN AMERICAN MEN
BECAUSE THE BARBERSHOP IS SEEN
AS A SAFE PLACE TO DISCUSS
SENSITIVE TOPICS AND IT'S
ENCOURAGED SMOKING CESSATION AND
SCREENING.
IT HASN'T BEEN STUDIED NEARLY AS
MUCH IN MY OPINION SURPRISINGLY
SO FOR ALCOHOL MISUSE.
THE BOTTOM LINE IS CDC IS DIDN'T
INDICATING A HANDFUL OF THE
ADULT POPULATION DISCUSSION
THEIR ALCOHOL USE WITH A HEALTH
PROFESSIONAL.
AND THE POPULATION GROUPS THAT
ARE THE FOCUS OF THIS NOFO
RECEIVED SCREENING FOR HIGH RISK
SCREENING THAN OF LESS
THOROUGHLY THAN THE WHITE
POPULATION AND THE COMMUNITIES
CAN HELP REDUCE THE RACIAL
HEALTH DISPARITIES.
THE APPLICATIONS AS WE SEE IT
RIGHT NOW WOULD INCORPORATE THE
CORE PRINCIPLES OF INVOLVEMENT
OF THE COMMUNITY MEMBERS AND
RECRUITMENT FOR THE SCREENING
AND SUBSEQUENT NEEDS ASSESSMENT
AND INTERVENTION DESIGN AND
EVALUATION AND DISSEMINATION OF
THE INTERVENTION.
IT WILL BE OBLIGATED TO USE THE
BARBERSHOP AND THERE ARE THINGS
LIKE BEAUTY PARLORS, GYMS,
RECREATIONAL CENTERS, TATTOO
SHOPS AND CHURCHES.
W
WE'RE TRYING TO GET AT
COMMUNITIES DESIGNATED TO HELP
DISPARITY POPULATIONS INCLUDING
BLACKS, AFRICAN AMERICANS,
HISPANIC, LATINOS, NATIVE
AMERICANS AND NATIVE HAWAIIANS
AND OTHER PACIFIC ISLANDERS AND
SOCIO ECONOMICALLY AND RURAL
POPULATIONS.
SO WE ENVISION THEY'LL PROPOSE
THE ALCOHOL SCREENING AS THE
FIRST STEP.
AS FAR AS THE PULL TREATMENT
MODEL, IF YOU ADHERE STRONGLY TO
THE PRINCI PRINCIPLES THE COMMU
SHOULD HAVE A SAY IN HOW TO
PROCEED.
THIS IS OPEN TO QUESTION AND
INPUT FROM THIS GROUP WHETHER
HOW MUCH YOU WANT TO INSIST ON
THE FULL SBIRT MODEL FOR
COMMUNITIES THAT PERHAPS DON'T
FEEL WHAT THEY DESIRE.
AND THE IDEA FITS WELL WITH AN
R61 PHASED MECHANISM TO
ESTABLISH SCREENING AND GET
BRIEFLY INTERVENTION REFERRAL TO
TREATMENT.
IT SEEMS IT LENDS ITSELF TO A
PHASED AWARD FOR APPROACHING FOR
HEAVY DRINK USING PRINCIPLES
LOCATED IN HEALTH DISPARITY
AREAS AND I THINK IT'S GOOD TO
USE A SPECIAL REVIEW PANEL
BECAUSE THESE ARE NOT PHASE III
TRIALS.
IT'S NOT -- YOU CAN'T HAVE IT
REVIEWED AS A GOLD STANDARD
CLINICAL TRIAL IT'S GAIN
COMMUNITY PARTICIPATION, TRUST,
CULTURALLY SENSITIVE RESEARCH
TEAM.
INDIGENOUS INTERVIEWERS
COMMUNITY ENDORSEMENT IS THE
ESSENCE OF THE APPROACH GETTING
IN THERE AND IT PUTS THE OWN US
ON A SKILLED P.I. WHO CAN
UNDERSTAND IT'S RESEARCH AND
THEY'RE TESTING HYPOTHESES BUT
THE COMMUNITY HAS A LOT OF
INPUT.
THAT'S WHERE I'LL ASK QUESTIONS
AND ASK FOR A VOTE.
>> I LOVE THE IDEA AND IT'S
WONDERFUL AND MAYBE ADDING
IMPLEMENTATION DESIGNS SO THAT
WHATEVER IS DEVELOPED COULD HAVE
DIRECT IMPLEMENTATION PART OF
IT.
HEAL ARE INCORPORATING
IMPLEMENTATION DESIGNS TO MAKE
YOU ARE IT DOESN'T JUST END WITH
THE GRANT ENDING AND A I AGREE
WITH THE PER FOR THE MECHANISM
AND I LOVE THE R61, R33 BUT THE
RO1 OPTION IS GOOD BECAUSE
PEOPLE ARE ALREADY WORKING THIS
AREA AND PEOPLE CAN COME IN WITH
DATA.
I LOVE IT.
I ENDORSE IT.
>> I HOPE YOU SEE THE TREND
THERE'S A MOVEMENT TO MOVE TO
COMMUNITY APPROACHES.
IT'S NEEDED BECAUSE AS NANCY
POINTED OUT WE WORKED WITH THE
POPULATION OF COLLEGE STUDENTS
AND IT'S MOVED IT QUITE FAR
ALONG.
WE HAVE ANOTHER PART OF SOCIETY
YOU THINK ONLY 40% OF AMERICANS
GET A BACHELOR'S DEGREE.
60% OF THE POPULATION IN A SENSE
WE'RE NEGLECTING.
BOB, THANKS.
DO I HAVE A SECOND ENDORSEMENT?
WE'RE DONE.
YOU'RE ENDORSED.
ALL RIGHT.
I THINK WE'VE RUN OUT OF TIME
FOR A DISCUSSION SECTION.
WE DO HAVE A PUBLIC COMMENT.
JUAN PABLO IS THE -- DR. JUAN
PABLO IS THE CHAIR OF THE
ALCOHOL ASSOCIATED LIVER DISEASE
SPECIAL INTEREST GROUP FROM THE
AMERICAN ASSOCIATION FOR THE
STUDY OF LIVER DISEASES.
HE HAS A BRIEF HE'D LIKE IT
MAKE.
>> THANK YOU.
FOR THE OPPORTUNITY TO TALK IN
FRONT OF ALL OF YOU TODAY.
SO I DON'T NEED TO TELL YOU HOW
IMPORTANT ALCOHOL IS FOR THE
LIVER FIELD.
ALCOHOL RELATED LIVER DISEASE IS
STILL ONE OF THE MAIN CAUSE OF
LIVER CANCER IN THE MUCH
RESEARCH WAS DEVOTED FROM THE
LIVER FIELD.
THAT'S CHANGING IN THE ASLB.
THERE'S A NEW MOVEMENT.
I THINK EVERYTHING STARTED
BECAUSE OF THE CHANGE IN THE
NOMENCLATURE FOR FATTY LIVER
DISEASE STARTED THREE YEARS AGO
AND ON THE INITIATIVE TO RENAME
THE NON-ALCOHOLIC FATTY LIVER
DISEASE AND ENDED UP BEING A BIG
UMBRELLA CONSIDERING THE
METABOLIC DYSFUNCTION ASSOCIATED
WITH THE LIVER DISEASE.
ALCOHOL WAS ASSOCIATED DISEASE
BUT A NEW TERM IN TRYING TO
HIGHLIGHT THE METABOLIC PART AND
THE ALCOHOL ASSOCIATED PART.
THIS WILL HIGHLIGHT HOW LITTLE
WE KNOW ABOUT THE STEATIC LIVER
DISEASE IN 2025 WE'LL HAVE A
CONFERENCE ON MED ALD.
WE INVITED THE NIAAA TO
PARTICIPATE.
IT WILL BRING TOGETHER ADDICTION
SPECIALISTS AND RESEARCHERS TO
TRY TO ESTABLISH THE RESEARCH
PRIORITIES FOR THE MED ALD
FIELD.
WE NEED TO DO BETTER ON
BIOMARKERS ON THE DIFFERENT
PHENOTYPES AND EXPLORE NEW
THERAPEUTIC APPROACHES.
ALSO IN OUR ANNUAL LIVER MEETING
THIS YEAR IN NOVEMBER ALCOHOL
ASSOCIATED LIVER DISEASE HAS A
SPECIAL EMPHASIS DURING THE
PROGRAM.
WE'LL HAVE A SPECIAL SESSION ON
MED ALD AND MULTIPLE SESSIONS ON
ALD.
AND THE IDEA IS TO TRY TO FOCUS
ON CUTTING EDGE RESEARCH TO
BIOMARKERS AND NEW THERAPEUTIC
OPTIONS FOR ALD AND FOR MED ALD.
SO IN SUMMARY, IT'S TRYING TO DO
MORE RESEARCH AND INVEST MORE ON
ALD AND ALSO WITH ALL THE
RESEARCH AVENUES THAT ARE OPEN
WITH THE NOMENCLATURE AND THE
MED ALD SIDE.
THANK YOU VERY MUCH.
>> THANK YOU.
YOUR TALK LED ME TO THINK AT
SOME POINT WE NEED TO HAVE
SOMEONE FROM YOUR ORGANIZATION
COME AND SPEAK TO THE COUNCIL
AND TELL US HOW THESE
NOMENCLATURE HAVE FALLEN OUT AND
WHAT THE SYMPTOMS ARE IN EACH
CATEGORY AND THINGS OF THAT
NATURE.
REMIND ME I SAID THAT.
THE CONFERENCE IS FEBRUARY.
>> ARE THE INVESTIGATORS WHO
WORK ON ALCOHOL ASSOCIATED LIVER
FATTY DISEASE ASSOCIATED GOING?
>> I'M GOING TO GIVE REMARKS IN
SAN DIEGO.
>> THERE'S INTRAMURAL
RESEARCHERS AT THE CONFERENCE
AND WE INVITED THE NIAAA FOR THE
MED ALD PERSPECTIVE.
>> THANKS.
>> WE'RE NEARLY THE END.
IT'S PHILIPPE'S TURN TO TELL US
WHEN WE'RE HAVING TO CONSIDER A
BUNCH OF THINGS QUICKLY.
>> NOT THAT MANY.
I WANT IT MOVE TO THE
CONSIDERATION OF THE MINUTES FOR
THE LAST MEETING IN MAY THE
166th NATIONAL ADVISORY COUNCIL
MEETING MINUTES AS WELL AS THE
MINUTES FOR THE MEETING LAST
PLAY AND THE COUNCIL SLP NO
CLA
CHANGE.
I WOULD LIKE TO MOVE TO
ENTERTAIN A MOTION TO APPROVE
THE DOCUMENTS.
MOVED?
SECOND.
ALL IN FAVOR?
ABSTAIN?
OPPOSED?
MOTION IS APPROVED.
THANK YOU VERY MUCH.
AND ANOTHER POINT ON THE AGENDA
IS TO PRESENT THE NEXT DATE FOR
THE NIAAA COUNCIL IN 2025 IT'S
GOING TO BE FEBRUARY 6 AND
SEPTEMBER 4 AND 2026 FEBRUARY 5,
MAY 5 AND SEPTEMBER 17 AND THE
FUTURE DATE FOR THE CRAN MEETING
FOR NIAAA NIDA AND NCI, 2025 IS
GOING TO BE FOR 2026, MAY 6.
THAT'S IT.
>> THANK YOU ALL FOR JOINING US.
AND PARTICULARLY ARE THERE ANY
COMMENTS FROM ONLINE?
I KNOW I NEGLECTED YOU BUT I
DIDN'T SEE ANYTHING ANY FLAGS
RAISED.
ARE THERE COMMENTS FROM COUNCIL
ONLINE YET IF THEY ARE.
I HAVE TO GET BETTER AT CHECKING
IN WITH THE ONLINE PARTICIPANTS.
THINGS I STILL NEGLECT.
ANYWAY, THANK YOU ALL FOR FLEW
IN TO BE WITH US TODAY.
I THINK IT WAS A PRETTY GOOD DAY
AND LIKE I SAID YOU MAY HAVE
BEEN OVERWHELMED WITH THE BRAIN
INITIATIVE BUT I THINK EVEN FOR
THOSE THAT DON'T DO BRAIN YOU
GET A SENSE OF WHAT AN
EXTRAORDINARY EFFORT IT'S BEEN.
I'VE BEEN FOLLOWING IT SINCE DAY
ONE.
WE START THE BRAIN INITIATIVE
MORE OR LESS THE FIRST WEEK I
ARRIVED IN 2014.
IT'S TAKEN OFF.
MONEY DOES EVENTUALLY REDUCE
RESULTS ESPECIALLY WHEN LED WITH
GOOD LEADERSHIP AND
COORDINATION.
THE BRAIN TEAM ANTONIO CAN
ATTEST TO THIS BECAUSE HE'S PART
OF IT THEY'RE EXTRAORDINARY IN
THEIR UNDERSTANDING AND ABILITY
TO RATE PROPOSALS.
DON'T YOU THINK, ANTONIO.
>> THERE'S DETAILED DISCUSSIONS
BY NIH STAFF FROM DIFFERENT
INSTITUTES.
WE HAVE TEAMS AND THE I.C.
DIRECTORS.
THEY DON'T APPROVE IT.
THEY QUESTION IT.
THERE'S BEEN INSTANCES WHERE
THEY'LL COME UP WITH SUGGESTIONS
MAKING IT BETTER FOR PEOPLE
GETTING THE FEEDBACK SO NEXT
TIME AROUND WHEN THEY ARE COME
IN AN THEY DO MUCH BETTER.
>> IMAGINE PLANNING WITH 10
INSTITUTE DIRECTORS.
THINK OF THE PAY PLAN WITH 10
INSTITUTE DIRECTORS IT'S VERY
CONGENIAL AND QUITE FUN BUT THE
QUESTIONS CAN BE A LITTLE BIT
INTENSE AT TIMES.
ALL RIGHT.
SO AGAIN, THANKS EVERYBODY FOR
COMING AND PARTICIPATING AND
GREAT IDEAS AND YOU CAN SEE
SOMETIMES THEY CAN GET CONVERTED
TO A NOFO.
ALL RIGHT.
HAVE A GOOD WEEK.
I HAVE TO ADJOURN.
WE'RE ADJOURNED.
THANK YOU.