>> GOOD AFTERNOON.
I WILL
INTRODUCE ANDY.
IT'S TRULY A PLEASURE.
ANDY IS -- I WOULD LIKE ONLY TO
SAY THAT HE IS A FANTASTIC
SCIENTIST AND AN EVEN BETTER
PERSON, AND I THINK THAT WILL
QUALIFY HIM FULLY, BUT I WILL,
YOU KNOW, GIVE YOU A FEW
DETAILS.
ANDY RECEIVED HIS CFBS FROM THE
UNIVERSITY OF SUTHERLAND U.K.
AND UNIVERSITY OF NEW CASTLE IN
THE U.K.
HIS RESEARCH WAS INITIALLY
FOCUSED ON THE GENETIC
DETERMINANTS OF DEMENTIA.
HE DID HIS POSTDOCTORAL WORK AT
THE MAYO CLINIC AND THEN MOVED
TO THE NATIONAL INSTITUTE ON
AGING AND BECAME LABORATORY
CHIEF IN 2008.
IN 2016, HE BECAME ANION AN NIA
DISTINGUISHED INVESTIGATOR AND
DIRECTOR OF THE NEW CENTER FOR
ALZHEIMER'S DISEASE AND RELATED
DEMENTIA, CARD.
IN THIS NEW ROLE, ANDY HAS
DEMONSTRATED THAT HE'S NOT ONLY
A WONDERFUL SCIENTIST BUT ALSO A
LEADER OF PEOPLE AND A WONDERFUL
ORGANIZER.
ANDY HAS ORGANIZED -- HAS
PUBLISHED MORE THAN 700
ARTICLES, SO NEVER TRY TO PRINT
HIS CV BECAUSE YOU HAVE TO SAVE
TREES.
HIS WORK HAS WORKED MOSTLY ON
THE GENETIC OR NEUROLOGICAL
DISORDER, INCLUDING PARKINSON'S
DISEASE, DYSTONIA, ATAXIA,
DEMENTIA, AND LEWY BODY DISEASE
AND -- REALLY TO GLIMPSE AN
OPPORTUNITY FOR TREATMENT THAT
CAN BE OPEN IN THE FUTURE IN A
FIELD THAT REALLY NEEDS NEW
TREATMENT, NEW EFFECTIVE
TREATMENT DESPERATELY.
ANDY SERVES ON SEVERAL EDITORIAL
BOARDS AND ADVISORY BOARDS AND
AS THE GOOD SCIENTIST HE IS, HE
HAS WON MANY, MANY AWARDS.
THE AWARD FOR PARKINSON'S
DISEASE RESEARCH, AWARD FOR
OUTSTANDING ACHIEVEMENT IN
PARKINSON'S DISEASE RESEARCH AND
THE AMERICAN ACADEMY OF
NEUROLOGY DISORDER AWARD.
THANK YOU, ANDY, FOR ACCEPTING
TO GIVE THIS LECTURE, WE ARE
HEADING FOR A TREAT, AND I LOOK
FORWARD TO LISTENING FROM YOU OF
YOUR WONDERFUL SCIENCE.
>> THANK YOU, LUIGI, THANK YOU
SO MUCH FOR THE KIND
INTRODUCTION.
AND IT'S A REAL PLEASURE TO GIVE
THIS TALK TODAY.
I WISH IT WAS IN PERSON.
BUT THIS WILL HAVE TO DO.
SO I'VE BEEN IN THE INTRAMURAL
RESEARCH PROGRAM AS LUIGI SAID
FOR 21 YEARS NOW, WHICH IF
SOMEONE HAD TOLD ME THAT 21
YEARS AGO, I WOULD NEVER HAVE
BELIEVED IT.
BUT KIND OF THE THEME OF -- AN
UNDERLYING THEME OF THIS TALK IS
HOW SPECIAL THE INTRAMURAL
PROGRAM IS.
AND I THINK THAT'S A LARGE PART
OF THE REASON WHY SO MANY OF US
WHO CAME HERE SLIGHTLY LESS GREY
AND QUITE A LOT YOUNGER TEND TO
HANG AROUND FOR A WHILE, BECAUSE
IT REALLY IS A WONDERFUL PLACE
TO WORK.
MANY OF YOU KNOW THIS ALREADY,
BUT THERE ARE SOME -- I THINK
WE'RE IN A REALLY PRIVILEGED
POSITION IN INTRAMURAL RESEARCH
PROGRAM.
WE CAN DO SOME THINGS THAT ARE
SLIGHTLY DIFFERENT TO THE REST
OF THE WORLD, LARGELY BECAUSE OF
THE THINGS I HAVE WRITTEN HERE.
WE HAVE STABLE, GENEROUS
RESOURCES, WE'RE PRETTY SECURE,
OUR REVIEW ISN'T ENTIRELY
PROSPECTIVE, WE CAN DEFINE OUR
OWN METRICS OF SUCCESS, WE CAN
FAIL, WE HAVE THIS TOLERANCE FOR
FAILURE.
AND ALL OF THESE THINGS, I
THINK, COME TOGETHER TO MEAN
THAT WE CAN TAKE ON SOME THINGS
THAT CAN'T READILY BE TAKEN ON.
AND THIS WILL BE PART OF THE
THEME OF WHAT I'M GOING TO TALK
ABOUT TODAY.
REALLY THE THEME IS WE'VE USED
OUR POSITION OR I'VE USED MY
POSITION IN MY LAB AND MY
COLLEAGUES IN THE LAB TOO, TO
REALLY CREATE A COOPERATIVE
RESEARCH NETWORK, AND I'M GOING
TO TALK ENTIRELY ABOUT
PARKINSON'S TODAY, AND I'M GOING
TO TALK ENTIRELY ABOUT
PARKINSON'S GENETICS TODAY.
BUT I WOULD SAY THIS CERTAINLY
STRETCHES TO OTHER DISEASES BUT
ALSO OUTSIDE OF GENETICS, INTO
FUNCTIONAL DOMAINS.
AND WE'VE REALLY TAKEN THAT
SERIOUSLY IN OUR LAB AS LUIGI
MENTIONED, I RAN THE LAB OF
NEUROGENETICS FOR A FAIRLY LONG
TIME, BUT WE HAD A COLLECTIVE
MANAGEMENT STRUCTURE AND ALL THE
LEADERS WERE ON THE SAME PAGE
ABOUT HOW WE CAN ESSENTIALLY USE
OUR POSITION IN THE INTRAMURAL
PROGRAM AND THE COLLABORATIVE
FRAMEWORK OF OUR LAB TO REALLY
EFFECT FUNDAMENTAL CHANGE IN
NEURODEGENERATIVE DISEASE
RESEARCH.
SO I'M GENETICIST, WE ARE
INCREDIBLY SIMPLE PEOPLE, WE ARE
THE SIMPLEST OF SCIENTISTS, I
THINK.
AS YOU CAN SELL TELL TELL BY THIS
FRAMEWORK HERE, REALLY, I THINK
THIS IS WORTH THINKING ABOUT AT
THE BEGINNING OF EVERY TALK
THAT'S CENTERED ON GENETICS.
WHY DO WE FOCUS ON TRYING TO
IDENTIFY GENES THAT UNDERLIE
DISEASE?
OF COURSE THE IDEA IS, IF YOU
CAN FIND A GENE THAT IS
CAUSATIVE ORIS OR A RISK FACTOR FOR
DISEASE, IT'S LIKE SEEING THE
OPENING TITLE SEQUENCE OF A
MOVIE.
IT GIVES YOU AN IDEA ABOUT WHAT
THE MOVIE -- WHERE THE MOVIE IS
GOING TO GO.
YOU GET AN IDEA OF KIND OF WHAT
THE FRAMEWORK IS FOR THE MOVIE,
AND YOU GET A STARTING POINT TO
START TO TRY AND TEASE OUT
WHAT'S GOING TO HAPPEN.
SO WE USE GENETICS AS A STARTING
POINT TO UNDERSTAND THE
PATHOBIOLOGY OF DISEASE.
ALL WITH THE IDEA OF NOT JUST
UNDERSTANDING BIOLOGY, BUT WITH
IDENTIFYING VIABLE POINTS FOR
THERAPEUTIC INTERVENTION.
I THINK OVER RECENT YEARS, IN
THE LAST DECADE OR SO, WE'VE
REALIZED THAT THERE IS MORE TO
IT THAN JUST THAT.
THAT IT'S NOT ENOUGH JUST TO
UNDERSTAND THE BIOLOGY OF THE
DISEASE AND LOOK FOR TARGETS,
BUT FOR PARTICULARLY THE
DISEASES THAT WE WORK ON, LATE
ONSET NEURODEGENERATIVE
DISEASES, WE NEED TO DISSECT THE
DISEASE AS WELL.
WE NEED TO BE ABLE TO PREDICT
WHEN SOMEONE IS GOING TO GET A
DISEASE WELL BEFORE THE ONSET OF
SIGNS AND SYMPTOMS, AND WE ALSO
NEED TO BE ABLE TO CLASSIFY THE
DISEASE INTO MECHANISTIC
SUBTYPES.
SO THIS IS ALL MOVING TOWARDS
THE NOTION OF BEING ABLE TO
IDENTIFY THE RIGHT PATIENT AT
THE RIGHT TIME AND APPLY THE
RIGHT TARGET.
SO I'M GOING TO TALK ABOUT THE
WORK FROM MY LAB.
THIS IS NOT THE ONLY GENETICS
WORK THAT'S BEEN GOING ON IN
PARKINSON'S DISEASE.
OTHER GROUPS HAVE BEEN WORKING
AROUND THE WORLD ON PD BUT I
THINK WE'VE HAD A REALLY
OUTSIZED CONTRIBUTION.
SO I'M GOING TO TALK ABOUT THE
THINGS THAT WE'VE REALLY
CONTRIBUTED TO, AND I'M GOING TO
SPLIT IT INTO TWO BROAD DOMAINS.
FIRST OF ALL, KNOW MONOGENIC DISEASE
AND THEN COMPLEX DISEASE.
SO IT'S GOING TO BE A LITTLE
ASYNCHRONOUS BECAUSE WE DID BOT
AT THE SAME TIME.
SO I'LL TALK ABOUT PROGRESS,
THEN I'M GOING TO TALK ABOUT
WHERE WE'RE GOING NEXT, WHAT THE
CHALLENGES ARE THAT I SEE IN
THIS PARTICULAR SPACE.
SO SO REALLY THIS IS THE FIRST --
BEFORE I MOVED TO THE U.S., I
WORKED IN THE GENETICS OF
DEMENTIA WITH LEWY BODIES AND
ALZHEIMER'S DISEASE.
WHEN I MOVED TO THE U.S. AROUND
1999, I STARTED TO WORK ON
PARKINSON'S DISEASE, AND THIS
WAS REALLY ONE OF THE FIRST
PIECES OF WORK WE STARTED TO
WORK ON.
IT'S WHAT I'VE BEEN INVOLVED IN
IN THE MOST RECENT FIVE OR SIX
YEARS.
SO THIS WAS A FAMILY THAT WE
STUDIED ACTUALLY FROM THE D.C.
AREA, THIS IS A BLACK FAMILY
WITH PARKINSON'S DISEASE.
INCREDIBLY SURPRISINGLY AT THE
TIME, WE FOUND THAT THE MUTATION
UNDERLYING THE DISEASE WAS A
SPINOCEREBELLAR ATAXIA TYPE 3.
THESE SYMPTOMS REALLY WEREN'T
ASSOCIATED WITH PARKINSON'S
DISEASE.
AS WE STARTED TO COLLECT MORE
FAMILIES AND LOOK AT MORE
LITERATURE IN THIS SPACE, IT
BECAME APPARENT THAT WHAT WE
WERE SEEING HERE IS THAT A
GENETIC CAUSE OF DISEASE CAN
PRESENT IN DIFFERENT WAYS BASED
ON ANCESTRAL BACKGROUND.
SO THIS FINDING BACK -- WHICH WE
MADE ACTUALLY IN 1999 TOOK US
2 1/2 YEARS TO PUBLISH BECAUSE
ACTUALLY NOBODY BELIEVED IT,
THEY THOUGHT IT WAS JUST SIMPLY
MISDIAGNOSIS OF DISEASE, AND
THAT IN PART IS BECAUSE
PARKINSON'S DISEASE IS REALLY
TRADITIONALLY A WHITE CONSTRUCT.
WHAT WE KNOW ABOUT PARKINSON'S
DISEASE, WHAT WE KNOW ABOUT THE
CLINICAL PRESENTATION OF
PARKINSON'S DISEASE IS BASED
LARGELY ON WORK DONE IN
INDIVIDUALS OF NORTHERN EUROPEAN
ANCESTRY.
I WILL COME BACK TO THIS POINT
LATER ON IN THE SLIDE.
NOT LONG AFTER MOVING TO THE
U.S., WE MADE THIS DISCOVERY.
SO THE FIRST GENE THAT WAS FOUND
IN PARKINSON'S DISEASE WAS FOUND
IN 1997 AT NHGRI IN THE
INTRAMURAL PROGRAM AND IT WAS
THIS GENE ALPHA SYNUCLEIN, A
CONSTITUENT PART OF LEWY BODIES,
THE PATHOMO NICK HALLMARK FOR
PARKINSON DISEASE.
THE MUTATIONS THAT HAD BEEN
FOUND WERE POINT MUTATIONS SO
THEY WERE QUALITATIVE CHANGES IN
SYNUCLEIN.
WHAT WE FOUND IN 2003 WAS
ACTUALLY A RARE CAUSE OF
PARKINSON'S DISEASE IS THESE
QUANTITATIVE CHANGES IN
SYNUCLEIN WHERE EXTRA GENE
COPIES OF LEAD TO EXTRA
PRODUCTION OF SYNUCLEIN AND THAT
IS ENOUGH TO DRIVE DISEASE IN
INDIVIDUALS 20s OR 30s.
SO THIS TOOK A LONG TIME TO
FIND, THIS CERTAINLY TOOK MANY
YEARS TO FIND, AND IT'S
SOMETHING THAT YOU COULD FIND
NOW IN A COUPLE OF DAYS WITH
MODERN TECHNOLOGY.
BUT AT THE TIME, IT WAS FAIRLY
GROUNDBREAKING.
IT TOLD US WHAT I'VE ALREADY
STATED, JUST INCREASING THE
AMOUNT OF SYNUCLEIN WAS ENOUGH
TO CAUSE DISEASE, AND THIS IS A
MECHANISM WHICH I THINK STILL
HOLDS TRUE TODAY, AND IS
RELEVANT NOT ONLY FOR MUTATIONS
BUT FOR RISK FACTORS.
IT TOLD US -- IT ALSO TOLD US
THAT WE HAD TO BE REALLY CAREFUL
ABOUT MODELING, HOWEVER,
EXPRESSION LEVELS -- THAT
CERTAINLY HAS AN IMPACT ON THE
IMPLICATIONS OF THE MODELS.
LASTLY, IT TOLD US SOMETHING
ABOUT THERAPEUTIC OPPORTUNITIES.
IF PRODUCING TOO MUCH SYNUCLEIN
CAN CAUSE RARE DISEASE, A RARE
FORM OF PARKINSON'S DISEASE, AND
WE THINK THE COMMON VARIABILITY
ALSO AFFECTS SYNUCLEIN LEVELS,
THEN MAYBE TARGETING SYNUCLEIN
CLEARANCE OR REDUCING ITS
EXPRESSION IS A VIABLE PART OF
THERAPEUTIC INTERVENTION AND
I'LL TALK A LITTLE MORE ABOUT
THAT LATER.
NOT LONG AFTER THAT, A YEAR OR
SO LATER, OUR LAB ALONG WITH A
COUPLE OF COLLABORATORS AND SOME
COMPETING LABS FOUND THE LRRK2
MUTATION THAT CAUSE PRETTY
TYPICAL PARKINSON'S DISEASE.
SO THIS LRRK2 -- KINASE.
WHAT WAS PARTICULARLY
INTERESTING ABOUT THIS DISCOVERY
WAS THAT ALL OF THE PREVIOUS
GENES THAT HAD BEEN IDENTIFIED
AND ASSOCIATED WITH --
ASSOCIATED WITH RARE FORMS OF
DISEASE WERE GENERALLY QUITE
RARE, SO SYNUCLEIN MUTATIONS
WERE EXTREMELY RARE.
THIS IS NOT TRUE FOR LRRK2.
LRRK2 MUTATIONS, PARTICULARLY
ONE MUTATION OF THE KINASE
DOMAIN, THIS IS RESPONSIBLE FOR
ABOUT 1 IN 50 CASES OF
PARKINSON'S DISEASE IN NORTH
AMERICA.
SO ABOUT 20,000 INDIVIDUALS IN
NORTH AMERICA HAVE PARKINSON'S
DISEASE. THIS CHANGES PRETTY
DRASTICALLY FROM POPULATION TO
POPULATION.
IF YOU LOOK NE NORTH AFRICA
POPULATION, IT'S ALMOST 1 IN 2.
THIS WAS ALSO A REALLY GREAT
LEARNING EXPERIENCE FOR ME.
THIS WAS A GREAT LEARNING
EXPERIENCE ABOUT THE POWER OF
THE INTRAMURAL PROGRAM AND ABOUT
COLLABORATION.
WE KNEW IN THOSE DAYS, WE WERE
RACING OTHERS TO FIND THIS GENE
AND WE KNEW THE WAY TO DO THIS
WAS TO COLLABORATE.
SO USING THE RESOURCES WE COULD
BRING TO BEAR FROM THE IRP,
ABILITY TO SEQUENCE AT GREAT
SPEED, BRING INFORMATION
TOGETHER, WE WORKED WITH GROUPS
FROM SPAIN, LONDON, AND REALLY
THAT COLLABORATION AND THAT
SPEED LED US TO WIN THIS RACE TO
IDENTIFY THE GENE.
THE SECOND PART THAT I THINK WAS
REALLY REVEALING WAS THE BEAUTY
OF THE INTRAMURAL PROGRAM IN
THAT WE CAN PIVOT VERY QUICKLY
AND WE CAN CHANGE RESOURCES VERY
QUICKLY.
SO THE DAY WE FOUND THIS MODEL,
COOKSON, WHO'S A PI OOF WORKED
WITH FOR 25 YEARS, BEEN
WONDERFUL TO WORK WITH, MARK
COOKSON CHANGED THE DIRECTION OF
HIS LAB ALMOST OVERNIGHT TO
START WORKING ON LRRK2.
AND ACTUALLY THE WORK HE DID
SHOWING KINASE ACTIVITY WAS KEY
FOR THE -- GAIN OF FUNCTION --
CONSEQUENCES WHICH I'LL TALK A
LITTLE BIT ABOUT LATER.
NOT LONG AFTER THIS, AND AGAIN
IN THIS THEME OF FINDING
MUTATIONS THAT PRESENT
DIFFERENTLY, OR CAN HAVE
DIFFERENT OUTCOMES, WE FOUND
THIS GENE, PLA2G6, WHICH HAD
PREVIOUSLY BEEN SHOWN TO
MUTATIONS PREVIOUSLY ASSOCIATE
WITH AN INFANTILE
NEURODEGENERATIVE DISEASE.
WE SHOWED THESE CAN CAUSE A
DYSTONIA-PARKINSONISM SYNDROME.
SO NOW WE'RE AROUND 2009, WE'VE
GONE THROUGH THESE EXPERIENCES
OF INDIVIDUAL GENE HUNTING
ESCAPADES WHERE WE'RE CHASING
GENES LIKE CRAZY, STARTING TO
THINK ABOUT WORKING MORE
COLLABORATIVELY WITH OTHER
GROUPS.
GENETICS WAS AN INCREDIBLY
COMPETITIVE ENDEAVOR BACK IN THE
LATE '90S AND EARLY 2,000s,
BUT AROUND THIS TIME, OUR GROUP
REALLY STARTED TO THINK ABOUT
THE POWER OF WORKING WITH
OTHERS.
SO IN 2009, ALONG WITH AROUND 10
OR SO OTHER INVESTIGATORS FROM
AROUND THE WORLD, WE FORMED THIS
CONSORTIUM, THE INTERNATIONAL PD
GENOMICS CONSORTIUM, AND THE
IDEA HERE WAS TO CREATE A GROUP
THAT COULD WORK TOGETHER REALLY
QUICKLY AND SHARE DATA VERY
QUICKLY WITHOUT TOO MANY
INENCUMBRANCES.
AGAIN, THE IRP WAS REALLY
ESSENTIAL IN THE SUCCESS OF IGC.
WE WERE ABLE TO PROVIDE QUICK
SEQUENCING, QUICK RESOURCES TO
GET THINGS OFF THE GROUND AND
GET THINGS MOVING.
WHEREAS THE OTHER INVESTIGATORS
WERE HAVING TO WRITE GRANTS AND
APLAY FOR FUNDING, WE COULD
REALLY SEED PROGRESS VERY, VERY
QUICKLY AND I'LL TALK A LITTLE
BIT MORE ABOUT THAT LATER.
IPDGC HAS ALSO DISCOVERED
MUTATIONS, FASCINATING CAUSE OF
PARKINSON'S DISEASE, AND ALSO
CREATED A NETWORK TO KIND OF
CORRECT OR COURSE CORRECT THE
LITERATURE, NOW GENETICS IS
RELATIVELY ACCESSIBLE FOR MANY
PEOPLE.
WHAT THIS HAS EFFECTIVELY LED
TO, THOUGH, IN THE PARKINSON'S
FIELD IS A VERY LARGE NUMBER OF
GENES PUBLISHED OR MUTATIONS AND
GENES PUBLISHED THAT JUST REALLY
PROBABLY AREN'T RIGHT.
SO WE'VE BEEN ABLE TO USE THE
STRUCTURE OF THE IPDGC TO
CORRECT THE LITERATURE AS TIME
HAS GONE ON.
ACTUALLY THIS HAS BEEN A DOUBLE
WHAMMY BECAUSE EVE USED THIS WE'VE USED T HIS
PROGRESS TO TRAIN STUDENTS.
THEY'RE TASKED WITH CHECKING UP
ON NEW GENES AND PUBLISHING
THESE STUDIES IN VERY LARGE
COHORTS.
SO WHERE HAS THIS WORK IN
MONOGENIC DISEASE LED US?
IT'S LED US TO AROUND 17 OR SO
PLAUSIBLE GENES THAT CONTAIN
MUTATIONS THAT CAUSE PARKINSON'S
DISEASE.
I SAID I WOULD TALK ONLY ABOUT
THE THINGS THAT WE REALLY
HEAVILY DROVE.
I'M GOING TO MAKE ONE EXCEPTION.
SO THIS IS WORK REALLY DRIVEN BY
ELLEN SIDRANSKI.
WE CERTAINLY PARTICIPATED IN
MIKE NOLES, A YOUNG STATISTICIAN
AT THE TIME, THE LEAD ANALYST
FOR THIS, BUT THIS IS REALLY
BEAUTIFUL WORK THAT ELLEN DROVE
THAT SHOWED GLUCOCEREBROSIDASE
MUTATIONS, A RECESSIVE FORM THAT
CAUSED GAUCHER'S DISEASE, A
SIGNIFICANT RISK FACTOR FOR
PARKINSON'S DISEASE.
THERE HAD BEEN IMPLICATIONS
BEFORE THIS, IMPLICATING -- I
THINK THIS PUBLICATION REALLY
PROVED THIS BEYOND A DOUBT.
AND AGAIN, THIS WAS ABOUT
BRINGING PEOPLE TOGETHER, AND I
THINK IT'S NO SURPRISE THAT
SOMEONE FROM THE INTRAMURAL
PROGRAM, ELLEN, WAS ABLE TO
BRING GROUPS TOGETHER FROM
AROUND THE WORLD.
SO WE HAVE GENES THAT CONTAIN
DISEASE-CAUSING MUTATIONS, A
COUPLE OF MODERATE RISK PROTEIN
CODING VARIANTS THAT I MENTIONED
HERE, AND ALSO ACTUALLY AGE
AGING-SPECIFIC VARIANTS.
SO AGAIN SPEAKING TO THE POWER
OF THE INTRAMURAL PROGRAM, THIS
WAS SOMETHING WE GOT INVOLVED IN
REALLY, REALLY EARLY.
BECAUSE AT THE TIME, WHEN WE
STARTED DOING THIS IN 2004,
2005, HIGH CONTENT GENOTYPING
WAS REALLY NEW TECHNOLOGY, AND
THERE WAS STILL A HUGE AMOUNT OF
BAIT AS TO WOULD THIS REALLY
WORK, WOULD GENOME-WIDE
ASSOCIATION WORK.
AND WE WERE ABLE TO TOLERATE THE
POTENTIAL OF IT NOT WORKING,
BRINGING GENOME-WIDE GENOTYPING
INTO THE LAB AND JUST BEGIN
WORKING AND BEGIN GENERATING
DATA.
ACTUALLY OUR FIRST STUDY WAS THE
FIRST STUDY TO RELEASE
GENOME-WIDE GENOTYPING SNP DATA
INTO THE PUBLIC DOMAIN.
I THINK IT WAS ONLY THE THIRD
GENOME-WIDE ASSOCIATION STUDY
PUBLISHED AT THE TIME.
WE PUBLISHED IT IN 2006.
AND IT WAS AN EMBARRASSINGLY
SMALL NUMBER OF SAMPLES, 267
CASES AND 267 CONTROLS.
SO AS YOU CAN SEE IN THIS PLOT
HERE, ZERO NEW LOCI, AS ONE
WOULD EXPECT.
BUT IT WAS INCREDIBLY USEFUL FOR
US, IT WAS INCREDIBLY USEFUL FOR
US BECAUSE IT TAUGHT US
IMMEDIATELY THE RIGHT THING TO
DO WAS TO PUT DATA INTO THE
PUBLIC DOMAIN SO THAT IT COULD
BE MINED BY OTHERS AND ACTUALLY
ADDED TO BY OTHERS.
THE DATA IS ESSENTIALLY DIGITAL
IN ITS FORM, SO CONTRIBUTING THE
DATA TO THE GENERAL PUBLIC OR
THE GENERAL RESEARCH PUBLIC
MEANS THAT OTHERS CAN ADD
SAMPLES AND WE CAN INCREASE
SAMPLE SIZES.
IT ALSO SHOWED THAT WE COULD
HANDLE THE DATA, WE COULD DO
THIS KIND OF WORK IN THE LAB,
AND I THINK THIS WAS REALLY KEY
IN MAKING US A LEADER IN THIS
SPACE.
NOT MUCH LONGER AFTER THIS, IN
2009, AGAIN, AROUND THIS TIME
THAT WE'RE STARTING TO THINK
ABOUT REALLY COLLABORATING
HEAVILY, WE WORKED WITH A
COMPETING GROUP, THE GROUP THAT
WE'D BEEN RACING TO DISCOVER THE
LRRK2 MUTATION BACK IN 2004, AND
WE BROUGHT TOGETHER GENOME-WIDE
DATA FROM THE U.S. AND FROM
GERMANY, AND STARTED TO IDENTIFY
NEW RISK LOCI.
THE TWO YOU SEE HERE, ONE IS IN
SYNUCLEIN, SO AGAIN, YOUR
MUTATIONS IN SYNUCLEIN CAUSE
PARKINSON'S DISEASE, BUT NOW WE
KNOW THE COMMON VARIABILITY
AROUND SYNUCLEIN IS A RISK
FACTOR FOR PARKINSON'S DISEASE.
THE OTHER IS A LOCUS ON
CHROMOSOME 17 THAT'S VERY
INTERESTING.
IT CONTAINS THE GENE MICROTUBULE
ASSOCIATED PROTEIN TAU.
WE DON'T KNOW IF TAU IS THE
EFFECTOR GENE THERE, BUT THIS IS
AN IMPORTANT FINDING.
NOT MUCH LONGER AFTER THAT, OF
COURSE, WE FORMED IPDGC AND HAVE
BEEN INCREDIBLY PRODUCTIVE EVEN
MORE SO IN THE COMPLEX SPACE.
AGAIN, WE WERE ABLE TO BRING
RESOURCES TO BEAR FROM THE
INTRAMURAL RESEARCH PROGRAM TO
REALLY GET THIS CONSORTIUM
STARTED AND REALLY START TO PUSH
DOWN ON THE ACCELERATOR FROM DAY
ONE, AND I THINK THAT WAS
ABSOLUTELY KEY.
SO IPDGC THEN STARTED TO RAMP
UP, WE STARTED TO GENERATE
GENOTYPE DATA, STARTED TO BRING
DATA TOGETHER INTO ONE SPACE.
2011, WE MOVED TO 11 NEW LOCI,
AND ACTUALLY FOR THE FIRST TIME
STARTED TO DO IMPUTATION.
IMTEU PAITION WAS IMPUTATION WAS REALLY ST ARTING
TO GET USED AROUND 2010, 20 LEN.
IN PARTNERSHIP WITH THE WELLCOME
TRUST -- WE WERE STARTING TO
GAIN SOME TRACTION.
AS YOU CAN SEE, ONE OF THE
REALLY NEAT THINGS ABOUT
GENOME-WIDE ASSOCIATION STUDIES
ON THE BOTTOM LEFT-HAND SIDE OF
THE SCREEN S THEY'RE PREDICTABLE
IN NATURE.
YOU KIND OF KNOW HOW MANY MORE
LOCI YOU'RE GOING TO GET BASED
ON HOW MANY MORE SAMPLES YOU
ADD.
SO WE CONTINUED TO ADD OVER THAT
TIME.
2014, NOW WE'RE STARTING TO
REALLY GET SOMEWHERE.
WE'D GONE FROM A SPACE ONLY
SEVEN OR EIGHT YEARS PREVIOUSLY
WHERE WE WERE GENOTYPING
260 SAMPLES TO THE SPACE HERE
WHERE WE'RE GENOTYPING 19,000
CASES, AND ALMOST 100,000
CONTROLS, AND REALLY STARTING TO
IDENTIFY NUMEROUS LOCI
ASSOCIATED WITH PARKINSON'S
DISEASE.
A FEW YEARS LATER, WE STARTED TO
WORK WITH INDUSTRY.
SO THIS IS INCLUDING DATA FROM A
GROUP AT GENENTECH WHO WERE KIND
OF ACADEMIC INDUSTRY, AND AGAIN,
REALLY EXPANDING THE NUMBER OF
RISK LOCI, EXPANDING THE NUMBER
OF CASES, SO 26,000 CASES,
400,000 CONTROLS.
THEN MOST RECENTLY, IN 2019, WE
HAVE THE LARGEST JOE NEEM WIDE
ASSOCIATION STUDY REALLY DRIVEN
BY MIKE NOLES I MENTIONED
EARLIER, IN COLLABORATION WITH
23ANDME, AND HERE WE WERE ABLE
TO IDENTIFY 90 INDEPENDENT RISK
LOCI.
WHEN YOU START TO BRING THOSE
RISK LOCI TOGETHER, YOU CAN
CREATE THINGS LIKE GENETIC RISK
SCORES AND GIVE EACH INDIVIDUAL
WITHIN YOUR GENOME WHAT
ASSOCIATION A RISK SCORE, AND
YOU CAN SEE IN THE BOTTOM
RIGHT-HAND CORNER OUR ABILITY TO
KREE
PREDICT -- AROUND 70%, IT'S
DEFINITELY NOT PERFECT, BUT IT
WORKS EXTREMELY WELL WHEN YOU
START TO BRING IN DIFFERENT
TYPES OF DATA, YOU START TO USE
GENETICS AS PART OF THE
MULTIMODAL PREDICTOR FOR
DISEASE.
ONE OF THE THINGS WE'D DONE
REALLY EARLY ON, WHICH I HAVEN'T
SHOWN, IS START TO USE THESE
TYPE OF GENOME-WIDE APPROACHES
NOT JUST FOR DISEASE BUT FOR
LOOKING AT OTHER TRAITS, SO
WE'VE DONE A WHOLE SERIES OF
WORK IN GENERATING QTL DATA IN
HUMAN BRAIN, SO EXPRESSION PTL
DATA, DNA METHYLATION, QTL DATA,
AND MERGING THE QTL DATA FROM
BRAIN, OUR TISH EU OF TISSUE OF INTEREST,
WITH PARKINSON'S DISEASE OR ANY
OTHER DISEASES WE WERE WORKING
ON AND LOOKING FOR INTERSECTION,
IS THIS ASSOCIATED WITH DISEASE,
IF SO, WHAT EFFECT DOES THAT
HAVE ON GENE EXPRESSION, WHAT
GENE DOES IT AFFECT, WHAT
DIRECTION, AND WHAT TISSUE.
WHILE SOMEWHAT SHOWING THAT DATA
HERE, I'M SHOWING SOME SIMILAR
DATA, WHICH IS REALLY SINGLE
CELL EXPRESSION DATA HERE, AND I
THINK THAT MUCH AS GENETICS HAS
BEEN REVOLUTIONIZED BY
TECHNOLOGY OVER THE PAST 20
YEARS, I THINK THE NEXT KIND OF
FOUNDATIONAL FUNCTIONAL STEPS
ARE BEING REVOLUTIONIZED WITH
SINGLE CELL METHODOLOGIES.
WHAT THIS SIMPLY IS HERE IS AN
ANALYSIS WHERE YOU TAKE ALL OF
YOUR GENES UNDERNEATH YOUR RISK
LOCI AND YOU LOOK AT THEIR
EXPRESSION IN SINGLE CELL
DATASETS.
THIS IS A SINGLE CELL DATASET
FROM MOUSE, AND YOU LOOK TO SEE
WHETHER THOSE GENES UNDERNEATH
YOUR GENOME-WIDE ASSOCIATION
PEAKS ARE PARTICULARLY EXPRESSED
IN ANY PARTICULAR CELL TYPE.
SO THIS TELLS YOU SOMETHING
ABOUT THE CELLULAR CONTEXT OF
RISK.
WHAT WE SEE HERE IS THAT
GENERALLY, NOT EXCLUSIVELY, BUT
GENERALLY, GENOME-WIDE
ASSOCIATION -- FOR PARKINSON'S
DISEASE, THE GENES UNDERNEATH
THOSE ARE HIGHLY EXPRESSED IN
NEURONS, PARTICULARLY NEURONS,
SUBSTANTIA NIGRA AND -- NEURONS
THIS IS NOT EXCLUSIVE.
THERE ARE SOME REALLY NEAT DATA
COMING OUT SHOWING THE
PARTICULAR GENES HAVE EFFECTS ON
OTHER CELL TYPES, BUT IT TELLS
YOU THAT A GOOD PLACE TO START
MODELING AND TRYING TO
UNDERSTAND THE EFFECTS OF
GENETIC VARIABILITY ASSOCIATED
WITH RISK FOR PD IS DOPE ANY DOPE -- NEUR ONS.
UNDERSTANDING FUNCTIONAL
PATHWAYS ASSOCIATED WITH
PARKINSON'S DISEASE, THIS IS
WORK DONE -- REALLY A MONUMENT
TUS EFFORT BRINGING TOGETHER A
LARGE AMOUNT OF GENOTYPE DATA, A
LARGE AMOUNT OF EXPRESSION DATA,
TRANSCRIPT OMIC COMMUNITY MAPS,
REALLY STARTS TO GIVE US A
FLAVOR OF -- AN IDEA OF WHAT ARE
THE KEY CONTRIBUTORS IN TERMS OF
MECHANISM FOR RISK IN
PARKINSON'S DISEASE THAT ARE
BEING DRIVEN GENETICALLY, AND
HERE YOU CAN SEE THAT THE THINGS
SHE IDENTIFIED ARE COLLABORATORY
SIGNALING PATHWAYS, CELL DEATH
MACHINERY AND MITOCHONDRIAL
HOMEOSTASIS.
WE'VE ALSO LOOKED OUTSIDE OF
JUST RISK FOR DISEASE, SO YOU
CAN DO A GENETIC ANALYSIS ON
ALMOST ANYTHING.
SOMETHING VERY OBVIOUS TO DO
HERE, TO LOOK AT AGE OF ONSET.
I HAD ASSUMED WHEN WE DID THIS,
AND WE HAD GOOD EVIDENCE FOR
THIS, THAT SIMPLY WE WOULD FIND
THE SAME THINGS THAT WE'D FOUND
FOR RISK THAT WE'D FIND FOR AGE
OF ONSET.
SO WE KNEW THAT THE MORE -- THE
HIGHER GENETIC RISK SCORE, THE
YOUNGER YOUR AGE OF CONCEPT IS
LIKELY TO BE.
AND BY AND LARGE, THAT'S TRUE,
WHEN YOU DO A GENOME-WIDE
ASSOCIATION STUDY AND YOU LOOK
AT THE BETA VALUES FOR RISK
VERSUS THE BETA VALUES FOR AGE
OF ONSET AS WE'VE DONE ON THIS
PLOT ON THE RIGHT-HAND SIDE,
THEY LINE YOU IN A DIAGONAL, THE
SAME LOCI IDENTIFIED AS RISK
FACTORS FOR DISEASE ALSO
MODULATE AGE OF ONSET.
THE MAP T LOCUS, ONE OF THE
FIRST YOU IDENTIFY WHEN YOU DO A
GENOME-WIDE ASSOCIATION STUDY IN
PD HAS ABSOLUTELY NO EFFECT ON
AGE OF ONSET.
SO I THINK THIS IS A REALLY
INTERESTING OBSERVATION, WE'RE
WORKING PRETTY HARD AT TRYING TO
UNDERSTAND THAT.
UNFORTUNATELY THE TAU LOCUS IS
INCREDIBLY COMPLICATED, ABOUT A
1 1/2 MILLION BASE PAIR
INVERSION ON CHROME ZONE 17, BUT
WHAT WE'RE REALLY SEEING HERE
IS, THERE'S SOMETHING THAT
AFFECTS WHETHER YOU GET DISEASE
BUT HAS NO EFFECT WHATSOEVER ON
WHEN YOU GET DISEASE.
THIS IS AN EXCEPTION FROM THE
NORM.
WE'VE ALSO LOOKED AT GENETIC
INFLUENCE ON GENETIC FORMS OF
DISEASE.
I MENTIONED EARLIER CARRYING A
SINGLE GBA MUTATION IS A RISK
FACTOR FOR PARK SONS DISEASE,
INCREASES SOMEWHERE BETWEEN
2 AND 5 FOLD.
BY DOING A JOE GENOME WIDE
ASSOCIATION STUDY, WE CAN START
TO IDENTIFY GENETIC RISK FACTORS
THAT MODULATE THE PENETRANCE OF
GBA MUTATIONS.
YOU SEE TWO BIG HITS HERE,
SYNUCLEIN AND -- IT SHOWS UP
EVERYWHERE WITH EVERYTHING.
CTSB WAS PARTICULARLY
INTERESTING AND I'LL COME BACK
TO THAT IN A SECOND.
WHAT WE DID SHOW IS THAT IN
GENERAL, ALL OF THE GENETIC RISK
FACTORS FOR TYPICAL DISEASE, FOR
THOSE THAT DON'T CARRY THE
MUTATION, IF YOU PUSH THOSE INTO
A GENETIC RISK SCORE, THAT
GENETIC RISK SCORE AFFECTS
WHETHER A GBA CARRIER GETS
DISEASE OR NOT.
SO IN GENERAL, THE MECHANISMS
BETWEEN TYPICAL PD AND
GBA-LINKED PD SEEM TO OVERLAP.
WE DON'T EXCLUSIVELY -- THEY
DON'T EXCLUSIVELY OVERLAP BUT
SEEM TO OVERLAP FOR THE MOST
PART.
THIS IS THE ONE EXCEPTION.
SO THE CTSB LOCUS, WHICH I
SHOWED TWO SLIDES AGO, CTSB
CERTAINLY SHOWS UP AS A RISK
FACTOR FOR TYPICAL PARKINSON'S
DISEASE, BUT IF IT'S MUCH, MUCH,
MUCH STRONGER IN GBA-LINKED
DISEASE, ABOUT THREE TIMES AS
STRONG AS GBA-LINKED DISEASE.
AND WHAT IS PARTICULARLY
COMPELLING ABOUT THIS IS
LYSOSOMAL PROTEASE.
WE OF COURSE KNOW THAT GLUCOVEE
BRO SIDASE IS A LYSOSOMAL
PROTEIN, SO JUST THE VERY FACT
THAT OUT OF ALL OF THE GENES WE
COULD FIND A LYSOSOMAL CYSTINE
PRO TEE'S POPS UP TELLS ME
SOMETHING MECHANISTICALLY IS
GOING ON THERE AND WE'RE SEEING
A GENUINE GENE BY GENE
INTERACTION AND MAYBE SOME HINTS
OF MECHANISTIC SUBTYPES.
SO THIS HAS LED US TO THIS
SPACE, ALL THERE WORK THAT I'VE
TALKED ABOUT THIS FAR.
17 GENES THAT CONTAIN MUTATIONS
THAT CAUSE DISEASE, A COUPLE OF
MODERATE RISK FACTORS AND 90
INDEPENDENT -- WE ACTUALLY DON'T
KNOW THE GENES FOR THE VAST
MAJORITY OF THEM.
WE'VE COME A FAIRLY LONG WAY.
LIKEWISE, THE UNDERSTANDING OF
THE MECHANISM OF THESE GENES AND
THEIR PRODUCTS HAS ALSO COME A
FAIRLY LONG WAY.
MANY OF THESE HAVE STARTED TO BE
LINKED TOGETHER MECHANISTICALLY,
SO MARK COOKSON'S LAB HERE AT
NIH -- HAS LINKED SOME OF THESE
TOGETHER.
GENETICALLY WE'VE LINKED THINGS
TOGETHER.
SO WE'RE REALLY STARTING TO GET
TOWARDS DEFINING A NETWORK OF
GENES THAT UNDERLIE DISEASE
PROCESSES.
THIS HAS HAD AN IMPACT
THERAPEUTICALLY, SO IF WE JUST
THINK ABOUT THE MAJOR GENES THAT
WE'VE IDENTIFIED AND I'VE TALKED
ABOUT TODAY, ALPHA SINAI CLEAN,
THERE ARE CURRENTLY 15 TRIALS
ONGOING TARGETING SYNUCLEIN,
MANY TARGETING CLEARANCE OR
CELL-TO-CELL TRANSPORT OF
SYNUCLEIN.
MARK'S WORK HAS SHOWN THE KINASE
ACTIVITY IS PART OF THE TOXIC
GAIN OF FUNCTION AND WE KNOW
KINASE ACTIVITY IS INCREASED IN
MUTATION CARRIERS, SO THERE ARE
TWO CURRENT TRIALS TARGETING
LRRK2 AND INTERESTINGLY A VERY
LARGE CLINICAL PHASE 3 TRIAL
BEGINNING NOW RUN BY DENALI.
GLUCOCEREBROSIDASE, FOUR CURRENT
GBA-DIRECTED THERAPIES IN
TRIALS.
THERE'S A TON OF WORK GOING ON
IN INDIVIDUALS THAT CARRY THESE
MUTATIONS, TO UNDERSTAND THE
NATURAL HISTORY.
SO I THINK IDENTIFYING THESE
MUTATIONS IS HAVING A REALLY
LARGE EFFECT.
SO IF WE OVERLAY WHAT I TALKED
ABOUT SO FAR, I THINK WE
CERTAINLY HAVEN'T SUCCEEDED, BUT
WE'VE KIND OF HIT THE THINGS WE
SAID WE WOULD TRY AND HIT.
WE'RE USING GENETICS TO
UNDERSTAND THE PATHOBIOLOGY,
WE'RE USING TO IDENTIFY TARGETS,
WE'RE STARTING NOW, BUT I'D SAY
IN THE EARLY DAYS, TO USE TO TRY
AND DISSECT THE DISEASE, TO TRY
AND PREDICT WHO'S GOING TO GET
DISEASE BEFORE THEY GET IT, TO
TRY AND FIND MECHANISTIC
SUBTYPES OF DISEASE.
ALL WITH THIS AIM TOWARDS
PRECISION TREATMENTS.
MATCHING THE RIGHT PATIENT TO
THE RIGHT TREATMENT AT THE RIGHT
TIME.
SO SUMMARY OF WHERE WE ARE SO
FAR.
I THINK WE MADE REALLY
SIGNIFICANT PROGRESS IN THE
GENETICS OF PD.
ORIGINALLY THIS WAS DRIVEN BY
INDIVIDUAL LABS, NOW IT'S JUST
MASSIVELY COLLABORATIVE.
I WILL SAY THE PARKINSON'S
DISEASE FIELD IS AN INCREDIBLY
NICE ONE TO WORK IN, VERY
COLLABORATIVE.
I THINK THE COLLABORATION WAS
ENABLED BY THE WILLINGNESS OF
THAT COMMUNITY.
IT WAS A GOOD COMMUNITY.
BUT ALSO WHAT WAS KEY WAS THE
USE OF THE IRP, TO REALLY SERVE
AS AN ANCHOR FOR THAT
COLLABORATION.
AS A SAFE PLACE TO START WORK
AND TO REALLY GENERATE DATA AND
BRING PEOPLE TOGETHER, THAT
WORKED INCREDIBLY WELL.
WE NOW HAVE A DOZEN OR SO GENES
THAT CONTAIN MUTATIONS THAT
CAUSE DISEASE, 90 OR SO, RISK
LOCI.
AS I TALKED ABOUT, I THINK THE
CELLULAR CONTEXT IS LARGELY
DOPAMINERGIC, WE'RE STARTING TO
GET A HANDLE ON THE FUNCTION AND
WHAT IS THIS NETWORK OF GENES
AND THEIR PRODUCTS THAT
CONTRIBUTE TO DISEASE.
I THINK THAT SOME OF THE THINGS
I'M REALLY EXCITED ABOUT ARE
THESE OUTLIARS, THESE GENETIC
FACTORS THAT HAVE MORE OF AN
EFFECT ON AGE OF ONSET OR LESS
OF AN EFFECT ON AGE OF ONSET
THAN THEY DO ON RISK.
AND I THINK THESE ARE
PARTICULARLY EXCITING FOR US TO
CHASE OVER THE COMING PERIOD.
SO GIVEN THAT, WHICH I THINK IS
PRETTY SUCCESSFUL, WHERE DO WE
GO NEXT?
SO HERE'S WHERE IT'S NOT SO
SUCCESSFUL.
SO THE HERITABLE COMPONENT OF
PARKINSON'S DISEASE NOW WE KNOW
IS ABOUT 25%, SO THE AVERAGE
PARKINSON'S DISEASE PATIENT, 25%
OF THEIR LIABILITY, 25% OF THE
REASON THEY HAVE DISEASE IS
GENETICS.
WE ONLY KNOW I'DITE OF ABOUT IDENTITY OF ABOUT A
THIRD OF THAT SO WE HAVE MORE TO
FIND.
THE VAST MAJORITY OF WORK WE'VE
DONE HAS BEEN IN NORTHERN
EUROPEAN ANCESTRY.
SO PARKINSON'S DISEASE IS
CLEARLY A GLOBAL DISEASE, BUT WE
HAVE -- IF WE ARE TO TREAT THIS
GLOBAL DISEASE AND USING THIS
SCHEMA AGAIN, WE HAVE TO REALLY
INVEST IN UNDERSTANDING GENETIC
BASIS OF DISEASE IN GLOBAL
POPULATIONS.
SO I'M GOING TO TALK AS I'M IN
THE LAST 10, 15 MINUTES OR SO,
ABOUT THIS PROGRAM, THE GLOBAL
PARKINSON'S GENETICS PROGRAM, SO
THIS IS A PARTNERSHIP BETWEEN US
AND THE ALIGNING SCIENCE ACROSS
PARKINSON'S INITIATIVE THAT ARE
SUPPORTING THIS WORK AND THE
MICHAEL J. FOX FOUNDATION WHO
ARE WORKING EXTREMELY CLOSELY
WITH US ON THIS PROGRAM.
SO THE MISSION OF THE GLOBAL
PARKINSON'S GENETICS PROGRAM IS
TO DRAMATICALLY UNDERSTAND OUR
UNDERSTANDING OF THE BASIS OF PD
AND TO MAKE THAT KNOWLEDGE
GLOBALLY RELEVANT.
WHAT I'M GOING TO TALK A LITTLE
BIT HERE ABOUT IS NOT REALLY
RESULTS BUT HOW WE'RE TRYING TO
DO THAT.
WE'RE FUNDED AS A RESOURCE,
WE'RE SUPPORTED AS A RESOURCE
PROGRAM, SO THE IDEA IS THAT WE
ARE NOT A SPACE WHERE WE TAKE
ALL OF THE GENETICS AND WE
PROVIDE ALL OF THE ANSWERS BUT
RATHER WE PROVIDE THE TOOLS AND
THE RESOURCES AND THE DATA TO
ASK QUESTIONS.
TO ALLOW INVESTIGATORS TO ASK
GENETIC QUESTIONS.
SO WE HAVE THREE PRIMARY
SCIENTIFIC OUTCOMES WE'RE
ATTEMPTING TO ATTACK.
UNDERSTANDING A COMPLEX DISEASE,
WE'RE TARGETING UP 150,000
INDIVIDUALS.
IDENTIFYING AND PROVING RAPIDLY
NEW GENETIC CAUSES OF DISEASE,
SO TO DO THIS WILL BE ALL GINO
SEQUENCING, 10,000 INDIVIDUALS,
LONG -- SEQUENCING A COUPLE
THOUSAND INDIVIDUALS, AND DOING
ALL OF THIS AND MAKING ALL OF
THIS GLOBALLY RELEVANT.
SO PRIORITIZING COLLECTION OF
NEW SAMPLES AND NEW COHORTS,
CREATION OF NEW COHORTS FROM
BLACK AMERICANS, SUB-SAHARAN
AFRICA, NORTH AFRICA, SOUTH AND
CENTRAL AMERICA, THE CARIBBEAN,
EAST ASIA, CENTRAL ASA.
AS IMPORTANT, I THINK, AS
ANYTHING TO ACHIEVE THESE
SCIENTIFIC OUTCOMES, WE HAVE
THESE REALLY STRONG STRUCTURAL
PRIORITIES.
SO DEMOCRATIZING THE DATA,
MAKING THE DATA AVAILABLE AND
USABLE FOR THE RESEARCH
COMMUNITY AND FOR THE FOLKS
ACTUALLY -- COOPERATING WITH
EVERYBODY, AGAIN, THE IDEA IS TO
CREATE A STUCK TREUR IN WHICH
REALLY A COLLECTIVE WHERE
INVESTIGATORS FROM ALL OVER THE
WORLD HAVE EQUAL ACCESS TO
RESOURCES AND ARE ABLE TO
ANALYZE TATA.
ALL THIS HAS TO BE DONE USING
SAFE, RESPONSIBLE RESPONSIBLE DATA SHARIN G,
WE'RE PROMOTING DIVERSITY IN RAO
SEARCH AS WELL AS THE WORK WE'RE
DOING AND I'LL TALK A LITTLE
ABOUT THAT, AND BEING AS
TRANSPARENT AS WE POSSIBLY CAN.
SO WE HAVE THIS ORGANIZATIONAL
SCHEME THAT INCLUDES A WHOLE
SERIES OF WORKING GROUPS.
IT ALSO INCLUDES SOMETHING
REALLY NEAT, WHICH IS WE HAVE
LEADS AND CO CO-LEAGUE
INVESTIGATOR, NEW TO PARKINSON'S
DISEASE, SO YOU GET THIS REALLY
NICE MIX OF LEADERS WHO ARE THE
UP AND COMING LEADERS OF THE
FIELD ALONG WITH THE OLDER
ESTABLISHED INDIVIDUALS.
THE WAY THAT IT WORKS IS THAT WE
ACCEPT DATA AND SAMPLES FROM
INDIVIDUALS, SO CLINICAL DATA,
SOMETIMES GENETIC DATA, DNA,
BLOOD, TISSUE, WE DO ALL OF THE
HARMONIZATION CENTRALLY, WE
PRODUCE ALL OF THE EITHER
SEQUENCE DATA OR GENOTYPE DATA,
RETURN THAT TO THE
INVESTIGATORS, AND THEN WE'VE
WORKED WITH A REALLY FANTASTIC
PROGRAM, THE ACCELERATING
MEDICINES PARTNERSHIP FOR
PARKINSON'S DISEASE PROGRAM, TO
ALLOW US TO SHARE GP2 DATA IN
REALTIME.
SO AGAIN, THE IDEA HERE IS FOR
US TO GENERATE DATA AND GET IT
OUT TO THE EXEUNT AS COMMUNITY AS QUICKLY
AS POSSIBLE, SO THERE WILL BE NO
WAITING FOR PUBLICATION, NO
EMBARGOES, IT'S ABOUT GETTING
DATA OUT AS QUICKLY AS POSSIBLE.
THE OTHER PART OF THIS PROCESS
IS THAT THE MPD STRUCTURE
INCLUDES NOT ONLY A DATA STORE
BUT THE COMPLETE RESOURCES TO
ACTUALLY DO DATA ANALYSES IN
PLACE.
SO WHAT THIS EFFECTIVELY MEANS
IS THE DATA IS REALLY TRULY
DEMOCRATIZED.
ANYBODY WHO HAS ACCESS TO THE
INTERNET CAN ACCESS THE DATA.
CAN SPIT OUT POWERFUL RESOURCES
TO ANALYZE THE DATA IN PLACE,
AND WE WILL PAY FOR THAT
ANALYSES, SO WE COVER THE COSTS
OF THAT ANALYSES.
SO NOW INDIVIDUALS WHO ARE
CONTRIBUTING SAMPLES FROM LEGOS,
FOR EXAMPLE, ARE ABLE TO LOG ON,
ACCESS OUR RESOURCES AS PART OF
THIS PROJECT AND ANALYZE
GP2 DATA.
THERE IS AN ADDITIONAL FACT TO
THIS, WHICH IS AROUND TRAINING,
WHICH I'LL COME BACK TO LATER.
SO WHERE ARE WE IN GP2?
WE'RE ENDING REALLY THE STARTUP
PHASE, BEGINNING IN YEAR THREE.
DONE A HUGE AMOUNT IN TERMS OF
UNDERSTANDING THE ISSUES OF
COMPLIANCE AND OPERATIONS.
THIS, I WILL SAY, HAS BEEN
INCREDIBLY CHALLENGING.
GENETICS IS RELATIVELY EASY.
TRYING TO NAVIGATE THE CHANGING
ENVIRONMENT OF WHERE DATA CAN BE
AND HOW DATA CAN MOVE
PARTICULARLY BETWEEN COUNTRIES,
MUCH MORE CHALLENGING.
A WHOLE SERIES OF THINGS ABOUT
HOW DATA AND SAMPLES SHOULD
FLOW, HOW WE EVALUATE PROJECTS,
HOW WE ENSURE THAT IF SOMEONE
PROPOSES TO ANALYZE SAMPLES,
THAT WE MAKE SURE THERE IS
INCLUES
INCLUSION FROM OUR
UNDERREPRESENTED COLLEAGUES WHO
WHO -- WHICH ALLOWS US TO LOOK
AT NEURODEGENERATIVE ASSOCIATED
VARIANTS ACROSS ANCESTRIES.
SO THIS IS A 2 MILLION VARIANT
ARRAY THAT IS NOW COMMERCIALLY
AVAILABLE.
FORM STRATEGIC PARTNERSHIPS, I'D
MENTIONED AMP PD, THE MICHAEL J.
FOX ASSOCIATION, SEVERAL GROUPS
THAT HAD ALREADY STARTED TO
COLLECT SAMPLES FROM AROUND THE
WORLD.
A REALLY IMPORTANT PART OF THIS,
AGAIN, GIVEN OUR AIM, WHICH IS
TO TRY AND LEVEL THE PLAYING
FIELD FOR RESEARCHERS AROUND THE
WORLD, IS TO BUILD GLOBAL WILL
AND TO BUILD CAPACITY AT THOSE
RESEARCH SITES THAT HAVE
TRADITIONALLY BEEN
UNDERREPRESENTED.
SO I TALKED A LITTLE BIT ABOUT
HAVING RESOURCES FOR THOSE SITES
TO BE ABLE TO ACCESS AND ANALYZE
DATA, BUT OF COURSE TRAINING IS
KEY HERE.
SO WE HAVE CREATED SEVERAL
TRAINING MODULES THAT ARE --
THERE ARE 50 TRAINING MANUALS
HERE THAT GO FROM SOUP TO NUTS.
IF YOU'VE NEVER LOGGED ON TO A
DPEUTER TO
COMPUTER TO DO ANALYSIS, IT
TAKES YOU TO THAT FUNCTIONAL
ANALYSES YOU CAN PERFORM.
THESE 50 LESSONS ARE TRANSLATED
INTO MORE THAN 100 DIFFERENT
LANGUAGES.
AGAIN, TRYING TO REDUCE THE
BARRIER FOR FOLKS TO BE ABLE TO
ACCESS THIS RESOURCE AND LEARN
AND ALLOW US TO CREATE A GROUP
OF EXPERTS AROUND THE WORLD THAT
CAN GENERATE INTERESTING
RESEARCH QUESTIONS.
THAT LEARNING MANAGEMENT SYSTEM
HAS MORE THAN 500 USERS NOW,
AROUND A THIRD OF WHICH ARE FROM
LOW TO MEDIUM INCOME COUNTRIES.
WE HAVE LIVE Q & A SESSIONS WITH
LMS USERS, HELPING THEM NAVIGATE
THE PROCESS AND HELPING THEM
DEAL WITH ANY PARTICULAR
ANALYTICAL QUESTIONS THEY HAVE.
AS PART OF GP2, WE HAVE HELPED
SUPPORT A COMPETITIVE PH.D.
PROGRAM, SO I MENTIONED THAT WE
HAVE REALLY IN THE FIRST PHASE
TARGETED NEW COLLECTIONS ACROSS
AFRICA, SOUTH AMERICA, AND
THROUGHOUT ASIA.
THIS WAS TARGETED FOR CENTRAL
SOUTH AMERICA AND ASIA, SO WE
HAVE NEW PH.D. PROGRAMS, WORKING
ON GP2, THESE STUDENTS FROM
MEXICO, CHILE, TAIWAN AND
BRAZIL.
WE'VE ALSO SUPPORTED CLINICAL
TRAINING FOR CLINICIANS FROM
AFRICA, SO THESE ARE CLINICIANS
FROM ETHIOPIA, GHANA, NOW IN A A
MASTER'S CLINICAL PROGRAM IN
PARTNERSHIP WITH THE UNIVERSITY
COLLEGE LONDON, WHERE THEY COME
OVER AND TRAIN SPECIFICALLY IN
MOVEMENT DISORDERS.
OFTEN THESE ARE COUNTRIES WHERE
THERE ARE NO MOVEMENT DISORDER
SPECIALISTS, WHERE THERE MAY
ONLY BE ONE OR TWO NEUROLOGISTS.
SO AGAIN, THIS IDEA OF TRYING TO
BUILD GLOBAL WILL AND CAPACITY.
WE'VE WORKED WITH FUNDERS ON
CREATING RFAs THAT REALLY
TARGET DIVERSITY, EQUITY AND
INCLUSION AND HOW TO ACCESS
GP2 DATA, HOW HOW TO USE
GP2 DATA, AND WE'RE EVEN
PRODUCING DALE TA FOR SOME OF
THESE SUCCESSFUL APPLICANTS.
WE'VE ALSO BROUGHT PEOPLE
TOGETHER.
WE RUN HACKATHONS FOCUSED ON
LEARNING HOW TO DO ANALYSES AND
BRINGING TEAMS TOGETHER AROUND
THE WORLD, SO ESSENTIALLY WHAT
YOU DO IS BRING A GROUP OF
INDIVIDUALS TOGETHER WITH
DIFFERENT SKILLSETS, THEY ARE
PUT INTO TEAMS AND THEY SET ACCEPT A
CHALLENGE OF SOME KIND THEY HAVE
TO DO OVER TWO OR THREE DAYS.
USUALLY A CODING CHALLENGE.
THE LAST ONE WE RAN INCLUDED
ALMOST 50 PARTICIPANTS FROM A
DOES DIFFERENT COUNTRIES.
WE ALSO HAVE MEETINGS TO BRING
THE COMMUNITY TOGETHER WITH A
LARGE NUMBER OF ATTENDEES.
GP2 HAS ALSO SUPPORTED THE
CREATION OF A NEW COHORT.
THIS IS THE BLACK AND AFRICAN
AMERICAN CONNECTIONS TO PD STUDY
OR THE BACK PD STUDY.
BLACK AND AFRICAN AMERICAN
PARKINSON'S DISEASE PATIENTS ARE
INCREDIBLY UNDERREPRESENTED IN
PARKINSON'S RESEARCH, SO OUR AIM
IS TO COLLECT AROUND 500,000
PATIENTS.
THE FIRST PART AIMED AT
UNDERSTANDING GENETICS, HOPING
THIS WOULD FORK AS THE HUB FOR
FUTURE STUDIES, AND GP2 ALSO
STARTED -- WITH THE IDEA
ALLOWING THESE GROUPS FROM
AROUND THE WORLD TO REALLY
EXECUTE THEIR OWN RESEARCH
PROJECTS.
SO WHERE ARE WE?
I TOLD YOU ABOUT ALL THE THINGS
WE PLANNED AND HOW IT'S GONE.
SO SO FAR, WE'RE STILL ONLY TWO
YEARS IN.
WE'RE ABOUT TO REALLY START
RAMPING UP.
WE HAVE 170 COHORTS.
AT SOME POINT IN THE PROCESS OF
ONBOARDING INTO GP2, UP 170,000
SAMPLES AVAILABLE, NOW GENOTYPES
OVER 20,000 SAMPLES AND THE
FIRST 5,000 ARE ACTUALLY
RELEASED, ARE AVAILABLE IN AMP
P, YOU CAN GO THERE NOW AND
ACCESS JOE KNOW TYPE DATA FROM GENOTYPE DA TA FROM THOSE
SITES.
IT'S CERTAINLY BETTER THAN IT
WAS, BUT THERE ARE COUNTRIES WE
NEED TO FOCUS ON AND REALLY
IMPROVE REP 16 TAITION.
SO THERE ARE A CON OF THINGS WE
CAN DO IN PD -- SORRY -- IN GP2,
AND OF COURSE THERE ARE THE
OBVIOUS GENETIC THINGS I KIND OF
TALK ABOUT ON THE LEFT-HAND SIDE
OF THIS SLIDE CENTERED AROUND
DISCOVERY, FINDING NEW RISK
FACTORS, FINDING NEW GENES,
FINDING MODIFIERS, ALSO CREATING
RESOURCES, PROVIDING INDIVIDUALS
WHO ARE WORKING ON THE
FUNCTIONAL SIDE OF THIS WORK
WITH DIVERSE IPS LINES, WITH
DIVERSE BRAIN TISSUE.
BUT THERE ARE MORE AND MORE
OTHER THINGS COMING ALONG, MO
EMERGING OPPORTUNITIES AND
ADJACENT OPPORTUNITIES.
THIS REALLY SPEAKS TO, I THINK,
THE POWER OF WHAT WE'RE TRYING
TO CREATE HERE.
AGAIN, WE'RE NOT TRYING TO
CREATE SOMETHING WHERE GP2 DOES
ALL OF THE ANALYSIS, AND WE'RE
DONE.
WE'RE TRYING TO CREATE A
FRAMEWORK THAT ALLOWS OTHERS TO
BE ABLE TO ACCESS DATA AND
RESOURCES IN ORDER TO BE ABLE TO
EFFECT RESEARCH ON A GLOBAL
SCALE.
SO A SUMMARY.
I THINK IT MAKES SENSE TO GIVE
AN OVERALL SUMMARY OF WHAT I'VE
TALKED ABOUT TODAY.
I THINK PROGRESS IN PD HAS BEEN
REALLY SUBSTANTIAL OVER THE LAST
25 YEARS.
WE'VE LITERALLY GONE FROM ZERO
TO 100 IN THAT PERIOD OF TIME.
I THINK WHAT IS CRITICAL FOR
PARKINSON'S DISEASE, LIKE MANY
OTHER DISEASES, IS THAT WITH WE HAVE
TO EXPAND THIS WORK TO ENCOMPASS
DIVERSE POPULATIONS.
IT IS, OF COURSE -- IT IS, OF
COURSE, IMPERATIVE THAT WE DO
SO, NOT JUST BECAUSE IT'S THE
RIGHT THING TO DO, BUT OF COURSE
IT IS, BUT ALSO BECAUSE
SCIENTIFICALLY, IT'S ESSENTIAL.
IT'S ESSENTIAL BECAUSE IT SPEEDS
UP OUR ABILITY TO MAP NEW LOCI,
THAT HAVE A PARTICULAR GENETIC
FORM AND, THEREFORE, WOULD BE
USEFUL FOR APPLYING CLINICAL
TRIALS.
THERE ARE JUST A MYRIAD OF
REASONS THAT WE REALLY NEED TO
FOCUS IN THIS SPACE.
OUR AIM IN CREATING GP2 REALLY
IS AN EXTENSION OF WHAT WE'VE
DONE IN GPDC AND IN THE LAB MORE
BROADLY, IS TO CREATE A GLOBAL
RESEARCH COMMUNITY, AVOIDING
COMPLETELY THE APPROACHES THAT
HAVE SOMETIMES BEEN USED IN THE
PAST, WHERE WELL FUNDED LABS
HAVE COME IN, TAKEN SAMPLES AND
WAY AND PUBLISHED.
WE'RE REALLY TRYING TO WORK WITH
THESE COMMUNITIES TO CREATE A
RISING TIDES.
ANY SUCCESS WE'VE HAD HAS BEEN
ESSENTIAL IN THAT SUCCESS, HAS
BEEN THE IRP.
IT REALLY IS A SPECTACULAR PLACE
TO WORK, I THINK.
I THINK IT ALLOWS US TO DO SOME
THINGS THAT JUST CAN'T QUITE BE
DONE EASILY OR AS EFFECTIVELY IN
THE OUTSIDE WORLD.
I'M NOT SAYING EVERYONE SHOULD
BE DOING PROJECTS LIKE THIS, I'M
NOT SAYING ALL RESEARCH SHOULD
BE DONE LIKE THIS, BUT I THINK
THERE'S SOME REALLY UNIQUE AND
SPECIAL THINGS ABOUT THE IRP
THAT REALLY ALLOWS US TO EFFECT
CHANGE, AND IT'S BEEN AN
ABSOLUTE PLEASURE TO WORK IN THE
IRP OVER THE LAST 20 YEARS OR
SO.
I STARTED TO PUT TOGETHER A
THANK YOU SLIDE BUT THERE ARE
TOO MANY PEOPLE TO THANK.
THESE ARE FOLKS WORKING IN MY
LAB OR I'M WORKING WITH ON
VARIOUS PROJECTS.
I WOULD LOVE TO GIVE A PICTURE
OF GP2 BUT THERE ARE AROUND 500
MEMBERS, SO THAT WOULD BE
DIFFICULT TO DO, BUT THE CLEAR
MESSAGE HERE IS, ALTHOUGH I'M
THE MESSENGER, THIS INVOLVES
HUNDREDS OF PEOPLE WHO WERE ALL
WILLING TO WORK TOGETHER IN A
COLLABORATIVE, EASY WAY, AND
IT'S BEEN A REAL PLEASURE TO BE
A PART OF THAT OVER THE LAST 20
YEARS.
I DON'T KNOW THAT I HAVE ANOTHER
20 YEARS OF IT IN ME, BUT I
GUESS WE'LL SEE.
SO WITH THAT, I WILL STOP AND
THANK YOU FOR YOUR KIND
ATTENTION.
>> THANK YOU VERY MUCH, ANDY.
THAT WAS A WONDERFUL
PRESENTATION.
WE HAVE ONE QUESTION IN THE
CHAT.
THE MESSAGE IS, DATA ON -- AND
ANCESTRIES IS VERY INTRIGUING.
HOW PRODUCTIVE DO YOU THINK IT
WOULD BE MINING FOR GENETIC LOCI
THAT -- RESILIENCE?
DO YOU HAVE ANY SUGGESTION ON
APPROACH IN THIS AREA?
>> I CAN TELL YOU, WE HAVE
SOMEONE IN OUR LAB THAT IS
REALLY INTERESTED IN THIS NOTION
OF RESILIENCE.
I MENTIONED HER EARLIER, SARAH
BANDRESS S IGA.
I THINK WE HAVE A WAYS TO GO IN
THAT SPACE, FRANKLY, BUT I DO
THINK IT'S A REALLY INTERESTING
IDEA.
AND THE IDEA OF WHETHER
RESILIENCE IS ONE OF THE THINGS
WE'D SEE, LET ME STEP BACK A
LITTLE BIT.
ONE OF THE THINGS WE SEE
SURPRISINGLY IS THERE'S NOT A
LOT OF GENETIC OVERLAP BETWEEN
MANY NEURODEGENERATIVE DISEASES.
SO ALZHEIMER'S DISEASE AND
PARKINSON'S DISEASE ARE PRETTY
DIFFERENT GENETICALLY, BUT I DO
WONDER, AND THIS IS REALLY
DRIVEN BY SARAH'S RESUCH,
WHETHER THERE MIGHT BE SHARED
FACTORS FOR RESILIENCE ACROSS
THESE DISEASES.
SO I THINK IT'S A GOOD IDEA.
>> I WANTED TO ASK YOU A
QUESTION IF I DON'T MIND.
I REALLY ENJOY YOUR
PRESENTATION.
I THINK THAT THERE IS KIND OF A
TRADEOFF IN THE FIELD OF
NEURODEGENERATIVE DISEASE
BETWEEN THE NEED TO
HYPERPHENOTYPE, SO BREAK ALL THE
PHENOTYPE IN MANY, MANY
DIFFERENT SUBGROUPS, AND AT THE
SAME TIME, PEOPLE ARE TALKING
ABOUT, YOU KNOW, GLOBAL
MECHANISMS, OVERALL PATHWAY THAT
AFFECT THE MULTIPLE
NEURODEGENERATIVE DISEASE AT THE
SAME TIME.
HOW WE ADDRESS THIS --
INTERPRETATION OF
NEURODEGENERATIVE DISEASE, I
WONDER IF YOU'VE EVER THOUGHT
ABOUT IT.
>> I THINK I UNDERSTAND YOUR
QUESTION.
I MEAN, I THINK THE CHALLENGE
FOR US HAS BEEN -- MUCH OF WHAT
WE DO IS DEPENDENT ON NUMBERS.
SO EXTREMELY DEEP PHENOTYPING
WHERE YOU START TO SEE
DIFFERENCES CLINICALLY,
PATHOLOGICALLY, OR MAYBE, YOU
KNOW, MECHANISTICALLY IF YOU'RE
LOOKING AT BIOMARKERS, IS
JUST -- WE JUST CAN'T QUITE GET
THERE IN TERMS OF THE NUMBERS.
THERE ARE SOME GROWING STUDIES.
CERTAINLY IN THE AD FIELD AND
ALSO IN THE PD FIELD, THE PKMI
STUDY, WHERE LONG -- STARTING TO
GET US TO WHETHER THERE ARE
SUBTYPES.
I THINK ONE OF THE THINGS THAT
WE'VE TRIED AND I THINK IS THE
WAY FORWARD IS TO STOP THINKING
ABOUT PHENOTYPING IN TERMS OF
WHAT IS BEING PRESENTED TO US
CLINICALLY, WHAT IS BEING
PRESENTED TO A CLINICIAN AS THEY
SEE THE PATIENT AND RATHER
TAKING QUANTITATIVE MEASURES AND
USING APPROACHES LIKE AI OR ML
TO TELL US WHAT PROGRESSION
LOOKS LIKE, TO TELL US WA
SUBTYPES LOOK LIKE.
WE HAVE A COMPUTER SCIENTIST IN
OUR GROUP WHO HAS BEEN WORKING
ON THIS IN PD AND CERTAINLY
STARTS TO SEE, BASED ON
PRESENTATION AND PROGRESSION,
DIFFERENT CLUSTERS OF MD,
DIFFERENT CLUSTERS OF PD
PATIENTS.
>> TWO MORE QUESTIONS.
ONE FROM CAN THESE BE USED TO
UNDERSTAND -- FACTORS ACROSS THE
WORLD?
>> THE MAJORITY OF THE -- IN THE
GP2 STUDY HAVE ALREADY BEEN
COLLECTED THERE, NARE
PERSPECTIVE COLLECTIONS THAT
WERE EXISTING.
HOWEVER, THERE ARE QUITE A FEW,
PARTICULARLY IN UNDERREPRESENTED
POPULATIONS, THAT ARE ONGOING.
SO WE HAVE STARTED TO DO THINGS
LIKE DEPLOY QUESTIONNAIRES ON
DIET AND EXPOSURE.
THAT IS A TOUGH THING TO DO FOR
SURE, AS LUIGI KNOWS BETTER THAN
ANYONE ACTUALLY, BUT WE'RE AT
LEAST STARTING TO GET THERE.
THIS KIND OF ILLUSTRATES MAYBE
THE POTENTIAL OF GP2.
IT'S SET UP AS A GENETIC STUDY,
BUT IF SOMEONE COMES ALONG WITH
A RESEARCH QUESTION LIKE THAT,
WE HAVE THE CONNECTIONS ALL IN
PLACE TO BE ABLE TO INITIATE A
STUDY, TO BE ABLE TO TAKE A
STUDY LIKE THAT FORWARD?
>> I HAVE ONE QUESTION, HAVE YOU
FOUND NON-CODING VARIANT, FOR
IMAM, -- UTRS, SOMETHING THAT IS
NOT CODED?
>> AS CAUSATIVE?
>> AS CAUSATIVE.
>> AS CAUSATIVE, NO, NOT REALLY.
OF COURSE AS RISK, YES, TONS OF
THEM, IT'S KIND OF UNDERSTANDING
WHAT THE FUNCTIONAL REGION IS.
I THINK THIS MIGHT, THOUGH, IN
PART BE BECAUSE WE WEREN'T
REALLY LOOKING.
SO MY GUESS IS, THERE ARE THINGS
IN UTRs, THERE ARE THINGS IN
REGULATORY REGIONS THAT MAY
AFFECT -- THAT MAY NOT JUST
AFFECT A RISK THAT MAY BE
CAUSATIVE, WE JUST HAVEN'T
LOOKED.
ONE OF THE THINGS ABOUT
TRANSFORMATIVE TECHNOLOGIES, IS
LONG -- SEQUENCING AND MY HOPE
IS I WILL HELP RESOLVE SOME OF
THOSE THINGS THAT WE'VE MISSED.
>> OKAY.
THANK YOU SO MUCH, ANDY, FOR
YOUR SCIENCE, FOR YOUR
GENEROSITY, FOR PRODUCING THIS
WONDERFUL -- I'M SURE WE'RE
REFLECTING THE HELP OF THE
POPULATION.
AND THANK YOU, EVERYBODY, THAT
HAS BEEN LISTENING.
THIS CONCLUDES OUR PRESENTATION.
>> THANK YOU.