>> WELCOME, EVERYBODY, WELCOME TO THOSE WHO TRAVELED NEAR AND FAR TO BE HERE AND ON THE WEB AND TWITTER AND ALL THE OTHER CONNECTS WE HAVE. MY NAME IS BOB CROYLE, DEVELOPER OF CANCER CONTROL AND POPULATION SIGNS AT NCI AND IT'S MY PLEASURE TO WELCOME YOU TO THIS IMPORTANT TIMELY MEETING. MANY OF YOU WERE AT A MEETING SEVERAL YEARS AGO WE HAD ONE OF OUR FIRST LARGE EPIDEMIOLOGY INVESTIGATORS MEETING WHERE WE TALKED ABOUT A LOT OF ISSUES THAT WE'RE GOING TO BE REVISITING TODAY BUT HOPEFULLY ONE SENSE YOU'LL GET IS IN THE LAST 6, 7 YEARS SINCE THAT MEETING THERE'S BEEN SOME REMARKABLE PROGRESS IN TERM OF DEVELOPMENT OF PROJECTS, INFRASTRUCTURE, TECHNOLOGY, STILL HUGE CHALLENGES ABOUT METHOD, STRATEGY, RESEARCH DESIGN, PRIORITYZATION OF RESEARCH GOALS AND TRANSLATION, ALL THE THEMES WE'LL TOUCH ON TODAY. BUT WE APPRECIATE THE PARTICIPATION. SO MANY FOLKS NOT ONLY FROM THE IMMEDIATE NCI FAMILY AND CONSTITUENCY BUT OUR COLLEAGUES FROM OTHER NIH INSTITUTES AND ORGANIZATIONS. WHO ARE PARTICIPATING WITH US TODAY. ALSO WE'RE GOING TO BE MAKING SURE THAT THOUGH WE'RE THIS A RELATIVELY SMALL ROOM AND MANY PEOPLE ARE PARTICIPATING REMIND EVERYBODY THAT WE HAVE MANY OFF SITE PARTICIPANTS SO IF YOU HAVE GOT YOUR SMART FEBRUARY YOU CAN READ THE TWEETS AS THEY COME IN ON THE TWITTER FEED. WE'RE GOING TO BE ALSO MAKING SURE THAT WE HAVE FULL ENGAGEMENT NOT ONLY WITH PARTICIPANTS IN THE ROOM BUT FOLKS WHO ARE EMAILING AND TWEETING COMMENTS TO US. BECAUSE THERE ARE SO MANY TOUGH DECISIONS AND CHALLENGES FACING US RIGHT NOW IN THIS AREA OF SCIENCE, WE WANTED TO MAKE SURE THAT THIS WAS PARTICIPATORY MEETING WITH BROAD ENGAGEMENT AND THEN THAT'S WHY AS MANY OF YOU KNOW WHO PARTICIPATED ALREADY IN THIS PROCESS, THIS MEETING IS NOT THE ONLY PIECE, WE HAVE ALREADY HAD BLOGS AND COMMENTS AND INTERCHANGE LEADING UP TO THIS AND THERE WILL BE MORE AFTERWARD SO THIS IS PART OF A PROCESS, NO JUST A ONE SHOT MEETING. SO THIS IS TO ENSURE WE HAVE BROAD INPUT THERE'S MANY OF YOU WHO WE HEAR FROM A LOT BUT THERE ARE EVEN MORE OF YOU WE HEAR FROM A LITTLE. AND WE REALLY WANT TO BROADEN THE CONVERSATION. BEYOND FAMILIAR FOLKS WHO TIPPEDLY ATTEND MEETING AND PARTICIPATED ACTIVELY. SO THOSE OUT THERE WHO ARE JUNIOR INVESTIGATORS, POST DOCS, ASSISTANT PROFESSOR, REALLY ENCOURAGE YOU TO WEIGH IN AND PARTICIPATE, YOU DON'T HAVE TO BE A BIG POOBA LIKE THE ONES TODAY TO PARTICIPATE, WEIGH IN, HAVE AN OPINION. IT'S ESSENTIAL IN THIS DISCUSSION THESE ISSUES TODAY THAT WE HAVE AN HONEST DISCUSSION. SO IT'S REALLY -- WE ENCOURAGE PEOPLE TO DISAGREE, TO EXPRESS YOUR BLUNT OPINION. WEIGH IN ON A HOST OF ISSUES BECAUSE IN ORDER TO MAKE INFORMED DECISIONS HOW TO PROCEED FORWARD IT'S ESSENTIAL TO LAY OUT WHAT ISSUES AND CONCERNS ARE FROM A VARIETY OF PERSPECTIVES. SO NOT JUST FROM FOLKS IN POPULATION SCIENCE BUT THOSE IN BASIC AND CLINICAL SCIENCE. AND ALSO THOSE WHO WORK OUTSIDE THE CANCER DOMAIN WHETHER IT'S OTHER CHRONIC DISEASE DOMAINS SUCH AS CARDIOVASCULAR DISEASE THE, INFECTIOUS DISEASE, GLOBAL HEALTH, AND WE HAVE SPRINKLED THE PARTICIPANTS TODAY WITH FOLKS FROM THOSE VARIOUS PERSPECTIVES THAT YOU'LL BE HEARING FROM IN THESE DISCUSSIONS. ALSO I WANT TO INDICATE THAT AS WE SPEAK, AND JUST WITHIN THE PAST MONTH OR TWO, WE'RE MOVING FORWARD ON A TERRIFIC NUMBER OF EXCITING PROJECTS MANY OF YOU HERE PARTICIPATE IN, IN GLOBAL HEALTH, EPIDEMIOLOGY CONSORTIA, WE MADE MAJOR DECISIONS ON SOME COHORTS. WE APPROVED THE EXTENSION OF THE MULTI-ETHNIC COHORT, WE IMPROVED SIGNATURE PROJECTS PIGGY BACKING ON OTHER COHORT, PARTICULARLY NHLBI, ALSO NIDDK. WE HAVE INSTIGATED NEW COLLABORATIONS TRANS-NIH IN TERMS OF INTEGRATING PREVENTION AND POPULATION SCIENCE, AND LARGE SCALE TRIALS ACROSS THE INSTITUTES. AND SOME FOLKS TODAY ARE INVOLVED IN THOSE EFFORTS AND ONGOING EFFORTS BRIDGING POPULATION SCIENCE POINT USE OF TECHNOLOGY, YOU'LL HEAR ABOUT EVIDENCE SYNTHESIS TODAY CRITICAL TO THIS AND ALSO TRANSLATION TO POLICY AND PRACTICE. THIS HAS NOW OBVIOUSLY A GLOBAL ENTERPRISE. IT'S AN ENTERPRISE THAT INVOLVES MANY FUNDERS, MANY CONSTITUENCIES. AND WE'RE WORKING NOT ONLY WITHIN THE NIH BUT WITH ORGANIZATIONS LIKE PCORI, WITH THE DEPARTMENT, ON KEY PUBLIC HEALTH ISSUES TO MAKE SURE THAT EVIDENCE GETS TO POLICY AND PRACTICE AS QUICK AS POSSIBLE. LAST THURSDAY AND FRIDAY IN THE SAME ROOM WE HAD A MEETING OF THE ADVISORY COUNCIL TO THE DIRECTOR. THIS IS THE NIH LEVEL ADVISORY COUNCIL MEETING. AND I WANT TO MENTION THAT VERY BRIEFLY BECAUSE A LOT OF EXCITING TOPICS DISCUSSED THIS LAST THURSDAY AND FRIDAY, INCLUDING THE THE ANNOUNCEMENT OF A LAUNCH OF A MAJOR NEW BIOMEDICAL AND DATA INFORMATICS PROJECT WHICH IS NOW UNDERGOING THE NAME OF BD 2K, THAT STANDS FOR BIG DATA 2 KNOWLEDGE. SO THIS IS NOT ON THE STREET, THE FUNDING OPPORTUNITY ANNOUNCEMENTS ARE NOT OUT YET BUT FOR FORECAST WHAT WAS DISCUSSED WITH DR. COLLINS AND NIH LEADERSHIP, A MAJOR COMMITMENT, A NEW COMMITMENT THAT WILL BE MADE BY THE NIH OVER $100 MILLION A YEAR AND MANY COMPONENTS BUT ONE PIECE IS FUNDING OF NEW CENTERS OF EXCELLENCE, FOCUSED ON DATA AND DATA INFRASTRUCTURE AND BIG DATA. ERIC GREEN PLAYED A ROLE IN THIS AND YOU'LL HEAR MORE IN THE COMING MONTHS. THIS ENHANCEMENT OF INFRASTRUCTURE RESOURCES STORAGE AND TRAINING RELATED TO BIOMEDICAL BIG DATA WHICH IS A TRANS-NIH EFFORT IS REALLY KEY. TENTATIVETY WE'RE TALKING FUNDING UP TO 20 CENTERS. SO THIS IS A MAJOR EFFORT THAT INVOLVES COMMON FUND RESOURCES AN COVERS THE SPAN OF DATA FROM ELECTRONIC MEDICAL RECORDS, PRIVACY ISSUES, IMAGING DATA, SEQUENCE DATA, SO A BROAD AMBITIOUS EFFORT AND YOU'LL HEAR MORE ABOUT THAT IN THE COMING MONTHS AS WE HAVE MORE MEETINGS AND WORKING GROUPS TO DEVELOP THOSE INITIATIVES. SO I WANTED TO MENTION THAT BECAUSE CLEARLY RELEVANT TO TODAY'S EFFORTS. SO WITHOUT FURTHER ADIEU I WANT TO INTRODUCE MINE KHOURY FROM EPIDEMIOLOGY AND GENOMICS AND THE BRAIN CHILD OF THIS WHOLE MEETING BOTH PROCESS AND STRATEGY AND HE'S GOING TO INTRODUCE YOU TO STRUCTURE AND STRATEGY OF THIS MEETING WHICH IS DIFFERENT THAN SOME OF YOU MAY HAVE PARTICIPATED IN. SO MINE, WELCOME TO COME UP AND GET THINGS STARTED. THANKS, EVERYONE, FOR COMING. >> THANK YOU SO MUCH, BOB. WELCOME TO ALL OF YOU. SO GLAD TO BE HERE. I HAVE BEEN WAITING ALL YEAR TO SAY THE WORDS WELCOME TO 12/12/12, BEEN PRACTICING A LOT. SOME OF THE PEOPLE AT WORK ARE SICK AND TIRED OF ME SAYING 12/12/12, BECAUSE THIS IS A TIME TO CONVENE AND DO GOOD FOR EPIDEMIOLOGY. THIS MEETING IS TRULY PART OF A LARGER CONVERSATION AS BOB MENTIONED AND IT'S HE REFERRED TO THE BLOG WHICH HAS BEEN GOING ON SINCE JUNE OF 2012, WE HAVE SEVERAL ENTRIES MANY OF YOU HAVE CONTRIBUTED PIECES AND WE HAVE PUT OUT A NUMBER OF QUESTIONS THERE. THOSE WHO HAVEN'T PUT IDEAS ON LINE WE ENCOURAGE EVERYONE, WE CHALLENGE RESEARCH COMMUNITY THROUGH THIS COMMENTARY PUBLICKING ON CANCER EPIDEMIOLOGY BIOMARKERS. SO OUR JOB FOR THE NEXT 24 OR 26 HOURS TOGETHER IS ONLY A CROSS SECTION IN TIME AND ONE COULD EASILY MAKE THE CASE THIS IS LIKE 15 MEETINGS IN ONE AND YOU'RE NOT GOING TO BE PAYING ENOUGH SERVICE OR ENOUGH ATTENTION TO ALL THESE AREAS. THIS IS A BIG PICTURE MEETING AND IT'S A LONGITUDINAL DISCUSSION. I HAVE BEEN IN EPIDEMIOLOGY FOR 30 YEARS AND I NEVER HAD A DULL MOMENT THOUGH OVER 30 YEARS PEOPLE HAVE WRITTEN OBITUARIES ABOUT EPIDEMIOLOGIES AND I READ THEM BUT AT THE END OF THE DAY YOU CAN'T LIVE WITHOUT EPIDEMIOLOGY. IF YOU'RE GOING TO MAKE PROGRESS IN MEDICINE AND PUBLIC HEALTH YOU HAVE TO INVOLVE EPIDEMIOLOGY ONE WAY OR ANOTHER. IT'S THE SCIENCE BASIC SCIENCE OF MEDICINE AND PUBLIC HEALTH AND IT'S GOING TO BE WITH US. AND THE PROBLEM IS WITH ALL THE EXCITEMENT AND -- AROUND US FROM TECHNOLOGY, WITH WE HAVE TO PRIORITIZE. THE FISCAL RESOURCES ARE NOT GETTING ANY EASIER SO I THINK IT'S GOOD THAT WE WANT TO DO EVERYTHING FOR EVERYONE AS SOMEONE IN THE AUDIENCE I WOULD QUOTE BUT HE CAN DEFEND HIMSELF WHEN TIME IS UP. BUT YOU REALLY CAN'T DO EVERYTHING FOR EVERYONE. SO WE HAVE TO BE A LITTLE BIT CHOOSE IN WHAT WE DO. A COUPLE OF YEARS AGO PETER GREENWHAT WOULD FROM DIBETTIC PREVENTION HAD A WONDERFUL CANCER EPIDEMIOLOGY, THIS IS FROM THE PAPER E NOT GOING TO GO AND STEAL THE THUNDER OF BOB HOOVER WILL BE OUR FIRST SPEAKER BUT FOR THE LAST LESS THAN 100 YEARS SINCE THE ESTABLISHMENT OF NCI THERE'S BEEN QUITE A BIT OF SUCCESS THAT HAVE BEEN PART TO A LARGE EXTENT DRIVEN BY THE EPIDEMIOLOGYCAL ENTERPRISE FROM ASBESTOS TO CIGARETTE SMOKING TO DES, HEPATITIS AND VACCINES AND HPV AND H PYLORI AND MODELING OF BREAST CANCER OCCURRENCE. , THIS IS A BRIEF TIME LINE, YOU CAN FILL IN THE BANK BETWEEN THE YEARS. OF COURSE THE MAP GETS DENSER AN DENSER. AND ONE THING WE CANNOT FORGET WHEN WE TALK ABOUT CANCER EPIDEMIOLOGY, NOT JUST JOE FROM MINI SYNDROME BUT THE MAIN MIND THE LEE FREMINI SYNDROME WHO COULDN'T ATHE TEND THE MEETING TODAY BUT WE OWE A LOT BOTH SORT OF GRATITUDE AND RESPECT FOR LAUNCHING THE FIELD OF CANCER EPIDEMIOLOGY FOR THE LAST FEW DECADES. I THINK WE ALL STAND ON HIS SHOULDERS, AS WE MOVE FORWARD. AND IS SO I HOPE JOE YOU'RE LISTENING ON LINE BECAUSE HE SAID HE WILL TRY TO MAKE IT ONLINE. MY OWN FEEL GENETICS AN GENOMICS HAVE BECOME MORE AN MORE PERMANENT -- PROMINENT OVER LAST FEW YEARS FROM THE HUMAN GENOME PROJECT TO GWAS AN NOW GENE ENVIRONMENT INTERACTION AND THEN SEQUENCING WILL ENTER THE NEXTER RA OF SEQUENCING AND BEYOND. HERE WE ARE 12/1/1, AND WHAT WE NEED TO DO IS UNLESS THE MAYANS WERE RIGHT AND THE END OF THE WORLD IS NEXT WEEK, 12/21/12, WE REALLY NEED TO PLAN FOR THE FUTURE AND HOW TO GET THERE. WE NEED TO HAVE THIS CONVERSATION AMONG OURSELVES AND MANY PEOPLE AND FOR THOSE OUT THERE LISTENING AND WATCHING THIS VIDEOCAST I ENCOURAGE THE SPEAKERS SMILE AND LOOK AT THE CAM R. THERE ARE SEVERAL CAMERAS AROUND. THAT APPLIES TO YOU DAVID HASSELHOF AS WELL. SO DON'T SHAKE YOUR HEAD. WE WANT TO ENGAGE YOU, WE WANT TO HEAR FROM YOU. THIS IS THE TIME TO THINK ABOUT THIS. EPIDEMIOLOGY COMES IN DIFFERENT FLAVORS LIKE ICE CREAM. SOME OF US WORK IN APPLIED SETTING LIKE I WORK AT CDC WHERE WE'RE TRYING TO IMPLEMENT AND SAVE LIVES TO THE CANCER DISCOVERY MOLD MODE. WE DIVIDE OUTSIDES IN-- OURSELVES INTO OUTCOMES AN RISK FACTORS AN LIFE STAGES AND COMPLEX EPIDEMIOLOGIES BUT THERE IS ONE WAY THAT TIES IT ALL TOGETHER. IT'S SORT OF REGARDLESS OF WHAT YOU DO. YOU HAVE TO WORRY ABOUT TRANSLATIONAL FRAMEWORK SO WHAT THE WAY WE HAVE CONSTRUCTED THIS MEETING IS TALK ABOUT EPIDEMIOLOGY AND THE CONTEXT OF THE TRANSLATIONAL RESEARCH ENTERPRISE. I AND OTHERS HAVE WRITTEN ABOUT THIS T-1 TO T-OF 4 CONCEPT. THE LATEST ITERATION OF LIFE CYCLE OF TRANSLATION THANKS TO TOM AND SHERRY SHIRLEY FROM EGRP FOR OUTING IT TOGETHER. WE'RE GOING TO FOCUS OUR CONVERSATION ON THESE FOUR DRIVERS. BUT THIS SORT OF TRANSLATIONAL ENTERPRISE, WE REGARDLESS OF WHETHER YOU DO CLINICAL MEDICINE OR PUBLIC HEALTH WE'RE INTERESTED IN DISCOVERIES AND WITH THOSE DISCOVERIES WE JUST START HAVE TO MOVE THEM ALONG THE TRANSLATIONAL SPECTRUM. I HAVE BEEN THINKING ABOUT THIS FOR A LONG TIME. AND I THINK THE TOOLS OR THE DRIVERS THAT WE HAVE RIGHT NOW GO THROUGH THEM QUICKLY BECAUSE WE'LL BE TALKING ABOUT THEM OVER THE LAST DAY AND A HALF, COLLABORATION TECHNOLOGY, MULTI-LEVEL ANALYSIS KNOWLEDGE INTEGRATION WILL BE WITH US MANY YEARS AN WILL PROVIDE THE NECESSARY INGREDIENTS FOR MORE QUICKER TRANSLATIONAL DISCOVERIES. EPIDEMIOLOGY IS NOT ALONE, IT'S PART OF MANY DISCIPLINES THAT. COME TOGETHER FROM BASIC CLINICAL AND POPULATION SCIENCES THAT DOES THAT. SO THIS PAPER WHICH Y'ALL HAVE STILL EMBODIED BY CAPP, WE WERE HOPING WOULD BE OUT BY NOW. SO IT'S NOT EMBARGOED ANY MORE. WHEN KID THAT HAPPEN. (INAUDIBLE) THANK YOU FOR HELPING US, SHERRY AND I PUT THIS FRAMEWORK TOGETHER FOR THE MEETING -- FOR THE MEETING TO TALK DRIVERS. AS PART OF OUR DISCUSSION, WE FOCUS, WE KNOW FROM WHAT WE FUND HERE. EGRP IN THE DIVISION FUNDS A LOT OF EPIGRANTS EVERY YEAR. WE HAVE SEEN AND KNOW THAT CONSORTIA DRIVEN EPIGRANTS HAVE GONE UP OVER TIME AND I WOULD LIKE TO ACKNOWLEDGE (INDISCERNIBLE) FOR BEING THE COORDINATOR FOR THESE EFFORTS. COHORTS IN THERE BECAUSE SOMETIMES THEY GOING TO. COHORTS AN CONSORTIA, THERE ARE CONSORTIA OF COHORTS. MOST FAMOUS IS THE COOR CONSORTIUM. SO THAT THE TEAM SCIENCE IS WITH US, WHETHER YOU CLUSTER EPIDEMIOLOGISTS TOGETHER OR EPIDEMIOLOGIES WITH OTHER DISCIPLINES, BUT WE NEED TO KNOW HOW IT WILL SHAKE THE FIELD IN THE NEXT FEW YEARS. MULTI-LEVEL ANALYSIS IS WITH US AS DATA ACCUMULATES FROM VARIOUS LEVELS FROM THE SOCIAL TO BIOLOGICAL LEVEL AND THE INTERPERSONAL INTERACTIONS, EVERY SINGLE LEVEL HAS SOMETHING TO DO WITH HOW WE CAN DEFINE DETERMINE RISK FACTORS AND EVENTUALLY CONTROL THINGS LIKE OBESITY. WHEN WE LOOK AT THE LITERATURE AND WE DIDN'T HAVE TIME TO DO IN DEPTH ANALYSIS OF MULTI-LEVEL WORK, THERE'S LITTLE OF THAT GOING ON IN EPIDEMIOLOGY. EPIDEMIOLOGY TENDS TO FOCUS FOR THE MOST PART ON INDIVIDUAL LEVEL TYPE ANALYSES APPROXIMATE RIGHT NOW WE TALK GENE ENVIRONMENT INTERACTION BUT IT'S TRULY AT THE INDIVIDUAL LEVEL. WE HAVE HAD AS PART OF THE CDC ON LINE TOOL CALLED THE HUMAN GENOME EPIDEMIOLOGY -- WE HAVE BEEN TRACKING THE GENETIC EPI FIELD FOR 12 YEARS. EVEN BEFORE GWAS THE CANDIDATE GENER RA AND AFTER IT. WE HAVE SEEN MORE AND MORE THAT PEOPLE ARE PUTTING GENE AND ENVIRONMENT TOGETHER. THIS WHOLE DATABASE IS RELATED TO GENES BUT THE ENVIRONMENTAL SIDE AND PHARMACO GENOMIC IS BEGINNING TO FACTOR IN, BUT WE HAVE A LONGER WAY TO GO IN TERMS OF PUTTING STUFF TOGETHER. IN TERMS OF TECHNOLOGY WE ALL TALK ABOUT OMICS FROM GENOMICS ALL THE WAY TO OTHER OMICS AS WELL. IT'S OUT THERE. WE SEE IT IN THE PUBLICATIONS. ESPECIALLY IN CANCER, IN BOTH GENETIC, GENE EXPRESSION, METHYLATION, ET CETERA, NOTICE THAT SPIKE IN MICRORNA OVER THE LAST FEW YEARS, TELOMERE, PROTEOMES, THERE'S NO -- THE IS BEGINNING TO SEE AND MORE PUBLICATION IN THESE LARGE SCALE EPIDEMIOLOGYCAL STUDIES WHICH ARE USING MORE AND MORE OF THESE TOOLS. DON'T WANT TO BE TOO THE OMIC CENTRIC SO WE DID ANALYSIS TO SHOW THERE ARE TECHNOLOGIES ABOUT OTHER DOMAINS LIKE MEASURING PHYSICAL ACTIVITY WHICH ARE BEGINNING TO HAVE A PLAY IN THE PUB ESTABLISHED LITERATURE. YOU CAN THINK ABOUT SMART PHONES, DIET AND OTHER THING, IT'S HARD TO SEARCH THROUGH THAT LITERATURE IN A QUICK WAY. BUT WE'RE SEEING MORE TECHNOLOGY BEING USED AND EPIDEMIOLOGY STUDIES AS WELL. WE'LL HAVE A SESSION OF KNOWLEDGE INTEGRATION. KNOWLEDGE INTEGRATION IS IN THE EYE OF THE BEHOLDER BUT IT REALLY IS ABOUT PUTTING IT TOGETHER. TRYING TO PUT BASIC CLINICAL AND POPULATION SCIENCES TOGETHER. AND ONE OF THE FRAMEWORKS FOR PUTTING STUFF TOGETHER IS METH ANALYSIS AND SYSTEMATIC REVIEW. WE'RE SEEING MORE OF THIS IN THE LITERATURE, THE NARRATIVE REVIEWS WHICH ARE STILL PREDOMINATE PEOPLE WRITING A REVIEW ARTICLE ABOUT TOPIC AND WHAT WE KNOW AND WHAT WE DOPE KNOW, SYSTEMATIC ATROCHE POACHES OF SEARCHING AND CO-LATING THE LITERATURE IS ART AND SCIENCE BY ITSELF. AND JOHN HAS AS PART OF SPECIAL CEBP, SERIES OF ARTICLES RECENTLY PUBLISHED THIS ARTICLE ALONG WITH SHERRY TRAN AND OTHERS AND I THINK YOU ALL HAVE THAT PACKAGE. HERE WE ARE. WE ARE IN A DATA RICH TECHNOLOGY DRIVEN MULTI-LEVEL WORLD WHERE WE CAN EXAMINE A LOT OF FACTORS SO THE QUESTION THAT I HAVE I ALWAYS HAVE FOR MYSELF AND -- IS TO THINK ABOUT WHICH PLAN OF EPIDEMIOLOGY WILL SHOW UP MANY THE 21st CENTURY, IS IT THIS KIND OF BRAND WHERE PEOPLE HAVE INCIDENTAL FINDINGS AND INCIDENT ALONE IS A WORD COINED BY SOMEBODY AT HARVARD, I THINK ISAAC (INAUDIBLE) WHERE EVERYTHING IS INCIDENTAL FINDINGS. AND THIS IS A CARTOON SHOWING THAT COFFEE CAUSES DEPRESSION ONLY IN TWINS. THAT WAS PUBLISHED IN THE FAMOUS NEW ENGLAND JOURNAL OF PANIC INTUESDAYING WHATEVER THAT WORD IS. SO WITH MORE DATA, WITH MORE DATA DREICH DREDGING, WE HAVE SIGNAL TO NOISE RATIO VERY SMALL IN THIS NEW WORLD SO WE HAVE TO BE SAVVY. SO THE OTHER BRAN OF EPIDEMIOLOGY WHICH I SUBSCRIBE TO IS EPIDEMIOLOGY THAT TRANSLATES THE EPIDEMIOLOGY THAT CALCULATES, COMMUNICATES AN INTERVENES. THIS IS WHERE I'M ASPIRING TO BUT THE BALANCE BETWEEN A LINE MASTER LEVEL Ph.D. AND POST DOC THAT WRITES A LOT OF PAPERS FROM THE DATA SETS YOU HAVE AMASSED VERSUS TRANSLATIONAL EPIDEMIOLOGY THAT LOADS TO INTERVENTIONS AN POLICIES AND TREATMENTS. SO OUR BIG OBJECTIVE FOR THE NEXT LITTLE WHILE IS TO COME UP WITH REALLY 12 BIG IDEAS BIG RECOMMENDS TO INFLUECE THE FIELD. WE'RE NOT GOING TO DO THAT IN THE SPAN OF 24 HOURS. WE HAVE ALREADY AMASSED A NUMBER -- A LOT OF INPUT ON LOIN AND WE WILL CONTINUE THE CONVERSATION. I WOULD LICK TO GO OVER THE SESSION VERY QUICKLY TO TELL YOU WHAT'S AHEAD AND THEN WE'LL START WITH THE FIRST SESSION. SO BOB FIRST SESSION WOULD BE QUICKLY REVIEWING THE EVOLUTION OF EPIDEMIOLOGY AND APPLICATION FOR CANCER, BOB HOOVER WILL LEAD US INTO THAT DISCUSSION. THE PANEL WAS CHARGED WITH ANSWERING TWO QUESTIONS, WHAT LESSONS AN SUCCESS STORIES LEARNED FROM 20th CENTURY CANCER EPIDEMIOLOGY AND THINK ABOUT THE MAJOR SCIENTIFIC QUESTIONS THAT CANCER EPI SHOULD ADDRESS NEXT DECADE THAT IMPACT PUBLIC HEALTH. IN THIS CONTEXT IT'S TIMELY TO MENTION THAT NCI OVER THE LAST COUPLE OF YEARS UNDER DIRECTION OF HAROLD VARMUS HAS BEEN ENGAGING IN NCI-WIDE THINKING ABOUT THE PROVOCATIVE QUESTIONS THAT FACE US ALL IN THE WAY WE DEAL WITH CANCER. WE'RE GOING TO IN SOME OF US ARE LOOKING AT THE PROVOCATIVE QUESTIONS FROM AN EPI PERSPECTIVE SEEING HOW MANY OF THEM LAND THEMSELVES TO AN EPI TYPE ANALYSIS. TO ME ALL ROADS LEAD TO EPICS ONE TIME OR ANOTHER, WHETHER BASIC SCIENCE QUESTION OR A HEALTH SERVICES QUESTION ANYWAY. SO THAT'S OUR CHANCE FOR THE FIRST SESSION. THE SECOND SESSION WILL ESSENTIALLY BE FOCUSED ON THE METHODS AND TECHNOLOGIES AND JEFF GINSBURG, I SEE A TYPO HERE, JEFF, FOR GIVE ME. -- FORGIVE ME. TOO MANY THINGS HERE. WE WILL -- YOU WILL LEAD US INTO A DISCUSSION OF THE TECHNOLOGY-DRIVEN FIELD AND WE'LL ASK THE PANEL TO RESPOND TO TWO QUESTIONS, WHICH TECHNOLOGIES FEEL RIGHT ALREADY FOR PRIME TIME IN RESEARCH AND FOR WHAT PURPOSE. SECOND, WHAT CRITERIA WOULD YOU USE TO DETERMINE WHETHER EMERGING TECHNOLOGY COULD BE INTEGRATED OR SHOULD BE INTEGRATED INTO EPI RESEARCH. THEN WE MOVE ON, I THINK THAT'S TOMORROW MORNING, TO TALK ABOUT EVOLUTION OF EPIDEMIOLOGIC COHORTS. SOME OF YOU MAY HAVE ATTENDED THE COHORT CONSORTIUM THE END OF OCTOBER. THERE'S A LOT OF RICHN 'T AN WEALTH OF INFORMATION AND EXPERIENCE THAT HAS ARISEN OUT OF THAT SPACE. AND JULIE BURN WILL LEAD US INTO A DISCUSSION OF WHAT WE HAVE LEARNED FROM THE COHORTS AN WHERE WHERE WE'RE GOING NEXT. AND ASK THE PANELISTS TO RESPOND TO TWO QUESTIONS. DEVELOPMENTS NEEDED TO MAKE THE COHORTS A CONNER STONE OF DISCOVERY TO PRACTICE CONTINUUM. NOT JUST DISCOVERY BUT THE TRANSLATIONAL PATHWAY AND HOW WOULD NCI AND NIH IN GENERAL FACILITATE THAT KIND OF MULTI-DISCIPLINARY COLLABORATION TO INTEGRATE THESE DEVELOPMENTS IN OUR RESEARCH PORTFOLIO. THEN WE MOVE TO SESSION 4 FOCUSING ON THE TRANSLATIONAL ASPECT AND DAVID WILL LEAD US INTO ROLE OF EPIDEMIOLOGY AND RESEARCH ALONG THE CANCER CASE CONTINUUM, PREVENTION TO TREATMENT. WE'RE GOING TO ASK THE PANELISTS TO RESPOND TO TWO QUESTIONS, NEW WAYS FOR EPIDEMIOLOGY TO BE USED TO FILL GAPS BETWEEN AT THIS COVERRY AND IMPACT AND IMPORTANTLY, HEARD THAT DISCUSSION OVER THE YEARS ABOUT SORT OF THE INTERPLAY OR CONVERGENCE BETWEEN OBSERVATIONAL EPIDEMIOLOGY AND RANDOMIZED CLINICAL TRIALS. I WAS IN ENGLAND LAST WEEK WHERE SOMEBODY WAS CAUSED US -- IN A TALK ON GENOMICS THERE'S NOT ENOUGH PEOPLE TO DO RANDOMIZED CLINICAL TRIAL WHERE IS YOU STRATIFY EVERYBODY BY EVERY SINGLE VARIABLE IN THE WORLD BUT SOME OF THE PANELISTS HERE MAY DISAGREE WITH THAT AND WOULD LIKE TO HAVE A LIVELY BATTLE. THEN WE MOVE TO KNOWLEDGE INTEGRATION AS THE LAST DRIVER AND JOHN WILL LEAD US INTO EMERGING ROLE OF EPIDEMIOLOGY AND RESEARCH. THE QUESTION IS VERY SIMPLE, EPIDEMIOLOGY DO THE NEXT FEW YEARS TO INTEGRATE KNOWLEDGE. THAT'S RAPIDLY ACCUMULATING FROM A DATA RICH ENVIRONMENT. LAST BUT NOT LEAST TRISH HARDY FROM OUR OWN NCI WILL HAVE A GENERAL SESSION FOR DISCUSSION WHERE RICHNESS OF DISCUSSION OVER THE LAST -- OF THE DAY AHEAD OF US PLUS WHATEVER WE HAVE HEARD ONLINE AND HEARING ON LINE THE NEXT 12 HOURS WILL BE FOR GENERAL DISCUSSION BY THIS AUDIENCE, OUR OBJECTIVE WILL CONTINUE DIALOGUE AFTER THAT. TO COME UP WITH 12 IDEAS WHETHER THEY LEAD TO 12 INITIATIVES OR THOUGHT PIECES, THAT YOU CAN MULL OVER, THIS IS A SHARED EXERCISE AND WE WOULD LIKE TO GET THE MOST OUT OF IT AS WE CAN. SO OUR OBJECTIVE IS TRULY TO ENGAGE SCIENTIFIC COMMUNITY IN THE CONVERSATION AS. AS BOB SAID WE STARTED SICK MONTHS AGO AND WE HAVE A LITTLE BIT OF EXPERIENCE THERE AS I SAID THE MEETING IS WEBCAST FOR THE IMMUNITY SO SPEAKERS AND PANELISTS KEEP SMILING. WE WILL BE MONITORING. WE HAVE A GROUP NEXT DOOR, COMMUNICATION GROUP THAT'S MONITORING OUR NEW TWITTER, NCI EPI WHICH IS JOINED TWITTER BETWEEN THE INTRAMURAL AND EXTRAMURAL DIVISION IN EPIDEEM THEOLOGY AT NCI. WITH I'LL CONTINUE THE DIALOGUE AFTER TOMORROW. A FEW HOUSEKEEPING THINGS. I WAS TOLD TO TELL YOU THAT WHEN YOU WANT TO TALK USE THE MICROPHONE. PUSH IT ON, PUSH IT OFF BECAUSE ONLY TWO OF THEM CAN BE ON AT THE SAME TIME. PLEASE SIGN UP THE DESK NO LATER THAN 3:15. THE DINNER WILL BE TWEET, EMAIL QUESTIONS ENGAGE OTHERS AN CONTINUE THE CONVERSATION AFTER YOU LEAVE TOMORROW. NOW I CAN'T THANK ENOUGH THE PEOPLE ON THIS SLIDE. OUR COMMUNICATION TEAM HAS BEEN WORKING INCESSANTLY THE LAST COUPLE OF MONTHS TO MAKE THIS WORK. WE HAD A COUPLE OF FELLOWS AND TONS OF GRATITUDE FOR PUTTING IT ALL TOGETHER. SO THANK YOU AGAIN FOR BEING HERE. LOOKING FORWARD TO A GOOD DISCUSSION UNLESS YOU HAVE QUESTIONS ON DESIGN OR WHAT LIES AHEAD, I'M GOING TO TURN IT OVER TO THE FIRST SESSION. GOOD TIMING. >> GOOD AFTERNOON. THANK YOU FOR ALLOWING ME TO HELP KICK OFF THIS RASHABLE MEETING. THOUGH I MUST SAY IT SEEMS A LITTLE MORE THAN COUNTER INTUITIVE TO START A MEETING TOTALLY FOCUSED ON THE FUTURE, WITH A LOOK AT THE PAST. BUT I THINK IT'S APPROPRIATE IN THIS CIRCUMSTANCE IF WE LOOK BACK AND SEE HOW WE HANDLED THE CHALLENGES AND THE OPPORTUNITIES IN THE PAST, MAYBE WE CAN GET SOME LESSONS FOR HOW TO DO A LITTLE BETTER IN THE FUTURE. SO OVER SEVERAL CENTURIES THERE WERE OCCASIONAL ALERT OBSERVATIONS LINKING EXPOSURES TO CANCER. GERMAN SURGEON (INAUDIBLE) RIGONI STERN, SEVERAL OTHERS, BUT AS MINE ALLUDED TO, -- MUIN ALLUDED TO THESE ARE ISOLATED EVENTS, THE SYSTEMATIC FORMAL STUDY OF CANCER EPIDEMIOLOGY MOST WOULD AGREE DIDN'T START UNTIL THE 1940s. AND WAS HERLED BY PUBLICATION OF THE TWO SEMINOLE STUDIES LINKING CIGARETTE SMOKING TO LUNG CANCER PUBLISHED IN 1950. OVER THE NEXT 25 YEARS THERE WERE MULTIPLE OTHER CANCERS LINKED TO MULTIPLE OTHER EXPOSURES. ALSO A FAIRLY SONG ASSOCIATION -- STRONG ASSOCIATION USUALLY 4 TO 1 UNFOLD, OVERALL OR IN THE HIGHEST DOSE GROUP. HOW DID EPIDEMIOLOGY BACK IN THIS PERIOD COMPARE TO WHAT'S GOING ON NOW? ONE WAY OF GETTING A HANDLE ON THAT IS TO ASK WHAT WERE EPIDEMIOLOGIES DOING -- EPIDEMIOLOGISTS DOING BACK THEN VERSUS NOW. SINCE I'M ONE OF THE FEW IN THE ROOM DOING BACK THEN AND DOING NOW, I'M IN A POSITION TO TELL YOU. THESE ARE GENERALZATIONS AND THERE'S EXCEPTIONS TO EVERYTHING I'M GOING THE SAY. BUT IN GENERAL BACK THEN WE WERE DOING SMALL SIMPLE STUDIES, RARE TO HAVE A STUDY OVER A FEW HUNDRED CASES. EXPOSURESES WERE ASSESSED WITH RECORD AND BEE QUESTIONNAIRES. THIS WAS RUN BY STUDY TEAM, ONE OR TWO EPIDEMIOLOGIST, A FIELD PERSON, THAT WAS ABOUT IT. AND THE PI DID VIRTUALLY EVERYTHING, CREATED THE QUESTIONNAIRE, TRAINED THE FIELD STAFF, SUPERVISED THEM, DID THE CODING, AND DID THE ANALYSIS ON A MECHANICAL CALCULATOR. WHILE WE WERE PRETTY PRODUCTIVE WE WERE DEFINITELY A COTTAGE INDUSTRY. WHAT DID IT LOOK LIKE NOW? NOW WE SPENT TIME ON LARGE COMPLEX STUDIES. NOT UNUSUAL TO HAVE THOUSANDS OF CASES, TENS OF THOUSANDS OF CASES AN MULTIPLE WAYS OF EXPOE SHOWER AND SUSCEPTIBILITY. THESE ARE LARGE MULTI-DISCIPLINARY TEAM BIOSTATISTICIANS AN EPIDEMIOLOGISTS BUT CLINICAL SCIENTISTS AN BASIC SCIENTISTS FROM DISCIPLINE, INFOR MATITIONS, PHYSICISTS, CHEMISTS, YOU MAIM IT, AND THE NEED FOR EACH OF THESE, THE NEED FOR DEPTH IN EACH AREA IS SO IMPORTANT THAT THE SPECIALIZATION IS SO IMPORTANT THAT THERE IS REALLY NO ONE PERSON RESPONSIBLE FOR ALL SCIENCE IN EACH STUDY. WE HAVE TO RELY ON YOUR COLLEAGUES IN THE IT IS MINUTES RESPONSIBLE FOR SCIENCE. SO WE DEFINITELY MOVEED FROM COTTAGE INDUSTRY TO BIG SCIENCE. THE BIG SCIENCE HAS COME TO A BUNCH OF DIFFERENCE AREAS IN SCIENCE OVER THE YEARS, PROBABLY THE FIRST WAS PHYSICS THIS HAPPENS TO BE IN A SMALL PHYSICS LAB IN CALIFORNIA, THERE'S TWO PHYSICISTS DOWN THERE WORKING ON THIS LASER OPERATION. SO WHY THIS DIFFERENCE? WHY EPIDEMIOLOGIC PRINCIPLES OVER TIME HAVE NOT CHANGED SO WHY HAS THE WAY WE DO BUSINESS CHANGEDDED DRAMATICALLY? TWO REASONS. ONE IS MAJOR CHANGES IN THE GOALS FOR CLASSICAL EPIDEMIOLOGY AN INTRODUCTION AND SHIFT TO MOLECULAR EPIDEMIOLOGY. FOR CLASSIC EPIDEMIOLOGY BACK THEN WE WERE INTERESTED IN LARGE RISKS AS NOTED IN THE FIRST SLIDE, ONE FOUNDER OF OUR FIELD WAS QUOTED SAYING HE WOULDN'T BELIEVE ASSOCIATION WITH RELEVANT RISK UNDER THREE. WE WERE TEALING WITH EVIDENT EXPOSURES ASSESSED BY EXTRACK OR QUESTIONNAIRES AN INTERESTEDDED IN MAIN EFFECTS. NOW WE'RE INTERESTD IF LOW LEVEL RISK CERTAINLY UNDER 3. UNDER 1.5, AS WE'LL SEE IN A MINUTE, UNDER 1.1. AND DEALING WITH DIFFICULT EXPOSURES FOR HAVING MULTIP BILL WAYS OF DOING THAT AND INTERESTED IN MODIFICATION OR INTERACTION AS WELL AS MAIN EFFECTS. WITH RESPECT TO MOLECULAR EPIDEMIOLOGY, THE REVOLUTION OVER THE LAST 25 YEARS IS, RAABLE AND KEEPS GETTING FASTER AND HAS GIVEN REMARKABLE TOOLS TO OVERCOME WEAKNESSES OF THE CLASSICAL APPROACHES MEASURING EXPOSURE, OUTCOME, ASSESSING SUSCEPTIBILITY, INSIGHTS TO CAR SIP GENIC MECHANISMS AN ASSESSING VERY LARGE NUMBERS OF MARKERS SIMULTANEOUSLY. HOW DID WE START DOING THINGS DIFFERENTLY? WAS IT WELL THOUGHT OUT LOGICAL AND TIMELY? THE ANSWER WAS NO TO ALL THREE. A COUPLE OF EXAMPLES ARE ILLUSTRATIVE. HORMONE THERAPY FOR MENOPAUSE WAS INTRODUCED IN EARLY 1940s. BY MID 1960s OVER 50% OF MENOPAUSAL WOMEN WERE ON LONG TERM USERS OF THIS DRUG. DESPITE THIS AND DESPITE THE FACT THERE HAD BEEN CONCERNS RAISED BY LABTOR SCIENTISTS AND CLINICAL SCIENTISTS THAT IT COULD BE CARCINOGENIC THERE WERE VERY FEW STUDIES. INDEED IN 1971, THE SUM TOTAL OF LITERATURE OF COHORT STUDIES OR CLINICAL FOLLOW-UP STUDIES WAS PUBLISHED WITH A THOUSAND EXPOSED INDIVIDUALS WHICH CHOSE PROFOUND PROTECTION AND LED THE AUTHOR TO SUGGESTION IT MIGHT BE A PROPHYLAXIS AGAINST ALL CANCERS. IT WAS ABOUT FIVE YEARS LATER THAT THE FIRST SUGGESTION THAT IT MIGHT BE BAD FOR YOU WAS PUBLISHED WITH THE INCREASING RELATIVE RISK WITH INCREASING DURATION OF USE. BUT WHILE SIGNIFICANTLY BELOW THE TREND WAS SIGNIFICANT THIS WAS A SMALL STUDY, A LITTLE OVER A THOUSAND WOMEN. AND 49 EXPOSED CASES. SO WHAT HAPPENED AFTER THIS? WE HAD 20 YEARS ONLY DESCRIBED AS A DISASTER. WE HAD MULTIPLE STUDIES, SMALL TO MEDIUM-SIZE STUDIES THAT FOUND RESULTS NOT COMPATIBLE WITH WITH EACH OTHER. BASICALLY NO CONSISTENCY AT ALL. SOME TIME RISK SOMETIME PROTECTION, SOMETIME NOTHING, SUBGROUPS DIFFER FROM STUDY TO STUDY. IT WAS ACTUALLY ESSENTIALLY CHAOS. LEADING TO KNOW PUBLIC HEALTH RECOMMENDATIONS. IN 1997 THIS ALL CHANGEDDED DRAMATICALLY. IT HAD THE POWER AND ABILITY TO LOOK AT A LOT OF THINGS TWO WHICH WERE PARTICULARLY IMPORTANT. ONE THE ABILITY TO SEPARATE HIGHLY CORRELATED VARIABLES AND THE ONE MOST IMPORTANT HERE WAS IF YOU WERE A USER WHO STOPPED OR IF YOU USED FOR A LONG TIME YOUR RISK WEPT TO RISK OF NON-USER VERY RAPIDLY. IF YOU ARE RESEN OR CURRENT USER THERE -- THE RISK WENT UP CONSISTENTLY ACROSS STUDIES. WITH DURATION OF USE. WAS THE ABILITY TO LOOK FOR INTERACTIONS. ONE SIMPLY JUMPED OUT, LEVEL OF O PAUCITY. IF A WOMAN WAS LEAN OR NORMAL WEIGHT RISK WAS QUITE HIGH. IF YOU WERE OBESE THERE WAS ESSENTIALLY NO RISK AT ALL. AS IT TURNS OUT THESE TWO FEATURES ACCOUNT FOR VAST MAJORITY OF CONSISTENCY OVER THE PREVIOUS 20 YEARS SO AT THIS POINT WE HAD A PRETTY GOOD GRASP OF THE RELATIONSHIP BETWEEN HORMONES AND BREAST CANCER AND AS IS REMARKABLE BECAUSE IT WAS ONLY 60 YEARS AFTER IT WAS INTRODUCED, 30 YEARS AFTER 50 PERCENT EXPOSURE RAY IN THE POPULATION, AND ONLY 20 YEARS AFTER THE FIRST SUGGESTING THAT IT MIGHT BE HAZARDOUS. I DON'T KNOW WHETHER YOU CONSIDER THAT SUCCESS OR NOT. SECOND EXAMPLE IS MOLECULAR EPIDEMIOLOGY, GENETIC EPIDEMIOLOGY. IN 1980s WITH GENOME ANALYSIS INVENTED WE WERE ABLE THE START USING THESE TOOLS TO IDENTIFY GENES THAT ARE RESPONSIBLE FOR THE MENDELIAN INHERITANCE LEADING TO HIGH RISK FAMILIES. SHORTLY THEREAFTER THE DEVELOPMENT OF RFLP AND OTHER TECHNOLOGIES GAVE THE OPPORTUNITY TO ASSESS RISK WITH COMMON SUSCEPTIBILITY GENES IN THE GENERAL POPULATION. WE STARTED TO DO THIS BY LOOKING AT THE CANDIDATE GENES LIKE HAVING OUR LABORATORY COLLEAGUES TELL US WHAT WAS LIKELY IMPORTANT BIOLOGICALLY AND CHECKING THAT. AND WHAT THIS LED TO, I HAVE TO REFER TO DAVID HUNTER FOR THIS AS HE USED H TERM, IS A LOST DECADE. ACTUALLY A LOST DECADE AND A HALF, ABOUT 15 YEARS WHERE THOUSANDS OF CANDIDATE GENES WERE PURSUED TO EXTINCTION IN TENS OF THOUSANDS OF STUDIES AND ONLY A FRACTION REPLICATED. BY 2006 WE HAD A GRAND TOTAL OF SIX SUSCEPTIBILITY GENES RELIABLY REPLICATED. TRACK RECORD FOR ROUTINE ENVIRONMENT INTERACTIONS WERE EVEN WORSE IF THAT'S POSSIBLE. WHAT HAPPENED NEXT? THE COMPLETION OF THE HUMAN GENOME PROJECT AND HAT MAP PROJECT, GAVE US ANNOTATED DATABASE OF VARIANTS IN THE GENOME AND THE RELATIONSHIP TO EACH OTHER. AND THE P DEVELOPMENT OF SNP CHIP, THE ABILITY TO MEASURE MANY, MANY, MANY VARIANTS FOR INDIVIDUAL IN AN EXTRAORDINARILY RELIABLE AND VALID MANNER. CREATE TO NOT DO THE CANDIDATE GENE APPROACH BUT TO DOING ANOSTIC SEARCHES OF THE GENOME AND GENOME WIDE ASSOCIATION STUDIES SO THAT WE COULD LET THE GENOME TELL US WHAT WAS IMPORTANT. AT THIS POINT IN TIME WE HAD IDENTIFIED SIX COMMON SUSCEPTIBILITY GENES ASSOCIATED WITH MALIGNANCY. AS MIDDLE OF OCTOBER WE HAD GENOME WIDE ASSOCIATION STUDIES, ABOUT 265 FOR MULTIPLE SITES OF CANCER. AND WITH ANOTHER 90 COMING SOON TO A THEATER NEAR YOU, MAKING THEIR WAY THROUGH THE LITERATURE SO BY JUNE WE SHALL HAVE OVER 400. THIS IS JUST FROM SOME OF THE EARLY HITS IN BREAST CANCER FROM GWAS JUST TO ILLUSTRATE TWO POINTS. ONE IS THAT THE RISKS INVOLVED ARE FAIRLY LOW. IN GENERAL, THESE GENOME WIDE ASSOCIATION STUDIES HERE, THEY RANGE FROM 20% TO 6%. DIFFERENCE PER DOSE OF GENE. BUT THEY ARE COMMON. IN THE POPULATION WHICH LEADS TO FAIRLY MEANINGFUL INTERPRETABLE RISKS OR IN THE GENERAL POPULATION. SO THEY ARE ACTUALLY QUITE IMPORTANT. SO IF THIS KIND OF BIG SCIENCE AND TECHNOLOGY COMING TOGETHER HAS LIBERATED US TO IDENTIFY SPECIFIC GENES HOW HAS IT WORKED FOR A GENE BY ENVIRONMENT INTERACTION? WELL, THUS FAR NOT SO WELL BUT I'M GOING TO TAKE ONE EXAMPLE BECAUSE IT MAKES A POINT I THINK IS IMPORTANT TO MAKE. IN THE MID 1990s THERE WAS STUDY THAT SUGGESTED THE RELATIONSHIP BETWEEN CIGARETTE SMOKING AND BREAST CANCER WHICH WAS SOMEWHAT INCONSISTENT AND FAIRLY LOW LEVEL WAS ACTUALLY INTERACTED WITH THE NAT-2 PHENOTYPE. RESPONSIBLE FOR AEROMATIC AND MEAN METABOLISM. AND TYPICAL OF THE TIME PEERED AFTER THAT WAS PUBLISH WED HAD TEN YEARS OF CONFLICTING STUDIES ACTUALLY 30 WERE REACHED NO LOGICAL CONCLUSION EXCEPT MORE RESEARCH WAS NEEDED WHICH PROBABLY MEANT BIG TROUBLE STUDIES SO WHAT HAPPENED AFTER THE CURRENT REVOLUTION IN GENOMICS? THERE WAS A PUBLICATION IN 2008 JUST ABOUT 7,000 BREAST CANCER CASES AND FAIRLY CONVINCINGLY SHOWING THERE IS ASSOCIATION AND IT IS A SIGNIFICANT INTERACTION WITH ACETYLATION PHENOTYPE WITH RISK BEING ESSENTIALLY ONLY AMONG THE SLOW SIMULATORS. SO WE HAVE JUST (INAUDIBLE) FROM GENES WERE LIBERATED IF THE AREA OF G BY E ALSO. NOT SO FAST. DAVID COX A YEAR AGO PUBLISHED ANOTHER STUDY SIMILAR SIZE, FOUND THE SAME OTHERALL ASSOCIATION WITH ABSOLUTELY NO EVIDENCE OF INTERACTION. SO (INAUDIBLE) NOT HAVE -- THIS ISN'T ABOUT NOT HAVING A BIG ENOUGH STUDY. SO WHAT'S GOING ON HERE? THIS IS AS I SAY A LESSON USING GENOMICS HISTORY AS A LESSON IS GREAT. HOPE YOU AGREE AFTER YOU GET DONE WITH TWO CAVEATS. ONE TO THE IMPORTANCE OF HIGH QUALITY EPIDEMIOLOGY METHODS. IT IS NOW ESTABLISHED AND A STANDING JOKE BETWEEN EPIDEMIOLOGISTS AND YES NET CYSTS THAT WORK ON -- GENETICISTS THAT WORK ON THESE, HIGH QUALITY EPIDEMIOLOGIC METHODS DON'T MEAN CRAP FOR THESE STUDIES. YOU GET THE SAME ANSWER WHAT THE IMPORTANT GENES ARE IF -- FROM THE WORST STUDIES COMPARED TO THE MOST PRISTINE DESIGN STUDIES. SO IN RETROSPECT THAT MAY NOT BE -- THAT MAYBE QUITE UNDERSTANDABLE. THE ACTUAL HUMAN GENOME IS A RESULT OF MILLENNIA OF EVOLUTIONARY PRESSURE DEVELOPING HETERO GENETIC PROFILE. THOSE AREN'T TERRIBLY SUSCEPTIBLE TO THE THINGS GENERALLY ASSOCIATED WITH ENVIRONMENTAL AND LIFESTYLE FACTORS. WHAT THIS THING MAYBE A WAKE UP CALL WITH GBIE INTERACTIONS, ONCE YOU PUT THE ENVIRONMENT BECOME IN WE'RE IN TROUBLE IF WE DON'T PAY ATTENTION TO THE QUALITY. THAT WILL EXPLAIN THE DILEMMA ON THE PREVIOUS SLIDE ONCE WE UNDERSTAND IT. AND I THINK THAT IT IS A REAL LESSON FOR THE FUTURE BECAUSE VIRTUALLY ALL THE OMICS ONCE BEYOND GENOMICS HAVE ENVIRONMENT IN THEM. THEY ARE ACTUALLY MEASURES OF THE ENVIRONMENT, OR MEASURES OF THE INTERACTION BETWEEN ENVIRONMENT AND THE GENE. SECOND CAVEAT IS ASSAY DEVELOPMENT. GENETICIST HANDED US AND A SILVER PLATTER EPIDEMIOLOGY GRADE READY TO GO TOOL TO MEASURE THOUSANDS, MILLIONS OF SNPS IN AN INDIVIDUAL WITH -- IN A HIGHLY RELIABLE INCREDIBLY VALID AND -- TOOL. THAT'S NOT GOING TO HAPPEN OFTEN AND IT CERTAINLY ISN'T GOING TO HAPPEN OFTEN WITH THE OTHER OMICS. THEY'RE NOWHERE NEAR THAT LEVEL OF SOPHISTICATION. AND NOWHERE NEAR THAT LEVEL OF ABILITY TO USE IN THE KIND OF STUDIES WE ENVISION. SO WE'RE GOING TO HAVE TO GET IN BED WITH OUR LABORATORY COLLEAGUES AND ACTUALLY WORK WITH THEM TO BRING THESE ASSAYS INTO UTILITY FOR US AT -- AND FULFILL THE PROMISE THEY HAVE, THE GREAT PROMISE THEY ALL HAVE. SO THIS BRINGS ME TO WHAT LESSONS WE HAVE. I THINK WE CAN LEARN FOR THE FUTURE FOR THIS PARTICULAR CONFERENCE FOCUS FROM WHAT DONE IN THE PAST. ONE, WE NOT AS SMART AS WE WISH WE WERE. THAT MEANS WE NEED TO DO LESS A PRIORI HYPOTHESIS TESTING AND MORE LISTENING TO THE DATA. IF YOU TOLD ME IN THE 1970s YOU SHOULD CONTINUE TO PURSUE THE ISSUE OF MENOPAUSAL HORMONES AND BREAST CANCER BUT ONLY LOOK IN CURRENT USERS BECAUSE THOUGH WE WERE A USER 15, 20 YEARS GOING TO HAVE RISK OF NON-USER ONCE THEY STOP. AND ONLY LOOK IN LEAN WOMEN BECAUSE YOU WON'T SEE IT -- SIMPLY NOT ON THE RADAR SCREEN FOR BEING A PRIOR AT THAT POINT IN TIME. YOU CAN SEE WHETHER OUR TRACK RECORD WAS FOR PRIORS IN THE AREA OF CANDIDATE GENES. SIX OUT OF SEVERAL THOUSAND. IF WE DO THIS THE MANDATORY COROLLARY WAS REPLICATION, REMYCATION, REPLICATION, BIG STUDY, A LOT OF STUDIES IN ORDER TO AVOID THE FALSE POSITIVE PROBLEM. REMARKABLE OPPORTUNITIES FROM SCIENCE AND TECHNOLOGY IN CLASSICAL EPIDEMIOLOGY AS POINTED OUT BY MUIN AS WELL AS MOLECULAR EPIDEMIOLOGY, BUT ALL THE OMIC, IS WITH WITH MANDATORY COROLLARIES HERE BEING AS WE DISCUSSEDDED, WE HAVE TO WORK WITH WITH LABORATORY COLLEAGUES CLOSER THAN WITH THE GENETICISTS TO BRING TO PRIME TIME. WE NEED TO USE BEST EPIDEMIOLOGIC METHODS. FAMOUS TITLE TO FAMOUS PAPER, BIGGER BETTER SOONER. MANY IMPORTANT COP TEMPORARY QUESTIONS CAN BE ADDRESSED BY HIGH QUALITY EPIDEMIOLOGIC DATA. SO THOSE ARE THESE THREE. THERE'S WITH ONE MORE THAT I WOULD LIKE TO ENCOURAGE, WE HAVE TO BE MUCH FASTER AND BETTER ADAPTING METHS TO MEET THE NEW SCIENTIFIC NEEDS AND OPPORTUNITIES AS THEY OCCUR, WE CANNOT WAIT 20 YEARS TO GET -- TO TEST APPROPRIATELY A HYPOTHESIS THAT HAS IMPORTANT HEALTH IMPLICATIONS LIKE I SHOWED FOR HORMONES. WE CANNOT WASTE HUNDREDS OF MILLIONS OF DOLLARS IN USING FAILED METHODOLOGIES AS WE HAVE DONE FOR CANDIDATE GENES. WE HAVE TO GET BETTER AT SEEING AN OPPORTUNITY, SEEING AN OBSTACLE IN DECIDING WHAT NEEDS TO BE DONE TO GET THE ANSWER. I SPEND ALL THAT TIME TALKING THE NEEDS OF THE SCIENCE AN WHERE IT SHOULD GO. I SPENT NO TIME TALKING ABOUT FORMIDABLE ON STACKCLES IMPLEMENTING THESE LESSONS. THEIR REGION BUT THIS COULD BE THE SUBJECT MATTER OF AN ENTIRELY DIFFERENT MEETING IN AND OF ITSELF. WHAT I WOULD LIKE TO EMPHASIZE THE SECOND ADJECTIVE HERE. THESE ARE FORMIDABLE BUT SURMOUNTABLE. WE'RE MT. PROCESS OF SURMOUNTING SOME IN OUR OWN STUDIES AND OTHER DISCIPLINES GONE OVER TO BIG SCIENCE TECHNOLOGY ORIENTED BIG SCIENCE, HAVE IN FACT SOLVED THIS. SURMOUNTED THESE I THINK EPIDEMIOLOGY SHOULD BE AS GOOD AS PHYSICS IN DOING ABLE TO DO THIS. SO I ACTUALLY OPTIMISTIC ABOUT THE FUTURE. ANY QUESTIONS YOU HAVE? [APPLAUSE] >> THANK YOU BOB. WE'RE GOING TO ASK THE PANEL TO COME TO THE TABLE IN THE FRONT AND JOIN US. AND WE'RE FOLLOWING A FORMAT OF A FEW BRIEF PRESENTATIONS, EACH SPEAKER WAS ASKED TO LIMIT THEMSELVES TO A SLIDE. NOT EASY TO DO. HARD FOR SOME AND HARDER AND PAINFUL FOR OTHERS. SO THANK YOU BOB HOOVER FOR LAYING THE LANDSCAPE AND SETS US UP FOR THE NEXT SESSION. THIS IS SETTING THE THE STAGE SESSION WHERE YOU'RE GOING TO BE HEARING ABOUT BROAD OVERARCHING ISSUE LIKE TECHNOLOGY, METHODOLOGY COHORTS, ET CETERA. SO WE WILL FOLLOW THE ORDER ON YOUR PROGRAM, FIRST DAVID HUPPER FROM HARVARD. THEN TIM REBBECK FROM UNIVERSITY OF PENNSYLVANIA. MARGARET SPITZ FROM BAILOR COLLEGE OF MEDICINE. NO LEPPINGTHY ANECDOTES OR PERSONAL STORIES OR EMBRACING TALES, THEIR BIOS ARE IN YOUR MEETING MATERIALS. IF YOU'RE AN EPIDEMIOLOGIST AND YOU DON'T KNOW THAT'S PEEP ARE YOU'RE A LOST BALL IN HIGH WEEDS. SO LET'S DIVE IN AND I'LL ASK DAVID TO START US OFF. >> I WOULD LIKE TO THANK THE ORGANIZERS FOR BEING PART OF THIS MEETING, IT'S A TIMELY MEETING AN PERFECT TIME. H SESSION IS ENTITLED EVOLUTION OF CANCER EPIDEMIOLOGY. WE HEARD STRONG INDICATIONS OF THIS THAT THE DRIVING PRINCIPLE BEHIND OBTAINING ROBUST RESULTS, THE DRIVING EVOLUTIONARY PRINCIPLE IN CANCER EPIDEMIOLOGY IS SURVIVAL OF THE FATTEST. THAT'S A BIT OF AN -- SO MAYBE WE SHOULD SAY SURVIVAL OF BIGGEST. THE BOXING ANALOGY IS GOOD BIG STUDY WILL BE A GOOD SMALL STUDY AND BOB HOOVER SUMMARIZED GWAS RESULTS AND IF YOU TOLD ME WE WOULD BE TALKING IN 2012, WE AS EPIDOMOLOGISTS COULD GET RELATIVE RISK OF 1.03 AND 1.04 AND GET THEM RIGHT ALBEIT IN A SETTING OF MINIMUM INFORMATION BIAS, MINIMUM SELECTION BIAS, CONFOUNDING I WOULDN'T BELIEVE IT, THE ANSWER WAS MACY SAMPLE SIZE, SO BIGGER BETTER SOONER, WE HAVE BEEN THROUGH THIS THAT'S MY CONTRIBUTION TO THE BLOG. NONE OF THIS IS TO BE CAREFUL HERE REVOLUTIONARY WHICH IS SHOWING US THE MATH BEHIND THIS MORE THAN 30 YEARS, JOHN (INAUDIBLE) HAS BEEN SAYING THIS ONE WHICH OR ANOTHER FOR THE LAST DECADE. SO MUIN SHOWED US THE PROGRESS MADE IN TERMS OF META ANALYSES POOLED ANALYSES AN DATA SHARING. BUT I WANT TO SORT OF TRY AN ANALOGY HERE TO SEE HOW FAR ALONG WE HAVE GOT. THE POLITICAL SEASON JUST FINISHED. JUST IMAGINE YOU (INAUDIBLE) ABOUT TWO MONTHS AGO PRIOR TO ELECTION. AND YOU GO OUT TO BASICALLY GET THE DATA YOU NEED TO PREDICT RESULTS OF THE U.S. PRESIDENTIAL ELECTION. SO YOU TOTAL THE LITERATURE AND FIND THE GROUP FROM WORK PUBLISHED THE NEW YORK POLLING DATA IN AMERICAN JOURNAL OF EPIDEMIOLOGY. AND ABOUT FIVE POINTS OFF. THE GROUP FROM TEXAS HAS PUBLISHED THE TEXAS DATA. IN JOURNAL OF NATIONAL CANCER INSTITUTE AND ROMNEY IS 5 POINTS UP BUT IN CBP THE COCOLE GROUP PUBLISHED THE COLORADO DATA AND IT'S JUST TOO CLOSE TO CALL. SO NOW YOU CAN DO A META ANALYSIS. BUT YOUR INTERESTED IN PREDICTING RESULTS, THE ENTIRE COUNTRY, AND YOU'RE AWARE OBVIOUSLY THERE'S VAST AMOUNTS OF DATA MISSING. SO YOU GO HUNTING FOR THESE. SO YOU CALL FLORIDA AND THEY SAY WE WILL THE OUR NIH GRANTS AND WE DON'T HAVE MONEY TO ANALYZE THE DATA. I CALLED A GROUP IN NORTH CAROLINA AND THEY SAY THERE'S A (INAUDIBLE) WE WANT TO PUBLISH RESULTS FOR STATE SENATE, PUBLISHED THE PRESIDENTIAL RESULTS BEFORE THAT, EVERYBODY WILL INFER WHAT THE SENATE RESULTS ARE AND WITH WE'LL SCOOP OURSELVES SO IN A COUPLE OF WEEKS WE'LL GIVE YOU THE PRESIDENTIAL DATA. PEOPLE IN OHIO KNOW EVEN WITNESS OHIO SO YOU CALL UP OHIO AND THEY SAY WE HAVE ARRANGED PUBLICATION IN A -- BUT IT'S EMBARGOED UNTIL THEN. SO IF ANY OF THIS SO YOU WANT FAMILIAR, IT'S BECAUSE WE STILL SUBSTANTIALLY BEHAVE IN THAT WAY. WE KIND OF PING-PONG BACK AND FORTH IN THE LITERATURE UNTIL SOMEONE DOES META ANALYSIS OF LESS THAN THE COMPLETE THEORETICALLY AVAILABLE DATA. WE HEARD REASONS WHY IT'S PROBABLY DESIRABLE TO OHIO, EPIDEMIOLOGY OH IS GETTING BACK TO US AND THEY MIGHT AGREE TO CONTRIBUTE DATA BUT ONLY IF THEY GET A JOINT FIRST ORDER SHIPMENT, JOINT LAST ORDER SHIP IN THE NEW YORK TIMES. SO WE OTHER STILL BEHAVING IN THIS WAY BY AND LARGE. QUESTION IS HOW WE MOVE FORWARD. SO MY ONE SLIDE, ONE SOLUTION WOULD BE A NATIONAL COHORT STUDY, IF YOU'RE PARTICULARLY LINGUISTIC YOU MIGHT CALL IT THE U.S. NATIONAL COHORT STUDY. TERRY MA KNOLL OWE AN FRANCIS COLLINS HAVE BEEN PROMOTING THIS IDEA FOR QUITE SOME TIME, I THINK IT'S VERY SENSIBLE IDEA, HOW OTHER COUNTRIES OFTEN BEHAVE. BUT IT'S NOW SIX, SEVEN YEARS LATER AND WE HAVEN'T GOT THERE AND PRESUMABLY THE REASON IS SOMETHING TO DO WITH THE FACT THAT NIH IS BROKE AND THIS COSTS A LOT OF MONEY. IN CANCER EPIDEMIOLOGY WE'RE PRIVILEGED DUE TO THE FACT PEOPLE HAVE DONE WORK AND NCI INVOLVED IN THAT -- INVOLVED IN THAT WORK TO HAVE EQUIVALENT OF U.S. NATIONAL CANCER CASE CONTROL STUDY. CASE CONTROL STUDIES NEED TO BE PART OF THIS FOR LESS COMMON DISEASES. HERE IS THE SLIDE I MODIFIED FROM A SLIDE PUT TOGETHER FOR THE COHORT CONSORTIUM. WE HAVE BEEN BEEN AS MUIN SHOWED GOOD IN THE CANCER EPIDEMIOLOGY COMMUNITY LAST TEN YEARS COMBINING DATA. I CAN TALK PERSPECTIVE STUDIES TOP SET OF STUDIES HERE, BOB HOOVER CONVENED US AND TOLD WHAT BECAME NCI BREAST AND CANCER COHORT CONSORTIUM, TRISH HOGI AND OTHERS EXPENDED TO PANCREAS, GLIOMA IN THE CONTEXT OF GWAS BUT ALSO IN THE CONTEXT OF G WEST TO AVOID PROBLEMS WE WERE RUNNING INTO WITH CANCER CANDIDATE APP DATE GENES BUT WORK IS NOW EXTENDED WELL BEYOND MASS INDEX, PHYSICAL ACTIVITY AND RANGE OF OUTCOMES. JUST TO NOTE NCI IS NOW I THINK WISELY MOVED TOWARDS INFRASTRUCTURE FUNDING OF MAY THESE COHORTS SO PEOPLE USED TO HAVE A LEGITIMATE STATEMENT THEY HAD TO PUBLISH THEIR OWN DATA FIRST THEY HAD STUFF TO PUT IN THE PROGRESS REPORT. WE'RE MOVING IN THE RIGHT DIRECTION THERE. AT LEAST NOT IN THIS COMMUNITY PERHAPS BUT OTHER COMMUNITIES THERE IS A COMMON ASSUMPTION THAT WE CAN'T MEASURE EXPOSURE. THE PROBLEM IS WE KNOW MORE IF WE CAN MEASURE EXPOSURE, WE CAN BECAUSE WE HAVE THESE EXPOSURE DISEASE ASSOCIATIONS. NHGI AND NIEHS PUT TOGETHER THE PHOENIX PROJECT, US A LOT OF SMART PEOPLE HERE GOT TOGETHER IN WORKING GROUPS AN CAME UP WITH BEST PRINCIPLES FOR MEASURING EXPOSURE, PHENOTYPES AN CAME UP WITH BEST PRACTICE VERSIONS OF WHAT EVERYBODY HAS BEEN DOING. MAYBE THERE WILL BE GIZMOS AND OTHER THINGS THAT HELP ALL THE TIME BUT THEY'RE IN THE HERE YET. AND P IT IS OFTEN SAID THESE COHORTS AREN'T DIVERSE AND I WOULD POINT OUT THAT YES, THEY ARE DIVERSE OR AT LEAST SOME ARE CONTRIBUTING DIVERSITY IF WE PUT THEM ALL TOGETHER. SO MY SENSE IS THAT IF WE'RE SEROUS ABOUT THE RIGHT ANSWERS, AS REALLY ESSENTIALLY MUIN AND BOB PREFIGURED, IT ANSWER IT IS QUESTION WE HAVEN'T TALKED ABOUT AND MY COLLEAGUES TALK ABOUT THE QUESTIONS THEN WE NEED A RENEWED DRIVE TOWARDS PUTTING THE DATA TOGETHER IN A FORMAL PERSPECTIVE FASHION AND NCI DECLARES THE U.S. NATIONAL CANCER COHORT CONSORTIUM, SOMETHING SIMILAR FOR CASE CONTROL STUDIES AND P MATTER OF URGENCY CONVENES THE PEs TO WORK OUT WHAT THE CONSTITUTIONAL ISSUES ARE AND WHAT THE BUDGET WOULD NEED TO BE. >> THANK YOU, DAVID. I'LL MOVE TO TIM REBBECK. >> THANK YOU VERY MUCH. >> TODAY THERE WILL BE SECRETARY MORE IN A SERIES. THESE WILL BE FOCUSED AROUND ISSUES WE'RE DISCUSSING TODAY AND WE'RE GOING TO ALL PRINT THOSE AND HAVE THEM AS A SEPARATE SECTION, THEY'RE ALL READY AND BOUND FOR THE AACR ANNUAL MEETING IN APRIL SO LOOK FOR THAT AND SOME OF THE STINGS THAT Y'ALL ARE GOING TO BE SAYING TODAY AND COMMENTS WE'RE GETTING BACK WILL INFLUENCE SOME OF THOSE PAPERS. SO WE HOPEFULLY WILL HAVE A BODY OF KNOWLEDGE OF THIS PROCESS AND MEETING AND HOPE Y'ALL PAY ATTENTION AND THINK ABOUT THAT BUT MAKE YOUR COMMENTS AS MUIN ASKED YOU BECAUSE IT WILL INFLUENCE WRITTEN THINGS IN THE COMING MONTHS. SO MY THOUGHTS ARE SUMMARIZED ON THIS SLIDE, NOW THAT I CAN BARELY SEE IT, SO HOPEFULLY YOU CAN SEE IT. WHAT I WANTED TO DO WAS AMPLIFY A LITTLE BIT ON THINGS THAT MUIN SAID AND BOB HOOVER ALSO MENTIONED. THAT IS THAT WHAT WE HAVE BEEN COOING IN THE PAST LARGELY UNIDISCIPLINARY KINDS ROUGH RESEARCH, THAT HASN'T BEEN BAD, MAYBE WE HAVE TWO DISCIPLINES COME TOGETHER AND WE TALK BUT REALLY WHAT WE HAVEN'T BEEN ABLE TO DO IN VERY WELL IS ADDRESS COMPLEXITY OF CANCER IN A VERY SYSTEM MA I CAN WAY SO THIS SLIDE TRIES TO GIVE A SENSE HOW WE MIGHT THINK ABOUT THAT. SO YOU CAN'T READ ALL THIS. LET ME JUST GIVE YOU THE LITTLE OVERVIEW. ON THE LEFT HAND PANEL ARE LEVELS WE MIGHT WANT TO THINK ABOUT WHEN WE ARE INTERESTED IN CANCER. SO VERY BOTTOM WE HAVE BIOLOGY, HEN WE HAVE -- BIOLOGY, INDIVIDUAL LEVEL EXPOSURES. SOCIAL, POLITICAL KINDS OF MECHANISMS, WE HAVE HEALTHCARE ACCESS. ALL THESE NEED TO BE TAKEN INTO ACCOUNT. I DON'T NEED TO CONVINCE YOU OF THAT BECAUSE YOU PROBABLY AGREE MULTI-LEVEL ANALYSIS, AS MUIN INTRODUCED IS SOMETHING THAT IS PROBABLY GOING TO HELP US UNDERSTAND THIS VERY COMPLEX PROBLEM THAT WE HAVE IN CANCER. BUT MOST PART WE HAVEN'T DONE THAT VERY WELL. SO NEXT PANEL IN THE MIDDLE THE NEXT SET OF BOXES REFLECT HOW IT'S BEEN IN THE 20th CENTURY WHERE WE HAVE HAD ENVIRONMENTAL EPIDEMIOLOGY WORKING ON PROBLEMS AN MOLECULAR GENETIC EPIDEMIOLOGYING ON PROBLEMS. TO REFLECT WHAT BOB WAS SAYING MINUTE AGO, THE BOTTOM MIDDLE BOX DOWN THERE IS SORT OF REPRESENTATIVE OF THE SUCCESS WE HAVE SEEN IN GWAS. SO WE HAVE HAD THROUGH LAST DECADE AMAZING RESULTS AND PROGRESS.ST THAT'S BEEN IN THAT BOX I WOULD SAY. IT'S VERY INTEREST PING FOR ME, AND WOULD BE USEFUL FOR THIS GROUP AN PEOPLE THINKING ABOUT THIS PROBLEM TO REFLECT ON WHY EPIDEMIOLOGY WHEN IT WAS LED BY EPIDEMIOLOGY, THE PROBLEM WAS DONE IN A PRODDING KIND OF WAY AN AS BOB MENTIONED NOT SUCCESSFULLY, WHEN THE GENETICISTS TOOK OVER, THERE'S MANY EPIDEMIOLOGISTS INVOLVED BUT WHEN GENETICS TOOK OVER THE PROBLEM WAS SOLVED IF A DIFFERENT WAY, WE CAN PROBABLY DO HISTORICAL DESCRIPTION WHY THAT IS BUT WHY DOES THE DISCIPLINE OF EPIDEMIOLOGY, NOT ABLE TO COME UP WITH THAT LEVEL, THAT KIND OF SUCCESS? WHEN IT WAS LEADING THE PROBLEM? THE ANSWER TO THAT, YOU CAN GUESS WHAT YOU THINK MIGHT HAVE BEEN THE REASONS. I THINK IT'S INTERESTING TO ME THAT LOOKING AT EPIDEMIOLOGY WE HAVE ACE AND SER AND AES AN LOTS OF SOCIETIES AND WE'RE SPLINERRED AND WE WORK MANY DIFFERENCE WAYS AND WE DON'T TALK TO EACH OTHER IN THE RIGHT WAYS AND SOME OF THAT IS REFLECTIVE OF THE PROBLEM YOU MIGHT HAVE SEEN IN THE IDENTIFICATION OF GENES. IN COMMON DISEASE. SO I THEY'S WORTHYING ABOUT AND THINKING ABOUT WHY LEARNING IN MY 12 SECONDS LEFT, CAN'T GO THROUGH ALL THE REASONS BUT YOU CAN THINK ABOUT THOSE AND THAT'S VERY ILLUSTRATIV,=– SITUATION TO ASK WHY EPIDEMIOLOGY WAS NOT SUCCESSFUL WHERE THE GWAS SETTING BECAME SUCCESSFUL, PART OF THAT WAS THE EMERGENCE OF THE COHORTS AN DIRECTION OF NCI AND OTHER GROUPS. YOU PROBABLY HEARD PEOPLE SAY THIS NEEDS TO BE A DIRECTED PROCESS OR PROCESS LED BY SOMEBODY IN SOME WAY. YOU WANT TO KNOW HOW TO HERD CATS YOU HAVE TO MOVE THE CAT FOOD. YOU HAVE TO BE -- CATS WON'T BE HERDED IN ANY OTHER WAY SO A GROUP LIKE NCI CAN HERD CATS IN WAYS THAT A LOT OF OTHER ORGANIZATIONS OR INDIVIDUAL SCIENTISTS CAN'T DO. WHAT DO WE NEED? IN ORDER TO START ADDRESSING IN MY OPINION IMPORTANT QUESTIONS MULTI-LEVEL SCIENCE THAT IS -- THAT REFLECTS THE SUCCESS THAT THE GWAS HAVE SHOWN US IN THE PAST FEW YEARS AND DAVID HUNTER TOLD US ABOUT SOME OF HIS IDEAS, BOB HOOVER, EVERYBODY IS THINKING ABOUT THAT. BUT I THINK THAT CAN BE EXPANDED INTO THE MULTIPLE LEVELS OF ANALYSIS AND I THINK THAT IT'S BIGGER BECAUSE WHEN YOU DO MULTIPLE LEVELS OF ANALYSIS YOU NEED BIGGER SAMPLE SIZES BUT WE ALSO NEED TO BE SMARTER WHICH REFLECTS THE EDITORIAL, THE NCEBP THAT WAS OUT AND WE NEED TO THINK NEW CLEVER WAYS OF DOING THESE ANALYSES, ONE WAY REFLECTED ON THIS SLIDE IS LOOKING AT NEW EXPOSURES. SO ONE THING THAT PEOPLE TALK ABOUT IS THE MACRO ENVIRONMENT, NOT JUST INDIVIDUAL LEVEL EXPOSURE BUT THE EXPOSURE IN THE CONTEXTUAL ENVIRONMENT AND WHERE YOU LIVE. SO AS AN EXAMPLE WE HAVE DONE A PAPER REACCEPTLY, WE HAVE ASKED ABOUT IN PROSTATE CANCER WHICH HAS VERY POOR SUCCESS IN TERMS OF ENVIRONMENTAL EPIDEMIOLOGICAL RISK FACTORS BUT SUCCESS IN GENETICS, 72 SNPS AT GENOME WIDE LEVELS SIGNIFICANCE. ESSENTIAL iZERO EPIDEMIOLOGICAL RISK FACTORS. AS OF TODAY. SO MAYBE WE CAN THINK OF INDIVIDUAL SUSCEPTIBILITY GENOTYPE SUSCEPTIBLE TO PROSTATE CANCER, OUTCOMES AND WHAT MEAN HAVE BAD OUTCOMES AND P CAN WE PREDICT OF MEN WHO ARE SUCK ACCEPTABLE BASED ON WHERE THEY -- SUSCEPTIBLE BASED ON WHERE THEY LIVE. THE NEIGHBORHOOD THEY LIVED IN. SO WE FOUND VERY STRONG INTERACTION P VALUES, AGAIN MAYBE THOSE ARE FALSE POSITIVES, I DON'T KNOW. IT IS A DIFFERENT ENVIRONMENTAL EXPOSURE. MAYBE IT'S NOT JUST AFRICAN AMERICAN MEN WHO HAVE BAD OUTCOMES OR MEN WITH PARTICULAR SUSCEPTIBILITY GENOTYPE BUT MAYBE IT'S AFRICAN AMERICAN MEN WHO LIVE IN A PARTICULAR NEIGHBORHOOD ENVIRONMENT, A SURROGATE FOR ACCESS TO HEALTHCARE AND BIOLOGY LAYERED IN. SO WE CAN START THINKING ABOUT ADDRESSING MULTIPLE DISEASE LEVELS AND DOING SOMETHING THAT BUILDS BEYOND WHAT SURROGATES WE CURRENTLY USE, SOMETHING LIKE THAT OR FAMILY HISTORY, PRETTY SURROGATES IN A LOT OF WAYS. SO THIS IS MAYBE UNCOMFORTABLE FOR SOME PEOPLE BECAUSE WHAT I JUST DESCRIBED IS NOT BIOLOGICALLY BASED. SO SOME THING IS WE MIGHT GET AWAY FROM IT HAS TO BE BIOLOGICALLY JUSTIFIED. WE USED VERY WELL TO PREDICT BUT IT'S HARD TO MAKE BIOLOGICAL INFERENCES FROM THAT. SO THAT MIGHT BE UNCOMFORTABLE BECAUSE WE'RE LOCKED INTO THE IDEA TO MAKE BIOLOGICAL INFERENCES AND THAT MIGHT BE TOUGH. SO THINK ABOUT MULTIPLE LEVELS, THINK ABOUT NOVEL EXPOSURE THAT MIGHT NOT BE THE INDIVIDUAL AND THINK ABOUT HOW THAT MIGHT BE USED TO CAPTURE WHAT WE HAVEN'T BEEN ABLE TO CAPTURE WITH TRADITIONAL EPIDEMIOLOGY. THANK YOU. >> THANK YOU, TIM. MARGARET FITS -- SPITZ. (OFF MIC) >> SORRY. I AM GUILTY AS CHARGED OF HAVING SPENT MOST OF MY TIME AND EFFORT ON ETIOLOGICAL RESEARCH IN THE DISCOVERY PHASE AND I HAVE NOT PAID SUFFICIENT ATTENTION TO TRANSLATION TO PUBLIC HEALTH IMPACT, THEREFORE I HAVE FALLEN INTO THE SO-CALLED TRANSLATIONAL VALLEY OF DEATH. I THINK MUIN COINED THAT PHRASE. IN THINKING ABOUT THE QUESTION OF WHAT ARE BIG QUESTIONS OR AS DR. VARMUS CALLED IT, THE PROVOCATIVE QUESTION, I FOCUS ON TWO RISK FACTORS RESPONSIBLE FOR THE MAJORITY OF MOST OF THE 60% CAUSE OF CANCER AND LEADING CAUSE OF MORTALITY IN THE U.S. IN GENERAL. THESE HAVE BOTH BEEN EXTENSIVELY AND HIGHLY SUCCESSFULLY STUDIED IN EPIDEMIOLOGICHOx STUDIES. HOWEVER THE CHALLENGE FOR US NOW IS HOW DO WE PURSUE THESE DISCOVERIES, EXPLOIT EVOLVING TOOLS SO THAT WE CAN KNOW THE WIDE GAP THAT STILL EXISTS BETWEEN DISCOVERY AND CLINICAL APPLICATION. THESE ARE OBVIOUSLY SMOKING AND OBESITY WITH FIST PHYSICAL INACTIVITY. SO THE OVERARCHING QUESTION FOR SMOKING IS HOW DO WE CHARACTERIZE THE BIOLOGIC BASIS OF SUSCEPTIBLE. WE LEARNED FROM THE GWAS WHICH HAVE BEEN HIGHLY SUCCESSFUL WE KNOW SOMETHING ABOUT THE GENETIC BASIS NOW OF LUNG CANCER BUT THIS EXPLAINS VERY LITTLE OF THE INHERITED VARIATION. THIS IS LED TO THE HOTLY DEBATED TOPIC OF IS THERE A MISSING HERITABILITY OF CANCER WHICH HOPEFULLY WE WON'T GO INTO TODAY. IN ADDITION WE DON'T KNOW THE RELATIVE IMPACT OF GENES CONTROLLING NICOTINE DEPENDENCE THE FOR INSTANCE GENES DIRECTLY RESPONSIBLE FOR LUNG CARCINOGENESIS. DO WE NEED NEW TOOLS FOR STUDYING GENE ENVIRONMENT INTERACTIONS? PERHAPS WE CAN CHARACTERIZE THE ENVIRONMENT EVEN MORE ACCURATELY THAN WE HAVE BEEN IN THE PAST. MOST IMPORTANTLY OF ALL, OUR RISK PREDICTION HAS NOT BEEN SUFFICIENTLY ROBUST SO THAT WE'RE ABLE TO SUCCESSFULLY INTEGRATE DISCOVERED SNPS INTO RISK PREDICTION THAT IS CLINICALLY VALID. IN TERMS OF OBESITY, WE HAVE DISCOVERED THERE IS A SUBSTANTIVE GENETIC CONTRIBUTION TO OUR VARIATION IN SUSCEPTIBILITY OR RESISTANCE TO THE OBESE GENIC ENVIRONMENT WHICH WE LIVE. MOST WOULD AGREE EPIDEMIOLOGIC STUDIES WILL DO VERY LITTLE TO ACCELERATE FURTHER MECHANISTIC UNDERSTANDING OF ASSOCIATION BETWEEN OBESITY AND CANCER RISK. I THINK WE HAVE TO THINK OUTSIDE THE BOX AND CONSIDER MORE INTERESTING CHALLENGING QUESTIONS TO EXPLORE OBESITY CANCER ASSOCIATION. ONE OF THE QUESTIONS AND MOST IMPORTANT OF ALL IS CAN WE CLEARLY SHOW THAT IN INDIVIDUAL WHOSE LOSE WEIGHT THERE IS REDUCTION IN CANCER INCIDENCE AN MORTALITY COMPARED TO INDIVIDUALS WHO DO NOT LOSE WEIGHT. BECAUSE THIS COULD BE SUBSTANTIVE IMPLICATIONS FOR MODIFYING BEHAVIOR, IT COULD BE A POWERFUL BEHAVIORAL INCENTIVE. ANOTHER QUESTION IS WHAT IS THE ROLE OF ENERGY EXPENDITURE AND THIS BE USED TO PROMOTE WEIGHT REDUCTION WITHOUT CHANGING ALTERING DIET. INTERESTINGLY ENOUGH NOVEL IMAGING TOOLS WE'RE ABLE TO IDENTIFY AREAS OF BROWN ADIPOSE TISSUE WE PREVIOUSLY THOUGHT ONLY PRESENT IN NEWBORN INFANTS. ANOTHER QUESTION WHAT IS THE ROLE OF THE MICROBIOME IN ITS ASSOCIATION WITH OBESITY? WITH WE KNOW THIS IS SUCH A THING AS OBESE MICROBIOME WHICH HAS ABILITY TO INCREASE, HARVEST CALORIES FROM THE DIET. SO THERE IS SUCH A THING AS OBESE MICROBIOME. SO THERE ARE MANY OTHER QUESTIONS WE COULD HAVE ASKED AS WELL. HOWEVER, IN THE TIME WE HAVE I HAVE SELECTED THESE TWO. IT'S CLEAR, YOU HEARD THIS FROM ALL SPEAKERS BEFORE, IN ORDER TO ANSWER THESE AND OTHER QUESTIONS WE NEED INTEGRATIVE COHESIVE APPROACHES THAT COALESCE IS EXISTING SILOS AND DICHOTOMIES THAT ARE LARGELY DRIVEN BY DISCIPLINE SPECIFIC INTERESTS AND FOR EXAMPLE, SOME ARE INTERESTED MORE IN THE ENVIRONMENT THAN THE GENOME. OTHERS ARE INTERESTED IN RISK VERSUS OUTCOME, POPULATION BASED VERSUS LAYER BASED STUDIES. WE NEED TO COALESCE DIFFERENT INTERESTS E EXPAND BOUNDARIES OF MOLECULAR EPIDEMIOLOGY TO INCLUDE STUDIES OF TUMOR MOLECULAR GENETICS. WE NEED TO WORK WITH BASIC CANCER BIOLOGIST, SYSTEMS BIOLOGIST, SYSTEMS, BEHAVIORAL BIOLOGIST, WE NEED TO SET UP MULTI-DISCIPLINARY AND INTERDISCIPLINARY COLLABORATIVE VENTURES BUT MUST NEVER FORGET THE IMPORTANCE OF EXCELLENT DESIGNED STUDIES, PRISTINE DATA COLLECTION AND CAREFUL STATISTICAL ANALYSES. WE ADMIT THESE STUDIES ARE EXPENSIVE BUT IF WELL DONE THE SCIENTIFIC PAY OFF IS BETTER. IN TERMS OF ANSWERING THE QUESTIONS ASSOCIATED WITH SMOKING, OUR U-19 POST GWAS IS DOING A GREAT APPROACH OF EXPLORING THE FUNCTIONAL SIGNIFICANCE OF VARIANTS IDENTIFIED. IN ADDITION I THINK IT'S IMPORTANT WE DESIGN MUCH SMARTER AN MORE RATIONAL STUDIES TO ANSWER THE QUESTIONS, FOR EXAMPLE WE COULD IN LUNG CANCER LOOK AT INTERMEDIATE PHENOTYPES SUCH AS COPD, A MAJOR RISK FACTOR FOR LUNG CANCER OR DNA REPAR CAPACITY OR METABALOMIC STUDIES. WE ALSO NEED TO USE EXTREME PHENOTYPES BECAUSE IT'S WELL THOUGHT AND PROBABLY TRUE, WE KNOW IT'S TRUE THAT GENETIC VARIANTS ARE ENRICHED AT ONE OR BOTH EXTREME ENDS OF PHENOTYPE SO EXTREME PHENOTYPES FOR LUNG CANCER MIGHT BE HIGH RISK LUNG CANCER FAMILIES, EARLY ONSET LUNG CANCER OR PERHAPS LIFE SMOKERS WHO DEVELOPED LUNG CANCER AN SEVERE COPD AS WELL. BUT ABOVE ALL WE NEED TO DEVELOP RISK PREDICTION MODELS BECAUSE IT'S NOW BEEN SHOWN THAT LOW DOSE CT SCREEN REDUCES MORTALITY FROM LUNG CANCER, WE DO NOT HAVE RESOURCES TO SCREEN ALL 45 MILLION CURRENT SMOKERS AN 49 MILLION FORMER SMOKERS. WE NEED TO BE ABLE TO IDENTIFY THE HIGHEST RISK SMOKERS BECAUSE IF WE'RE ABLE TO REDUCE BY 10% LUNG CANCER MORTALITY TO BE EQUIVALENT TO PREVENTING DEATH FROM GLIOMA OR OVARIAN CANCER IN A YEAR. TO ANSWER QUESTIONS ABOUT OBESITY, I THINK THE MOST IMPORTANT IS WE NEED TO DEVELOP NEXT GENERATION MEASUREMENTS OF THE EXPOSURE IN TERMS OF THE DIET WE CAN USE PERHAPS DIGITAL PHOTOGRAPHY IN TERMS OF BODY FAT DISTRIBUTION WE CAN USE ULTRASOUND AND CT, WE CAN MEASURE ADIPOSE TISSUE EASILY NOW WITH PEAKED SCANS WITH CT SCANS. WE CAN USE EXTREME PHENOTYPES, WE CAN LOOK AT COMPARATIVE STUDIES OF POPULATIONS WITH DIFFERENCE TYPES OF BODY FAT DISTRIBUTION. WE CAN FOLLOW INDIVIDUALS WHO ARE EXTREMELY THIN AND I BELIEVE THERE ARE SUCH INDIVIDUALS, I HAVEN'T SEEN P THAT MANY IN THE UNITED STATES. WE CAN SCREEN CHEMICAL LIBRARIES TO LOOK FOR REGULATORS OF BROWN ADIPOSE SHIRE SHOE TO DEVELOP NOVEL ANTI-OBESITY MEASURES TARGETING CELLULAR ENERGY EXPENDITURE. PRE-CLINICAL STUDY, MOUSE MODELS, EXPOSE THEM TO DIETS AND SEE WHAT TYPES OF MOLECULAR PATHWAYS ARE PERTURBED. MOST IMPORTANT WE HAVE POPULATIONS WHO HAVE LOST WEIGHT AND MAINTAINED WEIGHT LOSS FOR LONG PERIODS OF TIME AND THESE ARE BARIATRIC SURGERY PATIENTS. THE FIX ON METABOLISM ARE SO PROFOUND THIS ACTUALLY CALLED METABOLIC SURGERY, WE CAN DO SERIAL SAMPLES OF THESE INDIVIDUALS AND SCREEN FOR METABALOMIC CHANGES. THIS WOULD HELP US UNDERSTAND NOT ONLY WHAT ARE THE CHANGES BUT WHAT IMPACT IT HAS ON REDUCTION IN BOTH CANCER INCIDENCE AND CANCER MORTALITY. FINALLY, WE CAN BEGIN TO LOOK AT THE DYNAMIC RELATIONSHIPS BETWEEN THE INTERESTINGLY CO-SYSTEM AND ITS ROLE ON HUMAN PHYSIOLOGY AND PATHOPHYSIOLOGY AND WE CAN SHOW IT HAS BEEN SHOWN THAT CHANGES IN DIET ALTER AND SHIFT THE CONSTITUTION OF THE GUT MICROBIOME. THIS COULD BE ANOTHER INTERESTING APPROACH TO WEIGHT REDUCTION TECHNIQUES. SO I AM VERY READY TO JOIN THIS FASCINATING DIALOGUE. I THINK EPIDEMIOLOGY PROVIDES A FRAMEWORK FOR THESE TYPES OF HEIDI MENTIONAL DATA, VERY LARGE STUDIES. I THINK WE DO HAVE TO RESHAPE THE FRAMEWORK A LITTLE BIT IN ORDER TO ACCELERATE TRANSLATIONAL RESEARCH BUT I DO BELIEVE WE CAN DO THIS AND I'M EXCITED TO JOIN YOU IN DOING THIS. THANK YOU. >> THANK YOU, MARGARET AND TO THE PANEL FOR THOSE COMMENTS. MAYBE I'LL START OFF THEN OPEN UP BOTH ON LINE AND IN PERSON FOR DISCUSSION QUESTIONS. ONE OF THE I THINK A LOT OF BASIC SCIENTISTS LOOK BACK ON THE FIRST COUPLE OF EPIDEMIOLOGY, A COMMON IMPRESENTATION IS THAT NAIVETY AMONG EPIDEMIOLOGY COMMUNITY, LUMPING ALL BREAST CANCER OR PROSTATE CANCER THAT WHY WOULD ONE EXPECT TO DISCOVER STRONG RELATIONSHIPS WITHOUT GOOD MOLECULAR PHENOTYPING OF TUMORS AND WHAT WE KNOW ABOUT SUBTYPES OF CANCER. SO NOW THAT WE HAVE SEEN NEW CASES COMING OUT DOING THAT, I'M WONDERING ABOUT THE CHALLENGES YOU SEE, FOR EPIDEMIOLOGISTS THAT WE RECOGNIZE THE IMPORTANCE OF DOING THIS AN LEADS US TO REVISIT ANDREA INTERPRET PREVIOUS FININGS, ESPECIALLY NULL FINDINGS. HOW DO YOU SEE THAT ISSUE GOING FORWARD? >> I WILL TAKE A STAB AT THAT. I THINK ONE OF THE THINGS THAT WE LEARNED FROM GWAS THAT WAS OCCURRING AT THE TIME WE STARTED GETTING MOLECULAR MARKERS FOR TUMOR SUBTYPES IS WHAT YOU DESCRIBED. IT SEEMS LIKE WHAT WE NEED TO DO IS MOVE AWAY FROM -- THIS IS CONTROVERSIAL BIOLOGY AN THINK ABOUT NOVEL MEASURES OF HETEROGENEITY NOT NECESSARILY BIOLOGICALLY DRIVEN, NOT TO ABANDON BIOLOGY AND DEVELOP BIOLOGICALLY BASED DIFFERENCES IN TUMOR PHENOTYPES BUT THERE ARE PROBABLY OTHER WAYS TO IDENTIFY HETEROGENEITY AND NOVEL METRICS OF DISPARITIES, HEALTHCARE ACCESS. SO THINGS THAT REFLECT DIFFERENCES AMONG CANCER CASES THAT WE HAVEN'T BEEN THINKING ABOUT. SO WE CAN SAY THERE ARE MULTIPLE TYPES OF BREAST CANCER BASED ON MOLECULAR MODEL. WHY ARE THERE NOT 20 KINDS OF BREAST CANCER BASED ON WHERE YOU LIVE AND HEALTHCARE ACCESS AND DIET AND THINGS LIKE THAT. WHY IS THAT NOT A MODEL FOR HETEROGENEITY AS WELL. HARDER TO PLACE BIOLOGICAL FRAMEWORK AROUND THAT BUT ALLOWS US TO HAVE A TRANSLATABLE FRAMEWORK TO GET PEOPLE TO THE RIGHT CARE AN PREVENTION SETTING AND THINGS LIKE THAT, EVEN IF WE CAN'T EXPLAIN THE BIOLOGY AND TELLING PEOPLE STOP SMOKING FOR DECADES AND E DON'T KNOW THE VALUE YET SO WHY NOT OTHER NON-BIOLOGICALLY RELATED HYPOTHESES TO DO THE SAME? >> GENERICALLY THAT'S A GOOD POINT. AS A COMMUNITY WE NEED TO BE ABLE TO DO WHAT WE CAN TO ACCESS TUMOR SUBTYPES. FORTUNATELY IT SEEMS TO TURN OUT HIGH LEVEL A LOT OF TIME THE EXPRESSION ARRAY, THE FINE PATENTS TRACK WITH WITH A PREVIOUSLY KNOWN HISTOPATHOLOGIC MARKER, FOR BREAST CANCER FOR INSTANCE ER NEGATIVE, ER POSITIVE HER 2 NEW DEFINES MOST OF THE MAIN SUBTYPES. WE HAVE HAD THAT INFORMATION ALL ALONG AND BY AGGREGATING LARGE AMOUNTS OF DATA WE HAVE MADE SOME PROGRESS IN DISCERNING BETWEEN RISK FACTORS FOR ER POSITIVE AND NEGATIVE DISEASE IN PARTICULAR ESTROGEN RELATIONSHIP FOR ER POSITIVE. WE HAVE TO ASK THE QUESTION WHAT DOES THAT TRANSLATE TO IN TERMS OF PUBLIC HEALTH ADVICE? THE ANSWER IS PROBABLY NOT A LOT UNLESS YOU DISCOVER A UNIQUE PREVIOUSLY UNDISCOVERED RISK FACTOR, WHAT WE TEND TO DISCOVER IS RISK FACTORS WE FOUND ARE STRONGER IN ONE STRATUM OR THE OTHER. I THINK WE HAVE TO BE REALLY CAREFUL NOT TO GO TOO FAR DOWN THIS TRACK. I WAS AT A TCGA TYPE MEETING LAST WEEK AND IT IS TRULY TERRIFYING. THE DEGREE OF HYBRIS IN THE CLINICAL COMMUNITY ABOUT THE IDEA THAT ESSENTIALLY EVERYONE'S CANCER IS DIFFERENT AND WE'RE GOING TO SEQUENCE A TUMOR AND PULL A DRUG OFF THE SHELF. TO TREAT EACH PERSON'S TUMOR AND WHEN THAT RESULTS IN DRUG RESISTANCE WE'LL ADD A SECOND AND THIRD DRUG. SO WE DON'T HAVE THE DRUGS. WE DON'T HAVE MONEY. BUT WE HAVE PLENTY OF ANECDOTAL LAZARUS TYPE AFFECTS. BUT LOOK AT WHAT'S SO FAR, I SAY THIS WITH NO PLEASURE BECAUSE ALL OF US IF WE GET DIAGNOSED SOMEONE WE KNOW GETS DIAGNOSED WE (INAUDIBLE) TO BE THERE. THERE'S A FEELING IF WE THROW MUCH AT THE TUMOR RESEQUENCING PROBLEM THAT'S GOING TO SOLVE CANCER. YOU CAN'T CURE YOUR WAY OUT OF THIS AND YOU CERTAINLY CAN'T CURE YOUR WAY OUT OF A GLOBAL DISTRIBUTION OF CANCER WHEREBY 2030 YOU'RE 75% MORE CANCER EVERY YEAR THAN NOW. SO THAT WAS A LITTLE BIT OF A EVENT ABOUT SLIGHTLY DIFFERENT PROBLEM. I DO WORRY ABOUT THIS DOGMA SET IN EACH PERSON'S CANCER IS DIFFERENCE, HOPELESS. THEY SEEM TO CLUSTER IN CATEGORIES AND WE CAN OFTEN ACCESS THE WAYS OF PUTTING THEM INTO CATEGORIES BUT IT COMES BACK TO SAMPLE SIZE BUZZ YOU NEED SUBSTANTIAL SAMPLE SIZES ONCE YOU START TO DIFFERENTIATE SOMETHING. >> MARGARET. >> THE DAY -- KEEPS GOING OFF. I AGREE WITH YOU BUT ON THE OTHER HAND THERE HAVE BEEN AMAZING SUCCESS STORIES IN PERSONALIZED MEDICINE SOME OF WHICH ARE HELPED BY EPIDEMIOLOGIC STUDIES. ONE PROBLEM IS NEVER SMOKERS WITH LUNG CANCER WHO HAD EGFR MUTATIONS AND RESPOND BEAUTIFULLY INITIALLY TO SOME OF THE TYROSINE KINASE I HAVE BEEN INHIBITORS SO THERE ARE SOME EXCELLENT SUCCESS STORIES SO WE NEEDN'T THOUGH ALL WATER AWAY OR THE BABY AWAY WITH THE WATER. >> I WOULD SUGGESTION -- BUT YOU KNOW AS WELL AS EVERYBODY ELSE THOSE ARE (INAUDIBLE) NOT CURES. WE HOPE THEY TURN INTO CURES BUT THEY'RE TROTTED OUT, CAP PLAN MIRE CURVES YOU CAN SEE ACROSS THE ROOM BUT JUST LOOK AT WHERE THE PEOPLE WITH DELAY REMISSION WIND UP. 95% PROGRESSION A FEW MONTHS LATER. SO I REALLY AS A COMMUNITY INEVITABLY DOMINATED BY PEOPLE WHO TREAT CANCER, CANCER CENTERS ELSEWHERE. AGAIN, THIS IS ENORMOUSLY EXCITING BUT WE NEED TO BE PREVENTING CANCER AN WHILE WE ALSO HAVE CURES. >> ONE QUICK ADDITION, I THINK WHAT I WAS SAYING HERE IS IT'S NOT ONE APPROACH. TCGA AND MOLECULAR IS VERY IMPORTANT IN THE CORRECTION HAS TO BE MULTI-PRONGED. NOT ONE -- THAT'S NOT ONE SOLUTION. >> ALSO PREVENTION (INAUDIBLE) PREVENTION AND TREATMENT HAVE TO BE DONE AT THE SAME TIME EVEN IF WE GOT EVERY ADULT IN AMERICA TO STOP SMOKING, WE STILL FACE AN EPIDIMMIC IN FORMER SMOKERS FOR MANY YEARS TO COME SO WE HAVE TO DO BOTH AT THE SAME TIME. WE HAVE TO FIND GOOD TREATMENTS AS WELL. IT'S EASY TO GET IN A PREVENT VERSUS CURE DEBATE. THE PENDULUM IS SWINGING TOWARDS THE IDEA THAT'S ILLUS AREA THAT CURES ARE AROUND THE CORNER AN WE HAVE BEEN HEARING THAT FOR DECADES. WE HAVE TO FOCUS ON PREVENTION A LITTLE SIDE BAR TO CONTINUE EVENT. THEY@ SAMPLES WITH EVERY EFFORT AND EXTRA WORK. THEY HAVE ENVIRONMENTAL INFORMATION. AND WE MIGHT BE ABLE TO (INAUDIBLE) FORWARD. BECAUSE THERE'S A SWING TO GET MORE SAMPLES, THAT MEANS THEY HAVE TO GET INTO THE CONSENT BUSINESS AND THE QUESTION IS CAN WE PERSUADE THEM TO ADD ONE AND A HALF HOUR EXTRA IT TAKES TO ADMINISTER A QUESTIONNAIRE. >> STEVEN IS ABOUT THE JUMP OUT OF HIS SEAT. >> I THINK THAT NUMBER OF REALLY TERRIFIC POINTS WERE RAISED BY PANELISTS IN RESPONSE TO YOUR QUESTION, BOB. I THINK WHAT WE HAVE TO DO IS TAKE A STEP BACK AND REALIZE THIS IS A VERY LONG COMPLEX PROCESS. IT GOES THROW MULTIPLE ITERATIONS. SO IF YOU TAKE STARTING WITH GWAS BREAST CANCER HAS BEEN INCREDIBLY SUCCESSFUL, 75 REGIONS FOUND BY LOCHING. NOW AS E WE START TO SPLIT WE SEE DIFFER THINGS. LUNG CANCER, WE SEE OVERALL LUNG CANCER AN SMOKERS VERSUS NON-SMOKERS. SO THIS IS WHERE THE EPIDEMIOLOGISTS BECOMES VERY IMPORTANT, THE PRECISION ART OF SEPARATING THESE THINGS. AND GIVING YOU GREATER GRANULARITY. IT DOESN'T MEAN THE JOB IS FINISHED. WE'RE JUST STARTING. TCGA IS THE FIRST PROJECT. THERE'S A VERY, VERY LARGE COMMITMENT TO CONTINUE THAT AND THAT COMMITMENT IS WITH ALL EPIDEMIOLOGISTS AND GERM LINE. IT'S AN -- I WILL SHOW SLIDES FROM OUR ESTEEMED DIRECTOR, ACKNOWLEDGING THIS AND THE VALUE OF THAT. IN TOKING THAT WE HAVE TO BE CAREFUL THINKING ABOUT WHAT THE PURPOSE OF OUR STUDY. I THINK IT WOULD BE WONDERFUL TO DO THE PREVENTION AN THERAPY AND DISCOVERY ALL THIS ONE STUDY BUT WE HAVE NEVER ONCE DONE THAT IN WANNEST CAN DI. WE HAVE BEEN GOING BACK TO WHAT BOB WAS TALKING ABOUT HRT. I REALIZE NURSES HEALTH IS CLOSE BUT NOT CLOSE ENOUGH. SO WE HAVE TO BE (INAUDIBLE) ABOUT THE LIMBS ABOUT WHATEVER SYSTEM AND STUDY WE'RE USING SO WE DONE OVERINTERPRET OR OVERVALUE POPULATION ATTRIBUTABLE RISK IN GWAS FOR PROSTATE 72, NOW AT 326% IF YOU ADD THEM UP INDIVIDUALLY. THINGS DONE MEAN ANYTHING OTHER THAN WASHINGTON POLITICIANS PUTTING TOGETHER BUDGETS. SEPARATED FROM REALITY. SO I THINK AGAIN IT'S THAT CONTEXT OF GOING THROUGH OVER AND OVER THESE DATA SETS HAVING THEM AVAILABLE AND ALLOWING PEOPLE TO LOOK AT DEATH AND COME UP WITH HYPOTHESES, IT'S GOING TO BE CRITICAL TO BE ABLE TO EFFICIENTLY GET THE RESOURCE WE HAVE IN HAND. >> JOHN. >> I WANT TO MAKE TWO COMMENTS. ONE IS ABOUT TAKING A BIG PICTURE THAT DAVID VERY ELOQUENTLY PUT TOGETHER U.S. AND NATIONAL COHORT IDEA THAT'S IN THE WORKS FOR QUITE A WHILE AND I HOPE IT'S SUCCESSFUL EVENTUALLY. I THINK ONE COULD TAKE A GLOBAL VIEW. PUTTING THE NUMBERS TOGETHER, THOUGH WE HAVE THE BEST EPIDEMIOLOGISTS AROUND THE WORLD, SITTING IN THE ROOM, DOES ANYONE KNOW WHETHER THE TOTAL SAMPLE SIZE OF STUDIES AVAILABLE? MY GUESS IS SOMETHING IN THE RANGE OF 100 MILLION PARTICIPANTS. THAT COULD TAKE INTO ACCOUNT NOT TRADITIONAL BUT BIOBANKS. THERE'S COUPLE OF DOZEN, HALF A MILLION EACH AND THEN THAT'S NATIONAL STUDIES WITH REGISTRIES, ESPECIALLY SCANDINAVIAN COUNTRIES, MAYBE ELSEWHERE. I DON'T KNOW THAT NUMBER. AND I THINK IT'S PROBABLY REALLY HUGE. THAT CREATES BOTH AN OPPORTUNITY BUT ALSO A PROBLEM. BUT MOST TIME WHAT WE DO, WE WAIT FOR PEOPLE TO COALESCE INSO CONSORTIA OR TEAMS TO JOIN FORCES. WE DONE KNOW WHAT IS THE BOUNDARY OF THE TEAM THAT COULD DO THAT SO IN THEORY, 100 MILLION WOULD BE PERFORM FOR ANSWERS IN CANCER EPIDEMIOLOGY AND OTHER TOPICS. WE SHOULD TRY TO MAP THAT AVAILABILITY OF INFORMATION, HAVE SOME PLAIN REGISTRATION OF EPIDEMIOLOGICAL INFORMATION, IDEALLY I WOULD LIKE TO SEE PROTOCOLS REGISTERED BUT I UNDERSTAND LOTS OF EPIDEMIOLOGISTS IS EXPLORATORY AND HYPOTHESIS GENERATING SO DIFFICULT TO COME UP WITH A PRODUCT UP FRONT. BUT MAP WHAT IS AVAILABLE. WE HAVE 110 MILLION, 100,000,001,000,000,000, FOR GENOMICS WORK, VERY SONG IN THE BILLION RANGE BECAUSE PEOPLE WILL BE RUNNING THESE TESTS AND GETTING TONS OF INFORMATION BASED ON THEIR OWN INITIATIVE. NOBODY WILL KNOW WHO HAS WHAT AND WHO IS REALLY CONTROLLING THE DATA ONE WAY OR ANOTHER. SECOND POINT IS WHAT MARGARETh– GAP TWEAK SMOKING AND OBESITY, THESE ARE NICE BECAUSE THEY SHOW SOMETIMES WE DON'T RECOGNIZE OUR POWER IN EPIDEMIOLOGY. SO TOBACCO IS A CLASSIC EXAMPLE WHERE EPIDEMIOLOGY IS VERY SUCCESSFUL. I THINK I CAN HARDLY THINK OF A FEEL THAT WE KNOW SO WELL WHAT CAUSES WHAT. AND WITH SUCH HUGE RELATIVE RISKS. NEVERTHELESS, AT THE IMPLEMENTATION LEVEL WE HAVE NOT REALLY BEEN SUCCESSFUL, MORE PEOPLE SMOKE EVERY YEAR, THAT WILL CON TO BE THE CASE FOR ANOTHER 20 YEARS AT LEAST. EVEN IF THE MEASURE THAT WE APPLY NOW ARE SUCCESSFUL AS INTENDED TO BE. SO WHAT ARE REALLY THE HOT QUESTIONS HERE? I WOULD ARGUE EVEN THOUGH UNDERSTANDING HOW WE CAN SCREEN AND USING THE SCAN AND GENOMICS AND INDIVIDUALIZE PREVENTION AND PREDICTION AND TREATMENT, I WOULD ARGUE FOR TOBACCO, WITH KNOW WHAT'S THE PROBLEM, JUST FIX IT, WHICH MEANS WE NEED IMPLEMENTATION RESEVERAL, PUBLIC HEALTH -- EVEN POLITICAL SCIENCE RESEARCH. MAYBE NOT JUST RESEARCH BUT TELL PEOPLE THAT YOU NEED TO LOOK AT YOUR GOVERNMENT BALANCE SHEET AND THE MONEY THAT YOU GET FROM TAXES OR EVEN IF YOU INCREASE THAT THE MONEY YOU LOSE FROM PRODUCTIVITY AND COST AND HEALTH DOESN'T MATCH THAT, IT'S FAR MORE. SO YOU NEED TO CUT SUPPLY AND CUT DEMAND OR BOTH AND FIND A WAY THE INDUSTRY FIND A WAY OUT OF THAT BUSINESS AND DO SOMETHING ELSE. I DON'T KNOW, MEMBER WE WILL THE TOBACCO INDUSTRY WILL TRY TO FIX A HEALTHIER SYSTEM BUT DO SOMETHING DIFFERENT. THEN EPIDEMIOLOGY IS TAKEN TO A DIFFERENCE LEVEL. IT'S FINE TO DO DISCOVERY WORK WHEN WE HAVE IMPLEMENTATION WORK TO DO WE SHOULDN'T STEP BACK. >> I THINK SO. NOT ONE AREA WHERE STILL WOULDN'T BE CONDITION BUT I THINK I HAVE NOTICED MY TIME AT THE NIH PRETTY REMARKABLE CHANGE IN MIND SET OR SUITABILITY OF DETERMINANTS OF HEALTH OF SOCIAL DETERMINANTS OF HEALTH. EARLY THIS WEEK THERE WAS A TRANS-NIH MEETING OF INVESTIGATORS SPONSORED BY 7 INSTITUTES ON OBESITY POLICY RESEARCH. I CAN'T IMAGINE A DECADE AGO NIH HAVING THIS SUBSTANTIAL INVESTMENT IN OBESITY. RESEARCH BUT REJECTED OUT OF HAND SO A LOT OF ERRORS IN TERMS OF BROADER CONTEXT, OTHER VARIABLES, NON-BIOLOGICAL VARIABLE, HOPEFULLY MORE -- TIM TALKED SOCIAL DETERMINANTS OF HEALTH, WE WERE AT A ROBERT WOOD JOHNSON MEETING LAST WEEK SURROUNDED BY PEOPLE WHO STUDY SOCIAL DETERMINANTS OF HEALTH WHO VIEW THEMSELVES AS POPULATION HEALTH RESEARCHERS, NOT DISEASE SPECIFIC; WHO ARE CRYING OUT FOR COLLABORATION WITH FOLKS IN MOLECULAR EPIDEMIOLOGY. AND CLINICAL EPIDEMIOLOGY. SO THE ISSUE ABOUT SOCIAL CONTEXT DETERMINANTS WHICH DOES ACCOUNT FOR VARIANTS IN TERMS OF POPULATION VARIATION WE BARELY SCRATCH THE SURFACE IN TERMS OF THOSE EMERGING DISCIPLINES. MARGARET. >> I WOULD ADD THAT THE THERE'S ALSO A LOT OF EXCITING WORK IN BIOBEHAVIORAL RESEARCH AND BEHAVIORAL GENETICS WHICH ALSO CONTRIBUTED PERHAPS IN THE FUTURE TO SUCCESS IN SMOKING CESSATION. I THINK EVERYBODY WOULD AGREE THE ONE SIZE FITS ALL APPROACH TO SMOKING CESSATION REALLY DOESN'T WORK. IN FACT, WHAT I FIND AMAZING, THE TOP HITS IN LUNG CANCER ARE ALL IN THE LOCUST WHICH INCLUDES A CLUSTER OF THREE NICOTINIC ACETYL COLINERGIC RECEPTORS ASSOCIATED WITH SMOKING INTENSITY AND IT'S HOTLY DEBATED. IS THE LOCUST HER LIE ASSOCIATED WITH LUNG CANCER BECAUSE IT'S WITH SMOKING INTENSITY. I KNOW HE'S NODDING HIS HEAD, OR AS I STILL BELIEVE A LITTLE BIT, THERE IS ALSO DIRECT CITYTHER GENIC EFFECT AS WELL. BUT THERE'S RESEARCH AND UNDERSTANDING WHY SOME PEOPLE ARE HAVING MUCH HARDER TO QUIT THAN OTHERS. I THINK WE WILL DEVELOP MUCH BETTER PHARMACOLOGIC INTERVENTIONS. I'M NOT A BEHAVIORAL SCIENTIST, I DEFER THE BOB BUT I THINK THAT'S PART OF AN APPROACH NEEDED AS WELL. >> I GUESS RELATED QUESTION TO JOHN'S FIRST PART, ESPECIALLY DAVID'S SLIDE IS WHAT IS THE IDEAL COHORT? IT'S NOT OBVIOUS IF YOU PUT THAT TOGETHER YOU HAVE GOT WHAT YOU REALLY WANT. SO I GUESS SINCE IT IS A PAM I WANTEDED TO THROW THAT OUT TO YOU ON WHAT YOUR THOUGHTS ARE. WHAT WOULD BE IN YOUR PERFECT COHORT. >> I MENTION WE HAVE A SESSION TOMORROW FOCUSED ON THAT TOPIC. BUT IT'S SUCH AN IRRESISTIBLE QUESTION SURE ALL PANELISTS HERE WILL BE WILLING TO WEIGH IN ON IT AS WELL. >> NO SUCH THING AS PERFECT COHORT IN REALITY. WE CAN IMAGINE WHAT THE CONCEPT IS, RANDOMLY SAMPLED COHORT OF PEOPLE YOU KNOW AHEAD OF TIME BEFORE YOU ASK THEM WILL AGREE TO BE IN YOUR STUDY FOR 50 YEARS. CUT COMPLAINT AND GIVE YOU ALL SORTS OF BIOLOGIC SAMPLES WITH MINIMAL NEED FOR FEEDBACK AND WITHOUT ANY CLINICAL CARE COSTS BUILT IN. SO WE P CAN LET THE (INAUDIBLE) BE ENEMY OF GOOD. MY UNDERSTANDING A LITTLE BIT, THAT'S WHAT HAPPENED WITH THE NATIONAL COHORT IDEA, OTHERS MAY KNOW BETTER, BUT THE VISION WAS SOMETHING THAT WOULD HAVE A RANDOM SAMPLING GEOGRAPHIC DISTRIBUTION FLAVOR AND IT GOT TOOICS PENSIVE TOO FAST. SO WE'LL ENROLL PEOPLE AT SHOPPING MALLS, FLAG THEM DOWN AS THEY WALK PAST, COME TO OUR BOOTH, WE GET BLOOD PRESSURE, WEIGHT, GET BLOOD SAMPLE, WE'LL DO THINGS YOU COULDN'T NORMALLY DO LIKE HAVE THEM GET THEIR REACTION TIME TENDING ON A COMPUTER SCREEN. SHOPPING MALL COHORT, CAN YOU IMAGINE ANY OF US SIGNING OFF ON THAT OPT STUDY SECTION BUT THAT'S BIOBANK. WE CAN'T BE TOO RIGOROUS METHOD LOGICALLY RIGOROUS, WE HAD TO HAVE ALLOSOME DETERMINANT INFORMATION AS WELL TO MAKE SURE THAT WHATEVER WE WENT UP WITH WE'RE NOT TRYING TO INFER BEYOND THE LEGITIMATE GENERALIZABILITY OF THE INFORMATION. IF WE WAIT FOR THE PERFECT COHORT, WE'LL NEVER GET IT. >> I WOULD ADD, JOHN'S REFLECTING ON JOHN'S COMMENT ABOUT THE 100 MILLION, WHATEVER IT IS PEOPLE THAT MIGHT BE OUT THERE, AND ON BOB'S COMMENT ABOUT HOW SUCCESS OF GWAS MATTERS NOT AT ALL STUDY DESIGN USED. SURE IT DID BUT THEY HAD SUCCESS WITHOUT OVERSTUDY DESIGN AN EPIDEMIOLOGICAL CHARACTERISTICS SO I GUESS THE QUESTION IS, A STUDY DESIGN, A COHORT IS JUST A TOOL AND JUST SOMETHING WE USE TO GET TO THE ANSWER ANSWER. SO WHAT IS THE 100 PER MILLION PEOPLE OR CONGLOMERATION OF PEOPLE WE CAN COME UP WITH WITH TO DO STUDIES? WHAT IS THAT AN APPROPRIATE TOOL FOR? IT'S NOT APPROPRIATE FOR SOME QUESTIONS BUT IT MINE APPROPRIATE FOR A SUBSET OF QUESTIONS WE REALLY NEED TO ANSWER. SO WHEN TO WE NEED TO PRESECOND RATE OVER DESIGN AND BIAS. SOMETIMES WE NEED TO DO THAT BUT THERE MIGHT BE TIMES NOT TO DO THAT OVER THOSE THINGS BUT WE HAVE PEOPLE TOLL WORK WITH AND FIND SOMETHING TOOL COOL. SO WE NEED TO THINK LIBERALLY WHEN IT'S APPROPRIATE TO USE A QUOTE UNQUOTE BAD STUDY DESIGN. >> IT WAS REFLECTED THERE'S A SIGNIFICANT SHIFT REFLECTED IN SOME OF THE SIGNATURE PROJECTS MOST RECENTLY FUNDED. IN TERMS OF WHERE TO LOOK FOR DATA AND WHAT QUESTION FITS WHAT INFRASTRUCTURE OR COHORT. GOOD EXAMPLE IS GARNET ANDERSON AND NEW SURVIVORSHIP COHORT PROJECT PIGGY BACKED ON WOMEN'S HEALTH INITIATIVE. SO IT'S LOOKING AT OVER 5,000 CANCER SURVIVORS BUT WITH ALL THE PRIOR DATA COLLECTION THAT WHI PROVOIDS ANOTHER EXAMPLE, NEW PROJECT PIGGY BACKED ON THE (INAUDIBLE) COHORT SO BACK TO THE ISSUE, DO YOU HAVE A FOCUS OR QUESTION OR SUBTYPE YOU'RE INTERESTED IN. AND THEN WHERE DO YOU LOOK FOR THE PRIOR DATA. I THINK THE CHALLENGE WITHIN INTERNAL NIH DISCUSSION IS THAT IF YOU PERSONAL EYE HAVE A SPECIFIC QUESTION IN MIND, THEN THE MORE GENERIC THE COHORT AND LESS SOPHISTICATED OR EXTENT THE EXPOSURE ASSESSMENT THE LESS IT WILL BE A RIGOROUS ANSWER TO YOUR PARTICULAR QUESTION. SO WHAT I THINK IS ALREADY STARTING TO EVOLVE IS INVESTIGATORS NOW ARE OFTEN TYPES PERSON IN MIDDLE GROUND, I DO HAVE A PARTICULAR QUESTION OR A PARTICULAR CANCER I'M INTERESTED IN AND TRYING TO MARRY THE BOTH OF THESE. THAT IS EITHER LOOK TO SEE WHAT'S OUT THERE, BUT I THINK WORKING ACROSS DISEASE DOMAINS AND INFRASTRUCTURES IS ALREADY OPENING UP A LOT OF OPPORTUNITIES WHICH IS STILL YET TO BE FULLY EXPLOITED. BECAUSE PEOPLE TEND TO LOOK WITHIN THE DISEASE DOMAIN THEY LOOK IN IN TERMS OF INFRASTRUCTURE. IF I HAVE A CANCER I LOOK TO REGISTRY, I LOOK TO CANCER COHORTS. SO BOTH POLLING PROJECTS BUT ALSO I THINK THIS ISSUE ABOUT WHAT PRIOR EXPOSURE ESPECIALLY CHALLENGE AND ONE OF THE MOST COMMON CONCERNS FROM INVESTIGATORS IS WHEN KNOWLEDGE CHANGES ABOUT WHAT THE EXPOSURES YOU WANT TO OBTAIN ARE AND YOU'RE LEFT WITH WHAT WE THOUGHT WAS IMPORTANT 15, 20 YEARS AGO, IN PARTICULAR METABALOMICS IS A GREAT EXAMPLE WHERE BMI IS A ROUGH PHENOTYPE. AND NOW WE HAVE A FAIRLY SIGNATURE PROJECT, (INAUDIBLE) LEADING ON CAN WE GET MORE EXPENSIVE PHENOTYPING RELATE EVENTUAL TO OBESITY AND RISK FACTORS. A LOT OF CANCER COHORTS ESTABLISHED BUT NOT OTHER END POINTS. >> IN THIS TIME OF FISCAL CONSTRAINT WE NEED TO USE EXISTING COHORTS DEVISE ANCILLARY STUDIES AND LOOK AT MULTIPLE END POINTS, THERE ARE MANY, FOR EXAMPLE, CARDIOVASCULAR COHORTS WITH THE SAME RISK FACTORS AS MANY CANCERS AND WE COULD CERTAINLY USE THEM TO EXPEND ONGOING RESEARCH IN A MORE COST EFFECTIVE WAY THAN ESTABLISHING BRAND NEW COHORTS. AS WONDERFUL AND EXCITING AS THAT WOULD BE. >> WE HAVE QUESTIONS COMING FROM THE OUTSIDE. WHERE DID STEPHANIE GO? >> OKAY. MORE JUST CAME IN SO WE GET THE TOLL GROUP AND BRING THOSE BACK BECAUSE WE WAN THE MAKE SURE FOLKS LISTENING ONLINE HAVE THE DONE TO ASK QUESTIONS. STEVEN YOU HAD YOUR HAND UP. >> >> IN THE CONTEXT OF LOOKING AT COHORTS CASE CONTROL STUDIES THE TECHNOLOGIES YOU TALK ABOUT DO EVOLVE AND BECOME THESE MOMENTS OF INFLECTION WHERE IN FACT OPPORTUNITIES CHANGE DRAMATICALLY AND WE'RE AT ONE OF THOSE RIGHT NOW BASED ON NUMBER OF STUDIES DONE WITHIN TCGA THAT ARE PILOTS THAT TELL US WE CAN DO COMPLETE WHOLE GENOME SEQUENCING, RNA SEQUENCING EXPRESSION ANALYSIS AN CHIP ANALYSIS, FFPE SAMPLES SO THE COVERS OF THE EPIDEMIOLOGIC STUDIES CHECK COLLECTED THESE AS WELL AS CASE STUDIES CAN GO BACK TO ADDRESS THE QUESTION YOU STARRED WITH, LET'S LOOK AT SUBTYPES. NOW WE HAVE CAPACITY CAN GREATER PRECISION, NOT PERFECT, TO I DRESS MANY OF THESE KINDS OF QUESTIONS. SO HOW AND WHAT WAYS DO WE GO BACK AND THINK ABOUT REVISITING CURRENTLY AVAILABLE DATA SETS TO HAVE MORE IN TENth UNDERSTANDING OF RELATION L SHIPS AND WHAT WE FOUND FROM EXPOSURE AN GERM LINE TO SEMATIC ALTERATIONS. >> THESE ARE COMING IN WILL MORE ADVANCED CHARACTERZATION OF RISK FACTORS PHENOTYPES AN EPI RESEARCH REQUIRE ADVANCED TECHNOLOGY AND HEALTHCARE? >> YES. [LAUGHTER] >> I GUESS THIS IS PROBABLY THE SAME QUESTION YOU GET IN THE GWAS OR ANY OTHER SETTING. WE GET ALL THE TIME THINKING VERY DETAILED HISTOPATHOLOGICAL CHARACTERIZATIONS HOW READILY IS THAT GOING TO BE IMPLEMENTABLE IN A COMMUNITY SETTING. SO THE ANSWER IS YES, IF YOU DO SOMETHING NOT EVERYONE IN THE COMMUNITY HAS ACCESS TO OR CAN DEVELOP EASILY IT WILL BE LESS MEANINGFUL ON PUBLIC HEALTH SCALE. QUESTION IS, SOME ARE NOT GOING TO BE IMPLEMENTABLE BUT IF THEY'RE REALLY GOOD, IF THEY'RE GOING TO DO A GREAT JOB, THEY'RE GOING TO BECOME PART OF HEALTHCARE PRACTICE. AND IT WILL BE INCOUPLE BENEFIT BECAUSE INSURANCE COMPANIES AN LAWYERS AND EVERYTHING ELSE WILL TELL US WE FIND SOMETHING THAT REALLY HAS A HUGE IMPACT ON SOMEONE'S OUTCOME, IT WILL BECOME PART OF HEALTHCARE PRACTICE EVEN IF IT ISN'T NOW, IF IT'S EXPENSIVE. THAT'S EXPENSIVE THINGS WE HAVE IN HEALTHCARE THAT LAWYERS AND INSURANCE COMPANIES HAVE DRIVEN. SO THE ANSWER IS YES BUT WE CAN DO IT IF IT REALLY MEANS SOMETHING. >> MAYBE THE KEY POINT IN THAT QUESTION IS HEALTHCARE. SO WE HAVEN'T TALKED OPPORTUNITIES TO INTEGRATE EPIDEMIOLOGIC RESEARCH IN WHAT USED TO BE CALLED HMOs, REPRESENTATIVES HERE FROM KEISER PEOPLE WHO ARE WORKING ON THIS BIG DATABASE AND AS MORE INFORMATION IS ESSENTIALLY AVAILABLE THROUGH ROUTINE HEALTHCARE WE'RE CRAZYJÖ IF WE DON'T FIND WAYS OF DOING EPIDEMIOLOGIC STUDIES IN THAT VENUE AND ELECTRONIC MEDICAL RECORD IF WE GET IT, SHOULD HELP THAT, THERE ARE QUESTIONS OF CONSENT AND OTHER ISSUES BUT THAT REALLY COULD BE A MAJOR BOON. >> DAVID, YOU SAID THE COMMENT AS YOU MIGHT EXPECT, RESPONSES SUCH AS IF WE ARE UNABLE TO TREAT OUR WAY OUT OF CANCER ARE WE ABLE TO PREINVENTORY OUR WAY OUT OF CANCER. SIMILAR COMMENTS ALONG THOSE LINES. SO I GUESS WE CAN ACKNOWLEDGE THAT THAT'S AFTER OF OF COURSE OPENING A CAN OF WORMS. >> LOOK AT CLASSIC GRAPHS OF 20th CENTURY CANCER INCIDENCE AN MORE IT WILLTY. MOST IMPACT IS A FORM OF TREATMENT INCLUDING EARLY DETECTION AND SCREENING AND BETTER MANAGEMENT OF, BETTER ACCESS TO HEALTHCARE. IT BY AND LARGE ISN'T MAGIC BULLET DRUGS, IT'S STILL SUBSTANTIALLY GETTING THE RIGHT SURGEON T THE RIGHT TIME WITH MAYBE SOME RADIOTHERAPY AND MAYBE SOME DRUGS. I WANTED TO THROW IN ONE OF THE THINGS OF SEEING (INAUDIBLE) AND OTHERS. THERE'S A LOT OF VALUE IN US AS A COMMUNITY MODELING THESE RISK FACTORS, MODELING PREVENTION AND TREATMENT IN A WAY (INAUDIBLE) DOES FOR INSTANCE. I GET A LOT OF VALUE WHEN I READ THOSE PAPERS. SOME LOOK AT IT AND THINK THAT'S SECONDARY DATA ANALYSIS, I THINK IT'S INCREDIBLY MEANINGFUL, IT'S THE BRIDGE BETWEEN WHAT WE FIND AND POTENTIAL INTERVENTIONS BOTH PREVENTION SCREENING AND CURE. SO THE WORK ON BREAST CANCER PAUSING HOW MUCH BREAST CANCER AND MORTALITY, HOW MUCH IS SCREENING AND HOW MUCH IS TAMOXIFEN TELLS A HUGE AMOUNT WHERE WE SHOULD PUT OUR POLICY AND TREATMENT RESOURCES. WITHOUT THOSE CAREFUL ANALYSES WE'RE GUESSING WHERE -- RUSH TO HIGH RELATIVE RISK END OF THE SPECTRUM WHICH MIGHT ONLY APPLY TO A FEW PEOPLE AND NOT HAVE A MAJOR IMPACT ON THE POPULATION. >> SO WE HAD COMMENTS SUBMITTED BEFORE THE MEETING, AND WANT PED TO MENTION THOSE. AND THE MEMORANDUM WITH THE ISSUES WE TALKED ABOUT BEFORE MULTI-LEVEL ANALYSIS THAT TIM DESCRIBEDDED INTEREST DISCIPLINARY TEAM SCIENCE APPROACHES, THE ISSUE OF THAT CAME UP IN TERMS OF BLOG COMMENTS ALSO HAD TO THE WITH GRAND ISSUES BEING DISCUSSED HOAR, HAD TO DO WITH WHO DECIDES WHO THE DECISION MAKER IS, THE STRATEGIC QUESTIONS ABOUT MERGING COHORT, GLOBAL COLLABORATION CENTRALIZED VERSUS DISTRIBUTED RESOURCES. SO CLEARLY THERE'S THE TRADITION ROWS OF THE FUNDERS IN THAT BUT SOME OF THE COMMENTS ON THE BLOG POST, CHALLENGE, COMMENTS ABOUT THIS, ALLOCATION OF LIMITED RESOURCES SO WE IDENTIFIED A LOT OF NEEDS AND AREAS THAT WE CAN SPEND MORE MONEY ON INFRASTRUCTURE, ET CETERA. BUT ABOUT THE DECISION MAKING PROCESS AN STAKEHOLDERS AND HOW THAT'S DONE, DAVID AND I TALKED ABOUT THIS ON SEVERAL OCCASIONS IN TERMS OF INTERNATIONAL COLLABORATION. INTERESTD IF YOUR THOUGHT IN REACTION TO BLOG COMMENTS. >> I WOULD SAY REPEAT THE FEED THE CATS ANALOGY. OBVIOUSLY, I GETS I JUST THINK DEMOCRACY IS OVERRATED IN SCIENCE IN SOME WAYS OBVIOUSLY. BUT NCI AND COHORT CONSORTIA F YOU LOOK AT GWAS OR HOW PEOPLE ARE FUNED TO ACCOMPLISH THOSE THINGS AN INCENTIVIZEED TO ACCOMPLISH THOSE THINGS, IT WAS A GROUND SWELL, IT WAS GRASSROOTS BUT DRIVEN BY SOMETHING. IT WASN'T JUST SO I MEAN SOMEBODY HAS TO PUSH IT WHO HAS LEVERAGE MONEY RESOURCES B, THAT'S AN NCI JOB BUT COULD BE AN HHS JOB, A HIGHER LEVEL JOB. BUT SOMEBODY HAS TO DRIVE IT. >> I AGREE SOMEBODY SHOULD SPONSOR IT. BUT QUITE FRANKLY IT IS GRASS ROOTS, IT IS THE PEOPLE THEMSELVES WHEN WE STARTED THE COHORT CONSORTIUM CAN ADMIT BOTH BOB AND I DIDN'T THINK IT WAS GOING TO WORK. BECAUSE WE WERE PUTING A BUNCH OF PEOPLE TOGETHER COMPETING AGAINST EACH OTHER FOR DECADES AND SOME QUITE FRANKLY DIDN'T LIKE EACH OTHER MUCH. INSTANTANEOUSLY THAT WENT AWAY. THEY MAY STILL NOT LIKE EACH OTH> ANOTHER THEME THAT SOME OF THE BLOG POSTS HAD TO DO WITH THIS ISSUE OF LINKING EPIDEMIOLOGICAL RESEARCH TO MECHANISTIC PATHWAY RESEARCH, TRYING TO SUMMARIZE BUT HAD TO DO WITH ISSUE OF UNDERSTANDING CARCINOGENESIS OVER TIME. SO WE KNOW EVERYBODY BUYS INTO VALUE OF PROSPECTIVE DATA BUT THEN WHEN YOU GET DOWN TO STUDY DESIGN AND COHORTS AND OTHER STUDIES ISSUES HOW FREQUENTLY DO YOU COLLECT BIOSPECIMENS AND HISTORY OF THE DISEASE ONCE WE UNDERSTAND TRADITIONAL EPIDEMIOLOGIC RESEARCH. SO COMMENTS POSTED HAD TO DO WITH WHAT ARE SMARTER STUDY DESIGNS TO ADDRESS THIS ISSUE. MARGARET YOU BROUGHT UP ISSUES IN YOUR COMMENTS AS WELL AND WHAT ARE SOME OF THE ANALYTIC TOOLS TO TRY TO AGAIN MARRY THIS TIME COURSE OF THE DISEASE TO OFTENTIMES WHAT MAYBE AN ANNUAL FOLLOW-UP QUESTIONNAIRE AS OPPOSED TO TRUE SERIAL L BIOMARKER COLLECTION. >> LOOKING AT ME. I THINK CORELY SERIAL MEASUREMENTS ARE VALUABLE BUT SOMETIMES ONE IS LIMITED BY RESOURCES IN HOW MUCH FUNDING ONE HAS. I THINK WE NEED TO -- ALWAYS. OKAY. OKAY. >> GOT TO GET THAT ON THE RECORD. >> BUT I THINK WE -- I SAY IT AGAIN, WE NEED TO TAKE ADVANTAGE OF WHAT IS GOING ON IN EXISTING COHORTS. FOR EXAMPLE, THERE'S NOW NATIONAL CHILDREN'S STUDY. AND I'M NOT -- IF WE WANT TO LOOK AT EARLY LIFE EXPOSURES AND EXPOSURES OVER TIME THIS IS THE WAY TO DO IT. RECRUITING NEWBORN BABIES I BELIEVE, IN UTERO STILL AND FOLLOWING THEM THROUGH AGE 21. I DON'T KNOW ENOUGH ABOUT THE STUDY. I'M NOT INVOLVED. ARE WE COLLECTING SERIAL SAMPLES OVER TIME. WITH THE INTENT OF ANALYZING ALL THESE EXPOSURES AND OUTCOMES IN GREAT DEAL, THIS WOULD BE THE WAY TO DO IT BUT YOU HAVE TO GET IN AT THE BEGINNING WHEN THE STUDY HAS STARTED. I KNOW IT'S ALREADY STARTED. PERHAPS SOMEONE CAN ANSWER THESE QUESTIONS. >> MORE QUESTIONS COMING IN ONLINE. >> WE HAVE A TWITTER QUESTION ABOUT HOW COMPARATIVE EFFECTIVENESS RESEARCH CAN BE LEVERAGED BETTER FOR EPI STUDY. EPIDEMIOLOGY BIOSTATISTICAL AS IT RELATES TO SCIENCE. THAT'S NOT THE ANSWER TO THE QUESTION BUT NOT SURE WHY EPIDEMIOLOGY ISN'T CENTER OF COMPARATIVE EFFECTIVENESS RESEARCH, MAYBE IT IS IN A LOT OF CASES BUT THE METHODOLOGY AND APPROACHES AN TOO MANIES THAT IMMEDIATE TO BE USED SO IT SHOULD BE IN THE MIDDLE. >> SO I'M THINKING I HAD TRISH'S SESSION TOMORROW WITH THE 12 RECOMMENDATIONS THAT WE'RE GOING TO COME UP WITH. AND EVERYTHING THAT WE HAVE TALK ABOUT SO FAR IS HOW WE DO EPIDEMIOLOGY BETTER. WE NEED TO TALK ABOUT THAT AND GET THAT RIGHT. ONE THING I WORRY ABOUT, I'LL ADDRESS THIS TO TIM, IS NOT ONLY DO WE HAVE TO UNDERSTAND THE COMPLEXITY AND SOCIAL DETERMINANTS AND THE CONTEXT OF WHAT WE DO IN EPIDEMIOLOGY, BUT WE HAVE TO FIGURE OUT SOME WAY TO MAKE IT MORE EFFECTIVE. INSTEAD OF DOING WHAT WE DO JUST DOING WHAT WE DO BETTER, DO WE ALSO HAVE RESPONSIBILITY AS EPIDEMIOLOGISTS TO WORK WITH THE LAW OF POLITICAL SCIENCE EDUCATION AND HOW DO WE DO THAT? >> THANKS FOR ADDRESSING THAT TO ME. I MEAN, YOU'RE ABSOLUTELY RIGHT. THE QUESTION I THINK WE ALL AGREE, INTEGRATIVE SCIENCE TRANSDISCIPLINARY WORK IS VERY IMPORTANT FOR THE FUTURE. I THINK ONE OF THE HISTORICAL LIMITATIONS OF EPIDEMIOLOGICAL RESEARCH IS WE KIND OF DO OUR RO-1 FOR FIVE YEARS AND WRITE THE PAPER AND WE GET OUR ODDS RATIO THEN WE DO OUR NEXT R OBJECTION-1, THERE'S A LOT OF WAYS YOU CAN TRANSLATE OUTSIDE OF THAT KIND OF FRAMEWORK OR THAT WAY OF THINKING. BECAUSE THE NOTION OF IMPLEMENTATION SCIENCE THAT WAS MENTIONED EARLIER AND EVALUATION SCIENCE, WE DONE DO A LOT OF THAT. AND THAT MIGHT BE ONE WAY TO THINK ABOUT TRANSLATION, BECAUSE IF WE DO OUR STUDY AND PUBLISH PAPER BUT DON'T TAKE IT FURTHER, THEN IT DOESN'T HAVE THE TRANSLATIONAL VALUE. YOU'RE SHAKING YOUR HEAD YES BUT I DON'T KNOW WHAT THAT MEANS. >> IT MEANS I AGREE WITH THAT. BUT THERE IS A -- IN TERMS OF WHAT EPIDEMIOLOGISTS DO IN THE 21st CENTURY ARE WE GOING TO DO EPIDEMIOLOGY BETTER FULL STOP. OR ARE WE GOING TO TAKE ON ANOTHER ROLE Z UNIQUE DISCIPLINE THAT'S COMFORTABLE WITH CELLS TO SOCIETY AND WORK WITH OTHER SECTIONS OF SOCIETY TO MAKE WHAT WE KNOW THE KNOWLEDGE THAT WE HAVE INTEGRATED. >> THE THING I WOULD SAY IS WE DID WELL DOING GWAS STUDIES. PEOPLE FROM DISCIPLININGS CAME TOGETHER AND INTEGRATED MOLECULAR TOOLS. WHY CAN'T WE BE AS EFFECTIVE IN INTEGRATING SOCIAL BEHAVIORAL RESEARCH, HEALTH SERVICES RESEARCH, IMPLEMENTATION SCIENCE, LIKE WE DID WITH GENES. IT WAS A NICE CONFLUENCE THAT THE TECHNOLOGY CAME ALONG AND HUMAN GENOME INITIATIVE CAME AND IT WAS INTERESTING AND WE LEARNED A LOT. WHY CAN'T WE DO SOMETHING WITH WITH OTHER DISCIPLINES THE WAY WE DID WITH GENETICS. >> BARRY, THEN MUIN AND THEN FINISH WITH QUESTIONS OVER THE TWITTER. >> SO THIS IS BASTE BASIC I'M SURE EVERYONE AGREES WITH THE CONCEPT THAT WE SHOULDN'T CONFLATE PRECISION WITH GETTING VALID ANSWER. AS WE GET MORE AND MORE SATISFIED WITH COMING UP WITH RELATIVE RISK ODDS RATIOS OF 1.5 OR 1.1 OR UNDER 1.1 AND FEEL CONFIDENT WE HAVE THE RIGHT ANSWER BECAUSE THE CONFIDENCE BOUNDS ARE SO TIGHT, WE HAVE TO KEEP IN MIND THAT WE PUT OURSELVES AT RISK OF MORE CONFOUNDERS. LET ME JUST GIVE AN EXAMPLE BECAUSE IT WAS I THINK I HEARD A THEME THAT WHEN YOU HAVE A PRECISE MEASURE OF A GENE OR GENETIC MUTATION, YOU MAY NOT WORRY QUITE SO MUCH ABOUT DESIGN. I'LL GIVE AN EXAMPLE WHERE YOU HAVE TO AND IT'S AN EXTREME EXAMPLE. BUT WE DON'T USUALLY COLLECT A VERY IMPORTANT CONFOUNDER OR EXPOSURE, THAT IS SCREAMING. BUT WE KNOW FROM NEUROBLASTOMA LITERATURE, IF YOU SCREEN ALL NEWBORNS THEN YOU'RE GOING TO DRAMATICALLY INCREASE INCIDENCE OF NEUROBLASTOMA. AND MIC AMPLIFICATION IS KNOWN TO BE POOR PROGNOSTIC FACTOR FOR NEUROPALACE TOE MAVMENT TURNED OUT THERE WAS -- PALACE TOE MA'AM THERE WAS ALMOST NO MIC DECKD IF SCREEN CASES AND THERE WAS END MIC AMPLIFY CASE IN THE USUAL CLINICAL CASES THAT INEVITABLY SLIP THROUGH SCREENING. SO THAT'S OF COURSE A STARK EXAMPLE WHERE WE COULD GO WAY OFF BASE IF WE DON'T KNOW HOW THE TUMORS WERE EVEN DETECTED IN THE FIRST PLACE. ANOTHER STARK EXAMPLE IS YOU CAN DO AWAY WITH RISK FACTORS AS POWERFUL AS SMOKING IN LUNG CANCER WITH A SCREENING TEST. SO THERE ARE TWO EXPERIENCES IN JAPAN WHERE THEY HAPPEN TO DO HELICAL CT SCANNING ON BOTH SMOKERS AND NEVER SMOKERS AND THEY FOUND TO MY ARAISEMENT THAT THE RISK OF LUNG CANCER WAS ALMOST IDENTICAL IN SPOKERS AS NEVER SMOKERS SO IF YOU HAD DONE EPIDEMIOLOGY NOT KNOWING SMOKING IS A RISK FACTOR IN A SCREENED POPULATION YOU WOULD HAVE NEVER DISCOVERED THE MOST POWERFUL RISK FACTOR OF ALL WAS A RISK FACTOR IN THE FIRST PLACE. SO ONE THING WE NEED TO DO FOR LARGE COHORTS AS MORE SETS OF SCREENING TESTS COME UP AND AS WE GET MORE DETECTION OF NEW FLAVOR OF CANCER IS TO COLLECT THE INFORMATION PROSPECTIVELY, HOW THE TUMOR WAS DETECTED IN FIRST PLACE. >> I WANT TO FOLLOW-UP HERE WITH -- BECAUSE I LISTEN TO THE PAM AND I'M LISTENING TO THE -- WATCHING THE TWITTER FEEDS HERE. PEOPLE ARE SAY LET'S GO TO COLLABORATE. WE NEED BIGGER FASTER BUT THEN HOW TO CHANGE THE CULTURE. YOU ASKINGS TO MOVE THE CAT FOOD. BUT WHERE DO WE MOVE IT TO? I THINK THAT'S THE QUESTION BOB WAS ASKING US. WE ARE ALL ACCUSTOMED TO T-0 EPIDEMIOLOGY. T-1 EPIDEMIOLOGY SOME OF US DO. T-2 EPIDEMIOLOGY, T-3 AND T-4 EPIDEMIOLOGY, FORGET IT. AS A MATTER OF FACT SOME PEOPLE CALL IT HEALTH SERVICES RESEARCH, EPIDEMIOLOGISTS, MANY HEALTH SERVICE RESEARCH MUST ADHERE TO -- I THINK HE'LL BE HERE TOMORROW, BUT THEY ARE TRAINED IN EPIDEMIOLOGY BUT MOST EPIDEMIOLOGISTS THAT I WENT TO SCHOOL WITH AND I TALK TO ARE ESSENTIALLY GOING AFTER DISCOVERY. WHEN IS IT WE STOP DOING THE NEXT STUDY THAT SHOWS SMOKING IS BAD FOR US. ARE WE GOING TO KEEP INVESTING IN THAT -- MORE INVEST IN HOW AND WHAT AND HOW DO WE MOVE IT AND POLICY AROUND AND LEGAL IMPLICATIONS. SO IT LOOKS MORE A MULTI-LEVEL ANALYSIS. AS YOU MOVE DOWN THE TRANSLATION HIGHWAY, MANY OF THESE OTHER DISCIPLINES BECOME MORE IMPORTANT. SO I'M JUST TRYING TO PUSH THE PANEL TO SEE IF THERE'S REACTION HERE. >> YOU SHOULD MENTION LEGAL PALMER IS HERE AND SO OUR TRAINING COLLEAGUES IS LEADING ONTARIO HEALTH STUDY, EPIDEMIOLOGICAL STUDY EXPLICITLY DESIGNED A PRIORI TO BE TRANSLATIONAL IN TERMS OF WHAT'S PROVIDED BACK. SO WE'RE NOW STARTER STARTING TO SEE EXAMPLES OF EPIDEMIOLOGICAL RESEARCH INFRASTRUCTURE BUILT WITH TRANSLATIONAL CAPACITY BUILT IN. I DON'T KNOW IF YOU WANT TO COMMENT ON THAT. >> I WOULD LIKE TO MAKE A MORE GENERAL COMMENT. FIRST I WOULD LIKE TO ECHO MARGARET'S THOUGHTS ABOUT RESEARCH AND BIRTH AND PREGNANCY COHORTS AND ONE THING I THINK THAT BOTHERS US ABOUT CANCER RESEARCH IN GENERAL, WE'RE MOSTLY LOOKING AT MIDDLE AGE ADULTS AND SOME ARGUE THE RELEVANT EXPOSURES MOSTLY HAPPENED BEFORE THAT POINT. SO THAT IS A PROBLEM FOR OUR FIELD. THE MORE GENERAL POINT TO MAKE WHICH IS PROVOCATIVE IN THE UNITED STATES OF AMERICA, THE IDEAL COHORT WOULD BE TO HAVE COMPLETE MEDICAL INITIATIVE AROUND THE ENTIRE POPULATION SO EVERY TIME EVERYONE TOUCHED THE SYSTEM THAT WAS RECORDED, DATA WAS AVAILABLE, MANY COUNTRIES MANDATED THIS AND THINK IT'S A GOOD IDEA. SO MOVING TOWARDS THAT WOULD GIVE YOU A LONGITUDINAL COHORT STUDY THAT WAS INHERENT HI PART OF THE SYSTEM. SO MAKING OUR RESEARCH INHERENTLY PART OF THE CLINICAL SYSTEM INHERENTLY PART OF THE FABRIC OF OUR SOCIETY IS PROBABLY WHERE WE WANT -- WE NEED TO GO LONG TERM. WE HAVE DNA AND EVERYONE IN OUR SOCIETY FROM GUTHRIE CARDS SO YOU HAVE COMPLETE CAPTURE. WHATs'S'S MISSING EXPOSURE DATA. WE CAN THINK ABOUT HOW TO GET THERE. EXPOSURE DATA IT'S IN CLINICAL CASE NOTES, INSURANCE COMPANIES LECTS VERY GOOD, KEISER PERMANENTE DATA, DO YOU SMOKE, DRINK, WHAT ARE YOUR LIFESTYLE SOURCES. WE CAN THINK AROUND THAT. THIS IS NOT A SHORT TERM FIX IN THE UNITED STATES BUT CERTAINLY (INAUDIBLE) IS MOVING IN THAT DIRECTION. AND THAT'S WHERE I THINK WE WANT TO GO. AND THAT WOULD BE IT'S NOT THINKING STUDIES AS INDIVIDUAL THINGS SHOPPING MALLS OR ANY OF THAT, BUILDING IT INTO OUR SYSTEM. I THINK CERTAINLY THAT'S WHAT WE'RE TRYING TO DO IN ONTARIO IS BUILD INTO THE FABRIC OF THE SYSTEM AND BUILDING ON TOP OF 40 YEARS OF LINKED HEALTH DIET AND OTHER RESOURCES ALREADY IN PLACE. >> SO WE STILL HAVE SOME QUESTIONS WE DIDN'T GET TO BUT WE CAN BRING THESE BACK TO FUTURE DISCUSSION SECTIONS SO THOSE WHO SUBMIT AD COMMENT EMAIL BY TWITTER WE DIDN'T GET TO WE'RE HOLDING ON TO THESE. MANY CUT ACROSS THE THEME THEMES OF THE ENTIRE MEETING SO WE'LL COME BACK WITH THOSE. WE WANT TOOTHING OUR PAMMISTS FOR THIS SESSION -- THANK OUR PANELISTS FOR THIS SESSION AND FOR PARTICIPATING AS WELL. [APPLAUSE] >> WE'LL TAKE A SHORT BREAK, THEN WE'LL RESUME IN ABOUT TEN MINUTES. SO THE NEXT SESSION IS NOW GOING TO BEGIN ON TECHNOLOGY AND IT'S OUR PLEASURE TO HAVE GEOFFREY GINSBURG GIVE THE FIRST TALK, SURE HE WILL BE VERY EXCITING PROVOCATIVE AND INSIGHTFUL. >> THANK YOU. CAN EVERYBODY HEAR ME OKAY? I WANT TO ALSO THANK MUIN AND SHEARRY FOR INVITING ME TO BE PART OF THIS MEETING. I'M NOT AN EPIDEMIOLOGIST. THIS MAYBE ONE OF THE FIRST TALKS I HAVE EVER GIVEN WHERE EPIDEMIOLOGY IN THE TITLE SO IT MAY SHOW. BUT WHAT I THINK -- WHAT I HOPE TO DO TODAY IS GIVE A SENSE OF EVOLVING TECHNOLOGIES THAT ARE AT OUR DISPOSAL THAT ARE ENHANCING OUR ABILITY TO DISCOVER NEW ASPECTS AND MECHANISMS OF DISEASE BUT ALSO THAT CAN ENHANCE EPIDEMIOLOGIC STUDIES AND ALSO BE THE SAME TOOLS THAT MIGHT BE USED BY RESEARCHERS AND CLINICIANS ALIKE PARTICULARLY FOR MEDICAL APPLICATIONS. DESPITE THE FACT THAT THE TECHNOLOGY IS EVOLVING I SAY THE GOALS REMAIN THE SAME. OUR GOALS ARE TO DISCOVER THE UNDERSTOOD PINNINGS OF THE DISEASE EXPLAINING THE ETIOLOGY OF THE DISEASE AND ALSO OTHER HEALTH CONDITIONS, AS DISCUSSED IN THE LAST PANEL, WE CAN MOVE THE NEEDLE FORWARD AND TRANSLATE THAT INFORMATION SO IMPLEMENT CLINICAL INTERVENTION AND CONTROL MEASURES AN ENCOURAGE US TO BE EDUCATING THE WORK FORCE THAT CAN ACTUALLY DO THE WORK THAT IS THE FRUITS OF EPIDEMIOLOGIC RESEARCH THAT MANY OF YOU DO. PROVIDING CLINICIANS, PROVIDERS, AND PUBLIC HEALTH POLICY MAKERS TO REALLY FULLY REALIZE THE FRUITS OF THESE TECHNOLOGIES. AS CARDIOLOGIST I TEND TO HARKEN BACK TO ICONIC STUDY 50 YEARS AGO, THE FRAMINGHAM HEART STUDY, WHICH GAVE US THE FIRST I THINK IN THE LITERATURE THE RISK FACTOR, THAT ALSO HAS GIVEN MANY PROVIDERS BOTH IN THIS COUNTRY AS WELL AS INTERNATIONALLY A SERIES OF CHARACTERISTICS THAT THEY CAN USE TO STRATIFY INDIVIDUAL PATIENTS, PUT THEM ON PERHAPS BETTER PERSONALIZED MEASURES TO IMPROVE -- REDUCE RISK OF DEVELOPING CARDIOVASCULAR DISEASE. OVER THE LAST FIVE DECADES SINCE THAT SEMINOLE PUBLICATION THE SCIENCE AND TECHNOLOGY TO DISSECT DISEASE CHANGED SIGNIFICANTLY. 50 YEARS AGO WE DESCRIBED DISEASE ON BASIS OF OBSERVATION OF ANATOMIC LOCATION AND HISTOLOGIC DESCRIPTION. OHING TO THE MOLECULAR BIOLOGY EVOLUTION IF YOU WILL OF THE 1980s, 1990s WE DESCRIBE DISEASE IN TERMS OF PROTEIN ON, PROTEIN OFF TYPES OF CHARACTERISTICS AND P NOW WITH THE ADVENT OF PLETHORA OF INFORMATION FROM GENOMIC DATA I THINK WE'RE IN THE REALM TO START TO DIGITIZE DESCRIPTION OF DISEASE, COLLIELY A VERY -- CLEARLY A VERY DISTINCT OPPORTUNITY FOR HOW THE SCIENCE MOVES FORWARD. IN MY VIEW OF GENOMICS IS THAT IT'S PROVIDED US WITH A VARIETIABLE TOOLBOX OF HEIDI MENTIONAL DATA RANGING FROM THE NOW TENS OF MILLIONS OF NUCLEOTIDE VARY I CAN'T WANTS IN A SINGLE HUMAN GENOME SEQUENCE AS WELL AS COPY NUMBER VARIANTS AND OTHER REARRANGEMENTS, ABILITY TO MEASURE TENS OF THOUSANDS OF TRANSCRIPTS FROM RNA AS WELL AS MICRORNA AT THIS CUSSED EARLIER, THE PROTEOME DEFINED BY COMPLIMENT OF NOT JUST PROTEINS BUT SPLICE VARY I CAN'T WANTS AND POST TRANSLATIONAL MODIFICATION AND EMERGING CATALOG OF METABALOME THE NON-PROTEIN SMALL MOLECULE METABOLITES THAT MAYBE ARE DOING PHYSIOLOGIC WORK OF THE GENOME. GIVE US THIS NEW DIMENSIONALITY FOR PERHAPS DEVELOPING A NEW WAY OF CLASSIFYING DISEASE WHICH WE HEARD ABOUT A LITTLE BIT EARLIER. AND PROBABLY WILL HEAR AGAIN. THE REAL OPPORTUNITY LIES IN THE OPPORTUNITY TO TAKE TRADITIONAL CLINICALLY DESCRIBED CHARACTERISTICS AND RISK FACTORS AN MERGE THEM WITH THIS PLETHORA OF GENOMIC DATA TO REFINE ENHANCE PREDICTABILITY OF DISEASE AS WELL AS REFINE ENHANCE ABILITY TO PROGNOSTICATE RESPONSE TO DRUGS AND ENVIRONMENTAL EXPOSURES. WHILE GENOME TECHNOLOGIES HAVE BEEN MOVING FORWARD, SO HAVE SOCIAL MEDIA AND THE CROWD. I THINK THIS SLIDE WILL ILLUSTRATE AT LEAST SOME OF THE IMPORTANT PLATFORMS THAT HAVE EMERGED OVER THE LAST DECADE USING THE CROWD, WE ALL RECOGNIZE THE POWERFUL KNOWLEDGE BASIS WIKIPEDIA AS A CROWD SOURCE ENTITY AND MORE HEALTH RELATED PLATFORMS HAVE EMERGED OVER THE LAST DECADE SUCH AS PATIENTS LIKE ME, SOME DIRECT TO CONSUMER GENOMICS COMPANIES AND PERM GENOME PROJECT ARE HARNESSING PERSONAL REPORT INFORMATION. AND I THINK PATIENTS LIKE ME IS A VERY IMPORTANT EXAMPLE TO HIGHLIGHT HOW A CROWD SOURCED PLATFORM HAS PROVIDED POTENTIALLY NEW INSIGHTS IN RARE DISEASES, HAS BEEN USED TO CARRY OUT CROWD SOURCE CLINICAL TRIAL, EXAMPLE BEING FOR LITHIUM TREATMENT AND AMYOTROPIC LATERAL SCLEROSIS. SO WE RECOGNIZE THESE ARE GOING TO BE IMPORTANT ENTITIES THAT MAY CONTRIBUTE OVERALL TO EPIDEMIOLOGIC PLATFORMS AN TECHNOLOGIES THAT WE'RE TALKING ABOUT TODAY. THE CELL PHONE HAS BECOME UBIQUITOUS, PREDICTED BY 2018 THERE WILL BE AS MANY CELL PHONES ON THE PLANET AS PEOPLE. AND IN PARTICULARLY IN UNDERSERVED COUNTRIES WHERE THE INFRASTRUCTURE IS NOT AS IT IS IN PLACES LIKE THE UNITED STATES, TEXT MESSAGING SYSTEMS ARE USED TO HELP ENCOURAGE PEOPLE TO ADHERE TO AND FOSTER PREVENTATIVE HEALTH MEASURES TO PREVENT CARD YES VASCULAR DISEASE TO PREVENT DIABETES, ALSO BEING REMINED ABOUT TAKING MEDICATIONS SPECIFICALLY IN COUNTRIES WHERE HIV AND AIDS ARE ENDEMIC. AT THE SAME TIME WE HAD THIS PROLIFERATION OF CELLULAR TECHNOLOGY, AS WAS DISCUSSED EARLIER, THE COST OF GENOME SEQUENCING HAS HAD PLUMMETED FROM THE HUMAN GENOME PROJECT THE $3 BILLION, 13 YEAR ORDEAL TO PROSPECT OF ANY OF US HAVING A WHOLE GENOME SEQUENCE FOR LESS THAN $1,000, MAYBE IN LESS THAN A DAY AN AS THE NANOFLORATECHNOLOGY PICTURES SHOWS US PERHAPS ONE THAT IS A TECHNOLOGY THAT CAN BE PLUGGED INTO USB PORTS OF OUR COMPUTERS. SO WHAT WE HAVE BEEN SEEING OVER THE DECADE OR SO IS CONVERGENCE OF MOORE'S LAW WHICH BASICALLY STATES THAT THE CAPACITY OF A TRAN SISTER, THE AMOUNT OF INFORMATION TRANSSISTER CAN HOLD WILL DOUBLE APPROXIMATELY 18 MONTHS AND OBVIOUSLY AS LEFT HAND DIAGRAM SHOWS US, THAT THE CAPACITY OF GENOME SEQUENCING AND COSTS PLUMMETED MORE SIGNIFICANTLY THAN MOORE'S LAW PREDICTED FOR ELECTRONICS INDUSTRY AND MET CALF'S LAW WHICH SAYS THE VALUE OF NETWORK IS PROPORTIONAL TO SQUARE OF ITS USERS. SO ONE MAYBE SOME TRIVIAL EXAMPLE OF CONVERGENCE OF THESE TWO, THE DATA WE SEE IN GWAS STUDIES SUCH AS THIS FROM 23 ME USING GENOME GENOTYPING TECHNOLOGY AND MAYBE IN THE NOT TOO DISTANT FUTURE GENOTYPING TECHNOLOGY AND SOCIAL NETWORK AND SELF-REPORTED DATA TO EFFECTIVELY AND EFFICIENTLY REPLICATE A NUMBER OF EXISTING GENOME WIDE ASSOCIATION STUDIES. THIS IS JUST THE BEGINNING. IT WAS MENTIONED THE LAST SESSION THAT WE NEED TO ACTUALLY TAKE MORE STOCK IN THE ABILITY OF HEALTH SYSTEMS TO ACT AS RESEARCH TOOLS AND MANY OF YOU ARE FAMILIAR WITH THE EMERGE NETWORK ELECTRONIC MEDICAL RECORDS AND GENOMICS DEVELOPED TO FOSTER THE USE OF LATENT ASSETS IN THE REALM OF BIOSPECIMENS LINKED TO ELECTRONIC MEDICAL RECORDS TO CHANGE THOSE BIOSPECIMENS, CONVERT THEM TO GENOMIC DATA. THE PROSPECT WITH WAS TO USE THESE FOR LARGE SCALE STUDIES USING EMR PHENOTYPES AND SECOND ROUND OF PROJECTS THE GOAL IS TO PUT THE GENOMIC INFORMATION INTO THE EMR AND ALSO TO FOLLOW PHYSICIAN BEHAVIORS AND DECISIONS ON THESOMIC INFORMATION AND MEASURE OUTCOMES. THERE'S A NUMBER OF STUDY, A SMALL SUBSET MENTIONED HERE, THAT VALIDATED THE USE OF EMR BASED PHENOTYPES LINKED TO GENOMIC DATA TO DE NOVO DISCOVER NEW FINDINGS IN CHRONIC COMPLEX DISEASES AND A NUMBER HAVE BEEN SUMMARIZED IN A PAPER LAST YEAR FROM A SON SOURCE YUM BUT I MAYBE RIGHT HERE BUT NOT SURE THERE'S AN EQUIVALENT PROJECT IN THEw AREA OF CANCER, THIS IS THOSE OF YOU IN THE ROOM MORE FAMILIAR WITH THAT MAY BEG TO DIFFER AND MAYBE AN OPPORTUNITY TO DISCUSS A BIT LATER. DISCUSSION TODAY HAS ALREADY TANKEN PLACE ON THE OVERLOOKED OR UNDERMEASURED WAY, UNDER-- A WAY WE MEASURE EXPOSURES. I PARTICULARLY LIKE THIS EDITORIAL BY CHRISTOPHER WILD FROM 2005 TALKING ABOUT THE DESPERATE NEED FOR METHS TO MEASURE WITH PRECISION AND INDIVIDUALS ENVIRONMENTAL EXPOSURE AS FOR INDIVIDUAL'S GENOME AND THAT POINT THE TERM EXPOSEOME WAS COINED. AND WHETHER GENOMIC TECHNOLOGIES COULD BE USED TO ACTUALLY HELP US UNDERSTAND ONE'S ENVIRONMENTAL EXPOSURE AND AS DISCUSSION OF THE LAST PANEL HIGHLIGHTEDD THE NEED TO BE HIGHLY MULTI-DISCIPLINARY RESEARCH VENUE WAS ALSO EXHORTED BY HIM IN THIS EDITORIAL. SO WE HAVE THE NOTION OF EXPOSURES CONSTANTLY BEING BOMBARDED WITH IN OUR DAY TO DAY LIVES, THE NOTION OF THE EXPOSEOME THAT FULL COMPLIMENT OF EXPOSURE WE MIGHT EXPERIENCE DURING OUR LIFETIME, AND THE ABILITY PERHAPS OF A PLETHORA OF GENOMIC TECHNOLOGIES AND OTHER TECHNOLOGIES TO HELP REALLY UNDERSTAND BETTER WHAT WE HAVE BEEN EXPOSED TO AND THEN FOLLOW ON WHAT THE OUTCOMES MIGHT BE CLINICALLY FROM THOSE EXPOSURES. MIKE SNYDER, NOT TRYING TO STEAL HIS THUNDER HE WILL GIVE DURING THE PANEL DISCUSSION, I THINK INCREDIBLY ELEGANT JOB OF DEMONSTRATING THE POWER OF THIS IN A SINGLE INDIVIDUAL SHOWING HIMSELF MEASURES OVER A WIDE VARIETY OF GENOMIC MEASURES OVER 14 MONTHS COULD BE INTEGRATED AND MATHEMATICALLY QUANTITY AT A TIME EXPOSURES THAT WE EXPERIENCED BOTH IN TERMS OF INFECTIOUS DISEASE WITH RHINO VIRUS AN RSV AS WELL AS UNMASKING OF HOMICIDE GENOME PREDICTED, TENDENCY TO TYPE 2 DIABETES IN THE LOWER LEFT HAND CORNER. SO I THINK WE'LL HEAR MORE ABOUT THIS IN THE PANEL DISCUSSION BUT THAT'S ALSO THE NOTION OF PERSONAL MICROBIOMICS. WHAT I MEAN IS THIS IS A STUDY MY COLLEAGUE LAWRENCE DAVID AND HIS COLLEAGUE ERIC OMM HAVE CONDUCTED ARE TWO INDIVIDUALS FREQUENTLY SAMPLING WITH GUT MICROBIOME OVER TWO YEARS OF A PERIOD OF A YEAR IN TWO SUBJECTS. WHAT YOU CAN SEE DESCRIPTIVE TAXONOMY IN THE MICROBIAL FLORA, ONE INDIVIDUAL WHO TRAVELED ABROAD WITH DIETARY AND OTHER ENVIRONMENTAL CHANGES EXPERIENCED FAIRLY DRAMATIC CHANGES IN HIS OR HER MICROBIAL FLORA FOR ACUTE PERIOD THEN A RETURN TO THEIR BASELINE AN ANOTHER INDIVIDUAL, THE OTHER INDIVIDUAL EXPERIENCED A SALMONELLA ILLNESS WHO HAD A DISRUPTIVE CHANGE IN SOME OF THE MICROBIAL COMMUNITIES AND LASTED FOR QUITE A LONG TIME. THIS IS OBVIOUSLY INCREDIBLY DESCRIPTIVE, IT IS IMPLYING A CAUSE MECHANISTIC IMPLICATION TO THIS BUT I THINK IT HIGHLIGHTS THE OPPORTUNITY THERE IS TO EXPLORE MICROBIAL FROM THE SKIN ORAL PHARYNX GUT AND GENERAL TRACK AS PART OF OUR -- THE DATA WE MIGHT CAPTURE FOR THESE TYPES OF ENVIRONMENTAL EXPOSURES. YOU MAY BE AWARE THERE'S PUBLICATIONS LOOKING AT MODEL SYSTEMS TO HARNESS BLOOD BASED TRANSCRIPTIONAL PROFILING TO QUANTITATE EXPOSURES TO TOXIC -- TOXICITIES IN OUR ENVIRONMENT ON THE LEFT-HAND SIDE IS A MOUSE STUDY SHOWING TWO DISTINCT BLOOD GENE EXPRESSION BIOMARKER PAMS FOR LOW AND HIGH DOSE LED EXPOSURE OVER A PERIOD OF SEVERAL WEEKS. AND RIGHT HAND SIDE IS A STUDY DONE ALSO IN MICE EXPOSING INTO VARIOUS DOSES OF CC 137 IONIZING RADIATION DOSE DEPENDENT SIGNATURES ELICITD THE THE ANIMALS. THE RIGHT HAND STUDY WAS VALIDATED IF A HUMAN COHORT THAT WAS UNDERGOING MYELOABLATIVE RADIATION FOR TREATMENT OF CANCER. THIS PROJECT IS ACTUALLY MOVED ON TO ONE THAT'S THE US GOVERNMENT IS UNDERTAKING TO DEVELOP A DEVICE THAT COULD BE USED TO TRIAGE INDIVIDUALS EXPOSED TO RADIATION IN A SETTING OF NUCLEAR DISASTER OR BIOTERRORIST EVENT. LAST WEEK THIS STUDY WAS PUBLISHED DEMONSTRATE -- FROM A COHORT OF PATIENTS FOLLOWED FOR CARDIOVASCULAR DISEASE DEMONSTRATING THAT NEVER OR FORMER SMOKERS&r HAVE A DISTINCT GENE EXPRESSION PATTERN MEASURED IN BLOOD FROM INDIVIDUALS RECENT AND CURRENT SMOKERS. AND 4 OR 5 GENE MODEL WAS DEVELOPED TO CLEARLY DISTINGUISH BETWEEN THOSE TWO BROAD CLASSES OF INDIVIDUALS WITH SMOKING EXPOSURE. CLAUDE RICHARD DEMONSTRATED PHYSIOLOGIC CHALLENGE USING EXERCISE ELICITS A RESPONSE ALSO IN A BLOOD BASED RNA PROFILING MEASURE ASSOCIATED WITH VO-2 MAX SO THIS IS ADAPTIVE AEROBIC TRAINING ASSOCIATED WITH A BLOOD BASED GENE EXPRESSION PROFILE. LEAVING OPEN THE POSSIBILITY THAT WE MIGHT BE ABLE TO LOOK AT EXPOSURES MORE BROADLY USING THESE TYPES OF BIOMARKERS. IN OUR OWN RESEARCH THIS HAD BEEN ONE OF THE PARADIGMS WE'VE USED AND I'LL SHOW YOU AN EXAMPLE OR TWO OF THIS, REALLY TO CAREFULLY CONTROL FOR EXPOSURES IN EXPERIMENTAL SETTING USING HEALTHY VOLUNTEERS AND SOMETIMES PATIENTS DOING VERY DETAILED PHENOTYPIC PHYSIOLOGIC AND TYPES OF MEASURES AN DENSE DETAILED MOLECULAR PHENOTYPING FOLLOWING PRIOR TO AND FOLLOWING EXPOSURES WITH THE GOAL OF GENERATING CLINICAL MOLECULAR MODEL OF THE EXPOSURE AS WELL AS PREDICTORS OF RESPONSE. SO OUR WORK IN THIS REGARD FOCUSED ON INFECTIOUS DISEASE. WE COMPLETED 8 HUMAN STUDIES EXPOSING HEALTHY VOLUNTEERS TO LIVE RHINO VIRUS RESPIRATORY INTERSTITIAL VIRUS AND P TWO STRAINS OF INFLUENZA, AS YOU CAN SEE INDIVIDUALS WHO ARE SCREENED FOR NEUTRALIZING ANTIBODY, NOT EVERYBODY SUCCUMBS OR RATHER CONTRACTS THE DISEASE FOLLOWING THE VIRAL CHALLENGE. SOME PEOPLE PEOPLE GET INFECTED, OTHERS REMAIN APPARENTLY PERFECTLY HEALTHY. WHAT HAS BEEN FAIRLY UNIQUE ABOUT THESE STUDIES IS ONE, WE HAVE THE CHANCE TO LOOK AT THE DISEASE FROM ITS BEGINNING TO ITS VERY END. IN WAYS THAT HAVE NOT BEEN DONE BEFORE. WE DO VERY DENSE TIME SAMPLING OF THESE INDIVIDUALS BEFORE AND AFTER EXPOSURE. PERHAPS AS MUCH AS EVERY SIX HOURS FOR FIVE TO SEVEN DAYS. WE HAVE ALSO HAD THE OPPORTUNITY TO LOOK AT MULTIPLE TYPES OF BIOLOGICAL SPECIMENS WITH MULTIPLE TYPES OF GENOMIC PLATFORMS. I CAN'T GO INTO ALL DETAILS OF THE RESULTS OF THESE STUDIES BUT I WANT TO SHOW YOU A A FEW. AN EXAMPLE OF A RNA PROFILING EXPERIMENT FROM INFLUENZA CHALLENGING STUDY. THE INDIVIDUALS DEPICTD IF BLUE DEVELOP SYMPTOMATIC INFLUENZA, THE INDIVIDUALS IN RED REMAIN ESSENTIALLY HEALTHY AND USING VECTOR MODELING FROM THE RNA PROFILING DATA WE IDENTIFIED SEVERAL FACTORS, THIS IS ONE CALLED FACTOR 3, 50 GENES THAT DISTINGUISH BETWEEN INDIVIDUALS EXPOSED AND WHO GET SICK FROM INDIVIDUALS WHO REMAIN HEALTHY. THE DOTTED LINE ON THE RIGHT HAND SIDE IS THE TIME OF PEAK SYMPTOMS, THE DOTTED LINE ON THE LEFT-HAND SIDE IS THE TIME WHICH THE MOLECULAR PROFILE ACTUALLY BECOMES APPARENT. NOT ONLY CAN WE TELL THE DIFFERENCE BETWEEN HEALTH AND DISEASE STATE BUT POSSIBILITY FOR EARLY DETECTION AND PREDICTION OF FUTURE SYMPTOMATIC DISEASE. THAT WAS USING A RNA BASED ARRAY PROFILE, WE HAVE BEEN ABLE TO ALSO MOVE THAT ON TO AN RT PCR PLATFORM MORE CLINICALLY TRACTABLE. AND SHOWING EVOLUTION OF THE PCR SIGNATURE FOR INFLUENZA, PRECEDES WITH HISTORY OF 50 HOURS, THE PEAK OF CLINICAL SYMPTOMS. NOT ONLY CAN WE LOOK AT ONE TYPE OF PATHOGEN BUT BEGIN TO ALSO DEVELOP UNIQUE HOST BASED CLASSIFIERS OF SEVERAL PATHOGENS. THIS IS ONE EXAMPLE OF A GENE EXPRESSION PROFILE FROM WHOLE BLOOD THAT DISTINGUISHES BETWEEN CLEARLY INFECTION OF VIRAL ETIOLOGY IN THIS CASE INFLUENZA A FROM TWO WELL DOCUMENTED CULTURE POSITIVE BACTERIAL INFECTION, WITH GRAIL NEGATIVE E. COLI OR STREP PNEUMOCOCCUS. ALL OF US IN THE ROOM APPRECIATES THE POSSIBILITIES OF USING THIS TYPE OF TECHNOLOGY DAY TO THEY CLINICAL SITUATION DO I TREAT THE PATIENT WITH ANTIBIOTIC OR NOT WITH THE FEBRILE ILLNESS. SO I WOULD LIKE TO POSIT THE POSSIBLY THAT WE HAVE AN OPPORTUNITY TO REALLY GET INTO THIS EXPOSURE PROBLEM IN A VERY COMPREHENSIVE SYSTEMATIC WAY AS ILLUSTRATED IN THIS CARTOON, WHERE WE MIGHT BE ABLE TO LOOK AT RELEVANT FIZZ QUO LOGIC, PHARMACOLOGIC, CHEMICAL AND PERHAPS PATHOGEN EXPOSURES AND BEGIN TO DOLL A ROBUST CATALOG THAT WE CAN BEGIN TO MERGE BACK INTO EPIDEMIOLOGIC AND COHORT STUDIES DISCUSSED EARLIER THAT WILL BE DISCUSSED GOING FORWARD. THE OTHER ASPECT OF TECHNOLOGY WE CAN OVERLOOK IS SENSORS. THEY ARE GIVING AN UNBELIEVABLE OPPORTUNITY IF TREATED RIGHT TO DO ROBUST PHENOTYPING. SOME MAY USE THESE, THEY NEAR YOUR SHOES, AROUND YOUR WRIST LIKE THIS ONE I HAVE OR ON YOUR NECK AND BELTS AN MEASURING YOUR MOVEMENT ALL THE TIME, REPORTING ON ALL KINDS OF POTENTIALLY RELEVANT PHYSIOLOGIC DATA. DEVICE LIKE THIS APPROVED BY THE FDA LAST WEEK FOR MEASURING ELECTROCARDIOGRAMS. SO THIS IS AVAILABLE AS WELL. PHYSIOLOGIC MONITORS. AND ALSO SUGGEST THAT WE CAN GET A LOT OF RELEVANT INFORMATION FROM GAMING PROGRAMS AND SOME OF MY COLLEAGUES AT DUKE ARE USING INDIVIDUALS PERFORMANCE IN GAMING PROGRAM TO CORRELATE COGNITIVE FUNCTION MENTAL HEALTH AND PERFORMANCE AND TIE IT BACK TO SERIES OF BIOLOGICAL MEASURES SUCH AS GENOMIC PROFILING I SHOWED YOU EARLIER. I CAME ACROSS THIS NOT TOO LONG AGO. THIS IS A ESSENTIALLY MEASURES INTEROCULAR PRESSURE ON CONTACT LENS AN REPORTS 24 HOURS REEDINGS TO A BLUE TOOTH ENABLED DEVICE TO MODULATE DOSES FOR GLAUCOMA AND OTHER TYPES OF DISEASE RELATED TO THE EYE. IF YOU THINK THIS IS A TECHNOLOGY FOR THE RICH, THERE'S PAPER BASED SENSORS DEVELOPED THAT COST LITERALLY MANUFACTURED THOUSANDS PER PENNY AND THEY CAN BE DEPLOYED IN THE DEVELOPING WORLD FOR MULTI-ANOLYTE DETECTION AS YOU SEE ON THE LEFT. AND THIS IS FROM GEORGE WHITE SIDES AT HARVARD. IF YOU EXTEND THE FLU PARADIGM TO THAT TECHNOLOGY, IF WE CAN MEASURE PATHOGENS DISCRIMINATING PROTEINS, PERHAPS A SIMPLE TISSUE MIGHT BECOME AN IMPORTANT DIAGNOSTIC TESTING DEVICE USING PAPER BASED TECHNOLOGY. LAST FEW MINUTES I WANTED TO MENTION THE FACT THAT THE INTERNET INCREDIBLY POWERFUL TECHNOLOGY CAPTURING INFORMATION, THIS HIGHLIGHTS THE ACTIVITY WE EXPERIENCE AND SOME OF YOU HAVE SEEN THIS TYPE OF DATA BUT WE ARE ALL BEING WATCHED AS WE MAKE OUR KEY STROKES AND COMPUTER AND DO OUR SEARCHES. THIS TYPE OF DATA IS MINED AS ILLUSTRATED FOR SHOWING THE KINDS OF SEARCHES DONE ON A GLOBAL BAY FOR REMEDIES FOR THE FLU OR SYMPTOMS OF THE FLU OR OTHER FLU LIKE SEARCHES READILY AND PUBLICLY AVAILABLE FROM GOOGLE SIMILARLY THIS DATA MINED FROM TWITTER FEEDS SEARCHING FOR INDIVIDUAL COMMENTS ON FLU LIKE SYMPTOMS AND COMPARING TO INFLUENZA ILLNESS PATTERNS IN THE IMMUNITY AND BUILDING A MULTI-DIMENSIONAL MODEL OF THIS TYPE. I WOULD POSIT THAT RELEVANT TO DISCUSSION WE JUST HAD AND MAYBE DISCUSSION WE'RE GOING TO HAVE, IT'S NOT NECESSARILY ABOUT THE TECHNOLOGIES BUT DATA GENERATED FROM THE TECHNOLOGIES AND MAYBE 21st CENTURY EPIDEMIOLOGY NEEDS TO THINK HOW TO INTEGRATE DATA IN A WAY MUCH MORE USABLE WHETHER COHORT STUDIES, HOSPITAL SYSTEMS OR OTHER SOURCES. I WANTED TO -- I HAVE TWO MORE SLIDES, ONE IS THIS VIDEO WHICH I HOPE WILL PROJECT, I SAW THIS LAST WEEK ON GEZMODO.COM. THE START TREK MEDICAL IS REAL AND ONLY $150. I COUP RESIST READING THE ARTICLE. AND I FOUND THIS VID -- >> TECHNOLOGY HAS GIVEN US UNPRECEDENTED WINDOW INTO THE HUMAN BODY. ON A DAY-TO-DAY BASIS, WE'RE STILL IN THE DARK ABOUT OUR OWN HEALTH. WE ARE CHANGING THAT. WHAT IF INSTEAD OF FEARING THE WORSE WHEN YOU NOTICE SOMETHING OUT OF THE ORDINARY? YOU COULD IDENTIFY THE CONDITION YOURSELF. GETTING RIGHT DIAGNOSIS WOULD SAVE WORRY. AND UNNECESSARY DOCTOR'S VISIT. INSTEAD OF HEARING ABOUT VIRAL OUTBREAK ON THE NEWS IMAGINE YOU HAVE AN ALERT. IT WAS TAILORED TO FAMILY'S NEEDS. IT WOULD ALSO GIVE YOU ADVICE ABOUT WHAT TO DO NEXT. WHAT IF YOU HAD A WAY TO IDENTIFY WHAT WAS WRONG RIGHT AWAY? TO GET THE INFORMATION YOU NEED TO UNDERSTAND THE SITUATION. ANY SERIOUS CASES? YOU KNOW WHEN AND WHERE. WE'RE BUILDING A WAY FOR PEOPLE TO PROTECT THEIR BODIES AS OFTEN AS THEY CHECK THEIR EMAILS. >> OKAY. I LIKE THAT TAG LINE, CHECK YOUR HEALTH AS OFTEN AS YOU WHICH CAN YOUR EMAIL BUT I THINK THIS IS PROVOCATIVE WAY TO THINK ABOUT WHERE MEDICINE MIGHT GO IF WE HARNESS TECHNOLOGIES IN A THOUGHTFUL WAY AND I TEED UP QUESTIONS WE MIGHT GET INTO IN THE PANEL DISCUSSION. WHAT DATA IS REALLY IMPORTANT HOW DO WE REALLY CAPTURE AND KNOW IT'S QUALITY DATA. SYSTEMATIZING EXPOSURE DATA THE, CREATING THE PLATFORM OF INTEROPERABILITY AND STANDARDS THAT ALLOW ALL THIS COME TOGETHER AND WE CANNOT OVERLOOK THE FACT THAT WITH ALL THE GREAT STATISTICIANS IN THE ROOM STILL DON'T HAVE THE METHODOLOGY THAT WE NEED TO REALLY TAKE FULL ADVANTAGE OF THE DATA THAT WE'RE -- THAT WE'RE SEEING. AND WOULD ARGUE RELENTLESSLY TO VALIDATE FINDINGS AND SHOW UTILITY BEFORE WE CONSIDER IMPLEMENTING THEM AND THEN THE QUESTION IS THE LAST SESSION HOW DO WE IMPLEMENT RESULTS TYPICALLY FROM COMPLEX TECHNOLOGIES SUCH AS THIS. THANK YOU. [APPLAUSE] >> LET ME JUST SAY, I WANT TO POINT OUT TO THE MEMBERS OF THE -- EVERYONE IN THIS ROOM THE DISCUSSION IS OPEN TO EVERYONE IN THIS ROOM, NOT JUST THOSE AROUND THE TABLE, A LITTLE CONFUSION ABOUT MORNING OR EARLIER SESSION SO QUESTIONS AN COMMENTS NOT ONLY FROM THE TWEETS AND THE CATS AND THE BIRDS AND ALL THE PEOPLE IN THE BLOGS BUT EVERY IN THIS ROOM, AROUND THE TABLE AS WELL AS THE YOU AROUND THE TABLE SO TO SPEAK. SO PLEASE FEEL FREE TO JOIN IN. DO WE HAVE BURNING QUESTIONS? >> NOT SURE IT'S BURNING BUT IT'S PROBABLY QUESTION YOU HAVE BEEN THINKING ABOUT. SO ONE OF THE MAIN DIFFERENCES BETWEEN GENOMICS WHICH AS EVERYONE SAID DANCE TO BIG SCIENCE AND IT WAS FIXED, WHAT'S ATTRACTIVE, IT MIGHT HAVE HIGHER RELEVANT RISK BUT IS A VERY DIFFERENT OPPORTUNITY, I THINK DO YOU SEE QUITE A DIFFERENT OPPORTUNITY FROM THE GENOME AND ANOTHER PAIR THAT KEEPS COMING UP, MAYBE THIS IS THE TEMPERMENT THAN STATE OF THE SCIENCE. BUT AS I REMEMBER IT WE FELT THEN SEVEN, 8 YEARS AGO, THERE WAS A BLESSING AND CURSE IN FRONT OF US, NOT ONLY IF WE COULD DO GWAS RIGHT WE LEARN A LOT, WHICH WE DID. BUT WE HAD A STRONG SENSE THAT IF WE DIDN'T DO IT RIGHT, IT WOULD BE DONE WRONG AND MISLEAD US. SO QUESTION IS AMONG METABALOMEICS IDEAS MANY FRONT OF US, AND GIVEN IT'S NOT FIXED AND TAKE MULTIPLE MEASURES, IS THIS ONE, IS THERE AN AREA, PART OF THAT DOMAIN FOR YOU HAS THAT SAME FLAVOR OF NOT JUST POLLING US FORWARD, BUT ALSO PUSHING US IF WE DON'T DO IT WELL, GOOD EPIDEMIOLOGY AN SIZED PROPERLY FROM THE GET GO, WITH WE'LL BE IN BAD SHAPE. DO YOU SEE WHAT I MEAN? IS THERE ONE OF THESE THAT CALLS IN THE SAME WAY THAT WE REALLY RATHER QUICKLY RECOGNIZED WE HAD TO DO THIS IN GENOMICS OR GWAS WOULD BE NOT GWAS, IT WOULD BE SMALL AND MISLEADING. >> SO MAYBE YOUR QUESTION HAD A LOT OF LAYERS BUT ONE LAYER THAT I SEE IS THAT THE ADVANTAGES OF SOME OF THE MEASURES OF WHAT I LIKE TO THINK ABOUT IS DYNAMIC GENOME AS FIXED GENETIC OF GWAS, THERE'S A LOT OF POTENTIAL CONFOUNDERS THAT MIGHT REDUCE SIGNAL IN WHAT WE'RE SEEKING ANSWERS TO USING GWAS. BUT IF YOU LOOK AT DRUG EXPOSURE STUDIES IN GWAS, THEY HAVE TREMENDOUS SIGNALS RESPONSE TOKING WELATED INTERFERON FOR HEPATITIS C. SO THERE ARE WE MAY BE ASKING A LOT TO GIVE HOOKS INTO WHAT MIGHT BE RELEVANT FOR EPIDEMIOLOGY GIVEN LENGTH OF TIME AND MULTIPLE CONFOUNDERS THAT EXIST BETWEEN WHENEVER WE'RE BORN, OUR DNA IS MADE AND TO THE POINT WE HAVE THAT DISEASE OUTCOME. I SEE THE VALUE FOR THE DYNAMIC GENOME, IT'S PROXIMAL TO THE OFTEN TIMES TO THE DISEASE OUTCOME WE LOOK AT AND THEREFORE IT COULD BE A MUCH MORE POWERFUL SERIES OF TOOLS TO HELP EITHER PREDICT FUTURE EVENTS OR EVEN CLASSIFY EVENTS THAT WE'RE SEEING. BUT WE'RE MUCH TOO EARLY IN OUR GESTATION OF THE TECHNOLOGY TO PIN -- COMMIT TO ONE VERSUS ANOTHER OF THE GENOME BASED TECHNOLOGY PLATFORM BUT I WOULD ECHO WHAT YOU JUST SAID. HIGH QUALITY EPIDEMIOLOGIC STUDIES WITH HIGH QUALITY SPECIMEN AND ATTENTION THE DATA GENERATION, DATA MANAGEMENT, ANALYSIS HAVE TO BE PART OF THIS EQUATION. I HOPE I TOUCHED SLIGHTLY ON WHAT YOU WERE TRYING TO GET AT. >> MIKE MAY ALSO HAVE SOME -- SURE YOU DO HAVE SOME OPINIONS ON THAT. MAYBE TALK ABOUT THEM HATER. >> DO YOU WANT NOW OR -- OKAY. CAN I FOLLOW-UP ON THAT WITH A QUESTION? ONE THING THAT IS ALWAYS TROUBLING ABOUT GWAS IS IT'S TWO DIMENSIONS, CASE CONTROL WITH NO EVIDENCE OF TIME IN THERE. WHAT YOU WERE TALKING ABOUT WHEN YOU SHOWED EXAMPLES WAS THE DYNAMIC SERIAL SAMPLING. HOW DO YOU SEE GOING FORWARD WE'RE ABLE TO BEGIN TO MODEL AND ASK QUESTIONS PARTICULARLY THINGS LIKE CANCER WHICH I THINK IN MANY WAYS MORE COMPLICATED THAN RESPONSE TO RSV OR INFLUENZA WHICH IS A DISSCREAM CHALLENGE AT CERTAIN POINT AND YOU SEE OVER 48 HOURS SIGNATURE SWITCH THAT TELL YOU ONE THING TO THE OTHER. WITH CANCER WE LEARN FROM PANCREATIC CANCER SEQUENCING MODELING 10, 12 YEARS IN DEVELOPMENT FROM THE TIME THE FIRST MUTATIONAL EVENTS AT LEAST BEING RECOGNIZED. SO THE MODELING OF TIME BECOMES IMPORTANT. THE SECOND, HOW CAN WE USE NON-CONVENTIONAL RESOURCES LIKE YOU TALK FACEBOOK, 23 AND ME, SOCIAL MEDIA, CROWD SOURCING, THE GATHERING OF THIS INFORMATION. WHICH MAY HELP US IDENTIFY WE DID WITH GWAS IN LESS PRESSSTEEN WAYS. TRAJECTORIES AN PATTERNS THAT MAYBEY‡K USED. >> SEEMS TO ME ONE OF THE 12 THINGS PUTTING OUT FOR TOMORROW MAYBE HOW TO CAPTURE THAT DEEM PERFORM DIMENSION BECAUSE IT SEEMS SO CRITICALLY IMPORTANT NOT FOR GENOMIC STUDIES BUT HOW WE THINK ABOUT DESIGNING EPIDEMIOLOGIC STUDIES THAT ARE ONES THAT HIGHLIGHT RISK AND ALSO PROGRESSION OF CANCERS IT IS A CHALLENGE AND WE NEED TO THINK ABOUT ARE THERE RELEVANT CANCER ENTOE PHENOTYPES THAT MAYBE SHORT OF GETTING ACCESS TO A TUMOR BEFORE IT BECOMES A TUMOR. AND ALSO CAN WE USE MORE ELEGANT USE MODEL SYSTEMS IN A BETTER WAY TO GET AT TEMPORAL QUESTIONS, PARTICULARLY DEVELOPING XENOGRAPH MODELS AND THE LIKE TO GIVE A CHANCE TO DO MULTIPLE BIOPSIES, MULTIPLE DATA GENERATING EVENTS OVER THE TIME COURSE OF A TUMOR AND MAYBE EVEN IN RESPONSE TO THERAPIES BECAUSE THAT QUESTION CAME UP AS WELL. IS THE TUMOR YOU TREAT AFTER RESISTANCE IS SHOWN CHINICALLY IS THAT THE SAME TUMOR THAT YOU STARTED WITH BEFORE YOU STARTED TREATING THEM. SO IT'S A TREMENDOUSLY IMPORTANT QUESTION AND I DON'T HAVE A SUCCINCT ANSWER FOR YOU. >> YOU SAID AN INCREDIBLY IMPORTANT BUOYANT, BARRY IS INTERESTD IF THAT, PREVENTION IS PROBABLY NOT DONE WITH A POLAROID SNAP SHOT ALONE. THERE MAY BE A DYNAMIC TO SEEING CERTAIN CHANGES AND THE QUESTION IS, AGAIN, GOING BACK TO CANCER, HOW LENGING IS THAT GOING TO BE B THE IN SITU, THE FEEL EFFECT, THE AGGRESSIVE DISEASE, METASTATIC. RECESSTANT, -- RESISTANT, A PROGRESSION OF THINGS WE USUALLY MEASURE IN YEARS, NOT IN MINUTES TO DAYS AS THE INFECTIOUS DISEASE WORLD DOES. >> RIGHT. >> SO I AGREE WITH YOU, I THINK WE EITHER YOU NEED TO FIND CANCER THAT HAVE RAPID COURSES AS PROTOTYPE OR RESOURCING TO MODEL SYSTEMS AND CELL BASED SYSTEMS IN WAYS NOT DONE BEFORE. PROBABLY A LOT OF CANCER BIOLOGISTS AND EPIDEMIOLOGISTS THAT MIGHT HAVE ANSWERS ABOUT TEMPORAL ASPECTS AS WELL. I WOULD BE INTERESTD IF HEARING THOSE TWO. -- INTERESTED IN HEARING THOSE TWO. >> OTHER QUESTIONS? WHY TONE WE ASK THE PANELISTS TO COME UP AND WE'LL BEGIN THE PANEL. >> THIS IS SOMETHING I'M NOT SURE OUR -- PROJECTED ON TO -- (OFF MIC) ALL RIGHT. WHY DON'T WE LEAVE -- THIS WILL BE INTERESTING, ONE IS THIS IS -- WHAT I WANTED TO DO IS SHOW A SLIDE FROM A MEETING DAVID HUNTER HAD REFERRED TO NOVEMBER 30th WHERE 50 PEOPLE WERE BROUGHT TOGETHER CONVENED BY DIRECTOR HAROLD VRMUS TO TALK FUTURE OF CANCER GENOMICS. AND THIS IS REALLY ON THE HEALS OF SUCCESS OF TCGA AND TARGET PROGRAMS ASKING WHAT IS THE FUTURE OF CANCER GENOMICS GOING TO LOOK LIKE AND WHAT ARE WE FUNDING FUNDING FROM BOTTOM UP AND TOM DOWN. AND IT WAS A -- TOM DOWN. IT WAS A -- TOP DOWN. IT WAS A VERY EVENTFUL SIX INTENSE HOURS AN DR. VARMUS PUT UP SLIDES NOT ON THE BACKGROUND OF IRC. PROBABLY SOMEWHERE IN CALIFORNIA ROLLING OVER RIGHT NOW IF HE SEES THIS. BUT I THINK THE KEY THING IS HE PUT UP A PARTICULAR SLIDE THAT I WANTED TO SHOW, AND THAT WAS THE ATTITUDENAL CHANGES THAT HE HAD WITNESSED IN THE DISCUSSION AND OVER THE COURSE OF TCGA AN ACTIVITIES IN THE MOLECULAR EPI WORLD. THE FIRST IS THE EMBOLDENED APPROACH TO NUMBERS DEPTH AND PLEASE IN THE APPRECIATION OF COMPLEXITY OF CANCER. AND THAT THE AGE OF WHETHER MOLECULAR EPIDEMIOLOGY OR SOMATIC RELIES UPON VERY LARGE NUMBERS AND USING THEM IN THE COMPARATIVE PURPOSES ARE REALLY CRUCIAL. AND THIS WAS SOMETHING THAT WAS BROUGHT A GREAT SMILE TO A NUMBER AND DAVID HUNDRED DOLLAREr. PRESENTATION. THE EAGERNESS TO THINK ABOUT INTEGRATION OF GENETIC, GERM LINE SOMATIC WITH–o THE ENVIRONMENT FUNCTIONAL AND CLINICAL DATA, THAT THIS HAD TO BE CENTRAL TO ALL OF OUR STUDIES GOING FORWARD IN THE PORTFOLIO CENTER FOR CANCER GENOMICS, AS TCGA ENDS 2013, THE 12,000 SEQUENCED CANCERS WILL BECOME A MUCH LARGER NUMBER. AND WE HAVE TO INTEGRATE WITH THE NEXT SET OF STUDIES, SPECIFIC AND TRANSLATABLE QUESTIONS. OR THE LAST ONE HE SAID WAS THE SHIFT OF ESSENTIAL CONCERNS FROM THE GENERATION OF DATA, THE DATA STORAGE USE AND INTEGRATION AND SHARING. THIS IS SOMETHING THAT PARTICULARLY IN THIS COMMUNITY WE DO SORT OF WELL BUT NOT WELL ENOUGH. SHARING OUR DATA AT EARLIER OPPOSED TO HATER POINT OF VIEW. GWAS PUSHED US TO START TO DO THAT BUT WE HAVE TO LOOK AT WHAT OUR COLLEAGUES IN THE GENOMIC WORLD HAVE DONE PUT OUT AT A VERY EARLY POINT AND ALLOWED MANY PEOPLE TO BE ABLE TO USE THAT. GETS TO A VERY UNCOMFORTABLE POINT FOR A LOT OF EPIDEMIOLOGISTS IS THE OWNERSHIP OF THAT DATA AND HOW IT'S SHARED COMBINED OR USED WITH OTHERS BUT THIS IS SOMETHING WE AS A COMMUNITY HAVE TO WORK TOGETHER TO CONTINUE TO IMPROVE IT. IT'S NOT IS A TO SAY WE'RE GOING TO GET THERE OVERNIGHT BUT I THINK THIS IS A REALLY KEY ISSUE THINKING ABOUT THE 12 POINTS TOMORROW AND THAT IS DATA SHARING, DATA AVAILABILITY AND IT'S JUST NOT IN THE ACADEMIC STUDY. BUT TO BE ABLE TO MAKE SENSE OF CANCER GENOMICS WITH TECHNOLOGIES GOING ON, I WAS AT THE INTERNATIONAL CANCER GENOME CONSORTIUM YESTERDAY IN IDLEBERG AND THERE'S 25,000 GENOME SEQUENCED IN THE NEXT TWO YEARS. THE ISSUE IS PROBABLY BE 100,000 SEQUENCED CLINICALLY NOT AVAILABLE NECESSARILY TO THE ACADEMICS AND THE QUESTION IS HOW ARE WE GOING TO ACCESS AND WORK WITH COLLEAGUES GENERATE THESE FOR CLINICAL PURPOSES SO THE DATABASES ARE LARGER SO THE AGNOSTIC ANALYSES CAN TAKE PLACE. THIS IS A MAJOR CHALLENGE IN THINKING ABOUT HOW WE'RE GOING TO USE THIS INFORMATION AND GETS AT WHAT JOHN WAS ASKING ABOUT, HOW IS THE BIG THAT'S OUT THERE. FOR THESE TECHNOLOGIES, THEY'RE GETTING BIG AND THE QUESTION IS WE HAVE TO BREAK DOWN SOME OF OUR OLD BARRIERS AND THINK ABOUT CREATIVE WAYS TO GO ACROSS THE AISLE TO 23 MILLION OTHER PEOPLE IN THE CLINICAL ENTITIES AND PRIVATE ENTITIES AND COME UP WITH CREATIVE WAYS OF SOLVING THOSE THAT'S WHAT I WANTED TO START THE SESSION AND PROJECTING THE IMPORTANCE OF THE ATTITUDENAL CHANGE EVOLVING AT THE NCI AND DIRECTORS LEVEL IS RECOGNIZE THAT AND SOME OF THE APPOINTMENTS AND IDEAS HE PUT IN PLACE FOR FUTURE OF CANCER GENOMICS ATTEST TO THAT AND H SHOULD COME AS REASSURANCE BUT ALSO WAKE UP CALL TO MEMBERS OF THIS COMMUNITY WHO ARE HERE TWEETING BLOGGING AND DOING WHATEVER THEY'RE DOING AND WHATEVER CORNER OF THE WORLD FOLLOWING THIS DISCUSSION. SO WHAT I WANT TO DO IS ONE OTHER THING. TO SHOW TWO SLIDES. AS WE THINK ABOUT THE STATE OF EPIDEMIOLOGY AND THE USE OF TECHNOLOGY, WE HAVE TO THINK THE CLARITY WHICH WE SEE THINGS. WE KNOW THERE ARE WONDERFUL EXAMPLES FROM HUMANITY, THINGS CALLED PAINTINGS. HERE IS PAINTING OF AN 8-YEAR-OLD TAKEN OFF THE WEB. USING THE SAME PAINT THIS GENTLEMAN USED. WHEN WE LOOK AT THE THIS WE REALIZE THERE ARE FEATURES WE CAN RECOGNIZE BUT IF WE OVERANALYZE ANY ONE CORNER WE FAIL TO UNDERSTAND WHAT THAT BIGGER PICTURE LOOKS LIKE. WITHOUT IATRIASIVE LOOKS WE CAN'T UNDERSTAND WHAT'S GOING ON IN THIS PAINTING PAINTING THAT YOU CAN SEE THE OUTLINES OF PARLIAMENT, THE TIME OF DAY AND COLORS AND MORE IMPORTANTLY THE PORTFOLIOROID YOU'RE SEEING AND INTERPRETING WHAT YOU THINK IS GOING ON THERE AND IT MAYBE DIFFERENT BETWEEN EACH ONE OF THIS ROOM, IN A LITTLE WAY BUT ALSO IN A MUCH LARGER WAY, SO THE CHALLENGE OF EPIDEMIOLOGY IS TO VISIT THE DATA SETS WE HAVE AND HOPEFULLY COMING TO GRATER FOCUS SO LESS LIKE THE ONES WE SAW BEFORE IN MORE MEANINGFUL HERE WE NOW KNOW WOULD BE PRICED SOMEWHERE 250 MILLION EWE ROWS IF IT WERE TO AUCTION AT CHRISTIES. NO GRANT IS EVER THAT LARGE SO DON'T WANT ANYONE TO DRAW CONCLUSIONS ON THAT. BUT TO SET UP THIS TECHNOLOGY SESSION I WANT TO ADD SOME QUESTIONS HERE. IN LOOKING AT THIS, AS WE START TO ANALYZE THIS AND PULL THIS APART, BY DEFINITION WE ARE ALUM PERS AND SPLITTERS AND WE WANT TO UNDERSTAND ONE OR MORE ASPECTS, WE HAVE TO ASK THE QUESTION, HOW DOES TECHNOLOGY HELP RECOGNIZE THE FEATURES OF HUMAN DISEASE AS WE LOOK AT A PAINTING AND WE CAN SEE CERTAIN THINGS THAT SAY OH, YEAH, WE CAN RECOGNIZE THAT'S RIGHT BUT I MAY NOT BE ABLE TO DEFINE EACH OF THE CORNERS IN EACH OF THE VERY SPECIFIC ELEMENTS THAT MAKE THAT A WONDERFULo#3 PAINTING. WHIP IS THE RIGHT TIME TO APPLY NEW TECHNOLOGIES TO LOOK AT THIS. WHAT ARE THOSE MOMENTS OF OPPORTUNITY. I THINK THE PAMMIST ALSO ATRESS THAT. WHAT IS THE VALIDITY? IT MEAN AS LOT OF THINGS TO A LOT OF PEOPLE, WHETHER TECHNICAL, WHETHER SCIENTIFIC, WHETHER STATISTICCAL, WHETHER IT'S CLINICALLY USEFUL, PREVENTION, WHETHER IT'S TRANSLATEABLE. CURING OR WHATEVER, I THINK THE IMPORTANCE THAT I WOULD LIKE TO ASK EACH OF THE MEMBERS IS HOW THEY SEE THE WORD VALIDITY IN THE USE OF TECHNOLOGY THEY'RE THINKING ABOUT AND INTRODUCING. THE OTHER ISSUE IS SHARING AN PERSPECTIVES AND HOW WE LOOK AT THESE THINGS. WE ARE AT A POINT WE NEED TO START TO IN THE FUTURE AS ONE 12 POINTS, I WANT TO PUT DOWN THIS CONCEPT OF SOMATIC MOLECULAR EPIDEMIOLOGY THAT GOT LOST FROM EXPOSURE TO SUSCEPTIBLE TO SOMATIC CHANGES TO OUTCOMES AND WHAT THOSE RELATIONSHIPS ARE. THESE ARE THINGS I THINK WE HAVE CLINICAL PREVENTIVE OPPORTUNITIES AS WE START TO THINK IN A MORE DYNAMIC IN A BIT MOVE COMPLEX FASHION. O WHY DON'T I STOP THERE AND WE'LL GO TO THE FIRST SPEAKER. >> SO I WOULD LIKE TO THANK THE ORGANIZERS FOR THIS OPPORTUNITY. I'M NOT EPIDEMIOLOGIST,OT MOLECULAR BIOLOGIST I'M INTERFACING ALSO WITH EPIDEMIOLOGISTS, I WORK IN EPIGENETICS SO WE HAVE THREE COMMON FIRST THREE LETTERS IN COMMON. SO THAT'S OOH A GOOD START. SO MY THOUGHTS ACTUALLY HERE SUMMARIZING THIS FEW BULLET POINTS, FIRST FOR TECHNOLOGIES THAT ARE ALREADY FOR PRIME TIME AND BY NO MEANS I'M BIASED THIS MY OVERLAP SUBSEQUENT PANELISTS. SO THE OBVIOUS WE HAVE THERE HAS BEEN ALREADY A MENTION THAT PREVIOUS SPEAKERS WE ARE REALLY EXCITING TIME WITH COMPLETION OF MANY INTERNATIONAL SEQUENCING INITIATIVES WE HAVE A COMPREHENSIVE PORTRAIT OF HUMAN CANCER BUT ALSO NORMAL TISSUE. THIS PROVIDES US WITH -- THIS WILL PROVIDE US WITH CRITICAL INFORMATION ABOUT BIOLOGICAL PATHWAYS BUT ALSO THE SO CALLED SECOND GENERATION WHAT I CALL SECOND GENERATION BIOMARKERS WHICH ARE RESULTING FROM APPLICATION OF OMICS TECHNOLOGY. AND ADVANCES IN EPIGENOMICS MY AREA OF RESEARCH AND I THINK YOU WOULD AGREE THERE HAS BEEN A SPECTACULAR PROGRESS IN TECHNOLOGY. IN THIS AREA. AND WE ARE MAYBE NOT THERE YET BUT WE ARE ABOUT TO HAVE MORE COMPLETE UNDERSTANDING OF WHAT THE NORMAL EPIGENOME LOOKS LIKE. THE RATIO ABOUT DYNAMIC VARIABLE IN TISSUE, TISSUE HETEROGENEITY. BUT THIS IS I FEEL PROBABLY READY FOR APPLICATION IN CONTEXT OF LARGE POPULATION BASED COHORT AND PERSPECTIVE COHORTS. THEN EXPOSE OBJECTIONME GOES BEYOND THE TECHNOLOGY REALLY BUT IT'S HER BEEN SPEAKER WHERE I DID AGREE TO HAVE A MORE COMPREHENSIVE PICTURE OF ENVIRONMENTAL EXPOSURE WHERE WE HAVE TO DO THE REFINEMENT IN PERSONAL GEOGRAPHICAL SYSTEMS AND MORE SOPHISTICATED TO QUESTIONNAIRES THAT SHOULD OMPLIMENT -- SHOULD PROVIDE COMPLIMENTARY APPROACHES TO MEASUREMENTS AND OMICS. SOME MAY KNOW WE HAVE MORE CONVINCENING YOUR AND THE EUROPEAN UNION FILING BIG PROJECTS ON EXPOSEOMICS WE HAD A KICK OFF COMMITTEE A COUPLE OF WEEKS AGO. AND ANOTHER POINT IS THE BIOINFORMATICS TOOLS AN GENOMIC DATABASES WHICH ALLOWS US TO REINTEGRATE MOLECULAR DATA THROUGH DIFFERENT PLATFORMS AND PROVIDE COMPREHENSIVE PORTRAIT OF DIFFERENT KAREN SUBTYPES AND WHICH THEN OF COURSE COULD BE USED TO REVEAL OR FILL GAPS ABOUT ETIOLOGY AND PREVENTION OPPORTUNITIES. WHAT DID I DO. SORRY. WRONG BUTTON. SO THE SECOND PART ON THE CRITERIA FOR INTEGRATING EMERGING TECHNOLOGIES INTO EPIDEMIOLOGICAL RESEARCH, I GUESS THIS TO ME CANNOT COMMON SENSE BUT I LIST THIS WHAT CRITERIA WE SHOULD REALLY CONSIDER TO HAVE A SENSITIVE QUANTITY MEASUREMENTS OF THE EVENTS AND ONE CHALLENGE TO HAVE TO OPTIMIZE SINGLE CELL OMICS APPROACHES AND WHICH IS OF COURSE IMPORTANT DIFFERENT TECHNOLOGIES. WE HAVE TV HIGH THROUGH PUT AND GENOME WIDE SETTING. THERE SIN CREASING USE OF NEXT GENERATION SEQUENCING. WE HAVE THE CONSIDER MULTI-PLEXING WHICH IS COMPATIBLE WITH LARGE SERIES OF SAMPLES. APPROXIMATE MY ABILITY TO BIOBANKS ASSOCIATED LARGE PROSPECTIVE COHORTS AND POPULATION BASE COHORTS. AND COST EFFECTIVENESS VERY IMPORTANT. WHILE THESE CRITERIAS ARE MET WE CAN SAY THEY MAYBE READY TO APPLY TO TECHNOLOGIES. SO THAT'S VERY BRIEF SUMMARY OF MY THOUGHTS ON THESE TWO TOPICS. >> WE'LL GO THROUGH PRESENTATIONS AND OPEN UP DISCUSSION. >> SO I WILL START BY SHOWING I CAN'T FOLLOW DIRECTIONS BECAUSE RATHER THAN SPEAK TO BOTH QUESTIONS I WAS ASKED TO TALK ABOUT ONE SPECIFIC APPLICATION AND TO PUT IT IN CONTEXT, IN 2006 WE STARTED IRB PROTOCOL TONE ROLE EVERY PATIENT THROUGH THE DOOR OF OUR HOSPITAL. THEY'RE ASKED TO GET PERMISSION TO USE MEDICAL RECORD FOR RESEARCH, ASKED THE PROVIDE A BIOSPECIMEN. TUMOR TISSUE BLOOD THAT WE CAN USE FOR RESEARCH PURPOSES, ALLOW US TO FOLLOW THEM OVER TIME, ACTUALLY FOR LIFE. AND THEN LASTLY TO BE I BELIEVE TO RECONTACT THEM. FOR A STUDY SHOULD SUCH AN OPPORTUNITY PRESENT AT THIS TIME, MAYBE BASED ON RECORD, TISSUES OR BECAUSE SOMEBODY HAD A GREAT IDEA AND NEEDED TO RECONTACT THE PATIENT. SO ONE OF THE THINGS THAT HAS BEEN CONTRACTCAL TO THE PORTAL, TO THE PROTOCOL IS A PATIENT PORTAL. I THINK I JUST HIT THE RIGHT BUT TOP. THAT'S CRITICAL TO THE SUCCESS IS PATIENTS USE IT. I WANT TO START BY TELLING ADVANTAGES OF THE PATIENTS TO GET THEM TO USE THIS AND THEN SEGUE TO RESEARCH APPLICATIONS. FOR THE PATIENTS, IT MEANS THEY HAVE A WAY TO INTERACT WITH THE MEDICAL FACILITY THAT INCLUDES SCHEDULING APPOINTMENTS, GETTING PRESCRIPTION, PAYING BILLS, WHEN A PATIENT CONTACTS US TO GET SERVICES WE GIVE THEM A NUMBER AND THEY ACCESS A WEBSITE WHERE THEY COMPLETE A QUESTIONNAIRE. THAT IS SOMETHING REQUIRED PRAYER TO SRI IT. THEY DO IT THROUGH THE PATIENT PORTAL. THEY WANT THEIR MEDICAL RECORD. WHAT ARE THE RESULTS OF THE TEST. WE DO THAT. THEY CAN ACCESS THROW THE PATIENT PORTAL AND WITHIN FIVE DAYS OF A LABORATORY TEST IT'S THERE. THEY HAVE ACCESS TO DOCTORS NOTES WHICH MEANS THEY NEED SENSITIVITY TRAINING TIMES WHAT THEY PUT IN THERE. THEY'RE CONNECTED TO VARIOUS SUPPORT GROUPS SPECIFIC TO THEIR DISEASE. SOMETHING CRITICAL AND VERY MUCH APPRECIATED. PATIENTS PEPPED TIME ON INTERNET SEARCHING FOR INFORMATION ABOUT THEIR DISEASE AND THERE'S A MESS OF SITES OUT THERE, MANY OF THEM ARE IRRELEVANT OR INCORRECT. WE DO PRE-SCREENING AND PROVIDE WEB SITES FROM THEM BASED ON DOUG DIAGNOSIS SITES WE TRUST. THAT'S WELL RECEIVED AS WELL. THERE IS A LINK TO CLINICAL TRIALS AND RIGHT NOW IT'S NOT A SMART LIST THAT'S TAILORED TO SPECIFIC DISEASE BUT NUMBER THEY CAN'T SEARCH THROUGH TRIALS THAT WE HAVE ON OUR WEBSITE. SO GETTING PATIENTS TO COME AND USE IT, ENABLES US TO DO RESEARCH WITH THIS CAPTIVE POPULATION. SO I MENTIONED EARLY PATIENTS ARE REQUIRED TO GO ONLINE AND THEY COMPLETE THEIR REVIEW OF SYSTEMS AND THE CHIEF COMPLAINT AND THINGS THE DOCS NEED TO SEE THEM IN THE CLINIC THE FIRST TIME BUT ALSO ALLOWS THE EPIDEMIOLOGISTS AND BEHAVIORAL SCIENTISTS TO STANDARDIZE THE RISK COLLECTOR DATA COLLECTED. WE USE VALID INSTRUMENTS PRESENTED TO THEM BASED ON GENDER AND MORE DETAILS, IF THEY'RE SMOKERS OR NOT, ET CETERA. BUT THAT'S POPULAR AND VALUABLE TO US AS RESEARCHERS. WE HAVE JUST GOTTEN IRB APPROVAL AND HAVE JUST FINALIZING THE ACCEPTANCE TESTING FOR ONLINE VIDEO CONSENT. SO ATTRACTIVE TO US BECAUSE IT EXPANDS OUR REACH AND WE DON'T HAVE TO RUN PEOPLE DOWN IN THE CLINIC ARE YOU MRS. SMITH OR MS. JONES, WE CAN DO IT ONLINE AND COST EFFECTIVE MANNER. BIT STUNNING TO US IS WE HAVE ASKED PATIENTS ENROLLED IN POT PROTOCOL, SHORT TIME LATER REMEMBER CONSENTS AND MANY DON'T. SO WE ACTUALLY HAVE CONSENT ONLINE THE PULL DOWN FOR THEMSELVES AND KEEP TRACK OF IT. IT'S A VEHICLE FOR FOLLOW-UP SURVEYS. SO ONE YEAR THE ANNIVERSARY DATE WE FOLLOW FOR PATIENT REPORTED OUTCOMES. QUALITY OF LIFE TYPES MEASURES AN SYMPTOMS THEY MIGHT BE HAVING. BY HAVING REGULAR PATIENT ENGAGEMENT WITH THE PORTAL GIVES THEM AN OPPORTUNITY TO COME BACK AND HOPEFULLY ENSURE HIGH PARTICIPATION FOR THE FOLLOW-UPS. BASELINE WE'RE DOING WELL. SO PATIENT PORTAL WAS LARGED IF -- WE HAVE OVER 29,000 ACCOUNTS CREATED FROM PATIENTS COMING FOR OUR SERVICES. THE MONTHLY LOG INS, 12,000 AND RISING, 84% NEW PATIENTS CREATE AN ACCOUNT SO WE SEE CONSISTENT INCREASE AS WE LAUNCHED THIS. WE WERE CONCERNED THERE WAS GOING TO BE A DEMOGRAPHIC BIAS, LIKE OLDER PEOPLE WOULDN'T TO IT. THERE'S NO SYSTEMATIC BIAS IN TERMS OF WHO IS GETTING ON USING THE PATIENT PORTAL. THIS TOOL ON VALIDITY, A FEW THINGS I WOULD SAY IN GENERAL WHEN YOU ROLL OUT A NEW TOY, YOU CAN'T GENERALIZE THAT, IT DEPENDS ON A QUESTION, A NEW TOOL AND LOTS OF ISSUES SO NO GENERAL STATEMENTS BUT IN TERMS OF PATIENT PORTAL AS RESEARCH TOOL SECURITY WAS A REALLY BIG ISSUE FOR US. AND MAKING SURE THAT THE ID OUT TO THE PATIENT IS TO THAT PATIENT NOT SOMEBODY ELSE AND WHO IS LOGGING IN AND SINCE WE'RE GETTING ACCESS TO MEDICAL RECORD THAT WAS CRITICAL. IT HAD TO BE ACCEPTABLE. OUR ELDERLY PATIENTS WOULDN'T LIKE IT, TURNED OUT TO BE THAT WASN'T THE CASE BUT ACCEPTABILITY AND ACCESS. DIFFERENT PLATFORMS, NOT EVERYBODY -- I GUESS THERE'S A DEMOGRAPHIC ISSUE WHO USES INTERNET EXPLORER VERSUS USING SAFARI AND MORE HIP COOL THINGS SO WE HAD PATIENTS USING THE OLD FASHIONED DEVICES BUT IT HAD TO BE ACCEPTABLE TO A VARIETY OF DIFFERENT INTERNET SEARCH TOOLS. IT HAD TO BE FLEXIBLE AND ADAPTABLE, AND IT HAD TO ACHIEVE THE DESIRED INTENT. SO WE NEEDED IT FOR CLINICAL CARE BUT WE THINK IT'S A GOOD TOOL FOR RESEARCH. THOSE ARE CRITERIA THAT I THINK WOULD BE OF THE CONSIDERATION AND ADOPTING NEW TECHNOLOGIES. I WILL STOP THERE. >> THANKS. SO COMMENTS I WAS THINKING ABOUT HAVE BEEN SAID BY JEFF AND SOME EXTENT BY ZDENKO. WE'RE HUGELY OMIC LONGITUDINAL PROFILING. THE BIG ARGUMENT IS YOU CAN SEE MUCH MORE THAN YOU CAN SEE WITH ANY SINGLE OME. SO THIS IS A STUDY THAT JEFF INTRODUCED THAT WE DID, STARTED OVER THREE YEARS AGO WHERE WE PROFILED ONE PERSON, HAPPENS TO BE ME. WITH AS MANY OMICS TECHNOLOGIES AS WE CAN THROW AT IT, DISCOVERY BASED RESEARCH PROJECT. EVERYTHING IN THE CENTER IS OME DUB, SEQUENCED BY GENOME, DNA METH LOAM, TRANSCRIPTOME FOR RNA AND MICRORNA AND THE NON-CODING ISOFORMS. PROTEOME DEFINED BY MASS MASS SPECTROMETRY, THE IMMUNE SYSTEM IS A EXQUISITE MONITOR OF DISEASE STATE SO WE WANT TO MAKE SURE THAT WAS NOT MISSING FROM THE PROFILING SO WE ADDED CYTOKINES WHICH YOU WILL NOT FIND BY MASS SPECTROMETRY. WE HAVE INVENTED PROTEIN CHIPS WE FOLLOWED IMMUNE RESPONSE, AT LEAST B CELL BY FOLLOWING ANTIBODY PROFILES. THE AUTOANTIBODY OME. THERE'S THE METABALOME UP THERE, MOSTLY PEAKS, THAT'S ONE CHALLENGE, THOUSANDS METABOLITES, THAT'S 4,000 PEAKS WITH E DOPE KNOW WHAT THEY ARE. LASTLY MOST RECENTLY WE HAVE ADDD THE MICROBIOME SO WE'RE DOING ALL THESE THINGS, AND AS I SAY, WE PUBLISHED THE FIRST 14 MONTHS OF THIS NOT SO LONG AGO BUT NOW WE HAVE DONE THREE YEARS AND THE SAMPLING IS IN THE TOP RIGHT. BASICALLY WHENEVER I'M SICK WE DO DENSE PROFILING SO EVERY DAY EVERY FEW DAYS, HEALTHY EVER FEW MONTHS. I HAVE BEEN SICK FIVE TIMES DURING THIS STUDY. WE COLLECT DATA DURING THESE VARIOUS TIMES. THE GOAL IS WHEN YOU PULL THIS DATA YOU CAN START SEEING THE PROFILES THAT EMERGE INTEGRATING THE DATA SETS AN YOU WILL SEE MUCH MORE BY THE MULTI-OMIC PROFILING THAN BY ANY INDIVIDUAL PROFILE. SO WHAT SHOUT OUT THERE IS A PROFILE THROUGH RSV INFECTION. I DID GET DIABETES DURING THIS TIME WHICH GENOME HAD SAID I WAS AT RISK FOR AND THAT ADDED AN INTERRING SCIENTIFIC COMPONENT TO THIS WHOLE THING. BUT BOTTOM LINE IS, IF WE ONLY LOOKED AT TRANSCRIPTOME WE WOULD SEE SOME THINGS AND ONLY LOOKED AT PROTEOME SAMPLING LESS WE WOULD SEE SOME THINGS AS WELL AND TRANSCRIPTOME WOULD SEE AND METABALOME REVEAL OTHER THINGS AND TOGETHER WE SEE THINGS NONE OF THEM WOULD REVEAL. SO YOU COLLECT ALL THE INFORMATION YOU GET A CLEARER PICTURE. WE'RE MEASURING 40,000 THINGS AT ANY ONE COMPONENT, DNA METH LOAN AND MICROBIOME IS HIGHER. NOT SURE WHAT IT IS. BUT>w THE POINT IS WE SEE A LOT AND LIKE TO THINK IT'S BETTER THAN FUZZY PARLIAMENT BUILDING SHOWN EARLIER BUT I RECOGNIZE IT CAN GO HIGHER RESOLUTION AND CERTAINLY WE WANT TO ADD THAT. AND I GUESS THAT'S THE BOTTOM LINE. WE THINK DOING THIS IN A PANOMIC FASHION GIVES A CLEARER PICTURE BETTER UNDERSTANDING OF DISEASE STATE. THAT'S THE BIGGEST ARGUMENT, THE ORGANIZE ARGUMENT IS WE DON'T KNOW WHAT WE DON'T KNOW. EVERYBODY WILL ALWAYS BE PROFILING FAVORITE OMES. IN A SEGREGATED FASHION IS VERY WASTEFUL, YOU WANT TO DO THIS SAME SAMPLE FOR ALL THE DIFFERENT THINGS SO I WOULD ARGUE IT PAYS TO DO THE MOON SHOT RATHER THAN CLINICAL L WHICH WILL BE MORE EXPENSIVE AND MAY NEVER GET TO THE SAME GOAL. SO THAT IS MY BIGGEST PUSH. I WANT TO EMPHASIZE LONG TUESDAYNAL PROFILES WITHER CRITICAL BECAUSE YOU SEE WHAT'S GOING ON IN A MUCH CLEARER FASHION. DON'T KNOW THE RIGHT CANCER FREQUENCY SAMPLING BUT THAT WILL TAKE SOME THOUGHT BUT THE DYNAMIC ASPECT IS A NO BRAINER. WHAT'S MISSING HERE ON THIS IS THE EXPOSEOME. I THINK WE NEED THAT. SOME IS SOMEWHAT PERMANENT AND WE ARE TOKING TO TRY TO MEASURE THAT BUT WE TRY TO MEASURE REAL TIME WHAT JEFF DESCRIBED AND THAT HAS TO BE INCORPORATED AS WELL. I THINK THERE'S THINGS MISSING FROM THE SLIDE THAT THE TECHNOLOGY IS NOT THERE, INATE IMMUNITY RESPONSES ARE THERE YET AND WE GET THAT IN AND THERE'S A FEW OTHER THINGS, I'M RUNNING OUT OF TIME. HOW TO IMPLEMENT THIS, ONE DOES THIS IN A PILOT PHASE, HOW DO YOU ROLL OUT SOMETHING LIKE THIS, YOU WON'T ROLL OUT ON A MILLION PEOPLE. I BELIEVE THERE WILL BE MILLIONS OF PEOPLE IN GENOME SEQUENCES. RAND MINIMUMS LINKED WITH ELECTRONIC HEALTH RECORDS. IF WE CAN ADD PROFILES THERE WILL BE A LEVEL OF UNDERSTANDING THAT WILL GO WELL BEYOND WHAT WE CURRENTLY HAVE. MANY MILLION AT ONCE IS DO MORE FOCUSED PILOTS TO SEE HOW THIS GOES. THIS IS SUCCESSFUL FOR THE IN CODE PROJECT THOUSAND GENOMES OR SCIENCE PROJECTS OCCURRED. I THINK THAT'S HOW I WOULD RECOMMEND GOING FORWARD. GUESS WE'LL SAVE VALIDITY FOR LATER. >> THANK YOU. >> I WOULD LIKE TO (INAUDIBLE) ROLE OF TECHNOLOGIES IN CANCER EPIDEMIOLOGY. I'M GOING TO PRESENT DATA SCIENCES AND I REPRESENT A NAT ONAL LAB WHERE HIGH PERFORMANCE COMPUTING BIG DATA AND KNOWLEDGE DISCOVERY IS ONE FIRST REST AREAS SO WE KNOW ALL THE CHALLENGES. THAT THE NUMBERS ENTAILS. THERE'S NO DOUBT THAT THE ADVANTAGE OF INFORMATION TECHNOLOGY SHAPING THE LANDSCAPE OF EPIDEMIOLOGY. EPIDEMIOLOGY IN GENERAL AND CANCER EPIDEMIOLOGY, THE PREVIOUS SPEAKERS GAVE SOME EXCELLENT EXAMPLES PARTICULARLY WITH THE ONLINE COMMUNITIES AND DATA WE CAN COLLECT AND COST EFFECTIVE WAY THAT WE COULD NOT DO DO THAT IN THE P&A. THIS TREND WILL CONTINUE PARTICULARLY NOT BECAUSE OF THE DIVIDE AMONG PEOPLE WILL DECREASE BUT WE EXPECT TO SEE OTHER TECHNOLOGIES MOBILE TECHNOLOGIES AS WELL AS ADVANCE IT IS OMICS TYPES OF TECHNOLOGIES THAT WE KEEP GENERATING VAST VOLUMES OF DATA. SO THE QUESTION IS, ARE WE THERE YET IN TERMS OF INFORMATICS TOOLS WE HAVE AVAILABLE TO MAKE THE MOST OF THE DATA WE COLLECT. THERE'S PLENTY OF EVIDENCE OUT THERE THAT INFORMATION TECHNOLOGIES EXIST TO HELP WITH ANY OBSERVATIONAL STUDIES. AS WE MOVE FROM CONTINUUM FROM DATA ALL THE WAY TO ACTION, BECAUSE THIS IS WHAT WE GET ABOUT -- WHAT WE CARE ABOUT, WE HAVE TO BE?:¨ CAREFUL IN TERMS OF HOW WE USE DATA AND CRY CRITERIA IN TERMS OF VALUE DATING TECHNOLOGIES. FROM THE DATA SCIENCES I WOULD LIKE THE SAY THERE ARE THREE WELL KNOWN MYTHS. THEY ARE MORE DATA IS BETTER. INFORMATION EQUALS KNOWLEDGE. KNOWLEDGE LEADS TO IMPACTFUL ACTS. THESE ARE NOT NECESSARILY TRUE STATEMENTS. AND OF COURSE HOW WE SET UP THE CRITERIA CHANGES FROM APPLICATION DOMAIN TO APPLICATION DOMAIN. SO I TRY TO THINK IN A VERY HOUR ARCCAL WAY. FIRST WE NEED TO ENSURE THE QUALITY OF THE DISCOVERED KNOWLEDGE IS GOOD. IT DEPENDS ON RELIABILITY AND TO FISTCATION OF KNOWLEDGE PROCESS. EACH COMPONENT REQUIRES DIFFERENT TYPES OF CRITERIA. EVEN THOUGH I CANNOT GIVE WHETHER OR NOT I HAVE THE RIGHT CRITERIA, THERE ARE 35 LESSONS WE CAN LEARN FROM THE MACHINE LEARNING COMMUNITY, IT H RELY ON OPEN ACCESS DATA SETS. SO THE PEOPLE FROM DIFFERENT ENTITIES CAN ACTUALLY USE THE DATA TO DEVELOP AND VALIDATE SYSTEMS. WE RELY ON BENCHMARK DATA SETS WITH CAREFULLY CURATED DATA BECAUSE IT'S VERY IMPORTANT TO DIFFERENTIATE BETWEEN CELLULAR DATA -- FAILURE OF DATA COLLECTION PROCESS AND FAILURE OF INFORMATICS TOOLS WE USE TO DO KNOWLEDGE DISCOVERY. HAVING BENCHMARK DATA SETS WHERE PEOPLE CAN COMPARE THEIR DIFFERENT TOOLS IS CRITICAL. CROSS VALIDATION IS EQUALLY IMPORTANT. WE NEED SOPHISTICATED CROSS VALIDATION BECAUSE WE NEED TO BE ABLE TO TRANSFER THOSE TOOLS FROM ONE DATA SET TO ANOTHER. FINALLY WE DO RELY ON SEQUESTERED DATA SETS. IT IS VERY WELL KNOWN THAT REPEATED USE OF DATA SETS FOR KNOWLEDGE DISCOVERY DOES LEAD TO POSITIVE VARIANTS SO IT IS IMPORTANT TO HAVE A HONEST (INAUDIBLE) ENTITY THAT WILL KEEP -- WILL MAINTAIN SEQUESTERED DATA SETS SO THE DIFFERENT DEVELOPERS CAN CONTRIBUTE TO THE ALGORITHM AND EVENTUALLY GET A SCORE BACK AND SOME FEEDBACK AS TO HOW WELL THEY HAVE DONE, WHERE THEY HAVE FAILED SO THEY CAN GO BACK TO THE DRAWING BOARD, KEEPING IMPROVING THE ALGORITHM WITHOUT RELYING ON BETTER UNDERSTANDING OF THE SAME DATA SET THAT THEY HAVE ACTUALLY LEARNED THROUGH THE PROCESS OF LOCKING AT IT. -- LOOKING AT IT. THAT RELATES TO THE QUALITIES OF THE KNOWLEDGE DISCOVERY. OF KNOWLEDGE DISCOVERED BUT WILL IT LEAD TO IMPACTFUL ACTIONS? THAT IS WHERE CLINICAL SIGNIFICANCE AS SPECIAL COMES IN AND IMPORTANT TO CONSIDER COST EFFECTIVENESS ANALYSIS VERY EARLY ON. BECAUSE THE LEVEL OF ACTION DEPENDS ON THE RISK OF THE ACTIONS WE CONSIDER. AND THE RISK OF THE ACTIONS WE CONSIDER DEPENDS ON THE MARGIN OF ERROR WE GET FROM DATA WE HAVE CHECKED AND INFORMATICS TOOL. ALL OF THIS IS UNECOSYSTEM. WE CANNOT WAIT TO DECIDE WHAT WE HAVE ACHIEVEED DURING THE KNOWLEDGE DISCOVERY PROCESS, IT'S GOING TO LEAD TO BETTER ACTIONS BUT NEITHER ACTIONS WE'RE GOING TO HAVE THE DRAMATIC BENEFIT WE EXPECT AT THE COST T. ANTICIPATED SO IN ORDER TO THIS EPIDEMIOLOGICAL COMMUNITY NEED TO THINK PROACTIVELY ABOUT INVESTING ON INFRASTRUCTURE THAT ARE CAPABLE, SCALABLE, VERY IMPORTANT AND SUSTAINABLE. BECAUSE WE DO EXPECT THE VOLUMES OF DATA WILL KEEP INCREASE. SO SOLUTIONS THAT FIT OR NEEDS NOW AND NOT SCALE APPROPRIATELY IN THE FUTURE INVESTMENTS WAS NOT GOOD PAY BACK. SO EEL STOP HERE. >> THANK YOU. BEFORE I ASK A COUPLE OF QUESTIONS, GEOFFREY, YOU LISTENED TO THESE AND GIVE A NICE OPENING DISCUSSION. ANY POINT THE ADD OR HIGHLIGHT OR THINGS THAT YOU THINK WORTH POINTING OUT AT THIS POINT? >> I HEARD A NUMBER OF RECURRING THEMES THAT CAME THROUGH BOTH IN TERMS OF THE -- THAT WE DON'T KNOW ENOUGH ABOUT WHICH TECHNOLOGY TO INVEST IN TODAY THE DATA COMING OUT OF THESE TECHNOLOGIES IS EYELY VALUED AND -- HIGHLY VALUED. AS[¨ GEORGIA JUST SAID, THE APPROPRIATE ATTENTION NEEDS TO BE PAID TO MAKING THE DATA ACCESSIBLE, INTEROPERABLE SO THERE'S AN INVESTMENT HERE. I DON'T THINK IT'S UNIQUE TO NCI BECAUSE I THINK THIS IS THE ECOSYSTEM IS BROADER AND IT ALSO GOES BEYOND NIH. WE CAN TALK ABOUT THIS LATER BUT THE ROLE OF INDUSTRY DRUG AND DIAGNOSTIC DEVELOPERS ALSO SEQUESTERED AND VALUABLE DATA CANNOT BE IGNORED. SO I WANT THE MAKE SURE WE ADD THAT DIMENSION NCI'S APPROACH TO DISCUSSION ABOUT DATA. >> THAT SEGUES RIGHT TO WHERE I WANTED TO START THIS DISCUSSION. THAT IS, PRIME TIME, WHEN TECHNOLOGIES ARE READY FOR GOING BEYOND THE PILOT STUDIES. WE ALL WOULD AGREE PILOT STUDIES ARE VERY IMPORTANT. WHAT ARE THE CRITERIA THAT WE WOULD THINK WOULD BE IMPORTANT CONSIDERING WHEN WE WANT TO SCALE UP SOMETHING WHEN THE STABILITY AND VALIDITY IS WORTHWHILE THAT YOU DON'T HAVE TOO MUCH SIGNAL TO NOISE BACKGROUND THAT YOU CAN TEST THE SCIENTIFIC QUESTIONS OF THE DISCOVERIES OR THE UTILITIES OR THE APPLICATIONS THEREOF. AND I'LL START WITH YOU, MIKE. BECAUSE I KNOW YOU HAVE BEEN THINKING ABOUT THIS AND YOU HAVE A BEAUTIFUL STUDY (OFF MIC) >> YEAH. IT'S A BIT OF A ISSUE IN MANY RESPECTS WE SPEND A LOT OF TIME COMPARING DNA SEQUENCING TECHNOLOGIES AND LOOKING AT ACCURACIES. THAT AS AN EXAMPLE. NO ONE WOULD ARGUE IT'S A GREAT RESEARCH TOOL BUT IT'S INTERESTING. IF YOU LOOK AT A CLINICAL TOOL YOU MAY NOT BE AWARE OF THIS BUT WE COMPARE COMPLETE GENOMICS AN OVERLAP WITH SINGLE NUCLEOTIDE VARIANTS EASIEST TO CALL USING SINGLE BASE CHANGE IS 89%. FOR INTELS IT'S 28% STRUCTURAL VARIANTS, FORGET IT, IT'S NOWHERESVILLE. SO THERE IS A LOT TO DO. HAVING SAID THAT THERE IS UTILITY FROM A CLINICAL STANDPOINT FROM ANECDOTAL THINGS THIS MORNING AN RESEARCH STANDPOINT THERE'S NO QUESTION THERE'S UTILITY. YOU CAN EXTRACT USEFUL INFORMATION. IT'S CRITICAL THAT YOU KNOW WHAT YOUR ERRORS ARE, WHAT THE -- YOU HAVE SOME SENSE OF THE QUALITY OF THE DATA. YOU NEED A GOLD STANDARD, I THINK AS GEORGIA SAID. YOU NEED THAT FOR ANY GIVEN TECHNOLOGY. WHAT ARE YOU MISSING, WHAT IS THE ACCURACY, WHERE ARE THE KINDS OF ERRORS COMING FROM SO THAT YOU KNOW HOW TO EVALUATE THAT TECHNOLOGY AS YOU MOVE FORWARD. AND YOU CAN'T ALL WAIT FOR THINGS TO BE PERFECT. WITH IF WE WAITED FOR THAT WE WOULD NEVER USE A COMPUTER RIGHT NOW. THERE'S ALWAYS A BETTER ONE TWO YEARS FROM NOW BUT WE ALL BOUGHT ONE TEN YEARS AGO. SO THE POINT IS, I GUESS YOU USE IT AS A FITS THE NEED AND REALIZE THAT IT WON'T GET BETTER BUT MAKE SURE YOU UNDERSTAND LIMITATIONS WHAT YOU'RE WORKING WITH. >> GEORGIA, COULD I BRING YOU INTO THIS DISCUSSION IN? YOU RAISE THIS IMPORTANT QUESTION DATA STANDARDS AND HAVING PLATINUM OR TRUSTED SETS. ONE OF THE KEY QUESTIONS IS HOW DO WE KNOW HOW TO DEFINE THIS? A PRIORI OR THEY EMERGE AND BECOME USEFUL FOR THE IMMUNITY WITH THAT, HOW ARE WE SURE THEY GET DISSEMINATED? THE QUESTION IS HOW EVERYONE CAN SEE THEM AS OPPOSED TO A FEW BEHIND THE FIREWALL OR COMMERCIAL OR SPECIAL PROJECT. >> THE ANSWER IS TO YOUR FIRST QUESTION, IS BOTH. WE STAR -- WE MAKE THE CONSCIOUS EFFORT OF CREATING THESE CAREFULLY CREATED DATA SETS WITH WHATEVER THE GOLD STANDARD IS, ACCEPTABLE GOLD STANDARD AND MAKE IT AVAILABLE TO THE IMMUNITY. AND OF COURSE, AS MORE STUDIES ARE DONE AND PEOPLE SHARE DATA AT THE COMPLETION OF PROJECTS YOU PUT THEM OUT IN THE REPOSITORY. THE MOST EFFECTIVE IT WAS TECHNOLOGY ARE ONES WHERE WE GO IN AND SAY I CAN ACHIEVE HIGH DISCOVERY USING A WIDE RANGE OF DATA SETS THOUGH WE UNDERSTAND THAT SOMETIMES THAT MUCH FLEXIBILITY IS NOT POSSIBILITY. NOW, WHO IS GOING TO BE THE GATEKEEPER OF THOSE DATA SETS? THAT'S A VERY GOOD QUESTION CONSIDERING THE SIZE OF THE DATA WE'RE TALKING ABOUT. THAT IS WHY I SAID THIS IS PART OF THE INFRASTRUCTURE THAT I BELIEVE WE NEED TO CONSIDER, WE NEED TO BUILD THINKING FORWARD THAT IT'S GOING TO KEEP GETTING BETTER. THE BEACH OF NATIONAL LAB, THAT WOULD BE A PLACE AS AN HONEST BROKER. >> WHAT DO WE THINK OF SOMETHING LIKE THE INTERNET 1990, 91, 92, PEOPLE ARE WRITING DIFFERENCE CODES AND USING DIFFERENT TECHNOLOGIES AND THERE WAS A COMMUNITY SET OF STANDARDS. IT WAS PAINFUL A COUPLE OF YEARS BUT WHAT EMERGED FROM THAT WAS A SYSTEM THAT THEN BECAME WHAT WE ALL NOW USE IS THE WORLD WIDE WEB. AND THAT WAS COMMUNITY BUY-IN. THERE WAS GOVERNMENT MONEY, PRIVATE MONEY, PHILANTHROPIC ACADEMIC ACTIVITIES GOING INTO THAT. HOW -- DO YOU THINK THAT'S ATTAINABLE IN THIS CONTEXT? >> I THINK ONE OF THE BIGGEST DRIVERS ARE THE FUNDERS SO WHEN YOU FORM THESE CONSORTIA, THE FIRST THING YOU HAVE TO DO IS GET TOGETHER AND DECIDE ON STANDARDS, SO PEOPLE CAN DRIVE DATA. I THINK THAT WORKED WELL FOR SEQUENCING FIELD, IT WORKED WELL FOR THE N CODE PROJECT AS WELL. YOU BRING THESE GROUPS TOGETHER AND THAT BASICALLY LEAD TO FORMING THE GOLD STANDARD AND EVALUATING TECHNOLOGIES. ALSO FORCES PEOPLE TO BE HONEST ABOUT RESULTS BECAUSE WHEN YOU WORK CONSORTIA, THE FIRST TO CATCH ERRORS ARE OTHERS IN THE CONSORTIA BECAUSE THEY'LL BE SCRUTINIZING YOUR DATA WONDERING HOW YOU'RE PITTING OUT MORE DATA SETS THAN THEY ARE. YOUR DATA SETS MUST NOT BE AS GOOD SO YOU EVALUATE THEM SO YOU GET INSTANT FEEDBACK BUT YOU NEED THE GOAL STANDARDS, I WOULD -- I WOULDN'T BELITTLE THAT. >> IN TERMS OF YOUR COMMUNITY WILL CREATE THE DATA, BY CREATING ECOSYSTEM SUCH AS THAT YOU OPEN FIELD TO INFORMATION SCIENTISTS OUT THERE WE CAN START GENERATING DIFFERENT APPS. YOU CAN GENERATE APPS AND MAKE IT AVAILABLE SO PEOPLE CAN ACTUALLY USE THE DATA, THEY DON'T NEED TO BE SOPHISTICATED COMPUTER SCIENTISTS TO DO DIFFERENT LEVELS OF KNOWLEDGE DISCOVERY, BUT THEY WANT TO DO. SO WE CAN THINK OF THAT INFRASTRUCTURE AS AN INFRASTRUCTURE THAT CAN HAVE DIFFERENT TYPES OF TOOLS AND DIFFERENT TYPES OF APPLICATIONS TO SERVE THE DIFFERENT TYPES OF STAKEHOLDERS. OF COURSE ACCESSIBILITY WILL BE MONITORED ACCORDING TO STANDARDS REQUIRED FOR THAT STAKEHOLDER COMMUNITY. ALL THESE ARE TILTLY FEASIBLE SCENARIOS. >> iPHONE. APPS FOR APPLE IS A GOOD IDEA OF COMMUNITY STANDARDS AND CAPACITY TO IMPROVE. >> I THINK SOME OF THIS EXISTS NOT THAT WE DON'T NEED TO INVEST IN MORE BUT WITH DB GAP,ko2 GO, THERE ARE A NUMBER OF MINEABLE DATA REPOSITORIES THAT HAVE REALLY HELPED INVESTIGATORS RAPIDLY VALIDATE RESULTS OR GENERATE NEW DISCOVERIES. I THINK ONE OF THE QUESTIONS HAS TO BE WHAT'S THE INCENTIVE IN THE PAST OR RECENT PAST IT'S BEEN MORE A CARROT APPROACH. BUT THERE'S ALSO THE STICK APPROACH WHERE PERHAPS JOURNALS NEED TO REQUIRE ABSOLUTELY REQUIRE THAT ALL DATA BE PLACED INTO THESE PUBLICLY AVAILABLE DATABASES AT TIME OF PUBLICATION. AND ALLOW THE RESEARCH IMMUNITY TO CONTINUALLY POKE HOLES OR VALIDATE IT'S REALLY THE RIGHT DATA FOR THE RIGHT QUESTION. BUT I THINK WE HAVE TO MOBILIZE THE RESEARCH COMMUNITY TO PROVIDE STICKS HERE THAT WILL GET US LINED UP TO DEDICATE O DATA TO THIS EFFORT. >> NATURE JOURNALS CLAIM TO DO THIS BUT THEIR ABILITY TO FOLLOW THROUGH AND REACH IN AND BE SURE YOU DO MORE THAN JUST FILL OUT A WEBSITE OR COMMENT THAT THIS IS AVAILABLE ONE WAY OR ANOTHER IS NOT WELL PROSECUTED, SO TO SPEAK. SO THE QUESTION IS DIFFERENT STAKEHOLDERS HAVE TO ENGAGE IN THAT. BEFORE I OPEN IT UP TO BRING IN THE OTHER TWO DISCUSSANTS. YOU DESCRIBE TOM YOUR SYSTEM THE CAPACITY TO DO THIS AND REACH A CERTAIN GROUP OF INDIVIDUALS AN ENGAGE THEM HOW AND IN WHAT WHAT WAY DO YOU SEE UTILITY OF MAKING DECISIONS WHEN THOSE TECHNOLOGIES ARE APPLICABLE TO PEOPLE IN MY MOFFETT. AND HOW YOU WILL COMMUNICATE WHEN YOU THINK THINGS ARE READY AND NOT. BECAUSE YOU HAVE ALL THE WEB SITES FOR DISEASE, BUT AS YOU START TO TEST AND SEQUENCE AND/OR DO CYTOKINES, OTHER PROFILES, THIS WILL BE A KEY QUESTION DECISIONS AN WAYS TO MAKE THOSE DECISIONS. >> THROW ME AN EASY ONE. IT'S A GREAT QUESTION. WHEN I MENTION LABORATORY RESULTS I SHOULD SAY THE FOCUS OF THE TOTAL CANCER CARE PROTOCOL IS TO GET TO PRECISION MEDICINE. THAT'S WHAT WE WANT TO DO, THAT'S A GOAL, WHY YOU WANT THE DEPTH OF PHENOTYPING, GENOTYPING THE OMICS YOU TALK ABOUT. THERE'S HAMMERS THAT ONE CAN THROW AT THAT AND WE CREATED A COLLIEIA LABORATORY AND PUTTING IN A LOT OF BOXES THERE. I DON'T KNOW THAT THE PATIENT WILL KNOW IS DIFFERENCE BETWEEN SEQUENCEOME OR MY SEEK. WHEN I COMES TO THE PLATFORM I DON'T THINK PATIENTS CARE. THEY SHOULD BE AGNOSTIC AND WE NEED TO PRESENT IT TO THEM, WE NEED TO PRESENT TO IT THE DOC THES SO THEY UNDERSTAND HOW THEY CAN TAKE THAT INFORMATION AND MAKE TREATMENT DECISIONS. I DON'T THINK ANYBODY HAS THAT FIGURED OUT AS WELL. SO IT'S A GREAT QUESTION. I DON'T HAVE AN ANSWER FOR IT. >> RIGHT. BUT Y'ALL ARE STRUGGLING WITH IT OBVIOUSLY. AND LET ME REPHRASE THE QUESTION. WHAT DO YOU SEE IS IMPORTANT SORT OF MILESTONES TO MAKE THOSE ASSESSMENTS TO SAY ALL RIGHT WE'RE NOW READY TO INTRODUCE THIS INTO OUR SYSTEM? YOU OBVIOUSLY -- I ASSUME YOU THOUGHT THROUGH THAT QUESTION. WE RELY ON RESEARCH THAT'S DONE THE ELSEWHERE. OF THE MELANOMA PATIENT SHOWING UP FEBRUARY CARE. SO WE GO FROM RESEARCH THE TO VALIDATION IN THE CLIAA LABORATORY. THAT'S THE BIG BOTTLENECK IS COMING UP WITH A VALID TEST THAT A PATHOLOGIST IS WILLING TO PUT THE GOLD STAMP OF APPROVAL ON. SO THE FINAL COMES FROM YOUR RESEARCHERS, I'M GOING TO THE A CLINICAL TRIAL AND NEED TO STRATIFY TO RANDOMIZE PATIENTS OR CLINICIAN SAYING THERE WAS A TRIAL THAT WAS PUBLISHED, AND WE NEED TO KNOW THIS TO BE ABLE TO TREAT THIS DRUG. SO IT COMES FROM OUR PROVIDE PHYSICIAN AND RESEARCHERS TO DO CLINICAL TRIALS. HOW THEY PRIORITY THAT AND PLATFORM, IT'S MORE ART THAN SCIENCE >> YOU THINK TO BRING YOU TO THIS CONVERSATION AS YOU TALKED ABOUT MORE CLASSICAL VIEW SIGN ACTIVIC VALIDITY HOW YOU FUNCTIONALLY UNDERSTAND SOMETHING AND TECHNOLOGY AND APPROACHES. I WANT TO BE SURE EVERYBODY HAD THE OPPORTUNITY TO COMMENT. AND WASN'T JUST BEING POLITE. THERE'S BEEN CONCEPTUAL PROGRESS AND TECHNOLOGY THIS SEQUENCING INTERNATIONAL SEQUENCING INITIATIVES WE ARE NOW ACTUALLY HAVING COMPREHENSIVE PORTRAIT OF CANCER TYPES AND NORMAL TISSUES AND THE MECHANISTIC UNDERSTANDING OF BASIC SCIENCE. HOW DO WE APPLY IN FUTURE OF EPIDEMIOLOGY? I GUESS WORKING WE HAVE A MORE GLOBAL VIEW AND THE MOST CANCER SEQUENCED, MAYBE I'M WRONG BUT COMING FROM A RICH COUNTRIES, THIS IS JUST THE OPPORTUNISTIC BECAUSE BIOBANKS (INAUDIBLE). HOWEVER THE PROJECTION IS MAJORITY COME 20, 30 YEARS COME FROM IN A LOW MIDDLE RESOURCE COUNTRY. HOW DO WE -- HOW DO WE -- WE HAVE TO HAVE MORE GLOBAL APPROACHES AND GLOBAL STRATEGIES IN TERMS OF THE CANCER INCIDENCE BUT TO STUDY ETIOLOGY AND PREVENTION. WE DONE HAVE TO SEQUENCE NOW GENOMES FROM ALL AFRICAN COUNTRIES. ASIAN COUNTRIES AND SOUTH AMERICA. BUT I GUESS WE COULD EXTRACT THIS BASIC CRITICAL INFORMATION ABOUT PATHWAYS. THEN PERHAPS WE CAN HAVE A -- DESIGN MORE FOCUS APPROACHES USING THE TECHNOLOGY WE COULD VALIDATE, PERHAPS BETTER RISK FACTORS, IMPORTANT PATHWAYS. WHETHER THE SAME IS TRUE FOR THOSE COUNTRIES OR NOT. SO THIS MIGHT BE -- >> I DON'T THINK WE'RE THERE YET. >> WE HAVE A LONG WAY TO GO. BURKETT'S LYMPHONA IS A GOOD EXAMPLE OF SEQUENCING QUITE REVEALING AS WE GO DIFFERENT PLACES IN THE WORLD. THERE ARE A COUPLE OF BURNING QUESTIONS HERE, I SAW DAVID AND BOB. WE HAVE TIME, DINNER IS NOT UNTIL 6:30. >> THIS IS FAIRLY QUICK. MICHAEL SNYDER. I ADMIRE YOUR SELF-EXPERIMENTATION THAT COMES FROM -- EVOKES SELF-EXPERIMENTATION EPIDEMIOLOGY, IT'S MORE SCALE UP QUESTION. EPITEAMOLOGISTS WANT TO KNOW HOW MUCH BLOOD SO I'M WONDERING HOW MUCH OF YOUR BLOOD YOU HAD TOIOUS TO GET WHERE YOU DID AND WHERE YOU THINK IT'S GOING IN TERMS OF PRACTICAL BIOSPECIMEN AMOUNT IN TERMS OF FUTURE. >> WE TYPICALLY DRAW ABOUT 80 MLs OF BLOOD BUT MAYBE 50 WHEN SICK BECAUSE WE'RE DRAWING MORE FREAKILY. HAVING SAID THAT WE'RE WORKING TECHNOLOGIES TO DO THIS FROM A DROP OF BLOOD LOOK YOU DO DIABETES. THAT'S THE WAY TO GO. THAT WILL BE A HOME TEST IN THE FUTURE. THERE IS A SACRIFICE. ON THE OTHER HAND IT'S CHEAPER. SO WE'RE STILL BALANCING SOME OF THESE THINGS BUT I DO SEE THOSE WHERE IT'S GOING. WE ARE ROLLING OUT, A STUDY OF TEN PEOPLE NOW, DRAWING 50 TO 60 MLs OF BLOOD. >> SO SNYDER'S LAW INSTEAD OF MOORE'S LAW. >> WHATEVER THAT MEANS. >> 2 TO 3 ML YOU GET GENOMES SEQUENCED. SCALABILITY IS COMING DOWN. >> COOL TOOLS BUT THE ISSUE OF HOW TO COLLECT AND AGGREGATE PEOPLE AND FOLLOW PEOPLE. TOM GAVE THE ANSWER. COUPLE OF QUESTIONS FOR TOM. I WON'T PUSH YOU ON (INAUDIBLE) RATE. WE ALL SAY THERE'S ENOUGH (INAUDIBLE) YOU'RE GOING TO WIND UP UNDER LET ME ASK OUR A COUPLE OF QUESTIONS. IF YOU'RE ADMINISTERING A QUESTIONNAIRE, WHAT'S THE DISTRIBUTION OF TIME YOU CAN GET FROM PEOPLE TO DO THIS, 10, 20 MINUTES, HOUR, HOUR AND A HALF? (INAUDIBLE) SECONDLY IN TERMS OF TOPIC IDEAS FOR TOMORROW, WOULD YOU BE PAID LICENSES ON 66 CANCER CENTERS IN A WAY TO AGGREGATE DATA ACROSS A MAJORITY OF CANCER PATIENTS IN THE COUNTRY IN SHORT ORDER? >> GREAT QUESTION. SO TO THE FIRST PART, IF PATIENTS DON'T HAVE ACCESS TO COMPUTER THEY COME IN, IT CAN TAKE 30 TO 40 MINUTES TO DO IT. WHAT WE HAVE LEARNED THROUGH THE SCREENING CENTER IS THAT WE TELL THEM THIS IS WHEN YOUR APPOINTMENT IS, IF THEY COMPLETE IT ON LION WE CALL THEM BACK AND SAY GUESS WHAT, YOU DID IT. HERE IS ONE OF YOUR APPOINTMENT TIME IS,AND THEY GET -- THEY COME IN LATER. SO CREATES AN INCENTIVE. WE DON'T TELL THEM UP FRONT F. THEY DONE DO IT BEFORE THEY LEAVE WE TRY TO CHASE DOWN AFTER. SO IT'S NOT 100% BUT IT'S IN THE BAD. ONE OF THE REASONS WE -- IT'S OPINION SUCCESSFUL WE CREATED INCENTIVE FOR THE PHYSICIANS. THAT IS THE PATIENT PUT ALL THIS INFORMATION IN AND IT GETS SUM RIDESED TO A FOUR PAGE OUTPUT OF THE DOCTOR'S NOTES SO THEY CAN START NOTES WITH SEE PATIENT REPORT, CORRECT THIS, ADD THAT. SO THERE'S INCENTIVES TO THE DOCTORS TO ENCOURAGE THE UPTAKE AS WELL SO THAT WAS QUESTION OF ACCESS, THE OTHER ONE WAS -- REMIND ME. >> JUST THE VOLUME AND TIME THAT YOU CAN EXPECT. LICENSE TO THE OTHER CAMPUSES. >> THE TIME IT REALLY DEPENDS BUT LET ME SAY THESE ARE MOTIVATED INDIVIDUALS THEY'RE COMING IN WITH A DEADLY DISEASE. NOT LIKE VOLUNTEERS THAT HANG AT THE MALL AND GET SOMEBODY TO COME TO THESE QUESTION SO THEY'RE MOTIVATED AND WILL SPEND TIME TO GET THE ANSWERS RIGHT. ALL ABOUT SHARING. ONE OF THE THINGS THAT WE LEARNED IS THERE'S PLATFORM DIFFERENCES, WE STARTED THIS WITH ONE PARTICULAR PLATFORM AND DIDN'T DO AS ADVERTISED. WE HAD TO CHANGE IT AND INTERFACING IT WITH THE MEDICAL RECORD IS PROBABLY THE BIGGEST HURDLE ANDxD E ENDED UP HAVING TO INVEST, IT WAS A PARTNERSHIP WITH A $9 MILLION PARTNERSHIP WHERE WE PAID TO INTEGRATE THE BIBANK, THE PATIENT PROVIDED DATA AND THAT'S JUST SCRATCHING THE SURFACE. THERE'S SO MANY -- THE IMAGING DATA, THERE'S SO MANY THINGS THAT WE WANT TO BRING IN. THAT'S THE EXPENSIVE PART SO EVEN IF WE WANTED TO SHARE IT, PEOPLE WOULD HAVE TO BE ON (INAUDIBLE) FOR EMR SO THERE'S CHALLENGES THERE BUT THERE'S ALSO OPPORTUNITIES CANCER REGISTRY DATA. EVERYBODY REPORTS OUT TO AMERICAN COLLEGE OF SURGEONS OR NCRR SO YOU CAN GET THAT IN A STANDARD FORMAT AND IT'S PLATFORM INDEPENDENT. WE WOULD BE HAPPY TO DO THAT. >> MY QUESTION IS FOR TOM. FANTASTIC SYSTEM AND I KNOW SOME OF THE OTHER COMPREHENSIVE CANCER CENTERS WORK ON SIMILAR THINGS, WERE YOU ABLE TO GET THE PATIENT CONSENT TO SHARING THE DATA WITH ALL SORTS OF OTHER INVESTIGATORS? BECAUSE I KNOW THEY ARE REALLY COMMITTED TO THIS. SO THAT LATER ONCE YOU FIGURE OUT LOGISTICS OF IT, YOU CAN SEND ALL THEIR DATA TO OTHER INVESTIGATORS IN A PUBLIC REPOSITORY. >> THAT'S A GREAT QUESTION. IN FACT, I SHOULD SAY WE HAD A PATIENT FAMILY ADVISORY BOARD TO PROTOCOL. THEY TOLD US UP FRONT, IF WE'RE CONTRIBUTING DATA SAMPLES, YOU BETTER SHARE IT WITH EVERYBODY AND THEIR BROTHER. SO THEY ENCOURAGED SHARING. ALSO IN THE PROTOCOL IT SAYS IT WAS A COLLABORATION WITH MERCK PHARMACEUTICALS. IT WAS -- THIS HAS BEEN A VERY EXPENSIVE PROTOCOL SO WE TOLD THEM WE'D BE SHARING THE IDENTIFIED DATA AND SAMPLES, IT HAS NOT BEEN A MAJOR BURDEN. PATIENTS ARE HOPING THIS BENEFITS THEM. IF IT LEADS TO A CLINICAL TRIAL DOWN THE ROAD, SO AGAIN IT'S NOT LIKE PEOPLE AT THE MALL, WHO ARE FREE OF ANY DISEASE, IT MIGHT BE DIFFERENCE, I'M SURE -- >> I LOVE THE PORTAL IDEA AND SEEING THE KIND OF DATA YOU'RE ABLE TO COLLECT AND EXPECT IT WILL YIELD INTERESTING THINGS. MY QUESTION IS AT THIS TIME AND EVEN WHILE BUILDING THIS, IS YOUR GROUP THINKING ABOUT THE KINDS OF QUESTIONS WHICH HAD THE END OF THE DAY IF WE GOT THESE DATA WE WOULD BE ABLE TO ANSWER SOMETHING ABOUT PROGNOSIS RESPONSE TO THERAPY, RISK -- THERE'S SO MANY KINDS OF QUESTIONS WE APPLY EPIDEMIOLOGY TOO, ETIOLOGY, DIAGNOSIS, PROGNOSIS, RESPONSE TO THERAPY, ALL WHICH REQUIRE DESIGNS, COMPARISONS, THERE'S LOTS OF DEVILS IN DETAIL THAT IF YOU THINK IN ADVANCE YOU MIGHT TWEAK THE WAYS YOU GET THE DATA. I'M WONDERING IF THAT'S SORT OF ON YOUR RADAR AND PART OF THE INFRASTRUCTURE OR HOW YOU THINK ABOUT THAT. >> WITH UNLIMITEDDED RESOURCES, WE WOULD HAVE ALL THE ANSWERS. BUT WE HAVE BEEN -- WE'RE COBBLING IT TOGETHER AND TRYING TO FIGURE IT OUT BUT THE ANSWER IS YES, WHAT WE DECIDED AS A STRATEGY UP FRONT IS TO TRY TO DETERMINE WHAT IS THE CORE SET OF DATA, THE ENTERPRISE LEVEL DATA APPROPRIATE ACROSS ALL 15 CLINICAL PROGRAMS. THEN GIVE EACH INDIVIDUAL PROGRAM THE CAPACITY TO DETERMINE WHEN TO I NEED THAT FOLLOW-UP BIOPSY. HOW MANY SAMPLES OF BLOOD, WHAT ARE QUESTIONS I NEED TO ASK FOR THOSE PARTICULAR PATIENTS. THAT'S WHERE WE ARE. >> I'M THINKING WITHOUT UNLIMITED RESOURCES ONE OR TWO LOW HANGING FRUITS AS KIND OF PRELIMINARY DATA JUST TO URGE THAT KIND OF THINKING YOU DON'T NEED THE UNLIMITED DATA BUT SOUNDS LIKE A REAL NEAT THING. >> ARE YOU TALKING THE FOLLOW-UP DATA? >> YEAH. >> JUST THINKING ABOUT ONE OR TWO KINDS OF QUESTIONS AND SAY BECAUSE THEN IF YOU START ANSWERING REAL QUESTIONS YOU CAN COME BACK AND SAY WE USE THIS INFRASTRUCTURE TO DO THIS BECAUSE OF THE TWEAKING WE DID AND THE WAY WE THOUGHT ABOUT THE QUESTION AND FOCUSED, THE PROBLEM IS WE COLLECT LOTS OF DATA. WE HAVE GOT LOTS OF EXPERIENCE PERSONALLY AND AT THE NIH OF DATA SETS AND HUGE COLLECTION EFFORTS THAT REALLY DIDN'T PRODUCE MUCH AND THE PROBLEM IS, IT'S NOT JUST DATA WE NEED BUT DAY THAT WE'RE COLLECTED IN ORGANIZED WAY RELATED TO COMPARISONS, DETAILS WITH QUALITY OF THE DATA TO WRITE UP IN THE METHODS SECTIONS AND WE NEED TO ANTICIPATE THAT EARLY. >> TO DAVID'S QUESTION EARLIER, WE'RE SENSITIVE TO THE BURDEN OF PATIENT BURDEN, SO WE HAVE A COMMITTEE THAT REVIEWS EVERY SINGLE QUESTION THAT A CLINIC WANTS TO ADD, WE WANT VALIDATED INSTRUMENTS, SO THAT'S REALLY IMPORTANT AND WITH THE FOLLOW-UP THERE ARE SOME MODULES THAT ARE COLLECTED BASELINE THAT ARE REPEATED IN FOLLOW-UP AND THEY OTHER VALIDATED INSTRUMENTS SO WE'RE STARTING TO THINK ABOUT THESE, DON'T PRETENDED TO HAVE ALL ANSWERS BUT HELPS WHEN THE FORMER CEO AND CENTER DIRECTORS SAY THOU SHALT BUILD SURVIVORSHIP (INAUDIBLE). >> WE HAVE HEADING TOWARDS (INAUDIBLE) SO WE NEED SHORT ANSWERS AND QUESTIONS. JOHN, THEN PEOPLE IN THE BACK AS WELL. THEN I HAVE A COUPLE OF QUESTIONS. >> COMING BACK TO THE MAJOR QUESTION FOR THE SESSION WHICH IS WHEN PRIME TIME AND FOR WHICH TECHNOLOGIES FOR EPIDEMIOLOGICAL RESEARCH, I WOULD ARGUE IT'S PRIME TIME FOR ANYTHING THIS RESEARCH BUT PRIME TIME TO BE USED IN HEALTHCARE REAL LIFE EVERY DAY ROUTINE. SEEMS MANY INITIATIVES ARE REALLY CONFOUNDING IN HEALTHCARE WITH RESEARCH. DO YOU SEE THAT CAUSING A PROBLEM AT SEVERAL LEVELS IN RESEARCH AND IN COST, IMPLEMENTATION, AND IF SO, SHOULD WE TRY TO IMBED MORE RIGOROUS EMPERIMENTAL APPROACHES LIKE RANDOMIZED TRIALS TO TEST TECHNOLOGIES. OBVIOUSLY SOMETHING HAS HIGHER RATE. AND DOESN'T HAVE DISCRIMINATING ABILITY. SOMETHING THAT'S PROMISING SHOULD WE TAKE AN EXTRA STEP TO TEST IT. >> THE FIRST BROUGHT UP BLURRING OF DISTINCTION BETWEEN RESEARCH AND CLINICAL CARE AND THIS IS AN ISSUE IT COMES TO GENOME SEQUENCING OR SEMATIC SEQUENCING THE PATIENTS SEEM TO BE EXPECTING THEY MIGHT HAVE ACCESS TO RESULTS OF TECHNOLOGIES, YOU HAVE BEEN INVOLVED IN SOME OF THESE YOURSELF BUT THIS IS AN AREA WE DO NEED TO FIND MORE CLEARLY WHAT IS RESEARCH AND WHEN WE WILL NOT REPORT RESULTS BACK TO INDIVIDUALS BECAUSE THIS IS STILL NOT READY FOR PRIME TIME AS WE SAY. OR FEEL TECHNOLOGY HAS GOTTEN SUFFICIENTLY ROBUST THAT WE THINK THAT THE DATA IS VALID AND MAY HAVE A TRUE IMPACT ON CLINICAL CARE. SO THAT QUESTION IS ONE WE STRUGGLE WITH ALL THE TIME. I DON'T THINK WE HAVE THAT BRIGHT LINE FOR MAKING THE DISTINCTION. SO ROOM FOR DISCUSSION AND DEBATE BUT MOVE FETE AND OTHER WHOSE HAVE PATIENTS AS PART OF THE DISCUSSION, WE CAN'T IGNORE THEM, WE CAN'T BE PATERNALISTIC AND EXPECT THAT WE KNOW EVERYTHING THAT THEY WANT OR DON'T WANT SO WE NEED TO HAVE THAT AS PART OF OUR SOCIAL DIALOGUE HOW WE USE THESE TECHNOLOGIES, THAT'S ONE (INAUDIBLE). >> IT'S ALL RESEARCH AT SOME LEVEL BECAUSE WE'RE USING IT BUTITE CLEAR STUFF IS EARLY PHASE WHEN WE'RE DOING DISCOVERY BASED THINS, PROTEOMICS, METABALOMICS. NONE OF THAT IS READY AT ALL FOR CLINICAL PARTS. ONLY WHEN WE THINK WE HAVE SOMETHING TO GO THROUGH APPROPRIATE TRIALS AND THEN BECOME CLINICAL TEST BUT THERE WILL STILL WILL RSEARCH BECAUSE WE CHECK THAT INFORMATION. THAT'S THE NATURE OF THE DISEASE WE'RE TALKING ABOUT WHETHER CANCER OR DIAGNOSE BEE TEASE. THESE ARE COMPLEX DISEASE, EVERY PERSON IS DIFFERENT IN THE SENSE DIFFERENT PATHWAYS ACTIVATED DO FOLLOW THE THEMES BUT THE RESPONSES WILL DIFFER BECAUSE THEY HAVE DIFFERENCE CYTOCHROME P-450 SO THERE WILL BE RESEARCH HELMET TO THIS AND THEY SHOULD BE CLASSIFIEDED IN KNOWLEDGE DATABASES, WHATEVER YOU WANT THE CALL THEN, THAT'S SOMETHING WE AGREE SHOULD BE OUT THERE THAT WE CAN ALL UT LIZE SO WE'RE YOU HEARD THE PHRASE DATA DRIVEN MEDICINE, THATS WHERE WE OUGHT TO GO. THE REASON WE OR SUCCESSFUL IS CLOSE INTEGRATION BETWEEN RESEARCH AND PRACTICE THAT ENABLED IT. >> SO I FOUND THIS HELPFUL THINKING ABOUT THE AFTERNOON ONE OF THE BEST DELIVERABLE THAT COME FROM THIS MEETING IS BEST PRACTICES OF WHAT EPIDEMIOLOGIC DATA WE WANT TO COLLECT IN CANCER CENTERS. WE STRUGGLED WITH THIS. P WE HAVE BIOSPECIMEN REPOSITORIES, WE HAVE BEEN ADDING EPIDEMIOLOGIC QUESTIONS, EXPOSURE DAY. WE HAVE DONE IT ON ORGAN SITE SPECIFIC BASIS BECAUSE WE FELT THE QUESTIONS WE WANT TO ASK FOR OUR LUNG CANCER PATIENTS ARE DIFFERENT THAN QUESTIONS FROM OVARIAN CANCER PATIENTS. SO IF WE COULD HAVE TUMOR SITE SPECIFIC MOLECULES AN TUMOR TO COLLECT THE METRICS THAT WOULD FACILITATE THE POOLING. WE HAVE A CLIA APPROVED GENERAL IT CAN FACILITY AT YALE AND WE WERE -- GENETIC FACILE AT YALE. WHAT'S USED FOR CLINICAL CARE AND RESEARCH, WE'RE DOING BOTH IN PARALLEL SO WE HAVE A KLIA ONE USED TO DRIVE CLINICAL DECISION MAKING AND RESEARCH GOING BEYOND THAT SO WE'RE NOT THE ONLY ONES DOING THIS, SO IF CANCER CENTERS WORK TOGETHER THAT PULLS TOGETHER EXPOSURE DATA ALONG WITH GENOMIC DATA WE KNOW WILL GO FORWARD EITHER WAY. THE OFFICE CENTER OF CANCER GENOMICS IN OUR MEETING THERE'S A STRONG CONSENSUS AT THE TOP WITH DR. VARMUS THAT ALL VIEW FEW CLINICAL TRIALS WILL HAVE CONSIDERATION TO HAVE COLLETION NOT ONLY BIOSPECIMENS BUT QUESTIONNAIRE INFORMATION AS WELL AS CLINICAL OUTCOMES SO THAT THE OPPORTUNITY TO LOOK FORWARD AND BACKWARDS IN TERMS OF SUSCEPTIBILITY, GENE ENVIRONMENT EXPOSURE AND SUSCEPTIBILITY QUESTIONS AND WHAT HAPPENS ONCE YOU HAVE THAT CANCER IN YOUR RESPONSE TO THE THERAPY, THIS IS A VERY ACTIVE DISCUSSION. AND THERE ARE SUBSTANTIAL FINANCIAL CONSEQUENCES. WON'T HAPPEN RIGHT WAY BUT THIS DIALOGUE IS ACTIVELY IN PLACE RIGHT NOW. WHICH SHOULD HE P ALONG LINES. >> COMMON DATA METRICS. IF WE CAN ANTICIPATE WE WANT TO POOL IT TO SEE PEOPLE WITH WITH THIS PARTICULAR MUTATION ANK POE SURE THAT WOULD BE SO HELPFUL. >> JOHN. >> THIS HAS BEEN VERY EXCITING. WE'RE AT A UNIQUE POINT IN TIME WITH POTENTIAL FOR COLLECTING INFORMATION I DON'T KNOW IF ANYONE -- THERE WAS AN ARTICLE YESTERDAY NEW YORK TIMES APT APPS THAT CHILDREN PLAY WITH COLLECTING A LOFT INFORMATION THAT PARENTS AN KIDS DIDN'T KNOW ABOUT. WHICH IS A WEIRD TWIST BUT I THINK THAT'S A HUGE AMOUNT OF POTENTIAL FOR US COLLECTING THE DATA THROUGH EVERYONE'S PHONES AN APPS. BUT WHAT I'M HAVING A HARD TIME GETTING THE HEAD AROUND THE EXPOSEOME AN POTENTIAL COST FOR THAT. I DON'T KNOW IF I COULD GET OPINIONS HOW LOW WE'LL BE ABLE TO GO WITH COST OF RUNNING EVERYTHING. I THINK MOORE'S LAW AND STEEPER DECLINE IN SEQUENCING COSTS. BUT I ALSO THINK ABOUT HOW NO MATTER WHAT MY LAPTOP COMPUTER STILL COSTS A CERTAIN AMOUNT OF MONEY, I THINK THEY COST MORE BECAUSE THERE'S MORE IN THEM AND IT COSTS THE SAME BECAUSE THERE'S MORE COMPUTER POWER AN GREAT SCREEN THAT GETS PUT IN AND I WONDER THESE TESTS WILL WE ADD MORE THINGS APPROXIMATE KEEP THE COST STILL AT $1,000 PER SEQUENCE. I DON'T KNOW IF MIKE OR OTHERS HAVE A SENSE WHAT TECHNOLOGIES ARE ON THE NEAR HORIZON THAT MAY BRING THE COSTS DOWN TO A POINT WHERE WE COULDN'T GET MILLIONS OF PATIENTS SEQUENCED AND HAVE OTHER MEASUREMENTS ON THEM. >> I PROBABLY AGREE WITH YOU. FORME IT'S A $2,000 COMPUTER AND THAT'S WHAT I HAVE ALWAYS PAID FOR THE LAST I DON'T KNOW HOW LONG. THAT WILL PROBABLY BE TRUE GOING FORWARD. IS YOU'LL DO A GENOME SEQUENCE FROM ONE PART BUT ESPECIALLY THE AREA OF CANCER, ONE GENOME SEQUENCE ISN'T GOING TO BE GOOD ENOUGH IN THE FUTURE WHEN THE PRICE HITS $200 A GENOME YOULL WANT MULTIPLE SEQUENCES FROM MULTIPLE SITES. SO THAT MAYBE THE CASE. BUT WE SHOULD DIVISION WHAT'S RESEARCH VERSUS CLINICAL CARE. QUESTION IS HOW MANY SITES YOU NEED FROM A SAMPLE TO FROM A PERSON TO MAKE GOOD DIAGNOSIS TO TAKE ACTION ON. THAT'S THE RELEVANT INFORMATION FROM THAT PERSPECTIVE F. THE RESEARCH SIDE THE LONGITUDINAL SAMPLES ARE STILL INCREDIBLY VALUABLE YOU WANT THOSE. SO IF YOU CAN SAMPLE MORE YOU CHECK MORE INFORMATION THAT WILL HELP YOU PROBABLY MAKE BETTER DISCOVERIES, I WOULD ARGUE. AT LEAST THAT'S MY THINKING. IN THE END WE'LL PROBABLY -- >> JUST QUICKLY, I THINK TO THINK ABOUT THE AMORTIZATION OF THE GENOME EXPENSE OR OTHER ONLIES THAT WE CAN --OMES, WE CAN USE A GENOME NOT JUST ONCE BUT PRESUMABLY OVER A LIFETIME WITH THE CAVEAT THE TECHNOLOGY MIGHT GET BETTER AS INTERPRETATION IMPROVES. SO IT'S LIKE THE ANALOGY IS NOT REALLY THE COMPUTER BUT IT'S HOW MANY TIMES DO YOU USE POWERPOINT. YOU PAID FOR IT ONCE BUT USE IT HUNDREDS OF TIMES A DAY. SAME WOULD BE FOR SOME OF THE OTHEROMES, YOU HINK ABOUT EXPOSURES, AS WE GET BETTER AT THIS, MY VIEW IS WE'LL HAVE A CATALOG OF BIOMARKERS DERIVED FROM A SINGLE MEASUREMENT SO YOU'LL GET THE FULL PANOPLY OF MEASUREC RATHER THAN ONE AT A TIME. I THINK THAT'S ALSO GOING TO CREATE SOME COST EFFICIENCIES. I DON'T THINK IT'S NECESSARILY GOING TO DRIVE THE COSTS DOWN BUT I THINK ITS NOT GOING TO BE AS EXPENSIVE AZURE QUESTION SEEMS TO SUGGEST. FINAL FROM THE AUDIENCE THEN TO -- WAIT DON'T TELL, FILL IN THE BLANK. THERE'S FIVE QUESTIONS. WE'LL DO LIGHTNIENING FILL IN THE BLANK. FROM THE PANEL OF TWEETS. >> THIS IS A COMMENT FOR YOU, STEVE. IT WAS YOUR JOUNCIEST OF SEMATIC EPIDEMIOLOGY. WE REALIZE IMPORTANT TO INTEGRATE GENETIC CHANGES WITH GERM LINE CHANGES. WE ALSO KNOW GENE DISCOVERY AND EXPLORATION OF MOLECULAR PATHWAYS SHOULD MOVE SEAMLESSLY BETWEEN MOLECULAR GENETIC STUDIES AND MOLECULAR EPIDEMIOLOGY STUDIES. APPEAR IF -- I FEAR IF WE BRING IN A NEW TITLE, IT CREATE AS SILO AND IT PREVENTS US DEVELOPING INTEGRATIVE EPIDEMIOLOGY AND COALESCING THE DISCIPLINE SPECIFIC INTERESTS. IT'S JUST A COMMENT. >> ALL RIGHT. >> YOU'LL PROBABLY DISAGREE BUT THAT'S OKAY. >> I BEG TO DISAGREE. WE HAVE LIVED IN THAT WORLD HAND HAD THE SILOS. THE IDEA IS TO BRING ITING TO SO THIS BECOMES SEAMLESS BECAUSE I DON'T THINK IT HAS BEEN SEAMLESS. SO IF FUNDING MECHANISMS, RFP AND DISCUSSIONS ABOUT THIS, THE GAME ON U-19 STARTED DOWN THAT ROAD, HOPEFULLY WE'LL DO THAT. NOW WE'RE PLAYING FOR FRANCIS COLLINS AND HAROLD VARMUS. FILL IN THE BLANK. WE HAVE CARL CASTLE TO KEEP SCORE. I HAVE TWEET QUESTIONS THAT I'M GOING TO ASK EACH OF THE MEMBERS OF THE PANEL, THERE NEEDS TO BE A BRIEF ANSWER, OKAY? WHAT HAPPENS TO PRIVACY IF EPIDEMIOLOGISTS USES SENSORS AN SOCIAL MEDIA TO GATHER DATA. HOW ARE WE GOING TO ADDRESS THOSE QUESTIONS? >> I WIL QUOTE HEAD OF OACLE. PRIVACY, GET OVER IT. ALL OF US HAVE ALREADY RELINQUISHED OUR PRIVACY BY JUST LOGGING ON TO -- USING THE INTERNET AND THOSE OF US THAT PARTICIPATE IN SOCIAL MEDIA HAVE ALSO RELINQUISHED PRIVACY TO THE EXTENT THERE ARE PRIVACY RULES SO I THINK WE ARE ALREADY IN THIS ZONE OF HAVING A NEW DEFINITION OF PRIVACY PERHAPS. >> I FULLY AGREE. IF WE BELIEVE WE HAVE PRIVACY, WITH SOCIAL MEDIA THE WAY WE'RE OUT THERE EXPOSED? I DON'T KNOW. >> YOU DO HAVE IRB. >> DEFINITELY. I'M NOT SUGGESTING THAT THESE ARE -- THESE SHOULDN'T BE IRB REGULATED STUDIES DOWN THE LINE I EXPECT FROM THE MOMENT WE PARTICIPATE IN SOCIAL MEDIA, WE CAN HAVE ALL THIS DONE. WE CONTRIBUTE INFORMATION. SO I DON'T SEE THAT AS BOTTLENECK. >> AGREE. IT SHOULD BE. IF YOU PARTICIPATE YOU SHALL BE OPEN. BUT I DON'T THINK YOU SHOULD ASSUME THAT EVERYONE WILL WANT TO PARTICIPATE AND HAVE THEIR INFORMATION OPEN. DON'T MAKE ANY ILLUSION THERE IS. THERE'S SOME PEOPLE WHO SHOULDN'T GET GENOME SEQUENCED. SO EVEN ON A THOUGH I'M A BIG PROPONENT IN THIS AREA, THAT'S A DIFFERENCE TIME. IF YOU WORRY A LOT YOU SHALL GET YOUR GENOME SEQUENCED YOU'LL SPEND A LOT OF TIME WORRYING ABOUT THE MUTATIONS YOU HAVE BUT IF YOU DO PARTICIPATE YOU PROBABLY COULD ASSUME THAT IT WILL BE OUT THERE. >> I THINK THE SOCIETAL ATTITUDES ARE CHANGING EXTENSIVE HI AND WOULD BE WORTH PUTTING A TOW IN THE WATER TO SEE THE READ ON THAT. FROM PERM EXPERIENCE AN PATIENTS THAT I HAVE TALKED TO, THERE'S A HUGE DIFFERENCE BETWEEN WHEN YOU CROSS FROM I'M A CONTROL TO I'M A CASE. EVERYBODY THAT I KNOW WHO IS A CASE GETS A DATA OUT THERE, GET AN ANSWER. >> THE STRIKING BALANCE BETWEEN THE BENEFITS OF REVEALING AND ALSO THE PRIVACY, THAT'S KIND OF (INAUDIBLE). >> ALL RIGHT. NEXT LIGHTNING FILL IN THE BLANK. WHAT INFORMATICS NEEDS MIGHT THERE BE WITH A TSUNAMI OF DATA FROM THESE SENSORS AN THESE NON-OMIC -- THESE NON-GENOMIC TECHNOLOGIES PER SE? AND HOW DO WE INTEGRATE THOSE? >> >> PROBABLY MORE JOINT VENTURES AND FOR THIS TYPE OF LARGE INITIATIVES. I THINK THAT'S MY APPROACH. >> ONE PIECE OF THE PUZZLE IS TO MAKE SURE WE HAVE COMPUTER SCIENTISTS AT THE TABLE. IT'S TSUNAMI MASSIVE DATA SETS, WE NEED TO THINK ABOUT MORE CLEVER WAYS TO STORE THE DATA SO THAT WE CAN DO THE INTEGRATION AND ANALYSIS. >> NOT WORRIED ABOUT INTEGRATION. THERE'S LOT OF SMART PEOPLE WHO THINK ABOUT THIS ALL THE TIME HOW TO TO THIS, HOW TO BRING IN DIVERSE DATA TYPES SO THAT PART I THINK IS -- NOT THAT IT IS AN ISSUE BUT IT'S PRETTY SOLVABLE. STORING THE DATA, IT WILL GET CONDENSED AND YOU WILL LOSE SOME INFORMATION. HAVE YOU LIKE WE DON'T SAVE IMAGES FROM SEQUENCERS, THAT'S WE'LL HAVE TO COMPROMISE GOING FORWARD. >> (INAUDIBLE) SCIENTIFIC COMMUNITY IS ALREADY THINKING AHEAD OF THAT FOR EXAMPLE THIS IS WHAT WE'RE DOING, WE RECENTLY GOT OUR NEXT COMPUTER WHICH IS THE FASTEST SUPER COMPUTER IN THE WORLD, IT IS NOT JUST THE COMPUTATIONAL POWER, IT'S ALSO WHAT IT MEANS IN TERMS OF ENERGY REQUIREMENTS SO THE SCIENTIFIC COMMUNITY IS ALREADY THINKING AHEAD. WE HAVE POSITIONING OURSELVES TO BE DOING EXTRA SCALE COMPUTING IN THE NEXT FEW YEARS. >> I THINK ABOUT THE INFORMATICS ISSUES ON THREE LAYERS. I DISAGREE WITH MIKE A LITTLE BIT THAT IT'S A SLAM DUNK TO MAKE YOU WILL ALL THEE SYSTEMS TALK TO EACH OTHER. MOST HEALTH SYSTEMS ARE STRUGGLING TO GET MEDICAL RECORDS TRANSFERRED ELECTRONICALLY ACROSS THE STREET. INTEGRATING ONLYICS DATA AND --OMEICS DATA AND PATIENT REPORTED OUTCOMES DATA AS MOFFETT THE TRYING TO DO PRESENT AS HUGE INTEROPERABILITY CHALLENGE. SECOND IS AS WAS ALLUDED TO WAS THE ANALYSIS PIECE, AND WE SHOULD BRING IN NOT JUST COMPUTER SCIENTISTS BUT INDIVIDUALS THAT LOOK AT LARGE DATA SETS FROM WEATHER AN SAT LIED IMAGERY LOOKING FOR SIGNAL TO NOISE PROBLEMS FROM THESE COMPLEX DATA SETS TO COME TO BEAR ON SOME OF THE BIOLOGICAL DATA WE'RE TALKING ABOUT AND THEN THE LAST PIECE IS THE ENTERPRETIVE LAYER. HOW DO YOU MATCH THE DATA THAT YOU HAVE WITH KNOWLEDGE BASE OF BIOLOGY SO YOU UNDERSTAND WHAT IT MEANS. >> TWO MORE QUESTIONS. THIS FOLLOWS ON P THE LAST ONE. GEOFFREY, WITH THE OPEN DATA, REALLY THE TWEETER COMMENTED THAT ONLY USEFUL IF WELL CURATED AND DOCUMENTED. AND IN A USABLE FORMAT. WHAT DO YOU SEE THE KEY ISSUES AN KEY INCENTIVES FOR INTEROPERABILITY SO TO SPEAK? SO THAT THE COMMUNITY CAN USE AND MOVE I CROSS DATA SETS AND GET FAR MORE OUT OF ANY INDIVIDUAL DATA SET BY COMPARATIVE NATURE? >> YOU JUST SAID IT. I THINK THOSE ARE THE REASONS MY MIGHT DRIVE STAKEHOLDERS TO CREATE STANDARDS AS HAVE OCCURRED IN OTHER -- IN THE FINANCE INDUSTRY, IN OTHER AREAS WHERE MOVEMENT OF LARGE SETS OF DATA IS CRITICALLY IMPORTANT TO THE BUSINESS PROPOSITION. AND HEALTHCARE IS CERTAINLY HAS SOME SERIOUS BUSINESS PROPOSITIONS ASSOCIATED WITH DATA INTEROPERABILITY. I WOULD ALSO DIFFER WITH THE TWEETER, THAT IT HAS TO BE HIGHLY CURATED BECAUSE CLEARLY NATIONAL -- NATURAL LANGUAGE PROCESSING APPROXIMATE ALSO MINING OF VERY DIRTY DATA SETS THAT EXIST IN THE PUBLIC DOMAIN HAVE YIELDED INTERESTING FINDINGS WITHOUT STANDARD. >> I DON'T HAVE ANYTHING TO ADD. >> I WAS SAYING YEAH, I THINK WE NEED IT, I THINK EVERYBODY'S DESIRE FOR IT WILL DRIVE IT FOR SOME COMMON SYSTEMS. >> I THINK IT'S'S REALLY IMPORTANT. WE HAVE INVESTED HUNDREDS OF HOURS CREATING A DEATH DICTIONARY ONLINE THAT PROVIDES THE SOURCE, DIFFERENT REPRESENTATIONS DIFFERENT VERSIONS, METADATA ABOUT THE DATA. IT'S WAY TO COMPLEX FOR MY BRAIN BUT THE MEDICAL CLINICAL INFORMATICS PEOPLE LOVE IT AND THAT IS CRITICAL TO INTERPRET WHAT WE HAVE GOT. AND UNFORTUNATELY WE TEND TO HAVE TO GET FUNDED TO TO IN AN ON INDIVIDUAL STUDY SO IT'S A CHALLENGE FOR THE COMMUNITY. >> QUESTION, I THINK WE HAVE TO TALK TO APPLE HOW TO MAKE THE VERY USER FRIENDLY INTERFACE >> THANK YOU. WE HAVE ONE MORE QUESTION, LIGHTNING FILL IN THE BLANK. TOMORROW MORNING WE START AT 8:00 O'CLOCK SHARP IN THIS ROOM. OF ALL DISCUSSIONS ABOUT METHODS AND DATA WHAT IS THE MOST PERTINENT RESEARCH QUESTION CURRENT TECHNOLOGIES DO NOT ADDRESS THAT NEED TO BE BETTER ADDRESSED AT THIS TIME? >> EXPOSEOME. >> SO TISSUE HETEROGENEITY AND SINGLE CELLOMICS. >> I'LL BE SARCASTIC. WHAT WE NEED IS TO FIGURE OUT A WAY FOR THE GENERAL PUBLIC TO BUY WHAT IT IS THAT WE DO. THEY'RE NOT BUYING RESEARCH. I DON'T THINK THEY CARE ABOUT THE (INAUDIBLE). >> WE NEED TO INVEST MORE DEVELOPING THE ADVANCED MODELING AND SIMULATION INFRASTRUCTURE THAT ALLOW US TO MODEL THE FACT AT A POPULATION LEVEL. SO WE CAN ACTUALLY EXPLORE HYPOTHETICAL SCENARIOS OF USING NEW TECHNOLOGY THAT APPEARS TO PERFORM AT THE CERTAINLEVEL. IF I PUT IT IN THE PIPELINE AND EXPLORE SEVERAL DIFFERENT SCENARIOS CAN I COME UP WITH A COST EFFECTIVENESS METRIC IN THE END? ANDTHAT IS A VERY ELABORATE MODEL AND SIMULATION INFRASTRUCTURE. IT CAN BE DONE. SO INSTEAD OF LOOKING AT SILOS HERE THE TECHNOLOGIES DEVELOPING AND NEED VALIDATED MAKE SURE THAT WHAT I'M GETTING IS RIGHT WHAT DOES IT MEAN BIG PICTURE? WE NEED TO BE ABLE TO SIMULATE BIG PICTURE. >> WE NEED TO FIND PATHWAYS TO VALIDATION. THAT'S CRITICALLY IMPORTANT RESEARCH QUESTION BECAUSE WE'RE SITTING ON A BOAT LOAD OF VERY INTERESTING DISCOVERIES AN EVERYBODY IS USING THE TERM VALIDATION IN A DIFFERENT CONTEXT. BUT CAN WE ACTUALLY BEGIN TO CREATE SOME PATHWAYS TO VALIDATION THAT ALLOW US TO MAKE THE MOST USE OF WHAT IS IN DISCOVERY. >> EXCELLENT POINT TO END ON. I WOULD LIKE TO THANK THE PANELISTS FOR THEIR VERY ENLIGHTNING DISCUSSIONS. THEY ALL WIN CARL'S VOICE ON THE HOME ANSWERING MACHINE. THANK YOU, AUDIENCE FOR YOUR PARTICIPATION AND STAYING FOR A LITTLE EXTRA TIME. THIS HAS BEEN A GREAT SESSION. THANK YOU AGAIN.