>> GOOD AFTERNOON EVERYONE. THANK YOU FOR JOINING US TODAY. I'M JEFF FROM THE NATIONAL INSTITUTE OF DRUG ABUSE. I WANT TO FIRST OFF START BY THANKING THE OFFICE OF BEHAVIORAL AND SOCIAL SCIENCES RESEARCH FOR ORGANIZING THIS TALK TODAY. IT IS MY GREAT HONOR TO INTRODUCE TODAY'S SPEAKER DR. SANDRO GALEA. SHE'S CHAIR OF EPIDEMIOLOGY -- SCHOOL OF PUBLIC HEALTH. A PHYSICIAN IN EPIDEMIOLOGIST BY TRAINING DR. GALEA'S RESEARCH HAS SOUGHT TO UNCOVER HOW AT DETERMINANT MULTIPLE LEVELS DURING THE INFLUENCE TO HELP THE COMMUNITIES. A PRIMARY FOCUS OF HIS WORK HAS BEEN ON THE CAUSES OF MENTAL DISORDERS, PARTICULARLY ANXIETY AND SUBSTANCE ABUSE DISORDERS. HE DOCUMENTED FURTHER HEALTH CONSEQUENCES OF MASS TRAUMA AND CONFLICT WORLDWIDE, INCLUDING THE SEPTEMBER 11 ATTACKS, HURRICANE KATRINA, CONFLICTS IN AFRICA AND THE AMERICAN WARS IN IRAQ AND AFGHANISTAN. HE HAS PUBLISHED OVER 400 SCIENTIFIC JOURNAL ARTICLES, 50 CHAPTERS IN COMMENTARIES IN SEFNLG BOOKS. HE'S BEEN FEATURED IN MULTIPLE NATIONAL AND INTERNATIONAL MEDIA OUTLETS, INCLUDING THE "NEW YORK TIMES," THE "WALL STREET JOURNAL" AND NPR. DURING HIS TENURE AS CHAIR THE DEPARTMENT OF EPIDEMIOLOGY HAS LAUNCHED SEVERAL NEW EDUCATIONAL INITIATIVES AND SUBSTANTIALLY INCREASED ITS FOCUS IN MULTIPLE FOUR RESEARCH AREAS. DR. GALEA ALSO CHAIR THE NEW YORK CITY DEPARTMENT OF HEALTH AND MENTAL HYGIENE COMMUNITY SERVICES BOARD, EPIDEMIOLOGY RESEARCH AND A SELECTED MEMBER OF THE INSTITUTE OF MEDICINE AT THE NATIONAL ACADEMY OF SCIENCE. DR. GALEA'S TALK TODAY IS TITLED IS IT ALL ABOUT ME, THE ROLE OF PUBLIC HEALTH IN AN ERA OF PERSONALIZED MEDICINE. PLEASE JOIN ME IN WELCOMING DR. GALEA. [APPLAUSE] >> GOOD AROUND, THANK YOU ALL FOR COMING. THANK YOU BSSR FOR INVITING ME AND JEFF FOR THE INTRODUCTION. SO I WANT TO TALK ABOUT PUBLIC HEALTH, AND I REALIZE THAT COMING TO NIH TO TALK ABOUT PUBLIC HEALTH IS A LITTLE BIT INCONGRUOUS. I WANT TO SHARE A PUBLICATION AND SEE WHAT YOU ALL THINK ABOUT IT. AND BROADLY SPEAKING, I AM GOING TO TRY TO TALK ABOUT HOW AN ERA WHEN WE ARE THINKING MORE AND MORE ABOUT A NARROWER APPROACH, THAT APPROACH IS EXCLUDING APPROACHES WE MUST TAKE TO GET OUR SCIENCE RIGHT. LET ME START WITH MY TITLE. WHERE DOES IT COME FROM IT'S ALL ABOUT ME. IT COME FROM THE GAME OF SOCCER AS ALL GOOD THINGS DO. THERE'S NOTHING MORE ENTHUSIASTIC THAN A BUNCH OF SEVEN YEAR OLDS PLAYING SOCCER. THIS PARTICULAR FELLOW HERE IS MY SON. THAT WAS A COUPLE YEARS AGO BUT THE REASON I SHOULD BRING THIS PICTURE UP IS BECAUSE MY SON IS A BIG FAN OF ENGLISH SOCCER AND PARTICULARLY A BIG FAN OF THIS GUY. AND FOR THOSE WHO DON'T KNOW, THIS IS MARIO BARATELLA WHO IS AN ITALIAN PLAYER WHO USED TO PLAY IN ENGLAND AND IS IN ITALY AGAIN. HE'S A STRIKER AND HAS EXUBERANT SELF REGARD. HERE HE HAS SCORED ON GOAL AGAINST MANCHESTER UNITED AND HE PULLED UP HIS SHIRT TO SHOW THIS QUESTION, WHY ALWAYS ME. I'M STARTING WITH THIS ON PURPOSE BECAUSE I WOULD ARGUE THAT MARIO'S QUESTION IS A NICE EXAMPLE OF WHAT ECONOMISTS CALL FUNDAMENTAL ATTRIBUTION ERROR WHICH IS ESSENTIALLY WE IGNORE CONTEXT AND THE INDIVIDUAL'S SUCCESS OR FAILURE SOLELY TO INHERENT QUALITIES. IN ANSWER TO HIS QUESTION WHY IS IT ALWAYS ME. WELL IN PART, YOU'RE GOOD BUT IN MANY LARGE PARTS BECAUSE YOU'RE PLAYING FOR REALLY REALLY GOOD TEAMS AND REALLY REALLY GOOD PLAYERS GIVE YOUPLHE BALL SO YOU CAN SCORE. AND I'M OBVIOUSLY STARTING WITH A LIGHT HEARTED METAPHOR AND I'M DOING THAT ON PURPOSE BECAUSE I THINK IT IS EMBLEM MATIC OF THE ERRORS WE'RE MAKING TODAY IN OUR BROADER BIOMEDICAL HEALTH ENTERPRISE. SO LET ME MAKE THIS ARGUMENT. I'M GOING TO MAKE IT IN TEN STEPS SO YOU'LL KNOW EXACTLY HOW MUCH, HOW FAR I'VE GONE IN CASE YOU START WANDERING OFF. LET ME START WITH OUR CENTRAL MOTIVATION. AND WOULD -- BY OUR CENTRAL MOTIVATION, MOST OF US IN THE BIO MEDICAL WORLD, WHY DO WE DO WHAT WE DO. I THINK IT'S USEFUL 1250EU78Z TO ASK OURSELF THAT. I REALLY LIKE THIS QUOTE. THIS IS FROM MIKE AND BILL. HERE'S WHAT THEY SAY. THEY SAY ONE OF OUR MOST DIFFICULTY CHALLENGES IS TO ENSURE THAT THE URGENT DOES NOT CROWD OUT THE IMPORTANT. IN HEALTH THE CHALLENGE IS ESPECIALLY DIFFICULT BECAUSE URGENT MATTERS CAN BE SO RIFTING. - RIVETTING. THE POINT IS WE SHOULD BE INTERESTED IN DOING WHAT IS IMPORTANT. AND HERE'S WHERE IT GETS COMPLICATED. IT GETS COMPLICATED BECAUSE MY HEALTH IS URGENT. JUST BECAUSE MY HEALTH IS URGENT DOESN'T MEAN IN THE BIG PICTURE MY HEALTH IS IMPORTANT. WHAT IS IMPORTANT IN THE BIG SCHEME OF THING IS IMPROVING THE HEALTH OF ALL. AND THIS CHALLENGE THAT I THINK UNDERLIES THIS COGNITIVE MISTAKE WE'RE MAKING AND DISCUSS WHAT'S AT STAKE AND HOW WE GO ABOUT OUR BIO MEDICAL WORK TODAY. SO HERE'S MY CENTRAL PREMISE. MY CENTRAL PREMISE OF MY TALK IS TO. IS THAT OUR FOCUS ON THE INDIVIDUAL IS CURATIVE IS CROWDING OUT OUR RESPONSIBILITY FOR PREVENTION POPULATION LEVEL AND IT LEADS US IMPORTANTLY TO CONCEPTUAL AND INFERENTIAL ERRORS. AND EQUALLY IMPORTANT IS CONSEQUENCES FOR SCIENCE AND PRACTICE. I WILL TRY TO MAKE THE ARGUMENT THERE ARE THESE ERRORS NEED TO MAKE AND THAT THESE ERRORS HAVE CONSEQUENCES. IF WHAT I'M TALKING ABOUT HAS NO CONSEQUENCES, THEN IN SOME RESPECT IT DOES NOT MATTER. BUT I'M GOING TO TRY TO CONVINCE YOU THAT THIS IS THE CASE. SO LET ME START WITH THIS POINT. SO THEY USED THIS TERM WHICH I LIKE VERY MUCH THAT THERE'S THIS RIVETTING DISTRACTION. I LIKE THAT TERM, IT'S VERY EVOCATIVE TERM. OUR DISTRACTION IS THE ENTHUSIASM FOR THE INDIVIDUAL. PARTICULARLY GENOMICS. NOW I WANT TO STOP AND MAKE A CAVEAT HERE. AND NOTHING IN MY TALK IS TAKING ON GENOMICS AS AN AREA OF IMPORT. WHAT I'M DOING I COME HERE NOT TO BURY, I COME TO ELEVATE THE POPULATION OF HEALTH. NOTHING IN MY TALK THOSE GOING TO SAY ANYTHING THAT SUGGESTS A DEEPER UNDERSTANDING OF GENES AND MOLECULES IS NOT GOING TO ADVANCE OUR UNDERSTANDING OF THE PATHOGENESIS OF HUMAN DISEASE. WHAT I'M HERE TODAY IS TO TRY TO HELP US UNDERSTAND WHY THAT FITS IN CONTEXT AND WHY IT IS JUST FOCUSING ON THAT IS NOT ENOUGH FOR US TO UNDERSTAND THE PRODUCTION OF HEALTH. SO THIS RIVETTING DISTRACTION. WHAT FORM DOES IT TAKE? WELL IT TAKES THE FORM OF A TREMENDOUS FOCUS ON INDIVIDUAL BEHAVIOR CHANGE. NOW IF ANYBODY HAS A SPARE 45 MINUTES I WOULD RECOMMEND THIS EXERCISE. IT'S A LOT OF FUN. AMAZON AND YOU GOOGLE INDIVIDUAL SELF HELP OR INDIVIDUAL HEALTH IMPROVEMENT AND YOU GET THIS FANTASTIC LIKE ARRAY OF BOOK. IT'S MIND-BOGGLING AND THIS IS SOME OF MY FAVORITES. THIS IS MY FAVORITE ONE FROM MR. MARK LOREN BECAUSE HE DOESN'T KNOW ME AND HOW FAR I AM FROM BEING MY OWN GYM. IT'S A TERRIFIC ILLUSTRATION OF IF YOU GO TO THE POPULAR PRESS WHAT'S WRITTEN WITH POPULAR BOOKS, THE MOTION OF HOW TO MAKE HEALTH BETTER IS ALMOST EXCLUSIVELY RESTING ON THIS IDEA THAT I CAN MAKE MYSELF BETTER. NOW, HERE'S THE KEEP POINT WHICH I'M GOING TO GET TO THAT IDEA IS PREDICATED ON THE NOTION THAT IF I IMPROVE ME, I CAN PREDICT THAT IT'S GOING TO MAKE MY HEALTH STAY BETTER. RIGHT? OTHERWISE WHY WOULD I DO IT. I COULD DO IT BECAUSE I WANT TO LOOK GOOD. THESE BOOKS ARE ABOUT IF I IMPROVE ME I'M GOING TO MAKE MY HEALTH BETTER. IT'S THAT NOTION THAT THROUGH INDIVIDUAL ACTING ON INDIVIDUALS WE CAN PREDICT INDIVIDUAL HEALTH AND I AM THE CORE CHALLENGE HERE. THERE IS THIS SELF HELP BEHAVIORAL MODIFICATION INDUSTRY. THE OTHER PART OF COURSE IS GENOMICS. THAT ON COVER OF TIME WHEN THE GENETIC CODE WAS CRACKED. THE DIRECTOR IS HERE ON THE COVER. THERE'S NO QUESTION THAT THIS HAS HAD A DRAMATIC EFFECT ON HOW WE GO ABOUT OUR BUSINESS IN THE BIO MEDICAL STROY. THERE ARE A LARGE NUMBER THAT QUADRUPLED IN A DECADE WHICH IS REALLY IMPOSSIBLE TO FIND IN ANY OTHER AREA. SO WE REALLY HAVE BEEN INVESTING A LOT MORE OF OUR RESOURCES, FINANCIAL RESOURCES BUT ALSO OUR INTELLECTUAL RESOURCES ON FOCUSING ON INDIVIDUAL DRIVERS OF INDIVIDUAL HEALTH. ON TRYING TO UNDERSTAND HOW WE MAY BETTER GET THE NEUTRAL DRIVERS THAT MAY PREDICT THE HEALTH OF INDIVIDUALS. NOW THIS APPROACH HAS SEVERAL SUCCESSES. ONE CAN ARGUE ABOUT GENOMICS. ONE CAN TALK ABOUT DIAGNOSTIC CANCERS, I HIGH LATE BREAST CANCER. ONE CAN TALK ABOUT GENOMICS IMPROVED SCREENING AFTER BIRTH. THERE'S NO QUESTION THAT THIS APPROACH HAS HAD MANY SUCCESSES. SO AS WE MOVE IN THIS WAY AND KEEPING IN MIND THIS VERY HUMAN, THIS VERY HUMAN TENDENCY TO THINK ABOUT IMPROVING HEALTH SO WE CAN IMPROVE INDIVIDUAL SO WE CAN PREDICT BETTER HEALTH HERE IS WHERE THE MISTAKE HAPPENS. IT LMS IN THIS SYLLOGISM. FOR THOSE WHO REMEMBER LOGIC IN UNDERGRADUATE COLLEGE, SYLLOGISM IS A EQUALS B AND B EQUALS C. HERE'S THE SYLLOGISM WE MAKE ALL THE TIME. THIS IS ASSOCIATED WITH DISEASE. ONE CAN FIGHT THIS A MILLION FOLD. THAT'S A. B IS WE CAN GENOME INDIVIDUALS. IT'S ALSO INARGUABLE. WE DO THIS INCREASINGLY EVER BETTER AND BETTER. SO THEREFORE WE CONCLUDE THAT BY GENOMIZING INDIVIDUALS OR BY FOCUSING ON INDIVIDUAL BEHAVIOR, WE CAN PREDICT DISEASE OR TREATMENT RESPONSE IN INDIVIDUALS. IF YOU THINK ABOUT THIS THERE'S NOTHING HERE IN THIS SENTENCE THAT'S PARTICULARLY CONTROVERSIAL. A LOT OF THIS IS ADMITTED IN THE PERSONALIZED MEDICINE AGENDA. NOW I'M SHOWING YOU PAPERS THIS ONE BEING MY FAVORITE BECAUSE I LIKE ALL THINGS LEADING TO THE INEVITABLE. THE -- VERY BROAD AGENDA AND HAS A LOT OF NUANCE AND I'M WELL AWARE OF THE FACT THAT NEWER MOVEMENTS LIKE STRATIFIED MEDICINE WHAT'S MORE NUANCES THAN SOME OF THE SORT INITIAL FLEDGED HAMMERED PERSONALIZED MEDICINE APPROACHES. BUT IT'S CORE. IT'S PREDICATED ON THIS IDEA THAT EMERGES FROM THE SYLLOGISM THAT BECAUSE GENES AND DISEASE GO TOGETHER, WE CAN GENOTYPE, WE CAN NOW USE GENES OR INDIVIDUAL BEHAVIOR. IN MY TALK THE TWO ARE PRETTY ENTER CHANGEABLE TO PREDICT DISEASE, TO PREDICT DISEASE AND BY PREDICTING DISEASE TO MAKE HEALTH BETTER. THIS AGENDA AS EVERYBODY HERE KNOWS HAS TAKEN FAIRY. THIS IS SOMETHING THAT HAS REALLY DOMINATED A LOT OF BIO MEDICAL RESEARCH PARADIGM OVER THE PAST DECADE. THAT THE NOTION THAT THROUGH BETTER AND BETTER MOLECULAR DIAGNOSIS THROUGH BETTER AND BETTER GENETIC TYPING WE CAN GET AT BETTER INDIVIDUAL HEALTH. WE CAN PREDICT AND GET BETTER INDIVIDUAL HEALTH AND THEREFORE IMPROVE THE HEALTH OF THE NATION, IS AT THE ROOT OF A LOT OF OUR DIRECTION TOGETHER. ALL OF US COLLECTIVELY AS BIOMEDICAL RESEARCHERS. STEPPING OUTSIDE OURSELVES FOR A SECOND THIS IDEA HAS TAKEN HOLD IN GENERAL PUBLIC. NO WHERE BETTER PERHAPS THAN THINGS LIKE THIS. THIS IS 23 AND ME. YOU CAN GO ON-LINE AND YOU CAN GET YOUR SELF A GENOTYPE FOR $99. YOU CAN ORDER NOW. WHAT IS OF COURSE DOMINATES A LOT OF THESE EFFORTS IS YOU LEARN VALUABLE HEALTH AND ANCESTRY INFORMATION. IT'S NOT JUST ABOUT LEARNING VALUABLE ANCESTRY INFORMATION. EVERYBODY LEARNS WHERE THEY COME FROM THESE THINGS. WHAT IS THE CELL HERE IS THAT THROUGH GENOTYPING YOU ARE LEARN VALUABLE HEALTH INFORMATION. NOW THAT, IF YOU STOP AND THINK ABOUT IT FOR A SECOND RIGHT, IMPLIES THAT THROUGH REGIONAL TYPING YOU CAN LEARN HOW YOU'RE TOGETHER TO PREDICT DISEASE IN YOU. OTHERWISE WHY ELSE WOULD YOU DO IT. THIS OBVIOUSLY BUILDS ON THIS GALLOPING INTEREST THAT WE'VE HAD IN THIS INDIVIDUAL JEANNIE GUYING, INDIVIDUAL BEHAVIORAL CHANGE FOR THE PURPOSE OF PREDICTING INDIVIDUAL HEALTH. AND THIS IS NOT -- THIS IS MAINSTREAM. THIS IS "TIME" MAGAZINE BEST INVENTIONS. THAT'S IN 2008 EIGHT. QUITE A BIT AGO WE'RE SAYING THE DNA TEST IS ONE OF THE BEST INVENTIONS OF THE YEAR. THERE'S BEEN WIDE SPREAD ACCEPTTANCE OF THIS IDEA THAT WE CAN DO THINGS AT THE INDIVIDUAL LEVEL TO PREDICT INDIVIDUAL HEALTH AND TO IMPROVE INDIVIDUALS. SO BUT WE'RE FALLING SHORT WE SPEND A LOT OF RESOURCES ON THIS AND ULTIMATELY WE ARE FALLING SHORT. COMPARED TO 1999, WE'RE IN 2013, WE'RE IN DIFFERENT GALAXY IN OUR UNDERSTANDING OF INDIVIDUAL DRIVERS BUT WE'RE FAR SHORT OF REVOLUTION IN GENOMICS THAT MANY PREDICTED. I CAN PUT UP SEVERAL QUOTES FROM SEVERAL LEADING SCIENTISTS IN THE FIELD. I WON'T. WE'VE HAD SUBSTANTIATE INVESTMENT SINCE 2000. AND OF COURSE WHAT'S THE BIGGEST EPIDEMIC WE ALL TALK ABOUT RIGHT NOW? OBESITY WHICH IS ALL MEDIA BEHIND INDIVIDUAL BEHAVIOR. SO WE HAVE BEEN INVESTING A LOT OF RESOURCES PREDICATED ON THE IDEA I'M PUTTING UP HERE. AND WE ARE NOT WHERE I WOULD ARGUE AN IRRATIONAL PERSON MIGHT BE ABLE TO STEP BACK AND SAY GEE WE'RE NOT WHERE WE SHOULD BE. OF COURSE WE ALL KNOW THERE'S BEEN A LOT OF RESOURCES THAT HAVE GONE INTO THINGS LIKE G WAS. THIS IS MEGA WAS WHICH WAS INCREDIBLY WELL DONE. THIS IS THE STATE OF THE SCIENCE. THERE'S ABSOLUTELY NOTHING WRONG WITH THIS PAPER. AND THE PAPER OF COURSE FINDS NOTHING. LARGE ANALYSIS OF THE PREDITION WERE ENABLE TO IDENTIFY THE FINDINGS. OF COURSE THE PAPER HAS A VERY VERY THOUGHTFUL DISCUSSION AS TO WHY THAT IS. BUT ULTIMATELY THE IMPETUS BEHIND PAPERS LIKE THIS, THE EFFORTS BEHIND IT HAVE BEEN THAT WE CAN ACTUALLY MOVE US FORWARD THROUGH INDIVIDUAL IDENTIFICATION OF INDIVIDUAL RISKS THAT CAN PREDICT INDIVIDUAL DISEASE SO THAT WE CAN IM PROVE IT. SO NOW LET ME JUST MOVE US A LITTLE BIT AWAY FROM THIS AND SAY HAVING SAID ALL THIS THERE REMAINS NO MATTER OF THE BIO MEDICAL ESTABLISHMENT, EVERYBODY IN THIS ROOM FOCUS OUR EFFORTS ON INDIVIDUALISM. THERE REMAIN PLENTY OF REASONS IF WE STEP OUTSIDE OF OURSELVES TO REALIZE THAT MAYBE IT'S NOT ALL ABOUT THE INDIVIDUAL. MAYBE IT'S NOT ALL ABOUT ME. PERHAPS THE OBVIOUS EASIEST EXAMPLE IS TO LOOK AT THINGS LIKE LIFE EXPECTANCY. THIS IS LIFE EXPECT SEE AT BIRTH. AND THIS IS ONLY FOR U.S. WHITE MEN. THIS IS JUST WHITE MEN REMOVED BLACK MEN, OTHER RACIST ETHNICITY HAVE REMOVED WOMEN AL TOGETHER. THIS IS LIFE EXPECTANCY AND THIS GOES 65 AND THIS GOES TO 80 IN THE SAME COMPANY. YOU HAVE 15 YEAR GAP IN LIFE EXPECTANCY JUST IN WHITE MEN. SOMETIMES WE SORT OF FORGET THIS BECAUSE WHEN WE TALK ABOUT GAPS AND DISPARITIES WE TEND TO CONFLATE ALL THE ISSUES OF SOAFS YOUR ECONOMIC -- THE WE WERE TO ADD BLACK MEN AND BLACK WOMEN LIKE WOMEN, THIS GAP GOES UP FROM 15 TO ABOUT 22 YEARS. I THINK INTUITIVELY WE REALIZE THIS HEATER GENEITY IN THIS COUNTRY IS NOT GIVEN BY HEATER GENEITY IN OUR CODES NOR HOUR BEHAVIORS. ULTIMATELY THERE'S SOMETHING GREATER THAN THAT. THERE'S SOMETHING HAPPENING AT THE POPULATION LEVEL THAT IS DRIVING THESE TOP LEVEL DIFFERENCES IN LIFE EXPECTANCY WITHIN THE SAME COUNTRY. WITHIN THE POPULAR PRESS THERE'S SOME RECOLLECT SNITION OF THIS. THIS IS ABOUT TEN YEARS AGO IN "NEW YORK" MAGAZINE -- AND IT WAS A PAPER WHO WROTE THIS ARTICLE AND IT WAS AN AWAKENING IN THE POPULAR PRESS AROUND THAT SOCIETY MATTERS, POPULATION MIGHT MATTER. IT'S ALMOST BEEN SUPPRESSED BUT THERE IS A STRAND OF THINKING OUT THERE AND THERE'S A STRAND OF INTUITION THAT SAYS TO US MAYBE ALL OUR EGGS IN THE INDIVIDUALIST BASKET MAY NOT BE THE SMARTEST THING AFTER ALL. LET ME MOVE ON TO THE CORE OF MY PRESENTATION. I WANT TO TALK ABOUT THE CONCEPTS AND I WANT TO TALK ABOUT THE MATHEMATICS. I'M GOING TO TALK CONCEPTUALLY FIRST OF ALL WHY CONTEXT WHICH I WOULD ARGUE IS THE HEART OF WHAT PUBLIC HEALTH SHOULD BE ABOUT. MATTERS, NO MATTER HOW MUCH WE LOVE THE IDEA OF INDIVIDUAL BEHAVIOR AND INDIVIDUAL CHANGE. THEN I'M GOING TO MOVE ON TO SHOWING YOU MATHEMATICAL SIMULATIONS THAT SHOW WHY IT IS THAT UNLESS ONE ALSO TAKES INTO ACCOUNT CONTEXT OUR ANALYSIS NATION WITH INDIVIDUAL DETERMINANTS IS INEVITABLY NOT CONCEPTUALLY BUT INEVITABLY MATHEMATICALLY GOING TO FALL SHORT IN IMPROVING THE HEALTH OF THE POPULATION. SO OUR DOMINANT APPROACH ESSENTIALLY ARGUES THE POPULATION OF GENOMIC IS GOING TO BE THE AGGREGATE OF IMPROVEMENT OF DIAGNOSIS AND CARE AT THE INDIVIDUAL LEVEL. RIGHT. THIS IS WHAT THE PERSONALIZED MEDICINE AGENDA IS ABOUT. WE'RE GOING TO IMPROVE YOU, AND IMPROVE YOU AND YOU. THEREFORE BY DOING THAT WE'RE GOING TO IMPROVE ALL OF US. WHICH AT FACE VALUE MIGHT MAKE SENSE. THERE'S ONLY ONE PROBLEM WITH THAT WHICH IS IT'S WRONG. SO LET ME SHOW YOU WHY IT'S WRONG. YOU WON'T TAKE MY WORD FOR IT SO LET ME EXPLAIN WHY IT'S WRONG. THIS IS A FOUNDATIONAL PARADIGM. OTHERS MIGHT ARGUE THERE ARE OTHER FOUNDATIONAL PARADIGM. I'M AT THE PODIUM AND THIS IS MY FOUNDATIONAL PARADIGM. THIS IS WORK ARTICULATED BEST BY JEFFREY ROSE ABOUT I GUESS 30 YEARS AGO NOW. AND HERE'S THE PARADIGM MUCH IT'S PRETTY SIMPLE. IT'S THAT THIS IS BLOOD PRESSURE AND THIS IS A CURVE OF BLOOD PRESSURE AND THESE ARE CIVIL SERVANTS. SO THE BLACK COVER ARE LONDON CIVIL SERVANTS. THIS IS ACTUAL DATA. AND WHAT YOU HAVE HERE IS YOU LOOK AT A CERTAIN NUMBER OF PEOPLE, PERCENT OF PEOPLE. WELL MOST PEOPLE SIST TALLIC BLOOD PRESSURE IS SOMEWHERE AROUND 125 RANGE. THERE ARE SOME EXTREME PEOPLE IN THE 150 AND EXTREME LOW IN THE HUNDREDS. WHAT DOES OUR RESEARCH DO? WHAT OUR RESEARCH DOES IS IT ASKS THE QUESTION TIME AND TIME AGAIN WHY IS IT THAT MR. JONES HAS A HIS TALLIC BLOOD PRESSURE OVER HERE WHILE MS. SUBMIT AS A BLOOD PRESSURE OVER HERE. SO OUR RESEARCH THAT IS THE DOMINANT RESEARCH IN BIO MEDICAL RESEARCH ESTABLISHMENT KEEPS ASKING THE QUESTION WHY ARE INDIVIDUALS IN THIS POPULATION HERE VERSUS THERE RATHER THAN ASKING THE LARGER QUESTION, WHY IS IT THAT LONDON CIVIL SERVANTS CURVE IS HERE WHILE THIS CURVE IS OVER HERE. BECAUSE WERE WE ABLE TO UNDERSTAND THAT WE MIGHT BE ABLE TO MOVE ALL OF THESE. AND OF COURSE BY DELVING DEEPER AND DEEPER INTO THE EXPLANATION WHY I EXIST HERE AND HERE, WE'RE MOVING FURTHER AND FURTHER AWAY FROM THE NOTION WHY IS THIS CURVE HERE. WELL THAT CURVE IS THERE. WHY ARE WE THERE VERSUS THERE. NOW, THIS IS CONCEPTUAL BUT LET'S TAKE THIS A LITTLE BIT MORE CONCRETELY. LET ME MOVE TO A DIFFERENT RISK FACTOR WHICH EVERYBODY RECOGNIZES. SO LET'S TALK ABOUT CHOLESTEROL. EVERYBODY HERE WHO IS OVER 40 WHICH IS MOST OF US IN THE ROOM KNOWS THERE'S A FUNNY RITUAL YOU GO TO YOUR HEALTH CARE PROVIDER. SHE TAKES A BLOOD SAMPLE AND SENDS IT OUT TO CHECK FOR CHOLESTEROL. DEPENDING ON HOW EFFICIENT YOUR HEALTHCARE PROVIDER IS IT MIGHT COME BACK THE NEXT DAY OR MY PROVIDER IN COLUMBIA IT TAKES THREE WEEKS. I DON'T KNOW WHERE THE BLOOD GOES FOR THREE WEEKS. THEN THE BLOOD COMES BACK. WHAT DOES YOUR HEALTH PROVIDER DO? SHE LOOKS AT THE RESULTS AND SAYS IT LOOKS FINE. GO HOME AND DO WHAT YOU'RE DOING. DON'T EAT BIG MACS, EXERCISE. EVERYBODY RECOGNIZES THAT ENCOUNTER. IF YOUR HEALTH PROVIDER IS ENLIGHTENED THERE MIGHT BE SOPHISTICATED HAND HOLDING THERE BUT THAT'S ROUGHLY WHAT HAPPENS. SO WHY DOES THAT HAPPEN? WHY DOES THAT RITUAL HAPPEN. WHY ARE BILLIONS OF DOLLARS SPENT IN THE COUNTRY ON THAT RITUAL. WE KNOW THAT CHOLESTEROL IS ASSOCIATED WITH HEART DISEASE. AND OUR HEALTHCARE PROVIDER WAS TAUGHT THAT IN MEDICAL SCHOOL OR NURSING SCHOOL OR WHEREVER SHE WENT. CHOLESTEROL EQUALS HEART DISEASE SO THEREFORE YOU NEED TO TAKE CHOLESTEROL AND LOWER THE CHOLESTEROL. IT COMES 23R THE STUDY YOU'RE ALL AWARE IT FROM FRAMINGHAM. THIS IS THE DATA THAT THE NOTION WE GET A CHOLESTEROL CHECK EVERY YEAR COMES FROM. SO THIS IS SERUM CHOLESTEROL, AND THIS COVER IS A CURVE OF PEOPLE WITH HEART DISEASE AND THE DARK CURVE IS PEOPLE WITHOUT HEART DISEASE. SO WHAT DO YOU SEE WHEN YOU SEE THIS? THE CURVE'S LOOKING AN AWFUL LOT ALIKE, RIGHT? NOW THIS IS THE DATA THAT HAS INFORMED WHY YOU GET YOUR CHOLESTEROL CHECK EVERY YEAR. ARE WE JUST WRONG, IS THIS JUST NUTS OR WHY IS THAT? THIS IS ACTUAL DATA. IT'S NOT NUTS. I'LL SHOW YOU WHERE IT COMES FROM. HERE IS WHERE THE NOTION THAT YOU SHOULD GET A CHOLESTEROL CHECK EVERY YEAR COMES FROM. HERE'S WHAT WE DO. WE DRAW A LINE AND WE COUNT TO THE RIGHT OF THE LINE WHICH WE CALL HIGH CHOLESTEROL AND LEFT IS LOW CHOLESTEROL. I DREW THE LINE JUST TO MAKE A POINT HERE. WE COUNT THE NUMBER OF PEOPLE HEART DISEASE UNDER THE DOTTED LINE WHO ARE TO THE WRITE OF THE LINE HIGH CHOLESTEROL. WE CALL THOSE PEOPLE DISEASE HEART DISEASE AND EXPOSED. THEY GO TO THE DISEASE EXPOSED TWO BY TWO TABLE MUCH EVERYBODY SEE THAT. WE COUNT TO PEOPLE WHO ARE TO THE RIGHT OF THE LINE WHICH MEANS THEY ARE DISEASED. I'M SORRY THEY ARE EXPOSED BUT NOT DISEASED. SO THEY GO TO EXPOSED NON-DISEASE. WE COUNT THE PEOPLE TO THE LEFT OF THE LINE WHO ARE UNEXPOSED NON-DISEASED AND THE LEFT OF THE LINE WHO ARE DISEASED AND UNEXPOSED. WE FILL OUR TWO BY TWO TABLE. THIS BY THE WAY IS THE REASON THE DEPARTMENTS LIKE THE ONE I RUN EXIST. PEOPLE PAY LOTS OF MONEY TO GET DOCTORS. I'M GIVING IT TO YOU ALL HERE FOR FREE. NOW EVERYBODY SEE D IS BIGGER THAN C AND A IS BIGGER THAN B. IF YOU LOOK AT THE TWO BY TWO TABLE THE ODDS RATIO IS A TIMES B DIVIDED BY B TIMES C. A TIMES B DIVIDED BY B TIMES C. THAT'S CARDINAL MEASURE OF RELATIVE ASSOCIATION. WELL AD IS BIGGER THAN BC SO AD OVER BC IS BIGGER THAN ONE. WHICH MEANS THERE'S AN ASSOCIATION BETWEEN HIGH CHOLESTEROL AND HEART DISEASE. SO THE MULTIPLE CHOICE QUESTION THAT YOUR HEALTHCARE PROVIDER GOT CORRECT ON HER EXAM AND MEDICAL SCHOOL, THEY'RE RIGHT. THERE'S AN ASSOCIATION BETWEEN CHOLESTEROL AND HEART DISEASE. WHAT'S THE PROBLEM? WHY AM I BORING YOU WITH THIS? WELL THE PROBLEM IS THAT ASSOCIATION IS TRUE AT THE POPULATION LEVEL. AND THE INDIVIDUAL LEVEL IT TELLS YOU NEXT TO NOTHING AS TO WHETHER I WITH THE SERUM CHOLESTEROL OF 270 AND ON THE BLACK COVER OR THE DOTTED CURVE. SO THE NOTION THAT RISKS IDENTIFIED AT THE POPULATION LEVEL ARE GOING TO SUFFICE, PREDICT INDIVIDUAL DISEASE ARE GOING TO SUFFICE TO GUIDE US TO WHO WE SHOULD INTERVENE ON SO WE CAN IMPROVE OURSELVES ONE INDIVIDUAL AT A TIME IS FUNDAMENTALLY FLAWED. NOW YOU'RE ALL THINKING CHOLESTEROL, I KNOW THAT'S JUST PART, WE ARE ALL KNOW CHOLESTEROL IS ONE OF MANY RISK FACTORS. YOU'RE SYM FIX THE ARGUMENT, I'VE HEARD ALL THIS BEFORE. GENES ARE DIFFERENT. ASK NOT JUST GENES. THE DON'T JUST TELL US GENE, TALK TO US ABOUT COMPOSITE SCORES. LET'S THANK YOU ABOUT GENETIC RISK SCORES. THIS IS WHERE THE ACTION IS, I AGREE. SO OUR GENES BEHAVE DIFFERENTLY. LET'S GO TO ONE OF MY FAVORITE PAPERS. AN ASTONISHING PAPER. THIS LOOKS AT GENOTYPE SCORES AND INCIDENCE OF DIABETES. WHAT THIS MAY DID IS THEY LOOKED AT MULTIPLE GENES, THEY RATED A GENOTYPE SCORE AND THEY SHOWED THIS BEAUTIFUL DOSE RESPONSE RELATIONSHIP MUCH EVERYBODY SEE IT. MORE GENOTYPE SCORE MORE LEADS TO DIABETES. THE PAPER SAID THIS IS THE KIND OF THING THAT EPIDEMIOLOGISTS JUST LOVE. THIS IS THE KIND OF THING THERE'S A REASON WHY EXCESS. MORE GENOTYPE SCORE -- I SHOULD GO TO 23 AND ME GET MYSELF GENOTYPE SO I CAN FIGURE OUT MY GENOTYPE SCORE. THIS IS THE SYLLOGISM. WE SEE THIS AND WE SAY GET ME 23 AND ME. GET ME THE VALUABLE, VALUABLE HEALTH INFORMATION THAT CAN IMPROVE MY HEALTH AND YOU SHOULD DO THE SAME AND YOU SHOULD DO THE SAME SO WE CAN EACH IMPROVE OUR HEALTH SO WE CAN COLLECTIVELY IMPROVE OUR HEALTH. NOW THE REASON THIS PAPER'S SO BRILLIANT IS BECAUSE TOGETHER WE'RE SHOWING THIS BIGGER. THEY ALSO SHOW THIS FIGURE. THAT'S THE GENOTYPE SCORE. THE DARK LINE IS PEOPLE WITH DIABETES, THE GRAY LINE IS PEOPLE WITHOUT DIABETES. NOW THESE POINTS THAT I'M MAKING, THERE'S NOTHING PARTICULARLY SOPHISTICATED ABOUT THESE. THESE ARE FOUNDATIONAL POINTS ABOUT THE RELATIONSHIP BETWEEN POPULATION LEVEL RELATIVE MEASURES OF ASSOCIATION AND THEIR CAPACITY TO PREDICT INDIVIDUAL DISEASE. IN FACT, NONE OF THIS WOULD MATTER IF IT WAS NOT FOR THE FACT THAT OUR FASCINATION WITH THE INDIVIDUAL PREDICATED PRINCIPALLY ON OBSERVATIONS LIKE THIS ONE, A LONG TIME AGO CHOLESTEROL ON A GREATER INTEREST IN GENOMICS AND A GREATER INTEREST OF IMPROVING THE HEALTH OF INDIVIDUALS HAVE NOT STEERED OUR GOOD SHIP BIO MEDICINE IN A DIRECTION WHERE WE'RE FOCUSING SO MANY OF OUR EGGS IN THIS PARTICULAR BASKET OF IDENTIFYING INDIVIDUAL DRIVERS FOR THE PURPOSES OF IMPROVING INDIVIDUAL HEALTH. AND THE PROBLEM WITH THAT IS THAT THE PREMISE IS BASED ON A FLAWED CONCEPT. THAT JUST DOES NOT HOLD IS I'M SHOWING YOU HERE. YES? >> [INDISCERNIBLE] >> CORRECT, CORRECT. NO -- THAT'S CORRECT. I'M BEING CONSISTENT WHICH I TRY TO DO MOST OF THE TIME EXCEPT MY CHILD RAISING. I'M TRYING HARD AS POSSIBLE NOT TO MESS MY KIDS UP. SO HERE'S THE QUESTION. THE QUESTION IS OKAY HAVING SAID ALL THIS, SURELY THERE'S SOME LEVEL AT WHICH YOU EPIDEMIOLOGISTS ARE GOING TO FIND A MEASURE OF ASSOCIATION THAT MAKES YOU SATISFIED THAT IT CAN TELL YOU WHO ACTUALLY HAS DISEASE AND WHO DOESN'T, RIGHT. SO WHAT ODDS RATIO DO YOU THINK WE NEED IN ORDER TO SAY LOOK, WE SEE THIS AT THE POPULATION LEVEL AND FOR GOODNESS SAKES IT'S A MULTIPLE CHOICE FACTOR X IS ASSOCIATED WITH Y AND THE CAN DEPOSITS WHEN A PATIENT COMES INTO MY OFFICE AND SHE HAS FACTOR X, I KNOW SHE'S GOING TO HAVE DISEASE Y. I'M NOT GOING TO ASK YOU TO PRETEND BUT JUST THINK TO YOURSELVES WHAT ODDS RATIO THAT IS AND HERE'S THE ANSWER -- IT'S ALL SIMPLE AND MATHEMATICAL MODELING. WHAT YOU HAVE HERE IS DISEASE, NON-DISEASE -- YOU NEED AN ODDS RATIO AT 350 IN ORDER FOR YOU TO HAVE WHAT I WOULD CALL CURVE SEPARATION. IN ORDER FOR YOU TO HAVE THE CONFIDENCE THAT THE POPULATION LEVEL OF OBSERVATION IS ASSOCIATED WITH INDIVIDUAL DISCRIMINATION OF PEOPLE WITH AND WITHOUT DISEASE. TWO, MAKE THE SYLLOGISM WHICH I ARGUE UNDERLIES A LOT OF OUR PERSONALIZED MEDICINE CONCEPT VALID. AND OF COURSE YOU'RE ALL -- WHICH MEANS YOU'RE ALL INVOLVED IN EITHER RESEARCH INTERNALLY OR EXTERNALLY AND I WILL LET YOU ALL THINK BACK TO HOW MANY STUDIES YOU'VE BEEN INVOLVED WITH AN ODDS RATIO OF 350. I KNOW IT'S HARD FOR ME TO DO ANY STUDIES -- I KNOW THAT. IF I DID IT'S A POOR RETURN OF YOUR INVESTMENT ON THIS. THIS IS ESSENTIALLY CURVE SEPARATION WE JUST DON'T SEE. WE DON'T SEE IT I DON'T WANT SOME COMMON GENE VARIANCE ESSENTIALLY WHICH WE NOW DISCOVERED. OKAY. NOW I JUST WANT TO MAKE ONE MORE MOMENT ON CONCEPTS BEFORE I MOVE TO THE MATHEMATICS. ALTHOUGH WE KNOW THAT THE ROLE OF GENES IN HUMAN HEALTH IS COMPLEX, WE KNOW THIS. WE PLAY-WE KNOW THE INPOON OF ANY LOCUS IS UNDERSTOOD IN CONCEPT WITH OTHER LOCI. WE KNOW OTHER ENVIRONMENTAL FACTORS MATTER. OUR DOMINANT APPROACH IN OUR RESEARCH PARADIGM IS TO TRY TO DEVISE WAYS WHICH WE CAN BETTER UNDERSTAND INDIVIDUAL GENETICS BY FOCUSING ON EVER NARROWER SAMPLES. THIS IS IF YOU THINK ABOUT IT REALLY UNDERLIES MUCH OF WHAT WE DO TO TRY TO BETTER ISOLATE INDIVIDUAL DRIVERS. WE RECOGNIZE THESE COMPLEXITIES SO WHAT WE TRY TO DO IS WE TRY TO NARROW IT NARROWER -- EPIDEMIOLOGY CALLED COMPOUNDING BUT REALLY GETTING AT THE SAME CONCEPT. AND FUNDAMENTALLY THE POINT IS, AND THIS IS ACTUALLY A PAPER THAT'S NOW IN PRESS WHICH WAS TRIGGERED BY WORK THAT WAS DONE HERE. FOR EXAMPLE PAPERS ON -- MODIFICATION DISORDERS OF SUICIDE THERE ARE -- CASE CONTROL STUDIES ONLY THREE OF THEM COLLECT ANY INFORMATION BEYOND THE CORE MOLECULAR PROCESS AND THE OUTCOME. AND IF YOU THINK ABOUT THIS, YOU REALIZE THAT NO AMOUNT OF STRATIFICATION, NO AMOUNT OF RESTRICTION IS ULTIMATELY GETTING RID OF THE CONFOUND THAT A COMPANY, THE DISTRIBUTION, NOT JUST OF THE INDIVIDUAL FACTOR OF INTEREST AS WELL AS THE OUTCOME OF INTEREST AS WELL AS THE POTENTIAL LOCUS OF INTEREST. SO THIS IS A SIMPLE BAG LOOKING AT THE ENVIRONMENT OUTCOME WITH GENETIC LOCALS OF INTEREST. WHAT WE FORGET IS THERE'S A VIRD VARIABLE WITH THE ENVIRONMENT WITH 9 LOW SPECIFY AS WELL AS THE OUTSIDE. NO AMOUNT OF STRAIGHT -- STRATIFICATION ALLOWS US TO DO THAT -- DIFFERENT GENO TYPES. THESE ARE PEOPLE WITHOUT PHYSICAL ACTIVITY AND ON THIS SIDE IS PEOPLE WITHOUT PHYSICAL ACTIVITY. THIS DOESN'T REALLY MATTER MUCH FOR BMI BUT IT MATTERS QUITE A BIT WHEN YOU HAVE LOW PHYSICAL ACTIVITY. THE OTHER PART OF THIS IS THAT WE KEEP FORGETTING THE THIS IS -- INCIDENCE OF COMPOUNDING OVER TIME. THIS ALL TAKES PLACE OVER TIME AND IF YOU, ACTUALLY I'LL GET THAT IN A SECOND. IF YOU IGNORE THE EFFECT OF TIME YOU'RE INEVITABLY MISSING CERTAIN CONFOUND. WE KEEP INVESTING MORE AND MORE MONEY IN BETTER MOUSE TRAPS. IN BETTER SEQUENCING APPROACHES. MAYBE IT'S WHOLE GENOME SEQUENCING, MAYBE IT'S EXOME SEQUENCING. MAYBE ONE OF THEM ARE GOING TO GET US UNDERSTANDING THE INDIVIDUAL DRIVERS OF INDIVIDUAL HEALTH. AND THE POINT I'M MAKING HERE NOT THAT THOSE METHODS ARE NOT VALID. OF COURSE THEY'RE VALID. OF COURSE THEY'RE IMPORTANT AND HELP US UNDERSTAND MECHANISMS. BUT THEY'RE NOT GETTING AT ALL AT THE NOTION OF IMPROVING HEALTH OF POPULATIONS BECAUSE CONCEPTUALLY NO MATTER HOW GOOD YOU GET AT IDENTIFYING INDIVIDUAL CHARACTERISTICS YOU'RE NOT GOING TO BE ABLE TO PREDICT INDIVIDUAL HEALTH. OKAY. LET ME NOW FORMALIZE THESE CONCEPTS. AND I WANT TO MOVE ON TO MATHEMATICAL SIMULATIONS. TALKING ABOUT THE LIMITS OF INDIVIDUALS PREDICTION. WHAT I'M GOING TO DO IS I'M GOING TO TRY TO SHOW YOU SOME SIMULATIONS THAT WE DID. IT'S A VERY SIMPLE SIMULATIONS AND THEY REST ON VERY SIMPLE ASSUMPTIONS. THE ASSUMPTIONS ARE AS FOLLOWS. FIRST OF ALL THAT THERE ARE THREE DRIVERS THAT MATTER, ONLY THREE. ONE OF THEM IS GENES, THE OTHER ONE IS SOCIETY, SOCIETAL ACTIVITY LEVELS AND THE OTHER ONE IS INDIVIDUAL DIETARY CHOICES. SO THE ASSUMPTION IS, WHICH I THINK REASONABLE SCIENTISTS, REASONABLE BIO MEDICAL FOLKS WILL AGREE THAT SORT OF ALL OF THIS MATTERS. SO THE ONLY CORE ASSUMPTION HERE IS THAT SOCIETAL ACTIVITY LEVELS ENVIRONMENT MATTERS AND GENES MATTER. NOBODY IS DISAGREEING WITH THAT. WE'RE ALL SORT OF ON THE SAME PAGE. SO I'M GOING TO MODEL FROM A LOW GENETIC INFLUENCE TO A HIGH GENETIC INFLUENCE. I'M ALSO GOING TO MODEL SOCIETAL ACTIVITY LEVELS. NOW MY PICK TOE GRAPHS ARE MISLEADING. I'M NOT MODELING WHETHER THE INDIVIDUAL EXERCISES, WHETHER THE INDIVIDUAL DOES NOT INDIVIDUAL EXAMINER CISE. I'M MODELING WHETHER THE ENVIRONMENT IS CONDUCIVE TO THE INDIVIDUAL EXERCISE OR THE INDIVIDUAL NOT EXERCISE. SO IT'S ACTUALLY REALLY HARD TO FIND FIGURES THAT DO THAT SO THAT'S WHAT I'M TRYING TO GET AT. WHAT I'M FOCUSING ON HERE IS INDIVIDUAL DIETARY CHOICES WHICH I SYMBOLIZED HERE WITH A BIG MAC EATING AND THE CARROT EATING, TWO EXTREMES OF THE PLEASURE SPECTRUM. I'M GOING TO FOCUS ON OBESITY AND I'M GOING TO SHOW YOU MODELING RESULTS FROM A MILLION SIMULATIONS OF POPULATIONS OF A HUNDRED THOUSAND PEOPLE EACH WHICH ARE, HAVE AN UNDERLYING CAUSAL STRUCTURE THAT SAYS GENES AND ENVIRONMENTS GO TOGETHER AND ARE INFLUENCED BY INDIVIDUAL DIETARY BEHAVIORS. I'M GOING TO START WITH RELATIVE RISKS. HERE'S WHAT I'M GOING TO SHOW YOU. I'M GOING TO SPEND SOME TIME SETTING THIS UP BECAUSE I WILL SHOW YOU A LOT OF THE GRAPHS WHICH GETS A LITTLE BIT CONFUSING. THIS IS RELATIVE RISKS AND HERE ON THIS AXIS I'M GOING TO SHOW YOU THE POPULATION PREVALENCE OF EATING JUNK FOOD, OKAY. SO IF IT'S OVER HERE, 90% OF PEOPLE EAT BURGERS. OVER HERE 20 PERCENT OF PEOPLE E BURGERS IN POPULATIONS. SO I NEED TO REMEMBER THAT AS I'M GOING TO SHOW YOU THE SIMULATIONS. I'M GOING TO THEN ASK A QUESTION, I'M GOING TO ASK THE QUESTION WHAT'S THE RELATIVE RISK OF OBESITY, GIVEN JUNK FOOD EATING AT DIFFERENT LEVELS OF POPULATION PREVALENCE OF JUNK FOOD EATING. WHAT'S THE RELATIVE RISK OF OBESITY GIVEN YOUR EATING JUNK FOOD. IF YOU EAT JUNK FOOD YOU ARE X TIMES MORE LIKELY TO GET FAT VERSUS IF YOU'RE NOT EATING JUNK FOOD. AT DIFFERENT PREVALENCES OF JUNK FOOD EATING. AND I'M GOING TO SHOW YOU THAT AT DIFFERENT LEVELS OF GENETIC INFLUENCE AND DIFFERENT LEVELS OF ENVIRONMENTAL LIKELIHOOD OF PEOPLE WORKING OUT AND PEOPLE BEING SEDENTARY. THE REASON I'M SETTING THIS UP SLOWLY IS I WANT EVERYBODY TO NATURAL THE MOMENT AND I WANT TO THINK ABOUT WHAT YOU'RE GOING TO SEE. AHEAD OF MY SHOWING YOU THE SIMULATION, WHAT DO YOU THINK THE FINDINGS ARE GOING TO SHOW BASED ON YOUR PRECONCEPTIONS ABOUT HOW THE ROLE INDIVIDUAL BEHAVIOR PLAYS. SO, THIS IS MORE BURGER EATING, THIS IS MORE CARROT EATING. MOVING THIS UP HERE AND THEN I'M GOING TO SHOW YOU THIS AT LEVELS OF MORE SEDENTARY ENVIRONMENT, MORE ACTIVE ENVIRONMENT, HIGHER GENETIC INFLUENCE, LOWER GENETICKIC INFLUENCE. NOW OBVIOUSLY IN ALL THIS MODELING, EVERYTHING IS CONTINUOUS. BUT IF I WERE TO SHOW YOU A CONTINUOUS RESULT IT'S M SPACE WHICH I CAN'T DO SO I'M CATEGORIZING TO SHOW YOU MY MOMENT. I'LL SHOW YOU ONE, TWO, THREE WHICH MEANS I'M GOING TO SHOW YOU NINE OF THESE GRAPHS, OKAY. TO READ THIS IS UP HERE IS HIGH GENETIC INFLUENCE IN A SEDENTARY ENVIRONMENT. DOWN HERE IS LOW GENETIC INCIDENCE IN AN ACTIVE GENETIC ENVIRONMENT. THAT'S HOW THESE GRAPHS READ. SO WHAT DO YOU SEE WHEN YOU DO THIS MODELING, AND THIS IS AGAIN PRETTY STRAIGHTFORWARD MODELING. THIS IS A PAPER IN REVIEW BUT YOU COULD ALSO ALL DO THIS AT HOME AND AT YOUR DESK. SO WHAT IS THE RELATIVE RISK OF OBESITY GIVEN JUNK FOOD EATING AT DIFFERENT LEVELS OF POPULATION PREVALENCE OF JUNK FOOD EATING. SO HERE'S WHAT WE SEE. SO HERE'S WHAT WE SEE. SO WHAT'S THE FIRST OBSERVATION EVERYBODY MAKE. THE FIRST OBSERVATION EVERYBODY MAKE IS THESE LINES ARE ALL FLAT. EVERYBODY SEE THAT? THESE LINES ARE ALL FLAT. NOW WHAT'S THE IMPLICATION OF THAT. THAT ACTUALLY IS QUITE A DRAMATIC IMPLICATION BECAUSE WHAT IT MEANS IS THAT THE POPULATION PREVALENCE OF EATING BURGERS MAKES NO DIFFERENCE FOR THE RELATIVE RISK OF OBESITY GIVEN BURGER EATING. IN ANY OF THESE CONDITIONS. NOW WHAT DOES IT MATTER? WELL HERE'S WHY IT MATTERS. BECAUSE WHAT HAS BEEN LARGELY OUR NATIONAL RESPONSE TO THE EVEN DEPARTMENTIC, OUR NATIONAL RESPONSE TO EPIDEMIC LARGELY HAS BEEN THOU SHALT NOT EAT BURGERS. CONCEPTUALLY OUR APPROACH IS FOCUSING ON THE INDIVIDUAL TELLING ME THOU SHALT NOT EAT BURGERS. BY MAKING UNITY BURGERS WE'LL RULES THE -- BUT THESE LINES ARE FLAT AT ALL LEVELS. OBSERVATION ONE IS THE PREVALENCE OF JUNK FOOD EATING NEVER MATTERS TO THE RISK OF OBESE THEY AND JUNK FOOD. OBSERVATION TWO WHEN GENETIC INFLUENCE IS LOW WHICH I THINK WE'D ALL AGREE IN THE CONTEXT OF OBESITY IT'S THE ONLY PLAUSIBLE SCENARIO. NOBODY IS OUT THERE ARGUING THAT THERE'S HIGH GENETIC INFLUENCE ON OBESITY. NOBODY'S ARGUING THAT THIS IS THE CASE. REALLY DOWN HERE IS WHAT'S REALISTIC. THE RISK OF OBESITY FOLLOWING JUNK FOOD EATING IS HIGH ONLY IN THE ENVIRONMENT OF SEDENTARY LIFE-STYLE. EVERYBODY SEE IT. WHEN THE ENVIRONMENT IS SEDENTARY, THESE RISKS ARE HERE NOW IN THE 40'S. WHEN THE ENVIRONMENT IS ACTIVE, ARE THESE RISKS ARE LOW. SO NOT ONLY DOES THE DIFFERENT PREVALENCE MUST MATTER, THE RISK OF OBESITY GIVEN JUNK FOOD EATING IS NOT PARTICULARLY HIGH IN A HIGHLY ACTIVE ENVIRONMENT. IN THE THIRD, GENETIC INFLUENCE REALLY UPDATE THE ENVIRONMENT ONLY UNDER COMMON VARIANT CONDITION UP HERE WHICH IS IMPLAUSIBLE. I THINK THERE'S NO ARGUMENT IT'S IMPLAUSIBLE. SO THE COMMON -- THERE'S AN ASSUMPTION THERE'S A COMMON GENETIC VARIANT ASSOCIATED WITH A COMMON PHENOTYPE. IN OBESITIES EVERYBODY ACT DGESZ IT'S NOT A COMMON DISEASE. THERE'S NO ARGUMENT. SO THEREFORE UNDERSTANDING THE PREVALENCE OF JUNK FOOD EATING TELLS US VERY LITTLE ABOUT THE CONTRIBUTION OF JUNK FOOD TO RISK OF OBESITY WITHOUT UNDERSTANDING THE ENVIRONMENT. NOW I THINK THE MOTION THAT GENES AND ENVIRONMENTS GO TOGETHER IS NON-CONTROVERSIAL. IT'S NON-CONTROVERSIAL AMONG SCIENTISTS WHO STUDY ONLY GENETIC INFLUENCES. IT'S STILL NOT CONTROVERSIAL. WHAT I'M TRYING TO EXTRACT THOUGH IS THAT MATHEMATICALLY ONCE YOU ACCEPT THE CONCEPT, THAT GENES AND ENVIRONMENTS GO TOGETHER, YOU NEED TO THEN RECOGNIZE THAT UNDERSTANDING THE PREVALENCE OF A PARTICULAR BEHAVIORAL FACTOR TELLS YOU LITTLE ABOUT THE CONTRIBUTION OF THE BEHAVIORAL FACTOR TO RISK OF THE COMPLEX PHENOTYPE WITHOUT UNDERSTANDING THE ENVIRONMENT. AND THIS IS THE STEP THAT WE KEEP FAILING TO REACH. NOW LEFT ME TAKE THE RELATIVE RISKS AND BREAK THEM DOWN INTO CONSTITUENT RISKS. SO WE CAN ACTUALLY SEE WHAT'S DRIVING THIS. IS THE DRIVER WHAT I'M SHOWING YOU THE RISK OF OBESITY AMONG THOSE WHO EAT JUNK FOOD. OR THE RISK OF OBESITY AMONG THOSE WHO DON'T EAT JUNK FOOD. I WAS SHOWING YOU RELATIVE RISK RIGHT. THERE'S THE NUMERATOR AND DENOMINATOR. I'M NOW GOING TO BREAK THEM DOWN TO SHOW YOU THE CONSTITUENT RISKS. IN DOING THAT OF COURSE I'M GOING TO DOUBLE THE NUMBER OF LINES. WE NOW HAVE A NUMERATOR RISK AND DENOMINATOR RISK. LET ME NOW BREAK IT DOWN. SO IF YOU LOOK AT THIS, THE BLUE LINE IS THE RISK OF OBESITY GIVEN JUNK FOOD EATING. FOR THOSE IN THE BACK IT'S PD GIVEN A AND THE RED LINE IS THE RISK OF OBESITY GIVEN NO JUNK FOOD EATING PD GIVEN NON-A. NOW WHAT DO YOU SEE HERE? THE FIRST THING YOU SEE AGAIN ARE THE LINE ARE FLAT ALL AROUND. BUT THE SECOND THING YOU SEE WHAT'S REALLY CHANGING IS THE BLUE LINE. WHAT'S CHANGING IS THE NUMERATOR. WHAT'S CHANGING IS THE RISK OF OBESITY JUNK FOOD EATING. SO AGAIN OBSERVATION ONE. THE PREVALENCE OF JUNK FOOD EATING -- NEITHER THE RED LINE NOR THE BLUE LINE ARE SLOANING HERE. SECOND OBSERVATION UNDER CONDITIONS OF LOW HERIT BILLITY THE RISK OF OBESITY THOSE EATINGIAN FOOD IS DRIVEN ENTIRELY WHETHER ENVIRONMENT PROMOTES SEDENTARY LIFE-STYLE. THAT'S WHERE THE RISK OF OBESITY GIVEN JUNK FOOD EATING IS HIGH. NOW YOU MIGHT SAY OKAY BUT YOU'RE TALKING ABOUT RELATIVE RISKS. THE PROBLEM WITH RELATIVE RISKS THE GENOLOGISTS LIKE RELATIVE RISKS. THEY'RE NOT APPLICABLE TO THE SUBSTRATE OF PUBLIC HEALTH. PUBLIC HEALTH ULTIMATELY IS ABOUT THE POPULATION ATTRIBUTABLE FACTION, THE POPULATION ATTRIBUTABLE TO RISK WHICH TELLS US WHAT PROPORTION OF A PARTICULAR DISEASE IS ASSOCIATED WITH A PARTICULAR EXPOSURE. NOW FOR THOSE OF YOU WHO DON'T REMEMBER PAVMENT R OR PAR REPRESENTS THE OUT COME ATTRIBUTABLE TO THE EXPOSURE AND HERE'S THE AGAIN FORMULA. WHY ARE BF'S IMPORTANT. THEY HAVE BEEN INSTRUMENTAL IN THIS COUNTRY IN SHAPING OUR HEALTH AGENDA. HEALTHY PEOPLE WAS INFORMED IN NO SMALL DEGREE BY VERY INFLUENTIAL PAPER CAME OUT OF THE CDC IN 1993 WHICH CALCULATED THE CAUSES OF DEATH IN THE UNITED STATES. IT WAS REPLICATED IN 2004 AND CONCEPTUALLY IT REMAINS -- WHAT THEY SHOWED IS THEY SAID WELL THE CAUSES OF DEATH ARE NOT REALLY HARD DISEASE AND STROKE IN CANCER. WHAT THE CASES OF DEATH ARE TOBACCO, POOR DIET -- 1990 AND 2000. THIS PAPER A LOT OF IT WENT INTO PEOPLE IN 2010 TO SET TARGETS ON THINGS LIKE TOBACCO, DIET ETCETERA. SO PAFs ARE A WAY IN WHICH WE TRY TO ATTRIBUTE CAUSES OF DEBT -- IT'S NOT A MARGINAL APPROACH BUT ARE CENTRAL TO THE APPROACH. I WANTED TO TAKE WHAT I'M SHOWING YOU AND TURN IT TO PAFs. HERE IS TAKING WHAT I SHOWED YOU, TAKING IT TO PAFs. WHAT DO YOU SEE HERE? FIRST OF ALL THE PROPERSON OF OBESITY AND JUNK FOOD EATING NOW TURNING TO PAF IN POPULATION IS NOT ASSOCIATED WITH THE POPULATION EATING JUNK. OBSERVATION TWO -- IS DRIVEN LARGELY AGAIN BY OVERALL ACTIVE SEDENTARY CONDITIONS. YOU SEE THIS IS HIGHER HERE AND IT GOES LOW FURTHER. SO THEREFORE WHAT DO WE GET PRO THESE SIMULATIONS? THAT REDUCING THE PREVALENCE OF JUNK FOOD EATING IN THE POPULATION IS NOT PARTICULARLY RELEVANT TO REDUCING THE RISK OR POPULATION ATTRIBUTABLE TO THE RISK OF OBESITY SECONDARY TO JUNK FOOD EATING. IT'S THEREFORE IMPOSSIBLE TO PREDICT WHO IS GOING TO DEVELOP OBESITY WITHOUT FORMING THE ENVIRONMENTAL DRIVERS OF THE DISEASE. THE CENTRAL POINT WHICH I KEEP COMING BACK TO IS THIS, IF WE SAY LET'S ALL AGREE THAT ALL -- I WOULD SUSPECT THAT'S LARGELY ARGUABLE IN 99.99% IN THIS BUILD AND MY INSTITUTION AND OTHER ACADEMIC INSTITUTIONS AROUND THE COUNTRY. WE ALL AGREE ON THAT BUT THAT STATEMENT IN IT EMBEDS THE OBSERVATION THAT ENVIRONMENTS ARE INEVITABLE IN OUR CALCULUS TO UNDERSTAND WHAT PRODUCES HEALTH IN POPULATIONS. AND OUR QUEST DETERMINES INDIVIDUALS HEALTH BASED ON INDIVIDUAL DRIVERS ONLY IF FLAWED CONCEPTUALLY AND FLAWED MATTMATICALLY. BEING IN CHARGE OF A DEPARTMENT CHALLENGES THAT AND I THINK WE'RE COMING AROUND TO COMPLEX MATTERS. THE PAPER THE MEGA WAS OF THE EXPRESSION, WHAT I LIKE OF THE PAPER HAS A SOPHISTICATED DISCUSSION. IT SAYS IN IT IT'S POSSIBLE THAT DEPRESSION CAN ONLY BE IN ORDER IF VEET RISK FACTORS ARE MODELED SIMULTANEOUSLY. I AGREE WITH EVERYTHING IN THIS STATEMENT EXCEPT FOR THE ONE WORD AND THE WORD IS POSSIBLE. IT'S NOT POSSIBLE, IT'S ACTUALLY INEVITABLE. GO BACK TO USE OF THE WORD OF INEVITABILITY IN PERSONALIZED MEDICINE. THE MORE CORRECT VERSION OF THE STATEMENT IS YOU CAN NOT UNDERSTAND THE PRODUCTION OF DEPRESSION OR ANY OTHER PHENOTYPE OF INTEREST IF YOU DO NOT -- ANY FACTORS COMING IN FOR INDIVIDUAL PROJECTION IS JUST WRONG. GOING BACK TO THE PAFS I SHOWED YOU, WE ACTUALLY PUBLISHED A PAPER FOLLOWING UP ON THAT -- FRACTIONS WITH SOCIAL CAUSES WHERE WE CALCULATED USING THE EXACT SAME METHODS -- THIS IS A DEEPLY FLAWED PAPER. BUT IT IS NOT ANYMORE FLAWED IN THE PAPER THAN ON WHICH THE HEALTH OF PEOPLE IN 2010 WERE BASED. IF YOU'RE LIKE ME YOU CAN'T REMEMBER HOW MANY PEOPLE DIED OF WHATEVER. IT'S EITHER A LOT OR A LITTLE. THIS IS OUR PAPER AND THIS IS JUST THINGS FROM WHAT WE KNOW PEOPLE DIE OF JUST TO GIVE YOU A SENSE OF THIS MAGNITUDE. ROUGHLY THE SAME NUMBER OF PEOPLE DIE FROM MYOCARDIAL INFUNCTION -- RACIAL SEGREGATION. THE ONLY REASON I'M SHOWING YOU TO MAKE A POINT IS THERE IS IN ALL THIS THERE IS STILL A STRAIN OF WORK TRYING TO BRING BACK THE MOTION OF ENVIRONMENT THAT IS A CAUSE OF THAT AND NEEDS TO BE CONSIDERED. NOT MAY BE BUT HAS TO BE CONSIDERED IN UNDERSTANDING OF THE PRODUCTION OF THE HEALTH OF POPULATIONS. I PAUSE BEFORE I COMPLETE. IF I'M RIGHT ON ALL THIS, AND I SUSPECT SOME OF YOU DON'T THINK I'M RIGHT BUT THAT'S FINE. HOW DID WE GET HERE. WHY ARE WE IN PLACE THERE'S EVEN A NEED FOR ME TO BE GIVING THIS KIND OF TALK. I THINK WE GOT HERE WITH VERY REASONABLE REASONS BECAUSE WE THINK IT'S SOMETHING VERY COMPELLING. THIS IS THE DEFINITION OF COMPELLING WHICH EVOKES ATTENTION -- INSPIRING CONVICTION. I ACTUALLY THINK WHAT I STARTED WITH IS IMMENSELY COMPELLING. THE MOTION THAT I CAN GET VALUABLE HEALTH INFORMATION THAT CAN HELP MAKE MY HEALTH BETTER IS IMMENSELY COMPELLING AND IT INSPIRES CONVICTION AND INVOKES ADMIRATION. IT'S POWERFULLY IRRESISTIBLE. THE MOTION I CAN BE MY OWN GYM APART FROM THE STRESS INVOLVED THERE AND ACTUALLY MAKE MY HEALTH BETTER IS POWERFULLY COMPELLING. TO HELL WITH POPULATIONS, I WANT MY HEALTH BETTER. REMEMBER BACK TO THE CODE I STARTED FROM? MY HEALTH IS URGENT. I DON'T THINK THERE'S ANYTHING PARTICULARLY NOT FROM THE PATH WE'VE GONE DOWN I THINK IT'S A FAIRLY RATIONAL PATH. THE PROBLEM WITH IT IS THAT IT IS PREDICATED ON SOME FLAWED ASSUMPTIONS ABOUT THE CON SENSE AND MATH LIMITS OF PREDICTION. SO WHY DOES THIS MATTER? ALL OF THIS COULD BE AN INTELLECTUAL EXERCISE. ALL INSTITUTIONS HAVE ROUNDS AND INVITE PEOPLE TO SPEAK. I THINK IT MATTERS QUITE A BIT. THIS IS A QUOTE FROM RICHARD FOSTER. I DON'T KNOW IF PEOPLE KNOW WHO RICHARD FOSTER IS BUT HE'S THE MOST POWERFUL UNKNOWN PERSON IN AMERICA. RICHARD FOSTER IS THE U.S. CHIEF -- HERE'S A REPORT PUBLISHED UNDER AFFORDABLE CARE ACT. RICHARD FOSTER SAYS THERE'S NO CONSENSUS IN LITERATURE AMONG EXPERTS THAT PREVENTION OF HEALTH EFFORTS RESULTS IN LOWER COSTS. WHEN THE AFFORDABLE CARE ACT BATTLE WAS TAKING PLACE HERE IN WASHINGTON. THIS WE AND BY WE I MEAN THE ENTIRE BIOMEDICAL COMMUNITY, A ALLOWED RICHARD FOSTER PRESUMABLY A WELL MEANING PERSON TO HAVE TO SAY ABOUT US THAT YOU ALL IN THE BIO MEDICAL ESTABLISHMENT HAVE GIVEN ME NOTHING TO WORK O I ACTUALLY DON'T KNOW WHETHER PREVENTION WELLNESS EFFORTS RESULT IN LOWER COSTS OR HIGHER COSTS. NOW WHY HAVEN'T WE GIVEN HIM THIS. IT'S NOT HIS JOB TO COME UP WITH THAT, IT'S OUR JOB ROUGHLY. WHY HAVEN'T WE DONE THIS. WE'VE BEEN DISTRACTED, WE'VE HAD A RIVETTING DISTRACTION WHERE WE'VE BEEN FOCUSING ON THE INDIVIDUAL. SO I THINK IT'S NOT COST FREE TO MAKE THESE ERRONEOUS ASSUMPTIONS THAT LEAD US DOWN THE WRONG LINE. OF COURSE THERE'S THE CENTRAL QUESTION THE ENCOUNTERED INDIVIDUALIST APPROACH AND ARGUABLY WHAT THE NATIONAL INSTITUTES OF HEALTH SHOULD BE ABOUT IS THE PROMOTION OF HEALTH. GOING BACK TO MY CENTRAL PREMISE, I THINK THERE'S A CLEAR INESCAPABLE ROLE -- IN WE WANT TO INCLUDE HELP. AND HOPEFULLY WHAT I HAVE PROVOKED YOU TO THINK ABOUT IS THIS IS NOT AN ARGUMENT PREDICATED ON THIS IS MY PREFERRED WAY OF THINKING IT'S AN ARGUMENT PREDICATED ON THE LOGIC OF EXPOSURES AND OUTCOMES AND ON THE MATHEMATICAL LIMITS OF DOING THINGS ANY OTHER WAY. THIS IS FROM A RECENT MEDICINE REPORT WHICH SAYS NO ONE IS SUFFICIENT TO EXPECT THAT REFORMS IN THE MEDICARE DELIVERY SYSTEM ALONE WILL IMPROVE THE PUBLIC HEALTH -- ARE PREVENTIBLE. THIS CAME OUT LAST YEAR AND SHOWING THAT THE U.S. LAGS BEHIND MANY OTHER COUNTRIES. HUGELY IN A SHAMEFUL WAY. IT'S NOT FOR LACK OF SMART PEOPLE DEDICATED FOR FRYER TO IMPROVE HEALTH NOT AT ALL. WE ALL ARE JUST DUMBER THAN OTHER COUNTRIES. WE'RE DOING SOMETHING WRONG. MY ARGUMENT IS PART OF WHAT WE'RE DOING WRONG IS WE'VE BEEN CAUGHT IN THIS COMPELLING RIVETTING DISTRACTION THAT HAS PUSHED US TO FOCUS ON THE INDIVIDUAL AND THERE ARE STRONG CLEAR REASONS WHY FOCUSING ON THE INDIVIDUAL ONLY IS HITTING US UP AGAINST A GLASS CEILING OF THE CAPACITY OF OUR PREDICTION OF INDIVIDUAL HEALTH AND OUR CAPACITY TO IMPROVE THE HEALTH OF POPULATIONS. THERE IS A NUMBER OF COLLEAGUES. I WANTED TO THANK A LOT OF FUNDERS PARTICULARLY NIH HAS FUNDED MOST OF MY WORK AND -- WHO IS A CLOSE COLLABORATOR IN A LOT OF THIS WORK. I'LL STOP THERE. THANK YOU VERY MUCH. [APPLAUSE] DO WE TAKE QUESTIONS NOW? >> [INDISCERNIBLE] >> LET ME START WITH THE FIRST QUESTION. IT'S A GREAT QUESTION AND THAT'S ANOTHER WHOLE HOUR DISCUSSION BUT LET ME TRY TO DO IT QUICKLY. I THINK IT DEPENDS ON HOW ONE CONCEPTUALIZES THE BIO MEDICAL ENTERPRISE. I THINK IT CORRECTLY CONCEPTUALIZES BIO MEDICAL ENTERPRISE. WHEN I HAD MY HEART ATTACK I WANT VERY GOOD PHYSICIANS LOOKING AFTER ME SO I CAN GET BETTER. I THINK WE ALL DO. BUT THAT IS A BRANCH, A SECURIVE BRANCH OF THE LARGER QUESTION HOW DO IMPROVE THE HEALTH OF THE POPULATION. MATHEMATICALLY THE QUEST FOR USING POPULATION BASED DATA WHICH WE'RE DOING NOW TO GET VALID PREDICTORS OF INDIVIDUAL HEALTH IS FAILURE. IT HAS TO FAIL. SO THAT'S NOT THE APPROACH. THE APPROACH WOULD BE POPULATION BASE APPROACHES TO PREDICT. AND EFFORTS ON IMPROVING CURATIVE MEDICAL APPROACHES THAT PROBABLY WILL HAVE TO REST ON BETTER TYPING OF DISEASE OF PATHOGENS ETCETERA. WHICH ACTUALLY TO THINK ABOUT IT A LOT OF SUCCESSES OF GENOMICS HAVE BEEN -- ON BETTER CANCER TYPING. SO NOTHING I SAID -- BUT CANCER TYPING HAS NOTHING TO DO WITH POPULATIONS. WHAT IT IS, IT'S WITH USING OUR TECHNOLOGY TO UNDERSTAND PATHOLOGY WHEN IT AND HAPPEN TO INDIVIDUALS. SO THE QUEST TO FIND THE INDIVIDUAL PREDICTOR THAT'S GOING TO TELL YOU THE INDIVIDUAL IF YOU'RE GOING TO GET DISEASE RESTING ON ANALYSIS OF THE POPULATION LEVEL IS DOOMED TO FAIL. THAT'S NUMBER ONE. NUMBER TWO I PRESUME YOU ASKED THE QUESTION BECAUSE YOU KNOW I HIT ON THE HEALTH BOARD COMMITTEE AND WE ACTUALLY VOTED FOR THAT. I VOTED FOR IT. IT'S A MATTER OF PUBLIC RECORD SO I CAN SPEAK ABOUT IT. I THINK THERE IS EVIDENCE THAT LIMITING SODAS TO SMALLER SODAS THAT THAT IS GOING TO HAVE A DIRECT INDEPENDENT CAUSAL EFFECT ON OBESITY IS SCANT. I THINK THERE ARE MANY REASONS WHY A MOVE TO BAN LARGE SCALE SODAS IS IMPORTANT CENTRALLY AMONG THEM IS ALTERING POPULATION NORMS WHICH IS A CLASSIC CASE OF CHANGING THE POPULATION OF A CHARACTERISTIC AND SHIFTING THE CURVE. SO I WOULD CONSIDER ONE OF THE BEST POSSIBLE OFF-SHOOTS OF THE SODA BAN THAT RESULTED IN A VIBE RESULT DISCUSSION ABOUT CALORIE DENSE NUTRIENT POOR FOODS AND THE GREATER AWARENESS OF THAT IN POPULATIONS. AND BY SHIFTING NORMS, YOU ARE THEN GOING TO SHIFT CURVES. SO I THINK IT IS I THOUGHT THEN I STILL THINK IT'S A GOOD IDEA. ACTUALLY IT'S AN IDEA THAT WILL EVENTUALLY BE UPHELD BY THE COURTS. >> [INDISCERNIBLE] >> I'M GLAD YOU SAID THAT. I THINK SO. I ACTUALLY THINK TO BE FRANK I'M A LITTLE BIT ANXIOUS ABOUT SORT OF GIVING A TALK LIKE THIS TO THIS AUDIENCE BECAUSE I'M SAG THAT SEVERAL THINGS THAT ARE REALLY -- ARE DOMINANT HOW WE DO OUR BUSINESS ARE WRONG. BUT I ACTUALLY THINK WE ARE AND I THINK WE HAVE GROSSLY MISINTERPRETED OR IGNORED OR ESSENTIALLY NOT TO BUILD -- ON CONCEPTS THAT ROSE UNDERSTOOD CLEARLY WAY BACK IN EARLY 80'S AND WE HAVE GONE DOWN WRONG PATS THE POINT I'M TRYING TO MAKE HERE IT'S CONSEQUENTIAL THIS MATTERS -- THERE'S A CERTAIN I SUPPOSE ARROGANCE ON THAT KIND OF PROVOCATION AND SO I SAY IT CAREFULLY. I HAVE NOT BEEN DISSUADED BY NUN THAT THIS LINE OF LOGIC THAT -- BY ANYONE THAT THIS LINE OF LOGIC I PRESENTED TODAY IS WRONG. WHAT'S WRONG IS WHERE WE HAVE TAKEN A LOT OF THESE EFFORTS. UNFORTUNATELY I THINK ONE COULD ACTUALLY PROBABLY THE DEEPEST CRITICISM WHAT I JUST SAID IS THEY CAN SAY WELL NOTHING NEW BECAUSE WE KNEW THIS IN 1985. THAT'S TRUE WE DID KNOW ALL THIS IN 1985 WHAT I'M TRYING TO DO HERE IS CLARIFY. BUT THE CONCEPT HERE I THINK GROWS [INDISCERNIBLE] >> [INDISCERNIBLE] >> I'M CONSCIOUS OF THE FACT THERE'S A GUY THERE WHOSE PAPERING EVERYTHING I'M SAYING. I CAN EVEN SEE MY SO CAMERA. NO BUT HERE'S WHAT I WOULD DO. I WOULD ACTUALLY SAY THAT THIS IS NIH NOT NID. NI HMPLET AS A RESULT NEEDS TO FOCUS ON AGE NOT ON DISEASE. IF THESE ARGUMENTS I'M MAKING HERE ARE CORRECT, N IT H HAS A RESPONSIBILITY IN ITS ROLE TO PROMOTE HEALTH TO EMBRACE WITHIN ITS REMNANT RESEARCH THAT ENCOURAGES PROMOTION OF HEALTH. I WOULD SAY IF THERE'S A REPORT FROM THE INSTITUTE OF MEDICINE THAT SAYS WE HAVE HEALTH METRICS THAT ARE ROUGHLY SLOVENIA WHICH HAS BEEN EMERGING FROM A DECADE LONG CIVIL WAR THAT'S A NATIONAL TRAGEDY AND THE LARGEST INSTITUTION THAT IS CHARGED WITH RESEARCH ON HEALTH OF THIS COUNTRY IS SOMEHOW FALLING SHORT AND I SHOULD SAY WE SHOULD DO SOMETHING TO FIX THAT. IT'S A COMPLEX QUESTION HOW TO FIX THAT BUT CERTAINLY IT IS NOT AN ANSWER TO TURN EVER DEEPER AND DEEPER IN DIFFERENT TYPES OF NEW SEQUENCING TO TRY TO GET INDIVIDUAL DRIVERS OF INDIVIDUAL HEALTH OR INDIVIDUAL DISEASE BECAUSE THAT'S NOT GOING TO WORK. >> IT'S A GREAT QUESTION. SO THERE ARE PEOPLE IN SOCIAL EPIDEMIOLOGY WHICH IS BROADLY I GUESS MY DISAPPEARING LABEL WHO WOULD ARGUE THAT A QUEST FOR MECHANISMS A DISTRACTION FROM A QUEST TO FIGURE OUT HOW TO ACT FROM MORE FUNDAMENTAL CAUSES. IT'S EXTREME. I ACTUALLY THINK THERE'S MERIT TO STUDYING MECHANISM. THIS IS WHERE WILSON'S QUESTION COMES FROM I WANT US TO UNDERSTAND MECHANISMS ALTHOUGH I CARE ABOUT POPULATION HEALTH A SUBSET OF POPULATION HEALTH IS CURATIVE MEDICINE. AND THIS IS WHERE THE UNDERSTANDING MECHANISMS COMES IN. SO WHEN I HAVE MY DISEASE TER -- DISEASE AT THE END OF THE DAY ON A LARGE SCALE OR WHATEVER IT'S NOT GOING TO HELP YOU ONCE I HAVE MY DISEASE. I THINK THE MECHANISTIC KNOWLEDGE IS VERY IMPORTANT FOR THE PRACTICE OF CURATIVE MEDICINE. AND IT'S VERY IMPORTANT FROM THE POINT OF VIEW OF SCIENCE FROM THE POINTS OF VIEW OF UNDERSTANDING NATURE AND HOW THE DISEASE PROCESS WORKS. I AM NOT AT ALL OPPOSED TO THIS STUDY THAT GETS US MECHANISMS BUT MY WORRY IS ABOUT THAT AT THE EXPENSE OF ALL THIS. >> [INDISCERNIBLE] >> ULTIMATELY DISEASE PAT OWE GENESIS IS IN ME. PATHO GENESIS IS IN THE INDIVIDUAL. THE ENVIRONMENTAL INFLUENCE ON THE HEALTH OF POPULATIONS ULTIMATELY IS A SUM OF HEALTH INDIVIDUALS. THAT'S WHAT MARGARET THATCHER SAYS -- FUNDAMENTAL TRUTH. SO I DO THINK MECHANISMS DO MATTER. I THINK THE MISTAKE IS IN ALLOWING THE QUEST FOR MECHANISMS TO DISTRACT US IN THEN WORKING ONLY ON MODIFYING THESE MECHANISMS. THE QUESTION WAS HOW DID MY BACKGROUND, WHICH IS CHECKERED -- PRIMARY PHYSICIAN IN THE BACKGROUND BEFORE I DRIFTED BACK INTO DOCTORATE SCHOOL, INFLUENCED MY THINKING AND HOW THAT CONTRASTS WITH THE AMERICAN DOMINANT MEAN OF INDIVIDUAL EXCEPTIONALISM. I DON'T KNOW HOW MY THINKING HOW THAT INFLUENCED MY THINKING. I PROBABLY SHOULD ASK MY THERAPIST. I DO THINK THERE ARE, I DO THINK THERE ARE MANY COUNTRIES WHO ARE DOING BETTER THAN WE ARE. AND IT SEEMS TO ME THE ULTIMATE IN SELF DESTRUCTIVE HUBRIS THAT WE DON'T TRY TO LEARN FROM THEM. I DO UNDERSTAND THE NOTION THAT THERE ARE MANY THINGS AMERICA DOES RIGHT AND AS A RESULT WE SHOULD TAKE GREAT PRIDE IN THAT. BUT SOME THINGS, THERE SEEMS TO BE METRICS THAT BEG FOR US TO TRY TO LEARN FROM OTHER APPROACHES AND I THINK WE'RE VERY HESITANT TO DO THAT IN THIS COUNTRY. >> [INDISCERNIBLE] >> THAT'S A VERY GOOD POINT. IT'S A POINT AROUND VALUES. AND SO I HAVE WRITTEN AND I HAVE A BOOK -- WHICH EXPLICITLY MAKES THIS POINT THAT PUBLIC HEALTH TYPES SHOULD NOT RUN THE COUNTRY. IT WOULD BE A VERY BORING PLACE IF WE DO. BUT THE VOICE OF PUBLIC HEALTH IN ELEVATING, SURFACING THE DRIVERS OF THE HEALTH OF THE POPULATION NEEDS TO BE A MUCH MORE VIBRANT PART OF THE NATIONAL DISCUSSION THAN IT IS NOW. IT ULTIMATELY IS ABOUT VALUES AND I THINK IT IS AN ACCEPTABLE NATIONAL VALUE TO SAY WE ARE WILLING TO TOLERATE THREE YEARS LIFE EXPECTANCY DIFFERENT BETWEEN US AND SWEDEN SO WE CAN HAVE MORE, SO WE CAN CARRY OUR GUNS OUT. I'M JUST LISTING SOMETHING. I THINK THAT IS A VALUE THAT IS A NATIONAL VALUE WHICH A COUNTRY IS PROBABLY ENTITLED TO A SPOUSE. MY VOICE THAT ADVOCATES FOR PROMOTION OF PUBLIC HEALTH HAS BEEN LARGELY BURIED IN A LARGER NATIONAL DEBATE AND THE VOICES THAT PROMOTE INDIVIDUALISM FOR ITS OWN SAKE FAR OUT WEIGH. MY GREATER WORRY IS INSTITUTIONS LIKE THE NATIONAL INSTITUTES OF HEALTH WHO ARE CHARGED WITH BEING PARTED OF THE VOICE HAVE GOTTEN DISTRACTED ALONG THIS INDIVIDUALIST PATH GIVING US AN EVEN MORE DEEPER VOICE IN SPEAKING ABOUT THE FACTORS THAT WE SHOULD BE PROMOTING TO PROMOTE THE HEALTH OF POPULATION. SO I DON'T THINK ANYONE IN THIS ROOM SHOULD BE EMPOWERED TO DICTATE SOCIETAL STRUCTURES FOR SOCIETAL VALUES. WE ARE ONE VOICE AMONG MANY AND IT'S REASONABLE TO SAY WE ARE WILLING SACRIFICE SOME HELP FOR THE VALUE OF OTHERS IT'S REASONABLE. I DON'T THINK WE IN POPULATION HEALTH ARE CURRENTLY BEING HEARD. AND MY WORRY AGAIN IS COLLECTIVELY WE'RE DOWN IN THIS COMPELLING RIVETTING DISTRACTION WHICH IS MUDDYING OUR THINKING. THAT'S WHY I SHOWED YOU THE RICHARD FOSTER SLIDE. I THINK IT'S TERRIBLE PEOPLE OF GOOD CONSCIOUS DO IN THE FAR REACHING HEALTHCARE REFORM IN A CENTURY ARE SAYING IN PUBLIC REPORTS FROM A GEO REPORT THAT LOOK I JUST DON'T KNOW. I DON'T KNOW THE ANSWER TO THIS. YOU ALL IN HEALTH HAVEN'T TOLD ME THIS. IT'S EMBARRASSING. >> I ACTUALLY THINK IT'S NOT THE INDUSTRY RESPONSIBILITY. I THINK IT'S THE RESPONSIBILITY OF THOSE OF US WHO ARE IN THE BUSINESS OF PROMOTING THE HEALTH OF THE PUBLIC IN MULTIPLE WAYS. NIH DOES THAT'S TRUE SPONSORING RESEARCH. WE DO IT IN GENERAL RACE OF SCHOLARSHIP -- I ACTUALLY THINK IT'S OUR RESPONSIBILITY. THE INDUSTRY HAS OTHER DOMINANT ROLES. WE KID ARE OURSELVES IF WE THINK THE PRIMARY ROLES -- IT'S NOT. THE PRIMARY ROLE IS PROMOTING VALUE FOR THE SHAREHOLDERS. WHAT ONE CAN HOPE FOR IS THEY DON'T THAT BY ACTIVING HARMING POPULATIONS BUT IT'S NOT THEIR PRIMARY RESPONSIBILITY. WHAT CAN YOU DO AS EAR STARTING UP A PROFESSION. I GUESS MY DEEPEST ASPIRATION WOULD BE IN A NEW GENERATION OF HEALTH PROFESSIONALS GETS IT RIGHT. I THINK WE'RE DOING SOMETHING WRONG RIGHT NOW AND I THINK YOU CAN CHANGE SOMETHING. IN WHATEVER ROLE YOU TAKE WITHIN THE BIO MEDICAL ESTABLISHMENT.