>> ALL RIGHT.
WELL, GREETINGS AND SALUTATIONS!
WELCOME TO EVERYONE.
I'M DAN KASTNER, THE SCIENTIFIC
DIRECTOR EE MER TU TIS AND STILL
ACTIVE PHYSICIAN SCIENTIST IN
THE NATIONAL HUMAN GENOME
RESEARCH INSTITUTE AND IT IS MY
ENORMOUS PLEASURE THIS AFTERNOON
TO WELCOME YOU TO THIS, THE
FOURTH INSTALLMENT IN THE 2024
SERIES OF DEMYSTIFYING MEDICINE.
A SERIES OF PRESENTATIONS THAT
BRIDGES THE EXCITING
DEVELOPMENTS IN BIOLOGY AND
ENGINEERING WITH MEDICINE.
AT LEAST SOMETIMES.
AND OF COURSE WE HAVE THE ICONIC
PICTURE OF THE BROOKLYN BRIDGE,
SPANNING FROM MANHATTAN TO
BROOKLYN, GOING OVER THE EAST
RIVER, AND YOU SEE UP ON THE
CATWALK A COUPLE OF -- I THINK
IT'S A PHYSICIAN AND A SCIENTIST
UP THERE, EXCHANGING THEIR
OPINIONS WITH REGARD TO THE
ISSUES OF THE DAY BACK IN THE
1870s, WHEN THE BROOKLYN
BRIDGE WAS BEING CONSTRUCTED.
OF COURSE NOW YOU CAN IMAGINE
LES BIESECKER AND JOSH DENNY UP
ON THE CATWALK TALKING ABOUT
GENOMIC ASCERTAINMENT, OR
PERHAPS PHENOTYPE RISK SCORES,
AND PERHAPS THEY WILL GET
EXCITED ABOUT IT AND THEY'LL
FALL OFF THE CATWALK AND LAND IN
THE FIELD, IN THE CORNFIELD WITH
THE SILOS.
WHO KNOWS?
BUT IN ANY CASE, IT'S WONDERFUL
TO HAVE YOU ALL HERE, AND THIS
IS PART OF A SERIES THAT GOES
FROM THE BEGINNING OF JANUARY
THROUGH THE MIDDLE OF MAY, I
THINK, THIS YEAR, AND IT'S FROM
4:00 TO 6:00 IN THE AFTERNOON
EASTERN TIME, STANDARD TIME.
AND YOU CAN WATCH IT ON
VIDEOCAST, BUT WE WOULD PREFER
THAT YOU COME HERE, AND WE HAVE
THESE DELICIOUS AND NUTRITIOUS
COOKIES HERE FOR ANYONE WHO
ACTUALLY SHOWS UP IN PERSON, YOU
GET A FREE COOKIE.
AND COFFEE, YES INDEED, AND
COFFEE, COFFEE TO WHET YOUR
PALATE WHILE EATING THOSE DRY
COOKIES.
IN ANY CASE, YOU CAN ALSO GET
CME CREDIT HERE AND THE C ME.
CODE IS 52089.
I'LL GIVE YOU THE PHONE NUMBER
YOU HAVE TO CALL IN ORDER TO GET
THAT IN A MOMENT.
AND IF YOU HAVE QUESTIONS, YOU
JUST CLICK IF YOU'RE DOING THE
VIDEOCAST, ANYWAY, YOU USE THE
"SEND LIVE FEEDBACK" BUTTON ON
THE VIDEOCAST DISPLAY.
IF YOU'RE HERE IN PERSON, YOU'RE
ACTUALLY ALLOWED TO ASK THE
QUESTION YOURSELF.
YOU DON'T HAVE TO TYPE IT IN TO
THE "SEND LIVE FEEDBACK" BUTTON.
ANYWAY, ABOUT IF IF YOU WANT TOK
IN TIME, YOU CAN DO THAT TOO.
ALL OF THE SESSIONS ARE ARCHIVED
AND YOU CAN SEE THE LINKS THERE
FOR THE ARCHIVES.
HERE ON THE NEXT SLIDE, YOU JUST
HAVE THE CME INFORMATION, AGAIN,
THAT'S CME CODE 52089 AND TEXT
THAT CODE TO 844-980-1555.
IF YOU DO IT IN THE NEXT MINUTE,
YOU'LL GET AN EXTRA COOKIE.
SO IN ANY CASE, THEN HERE'S,
AGAIN, REPEATED, THIS CODE.
THE DISCLOSURES FOR THOSE OF YOU
WHO ARE INTERESTED IN THAT.
AND NOW WE BEGIN THE REAL MEAT
OF THE PRESENTATION HERE.
OF COURSE THIS PRESENTATION,
MANY OF YOU KNOW, IS THE
PROSPECT OF PRECISION MEDICINE
FOR ALL-OF-US, THAT'S THE TITLE
OF IT, A MADE-UP TITLE TO TRY TO
BRING TOGETHER TWO THEMES IN
THIS PRESENTATION.
OF COURSE PRECISION MEDICINE IS
AN IDEA THAT WAS SORT OF PUT OUT
THERE IN THE STATE OF THE UNION
ADDRESS BACK IN 2015, AND IT
REFERS TO THE IDEA OF HAVING A
SYSTEM WHERE WE CAN TARGET
THERAPIES TO INDIVIDUALS BASE
OND GENOMIC INFORMATION, BASED
ON ENVIRONMENTAL EXPOSURES,
BASED ON THE MICROBIOME, BASED
ON THEIR DIET, THEIR EXERCISE,
THEIR HEALTH HISTORY,
EVERYTHING, TO REALLY GET DOWN
TO A PRECISE TREATMENT FOR THAT
PERSON.
AND WE HAVE TWO LEADING EXPERTS
IN THE FIELD OF PRECISION
MEDICINE THIS AFTERNOON.
THE FIRST OF THEM, DR. LES
BIESECKER, IS AN NIH
DISTINGUISHED INVESTIGATOR AND
DIRECTOR FOR THE CENTER FOR
PRECISION HEALTH RESEARCH AT THE
NHGRI, THE NATIONAL HUMAN GENOME
RESEARCH INSTITUTE.
HE GOT HIS BACHELOR'S DEGREE
FROM UC RIVERSIDE, HIS
MEDICAL DEGREE AOA FROM THE
UNIVERSITY OF ILLINOIS.
HE DID HIS PEDIATRIC TRAINING AT
THE UNIVERSITY OF WISCONSIN, AND
THEN PEDIATRIC GENETICS AT THE
UNIVERSITY OF MICHIGAN.
HE'S WELL-KNOWN FOR HIS MANY
CONTRIBUTIONS TO THE ETIOLOGY
AND NATURAL HISTORY OF MULTIPLE
DISEASES, AND FOR BEING THE
FATHER OF THE, THE INITIATOR OF
THE CL CLINSEQ PROGRAM, ABOUT WH
I'M SURE YOU WILL HEAR A GOOD
DEAL DURING THE COURSE OF THIS
PRESENTATION.
HE'S PAST PRESIDENT OF THE
AMERICAN SEW SAMERICAN SOCIETY U
NAN GENETICS, I BELIEVE THAT WAS
IN 2019, AND HE'S AN ELECTED
MEMBER OF THE NATIONAL ACADEMY
OF MEDICINE.
HIS LAB CURRENTLY WORKS ON
CLINICAL, MOLECULAR AND NATURAL
HISTORY STUDIES OF NUMEROUS RARE
DISORDERS OF DEVELOPMENT AND
OVERGROWTH.
THEY'RE DOING A LOT OF TARGETED
THERAPY STUDIES FOR MOSAIC
OVERGROWTH DISORDERS AS WELL.
AND OF COURSE HIS GROUP OVERSEES
THE LARGE SCALE MEDICAL
SEQUENCING PROJECT, CLINSEQ, TO
ADVANCE OUR UNDERSTANDING OF THE
CONTRIBUTIONS OF RARE VERSUS
COMMON GENETIC VARIANTS TO
COMMON DISEASES,
PHARMACOGENOMICS AND NEW
APPROACHES TO STUDY DESIGN AND
SUBJECT PARTICIPATION IN
CLINICAL GENOMICS RESEARCH.
OUR SECOND PRESENTER IS THE GOOD
DR. JOSH DENNY, WHO IS THE CHIEF
EXECUTIVE OFFICER OF THE
ALL-OF-US RESEARCH PROGRAM AT
THE NATIONAL INSTITUTES OF
HEALTH, AND ALSO AN ADJUNCT
INVESTIGATOR AT THE NHGRI.
HE GOT HIS BACHELOR'S DEGREE
FROM VANDERBILT, HIS M.D.AOA
ALSO AT VANDERBILT AND A
MASTER'S DEGREE IN BIOMEDICAL
INFORMATICS AS WELL.
HIS POSTGRADUATE TRAINING
INCLUDED TIME AS A MEDICAL
SCHOLAR AT VANDERBILT AND AN
INTERNAL MEDICINE RESIDENCY
THERE.
HE'S WELL-KNOWN FOR HIS USE OF
ELECTRONIC HEALTH RECORDS.
HE'S A PIONEER IN THAT FIELD,
ELECTRONIC HEALTH RECORDS AND
GENOMICS DATA FROM LARGE SCALE
BIOBANKS TO BETTER UNDERSTAND
DISEASE AND DRUG RESPONSE.
HE'S THE FOUNDING DIRECTOR OF
THE CENTER FOR PRECISION
MEDICINE AT VANDERBILT, AND THE
RECIPIENT OF THE HOMER WARNER
AWARD OF THE AMERICAN MEDICAL
INFORMATICS ASSOCIATION.
HE'S ALSO AN ELECTED MEMBER OF
THE NATIONAL ACADEMY OF
MEDICINE, AND OF THE AMERICAN
SOCIETY FOR CLINICAL
INVESTIGATION.
HIS RESEARCH GROUP IS ACTIVELY
INVOLVED IN THE DISCOVERY OF
DISEASE GENE RELATIONSHIPS BY
GATHERING, ASSESSING AND
ANALYZING THE HUMAN PHENOME
COLLECTION OF ALL PHENOTYPES
JUST LIKE THE GENOME IS THE
COLLECTION OF ALL GENETIC
INFORMATION ACROSS GENOMIC AND
ENVIRONMENTAL EXPOSURES, KNOWN
FOR THE DEVELOPMENT OF THE
PHENOME-WIDE ASSOCIATION STUDY,
LIKE THE GENOME-WIDE ASSOCIATION
STUDY, AND THE DEVELOPMENT OF
TOOLS TO EXTRACT PRACTICAL
INFORMATION FROM THE ELECTRONIC
HEALTH RECORDS IN A SYSTEMATIC
AND UNBIASED FASHION.
SO, WITH THAT HAVING BEEN SAID,
I'M GOING TO TURN THINGS OVER TO
THE GOOD DR. BIESECKER, WHO'S
GOING TO TAKE THINGS AWAY FROM
HERE.
LES.
[APPLAUSE]
>> GREAT.
THANK YOU, DAN, FOR THE LOVELY
INTRODUCTION.
THANKS FOR COMING TONIGHT, AND
ALSO WE SHOULD ALSO THANK THE
DIRECTOR EMERITUS OF THE SERIES,
WIN ARIAS, FOR SETTING THE STAGE
AND BEING HERE WITH US TONIGHT.
OKAY, WE HAVE AN INTERESTING
PRESENTATION FOR YOU TONIGHT.
WE'RE GOING TO HAVE -- I THINK
THE FIVE STAGES TO THIS
PRESENTATION TONIGHT.
OKAY.
DAN ALREADY DID THE
INTRODUCTIONS.
AND WE ARE GOING TO SET THE
STAGE FOR THE PRESENTATION WITH
A PATIENT INTERVIEW.
THIS IS A LOVELY LADY WHO HAS
AGREED TO JOIN US TONIGHT, WHO
IS AS DAN MENTIONED A CURRENT
PARTICIPANT IN OUR CLINSEQ
RESEARCH PROGRAM AND REVERSE
PHENOTYPING PROGRAM, SO WE'RE
GOING TO START WITH THAT.
THEN I WILL PRESENT, THEN JOSH
WILL PRESENT, AND THEN WE'RE
GOING TO COME BACK TO OUR
PATIENT FOR THE DE NU MOUS.
SO STAY WITH US AND YOU'LL BE
FASCINATED HOW THIS TURNS OUT.
SO I WILL START BY NOW IN TURN
INTRODUCING CARRIE WOLSHEFSKI,
GENETICIST AND COUNSELOR WHO IS
IN OUR REVERSE PHENOTYPING CORE,
AND SHE'S GOING TO BRING OUR
RESEARCH PARTICIPANT UP, START
WITH AN INTERVIEW TO SORT OF
WHET YOUR APPETITE ABOUT WHAT
WE'RE GOING TO TALK ABOUT
TONIGHT, AND GET US GOING.
CARRIE?
[APPLAUSE]
>> THANK YOU, LES, FOR THE
INTRODUCTION.
SO AS LES MENTIONED, JOINING ME
TODAY IS MISLILI COLEMAN.
SHE IS A PARTICIPANT IN OUR
CLINSEQ PROGRAM, AS WELL AS A
PARTICIPANT IN OUR REVERSE
PHENOTYPING CORE, WHICH IS A
RELATIVELY NEW CORE FACILITY
HERE IN NHGRI.
SO WHAT WE'RE GOING TO DO TODAY,
MISS COLEMAN AND I ARE GOING TO
TALK A LITTLE BIT ABOUT HER
EXPERIENCES IN THESE RESEARCH
PROGRAMS.
AND A LITTLE BIT ABOUT HOW
GENOMICS HAS PLAYED A ROLE IN
HER CLINICAL CARE AND TREATMENT.
SO MISS COLEMAN, COULD YOU START
BY TELLING US A LITTLE BIT ABOUT
HOW YOU INITIALLY GOT INVOLVED
IN THE CLINSEQ RESEARCH STUDY?
>> YES.
IT WAS BACK IN 2014, WHEN I
HEARD ABOUT THE PROGRAM, AND THE
REASON WHY I WANTED TO GET
INVOLVED WAS PAUSE MY MOTHER,
MOTHER, HAD AN ENLARGED HEART.
SO THAT GAVE ME THE INTEREST IN
TRYING TO FIND OUT WHY THAT
HAPPENED, AND BY CHANCE, IT WAS
SOMETHING PASSED DOWN TO ME.
AND SO THAT WAS THE PRIMARY
REASON WHY I WANTED TO GET
STARTED.
>> THANKS.
SO YOU JOINED THE CLINSEQ STUDY
BACK IN 2014, AND BEFORE THEN
AND LEADING UP TO WHEN WE
RECONTACTED YOU IN 2022, I
UNDERSTAND THAT YOU HAD SOME
HEALTH ISSUES.
COULD YOU SHARE WITH US A LITTLE
BIT ABOUT WHAT SOME OF THE
HEALTH ISSUES WERE THAT YOU WERE
FACING UP UNTIL ABOUT 2022?
>> YES, IT STARTED BACK IN
2019 -- SORRY, 1990, JUST
ACCIDENTALLY I WAS WORKING WITH
AN OPHTHALMOLOGY GROUP, AND
HAPPENED TO LOOK AT MY EYES AND
DISCOVERY HAD SOME RETINAL
ISSUES GOING ON, AND SO I
STARTED SEEING A RETINA
SPECIALIST EVERY YEAR AFTER
THAT.
THEN I GO ON INTO 2000, AND I
STARTED HAVING PAIN AND TINGLING
IN MY FINGERS.
NO ONE COULD ACTUALLY TELL ME
WHY THAT WAS OCCURRING.
I PROCEEDED ON, THEN I DEVELOPED
WHAT THEY CALL COPPER TONE IN MY
HANDS, AND BACK IN THE 2020, I
STARTED TO HAVE THOSE SAME TYPE
OF SENSATIONS IN MY TOES.
I STARTED HAVING A TI TINGLING,
NERVOUSNESS, THE NERVE, AND NO
ONE COULD EXPLAIN THAT TO ME
EITHER.
SO BACK IN 2018, I SAW MY
PRIMARY DOCTOR, AND THEY
DISCOVERED MY HEART WAS SKIPPING
A BEAT, AND SO THEY HAD ASKED ME
TO WEAR A MONITOR, AND I DID
THAT FOR ABOUT A MONTH, AND
DISCOVERED THAT I HAD A VERY
SLOW HEARTBEAT AND I WAS PLACED
WITH A PACEMAKER IN 2018.
AND BACK IN THE -- I GUESS IT
WAS IN THE 2022, I WAS DIAGNOSED
WITH THYROID DISEASE.
AND STARTED TAKING MEDICATION
FOR THAT AS WELL.
SO AS YOU CAN SEE, I HAD A LOT
OF ISSUES GOING ON WITH IN, NO
ONE REALLY KNEW WHY.
>> SO UP UNTIL WE CONTACTED YOU
IN 2022, WHEN WE CALLED YOU AT
THIS GENETIC RESULT, YOU HAD
BEEN DIAGNOSED WITH CARPAL
TUNNEL SYNDROME, THAT NERVE
PAIN, THAT NEUROPATHY THAT
STARTED IN YOUR FINGERS AND THEN
LATER ON YOU ALSO DEVELOPED IN
YOUR TOES.
YOU HAD THAT SLOW HEART RATE FOR
WHICH YOU GOT A PACEMAKER, AND
YOU WERE DIAGNOSED WITH ATRIAL
FIBRILLATION.
>> MM-HMM.
>> AND THEN YOU ALSO HAD THE
RETINAL DYSTROPHY AND GLAUCOMA
WAS ALSO DIAGNOSED, RIGHT?
>> THAT'S TRUE.
THAT'S TRUE.
>> ALL RIGHT.
SO THOSE ARE JUST KIND OF A
BRIEF SUMMARY OF EVERYTHING THAT
WAS GOING ON WITH YOU.
HOW WAS ALL OF THAT KIND OF
IMPACTING YOUR LIFE AND YOUR DAY
TO DAY?
>> WELL, IT WAS A SEVERE IMPACT
FOR ME.
I WAS WONDERING WHY THOSE THINGS
WAS HAPPENING TO ME, AND SEEMED
LIKE NO ONE ELSE IN MY FAMILY
WITH THE EXCEPTION OF MY MOTHER
WAS HAVING THESE ISSUES, WHO'S
IN HER 90s.
SO I WAS LIKE, OKAY, THEN LET'S
BE -- THERE MUST BE SOME
CONNECTION WHY I SEEM TO BE
TRAILING BEHIND MY MOTHER WITH
THE SAME TYPE OF CONDITION THAT
SHE'S HAVING.
AND THAT JUST MADE ME WANTED TO
DIG MORE INTO WHAT WAS GOING ON.
>> I REMEMBER YOU MENTIONED WHEN
YOU WERE TALKING ABOUT WHY YOU
JOINED CLINSEQ, YOU HAD THIS
FAMILY HISTORY OF THE ENLARGED
HEART AND I REMEMBERED WHEN I
CALLED YOU IN 2022, YOU
MENTIONED THAT YOU WERE KIND OF
WORRIED THAT YOU WERE FOLLOWING
ALONG YOUR MOTHER'S HEALTH
PICTURE AND SHE WASN'T DOING SO
WELL, AND SO THAT WAS SOMETHING
THAT WAS KIND OF WEIGHING ON
YOU.
>> YES.
>> OKAY.
SO GIVEN THIS KIND OF
CONSTELLATION OF SYMPTOMS AND
ALL OF THESE DIFFERENT THINGS
THAT YOU HAD GOING ON, DID ANY
DOCTORS EVER SUGGEST A DIAGNOSIS
THAT MIGHT HELP UNIFY ALL OF
THAT'S DIFFERENT HEALTH ISSUES?
>> NO, I REALLY NEVER HAD A
PHYSICIAN TO I DON'T EVEN THINK
WONDER WHY I WAS HAVING ALL OF
THESE ISSUES BECAUSE EVERYONE
SEEMED TO BE SO BUSY.
I'D GO TO MY PRIMARY DOCTOR AND
I MENTIONED SOMETHING WAS GOING
ON WITH ME, THAT SHE WOULD REFER
ME TO THE SPECIALIST AN THAT SHE
FELT I NEEDED TO SEE, BUT BY THE
SAME TIME, I SAW THAT SPECIALIST
AND, WELL, IT WAS DIAGNOSED WITH
WHATEVER WAS GOING ON, BUT NO
ONE TOOK THE TIME TO PUT ALL THE
PIECES TOGETHER AND SAY, I
WONDER WHY THIS IS HAPPENING TO
YOU.
>> SO YOU WOULD GO SEE ONE
PERSON FOR YOUR EYES, ONE PERSON
FOR YOUR HEART, ONE PERSON FOR
THE CARPAL TUNNEL AND IT SOUNDS
AS THOUGH LIKE WHAT DR. KASTNER
WAS SAYING, EVERYONE WAS KIND OF
LIVING IN THEIR OWN SILO AND
THERE WEREN'T A LOT OF BRIDGES
OR CONNECTIONS BETWEEN THEM.
>> YES, YES, EXACTLY.
>> DID ANYBODY EVER MENTION THE
CONCEPT OF GENETICS IN ALL OF
THE DIFFERENT THINGS THAT WERE
GOING ON WITH YOU AT THE TIME?
>> NO, THAT WAS SOMETHING THAT
WAS NEVER EVEN DISCUSSED.
AS A MATTER OF FACT, IT WAS
SOMETHING THAT I DIDN'T EVEN
THINK ABOUT.
YOU KNOW, I THOUGHT ABOUT IT IN
THE SENSE THAT I SEEMED TO BE
TRAILING BEHIND MY MOM IN MY
SYMPTOMS, BUT I NEVER THOUGHT
ABOUT, OH, THAT COULD BE
GENETIC.
IT JUST NEVER OCCURRED TO ME.
>> SO YOU'RE THINKING FROM LIKE
A FAMILY PERSPECTIVE BUT NOT
NECESSARILY LIKE, OKAY, WHAT
MIGHT ALL BE CONNECTING ALL OF
THE DOTS TOGETHER.
>> RIGHT.
>> ALL RIGHT.
SO WE'LL PUT A PIN IN THINGS FOR
NOW AND WE'LL COME BACK AND KIND
OF TALK ABOUT, OKAY, WHEN WE
GAVE YOU A CALL IN 2022 2022 WE
GENETIC RESULT, HOW DID THAT TIE
ALL OF THESE DIFFERENT
COMPONENTS OF YOUR HEALTH ISSUES
ALL TOGETHER?
BUT FOR NOW, WE'LL TURN IT OVER
TO DR. BIESECKER TO GIVE A
LITTLE INTRODUCTION ABOUT THIS
IDEA OF USING GENETICS IN OUR
HEALTHCARE.
[APPLAUSE]
>> OKAY.
THANKS FOR THAT INTRODUCTION.
SO NOW WHAT I WANT TO DO IS
TRANSITION TO SOME SLIDES ON
THIS CONCEPT OF WHAT WE CALL
REVERSE PHENOTYPING OR
GENOTYPE-FIRST RESEARCH.
SO WHAT WE'RE REALLY TALKING
ABOUT HERE IS THE FUND MENTAL
STRUCTURE OF HOW DOCS THINK
ABOUT THEIR PATIENTS AND HOW
PATIENTS GET CARED FOR AND HOW
WE CAN USE INFORMATION TO BEGIN
TO THINK ABOUT CHANGING THAT.
SO THE CURRENT MODEL IS PRETTY
SIMPLE.
THIS IS THE DIFFERENTIAL
DIAGNOSTIC MODEL THAT
ESSENTIALLY ALL PHYSICIANS USE.
AND IT FIRST STARTS WITH THE
PATIENT GETTING SICK.
THEN THEY GO TO THEIR DOCTOR,
THEY SAY WHAT'S WRONG WITH THEM,
THEY GET -- THE DOCTOR ELICITS A
HIHISTORY AND DOES A PHYSICAL
EXAMINATION, AND THEN THE DOCTOR
CREATES WHAT'S CALLED THE
DIFFERENTIAL DIAGNOSIS.
SO THAT'S A LIST OF DIAGNOSTIC
POSSIBILITIES THAT COULD
POTENTIALLY EXPLAIN THAT
PATIENT'S SYMPTOMS.
THEN THE CLINICIAN WILL ORDER
ONE OR MORE TESTS ON THAT
PATIENT THAT DISTINGUISH, AMONG
THE DIAGNOSTIC POSSIBILITIES, IN
ORDER TO REFINE THAT
DIFFERENTIAL DIAGNOSIS AND
EVENTUALLY GET TO A SINGLE
DIAGNOSIS THAT EXPLAINS THEIR
PROBLEMS, AND THEN HOPEFULLY
TREAT THEM.
SO THAT'S THE SIMPLE
DIFFERENTIAL DIAGNOSTIC MODEL.
BUT OF COURSE IT'S NEVER THAT
SIMPLE.
RARELY THAT SIMPLE.
THERE'S OFTEN NUANCES,
COMPLICATIONS, AND IT'S VERY,
VERY COMMON FOR THIS PROCESS TO
HAVE TO LOOP OR ITERATE.
THAT IS, AFTER ONE PASS OF THE
TEST, THERE'S SOME HEAD
SCRATCHING, MAYBE IT ANSWERS
SOME QUESTIONS BUT NOT OTHERS,
BUT MAYBE ALL OF THE
CONSIDERATIONS ON THE LIST WERE
EXCLUDED SO THEN YOU HAVE TO
START OVER AND THINK, WELL,
MAYBE I WASN'T THINKING OF THE
POSSIBLE DIAGNOSIS RIGHT.
SO THIS PROCESS CAN GO ON.
NOW, THIS LITTLE LOOP HERE ON
THE SLIDE, THIS LOOKS LIKE KIND
OF NEAT HERE, BUT THIS IS A
MISERABLE GIGANTIC PROBLEM IN
OUR HEALTHCARE SYSTEM.
THIS IS WHAT WE IN GENETICS CALL
THE DIAGNOSTIC ODYSSEY, AND THIS
CAN GO ON FOR WEEKS, MONTHS,
YEARS, DECADES, AND SOME PEOPLE
WILL END UP LEAVING US, AND THIS
PROCESS NEVER GETS TO THE END.
THE DIAGNOSIS IS NEVER ACHIEVED,
AND TREATMENT IS NEVER
IMPLEMENTED.
IT'S A GIGANTIC PROBLEM.
AND ONE PART OF THAT PROBLEM,
THE BIG FLAW, THE ACHILLES HEEL
IN THIS WHOLE PROCESS IS THAT IF
THE CLINICIAN DOESN'T EVEN
CONSIDER THE CORRECT DIAGNOSIS,
THEY WON'T ORDER THE RIGHT TEST
BECAUSE THEY CAN'T ORDER IT
BECAUSE THEY'RE NOT THINKING OF
THE RIGHT CONDITION THAT COULD
EXPLAIN THE PATIENT'S SYMPTOMS.
SO YOU TOTALLY ARE RELIANT ON
YOUR PRIMARY CARE DOC OR THE
SPECIALIST WHO'S TAKING CARE OF
YOU TO KNOW WHAT THE RIGHT
CONSIDERATION IS IN ORDER TO
MOVE YOU THROUGH THIS PROCESS.
SO THE PROBLEM IS THAT THERE'S A
LOT OF DISEASES.
A LOT OF DISEASES.
AND IT'S TRUE, WE SAY IN
MEDICINE ALL THE TIME, COMMON
THINGS ARE COMMON, AND THE OLD
SAYING IS, IF YOU'RE IN CENTRAL
PARK, AND YOU HEAR HOOFBEATS,
DON'T THINK OF ZEBRAS.
THINK OF HORSES.
BUT THE PROBLEM IS, LOTS AND
LOTS OF PEOPLE DON'T HAVE A
HORSE FOR A DISEASE, THEY
ACTUALLY HAVE A ZEBRA.
AND THE CHALLENGE IS, HOW WE GET
THOSE PEOPLE THROUGH THAT
PROCESS.
SO THERE'S MANY DISEASES.
HOW MANY DO YOU THINK YOUR
DOCTOR KNOWS, OFF THE TOP OF HIS
OR HER HEAD.
COULD THEY LIST OFF ALL THESE
RARE DISEASES AND ALL THEIR
SYMPTOMS?
SO WE HAVE TO BE COMPASSIONATE
AND THOUGHTFUL AND REASONABLE
ABOUT THIS.
IT'S PROBABLY BEYOND REASONABLE
HUMAN EXPECTATIONS TO THINK THAT
EVERY DOCTOR CAN KNOW EVERY
DISEASE.
IT'S JUST TOTALLY UNREASONABLE.
SO WHAT TOOLS COULD WE PROVIDE
TO CLINICIANS, PRACTICING
CLINICIANS, THAT COULD HELP THEM
GET SUCCESSFULLY THROUGH THAT
PROCESS MORE OFTEN WITH MORE
PATIENT?
SO MANY DISEASES, AND NOT ONLY
ARE THERE MANY DISEASES, THEY
HAVE VARIABLE SYMPTOMS.
A SINGLE DISEASE CAN VARY IN HOW
IT PRESENTS FROM ONE PATIENT TO
THE NEXT.
DISEASES CAN HAVE WHAT WE CALL
INCOMPLETE PENETRANCE.
THAT IS, FOR GENETIC DISEASES,
JUST BECAUSE YOU HAVE THE GENE
VARIANT THAT'S ASSOCIATED WITH
THE DISEASE DOESN'T MEAN YOU
NECESSARILY WILL HAVE THE
MANIFESTATIONS OF THE DISEASE.
SO THEN IF THAT'S HAPPENING,
IT'S AN INHERITED DISEASE LIKE
MRS. COLEMAN WAS TALKING ABOUT,
BUT YOU'RE NOT SEEING THE
PATTERN IN THE FAMILY BECAUSE
NOT EVERYONE WHO HAS THE GENE
VARIANT EVEN HAS IT.
SO YOU'RE GOING TO HAVE A HARD
TIME SEEING THAT IT'S A FAMILY
HISTORY, POSITIVE FOR GENETIC
DISEASE.
THEN THERE'S VARIABLE
EXPRESSIVITY.
PATIENTS CAN HAVE PARTS OF A
DISEASE, HAVE ONE MANIFESTATION
VERY SEVERE, ANOTHER
MANIFESTATION VERY MILD, AND
RARE DISEASES CAN LOOK LIKE
COMMON DISEASES BECAUSE OF THIS
INCREDIBLE VARIATION.
IT'S A HUGE PROBLEM, AND PEOPLE
LIKE US AT THE NIH, IT'S VERY,
VERY UNFAIR FOR US TO PRETEND
THAT DOCS IN THE REAL WORLD, AS
MS. COLEMAN SAID, HAVE THE
LUXURY OF TIME AND THE ABILITY
TO SIT AND THINK, RUB THEIR CHIN
AND SAY, I WONDER IF THIS COULD
BE.
THEY DON'T HAVE THAT LUXURY.
THEY HAVE A PATIENT IN THEIR
CLINIC, AND THEY HAVE ANOTHER
ONE, OR MORE, IN THE WAITING
ROOM, AND THEY'VE GOT TO KEEP
MOVING.
THEY DO NOT HAVE THE LUXURY OF
TIME.
THEY NEED HELP, THEY NEED TOOLS.
SO WE'RE GOING TO TALK TODAY
ABOUT HOW WE THINK ABOUT HELPING
PEOPLE WHO HAVE THESE MYRIAD OF
RARE DISORDERS GET THROUGH THIS
PROCESS.
AND WE'RE FOCUSED HERE ON SINGLE
GENE DISORDERS.
THERE'S A WHOLE OTHER APPROACH
FOR MORE COMPLEX GENETIC
DISORDERS, BUT FOR THE SINGLE
GENE DISORDERS, THEY'RE PROBABLY
IN THE RANGE OF ABOUT 5,000 OF
THESE DISEASES.
5,000 DISTINCT DISEASES THAT ARE
INHERITED DUE TO ALTERATIONS IN
A SINGLE GENE.
AND OF COURSE THEY'RE
INDIVIDUALLY QUITE RARE.
SOME OF THEM, THE MORE COMMON
RARE DISEASES, IF THAT MAKES
SENSE, AFFECTING ABOUT 1- OR 200
PEOPLE.
SOME OF THEM, THOUGH, MOST
DOCTORS WILL NEVER SEE A SINGLE
PATIENT WITH THAT CONDITION IN
THAT CAREER.
1 IN 100,000 OR EVEN MORE RARE.
SO AGAIN, WE HAVE TO BE
COMPASSIONATE AND REALISTIC AND
SAY, ARE YOU GOING TO EXPECT THE
PRIMARY CARE DOC OR THE PERSON
AT THE GENERAL HOSPITAL TO KNOW
DISEASES THAT AFFECT ONLY 1 IN
100,000 PEOPLE?
NOT LIKELY.
SO HOW CAN WE GET THEM TOOLS SO
THAT THAT CAN STILL BE A GOOD
PATIENT CARE EXPERIENCE?
NOW, EVEN THOUGH THESE ARE
INDIVIDUALLY RARE DISORDERS AND
DISEASES, YOU START ADDING THEM
UP AND THEY AFFECT LOTS AND LOTS
OF PEOPLE.
AND IN FACT, WE NEED SOMETHING
DIFFERENT THAN THIS RARE
DISEASE, BECAUSE I THINK IT
MISLEADS A LOT OF PEOPLE,
BECAUSE THEY AFFECT MILLIONS AND
MILLIONS OF AMERICANS THAT ARE
WALKING AROUND WITH THESE
DISEASES, MANY OF THEM
UNDIAGNOSED.
SO THEY ARE DIAGNOSED, IF
THEY'RE EVER DIAGNOSED, LATER IN
LIFE AFTER THIS LONG DIAGNOSTIC
ODYSSEY, OFTEN AT HUGE EXPENSE
WITH SOMETIMES LOST
OPPORTUNITIES FOR TREATMENT
EARLIER IN THE STAGE OF THE
DISEASE.
SO JOSH AND I HAVE COMPLEMENTARY
RESEARCH APPROACHES TO THINK
ABOUT HOW CAN WE USE LARGE SCALE
DATA, BOTH GENOMIC AND
ELECTRONIC HEALTH RECORD DATA,
ACQUIRED PROSPECTIVELY ON
PATIENTS AND DYNAMICALLY AS
THEY'RE CARED FOR, TO ADDRESS
THESE SYSTEM FAILURES WHERE THE
HEALTHCARE SYSTEM, DUE T TO ITS
INHERENT LIMITATIONS,
LIMITATIONS OF HUMAN BEINGS
PRACTICING HEALTHCARE, HOW CAN
WE HELP PEOPLE GET THROUGH THOSE
ROAD BLOCKS, THOSE CHALLENGES,
THOSE OBSTACLES SO THEY CAN GET
THE CARE THEY NEED AND DESERVE.
WE THINK THAT LARGE SCALE DATA
CAN BEGIN TO ANSWER THESE
QUESTIONS.
SO I'M FOCUSED ON THE GENOMICS,
JOSH IS GOING TO FOCUS MORE ON
THE ELECTRONIC HEALTH RECORD
DATA.
SO IN THE GENOME INSTITUTE, THIS
IS A GRAPH WE LOVE TO SHOW, AND
THIS IS THE COST OF GENOME
SEQUENCING.
WHAT YOU CAN SEE HERE IS ABOUT A
23-YEAR HISTORY OF GENOME COSTS,
AND IT STARTS AT AROUND
$100 MILLION TO SEQUENCE ONE
GENOME IN 2001.
NOW IT COSTS -- LAST YEAR IT WAS
A THOUSAND, AND OUR SEQUENCING
CENTER JUST BOUGHT A NEW MACHINE
AND THEY'RE GOING TO START DOING
GENOMES FOR US FOR $400.
SO SEQUENCING THE ENTIRE
GENOMES.
THIS COLLAPSING COST COMPLETELY
CHANGES THE GAME.
HOW WE THINK ABOUT DIAGNOSING
GENETIC DISEASE IS COMPLETELY
DIFFERENT WHEN YOU'RE AT THE
LEFT SIDE OF THIS GRAPH VERSUS
WHEN YOU'RE AT THE RIGHT SIDE OF
THIS GRAPH.
SO THE NEW REALITY FOR GENETIC
TESTING IS THIS.
SO TODAY, AND I APOLOGIZE, THESE
ARE KIND OF MADE-UP NUMBERS
BECAUSE THE TRUTH IS, IN OUR
HEALTHCARE SYSTEM, NOBODY REALLY
KNOWS WHAT ANYTHING COSTS.
BUT THIS IS KIND OF BALLPARKING
AND IT MAKES THE POINT.
SO HERE'S THE WEIRD THING ABOUT
GENETIC TESTING.
A SINGLE GENE TEST PROBABLY
COSTS IN THE RANGE OF $250 TO
1,000 BUCKS THESE DAYS.
A GENE PANEL TEST, WHICH IS
GETTING TO BE MORE AND MORE
COMMON WHERE YOU TAKE A SET OF
GENES THAT ARE RESPONSIBLE FOR A
SET OF RELATED OVERLAPPING
DISORDERS, LET'S SAY A KIDNEY
FAILURE GENE PANEL, THEN THESE
PANELS INCLUDE SOMETIMES 2 TO 50
GENES.
PANELS CAN COST 250 TO $1,000.
OKAY?
ALL RIGHT?
THEN YOU CAN ALSO ORDER ON A
PATIENT AN EXOME.
I WAS JUST ON A CONFERENCE CALL
YESTERDAY WHERE A COLLEAGUE WAS
TELLING ME THAT A CLINICAL
TESTING COMPANY IN THE MIDWEST,
IN THE U.S., IS NOW MARKETING
EXOME -- CLINICAL EXOME
SEQUENCING FOR 2500 BUCKS.
NOW YOU SAY WAIT A MINUTE, LOOK
AT THESE NUMBERS.
WHAT AM I GETTING FOR MY MONEY
HERE?
IN THE FIRST EXAMPLE, I'M
GETTING ONE GENE TESTED.
SO I'M PAYING 250 TO $1,000 TO
GET THAT ONE GENE TEST.
WITH THE PANEL, I'M PAYING
BETWEEN 25 AND $5,500 A GENE.
WITH AN EXOME, I'M PAYING 50
CENTS.
50 CENTS PER GENE.
SO IF THAT'S TRUE, THEN I NEED
TO THINK ABOUT GENETIC TESTING
COMPLETELY DIFFERENTLY THAN HOW
I THOUGHT ABOUT IT 20 YEARS AGO.
SO THE OLD PARADIGM WAS THE
PATIENT WAS REFERRED THROUGH
THIS CASCADE OF DOCTORS AND
SPECIALISTS, AND WHAT WILL
HAPPEN IS THEY WOULD ORDER ONE
TEST AND THEN THEY'D ORDER
ANOTHER TEST AND THEN THEY'D
ORDER ANOTHER TEST AND THAT'S OF
COURSE, YOU KNOW, EVERY TIME I
SAY THAT, THAT'S 250 TO $1,000 A
POP.
AND THEY CONTINUED THAT UNTIL
SOMEBODY FINALLY THOUGHT OF THE
RIGHT TEST TO ORDER, ORDERED
THAT ONE, AND THE PATIENT GOT
THEIR DIAGNOSIS.
BUT, WE COULD DO THIS COMPLETELY
DIFFERENTLY.
WE COULD SEQUENCE A PATIENT
EARLY IN LIFE AND JUST SEQUENCE
THEIR ENTIRE EXOME OR THEIR
ENTIRE GENOME.
SEQUENCE ALL THE GENES.
IT COSTS $2,500.
AND THEN DURING THAT PATIENT'S
LIFETIME, YOU CAN BEGIN TO FLAG
THOSE GENES THAT HAVE VARIANTS
THAT MAY HAVE BENEFICIAL USE FOR
THAT PATIENT, EITHER TO PREVENT
DISEASES BEFORE THEY OCCUR,
BECAUSE REMEMBER WITH THAT VERY
FIRST SLIDE I SHOWED, THAT
MULTI-STEP PROCESS, STEP NUMBER
ONE WAS, PATIENT GETS SICK.
THAT'S WHAT STARTS THE PROCESS.
BUT IT DOESN'T HAVE TO BE THAT
WAY.
YOU CAN ACTUALLY SEQUENCE THEM
BEFORE THEY GET SICK, AND THEN
PREVENT THEM FROM GETTING SICK
IN THE FIRST PLACE.
AND THIS IS SOMETHING THAT WE'RE
DOING NOW WITH DISEASES LIKE
CANCER AND LIPID DISEASES, WHERE
YOU CAN DIAGNOSE THESE BEFORE
THEY EVEN MANIFEST AND START TO
GET THE PATIENT TREATMENT BEFORE
THEY RM SICK.
ARE SICK.
THEN AS THE PATIENT IS AGING,
GOING THROUGH THEIR LIFESPAN,
THINGS WILL HAPPEN, NO DOUBT.
AND AS SYMPTOMS ARISE, YOU CAN
THEN SAY, OH, I HAVE THEIR WHOLE
GENOME.
IS THERE ANYTHING GENETIC
DISORDER THAT IS POTENTIALLY
RELEVANT TO THAT SYMPTOM THEY'RE
COMING INTO MY OFFICE WITH
TODAY?
AND USE THEIR GENOME DYNAMICALLY
TO MANAGE THEIR CARE.
SO A COUPLE DEFINITIONS THAT I
NEED TO TALK ABOUT HERE AND HOW
WE'RE THINKING ABOUT THIS.
GENOTYPE, THAT'S AN ATTRIBUTE OF
AN INDIVIDUAL WHICH IS THEIR SET
OF GENE VARIANTS THAT THEY HAVE
IN THEIR DNA.
THEN THEIR PHENOTYPE.
WHICH IS PRETTY MUCH EVERYTHING
ELSE.
THEIR TRAITS, MANIFESTATIONS,
THE DISEASES THEY MAY HAVE,
THEIR LIABILITY FOR DISEASE,
THAT'S THEIR PHENOTYPE.
SO THEY HAVE TWO ATTRIBUTES,
GENOTYPE AND PHENOTYPE.
AND HOW WE THINK ABOUT THOSE TWO
THINGS ORGANIZES THE PRINCIPLES
OF HOW WE DIAGNOSE PATIENTS AND
HOW WE DO RESEARCH.
SO OUR TRADITIONAL OR OLD SCHOOL
GENOMIC RESEARCH, HOW WE DID
RESEARCH WHEN DAN AND I STARTED
WORKING HERE, RIGHT, WAS, WE
GATHERED A GROUP OF AFFECTED
INDIVIDUALS.
THAT WAS STEP 1.
YOU HAD TO KNOW WHAT DISEASE YOU
WANTED TO LOOK FOR, YOU WENT OUT
INTO THE WORLD AND YOU RECRUITED
PEOPLE WITH THAT DISEASE TO COME
TO THE NIH AND BE IN OUR STUDY.
AND YOU WOULD START WITH
IDENTIFIED AFFECTED INDIVIDUALS.
THEN YOU WOULD SEQUENCE THOSE
INDIVIDUALS, AND THEN WHAT YOU
WOULD TRY TO DO TO UNDERSTAND
THE RELATIONSHIP BETWEEN THE
VARIANT THAT THEY MIGHT HAVE AND
THEIR DISEASE, BECAUSE YOU
STARTED WITH WHATEVER VARIANTS
THOSE PEOPLE SHARE IS RELATED TO
THEIR DISEASE.
PRETTY STRAIGHTFORWARD.
AND WE DID IT THAT WAY BECAUSE
WHEN WE STARTED HERE, I STARTED
HERE IN '93, YOU WERE HERE IN
THE 80s?
'85.
WE COULDN'T SEQUENCE ANYBODY'S
EXOME.
IT WASN'T HAPPENING.
IT WAS VERY HARD TO DO.
NO ONE COULD AFFORD IT.
SO THIS WAS THE ONLY ECONOMICAL
WAY TO DO IT.
BUT THERE'S A NEW WAY TO DO IT
NOW WITH THESE COSTS COLLAPSING.
SO WHAT YOU CAN DO IS BRING
PEOPLE TO THE NIH, BRING THEM IN
VERY GENERICALLY, OPEN THE DOOR
AND SAY COME ON AND COME INTO
OUR STUDY, JOIN US, AND WE'RE
GOING TO SEQUENCE EVERY ONE OF
YOU FOR EVERY GENE.
NOT THINK ABOUT IT.
I'M NOT SAYING IN YOU THIS GENE,
IN YOU THAT GENE, IN YOU, THAT
GEEP.
SEQUENCE EVERY GENE IN EVERY
PERSON, AND THEN FROM THAT GROUP
OF PEOPLE, LOOK FOR PEOPLE WHO
SHARE A VARIANT IN A GIVEN GENE.
WE CAN DO THAT COMPUTATIONALLY,
FIND PEOPLE WITH JEAN VARIANTS.
THEN WE ASK THE OPPOSITE
QUESTION, DO THE PEOPLE WHO
SHARE A GENE VARIANT HAVE ANY
SHARED PHENOTYPE ATTRIBUTES?
DO THEY SHARE ANY DISEASE
ATTRIBUTES?
AND YOU CAN MAKE DISCOVERIES OF
THE RELATIONSHIP BETWEEN GENE
VARIANTS AND DISEASE THIS WAY AS
WELL, IN A MUCH MORE EFFICIENT
PATTERN, AND YOU CAN ADVANCE
SCIENCE IN THIS WAY.
SO WHAT WE'VE DONE, WE STARTED
WITH CLINSEQ IN 2006, STARTED
WITH A THOUSAND PARTICIPANTS AND
THEN WE DID 500 MORE LATER THAT
WERE -- THE FIRST COHORT WAS
OPEN TO ALL PARTICIPANTS, THE
SECOND COHORT WAS OPEN, TOTALLY
FOCUSED ON INDIVIDUALS OF
AFRICAN AMERICAN OR AFRICAN
DESCENT TO INCREASE OUR
DIVERSITY, AND YOU'LL SEE WHY
THAT WAS SO IMPORTANT, AND JOSH,
I'M SURE, IS GOING TO TALK A LOT
ABOUT THAT.
WE HAVE ALSO HAVE INDIVIDUALS
PARTICIPATING NOW IN WHAT WE
CALL OUR SUPER COHORT THAT HAVE
BEEN SEQUENCED AT THE
TRANSLATIONAL MEDICINE INSTITUTE
ACROSS THE RIVER, NIAID
SEQUENCES INDIVIDUALS AND
CONTRIBUTES THOSE SEQUENCES TO
OUR DATABASE, AND THE NIEHS HAS
A -- THEY'VE SEQUENCED 5,000
INDIVIDUALS.
SO WE HAVE THESE INDIVIDUALS'
GENOMES AND EXOME, WE CAN GO
THROUGH THOSE, SEARCH FOR
VARIANTS AND ASK QUESTIONS, DO
THE PEOPLE WHO HAVE THESE
VARIANTS SHARE ANY HEALTH
ATTRIBUTES?
WE HAVE AN EXAMPLE OF ONE.
SO WE SEARCHED THROUGH AND
LOOKED AT A GENE CALLED TTR, AND
WE SCREENED FOR VARIANTS IN THIS
GENE.
THIS IS A HIGHLY VARIABLE
DISORDER.
THE FORMAL NAME IS ASSOCIATED
WITH VARIANTS IN A GENE CALLED
TTR.
THE WAY THIS DISEASE IS CAUSED
IS THAT THE GENE VARIANT
ACTUALLY STRUCTURALLY SLIGHTLY
DESTABILIZES THE PROTEIN, THE
PROTEINS THEN CLUMP TOGETHER OR
AGGREGATE, AND THEN THOSE
AGGREGATES OF THAT PROTEIN
ACCUMULATE IN CERTAIN TISSUES
AND CAUSE SYMPTOMS OF DISEASE.
THERE'S A WIDE RANGE OF DISEASE
JUST LIKE I TALKED ABOUT
EARLIER, HIGHLY VARIABLE FROM
ONE PERSON TO THE NEXT.
THIS IS AN ADULT ONSET
MULTISYSTEM DISORDER DUE TO THE
BUILDUP OF THAT PROTEIN IN
DIFFERENT TISSUES, AND IT'S
CALLED AMYLOID, AND IT IS
ASSOCIATED WITH CARDIOMYOPATHY
OR HEART FAILURE, PERIPHERAL
NEUROPATHY, MOST COMMONLY CARPAL
TUNNEL SYNDROME BUT IT CAN BE
ANY PERIPHERAL NEUROPATHY,
GLAUCOMA OR CATARACTS, KIDNEY
DISEASE.
AND WHAT'S REALLY IMPORTANT
ABOUT THIS ONE IS THIS ISN'T
JUST THE SCIENTIFIC CURIOSITY.
THIS IS REALLY A MEDICALLY VERY
IMPORTANT DISORDER BECAUSE IN
THE PAST TWO YEARS, THE FDA HAS
APPROVED FIVE DIFFERENT
THERAPIES THAT HAVE BEEN SHOWN
TO BE EFFECTIVE FOR STOPPING THE
PROGRESSION OF THE SICTS SYMPTOF
THE DISEASE IN THE INDIVIDUALS
WHO HAVE IT.
AND THE BLOCKBUSTER FINDING HERE
IS REALLY THE INCREDIBLE
DISPARITY IN THIS DEELZ ACROSS
DIFFERENT POPULATIONS, AND THE
POPULATION GENOMICS SHOWS US
THAT ALMOST 1 IN 30 AFRICAN
AMERICAN INDIVIDUALS,
INDIVIDUALS WHOSE ANCESTORS CAME
FROM FAMILIES WHO WERE ENSLAVED,
NEARLY 1 IN 30 OF THOSE
INDIVIDUALS HAVE A VARIANT IN
THIS GENE THAT IS ASSOCIATED
WITH THIS DISEASE, WHEREAS IT'S
MUCH RARER IN NON-AFRICAN
AMERICAN INDIVIDUALS AND THUS
THERE'S A HUGE DISPARITY IN THE
RECOGNITION AND IMPORTANCE THAT
THIS RECEIVES IN OUR HEALTHCARE
SYSTEM.
SO THIS STORY ACTUALLY -- I
DON'T KNOW HOW MANY OF YOU READ
LISA SANDERS' COLUMNS IN THE
"NEW YORK TIMES," SHE HAS THESE
MEDICAL MYSTERY CASES.
SHE HAD AN INDIVIDUAL WHO HAD
THIS CONDITION A FEW -- WAS IT
LAST YEAR OR A COUPLE YEARS AGO,
I THINK IT WAS, AND IT'S A GREAT
EXAMPLE OF THIS SITUATION.
SO WHAT WE DID AGAIN, WE HAVE A
BROWSER THAT HAS ALL THESE
GENOMES AND EXOMES IN IT, AND WE
JUST PUT IN THE GENE TTR AND
ASKED TO SEE WHAT VARIANTS WE
HAVE, AND WE POPPED UP THESE
VARIANTS AND THESE ARE ALL
VARIANTS IN OUR COHORT OF
INDIVIDUALS IN OUR SEQUENCE
STUDY WHO HAVE VARIANTS IN THIS
GENE THAT HAVE BEEN SAID TO BE
ASSOCIATED WITH THIS DISEASE.
AND THE NUMBERS ARE PRETTY
IMPRESSIVE.
THERE'S MORE THAN 20 INDIVIDUALS
WHO HAVE THIS ONE VARIANT, AND
IT IS THE MOST COMMON VARIANT IN
INDIVIDUALS WHO, AGAIN, ARE
AFRICAN AMERICAN ANCESTRY, AND
HAS BEEN SHOWN TO BE
DEFINITIVELY ASSOCIATED WITH
THIS DISEASE, AND WHEN WE LOOK
ACROSS OUR COHORT, WHICH IS A
MINORITY OF THE INDIVIDUALS IN
OUR COHORT ARE OF AFRICAN
AMERICAN DESCENT, YOU CAN SEE
PEOPLE WHO HAVE THE VARIANTS,
THE GREAT MAJORITY OF THEM ARE
OF AFRICAN AMERICAN DESCENT.
SO MISS COLEMAN, AS YOU HEARD,
HAS CARDIOMYOPATHY, OVERACTIVE
BLADDER, LIGHT-HEADEDNESS, SHE
TALKED ABOUT HER THYROID
DISEASE, HAS SOMERMAN 'FESS
TAITIONS OF AUTONOMIC
DYSFUNCTION AND HER FAMILY
HISTORY IS INTRIGUING, I DON'T
THINK WE'VE TESTED ANY
INDIVIDUALS FROM HER FAMILY BUT
WE HAVE SEVERAL INDIVIDUALS WHO
ALSO HAVE COMPATIBLE
MANIFESTATIONS, BUT AGAIN,
COMPLETELY UNRECOGNIZED BY THE
HEALTHCARE SYSTEM.
ALL THE SYMPTOMS WERE THERE.
NOBODY PUT THE PIECES TOGETHER.
OKAY.
SO THAT'S PART 1, GENOMIC TOOLS
TO HELP IDENTIFY INDIVIDUALS.
JOSH IS GOING TO TALK ABOUT
EHRs.
>> THANK YOU, LES.
IT IS A PLEASURE TO BE HERE AND
A SPEAK WITH YOU ABOUT THE NEXT
PART OF THIS JOURNEY.
AND I'M GOING TO START WITH
LOOKING AT THE ELECTRONIC HEALTH
RECORDS THAT I SPENT A LOT OF
TIME LOOKING AT AS A PRACTICING
CLINICIAN AT VANDERBILT FOR A
WHILE, FOR ABOUT TWO DECADES, I
GUESS, AND THIS IS AROUND 2011,
IS WHAT OUR RECORD LOOKED LIKE.
THIS IS CLEARLY A FAKE PATIENT
HERE.
IF YOU'RE WORRIED ABOUT DATA
THAT YOU MIGHT SEE.
AND AS A PHYSICIAN LOOKS AT
THIS, IT'S A GREAT WAY TO
ORGANIZE THAT INDIVIDUAL RECORD
TO KEEP A LOG AND COMMUNICATE
ACROSS DIFFERENT PROVIDERS, AND
HAVE THAT RECORD TO MAKE SURE
YOU DON'T ACCIDENTALLY PRESCRIBE
A MEDICATION TO WHICH AN
INDIVIDUAL IS ALLERGIC TO, THAT
YOU ADJUST FOR THE RENAL
FUNCTION, ALL SORTS OF THINGS
LIKE THAT, BUT ONE OF THE THINGS
THAT REALLY INTRIGUED ME IS, HOW
COULD WE USE THESE KINDS OF
RESOURCES THAT WE ARE
AGGREGATING TONS AND TONS OF
DATA ON, AN A PATIENT BY PATIENT
APPROACH TO ACTUALLY LEARN, TO
LEARN TO MAKE THE SYSTEM
SMARTER, TO SYSTEMATIZE AND TAKE
THAT KNOWLEDGE AS A LEARNING
HEALTHCARE SYSTEM, IF YOU WILL,
TO APPLY IT BACK.
SO AT ABOUT THE SAME TIME WE
ALSO STARTED COLLECTING PATIENT
WHO AGREED TO SHARE GENETIC
INFORMATION FROM LEFTOVER BLOOD
SAMPLES, AND SO WE CREATED A
BIOREPOSITORY.
SO ONE OF THE QUESTIONS WE ASKED
IS WE HAVE THESE DENSE DATA, IS
HOW COULD WE FIND PEOPLE THAT
HAVE DISEASE?
AND USE THAT -- IF YOU'VE BEEN A
PHYSICIAN AND EXPLORED SOMETHING
THAT MAY BE A DIAGNOSTIC
ODYSSEY, YOU CAN GO SOMETIME
WITH MAYBE DIFFERENT DIAGNOSES
CONSIDERED, DIFFERENT THINGS IN
YOUR CHART BEFORE YOU FIND, FOR
INSTANCE, THE RIGHT MEDICATION
TO ACTUALLY TREAT YOUR
DEPRESSION, GET THE THYROID DOSE
ACCURATE, WHAT'S CAUSING THE
THYROID DISEASE.
ONE OF THE FIRST SUCCESSFUL
ATTEMPTS WE DID WAS USING
AUTOIMMUNE HYPOTHYROIDISM.
IT A VERY COMMON CONDITION, IT
AN AUTOIMMUNE CONDITION AND USED
TO BE REALLY SEVERE, BUT NOW WE
HAVE GREAT TREATMENTS, WE'VE HAD
GREAT TREATMENTS FOR DECADES,
AND WHAT WE FOUND IS WE FOUND A
VARIANT IN A GENE CALLED FOXE1,
WHICH ENCODES A PROTEIN THAT'S
INVOLVED IN THE FORMATION
NEUROLOGICALLY OF THE THYROID
AND ALSO ASSOCIATED WITH THYROID
CANCER, IN THIS CASE ASSOCIATED
WITH HYPOTHYROIDISM.
SO THIS SHOWED THAT YOU COULD DO
THIS KIND OF ANALYSIS USING
ELECTRONIC HEALTH RECORDS AND DO
THIS IN THE TYPICAL WAY.
AND IF YOU HAVEN'T SEEN ONE OF
THESE FIGURES BEFORE, WHAT WE'RE
LOOKING AT ON THE X AXIS ACROSS
THE BOTTOM ARE GENETIC LOCATIONS
AND VARIATION WITH THOSE
LOCATIONS, AND SO YOU CAN SEE
THAT PEAK OF POINTS THERE IN
CHROMOSOME 9, WHICH IS SHOWING
VARIATION IN THAT GENE IS
ASSOCIATED WITH PEOPLE WHO HAD
HYPOTHYROIDISM.
AND BY THE WAY, THIS TOOK US
ABOUT TWO YEARS TO DO AT THE
TIME, AND REALLY FIND AN
ACCURATE CONDITION AND ANALYSIS.
BUT THE OTHER THING WE THOUGHT
ABOUT, THIS IS THE TRADITIONAL
WAY SCIENCE HAD GONE IS, LET'S
PICK A DISEASE, LET'S ANALYZE
GENETIC ASSOCIATIONS AND FIND
WHAT PLACE MIGHT BE ASSOCIATED
OR SO CALLED GENOME WIDE
ASSOCIATION STUDY.
WE THOUGHT WE HAVE THE
ELECTRONIC HEALTH RECORD AND WE
HAVE ALL THE CONDITIONS FOR
WHICH A PATIENT IS SEEING A
PHYSICIAN.
WE ALSO HAVE ALL THEIR
MEDICATIONS, WE HAVE LAB
RESULTS.
THESE KINDS OF THINGS.
SO IT GIVES US THE ABILITY TO DO
THE INVERSE EXPERIMENT.
SO LET'S ASK, YOU KNOW, GIVEN A
GENETIC VARIANT, WHAT PHENOTYPES
MIGHT BE ASSOCIATED WITH THAT
GENETIC VARIANT?
WHAT LABORATORY ABNORMALITIES,
WHAT OTHER KINDS OF THINGS, NOT
JUST DISEASES BUT PHENOTYPES
THAT WE MIGHT FIND?
SO THAT SO CALLED PHEWAS
APPROACH, TAKING THAT SAME
GENETIC LOCUS WE FOUND IN THAT
GENOME-WIDE ASSOCIATION BUT
LOOKING AT IT IN A PHEWAS APROA.
HYPOTHYROIDISM IS ACTUALLY THE
STRONGEST SIGNAL, SO THAT MAY BE
REASSURING FROM THE OTHER,
INCLUDING ATRIAL FLUTTER.
SO A CARDIAC PHENOMENON.
IN THIS CASE PEOPLE WHO HAVE
BELOW ACTIVE THYROIDS ARE
ACTUALLY GOING TO BE LESS LIKELY
TO GET ATRIAL FLUTTER.
SO THAT IS A LOGICAL CLINICAL
CONCLUSION FOR WHAT WE SEE
THERE.
AND WE SEE MORE DETAIL ABOUT
THYROID DISEASES AS WELL.
SO THIS SHOWS US, WE CAN USE
THIS KIND OF RESOURCE, WE CAN
FIND LOTS OF PATIENTS USING
ELECTRONIC HEALTH RECORD, GET
THAT DENSE PHENOTYPING INSTEAD
OF JUST THE QUESTIONS YOU ASK
SOMEONE, YOU HAVE ALL REASONS
THEY COME TO THE DOCTOR, AND
THEN USING GENETIC INFORMATION,
ONE OF THE THINGS WE FOUND IN
DOING THAT IS THESE ARE FAR
CHEAPER THAN TRADITIONAL
STUDIES, AND SO THIS IS LOOKING
AT A CLUSTER OF DRUG EFFECT
STUDIES THAT WE DID COMPARED TO
OTHER FUNDED NIH STUDIES.
YOU CAN SEE THAT THE TIME TO DO
THE STUDY AND THE COST PERSON
THAT WAS PART OF THE STUDY WAS
FAR CHEAPER USING ELECTRONIC
HEALTH RECORDS THAN THE OTHER
STUDIES, AND FAR FASTER, AND SO
THAT SHOWS AGAIN THAT WE HAVE
SUPPORT THERE, BUT THE OTHER
THING THAT WAS HAPPENING AND WE
WERE OBSERVING AT THIS TIME
THROUGH ALL THE RESEARCH OUT
THERE WAS HIGHLY BIASED TOWARDS
PEOPLE WHO ARE OF EUROPEAN
ANCESTRY.
EITHER IN THE U.S. █OR IN EUROP,
BASICALLY SELF-IDENTIFIED WHITE
INDIVIDUALS, WHICH WERE BY FAR
AND AWAY THE MOST COMMON
INDIVIDUALS THAT HAD GENETIC
ANALYSES.
IN FACT, THESE ARE THE DATA FROM
NOW.
THESE AREN'T THE DATA FROM THEN.
SO IF YOU LOOK TODAY AND LOOK AT
ALL THE GENOMIC ASSOCIATION
STUDY, 94% OF THE PEOPLE IN
THOSE STUDIES ARE
SELF-IDENTIFIED WHITE OR
EUROPEAN GENETIC ANCESTRY.
SO THAT'S A REAL PROBLEM.
THAT CAUSES ALL SORTS OF
PROBLEMS IN UNDERSTANDING THE
IMPACT OF GENETIC VARIANTS, IT
CAUSES PROBLEMS IN US
UNDERSTANDING WHAT GENES CAUSE
DISEASE.
IT CAUSES PROBLEMS IN EVEN
CLASSIFYING VARIANTS ON PEOPLE
WHO ARE WHITE.
AND WHO ARE OF EUROPEAN
ANCESTRY.
AND SO -- AND OF COURSE IT'S A
BIG PROBLEM WITH EQUITY THAT WE
WOULD LOVE TO ADDRESS.
AND SO NOW ENTERS THE ALL-OF-US
RESEARCH PROGRAM.
THIS WAS ANNOUNCED AS
DR. KASTNER ALLUDED TO IN THE
2015 STATE OF THE UNION ADDRESS
TO ADVANCE PRECISION MEDICINE
AND THE PRECISION MEDICINE
INITIATIVE WHICH THE COWORK
PROGRAM BECAME KNOWN AS THE
ALL-OF-US RESEARCH PROGRAM.
THE GOAL IS TO PARTNER WITH NOT
JUST RESEARCH SUBJECTS BUT
PARTNER WITH PARTICIPANTS AT AT
LEAST A MILLION DIVERSE
PARTICIPANTS ACROSS THE UNITED
STATES TO ACCELERATE RESEARCH
AND IMPROVE HEALTH, AND THE
MISSION THERE, ACCELERATE
RESEARCH AND MEDICAL
BREAKTHROUGHS, ENABLING
INDIVIDUALIZED PREVENTION,
TREATMENT AND CARE FOR ALL OF
US, TO TACKLE THE EQUITY GAP
THAT WE HAVE IN HEALTHCARE IN
THIS COUNTRY AND IN THE WORLD.
THERE'S A SCREEN SCREENSHOT FROR
ORIGINAL BLUEPRINT OF THE
PROGRAM IN 2015.
DR. FRANCIS COLLINS WAS THE NIH
DIRECTOR AT THE TIME, AND REALLY
HIGHLIGHTED THE IMPORTANCE OF
THIS.
WE LAUNCHED NATIONALLY IN 2018.
SINCE THEN, WE'VE HAD OVER THREE
QUARTERS OF A MILLION PEOPLE
THAT HAVE CONSENTED TO BE PART
OF THE STUDY.
YOU CAN SEE NUMBERS THERE, WE
HAVE OVER 530,000 THAT HAVE
DONATED BIOSMES MEN, THAT
INCLUDES DNA, OTHER BIOSMES MENS
AS WELL, AND YOU CAN SEE --
PARTICIPANTS FROM ALL STATES IN
THE U.S. AND MOST U.S.
TERRITORIES.
SO WHAT DO WE DO WITH THE
PROGRAM?
SO IN THE PROGRAM, WE COLLECT --
YOU CAN COME IN ALL SORTS OF
DIFFERENT KINDS OF WAYS.
YOU CAN COME IN THROUGH A
HEALTHCARE PROVIDER ORGANIZATION
AND THAT'S THE MOST COMMON
RECORD PATH, BUT YOU CAN ALSO GO
TO THE WEBSITE, DOWNLOAD A
SMARTPHONE APP, JOIN AND GET A
SALIVA KIT SENT.
REGARD LES OF YOU HO YOU COME
IN, WE COLLECT THE SAME BASIC
KINDS OF INFORMATION.
ELECTRONIC HEALTH RECORDS ARE A
KEY PART OF HOW WE COLLECT DATA
AROUND DISEASE AND DEEDS
RESPONSE.
GETTING PARTICIPANT SURVEYS, WE
DON'T WANT TO JUST USE
ELECTRONIC HEALTH RECORD, WE
WANT TO USE SURVEYS TO AUGMENT
AND ASK DIFFERENT KINDS OF
QUESTIONS THAT WE CAN LEARN
ABOUT.
PHYSICAL MEASURES, BIOSAMPLES
ARE KEY, AND THEN WEARABLE DATA,
WE GIVE THOSE DEVICES OUT TO
SELECT POPULATIONS AND WELL AND
WE'RE ALWAYS LOOKING TO EXPAND
THAT.
THIS PROGRAM IS YOUNG.
WE JUST CELEBRATED OUR FIFTH
YEAR -- WE'RE ABOUT 5 1/2 YEARS
IN AT THIS POINT.
THE OTHER PART IS PARTNERSHIP WE
KNEW IS REALLY IMPORTANT AND OUR
PARTICIPANTS TOLD US, THEY
WANTED INFORMATION BACK.
AND WE THOUGHT THAT WAS AN
IMPORTANT WAY TO IMPROVE
HEALTHCARE AS WELL.
SO WE ASKED PEOPLE WHAT THEY
WANTED TO KNOW AND GENETIC
INFORMATION WAS AMONG THE TOP OF
THE KIND OF THINGS PEOPLE WOULD
WANT BACK.
THEY ALSO WANTED TO KNOW THINGS
ABOUT THEIR SURVEY DATA,
ELECTRONIC HEALTH RECORD DATA.
IF THEY COULD BE ELIGIBLE FOR
OTHER KINDS OF STUDIES AND HOW
WE CAN MAKE THOSE LINKAGES, AND
WHAT THEY WERE FINDING, AND THE
KIND OF RESULTS WE'RE FINDING,
HOW WE CAN RETURN THOSE IS A KEY
PART.
A KEY ASPECT OF THIS, VERY
RELEVANT TO THE STORY WE'RE
TALKING ABOUT TODAY AND LES'
PROJECT EVEN AS HE DESCRIBED
THESE OTHER COHORTS AND OTHER
INDIVIDUALS, IS PARTICIPANTS CAN
BE RE-CONTACTED FOR OTHER
RESEARCH OPPORTUNITIES.
SO TALKING ABOUT RETURNING
GENETIC RESULTS, WHAT WE STARTED
FIRST WITH, PARTIALLY BECAUSE IT
WAS EASIER WITH GENETIC ANCESTRY
AND NON-HEALTH-RELATED TRAITS,
AND THIS WOULD BE LIKE OTHER
COMMERCIAL COMPANIES THAT
PROVIDE THIS KIND OF RESOURCE.
IT'S AN ENGAGEMENT ORIENTED
EXERCISE, WHETHER OR NOT YOU CAN
TASTE CILANTRO, WHAT KIND OF EAR
WAX YOU HAVE, WHAT YOUR GENETIC
ANCESTRY IS, THOSE KINDS OF
THINGS.
AND WE'VE OFFERED THAT TO
244,000 PEOPLE AT THIS POINT,
OVER 170,000 HAVE VIEWED THOSE
KIND OF RESULTS.
ABOUT A YEAR AGO, WE STARTED
OFFERING HEALTH-RELATED GENETIC
RESULTS, WORGING WITH THE FDA IN
THIS PROCESS TO RETURN THIS TO
OUR PARTICIPANTS SUPPORTED BY
GENETIC COUNSELORS AS WELL.
THE FIRST OF THESE IS HEREDITARY
DISEASE RISK.
WE HAVE 59 GENES THAT HAVE
DISEASES ASSOCIATED WITH THEM
THAT ARE ACTIONABLE.
WE KNOW THE VAST MAJORITY OF
PEOPLE WON'T KNOW THEY HAVE UP
WITH OF THESE CONDITIONS IF WE
FIND A GENETIC VARIANT.
SO THAT'S AN OPPORTUNITY FOR
THEM TO LEARN ABOUT SOMETHING
NEW THAT COULD PREVENT
PREEMTIVELY AS LES WAS TALKING
ABOUT A CONDITION DEVELOPING.
SUCH AS BREAST AND OVARIAN
CANCER SYNDROMES, SUCH AS
CARDIAC ARRHYTHMIA, THEY CAN BE
FAY TELL.
SUPPORTING THEM IN THAT PROCESS,
AND THEN PHARMACOJI KNOW MIX OR
WHAT WE CALL MEDICINE IN DNA,
HOW MEDICINE AFFECTS HOW A DRUG
IS GOING TO WORK FOR YOU.
ACTUALLY -- I CARRY TWO THAT
WOULD CHANGE MEDICATIONS THAT I
WOULD BE PRESCRIBED, AND SOME OF
THESE ARE VERY COMMON IN THIS
PROCESS AND, IN FACT, I LEARNED
THAT FROM ALL-OF-US.
AND WE'VE OFFERED THIS TO ABOUT
212,000 PEOPLE, 108,000 HAVE
SAID THEY WANT THOSE RESULTS
WHEN THEY SAY YES, WE GO
GENERATE THE RESULT.
SO 87,000 OF THOSE HAVE ACTUALLY
HAD THEIR RESULT GENERATED AND
VIEWED THOSE RESULTS.
SO WE'VE ALSO CREATED, OF
COURSE, THIS RESOURCE TO DO
RESEARCH AND MADE IT AVAILABLE
TO RESEARCHERS IN A CLOUD-BASED
COMPUTABLE ENVIRONMENT WHERE
RESEARCHERS COME TO US TO USE
THE DATA IN OUR PROTECTED
ENCLAVE, GO THROUGH AN ACCESS
PROCESS.
WE PROTECT DE-IDENTIFIED THE
DATA AND MAKE IT AVAILABLE TO
RESEARCHERS.
AND WE RELEASE THOSE DATASETS,
ABOUT ONE A YEAR.
THESE ARE THE CURRENTLY
AVAILABLE DATASETS, 245,000
GENOMES AVAILABLE FOR RESEARCH
ACROSS OUR POPULATION.
LARGELY BECAUSE OF THE DIVERSITY
OF OUR POPULATION, AND I'LL SHOW
THIS IN THE NEXT SLIDE, OF THE
3 BILLION BASE PAIRS IN THE
GENOME, WE HAVE OBSERVED
VARIATION AT A BILLION
LOCATIONS, AND OF THOSE --
NEARLY A THIRD OF THE GENOME,
THAT'S A THOUSAND FOLD MORE
INFORMATION TH THAN SOME OF THEE
COMMERCIAL PROVIDERS TESTING
YOUR DNA, WE'VE ACTUALLY
OBSERVED VARIATION ON.
REAL OPPORTUNITIES TO THINK
ABOUT WHAT THIS VARIATION MEANS.
THOSE VARIANTS ARE LARGELY
UNKNOWN IN THE LITERATURE, AND
WHAT IMPACT THEY COULD HAVE.
SO I SHOWED THIS FIGURE BEFORE
IN THE GREY BARS OF WHAT'S
CURRENTLY OUT THERE IN TERMS OF
GENOMIC RESEARCH, AND NOW YOU
SEE COMPARED TO THE BLUE BARS,
WHICH ARE WHAT THE MAKE YUM OF
ALL-OF-US IS.
UP OF
ALL-OF-US IS.
SO WE'VE BEEN WORKING WITH
ENGAGEMENT PARTNERS ACROSS THE
COUNTRY, WORKING WITH HEALTHCARE
PROVIDER ORGANIZATIONS AND
REALLY TRYING TO SEEK TO
ESTABLISH TRUST FIRST, AND
MOVING SCIENCE AT THAT SPEED, AS
WE GO FORWARD TO BUILD WITH OUR
COMMUNITIES AND OVER FROM 5% OF
OUR POPULATION IS DIVERSE BY
RACE AND ETHNICITY, OVER 77% BY
A LARGER METRIC OF
UNDERREPRESENTATION IN
BIOMEDICAL RESEARCH, PEOPLE WHO
LIVE IN RURAL LOCATIONS,
DISABILITY STATUS, EDUCATIONAL
ATTAINMENT AND OTHER METRICS
LIKE THAT.
SO COMING BACK TO THE EXAMPLE OF
PHEWAS AND COMING BACK TO THE
VARIANT LES JUST TALKED ABOUT IN
A NUMBER OF DIFFERENT
CONDITIONS, THIS AS HE DISCUSSED
IS LARGELY PRESENT IN AFRICAN
ANCESTRY POPULATIONS, SO IF YOU
HAD THE EUROPEAN POPULATION JUST
IN YOUR COHORT LIKE IN MOST
COHORTS IN THE WORLD, YOU MAY
NOT SEE THE IMPACT OF THIS
VARIANT.
IN OUR DATASET, WE HAVE ABOUT
1400 INDIVIDUALS WHO CARRY THIS
VARIANT, AND YOU CAN SEE THE
ASSOCIATION RESULTS HERE.
YOU CAN SEE CARPAL TUNNEL, THAT
UPPER LIMB IS A KIND OF
NEUROPATHY, MONO NEUROPATHIES,
SOME OCULAR PHENOTYPES, AND ON
THE LEFT, AMELODOISIS. THIS IS
EARLY RESULTS DONE BY A
POSTBACCALAUREATE STUDENT IN OUR
LAB, AND IF YOU LOOK AT THESE
RESULTS, WE DON'T KNOW HOW MANY
OF THESE PARTICIPANTS ACTUALLY
KNOW IF THEY HAVE THE CONDITION
OR NOT.
THIS WAS SOMETHING THAT WE CAN
GO FURTHER DOWN IN THE ANALYSIS
AS WE THINK ABOUT THESE
CONDITIONS.
THERE'S A CLUSTER OF PHENOTYPES
THAT CAN BE ASSOCIATED WITH A
GIVEN GENETIC CONDITION.
IT CAN ALSO BE ANY SYNDROME.
WE THINK ABOUT HEART FAILURE,
SHORTNESS OF BREATH, SWELLING,
FATIGUE, ALL THESE THINGS THAT
ARE ASSOCIATED WITH THAT.
BUT ESPECIALLY WITH GENETICS AND
RARE DISEASE, DOCTORS AREN'T
NECESSARILY AS GOOD AT THINKING
ABOUT THIS.
LET'S THINK ABOUT THE EXAMPLE OF
CYSTIC FIBROSIS.
COUGH IS A COMMON CONDITION
ASSOCIATED WITH RECESSIVE
GENETIC DISEASE.
ONLY .3% OF PEOPLE WITH COUGH IN
THE ELECTRONIC HEALTH RECORD
WILL HAVE CYSTIC FIBROSIS.
MOST PEOPLE WHO HAVE SINUSITIS
DO NOT HAVE CYSTIC FIBROSIS.
1% WILL.
IF YOU LOOK AT BACTERIAL
PNEUMONIA, MOST PEOPLE WITH
PNEUMONIA WILL NOT HAVE CF.
4% HAVE CF.
IF YOU LOOK AT BRONCHIECTASIS,
STILL ONLY 9% OF THOSE PATIENTS.
BUT IF YOU PUT THESE FOUR
CONDITIONS TOGETHER, 50% OF
THOSE PATIENTS WILL HAVE CF.
SO CAN WE USE THIS KIND OF
PROCESS OF CLUSTERING AND USING
DIFFERENT WEIGHTING TECHNIQUES
TO FIND A DPIRCH CONDITION, AND
SO HERE'S AN EXAMPLE FROM THE
LITERATURE OF SOMEONE WHO'S
PRESENTING MORE ATYPICALLY.
A 47-YEAR-OLD THAT HAD -- THIS
IS A PATIENT WITH CYSTIC
FIBROSIS.
MOST PEOPLE THINK OF THIS
PRESENTING EARLIER IN LIFE.
IT'S ACTUALLY A DISEASE IN MY
FAMILY HISTORY, AND THE PEOP
PEOPLE -- WOULD BE AUNTS AND
UNCLE WOULD ALL MANIFEST VERY
YOUNG.
BUT PEOPLE DO MANIFEST OLDER,
AND THOSE CAN BE MISSED, THOSE
CAN BE THE DIAGNOSTIC ODYSSEYS
ESPECIALLY.
THIS INDIVIDUAL WAS IN THE TOP
2% OF INDIVIDUALS WITH HER SCORE
IN THE DATABASE.
AND SO MAYBE THERE'S AN
AUGMENTED WAY TO KIND OF DO
THIS.
WE LOOKED AT ALL THE PATIENTS WE
HAD DIAGNOSED, AND THEIR AGE OF
DIAGNOSIS OF CYSTIC FIBROSIS.
MOST PATIENTS WERE DIAGNOSED
YOUNG, BUT IF YOU LOOK OVER
TIME, THERE'S ACTUALLY AN
80-YEAR-OLD INDIVIDUAL WHO WAS
DIAGNOSED WITH CF IN THAT, AND
SHE ACTUALLY HAD SYMPTOMS FOR
ABOUT 20 YEARS GOING BACK THAT
YOU COULD LOOK AT.
DOCTORS WERE CONFUSED AS TO WHY
THIS HAPPENED.
OBVIOUSLY A VERY ATYPICAL AND
MUCH MILDER, FORTUNATELY FOR
HER, CASE OF CF, BUT STILL HER
GENETICS SHOWED THAT SHE HAD
THOSE CONDITIONS.
AND HOW DO WE FIND THOSE
CONDITIONS?
HOW DO WE HELP DOCTORS THINK
THROUGH THAT AND GET THE RIGHT
INTERVENTION?
THOSE ARE SOME OF THE THINGS
WE'D LIKE TO THINK ABOUT.
THIS IS JUST LOOKING AT THIS A
DIFFERENT WAY, AND HIGHLIGHTED
TWO PEOPLE WHEN THEIR GRAPH
CHANGES FROM THAT PINK COLOR TO
THE BLUE COLOR, WHEN THEY MADE
THE -- DOCTORS MADE A DIAGNOSIS
OF CF.
AND THE SCALE ON THE LEFT THERE
IS BASED ON STANDARD DEVIATIONS
OF SCORE, WHICH MEANS THAT WHEN
YOU'RE AT THE 5, 7, 10, YOU'RE
INCREDIBLY OFF THE CHART RARE IN
TERMS OF THE POPULATION OF
HAVING THAT CLUSTER OF SYMPTOMS
AT THAT AGE.
SO MAYBE THERE ARE WAYS WE CAN
ELECTRONICALLY HELP IN THAT
PROCESS.
EVEN IF WE DIDN'T HAVE THE
GENOME FIRST COMBINED WITH THE
PHENOME FIRST APPROACH.
I THINK THAT'S WHERE WE'RE
LEADED IS BOTH GENETICS AND
PHENOMES AT THE SAME TIME TO
HELP THEME GET CARE FASTER.
SO THIS IS ALSO WORK THAT CASIA
HAS DONE.
I WANT TO HIGHLIGHT A DIFFERENT
PART OF THE STORY WITH THIS.
THIS IS DOING THAT SAME
PHENOTYPE RISK SCORE APPROACH
FOR THE HEREDITARY AMYLOIDOSIS.
IN THIS CASE, WHAT SHE HAS DONE
IS SHE'S BROKEN IT DOWN BY
PEOPLE WHO HAVE DIABETES AND
PEOPLE WHO DON'T, AND THE ORANGE
COLORS ARE PEOPLE WHO HAVE THE
GENETIC VARIANT, THE BLUE PREP
CENTS -- SORRY, THE ORANGE COLOR
REPRESENTS DIABETES OR NOT, AND
ACROSS THE BOTTOM, HAVING THE
GENETIC VARIANT OR NOT.
SO DIABETES CAUSES FEWERROPATHY.
IT CAUSES KIDNEY DISEASE.
IT CAUSES EYE DISEASE.
SOME OF THE SAME THINGS YOU SEE
IN PEOPLE THAT HAVE THIS
CONDITION.
SO WHAT WE'RE THINKING IS,
PATIENTS WITH DIABETES, ARE THEY
THINKING OF THE POSSIBLE ALSO
PRESENT CONDITION OF HAVING
AMYLOID THAT COULD BE MAKING
THIS WORSE?
AND WILL PEOPLE THINK OF IT THE
SAME WAY?
AND IT REALLY HIGHLIGHTS THE
IMPORTANCE, I THINK, OF THINKING
ABOUT IN BOTH A GENOME AND
PHENOME APPROACH, AND THAT
PHYSICIANS THAT ARE SEEING LOTS
OF PATIENTS NEED SUPPORT IN AN
INFORMATICS APPROACH AND HOW
THEY CAN DO THIS KIND OF WORK
AND BETTER TAKE CARE OF
PATIENTS.
WHERE ARE WE HEADED WITH
ALL-OF-US?
WE'RE VERY EXCITED TO BE --
WE'RE LOOKING FORWARD TO
LAUNCHING IN KIDS AS WELL.
I TALKED ABOUT ALL THE GENOMES
WE HAVE OUT THERE NOW.
WE ARE RETURNING 59 GENES NOW TO
PATIENTS IF THEY WANT THOSE
BACK, WE'RE GOING TO EXPAND
THAT, TAKE NEW INFORMATION, WORK
WITH THE FDA IN HOW WE RETURN
THOSE RESULTS TO PARTICIPANTS,
BUT THESE ARE WAYS I THINK WE
CAN TANGIBLY IMPROVE PEOPLE'S
LIVES AND HOPEFULLY ADVANCE
PRECISION MEDICINE WRIT LARGE AS
THESE PEOPLE TAKE TO PROVIDES
ACROSS THE COUNTRY.
WE HAVE DIGITAL HEALTH DEVICES
MEANING LIKE APPLE WATCHES,
THINGS LIKE THAT.
EXPANDING THAT.
WE ALWAYS CAN THINK W THINKING W
DATA.
PARTICIPANTS CAN BE RECOCONTACTD
AND WE CAN ASK THEM DO THEY WANT
TO BE PART OF OTHER CLINICAL
TRIALS, LEARNING ABOUT
INFLUENCES OF THE ENVIRONMENT,
TO THINK ABOUT HOW WE BUILD THE
RESOURCE AS A PLATFORM TO
CONTINUE TO GET RICHER AND HAVE
MORE OF AN IMPACT ON SOCIETY'S
UNDERSTANDING OF HEALTH ACROSS
POPULATIONS, EVERY ONE OVER
TIME.
SO THANK YOU.
WITH THAT, I'M GOING TO INVITE
CARRIE BACK UP.
[APPLAUSE]
>> SO THANK YOU, LES AND JOSH,
FOR TEEING US UP.
SO WHERE WE KIND OF LEFT OFF
WITH, YOU MS. COLEMAN, WAS YOU
HAD BEEN GOING THROUGH SEVERAL
HEALTH CHALLENGES INCLUDING THE
HEART CONDITION, THE GLAUCOMA,
CARPAL TUNNEL SYNDROME, THE NA
NEUROPATHY, EVERYTHING ELSE THAT
WAS GOING ON WITH YOUR HEALTH,
AND NO ONE WAS REALLY CONNECTING
ALL OF THE DOTS BETWEEN ALL OF
THESE DIFFERENT THINGS.
AND THEN IN 2022, I CALLED YOU
UP.
AND I SAID, HI, MS. COLEMAN.
I'M CALLING FROM A RESEARCH
STUDY AT THE NIH, AND I THINK WE
MAY HAVE FOUND A GENETIC VARIANT
OR A CHANGE IN YOUR DNA THAT
COULD BE ASSOCIATED WITH THIS
CONDITION CALLED TTR
AMYLOIDOSIS.
AND WE TALKED A LITTLE BIT ABOUT
WHAT THAT DNA CHANGE COULD MEAN
FOR YOUR HEALTH.
WE TALKED A LITTLE BIT ABOUT IT.
TR AMYLOIDOSIS AND THE FACT THAT
IT'S ASSOCIATED WITH THIS HEART
CONDITION AND THESE NERVE
PROBLEMS, GLAUCOMA AND ALL OF
THESE OTHER DIFFERENT FEATURES,
AND WHAT DID YOU SAY TO ME?
DO YOU REMEMBER?
>> NO, FIRST OF ALL, I WAS
SHOCKED TO HEAR FROM YOU, AND I
COULDN'T BELIEVE IT.
I WAS LIKE, WHAT?
THIS IS BACK IN 2014, WHEN I
FIRST DID THAT FIRST STUDY, BUT
I CANNOT RECALL WHAT I SAID TO
YOU.
>> YOU SAID, OH, MY GOSH, I
THINK YOU FOUND IT!
IT WAS CRAZY.
I MEAN, IT WAS, YOU KNOW, I
THINK YOU WERE VERY SURPRISED
THAT AS I WAS DESCRIBING,
BECAUSE WHEN I CALLED YOU, I
CALLED YOU WITHOUT A LOT OF THE
PEN FIT OF THOSE UPD -- THE BENF
THOSE UPDATED MEDICAL HISTORIES.
I SAID THERE'S A CHANGE IN THIS
TTR GENE, HERE'S WHAT IT CAN BE
ASSOCIATED WITH, CARPAL TUNNEL
SYNDROME, GLAUCOMA, NERVE
PROBLEM, HEART PROBLEM.
AND I THINK THAT'S WHEN MAYBE
SOME OF THE PUZZLE PIECES REALLY
KIND OF STARTED TO FIT TOGETHER.
>> YEAH, AND I TELL YOU, AS A
RESULT OF THE CALL, I WAS HAPPY
TO GET -- I WAS HAPPY TO BE ABLE
TO TIE THE PIECES TOGETHER,
BECAUSE I HAD ALL OF THESE
THINGS GOING ON WITH ME AND NO
ONE COULD TELL ME WHY.
SO WHEN YOU CALLED ME, I WAS
JUST LIKE, OH, MY GOODNESS, I
FINALLY GOT AN ANSWER TO WHY I
HAVE ALL OF THESE ISSUES.
SO I WAS PLEASED TO GET THAT
CALL.
>> WHAT DID AN ANSWER MEAN TO
YOU, AT THAT TIME OR SINCE THEN?
>> AT THAT TIME, BELIEVE IT OR
NOT, I THOUGHT ABOUT MYSELF AND
MY ISSUE, BUT I IMMEDIATELY WENT
TO MY MOM, BECAUSE MY MOM WAS
HAVING ALL THE ISSUES THAT I'M
HAVING, AND I WAS JUST LIKE, OH,
MY GOD, I WONDER IF THIS IS
SOMETHING THAT MY MOM HAS, YOU
KNOW, CAN WE HELP HER, BECAUSE
SHE'S 90 AND SHE WAS HAVING ALL
THESE HEALTH ISSUES, AND I WAS
JUST HAPPY TO KNOW THAT TH THERE
WAS AN ANSWER TO THESE ISSUES.
AND HOPEFULLY BY HAVING AN
ANSWER, THERE WOULD BE SOME KIND
OF WAY WE COULD SLOW DOWN THE
PROCESS THAT I WAS GOING THRO
THROUGH, COULD MAYBE TRY TO
PREVENT SOME OF THE OTHER
SYMPTOMS THAT COULD BE
ASSOCIATED WITH THIS DISEASE.
SO, YEAH, IT WAS DEFINITELY AN
EYE OPENER FOR ME.
>> WE HAD MENTIONED YOU THOUGHT
ABOUT JOINING THESE RESEARCH
STUDIES BECAUSE OF YOUR FAMILY
HISTORY, AND YOU KNOW, I KNOW
THAT TRYING TO THINK ABOUT HOW
YOU COULD APPLY THIS INFORMATION
TO THE REST OF YOUR FAMILY WAS
SOMETHING THAT WAS REALLY
IMPORTANT TO YOU TOO.
SO THAT'S SOMETHING THAT I THINK
WE'LL COME BACK TO.
SO YOU KNOW, YOU CONNECTED IT
RIGHT AWAY TO YOUR OWN HEALTH
HISTORY AND WHAT WAS GOING ON
WITH YOU PERSONALLY.
AND SO AFTER I CALLED YOU WITH
THIS RESULT, WE OFFERED TO HAVE
YOU COME IN TO THE NIH CLINICAL
CENTER AND ACTUALLY GET CHECKED
OUT TO SEE HOW MANY OF THESE
FEATURES OF TTR AMYLOIDOSIS
COULD BE PRESENT IN YOU AND ALSO
HOW IT COULD TIE INTO SOME OF
THE DIAGNOSES THAT YOU HAD
ALREADY RECEIVED.
SO DO YOU WANT TO SHARE A LITTLE
BIT ABOUT WHAT WE FOUND WHEN YOU
CAME IN TO THE NIH AND WE HAD
YOUR VISIT?
>> WHEN I CAME INTO THE NIH, YOU
GUYS WERE VERY THOROUGH AND A
LOT OCCURRED THAT DAY.
WHEN IT CAME TO THE TINGLING AND
THE NERVE SENSATION THAT WAS
THERE IN MY LEG, MY TOES, MY
HAND, YOU FOUND THAT TO BE A
SIGNIFICANT PART.
I HAD A VERY THOROUGH EYE EXAM
AND LOOKED AT A COUPLE THINGS
THERE.
TOOK A LOOK AT THE HEART AND
THANKFUL YOU DIDN'T SEE ANYTHING
THERE, SO I WAS EXCITED ABOUT
THAT.
>> YES, WE WERE TOO.
DEFINITELY VERY GRATEFUL FOR
THAT.
SO YOU KNOW, WE DID THAT FULL
CHECKUP OF YOUR HEART, AND WE
DID FIND YOUR HEART RATE WAS A
LITTLE BIT SLOW BUT THAT IT WAS
PUMPING OUT BLOOD AT THE RIGHT
RATE AND WE DIDN'T SEE ANY
AMYLOID IN YOUR HEART WHICH WE
WERE ALSO VERY GRATEFUL TO SEE.
WE DID ATTRIBUTE -- WE THINK
THESE FEELINGS OF PAIN AND
NUMBNESS AND TINGLING YOU HAD IN
YOUR FINGERS AND TOES COULD BE
RELATED TO WHAT WE CALL A SMALL
AND LARGE FIBER PERIPHERAL
NEUROPATHY, WHICH WE KNOW CAN BE
ONE OF THE SIGNS OF TTR
AMYLOIDOSIS.
WE CONFIRMED THIS DIAGNOSIS OF
CARPAL TUNNEL SYNDROME AND
GLAUCOMA THAT YOU'D ALREADY
SEEN, AND THEN WE ALSO REFERRED
YOU TO JOHNS HOPKINS, WHERE THEY
ACTUALLY HAVE A CENTER OF
EXCELLENCE FOR TTR AMYLOIDOSIS
AND A LOT OF SPECIALTY DOCTORS
WHO ARE REALLY DEDICATED TO
WORKING SPECIFICALLY ON THIS
CONDITION.
AND SINCE THEN, YOU'VE BEEN ABLE
TO GO THERE AND GET SOME
FOLLOW-UP EVALUATIONS TOO.
>> YES, YES.
THANK YOU.
THAT WAS VERY HELPFUL.
I DID -- IT TOOK ME A WHILE TO
GET IN TO JOHNS HOPKINS, BUT I
GOT IN THERE, AND THE CARE I
RECEIVED WAS REALLY GREAT.
I HAD THE NM AMYLOID --
>> THE NUCLEAR MEDICINE STUDY?
>> YES, NUCLEAR MEDICINE STUDY
THERE, WHICH WAS EXTENSIVE.
I MEAN, I HAD TO DRINK AND I HAD
TO DO SOME INJECTION.
SO I'M HAPPY TO REPORT AFTER
THAT STUDY THAT CAME BACK
NEGATIVE FOR AMYLOID, SO I DON'T
HAVE ANY IN MY HEART AS WELL.
THEN I -- AND I DID THE NERVE
TESTING THERE AS WELL, AND AS A
RESULT OF THAT, I WAS REFERRED
AND I HAD SURGERY FOR MY CARPAL
TUNNEL, AND AT THE SAME TIME
WHEN I HAD THE SURGERY FOR THAT,
THEY DID DO A BIOPSY, AND I AM
HAPPY TO REPORT THAT BIOPSY CAME
BACK NEGATIVE FOR AMYLOID TOO.
BUT WILL O THE ONLY DISAPPOINTIG
IS THIS CAN BE SOMETHING THAT'S
VERY PATCHY, AND JUST BECAUSE I
DON'T HAVE IT HERE IN MY ARM
DOESN'T MEAN IT CANNOT BE
PRESENT IN OTHER PARTS OF MY
BODY.
SO I JUST WISH THERE WAS SOME
OTHER KIND OF WAY I COULD TELL
WHETHER OR NOT IT WAS PRESENT IN
ANOTHER PART OF MY BODY VERSUS
HAVING TO DO A BIOPSY OF
EVERYTHING TO MAKE SURE WITH THE
EXCEPTION OF THE HEART.
>> SO YOU KNOW, WE OBVIOUSLY
GAVE YOU THAT GENETIC RESULT AND
WE'VE TRIED TO DO TESTING FOR
ALL OF THOSE DIFFERENT SYMPTOMS,
BUT THAT STILL FEELS A LITTLE
DIFFERENT THAN BEING ABLE TO
POINT TO A PICTURE AND SAY OKAY,
WE DEFINITELY SEE SOME AMYLOID
DEPOSIT THERE OR, OKAY, WE COULD
ACTUALLY TEST THROUGHOUT YOUR
WHOLE BODY AND WE DEFINITELY
DON'T SEE ANY AMYLOID ANYWHERE.
IT SOUNDS LIKE THAT KIND OF
UNCERTAINTY HAS BEEN A LITTLE
CHALLENGING.
>> YES, YES.
AND THAT'S BEEN DISAPPOINTING,
BUT I UNDERSTAND THIS IS VERY
NEW, AND YOU STILL ARE LOOKING
AT WAYS TO STUDY, SO MAYBE YOU
GET TO THE .1 DAY, YOU WILL BE
ABLE TO SAY TO ME, OKAY, WE CAN
DO THIS ONE PARTICULAR TEST AND
WE CAN TELL YOU THAT THIS IS NOT
PRESENT ANYWHERE IN YOUR BODY,
AND THAT WOULD BE -- I WOULD BE
EXCITED TO HEAR THAT.
ONE OF THE THINGS JOHNS HOPKINS
IS GOING TO BE LOOKING AT NOW --
BECAUSE OF MY AGE, THEY WOULD
WANT ME TO COME BACK IN TWO
YEARS, AND THEY WILL REPEAT THE
SAME TEST THAT THEY DID FOR ME
LAST YEAR.
BUT EVEN THOUGH THEY'RE GOING TO
REPEAT THE TEST IN TWO YEARS,
THEY STILL WILL WANT TO SEE ME
ONCE A YEAR, UP UNTIL THE TIME
THEY REPEAT THE TESTS THAT THEY
GAVE ME BACK IN DECEMBER OF
2023.
>> SO THIS IS GOING TO BE KIND
OF LIKE AN ONGOING THING THAT
YOU'LL KEEP GETTING EVALUATED
FOR BECAUSE WE KNOW THAT THINGS
CAN DEVELOP AND CHANGE OVER
TIME.
>> YES.
YES.
>> SO I'M CURIOUS, YOU KNOW, HOW
DO YOU FEEL KNOWING THIS
INFORMATION ABOUT THE RISK FOR
TTR AMYLOIDOSIS NOW COMPARED TO
WHEN YOU WERE FACING ALL OF
THOSE DIFFERENT HEALTH ISSUES
WITHOUT HAVING A UNIFYING
EXPLANATION TO FIT EVERYTHING
TOGETHER?
>> WELL, IT A DIFFERENT FEELING
BECAUSE BEFORE, I DIDN'T HAVE NO
IDEA WHAT WE NEED TO LOOK FOR.
I WENT TO DIFFERENT SPECIALISTS
AND EVERYBODY WAS TELLING ME YOU
HAVE THIS, YOU HAVE THAT, BUT NO
ONE COULD TELL ME WHY.
SO NOW I KNOW WHAT TO BE LOOKING
FOR SO THAT I'M EXCITED ABOUT.
BECAUSE ONE OF THE THINGS, ALL
OF THESE DIAGNOSES THAT I'VE HAD
OVER THE YEARS, THE MOST SEVERE
DIAGNOSIS FOR ME WAS THE ONE
ASSOCIATED WITH MY HEART.
BELIEVE IT OR NOT, THAT WAS VERY
HARD FOR ME TO ACCEPT.
IT WAS BECAUSE I WASN'T
EXPERIENCING ANY SYMPTOMS FROM
THAT, WHICH THEY COULD NOT
BELIEVE, BECAUSE MY HEART WAS
BEATING AT SUCH A LOW RATE.
AND WHEN I RECEIVED A CALL TO
REPORT TO THE EMERGENCY ROOM, I
WAS LIKE, ARE YOU SURE YOU HAVE
THE RIGHT PERSON?
YOU KNOW, AND THEY WAS JUST
LIKE, YES, WE DO, AND I WAS
LIKE, OKAY, I WENT IN, THEY
HOOKED ME UP TO THE MONITOR, AND
DURING THAT WHOLE TIME, MY HEART
RATE WAS JUST DROPPING, THE
MACHINE WAS JUST GOING OFF, AND
I COULD NOT FEEL -- THAT WAS
VERY DISTURBING TO ME.
THE FACT THAT MY HEART WAS DOING
THAT, BUT I DIDN'T REALIZE.
SO I WAS VERY THANKFUL THAT MY
PRIMARY PHYSICIAN TOOK THE TIME
AND LISTENED TO MY HEART THAT
DAY AND ORDERED THAT MONITOR FOR
ME THAT I WORE FOR THAT MONTH
BECAUSE IT PROBABLY SAVED MY
LIFE, THE WAY I LOOK AT IT.
AND NOW I KNOW WHY.
WITH YOUR
TESTING.
>> YOU HAD ALL OF THESE KINDS OF
HIDDEN THINGS GOING ON THAT YOU
WOULD HAVE HAD NO IDEA, HAD
SOMEONE NOT THOUGHT TO ACTUALLY,
LIKE, CHECK YOU OUT FOR THEM,
LISTEN TO YOUR HEART, HAD
SOMEONE NOT THOUGHT TO LOOK
THROUGH YOUR DNA TO FIND THIS
SPECIFIC POTENTIAL EXPLANATION.
THERE'S A LOT GOING ON KIND OF
UNDER THE HOOD THAT REMAINED
HIDDEN.
>> YES, YES.
VERY MUCH SO.
YOU KNOW, AND IT WAS A RELIEF TO
ME BECAUSE I WAS REALLY
SURPRISED.
THEY HAD MY MOM TESTED AND SHE
CAME BACK NEGATIVE, SO THAT WAS
ANOTHER EYE OPENER FOR ME,
BECAUSE I WOULD HAVE ALMOST BET
MY LIFE ON THE FACT THAT MY MOM
HAD THIS TTR BECAUSE OF ALL THE
SYMPTOMS SHE WAS HAVING.
BUT SHE DOESN'T.
AND I'M HAPPY THAT SHE DOESN'T.
BUT IT'S JUST ONE OF THOSE
THINGS, IT'S HAPPENING TO HER.
IT'S NOT BECAUSE OF THE TTR.
>> JUST GOES TO SLOW YOU'VE GOT
TO DO THE TEST AND YOU DON'T
KNOW UNTIL YOU DO THE TEST.
CAN YOU TELL ME A LITTLE BIT
MORE ABOUT THAT?
HOW HAS -- SO WE OBVIOUSLY KNOW
WE SHARE GENES WITH OUR FAMILY
MEMBERS, AND SO SOMETIMES WE CAN
PASS DOWN OR SHARE THESE GENE
VARIANTS THAT CAN INCREASE OUR
CHANCE TO DEVELOP THESE
CONDITIONS.
HOW HAS THAT GONE FOR YOU,
SHARING THIS NEWS OF THIS
GENETIC RESULT WITH YOUR FAMILY
MEMBERS?
>> WELL, THEY WAS SURPRISED.
AS SURPRISED AS I WAS WHEN I
RECEIVED THE INFORMATION.
AND SINCE THEN, MY TWO SISTERS
HAVE TAKEN THE TEST BUT THEY
HAVEN'T RECEIVED THE RESULTS
BACK THROUGH JOHNS HOPKINS.
SO THEY'RE WAITING TO GET THE
RESULTS BACK.
AND THEN WE'RE JUST GOING TO
WORK ON IT FROM THERE.
THEY WERE SHOCKED.
NEVER HEARD OF IT, SAME AS ME,
SO -- YES.
>> HOW DID IT FEEL WHEN YOU HAD
TO KIND OF PICK UP THE PHONE AND
CALL THEM?
WAWHAT WAS THAT EXPERIENCE LIKE
FOR YOU?
>> WELL, ACTUALLY I WAS RELIEVED
OF THE FACT BECAUSE I'VE BEEN
TELLING THEM ALL OF THESE THINGS
THAT WAS GOING ON WITH ME AND TO
POSSIBLY HAVE A SOLUTION OF WHAT
COULD BE CAUSING ALL OF THIS,
REALLY I WAS RELIEVED, BECAUSE
SOMETIME WHEN YOU COMPLAIN ABOUT
SO MANY DIFFERENT THINGS, PEOPLE
HAVE A TENDENCY TO WONDER WHAT'S
WRONG WITH YOU, ARE THESE THINGS
REALLY GOING ON WITH YOU.
SO TO BE ABLE TO SAY YES, I HAVE
SOMETHING THAT I CAN SAY THIS IS
WHY THIS IS HAPPENING TO ME.
SO IT WAS VERY IMPORTANT, I WAS
VERY RELIEVED TO TELL MY FAMILY.
NOT SURE THEY WAS AS EXCITED AS
I WAS TO HEAR ABOUT IT.
>> THAT'S FAIR.
IT SOUNDS LIKE IT WAS A BIG
WEIGHT OFF OF YOU TO BE ABLE TO
SAY OKAY, NOW I HAVE, YOU KNOW,
GRANTED A VERY LONG TWO-WORD
PHRASE FOR WHAT IS GOING ON WITH
ME.
IT'S A RELIEF TO BE ABLE TO SAY
THAT OUT LOUD, PUT A NAME TO IT,
SAY OKAY, NOW HERE IS THIS PIECE
OF PAPER.
I JUST NEED YOU TO GO GET TESTED
FOR THAT BUT I'D IMAGINE ON THE
OTHER END RECEIVING THAT PIECE
OF PAPER CAN DEFINITELY COME AS
A SURPRISE AND LIKE AN OH,
GOODNESS, NOW WHAT AM I IN FOR.
>> YEAH, YEAH, IT TRULY WAS A
SURPRISE.
AND BECAUSE OF THE LOCATION OF
MY FAMILY, WHICH -- ALL MY
FAMILY IS LOCATED IN
MISSISSIPPI, AND THE TESTING
THERE IS NOT REALLY AVAILABLE
FOR THEM TO HAVE IT DONE.
THAT'S ONE OF THE REASONS WHY
THEY SENT THEM TO BE TESTED HERE
AT JOHNS HOPKINS, AND THAT'S ONE
OF THE OTHER PRIMARY REASONS I
WAS HAPPY THAT MY MOM TESTED
NEGATIVE FOR THAT, BECAUSE
THAT'S JUST NOT SOMETHING THAT
SHE COULD -- ABLE TO TRAVEL TO
BE TREATED FOR, EVEN EXPLORE THE
POSSIBILITY, DO SHE ACTUALLY
HAVE THE DISEASE ITSELF.
>> THAT MAKES PERFECT SENSE.
SO DEFINITELY THINKING ABOUT
THOSE KIND OF NEXT STEPS THAT
CAN COME FOR FAMILY MEMBERS WHO
MIGHT TEST POSITIVE ARE
IMPORTANT TO CONSIDER TOO.
DO YOU HAVE ADVICE FOR ANYBODY
ELSE WHO MIGHT BE IN A SIMILAR
POSITION WHO, YOU KNOW, MIGHT
RECEIVE ONE OF THESE GENETIC
RESULTS FROM THESE KINDS OF
STUDIES?
>> WELL, FIRST OF ALL, I THINK
MY ADVICE, I WOULD WANT TO
ENCOURAGE EVERYONE TO
PARTICIPATE TOMMY EVEN WHEN I
DID THE STUDY BACK IN 2014, I
WAS GOING AROUND BEGGING PEOPLE
TO PARTICIPATE BECAUSE I WANTED
TO GET TO THE -- SO WE CAN GET
THE RESULTS, SO I REALLY WANTED
TO FIND OUT, DID I HAVE ANYTHING
GOING ON WITH MY HEART, BECAUSE
OF MY GRANDMOTHER.
AND SO I WOULD SAY IT'S REALLY
IMPORTANT.
IT'S A LIFE AND DEATH SITUATION,
BECAUSE IF YOU HAVE ALL OF THE
DIFFERENT ILLNESS GOING ON, NOW
YOU KNOW WHAT TO LOOK FOR.
NOW THERE'S MEDICATION THAT'S
AVAILABLE.
THAT YOU COULD TAKE AND POSSIBLY
SLOW DOWN THE DISEASE.
SO IF YOU DON'T KNOW, THEN YOU
DON'T KNOW WHAT TO DO.
SO ADVICE, ONE, JOIN A STUDY,
TWO, THINK ABOUT WHAT YOU CAN
GET AND HOW YOU MIGHT USE IT IN
YOUR OWN HEALTHCARE.
I THINK THAT'S VERY GOOD ADVICE.
WELL, THANK YOU SO MUCH,
MS. COLEMAN.
WE REALLY APPRECIATE YOU SHARING
YOUR STORY WITH US.
I'M GLAD THAT WE COULD ALL LEARN
FROM YOUR EXPERIENCE AND I THINK
YOU GAVE EVERYBODY HERE AND
EVERYBODY LISTENING ONLINE A LOT
TO THINK ABOUT, SO THANK YOU.
[APPLAUSE]
>> THANK YOU.
SO I THINK NOW WE'LL OPEN IT UP
FOR SOME Q & A.
IF YOU HAVE ANY QUESTIONS,
PLEASE POST THEM ONLINE, AND IF
ANYBODY HAS ANY QUESTIONS.
>> ANYBODY ROOM, WE'LL DO THE
HANDHELD.
>> SO WE CAN START MAYBE -- SO I
HAVE A COUPLE OF QUESTIONS.
ONE FOR MS. COLEMAN, AND THAT
IS, SO YOU FOUND OUT THAT YOUR
MOM DOESN'T HAVE THIS TTR
VARIANT, IF I UNDERSTOOD
CORRECTLY.
NOW, HOW ABOUT YOUR DAD?
DID HE HAVE ANY SYMPTOMS THAT
WOULD GO ALONG WITH THE IDEA
THAT MAYBE YOU COULD HAVE GOTTEN
THE GENE FROM HIM?
>> WELL, UNFORTUNATELY, MY
FATHER PASSED AWAY WHEN I WAS
VERY YOUNG.
HE WAS LIKE IN HIS 40s.
AND AT THAT TIME, FROM WHAT I
CAN REMEMBER, HE HAD NO SYMPT
SYMPTOMS.
ALL OF HIS SISTERS ARE NOW
DECEASED, AND HIS BROTHER, SO
ONE THING THAT I KNOW THAT WAS
VERY PROMINENT IN HIS FAMILY WAS
DIABETES.
AND I THINK MY AUNT HAD THE
HODGKIN'S DISEASE, WHAT YOU CALL
THAT?
PARKINSON, THANK YOU.
PARKINSON.
ONE OF MY AUNTS HAD THAT.
BUT OTHER THAN THAT, I DON'T
KNOW ANYTHING ELSE ABOUT MY
FATHER'S SIDE OF THE FAMILY.
>> OKAY.
SO THAT'S STILL UP IN THE AIR.
OKAY.
SO NOW -- OKAY.
SO I'M JUST READING THESE AS
THEY COME IN OFF THE WIRE, SO TO
SPEAK.
SO HOW WOULD YOU ADDRESS HEALTH
INSURANCE THAT MAY REFUSE TO
SIGN YOU UP IF YOU HAVE THE
POTENTIAL FOR A DISEASE THAT IS
EXPENSIVE TO TREAT?
I DON'T KNOW IF THAT'S FOR
MS. COLEMAN.
I THINK THAT MIGHT BE MORE
FOR --
>> THIS SOUNDS LIKE A GENETIC
COUNSELING QUESTION.
SO THERE WAS ACTUALLY A LAW
PASSED BACK IN 2008 CALLED THE
GENETIC INFORMATION
NON-DISCRIMINATION ACT.
AND IT DOES PROTECT AGAINST
DISCRIMINATION WHEN IT COMES TO
HEALTH INSURANCE AND EMPLOYMENT.
THERE ARE SOME IMPORTANT CAVEATS
THERE, DEPENDS ON EMPLOYER SIZE
AND IF YOU'RE IN THE MILITARY.
BUT BUY A BY AND LARGE, IT PROTS
PEOPLE FROM BEING DISCRIMINATED
AGAINST BASED ON YOUR GENETICS.
SO THEY HAVE THOSE PROTECTIONS
IN PLACE SO THAT PEOPLE CAN GET
THE GENETIC TESTING OR SIGN UP
FOR SOME OF THESE GENETIC
RESEARCH STU DID Y D STUDIES ANN
VALUABLE INFORMATION THAT CAN BE
USED TO PROTECT YOUR HEALTH
WHICH WOULD HOPEFULLY ALSO BE
THE HEALTH INSURANCE COMPANIES'
GOAL.
>> OKAY.
SO ANOTHER QUESTION THAT OCCURS
TO ME IS GIVEN THE FREQUENCY OF
THESE VARIANTS AND THE TTR GENE
IN THE AFRICAN AMERICAN
POPULATION, HAS ANYONE LOOKED AT
THE POPULATIONS IN ESPECIALLY
THE WESTERN PART OF AFRICA WITH
REGARD TO THE FREQUENCY OF TTR
AMYLOIDOSIS?
BECAUSE YOU WOULD THINK THAT
PERHAPS IT WOULD BE COMMON IN
THAT PART OF THE WORLD.
>> HI, EVERYONE.
I'M THE DIRECTOR OF THE REVERSE
PHENOTYPING CORE.
THERE HAVE BEEN SOME STUDIES, SO
THERE ARE SOME COUNTRIES IN
WESTERN CENTRAL AFRICA THAT MAY
BE AS HIGH AS 8 OR 9% IN THAT
POPULATION.
THE ONE ISSUE THERE IS THAT THE
LIFE EXPECTANCY IS NOT OFTEN
NEARLY AS LONG AND SO MANY
PEOPLE DON'T DEVELOP THE
SYMPTOMS OF AMYLOIDOSIS.
>> THEN MAYBE A FOLLOW-UP
QUESTION ON THIS IS ARE THERE
ANY ENVIRONMENTAL FACTORS THAT
ANYONE KNOWS ABOUT, YOU KNOW,
THAT MIGHT IN SOME WAY INCREASE
THE LIKELIHOOD THAT YOU'D HAVE
SYMPTOMS FROM ONE OF THESE
GENETIC VARIANTS?
>> THAT'S A GREAT QUESTION THAT
I DON'T KNOW THAT WE HAVE A GOOD
ANSWER TO.
THERE DOESN'T SEEM TO BE -- LIKE
WITH SOME OF THE OTHER
CONDITIONS LIKE SICKLE CELL
DISEASE, THERE DOESN'T SEEM TO
BE AN ENVIRONMENTAL REASON FOR
WHY WE HAVE SUCH A HIGH
INCIDENCE OF TTR VARIANTS.
AND IT DOESN'T SEEM TO BE
NECESSARILY A KNOWN TRIGGER FOR
WHAT CAUSES THE AMYLOID TO
DEPOSIT IN CERTAIN ORGANS.
THAT'S STILL WORK TO BE FIGURED
OUT.
THERE ARE LOTS OF OTHER TYPES OF
AMYLOID, LIKE LIGHT CHAIN AND
OTHER FORMS.
THIS IS JUST ONE PARTICULAR FO
FORM.
AND DIABETES.
>> MAYBE YET ANOTHER QUESTION,
SO DR. BIESECKER MENTIONED FIVE,
I THINK, MEDICATIONS THAT NOW
HAVE BEEN FDA-APPROVED FOR THE
TREATMENT OF TTR AMYLOID.
I ACTUALLY HADN'T BEEN FOLLOWING
THAT VERY CAREFULLY.
I'D SEEN IN THE NEW ENGLAND
JOURNAL THAT AT LEAST THERE WERE
ONE OR TWO OF THEM.
I DIDN'T KNOW THAT THERE WERE
FIVE OF THEM.
THAT'S PRETTY AMAZING.
AND THE AVAILABILITY AND COST OF
THOSE TREATMENTS, HOW DOES THAT
STACK UP NOW?
>> THEY'RE ALL AVAILABLE AND
FDA-APPROVED.
THEY ARE VERY EXPENSIVE.
AS MANY OF THESE NEW PRECISION
HEALTH, PRECISION MEDICINE DRUGS
ARE.
AND SO THEY CAN COST QUITE A BIT
OF MONEY, ALTHOUGH INSURANCE
COMPANIES ARE PAYING FOR THEM.
>> SO I HAVE A COUPLE OF
QUESTIONS THAT I MAY HAVE
MISSED.
HOW MANY PATIENTS DO YOU THINK
THERE ARE WHO HAVE THIS
PARTICULAR VARIANT?
I MEAN, IT'S A RARE DISEASE.
DO WE HAVE SOME ESTIMATE?
ARE WE TALKING ABOUT DO YOU
THINK HUNDREDS, THOUSANDS,
HUNDREDS OF THOUSANDS?
AND THE SECOND QUESTION IS, WHEN
YOU GO TO ANOTHER PART OF THE
WORLD, SAY TO SUB-SAHARAN AFR
AFRICA, BY WHAT CRITERIA WOULD
YOU DO A STUDY THERE?
WOULD YOU BE DOING IT SIMILAR TO
WHAT YOU'RE DOING AT THE NIH?
ALL-OF-US?
OR WOULD YOU BE RESORTING TO THE
TRADITIONAL METHOD OF
IDENTIFYING SOME SYMPTOM POLG
WHICHSYMPTOMATOLOGYWHICH WOULD E
CATCHMENT AREA?
HOW DO YOU GO ABOUT THAT KIND OF
A STUDY IN A SITUATION REMOVED
FROM AN ENVIRONMENT SUCH AS WE
HAVE HERE?
AND I GUESS THE LAST QUESTION I
HAVE IS, TO WHAT EXTENT IS THERE
INTERNATIONAL PARTICIPATION AND
COOPERATION?
WE HEAR OF MANY CENTERS AROUND
THE WORLD THAT ARE SEQUENCING
LARGE NUMBERS OF EXOMES AND SO
FORTH.
DO THEY TALK TO ONE ANOTHER, AND
TO WHAT EXTENT DO YOU SHARE
INFORMATION?
>> LES, I CAN ANSWER THE
INCIDENCE QUESTION.
>> GO AHEAD.
>> SO THERE'S -- THE CURRENT
ESTIMATE IS BASED ON ONE OF
THE -- THE COMPANY THAT MOST
RECENTLY HAD THEIR DRUG
APPROVED.
IT'S ABOUT 3- TO 500,000 PEOPLE
ARE ESTIMATED TO HAVE
AMYLOIDOSIS, SYMPTOMATIC
AMYLOIDOSIS IN THE WORLD.
>> TTR?
>> TTR, YES.
SORRY.
>> HALF A MILLION PEOPLE.
THAT'S A LOT OF PEOPLE.
BUT IT'S A COMPLICATED QUESTION,
BECAUSE YOU KNOW, IT DEPENDS ON
WHAT YOU MEAN BY "HAVE THE
DISEASE."
RIGHT?
BECAUSE WE CAN VERY ACCURATELY
TELL YOU HOW MANY PEOPLE HARBOR
PATHOGENIC VARIANTS FOR THAT
DISEASE AND IT'S A SLIGHTLY
DIFFERENT QUESTION HOW MANY
PEOPLE ACTUALLY HAVE
MANIFESTATIONS OF THE DISEASE,
BECAUSE OF OF COURSE THAT
PENETRANCE AND EXPRESSIVITY
QUESTION.
AND YOU KNOW, WHEN YOU GET DOWN
TO INDIVIDUAL PATIENTS, IT CAN
BE A LITTLE TRICKY BECAUSE, OF
COURSE, AS YOU WELL KNOW, PLENTY
OF PEOPLE HAVE CARPAL TUNNEL
SYNDROME AND DON'T HAVE TTR
AMYLOIDOSIS.
JUST BECAUSE THE PERSON HAS THE
VARIANT DOESN'T ACTUALLY MEAN
THAT THE VARIANT CAUSED THEM TO
HAVE CARPAL TUNNEL SYNDROME.
SO THE CALCULATIONS ARE TRICKY.
BUT THERE'S A TON OF PEOPLE THAT
HAVE THIS.
AND I THINK THE MOST IMPORTANT
TAKE-HOME LESSON IS THAT THIS
DISORDER IS SEVERELY, WILDLY,
TERRIBLY UNDERDIAGNOSED.
THERE'S HUNDREDS AND HUNDREDS OF
THOUSANDS OF PEOPLE WHO HAVE
THIS CONDITION, AND ALMOST --
AND A VERY SMALL FRACTION OF
THEM HAVE THE DIAGNOSIS OF IT.
>> SO IS THIS ON THE ACMG?
>> IT IS NOW.
YES, IT'S ON THE NEW 81-GENE
LIST.
JOSH MENTIONED THAT FOR
ALL-OF-US, THEY WERE APPROVED TO
DO THE 2.0 LIST, WHICH IS 50
FLIEN GENES, A -- 59GEANS AND I.
SO WE'VE ACTUALLY BEEN TALKING
ABOUT APPROACHING THIS PROBLEM,
HOW WE CAN CREATIVELY APPROACH
THIS IN ALL-OF-US SINCE IT WON'T
BE IN THAT SET OF GENE VARIANTS
THAT THE ALL-OF-US PARTICIPANTS
WILL BE OPTING IN TO GETTING
BACK.
DO YOU WANT TO SAY ANYTHING MORE
ABOUT THAT?
>> I'LL JUST SAY THAT IT'S AN
EVOLVING STORY WITH ALL-OF-US,
IN THAT WE HAVE OUR PARTICIPANTS
HOPEFULLY FOR DECADES AS
PARTNERS WITH US, AND IT'S ONE
OF THOSE THINGS THAT I THINK
IT'S A GREAT CANDIDATE TO EXPAND
TO AS WE LOOK AT OUR NEXT BATCH
OF THINGS WE DO WITH THE FDA.
>> I THINK ANOTHER PART OF YOUR
QUESTION IS HOW WE MIGHT
CONSIDER DOING THIS IN SOME
PLACE LIKE SUB-SAHARAN AFRICA.
I THINK THERE ARE LOTS OF REALLY
IMPORTANT COLLABORATIONS THAT
THINKING OF CHARLES ROTIMI AND
THE H3 AFRICA CONSORTIUM WHO ARE
TRYING TO TAKE THIS
GENOTYPE-FIRST APPROACH TO
MEDICINE IN AFRICA AS WELL, SO I
THINK THERE ARE WAYS THAT IT CAN
BE DONE.
IT'S JUST A MATTER OF MOBILIZING
AND DEDICATING RESOURCES AND
SAYING IT'S ALSO A PRIORITY TO
IDENTIFY PEOPLE IN A GENE
TYPE-FIRST MANNER SO THEY HAVE
THE OPPORTUNITY TO HAVE ACCESS
TO THESE SAME TREATMENTS BEFORE
THEY END UP GETTING DIAGNOSED
WITH HEART FAILURE.
BECAUSE BY THE TIME SOMEONE
SHOWS UP TO A CLINIC WITH THOSE
TYPES OF SYMPTOMS, IT'S REALLY
HARD TO TREAT THEM AND MAKE A
DIFFERENCE IN TERMS OF LONGEVITY
AND LIFESPAN.
>> WHAT DO YOU SEE DOWN THE LINE
FROM THE STANDPOINT OF THE
TECHNOLOGY OF EXOME SEQUENCING?
HAVE WE REACHED THE END OF THE
LINE?
OR CAN YOU VISUALIZE ENGINEERING
OR OTHER DEVELOPMENTS THAT ARE
GOING TO EVEN FURTHER AUTOMATE
AND ULTIMATELY, WHO KNOWS, IS IT
CONCEIVABLE THAT SOMEBODY WILL
HAVE A HOME KIT?
I MEAN, WHAT DO YOU SEE IN THIS
FUTURE COMING WITH ALL SORTS OF
EXCITING THINGS BEING POSSIBLE?
>> I THINK IT'S FAIR TO SAY, WE
ARE APPROACHING THE POINT WHERE
THE SEQUENCING PROBLEM, THE
SEQUENCING ITSELF, IS A SOLVED
PROBLEM.
THE COST OF IT IS GETTING SMALL
ENOUGH THAT THE COST OF
GENERATING THE DATA IS REALLY
NOT A BARRIER TO MUCH OF
ANYTHING.
NOW, GENERATING THE DATA,
THOUGH, IS ONLY PART OF THE
STORY.
SOMEBODY HAS TO CLASSIFY THE
PATHOGENICITY OF ALL THESE
VARIANTS, EACH ONE OF US HAS
3 MILLION.
JOSH HAS A BILLION.
IN HIS STUDY.
AND IT'S GOING TO TAKE SOME WORK
TO CLASSIFY AND UNDERSTAND WHAT
THOSE MEAN.
MOST OF THEM PROBABLY MEAN
NOTHING.
BUT SOME OF THEM MEAN A LOT.
SO THE BIG CHALLENGE NOW IS NOT
IN GENERATING THE DATA OR WHAT
THE DATA COST.
THE BIG CHALLENGE NOW IS
DEVELOPING MORE EFFICIENT WAYS
TO UNDERSTAND THE RELATIONSHIP
OF THE VARIANTS TO HEALTH AND
DISEASE, AND THAT'S WHERE THE
BIG ADVANCEMENTS HAVE TO COME,
BECAUSE THAT IS CURRENTLY LOW
THROUGHPUT AND EXPENSIVE.
>> HOW DO YOU VISUALIZE ONE WHO
GOES ABOUT ADDRESS BEING THAT --
>> HOW WILL WE INCREASE THE
THROUGHPUT AND LOWER THE COST OF
VARIANT CLASSIFICATION.
WELL, OF COURSE ONCE WE KNOW THE
RELATIONSHIP OF A VARIANT TO
HEALTH, THAT'S MOSTLY THEN A
SOLVED PROBLEM.
THAT'S IN THE BANK AND YOU CAN
JUST USE IT.
THE RELATIONSHIP OF V142I TO TTR
AMYLOIDOSIS, SOLVED PROBLEM.
NOW IT DOESN'T TAKE ANYBODY MUCH
OF ANY TIME TO WRITE A REPORT
THAT SAYS THAT.
SO YOU ACCUMULATE EXPERIENCE AND
YOU SOLVE THE PROBLEMS, AND THEN
YOU BUILD UP A BANK OF ANSWERS
THAT YOU CAN RE-USE AND THE
MARGINAL COST OF THAT IS
NOTHING.
BUT THERE ARE ALWAYS GOING TO BE
MORE RARE VARIANTS, AND IT'S
GOING TO TAKE SOMEONE TIME TO
FIGURE THAT OUT.
YOU KNOW, EVERYONE THROWS AROUND
MACHINE LEARNING AND A.I.
I'M SURE THAT WILL HELP US, AND
I'M EQUALLY SURE IT'S NOT THE
WHOLE ANSWER.
BECAUSE IT TAKES HUMAN BEINGS TO
ACTUALLY THINK ABOUT THEM AND
MAKE SENSE OUT OF IT SO THAT A
LABORATORY GENETICIST CAN TURN A
RESULT COMING OUT OF A MACHINE
INTO A TEST RESULT THAT A DOCTOR
CAN ACTUALLY USE.
>> SO LES, I KNOW THAT YOU'VE
DONE SOME STUDIES THROUGH
CLINSEQ LOOKING AT ALTERNATIVE
WAYS OF RETURNING INFORMATION TO
SUBJECT IN TERMS OF WHETHER OR
NOT A GENETIC COUNSELOR IN
PERSON RETURNS THE RESULTS OR
WHETHER THAT MIGHT BE DONE
THROUGH A COMPUTER OR SOMETHING
LIKE THAT.
DO YOU WANT TO SAY A FEW WORDS
ABOUT THAT?
THAT SEEMS TO BE ALSO RELATED TO
THIS ISSUE OF SORT OF
DISSEMINATION OF THE TECHNOLOGY.
>> TALK ABOUT LOW THROUGHPUT.
SO THAT'S ONE OF OUR CHALLENGES,
IS FIGURING OUT HOW TO GET THESE
RESULTS BACK TO PATIENTS, AND
THE OLD MODEL OF GENETICS IS FOR
A HUMAN BEING, A GENETIC
COUNSELOR MOST OFTEN, SITTING IN
A ROOM WITH A PATIENT FOR AN
HOUR, TALKING ABOUT A VARIANT.
A SINGLE VARIANT.
AND THAT IS TOTALLY NOT
SUSTAINABLE, NOT SCALABLE, AND
IS PROBABLY THE BIGGEST BARRIER
TO PRECISION HEALTHCARE, GENOMIC
HEALTHCARE THAT THERE IS.
SO IT HAS TO CHANGE.
AND IT IS CERTAIN THAT SOME
PEOPLE DO NEED A HEALTH
PROFESSIONAL TO TALK TO THEM IN
PERSON TO UNDERSTAND AND MAKE
DECISIONS THAT SHOULD ALWAYS
HAPPEN, BUT IT SHOULDN'T HAVE TO
ALWAYS HAPPEN.
SO NEGATIVE RESULTS, WE HAVE
FOUND WE CAN PROVIDE THOSE TO
PATIENT THROUGH A COMPUTER
INTERFACE, AND THE PATIENTS
UNDERSTAND AS MUCH AS THEY DO
WHEN THEY COME AND TALK TO US.
THEY'RE AS SATISFIED AS WHEN
THEY COME AND TALK TO US, AND
THEY DO NOT FEEL MUCH OF A NEED
TO COME AND TALK TO US.
SO WE'VE SOLVED THAT PROBLEM,
AND IT'S A VERY INEXPENSIVE MODE
TO GET OUT NEGATIVE RESULTS,
WHICH MANY TEST RESULTS ARE.
POSITIVE RESULTS, THE PANDEMIC
FORCED US TO DO THAT WITHOUT
SEEING PATIENTS.
AND WE JUST HAD TO DO IT.
AND MANY OF OUR CLINICAL
COLLEAGUES DID THE SAME THING.
AND IN FACT, IT WORKS.
SO SOME OF US IN GENETICS, MANY
OF US PROBABLY IN HEALTHCARE, IN
GENERAL HARBOR UNREASONABLE
BELIEFS ABOUT HOW MUCH PEOPLE
LIKE TO COME AND BE WITH US IN
THE HOSPITAL, IN THE CLINIC.
I THINK THEY MOSTLY LIKE TO BE
IN THEIR HOMES, TO BE HONEST
WITH YOU.
SO THE MORE THAT WE CAN GIVE
PEOPLE OPTIONS TO RECEIVE
RESULTS EITHER THROUGH A
COMPUTER OR THROUGH A PHONE CALL
OR THROUGH A TELEHEALTH VISIT
WITH AN OPTION TO COME AND SEE
US AND SIT WITH US IF THEY FEEL
THAT NEED AND IF THAT SERVES
THEIR INTERESTS, THAT'S WHERE WE
HAVE TO MOVE TO.
>> JUST TO ADD ON TO THAT A
LITTLE BIT, WE'VE BEEN RETURNING
TO THIS NOW FOR ABOUT A YEAR.
WE OFFER TO ABOUT 5,000 PEOPLE
EVERY WEEK NOW.
ABOUT HALF OF THAT ASKS FOR THE
REPORT, AND IT'S COMPLETELY
VIRTUAL.
SO WE OFFER THE -- IF IT'S THE
UNINFORMATIVE REPORT, THEY CAN
CALL A GENETIC COUNSELOR IF THEY
WANT.
THEY CAN CALL A GENETIC
COUNSELOR AT ANY POINT, WE'LL
SCHEDULE A SESSION, THEY CAN ASK
ABOUT THEIR GENETIC ANCESTRY,
THEY CAN ASK BEFORE, HEY, WHAT
DOES IT MEAN, SHOULD I SAY YES
OR NO, TALK ME THROUGH WHAT THAT
MEANS.
BUT ESSENTIALLY IT'S WORKING.
I MEAN, WE HAVE INCREDIBLY HIGH
UNDERSTANDING RATES, SORT OF --
THESE STANDARD SURVEYS LIKE
CUSTOMER SATISFACTION, NET
PROMOTER SCORE, THAT KIND OF
STUFF, AS WELL AS THE NORMAL
COMPREHENSION KIND OF SCORES,
AND TALKING THROUGH THEIR
PATHOGENIC RESULTS.
THAT'S 2200 OR SO PEOPLE THAT
HAVE RECEIVED NEW TO THEM
PATHOGENIC RESULTS ON THESE 59
GENES NOW THAT ARE ESSENTIALLY
LIFE-ALTERING THROUGH THIS, YOU
KNOW, VIRTUAL PROCESS.
AND, GOSH, 70, 80,000 PEOPLE
THAT HAVE POTENTIALLY ACTIONABLE
PHARMACOKINETIC RESULTS THEY'VE
RECEIVED.
SO IT SEEMS LIKE IT IS VERY
DOABLE IN THIS WORLD.
>> SO ONE OF THE BIGGEST BRIDGES
WE ALWAYS GET INVOLVED IN IS THE
GAP BETWEEN BOTH THE SCIENCE ON
ONE SIDE, MEDICINE ON THE OTHER
SIDE, AND THE PUBLIC ON THE
OTHER SIDE.
AND THE BIGGEST STRUTS IN THOSE
BRIDGES ARE EDUCATION.
SO IS THERE SOME THINKING, IS
THERE SOME -- IS THE QUESTION
BEING ADDRESSED ABOUT HOW WE'RE
GOING TO INFORM YOUNG PEOPLE,
HIGH SCHOOL STUDENTS, COLLEGE
STUDENTS, PHYSICIANS, MEDICAL
STUDENTS, THE WHOLE 9 YARDS, TO
WHAT EXTENT ARE DEVELOPMENTS
LIKE THE KIND THAT YOU ARE
SPEAKING ABOUT, GOING TO BE
INTRODUCED INTO THEIR EVEN WAY
OF THINKING, NOTNESS SAIR LEGAL
UNDERSTANDING ALL THE NUANCES
THAT HAVE BEEN PRESENTED?
>> IT'S PROBABLY MORE FOR YOU
THAN ME.
I MAIN PRINCIPLE IS WE JUST HAVE
TO REDUCE THE FRICTIONS IN THE
SYSTEM.
THERE ARE SO MANY FRICTIONS AND
BARRIERS BETWEEN THIS
INFORMATION THAT WE CAN HAVE OR
CAN GENERATE AND PEOPLE ACTUALLY
GETTING IT AND USING IT, AND WE
HAVE TO DO ALL OF THE ABOVE,
INCLUDING OUR PATIENTS, HAVE TO
IN SOME WAYS BE THEIR OWN
ADVOCATES.
LAKLIKE YOU JUST SAID EARLIER,
ENCOURAGE PEOPLE TO SIGN UP FOR
THESE THINGS AND GET ENGAGED,
SIGN UP FOR THE THING AT THE
HEALTH FAIR THAT ALLOWS YOU TO
PARTICIPATE IN THESE KINDS OF
THINGS.
AND MANY OF OUR PATIENTS WHO
PARTICIPATE IN THESE STUDIES,
THEY'RE THE ONES WHO ARE
MOTIVATING THEIR CLINICIANS TO
ENGAGE WITH THIS PROCESS.
MORE THAN THE PHYSICIANS.
SO I THINK -- BUT I THINK YOU
PROBABLY HAVE A LOT TO SAY ABOUT
HOW EHRs CAN HELP DO THAT.
>> I THINK -- YOU KNOW, BACK TO
THIS, THE MEDICAL EDUCATION PART
TOO, I THINK PROBABLY MEDICAL
EDUCATION HAS ALREADY SHIFTED
FROM TRYING TO TEACH YOU
EVERYTHING YOU NEED TO KNOW TO
HOW TO LEARN, AND THE
FOUNDATIONS OF WHAT THE PROCESS
SHOULD BE.
AND I THINK WE PROBABLY NEED TO
CONTINUE TO EVOLVE WHAT MEDICAL
EDUCATION SHOULD BE ABOUT, AND
HOW WE CREATE THE RIGHT KIND OF
TEAM-BASED NAVIGATION AND
THOUGHTFULNESS ABOUT
INFORMATION-FINDING AND
MANAGEMENT OF CARE, CONTINUE TO,
BUT YOU KNOW, FROM THE
IMPLEMENTATION SIDE, I DID ALL
THE WORK ON SOME OF THE
PHARMACOGENETIC PIECE ESPECIALLY
WHEN I WAS AT VANDERBILT, AND A
PHYSICIAN CAN'T PROCESS AND
ACCURATELY ACT ON, YOU KNOW, TWO
C19 "*2" AND THUS I SHOULD NOT
DO DRUG X AND I SHOULD DO DRUG
Y, VERSUS STAR 1, WHICH IS
NORMAL, STAR 17 WHICH IS GOING
TO WORK EVEN BETTER.
THAT'S NOT GOING TO BE PART OF
THEIR LEX COP.
LEXICON.
WE HAVE A HARD ENOUGH TIME
GETTING THEM FOR RENAL DOSING
AND WE ALL UNDERSTAND RENAL
DOSING.
YOU HAVE TO HAVE THE COMPUTER
SYSTEM INTERCEPT THOSE ORDERS
AND AUTOMATICALLY DO WHAT'S
NECESSARY IN A VERY SEAM LES ONE
CLICK KIND OF WAY.
AND YOU DO SEE IF YOU MAKE IT
SIMPLE LAKE THAT, PEOPLE FOLLOW
IT.
IT'S REALLY INTERESTING, WE
FOUND THAT PEOPLE THAT HAD
BASICALLY -- IF YOU GO OVER THAT
PARTICULAR EXAMPLE, IF YOU HAVE
TWO VARIANTS VERSUS ONE, YOU
WERE LIKE -- THE PHYSICIANS WERE
TWICE AS LIKELY TO DO THE
GENETIC-GUIDED CARE THAN IF THEY
HAD ONE VARIANT.
THEY DIDN'T REALLY UNDERSTAND
ALL THE GENETICS BEHIND IT, BUT
THEY SORT OF HAD SOME CONCEPT
AND SOME OF THEM CLICKED THE
LINK WE HAVE, THE NEXT TIME THEY
COME TO THE DATA AND THEY COME
TO PRESCRIBING FOR A PATIENT,
THEY REALIZE, YES, I CAN DO THIS
GENETIC THING, AND IT'S NOT THAT
HARD.
IF YOU KIND OF FACILITATE THE
PROCESS.
SO I THINK OUR EHRs HAVE TO
COME AND ASSIST AND I THINK
THERE'S LOTS OF OPPORTUNITIES
FOR THAT.
THAT IS TO THE ARTIFICIAL
INTELLIGENCE PIECE IN THE
FUTURE, I THINK THAT'S A MODEL
FOR HOW IT CAN WORK, IN AN
EXPLAINER -- ONE OF THE THINGS
WE DID ACTUALLY IS CAN YOU
PRESENT TO THE PHYSICIAN AS
THEY'RE ORDERING BOTH YOUR
RECOMMENDATION AND IF THERE'S
UNCERTAINTY AROUND IT.
SO WE DID SOME WORK ON LIKE SH
SHOWING WHAT'S KIND OF THE
CONFIDENCE LEVEL ABOUT HOW MUCH
THIS MATTERS?
TBIZS PHYSICIANS CAN QUICKLY ACN
THAT INFORMATION, IT SEEMS.
>> AN IN-PERSON QUESTION, DAN.
>> A PERSON, WOW.
>> THANK YOU SO MUCH FOR THE
WONDERFUL PRESENTATIONS, AND
MISS COAL MAN, THANK YOU VERY UU
MISS COLEMAN THANK YOU FOR YOUR
PERSPECTIVE.
BASED ON THE MOTIVATION BEHIND
THE ALL-OF-US SPHU DI, WHETHER
YOU FORESEE OR MIGHT EVEN
ADVOCATE IN THE FUTURE KIND OF
MORE GENETIC, MORE COMPREHENSIVE
GENETIC TESTING AS PART OF
NEWBORN SCREENING, IS THAT
SOMETHING THAT YOU KIND OF
ENVISION MOVING FORWARD BASED ON
WHAT YOU'VE KIND OF EXPERIENCED
WITH THE ALL-OF-US STUDY?
ACTUALLY JUST A SECOND QUESTION
FOR MISS COLEMAN.
I WAS ALSO CURIOUS, HOW DID YOU
ACTUALLY LEARN ABOUT THE STUDY,
AND HOW DO PEOPLE IN GENERAL
LEARN ABOUT WHETHER THEY CAN
PARTICIPATE?
>> WELL, I LEARNED ABOUT THE
STUDY BECAUSE FIRST OF ALL, I
WORK HERE AT NIH, AND I WAS
SITTING AT MY DESK ONE DAY AND
IT JUST CAME ACROSS MY DESK, YOU
KNOW, WE WERE LOOKING FOR 500
AFRICAN AMERICANS TO PARTICIPATE
IN THE STUDY ABOUT THE HEART,
AND RIGHT AWAY, WHEN THEY SAID
THE HEART, BECAUSE OF MY FAMILY
HISTORY, I WANTED TO PARTICI
PARTICIPATE.
AND TRY TO REACH OUT AND GET AS
MANY OTHER TO PARTICIPATE AS I
WAS DOING.
THAT'S HOW I FOUND OUT ABOUT IT.
>> I'LL TAKE A STAB AND THEN LET
LES ADD AND CORRECT WHAT I SAY.
IN TERMS OF SEQUENCING AT THE
NEWBORN LEVEL AND WHAT YOU CAN
GAIN, THE REAL EXPERT HERE IS
NOT -- NEITHER OF US, BUT DIANA
BIANCHI, WHO DOES A LOT OF WORK
IN THIS SPACE.
BUT I'LL JUST SAY THAT AS WE
MOVE INTO THE PEDIATRIC SPHERE
WITH ALL-OF-US, WE'RE THINKING A
LOT ABOUT -- THAT'S NOT IS
MUCH -- LIKE THE PRENATAL, BUT
THAT WOULD BE NEWBORN, WHAT
KINDS OF THINGS WE RETURN TO
PARTICIPANTS AND WHAT THAT MIGHT
LOOK LIKE AS AN EVOLVING STORY
OVER TIME, SO WE THINK IN OUR --
OUR ANSWER, FOR INSTANCE, SOME
OF THESE VARIANTS LIKE BRCA1,
THE BREAST OVARIAN CANCER
SYNDROME VARIANTS, YOU DON'T
NECESSARILY NEED TO TELL SOMEONE
WHEN THEY'RE A BABY.
YOU CAN LET THEM MAKE THAT
CHOICE WHEN THEY'RE 18.
AND SO -- BUT OTHER KINDS OF
THINGS MIGHT BE VERY RELEVANT
WHEN THEY'RE AN INFANT.
SO I'M NOT A PEDIATRICIAN.
BUT WE'RE SORT OF REALLY
THINKING ABOUT WHAT THAT IS.
I THINK WE'LL SEE, THOUGH, IN
GENERAL THERE'S A REAL POWER
TOWARDS HAVING SEQUENCE DATA
AVAILABLE, AND THEN USING IT AS
YOU NEED IT, AND THERE'S SOME
MODELS OUT THERE WHERE YOU GET
THE SEQUENCE AND THEN YOU'RE
PRESCRIBING A NEW DRUG, YOU HAVE
A NEW SET OF CONDITIONS AND YOU
ACTUALLY INTERROGATE IT WHEN YOU
NEED TO FOR THAT QUESTION YOU
HAVE IN MIND.
LIKE THERE'S A SET OF THINGS
MAYBE YOU DO AS A PANEL SO TO
SPEAK AT BIRTH AND ANOTHER PANEL
YOU DO AT 18 AND ANOTHER PANEL
WHEN YOU HAVE ANY HEART
CONDITION.
I THINK THERE COULD BE -- WE'LL
SEE DIFFERENT MODELS THAT EVOLVE
OVER TIME AND THAT'S ONE WAY TO
LOOK AT IT.
LES, WHAT WOULD YOU SAY?
>> I THINK IT'S A GREAT -- IT'S
A HEALTH ECONOMICS QUESTION
REALLY PRIMARILY.
AND OF COURSE THE HEALTH
ECONOMICS PRINCIPLE IS THAT THE
NUMBER OF QUALITY ADJUSTED LIFE
YEARS YOU ADD TO SOMEONE GOES UP
THE YOUNGER YOU IMPLEMENT A
TOOL.
AND SO IF I CAN IMPROVE
SOMEONE'S QUALITY OF LIFE BY A
CERTAIN INCREMENT AND I START
DOING THAT WHEN THEY'RE AN
INFANT, THEN I AM GAINING MUCH
MORE VALUE OUT OF MY HEALTHCARE
INTERVENTION THAN IF YOU START
WHEN YOU'RE 67, OKAY?
YOU'RE NOT GOING TO GET THAT
MUCH OUT OF ME.
SO -- NOT AS MUCH.
AND SO WHAT WE HAVE TO THINK
ABOUT, AND THE DATA ARE VERY
CLEAR, AND JENNIFER PUCK, YOUR
FIRST PRESENTER, IS A VERY
STRONG ADVOCATE OF THAT.
THERE IS NO DOUBT THE DATA ARE
ABSOLUTELY CLEAR THAT IF YOU
PARAGENOME WITH A STANDARD
METABOLIC OR TREX NEWBORN
SCREEN, YOU SIGNIFICANTLY
INCREASE THE YIELD.
THAT HAS BEEN PROVEN BY STUDIES
DONE IN OUR INSTITUTE IN CHILD
HEALTH.
SO WE KNOW THAT THE MARGINAL
BENEFIT IS THERE.
WHAT WE HAVE TO DO IS DEVELOP
THE TOOLS TO DO LIKE WHAT JOSH
WAS SAYING, IS TO THINK ABOUT
STAGING IT AND ROLLING IT OUT
OVER THE PERSON'S LIFETIME
BECAUSE YOU DON'T WANT TO TELL
THEM ABOUT COLON CANCER UNTIL
THEY'RE PROBABLY IN THEIR 20s
OR 30s, AND YOU PROBABLY DON'T
WANT TO TELL THEM ABOUT
ALZHEIMER'S IN THE NURSERY.
IT'S JUST NOT HELPFUL TO STOP
IT.
SO WE HAVE TO THINK ABOUT WAYS
TO BUILD A SYSTEM THAT CAN
RESPOND TO THAT AND DO THAT IN A
SENSIBLE WAY SO THAT THE PATIENT
CAN MAXIMALLY BENEFIT, BECAUSE
IF YOU SEQUENCE ME WHEN I'M 40
YEARS OLD, THAT MEANS THAT YOU
HAVE LOST THE OPPORTUNITY FOR ME
TO BENEFIT FROM THAT IN MY
PRECEDING 40 YEARS.
SO WE HAVE TO THINK ABOUT IT
THAT WAY.
>> ALL RIGHT.
WELL, HERE'S ANOTHER QUESTION
THAT CAME IN OVER THE WIRE.
SO INCOMPLETE PENETRANCE AND
VARIABLE EXPRESSIVITY IMPLY THAT
THERE ARE OTHER SIGNIFICANT
FACTORS AT PLAY ON GENETIC
DISEASES.
SUCH AS, THAT YOU HAVE PRESENTED
HERE TODAY.
WHAT ABOUT THE ROLE OF
EPIGENETIC FACTORS?
>> MODIFIERS.
CERTAINLY OTHER VARIATION IN THE
GENOME CAN AFFECT PENETRANCE AND
EXPRESSIVITY THAT CAN BE CHANGES
IN THE GENOME SEQUENCE.
IT COULD BE CHANGES IN
METHYLATION.
AND IT IS ABSOLUTELY ALSO
ENVIRONMENT.
ENVIRONMENT HAS A HUGE EFFECT.
SO ALL OF THE ABOVE, AND IT
VARIES, THE MIX OF THOSE
ATTRIBUTES THAT DETERMINE
PENETRANCE AND EXPRESSIVITY IS
SLIGHTLY DIFFERENT FOR EVERY
DISORDER, AND WE'RE MAKING
PROGRESS ON THAT IN THE WHOLE
GENOTYPE RISK SCORES ARE
PROBABLY GOING TO BE ONE OF THE
EARLIER IMPLEMENTATIONS I THINK
OF YES NE TICK MODIFIERS.
WOULDN'T YOU SAY, FOR LIKE
CANCER, THINGS LIKE THAT.
SO YOU MAY HAVE A LYNCH SYNDROME
VARIANT THAT SAYS YOU HAVE LYNCH
SYNDROME, BUT NOT EVERYBODY WITH
LYNCH SYNDROME ENDS UP HAVING
CANCER AND PROBABLY THAT, WE CAN
BEGIN TO FINE-TUNE THAT BY
UNDERSTANDING THE OTHER
MODIFIERS.
>> WE HAVE A QUESTION.
>> HI.
THANK YOU.
I'M ACTUALLY GOING OFF OF YOUR
QUESTION AND KIND OF MY
EXPERIENCE IN THE CLINICAL
GENETIC COUNSELING FIELD AS
WELL.
HAVING COUNSELED PATIENTS AND
FAMILIES FROM RECLASSIFICATION
OF RESULTS OVER TIME AND I KNOW
EARLIER WE WERE TALKING A LITTLE
BIT ABOUT TIME SCAPE AND
PERSONHOOD ESSENTIALLY OF HOW
MUCH TIME IT WILL TAKE TO
REANALYZE RESULTS OVER TIME, ONE
THING THAT IN THE CLINIC WE
WOULD ASK FOR RE-ANALYSIS OF
EXOME AND GENOME AND WAIT AGAIN
6 TO 8 WEEKS FOR THOSE RESULTS,
I CAN IMAGINE IF WE START DOING
GENOME EXOME EARLY ON IN LIFE,
AS SYMPTOMS START COMING UP WITH
MORE PHENOTYPIC DATA, THAT WOULD
KIND OF MAKE THAT SESSION GO
AGAIN, BUT ESSENTIALLY IT MORE
OF JUST A OTHER THINGS TO
CONSIDER AS WE START TALKING
ABOUT DOING THESE LARGER TESTS
EARLIER WITHOUT PHENOTYPIC DATA
IS ONCE IT OCCURS, THAT CHANGES
THE ANALYSIS OF THE DATA AS
WELL.
DOES THAT MAKE SENSE, KIND OF?
>> SO IT'S ALL GOING TO BE
DYNAMIC AND I THINK THE
IMPLICATION OF YOUR QUESTION, I
AGREE WITH, WHICH IS THAT
PATIENTS KIND OF DON'T LIKE
THAT.
THEY DON'T LIKE IF YOU SAY ONE
THING ONE TIME AND YOU SAY A
DIFFERENT THING ANOTHER TIME.
HUMANS DON'T THINK THAT'S FUN.
SO -- BUT IT'S REALITY.
AND KNOWLEDGE, THANK GOODNESS
KNOWLEDGE IS GOING TO IMPROVE,
RIGHT?
AND SO OUR CLASSIFICATIONS AND
OUR INTERPRETATIONS ARE GOING TO
CHANGE OVER TIME, AND THAT'S
ANOTHER THAI THING THAT WE NEEDO
PROVIDE PROVIDERS WITH TOOLS TO
SUPPORT THEM IN DOING THAT.
AND ALSO PROBABLY TOOLS LIKE WE
WERE TALKING ABOUT EARLIER,
WHERE IT DOESN'T INVOLVE A
CLINICIAN AND THEY CAN GET --
THEY CAN CHECK IN ON THEIR
GENOME AND GET AN UPDATED
CLASSIFICATION OVER THE COMPUTER
FROM THE COMFORT OF THEIR HOME,
AND SAY WELL MAYBE YOU SHOULD GO
TALK TO SOMEBODY ABOUT THIS.
OR THIS, THAT AND THE OTHERS
CHANGE BUT IT'S PROBABLY NOT
THAT MEANINGFUL.
>> I THINK THAT'S SUCH A GREAT
QUESTION.
I JUST WANT TO ADD A
PERSPECTIVE.
WE'RE SO YOUNG WITH ANALYSIS OF
JEA NOFGENOMES AND CLINICAL
INTERPRETATION.
WE NEED TO THINK OF IT MORE LIKE
GETTING YOUR BMP OR CBC,
CHOLESTEROL PANEL, THESE KINDS
OF THINGS WE TEST CLINICALLY.
JUST BECAUSE WE'RE NOT DRAWING
ANOTHER BLOOD SAMPLE DOESN'T
MEAN THAT WE'RE NOT REANALYZING
THIS.
AND I THINK THAT COMMUNICATION
IS HARD BECAUSE PEOPLE AREN'T
USED TO THINKING -- IT ONLY IF
YOU'RE LIKE DOING SOMETHING NEW
TO ME, BUT THAT'S ESSENTIALLY --
THERE'S SO MANY FACTORS THAT
INTERACT.
IN THE CLINICAL, EVEN BEYOND
LIKE VARIANT INTERPRETATION, THE
CLINICAL FACTORS THAT ARE
CHANGING TO THE PERSON ARE GOING
TO CHANGE RISK PROFILES THAT
MAKE THE RISK SCORE PLUS THESE
OTHER THINGS MATTER WHEN IT
DIDN'T USED TO MATTER.
EVEN IF WE DIDN'T HAVE ANY NEW
SCIENCE.
SO I THINK THE SORT OF DIGITAL
ANALYSIS NEEDS TO BE ALMOST AKIN
TO LIKE THAT BMP YOU GET EVERY
YEAR, OR MORE.
>> SO WHAT'S THE CURRENT STATUS
OF THE PRIVACY ISSUE OF WHEN YOU
IDENTIFY GENETIC MUTANTS AND SO
FORTH?
IN PATIENTS WHETHER THEY'RE
SYMPTOMATIC OR NOT, WHAT IS THE
PRIVACY PARTICULARLY WHEN IT
COMES WHEN THEY APPLY FOR LIFE
INSURANCE AND ALL THAT SORT OF
THING?
>> WELL, OF COURSE WE'VE ALREADY
DISCUSSED GENA, WHICH IS FOR
HEALTH INSURANCE AND EMPLOYMENT,
AND LIFE DISABILITY AND
LONG-TERM CARE, THANK YOU.
I KNEW THERE WAS A THIRD ONE,
ENSURES CAN DISCRIMINATE BASED
ONON GENETIC TEST RESULTS.
IN SOME OF THEM IF YOU APPLY FOR
INSURANCE, THEY MAY ASK YOU IF
YOU HAVE SUCH INFORMATION, AND
IF THEY ASK YOU, YOU ARE
OBLIGATED TO TELL THEM THAT YOU
HAVE BEEN TESTED AND YOU HAVE
THIS, THAT AND THE OTHER RESULT.
SO IT'S A FACTOR.
SO THAT IS AN ISSUE THAT PEOPLE
HAVE TO ADDRESS AND THEY HAVE TO
WEIGH THE PROS AND CONS OF THAT.
THE OVERALL PRIVACY AND
CONFIDENTIALITY, I THINK WE'RE
REALLY -- GENETICS WAS VERY
EXCEPTIONAL 10 OR 15 YEARS AGO.
AND PEOPLE WERE BORDERLINE
TERRIFIED ABOUT PRIVACY AND
CONFIDENTIALITY WITH GENETICS.
I THINK WHAT WE'VE LEARNED IN
THE ENSUING 10 OR 15 YEARS IS
THAT IT'S REALLY PRETTY MUCH THE
SAME AS ALL THE REST OF YOUR
HEALTHCARE INFORMATION THAT YOU
VERY APPROPRIATELY PROBABLY
DON'T WANT EVERYONE TO KNOW
ABOUT.
AND SO IT'S JUST HEALTHCARE
INFORMATION.
AND IT IS NO MORE PREDICTIVE OF
WHEN YOU'RE GOING TO DIE THAN
YOUR CHOLESTEROL.
AND SO WE NEED TO THINK ABOUT IT
LIKE JUST ALL THE OTHER KINDS OF
HEALTH INFORMATION WITH THAT ONE
EXCEPTION OF THOSE THREE KINDS
OF INSURANCE.
>> SO A GENETIC RISK FACTOR IS
COMPARABLE TO AN ENVIRONMENTAL
OR PHYSICAL ACTIVITY RISK FACTOR
AS FAR AS ITS RELATIONSHIP TO
LIFE INSURABILITY AND ALL?
>> IT CAN BE MUCH LESS
SIGNIFICANT.
YOUR BMI IS A MUCH BETTER
PREDICTOR OF HOW LONG YOU'RE
GOING TO LIVE THAN MOST VARIANTS
IN YOUR GENOME.
AND THAT'S NOT PRIVATE.
[LAUGHTER]
>> SO IT'S NOW 5:56 P.M., AND SO
WE'RE COMING UP ON THE END OF
THIS, AND SO FIRST OF ALL, I DO
WANT TO REMIND ANYONE WHO WANTS
TO GET CME CREDIT THAT THE
NUMBER IS 5289, THAT 520 -- THES
52089 THAT YOU WOULD HAVE TO
CALL IN THAT NUMBER.
SECOND THING, I'LL BE -- MAYBE
THE AD MAN FOR CLINSEQ AND
ALL-OF-US IN THE LAST THREE
MINUTES.
HOW WOULD SOMEONE SIGN UP FOR
ALL-OF-US OR CLINSEQ IF THEY
WANTED TO, OR CAN THEY?
>> RIGHT NOW, CLINSEQ IS NOT
OPEN.
BUT ALL-OF-US DEFINITELY IS.
>> WE ARE DEFINITELY OPEN.
JOIN ALL-OF-US.ORG.
AND --
>> THAT'S IT?
>> THAT'S THE URL.
JOINALLOFUS.ORG.
YOU CAN JOIN FROM ANYWHERE.
WE CAN SEND A SALIVA KIT TO YOUR
HOUSE, WE CAN SEND YOU TO A
QUEST LOCATION, WE HAVE ALL IF
STATES AND U.S. TERRITORIES THAT
WE CAN SUPPORT.
YOU HAVE TO BE OVER 18 RIGHT
NOW.
THAT'S THE ONLY REQUIREMENT
TODAY.
>> ALL RIGHT.
SO I THINK WE'RE JUST ABOUT
READY TO CLOSE, AND I WANT TO
THANK THE SPEAKERS, I WANT TO
THANK CARRIE, I WANT TO THANK
MISS COLEMAN, I WANT TO THANK
DR. TURNER FOR BEING SUCH
WONDERFUL PRESENTERS HERE AND
ALL OF THE AUDIENCE HERE IN THE
ROOM AND ONLINE AS WELL.
WE DO HAVE SOME COOKIES HERE,
FOR THOSE WHO ACTUALLY CAME IN
PERSON, THAT ARE JUST CALLING
YOUR NAME IF YOU WANT TO HAVE A
COOKIE BEFORE YOU GO, IF YOU
HAVEN'T BEEN SCARED OFF BY THAT
COMMENT ABOUT THE BMI.
[LAUGHTER]
BUT -- AND COFFEE, THAT'S RIGHT.
I THINK WITH THAT, WE'LL CALL TO
A CLOSE.
THANK YOU ALL VERY MUCH, AND
WE'RE VERY MUCH LOOKING FORWARD
TO NEXT WEEK'S PRESENTATION AS
WELL.
[APPLAUSE]