>> GOOD AFTERNOON I'M THE
DIRECTOR OF THE OFFICE AND
INTRAMURAL RESEARCH AND NHGRI,
IT'S A PLEASURE TO WELCOME YOU
TO THE TRANS-ATLANTIC
CIRCULATION COMPARING THE HUMAN
GENOME PROJECT WITH THE EXPOSOME
AND THIS IS BEING RECORDED AND
ARCHIVED ON THE NIH VIDEOCAST
WEBSITE.
WELCOME TO ALL WATCHING LIVE.
IF YOU HAVE QUESTIONS, THERE'S A
SEND LIVE FEEDBACK BUTTON AND IF
WE CAN'T ANSWER YOUR QUESTION
TODAY, WE'LL HAVE SOMEBODY GET
BACK IN TOUCH WITH YOU WITH
ANSWERS.
IT'S MY HONOR TO INTRODUCE THE
ACTUAL HOST AND MASTER MIND, HE
COMES TO US FROM PARIS WHERE HE
IS PROFESSOR OF HISTORY ATE AND
PRESIDENT OF THE COMMITTEE FOR
THE HISTORY OF INSERM.
HIS RESEARCH FOCUSES ON
INNOVATION, RESEARCH POLICIES
AND RESEARCH ORGANIZATIONS
LARGELY IN FRANCE AND EUROPE AND
WE'RE GRATEFUL HE'S INCLUDED NIH
AND DELIGHTED TO HOST HIM HERE
FOR THE HISTORY OF THIS
RESEARCH.
HE HAS CHAIRED A NUMBER OF
CONSEQUENTIAL PROJECTS AND
INVENTING A SHARED SCIENCE
DIPLOMACY FOR EUROPE AND
CO-CHAIRS IN SCIENCE DIPLOMACY.
WELCOME DIRECTOR GRISET.
>> THANK YOU FOR THIS PROTOTYPE
OF WHAT COULD BE THE CONTEXT OF
THE RESEARCH INSTITUTION.
I'M QUICKLY INTRODUCING THE
PEOPLE AND THEY ACCEPTED AND
WILL SHARE THEIR CAREER WITH
THIS IMPORTANT PART OF RESEARCH.
THEY ARE NOT SUPPOSED TO GIVE A
LARGE BUT THIS IS AN EXCHANGE TO
FILL THE BIG MOMENT OF THIS I
FIND THEM LIKE I FIND THE SECTOR
FOR THE ORGANIZATION OF THE
TRANSACTION EXCHANGE.
FROM RIGHT TO LEFT I'LL PRESENT
MR. GARY MILLER, DIRECTOR OF
CENTER FOR INNOVATIVE EXPOSOMICS
AT COLUMBIA UNIVERSITY.
IN RESEARCH AND INNOVATION AND
PROFESSOR OF MOLECULAR
PHARMACOLOGY AND DIRECTOR OF THE
CENTER FOR INNOVATIVE EXPOSOMICS
AND IS A LEADER IN THE FIELD FOR
THE CONFERENCE AND CUMULATIVE
EFFECTS OF MEDIATORS THAT IMPACT
CONSISTENCY.
HE SERVES ON THE ADVISORY PANEL
OF THE NATIONAL INSTITUTE OF
HEALTH, ALL OF US RESEARCH
PROGRAM.
THEN WE MOVE TO MR. BALSHAW THE
DIRECTOR OF THE DIVISION OF
EXTRAMURAL RESEARCH AND TRAINING
AT THE NATIONAL INSTITUTES OF
SCIENCES.
AND OVER 500 MILLION COMBINING
BIO PHYSICS AT THE UNIVERSITY OF
CINCINNATI AND UNIVERSITY OF
CHAPEL HILL AND HAS LED
PORTFOLIO FOR ADVANCING OMICS
TECHNOLOGIES SYSTEMS, EXPOSURE
AND CONCEPT OF THE EXPOSOME.
HE ALSO REPRESENTED NIEHS IN THE
GOVERNMENT AND INTERNATIONAL
PROGRAMS TO ADVANCE EXPOSURE AND
THE EXPOSOME CONCEPT.
THEN WE MOVE TO DR. BAROUKI A
RESEARCH PROFESSOR AND THE U85
AND PROFESSOR OF THE FRENCH
SCHOOL OF PUBLIC HEALTH AND DOES
RESEARCH WORK AT THE INSTITUTE
FOR ENVIRONMENTAL AND
OCCUPATIONAL HEALTH IN FRANCE
AND HAS DEVELOPED THROUGH THE
YEARS USING MASS SPECTOMETRY TO
LOOK AT THE CHEMICAL EXPOSOME IN
A VARIETY OF BIO SPECIMENS.
IT'S OPEN ACCESS TOOLS DEVELOPED
WITH HIS GROUP AND NOW BEING
APPLIED IN EPIDEMIOLOGICAL
STUDIES TO INVESTIGATE THE
METHODOLOGY TO STUDY THE
INFERENCE OF ENVIRONMENTAL
FACTORS IN PHARMACO KINETICS.
AND ALSO PROFESSOR OF BIO
CHEMISTRY AT UNIVERSITY AND HEAD
OF THE INSTITUTE OF PUBLIC
HEALTH.
HES RESEARCH IS FOCUSSED ON THE
IMPACT OF ENVIRONMENTAL
CONTAMINANTS AND HUMAN HEALTH
AND THE LINKS BETWEEN EXPOSOMES
AND HEALTH AND INVOLVED IN
SEVERAL E.U. PROJECTS.
HE HAS ALSO BEEN INVOLVED IN
EUROPE RESEARCH ENVIRONMENT OF
HEALTH AND COMBINING SCIENTIFIC
DATA.
BEFORE GIVING THE FIRST
INTERVENTION I WILL ALSO MENTION
THE HISTORIAN IN THE CONTEXT OF
NIH AND MENTION POINTS AND THANK
YOU VERY MUCH FOR BEING HERE AND
YOU COULD BEGIN THIS EXCHANGE.
>> THANK YOU, VERY MUCH PASCAL.
THANK YOU FOR HOSTING US HERE TO
DISCUSS THESE ISSUES.
I THINK THE IDEA BEHIND THIS
CONVERSATION IS I TRACE IT TO
DISCUSSIONS WITH RICK WOYCHIK
THE DIRECTOR OF THE NIEHS WE
DISCUSS A LOT THE PROGRAMS FOR
THE EXPOSOME.
HE USUALLY SAYS, WELL, I LIVED
THROUGH THE HUMAN GENOME PROGRAM
AND IT WAS RELATIVELY CLEAR
THERE WAS A BEGINNING AND END.
THE BEGINNING STARTS THE
SEQUENCING AND THE END WHICH IS
AT LEAST THERE IS SOMETHING.
IT HAMD ONLY A COUPLE YEARS AGO.
BUT HE SAID, WELL, I WOULD LIKE
TO SEE SOMETHING SIMILAR IF
POSSIBLE.
MAYBE IT'S NOT POSSIBLE BUT IF
POSSIBLE WITH THE EXPOSOME
PROGRAM.
IN ONE CASE WE HAVE A LOT OF
HISTORY ALREADY.
IT'S HISTORY IN ACTION AND WE
DON'T REALLY KNOW EXACTLY WHEN
THIS BEGAN EXACTLY BUT MAYBE
BEGAN, I THINK WE CAN SAY IN
2005 THAT'S THE PUBLICATION,
THAT'S THE BEGINNING.
WHERE IT WILL END AND WHETHER IT
WILL END IS ANOTHER QUESTION WE
WOULD LIKE TO DISCUSS A LITTLE
BIT LATER.
BUT LET ME GIVE YOU BECAUSE I'M
VERY MUCH INVOLVED LIKE SINCE 20
YEARS IN THE EXPOSOME PROGRAM
AND ISSUES BUT I HAVE WITNESSED
PART OF THE HUMAN GENOME
PROBLEM.
I WAS IN THE LAB WHERE MOST THE
ACTIVITIES WAS IN BIO CHEMISTRY.
MOSTLY ON RECEPTORS AND ENZYMES.
THE LAB WAS LED BY SOMEONE VERY
MUCH IN CONTACT WITH AMERICAN
COLLEAGUES INCLUDING NIH.
AND ONE OF THOSE COLLEAGUES WHO
VISITED OUR LAB A NUMBER OF TIME
CALLED CRAIG VANTER.
I KNOW A LITTLE OF THE HISTORY
OF THE GENOME PROGRAM THROUGH
MOSTLY CRAIG RATHER FROM FRANCIS
COLLINS AND HIS WIFE WAS
INVOLVED IN THE WORK AND WAS AT
THIS TIME AT THE NIH.
THIS IS SOMEBODY WITH WHOM WE
HAD REGULAR CONTEXT AS WE HAVE
IN SCIENCE.
GOING TO SIMILAR MEETINGS AND
DISCUSSING THINGS.
AT ONE POINT HE TOLD JACK, WELL,
HE IS TRYING TO GO INTO MORE
MOLECULAR BIOLOGY AND MAYBE
SEQUENCING ISSUES.
IN THE BEGINNING IT WAS MOSTLY
SEQUENCING NOT THE GENE.
CDNA IS THE MESSENGER RNA
EXPRESSED SO IT'S THE GENES
BASICALLY EXPRESSED.
BECAUSE IT WAS THOUGHT THAT THE
GENOME WAS FULL OF JUNK AND SO
IT'S JUST FOCUS AND IN THE LAB
WE STARTED DOING SOMETHING LIKE
THAT.
IT STARTED LIKE THAT AND I
DIDN'T FOLLOW EXACTLY THE
HISTORY BUT HAD SOME ISSUES WITH
THE NIH.
MAYBE MORE THAN SOME ISSUES.
AND DECIDED, IF I CAN'T DO IT AT
THE NIH, I'LL DO IT OUTSIDE THE
NIH.
FOR US, HE WAS AN ENTREPRENEUR.
HE WENT FOR IT AND HE FOUNDED
THIS COMPANY AT THIS BEGINNING
AND IT WAS THE IG ERA AND WE
KEPT IN TOUCH BECAUSE AS IT
HAPPENED MY BOSS WAS THEN AN
ADVISER FOR THE MINISTRY AND
ASKED HIM TO DEVELOP A HUMAN
GENOME PROJECT IN FRANCE.
SO HE KEPT IN TOUCH WITH CRAIG
AND THEN CRAIG SAID A FEW YEARS
LATER STARTED SAYING I'LL GO ALL
THE WAY FOR THE GENOME AND
COMPETING AND THE PRIVATE
PROGRAM STARTED.
AND WE KEPT IN TOUCH.
IT WAS A SURPRISE TO SEE FRANCIS
COLLINS AND CRAIG IN 2000
BECAUSE WE KNEW THE GUY.
AND IN FRANCE AT THE TIME I
THINK MOST OF THE SEQUENCING WAS
SOME MAPPING.
THAT WAS EXTREMELY USEFUL.
AND A LARGE NUMBER AND IT WAS
POSSIBLE THEN TO MAP THE GENES
PHYSICALLY AND HIS WAS ESSENTIAL
TO FULFILL THE SEQUENCING.
THERE WERE ACTIVITIES IN CDNA
AND SOME IN SEQUENCING 1
CHROMO
CHROMOSOME.
THE PROGRAM WAS AN INTERNATIONAL
ONE BECAUSE THE BRITISH WERE
THERE AND THERE WERE IMPORTANT
CONTRIBUTIONS.
AND IN FRANCE THERE WERE I THINK
AND MAPPING AND ESSENTIALLY AND
FOCUSSED LATER ON HOW THE GENES
ARE IMPORTANT AND THIS HAS BEEN
SUCCESSFUL.
IN FRANCE WE HAVE BEEN
SUCCESSFUL AND NOW SAYING IT'S
THIS REALLY MAPPING GENES
INVOLVED IN DISEASES AND
IDENTIFYING THEM.
IT DIDN'T END THERE.
I DID MY POSTDOC IN BALTIMORE IN
THE '80s, '85, SOMETHING LIKE
THAT.
AT THE TIME THE GENOME WAS
STARTING AND PEOPLE WERE
THINKING ABOUT IT AND HE
IDENTIFIED AND DISCOVERED THE
RESTRICTION SO IT'S IMPORTANT
FOR ANYBODY INVOLVED IN THE
GENE.
HE WAS A VERY NICE GUY.
I LOVED HIM.
AND WELL, I WORKED WITH HIM ON
BACTERIA BECAUSE I WANTED TO GET
INVOLVED IN MOLECULAR BIOLOGY
AND IT WAS THIS RESEARCH AND
MAYBE LESS THAN A FEW YEARS
LATER AT ONE POINT I DISCOVERED
HE DECIDED TO SHIFT COMPLETELY
AND TO JOIN THE NOBEL PRIZE TEAM
WORKING ON THE BACTERIA AND THE
ORGANISM FOR SEQUENCED AND I
HAVE SEEN.
MORE INVOLVEMENT IN SYNTHETIC
BIOLOGY AND PUBLISHING PAPERS IN
SCIENCE AND NATURE AT THE AGE 18
OR MORE ALL WITH CRAIG.
MY HISTORY OF THE HUMAN GENOME
PROJECT IS THE HISTORY ONCE OR
TWICE OR THREE TIMES THROUGH
CRAIG VENTER AND THROUGH THE
FRENCH.
AND THEN I CHANGED AROUND ENDED
UP IN THE EXPOSOME.
IT'S TIME TO LET SOME OF MY
COLLEAGUES GET THEIR OWN FEELING
ABOUT IT.
>> I CAN TELL A CRAIG VENTER
STORY TOO.
SO WHEN I WAS THE EDITOR OF
TOXICOLOGY SCIENCES HE WAS
SPEAKING AT AN ANNUAL MEETING
AND I ASKED IF I COULD INTERVIEW
HIM.
I READ STORIES AND THINGS ABOUT
IT AND REMEMBER TALKING TO HIM
LIKE BEFORE HE SPOKE THAT DAY
AND I TOLD HIM I HAD TRAINED WIN
MARK AND BOB AT DUKE THE
ADJUVANT RECEPTOR PEOPLE AND
STARTING MUMBLING UNDER HIS
BREATH.
HE SAID THAT'S A BIG REASON I
WAS DOING GENETICS BECAUSE EVERY
PAPER I WORKED ON BOB ALWAYS
BEAT ME TO IT AND GOT FRUSTRATED
AND SAID I BETTER WORK ON
SOMETHING ELSE.
WHEN I THINK ABOUT THE APPROACH
THAT VINTER TOOK TO THE HUMAN
GENOME PROJECT WE THINK ABOUT
WHAT WE WANT TO DO WITH
EXPOSOMICS AND PEOPLE THINK
ABOUT HOW EXPENSIVE IT IS AND
HOW IT'S TOO BIG OF AN EFFORT TO
DO, I KEEP THINKING ABOUT WELL,
IF VENTER COULD BUILD 300
SEQUENCERS WE COULD JUST GET 300
MASS SPECS AND THE IDEA IS IF
ENGINEERING CAN SOLVE PROBLEMS
AT SCALE AND CAN BE DONE IN A
BIO MEDICAL SPACE, I THINK IT'S
BEEN FOR ME I THINK THE EXAMPLES
OF WHAT WE SAW FOR THE HUMAN
GENOME PROJECT TO ME MAKE MUCH
OF WHAT WE'RE TRYING TO DO IN
EXPOSOMICS FEASIBLE BECAUSE IT'S
JUST A MATTER OF THINKING AT
THAT VERY HIGH LEVEL AND GEKT
THE RIGHT PEOPLE AT THE TABLE.
GETTING PEOPLE AT HAMILTON SMITH
TO DO THAT FOR YOU IN HIS '80s.
IT'S ALL IN THE MASS SPEC YOU
THINK?
>> I THINK A LOT OF THE EXPOSOME
AND HOW OR BODY RESPONDS TO THE
COMPLEX EXPOSURES RESIDES IN OUR
BODY AND BLOOD.
SO MASS SPECTOMETRY CAN DETECT A
LOT OF IT.
DOES IT CAPTURE ALL OF IT?
PROBABLY NOT BUT I CAPTURES A
LOT OF IT AND THE BETTER WE CAN
GET IT MEASURING THE THINGS IN
OUR BLOODSTREAM AND HOW OUR
BODIES RESPOND TO THE VARIOUS
EXPOSURES AT THIS POINT MASS
SPECTOMETRY IS I WOULD THINK IN
THE LEAD FROM A TECHNOLOGICAL
STANDPOINT IN HOW TO DO THAT.
>> I THINK YOU TOUCHED ON A
CHALLENGE ON WHAT WOULD BE A
HUMAN EXPOSOME PROGRAM.
TO MIRROR THE HUMAN GENOME
PROGRAM BECAUSE WE CAN MEASURE
SURROGATES IN BLOOD.
WE CAN MEASURE THE EXTERNAL
SOURCES THROUGH OTHER MEANS BUT
WE AS A COMMUNITY I THINK HAVE
OFTEN STRUGGLED IN COMING
TOGETHER TO ADDRESS WHAT YOU'RE
MORE COMFORTABLE WITH AND IF
YOU'RE MEASURING SOMETHING IN
BLOOD AND URINE YOU'RE MEASURING
SOMETHING NOW BUT WHAT HAPPENED
20 YEARS AGO?
WE HAVE SOME UNIQUE CHALLENGES
AS TRYING TO WRAP OUR HEAD
AROUND JUST WHAT WOULD THAT BE.
AGAIN, I AGREE WITH YOU, THEY
ARE SURMOUNTABLE CHALLENGES BUT
WE AS A COMMUNITY NEED TO COME
TOGETHER TO HAVE A CONSENSUS ON
THAT.
>> THIS IS HOW I STARTED INTO
THE EXPOSOMICS FIELD BECAUSE I
WAS TOO YOUNG TO BE IN THE HUMAN
GENOME AT THE TIME BUT I STARTED
WITH MASS SPECTOMETRY AND WAS
CLEARLY A TECHNOLOGY THAT COULD
HELP US TO GET COMPREHENSIVE IN
TERMS OF EXPOSURES AND MAP TO
CHEMICALS AND AFTER ALL THE
EXCITEMENT THEN YOU GIVE BLOOD
SAMPLE AND TRY MASS SPECTOMETRY.
THERE WAS FRUSTRATION WAS AT
THAT TIME, IT WAS 12 YEARS AGO,
THE INSTRUMENTS WEREN'T AS
SENSITIVE AS NOW AND WAS TRYING
TO GET FROM THE PAST
SPECTROMETRY AND AFTER THE
EXCITEMENT THERE WAS FRUSTRATION
AND GOING BACK TO YOUR POINT,
ACTUALLY, THIS IS CLEARLY WHERE
I STARTED TO THINK WE SHOULD
HAVE THIS SAME APPROACH FOR THE
HUMAN GENOME PROJECT.
WE SHOULD PROBABLY THINK ABOUT
THE METHODOLOGY AND SEE HOW WE
CAN GET THIS METHODOLOGY AS
COMPREHENSIVE AS POSSIBLE.
BUT THEM THE DIFFICULTY AND A
FEW HOURS WITH GARY IS WE NEED A
BALANCE BETWEEN HAVING SUCCESS
STORY MOVING TO THE WORLD AND
YOU CAN DO EXPOSOMIC WITH MASS
SPECTOMETRY AND GOING DEEPER IN
THE CHARACTERIZATION AND WE
DIDN'T FIND THE TIME YET TO GO
DEEPER AND I THINK THIS IS WHERE
SOMETHING MIGHT HAPPEN IN THAT
DIRECTION BUT WE NEED TO BE VERY
CAREFUL BECAUSE WE NEED TO PROVE
IT CAN WORK.
THE POINT I WANT TO MAKE IS THAT
IF THE METHODOLOGY IS NOT RIGHT,
WE MAY HAVE SOME BIAS.
WE MIGHT PROVIDE THOUSANDS OF
SAMPLES BUT DON'T GET THE
CORRECT EXPOSURE AND TO MAKE THE
RIGHT ASSOCIATIONS.
AND HIGH RESOLUTION MASS
SPECTOMETRY THOUGH WE DON'T KNOW
HOW TO DO THE ANNOTATION WE HAVE
MANY UNKNOWN LIKE WE ARE
ANNOTATING LIKE MAYBE 2% OF THE
DATA SETS.
SO, TO ME THIS IS DATA FOR THE
NEXT GENERATION.
IT WILL HAVE THE TECHNOLOGY AND
TOOLS TO PUT AN I.D. ON ALL THE
SIGNALS WE ARE GENERATING BUT WE
DON'T KNOW HOW TO DO IT.
SO I KIND OF HAVE A
RESPONSIBILITY TO LOOK AT THE
METHODOLOGY AND IF IT'S NOT
SENSITIVE ENOUGH, IF THEY WANT
IT GO BACK AND TIME AND SAY WE
ARE EXPOSED TO THAT CHEMICALS,
THERE MIGHT BE SENSITIVITY.
SO THERE'S THIS RESPONSIBILITY
AND WHERE WE LOOK AT THE GENOME
MAYBE AS A COMMUNITY BUT WE FEEL
THERE IS SOMETHING GOING ON AT
THE MOMENT BETWEEN U.S.-EUROPE.
>> SO YOU ARE THE NEXT
GENERATION AND YOU HAD THIS
PROBLEM BECAUSE YOU DIDN'T KNOW
THE GENOME PROGRAM AND NOW YOU
SEE THE EXPOSOME PROGRAM.
I THINK WHEN WE SEE WHAT
HAPPENED WITH THE GENOME
PROGRAM, THEY ARE STARTED BY
MAPPING THE GENES BECAUSE IT WAS
ESSENTIAL OTHERWISE THEY ARE
WOULDN'T HAVE BEEN ABLE TO VIEW
THE SEQUENCES THEY ARE WERE
GETTING.
THEY NEEDED TO MAP WHERE THE
GENES ARE ON WHICH CHROMOSOME,
ETCETERA.
IS THERE AN EQUIVALENT IN THE
EXPOSOME?
IS IT JUST GOING AFTER AND DOING
AS MUCH AS MASS SPECTOMETRY AS
POSSIBLE OR COMBINE ALL THE
TIME.
I KNOW YOU LIKE TO COMBINE THE
METABOLOMICS WITH EXPOSOMIC BUT
SHOULD WE COMBINE SOMETHING THAT
TELLS US ABOUT THE HISTORY LIKE
EXPOSOMICS AND START WITH RULES
SOMEWHERE TO THE EXPOSOME AND
GET INTO THE FULL ACTIVITY?
>> I THINK THERE ARE.
WE KNOW THE MAJOR FACTORS.
I WAS HAVING DINNER WITH A
COLLEGIATE A CONFERENCE LAST
WEEK AND SHE WAS NOT GOING
AGAINST THE EXPOSOME BUT SAYING
WHAT'S THE MAJOR THING PEOPLE
ARE EXPOSED TO WE DIDN'T KNOW
ABOUT?
WE PROBABLY KNOW THIS MAJOR
THINGS PEOPLE ARE EXPOSED TO.
WE CAN DO SCREENING AND MEASURE
THE 200, 500 THINGS THAT ARE THE
MAJOR CLASSES OF EXPOSURE AND
START TO THINK ABOUT WHAT IS THE
ENVIRONMENTAL EQUIVALENT OF A
HAT MAP AND LOOK AT THE
CORRELATION MATRIX OF
ENVIRONMENTAL EXPOSURE AND MAYBE
WE DON'T KNOW THE SPECIFIC
CHEMICAL BUT WE KNOW THE CLASS
OR KNOW THE BIOLOGICAL EFFECT
AND LOOK AT DESTRUCTION OR
METABOLIC DISRUPTION AS
BIOLOGICAL DRIVERS AND MEASURE
THE UNKNOWN FEATURES TO FIND OUT
WHAT THE CHEMICAL IS BECAUSE
THEY'RE ASSOCIATING WITH THE
CRITICAL BIOLOGICAL END POINTS
WE DON'T KNOW THE FACTORS
CONTRIBUTING TO PROGRESSION OR
SEVERITY OF DISEASE.
>> I WAS GOING TO POINT OUT THE
HOT MAP IS AN INTERESTING M
METAPHOR BECAUSE IT COULD
PROVIDE A MODEL FOR THE
DISCUSSIONS BECAUSE THE PURPOSE
HOT MAP WAS IN ESSENCE TO DESIGN
A PROGRAM TO LOOK AT HUMAN
VARIATION AND RELATIONSHIP TO
DISEASE AND ESSENTIALLY SAY THAT
IN LARGE PART A SIGNIFICANT
AMOUNT OF BASICALLY DISEASE
PHENOTYPE IS CAUSED BY
VARIATION.
FOR THE HAT MAP THERE WAS A
CLEAR UNDERSTANDING YOU ONLY HAD
A SPECIFIC SCIENTIFIC DESIGN
WITH A BASIC SCIENTIFIC QUESTION
TO ANSWER BASIC IDEAS ABOUT WHAT
IS THE CONNECTION, WHAT ARE
FUNDAMENTAL QUESTIONS IN GENETIC
EPIDEMIOLOGY BECAUSE WE KNEW
ENOUGH ABOUT EVOLUTION AND THE
DEGREE TO WHICH THERE WITH US
HUMAN GENETIC DIVERSITY ACROSS
POPULATIONS AND YOU GET A SENSE
WHAT QUESTIONS WE COULD ANSWER
AND WITH THE SPECIFIC AMOUNT OF
DATA OF WELL DESIGNED SCIENTIFIC
RATIONALE AND FIT TO THE DEGREE
EVERYTHING CAN GET FUNDED AND
COME TOGETHER TO ANSWER A
CERTAIN SET OF VERY SPECIFIC
QUESTIONS AND FROM THAT YOU GET
SOMETHING LIKE 1,000 GENOMES AND
ALL THE OTHER INQUIRIES TO
VARIATION, WHICH I THINK IF YOU
LOOK BACK AT THE COMMON DISEASE
AND COMMON VARIANT HYPOTHESIS,
IT'S ABSOLUTELY INCREDIBLY
USEFUL BUT ALSO SOMETHING
SUPPLEMENTED BY A GREAT DEAL OF
MORE DATA.
THAT'S WHAT I WANTED TO
CONTRIBUTE IN TERMS OF WHAT ARE
WHERE HE MEASURING, HOW DO WE
MEASURE IT AND HOW DO WE MAKE
SURE THE PROBLEM ISN'T TOO BIG
OR TOO SMALL.
>> ANOTHER COMPARISON WITH
GENETICS AND GENOMICS THAT'S
CRITICAL IS GENETICISTS DON'T
LIKE TO TALK ABOUT THE ERA OF
CANDIDATE GENE SEARCHS BECAUSE
IT DIDN'T TURN OUT VERY WELL.
WITH EXPOSOMICS IF YOU FOCUS ON
WHAT YOU THINK YOU KNOW IS OUT
THERE YOU RUN THE SAME RISK.
WHEN GENOME WIDE ASSOCIATION
STUDIES CAME ALONG IT GAVE AN
AGNOSTIC WAY OF DOING THIS AND
REMOVED THE BIAS OF THE
CANDIDATE GENE SEARCH AND
PUBLISHING THE POSITIVE DATA AND
EXPOSOMICS NEEDS AN APPROACH
WITH THE SAME LEVEL OF
SYSTEMATIC ANALYSIS TO AVOID
THAT LOOKING UNDER THE STREET
LAMP SITUATION.
>> IT'S FOR RARE DISEASES.
REALLY, I'VE BEEN WORKING IN A
HOSPITAL IN FRANCE WHERE THERE
WERE RARE DISEASES AND IT'S
FANTASTIC WHAT LHAPPENED THERE
BUT FOR COMPLEX DISEASES THERE
WAS GWAS AND THEN IDENTIFYING
THE VARIANTS IMPORTANT FOR
CHRONIC COMPLEX DISEASES.
IT DIDN'T ACHIEVE BECAUSE I
THINK IT WAS ALREADY TOO COMPLEX
FROM A GENETIC POINT OF VIEW AND
OTHERS THAT ARE IMPORTANT IN
THOSE DISEASES.
I LIKE THE DISCUSSION BECAUSE
IT'S GETTING TO THE DISEASE.
FROM THERE WE HAVE THE
RELATIONSHIP WITH TO THE GENOME
AND I WONDER WHETHER IN THE
EXPOSOMICS IF WE START WORKING
ON WHICH DISEASES ARE MORE
LIKELY TO BE THE BEST TO WORK ON
MAY BE WE'LL KNOW WHAT'S
ACHIEVABLE.
>> IT MAY BE A WHILE IN TALKING
ABOUT WHICH DISEASE WE COULD
STUDY.
THE DESIGN OF THE STUDY WAS GWAS
THIS IS A QUESTION I DON'T HAVE
THE ANSWER BUT FOR THE GWAS WE
HAVE SOMETHING THAT IS STATIC.
IT DOESN'T MOVE.
THAT'S THE SAME.
YOU CAN GET MORE PEOPLE HOW YOU
CAN HAVE AN ASSUMPTION AND GET A
LOT OF PEOPLE AND YOU TRY BUT
FOR EXPOSOMICS, I'M NOT THE SAME
GUY I'D BE TOMORROW.
THAT'S FOR SURE.
SO THERE ARE A LOT OF
CLASSIFICATION IF YOU DO EWAS
THE SAME WAY YOU DO GWAS.
I DON'T HAVE THE ANSWER BUT I
DON'T LIKE THE WAY
EPIDEMIOLOGICAL STUDIES ARE DONE
WITH JUST A SINGLE TIME POINT.
OF COURSE YOU HAVE SOME STUDIES
WHEN YOU LOOK AT DIFFERENT TIME
POINTS BUT YOU HAVE EXPOSURE
SPECIFICATIONS AS A QUICK
EXAMPLE FOR MANY CHEMICALS WE
LOOK AT HOW IT'S METABOLIZED
BECAUSE IT'S MORE CONSISTENT AND
IT'S GOING TO GO THROUGH
DIFFERENT ENZYMES AND FROM ONE
TO ANOTHER I HAD SOME
COMMUNICATION OR SOMETHING ELSE
I WOULD METABOLIZE DIFFERENTLY
AND IT WILL MAKE IT DIFFERENT
FROM ONE TO ANOTHER.
AND SO THERE ARE PEOPLE THAT ARE
TRYING TO ANSWER THIS.
IT'S VERY GOOD COMPARED TO JUST
A ONE SNAP SHOT BUT I DO THINK
THAT MAYBE WE NEED LESS PEOPLE
AND MORE HISTORY IN TERMS OF
LONGITUDINAL DATA BECAUSE WE
DON'T ADDRESS IN TERMS OF
CHEMISTRY.
WE DON'T ADDRESS VERY WELL THIS
EXPOSOMIC CLASSIFICATION.
IF WE'RE VERY LARGE I DON'T KNOW
IF IT'S GOOD ENOUGH BUT IT'S A
QUESTION THAT GWAS IS ASSOCIATE
WITH PHENOTYPE OR DISEASE WITH
SOME VARIATION IN THE GENOME AND
EWAS IS SOMETHING IN THE
ENVIRONMENT.
IT'S TRUE OUR ENVIRONMENT
CHANGES BUT IT SEEMS TO ME WE'RE
LOOKING FOR ALL THE GOOD REASONS
WHY IT WOULD NOT WORK AND NOT
THE REASONS WHY IT COULD WORK.
>> I THINK THERE ARE.
IT COMES BACK TO THE OTHER
CONVERSATION WE WERE HAVING AND
CHRIS, I WOULD LIKE TO GET YOUR
THOUGHTS ON THIS, WAS RATHER
THAN HAVING A FOCUS ON DISEASE
INITIALLY, LET'S HAVE A FOCUS ON
NORMAL AND CAN WE DEFINEDEFINE
BUILDING ON THE EXPOSOME AND CAN
WE FIND A REFERENCE BASELINE AND
VARIATION OF THAT EXPOSOME TO
START TO LAYER ON TOP OF THAT
THE PERTURBATION CONTRIBUTING TO
THE DISEASE STATE.
HOW IMPORTANT IS IT TO DEFINE
HEALTHY OR NORMAL BEFORE WE
START ASKING QUESTIONS ABOUT
DISEASE.
>> IT'S NOT TO THE EASIEST
QUESTION YOU'RE ASKING BUT ON
ONE HAND EXPOSOME CHANGES EVERY
DAY.
ON THE OTHER HAND, WE MENTIONED
EXPOSOME IS A HISTORY.
WE'RE NOT TODAY WHAT YESTERDAY'S
EXPOSOME TOLD US TO BE.
ALL THE YEARS WE LIVED THROUGH
ALL THE EXPOSURE WE HAD AND THIS
IS THERE'S A HISTORY THAT'S
IMPORTANT AND NOT EVERY DAY.
>> I'M OPTIMISTIC WE CAN DO IT.
THAT'S ALL TO EVERYTHING FROM
SCRATCH.
WE DON'T HAVE TO DO EVERYTHING
FROM THE GENOME AND IT'S A GOOD
POINT.
THE POINT ABOUT THE EXPOSOME
CONCEPT AND WE NEED TO
UNDERSTAND THE EXPOSURE.
THAT'S HOW WE SHOULD START
TRYING TO UNDERSTAND HOW IT IS
WITH NORMAL PEOPLE AND NOT
NECESSARILY AFFECTED BY A
DISEASE.
I'M OPTIMISTIC OF THE FACT WE
CAN DO IT AND IT'S A GOOD TIME
TO ASK THE QUESTION EVEN IF
DON'T HAVE THE ANSWER YET.
>> I ALWAYS ARGUED IF I WERE TO
WALK INTO MY DOCTOR TODAY,
THAT'S WHO I AM AT THAT POINT IN
TIME.
THE DOCTOR WILL TAKE BLOOD OUT
AND TAKE THE VIAL OF BLOOD BUT
THERE'S THINGS THAT COULD BE
MEASURED AND IF YOU COULD
COMPREHENSIVELY MEASURE ALL THE
SMALL MOLECULES, THERE HAS TO BE
USEFUL INFORMATION IN THERE.
IT DOESN'T CAPTURE ALL THE
HISTORY BUT CAPTURES WHAT I'M
DOING AT THAT ONE POINT IN TIME.
TO ME, IMPROVING OUR ABILITY TO
MEASURE AND INTERPRET THAT DATA
WILL END UP HAVING VALUE.
>> I AGREE.
I WAS ASKED RECENTLY TO GIVE A
TALK IN BUSSELS AND THE TOPIC
WAS HEALTH IN BRUSSELS IN 2050.
IT SEEMS COMPLEX, CLIMATE CHANGE
AND THINGS THAT WILL CHANGE BUT
IN FACT I THOUGHT IT WAS NOT SO
COMPLEX BECAUSE I TOLD THEM THAT
THE HEALTH IN 2050 IS NOW BEING
MORE OR LESS INFLUENCED BY ALL
THE EXPOSURES WE ALREADY HAVE
NOW.
BECAUSE FROM WHAT WE KNOW FROM
THE DEVELOPMENT AND ORIGIN OF
DISEASE, IT'S PART OF IT IS
THERE.
NOT ALL OF IT, OF COURSE, BUT IT
WASN'T AS DIFFICULT AS I THOUGHT
IT WAS INITIALLY.
I THINK YOU SAID YOU'RE NOT
DISMISSING AND I AGREE WE HAVE
TO BE SKEPTICAL ON SOME THINGS
AND BE CAREFUL AND THIS IS
SOMETHING WE HAVE TO LEARN FROM
THE GENOME PROGRAM BECAUSE WE
HAVE READ THINGS AND YESTERDAY I
WAS READING AGAIN BECAUSE I WAS
PREPARING THIS AND READING WHAT
PEOPLE SAID IN THE '90s AND
THERE WAS A COMMENT ON NEW
JERSEY HAVING SO MANY CHEMICAL
FACTORIES AND MAYBE CANCER -- I
DON'T KNOW HOW THAT WAS SAID AND
HE SAID IT'S NOT THE FACTORIES.
IT'S THE GENES.
SOMETHING LIKE THAT.
YOU UNDERSTAND ONCE YOU HAVE THE
GENES AND THIS WAS OVER
OPTIMISTIC IN STUDYING COMPLEX
DISEASES.
>> I HAVE A LOT OF THINGS TO SAY
ABOUT THAT.
WHAT'S INTERESTING IS THE DEGREE
TO WHICH I THINK THERE'S A LOT
OF ISSUES CIRCULATING AROUND
HERE.
ONE OF WHICH IS THE DISCOVERY OF
THE ENVIRONMENT BY THE HUMAN
GENOME PROJECT WAS I THINK
RATHER LATE.
YOU CAN'T HAVE ENVIRONMENT
STUDIES OF THE HUMAN GENOME WHEN
YOU'RE JUST ONE.
YOU HAD TO MOVE FROM AN
INDIVIDUAL OR CONSENSUS SEQUENCE
TO WHERE YOU'RE SEQUENCING
MULTIPLE GENOMES AT THE SAME
TIME.
I ALSO THINK THIS GOES BACK TO A
SIGNIFICANT ISSUE CAN ACTUALLY
THEN TRACE SPECIFIC PAPERS IN
THE HISTORY OF GENETICS WHERE
THERE'S A DISCOVERY OF
INCOMPLETE AND PARTIAL
PENETRANTS.
IT GOES TO THE BASIC QUESTION IN
MEDICAL GENETICS WHEN
INDIVIDUALS HAVE VARIATION OR
VARIATION THEY THINK WILL CAUSE
DISEASE, WHY IS IT THAT
INDIVIDUALS DON'T THEREFORE GET
IT OR DISPLAY CERTAIN FEATURES
OF SOME CONDITIONS AND NOT
OTHERS.
AND IT GOES BACK TO WHAT IS THE
DIFFERENCE BETWEEN GWAS AND
SOMETHING LIKE MENDELIAN
FRAMEWORKS AND THAT FOR ME IS
THE BIG CHUNK THAT'S AN
INTERESTING DISCUSSION AND A LOT
OF DISCUSSION AROUND GENETICS
AND DISEASES.
WE KNOW THAT LOTS OF THINGS
CORRELATE BUT THERE'S A DEGREE
TO WHICH THAT CAUSATIVE
FRAMEWORK IS ONE OF THE WAYS IN
WHICH YOU HAVE -- WHEN PEOPLE
LOOK AT GWAS METHODOLOGICALLY IS
THE DRAW BACK.
>> WHEN IT WAS SPOKEN ABOUT LOW
PENETRANTS, MOST OF THEM WERE
THINKING THERE ARE OTHER GENES
THAT INFLUENCE THIS.
I DIDN'T CONSIDER THE HISTORY OF
ENVIRONMENTAL PRESSURES OR
WHATEVER WAS THE EXPLANATION WHY
THE PENETRANTS WERE DIFFERENT.
MOST THE TIME THEY THOUGHT IT
WAS BECAUSE THE OTHER VARIATIONS
IN THE GENOME THAT WOULD ACCOUNT
FOR THIS AND THEY ARE DIDN'T GET
IT MANY GENES.
A LOT OF THE HUMAN GENOME
PROJECT WAS MODELLED ON THIS FEW
GENES OF GREAT EFFECT AND
THERE'S A LOT OF DISCUSSION IN
THE HISTORY OF GENETICS AROUND
MANY GENES OF SMALL EFFECT.
WHAT WE'RE LOOKING FOR IS THE
MIDDLE LAYER I THINK WOULD BE
INSTRUCTIVE.
>> I HAVE TO THE FEELING YOU
WERE TELLING US YOU WERE
INVENTING A NEW DISCIPLINE
TOGETHER.
THAT'S AN INTERESTING POINT IN
THE HISTORY OF SCIENCE AND
KNOWLEDGE AND I WOULD LIKE YOU
TO COME BACK AND WHAT WAS THE
CONNECTION BETWEEN YOUR ORIGINAL
TRAINING AND THIS NEW
DISCIPLINE.
HOW CAN YOU EXPLAIN HOW YOU
MOVED FROM SOMETHING WHICH I
SUPPOSE WAS A LITTLE BIT
COMFORTABLE TO THIS NEW FIELD
AND TELL US WHAT IN YOUR
DECISION WAS IMPORTANT AND HOW
IT'S A DISEASE.
>> I REMEMBER MY STORY.
25, 30 YEARS AGO I WAS STUDYING
ENVIRONMENTAL CONTRIBUTORS TO
PARKINSON'S DISEASE.
THERE WAS GOOD EVIDENCE
PESTICIDE EXPOSURE WAS RELATED
AND I KNEW THERE WERE HUNDREDS
OF PESTICIDES WITH SO MANY
CHEMICAL STRUCTURES AND USES AND
IT SEEMED FUTILE TO STUDY A
DISEASE BY LOOKING AT ONE
CHEMICAL AT A TIME.
AND WE WALKED AWAY FROM THE
ENVIRONMENTAL PIECE AND I HEARD
ABOUT THE CONCEPT OF THE
EXPOSOME AND THAT'S WHEN I SAID
I NEED TO HELP ESTABLISH THE
TOOLS TO DO EXPOSOMICS AND THE
TOOLS WERE NOT THERE YET.
>> I THINK MY STORY IS FAIRLY
SIMILAR TO GARY'S THOUGH
DIFFERENT MODEL SYSTEM.
I HAD THE ADVANTAGE OF BEING A
PROGRAM OFFICER AT NIH WHICH IS
A POSITION THAT GIVES YOU
FLEXIBILITY TO SAY THIS IS WHERE
SCIENCE IS TODAY.
BUT THIS IS WHERE SCIENCE NEEDS
TO BE IN THE FUTURE.
AND WHEN I STARTED AT NIEHS,
ACTUALLY, BEFORE CHRIS PUBLISHED
THE 2005 ARTICLE, I WAS ALREADY
FEELING THE FRUSTRATION GARY WAS
SAYING WE'RE IN THE EXPOSED TO
ONE THING AT ONE TIME IN ONE
SPACE.
WE'RE EXPOSED TO A VERY COMPLEX
ENVIRONMENT AND CAN WE DEVELOP
THE TECHNOLOGIES TO REALLY START
TO PUSH THIS FORWARD TO SAY,
RATHER THAN MEASURING AND EVEN
THEN WE WERE MEASURING A CLASS
OF CHEMICALS TOGETHER IN A
SINGLE PANEL BUT RATHER THAN
FOCUSSING ON THE ONE CLASS OF
CHEMICALS OR AN AIR POLLUTANT AT
ONE REGULATORY MONITOR CAN WE
DEVELOP A WEARABLE TECHNOLOGY TO
MEASURE AIR POLLUTION IN TIME,
IN SPACE.
SO, AS CHRIS WAS PUBLISHING THAT
ARTICLE, THAT RFA WAS ALREADY
BEING DRAFTED.
WE HAD BEEN ALREADY THINKING
ABOUT THAT AT NIEHS AND DEVELOP
THE TOOLS AND TECHNOLOGIES TO
START TO THINK ABOUT
ENVIRONMENTAL EXPOSURE AS A
SYSTEMS SCIENCE.
>> THAT WOULD BE QUICKER FOR
PLME.
I WAS DOING METABOLOMICS USING
INSTRUMENTS TO LOOK AT ALL THE
SMALL MOLECULES IN THE BODY AND
I WAS LOOKING AT EXPOSURE AND I
ALREADY I SAW THIS ALREADY AS A
WAY TO MAKE THE REVOLUTION AND
DOING CHEMICAL BY CHEMICAL.
WE'LL HAVE A GREAT OPPORTUNITY
TO DO IT AS A COMPLEX CHEMICAL
FINGERPRINT AND THAT'S HOW IT
STARTED.
IT WAS A TECHNOLOGICAL
REVOLUTION THAT LED ME TO DO
THAT.
>> THE NEED LIKE OFTEN IN
FRANCE, EVERYTHING CYCLES.
AND MAYBE ENDS.
BUT I WAS IN A LAB WHERE MOST OF
MY EFFORTS AT ONE POINT WERE HOW
SOME HORMONES INFLUENCE GENE
EXPRESSION AND I WORKED QUITE A
BIT ON INSULIN BECAUSE IF WE
KNEW HOW GLUCOCORTICOIDS HAD AN
EFFECT AND INSULIN BINDS TO THE
RECEPTOR AND SOMETHING HAPPENS.
BUT IT WAS A LAB WHERE THERE WAS
ALSO THE LIVER AND HEPATOLOGISTS
IN THE LAB AND I HAD A SIDE
PROJECT ON THE INFLUENCE OF
ALCOHOL ON GENE EXPRESSION AND
ENZYMES, ETCETERA.
IT WAS LIKE SOMETHING I KEPT
WORKING ON BUT NOT VERY
ACTIVELY.
AND THEN I REALIZED BASICALLY IN
THE HOME AND BUSINESS, A LOT WAS
ALREADY KNOWN.
A LOT IN THE FIELD WAS ALREADY
KNOWN.
AND THERE WAS MANY ISSUES.
IS IT METABOLISM OR OXIDATIVE
STRESS.
I DECIDED AT ONE POINT IT WAS
MAYBE AFTER HAVING WORKED IN
RESEARCH FOR MAYBE 15, 20 YEARS
I DECIDED THIS IS IT.
I'M GOING TO CHANGE THAT AND I
FOUND THAT ANYTHING TOXIC AND
THE BUSINESS I STARTED, I
STARTED LOOKING AT ENVIRONMENTAL
FACTORS BECAUSE I THOUGHT THERE
WERE LESS KNOWN FOR
ENVIRONMENTAL FACTORS AND
DECIDED TO MOVE TO A DIFFERENT
LAB TO BUILD MY TEAM AND LAB
MOSTLY ENVIRONMENTAL TOXICOLOGY.
I WORK ON THE BEST SYSTEM WHICH
IS HOW DIOXIDES WORK BUT NOTHING
BASICALLY WAS KNOWN AND EVEN IN
THE DIOXIN FIELD I WORKED
INITIALLY A LOT ON RECEPTOR AND
IT WAS BINDING AND USE
ADAPTATION TO THIS AND THEORY
RECEPTOR WAS FOUND TO BIND
METABOLITES AND THEN WE SHOWED
AND WORKED ON IT WAS ABLE TO
BIND THINGS IN OUR DIETS AND IT
WAS SHOWN IT WAS BOUND
METABOLITES COMING FROM THE
BACTERIA.
AND IT HAD IMMUNE FUNCTION THAT
WAS EXTRAORDINARY AND
PUBLICATIONS STARTED BEING IN
SCIENCE AND NATURE ONCE THE
IMMUNOLOGISTS GOT IN THE
BUSINESS.
WE WERE NOT ABLE TO DO MUCH
ABOUT THAT.
IT WAS THE EXPOSEOME AND THIS IS
REALLY CONVINCING TO SAY THAT WE
HAVE TO HAVE THIS BIG PICTURE.
EVEN FOR SI IT WILL RECEPTOR SO
WHAT ABOUT THE FULL BUSINESS?
THIS IS HOW I GOT MORE AND MORE
INTO THIS EXPOSOME BUSINESS.
>> IF I CAN CONTINUE ON THAT, I
UNDERSTAND VERY WELL THAT
EXPOSOME WAS THE KEY FOR YOUR
RESEARCH, YOU HAD DONE YOUR
RESEARCH AND TO CREATE A
COMMUNITY.
AND AT THE RISK OF BEING A
LITTLE BIT PROVOCATIVE IS
EXPOSOMIC AND MARKETING WORK TO
EXCHANGE WITH THE SOCIETY AND
GET FUNDING.
>> I CAN TELL YOU WORKING ON THE
EXPOSOME 10 YEARS AGO WAS NOT
THE WAY TO GET FUNDING.
IT'S GETTING BETTER BUT STILL A
CHALLENGE.
IF YOU COMPARE IT TO
ENVIRONMENTAL HEALTH SCIENCES
AND TOXICOLOGY, IT REQUIRES A
DIFFERENT TYPE OF THINKING.
IT'S NOT A MARKETING OF THE OLD
WAY OF DOING IT.
IT'S AGAIN THIS LIKE SYSTEMS
BIOLOGY LEVEL, COMPLEX SYSTEMS
LEVEL ANALYSIS OF THESE
EXPOSURES AND IT IS VERY
DIFFERENT BECAUSE THE PEOPLE
TRAINED AS ENVIRONMENTAL
EPIDEMIOLOGISTS OR EXPOSURE
ASSESSMENT PERSON ARE NOT
THINKING AT THIS LEVEL, LIKE
THIS MULTIOMIC LEVEL OF
ANALYSIS.
I THINK THE EXPOSOMICS
REPRESENTS A DIFFERENT
DISCIPLINE THAT REQUIRES LIKE
THAT CONSTELLATION OF BELIEFS
AND THOUGHTS THAT ARE VERY
DIFFERENT FROM WHAT WAS THERE
BEFORE.
>> I DON'T THINK THERE'S
ANYTHING WRONG WITH IT.
AT ONE POINT YOU CAN SAY IT'S
COMMUNICATION OR TRYING TO MAKE
WHAT WE DO UNDERSTANDABLE BY
PEOPLE WHO ARE NOT SPECIALISTS
AND PEOPLE GOT USED TO THE
GENOME.
WHY NOT CALL IT DNA?
AND IT'S THE COMPLEMENT OF THE
GENOME.
LET'S PUT IT UNDER THE BIG
UMBRELLA CALLED THE EXPOSOME AND
BROUGHT NEW THINKING AND IN
APPROACH IN ADDRESSING THE
EXPOSURE.
MUCH OF THE DISCUSSION HAS BEEN
MOSTLY ABOUT CHEMICALS BUT THE
EXPOSOME IS MUCH MORE AND EVEN
PEOPLE IN THE SOCIAL OR
PSYCHOSOCIAL BUSINESS ARE
INTERESTED IN THAT BECAUSE THERE
ARE MANY DIFFERENT SOCIAL
EXPOSURES THAT CAN INFLUENCE OUR
HEALTH AND WAY OF BEING AND
COLLECTING THOSE AS A WHOLE AND
NOT AND LOOKING AT WHAT HAPPENS
IN THE WORKPLACE OR AT HOME OR
IN RURAL AREAS.
GETTING A GLOBAL IDEA AND
LOOKING AT MAYBE STRESS YOU ARE
ALSO EXPOSED AT HOME AND IN THE
METRO.
HAVING THIS BIG PICTURE, I THINK
NEEDED A NEW NAME.
I THINK EXPOSOMICS ALLOWS TO GO
TO BIOLOGY TO BIOGRAPHY.
AND FROM MY PERSPECTIVE AS
SOMEONE WHO WORKS ON THE HISTORY
OF HUMAN AND POPULATION BUT
WORKS ON THE ETHICAL ISSUES THAT
A LOT OF THE ISSUES AROUND GOOD
MORNING DETERMINISM AND
ESSENTIALISM ARE
REALLY-INTERPRETED NICELY IN THE
CONTEXT OF EXPOSOMICS THINKING
ABOUT IRRITABILITY AND GENETICS
AS ONE OF MANY CHARACTERISTICS
OF HEALTH AND DISEASE RATHER
THAN THE TOTALITY OF A SPECIFIC
NUMBER AND THINKING OF IT RATHER
THAN SOMETHING STATIC THINKING
OF IT AS SOMETHING DYNAMIC.
IN THAT WAY IT GIVES A REAL
BASIS FOR HEALTH EDUCATION THAT
ALLOWS FOR US TO ALSO TALK ABOUT
IMPORTANT COMPLEX THINGS LIKE
PRECISION MEDICINE.
>> GOING BACK TO TOXICOLOGY AND
AND WE'RE SEEING THE EXPOSOME
THROUGH THE BIO MEDICAL PEAR
DIME.
WE HAVE OTHER DISEASE WE WANT TO
INFORMATION AND IT'S ESSENTIAL.
THERE'S OTHER WAYS I THINK.
AND HOW YOU ARE AGING WITH THE
EXPOSOME.
IT DOESN'T NECESSARILY MEAN YOU
ARE GOING TO GET SICK NOW BUT WE
CAN SEE THE CHEMICAL EXPOSOME AS
A WAY OF AN ALTERATION OF YOUR
ENVIRONMENT AND YOU HAVE TO
DEDICATE SOME BIOLOGICAL
RESOURCE TO DETOXIFY YOUR BODY.
EVEN IF YOU DON'T GET SICK
BECAUSE OF THIS IT'S EVERY DAY
YOU NEED TO GET OUT OF THIS
SYSTEM AND IT TAKES A LOT OF THE
SYSTEM AND MANY DIFFERENT THINGS
AND YOU CAN ACCUMULATE EXPOSURE
WHEN YOU HAVE SOME SOCIO
ECONOMIC PRESSURES THAT MAKE YOU
AGE DIFFERENTLY YOU THAN ANOTHER
PERSON.
INSTEAD OF SEEING THE DISEASES
WE SHOULD LOOK AT THE DISEASE
AND THE HEALTHY SYSTEM FROM AN
EVOLUT
EVOLUTION POINT OF VIEW IT'S
INTERESTING.
>> THAT'S AN YOU ARE CURRENT OF
PASCAL'S QUESTION WE PROBABLY
SHOULD ACKNOWLEDGE WHICH IS THE
CONCERN THAT THIS IS BUZZWORD
SCIENCE.
THE REALITY THE TERM WAS FIRST
COINED IN 2005.
THE SECOND PAPER THAT USED THE
TERM WAS PUBLISHED IN THE PAPER
FROM 2010.
WE'VE HAD 15 YEARS OF
PUBLICATIONS THE OVERWHELMING
MAJORITY OF WHICH ARE THIS IS
WHAT THE EXPOSOME IS AND FEW OF
THEM AND YOU'LL SEE MORE OF THEM
COMING OUT ARE ACTUALLY
DEMONSTRATIONS OF THE POTENTIAL
KNOWLEDGE THAT CAN BE GAINED BY
DOING THAT RESEARCH.
I THINK WE AS A COMMUNITY NEED
TO EMPHASIZE THE REALITIES OF
WHAT WE CAN DO TODAY TO AVOID
THOSE CONCERNS THAT THIS IS JUST
BUZZ WORD SCIENCE.
>> THE NEW THING IS THE TIME
DIMENS
DIMENSION WHICH WE DOESN'T
DISCUSS SO MUCH BEFORE EXCEPT
FOR THE HISTORY AND THIS IS
SPART OF THE DEFINITION IT'S NOT
ONLY THE MIXTURE OF OTHER TYPES
OF EXPOSURE BUT WITH TIME.
WITH THE POSSIBILITY IT'S NOT
ONLY ON ONE BUT MAYBE
GENERATIONS TO COME.
IT'S BEEN REALLY DIFFICULT
BECAUSE AT ONE POINT SOME PEOPLE
STARTED SAYING GENETIC
MODIFICATIONS COULD BE FROM ONE
GENERATION TO ANOTHER AND THIS
HAS SHOCKED SOME AND I'VE SEEN
REVIEWS SAYING THIS IS -- I WILL
NOT SAY THE WORD BUT IT'S NOT
REALLY EXCELLENT SCIENCE BECAUSE
EPIGENETICISTS BELIEVE THERE'S
AN ERASURE ON EVERY GENERATION
AND YOU DON'T KEEP THE MEMORY.
BUT THERE IS EVIDENCE THAT IS
CONTRADICTING THIS.
AND NOW WE ARE GETTING A LITTLE
BIT CLOSER.
THE CRITICISM ARE MILDER ON THIS
PART AND WHETHER IT'S EPIGENETIC
OR NOT BUT THIS MEANS WHAT WE
ARE EXPOSED TO MAY HAVE A
GENERATION ON THE FUTURE
GENERATION.
WHICH IS NOT EXACTLY THE EFFECT
ON NEXT GENERATION AND THIS IS
SOMETHING IMPORTANT WE SHOULD
KEEP IN MIND THAT WE ARE NOT
INHERITING ONLY WHAT IS IN OUR
GENE BUT WHAT IS INHERITING OUR
GENE.
IN MY OPINION, ONE WAY AROUND
WHEN WE THINK WHAT TO DO WITH
THE EXPOSOME AND HOW TO MAKE IT
MORE FRUITFUL IS TO ASSOCIATION
ALL THE TIMED EXPOSURE WITH
IMPACTS AND MAYBE EPIGENETICS
AND MAYBE OTHER IMPACTS ALL THE
TIME.
IT HAS TO BE ASSOCIATED
OTHERWISE WE WILL NOT GO VERY
FAR.
IT'S SOMETHING I BELIEVE VERY
MUCH BUT I DON'T KNOW WHAT YOU
THINK.
NOT NECESSARILY EVERYBODY
BELIEVE THAT.
WHEN WE SAID EXPOSOME WE THINK
EXPOSURES BUT NOT EXPOSURE AND
THEIR IMPACT AND THEIR IMPACT
OVER A LONG TIME.
>> MAYBE IT'S A MEET IN THE
MIDDLE.
WE DIDN'T DISCUSS THIS BUT
THAT'S WHAT THE EXPOSOME IS
PROVIDING THE BIOMARKERS BECAUSE
YOU HAVE A BLACK BOX AT THE
ENTRY AND EXPOSURE OF THE
DISEASE AND IF YOU DON'T
UNDERSTAND WHAT'S IN THE MIDDLE,
IT'S DIFFICULT TO MAKE THE
CONNECTION BETWEEN THE EXPOSOME.
HAVING THIS MAPPED OUT AND
GENETICS IS A WAY TOE HAVE AN
UNDERSTANDING OF HOW THE DISEASE
IS PROGRESSING.
THAT'S WHAT HE BROUGHT TO THE
FIELD WAS THE BIOMARKER AND THE
STATE.
YEAH.
>> I THINK FOR THE GENERAL
AUDIENCE MEMBERS HERE, MAYBE A
LITTLE BIT OF A DISCUSSION OF
WHAT'S THE DIFFERENCE OR
DISTINCTION AND INNOVATION IN
THE EXPOSOME VERSUS THE
ENVIRONMENTAL STUDIES AROUND
SINCE THE 1950s AND IT'S TWINS
REARED TOGETHER AND REARED A
PART.
IS THAT WE SHOULD MAKE SOME
DEFINITIVE STATEMENT AS TO
WHAT'S THE DIFFERENCE IN THE
ENVIRONMENTS AROUND SINCE THE
DAWN OF GENETICS VERSUS
EXPOSOMICS WHICH IS A SPECIFIC
NEW INNOVATION.
>> I HAVE SLIDES.
I USED TO USE SEVEN OR EIGHT,
NINE YEARS AGO WITH THE LEVEL OF
RESOLUTION FOR GENOMICS AND THE
E PART YOU HAD DOZENS OF THINGS
YOU MEASURED.
MAYBE THE NHANES ANALYSIS BUT
NOT THOUSANDS OR TEN THOUSANDS
OR A HUNDRED THOUSAND AND
EXPOSOMICS IS TRYING TO GET THE
LEVEL OF RESOLUTION FOR
GENETICS.
IT'S BIG G TIMES LITTLE E
HISTORICALLY.
THE E NEEDS TO BE THE SAME SIZE
AS THE G TO GET THE RIGHT
ANSWER.
YOU BUILD A DISCIPLINE.
COULD YOU TELL US WHEN YOU'VE
HAD THE FEELING TO REPORT THE
COMMUNITY IN YOUR PERSONAL
EVOLUTION.
>> IN 2012 I TAUGHT A COURSE IN
EXPOSOMICS AND REALIZED HOW
LITTLE THERE WAS OUT THERE.
FROM THE STANDPOINT OF A
SCIENTIFIC COMMUNITY THERE'S
LITTLE TO DRAW UPON WHICH
PROMPTED ME TO WRITE MY FIRST
BOOK ON IT BECAUSE THERE WAS
NOTHING THERE.
IN THE PROCESS OF DOING IT LIKE
YOU NEED A COMMUNITY TO CREATE
THIS FIELD SHIFTING ISSUE AND
THAT IS WHERE I STARTED THINKING
ABOUT HOW DO YOU BUILD THAT
COMMUNITY AND I THINK THIS IS
WHERE A LOT OF MY COLLABORATIONS
WITH PEOPLE IN EUROPE WERE ABOUT
BECAUSE THEY ARE WERE DOING MORE
OF THIS WORK.
AND I'D ARGUE THE INTERACTION
YOU AND I HAVE HAD HAVE REALLY
FORGED THAT CONNECTION BETWEEN
THE U.S. AND EUROPE, WHICH
STARTED WHEN I WAS A VISITING
PROFESSOR AT THE INVESTIGATOR OF
PARIS DESCARTES AND I'VE LEARNED
THEY CHANGE THE NAME OF
UNIVERSITIES FREQUENTLY.
IT WAS LIKE TRYING TO MAKE THOSE
CONNECTIONS BECAUSE YOU HAD TO
HAVE EVERYONE THAT WAS THINKING
ABOUT THE EXPOSOME CONTRIBUTE
BECAUSE IT WAS SUCH A NEW THING.
IT WAS TRYING TO REACH OUT AND
EXPAND THAT BECAUSE IT FELT
ISOLATING WHEN YOU WERE STUDYING
THIS THING COMPETING WITH THE
GENETICISTS AND CANCER BIOLO
BIOLOGISTS THAT HADN'T HEARD OF
THE TERM.
>> UNTIL 2011 I DON'T THINK I
HEARD OF THE EXPOSOME.
IN 2011 THE E.U. LAUNCHED A CALL
ON EXPOSOME.
THE COMMISSION.
THERE WERE ONE OF MANY PEOPLE
WHO TRIED TO WRITE AN
APPLICATION AND ONE OF THEM WAS
SOMEBODY FROM GREECE AND HE
CALLED ME AND HE SAID, I WANT
YOU TO BE IN THAT CALL.
I WAS AN ENVIRONMENTAL
TOXICOLOGIST KNOWN FOR DOING
WORK ON ENDOCRINE DISRUPTORS.
I WAS A TOXICOLOGIST.
AT THAT TIME, TWO OF THE
APPLICATIONS WERE SUCCESSFUL.
NOT OURS BUT THE ERAFTER 2012
WAS SUCCESSFUL.
AND THERE WERE LIKE THREE BIG
PROGRAMS IN THE E.U. ON THE
EXPOSOME.
I THINK I WAS THE ONLY
TOXICOLOGIST AMONG THE THREE
PROGRAMS.
IT'S MOSTLY AN EPIDEMIOLOGIST OF
EXPOSURE SCIENTISTS AND
ANALYTICAL SCIENTIST AND
TOXICOLOGISTS, THEY ARE DIDN'T
BELIEVE THEY SHOULD.
BUT GARY IS A TOXICOLOGIST.
THAT'S WHEN I THOUGHT TOXICOLOGY
HAS A PLACE AND I AM GRATEFUL
BECAUSE HE'SI HE'S A COMPUTER
PERSON.
HE LIKES COMPUTERS AND TO DO
THIS ACTUALLY THERE WAS
INFORMATICS PERSON AND BRINGS
MODELS.
YOU THINK HE HAD THIS VISION.
I'M NOT SAYING OUR PROGRAM WAS
MOST SUCCESS.
.
OTHER PROGRAMS WERE MORE
SUCCESSFUL AND I CONTRIBUTED FOR
MANY REASONS.
THEY INCLUDE PEOPLE NOT IN THE
OTHER PROGRAM AND SUDDENLY I
FELL THIS IS ALSO MY HOME.
>> WE HAVE TO ACKNOWLEDGE A BIG
ROLE TO CREATE THIS COMMUNITY IN
FRANCE.
AND IT TAKES WORK TO DO THIS IN
THE U.S. AND THEN IT'S A BALANCE
BETWEEN HOW MUCH I'M GOING TO
INVEST.
THAT'S A BIG ROLE.
IN FRANCE WE HAVE AN OPPORTUNITY
AND TO ME IT WAS WHEN THEY SAID
YOU SHOULD BE PART OF THIS OR
SHOULD DOUGH THAT.
YOU FEEL LIKE YOU ARE PART OF
SOMETHING.
TO BRING PEOPLE AROUND THE TABLE
MANY WE CAN SURE AND PROSECUTE.
I HAVE TO HAVE PEOPLE THAT TA
YOU CAN THIS LEAD.
AND THIS IS WHERE IT STARTS TO
CONVINCE THE PEOPLE THEY HAVE
THE OPEN FIELD TO DO THE
RESEARCH.
>> I THINK THAT PART OF MY
APPROACH TO LIFE IS I'M A PRETTY
START AND CAPABLE PERSON BUT ALL
THE PEOPLE I WORK WITH ARE ALSO
PRETTY SMART AND PRETTY CAPABLE
PEOPLE.
WHEN WE COMBINE OUR TALENT, THE
PRODUCT WHERE HE DEVELOP IS
GOING TO BE BETTER THAN WE WOULD
DO INDIVIDUALLY.
EVERYTHING I DO IS PART MUCH A
COMMUNITY.
I STRIVE TO BE PART OF A
COMMUNITY.
THE OTHER THING THAT'S TRUE IN
AN EXPLO
AN EXPOSOME IT'S A BIG AUDACIOUS
GOAL NO ONE WOULD BE ABLE TO DO
THIS THEMSELVES.
IT'S GOING TO REQUIRE EVERYBODY
TO COME TOGETHER AND WORK IN
PARTNERSHIP.
IT'S GOING TO TAKE A GLOBAL
PROGRAM IN ORDER TO BE ABLE TO
ACTUALLY MAKE SENSE OF WHAT
WE'RE DOING.
THERE'S AN INFINITE NUMBER OF
VARIABLES HERE INFINATELY
DYNAMIC AND THE ONLY WAY WE'LL
BE ABLE TOE ANSWER THE
QUESTIONS.
>> YOU ANTICIPATED MY NEXT WHY
IT US WITH SO TRANS-ATLANTIC IN
A WAY.
IT'S NOT SO OBVIOUS IN THE STORY
OF SIEBS A NEW DISCIPLINE IS
WE --
OF SCIENCE IS A NEW DISCIPLINE.
>> TO BE HONEST THE COMMISSION
WAS GOOD AT THAT.
I THINK THE LAUNCHED THE
EXPOSOME CALLS RELATIVELY EARLY.
2005 NOTHING FOR SEVERAL YEARS
AND 2010 APROPOS AND THEN IN
2011 THERE WAS A CALL FROM THE
COMMISSION SAYING WELL, WE NEED
TO HAVE A PROGRAM.
SOMETIMES WE -- IN THIS CASE
THEY DID WELL.
DO YOU KNOW WHICH SCIENTIST
PROPOSED THAT TO THE COMMISSION?
USUALLY THERE ARE TRACKS TO BE
AT THE ORIGINAL CAUSE.
>> I'M NOT SURE, I TEND TO
BELIEVE SCIENTISTS THAT WERE
MOSTLY EPIDEMIOLOGIST WERE
COHORTS AND SUDDENLY THEY ARE
WERE OFFERED TO LEARN MORE ONE
THE SAME SAMPLE AND THEN
SUDDENLY IT WAS POSSIBLE TO TEST
MANY MORE.
I'M NOT SURE EXACTLY.
I WASN'T INVOLVED AT THAT PERIOD
EXACTLY.
>> AT THE TIME CHRIS WAS THE
DIRECTOR OF IARC.
HE'S NOW IN A HIGH LEVEL
POSITION THAT HAS MRAERJ
INFLUENCE THROUGHOUT THE WORLD.
I SUSPECT HE MUST HAVE HAD SOME
INFLUENCE OWN THE COMMISSION'S
DECISION.
>> YOU'RE RIGHT.
I BELIEVE PEOPLE HAD MIGHT
SUGGESTED THIS AND THEY ARE WERE
IN THE COMMISSION IN THE JRC AND
THEY LEFT THE JRC TO LISTEN TO
WHAT WAS HAPPENING IN THE FIELD.
I THINK HE ALSO PLAYED A ROLE IN
THAT.
>> I ALSO WANT TO UNDERSCORE A
LITTLE BIT.
I AGREE WITH YOU.
THERE WERE SIGNIFICANT RESOURCES
INTO EUROPEAN EXPOSOME COMMUNITY
TOGETHER AS BE AN ACTIVE
COMMUNITY AND INTEGRATING THE
EXISTI IING EPIDEMIOLOGICAL STUS
GOING ON IN THE MIDDLE.
THERE'S ANOTHER MEAT IN THE
MIDDLE PIECE OF THE EXPOSOME, IN
THE UNITED STATES WAS MORE ON
BUILD THE CAPACITY.
LET'S BUILD THE CAPABILITY TO DO
THE WEARABLE SENSING AND HIGH
RES MASS SPECT AND LOOK AT NO
CHEMICAL THAT UNDER LIES THAT
UNKNOWN FEATURE.
MOST OF THOSE PROGRAMS WE'VE
DEVELOPED HAVE NOT BEEN BRANDED
AS EXPOSOME ACTIVITIES BUT
ABSOLUTELY ARE EXPOSOME
ACTIVITIES THAT ARE BUILDING THE
CAPACITY AND NOW WE'RE STARTING
TO BUILD THAT INTERNATIONAL
CONNECTION BETWEEN WHAT WE'RE
DOING AND WHAT EUROPE IS DOING
AND MAYBE THE RESEARCH
INFRASTRUCTURE PROGRAM TO
MAXIMIZE THE TECHNOLOGICAL
DEVELOPMENTS WE BUILT HERE.
>> I AGREE.
I THINK IN THE UNITED STATES
THERE WAS HER CULESE AND
BUILDING CAPACITY AND IN EUROPE
IT WAS PROJECTS MOSTLY.
AND THE CAPACITY CAME AFTER.
I REALLY WAS PRESENT IN THE
BUILDING OF IRENE.
IT WAS NOT SO EASY TO BUILD.
EVEN IN FRANCE, THE
INFRASTRUCTURE WHERE YOU ASSAY
THE MEASURE TOGETHER AND WE LAD
TO GO TO THE MINISTRY A NUMBER
OF TYPES.
AND SOMETIMES YOU HAVE PEOPLE IN
FRONT OF YOU.
AT ONE POINT ONE OF THEM ASKED
ME SO, IT'S RAUL -- ALL
INFORMATICS THEN AND, NO.
YOU NEED INFORMATICS TO
INTERPRET.
THEY DIDN'T UNDERSTAND.
IT WAS A TOUGH ONE.
THE INFRASTRUCTURE STARTED IN
THE U.S. BUT WE CAME AFTER.
THE PROJECT STARTED AND THERE
WERE MORE STRUCTURED PROJECTS.
IT CAME UP TO A GOOD
INTERACTION.
>> THE ONE COMMENT ABOUT THE
E.U.'S INVESTMENT IN THIS ONE
WAS I THINK THE LARGE EXPOSOMICS
DID WAS INSPIRE TRAINEES TO
PURSUE THAT DISCIPLINE.
THERE'S SO MANY MORE PEOPLE
THINKING ABOUT IT ON THAT SIDE,
THE JUNIOR SCIENTIST TO SOLVE
THE FUTURE PROBLEMS IN THE
U.S. WE'RE FURTHER BEHIND IN
PEOPLE WANTING TO GO IN THE
FIELD BECAUSE THEY ARE CAN'T SEE
IT AS A FIELD.
>> ONE PERSON IS FROM FINLAND.
IT'S DIFFICULT TO PRONOUNCE HIS
LAST FLAME.
HE WAS EFFICIENT AND KNEW
EVERYBODY IN THE FIELD.
I KNEW HIM AFTER THAT AND I
THINK HE WAS THE EARS THAT
LISTENED TO WHAT WAS SAID AND
DID HIS JOB.
>> WE WERE USING THE
PRESENTATION AND THE PEOPLE
DOING METABOLOMICS AND THAT'S
HOW WE HAD TO MAKE THE FIELD
EVOLVE WITH DEFINITION OF WHAT
WE WERE DOING AND WHAT THEY WERE
DOING AND YOU DIDN'T HAVE THE
PROGRAM IN THE U.S. I SOME THING
STARTING TO DRIFT.
FOR YOU IT'S NORMAL TO MEASURE
AND I USED TO USE THE DEFINITION
THAT METABOLOMICS CAN SEE
EVERYTHING.
PUT IN FRANCE WE HAD TO SAY FROM
INSTRUMENTATION TO METABOLOMICS
AND IT WAS DIFFICULT TO BE
UNDERSTAND AND TO EXPLAIN WHY WE
WANTED TO BUILD SOMETHING
DIFFERENT.
IT WAS AT THE END IMPORTANT.
THE EXPOSURE QUESTION WERE IN
THE METABOLOMICS BECAUSE WITH
METABOLOMICS YOU CAN --
>> I'M LEADING THE METABOLOMICS
AND DURBE --
-- METABOLOMICS I THINK WE
SHOULD KEEP THAT.
>> I WOULD LIKE TO ASK YOU
ANOTHER QUESTION MORE OPEN.
DO YOU THINK THAT A SCIENTIST
ENGAGED IN EXPOSOMICS IS
PERSONALLY MORE OPEN TO SOCIETY
THAN OTHER KIND OF RESEARCHER IN
BIOMEDICAL RESEARCH?
YOU MENTIONED A CONNECTION
BETWEEN HUMANITIES AND SOCIAL
SCIENCE AND DISCIPLINE.
DO YOU THINK IT'S YOUR OWN
EXPERIMENT YOU FEEL MUCH MORE
OPEN TO THE IMPACT OF SCIENCE
AND SOCIETY AND DON'T KNOW WHERE
SOCIETY WILL GO AND THINGS LIKE
THAT.
>> I WOULD THINK IF YOU LOOK AT
THE UNITED STATES AND SCHOOLS OF
MEDICINE AND SCHOOLS OF PUBLIC
HEALTH, YOU SEE A LOT MORE OF
THE EXPOSOMICS ON THE SCHOOL OF
PUBLIC HEALTH SIDE AND THEY ARE
MORE OF A POPULATION SOCIETAL
IMPACT.
WHEN I REACHED OUT TO PEOPLE TO
COLLABORATE, OFTEN THEY'RE
TRYING TO FIGURE OUT WHERE
THERE'S DESPAIRATE -- DISPARATE
POPULATIONS AND YOU SEE PEOPLE
MORE INTERESTED IN THE SOCIETAL
IMPACTS.
>> I THINK BUT TO MODULATE A
LITTLE BIT IT DEPENDS ON WHICH
HUM
HUMAN DISEASE YOU'RE TALKING
ABOUT.
THERE ARE THOSE THAT REFLECTED
ON THE ETHICAL FIELDS RELATED TO
THE GENOME AND SHOULD WE DO AND
KNOW THE SEQUENCES.
AND THIS PART OF HUMANITY THE
ONLY ETHICAL PART IS WITH
GENOMICS AND SOCIAL
CHARACTERISTICS ARE PART OF THE
EXPOSOME OR THE DETERMINATES OF
THE EXPOSURES WE HAVE.
WE'RE INTERESTED AND WHEN YOU
LOOK AT THOSE THAT ARE RICHER,
THERE ARE A BIG DIFFERENCE ON
THE EXPOSURE AND CONSEQUENCE.
WE NEED TO GET INVOLVED IN THAT.
>> I WILL LOOK AT THE SYSTEMIC
CONNECTION AND ENGAGE IN YOUR
OWN RESEARCH IN TERMS OF
HISTORY.
>> PLAY I ASK A DETAILED
QUESTION.
IN YOUR VIEW WHAT IS THE
DIFFERENCE BETWEEN EXPOSOMICS
THAT LOOKS AT SES AND SOCIAL AND
BEHAVIORAL GENOMICS?
THERE'S A LOT OF WORK THAT TRIES
TO TIE THE USE OF GWAS STUDIES
AND OTHER THINGS AND SAYING
SPECIFIC VARIANTS TO
OCCUPATIONAL AND EDUCATIONAL
ATTAINMENT.
IS THAT PART OF EXPOSOMICS OR IS
THAT A DIFFERENT FIELD AND TO
MAKE THE QUESTION SHARPER, HOW
DO YOU INTERACT WITH THAT SIDE
OF THE FIELD OR HOW WOULD YOU
WANT TO INTERACT WITH THAT SIDE
OF THE FIELD IN MOVING FORWARD
IN THE FUTURE?
TO THEO THOSE PEOPLE ARE
FOCUSSING ON GENOMICS AND
EVERYTHING IS THE INTERACTION
BETWEEN GENOME AND THE EXPOSOME.
EVEN THOSE RELATIVELY COMPLEX
SOCIETAL OR SOCIAL ISSUES ARE
MAYBE THE CONSEQUENCE OF AN
INTERACTION BETWEEN SOMETHING
HAPPENING IN THE GENOME AND
EXPOSOME AND THE RELATIVE WEIGHT
OF EACH IS NOT ALWAYS SOMETHING
THAT YOU COULD DECIDE LIKE THIS
SO WE HAVE -- WE WERE DISCUSSING
THIS EARLIER THIS MORNING.
THERE IS A VERY GOOD REASONS TO
COLLABORATE STRONGLY WITH
GENETICISTS AND INCLUDING IN THE
FIELD YOU MENTIONED WE HAVE TO
WORK WITH THEM.
>> ONE OF THE MORE EXCITING
PROJECTS I'M INVOLVED WITH IS A
CANCER GRANT CHALLENGE PROJECT
WHERE THERE'S A PACKAGE ON THE
SOCIAL DETERMINATES OF HEALTH
AND WORK PACKAGE ON THE GENETICS
AND TUMOR BIOLOGY AND
EXPOSOMICS.
THIS IS A PLACE TO START WORKING
WITH THE SOCIAL EPIDEMIOLOGIST
AND SCIENTISTS TO CONNECT THAT
TO HOW IT MAY CONNECT TO THE
BIOLOGY.
THAT'S NOT AN EASY TEAM TO BRING
TOGETHER.
AND IT TOOK A LOT TO BE ABLE TO
DO THAT BECAUSE TYPICALLY YOU
DON'T SEE THOSE COLLABORATIONS
ACROSS THE SOCIAL SCIENCES DOWN
TO THE GENETICS AN IN BETWEEN.
WE NEED MORE OF THOSE PROJECTS
THAT BRING TOGETHER MULTIPLE
DISCIPLINES IF YOU WANT TO
UNDERSTAND THE SOCIAL,
ENVIRONMENTAL AND GENETIC
DETERMINATANTES OF AN OUTCOME.
>> THE ONE DISCIPLINE I'VE NOT
HEARD MENTIONED IN THE LAST 90
MINUTES IS ECONOMICS.
THAT'S PRECISELY TO MY POINT OF
PEOPLE TRYING TO ATTACK FROM A
VARIETY OF ANGLES.
MAYBE ONE OF OUR WORKING
METHODOLOGIES IS TO GET
EVERYBODY IN THE ROOM TOGETHER
AND SAY WHAT HAVE YOU FOUND OUT
AND WORK FROM THERE ACROSS A
VARIETY OF GROUPS.
>> HISTORIANS HAVE BEEN USEFUL
FOR THE FUTURE AND NOW YOUR
DISCIPLINE CONNECTED TO A.I.
DO YOU THINK THAT COULD CHANGE
THINGS?
>> SO, I THINK THAT'S THE ANSWER
TO CHRIS'S QUESTION.
HOW DO WE ASSESS THE SOCIAL
ENVIRONMENT.
WE ASSESS THE SOCIAL ENVIRONMENT
THROUGH THE GEOSPATIAL DATABASES
CAPTURING COMMUNITY DEMOGRAPHIC
INFORMATION.
IF WE WANT TO INTEGRATE THAT
WITH MASS SPEC ON A COMPLETELY
DIFFERENT TEMPORAL AND
BIOLOGICAL SCALE, I THINK WE
NEED TO LEVERAGE THE POTENTIAL
OF MULTI-MODAL A LOT OF TO BE
ABLE TO FEED THAT INTO AN
ALGORITHM THAT SAYS THESE ARE
THE DRIVERS BECAUSE THEY'RE NOT
INDEPENDENT DRIVERS BUT THEY ARE
ALL CONTRIBUTING IN DIFFERENT
WAYS.
I THINK IT'S ACTUALLY CRITICAL
FOR US.
>> WHEN YOU GENERATE THE DATA
FOR MASS SPECTOMETRY YOU DON'T
KNOW WHAT IT IS AND CAN USE
MACHINE LEARNING FOR WHAT YOU
ARE GENERATING AND PROVIDE THE
RIGHT SET BECAUSE YOU NEED A LOT
OF DATA TO TRAIN THE MODELS.
SO WE'RE ALREADY DOING THIS.
IN TERMS OF UNDERSTANDING THEN
HOW THE EXPOSURE WORK TOGETHER
TO EXPLAIN AN EFFECT YOU CAN USE
MACHINE LEARNING MODELS BUT YOU
NEED TO DO DATA REDUCTION.
IT'S VERY DIFFICULT TO INTEGRATE
AND HAVE STEPS TO MAKE
PREDICTION.
>> IF YOU TAKE FROM THE CHEMICAL
POINT OF VIEW WE TO THE ABOUT A
FEW HUNDRED CHEMICALS AND
EXPOSURE AND EFFECT.
THERE'S MANY MORE.
THERE'S NO WAY YOU DO ALL THE
WORK WE'VE DONE IN THE FIRST 500
WE DO IT ON THE THOUSANDS OR
OTHERS.
THAT'S WHERE A.I. WOULD BE
EXTREMELY I THINK HELPFUL IN THE
FUTURE AND INDISPENSABLE.
IF YOU WANT TO KNOW MORE YOU
HAVE TO PREDICT.
>> FOR ME IN EXPOSOMICS I SPEND
TIME TRYING TO RECRUIT PEOPLE TO
HELP SOLVE OUR PROBLEMS.
SOME OF THAT IS TRYING TO STEAL
STATISTICAL GENETICISTS TO HELP
TACKLE OUR PROBLEMS.
IN THE LAST COUPLE WEEKS I'VE
TALKED TO AWS AND GOOGLE AND
INTEL.
RIGHT NOW IN THE A.I. FIELD THE
FINANCE SECTOR AND CYBER
SECURITY ARE GETTING THE TALENT
HOW DO WE GET THEM TO THE
BIOMEDICAL SIDE AND EXPOSOME
SIDE?
IT WILL BE CRITICAL TO SOLVE
THESE THINGS BUT WE HAVE TO
ATTRACT THEM TO OUR PROBLEMS.
I THINK WHEN YOU TALK ABOUT THE
COMPLEXITY, THE TEMPORAL -- WHAT
INFINITY YOU USE A COUPLE TIMES
ARE THE PROBLEMS PEOPLE IN A.I.
WANT TO WORK ON SO WE GIJUST HA
TO GET THEM TO DO THAT.
>> IN THE LAST MINUTE WE HAVE,
CONSIDERING WHAT COULD BE THE
THING YOU WOULD LIKE TO CHANGE
FOR THE FUTURE IN TERMS OF
ORGANIZATION OF RESEARCH IN
TERMS OF INTERCONNECTION BETWEEN
THE TECHNOLOGY, PRECISION AND
FUNDING.
>> I'M GOING TO TALK TO MY
COLLEAGUE ON THE LEFT.
NIEHS HAD JUST GONE THROUGH A
STRATEGIC PLANNING ACTIVITY.
AND OUR INSTITUTE DIRECTOR
CHALLENGED OUR ADVISORY COUNCIL
TO COME UP WITH BOLD PREDICTIONS
TAKING THE HUMAN GENOME MODEL OF
IF WE'RE SUCCESSFUL IN
IMPLEMENTING OUR STRATEGIC PLAN,
UP WITH OF THE ELEMENTS IS THE
EXPOSOME, HOW WILL THE WORLD
BEING DIFFERENT IN FIVE TO 10
YEARS THAN IT IS TODAY.
WHEN DR. MILLER WAS ASKED TO
COME UP ONE A BOLD PREDICTION,
SAID IN FIVE TO 10 YEARS, WHAT
HE WAS SAYING EARLIER, WHEN YOU
GO FOR YOUR ANNUAL CHECK UP WITH
YOUR PRIMARY CARE PHYSICIAN,
THEY DO A BLOOD DRAW AND GET
200, 500,000 EXPOSURES AND FEED
IT INTO AN A.I. ALGORITHM WHICH
SPITS OUT THESE ARE THE THINGS
YOU NEED TO BE CONCERNED ABOUT
AND ADDITIONAL TESTS WE NEED TO
BE RUNNING FOR THE INTERVENTIONS
WE NEED AND BEHAVIORAL INT
INTERVENTIONS TO IMPROVE YOUR
HEALTH AND WELL BEING.
THE PREDICT IS ONE THAT WE'RE ON
THE CUSP OF GETTING THERE.
I THINK WE'LL MAKE SUCCESS IN
THE NEXT FEW YEARS.
>> THAT PREDICTION, WHICH WE PUT
ON THE TABLE, ERIC GREENE HAD
TALKED ABOUT HOW THE HUMAN
GENOME PROJECT LED TO GENETIC
MEDICINE AND IT WAS LIKE, WELL,
THAT TOOK A LONG TIME.
THE FACT HE WAS LIKE WE'RE THERE
NOW AND HAVE GENOMIC MEDICINE
AND IF YOU HAVE THAT, WHY CAN'T
EXPRESS EXPOSOMICS DO THE SAME
THING?
>> YOU HAVE ALREADY ACHIEVED
SOMETHING.
THIS WOULD BE A MARKER.
THIS MY STRUCTURE TO A CERTAIN
EXTENT -- I AGREE THERE'S MANY
OTHER ISSUES NOT CLINICALLY
RELATED BUT THIS CAN STRUCTURE
AT LEAST SOME PART OF THE
PROGRAM WE'RE BUILDING.
BECAUSE IT'S REALLY COMPLEX.
MORE COMPLEX THAN THE GENOME.
WE HAVE TO HAVE SOME REDUCTION
IN THE COMPLEXITY.
AND THE EASIEST WAY IS TO START
FROM THE DISEASE OR SOME ISSUES
LIKE AGING AND THEN GO BACK AND
SEE HOW THE EXPOSOME COULD HELP.
THAT WOULD BE I THINK REALLY
FANTASTIC FOR EVERYBODY.
THAT'S WHERE A.I. COULD BE CAN
HELPFUL.
YOU GO TO THE DOCTOR AND MAYBE
HE'LL DRAW BLOOD BUT YOU CAN
GIVE YOUR ADDRESS TO HAVE A
GEOSPATIAL INFORMATION AND GIVE
HIM SOME PREVIOUS PATHOLOGIES.
WHAT'S YOUR WORK AND HOW MUCH DO
YOU EXERCISE AND THEN SAY YOU'RE
FINE OR OKAY, I'M GOING TO TAKE
BLOOD AND MAYBE MAKE A MORE
COMPLEX DETERMINATION OF WHAT
YOU HAVE OR A BOLDER APPROACH.
>> TO ME, I WISH WE HAD MORE
MOMENT FOR THE INITIAL QUESTION
ON THE OF EXPOSURE BECAUSE IT'S
DIFFICULT TO GET MONEY IF IT'S
NOT HEALTH RELATED BUT A LOT OF
QUESTIONS WE COULD ANSWER JUST
ON UNDERSTANDING THE EXPOSURE
AND COULD GET INFORMATION AND
HOW THEY GET EXPOSED.
JUST FOR THE QUESTION OF
EXPOSURE WOULD BE GREAT.
HAVE THEY SHUT US DOWN OR DO WE
HAVE A FEW MORE MINUTES?
OKAY.
CHRIS, DID YOU WANT TO SAY A FEW
CONCLUDING WORDS AND I'LL THANK
EVERYBODY.
I'LL CONCLUDE BUT IF YOU WOULD
LIKE TO SAY A FEW MORE WORDS
BEFORE I CONCLUDE.
>> I THINK ONE OF THE MOST
INTERESTING QUESTIONS FOR ME AND
MOST INTERESTING STORIES IS HOW
FROM MY STANDPOINT AS A
HISTORIAN OF GENETICS AND IN THE
BEGINNING OF HUMAN POPULATION S
THERE WAS INCREDIBLE EMPHASIS ON
NOT ONLY GENETICS BUT GENETICS
AND ENVIRONMENT INTERACTION.
YOU HAVE THROUGH THE 1980s, '70s
AND '80s A REAL REVOLUTION IN
MAPPING SEQUENCING AND EARLY BIO
INFORMATICS.
TO A CERTAIN DEGREE SOME OF THE
ENVIRONMENTAL COMPONENTS THE
ENVIRONMENTAL SENSE OF GENETICS
REALLY DROPPED OUT A LITTLE BIT.
SO YOU CAN SEE IN THE LATE '90s
WHAT I REFER TO AS THE DISCOVERY
OF ENVIRONMENT AND THE IDEA AND
IT WASN'T REALLY DISCOVERY BUT
THAT'S A PROVOCATION.
BUT A LOT OF WHAT EXPOSOMICS IS
DOING IS TRYING TO ANSWER
FUNDAMENTAL QUESTION THAT IS AT
THE ROOT OF MEDICINE, AT THE
ROOT OF SCIENCE AND ROOT OF 150
YEARS OF GENETIC INQUIRIES,
WHICH IS THE CONDITIONS FOR
HEALTH AND DISEASE AND CAN WE
PROVIDE SOME WAY TO IN ESSENCE
GIVE SOMEONE ENOUGH INFORMATION
WHERE THAT SENSE IS USEFUL AND
NOT MAKE OVER DRAWN CONCLUSIONS
ONE WAY OR THE OTHER.
SO EXPOSOMICS FOR ME IS A
FASCINATING DISCUSSION BECAUSE
IT SEEMS TO EXIST ALONGSIDE VERY
INTERESTING DEBATES ABOUT THE
NATURE OF INHERITABILITY AND
ANSWERS IN SOME WAYS THE
FOUNDATIONAL PREMISES OF THE
HUMAN GENOME PROJECT WHILE ALSO
ALLOWING US TO MOVE FORWARD IN
CONCEPTS LIKE PRECISION MEDICINE
WHERE THINK WE HAVE DONE A GREAT
DEAL BUT WE ALSO HAVE A LOT OF
TO DO AND A LOT TO LEARN.
>> I WANTED TO THANK ALL OF YOU
BUT I'M CURIOUS, PASCAL, WHAT'S
THE NEXT STEP FOR THE
DISCUSSION?
WE TALKED ABOUT NEXT STEPS FOR
THE DISCIPLINE BUT HOW ARE YOU
THINKING OF DOCUMENTING THIS AND
MOVING ON TO OUR NEXT PHASE SO
WE CAN CAPTURE THIS.
I THINK CHRIS WILL HAVE SOME
IDEAS TOO BUT I THINK IT WILL BE
A CONTINUING CONVERSATION.
>> ON THE SPECIFIC TOPIC I THINK
WE JUST OPENED A LITTLE BIT OF
THE BOX.
I HOPE WE CAN CONTINUE AND WITH
MORE DEEP OR PERSONAL INTERVIEW.
THERE'S A PROJECT MAYBE YOU
COULD PROPOSE TO THE COMMISSION
ABOUT THE HISTORY OF THAT
DISCIPLINE.
I DON'T KNOW.
THE OTHER POINT IS THAT WE TRIED
TO DEVELOP IN SOME COMMUNITY FOR
HISTORY THIS KIND OF WHAT WE
CALL SHARED HISTORY TO
EXCHANGING FREELY THE PERSONAL
EXPERIENCE.
MAYBE WE COULD CREATE IN THE
DYNAMIC NIH AND SHARE THEIR
STORY.
WHY NOT ON THE TOPICS?
BECAUSE I THINK THIS EXCHANGE
WAS VERY RICH.
AND THAT COULD BE THE IMPULSE
FOR OUR ORGANIZATION TO GIVE THE
SPACE AND IF YOU DON'T SPEAK
YOUR MEMORY ONE DAY OR ANOTHER
WHAT YOU SAY IS NOT ALWAYS IN
THE PAPERS.
>> VERY WELL SAID.
SO TO BE CONTINUED.
BUT THANK YOU ALL KNOW FOR A
FASCINATING DISCUSSION DID YOU
HAVE ANYTHING ELSE, CHRIS.
OKAY I'LL THANK EVERYBODY WHO
HELPED US PULL THIS TOGETHER.
THANK ALL OF YOU FOR YOUR
PARTICIPATION AND LOOK FORWARD
TO OUR CONDITIONING
CONVERSATIONS AND DIANA GOMEZ
NOT HERE WITH US.
SHE'S LISTENING.
HI, THANK YOU.
SHE'S BEEN FABULOUS.
AND THANKS EVERYBODY WHO'S BEEN
WATCHING.
WE DIDN'T HAVE TIME TO GET TO
YOUR QUESTIONS BUT IF THERE'S
SOME WE'LL PASS IT ALONG.
THANK YOU VERY MUCH.