WELCOME TO TODAY'S WALS LECTURE.
I'M THE DIRECTOR FOR THE
BEHAIRIAL SCIENCE IT IS RESEARCH
AT OBSSR OR THE OFFICE OF
BEHAVIORIAL AND SOCIAL SCIENCED
RESEARCH.
IT'S MY PLEASURE TODAY TO
INTRODUCE OUR SPECKER, DR. JENNY
TUNG, SHE'S THE DOCTOR AT THE
MAX PLANK INSTITUTE FOR
EVOLUTIONARY ANTHROPOLOGY AND
SHE'S A PROFESSOR OF BIOLOGY AT
DUKE UNIVERSITY.
DR. TONGUE RECEIVED HER Ph.D.
IN 2010, INVESTIGATING THE CAUSE
ANDS CONSEQUENCES OF GRENETTIC
VARIATION AND WILD BABOONS,
ADVISED BY BIOLOGY PROFESSORS
SUSARN ALBERTS AND GREGORY RAY,
AFTER A POST DOC WITH THE
UNIVERSITY OF CHICAGO, SHE
JOINED DUKE'S DEPARTMENT OF
EVOLUTIONARY ANTHROPOLOGY AND
THE DUKE POPULATION RESEARCH
INSTITUTE IN 2012.
WHILE AT DUKE DR. TUNG
INVESTIGATED THE GENETIC AND
GENOMIC CONSEQUENCES OF SOCIAL
AND ENVIRONMENTAL VARIATION AND
BABOONS, RECESS MA CABBINGS AND
OTHER SOCIAL ANIMALS AS WELL AS
BEHAVIOR IN PRIMATE
HYBRIDIZATION.
DR. TUNG CO DIRECTS THE
[INDISCERNIBLE] BA BOONE
RESEARCH PROJECT STARTED IN 1971
AND 1 OF THE LONGEST PRIMATE
RUNNING SITES IN KENYA, 1 OF HER
MAJOR CONTRIBUTIONS TO THE
FUTURE HAS BEEN ADDING
SOPHISTICATED ANALYSIS TO THE
OBSERVATIONS AND SEEING NOW
PATTERNS EMERGE OVER TIME.
DR. TUN'S RESEARCH MA CABBINGS
HAS SHOWN THAT THE STRESS OF
LIFE AT THE BOTTOM OF THE SOCIAL
LADDER CAN ALTER THE IMMUNE
SYSTEM, JUST AS IT DOES IN
BABOONS, THE RESULTS PROVIDE
EVIDENCE THAT LOW SOCIAL STATUS
LEADS TO DISPARITIES IN HEALTH,
NOT JUST THE OTHER WAY AROUND AS
SOME RESEARCHERS HAVE ARGUED, IN
2019, SHE WAS 1 OF 26 PEOPLE TO
WIN THE PRESTIGIOUS MACARTHUR
AWARD.
DR. TUNG'S LAB IS INTERESTED HOW
THE SOCIAL ENVIRONMENT
INFLUENCES GENE REGULATION,
POPULATION GENETIC STRUCTURE AND
HEALTH AND SURVIVAL ACROSS THE
LIFE COURSE.
NOW FOR A FEW HOUSEKEEPING ITEMS
FOR THOSE INTERESTED IN
RECEIVING CAMERICA E CREDITS FOR
THE LECTURE, THE CODE IS 5012.
ALSO FOR THOSE WATCHING YOU CAN
SUBMIT QUESTIONS FOR THE SPEAK
ARE BY CLICKING THE SEND LIVE
FEEDBACK BUTTON ON THE VIDEO
PAGE.
OTHERS OF YOU IN THE AUDIENCE
CAN GO TO THE MIC AFTER THE LECT
TOWER PREVENT, TO OFFER OR ASK
ANY QUESTIONS YOU WOULD LIKE, 1
QUICK BREAKING NEWS, JUST CAME
ON, I'M VERY PLEASED TO BE ABLE
TO SAY THAT JUST VERY RECENTLY
OUR SPECTER WAS ELECTED TO THE
NAGGAL ACADEMY OF SCIENCE MUCH
SO CONGRATULATIONS ON THAT
DR. TUNG.
[ APPLAUSE ]
EMPLOY WITHOUT FURTHER ADO,
WELCOME DR. TUNG.
NCAN YOU HEAR ME OKAY IN OKAY,
WE'RE IN BUSINESS.
OKAY.
OTHER THAN SLIDES.
LET ME SEE IF I CAN WAKE UP MY
COMPUTER.
ALL RIGHT.
GOOD.
THANK YOU VERY MUCH FOR THAT
INTRODUCTION AND FOR THE KIND
INVITATION TO PARTICIPATE IN THE
WINDOW--OH NO--IN THE WEDNESDAY
AFTERNOON LECTURE SERIES WHICH I
WILL DO SO SHORTLY RIGHT
AFTER ... GOOD?
OKAY.
IT'S A PARTICULAR HONOR TO BE
ABLE TO SHARE SOME OF OUR
RESEARCH HERE WHICH IS THE PLACE
THAT MAKES MUCH OF IT POSSIBLE.
SO, AS WAS MENTIONED, MY
RESEARCH FOCUSES ON NONHUMAN
SOCIAL MAMMALS, PRIMARILY OUR
CLOSE LIVING RELATIVES THE OTHER
LIVING PRIMATES BUT MUCH OF THE
RESEARCH WE DO, WE DO WITH
HUMANS IN MIND BECAUSE WE THINK
THAT BY STUDYING PROCESSES AND
OUR CLOSE LIVING RELATIVES, WE
MAY BE ABLE TO SHED LIGHT INTO
PROCESSES OF HUMAN BEHAVIOR THAT
INFLUENCE HOW WE DO OVER THE
LEFT COURSE.
SO PERHAPS TO INTRODUCE THAT I
WILL TART BY EXPLAINING MY TALK
TITLE, WHICH COMES FROM AN ESSAY
WRITTEN BY--IS THERE ANYTHING I
CAN DO TO KEEP IT FROM
ECHOING,--IS THAT BOTHERING YOU
GUYS
GUYS?
ALL RIGHT, WE'RE GOOD.
ALL RIGHT, SO THIS COMES FROM AN
ESSAY WRITTEN BY THE 18th
CENTURY SAT IRBIST ALEX
ADAPTEDDER POPE, AN ESSAY ON
MAN, THE MOST FAMOUS LINE OF
THAT ESSAY IS KNOW THEN THIGH
SELF, PRESUME NOT GOD TO SCAN;
THE PROPER STUDY OF MANKIND IS
MAN.
OUR ENDOWED WITH THE LOGICAL
FACILITIES THAT BE ABLE TO STUDY
THE SECRETS OF THE NATURAL WORLD
AND HE THOUGHT, AND HE WAS
EXORTING THE READER HERE, TO
FOCUS THOSE PARTICULAR ABILITIES
ON STUDYING WHAT HE THOUGHT WAS
THE MOST APPROPRIATE SUBJECT FOR
OUR OWN SPECY ANDS THAT WAS TO
UNDERSTAND THE HUMAN CONDITION
EMPLOY HOWEVER, I SHOULD ALSO
ACKNOWLEDGE, THE DIRECT PLACE
WHERE MY TALK OATH AND
ACKNOWLEDGMENT WHICH IS TO CLIFF
JOLLY, AN PROCESSOR OF
ANTHROPOLOGY AT NEW YORK CITY IN
THE STUDY OF HUMAN IRIGEINS WHO
TURNED AROUND THIS IDEA TO MAKE
THE ARGUMENT THAT YES, MUCH OF
WHAT WE CAN LEARN ABOUT HUMANS
COMING FROM STUDYING HUMAN
POPULATIONS PER SE BUT ACTUALLY
THERE'S ADILLINGAL COMPLIMENTARY
INFORMATION THAT WE CAN GET
THROUGH HOMOLOGY, SHARED DESCENT
OR ANALOGY WITH THE OTHER LIVING
PRIMATES.
HE WAS PARTICULARLY INTERESTED
IN THE INSIGHTS WE COULD GET NOT
NECESSARILY FROM THE GREAT APES,
OUR CLOSEST LIVING RELATIVES BUT
TRUSTEES A SLIGHTLY DIFFERENT
SET OF SPECIES, THESE ARE ASIAN
AFRICAN MONKEYS HERE OF THE P A
PIONIN GROUP THAT, INCLUDES
MACAQUES, AND ALL THE CHARIS MAT
BEING SPECIES LIKE THE 1S IN
ETHIOPIA AND THE MANDRELOT
BOTTOM RIGHT FROM WESTERN
CENTRAL AFRICA.
THE POINT CLIFF WAS PAIKING WAS
THAT LIKE US, THESE ARE LARGE
BODIED TERRESTRIAL OBLIGATELY
SOCIAL ANIMALS WHOSE SUCCESS IN
LIFE DEPENDS IN LARGE PART ON
HOW THEY IRPT ACT WITH
[INDISCERNIBLE] WHO LIVE
TOGETHER IN THE SAME GROUP.
MACAQUES AND BABOONS IN
PARTICULAR ARE ECOLOGICAL
GENERALISTS THAT CAN BE FOUND
ACROSS LARGE GEOGRAPHICAL SPACE.
IN FACT THEY COVER RANGES IN THE
WORLD THAT ARE SECOND ONLY TO
HUMANS AMONG THE PRIMATES.
AND SO CLIFF IMAGINED IMAGINED
AN ANALOGUE, THERE WAS NO IMAGE
OF ALEXANDER IN THE PAPER BUT
THIS IS COURTESY OF AI GENERATED
ART WHICH WILL GIVE US AN IDEA
TODAY AND WROTE IN THE BEGINNING
OF THIS PAPER THAT YOU KNOW TO
UNDERSTAND HUMANS WE SHOULD BE
LOOKING OUTSIDE OF HUMANS TO
GIVE OURSELVES SOME CONTEXT TO
WHERE OUR SPECIES CAME FROM AND
TO PROVIDE SOURCES OF POWER TO
GAIN IN HUMANS ALONE SO IN OTHER
WORDS WE SHOULD BE STUDYING
BABOONS, EVEN IF OUR IS TO JUST
UNDERSTAND THE HUMAN CONDITION
EMPLOY I THINK THAT'S
PARTICULARLY RELEVANT WHEN WE
TALK ABOUT ASPECTS OF SOCIAL
BEHAVIOR, SOCIAL ENVIRONMENT,
AND HOW THOSE THINGS INFLUENCE
LIFE OUTCOMES.
IN OTHER WORDS AT LEAST IN MUCH
OF THE RESEARCH OF TOPICS, THE
SOCIAL DETERMINANTS OF HEALTH.
UP HERE IS SOMETHING THAT'S
FAMILIAR TO MOST OF OF YOU IS
AGGREGATED EVIDENT THAT OUR
SOCIAL ENVIRONMENTS, ORBIO
ECONOMIC STATUS, OACIAL
INTEGRATION, SOCIAL IEBSOLATION
AND SUPPORT, ASPECT OF OUR
ENVIRONMENTS EARLY IN LIFE
DURING INFANCY AND DEVELOPMENT
HAVE OUTSIDE IMPACTS ON HOW WE
DO, AND ALL THESE CASES, THE
Y-AXIS SHOWS MEASURES OF
MORTALITY OR MORTALITY RISK OF
LIFE SPAN ANDOT X-AXIS MEASURES
SES SOCIAL INTEGRATION OR EARLY
LIFE ADVERSITY.
YOU WILL NOTICE THE AFFECT SIZES
HERE ARE VERY, VERY LARGE.
THESE PREDICTIVE RELATIONSHIPS
ARE SOME OF THE MOST ROBUST,
LARGEST PREDICTERS OF HUMAN
MORBIDITY AND HUMAN MORTALITY
THAT WE KNOW OF.
FOR INITANCE HERE ARE DATA FROM
A PAPER BY ROGER [INDISCERNIBLE]
ET ARK L PUBLISHED A FEW YEARS
AGO ON AMERICAN POPULATIONS.
THE X-AXIS SHOWS INCOME AT AGE
40 AND THE Y-AXIS SHOWS LIFE
SPAN OR EXPECTED AGE AT DEATH
CONTINGENT ON REACHING AGE 40,
OKAY?
AND PERHAPS WHAT STANDS OUT MOST
OBVIOUSLY IS THAT WOMEN IN ALL
CASES LIVE LONGER ON AVERAGE
THAN MEN, BUT THE OTHER THING
THEY HOPE YOU'LL NOTICE HERE, IS
THAT THE DIFFERENCE BETWEEN THE
TOP PERCENTILES AND THE BOTTOM
PERCENTILES OF INCOME AT AGE 40
TRANSLATE ON AVERAGE TO A
DIFFERENCE OF ALMOST 10 YEARS IN
LIFE SPAN.
THIS IS A VERY, VERY LARGE
EFFECT SIZE AND IN ADDITION,
THIS IS NOT A STEP WISE PATTERN,
WHERE YOU GO FROM A MAJOR IMPACT
ON LIFE SPAN AT A LEVEL OF
INCOME THAT WE MIGHT THINK ABOUT
AS CONFERRING MATERIAL
DEPRIVATION, RIGHT?
THIS IS ACTUALLY A GRADIENT
ACROSS THIS ENTIRE X-AXIS.
SIMILARLY, THESE ARE OLD DATA,
THIS IS FROM ALMEDA COUNTY,
CALIFORNIA, FOLLOWING
INDIVIDUALS WHO WERE SCORED AS
EITHER LESS OR MORE SOCIALLY
INTEGRATED INTO THEIR GROUPS AND
AGAIN, YOU CAN SEE THE
DIFFERENCE IN THE PROPORTION
SURVIVING AFTER ABOUT A DECADE
OF FOLLOW UP, IS VERY, VERY
LARGE AND FIEPALLY THIS IS FROM
THE ADVERSE CHILDHOOD
EXPERIENCES STUDY, SHOWING THAT
THE NUMBER OF SEVERE SOURCES OF
DISADVANTAGE THAT KIDS FACE
EARLIER IN LIFE, REACHES FOR
DECADES INTO THE FUTURE, TO
INFLUENCE OR AT LEAST TO PREDICT
AGE OF DEATH, RIGHT?
THIS IS 6, 7, 8 DECADES LATER IN
LIFE.
THESE ARE SO CONSISTENT ACROSS
DIFFERENT SETTINGS, POPULATIONS,
STUDY TYPES, THAT THE SOCIAL
EPIDEMIOLOGIST [INDISCERNIBLE]
SUGGESTED SOCIAL FACTORS SUCH AS
SOCIAL STATUS AND SOCIAL
RELATIONSHIPS UPON THE OTHER
SHOULD BE TREATED AS WHAT THEY
CALL FUNDAMENTAL CAUSES OF
DISEASE THAT INFLUENCE MULTIPLE
DISEASE OUTCOMES THROUGH
MULTIPLE MECHANISMS WHERE THOSE
PARTICULAR OUTCOMES AND THE
MECHANISMS THAT MAY DETERMINE
THEM MAY VARY ACROSS DIFFERENT
SETTINGS.
INDEED THERE ARE IS EVIDENCE FOR
THIS TOO, THESE AREA PARALLEL
DATA FROM THE SAME IN MOST CASES
SAME STUDIES THAT SHOW
DIFFERENCES IN--SORRY NOT FROM
THE SAME STUDIES BUT SUPER THE
SAME X-AXIS THAT SHOW DIFFERENT
IN THE PREVALENCE AND ODDS
RATIOS OF DIFFERENT TYPES OF
DISEASES ACROSS THE SOCIALIO
ECONOMIC STATUS SOCIAL
INTEGRATION AND EARLY LIFE
EXPERIENCE GRADEIENCE.
I THINK THAT THIS IS A POWERFUL
IDEA, THAT SOWCIAL INTEGRATION
IS FUNDAMENTAL LIFE OUTCOMES.
HOWEVER THIS IS HARD TO IMRAPLE
WITH WHEN YOU DO BIOLOGICAL
RESEARCH IN A WET LAB.
IT'S VERY HARD TO THINK ABOUT
HOW TO COME UP WITH A CELLULAR
MODEL IF ARE A SOCIAL
RELATIONSHIP AND IT'S
PARTICULARLY SLIEPRY TO THINK
ABOUT STUDYING DISEASE MECHANISM
WHEN IS THE PREDICTOR VARIABLE
OF INTEREST INFLUENCES
CONDITIONS THAT ARE AS DIFFERENT
PRACTICES 1 ANOTHER AS PROPONENT
CHIETIS AND DIABETES AND HEART
DEC.
SO I THINK THIS IS PERHAPS 1 OF
THE REASONS WHY THESE KINDS OF
VERY, VERY STRONGLY PREDICTIVE
FACTORS IN LIFE OUTCOMES HAVE
NOT GOTTEN PERHAPS THE TEANGSZ
THAT THEY MIGHT MERIT IF YOU SAW
10 YEAR DIFFERENCES IN EXPECTED
LIFE SPAN FOR ANY INDIVIDUAL
CALLS OF SAY AN INFECTIOUS
DISEASE.
IT'S ALSO VERY HARD TO THINK
ABOUT WHAT POTENTIAL CAUSAL
PATHWAYS MIGHT BE.
RIGHT?
IT'S POSSIBLE THAT DIFFERENCES
IN SOCIAL STATUS OR SOCIAL
INTEGRATION HAVE DIRECT
CONSEQUENCES FOR MORBIDITY AND
MORTALITY OUTCOMES, THAT'S 1
POSSIBILITY.
ANOTHER POSSIBILITY THOUGH IS
THAT BOTH ARE INDEPENDENTLY
THIRD OUTCOME VARIABLE, LIKE
EARLY LIFE DIVERSITY, LIKE
GENETIC DIFFERENCES BETWEEN
INDIVIDUALS, A THIR POSSIBILITY
IS THAT THIS IS NOT REALLY A
QUESTION FOR BIOLOGISTS PER SE
BUT THAT IT'S REALLY A QUESTION
FOR PEOPLE WHO WORK IN PUBLIC
POLICY, RIGHT?
IF THESE EFFECTS ARE ENTIRELY
EXPLAINED BY DIFFERENCES IN
SMOKING BEHAVIOR, THEN PERHAPS
THE RESEARCH SHOULD FOCUS NOT ON
PHYSIOLOGICAL AND MODEL CITIZEN
LEAKULAR MECHANISMS, BUT ON THE
EFFECTS OF CHANGING CIGARETTE
TACKS, BUT AND SO THE DIFFICULTY
IN SOLVING THESE PATHWAY IS
DEMON TRAITED BY THE FACT THAT
WE'VE KNOWN ABOUT THE SOCIAL
DETERMINANTS OF HEALTH FOR A
VERY, VERY LONG TIME NOW.
IF I SPEAK TO COLLEAGUES OF MINE
WHO ARE SOCIOLOGISTS, WELL WE
KNOW ABOUT THE SOCIAL
INTEGRATION STUFF THAT YOU GUYS
ARE WORKING ON IN ANIMALS NOW
AND WE'VE KNOWN THAT SINCE
[INDISCERNIBLE].
SO THIS IS AN OLD IDEA BUT 1
THAT STILL HASN'T HAD MUCH
RESOLUTION IN TERMS OF CAUSAL
PATHWAYS.
SO AMOLOL GOING TO COME BACK NOW
TO THE IDEA THAT OTHER ANIMALS
ARE A SOURCE OF INSIGHT HERE.
AND I THINK THERE ARE 3 WAYS IN
WHICH THAT IS THE CASE.
ANIMAL MODELS OFFER
OPPORTUNITIES TO DO EXPERIMENTS
THAT WE CANNOT DO IN HUMANS
EITHER ETHICALLY OR PRACTICALLY.
WE CAN INTERVENE DIRECTLY ON THE
SOCIAL ENVIRONMENT AND ASK WHAT
ENSUES TO TRY AND ESTABLISH
STRONG INFERENTIAL POWER FOR
CAUSALITY.
IN ADDITION HUMANS LIVE A VERY
LONG TIME AND SO IT'S VERY HARD
TO FOLLOW INDIVIDUALS FROM
CRADLE TO THE GRAVE, SO EVEN
WHEN WE GO TO OUR CLOSE NONHUMAN
PRIMATE RELATIVES, THIS BECOMES
MANAGE THAT IS POSSIBLE, RIGHT
IN AND IT CAN BE PAIRED WITH
VERY GRANULAR DIRECT
OBSERVATIONAL DATA ON THE
EXPERIENCES THAT ANIMALS HAVE
FROM DAY-TO-DAY.
IN OTHER WORDS WE CAN WATCH THE
BABOONS I STUDY ON A NEAR DAILY
BASIS ACROSS THEIR WHOLE LIVES,
SOMETHING THAT IS NEARLY
IMPOSSIBLE TO IMAGINE DOING IN
HUMAN POPULATIONS.
AND OF COURSE COMPARATIVE
STUDIES CAN PROVIDE VERY
IMPORTANT INSIGHT INTO WHEN AND
WHERE PARTICULAR TYPES OF SOCIAL
ADVANTAGE OR SOCIAL ADVERSITY
MIGHT MATTER.
WE WORK IN ALL OF THESE SPACES,
BUT TODAY I WILL FOCUS ON THE
TOP 2.
FIRST TALKING ABOUT WORK THAT
WE'VE NOW BEEN DOING FOR ABOUT A
DOZEN YEARS, ON EXPERIMENTAL
MODELS OF SOCIAL HIERARCHY AND
CHRONIC SOCIAL STRESS IN RECESS
MACAQUES, AND THEN TALKING A BIT
ABOUT THE WORK WE DO IN WILD
BABOONS IN KENYA WHO ARE ABLE TO
REALLY WATCH PROCESSES UNFOLD
ACROSS THE LIFE COURSE.
SO THESE ARE RECESS MACAQUES
WHICH I WORK ON AT THE EMORY
NATIONAL PRIMATE RESEARCH CENTER
OUTSIDE ATLANTA.
THIS WORK HAS BEEN COLLABRATIVE
FOR QUITE SOMETIME WITH MARK AND
MRK KENNA AT EMORY UNIVERSITY
AND LUIS AT THE UNIVERSITY OF
CHICAGO.
WE STUDIED THESE ANIMALS BECAUSE
THEY FORM COMPLETELY NATURALLY
VERY CLEARLY DELINEATED AND
REGULARLY ENFORCED SOCIAL STATUS
HIERARCHIES.
SO THEY FORM LADDER LIKE SOCIAL
AT THAT TIMEUSIRE ARCHYS THAT
CAN REMAIN TABLE IN NATURAL
CONDITIONS FOR YEARS OR EENCH
INTERGENERATIONALLY.
WE ALSO STUDY THEM BECAUSE
AGAIN, UNLIKE IN HUMANS, IT'S
POSSIBLE TO PERTURB THE SOCIAL
HIERARCHIES IN A WAY THAT IS
LARGELY CONTROLLED.
SO WOE CAN WATCH ANIMALS, WHO
ARE IN UNIFORM DEMOGRAPHIC
CONDITIONS, GROUPS OF THE SAME
SIZE WHO ALL HAVE ACCESS TO
HEALTHCARE, VETERINARY
HEALTHCARE IN THIS CASE, BUT ALL
HAVE HEGHT CARE ACCESS, NONE OF
WHOM SMOKE, NONE OF WHOM DRINK,
ALL OF WHOM HAVE THE SAME DIET,
RIGHT IN SO WHAT WE CAN DO IS
TAKE ADULT FEMALE RECESS
MACAQUES WHO HAVE NO SOCIAL
HISTORY WITH 1 ANOTHER AND NOT
POST RELATIVES AND SERLLY
INTRODUCE THEM INTO A NEW SOCIAL
GROUP, WE MAKE 5 GROUPS OF EACH
IN THE PARADIGM I WORK IN AND IT
TURNS OUT THE 1 WHO IS ARE FIRST
IN TEBD TO BECOME THE HIGHEST
RANKING INDIVIDUALS IN THEIR
GROUP.
INDIVIDUALS WHO INSERT
AFTERWARDS, CONTROL ORDER OF
INTRODUCTION JUST KIND OF INSERT
IN THE DOMINANCE HIERARCHY
DIRECTLY BELOW THE INDIVIDUAL
WHO IS ARE ALREADY THERE.
SO WE CAN FORM THESE GROUPS AND
REPLICATE THEM SO TYPICALLY WHEN
WE'RE DONE WITH THESE GROUPS
WE'RE WORKING WITH 9 OR 10
GROUPS AND WE CAN WATCH WHAT
ENSUES OVER THE COURSE OF ABOUT
A YEAR OR SO.
ABOUT 10 YEARS AGO WE WERE USING
THIS KIND OF PARADIGM BUT WE
REALLY WANTED TO GET A VERY
CLEAR HANDLE ON CAUSALITY SO WE
DECIDED TO ADD ANOTHER
MANIPULATION WHEREBY AFTER A
YEAR WE TOOK THE INDIVIDUALS WHO
WERE AT THE TOP OF THE HIERARCHY
AND PUT THEM TOGETHER IN A GROUP
AND THEN WE PUT INDIVIDUALS WHO
ARE SECOND RANKING IN THE
PREVIOUS HIERARCHIES IN A GROUP
AND SO ON DOWN THE LIST BECAUSE
THESE ARE NATURALLY VERY HIGH
ARCHICAL ANIMALS THEY JUST
REFORM A NEW HIRE ARCH EXPE THEN
WE CAN WATCH WHAT HAPPENS NEXT
FOR THE NEXT YEAR OR SO UNTIL WE
RUN OUT OF MONEY.
SORRY, THAT'S THE TRUTH.
AND SO, WHAT THIS ALLOWS US TO
DO IS WATCH ANIMALS WHEN THEY'RE
HIGH RANKING AND THEN LOW
RANKING AND WHEN THEY'RE LOW
RANKING AND HIGH RANKING OR AT A
HIGH RANKING OVER THE WHOLE
PERIOD OR TAYLOE RANKING OVER
THE WHOLE PERIOD AND THAT'S WHAT
YOU'RE SEEING HERE, THE Y-AXIS
HERE IS A SOCIAL STATUS IT'S AN
ELO RATING AND IT'S USED TO RANK
TENNIS PLAYERS OR CHESS PLAYERS
AND SO OAND WHAT YOU'RE SEEING
ARE ANIMALS CONNECTED WITH
THEMSELVES FROM PHASE 1 VERSUS
PHASE 2 OF THE STUDY, THIS IS
UNCORRELATED AND THAT IS BY
DESIGN BECAUSE WE REALLY WANT TO
KNOW WHETHER IT'S THE ANIMAL
SOCIAL STATUS AND SOCIAL
ENVIRONMENT THAT CONFERS THAT'S
DRIVING THE OUTCOMES WE'RE
INTERESTED IN.
OKAY, SO THIS IS JUST WHAT
ACTUALLY HAPPENS IN PRACTICE, SO
WHAT I'M SHOWING HERE THERE WE
GO THOSE ARE INTERACTIONS ISSUE
THOSE ARE COMPETITIVE
INTERACTIONS BETWEEN ANIMALS AND
WE WATCH THEM AND COLLECT THEM
AND AS WE COLLECT THEM WE SEE
WHO'S WINNING AND LOSING THOSE
INTERACTION ANDS IT GIVES US
THIS INIAR HIERARCHY BETWEEN
INDIVIDUALS OVERTIME AND ONCE
THE ANIMALS FIGURE IT OUT AND WE
FIGURE IT OUT SEBLGDARLY, THOSE
STAY STABLE THE ENTIRE COURSE OF
OUR STUDY.
SO WE'VE USED THIS KIND OF
EXPERIMENTAL MANIPULATION TO
LOOK AT A VARIETY OF DIFFERENT
TYPES OF OUTCOMES AND I WON'T GO
THROUGH ALL THIS HERE EXCEPT TO
SAY THAT WE THINK OUR DATA
PROVIDES PRETTY GOOD EVIDENT FOR
A CAUSAL ROLE OF SOCIAL STATUS
ON SEVERAL DIFFERENT DIMENSIONS
THAT MEET BE OF INTEREST TO YOU
INCLUDES ASPECTS OF PRO SOCIAL
BEHAVIOR, SOCIAL BEHAVIOR,
MEASURES OF PERSONALITY
INCLUDING ANXIOUS AND BOLDNESS,
AT THE PHYSIO LONGICAL LEVEL,
HPAAC ASSESSES FUNCTION AND
GLUCOCORTICOID TYPES AND I WILL
MENTION HERE THE REASON WE THINK
THIS IS CAUSAL IS THAT WE CAN
SEE A RELATIONSHIP BETWEEN THE
SOCIAL STATUS OF THE ANIMALS IN
OUR STUDY AND THESE OUTCOME
VARIABLES WITHIN PHASE AND THEN
IF WE LOOK AT THE DIFFERENT
PHASES, THE DELTA WE ALSO SEE
THAT FOLLOWED BY THE DELTA IN
THE OUTCOME VARIABLE.
SO I WON'T GO INTO THIS IN MUCH
DETAIL HERE BECAUSE WHAT I WOULD
LIKE TO FOCUS ON SPECIFICALLY
FOR THE PURPOSE OF THIS TALK IS
THE WORK AT THE MOLECULAR LEVEL,
AT THE GENOMIC LEVEL FOCUSING ON
IMMUNE FUNCTION.
SO THIS WORK WAS REALLY
CATALYZED BY THE POST DOCTORAL
WORK OF 1 OF MY FORMER STUDENTS
NOAH SNYDER AT ARIZONA STATE AND
[INDISCERNIBLE] WHO WORK WIDE MY
COLLABORATOR LUIS WHO IS NOW AT
THE UNIVERSITY OF SARRA GOESA IN
SPAIN.
WE WERE BORROWING FROM A METHOD
THAT'S USE INDEED HUMAN
POPULATIONS, WE WERE GOING TO
THE ANIMALS VERY FAR THE
MANIPULATIONS AND WE WERE TAKING
BLOOD FROM THEM AND WE UPON
TAKING BLOOD IN MULTIPLE TUBES,
1 THAT WENT DIRECTLY INTO CELL
CULTURE MEDIA, THE MINIMUM
INGREDIENTS THAT CELLS NEED TO
LIVE OUTSIDE THE BODY FOR A
LITTLE WHILE AND THEN COLLECT
ANOTHER TUBE IN PARALLEL, WHERE
THE TUBE ALSO CONTAINED THE
MEDIA BUT WAS SPIKED WITH AN
ADDITIVE.
ON THIS CASE I WILL SHOW YOU
DATA ON LIP O POLYSACCHARIDES SO
WE WERE MIMICKING INFECTION BY
GRAM NEGATIVE BACTERIA EXVIVO.
THEN WE CULTURE THESE IN
PARALLEL FOR 4 HOURS AND STOP
THE REACTION, COLLECT THE CELLS
AND USE FUNCTIONAL GENOMIC
APPROACHES TO MEASURE THE
ACTIVITY OF ALL THE EXPRESSED
JEERNS IN THE CELLS BOTH IN THE
CONTROL CONDITION AND THE IMMUNE
STIMULATED CONDITION AND I'M
SQUISHING DOWN ALL OF THOSE HERE
ON THE RIGHT IN A PRINCIPAL
COMPONENT ANALYSIS SO THIS IN
THIS CASE, WE HAD 45 METRICS
FEALS IN THIS PARTICULAR DATA
SET AND EACH OF THEM IS
REPRESENTED BY 2 DOTS 1 IS THE
CELL AT BASE LINE AND THE OTHER
IS THE CELL WHEN IS THEY'VE BEEN
EXPOSED TO LIP O POLYSACCHARIDE.
BASICALLY WHEN THEY THINK
THEY'RE BEING INFECTED BY
BACTERIA.
AND IT WASN'T A SURPRISE TO US
THAT THIS FIRST PRINCIPLE
COMPONENT, SIMPLY CORRELATES
WITH WHETHER OR NOT THOSE CELLS
HAVE SEEN THIS BACTERIA WILL
COMPOUND OR NOT IT'S EXACTLY
WHAT HAPPENED TO OUR CELLS IF
THEY ARE EXPOSED TO LPS, BUT
WHAT WAS INTERESTING TO US AND
CATALOGED A LOT OF WORK SINCE IS
THE SECOND VARIATION OF ACTION,
PC 2 IS CORRELATED WITH THE
SOCIAL STATUS OF THE DONOR
INDIVIDUAL AT THE SAMPLE EYE
VIEW TO THIS KIND OF SCATTER
PLOT WHICH IS A YEEN EYE VIEW,
EACH DOT IS A DIFFERENT GENE
THAT WE WERE ABLE TO MEASURE AND
EXPERIMENT THE EFFECT SIZE IS
THE DOMINANCE GENE EXPRESSION IN
THE CONTROL CONDITION AND Y-AXIS
SHOWS THE AFFECTS SIZE FOR
DOMINANCE RINK AND YEEN
EXPRESSION IN THE LPS SIMULATED
CONDITION SO THIS IS SAYING IF A
GENE IS MORE ACTIVE IN HIGH
RANKING FEMALES AT BASE LINE, IT
ALSO TENDS TO BE MORE ACTIVE IN
HIGH RAIRCHGING FEMALES WHEN
THEIR CELLS ARE EXPOSED TO LPS
BUT WE DO SEE EXCEPTIONS TO
THAT, PARTICULARLY TO THIS CLOUD
POINT HERE, THESE ARE ALL GENES
THAT DON'T SHOW MUCH OF AN
EFFECTIVE SOCIAL STADUS IN CELLS
THAT MODEL RESTING STATE,
ANIMALS JUST SORT OF WALKING
AROUND IN GOOD HEALTH BUT WHEN
THEY'RE FACE WIDE A PATHOGEN
CUE, THEIR RESPONSE IS DIFFER,
WE DOE START SEEING THIS NEW
PREVIOUSLY MASKED EFFECT OF
DOMINANCE RANK AND WHAT THAT
MEANS IN THIS PARTICULAR STUDY
WAS THAT LOW RANKING FEMALES
TENDED TO RESPOND MUCH MORE
STRONGLY TO BACTERIAL
STIMULATION THAN HIGH RANKING
FEMALES.
GENES IN THIS PARTICULARLY SEEM
TO BE INVOLVED IN
PROINFLAMMATORY PROCESSES, WHERE
IF WE LOOK AT YEENS ON THE OTHER
SIDE UP HERE, THESE ARE THE FEW
THAT RESPONDED MORE STRONGLY IN
HIGH RANKING INDIVIDUALS, THAT I
TENDED TO BE INVOLVED IN TYPE 1
INTERFERON SIGNALING SO VERY,
VERY GROSSLY A DIFFERENCE
BETWEEN A SORT OF
PROINFLAMMATORY ANTIBACTERIAL
RESPONSE DOWN HERE AND SORT OF
THE INNATE-FOR SOME OF THE FIRST
LINE INNATE IMRUIN RESPONSES TO
VIRUSOT TOP SIDE.
SO, MY COLLEAGUE WHO HAS A
GENOMIC BACKGROUND SAID THAT WAS
REALLY INTERESTING AND I SAID
WHY IS IT REALLY INTERESTING
EMPLOY IT'S INTERESTING BECAUSE
WE TREATED THEM WITH LPS AND IT
HAS A WELL WORKED OUT SIGNALING
PATHWAY WITHIN CELLS.
LPS IS RECKIFIESED BY TOLL-LIKE
RECEPTOR 4, TYPICALLY EXPRESSED
ON MONOCYTES AND MACROPHAGES AND
ONCE IT BINDS LPS, IT CAN SIGNAL
SORT OF THROUGH 2 ALTERNAATIVE
PATHWAYS SHOWN HERE ON THE
LEFT-HAND SIDE AND THE RIGHT
HAND SIDE RESPECTIVELY.
YEENS THAT ARE SHOWN IN THESE
PATHWAYS IN BLUE ARE MORE HIGHLY
EXPRESSED IN LOW STATUS
INDIVIDUALS
INDIVIDUALS AND GENES IN PURPLE,
ARE HIGH STATUS, AND IF YOU
SQUINT A LITTLE BIT CAN YOU SEE
A POLAR EYATION AND SIGNALING
PATHWAYS AFTER EXPOSE TOWER LPS.
SO WHEN'S INTERESTING ABOUT THIS
IS THAT THESE PATHWAYS
CONVERGEOT BOTTOM ON THESE GUYS
HERE, THESE ARE TRANSCRIPTION
FACTORS AND THESE TRANSCRIPTION
FACTORS, PRODUCE A FURTHER
REGULATORY CASCADE WITHIN CELL.
SO WHAT WE WERE ABLE TO DO, IS
AUGMENT THE GENE EXPRESSION DATA
WITH DATA ON WHAT'S CALLED
CHROMATIN ACCESSIBILITY OR OPEN
CHROMATIN PROFILES WHICH ASKS
ABOUT THE PHYSICAL CONFIRMATION
OF DNA WITHIN THE CELL, MOST DNA
IS PACKAGED QUITE TIGHTLY AROUND
HISTONES BUT PARTS OF THE DNA
THAT ARE OPEN TO TRANSCRIPTION
FACTOR BINDING AND THEREFORE
OPEN TO JEEP REGGULES TEND TO BE
A BIT UNWOUND.
AND WHAT WE FOUND IS THAT IF WE
MEASURED UNWOUND DNA NEAR YEENS
THAT ARE MORE HIRELY EXPRESSED
IN LOW STATUS INDIVIDUALS, THEY
TENDED TO BE ENRICHED FOR
BIEBDING SITES FOR NF-KAPPAB AND
RELATED TRANSCRIPTION FACTORS
BUT IF WE LOOK AT OPEN
CHROMATIN, IN YEERPS THAT ARE
EXPRESSED IN HIGH RAIRCHGING
INDIVIDUALS ON THE RIGHT HAND
SIDE, WE SAW THE OPPOSITE
PATTERN, ENRICHMENT FOR BINDING
SITES FOR INTERFEREON REGULATORY
FACTORS.
SO IN OTHER WORDS OUR DATA
SUGGESTS SOCIAL ENVIRONMENT IS
CAUSAL TO CHANGES IN GENE
EXPRESSION FOR HUNDREDS TO
THOUSANDS OF YEENS EXPRESSED IN
CIRCULATING IMMUNE CELLS.
NOT ONLY DOES THAT MATTER AT
BASE LINE BUT IT MATTERS TO ARE
THE WAY THAT THOSE CELLS ARE
ABLE TO RESPOND TO OTHER
TRESESSORS, LIKE MIMICS OF
PATHOGEN INFECTION, WE THINK
THESE CHANGES ARE LINKED IN PART
TO THAT SORT OF PHYSICAL
STRUCTURING OF DNA AND ITS
ABILITY TO GET DNA BINDING THAT
IT TURN GET DOWN TO A GRANULAR
ENOUGH LEVEL THAT THEY CAN ALTER
THE USE OF DEFINITE SIGNALING
PATHWAYS WITHIN ITS CELLS.
SO THIS IS KIND OF WHERE WE WERE
MAYBE 6 OR 7 YEARS AGO AND WE
DID A LITTLE BIT MORE WORK TO
DELINEATE MORE OF THIS KIND OF
RELATED STUFF, RESPONSES TO
VIRUS, RESPONSES TO DPLIEWK O
CORD KOIDS AND SO ON, BUT
THERE'S A DEGREE TO WHICH
STOPPING AT THE LEVEL OF YEEN
REGULATION IS STILL SOMEWHAT
UNSATISFACTORY.
I CAN MAKE THE ARGUMENT THAT
WHAT'S GOING ON IN OUR IMMUNE
CELLS PROBABLY MATTERS TO, YOU
KNOW TO WHOLE ORGANISM,
MORBIDITY BUT WE CAN'T REALLY
SHOW IT IN THIS STUFF, THERE'S A
WHOLE BURCH OF LAYERS THAT GET
TO HERE TO SOCIAL DETERMINANTS
OF THEALGT WE TARTED WITH THAT
AREN'T THERE YET AND WE'RE NOT
THERE, YET, NOW, BUT WE WERE
INSPIRED A FEW YEARS AGO BY WORK
THAT SOME OF YOU MIGHT KNOW, THE
PITTSBURGH COLD STUDIES, WHERE
SHELDON CONAN AND COLLEAGUES
TOOK HEALTHY VOLUNTEERS AND
EXPOSED THEM TO LIVE VIRUS,
RHINO RIEROUS, CORONA VIRUS, FLU
VIRUS AND ASKED ABOUT THE
PREDICTORS OF WHICH CONVERTED TO
CLINICAL SYMPTOMS VERSUS NOT.
OKAY.
AND THIS IS A NICE REVIEW, THEY
DID THIS SORLT OF WORK FOR ABOUT
20 YEARS OR SO.
BUT IN GENERAL, THE PATTERN THEY
SHOWED WAS THAT GREATER LEVELS
OF PSYCHOLOGICAL TRESES,
INCLUDING THE STRESS OF CARE
IMIFFING TO CHRONICALLY ILL
CHILDREN AND ALSO EARLY LIFE
SOCIAL DISADVANTAGE OF THE
CONSISTENTLY A GOOD PREDICTER OF
WHO WHENKS POSED TO EXACTLY THE
SAME AMOUNT OF RHINO VIRUS OR
CORONA VIRUS GOT SICK, SO IT'S
NOT JUST EXPOSURE BUT IT'S
SUSCEPTIBILITY ON EXPOSURE.
WE THOUGHT THIS WAS A REALLY,
REALLY BEING IDEA AND SOMETHING
THAT MIGHT IN A VERSION WE COULD
IMPLEMENT, GET A CLOSER LOOK AT
THE QUESTIONS WE'RE INTERESTED
IN, WE ALSO HAD THE ADVANT
KNOWLEDGE IN THIS CASE, WE COULD
NONAPOPTOTIC THE DO THIS IN
HUMANS, WE COULD DO THE
MANIPULATION OF THE SOCIAL
FACTOR ITSELF AS OPPOSE TO
TAKING PEOPLE AS THEY WALKED
INTO THE STUDY.
IN ADDITION WITH THE RECESS
MACAQUES, WE COULD USE
CHALLENGES THAT THEY HAD NEVER
SEEN BEFORE SO WE COULD ALSO
LACK AT BOTH THE NAIVE RESPONSE
TO PATHOGENS AND THE SECONDARY
RESPONSE TO PATHOGENS.
SO THAT'S WHAT WE DID.
SO THIS ANOTHER SET OF MONKEYS,
NUMBER OF YEARS LATER WHERE
INSTEAD OF GIVING THEM LIVE FLU
VIRUS, WE JUST GAVE THEM FLU
VACCINATIONS AND THESE ARE HUMAN
QUADRIATIC FLU VACCINES AND WE
GAVE IT TO THEM IN PHASE 1 OF
THE STUDY AND PHASE 2 OF THE
TODAY ABOUT A YEAR LATER.
WE MEASURED THE YEEN EXPRESSION
AND ANTIBODY TITERS, BEFORE
VACCINATION AND AT SERL TIME
POINTS AFTER VACCINATION, UP
UNTIL COLLECTING ANTIBODY DATA
AT DAY 28, WHEN WE COULD MEASURE
VARIATION AND HOW WELL DIFFERENT
INDIVIDUALS MOUNTED A RESPONSE
TO THE VACCINE.
OKAY, AND YOU CAN SEE HERE, THEY
RESPOND TO THE VACCINE, THEY
MAKE ANTIBODIES VERY, VERY WELL,
SO THIS IS WHAT WE BELIEVE IS
BASICALLY NEVER EXPOSED TO HUMAN
FLU OR HUMAN FLU ANTIGENS, THIS
IS DAY 28, THESE ARE VACCINE
SPECIFIC ANTIBODY TITERS, THEY
ACTUALLY MAINTAIN THOSE ANTIBODY
TITERS PRETTY WELL, OVER THE
COURSE OF THE YEAR, MAYBE DROP
OFF A LITTLE BIT AND THEN THAT
SECOND SHOT IS BASICALLY A
BOOSTER EFFECT, OKAY IN THIS
SHOWS A SIMILAR KIND OF PATTERN
THIS IS THE AHA TITERS GOING
FROM NO ABILITY TO RESTRICT FLU
TO PRETTY GOOD ABILITY TO
RESTRICT FLU 28 DAYS AFTER THEY
SOLVE THAT.
SO IF OUR GENE EXPRESSION DATA
HAVE ANYTHING TO DO WITH
PREDICTING ANTIBODY RESPONSE,
THEN WE REASONED THAT GENE
EXPRESSION HAS TO PREDICT
ANTIBODY RESPONSE ITSELF AND SO
THAT'S WHAT WE ASKED FIRST,
THESE ARE JUST EXAMPLES ISSUE
THESE ARE SORT OF CHERRY PICKED
EXAMPLES OF YEEN EXPRESSION
LEVELS ON DAY 1, SO, THE DAY
AFTER THE ANIMAL HAD THE
VACCINE, ON THE Y-AXIS AND THE
FULL CHANGE ANTIBODY RESPONSE
FROM DAY 0-DAY 28.
SO BIGGER BODIES AND THESE ARE
STRONG RELATIONSHIPS, THESE
YEENS ARE CHOSEN BECAUSE THEY
ARE INVOLVED IN THE INNATE
IMMUNE RESPONSE,--THE INNATE
IMMUNE RESPONSE TO VIRUS, WEIRD,
AND OTHER ASPECTS OF THE
ANTIVIRAL RESPONSE BUT THEY ARE
ACTUALLY PRETTY RESPECT
RESENTATIVE OF WHAT WE SEE OVER
ALL, OUR ANALYSIS INDICATES THAT
JUST SHORT OF ABOUT 2000 YEENS
SHOW A PREDICTIVE RELATIONSHIP
ON DAY 1, THE FIRST DAY AFTER
INOCULATION AND THAT 28 DAY
RESPONSE AND MANY OF THOSE YEENS
ARE ENRICHED IN CATEGORIES THAT
WE MIGHT EXPECT LIKE THE
RESPONSE TO CYTOKINES, LIKE THE
INNATE IMMUNE RESPONSE, RESPONSE
TO VIRUS AND SO ON.
SO THEN THE QUESTION IS DO THESE
GENE VS ANYTHING TO DO WITH THE
YEEPS WE ANNOTATE AS RESPONSIVE
TO THE SOCIAL ENVIRONMENT, AND
THAT'S WHAT I'M SHOWING YOU
HERE.
SO AGAIN WE'RE MOVING FROM A
SAMPLE PERSPECTIVE TO A GENE
LEVEL PERSPECTIVE, EVERY DOT IS
A DIFFERENT GENE HERE AND THE
X-AXIS SHOWS RELATIONSHIP
BETWEEN DOMINANCE RANK AND GENE
EXPRESSION, SOCIAL STATUS AND
GENE EXPRESSION, THE DAY AFTER
THE VACCINE WAS ADMINISTERED AND
THE Y-AXIS SHOWS THE
RELATIONSHIP BETWEEN GENE
EXPRESSION ON DAY 1 AND THAT
ANTIBODY RESPONSE ON DAY 28
COMPARED TO DAY 0.
AND WHAT I HOPE YOU'LL SEE IS
THAT THIS IS NOISY BUT IT'S
ACTUALLY PRETTY WELL CORRELATED,
IT'S PRETTY POSITIVELY
CORRELATED MEANING THAT WE HAVE
A LOT OF CASES UP HERE, PERHAPS
MORE CASES UP HERE, BUT WE HAVE
CASES UP HERE WHERE HIGH AT THAT
TIMEUS DRIVES HIGHER EXPRESSION
OF THE YEEN AND HIGHER
EXPRESSION OF THE YEEN PREDICTS
A MORE ROUGH ATOM DUST ANTIBODY
RESPONSE, AND CASES DOWN HERE
WHERE LOW RANK DRIVES HIGHER
EXPRESSION OF THE YEEN BUT IN
THOSE CASES HIGHER EXPRESSION
LEADS TO A SMALLER ANTIBODY
RESPONSE.
EE THESE, YOU KNOW ADAPTIVE
IMMUNITY PREDICTIVE YEENS ARE
ALSO GENES THAT TEND TO BE
INVOLVED IN THE RESPONSE TO
SOCIAL CUES, IN THE SAME
ANIMALS, OKAY?
AND SO, OF COURSE, WHAT IS
POTENTIALLY MORE INTERESTING IS
TO ASK, WELL DOES SOCIAL
RESPONSE IMPROVE THROUGH THESE
INTERMEIATE REGULATORY PATHWAYS
AND WE FIND SOME THEAFS IT DID,
SO IF WE LOOK AT FAYE 1 OF THE
STUDY, IT'S NOISY ABOUT YOU WE
SEE A RELATIONSHIP BETWEEN
SOCIAL STATUS AND THE ANTIBODY
RESPONSE.
IT'S WEEK BUT WE THINK IT'S
THERE.
WHEN WE LOOK AT THE 2, WE SO
SOCIAL AT THAT TIMEUS AT THE
TIME OF SAMPLING AND THE EABT
BODY RESPONSE, THE BOOSTER LIKE
EFFECT.
WHAT'S INTERESTING ABOUT THIS IS
THAT THE SECONDARY RESPONSE IS
ALMOST COMPLETELY PREDICTED BY
HOW WELL THEY RESPOND HERE.
SO HOW MUCH THEY RESPONDED TO
THE FIRST INTRODUCTION OF
SOMETHING THAT LOOKED LIKE A FLU
VIRUS WHERE THEY LANDED ON DAY
28 HERE, BASICALLY EXPLAINED HOW
MUCH THEY RESPONDED HERE AND SO
AGAIN, QUITE NOISY BUT WHAT'S
RATHER INTERESTING TO US IS THAT
IT WE LOOK AT SOCIAL STATUS IN
FACE 1 WHICH IS COMPLETELY
UNFORALATED WITH PHASE 2, THAT
HAS WEAK PREDICTIVE POWER FOR
THE ANTIBODY RESPONSE IN PHASE
2, EVEN THOUGH YOU RECALL SOCIAL
STATUS IN PHASE 1 AND 2 ARE
UNCORRELATE WIDE 1 ANOTHER.
SO WHAT THIS SUGGESTS TO US IS
THE POSSIBILITY THAT IT'S THAT
FIRST EXPOSURE THAT MATTERS AND
THEN THAT HAS A SORT OF SOCIAL
HISTORY EFFECT THAT FOLLOWS
THESE ANIMALS DOWN THE ROAD
EMPLOY SO THAT'S SORT OF A
SNAPSHOT OF WHERE WE ARE ON OUR
RECESS MACAQUE STUFF WHICH WE
THINK IS QUITE POWERFUL FOR
DOING THESE KINDS OF REPEATED
BIOLOGICAL SAMPLES SOCIAL
MANIPULATION KIND OF STUFF BUT
IT'S BAD FOR STUFF WHERE YOU
WANT TO SEE WHAT HAPPENS OVER
THE COURSE OF QUEERS, WE'VE
NEVER BEEN ABLE TO RUN THESE
SORTS OF EXPERIMENTS MORE THAN A
FEW YEARS AND EVEN THAT'S PRETTY
HARD.
--THIS IN THE ECOSYSTEM ABOUT
NEAR THE BORDER OF TANS ANIA,
AND THEY ARE AND UNDER
CONTINUOUS STUDY BY THE BABOON
RESEARCH PROJECT AND NOW IN ITS
PEA ORDER YEAR OF DATA CLICK AND
WHAT WE MEAN BY THAT IS THAT
ANIMALS IN THIS POPULATION ARE
RECOGNIZED ON SITES WHERE THE
INFORMATION ON THEIR BEHAVIOR,
ENVIRONMENT, WHO THEY'RE
INTERACTING WITH AND WHAT THEY
HAVE TO EAT ARE ROUTINELY
MEASURED THROUGHOUT THEIR LIFE
SPANS.
I AM LUCKY ENOUGH TO WORK ON
THIS PROJECT THROUGH THE
LONG-TERM FORESIGHT OF JANE
ALTMANN, AND TUMOR SPECTRUM ART
ALTMANN, WHO FOUNDED THIS
PROJECT IN 9 FONNATES AND 1 OF
THE GREAT JOYS OF MY
PROFESSIONAL LIFE IS THAT I
CONTINUE TO BE ABLE TO CO-DIRECT
THIS PROJECT WITH BETH ARCHY AND
THE UNIVERSITY OF NOTRE DAME AND
SUSAN ALBERTS AT DUKE
UNIVERSITY.
I WOULD BE REMESS IF I DIDN'T
ACKNOWLEDGE THAT ALMOST ALL THE
DATA I'M ABOUT ON TO SHOW YOU,
CERTAINLY THE FIELD DATA IS TO
THE CREDIT OF THE EXPERTISE AND
PROFESSIONALISM OF OUR LONG-TERM
KENYA FIELD TEAM.
I HIGHLIGHTED 4 OF THEM IN
PARTICULAR HERE: WHO ARE THE
SENIOR OBSERVERS AT MANY SITES
AND IN FACT, HAPh JUST RETIRED
A FEW WEEKS AGO AFTER STUDYING
BA BOONES IN THE ECOSYSTEM SINCE
1981.
SO WE OWE THEM QUITE A LOT.
THIS IS A PICTURE OF KINYUA,
SHOWING YOU WHAT WE DO EVERY
DAY, THEY ARE HAIBITUATED TO OUR
PRESENCE, THEY DON'T CONSIDER US
THREATS OR SOURCES OF FOOD, SO
OUR GOAL IS FOR THEM TO TREAT US
LIKE THEY WOULD TREAT A TREE SO
WE CAN BE FLIES ON THE WALL,
IT'S A LOT OF METAPHORS, I KNOW,
BUT WE CAN BE FLIES ON THE WALL
AND WRITE DOWN WHAT THEY'RE
DOING WITHOUT AFFECTERRING IT,
SO THAT'S WHAT THEY'RE DOING
HERE, THIS IS THE IMAGE OF OUR
PEDIGREE, THIS IS 5 YEARS OUT OF
DATE NOW RUNNING FROM FIRST
GENERATION DOWN TO NINTH
GENERATION, THIS IS JUST SHY OF
2000 INDIVIDUALS THAT WE'VE BEEN
ABLE TO FOLLOW INCLUDING THEIR
DESCENDANT GENERATIONS.
SO WHAT DO WE DO WITH THIS DATA
1 THINK THIS WE ASK IS WHAT IS
TRUE IN HUMANS, TRUE IN BABOONS,
CAN WE DERIVE INSIGHT INTO THE
PATTERNS THAT HAVE BEEN REPORTED
IN HUMAN POPULATIONS BY STUDYING
THESE ANIMALS.
THERE HAVE BEEN 2 AREAS THAT WE
PAID A LOT OF ATTENTION TO
RECENTLY, WOKNOW IS RELATED TO
WHAT I SHOWED YOU EARLIER AND
SOCIAL INTEGRATION AND SOCIAL
SUPPORT AND ALSO SOCIAL BOND
STRENGTH EMPLOY I WILL MENTION
HERE BRIEFLY BECAUSE I WON'T GO
INTO THIS IN MUCH DETAIL THAT
THERE'S ALSO A STRONG
RELATIONSHIP BETWEEN SOCIAL
INTEGRATION AND SOCIAL ISOLATION
OF THESE ANIMALS BASICALLY HOW
MUCH THEY'RE GROOMING WITH 1
ANOTHER AND ANOTHER ANALYSIS,
WHETHER THEY HAVE STRONG STABLE
FRIENDSHIPS WITH A SMALL NUMBER
OF INDIVIDUALS AND WHETHER OR
NOT THEY'RE LIKELY TO SURVIVE IN
ANY GIVEN YEAR.
SO THIS BAR OVER HERE IS A
SURVIVAL PLOT THAT SEPARATES THE
TOP CORTILE OF SOCIALLY
INTEGRATED ANIMALS IN OUR
POPULATION, AND THE BOTTOM
CORTILE IS THE MOST SOWCIALLY
ISOLATED, THIS TRANSLATES TO
ABOUT 2-3 YEARS LIFE EXPECTANCY
DIFFERENCE IN THE ANIMALS.
THIS IS THE LARGEST EFFECT WE
SAW FOR EXPLAINING LIFE SPAN AND
SURVIVAL UNTIL WE LOOKEDDA THE
THIS THING, EARLY LIFE
ADVERSITY.
SO THE ACES,A PROACH IS A VERY
HUMAN CENTERED APPROACH, RIGHT,
IT'S ACTUALLY NOT AN APPROACH
THAT'S USED VERY OFTEN, EVEN IN
OTHER ANIMALS EVEN THOUGH PEOPLE
HAVE BEEN INTERESTED IN EARLY
LIFE CENTER FOR EXCELLENCE ON
AGINGS FOR A LONG TIME BUT WE
WERE SPENDING A LOT OF TIME
AROUND SOCIAL SCIENTISTS AND WE
SAID WELL, LET'S GIVE IT A SHOT
RECOLLECT ADD THEM UP AND SEE
WHAT HAPPENS, RIGHT IN SO THAT'S
WHAT WE DID, WE ADDED IT UP, 6
SOURCES OF EARLY LIFE ADVERSITY,
MAJOR LIVE ADVERSITY AS WE LEARN
ABOUT THEM IN BABOONS, THIS IS A
SURVIVAL PLOT AGAIN SHOWING
ADULT SURVIVAL SO WE'RE NOT
TALKING ABOUT INSULTS THAT LEAD
TO MORTALITY BUT INSULTS
SUSTAINED IN THE FIRST FEW YEAR
OF LIFE THAT TRANsALATE INTO
MEASURABLE OUTCOMES YEAR TO
DECADES LATER. THIS IS WHAT WE
THINK ABOUT OUR SILVER SPOON
BABIES, NOTHING PARTICULARLY BAD
HAPPEN TO THEM AND INDIVIDUAL
WHO IS HAD 1 MAJOR SOURCE OF
EARLY LIFE ADVERSITY, 2, 3 AND
SO ON, SO THIS IS THE PLOT WHERE
YOU THINK I AM NEVER GOING TO
GET THIS CLEAR OF A RESULT EVER
AGAIN IN MY CAREER, AND PROBABLY
WE SHOULDN'T HAVE HAD TO DO AT
THAT TIMISTICS TO SEE THIS BUT
WE JUST NEVER THOUGHT ABOUT
BEING LOOKING AT IT LIKE THAT
BEFORE EMPLOY SO THE DIFFERENCE
BETWEEN THESE DARK BLUE LINES
AND THESE RED LINES IS SOMEWHERE
UP TO ABOUT A DECADE DIFFERENCE
IN ADULT LIFE EXPECTANCY AND
JUST TO GIVE YOU SOME CONTEXT,
YOU KNOW MANY OF US ARE USED TO
THE DOG-HUMAN TRANSLATION, LIKE
1 DOG YEAR AND--1 HUMAN--YEAH,
7.
THANK YOU.
ONE DOG YEAR, 7 HUMAN YEARS
THIS, IS ABOUT A 1 OR 2 OR 3
RATIO, SO IFFY WOO WERE THINK
BEING THIS IN HUMAN TERMS WE
THIS WOULD BE A DIFFERENCE OF
ABOUT 20-30 YEARS.
IT'S HUGE.
THESE ARE THE MAJOR SOURCES OF
EARLY ADVERSITY WE CONSIDER,
RECALL LIFE MATERNAL LOSS, EARLY
SOCIAL STATUS, MATERNAL SOCIAL
CONNECTEDNESS VERSUS SOCIAL
ISOLATION, WHETHER THEY HAVE A
COMPETING YOUNGER SIBLING,
ANOTHER SIBLING BORN WITHIN THE
SHORTEST CORTILE OF INTERVALS IN
OUR POPULATION, SORT OF LOCAL
DENSITY, THEIR GROUP SIZE, WHICH
WE THINK IS AN INDEX OF RESOURCE
COMITITION IS THIS IS A PURELY
ECOLOGICAL FACTOR WHETHER THE
FIRST YEAR IS SPENT IN SEVERE
DROUGHT.
SO MANY OF THESE HAVE A SOCIAL
COMPONENT AND I THINK MANY OF
THEM HAVE EXPLICITLY A MATERNAL
COMPONENT.
I WANT TO POINT OUT--THIS IS
DISTRIBUTION BY THE WAY OF THE
ACES IN OUR POPULATION AND I
SHOULD SAY BECAUSE THIS IS OFTEN
NOT OBVIOUS, UNLIKE IN HUMAN
POPULATION WHERE DIFFERENT
ADVERSITY TENDS TO BE CORRELATE
WIDE EACH OTHER, THE 1 IN OUR
POPULATION ARE NOT CORRELATED,
IN OTHER WORDS THEY MOVE
PHOTOCOPIEDLY OF 1 ANOTHER
ALLOWINGITOUS DISSECT WHICH OF
THOSE SOURCES MATTER TO WHICH
OUTCOMES.
THIS MATTERS NOT ONLY TO THE
INDIVIDUAL EXPERIENCING EARLY
LIFE ADVERSITY, IT ALSO HAS DOWN
STREAM EFFECTS ON THE
COMPOSITION OF OUR POPULATION ON
SUBSEQUENT GENERATION, HERE IS
JUST A PLOT SHOWING THAT AGE AT
DEATH IN THESE FEMALE BABOONS IS
THE MAINLIOR PREDICTER OF HOW
MANY KIDS THEY SUCCESSFULLY
LEAVE BEHIND.
AND THOSE KIDS ARE AFFECTED BY
INTERGENERATIONAL AFFECTS.
SO IN WORK, LED BY SUSAN'S
FORMER GRADUATE MATTHEW ZIPLE,
HE SAID, OKAY, WE KNOW THAT THE
KIDS OF A MOM WHO DIED EARLY,
WHO EXPERIENCED MATERNAL LOSS,
THAT INDIVIDUAL IS LIKELY TO ARE
HAVE A TRUNCATED LIFE SPAN.
DO WE KNOW WHETHER A KID WHO
EXPERIENCED MATERNAL LOSS AND
THEN SUCCESSFULLY GROW UP AND
HAD HER OWN CHILDREN, THEN SEES
AFFECTS OF HER EARLY LIFE
PRESENCE ON HER OWN KIDS, THAT
MAKE SENSE?
OKAY, THANK YOU.
AND THIS IS WHAT HE FOUND, HE
SAID CONTROLLING FOR F2'S EARLY
LIFE EXPERIENCE, ALL THOSE
FACTORS I JUST SHOWED YOU, THE
MALE AND FEMALES MOTHER HAD LOST
HER OWN MOTHER, EARLY IN LIFE,
WHICH COULD HAVE HAPPENED QUITE
SOMETIME AGO, THE LIKELIHOOD
THAT THIS F2 INDIVIDUAL SURVIVES
TO SORT OF THE MINIMUM AGE OF RE
PRODUCTIVE AGE OF MATURATION AND
THIS POPULATION IS SIGNIFICANTLY
REDUCED SO THAT'S THIS RED LINE
HERE, THIS RED LINE IS, YOU KNOW
GRANDMA DIED WHEN MY MOTHER WAS
YOUNG.
WE THINK THAT THIS CAN PRIMARILY
BE EXPLAINED BY LONG LASTING
EFFECTS ON MATERNAL GENERATION
AND I AM HAPPY TO TELL YOU WHY
IF YOU'RE INTERESTED DOWN THE
ROAD.
SO THESE WERE BIG EFFECT SYSTEM,
VERY INTERESTING WHAT IS
HAPPENING, WE DON'T KNOW WHAT'S
HAPPENING, AND SO, SINCE THOSE
EARLIER OBSERVATIONS WE'VE SPEPT
A VERY LARGE PROPORTION OF OUR
SORT OF RESEARCH ENERGY ON
TRYING TO TEASE APART THE
PATHWAYS THROUGH WHICH THIS
MIGHT WORK AND THAT'S TAKEN KIND
OF AN ARMY OF OPPORTUNITIES AND
POAFULT DOCS AND COLLABORATORS
AROUND THE WORLD.
THESE ARE SOME OF THE THINGS
WE'VE BEEN ABLE TO LOOK AT
PRIMARILY IN FEMALES SO FAR.
SO I FOCUSED ON THESE
DEMOGRAPHIC OUTCOMES, ADULT AND
OFFSPRING PORTALLITY, THESE ARE
VERY CLEAR EFFECTS, OR VERY
CLEAR CORRELATES OF EARLY LIFE
ADVERSITY.
WE SEE DIFFERENCES IN THE SOCIAL
BEHAVIORS OF INDIVIDUALS WHO
EXPERIENCE MORE ADVERSITY, THEY
TEND TO BE MORE SOCIALLY
ISOLATED AND SOMETIMES THAT I
ACHIEVE LOWER SOCIAL STATUS WHEN
THEY'RE ADULTS.
WE SLEEP APNEA AND OBESITYY
CENTER FOR EXCELLENCE ON AGINGS
OF RESOURCE DEPRIVATION ON LONG
BONE GROWING, SO I THINK THAT
THEY'RE UNDERGOING SORT OF A
BABOON ANALOGUE OF STUNTING AND
WE SEE PHYSIOLOGICAL
CONSEQUENCES ESPECIALLY IN GLUE
COCORTICOID PHYSIOLOGY AND I'M
HAPPY TO TALK ABOUT ANY OF THAT
BUT FOR THE PURPOSES OF THE
REMAINDER OF THE TALK I WILL
FOCUS A LITTLE BIT ON WHAT WE'VE
DONE LOOKING AT GENOMIC AND
MOLECULAR OUTCOMES.
THIS IS INSPIRED BY THE
BIOLOGICAL EMBEDDING FRAMEWORK
WHICH MY BE FAMILIAR TO MANY OF
YOU.
THIS ARGUES THAT THE REASON THAT
EARLY IN LIFE ENVIRONMENT HAS A
SORT OF LONG REACH INTO
ADULTHOOD AND OLDER AGE IS
BECAUSE THE ENVIRONMENT IS ABLE
TO INFLUENCE WHAT'S HAPPENING
UNDER THE SKIN, IT'S ASHING
BIOLOGICAL, PHYSIOLOGICAL AND
PARTICULARLY DEVELOPMENTAL
PROCESSES IN THESE AREAS EARLY
IN LIFE.
SO SYSTEMATIC DIFFERENCES IN THE
ENVIRONMENT, AND EXPERIENCE,
THEN GENERATES SYSTEMATICALLY
DIFFERENT BIOLOGICAL STATES UPON
EXPOSURE WHICH REMAIN STABLE
OVERTIME.
AND IF SO, THOSE ENVIRONMENTS
EARLY IN LIFE, HAD THE CAPACITY
TO INFLUENCE TRAIT VARIATION
ACROSS THE LIFE COURSE.
ONE OF THE SPECIFIC BIOLOGICAL
PATHWAYS THAT IS OFTEN BEEN
INVOKED TO EXPLAIN THIS KIND OF
IDEA ARE CHANGES IN THE
EPIGENOME WHERE THE BULK OF THE
RESEARCH SO FAR ESPECIALLY IN
POPULATION CONTEXT HAS FOCUSED
ON 1 PARTICULAR TYPE OF
EPIGENETIC MARK AND THAT'S THE
COVALENT EDITION OF METHYL GROUP
TO CYTOSINE BASES IN THE GENOME,
SO THIS IS A CHANGE THAT CAN IN
SOME CONTEXT CHANGE THE WAY THAT
YEENS ARE REGULATED, SO THE IDEA
IS THAT SYSTEMATIC DIFFERENCES
AND ENVIRONMENT, CHANGE
EPIGENETIC MARKS IN THE GENOME,
AND FOR THIS TO EXPLAIN EARLY
LIFE CENTER FOR EXCELLENCE ON
AGINGS THEY MUST REMAIN STABLE
OVER TIME AND SO THE EARLY
ENVIRONMENT HAS TO BE CORRELATE
WIDE EPIGENIC MARKS MEASURED IN
ADULTHOOD AND THAT'S BEEN SHOWN
IN A VARIETY OF STUDIES
INCLUDING IN HUMANS AND THERE'S
ALSO THIS CONSIDERATION THAT WE
MIGHT BE DEALING WITH
CONFOUNDERS BECAUSE EARLY LIFE
ENVIRONMENTS OFTEN PREDICT ADULT
ENVIRONMENTS AND THIS MIGHT BE A
DIRECT EFFECT OF WHAT
INDIVIDUALS ARE EXPERIENCING AT
THE TIME OF SAMPLING RATHER THAN
A TRUE LONG-TERM EARLY LIFE
EFFECT.
IN ADDITION, IF THIS IS TRUE, I
THINK THIS REQUIREMENT HAS BEEN
PAID A LOT LESS TEAPGZ TO, THEN
THESE CHANGES MUST DO SOMETHING,
THERE ARE 28 MILLION CPG SITES
IN A HUMAN OR BABOON
GERONTOLOGYSTS MEMORY CLONE AND
MANY OF THOSE ARE FUNCTIONALLY
SILENT IN TERMS OF METHALATED OR
NOT AND SHOWING THAT DIFFERENCES
IN DNA METHYLATION ACTUALLY DO
SOMETHING TO GENE REGULATION, IS
I THINK AN IMPORTANT REQUIREMENT
THAT WE SHOULD START PAYING
ATTENTION TO OF STUDIES OF
SOCIAL EPIGENETICS AND
ENVIRONMENT OF THE
EPIGENERATEDETECSI SO HERE'S
WORK FROM NOW OVER A DECADE AGO,
THAT SHOWS IF YOU GO IN, AND
SORT OF SURMICALLY AFFAIRS TEAM
LEADERRER DNA METHYLATION AT
PARTICULAR SITES IN THE PROMOTER
OF HBB, ONLY SOME OF THEM LEAD
TO CHANGES IN GENE EXPRESSION
AND OTHERS DO NOTHING AT ALL.
SO IF WE'RE GOING TO PRIORITIZE
THINGS THAT WE THINK ARE
FUNCTIONAL IMPORTANT THEN WE
HAVE TO BE ABLE TO SEPARATE
THOSE 2 PROCESSES HERE.
SO WE HOSTLY DO OBSERVATIONAL
WORK AS I MENTIONED BUT
OCCASIONALLY WE DO HAVE REASON
TO WANT TO COLLECT BLOOD SAMPLES
AND THAT'S WHAT I'M SHOWING YOU,
THIS IS KENYUA AGAIN LOOKING
INNOCENTLY AS POSSIBLE EARLY IN
THE MORNING ON THE SAVANNAH
WHILE HOLDING A METER BLOW GUN
THERE, THAT CONTAINS A
ANESTHETIC BEARING DART SO WHEN
THE WIND IS STILL AND NOBODY'S
LOOKING HE WILL JUST QUICKLY
RAISE THE PLOA GUN, BREATH
PROPEL IT AND WE DART AN ANIMAL
OF INTEREST AND ARE ABLE TO
COLLECT BLOOD SAMPLES FROM THEM.
WE'VE DONE THIS IN A VERY SLOW
AND TORTUROUS WAY OVER MANY
DECADES ALLOWING US TO NOW TO
INTERROGATE THOSE SAME MEASURES
OF EARLY LIFE EXPERIENCE AND
GENOME WIDE DNA METHYLATION AND
ADULTHOOD, THIS IS WORK THAT WAS
LED BY MY FORMER STUDENT JORDAN
ANDERSON AND IN A STUDY THAT
CAME OUT ABOUT A MONTH AGO, WE
LOOKED AT ABOUT 250 UNIQUE
INDIVIDUALS IN OUR POPULATION,
AND ABOUT JUST UNDER HALF A
MILLION CPG SITES, TARGETS OF
DNA METHYLATION SPREAD ACROSS
THE GENOME AND IN THE CONTEXT OF
EARLY ADVERSITY, THOSE
INDIVIDUAL SOURCES OF ADVERSITY,
I MENTIONED EARLIER AND ALSO
JUST OVERALL SORT OF RESOURCE
AVAILABILITY AS INDEXED BY
HABITAT QUALITY, THESE ARE
PICTURES OF THE SAME PART OF OUR
ECOSYSTEM TAKEN ABOUT 15 YEARS
APART WHEN THE ENVIRONMENT WENT
THROUGH SIGNIFICANT
DETERIORATION.
SO ANYTHING STRAIGHT TO THE
RESULTS, WHAT WE FIND IS THAT WE
DO SEE PERSISTENT EFFECTS OF
EARLY LIFE BUT ONLY FOR
INDIVIDUALS WHO ARE BORN IN
REALLY LOW HABITAT QUALITY
ENVIRONMENTS, SO THIS, THIS IS A
GOOD WAY OF LOOKING AT IT, THESE
ARE THE EFFECT SIZES OF EARLY
LIFE ADVERSITY OF CUMULATIVE
ADVERSITY FOR INDIVIDUALS BORN
IN LOW QUALITY HABITATS VERSUS
HIGH QUALITY ABNORMALITIES AT
THAT TIMES SO IF THEY EXPERIENCE
MATERNAL LOSS OR LOW SOCIAL
STATUS EARLY IN LIFE, BUT THEY
WERE IN RESOURCE RICH
ENVIRONMENT, WE DON'T SEE MUCH
OF IT BUT IF THEY EXPERIENCE
THOSE THINGS AND WERE IN AN
OTHERWISE LOW QUALITY DETERIOR
8ED ENVIRONMENT OVERALL, WE
REALLY SEE THE EFFECT AND THAT
IS DETECTABLE FOR OVER A DECADE
IN LIFE.
NWE CAN BREAK DOWN AS I
MENTIONED EARLIER, THESE ARE
LARGELY UNCORRELATED PREDICTER
VARIABLES, ACROSS INDIVIDUAL
PREDICTER VARIABLES AND COUNT
THE NUMBER OF INDIVIDUAL SITES
IN THE GENOME ASSOCIATED WITH
EACH OF THOSE PREDICTERS, AND
WHAT WE FIND OVERALL IS THAT
IT'S REALLY IN OUR CASE MEASURES
OF RESOURCE DEPRIVATION RATHER
THAN SORT OF MEASURES WE THINK
ABOUT AS MAPPING MORE ON TO
THREAT, THAT LEAVE THIS
LONG-TERM EARLY LIFE SIGNATURE,
SO DROWBT HABITAT QUALITY,
MATERNAL LOSS WHICH PROBABLY HAS
MULTIPLE DIMENSIONS TO IT IN
TERMS OF THE EARLY LIFE
ENVIRONMENT SO IT'S A VERY
EXPOSURE DEPENDENT, EARLYAD
VERSITY ARE NOT INTERCHANGEABLE
WITH 1 ANOTHER.
NEVERTHELESS, I HAVE WRIT THEAN
THIS SIGNATURE AND SOMEWHAT
GENERALIZED SO THIS IS A PLOT
SHOWING THE NUMBER OF SITES
ASSOCIATED WITH WHATEVER'S
COLORED IN BLACK,OT BOTTOM, THIS
IS AN UPSET PLOT AND MANY OF
THOSE SITES ARE SHARED, THEY'RE
ASSOCIATE WIDE BOTH HABITAT
QUALITY AND EARLY LIFE DROUGHT.
SO THIS OVERLAP IS 4 FOLD
ENRICHED BY WHAT WE WOULD EXPECT
BY CHANCE AND ALMOST ALL OF
THOSE PATTERNS GO IN THE SAME
DIRECTION, RIGHT?
WHERE EXPOSURE TO ADVERSITY
POINTS TO THE SAME DIFFERENCE OF
DNA METHYLATION, SO SIGHTS THAT
ARE LINKED TO 1 SOURCE OF
ADVERSITY ARE MUCH MORE LIKELY
TO BE LINKED WITH A SECOND
SOURCE OF ADVERSITY BUT WE DON'T
THINK THERE IS SOME SORT OF
WEIRD PROPERTY OF OUR DATA
BECAUSE THEY DO NOT OVERLAP WITH
AGE ASSOCIATED SITES AND THAT
NOT OVERLAP WITH TECHNICAL BATCH
ASSOCIATED SITES.
FINALLY, WE WANTED TO ASK ABOUT
WHETHER THERE'S ANY EVIDENCE
THAT THESE THINGS MATTER TO GENE
REGULATION WHICH IS STILL
REALLY, REALLY FAR AWAY FROM YOU
KNOW RISK OF DEC LATE IN LIFE,
BUT AT LEAST GETS US THE NEXT
STEP DOWN THE ROAD.
WE THINK THERE'S SOME EVIDENCE
THAT THERE IS, SO WHAT I'M
SHOWING YOU HERE, ARE
ANNOTATIONS FROM THE EPIGENETIC
ROADMAP THAT JUST SORT OF COLORS
THE GENOME BASED ON WHETHER THE
GENOME HAS HIGH REGULATORY
ACTIVITY OR LOW REGULATORY
ACTIVITY AND REGIONS OF THE GOY
NOAM THAT ARE ASSOCIATED WITH
SOCIAL STATUS ALSO HABITAT
QUALITY OR DROUGHT TEND TO BE
ENRICH INDEED REGIONS THAT ARE
DOING SOMETHING, THAT WE BELIEVE
ARE DOING SOMETHING, WHEREAS
REGIONS OF THE GENOME THAT ARE
ASSOCIATE WIDE AGE ARE NOT.
OKAY IN SO THERE'S REASON TO
BELIEVE THAT THESE THINGS ARE
ACTIVE, AND FINALLY, AND SOME
WORK THEY WON'T TELL YOU
ANYTHING ABOUT OTHER THAN SAYING
WE DID IT, WE WENT ON THE LOCK
TETOUR BECAUSE WE'RE SO
FRUSTRATED WITHOUT KNOWING IF
THESE DID ANYTHING, AND DESIGNED
A HIGH THROUGH PUT GENOMIC ASSAY
WHERE WE COULD MANIPULATE ONLY
METHYLATION STATUS AND ASK
WHETHER DIFFERENCES IN METHYL
MARKS ON OTHERWISE IDENTICAL
SEQUENCES DROVE SCREEN
EXPRESSIONLY, OKAY IN AND SO
THAT'S WHAT WE DID HERE AND WE
DO FIND CASES WHERE DROUGHT
ASSOCIATED CPG SITES FOR
INSTANCE ARE ACTIVE IN YELLOW
WHEN THEY'RE UNMETHALATED, THEY
DRIVE GENE COMEGZ WHEN THEY'RE
METHALATED AND DRIVE IT WHEN
THEY'RE UNMETHYLASED.
AND WE DID THIS FOR WORK I WON'T
TALK ABOUT TODAY, BUT THAT
GENOME DATA SET IS AVAILABLE FOR
ANYONE WHO IS TRYING TO
INTERPRET THEIR EPIGENETIC DATA.
WE FIND THAT EARLY SITES ARE NOT
PARTICULARLY MORE LIKELY TO
DRIVE GENE EXPRESSION THAN
THINGS YOU MEASURE BUT FOR THOSE
THAT ARE IN ACTIVE REGULATORY
REGIONS, THE VAST MAJORITY OF
THEM DO SO EVIDENCE FOR
METHYLATION DEPENDENCE, IT DOES
MATTER WHETHER OR NOT THEY'RE
METHALATED OR NOT.
SO IN SUM, I HOPE I CONVINCED
YOU THAT THERE ARE WAYS THAT I
CONVINCED YOU STUDYING SPECIES
THAT ARE NOT OUR OWN SPECIES
NEVERTHELESS ABOUT OUR OWN
SPECIES, AND THERE ARE VERY,
VERY DIFFICULT CHALLENGES BOTH
THROUGH EXPERIMENTAL MECHANISMS
THAT GIVE US VERY DETAILED
INSIGHT INTO CAUSAL DIRECTIONS
AND ENTER LIFE COURSE STUDIES
THAT ALLOW US TO IDENTIFY MODELS
FOR THINGS THAT ARE IMPORTANT IN
HUMANS THAT CAN BE STUDIED IN
COMPLIMENTARY WAYS ELSEWHERE.
GOING BACK TO ALEXANDER P A PIO,
THIS IS PART OF THE
[INDISCERNIBLE] I SHOWED YOU IN
THE BEGINNING BUT A BIT FURTHER
DOWN, HE SAYS GO ON
[INDISCERNIBLE], WHICH I TAKE AS
FOLLOW THE SCIENCE AND GO TO USE
THE RESOURCES AND TOOLS
AVAILABLE TO YOU TO SOLVE THE
PROBLEMS THAT YOU NEED TO SOLVE.
I DON'T KNOW IF THAT'S WHAT HE
MEANT BUT THAT'S THE WAY WE WILL
INTERPRET IT HERE?
AND AN MODELS ARE INCREDIBLY
IMPORTANT IN THE RESEARCH AT NIH
IN MANY DIFFERENT DIMENSIONS OF
WHAT THE PORTFOLIO DOES, THEY'RE
ANIMAL MODELS FOR CANCER AND
ANIMAL MODELS FOR RESPIRATORY
DEC AND VACCINES AND THERE HAS
BEEN MUCH LESS OF THAT WORK DONE
IN THE CONTEXT OF SOCIAL
DETERMINANTS BUT I THINK THERE'S
AN ARGUMENT TO BE MADE THAT
ALTHOUGH THE HOMOLOGYYS AND
ANALOGIES WILL NEVER BE PERFECT,
YOU WANT EVERY TOOL IN THE
ARSENAL YOU CAN BRING TO BEAR
AND I HOPE THAT I MAY HAVE MOVED
YOU A LITTLE BIT IN THAT
DIRECTION TODAY.
WITH THAT I WILL JUST
THANK--THERE ARE MANY PEOPLE
INVOLVED IN IN WORK, SOME OF
WHOM I HAVE MENTIONED.
I ALSO WANT TO PARTICULARLY
ACKNOWLEDGE THAT A NUMBER OF THE
PEOPLE WHO HAVE LED THIS WORK
ARE TRAINEES THAT WERE SUPPORTED
THROUGH THE NRSA PROGRAM AND
THROUGH THE K99 PROGRAM AND WE
COULD NOT HAVE DONE ALL OF THE
WORK THAT WE'VE DONE WITHOUT
THAT SUPPORT.
SO THANK YOU VERY MUCH FOR THAT.
AND IF THERE'S TIME, I WILL
ANSWER ANY QUESTIONS.
[ APPLAUSE ]
>> ANYONE CAN USE THE MICs ON
EITHER SIDE.
THERE IS 1 QUESTION FROM ONLEAN
THEY CAN START WITH.
LET ME SAY THE CME CODE AGAIN,
IT'S 50123.
HOW DOES YOUR RESEARCH
COMPLEMENT STUDIES ON CHIMPS AND
GORILLAS IN THEIR RELATIONSHIP
TO HUMAN HEALTH IN SIMILARLY DO
DIFFERENT KINDS OF PRIMATES
OFFER DIFFERENT KINDS OF
INSIGHTS?
IF SO, HOW?
>> YEAH, SO CHIMPANZEES AND
GORILLAS ARE MUCH MORE CLOSELY
RELATED TO US THAN THE SPECIES I
TALKED ABOUT TODAY SO FROM THE
STANDPOINT OF DIRECT COMPARISONS
TO TRY TO IDENTIFY THE BASIS FOR
UNIEKLY HUMAN TRAITS, I THINK
THEY'RE THE RIGHT SORT OF
SPECIES TO STUDY, THAT BEING
SAID, THERE ARE--THIS IS THE
ARGUMENT THAT CLIFF JOLLY MADE
IN THE PAPER I MENTIONED IN THE
VERY
VERY BEGINNING, THERE IS A
REASON WHY GOING OUTSIDE OF THE
DPRAIT APES IS BECAUSE SOME OF
IT IS OF THE MOST IMPORTANT
BIOMEDICAL MODELS IN NONHUMAN
PRIMATES, IN FIELD STUDIES
BECAUSE OF THEIR FASTER
GENERATION TIME, WE ALSO HAVE
MUCH BIGGER SAMPLE SIZES FOR
THEM, THAN IS TYPICAL TO COLLECT
FOR EVEN VERY LONG-TERM STUDIES
FOR EXAMPLE OF CHIMPANZEES.
FROM A SORT OF BIOLOGICAL TANNED
POINT, THEY ALSO OFFER SOME
SIMILARITIES TO HUMANS, THAT
ACTUALLY WE DON'T SHARE WITH
OTHER GREAT APES, SO CHIMPANZEES
FOR INSTANCE ARE MUCH MORE
ECOLOGICALLY SPECIALIZED TO
FORESTED AREAS WHEREAS BABOONS
ARE LIKE US AND KIND OF LIKE
PIGEONS AND COCKROACHES AND
STUFF, THEY LIVE EVERYWHERE,
THEY DO VERY WELL, THEY ADOPT TO
DIFFERENT CIRCUMSTANCES AND
DEPENDING ON THE QUESTION YOU'RE
ASKING, I THINK THERE'S A HIGH
DEGREE OF LOOKING AT DNCH
SYSTEMS AND OF COURSE, I THINK
ABOUT PEOPLE HERE THINK ABOUT
MEDICARE AND MEDICAID O SETS AND
THERE ARE PEOPLE WHO STUDY
TT MONKEYS, THROUGH THE NIH
PORTFOLIO AND THOSE OFFER OTHER
OPPORTUNITIES THAT OUR GUYS
DON'T.
RIGHT, THIS GUYS DON'T PAIR BOND
BUT OTHER SPECIES DO SO IF
YOU'RE INTERESTED IN THE SORT OF
CONSEQUENCES OF PAIR PONDING AND
THE CONSEQUENCES OF SEVERE
MITRALLERRING OF PAIR BONDS FOR
INSTANCE, BABOONS ARE THE WRONG
PLACE TO LOOK BUT TT MONKEYS
MIGHT BE A GREAT PLACE TO LOOK.
>> I'M CURIOUS IF YOU LOOKEDDA
THE ANY PROTECTIVE FACTORS OR
BETTER WORDED ANYTHING THAT
MIGHT REVERSE SOME OF THESE
EFFECTS THAT YOU SEE OF EARLY
LIFE, STRESS OR ADVERSEIT?
>> SO WE'VE DONE SOME WORK ON
CAUSAL MEDIATION ANALYSIS, LIKE
REALLY WE'VE BEEN DOING, YOU
KNOW SOMETIMES WE'RE VERY MUCH
FOLLOWING IN THE FOOT STEPS,
TOO, IF PEOPLE ARE LIKE HUMANS
APPROXIMATE WE HAVE EARLY
ADVERSITY AND THEY'RE DYING
LATER ON AND WHAT COULD BE
HAPPENING IN BETWEEN SO THAT
COULD BE A TEST TO TEST THE
INTERMEDIATES I DIDN'T HAVE TIME
TO TALK ABOUT TODAY BUT IN THE
PROCESS OF BUILDING THOSE MODELS
WE TRIED TO ASK ANY BUFFERING
EFFECTS AND SO FOR EARLY LIFE
ADVERSITY, 1 OF THE THINGS THAT
BOTH, HIGH SOCIAL STATUS LATER
IN LIFE AND GREATER SOCIAL
INTEGRATION OR STRONGER SOCIAL
BONDS SEEM TO HAVE A MODERATING
EFFECT TO THAT SOMEWHAT OFFSET
THE EFFECTS OF EARLY LIFE
ADVERSITY, SO IT'S NOT THAT
WE'RE TRYING TO SAY, YOU KNOW
LIFE IS DETERMINED IN THOSE
FIRST FEW YEARS OF LIFE, THERE
ARE CENTER FOR EXCELLENCE ON
AGINGS OF THE ENVIRONMENT THAT
SEEM TO MOTIER A LOT BOTH TO
OUTCOMES WE MEASURE CONCUR EPTLY
AND ALSO TO THE MAGNITUDE OF
THOSE EARLY LIFE EFFECTS.
>> HOW ABOUT EXPERIMENTALLY IN
ANY THOUGHTS FOR ANY LATER LIFE
EXPERIMENTS?
>> WE HAVEN'T TRIED THAT SORT OF
THING.
THE LIFE COURSE STUFF WE DO DOES
NOT LEPPED ITSELF TO
EXPERIMENTATION.
AND THE CAPPIVE WORK WE DO, I
THINK THIS IS TRUE FOR EVERYBODY
WHO TRIED TO DO CAPTIVE WORK
WITH SOCIAL MANIPULATIONS, IT'S
REALLY HARD TO DO FULL LIFE
COURSE STUDIES, TO MY KNOWLEDGE
AND YOU WOULD KNOW PERHAPS
BETTER THAN ME ABOUT THIS, THE
ONLY EXPERIMENTAL MANIPULATION
WITH FULL LIFE COURSE OUTCOMES
THAT'S BEEN DONE TO DATE IS
DIETARY RESTRICTION, IT'S A HUGE
EFFORT.
I WOULD LOVE TO SEE IT DONE
BECAUSE WE HAVE ALL THESE PIECES
SUGGIEST IT'S GOING TO HAVE
CONSEQUENCES THAT UNFOLD ACROSS
THE LIFE COURSE BUT WE HAVEN'T
BEEN ABLE TO WATCH THESE SAME
INDIVIDUALS IN THE CIRCUMSTANCES
FOR LONG ENOUGH TO SAY THAT WITH
IM PERICAL DATA AND THAT'S
WHERE YOU WANT TO DO YOUR
INTERVENTION WORK.
NOKAY, WE WILL HAVE TO STOP AT
THIS TIME.
IS THIS MIC ON?
I WANT TO THANK DR. TUNG 1 MORE
TIME, FOR 1 MORE TALK AND
PRESENTATION AND AGAIN, 1813 01:01:46,069 CONGRATULATIONS.