OKAY. WHY DON'T WE GET STARTED. GOOD AFTERNOON. ON BEHALF OF MY ESTEEMED COHOST, DR. MARIBETH CHAMPOUX, OUR COLLEAGUES DR. JEANNE ALTMANN AND DR. STEVE COLE I WELCOME YOU. THE TITLE OF OUR SYMPOSIUM SESSION TODAY IS BIG MAN ON CAMPUS: SOCIAL REGULATION OF GENE AND ENDOCRINE EXPRESSION IN HUMAN AND NON-HUMAN PRIMATES. BEFORE I PROCEED WITH THE INTRODUCTION OF OUR ESTEEM PRESENTERS, I WANTED TO TELL YOU ATE WILL L BIT ABOUT OPPNET, ALTHOUGH JUDGING FROM EVERYONE EVERYONE IN THE AUDIENCE YOU'RE WELL AWARE OF THE MISSION. THE MISSION IS TO PURSUE OPPORTUNITIES FOR STRENGTHINGEN RESEARCH AT THE NATIONAL INSTITUTES OF HEALTH WHILE INNOVATING BEYOND ADVANCEMENTS. WE ADVANCE RESEARCH THROUGH ACTIVITIES AND INITIATIVES THAT BUILD A BODY OF KNOWLEDGE ABOUT THE NATURE OF BEHAVIORAL AND SOCIAL SYSTEMS. THIS SYMPOSIUM SERIES IS JUST SUCH ACTIVITY THAT WE SPONSOR TO HIGHLIGHT THE RELEVANT OF BASIC BEHAVIORAL AND SOCIAL SCIENCE RESEARCH TO THE NIGS OF NIH. AS YOU CAN SEE FROM OUR POSTER, WE'RE GLAD TO HOST DR. JEANNE ALTMANN AND DR. STEVE COLE. DR. ALTMANN WILL [NO AUDIO]. -- DISCUSSION THAT'S GOING TO HAPPEN AFTER BOTH OF OUR PRESENTERS HAVE THE OPPORTUNITY TO SHARE THEIR DATA WITH US. SO I WANT TO BRING UP MY ESTEEM COHOST, DR. MARIBETH CHAMPOUX TO INTRODUCE OUR FIRST SPEAKER, DR. JEANNE ALTMANN. >> THANK YOU, PAIGE. IT IS MY DISTINCT HONOR AND PLEASURE TO INTRODUCE TO YOU TODAY DR. ALTMANN. SHE'S A BEHAVIORAL ONCOLOGY WITH RESEARCH FOCUSED ON NATURAL POPULATIONS OF LONG-LIVED AND HIGHLY SOCIAL PRIMATES. ONE RESEARCH EVERY TIME HAS BEEN DEVELOPMENT OF WIDELY APPLICABLE NON-EVASIVE AND NON-MA LIPLATIVE TECHNIQUES FOR DATA COLLECTION AND THEIR USE. THESE TECHNIQUES STARTED WITH BEHAVIOR [INDISCERNIBLE] AND ECOLOGY. THEY HAVE EXPANDED TO OBSERVATIONAL ASSESSMENTS OF HEALTH AND AGING AND BIOMATERIAL MEASURES SUCH AS STEROID HORMONES AND GENETIC RELATEDNESS. THESE ENABLED DR. ALTMANN AND HER COLLEAGUES TO GET UNDER THE SKIN WITHOUT DESTUR BING EITHER BEHAVIOR OR OTHER PROCESSES. THE IMPER CALL RESEARCH ON INDIVIDUALLY KNOWN ANIMALS THROUGHOUT THEIR LIFE INVOLVED ALMOST DAILY DATA COLLECTION ON THE [INDISCERNIBLE] OF BAA BOONS IN KENYA. THE DATABASE OF THE [INDISCERNIBLE] BAA BOON RESEARCH PROJECT IS NOW FOUR DECADES LONG AND OVER SEVEN GENERATIONS DEEP; WHICH IS ONE OF THE LONGEST RUNNING FIELD SITES IN PRIMATOLOGY. THESE INCLUDE DATA ON ABOUT 1,500 INDIVIDUALS ABOUT 350 OF WHOM ARE CURRENTLY ALIVE AND STILL BEING FOLLOWED. THE QUESTIONS HAVE FOCUSED ON THE MAGNITUDE AND CONSEQUENCES OF BEHAVIORAL DIFFERENCES ACROSS INDIVIDUAL LIFETIMES AND AMONG FAM LIS AND SOCIAL GROUPS OR POPULATIONS. THE TEMPORAL DEPTH HAVE ENABLED THE CURRENT FOCUS ON LIFETIME OUTCOMES AND AGING. DR. ALTMANN IS CURRENTLY FUND BID THE NATIONAL INSTITUTE ON AGING AND THE NATIONAL SCIENCE FOUNDATION. DR. ALTMANN'S DATA PRESERVATION AND SHARING EFFORT INCLUDE BIOMATERIALS AND INFORMATION RESEARCH, IPBIR, AROUND PARTICIPATION IN A COMPARATIVE PRY MAIP MATE LIFE HISTORY DATABASE GROUP. THE DR. HAS SERVED ON EXTERNAL ADVISORY BOARDS INCLUDING WISCONSIN PRIMATES RESEARCH CENTER T MAX PLANK INSTITUTE AND THE INSTITUTE OF PRIMATE RESEARCH OF THE NATIONAL MUSEUMS OF KENYA. DR. ALTMANN RECEIVED HER FIRST DEGREE IN MATHEMATICS FROM THE UNIVERSITY OF ALBERTA CANADA, AN MAN MATHEMATICS TEACHING AND A Ph.D. IN BEHAVIORAL SCIENCE FROM THE UNIVERSITY OF CHICAGO. SHE WAS PREVIOUSLY PROFESSOR AND CHAIR OF THE COMMITTEE ON EVOLUTIONARY BIOLOGY AT THE UNIVERSITY OF CHICAGO, AND SHE IS CURRENTLY EUGENE HIGGINS PROFESSOR EMERITUS IN PRINCETON'S DEPARTMENT OF ECOLOGY AND EVOLUTIONARY BIOLOGY, AND THE PRINCETON ENVIRONMENTAL INSTITUTE AND AN HON NAR LECTURE YOU ARE AT THE UNIVERSITY OF NAIROBI, KENYA. PLEASE JOIN ME IN WELCOMING DR. ALTMANN. [APPLAUSE]KENYA. PLEASE JOIN ME IN WELCOMING DR. ALTMANN. [APPLAUSE]UNIVERSITY OF NAIROBI, KENYA. PLEASE JOIN ME IN WELCOMING DR. ALTMANN. [APPLAUSE]KENYA. PLEASE JOIN ME IN WELCOMING DR. ALTMANN. [APPLAUSE]UNIVERSITY OF NAIROBI, KENYA. PLEASE JOIN ME IN WELCOMING DR. ALTMANN. [APPLAUSE] >> CAN YOU HEAR ME? IS THIS ABOUT RIGHT? AND ADVANCING? BEING VERY COORDINATED WAS NOT ON BY CB. IT'S A DELIGHT TO BE HERE AND I REALLY, UM, VERY EXCITED BY THE AIMS AND THE PROJECTS THAT THIS GROUP IS DOING. I'D LIKE TO START WITH THE ACKNOWLEDGMENTS BECAUSE IN TRUTH ALL OF OUR DATA STARTS WITH PARTICULARLY THIS WONDERFUL FIELD TEAM IN KENYA AND SOMEBODY SAID DO YOU HAVE HIGH TURNOVER? WELL RAFEAL HERE HAS BEEN WITH US SINCE 1981, HAS HEADED UP TW THE FIELD TEAM WHEN WE'RE GONE FOR ABOUT 15 YEARS. AND THAT GIVES YOU A FEEL FOR SOME OF THE LONGEVITY AND EXPERIENCE OF THIS FIELD TEAM. WE'RE GRATEFUL, OF COURSE, TO OUR VARIOUS FUNDING AGENCIES AND TO THE OTHERS IN NAIROBI AND BACK IN THE STATES WHO MAKE THIS ALL POSSIBLE. WHEN I SAY I OR WE, IT REALLY IS EVERYONE VERY MUCH A JOINT PROJECT. SO I'M GOING TO [INDISCERNIBLE]. I'M GOING TO HAVE, SORT OF, FOUR SECTIONS HERE TODAY. THE LAST ONE ONLY IF WE'LL HAVE TIME AND OTHERWISE I'LL DEAL WITH IN QUESTIONS. I'M GOING SPEND SOME TIME TALKING ABOUT WHAT IS THIS ANIMAL MODEL? BECAUSE IT'S SOMEWHAT DIFFERENT ANIMAL MODEL THAN MANY OF YOU MAY BE FAMILIAR WITH, BOTH IN TERMS OF SPECIES AND CONTEXT, AND BECAUSE IT'S PARTICULARLY SUITED TO THE KINDS OF QUESTIONS THAT ARE THE TOPIC OF THIS GROUP AND MY TALK TODAY, AND I'LL DEAL WITH THOSE FIRST THREE QUESTIONS. THEN I'M GOING TO FOCUS ON SOCIAL STATUS, VARIOUS OTHER ASPECTS OF SOESH YALT THAT WE'VE DONE A LOT OF WORK ON INCLUDING BOND. STATUS IS SORT OF ONE DIMENSION AND A SORT OF ADVERSARIAL KIND OF DIMENSION. WE'VE ALSO WORKED ON SOCIAL BONDS, AND BRIEFLY INDICATE SOME OF THE THINGS WE KNEW GOING INTO THE TWO PROJECTS THAT I'LL TALK ABOUT TODAY. AND THEN USE TWO EXAMPLES; ONE SOCIAL STATUS PREDICTING STRESS IN ADULT MALE BAA BOONS, THE OTHER PREDICTING ILLNESS AND WOUND HEALING ILLNESS IN WOUNDS BOTH INCIDENCE AND HEALING. AND THEN AS WE -- IF WE HAVE TIME AND IF IT HASN'T BEEN OBVIOUS, I'LL ADDRESS SOME OF THE UNANSWERED QUESTIONS OR SOMETHINGS THAT WE'RE DOING NOW. THE ANIMAL MODEL IS AS WAS JUST MENTIONED, BABOONS, AND IN FACT WILD BABOONS OUT IN EAST AFRICA. THE LOCAL MESSIAH SAY THAT BABOONS ARE OUR CATTLE BECAUSE WE FOLLOW THEM AROUND ALL DAY. THEY THINK WE HAVE VERY POOR TASTE IN CATTLE, BUT NONETHELESS THEY SEE THAT KIND OF PARALLEL THERE AND THEY'RE NOT FAR OFF EXCEPT IT DOESN'T TAKE THEM AT ALL ANY TIME TO KNOW 100 OR 200 OF THEIR LIVESTOCK NOR THE MESSIAH ASSISTANCE WHO WE HIRE WHEREAS MOST OF OUR WESTERNERS TAKE A LITTLE MORE TIME TO GET TO KNOW THE 350 BABOONS WE'RE FOLLOWING AT ONCE ALL OF WHICH ARE KNOWN BY VISUAL SIGNS. WHY BABOONS? THEY HAVE THE ADVANTAGE AND DISADVANTAGE OF BEING QUITE LARGE AS PRIMATES GO, AND FOR THOSE OF YOU WHO ARE MORE FAMILIAR WITH [INDISCERNIBLE] HERE AT NIH AND ELSEWHERE, BABOONS ARE SORT OF THE AFRICAN MACACS AND THEY'RE WRITE-SPREAD THROUGHOUT AFRICA -- WIDE-SPREAD THROUGHOUT AFRICA. THEY HAVE GREAT ECOLOGICAL AND GEOGRAPHICAL RANGE AND THIS THEY'RE QUITE TERRESTRIAL IN THEIR LIFESTYLE. THAT COMBINATION MAKES THEM ECOLOGICALLY AND MORPH LOGICALLY IN MANY WAYS QUITE IDEAL FOR A HUMAN MODEL, AN AN MOD MODEL OF HUMANS PARTICULARLY FOR SOCIAL AND SOCIAL ECOLOGY QUESTIONS. THEY ALSO LIVE PREDOMINANTLY IN THE POPULATION WE STUDY N THE SAVANNAHS WHICH IS THOUGHT BY MANY TO BE AN IMPORTANT ENVIRONMENT OF HUMAN EVOLUTIONARY ADAPTIVENESS, AND BY GOOD LUCK, IT ALSO IS A MUCH EASIER ENVIRONMENT TO DO OBSERVATIONAL STUDIES IN BECAUSE IT'S EXTREMELY OPEN; YOU CAN SEE WHAT'S GOING ON, YOU CAN FOLLOW ANIMALS AND SO ON. WE DON'T GET A BROKEN NECK TRYING TO STUDY OUR PRIMATES. THEY ALSO HAVE HIGH SHARING OF GENES WITH HUMANS. THEY'RE EXTREMELY SOCIAL, AND I MEAN SOCIAL IN THE SENSE OF NOT JUST IN A HERD SOESH YALT, BUT THEY HAVE VERY DIFFERENTIATES RELATIONS, MUCH AS HUMANS DO. THEY -- THESE RELATIONSHIPS ARE OFTEN BUILT PRIMARILY ON RELATEDNESS, BUT THEY EXTEND QUITE BEYOND THAT. SO, FOR EXAMPLE, IF AN INDIVIDUAL DOESN'T HAVE ANY CLOSE RELATIVES, MEANING IN GENERAL, MOTHER, DAUGHTER OR SISTER-LEVEL RELATIONSHIPS, THEY WILL FORM CLOSE BONDS WITH NON-RELATIVES RATHER THAN FOREGOING HAVING CLOSE POSITIVE RELATIONSHIPS AT ALL. SO ONE OF THE OBVIOUS QUESTIONS THAT WE'VE BEEN PURSUING IS, WHAT'S THE NATURE AND THE FITNESS VALUE OF THESE RELATIONSHIPS OVER A LIFETIME? AS A RESULT, THE ANIMALS ARE IN THESE VERY CLOSE PROXIMITY GROUPS, AND THESE GROUPS CONSIST OF ANYWHERE FROM ABOUT 20-100 INDIVIDUALS, AND THEY MOVE ACROSS THE SAVANNAH, SOMEWHAT, AS A UNIT, AND THEY HAVE INTERESTING INTERACTIONS WITH OTHERGROUPS AND THAT EFFECTS THE SOCIAL WORLD AS WELL AS THE ECOLOGICAL WORLD THAT ANIMALS GROW UP IN AND THAT THEY LIVE THEIR ADULTHOOD IN. IN PARTICULAR, MALES, THEY'RE ABOUT 25 KILOS, A LITTLE OVER 50 POUNDS. THEY HAVE RETRUCK PRUK TI POTENTIAL AT AROUND 6 YEARS OF AGE, THAT WOULD BE LIKE OUR SORT OF ADOLESCENCE, BUT LIKE MANY MAMMALS, THEIR REPRODUCTION IS MUCH MORE SOCIALLY CONSTRAINED THAN THAT OF FEMALES. SO HAVING REPRODUCTIVE POTENTIAL UNLESS THEY'RE THE ONLY MALE IN A GROUP SOMEHOW, WHICH IN A NATURAL HABITAT NO OTHER MALES IN THE ENVIRONMENT WOULD LET THEM BE, THEY DON'T ACTUALLY REPRODUCE UNTIL LATER. MALES ARE THE DISPERSING SEX, AND SO THEY HAVE THE CHALLENGE OF MAKING A LIFE AND RELATIONSHIPS IN OTHER GROUPS DURING ADULTHOOD. SO THEY'RE RARELY LIVING WITH NON-DESCENDANT KIDS. UNLIKE THE FEMALES, THEY DON'T HAVE MOMS, SISTERS, BROTHERS IN GENERAL, IN THEIR GROUPS. NOW DOMINANCE RANK IN MALES IS ALSO VERY DIFFERENT FROM FEMALES. IT PEEKS AT THE BEGINNING OF ADULTHOOD AND THEN IT SORT OF A NOT-SO-SLOW SLIDE THERE AFTERWARDS. THE RESULT IS THAT BOTH REPRODUCTION AND STATUS HAVE THIS VERY CLEAR LIFE SPAN PATTERN. FEMALES, ABOUT HALF THE BODY MASS OF MALES. SO COMPARED TO HUMANS, THERE'S MUCH MORE SWAL DIE„i MORPHISM IN BABOONS. YOU WOULD THINK SEX DIFFERENCES IN BEHAVIOR WOULD BE MUCH GREATER THAN IN HUMANS. HUMANS ARE VERY LOW ON THE SEXUAL DIMORPHISM SCALE AMONG PRIMATES AND AMONG MAMMALS TO A GREAT EXTEND. FEMALES PREACH REPRODUCTIVE POTENTIAL AROUND FIVE AND THEY START HAVING OFFSPRING QUICKLY AND AT A FAIRLY STEADY PACE UNTIL LATE ADULTHOOD. SO THERE IS NOT THIS COMPARABLE VARIABILITY, AND THIS SETS THE STAGE FOR LOOKING AT AND PREDICTING VARIOUS DIFFERENT AGING PATTERNS IN MALES THAN FEMALES; ONE OF THE PROMPTS WE'VE BEEN DOING NOW. THEY ARE [INDISCERNIBLE] IS THE TERMS IN ANTHROPOLOGY; FEMALE FILL PATRICK IS ANOTHER TERM YOU MAY BE USING IN THAT FEMALES STAY IN THE GROUP THEY WERE BORN IN THEIR WHOLE LIVES. THEY LIVE WITH DIVERSE MATERNAL AND PATERNAL KIN. WITH PATERNAL WE'VE GOTTEN TO KNOW BY COLLECTING POOP, WHAT THE FIELD TEAM CALLS DONATIONS, AND SUSAN IN HER LAB AT DUKE DOESED THE PATERNITY ANALYSIS WHICH HAS ENABLED US TO GET A MUCH MORE GENDER UNBIASSED PICTURE OF RELATEDNESS THAN HAS TRADITIONALLY BEEN AVAILABLE. THE OTHER FEATURE THAT'S FAIRLY UNUSUAL FOR PRIMATES BUT SIMILAR TO HUMANS AND CHIMPANZEES IS THAT REPRODUCTION OCCURS THROUGHOUT THE YEAR. WE DON'T HAVE ANY SORT OF STRONG BIRTH SEASON OR NOT. SO THAT'S THE SPECIES AND THEIR BACKGROUND. WHAT'S THE KIND OF ECOLOGICAL CONTEXT AND WHY WOULD ONE CARE ABOUT IT? WELL, IT'S UNDER THE OUT THAT WE'VE FOUND THAT ALL SORTS OF BEHAVIORAL AN PHYSIOLOGICAL AND REPRODUCTIVE PARAMETERS IN FACT DO DEPEND ON THE ECOLOGICAL CONTEXT. THIS IS A SEMIARID ENVIRONMENT TO COMPARE IT TO WASHINGTON, THE PRECIPITATION IS ABOUT A THIRD OF WHAT WE GET HERE IN WASHINGTON, SO IT'S NOT YOUR GARDEN OF PARADISE, BUT SOME OF US ARE VERY FOND OF IT. IT'S HIGHLY SEASONAL BUT NOT IN TEMPERATURE, IN RAINFALL. SO THERE'S -- AND IT'S INTERESTING AND IN TERMS OF TESTING IDEAS ABOUT THE IMPACT ON PHYSIOLOGY AND LIFE COURSE EVENTS THAT, UM, THERE'S BOTH SOME HIGH PREDICTABLE VARIABILITY LIKE THIS DRY SEASON, FIVE MONTHS WITH NO RAIN IN THE YEAR AND THEN SOME HIGHLY UNPREDICTABLE VARIABILITY. THEY ALSO LIVE AMONGST ALL SORTS OF OTHER SPECIES. SO AGAIN, VERY MUCH LIKE WHAT HUMANS HAVE OFF ENCOUNTERED, AND THIS KIND OF ENVIRONMENT HERE, TO GIVE YOU A SORT OF VIEW OF THE AREA, UM, IS VERY OPEN SAVANNAH. IT'S RIGHT AT THE BORDER BETWEEN KENYA AND TANZANIA WITH THIS GREAT VIEW THAT THE BABOONS HERE LOOK LIKE THEY'RE APPRECIATING BUT I WOULDN'T CLAIM THAT THEY ARE. SO WHAT IS OUR RESEARCH STRATEGY? WELL, THERE ARE SORT OF TWO MAJOR RESEARCH STRATEGIES THAT SCIENTISTS USE. ONE OF THEM IS VERY MUCH A CONTROL EXPERIMENTAL AND EXPERIMENT STRATEGY THAT DEPENDS ON A LOT OF INSIGHT OR PRACTICAL DECISIONS INTO WHAT TO CONTROL AND WHEN AND HOW. ANOTHER SORT OF BEST EXPLICATED BY R.A. FISHER IS ONE THAT CALLS FOR MAKING USE OF THE EXISTING VARIATION AND LOOKING FOR PATTERNS, DOING THE CONTROL IN A STATISTICAL WAY. AND BY BOTH OBSERVATIONS SELECTION AND STATISTICAL APPROACH, THAT IS BOTH OF NECESSITY AND OF CHOICE THAN WHAT WE USE. EACH KIND OF STRATEGY CAN GAIN A FAIR BIT, BUT IT'S IMPORTANT TO HAVE A SENSE THAT THAT'S WHAT THIS STRATEGY IS DOING. SO WE HAVE A POPULATION, UM, THAT WE'VE BEEN FOLLOWING SINCE 1971. WE'VE BEEN FOLLOWING VARIOUS GROUPS; THE POPULATION IS SUB STRUCTURED INTO THE GROUPS THAT I DESCRIBED AND THEY HAVE GONE THROUGH VARIOUS CHANGES THROUGH THE YEARS AND WE HAVE PICKED UP ADDITIONAL GROUPS AND GROUPS OF FISSIONED AND SO ON, AND THIS .GIFS YOU A FEEL FOR HOW THOSE 350 ANIMALS THAT WE CURRENTLY FOLLOW AND THAT THE FIELD TEAM RECOGNIZES VISUALLY, UM, HOW THEY ARE DISTRIBUTED OVER TIME. THIS ENABLES US TO ASK THINGS ABOUT THE DIFFERENCES WITHIN AND BETWEEN GROUPS. OUR TECHNIQUES ARE A MIXTURE OF THINGS THAT HAVE BENEFITTED A LOT FROM MODERN TECHNOLOGY AND OTHER THINGS THAT ARE JUST PAPER BINOCULARS AND BROKEN VEHICLES AS THEY HAVE BEEN FOR DECADES. THIS IS THE FIELD TEAM COLLECTING SOME PAPER AND PENCIL DATA. RAFAEL THERE. SARAH COLLECTING ELECTRONICALLY, NOW, BEHAVIORAL DATA HERE. AND KENUA DOING OUR HIGH-CLASS COLLECTION OF GENETIC AND HORMONAL MATERIAL. ANY OF YOU WHO HAVE EVER RAISED CHILDREN MAY, LIKE I, HAVE SAID, I WILL NEVER TOUCH THIS STUFF AGAIN IN MY LIFE, AND WE DO LITTLE ELSE. WE FIND EVER MORE USES FOR WHAT THE BABOONS DROP AND LEAVE BEHIND. SO MUCH OF OUR HORMONAL AND GENETIC ANALYSES ARE DONE USING THESE FECAL SAMPLES, WHICH WE COLLECT EXTREMELY FRESHLY AFTER SEEING WHO DROPS THEM, AND FOR GENETIC ANALYSIS THEY GO TO DUKE AND SUSAN'S LAB AND THE HORMONAL ANALYSIS TO MINE. IT'S AMAZING HOW MUCH PRINCETON UNDERGRADUATES CAN GET INTO PURIFYING THIS MATERIAL TO LEARN ABOUT STEROID HORMONES AND THEY'RE ALL GREAT SPORTS ABOUT IT. ONE OF THE PIECES OF APPOINTMENT THAT IS NOT AVAILABLE IN EAST AFRICA ARE EXHIBITION -- DIXIE CUPS, SO WE IMPORT THOSE. THAT'S BASICALLY HOW DATA ARE COLLECTED. THIS HAS ENABLED US TO STUDY ANIMALS FROM BIRTH TO DEATH, AND THIS IS ONE INDIVIDUAL WHEN SHE'S VERY TINY, NOT MORE THAN A YEAR OLD, AND THIS IS THE SAME INDIVIDUAL SHORTLY BEFORE SHE DIED AT 27, WHICH IS THE OLDEST AGE THAT WE HAD. SHE, LIKE OTHER ANIMALS IF THEY LIVE INTO THEIR 20s, HAVE AT LEAST ONE BABY, ONE INFANT DURING THAT TIME. SO THAT'S ENABLED US TO, NOW, BE ABLE TO LOOK AT LIFETIME PATTERNS, AT AGING, AND AT STARTING TO LOOK AT THE EARLY EXPERIENCE [INDISCERNIBLE] OF LATE ADULTHOOD PROCESSES AND OUTCOMES. SO WHAT ARE SOME OF THE THINGS THAT, THAT JUST TO RUN THROUGH BRIEFLY A FEW OF THE KINDS OF THINGS THAT WE KNEW GOING INTO THE TWO STUDIES THAT I'LL DESCRIBE, AND I WANT TO YOU KEEP IN MIND THAT WE STUDY OUTCOMES AND SOMETIMES FIRST IDENTIFY THE OUTCOMES SUCH AS SOCIAL STATUS AND FERTILITY, OR SOCIAL STATUS AND A DAUGHTER'S SOCIAL STATUS -- A MOM'S SOCIAL STATUS AND A DAUGHTER'S SOCIAL STATUS. SOMETIMES WE START FROM MECHANISMS, BUT OFTEN WE START FROM NOTICING THESE OR TESTING FOR BASED ON BIOLOGICAL THEORY FOR THESE OUTCOMES AND THEN WE GO INTO PROBE WHAT ARE THE MECHANISMS, AND HERE I'M TALKING ABOUT MECHANISMS BEHAVIORAL MECHANISMS, ENDOCRINE MECHANISMS AND WHAT I WILL BE TALKING ABOUT LESS TODAY ARE IS WHAT IN HUMANS STEVE WILL BE TALKING ABOUT MORE ARE GENETIC MECHANISMS. WHAT I'LL WILL ADDRESSING HERE USING THE GENETICS IS THESE FIRST SET OF THINGS THAT WE DONE WHICH HAVE BEEN PRIMARILY TO IDENTIFY PATERNITY AND GO FROM THERE AND RELATEDNESS. SECONDLY WE'VE BEEN ADDRESSING QUESTIONS ABOUT HIGH BERNIZATION BECAUSE OF THE POPULATION, THINGS GOING ON IN THE POPULATION. WHAT WE'RE STARTING NOW AND PARTICULARLY WITH JENNY AND ALBERTS HEADING UP THAT PROJECTS ARE QUESTIONS ABOUT GENE EXPRESSION AND THE INITIAL RESULTS WE'RE HAVING WHICH WERE VERY CHALLENGING TO DEVELOP THOSE TECHNIQUES FOR DOING UNDER FIELD CONDITIONS AND THEN MOVING BACK TO THE STATES, FIRST TO THE PRIMATE CENTER IN NAIROBI, I WILL NOT BE FOCUSING ON TODAY. SO WHAT DO WE KNOW? WELL, FIRST OF ALL, MOMS MATTER, AND THAT WAS SOME OF THE EARLIEST OF THINGS KNOWN ABOUT MACACS AND BABOONS. A NUMBER OF [INDISCERNIBLE] PRIMATES. STATUS OF DAUGHTERS IS A VERY DIRECT FUNCTION OF STATUS OF MOTHERS. MOTHER'S STATUS, AND HERE I'M USING DOMINANCE RANK AND STATUS INTERCHANGEABLY, AND ONE OF THE ADVANTAGES OF STUDYING BABOONS IS THAT STATUS IS VERY IMPORTANT, BUT IT'S VERY EASY TO DEFINE AND DOESN'T GET AS COMPLICATED AS OTHER MEASURES OF STATUS IN HUMANS. MOTHER'S STATUS DETERMINES DAUGHTER'S STATUS. BOTH SONS AND DAUGHTERS MATURATION IS A FUNCTION OF MOTHER'S STATUS. AND ONE OF THE SURPRISING RESULTS A COUPLE OF YEARS AGO THAT MY KENYAN STUDENT, PATRICK, FOUND IS THATTED A LENT MALES LONG PAST THE TIME WHEN MOM'S TAKEN CARE OF THEM AND HALF THE MOMS ARE NO LONGER ALIVE AT THAT TIME, THEIR STRESS LEVELS, THEIR GLUCOCORTICOID LEVELS ARE PREDICTED BY MOM'S DOMINANCE RANK WHEN THESE GUYS WERE BORN SIX TO EIGHT YEARS EARLIER. SO THAT IN ITSELF IS SETTING US DOWN A WHOLE MINI AGENDA OF OTHER THINGS TO LOOK AT. AND THEN SOME SOCIAL EFFECTS WHICH COMES TO WHY WE CARE SO MUCH ABOUT THE ECOLOGY EMERGE ONLY UNDER CERTAIN ECOLOGICAL CONDITIONS. SO ONLY WHEN THERE ARE DRY SEASONS OR A DROUGHT DO YOU SEE CERTAIN STATUS EFFECTS. SO IF WE WEREN'T STUDYING BOTH THESE CONDITIONS, WE'D MISS SOME OF THESE OR WE'D SEE THEM AND SOME OTHER LAB OR GROUP WOULDN'T AND THERE WOULD BE QUESTIONS ABOUT HOW DOES THIS OCCUR. SO DADS MATTER TOO, ACTUALLY AND THAT CAME ONLY FROM OUR PATERNITY DATA ALTHOUGH PEOPLE WERE SUSPECTING THAT SOME OF THIS MIGHT BE GOING ON. THIS IS A MATING SYSTEM IN WHICH FEMALES MEAT WITH MANY MALES, MALES MEAT WITH MANY FEMALES. NOBODY THOUGHT THEY KEPT TRACK OR COULD TELL WHAT WAS GOING ON OR CARE, BUT IN FACT THROUGH SUSAN'S LAB, WE KNOW THAT THE MALES OR OFTEN HANG AROUND NEW INFANTS AND THIS THEIR MOTHERS ARE IN FACT COMMONLY, NOT ALWAYS T BIOLOGICAL DADS. THESE MALES PROVIDE A SAFE ZONE AGAINST HARASSMENT BY OTHER GROUP MEMBERS. THEY INTERVENE IN THEIR OWN YOUNGSTERS BUT NOT MORE THAN OTHER YOUNGSTERS, AGGRESSIVE ENCOUNTERS, AND THEN STRIKINGLY -- SO THIS WAS A CASE WHERE WE IDENTIFIED CERTAIN MECHANISMS AND SHORTER-TERM FE KNOWLEDGE NAH FIRST, AND THEN WE FOUND THAT SOMEWHAT TO OUR SURPRISE, IN FACT, THE LENGTH OF TIME A MALE STAYED IN THE GROUP, DIDN'T MOVE ON TO OTHER FAMILIES, IF YOU WILL, UM, THE EARLIER THE MATURATION OF THEIR OFFSPRING. SO THERE WE STARTED WITH A SHORTER-TERM, LOWER-LEVEL PHENOMENA AND WORKED TOWARD THE LONGER TIME FRAME ONE. SO THIS GIVES YOU A FEEL FOR JUST A FEW OF THE KINDS OF EFFECTS WE'VE SEEN SO FAR. ON FRIENDSHIPS, ON BONDS, WE'VE, IN FACT, SHOWN ALL SORTS OF PREDICTORS OF BONDS, INITIALLY, AND THEN THAT FEMALES WHO HAVE MORE FRIENDS, MORE POSITIVE SOCIAL BONDS, IN FACT, THEY'RE OFFSPRING HAVE HIGHER SURVIVAL. THAT'S AGAIN THE BEGINNING OF ANOTHER SORT OF MINI SET OF THINGS TO LOOK AT. SO NOW, UM, SOCIAL STATUS PREDICT -- I'M GOING TO DO IF IN WHAT TIME'S AVAILABLE TWO EXAMPLES, AND THIS IS SOCIAL STATUS PREDICTING STRESS LEVELS, HORMONE LEVELS, AND THIS IS THE ONLY TABLE I'LL SHOW YOU IS IT'S HERE PRIMARILY TO TELL YOU THAT AS PROMISED, I'M FOCUSING ON DOMINANCE RANK, ON STATUS, BUT IN OUR ANALYSES, WE TAKE INTO ACCOUNT A NUMBER OF OTHER THINGS THAT WE KNOW ARE HAVE BEEN POSTULATED TO AFFECT THE VARIABILITIES. WE KNOW BY NOW THAT SEASON IS ALMOST ALWAYS A PARTICULAR FACTOR PARTICULARLY IN HORMONE WORK AND OTHER THINGS. SOMETIMES TEMPERATURE AS WELL AS THE WET/DRY SEASON EFFECT AND THEN ALPHA STATUS IS THE TOP-RANKING INDIVIDUAL. THIS IS ALL THE OTHER RANKS AND THIS CAME ABOUT IN THE DATA YOU'LL SEE RATHER STRIKINGLY, AND AGE IS ALSO A BOTH SOMETHING WE'RE VERY INTERESTED IN AND SOMETHING THAT THROUGHOUT THE LIFE COURSE THERE ARE CHANGES IN ALL OF THESE RELATIONSHIPS OR IN THE GENERAL LEVELS AND SOMETIMES INTERACTIONS. SO THIS IS THE KIND OF ANALYSIS THAT WE OFTEN HAVE AS WELL AS PROBING INDIVIDUAL VARIABLES. SO THIS IS WHAT THE OUTCOME OF THIS PAPER THAT CAME OUT THIS PAST SUMMER WAS. THAT A PATTERN FROM HIGHEST STATUS TO LOWEST STATUS, YOU GO FROM, IN GENERAL, LOW STRESS LEVELS TO HIGH STRESS LEVELS, AND STATUS HERE IS JUST THAT IF WE ALL STOOD RANKED ACCORDING TO OUR STATUS T TOP-RANKING INDIVIDUAL IS THE ONE WHO HAS NOBODY BEATING UP ON THEM AND ON DOWN, AND ANIMAL NUMBER FIVE HAS FOUR INDIVIDUALS WHO ARE A HIGHER STATUS. SO THIS IS CONSISTENT WITH ONE POSTULATE IN THE LITERATURE, BUT SOMETHING THAT JUMPS OUT IMMEDIATELY AS YOU CAN SEE THE ALPHA MALE, THE TOP MALE, UM, IS WAY OUT OF LINE. HE HAS STRESS LEVELS THAT ARE COMPARABLE TO THE LOWEST-RANKING INDIVIDUALS. WE WANTED TO BE EXTREMELY SURE THAT THIS RESULT HELD, AND WE DID A LARGE NUMBER OF THINGS TO CHECK THAT OUT BECAUSE THIS COMES FROM MANY GROUPS AND INDIVIDUALS OVER TIME. THIS IS THE NUMBER OF INDIVIDUALS IN EACH OF THESE CATEGORIES, THIS IS THE NUMBER OF MONTHLY SAMPLES AND MONTHLY VALUES MADE UP OF MANY SAMPLES, OFTEN, IN THIS. WE DID NUMBER OF CHECKS ON THE SAME MALE WHO HAPPENED AT ONE TIME OR ANOTHER TO BE IN THESE TWO DIFFERENT POSITIONS. WE CHECKED ON AT THE SAME TIME IN A GROUP THE NUMBER ONE VERSUS THE NUMBER TWO. A NUMBER OF SUCH THINGS TO NAIL THIS DOWN, AND WHILE IT'S NOT TRUE OF EVERY PAIR AND EVERY MONTH IT'S A STRONG AND CONSISTENT RESULT, AND ONE THAT TOOK US AND OTHERS BY SURPRISE, BUT THAT LEADS TO A LOT OF OTHER QUESTIONS IN THAT IN ITSELF SUGGESTED SOME -- AS YOU CAN IMAGINE THE POPULAR PRESS JUMPED ON IT HUGELY -- BUT IT LEADS TO A QUESTION OF; HOW CAN THIS COME ABOUT? ARE THESE TOP-RANKING MALES SO MUCH MORE POWERFUL THAT THEY CAN WITHSTAND THAT EXTRA STRESS AND IN SO MUCH BETTER CONDITION? OR DO THEY, IN FACT, NOT STAY VERY LONG IN THIS SITUATION AND NOT SUFFER THE LIFETIME CONSEQUENCES? THESE ARE ALL THINGS THAT WE'RE STARTING TO EXPLORE NOW. SO THIS LEADS TO THE QUESTION -- THIS WAS A MECHANISM THAT WE STARTED WITH BOTH BEHAVIORAL AND PHYSIOLOGICAL -- AND WE'RE LOOKING AT SOME OF THE LONGER-TERM CONSEQUENCES. OH, THE OTHER THING ABOUT THIS, WHICH YOU MIGHT HAVE GOTTEN IN THAT FIRST GRAPH -- SORRY -- IS THAT THIS PATTERN IS TRUE BOTH THE DOMINANCE HIERARCHY IS STABLE AND WHEN IT'S UNSTABLE. IT WAS POSTULATED THAT SOMETHING LIKE THIS COULD PERHAPS HAPPEN SOMETIMES DURING PERIODS OF TURMOIL, BUT IS NOT THE CASE DURING PERIODS OF STABILITY. WE FOUND THAT EVERYBODY HAD HIGHER STRESS LEVELS IN PERIODS OF INSTABILITY, BUT IT DID NOT CHANGE THIS RELATIONSHIP. SO, OF COURSE, ONE OF THE OBVIOUS QUESTIONS WAS, SO IS IT REALLY BETTER TO BE NUMBER TWO THAN NUMBER ONE? AND THAT'S A BIG UNANSWERED QUESTION, BUT I THINK THERE ARE SOMEWHAT COMPLEX BUT REASONABLE THINGS GOING ON. AND JUST TO SHOW YOU IN CONTRAST, HIGH-RANKING MALES AND WITHOUT THE EXCEPTION OF THE ALPHA HAVE HIGHER-RANKING TESTOSTERONE LEVELS. KEEP IN MIND, ALL OF THESE ARE FECAL TESTOSTERONE METABOLITES OR GLUCOCORTICOID METABOLITES -- THAT'S WHAT WE CAN MEASURE. AND LOWER-RANKING MALES HAVE LOWER. HERE, IT'S IMPORTANT TO SAY -- AND THIS IS AGE-CORRECTED AS I MENTIONED IN THE OTHER BECAUSE BOTH DOMINANCE STATUS, THAT DOMINANT STATUS GOES DOWN AS ANIMALS AGE AND THE TESTOSTERONE DOES TOO. SO THIS IS TAKING AGE INTO ACCOUNT. SO ONE OF THE BIG QUESTIONS WAS; IS THIS PSYCHOSOCIAL STRESSOR IS THIS ENERGETIC STRESS? GLUCOCORTICOIDS CAN BE RAISED IN RESPONSE TOE THEY ARE KIND OF CHALLENGE, AND ALSO WHAT'S GOING ON WITH SOCIAL SUPPORT? SO THIS IS CHALLENGES, THIS IS COMPARING THE ALPHA MINUS THE BETA. SO IF WE LOOK DOWN HERE, THE BETA IS HIGHER, THE SECOND-RANKING MALE. IF WE LOOK UP HERE, THEN THE ALPHA, THE TOP-RANGING MALE, IS HIGHER. AND THIS VERY CLEARLY CAME THROUGH WITH THE TWO VARIABILITIES THAT WERE MORE SOCIAL SUPPORT OR SOCIAL STRESSOR ARE NOT DIFFERENT BETWEEN THE ALPHA AND BETA, WHEREAS THE ENERGETIC -- THESE ARE BOTH VERY EER JE TICKICALLY EXPENSIVE ACTIVITIES ARE MUCH HIGHER THAN THE ALPHA. WE HAVE TENTATIVELY PROPOSED THAT IT IS ECOLOGICAL AND ENERGETIC STRESS THAT -- STRESSORS -- THAT RESULT IN THIS DIFFERENCE IN THE STRESS MEASURE AND NOT PREDOMINANTLY PSYCHOSOCIAL ONES. SO HERE, AGAIN, WE GO FROM ONE LEVEL TO ANOTHER AND ONE TYPE OF ANALYSES TO ANOTHER. TO BEGIN TO LOOK AT THE NATURE OVER A LONGER TERM OF SOME OF THE KINDS OF CONSEQUENCES THAT ONE MIGHT PREDICT, WE HAVE NOT BEEN ABLE TO DO SOME OF THE KINDS OF IMMUNE MEASURES THAT ONE CAN DO IN CAPTIVITY AND WITH EXPERIMENTS. BUT, WHAT WE HAVE HAD SINCE ACTUALLY THE LATE 1970s, IS THAT WE KEEP TRACK MUCH LIKE A DOCTOR'S DOOIG DIAGNOSIS SHEET, BUT HANDS-OFF JUST AS WE DO NEONATAL ASSESSMENTS HANDS-OFF, VISUALLY AND WE KEEP TRACK OF ANY VISUAL SIGN OF„i ILLNESS OR WOUNDS AND ONCE THEY ARE DETECTED, WE FOLLOW THEM UNTIL RESOLUTION. SO BETH PUT TOGETHER THIS SEVERAL DECADES DATA SET FOR THE ADULT MALES IS WHAT THIS IS, AND WE TESTED HYPOTHESES ABOUT THE RELATIONSHIP BETWEEN SOCIAL STATUS AND ILLNESS ON THE ONE HAND -- THIS IS THINGS LIKE COUGHING, DIARRHEA, ALL THOSE THINGS YOU'D SORT OF THINK OF IN THAT CATEGORY -- VERSUS WOUNDS -- A NEW PUNCTURE WOUND ARK NEW SCRATCH. FOR MALES THEY GET ALL THEIR WOUNDS AT LEAST THE ONES FROM [INDISCERNIBLE] BY FIGHTING WITH OTHER MALES. AS YOU CAN IMAGINE, A FEMALE HAVE THE SIZE DOESN'T TEND TO INFLICT WOUND TONS MALES. THEY DON'T HAVE KNIVES AND WOUNDS THAT WOULD EQUALIZE THIS POWER DIFFERENTIAL. AND MALES FIGHT FRONT-TO-FRONT. SO LARGE DAY KAY NINES OR SLASH WOUNDS ARE A SIGNIFICANT SOURCE OF WOUND. THEY ALSO FALL FROM TREES, BREAK BONES AND SO ON. THESE HAVE BEEN FOLLOWED THROUGH TO A COUPLE OF YEARS AGO. THE HYPOTHESIS HAD BEEN THAT INJURY WOULD BECOME DISPRO POSH NATELY TO HIGHER-RANGING MALES AND THAT IT WOULD GO DOWN WITH RANK, STATUS, AND IT WOULD GO DOWN WITH AGE BECAUSE OF THIS CORRELATE. THIS IS JUST THE BIVARIATE ANALYSES. YOU CAN SEE THAT BOTH FOR RANK AND AGE, IN FACT, IT'S THE MID TO MID-HIGH RANKING, MUCH MORE THE MID-RANKING IN AGE AND THE WHOLE UPPER -- OKAY -- THAT ARE HIGHEST AND THEN IT DECLINES IN AGE. SO IT'S NOT THE TOP-RANKING MALES, BUT IT'S CERTAINLY IN THE UPPER HALF, AND THEN WOUNDS GO DOWN. FOR ILLNESSES, WE HAD EXPECTED THAT OLDER AND LOWER-RANKING INDIVIDUALS WOULD HAVE THE HIGHEST, AND IN FACT IN THAT CASE, THIS IS WHAT WE SEE, AND THE IDEA BEING THAT THEY GET LESS FOOD, THAT THEY'RE MORE VULNERABLE, THAT THEIR IMMUNE SYSTEMS ARE WEAKER. HERE WE SEE, AGAIN, FOR RANGE AND FOR AGE. AND THEN WE LOOKED AT THESE IN A MULTI-VARIATE WAY. RANK HAVING A STRONGER EFFECT AS IT TURNS OUT. SO WE THEN TURNED TO WOUND HEALING AND ILLNESS RECOVERY, AND WE ASKED; SO ASSUMING THAT ANIMALS IN THE BETTER CONDITION HEAL MORE RAPIDLY, IF GLUCOCORTICOIDS HAD A SIGNIFICANT EFFECT AND THEN WE'D EXPECT THAT HIGH-RANGING MALES AND THE LOWEST-RANKING MALES -- THE ALPHA MALE AND LOWEST-RANKING MALES WOULD HAVE BE COMPROMISED THAT WAY. IN FACT, NO MATTER HOW WE LOOK AT IT, HIGHER-RANKING MALES -- AND HERE IT WAS SORT OF THE TOP EIGHT MALES -- HAVE HIGHER, QUICKER RECOVERY FROM BOTH ILLNESS AND WOUNDING, AND THERE IS NO ALPHA/BETA DIFFERENCE, BUT THE HIGH-RANKING, THE ALPHA ARE HIGHER THAN ALL THE OTHER HIGH-RANKING AS A GROUP, AND IT IS ABOUT A ONE -- ABOUT I THINK IT WAS ABOUT A 50% DIFFERENCE IN THE HEALING RATES WHICH CAN BE QUITE SIGNIFICANT IN AN ENVIERLT WHERE LIFE IS A CHALLENGE EVERY DAY AND WHEN THERE ARE LOTS OF PREDATORS AROUND. SO, IN FACT, IT SEEMS THAT HIGH-RANKING ANIMALS FOR ONE REASON OR ANOTHER EITHER BECAUSE THEY START OUT IN BETTER CONDITION OR BECAUSE THEY DON'T STAY THERE LONG, HIGH-RANKING ANIMALS EITHER ARE NOT SUFFERING THE CONSEQUENCES OF HIGH GLUCOCORTICOIDS OR WHATEVER AMOUNT THEY'RE SUFFERING IS NOT ENOUGH TO OFFSET THE OTHER ADVANTAGES OF HIGH RANK. SO THAT IS SOMETHING WE'RE HOPING TO FOLLOW UP IN MORE DIRECT MEASURES OF OTHER MEASURES OF IMMUNE FUNCTION. IN FACT, THE WOUND HEALING IS SOMETHING EXPERIMENTALLY USED A LOT. WE JUST USED THE NATURAL WOUNDS. SO WHAT ARE SOME OF THE THINGS THAT ARE NEXT? WELL, IN PARTICULAR, WITH JENNY AND SUSAN LEADING IT, WE PLAN TO TAKE OUR GENETIC WORK IN A DIRECTION THAT JENNY'S ALREADY STARTED IN TERMS OF GENE EXPRESSION. WE'VE ALREADY IN THE FIRST LOOK FOUND SOME TANTALIZING RESULTS INCLUDING SOME GENE EXPRESSION DIFFERENCES THAT ARE ASSOCIATED WITH RANK IN SOME PUNITIVE FUNCTIONAL GENES. SO ON DOWN THE ROAD, WE HOPE TO HAVE MORE OF THAT DATA AND MORE OF THE OTHER STORIES FILLED IN, AND I THANK YOU. [APPLAUSE] >> OKAY. THANKS DR. ALTMANN. WE'RE GOING TO HOLD QUESTIONS UNTIL OUR DISCUSSION PERIOD. IT'S MY PLEASURE TO INTRODUCE MY COLLEAGUE AND FRIEND, DR. STEVE COLE WHO'S RESEARCH ANALYZES THE MOLECULAR PATHWAYS BY SOCIAL ENVIRONMENT INFLUENCES THE -- AND TUMOR GENOMES. HIS STUDIES USE VERY INNOVATIVE COMPUTATIONAL MODELLING TO INTEGRATE DATA FROM EPI STUDIES, NATURAL HISTORY ANALYSIS AND MOLECULAR AND BIOCHEMICAL STUDIES TO IDENTIFY THE PHYSIOLOGICAL SIGNALING PATHWAY THAT ALLOW ENVIRONMENTS TO -- SUCH AS INFLAMMATION, VIRAL REPLICATION AND TUMOR METASTASIS. HIS STUDIES HAVE -- REPLICATION OF VIRUSES, ALTER EXPRESSION OF KEY IMMUNE RESPONSE GENES AND UP REGULATE METASTASIS-RELATED GENES IN BREAST AND OVARIAN CANCER CELLS. HIS PLAN LABTORY HAS DEVELOPED AN ARRAY OF VERY NEW BIOINFORMATIC TOOLS TO INTERPRET [INDISCERNIBLE] DYNAMICS AND I WON'T GO INTO THE PARTICULARS OF WHAT THEY R BUT HE IS CERTAINLY A RENAISSANCE MAN. HE'S PIONEERED THE USE OF SOCIAL AND BEHAVIORAL RESEARCH AND PROVIDED CONSULTATION IN THE AREAS IN THOSE AREAS TO [INDISCERNIBLE] MEDICINE, NATIONAL CANCER INSTITUTE, NATIONAL INSTITUTE OF AGING, SANTA FE INSTITUTE AND A WHOLE WIDE ARRAY OF OTHERS. EVERYONE IS COLLABORATING WITH STEVE. [LAUGHTER] HE IS A PROFESSOR OF MEDICINE IN THE DIVISION OF HEMOLOGY-ONCOLOGY AT UCLA, A MEMBER OF THEIR CAN SIR CENTER, OF THE NOR MAN KUS INS CENTER AND UCLA BIOLOGY INSTITUTE. HE'S DIRECTOR OF THE UCLA CORE LABORATORY. I DON'T KNOW WHEN THIS GUY SLEEPS, BUT ANYWAY, IT'S MY PLEASURE TO INTRODUCE DR. COLE. [APPLAUSE] >> WELL, HOPEFULLY I DON'T SLEEP DURING TALKS. SO WHAT I'M GOING TO DO -- OH, THANKS -- IS BASICALLY SORT OF IN SOME SENSE PICK UP WITH DR. ALTMANN LEFT OFF IN TRYING TO MAKE THIS SORT OF GREAT LEAP BETWEEN THE SOCIAL WORLD AND SORT OF HEALTH AND DISEASE. SO AS SHE DESCRIBED, ACTUALLY I THINK QUITE NICELY, WE ARE, I WOULDN'T SAY WE'RE DONE WITH THIS STORY, BUT WE'VE MADE QUITE A LOT OF PROGRESS UNDERSTANDING HOW THE SOCIAL WORLD GETS CONVERT BID THE BRAIN INTO BIOCHEMICAL REPRESENTATIONS WITHIN THE BODY. THE EXPRESSION OF HORMONES, THE ACTIVITY OF NEUROTRANSMITTERS AND THE PERIPHERAL NERVOUS SYSTEM. WE NOW CAN MAKE SOME, YOU KNOW, NOT INVARIABLE CORRECT BUT DECENT GUESSES ABOUT HOW AN ANIMAL IS CONFRONTING SUBSTANTIAL LET'S SAY ONE POSITION IN A SOCIAL RANKING SYSTEM OR A CHANGE IN THE STABILITY OF THE SOCIAL CONTEXT. WE CAN MAKE GOOD PREDICTIONS ABOUT HOW THAT MIGHT TRANSLATE INTO DIFFERENCES IN THESE KINDS OF NEURAL OR ENDOCRINE REPRESENTATIONS. WHAT'S BEEN HARDER, FRANKLY, TO UNDERSTAND IS HOW THAT ACTUALLY PHYSICALLY STRUCTURES THE BIOLOGY OF HEALTH. SO MOST OF THESE HORMONES AND NEUROTRANSMITTERS ARE NATURAL COMPONENTS OF THE BODY, THEY'RE NOT DIRECTLY TOXIC SO TISSUE AND THAT RAISES THE QUESTION OF HOW IS IT THAT THESE DYNAMICS MAKE A LASTING DIFFERENCE AND WHEN DO THEY DO THAT? THERE'S THIS NOTION OF WEAR AND TEAR, BUT WE'D LIKE TO KNOW WHAT'S GETTING WORN AND TORN? WHAT EXACTLY IS GOING WRONG? WHY DO YOU SEE THE PARTICULAR STRUCTURE OF DISEASE RISK WHEN YOU DO? AND IT'S NOT THE CASE THAT INDIVIDUALS SUBJECT TO THESE KIND OF ADDS VERSETIES ARE UNIFORMLY MORE VULNERABLE TO ALL TYPES OF DISEASE, IN FACT THEY'RE SELECTIVE IN CERTAIN RESPECTS. SO WE'D LIKE TO UNDERSTAND THE NATURE OF THAT KIND OF SELECTIVITY. MUCH OF WHAT WE DO, IF WE'RE TRYING TO UNDERSTAND BASIC DISEASE PATHOGENESIS THESE DAYS, SORT OF THE DOMINANT PARADIGM FOR UNDERSTANDING THOSE DYNAMICS IS TO THINK ABOUT IT IN TERMS OF EXPRESSION OF GENES. GENES THAT ARE INVOLVED, LET'S SAY IN INFLAMMATION. STRUCTURING THE [INDISCERNIBLE] STRUCTURING THE DEGENERATION OF NEUROTISSUE, STRUCTURING THE GROOET AND DISSEMINATION OF CANCER CELLS. MUCH OF WHAT WE DO THESE DAYS IN TERMS OF ACTUALLY EXPLAINING DISEASE ON THE CONCRETE LEVEL IS DONE AT THIS LEVEL OF GENE EXPRESSION DYNAMICS. SO THAT'S GREAT. ONE, THAT PREVENTS A LANGUAGE TO SORT OF TRANSLATE DISEASE AS A CLINICAL ENTITY INTO SORT OF BIOLOGICAL OR CELLAR PROCESSES, IN PARTICULAR, AND IN ADDITION, IT PROVIDES US A FAIRLY SIMPLE CONCEPTUAL ROAD MAP FROM HOW YOU WOULD GET FROM THE SOCIAL WORLD INTO THESE CHANGES IN THE PHYSICAL MECHANICS OF DISEASE. WE KNOW IN PRINCIPLE HOW THIS HAPPENS, THAT IN GENERAL, THESE SORT OF NEUROOR ENDOCRINE REPRESENTATIONS OF SOCIAL CONDITIONS HAVE THE CAPACITY TO INTERRACKET ON THE SURFACES OF CELLS, THAT VENT WAIT INTO TRANGS KRIPGS FACTORS AND THESE BIND TO DNA AND FLAG INTO GENOTYPE PRODUCING PROTEIN. THIS CONNECTS ALL OF THESE DYNAMICS. WHAT WE DON'T UNDERSTAND SO WELL IS WHICH PARTICULAR TRANSCRIPTION FACTORS ARE INVOLVED. WHAT I'M GOING TO DO TODAY IS TALK A LITTLE BIT ABOUT WHAT WE'RE LEARNING IN THE CONTEXT OF WHAT I CALL SOCIAL SIGNAL TRANSDUCTION. STRETCHING THIS NOTION OF THAT CELL BIOLOGIST TYPICALLY USE -- SORT OF UPWARD TO ENCOMPASS THE ENVIRONMENTAL CONDITIONS THAT GET FILTERED THROUGH THE BRAIN INTO THESE SORT OF SYSTEMATIC NEUROAND BIOCHEMICAL DYNAMICS THROUGHOUT THE BODY AND THEN HOW THOSE PLAY ON THE PROGRAMMING OF THE HUMAN GENOME OR THE BABOON GENOME FOR THAT MATTER. AND THEN SORT OF HOW THAT WOULD INTERACT WITH MOLECULAR CASCADES THAT WE THINK ADD UP TO DIFFERENCES IN DISEASE PATHOGENESIS. I'LL BE TALKING ABOUT IN A KIND OF REALLY QUICK, BRIEF HEADLINE FORM ANSWERS TO SIMPLE QUESTIONS WE BEGAN ASKING A DECADE OR SO AGO ALONG THE LINES OF WHICH PARTICULAR SETS OF GENES ARE SENSITIVE TO THESE KINDS OF DYNAMICS. IT TURNS OUT DEPENDING ON THE CIRCUMSTANCES, MAYBE ONE TO FIVE AT MOST, 10% OF HUMAN GENES SEEM TO BE SENSITIVE TO CONDITIONS. 90% CONTINUE TO BE LIVER GENES AND STOMACH-LINING GENES AND GENES THAT ESTABLISH THE BASIC INFRASTRUCTURE OF OUR BODIES. BUT THAT SMALL FRACTION OF GENES IS THAT IS SOCIAL -- ANOTHER QUESTION WE'D LIKE TO UNDERSTAND IS WHICH PARTICULAR TRANSCRIPTION CONTROL PATHWAYS IN GENERAL AND WHICH TRANSCRIPTION FACTORS IN PARTICULAR ARE INSTRUMENTAL IN CARRYING SOCIAL INFORMATION INTO THE CONTEXT OF THE GENOME? ONCE WE UNDERSTAND THAT, ONCE WE UNDERSTAND THE PROXIMAL BIOCHEMICAL REPRESENTATION OF SOCIAL AND PSYCHOLOGICAL PROCESSES WITHIN THE CELL IN THE VICINITY OF THE NUCLEUS OF THE GENOME, MIGHT THERE BE DIFFERENCE INNINGS HOW THOSE DYNAMICS OPERATE DEPENDING UPON INDIVIDUAL GENETIC CHARACTERISTIC. WHAT ROLE DOES POLLY MORPH GENESIS PLAY IN -- ENVIRONMENTALLY-STRUCTURED GENE REGULATORY DYNAMICS? SO JUST TO KIND OF GIVE A BRIEF HEADLINE VERSION OF SOME OF THE ANSWERS THAT ARE EMERGING. IN THE CONTEXT OF THE PARTICULAR SETS OF GENES THAT ARE SENSITIVE TO SOCIAL PROCESSES, I'LL START OFF WITH WHAT TURNED OUT TO BE A [INDISCERNIBLE] EXAMPLE OF WHAT WE SEE PARTICULARLY WHEN WE LOOK AT THINGS IN THE CONTEXT OF CIRCULATING WHITE BLOOD CELLS WHICH IS OF COURSE THE EASIEST TISSUE SAMPLE THAT WE CAN PERSUADE HUMANS OR BABOONS TO GIVE US. WE SHOULD PROBABLY TRY DOING THIS IN POOH, BUT WE HAVEN'T GOTTEN AROUND TO THAT YET. [LAUGHTER] THIS IS A STUDY DONE QUITE A WHILE BACK NOW IN THE CONTEXT OF JON [INDISCERNIBLE] CHICAGO HEALTH AGING AND SOCIAL RELATION STUDIES. HE STUDIED A COHORT OF HEALTHY OLDER ADULTS IN THE CHICAGO AREA, PARTICULARLY INTERESTED IN THE ROLE OF SOCIAL NETWORKS, SOCIAL SUPPORT, BOTH OBJECTIVELY REPRESENTED BY ESPECIALLY SUBJECTIVELY EXPERIENCED AND THEIR CONTRIBUTIONS TO STRUCTURING INDIVIDUAL DIFFERENCES IN HEALTH AND DISEASE. SO HE HAD BLOOD SAMPLES AVAILABLE FOR A RELATIVELY SMALL COHORT WHEN WE ORIGINALLY DID THIS STUDY AND WE DID [INDISCERNIBLE] GENOME-WIDE TRANSCRIPTIONAL -- WHAT YOU SEE A HEAT MROOT OF ABOUT TWO HUNDRED GENES THAT WERE IDENTIFIED AS SHOWING GREATER THAN 50% DIFFERENCE IN AVERAGE EXPRESSION ACROSS A SUB COHORT THAT IS EXTREMELY LONELY ON A REGULAR BASIS OVER THE COURSE OF FOUR PREVIOUS YEARS AND A GROUP THAT WAS CONSISTENTLY HIGHLY SOCIALLY INTEGRATED. IN THIS HEAT PLOT ROSE CORRESPOND TO -- COLUMN CORRESPOND TO PARTICULAR GENES THAT CLEARED THIS FRESHHOLD OF 50% OR GREATER. THE EXTENT TO WHICH THE CELL -- RED THAT INDICATES RELATIVELY HIGH EXPRESSION OF THAT GENE TO THAT INDIVIDUAL. GREEN INDICATED LOW EXPRESSION. WHAT YOU CAN SEE IN THOSE BIG ORGANIZED BLOCKS OF READ AND GREEN ARE [INDISCERNIBLE] OF ABOUT 70 OR SO GENES THAT SHOW A GENERAL TENDENCY TO BE UP REGULATED IN SOCIALLY -- ANOTHER 130 GENES THAT ARE DOWN REGULATED. THESE GENES ARE NOT A RANDOM SAMPLE FROM THE HUMAN GENOME. THERE'S NOTHING PARTICULARLY SORT OF AD HOC ABOUT THE SETS OF GENES THAT EMERGED AS DIFFERENTIALLY EXPRESSED. SOME OF THE FUNCTIONS THAT ARE PARTICULARLY PROMINENT IN THE UP REGULATED GENE LIST INCLUDE THE PRODUCTION OF INFLAMMATORY RESPONSES, THE GROWTH AND DIFFERENTIATION OF CELLS, AND TRANSCRIPTIONAL CONTROL. PROMINENT AMONG THE DOWN REGULATED JEANNES WERE TRANSCRIPTS INVOLVED IN THE PRODUCTION OF ONE PARTICULAR ISOTYPE OF ANTIBODY AND TRANSCRIPTS INVOLVED IN INNATE ANTIVIRAL RESPONSES. ONE THING APPARENT HERE IS IN THIS PARTICULAR STUDY OF AT LEAST THIS KIND OF SOCIAL ADVERSITY, STRESS WAS NOT UNIFORMLY IMMUNOSUPPRESSIVE. SOME MODULES THAT ARE INVOLVED ARE SUBSTANTIALLY YOU BE REGULATED OTHERS ARE DOWN REGULATED THE MAJORITY ACTUALLY WERE NOT ALTERED, ONLY SMALL SUBGROUPS OF GENES. THIS GENERAL PATTERN OF INCREASED INFLAMMATORY GENE EXPRESSION AND REDUCED ANTIVIRAL GENE EXPRESSION HAS BEGUN TO RECUR FAIRLY CONSISTENTLY AS WE'VE LOOKED AT DIFFERENT TYPES OF SOCIAL ADVERSITIES. HERE IS ANOTHER EXAMPLE WHERE WE'RE LOOKING AT GENE EXPRESSION IN A SMALL PILOT STUDY THAT WE DID WHERE HE SAMPLED WHITE BLOOD CELLS FROM THE ANIMALS, BASICALLY THREE TO FOUR MONTHS AFTER BIRTH. SO THEY HAVEN'T BEEN ALIVE ALL THAT LONG. NOT A LOT OF ROOM FOR THE ANIMALS TO BE EXPOSED TO DIFFERENT KINDS OF PATHGENERALS. THESE ARE RANDOMIZED DIFFERENCES AND WE SEE THE SAME KIND OF PROFILE.RALS. THESE ARE RANDOMIZED DIFFERENCES AND WE SEE THE SAME KIND OF PROFILE.ALS. THESE ARE RANDOMIZED DIFFERENCES AND WE SEE THE SAME KIND OF PROFILE.LS. THESE ARE RANDOMIZED DIFFERENCES AND WE SEE THE SAME KIND OF PROFILE.S. THESE ARE RANDOMIZED DIFFERENCES AND WE SEE THE SAME KIND OF PROFILE.O GENS. THESE ARE RANDOMIZED DIFFERENCES AND WE SEE THE SAME KIND OF PROFILE.GENS. THESE ARE RANDOMIZED DIFFERENCES AND WE SEE THE SAME KIND OF PROFILE. SO THAT LEADS US TO SUSPECT THAT THERE IS SOME KIND OF CONSERVED GENE EXPRESSION PROGRAM BEING ACTIVATED BY THIS KIND OF ADVERSITY. IF WE LOOK THROUGH A VARIETY OF KINDS OF SOCIO ENVIRONMENT AND PSYCHOLOGICAL RISK FACTORS IN OBSERVATIONAL STUDIES OF HUMAN BEINGS, LOOKING THROUGH THE EYES OF THE LUKECYTE, WE SEE THIS PROINFLAMMATORY ANTI, ANTIVIRAL SKEWING IN THE BASIL GENE EXPRESSION OF IMMUNE CELLS. THIS HAS BECOME KNEW UBIQUITOUS THAT WE'VE BEEN TALKING IN GENERIC TERMS ABOUT THINGS LIKE ADVERSITY BECAUSE SO MANY DIFFERENT KINDS OF SPECIFIC RISK FACTORS LIKE THOSE ONES UP THERE AND UP HAVING SIMILAR GENE EXPRESSION DYNAMICS AND INCIDENTALLY OFTEN ARE ASSOCIATED WITH THE SAME KIND OF HEALTH OUTCOMES, SO WE SUSPECT THAT WHAT'S HAPPENING IS THAT THE BRAIN IS INTERPRETING THESE DIFFERENT RISK FACTORS AS IN SOME SENSE IE KOE MORPHIC AS BEING DIFFERENT VERSIONS OF THREAT OR UNCERTAINTY AND THAT MUCH OF WHAT WE'RE SEEING IS RELATIVELY CONSERVED RESPONSE THAT'S GENERATE BID THE BRAIN AND THUS REGULATING GENE EXPRESSION PROGRAMS IN PERIPHERAL TISSUES. WE NOW TALK A LOT ABOUT SOCIAL ADVERSITY GENERICALLY SPEAKING BECAUSE WE'RE NOT SURE THAT THERE'S A GREAT DEAL OF SPECIFICITY IN THESE RISK FACTORS. MOST OF THE SPECIFICITY IS COMING IN PROCESSING OF THEIR ENVIRONMENT RELATIVELY LITTLE OF THE DIRECT EFFECTS ON GENE EXFLAEGS WE SEE SEEMS TO BE STRUCTURED BY OBJECTIVE CHARACTERISTIC OF THE SOCIAL ENVIRONMENT. NOT TO SAY THERE'S NONE BUT THE BULK MAYBE ANYWHERE BETWEEN THREE AND TEN TIMES AS MUCH DIFFERENTIAL GENE EXPRESSION APPEARS TO BE ATTRIBUTE TO PEOPLE'S EXPERIENCES OF THE WOR WORLD. WELL, OKAY. SO IF THERE IS THIS KIND OF CONSERVED SYSTEM THAT'S HOOKING UP DIFFERENT KINDS OF SOCIAL ENVIRONMENT TO GENE EXPRESSION DYNAMICS, WHY WOULD THAT HAVE ARISEN IN THE FIRST PLACE? WHAT SENSE DOES THAT MAKE? WHY IS IT YOU WOULD WANT YOUR IMMUNE SYSTEM TO DO THINGS FUNDAMENTALLY DIFFERENTLY AT LEAST IN SOME RESPECTS AS A FUNCTION OF THE SOCIAL CONTEXT THAT YOU INHABILITATE AT ANY GIVEN POINT IN TIME? WE COULD IMAGINE CHANGES IN GENE EXPRESSION IN THE BRAIN SINCE THAT'S THE CHIEF ORGAN OF SOCIAL PERCEPTION, BUT WHY WOULD KWU WANT THINGS LIKE OVARIAN CANCER CELLS OR CIRCULATING WHITE BLOOD CELLS TO ALTER THEIR BEHAVIOR? ONE THING WE CAN DO IS WE CAN LOOK FOR THESE COMMONALITIES IN THE GENES THAT ARE BEING EMPIRICALLY REGULATED AND TRY AND MAKE A GUESS ABOUT WHAT THE CELL IS TRYING TO ACCOMPLISH BY HOOKING THESE GENES UP TO THIS KIND OF SOCIAL SIGNAL TRANSDUCTION. FOR INSTANCE N THE CONTEXT OF THESE WHITE BLOOD CELLS, WHAT WE'RE SEEING IS A BASIL GENE EXPRESSION PROFILE UNDER FAVORABLE CONDITIONS THAT'S GOOD AT DEFENDING ORGANISMS THAT'S GOOD AT -- LOW BASIL INFLAMMATORY SIGNALING. WHAT SEEMS TO BE HAPPENING WHEN ANIMALS RUN INTO SUBSTANTIAL ADVERSITY, AT LEAST FOR LONG PERIODS OF TIME IS THAT THE IMMUNE SYSTEM IS CLEARING OUT SOME BASE IN ITS BASIL TRAN SKRIM TOME AND UP REGULATING THE GENES THAT WOULD BE PARTICULARLY GOOD AT DEFENDING THE ORGANISM AGAINST BACTERIAL INFECTION. TO SOME EXTENT AT THE EXPENSE AGAINST INTRACELLAR PATHOGENS SUCH AS VIRUSES. THAT MOVES US A LITTLE BIT CLOSER -- I MEAN WE'VE NOW TRANSLATED THIS ABSTRACT VECTOR OF DIFFERENCES IN GENE EXPRESSION INTO SOME KIND OF, IF YOU WILL, IMMUNOLOGICAL REPRESENTATION OF WHAT'S GOING ON, BUT STILL THE QUESTION WOULD BE WHY WOULD THAT MAKE SENSE? IS THERE ANY PURPOSE TO HOOKING THAT KIND OF IMMUNOLOGIC DECISION MAKING UP TO EXPERIENCES OF THE SOCIAL WORLD? I CAN FAIRLY CONFIDENTLY TELL YOU THAT FOR THE LAST TEN THOUSAND YEARS THAT PROBABLY IS NOT A TERRIFICALLY GOOD IDEA BECAUSE OF THE CHANGES IN THE WAY WE LIVE, BUT BETWEEN A MILLION AND ABOUT MAYBE A THOUSAND YEARS AGO THIS ACTUALLY MIGHT HAVE MADE PRETTY GOOD SENSE, AND THE REASON IS THAT ESSENTIALLY THAT THE SOCIAL ECOLOGY THAT WE INHABIT AS FAR AS WE CAN TELL FROM [INDISCERNIBLE] PLAYED A ROLE IN STRUCTURING THE PATHOGEN ECOLOGY THAT WAS LIKELY TO PREVAIL WITHIN OUR BODIES. THE REASON THAT THERE WAS THIS CONNECTION BETWEEN THE SOCIAL ECOLOGY AND OUR PATHOGEN ECOLOGY COMES FROM THE FACT THAT MOST OF THE KEY PATHOGENS THAT WE CONFRONTED THEN AND ACTUALLY CONTINUE TO CONFRONT HAVE TRANSMISSION STRATEGIES THAT VARY SUBSTANTIALLY AS A FUNCTION OF SOCIAL CONDITIONS. THE MOST NOTABLE EXAMPLE WOULD BE VIRAL INFECTIONS. SO VIRUSES, IT TURNS OUT ARE HIGHLY HOST-SPECIFIC. THEY DON'T JUMP SPECIES EFFICIENTLY, THEY DON'T SURVIVE OUTSIDE OF HOST BODIES VERY EFFICIENTLY. IF YOU CONTRACT A VIRAL INFECTION, YOU ALMOST CERTAINLY GOT IT FROM CLOSE SOCIAL CONTACT WITH ANOTHER MEMBER OF YOUR OWN SPECIES. YOU PROBABLY DIDN'T GET THIS VIRAL INFECTION FROM YOUR CAT, YOUR DOG, OR OUR COW OR YOUR BABOON.YOUR COW OR YOUR BABOON. SO BEING AROUND ROTS OF HUMAN BEINGS IS A SUPERHIGHWAY FOR THE TRANSMISSION OF VIRUSES. HUMAN SOESH YALT, WHILE IT IS GOOD FOR LOTS OF THINGS IS A BASICALLY AN INVITATION TO INCREASED COMMUNICABLE VIRAL INFECTION IN THAT WAY THAT PARTICULARLY INTENSIVE FOR HUMANS AND HIGHLY SOCIAL PRIMATES. THE ADVANTAGE OF SOESH YALT THOUGH IS THAT IT BUYS YOU PROTECTION AGAINST LOTS OF FORMS -- IF YOU PUT A BUFRM OF HUMANS TOGETHER AND THEY COOPERATE, THEY CAN BEAT MUCH BIGGER TOUGHER THINGS AND ACTUALLY EAT THEM. THAT'S THE BET THAT EVOLUTION MADE ON SOESH YALT IS THAT SMALL NUMBERS OF HIGHLY MOBILE COORDINATED ACTORS CAN ACTUALLY PREVAIL AND IN FACT WE'VE ARGUABLY RUN OVER THE ENTIRE EARTH BY VIRTUE OF OUR ABILITY TO LEVERAGE SOCIAL INTERACTION. WHAT THAT MEANS IS THAT SOCIAL CONDITIONS CAN MAKE A BIG DIFFERENCE FOR THE TRANSMISSION OF PATHOGENS. IN THE CONTEXT OF VIRUSES THEY'RE GREAT AT HOPPING BETWEEN PEOPLE. WHAT HAPPENS WHEN YOU'RE SPENDING LOTS OF TIME WITH PEOPLE WHO HATE YOU? TWAEL THE PEOPLE WHO HEAT US DO INJURE US. IF WE GET HIT WITH THE SPEAR OF OUR ENEMY, WE ARE VULNERABLE TO BACTERIA INFECTIONS. SOCIAL ISOLATION -- A LONELY HUMAN BEING IS SOME OTHER ORGANISM'S LUNCH BECAUSE WE'RE NOT THAT BIG, FAST, STRONG AND COVERED WITH A KA RA PASTE OR ANYTHING LIKE THAT. SO BECAUSE [INDISCERNIBLE] ALSO PREDOMINANTLY EITHER BY HEMORRHAGING OR IF WE SURVIVE THE AGGRESSIVE ATTACK, BY THE BACTERIAL INFECTION THAT CAN HOP OFF THE SABER TOOTH TIGER'S DEATH, THAT KIND OF THING YOU'RE NOT GOING GET A VIRAL INFECTION BUT YOU'LL GET A BACTERIAL INFECTION. THIS CREATES THIS SORT OF ASSOCIATION BETWEEN THE SOCIAL ECOLOGY THAT HUMANS PROBABLY INHABITED FOR LONG, LONG PERIODS OF OUR EVOLUTIONARY HISTORY AND THE NATURE OF THE PATHOGEN DYNAMICS THAT WE'RE LIKELY TO BE CONFRONTED BY. WITH THAT IN MIND IT'S NOT INCONCEIVABLE THAT THE HUMAN GENOME MIGHT HAVE EVOLVED DISTINCT REGULATORY MODULES FOR THOSE. IT MAY HAVE EVOLVE WHAT HAD I WOULD CALL LIKELY THE DEFAULT INTEGRATED MODE THAT ASSUMES THAT HUMAN BEINGS ARE LIVING IN CLOSE SOCIAL QUARTERS WITH OTHER MEMBERS OF THEIR OWN SPECIES IN WHICH CASE BY DEFAULT THE IMMUNE CELLS ARE -- PARTICULARLY GOOD AT DEFENDING YOU AGAINST THESE SOCIALLY COMMUNICABLE PATHOGENS. ALTERNATIVELY, AND THIS IS PROBABLY LESS TYPICAL, BUT SORT OF A DIFFERENT MORE SORT OF INDIVIDUAL SURVIVAL MODE WHICH WE MIGHT CALL AUTONOMOUS MODE WHERE THE INDIVIDUAL IS NOT PART OF A COHERENT SOCIAL NETWORK AND SUDDENLY REALLY NEEDS TO CONTENT WITH THE PABLT OF A BACTERIA INFECTION.PABLT OF A BACTERIA INFECTION.OPABLT OF A BACTERIA INFECTION.SPABLT OF A BACTERIA INFECTION.SPABLT OF A BACTERIA INFECTION.IPABLT OF A BACTERIA INFECTION.BIPABLT OF A BACTERIA INFECTION.LPABLT OF A BACTERIA INFECTION.IPABLT OF A BACTERIA INFECTION.TYPABLT OF A BACTERIA INFECTION. OF A BACTERIA INFECTION. NOW THAT PROBABLY HAS SOME ADAPTIVE VALUE HISTORICALLY. IT ALLOWS THE IMMUNE SYSTEM TO ANTICIPATE THE PATHOGENS IT WILL CONFRONT. ANTICIPATORY REGULATION OF GENE EXPRESSION IS TREMENDOUSLY ADVANTAGEOUS, HIGHLY ADAPTIVE, BUT IN OUR CONTEMPORARY SOCIAL ENVIRONMENT, IT'S, OF COURSE, NOT A TERRIFIC IDEA. WHY? BECAUSE WE HAVE ENGINEERS FOR OURSELVES AN ENVIRONMENT THAT MAKES US FEEL THREATENED. OUR SYSTEM IS SITTING HERE RUNNING THAT AUTONOMOUS MODE RESPONSE WITH MORE INTENSITY THAN PROBABLY WAS THE CASE FOR HUNTER/GATHERERS IN THE PAST. THAT'S ONE PARTICULAR KIND OF GENE EXPRESSION DYNAMIC THAT SORT OF EMERGES FROM THESE KINDS OF STUDIES. ANOTHER ONE WE SEE OFTEN HAS TO DO WITH THE EXPRESSION OF JEANNES THAT STRUCTURE SYMPATHETIC AND ACTUALLY ANY KIND OF PERIPHERAL NERVOUS SYSTEM. THIS IS DATA FROM A STUDY THAT JOHN AT UC, DAVIS DOES WITH MACACS. HERE WE'RE LOOKING AT LYMPH NODES FROM THE ANIMALS AND WE SEE ABOUT A DOUBLING OF EXPRESSION OF A GENE CALLED NERVE GROWTH FACTOR WHICH ENCODES AS A GROWTH FACTOR THAT CAUSES THE SYMPATHETIC NERVE FIBERS IN THE LYMPH NODE TO ASH RISE. IT INCREASES THE NUMBER OF POINT SOURCES THROUGH WHICH THE BRAIN CAN COMMUNICATE WITH THE CELLS PRESENT IN THE LYMPH NODE. AS A FUNCTION OF THIS UP REGULATION OF POINT SOURCES FOR NOR EPINEPHRINE IN THESE PARTICULAR CASE IN THESE UNSTABLE SOCIAL CONDITIONS, YOU BASICALLY CREATE SORT OF A BRAIN-IMMUNE CONNECTION THAT'S A LOT MORE SENSITIVE. AS A FUNCTION OF THAT ANY DYNAMIC THOSE THOSE SYMPATHETIC NEUROTRANSMITTERS MIGHT BE INDUCING IN CELLS WILL HAPPEN WITH MORE VIGOR AND INTENSITY IN THESE ANIMALS THAT ARE SUBJECT TO TEASE UNSTABLE SOCIAL CONDITIONS THAT ARE BASICALLY NOT UNDERGOING ANY KIND OF VIOLATE CONFLICT, THEY'RE JUST IN AN ENVIRONMENT THAT'S A LITTLE BIT LESS PREDICTABLE AND MORE THREATENING, IF YOU WILL. SO FOR EXAMPLE AS A FUNCTION OF THAT YOU'LL SEE A 60-80% REDUCTION IN THE AMOUNT OF TYPE ONE INTERFERON PRESENT IN THOSE CELLS IN THE LIMB CH NODE. WHEN THEY ARE EXPOSED TO AN EXPOSED DOSE OF [INDISCERNIBLE] THOSE ANIMALS WILL GET SICK AND THEY WILL DIE FASTER AS A FUNCTION OF THIS PROGRAMMING OF THIS REPROGRAMMING OR REMODELLING OF THE NEUROCONNECTIONS BETWEEN CENTRAL NERVOUS SYSTEM AND THE PERIPHERAL IMMUNE SYSTEM. THAT'S A QUICK VERSION OF THE TYPES OF GENES THAT WE SEE RECURRENTLY REGULATED. HOW ARE THOSE GENE REGULATION DYNAMICS ACTUALLY TAKING PLACE? WHICH TRANSCRIPTION FACTORS ARE MEDIATING THESE EFFECTS? THE KEY TO TURNING ON GENE EXPRESSION IS TO BASICALLY GET A TRANSCRIPTION FACTOR TO BIND TO THE PROMOTER OF THE GENE ACTIVATE TRANSCRIPTION INTO PROTEIN AND A HEALTH PHENOTYPE. THIS IS ALL TAKES PLACE WITHIN CELLS THAT ARE SENSITIVE TO SOCIO ENVIRONMENTAL CONDITIONS. -- WHICH ULTIMATELY CONTROL THE ACTIVITY OF THESE TRANSCRIPTION FACTORS. YOU CAN THINK OF THIS AS THIS INPUT-OUTPUT RELATIONSHIP. WHAT TYPE OF RESPONSE IT PRODUCES DEPENDS ON WHICH GENES THESE FACTORS CAN INTERACT WITH AND THAT'S DETERMINED BY THE DNA SEQUENCES WITHIN THE PROMOTERS OF THESE GENES. THEY CAN BIND ONLY TO JEANNES THAT BEAR CHARACTERISTIC DNA MOTIFS THAT THEY RECOGNIZE. THAT'S WHAT ALLOWS GENE EXPRESSION TO TAKE PLACE. THAT'S WHAT IN SOME SENSE TURNS ON THE GENE. ONE THING WE CAN DO TO MAKE GUESSES ABOUT WHICH TRAN JIPGS FACTORS MIGHT BE CARRYING INFORMATION FROM THE SOCIAL ENVIRONMENT IS WE CAN PULL GENE EXPRESSION WITH GREAT PRECISION AND THEN GO TO THE ORG JICHL'S GENOME AND LOOK THROUGH THE PROMOTERS OF THE GENE THAT ARE SENSITIVE TO THIS SOCIAL RISK FACTOR AND ASK; DO WE SEE THOSE CHARACTERISTICS DNA MOTIFS FOR ONE OR ANOTHER PARTICULAR TRANSCRIPTION FACTOR HIGHLY OVERREPRESENTED AMONG THE PRO PROMOTERS OF THESE GENES. WE LOOK AT THAT RESPONSE TO ADVERSITY HERE VISUALLY REPRESENTED BY THAT STUDY I TALKED ABOUT, WE FIND JEANNES UP LEG RATED IN THESE LONELY OLDER ADULTS TEND TO HAVE RESPONSE ELEMENTS IN THEIR PROMOTERS FOR THIS PARTICULAR PROINFLAMMATORY TRANSCRIPTION FACTOR NF KAPPA B. -- THAT'S INTERESTING BECAUSE IN GENERAL WE DON'T FIND THAT INDIVIDUALS CONFRONTING ADVERSITY HAVE LOWER LEVELS OF GLUCOCORTICOIDS IN THEIR SYSTEM. GENERALLY THEY HAVE -- WHY WOULD WE SEE LESS GLUCOCORD NOID MEDIATED GENE EXPRESSION. BASICALLY IT LOOKS LIKE THE GLUCOCORTICOID RECEPTOR IN THESE CHRONICALLY STRESSED INDIVIDUALS ARE BECOMING DESENSITIZED TO THE AMBIENT GLUCOCORTICOID. THIS LEADS TO NF KAPPA B. MUCH FREER TO DO ITS WORK IN TERMS OF PROMOTING INFLAMMATORY GENE EXPRESSION. THAT'S ONE ILL LUS TRA TI DYNAMIC. THAT'S CERTAINLY NOT THE ONLY TRANSCRIPTION FACTORS WE FOUND TO BE EMPIRICALLY SENSITIVE BUT ONE EXAMPLE. THIS CAPACITY TO MAKE THESE KINDS OF INFERENCES WHICH WE CAN THEN VERIFY USING INDEPENDENT APPROACHES HAS PROVEN HIGHLY EFFECTIVE AT ALLOWING US TO MAKE GUESSES ABOUT HOW WE'RE GETTING FROM THE CENTRAL NERVOUS SYSTEM INTO CHANGES IN GENE EXPRESSION. THOSE HAVE ALLOWED US TO STRETCH FURTHER AND MAKE ADDITIONAL -- FOR EXAMPLE, WE CAN GO THROUGH THE GENOME AND ASK; HOW IS IT THAT THESE TRANSCRIPTION FACTOR REPRESENTATIONS TO THE SOCIAL ENVIRONMENT MIGHT INTERACT WITH THE GENOME DIFFERENTLY DEPENDING UPON INDIVIDUAL DIFFERENCES IN DNA SEQUENCE? IF FOR EXAMPLE SOMEBODY HAS A POLLY MORPHISM THAT PREVENTS THIS TRANSCRIPTION FACTOR FROM -- IN THIS PARTICULAR GENES EXPRESSION, THEN THERE WON'T BE ANY CHANGE THAT THAT GENE ES TRANSCRIPTION AND ANY PARTICULAR CHANGE IN CELLAR PHENOTYPE AS A FUNCTION OF THAT. HERE'S AN EMPIRICAL EXAMPLE OF THAT WHERE WE'RE LOOKING AT THE HUMAN IL SIX GENE. 174 BASE PAIRS UP STREAM OF THE [INDISCERNIBLE] IS THIS MOTIF RIGHT HERE WHICH IS HIGHLY ATTRACTIVE TARGET FOR ONE OF THOSE SOCIALLY SENSITIVE TRANSCRIPTION FACTORS. GADA TRANSCRIPTION FACTORS LOVE BINDING NO THE SEQUENCE AND THAT'S PRESENT IN THE MAJORITY OF US. IN A MINORITY OF US ABOUT 20% OF NORTH EUROPEAN ANCESTRY THERE'S A SINGLE POLLY -- CREATES A MUCH LESS APPEALING BINDING TARGET FAMILY. AS A RESULT OF THAT, IF YOU TAKE THE ANCESTRAL VERSION OF THE HUMAN GENOME AND YOU BASICALLY EXPOSE ITS HOUSING CELL TO SIGNAL FROM THE SYMPATHETIC NERVOUS SYSTEM TO NOR EPINEPHRINE YOU'LL FIND A STRONG ACTIVATION OF THAT ANCESTRAL OR WILD TYPE IL SIX PROMOTER. IF YOU LOOK AT THE PROMOTER THAT HAS THIS C ALLELE POLLY MORPHISM, YOU'LL FIND IT'S LESS -- THE SAME DESCENDING BIOCHEMICAL SIGNAL. AS A FUNCTION OF THAT, PRESUMABLY F YOU LOOK AT PEOPLE WITH THE, F YOU LOOK AT PEOPLE WITH THE F YOU LOOK AT PEOPLE WITH TI F YOU LOOK AT PEOPLE WITH THEF YOU LOOK AT PEOPLE WITH THE NORMAL VERSION OF THE IL SIX, YOU'LL FIND OLDER INDIVIDUALS THAT PEOPLE WHO CONFRONT SUBSTANTIAL LIFE ADVERSITIES HAVE A NOTABLE ACCELERATION IN THEIR MORTALITY RATES. THIS IS ACCELERATION THAT'S SPECIFIC FOR INFLAMMATION-RELATED CAUSES OF MORTALITY. THAT'S TRUE ONLY FOR INDIVIDUALS THAT HAVE THIS GSHG ADA-SENSITIVE GENE ALLELE OF THEIR IL SIX PROMOTER. IF THEY HAVE ONE OR MORE OF THESE GADA FACTOR C ALLELES THEY'RE PROTECTED FROM THAT EFFECT. THERE'S NO ACCELERATION IN MORTALITY RATES AS A FUNCTION OF THESE ADVERSE LIFE CIRCUMSTANCES. THEY STILL GET DEPRESSED, THEY STILL TURN ON THE GADA TRANSCRIPTION FACTOR, IT JUST DOESN'T INDUCE THE KIND OF PROINFLAMMATORY DRIVE FOR DISEASE THAT IT WOULD IN OTHER INDIVIDUALS. WE KNOW THIS IS PARTICULARLY MEDIATED, WE BELIEVE THIS IS MEDIATED BY DIFFERENCES IN INFLAMMATORY BIOLOGY, BECAUSE IF WE CONTROL FOR THOSE INDIVIDUAL DIFFERENCES IN INFLAMMATION, WE CAN LARGELY ABRA GAIT THOSE EFFECTS. WE'RE TRANSLATING ADVERSITY INTO SYMPATHET SYMPATHETIC NERVOUS SYSTEM ACTIVITY. IF YOU HAVE THE RIGHT PROMOTER IL SIX GETS ACTIVATED AND YOU GET ACCELERATED MORTALITY RISK FOR -- BLOCKS GADA BINDING YOU DISCONNECT THAT RELATIONSHIP. SO THAT'S THE END OF THE QUICK TOUR AS THE BEEPS TELL US. [LAUGHTER] WHAT I'LL DO IS TALK FOR A SECOND ABOUT SOME OF THE DIRECTIONS GOING FORWARD. SOME NOT-TO-SIMPLE QUESTIONS WE'RE WORKING ON. ONE ISSUE IS WHAT KINDS OF JEANNE EXPRESSIONS OCCUR IN OTHER TISSUE TYPES PARTICULARLY IN THE NERVOUS SYSTEM BECAUSE IT'S PLAYING A ROLE THERE'S THIS SUBSTANTIAL CAPACITY FOR RECURSIVE DYNAMICS WHERE -- [INDISCERNIBLE] THAT THEN LEAVES THE INDIVIDUAL MORE SENSITIVE TO A CERTAIN SOCIO ENVIRONMENTAL RISK FACTOR THAN IT WOULD IF IT HAD A DIFFERENT SOCIAL HISTORY AND THEN FINALLY THESE DYNAMICS ARE ALL TAKING PLACE IN COMMUNITIES. SO IF THE SOCIAL WORLD IS REGULATING ACTIVITY OF THE HUMAN GENOME IT MAY WELL BE THE CASE THAT WE CAN'T UNDERSTAND GENOME FUNCTION FOR ONE HUMAN GENOME IN ISOLATION. WE MAY NEED TO TALK ABOUT THE HUMAN METAGENOME AND THE ROLE THAT ALL OF THESE DIFFERENT GENOMIC SYSTEMS IN OUR PERSONAL COMMUNITIES ARE PLAYING IN CROSS REGULATING THE ACTIVITY OF OUR OWN GENOME. IF WE CAN DO THAT, WE MAY BE ABLE TO MORE EFFECTIVELY MAKE THIS GREAT JUMP FROM SOCIAL PROCESSES TO DIFFERENCES IN HEALTH AND DISEASE. THAT'S ALL VI TO SAY AS WELL. I NEED TO ACKNOWLEDGE LOTS OF COLLABORATOR WHO IS PARTICIPATED IN THESE STUDY AND THE TREMENDOUS SUPPORT FROM THE NATIONAL INSTITUTES OF HEALTH AND OTHER FUNDERS THAT MADE THIS RESEARCH POSSIBLE. [APPLAUSE] >> SO BOTH OF THOSE PRESENTATIONS WERE CLASSIC TOUR DEFORCES P SO I WANT TO INVITE OUR SPEAKERS UP TO THE PODIUM AND WE'LL OPEN THIS FLOOR FOR QUESTIONS. MARIBETH AS WELL.SPEAKERS UP TO THE PODIUM AND WE'LL OPEN THIS FLOOR FOR QUESTIONS. MARIBETH AS WELL.UP TO THE PODIUM AND WE'L L OPEN THIS FLOOR FOR QUESTIONS. MARIBETH AS WELL. DO WE HAVE ANY QUESTIONS? LIZ. YES, THANK YOU. >> [LOW AUDIO]. >> YOU GET THE MOST FEMALES WHO ARE STAYING AWAY. SO IT'S A VERY ACTIVE PROCESS. AND ONE OF THE THINGS WE LEARN IS THAT THESE REPRODUCT TIFF OPPORTUNITIES ACTUALLY ARE SOCIAL, SOCIALLY VARIABLE IN SOME OF THE KIND LIKE STEVE WAS TALKING ABOUT, IN ONE SOCIAL CONTEXT, THERE WAS LOTS OF MALES AND FEMALES IN A GROUP, MUCH MORE EQUITABLE DISTRIBUTION OF RESOURCES. IN A SMALL GROUP THOUGH THERE MAY BE FEWER FEMALES AVAILABLE LESS AUVENL, IT'S SORT OF THE TOP GUY TAKES ALL. SO THE SOCIAL CONTEXT IN THE WORLD AROUND THEM CAN MAKE A DIFFERENCE. WE SEE THAT MALES, IN OTHER WORDS TO REAP THESE BENEFITS, UM, HAVE SPEND LESS TIME FEEDING. THEY SEEM TO SOME OF THEM SEEM TO SPEND ALL THEIR TIME FIGHTING AND MATING AND THEY NOT DO SELF-MAINTENANCE ACTIVITY ENOUGH. THESE ARE, HOWEVER, BECAUSE OF THAT AGE PATTERN IN MALES, THEY ARE, THEY DO TEND TO BE YOUNGER, STRONGER MALES, BUT THEY DON'T ALWAYS SEEM TO BE THE MOST SAVVY MALES, JUST AS YOUNG LOW-RANKING FEMALES DON'T SEEM TO KNOW HOW TO STAY OUT OF TROUBLE. BY THE TIME THEY'RE HIGH, I MEAN, OLD LOW-RANGING FEMALES, THEY'VE DEVELOPED RESOURCES IN ALL SORTS OF NEAT BAYS. SO SOME OF THIS KIND OF LIFE COURSE ACTIVITY MAY BE FEEDING IN. DOES THAT? >> [LOW AUDIO]. >> POSSIBLY NOT BECAUSE WHAT WE DOING IS PUTTING TOGETHER IN SOME SENSE IN THESE PICTURES A LOT OF CROSS SECTIONS. THIS IS A WHICH SICK EXAMPLE OF WHERE CROSS SECTIONS DON'T MAKE A LIFE SO YOU NEED TO FOLLOW THE TIME COURSE TO GET -- I THINK DIFFERENT STYLES IS SOMETHING THAT YOU AND JOHN IN ALL HIS WORK HAVE LOOKED AT, PROBABLY GETS AT SOME THINGS. WE DO HAVE SOME SENSE THAT SOME MALES SEEM TO ACT AS IF THEY HAVE A SENSE THAT BEING NUMBER TWO FOR A REALLY LONG TIME MIGHT BE BETTER THAN BEING NUMBER ONE AND DOWN. I'M USING EVERYTHING IN QUOTES, YOU KNOW, OF COURSE. >> [LOW AUDIO]. >> SO THAT'S PARTLY A FUNCTION OF SAMPLE SIZE. SO IN EVERY GROUP, OR ACTUALLY WE DIDN'T INCLUDE OFTEN A GROUP WITH ONLY ONE MALE WITH THE IDEA THAT THAT MIGHT BE DIFFERENT, BUT ALMOST EVERY GROUP HAS A NUMBER ONE, A NUMBER TWO, A NUMBER THREE. NOT EVERY GROUP HAS A NUMBER 15, 16, AND 17. SO WHAT YOU'RE SEEING THERE IS PARTLY A SAMPLE SIZE VARIABILITY. WE DON'T KNOW THE ANSWER TO WHETHER, IN FACT, THERE'S ANY REAL DIFFERENCE IN VARIABILITY. IT'S A VERY GOOD QUESTION, AND WE'VE ALSO BEEN VERY CONCERNED TO LIKE IN THE TESTOSTERONE CHANGE WITH AGE TO BE VERY SURE THAT WE'RE NOT WHAT WE WEREN'T DESCRIBING WAS A SELECTION AS ANIMALS GET OLDER AND THAT YOU'RE JUST SEEING THE HIGH TESTOSTERONE GUYS DIE EARLY, AND SO WE'VE ALSO DONE INDIVIDUAL TRAJECTORIES TO THE EXTENT THAT WE CAN ON THAT. SO IT'S EACH -- >> [LOW AUDIO]. >> SO THAT'S A REALLY GOOD QUESTION, TOO. WE'RE TRYING TO GET A SENSE OF THAT. THERE ARE SEVERAL COMPLICATIONS AND YOU HAVE A LOT OF STOW KAS TISTY THAT COMES IN, AND WHETHER A YOUNG HOTSHOT COMES INTO THE GROUP AT SUCH A TIME OR SEVERAL, WHAT'S GOING ON IN THE REST OF THE POPULATION BECAUSE MALES DO MOVE AROUND CAN AFFECT THAT. ALSO DESPITE OUR BEST EFFORT BECAUSE MALES MOVE AROUND, WE DON'T ALWAYS -- THEY SOMETIMES SEEM TO GO TO OTHER GROUPS WHERE THE CHANCES MAY BE BETTER AND TO SOME EXTENT WE'RE ABLE TO TRACK THAT AND WE'RE DOING BETTER NOW WITH RADIO COLLARS AND SO ON, BUT NOT PERFECTLY, YET. SO IT'S -- WE HAVE THE SENSE THAT SOME OF THEM, YOU KNOW, DO STAY IN A LOWER POSITION AND ALSO STAY IN A GROUP -- ONE OF THE THINGS PATRICK WAS TRYING TO GET A BETTER HANDLE ON IS ARE THEY LESS LIKELY TO DISPERSE IF THEY HAVE ALREADY MADE MORE OFFSPRING IN A GROUP AND IS THAT AFFECTING THIS MOVEMENT? I MEAN, I WOULD WONDER, STEVE, IF THE KINDS OF INDIVIDUAL DIFFERENCES IN LIFETIME CONSISTENCIES IN SOME OF THE THINGS YOU WERE TALKING ABOUT ARE SOMETHING YOU'VE BEEN ABLE TO GET HANDLE AT, YOU KNOW, TO WHAT EXTENT DO YOU HAVE LONGITUDINAL INFORMATION FROM SOME OF THIS IN THESE WAYS? WAS I ALLOWED TO ASK A QUESTION? [LAUGHTER] >> WE WANT YOU TWO TO ASK EACH OTHER QUESTIONS. >> WE KNOW RELATIVELY LITTLE ABOUT LONGITUDINAL TRAJECTORIES IN GENE EXPRESSION, REALLY IN ANY RESPECT AT ALL IN HUMANS. THE STEVE STUDY IS GOING TO BE PROBABLY BY FAR OR MOST INTENSETIVE LONGITUDINAL STUDY OF ANYBODY IN TERMS OF [INDISCERNIBLE] GENE EXPRESSION PROFILES. WE DO KNOW A LITTLE BIT ABOUT THE SOCIO BEHAVIORAL PROFILES AND HOW STABLE THEY ARE. THAT'S CERTAINLY WHAT YOU MENTIONED, JOHN, [INDISCERNIBLE] IN HIS MONKEYS AND TO SOME EXTENT WHAT JOHN [INDISCERNIBLE] IS STUDYING WITH HIS LONELY OLDER ADULTS AND THERE'S DEFINITELY A HARD CORE OF SERIESLY -- YOU KNOW, IF YOU COULD CALL THEM CONSTITUTIONALLY LONELY INDIVIDUALS, BUT THERE ARE INDIVIDUALS THAT ARE TRANSIENTLY LONELY AND ISOLATED AND I DON'T KNOW IF WE GREGS TO THE MEAN IS THE RIGHT WAY TO DESCRIBE IT BUT THEY LEAVE THESE EXTREME STATES. I THINK PART OF WHAT WE HAVEN'T HAD MUCH OPPORTUNITY TO TALK ABOUT IS THE ROLE THAT THIS SORT OF BIOLOGICAL, IF YOU WILL, REEF KAGS OF SOCIAL EXPERIENCE PLAYS IN STRUCTURING YOUR FUTURE BEHAVIOR TO THE EXTENT THAT YOU HAVE EXPERIENCES THAT ALTER EITHER COGNITIVE PROCESSES OR GENE EXPRESSION OR MAYBE THEY'RE THE SAME THING, WHO KNOWS N THE BRAIN, LEADING TO YOU DEVELOP LET'S SAY A DIFFERENT THEORY ABOUT WHAT THE WORLD IS LIKE THAT CAN POTENTIALLY BECOME SELF-PERPETUATING. THAT'S JOHNS -- THAT SOCIAL EXPERIENCE CREATES A WORLD VIEW THAT STARTS BIASSING THE WAY YOU INTERPRET SUBSEQUENT AMBIGUOUS EVENT. A THEORY BECOMES A SELF-PROPAGATING REALITY. I THINK THAT IT'S HARD TO MAP THOSE KINDS OF PSYCHOLOGICAL THEORYS ON TO WHAT PRIMATES -- NON-PRIMATES ARE DOING IN THE FIELD. I WONDER IF IT'S POSSIBLE TO SEE DIFRPS IN SOCIAL STRATEGY OF THE THAT BOB ATTRIBUTES TO ANIMALS COMPLETELY UNCERTAIN ABOUT HOW EXTREMELY SERIOUSLY ONE CAN TAKE THIS KIND OF THING BUT NONETHELESS THERE MAY WELL END UP BEING THESE TEMPERAMENTS THAT STRUCTURE BOTH EXPERIENCES AND BIOLOGICAL EFFECTS OVER THE LIFE OF THE INDIVIDUAL. >> [LOW AUDIO]. >> I WOULD GENERALLY AGREE THAT FROM A [INDISCERNIBLE] STANDPOINT WE'RE JUST TALKING ABOUT NOISE ESSENTIALLY, THEY GENERALLY DON'T THINK ANYTHING BESIDES THE PATHOGEN AND IT'S DIRECT LUKE CITE RESPONDER IS DIRECT CONSEQUENCE AND YET THEY FIND THIS INFRUGS TROOUGS OF REALITY INTO THEIR ABILITY TO GENERATE SUITABLE ANTIBODY TIGHTERS. SO CLEARLY SOME OF THAT IS STRUCTURED BY THESE KINDS OF DYNAMICS AND THERE'S A FAIRLY DECENT, NOT HUGE, BUT WELL-DONE LITERATURE SHOWING THAT THESE KINDS OF ADVERSE SOCIAL CONDITIONS, BOTH OBSERVED IN CORRELATIONAL HUMAN STUDIES AND MANIPULATED IN PRIMATE STUDIES CAN INDEED INFLUENCE RESPONSES TO VACCINES. MOST OF WHAT'S BEEN STUDIED HAS BEEN ANTIBODY-MEDIATED RESPONSES. THERE'S RELATIVELY LITTLE STUDY OF THE RELATIVELY SMALL NUMBER OF VACCINES THAT ARE MORE TARGETED PRODUCTION OF CYTOTOXIC T CELL RESPONSES. ON THE RIGHT SIDE THEY'RE THE BULK OF WHAT ARE SORT OF PROFI LACKTIVE VACCINATION STRATEGIES SEEM TO EVOKE. THE OTHER PLACE WHERE THIS FIGURE'S PARTICULARLY PROM NEPTLY THE S IN OLDER INDIVIDUALS BY VIRTUE OF AGING TEND TO PRODUCE LESS ROBUST RESPONSES. IF YOU SUPERIMPOSE ON THAT THE SECOND HIT OF SOCIAL ADVERSITY AND IT'S ADDITIONAL QUANTITATIVE DEGRADATION OF IMMUNE RESPONSE, YOU END UP HAVING QUITE SUBSTANTIAL VARIATIONS IN THAT REGARD. WHAT WOULD WE DO ABOUT THIS? ONE OF THE KEY OPPORTUNITIES IS TO LEARN MORE ABOUT THE Mc MEK NICKS OF THE MECHANICS OF THE -- WE'RE NOT [INDISCERNIBLE] OF THE PHARMACOLOGIC -- IT SOUNDS CLOCK MAY MY TO BIOMEDICAL THOUGHT BUT THERE'S NOTHING PREVENTING YOU FROM ADMINISTERING HORMONAL [INDISCERNIBLE] MANIPULATIONS KIND OF IN TAB DEM WITH YOUR VACCINE IF YOU THINK THAT'S GOING THE PUSH AROUND THE NATURE OF THE RESPONSE. WE CAN ALSO TOY WITH AN ---AGE VENTS THAT HAVE THE POE TEN STHOOL BLOCK OR ENHANCE THE STEERING THAT THE NERVOUS AND ENDOCRINE SYSTEM ARE PRODUCING. BUT YOU KNOW THERE MAY BE SIMPLER THINGS. I'M THINKING IN PARTICULAR OF NOT THE GLAZERS AT OHIO STATE BUT I THINK THERE'S A GROUP THERE THAT WORKS ON EXERCISE. IT TURNS OUT THAT A TERRIFIC WAY TO GOOSE THESE ANTIBODY-GENERATING PRIMARY AND SECONDARY VACCINE RESPONSES. IT MAY WELL BE THE CASE THAT THE MOST TRACTABLE OR APPROPRIATE PREDICTION IS NOT FOR FANCIAGE VENTS OR BLASTING WITH VA BAY TA BLOCKERS BUT ARRANGING VAC NATION SCHEDULED TO -- BOUT OF PHYSICAL ACTIVITY OR SLEEP DYNAMICS OR OTHER INFLUENCES ON THE NATURE OF THE IMMUNE RESPONSE. >> [LOW AUDIO]. >> WE'VE LOOKED AT THIS TO SOME EXTENT. I WOULDN'T SAY THAT WE HAVE ENOUGH DIFFERENT STUDIES TO TALK ABOUT THAT GENERAL TRANSCRIPTIONAL RESPONSE. WHEN WE LOOK WITHIN THE RELATIVELY SMALL NUMBER OF STUDIES WHERE WE HAVE A ROBUST ENOUGH SAMPLE SIZE FOR SEX DIFFERENCE ANALYSES OR TO THE EXTENT THAT WE CAN SAY THAT THIS IS, YOU KNOW, EVEN A QUANTITATIVE DIFFERENCE IN RESPONSE, THERE HAVEN'T BEEN TERRIFICALLY NOTABLE DIFFERENCES IN THE NATURE OF THE CONNECTION BETWEEN SUBJECTIVE EXPERIENCE AND THE SORTS OF MOLECULAR RESPONSES IN WHITE BLOOD CELLS. SO ONCE YOU GET TO A CERTAIN PERCEPTION OF THE WORLD, THIS SEEMS TO BE A RELATIVELY BALLISTIC CONSEQUENCE OF THAT. WHERE WE DO SEE BIGGER DIFFERENCE IS IN THE NATURE OF THE BINDING BETWEEN EXTERNAL CONDITIONS AND THESE SUBJECTIVE INTERPRETATIONS OF THE WORLD. WOMEN FIND DIFFERENT THINGS THREATENING THAN MEN DO. IN SOME SENSE THIS IS THE ARCHITECTURE OF WHY YOU HAVE SUCH A VERY DIFFERENT RESULT, SOMETIMES, IN STATUS AND SORT OF BOTH CONFERRED STATUS FROM YOUR GROUP, YOUR FAMILY, AND INDIVIDUAL STATUS DYNAMICS IS THAT IN SOME SENSE MALES AND FEMALES ARE OFTEN IN THESE SOCIAL CONTEXT LIVING IN SLIGHTLY OR SOMETIMES DRAMATICALLY DIFFERENT WORLDS. TO TAKE DR. ALTMANN'S EXAMPLE IN HERE SITUATION TYPICALLY THE FEMALES AREN'T BEING TOSSED OUT OF THEIR BIRTH COMMUNITY AND HAVING TO MAKE THEIR WAY INTO OTHER GROUPS WHICH CAN BE A CHALLENGING PROCESS TO SAY THE LEAST. THAT'S NOT THE SAY THEY DON'T CONFRONT ANY STRESSES WHERE THEY'RE AT JUST THAT THE NATURE OF THESE STRESSES ARE SOMEWHAT DIFFERENT. TO IS RELATIVELY WEAK EXTENT THAT WE'RE ABLE TO TELL AT ALL, MOST OF THE SEX DIFFERENCES THAT WE SEE HAVE TO DO WITH THE NATURE OF THE EXTERNAL CONNECTIONS T EXTERNAL RISK FACTORS FOR DIFFERENCES IN GENE EXPRESSION, BUT ONCE YOU GET TO THE INTERNAL PERCEPTION OF THREAT OR DESTRESS, THE NATURE OF THE RESPONSES IS SO FAR FAIRLY SIMILAR. >> [LOW AUDIO]. >> PROBABLY TWO THINGS SAY IT ALL. ONE, I'M NOT THE PRIMARY GENE-END OF OUR TEAM AND WE'RE AT PRETTY EARLY STAGES THERE. THE TARGETING THOUGH SO FAR THERE IS A GOOD DEAL OF OVERLAP IN THINKING ABOUT PARTICULARLY IMMUNE AND ENDOCRINE-RELATED GENES, AND I THINK FOR THESE THE REASONS HAVING TO DO WITH THE GREAT WORK AND EVIDENCE OF THAT BEING A REALLY IMPORTANT PLACE TO TARGET AND TO SOME EXTENT WHAT TISSUES WE CAN GET. I MEAN, IT'S A MIXTURE. I MEAN IDEALLY, I WAS GOING TO ASK STEVE, CAN WE GET ANYTHING FROM POOP? [LAUGHTER] BUT, SOMEWHAT MORE ACCESSIBLE TO US WHEN WE DO A DARTING AND IMMOBILIZATION IS A SINGLE SAMPLING OF SKIN AND BLOOD, AND THAT'S WHAT JENNY HAS BEEN STARTING TO WORK WITH AND SO THE IMMUNE AND ENDOCRINE GENES THAT CAN BE SAMPLED THAT WAY. >> LET ME GO DOWN TO THE BOTTOM FIRST. [LOW AUDIO]. >> [LOW AUDIO]. >> YES. [LAUGHTER] SO PROBABLY BOTH OF THOSE THINGS CAN HAPPEN. MECHANICALLY, THE PSYCHOLOGY HAPPENS FIRST AND THEN THE JEANNES LAG JUST BECAUSE IT TAKES FIVE MINUTES TO GET THE TRANSCRIPTION FACTORS ON THE DNA, TAKES ANOTHER 30 MINUTES TO TWO HOURS FOR THE INITIAL PULLS OF GENE TRANSCRIPTION TO PEAK OUT. SO HUMAN PSYCHOLOGICAL PROCESSES ARE MUCH FASTER. SOCIAL CIRCUMSTANCES CAN CHANGE IN EVEN SHORTER TIME SCALES. SO IF YOU THINK OF THIS AS LIKE A SINGLE PULSETAL EVENT, PROBABLY THE GENES LAG BY A LOT. HOWEVER, THOSE GENES DON'T JUST KIND OF FLY OFF INTO THE EITHER. THEY THEN START TO INFLUENCE THE WAY YOU THINK ABOUT THETHEWAY YOU THINK AB OUT THE WAY YOU THINK ABOUT THETHER. THEY THEN START TO INFLUENCE THE WAY YOU THINK ABOUT THE WORLD. SO THIS SECONDARY EFFECT WHERE NOW YOU'VE GOT IN PLACE A SLIGHTLY DIFFERENT GENE EXPRESSION REGIME THAT IN SOME SENSE RESPONDS TO THE WORLD DIFFERENTLY, I THINK, IS A REAL OPPORTUNITY FOR THE JEANNES TO INFLUENCE THESE DYNAMICS. THE CURABLE QUESTION WOULD BE IN SOME SENSE THE EMPIRICAL QUESTION OF, ARE THE GENES THAT ARE ACTUALLY ACTIVATE BID THIS GOING TO MUTE THE EFFECT OF FUTURE THREAT OR ARE THEY GOING TO AMPLIFY THE EFFECT OF FUTURE THREAT? ARE THEY GOING TO -- SOME OF THEM ARE UNDOUBTEDLY NEUTRAL, BUT THAT'S KIND OF WHAT I WAS ELUDING TO WITH THAT BEING ONE OF THE MAJOR UNANSWERED QUESTIONS. HOW OFTEN IS IT THAT THE CASE THAT THESE BECOME SOMEWHAT SELF-SENSITIZING? HOW OFTEN IS IT THAT THEY'RE DOING ABATING OR DOWN REGULATING AFTER THIS INITIAL TRIGGER IS GONE? WE JUST REALLY DON'T KNOW THAT YET. THAT'S A GREAT OPPORTUNITY FOR FUTURE DISCOVERY AND I THINK PARTICULARLY WHEN WE HAVE THESE EXCELLENT ANIMAL MODELS OF WHAT I'LL CALL HIGH-STAKES CHANGES WHICH HAPPEN MUCH LESS DRAMATICALLY AND OFTEN FOR CONTEMPORARY HUMANS. I THINK OF US AS BEING A LOW SIMMER OF MISERY. IT'S NOT TERRIBLY HIGH, NOT TERRIBLY LOW, BUT IT'S NOT LIKE THE KINDS OF BEING AT THE MERCY OF YOUR ECOLOGY THE WAY A BABOON IN AFRICA IS. EVERY TIME SAY THAT THE PRIMATOLOGIST SAY, THEY GOT AN EASY LIFE, I WISH IR WERE A BABOON. THEY HAVE A RESPONSE TO THAT. [LAUGHTER] >> I WAS WONDERING WHETHER WHAT YOU'VE FOUND PREDICTS WHETHER THE KIND OF MATCH BETWEEN THE EXTERNAL SOCIAL WORLD THAT IS SO OFTEN MEASURED AND THAT OF COURSE WE CAN MEASURE TOO VERSUS THE PERCEPTION AND WHETHER, SAY, IF WOMEN LIKE FEMALE BABOONS, THE EXTENT TO WHICH THEY'RE MUCH MORE SOCIALLY INTEGRATED THAN IS THEIR PERCEPTION WHEN THERE'S A CHANGE OR THERE'S A LOSS? ONE CAN IMAGINE SAY, WELL, THEIR CUP IS STILL HALF FULL WHEREAS THE GUY WHO HAD ONLY ONE TWO OR BUDDIES, THEY LOSE ONE AND IT'S ALL OVER, OR, I MEAN, DOES ONE CAN ENVISION THE PERCEPTION GOING EITHER WAY IN SEX DIFFERENCES BACK TO JOHN'S QUESTION. HOW IS THE MATCH THERE AND DOES THAT THEN RELATE TO THE KIND OF THING YOU WERE ASKING? >> WELL, AS SOON AS KI GET PEOPLE TO GIVE ME LOTS OF PRIMATE BRAINS, WE'D HAVE SOME KIND OF A VIEW ON THAT, BUT THAT'S ACTUALLY ONE OF THE MAJOR CHALLENGES IS THE THINGS THAT MATTER FOR SOCIAL BEHAVIOR AREN'T AT LEAST IN FIRST PRINCIPLES THE LUKECYTES. WITH CAN GET PLENTY OF THEM AND ANALYZE THE EXPRESSION, BUT THERE'S NO TIGHT CORRELATION BETWEEN GENE EXPRESSION DYNAMICS IN LUKECYTES AND OTHER CITY SHOES. THEY JUST MAY BE DIFFERENT GENES TARGETED IN EACH TISSUE DEPENDING ON THINGS THAT ARE PRESENT. AT THIS POINT WE DON'T KNOW VERY MUCH AT ALL ABOUT THAT IN ANY CONTEXT OTHER THAN SORT OF PATHOGEN-RELATED SOESH YALT. IT REMAINS A CHALLENGE. >> IN THIS CHICAGO STUDY, FOR EXAMPLE, WHERE THE OBJECTIVE MEASURES OF SOCIAL CONTEXT AND THE NUMBER OF PEOPLE AND THE NUMBER OF HOURS AND ALL THAT THAT ARE OFTEN TAKEN AND ALSO THE SUBJECTIVE MEASURES, AND THERE'S THE EMPIRICAL RESULT THAT THE SUBJECTIVE MEASURES ARE A BETTER PREDICTOR, I DON'T RECALL THERE BEING ANY REAL EVALUATION -- AND THAT MAY BE STRICTLY MY IGNORANCE -- OF THE RELATIONSHIP BETWEEN THE SUBJECTIVE AND THE OBJECTIVE AND IN THE LIGHT OF SEX DIFFERENCES AND THAT. >> YEAH. >> WAS THERE? >> NOT IN SEX DIFFERENCES SENSE, BUT CERTAINLY THERE ARE DIFFERENT GENES THAT APPEAR TO BE EMPIRICALLY SENSITIVE TO SUBJECTIVE VERSUS OBJECTIVE MEASURES OF SOCIAL IMBEDDEDNESS IF YOU WILL. SUBJECTIVE AND OBJECTIVE SOCIAL IMBEDDEDNESS MEASURES CORRELATE .3 AT BEST, MAYBE .4, SO THERE'S PLENTY OF ROOM TO FIND OFF DIAGONAL THERE AND FIGURE OUT WHICH GENES TRACK THE SOCIAL WORLD SORT OF MORE THAN THEY TRACK -- SORRY THE SUBJECTIVE SOCIAL WORLD MORE THAN THEY TRACK OBJECTIVE THINGS LIKE SOCIAL NETWORK DENSITY AND THE NUMBER OF PEOPLE YOU TALK TO EACH DAY. THE NUMBER OF GENES THAT TRACK THE SUBJECTIVE SOCIAL WORLD TO MY GREAT SURPRISE WAS LARGER THAN THE NUMBER THAT TRACKED THE OBJECTIVE SOCIAL WORLD. THE GENES THAT TRACK THE SUBJECTIVE ARE NOTABLY DIFFERENT AT LEAST IN THE CONTEXT OF LUKECYTES THEY LOOK LIKE THEY'RE PRIMARY LAY BY PRODUCT OF THE FACT THAT LUKECYTES IN EXTROVERTS ARE RESPONDING TO MORE INFECTION EXPOSURES BECAUSE THEY LITERALLY ARE SEEING MORE PEOPLE WHO ARE TRANSMITTING MORE PATHOGENS TO THEM. THE SUBJECTIVE TRACKING GENES ARE MUCH MORE THIS SORT OF INEXPLICABLE DEFENSIVE STANCE. THIS SORT OF CHRONIC UP REGULATION OF THIS -- TYPE ONE INTERFERONS. I DON'T KNOW, UM, THAT WE SAW ENOUGH OF A DIFFERENCE IN THOSE TYPES OF RESPONSES ACROSS GENDER FOR ME TO FEEL LIKE THERE WAS A REAL DIFFERENCE. ONE OF THE BIG CHALLENGES IN GENE EXPRESSION PROFILING IS YOU'VE GOT 22,000 CANDIDATES, LOTS OF ROOM FOR ERRORS. YOU HAVE TO PUT UP A KIND OF A HIGH THRESHOLD FOR PATTERN RECOGNITION. YOU DON'T SAY THAT GENE WAS UP, MUST BE TRUE OR SOMETHING LIKE THAT. SO WE LOOK FOR THEMES BECAUSE WE DON'T TRUST INDIVIDUAL REPORTS VERY MUCH AND WE CERTAINLY DIDN'T SEE ANY THEME MA TICK DIFFERENCE ETCH THOUGH WE DID AT THE LEVEL OF SPECIFIC INDIVIDUAL GENES SEE GENES THAT WERE POTENTIAL SEX DIFFERENCES IN THAT KIND OF OK JEK TIFF, SUBJECTIVE DISCONTINUITY. THAT SAID, IT'S NOT CLEAR IN THE PARTICULAR SAMPLE WE WERE LOOKING AT THAT WE WERE NECESSARILY AT THE RIGHT PHASE OF PEOPLE'S LIVES TO SEE THE MOST DRAMATIC DIFFERENCES. THERE ARE SOME THEORETICAL ANALYSIS THAT WOULD SUGGEST YOU WANT TO LOOK AT ADOLESCENCE IN YOUNG ADULTS TO SEE THESE KINDS OF THINGS. THAT THESE PEAK YEARS WHERE THERE'S ARGUMENT THAT LIFE HISTORY DYNAMICS STRUCTURE BOTH INDIVIDUAL BEHAVIOR AND SORT OF HISTORICAL EVOLUTION VARY DIFFERENTLY. >> SO SHOULD DIFFERENT OBJECTIVE MEASURES BE TAKEN? IS IT JUST THAT, YOU KNOW, IS IT ONLY SUBJECTIVE OR IS IT THAT THERE ISN'T JUST A GOOD MATCH BETWEEN THE OBJECTIVE MEASURES THAT HAVE BEEN USED SO FAR AND THE SUBJECTIVE? AND I HAVE BOTH THEORETICAL AND AN EMPIRICAL INVESTMENT IN TRYING TO FIGURE OUT -- >> WELL YOU'LL BE HAPPY TO KNOW I THINK BOTH ARE IMPORTANT, AND I THINK THAT OUR ABILITY TO RESOLVE OBJECTIVE ECOLOGICAL INFLUENCES IN FREE-RANGE HUMANS IN WESTERN CULTURAL SETTINGS IS HIGHLY DEGRADED BECAUSE THEY'RE SO HOME GENIUS. WE DON'T HAVE -- WE LIVE RELATIVELY HOMOGENEOUS LIFE RELATIVE TO THE WAY I THINK WE MIGHT HAVE HISTORICALLY. >> HOW WOULD YOU TAKE THAT CROSS CULTURALLY AND WHAT WOULD YOU PREDICT FOR CULTURES? FOR EXAMPLE WHEN I WAS FIRST IN KENYA ON MY OWN INSTEAD OF WITH MY FAMILY, MY FRIENDS TOOK IT AS AN OBLIGATION THAT THEY -- MY AFRICAN FRIENDS -- THAT THEY OR ONE OF THEIR CHILDREN SHOULD COME SLEEP WITH ME, SHOULD COME STAY WITH ME. I MEAN THE IDEA OF BEING ALONE WAS JUST A HORRIFYING IDEA. THERE ARE BIG DIFFERENCES IN SOCIAL CONNECTEDNESS, STRESSFUL AS WELL AS SUPPORTIVE SOCIAL CONNECTEDNESS, I SHOULD SAY, IN DIFFERENT CULTURES AND ARE WE -- WOULD THAT BE VERY HELPFUL TO US TO GET AWAY FROM THAT HOMO GENEITY? >> THAT IS AN EXCELLENT QUESTION. I WON'T SAY THAT WE'RE NEAR TO HAVING AN ANSWER TO THIS, BUT THAT'S EXACTLY THE WAY THE LINE OF RESEARCH THAT JOHN CATCHOWEPOE IS PURSUING. THE REASON IT TAKES ME SO LONG TO SAY THEIR NAME IS BECAUSE FOUR YEARS AGO I PUT THEM TOGETHER THINKING THAT WOULD HELP THE PROGRESS OF RESEARCH IN THIS AREA BUT IT MEANS I CAN'T SAY JOHN C OR JOHN CA WITHOUT GETTING THE WRONG NAME OUT. I APOLOGIZE TO THEM. BUT TO MAKE A LONG STORY SHORT, WHAT WE'RE INTERESTED IN IS THE POSSIBILITY THAT THIS MATCH THAT YOU'RE TALKING ABOUT BETWEEN INDIVIDUAL PROCLIVITIES AND ONE'S SOCIAL NICHE BOTH SELF-SELECTED OR SUB JOINTLY SELECTED BY SELF-AND ECOLOGICAL INFLUENCES IS REALLY THE THING THAT MATTERS THE MOST. AND SO WE'RE FOR INSTANCE EXPLORING THE POSSIBILITY THAT LONELINESS OR SOCIAL DISCONNECTION IS POTENTIALLY A VERY DIFFERENT EXPERIENCE FOR WHAT YOU MIGHT CALL A TRUE INTROVERT, SOMEBODY WHO JUST DOESN'T NEED A LOT OF SOCIAL CONTACT TO BE HAPPY THAN IT IS FOR WHAT WE MIGHT CALL AN ANXIOUS LONELY PERSON. SOMEONE WHO DESIRES A GREAT DEAL MORE SOCIAL CONTACT THAN THEY HAVE AT THE MOMENT BUT FEELS FOR WHATEVER REASON THREATENED BY THAT POSSIBILITY OR THAT IT'S UNFEASIBLE OR SOMETHING LIKE THAT. AND SO WHAT JOHN HAS DONE IS HE'S USED A WHOLE BUNCH OF BEHAVIORAL PROBES -- I'M NOT EVEN GOING TO ANSWER WHICH JOHN IT IS -- A WHOLE BUNCH OF BEHAVIORAL PROBES WITH HIS MONKEYS LOOKING AT WHAT HAPPENS WHEN THEY SEE SORT OF DIFFERENT KINDS OF SOCIAL QUEUES TO TRY AND DISTINGUISH BETWEEN ANIMALS THAT WANT SOCIAL CONTACT AND ANIMALS THAT ARE PERFECTLY FINE BEING ON THEIR OWN. WE ARE JUST AT THE FIRST STAGES OF ANALYZING LUKECYTE GENE EXPRESSION PROFILES. I DON'T KNOW THAT WE'LL HAVE A LOT TO SAY ABOUT THE TRANSCRIPTIONAL BASIS OF THESE TEMPERAMENTAL DIFFERENCES BUT AT THE VERY LEAST WE MAY WELL FIND THAT INDIVIDUAL DIFFERENCES IN TEMPERAMENT COME TO -- >> [LOW AUDIO]. I THINK WE MAY HAVE TIME FOR A FEW MORE QUESTIONS. >> [LOW AUDIO]. [LAUGHTER] >> UM, YES. ALTHOUGH, UM, MY THEORY IS THAT PROBABLY THERE IS NO ONE SIMPLE ANSWER TO THOSE KINDS OF QUESTIONS, AND THAT IS MOST OBVIOUS THING JUST GIVING PEOPLE MORE SOCIAL CONTACT IS PROBABLY IN SOME SENSE COUNTER PRODUCTIVE AND I DON'T SAY THAT COMPLETELY BEREFED OF EMPIRICAL ED OF -- EVIDENCE OF THIS. -- THIS NOTION THAT WHAT YOU REALLY WANT IS THE OPTIMAL SOCIAL OPPORTUNITY GIVEN A SOCIAL TEMPERAMENT. SO AT THE VERY LEAST, IF THOSE KINDS OF SOCIAL INTERVENTIONS ARE DEPLOYED, THEY NEED TO BE DONE IN A WAY THAT'S HIGHLY RESPONSIVE TO THE PARTICULAR INDIVIDUAL. THEY NEED BE HIGHLY PERSONALIZED. ANOTHER POSSIBILITY IS TO INTERVENE IN SEVERAL DIFFERENT POINTS OF THESE KINDS OF INFLUENCE SYSTEM SIMULTANEOUSLY. TRYING TO CREATE THE MOST SALTORY WHILE AT THE SAME TIME HITTING THEM WITH BETA-BLOCKERS TO PREVENT WHATEVER LEAKAGE MAKES IT THROUGH THE CENTRAL NERVOUS SYSTEM. I SAY THAT BECAUSE IT MAKES THEORETICAL SENSE WHEN YOU'RE DRAWING IT ON A DIAGRAM DPOP I THINK WE SHOULD BE PUTTING BETA-BLOCKERS IN THE WATER. NO. BUT THEN SOMETIMES, IT SURE WORKS FOR THE ANIMALS, I HAVE TO SAY. SO I DON'T REALLY QUITE KNOW HOW TO LAND ON THAT ISSUE, BUT THE BIGGER PICTURE IS THAT IN MY READ OF THE INTERVENTION LITERATURE, WHAT WORKS BEST ARE THE KITCHEN SINK INTERVENTIONS WHERE THEY HIT PEOPLE WITH A WHOLE BUNCH OF DIFFERENT INTERVENTIONS SIMULTANEOUSLY. THEY TRY AND CHANGE AS MUCH OF THEIR LIVES AT POSSIBLE. NOT VERY POPULAR AMONG INTERVENTIONISTS BECAUSE IT'S NOT VERY CLEAN. YOU DON'T KNOW WHAT THE ACTIVE INGREDIENT WAS, BUT THOSE TYPES OF INTERVENTIONS HAVE EMPIRICALLY BEEN THE ONES THAT HAVE MOST OFTEN REDUCED DISEASE RATES AND PROLONGED LIFE IN PEOPLE WITH ALREADY INCIDENT DISEASE. SO THAT'S A FAIRLY BORING ANSWER TO YOUR QUESTION AND WHAT I WOULD SAY WITH OUR LAST MOMENTS IS THAT WE SHOULD ADDRESS THAT SO THE MORE CREATIVE MEMBER OF THE PANEL HERE AND JUST SIMPLY ASK IF BASED ON EVERYTHING YOU'VE LEARNED ABOUT BABOONS, HOW WOULD YOU HELP HUMANS IN THE FUNNY SOCIAL ECOLOGY THAT WE FIND OURSELVES? [LAUGHTER] >> WELL, I THINK YOUR POINT ABOUT INDIVIDUAL DIFFERENCES IS REALLY IMPORTANT, AND I DON'T KNOW WHETHER IT TAKES THE KITCHEN SINK TO DO IT OR INDIVIDUALIZED INTERVENTIONS, BUT, BABOONS SEEM TO MAKE THEIR OWN INTERVENTIONS IF THEY'RE IN THE WILD IN PARTICULAR WHERE THEY CAN GIVE THEMSELVES MORE SPACE OR NOT, WHERE THEY CAN CHOOSE TO TURN NON-RELATIVES INTO FRIENDS OR STAY MORE LONELY AND SO ON, AND I THINK IF WE CAN FIND A WAY TO GIVE A MENU FROM WHICH SOME THINGS ARE SELECTED, THAT WOULD BE MY GUESS. IT'S VERY, UH, I THINK YOU AND TALKED WHEN WE FIRST MET NOT SO LONG AGO, ABOUT HOW RAPIDLY IN THE WILD ANIMALS HEAL. THE OPPOSITE OF WHAT ANYBODY WHO'S WORKED FOR THEM IN CAPTIVITY SAY. I THINK IT HAS TO DO WITH SOME OF THESE THINGS, NOT JUST A LOT OF FRESH AIR. THERE'S A LOT OF OPPORTUNITY FOR BAD THINGS TOO, BUT THIS, DO THEY HAVE LOTS OF OPTIONS? I MEAN, STEVE REMEMBERS THOSE CAGES WHERE ANIMALS COULD GET OUT OF A BAD SITUATION. THEY'D WEAR A COLLAR, IT WAS A SMALLER HOLE BUT THE AGGRESSOR COUNT GET THROUGH AND HOW THESE DEGREES OF -- THAT STEVE I WAS TALKING ABOUT -- AND HOW BEING ABLE TO HAVE OPTIONS, AND I DON'T KNOW HOW THAT CAN BEST BE MANAGED IN THE INTERVENTION, BUT I WOULDN'T BE SURPRISED IF PEOPLE COULD CHOOSE THE RIGHT OPTION FOR THEM MAYBE BETTER THAN OTHERS CAN CHOOSE. >> SO ON THAT NOTE WOULD YOU CONSIDER MASSIVE INTERVENTIONS TO STRUCTURE PEOPLE'S SOCIAL EN[LOW AUDIO]. >> WELL, I WOULD THINK NOT TO IMPOSE A CERTAIN STRUCTURE ON THEM BUT TO FIND A PERMISSIVE, I MEAN LIKE WHEN OPPORTUNITY IS TALKED ABOUT RATHER THAN PERCENTAGES OR WHATEVER IN DOING THINGS. I THINK THE OPPORTUNITY AND THE VARIOUS CHOICES ON A FAIRLY LARGE SCALE COULD POTENTIALLY BE SOMETHING TO WORK ON. I THINK WE'RE OFTEN WORKING ON THE WRONG LEVEL ON THE SORT OF LOWER-LEVEL THAT SAYS HERE, DO THIS, RATHER THAN ON A STRATEGIC LEVEL THAT IN TERMS OF MOTHERING AND CARE OF YOUNG, IT'S NOT ON THE OH, THIS IS A GOOD MOTHER AND SHE DOES THIS. SO EVERYBODY SHOULD DO THIS. IT'S, IS SHE MAKING A BETTER MATCH FOR THE CIRCUMSTANCES SHE AND THE YOUNGSTER FIND THEMES IN? I THINK -- THEMSELVES IN? I THINK HUMANS MAY BE AS SMART AS BABOONS ON FINDING THE BEST THING FOR THEM. >> I'M SORRY, BUT I THINK WE DO HAVE TO END. CAN I INVITE MELISSA AND HER SEAT MAKES TO COME DOWN AND MINGLE WITH GENE AND STEVE AND CAN WE ALL JUST GIVE A WARM ROUND OF APPLAUSE? [APPLAUSE] SPECIAL THANKS TO OUR COHOST, MARIBETH CHAMPOUX IN THE >> I'D LIKE TO THANK PEOPLE FOR ALL THE GREAT QUESTIONS AND COMMENTS AND STEVE WHO I ONLY MET VERY RECENTLY AND IT WAS GREAT FUN.