WELCOME, EVERYONE, TO SESSION
FIVE OF ETHICAL AND REGULATORIES
A ASPECTS OF CLINICAL RESEARCH.
THANKS FOR JOINING US TODAY. IF
QUESTIONS DURING ANY OF THE
LECTURES PLEASE POST THEM IN THE
DISCUSSION BOARD TODAY IS
GENETICS DAY WE'RE GOING TO
STANDARD WITH BEN BERKMAN WHO
WILL GIVE US A GENERAL OVERVIEW.
DR. JULIE SAP IS GOING TO COME
TO THE MIC AFTER THAT TO TALK
ABOUT OUTCOMES RELATED TO
SECONDARY FINDINGS AND THEN WE
WILL ZOOM IN A GUEST DR. KATRINA
FROM UNIVERSITY OF COLORADO. SO
FIRST, WE HAVE BEN BERKMAN, A
FACULTY MEMBER IN THE NIH
DEPARTMENT OF BIOETHICS WHERE
HE'S ALSO JOINTLY AN APPOINTED
IN THE NATIONAL HUMAN GENOME
RESEARCH INSTITUTE SO HE HAS
LOTS OF EXPERTISE TO SHARE WITH
US TODAY. THANK YOU, BEN.
>> BEN: THANKS FOR HAVING ME I'M
EXCITED TO BE HERE. I AM GOING
TO TALK ABOUT THE ETHICS OF
RETURNING GENOMIC RESEARCH
RESULTS THERE'S A LOT OF TOPICS
I COULD TALK ABOUT IN THE AREA
OF GENETICS AND RESEARCH ETHICS
AND HUMAN SUBJECTS RESEARCH BUT
THIS IS THE ONE THAT REALLY HAS
BEEN TAKING THE MOST ATTENTION
OVER THE PAST DECADE AND A HALF
AND SO I THINK IT HAS PARTICULAR
RELEVANCE. I DO SOMETIMES SAY
CONTROVERSIAL THINGS AND WHEN I
DO THEY ARE MY VIEWS AND MY
VIEWS ALONE I DO NOT REPRESENT
ANYONE OF AUTHORITY IN THE
FEDERAL GOVERNMENT. SO LET ME
GIVE YOU SOME HISTORY, SOME
BACKGROUND, JUST SO YOU CAN SEE
WHERE, HOW WE GOT HERE. IT WAS
ABOUT 2008 THAT WE REALLY HAD A
REVOLUTION IN HOW WE DID
SEQUENCING, SEQUENCING
TECHNOLOGY. SOMETIMES PEOPLE
CALL IT NEXT GENERATION
SEQUENCING. THE HUMAN GENOME
PROJECT COST THREE BILLION
DOLLARS AND TOOK A DECADE -- THE
ABILITY TO SEQUENCE A WHOLE
HUMAN GENOME PRETTY QUICKLY IN A
FEW DAYS FOR AT THAT POINT IT
WAS ABOUT $10,000 NOW IT'S
ABOUT -- IT'S VERY, VERY CHEAP
TO DO SEQUENCE DATA AND SO THIS
WAS SORT OF A PARADIGMATIC SHIFT
IN THE WAY WE DO THINGS AND I
COME -- IT'S COMPARED HERE TO
MOORS LAW WHICH IS THE RULE OF
THUMB ABOUT COMPUTING
TECHNOLOGY. THE SUPERCOMPUTERS
WE CARRY AROUND IN OUR POCKETS.
THOSE DOUBLE IN POWER EVERY 18
MONTHS OR SO THINKING ABOUT HOW
MUCH THESE HAVE ADVANCED
SEQUENCING TECHNOLOGY HAS BEEN
THAT MUCH MORE IMPRESSIVE. SO,
IT'S A POWERFUL RESEARCH TOOL.
GENERATES HUGE AMOUNTS OF DATA
ABOUT AN INDIVIDUAL AND REALLY
BEYOND THAT WHICH IS NECESSARY
TO ANSWER MOST SCIENTIFIC
QUESTIONS. AND WHEN YOU'RE
GENERATING HUGE AMOUNTS OF DATA
LIKE THAT, YOU CAN OBVIOUSLY
FIND CLINICAL RELEVANT THINGS IN
SOMEONE'S GENOME. AND SO THE
ETHICAL QUESTION BROADLY STATED
IS WHAT SORT OF ETHICAL
OBLIGATIONS DO WE, AS
RESEARCHERS HAVE WITH REGARDS TO
THESE POTENTIALLY CLINICALLY
RELEVANT FINDINGS. LET ME JUST
GIVE YOU A FEW 2IR78 TERMS THAT
GOING TO THROW AROUND.
SOMETIMES PEOPLE TALK ABOUT
GENOME WIDE ASSOCIATION STUDIES.
GWAS, THAT'S WHEN YOU TAKE
SLIVERS OF SOMETHING. THAT'S
NOT WHAT WE'RE TALKING ABOUT
TODAY. WE'RE TALKING ABOUT
SPELLING OUT THE WHOLE GENOME,
XOM IS JUST A PROTEIN CODING
REGI
REGIONS, THE WHOLE REGION IS THE
WHOLE THING. I WILL TALK ABOUT
INSI DEN TANL OF SECONDARY
FINDINGS
INCIDENTAL FINDINGS CONCERN AN
INDIVIDUAL RESEARCH PARTICIPANT
WITH POTENTIAL HEALTH OR
REPRODUCTIVE IMPORTANCE
DISCOVERED IN THE COURSE OF
DOING THE RESEARCH BUT NOT
RELATED TO THE AIMS OF THE
STUDY. SO THEY'RE SORT OF
THE -- WE STUMBLE UPON THEM KIND
OF FINDING. SECONDARY FINDINGS
ARE RELATED BUT RELATED IN THE
SENSE THAT -- THEY HAVE THESE
IMPORTANT HEALTH IMPLICATIONS
AND NOT RELATED TO THE AIMS OF
THE STUDY BUT WE INTENTIONALLY
LOOK FOR THEM ACTIVELY ANALYZE
THE GENOME LOOKING FOR THEM. I
JUST EXPLAINED THIS PRIMARY
RESULTS JUST FOR REFERENCE ARE
THINGS THAT ARE RELATED TO THE
CONDITION UNDER INVESTIGATION.
SO, I'M GOING TO PRIMARILY BE
TALKING ABOUT SECONDARY FINDINGS
BECAUSE WE MOVED PAST INCIDENTAL
FINDINGS, THINGS THAT ARE
IMPORTANT THAT ARE UNRELATED TO
THE RESEARCH THAT WE'RE DOING.
SO LET ME GIVE YOU A WARMUP IN
CASE, EXCUSE ME, THIS IS
ACTUALLY A REAL CASE THAT I HAD
THAT WAS ONE OF THE FIRST ETHICS
CONSULTS THAT I RAN AS AN
ATTENDING. SO IMAGINE A
CLINICAL RESEARCHER STUDYING THE
GENETIC IDEOLOGY OF BREAST
CANCER IN PATIENTS, PATIENTS
THAT ARE PRESENTING FOR
TREATMENT AT AN ACADEMIC MEDICAL
CENTER THEY'VE GIVEN THEIR
CLINICAL CONCEPT, ALSO GET
RESEARCH SPECIFIC INFORMED
CONCEPT AND THE TEAM IS GOING TO
THEN SEQUENCE THEIR GENETIC
MATERIAL LOOKING FROM SURPLUS
TUMOR TO LOOKING FOR NOVEL BRCA
VARIANTS THAT MIGHT PREDICT
DISEASE. I SHOULD SAY THIS IS
AN UNDERSTUDY OF THE POPULATION,
A MINORITY POPULATION SO THERE
ARE LOTS OF BRCA VARIANTS THAT
HAVE BEEN IDENTIFIED BUT NOT AS
MANY IN THIS GROUP AT LEAST AT
THAT TIME. THEY PROPOSE TO
DE-IDENTIFY THE SEQUENCE DATA
THEY DON'T PLAN TO RETURN ANY
RESULTS. EVEN THOUGH THEY KNOW
THEY'RE LOOKING FOR NOVEL
DISEASE ASSOCIATED VARIANTS THEY
KNOW THAT IN SOME PERCENTAGE OF
THE POPULATION THEY'RE GOING TO
DISCOVER ALREADY ESTABLISHED
BRCA VARIANTS THAT COULD BE
CLINICALLY RELEVANT PARTICULARLY
FOR NEAR TREATMENT DECISIONS,
THESE ARE WOMEN WITH BREAST
CANCER PRESENTING FOR TREATMENT
AND SO KNOWLEDGE ABOUT THEIR
GENETIC VARIANTS CAN BE RELEVANT
SO THE QUESTION IS SHOULD THESE
RESEARCHERS BE ALLOWED TO DESIGN
THE STUDY IN THIS WAY WHERE THEY
FIND THINGS THAT ARE CLINICALLY
IMPORTANT BUT NOT GIVE THEM BACK
TO PATIENT TO THE PARTICIPANTS.
DOES ANYONE IN THE ROOM HAVE ANY
SORT OF INSTINCTS ABOUT THIS?
YEAH. NO, YOU DO?
>> AUDIENCE: I DON'T THINK THEY
SHOULD BE ALLOWED TO DO IT
BECAUSE THEY KNOW IN ADVANCE
THEY MIGHT FIND SOME THINGS.
>> RENU: SO THAT'S SORT OF THE
PUZZLE HERE IS THERE'S SOMETHING
BENEFICIAL THAT THE TEAM COULD
PROVIDE TO THE PARTICIPANTS THAT
COULD BE IMPORTANT FOR THEIR
HEALTH. SO THERE'S THIS BENEVER
SINCE ARGUMENT THAT YOU COULD
MAKE.
THE INVESTIGATOR HOWEVER, CAN
AND IN FACT DID SAY, YOU KNOW,
WE DON'T HAVE ANY GENETIC
COUNSELORS ON STAFF, IT WOULD
COST US A BUNCH OF MONEY TO HAVE
TO VALIDATE THESE FINDINGS WHICH
WE HAVE TO DO BY LAW BEFORE WE
CAN RETURN THEM. IT WOULD SLOW
US DOWN, ACTUALLY DELAY THE TIME
US FINDING THESE NOVEL BRCA
VARIANTS THAT COULD HELP
THOUSANDS OF PEOPLE AND SO
THERE'S THIS BURDEN ON THE
RESEARCH ENTERPRISE KIND OF
ARGUMENT THAT IS OFTEN MADE.
ALSO, HE MADE THE ARGUMENT, YOU
KNOW, OR COULD HAVE MADE THE
ARGUMENT THIS ISN'T MY JOB, I'M
A RESEARCHER, I'M NOT PROVIDING
CLINICAL CARE IF THEY WANT TO
GET TESTING, THEY CAN GO GET
TESTING, WHY SHOULD I HAVE TO
PROVIDE THIS SERVICE? BUT I
THINK WE'VE MOVED TO A POINT
WHERE THOSE KINDS OF ARGUMENTS
THAT THE RESEARCHER WAS MAKING
ARE NO LONGER BEING
WELL-RECEIVED SO LET ME GIVE YOU
SOME EARLY VIEWS. I TALKED
ABOUT THE STUMBLE STRATEGY.
EARLY ON WE WEREN'T ACTIVELY
LOOK FOR THINGS, WE WERE
STUMBLING ACROSS THEM AND DOING
A CASE-BY-CASE ANALYSIS. WERE
WE DOING CASE RESULTS? WE HAVE
TO LOOK AT THE SITUATIONS. IRBS
WERE RELUCTANT TO RETURN RESULTS
BECAUSE THEY WERE WORRIED ABOUT
PSYCHOSOCIAL RISKS BUT TODAY,
AND THIS IS THE TYPE LINE THING
I WANT TO STRESS, GENOMICS IS
YOO CHEAP, IT'S UBIQUITOUS, IT'S
ALL THROUGHOUT OUR RESEARCH
ENTERPRISE.
THERE'S A TON OF PROLIFERATION
OF EXPERTISE AND GUIDANCE.
WE'VE MOVED PAST THIS IDEA THAT
IT'S REALLY DANGEROUS, THAT...
TOWARDS THE IDEA THAT IT'S JUST
MORE INFORMATION. AND TOWARDS
THE IDEA THAT THESE PSYCHOSOCIAL
RISKS THAT WE UNDERSTANDABLY
WERE CONCERNED ABOUT REALLY ON
REALLY ACTUALLY WE'VE DONE TONS
OF RESEARCH AND THE RISKS SEEM
TO BE PRETTY MINIMAL EXCEPT IN
SOME ISOLATED AND VERY DISTINCT
DISCREET CASES. AND SO WE NOW
BROADLY HAVE THIS VIEW THAT
THERE'S SOME OBLIGATION TO LOOK
FOR AND RETURN A DEFINED SET OF
SECONDARY FINDINGS. BUT THAT'S
JUST SORT OF THE TOP LINE -- THE
TOP LINE ARGUMENT, LIKE, WE NEED
TO FLESH OUT THE CONTOURS OF
WHAT THAT OBLIGATION MIGHT LOOK
LIKE. AND ONE OF THE WAYS WE
NEED TO DO THAT IS TO TALK ABOUT
WHY THERE'S A DUTY TO LOOK FOR
GENETIC RESEARCH RESULTS. SO
I'VE ALREADY EXPLAINED IT'S
LARGELY BENEFICENCE BASED
ARGUMENT. TO GIVE PEOPLE BACK
IMPORTANT CLINICAL INFORMATION.
BUT RESEARCH ISN'T CLINICAL
CARE. I THINK THAT'S PROBABLY
SOMETHING YOU GUYS LEARNED IN
THE FIRST SESSION OF THIS
COURSE. THERE ARE POOR
DISTINCTIONS BETWEEN RESEARCH
AND CLINICAL CARE AND SO
RESEARCHERS CAN'T BE ON THE HOOK
TO GIVE THE SAME KINDS OF
SERVICES AS A DOCTOR WOULD. A
DOCTOR HAS TO DO WHAT'S BEST FOR
THE PATIENT IN FRONT OF THEM. A
RESEARCHER HAS OTHER OBLIGATIONS
TO THE RESEARCH ENTERPRISE TO,
THEIR DATA, TO WHATEVER
GENERALIZABLE KNOWLEDGE THEY'RE
TRYING TO PRODUCE. AND SO FROM
MY PERSPECTIVE, THE BEST MODEL
FOR THINKING ABOUT THIS AND FOR
BALANCING THOSE CONSIDERATIONS
IS A DUTY TO RESCUE OR ANCILLARY
CARE KIND OF MODEL, ANCILLARY
CARE FOR THOSE OF YOU WHO DON'T
KNOW IS A ROLE SPECIFIC
OBLIGATION DERIVED FROM THE DUTY
TO RESCUE WHICH IS A GENERAL
OBLIGATION. ANCILLARY CARE IS
THE IDEA THAT RESEARCHERS
SOMETIMES WILL HAVE
PARTICIPANTS, GROUPS OF
PARTICIPANTS IN FRONT OF THEM
WITH KNOWN MEDICAL NEEDS
UNRELATED TO THE RESEARCH
THEY'RE DOING AND THE RESEARCHER
COULD HELP THEM MEET THOSE NEEDS
AT RELATIVELY LOW COST. A
CLASSIC CASE IS IF YOU'RE GOING
TO DO RESEARCH IN A REGION WHERE
MALARIA IS ENDEMIC, MALARIA HAS
NOTHING TO DO WITH THE RESEARCH
YOUR DOING BUT YOU COULD BRING
ALONG A BUNCH OF ANTIMALARIA
MEDICATION AND PROVIDE A SERVICE
TO THEM BUT IT'S UNRELATED TO
RESEARCH. THAT'S THE BEST MODEL
FOR RETURNING GENETIC RESEARCH
RESULTS. AND REALLY THE REASON
I THINK IT'S THE BEST MODEL IS
BECAUSE IT SPECIFIES CONDITIONS
WHEN RESULTS SHOULD BE RETURNED.
I.E. HIGH BENEFICIAL CONDITIONS
WHERE THERE'S LOW BURDEN TO THE
RESEARCH TEAM AND WHERE THERE'S
THE RESEARCH IS IN A SORT OF
UNIQUE OPPORTUNITY TO PROVIDE
THAT BENEFIT. IF SOMEONE ELSE
WOULD BE ABLE TO PROVIDE THE MA
LAIR Y'ALL DRUG LIKE THE
RESEARCHER DOESN'T HAVE TO.
BUT IF THE RESEARCHER IS THE
ONLY ONE WHO COULD THAT HELPS
LIMIT THE CASES IN WHICH
ANCILLARY CARE OBLIGATIONS MIGHT
BE PRODUCED. SO, IT SORT OF
BALANCES THE BENEFIT TO THE
PARTICIPANT AND THE BURDEN TO
THE RESEARCH IN A WAY I FIND
VERY ATTRACTIVE IN THIS CASE BUT
IT'S NOT A PERFECT MODEL. FOR A
NUMBER OF REASONS I COULD GO
INTO BUT THE BIG ONE IS THAT IT
MAKES RETURN OF RESULTS
DEPENDENT ON RESEARCHER
EXPERTISE AND PROTOCOL SPECIFIC
RESOURCES, IF YOU'RE TALKING
ABOUT BURDEN TO THE RESEARCH
TEAM AS ONE OF THE PRIMARY
CONSIDERATIONS, IF THE RESEARCH
TEAM DOESN'T HAVE THE EXPERTISE,
DOESN'T HAVE THE STAFF TO DO
THIS, THEN THEY'D SAID THE
BURDEN IS TOO HIGH, I HAVE NO
OBLIGATION AND OBVIOUSLY IF
WE'RE MAKING RETURN OF RESULTS
DEPENDENT ON THOSE KINDS OF
CONSIDERATIONS THAT CAN LEAD TO
INEFFICIENCIES AND JUSTICE
CONCERNS BECAUSE SIMILARLY
SITUATED PARTICIPANTS WOULD GET
DIFFERENT ACCESS TO INFORMATION
BASED ON THE RESOURCES THE TEAM
HAD WHICH IS NOT IDEAL AND HERE
IS A PAPER WE WROTE ABOUT THIS
IF PEOPLE ARE INTERESTED. SO, I
AND OTHERS HAVE ARGUED THAT WE
SHOULD START THINKING ABOUT AN
INSTITUTIONAL DUTY OF RESCUE
THAT THIS SHOULD FALL NOT TO THE
INDIVIDUAL RESEARCH TEAM BUT TO
THE INSTITUTION SUPPORTING THAT
RESEARCH TEAM. AND THERE ARE A
NUMBER OF REASONS WHY THIS IS
ATTRACTIVE. THE MAIN ONES ARE
THAT SINCE INDIVIDUAL
RESEARCHERS LACK THE RIGHT
EXPERTISE IF THE INSTITUTION IS
PROVIDING THOSE IT CAN
CENTRALIZE THE EXPERTISE IN
THOSE RESOURCES AND DO IT MUCH
MORE EFFICIENTLY AND EFFECTIVELY
AND TAKE THIS OFF THE PLATE OF
THE RESEARCHERS AND LET THEM
FOCUS ON THEIR AIM. IT IS
EFFICIENT AND SOLVES JUSTICE
CONCERNS AND ALLOWS RESEARCHERS
TO DO WHAT THEY'RE AIMING TO DO.
SO, LET ME TRANSITION HERE. I
MAINLY DO RESEARCH BUT SOMETIMES
I HELP DO SOME POLICY THINGS TOO
AND SO THE NIH INTRAMURAL IRB,
ASKED ME AND MY COLLEAGUE SARA
HULL TO CHAIR A WORKING GROUP TO
COME UP WITH A GUIDANCE FOR HOW
OUR INTRAMURAL PROGRAM SHOULD
DEAL WITH THE GENETIC RESULTS
PROGRAM. SO IT'S GOING TO BUILD
ON SOME OF THE ARGUMENTS I JUST
MADE. SO THIS IS OUR SORT OF, I
CAN'T CALL IT A POLICY BECAUSE
THAT'S NOT FAIR BUT THIS IS SORT
OF OUR IRB'S RECOMMENDATIONS OR
GUIDANCE TO EXPECTATIONS FOR
RESEARCHERS. SO, THE FIRST
ARGUMENT IS, IT'S TIME FOR
SPECIFICITY, WE'VE EXISTED IN
THIS SORT OF LIMBO FOR FIFTEEN
YEARS WHERE WE SAID OH, THIS IS
A HARD PROBLEM, HERE'S SOME
INTERESTING IDEAS BUT NO ONE'S
BEEN WILLING TO PUT PEN TO PAPER
AND SAY WE NEED A FIRM
WELL-DEFINED POLICY AND I THINK
THAT'S WRONG. I THINK WE'RE FAR
ENOUGH INTO THIS DEBATE THAT THE
SORT OF WILD WEST LIKE EVERYONE
DOING WHATEVER THEY WANT AND
CASE-BY-CASE ANALYSIS, WE NEED
TO MOVE PAST THAT. I THINK IT'S
GREAT TO DEFER TO IRBS GENERALLY
BUT IN THIS CASE, THE -- WE USED
TO HAVE TWELVE IRBS INTRAMURALLY
IN NIH AND THEY ALL HAD
DIFFERENT WAYS OF DEALING WITH
THIS PROBLEM. NOW WE HAVE A
SINGLE IRB SO THAT'S BETTER BUT
IT WOULD BE IDEAL FOR
INSTITUTIONS OR EVEN THE WHOLE
RESEARCH ENTERPRISE NATIONALLY
OR INTERNATIONALLY TO TRY TO
COME UP TO A CONSISTENT WAY OF
DEALING WITH THIS. LIKE I SAID
GUIDANCE IS VERY HIGH LEVEL AND
SOMETIMES MAKING CONTROVERSIAL
CLAIMS WHICH WE'RE AT THE POINT
WHERE WE NEED TO MAKE THOSE
CLAIMS. THE IRB ASKED US TO
CREATE THIS POLICY. AND WE
ARGUED THAT THERE IS A BROAD BUT
SHALLOW OBLIGATION TO RETURN
GENETIC RESULTS GENERATED IN
RESEARCH, BROAD IN THE SENSE
THAT IT APPLIES TO MOST RESEARCH
PROTOCOLS. BUT SHALLOW IN THE
SENSE THAT THERE'S A VERY HIGH
BAR FOR THE KIND OF INFORMATION
YOU HAVE TO RETURN. THE
AMERICAN COLLEGE OF MEDICAL
GENETICS AND GENOMICS ACMG
CURATES A LIST THAT IT UPDATES
EVERY YEAR OR SO AND RIGHT NOW
HOW MANY? 83 THINGS ON THE LIST
RIGHT NOW SO IT'S A VERY HIGH
BAR FOR WHAT COUNTS AS THE KIND
OF THING THAT NEEDS TO BE
RETURNED. WHICH PROTOCOLS WE
ARGUED THAT THE DEEPER THE
CLINICAL RELATIONSHIP THE
STRONGER THE PRESUMPTION IN
FAVOR OF DISCLOSURE. SO IF YOU
ARE JUST GOING SECONDARY
RESEARCH WITH SAMPLES COLLECTED
ELSEWHERE WHERE YOU HAVE NO
RELATIONSHIP WITH THE
PARTICIPANTS THAT'S NOT A CASE
WHERE YOU NEED TO RETURN
SECONDARY FINDINGS. IF YOU HAVE
A MUCH MORE CLINICAL LIKE
RELATIONSHIP WHERE YOU'RE SEEING
SOMEONE EXTENSIVELY OVER TIME
REPEAT WORKUPS MAYBE OR
PROVIDING STANDARD OF CARE AS
PART OF THE RESEARCH PROTOCOL,
THAT'S THE KIND OF THING THAT
PROBABLY WOULD INVOLVE SECONDARY
FINDINGS. IT'S TRICKIER WHEN
YOU TALK ABOUT MINIMAL
INTERACTIONS LIKE ONE TIME
INTERACTIONS. IT'S JUST A ONE
TIME BLOOD DRAW MAYBE NOT BUT IF
IT'S A ONE TIME OR TWO TIMEX
TENSIVE WORKUP, MAYBE, WE'D LOVE
TO, IT'D BE EASIER BUT AS
FINDINGS EVOLVE IT CAN EXPAND.
A FEW MORE THINGS ABOUT THE IRB
EXPECTATIONS, THIS IS ONLY
PERSPECTIVE, OLDER STUDIES,
STUDIES THAT HAD ALREADY
GENERATED SEQUENCE DATA DIDN'T
NEED TO GO BACK AND ANALYZE AND
RETURN SECONDARY FINDINGS. ONLY
NEW STUDIES OR ONES THAT WERE
BEING SUBSTANTIALLY REVISED.
THIS IS IMPORTANT, THERE'S NO
NEED TO GENERATE GENOMIC DATA
BEYOND THAT NECESSARY TO ANSWER
THE RESEARCH QUESTION SO IF
YOU'RE ONLY INTERESTED IN A
PARTICULAR REGION OF THE GENOME
AND THAT'S ALL YOU NEED TO
GENERATE TO ANSWER YOUR
QUESTIONS, THERE IS NO
OBLIGATION TO DO SECONDARY
ANALYSIS. YOU DON'T HAVE TO GET
A WHOLE GENOME SEQUENCE IF YOU
DON'T NEED A WHOLE GENOME
SEQUENCE AND I THINK A LOT OF
INVESTIGATORS WERE WORRIED THAT
THE IRB WAS GOING TO START
REQUIRING THEM TO GENERATE ALL
SORTS OF DATA THAT WASN'T EVEN
CLOSE TO WHAT THEY NEED BUT
THAT'S DECIDEDLY NOT THE CASE.
AND AS I SAID, WE'RE
DISTINGUISHING BETWEEN STUDIES
BASED ON THE DEPTH OF THE
CLINICAL RELATIONSHIP. SO,
THAT'S SORT OF THE SKETCH OF THE
POLICY. WHAT I WANT TO DO NOW
IS TO RUN THROUGH RELATIVELY
QUICKLY SOME RELATED ETHICAL AND
POLICY ISSUES THAT COME UP. IF
THAT'S THE 10,000 FOOT LEVEL
THESE ARE SOME OF THE MORE
INTERESTING SUBSTANTIVE
PROBLEMS. SOME OF WHICH, WELL,
I HAVE ANSWERS FOR ALL OF THEM.
SOME OF WHICH PEOPLE AGREE WITH
ME. SOME OF WHICH PEOPLE DON'T.
BUT THESE ARE THE KINDS OF SORT
OF STICKY PROBLEMS THAT WE ARE
STILL WORKING THROUGH. OR NEED
TO WORK THROUGH. SO, A FIRST
ONE HAS TO DO WITH SEQUENCING
DATA QUALITY. THIS IS A MORE
TECHNICAL ONE. BUT AS I SAID,
RESEARCHERS ARE ONLY REQUIRED TO
GENERATE THE SEQUENCE DATA
NECESSARY TO ANSWER THEIR
QUESTION. BUT MORE THAN THAT,
IF THE KIND OF QUALITY THEY
NEED, THE SORT OF RESOLUTION OF
THE DATA THAT THEY NEED, IF THE
RESEARCH RESOLUTION IS LOWER
THAN PERHAPS THE CLINICAL
RESOLUTION IF YOU CAN'T USE THE
DATA TO, IF IT'S NOT AMENABLE TO
SECONDARY ANALYSIS, THEN THAT'S
FINE. YOU DON'T HAVE TO PRODUCE
DATA OF HIGHER QUALITY OR OF
DIFFERENT TYPE. TO DO SECONDARY
ANALYSIS. SECOND ISSUE IS
EQUITY WITHIN A PROTOCOL THIS IS
SOMETHING WE TALKED ABOUT A LOT
IN OUR WORKING GROUP SO THERE'S
A BASELINE EXPECTATION THAT'S
SIMILARLY SITUATION,
PARTICIPANTS WILL BE TREATED THE
SAME BUT IT CAN BE ACCEPTABLE TO
TREAT GROUPS WITHIN A PROTOCOL
DIFFERENTLY SO LET'S IMAGINE YOU
HAVE A PROTOCOL WHERE YOU'VE GOT
ONE GROUP OF PEOPLE WHO HAVE AN
ACTIVE DISEASE AND THEY'RE
GETTING LOTS OF CLINICAL CARE
AND BEING SEEN REPEATEDLY AND
YOU HAVE ANOTHER GROUP OF PEOPLE
WHO ARE MAYBE RELATIVES OF
THAT -- OF THOSE PEOPLE WHO
DON'T HAVE DISEASE BUT MAYBE
HAVE SOME GENETIC MARKERS. AND
ARE JUST BEING SEEN ONCE OR
TWICE FOR A SORT OF CONTROL KIND
OF PURPOSES. IT'S OKAY TO TREAT
THOSE TWO GROUPS DIFFERENTLY.
IF WE'RE FOCUSING ON CLINICAL
RELATIONSHIP, IF DIFFERENT
GROUPS WITHIN A PROTOCOL HAVE
DIFFERENT CLINICAL RELATIONSHIPS
WITH THE TEAM, THEN IT'S OKAY TO
GIVE SOME OF THEM SECONDARY
FINDINGS AND OTHERS NOT. AND
PARTICULARLY REMEMBER WE'VE GOT
AN ANCILLARY CARE MODEL WHERE
ONE OF THE CONSIDERATIONS IS
WHETHER THE RESEARCHERS ARE IN A
UNIQUE POSITION TO GIVE
SECONDARY FINDINGS. IF
PARTICIPANTS HAVE ALREADY HAD
CLINICAL SEQUENCING AND ALREADY
HAVE ACCESS TO THIS INFORMATION,
THEN THE RESEARCHERS SHOULDN'T
BE THE ONES TO PROVIDE IT. THEY
ALREADY HAVE GOTTEN IT THROUGH
THE NORMAL COURSE OF THEIR
MEDICAL CARE. AND I'LL TALK
ABOUT THIS AGAIN LATER. THERE'S
SOME END-OF-LIFE SITUATIONS
WHERE THE BENEFICENCE REASONS TO
PROVIDE THIS INFORMATION TO
PEOPLE BECOME LESS SALIENT IF
SOMEONE'S GOING TO DIE
IMMINENTLY THE FACT THAT THEY
HAVE RISK OF SOME SORT OF CANCER
THAT'S GOING TO DEVELOP FIFTEEN
YEARS ISN'T RELEVANT TO THEM.
IT'S OKAY PARTICULARLY IN THE
CANCER GENETICS REALM TO TREAT
PEOPLE DIFFERENTLY FOR THAT
REASON. BUT WHATEVER YOU'RE
GOING TO DO YOU HAVE TO CLEARLY
SET EXPECTATIONS AND EXPLAIN IT
TO PEOPLE IN THE PROT PROTOCOL
AND CONSENT FORM.
REANALYSIS THIS QUESTION COMES
UP A LOT. YOU'VE GOT THE
GENOME, YOU'VE SEQUENCED, YOU DO
THE ANALYSIS, SECONDARY ANALYSIS
YOU FIND OUT THEY DO OR DON'T
HAVE SOMETHING BUT OUR KNOWLEDGE
ABOUT GENETICS IS CONSTANTLY
EVOLVING AND THE QUESTION IS
WHETHER RESEARCHERS HAVE AN
OBLIGATION TO GO BACK TO THE
SEQUENCE DATA THEY'VE ALREADY
OBTAINED AND REANALYZE IT
PERIODICALLY AS THE STATE OF
GENOMIC KNOWLEDGE ADVANCES AND
OUR ARGUMENT WAS NO, IN THE
RESEARCH CONTEXT IT'S NOT
CLINICAL CARE SO ONE TIME
SECONDARY ANALYSIS IS
SUFFICIENT. YOU'RE WELCOME TO
DO MORE IF YOU HAVE THE
RESOURCES AND THE INCLINATION
BUT ONE TIME IS ENOUGH, AGAIN,
CLEARLY EXPLAIN THIS THIS THE
PROTOCOL AND THE CONSENT AND LET
PEOPLE KNOW THAT, SORRY, THAT IF
THEY WANT MORE CLINICAL GENOMIC
TESTING THAT'S AVAILABLE TO THEM
BUT OURZ -- OUTSIDE OF THE
RESEARCH CONTEXT.
NEGATIVE FINDINGS, THE ASMG LIST
IS THE ONE PEOPLE USE MOST OFTEN
AND I DON'T KNOW THE ACT --
EXACT NUMBER RIGHT NOW BUT
ESTIMATES ARE 3-4% OF PEOPLE
WILL HAVE ONE OF THOSE FINDINGS.
IT'S NOT A HUGE NUMBER BUT
SUBSTANTIAL THAT MEANS THAT
97-94% OF PEOPLE AREN'T GOING TO
HAVE A POSITIVE FINDING.
THE QUESTION IS HOW DO YOU
CONVEY THAT NEGATIVE INFORMATION
TO PEOPLE AND WE ARGUED IN OUR
REPORT THAT YOU DON'T NEED TO
GENERATE AND CONVEY A NEGATIVE
FINDINGS REPORT. THIS IS
SOMETHING YOU DO IN CLINICAL
CARE IF YOU HAVE CLINICAL
JEANEGENETIC TESTING AND NOTHINE
BACK YOU'D GET A REPORT SAYING
NOTHING CAME BACK. BUT WE SAID
THAT'S TOO MUCH WORK FOR THE
RESEARCH ENTERPRISE. LIKE WE
DON'T -- WE NEED TO CLEARLY
EXPLAIN TO PEOPLE THAT THEY'RE
ONLY GOING TO BE CONTACTED IF
THEY HAVE A POSITIVE FINDING AND
NOT TO ASSUME THAT THEY'VE GOT A
CLEAN BILL OF HEALTH BUT THAT
THE GOING THROUGH THE EXTRA STEP
OF A NEGATIVE REPORT IS USING
TOO MANY RESOURCES. NOW WITH
NORMATIVE QUESTIONS, WHAT DO YOU
DO WHEN YOU'VE GOT A PROBAND WHO
IS DECEASED BUT THE INFORMATION
IN THE GENOME COULD BE RELEVANT
TO THEIR RELATIVES? AND SO
I'VE -- I HAVE THE PAPER HERE,
YEAH, WE WROTE A PAPER, THE
FORMER FELLOW IF ANY OF YOU
WATCH JEOPARDY, BEN CHAN, HE HAD
A RUN THERE FOR A WHILE THAT GOT
A LOT OF ATTENTION, HE'S THE
FIRST AUTHOR ON THIS PAPER SO WE
ARGUED THAT WHILE OBLIGATIONS TO
RELATIVES HAVE TO BE LESS THAN
THE OBLIGATIONS YOU HAVE TO TO
THE PROBANDS, THERE CAN BE CASE
WHERE IS THE CLINICAL
INFORMATION IS IMPORTANT ENOUGH
THAT YOU'D WANT TO TRY TO GET IT
TO THEM.
AND SO, BUT WE ARGUE THAT THAT'S
A VERY HIGH BAR AND YOU SHOULD
ONLY BE RETURNING FINDINGS WHEN
THE INFORMATION HAS POTENTIAL
DIRECT AND REALLY SUBSTANTIAL
IMPLICATIONS FOR THEIR HEALTH
AND THE DEPTH OF THE
RELATIONSHIP WITH THE PROBAND
AND THEIR FAMILY IS RELEVANT
HERE AS OUR PROTOCOL RESOURCES,
THIS IS NOT AN EXPANSIVE
OBLIGATION. AND REALLY A
REASONABLE EFFORT STANDARD IS
SUFFICIENT BUT YOU SHOULD, YOU
KNOW, DOCUMENT WHAT YOU DID,
THERE'S NO EXPECTATION HERE THAT
YOU'VE GOT TO HIRE A PRIVATE
INVESTIGATOR AND RETURN
INFORMATION TO THEM BUT IF YOU
COULD DO SO EASILY AND IT'S
REALLY IMPORTANT IT'S A GOOD
THING TO DO. ANOTHER BIG
QUESTION THAT WE'VE BEEN
STRUGGLING WITH IS HOW TO THINK
ABOUT SETTINGS THAT HAVE
DIFFERENT STANDARDS OF CARE OR
DIFFERENT ACCESS TO HEALTH CARE
RESOURCES. SO THE QUESTION IS,
IS THERE A DUTY TO RETURN
FINDINGS IN LOW RESOURCE
SETTINGS WHERE BENEFIT WILL BE
SUBSTANTIALLY LESS CERTAIN? SO,
TO RETURN TO THE BREAST CANCER
CASE, IF YOU FOUND OUT THAT
SOMEONE HAD A BRCA VARIANT BUT
LIVE IN A COUNTRY WHERE THERE
ARE NO SURGICAL SUITES THAT CAN
TREAT BREAST CANCER SHOULD YOU
RETURN THIS INFORMATION IN THAT
KIND OF SETTING? CALLED THE
ACTIONABILITY PROBLEM. SO YOU
ONLY WANT TO RETURN THINGS, ONE
OF THE CORE REASONS WE'RE
RETURNING THINGS WHERE WE HAVE
THE FEEL, THIS OBLIGATION SO
PEOPLE CAN IMPROVE THEIR HEALTH.
BUT IF THEY CAN'T BECAUSE THEY
CAN'T ACCESS RESOURCES WHAT DO
YOU DO?
SOME PEOPLE HAVE ARGUED THAT YOU
SHOULD ONLY RETURN THINGS WHEN
THEY'RE ACTIONABLE IN THE
COMMUNITY WHERE THE PERSON
LIVES. I DISAGREE. -- WE WROTE
ANOTHER PAPER ABOUT THIS.
BUT I THINK THE ARGUMENT IS WE
SHOULD DEFAULT TO RETURNING
RESEARCH RESULTS GENETIC
RESEARCH RESULTS IN THESE
SETTINGS FOR A NUMBER OF REASONS
I'M HAPPY TO GET INTO IF PEOPLE
ARE INTERESTED BUT THERE ARE A
COUPLE OF CAVEATS, A COUPLE OF
REASONS THAT THIS CASE IS
DIFFERENT, FIRST BECAUSE,
COMMUNITIES CULTURES, HAVE
DIFFERENT RELATIONSHIPS WITH
GENETIC INFORMATION. IT'S
APPROPRIATE TO CONSULT WITH
THOSE XHTSZ COMMUNITIES BEFORE
YOU START RETURNING THE FINDINGS
TO SEE IF THESE ARE ACTUALLY
WANTED.
AND TWO, I WILL TALK ABOUT THE
RIGHT NOT TO KNOW IN A MINUTE
BUT I WILL TIP MY HAND I'M A
SKEPTIC. THIS IS ONE CASE WHERE
I THINK IT'S IMPORTANT TO ASK
PEOPLE, INDIVIDUALS, WHETHER
THEY WANT TO KNOW THIS
INFORMATION OR NOT BECAUSE IF
YOU CAN'T DO ANYTHING ABOUT IT,
THAT IS A CASE WHERE SOMEONE
MIGHT OR MIGHT NOT WANT TO KNOW.
ALL RIGHT. A FEW MORE. LEGACY
SAMPLES. THIS IS WHAT I CALL
THE FREEZER PROBLEM. SO A LOT
OF PROTOCOLS HAVE THESE SAMPLES
THAT WERE COLLECTED DECADES AGO
WITH SORT OF MINIMAL INFORMED
CONSENT BEFORE EVEN GENOMIC
SEQUENCING WAS A POSSIBILITY AND
THEN THEY WANT TO GO BACK TO
THESE SAMPLES. SOMETIMES
THEY'RE VERY VALUABLE
COLLECTIONS AND SEQUENCE THEM
NOW THAT THE TECHNOLOGY EXISTS
AND THE QUESTION IS WHAT DO YOU
DO ABOUT GENOMIC FINDINGS WHEN
YOU SEQUENCE THEM? OFTENTIMES
THEY HAVE GENERAL LANGUAGE IN
THE CONSENT LIKE WE WANT TO DO
GENETIC RESEARCH THAT DOESN'T
MENTION ANYTHING ABOUT
SEQUENCING OR SECONDARY FINDINGS
OR ANYTHING. IS IT ETHICAL TO
ALLOW RESEARCHERS TO
RECONSEQUENCE THESE? I HAVE A
LOT OF THOUGHTS ON THIS BUT
GENERALLY MY VIEW IS THAT REALLY
WE SHOULD ONLY BE THINKING
PROSPECTIVELY THAT IT'S FINE FOR
PEOPLE TO USE THESE SAMPLES AND
SEQUENCE THEM BUT THAT WE
SHOULDN'T BE RETURNING
INCIDENTAL FINDINGS IN THESE
CASES A LOT OF TIMES THESE
PEOPLE ARE DECEASED OR
IMPOSSIBLE TO FIND OR THEY'D BE
SHOCKED TO LEARN THAT THESE
THINGS WERE BEING DONE AND SO I
THINK IT'S OKAY IF YOU'VE GOT
CONSENT TO USE THESE SAMPLES
IT'S FINE TO SEQUENCE THEM BUT
THAT WE DON'T NEED TO BE
RETURNING SECONDARY FINDINGS IN
THESE KINDS OF CASES. THERE
MIGHT BE SOME EXCEPTIONS TO THAT
RULE WHERE IT'S A SORT OF VERY
DEFINED SMALL SET OF SAMPLES AND
WE COULD RECONTACT THEM BUT
GENERALLY UNLESS THAT'S THE CASE
I DON'T THINK WE HAVE TO RETURN
FINDINGS. THIS IS ANOTHER
TECHNICAL ONE THAT I ONLY
INCLUDE BECAUSE I AM -- I'D GET
A QUESTION ABOUT IT IF I DIDN'T.
CLEA THE CLINICAL LABORATORY
IMPROVEMENT ACT GOVERNS HOW THE
SORT OF QUALITY CONTROL IN LABS.
AND THERE'S THIS RULE UNDER CLEA
THAT YOU CAN'T TURN INFORMATION
THAT WILL BE USED FOR CLINICAL
DECISION-MAKING WITHOUT HAVING
VALIDATED IT IN A CLIA COMPLIANT
MANNER AND SO RESEARCHERS WHO
DON'T LIVE IN THE CLINICAL
TESTING SPACE SAY DO I HAVE TO
DO THAT?
AND ANSWER IS YES, I HAVE TALKED
TO VARIOUS LAWYERS IN OUR
INSTITUTION, IN HHS, THAT'S
ACTUALLY CMS, THAT GOVERNORS
CLIA AND THE ANSWER IS, YES, THE
LAW DOESN'T HAVE ANY WIGGLE ROOM
FOR RESEARCHERS IF YOU GIVE THEM
SOMETHING BACK THAT THEY COULD
PLAUSIBLY USE TO MAKE DECISIONS
YOU HAVE TO VALIDATE IT BUT THIS
IS GETTING EASIER AND EASIER AND
THIS SHOULDN'T BE A BARRIER,
IT'S NOT THAT EXPENSIVE AND IF
YOU PLAN AHEAD THE BIG THING IS
YOU NEED A SECOND SAMPLE TO SAL
VALIDATE SO IF YOU HAVE A SECOND
SAMPLE YOU CAN HAVE IT IN YOUR
BACK POCKET TO GO VALIDATE
BEFORE YOU RETURN RESULTS TO
PARTICIPANTS. PEDIATRIC
FINDINGS, THERE'S A WHOLE I'VE
WRITTEN A LOT ABOUT THIS. I
DON'T MEAN TO TO GET INTO TOO
MUCH DETAIL HERE BUT THERE'S
SOME REALLY INTERESTING POINTS,
THERE'S A DEBATE ABOUT THE RIGHT
TO AN OPEN FUTURE IF YOU'RE
DOING PEDIATRIC GENETIC
RESEARCH. THE IDEA IS THE RIGHT
TO AN OPEN FUTURE IS AN ARGUMENT
THAT WE SHOULD TRY TO PRESERVE A
CHILD'S ABILITY TO DECIDE FOR
THEMSELVES WHEN THEY'RE AN ADULT
AS MUCH AS POSSIBLE AND
SHOULDN'T BE GIVING THEM GENETIC
INFORMATION THAT WHEN THEY'RE 25
THEY MIGHT NOT WANT TO KNOW. I
THINK THERE'S SORT OF EVOLVING
VIEWS ON THIS. PEOPLE ARE, FOR
THE FIRST, I DON'T KNOW, FIFTEEN
YEARS OF THE GENETIC RESEARCH
ERA THIS WAS SORT OF DOGMA. BUT
NOW THE SECOND ARTICLE IS A SORT
OF PROFESSIONAL SOCIETY GUIDANCE
DOCUMENT I WORKED ON WHERE WE
STARTED WALKING AWAY FROM THE
IDEA THAT THIS RIGHT TO AN OPEN
FUTURE IS OF SUCH PARAMOUNT
IMPORTANCE AND THAT THERE CAN BE
CONDITIONS WHERE IT'S OKAY TO
GIVE FAMILIES ACCESS TO
INFORMATION ABOUT THEIR KID THAT
WOULDN'T BE RELEVANT UNTIL THEIR
ADULT YEARS. RE-CONSENT AT THE
AGE OF MAJORITY IS ANOTHER BIG
ONE YOU'VE SEQUENCED SOMEONE'S
GENOME WHEN THEY'RE A KID, THEY
TURN 18, NOW WHAT DO YOU DO? DO
YOU HAVE TO GO BACK TO THEM TO
GET RE-CONSENT TO CONTINUE USING
THEIR SAMPLES? TO RETURN
RESULTS? SOME COLLEAGUES AND I
HAVE ARGUED THAT YOU DON'T HAVE
TO DO THAT THIS IS ONE WHERE
WE'RE VERY MUCH IN THE MINORITY.
GENERALLY THE POLICY IS YOU GO
TO IRB AND THEY ASK FOR -- YOU
ASK THEM FOR AN EXCEPTION SO
FUNCTIONALLY THAT THE CASE IS
THAT YOU DON'T HAVE TO GET
RE-CONSENT BUT WE DON'T FOR
VARIOUS REASONS WE DON'T THINK
YOU EVEN NEED TO TAKE THAT STEP.
AND THIS ATTRIBUTED PARENT
DAMAGE AND THIS COMES UP
SURPRISINGLY FREQUENTLY.
THIS IS ANOTHER EARLIER CASE I
HAD IN MY ETHICS CONSULTATION
CAREER AND YOU'RE DOING TESTING
AND COMPARING GENOMES OF THE KID
AND THEIR PARENTS AND IT'S
OFTENTIMES YOU FIND THAT THE
PARENTS AREN'T GENETICALLY
RELATED TO THE KID OR THE FATHER
ISN'T RELATED TO THE KID. AND
WHAT DO YOU DO? DO YOU DISCLOSE
THAT INFORMATION TO PEOPLE?
I'VE ARGUED, NO, YOU DON'T. BUT
THIS IS ONE WHERE I THINK
REASONABLE PEOPLE COULD
DISAGREE. I'VE GOT ABOUT TEN
MINUTES, SO I AM GOING TO MOVE
ONTO THE LAST BIG POINT THAT I'M
GOING TO SET UP AND THEN LEAVE
TIME FOR QUESTIONS IF PEOPLE
WANT TO DISCUSS IT. THIS IS
SOMETHING I'VE LOOKED AT QUITE A
BIT AND REALLY A TOPIC THAT WAS
VERY CONTROVERSIAL AND SORT
OF -- THE VEHEMENCE THAT PEOPLE
THOUGHT ABOUT THIS TOPIC IS
SURPRISING TO ME WHICH IS WHY I
HAVE CHOSEN TO DIVE INTO IT AND
REALLY EXPLORE IT IN A LOT OF
DEPTH. LET ME GIVE YOU A CASE
TO SET THIS UP. SO IMAGINE P IS
HAVING HER GENOME SEQUENCED.
COULD BE RESEARCH, COULD BE
CLINICAL CARE, THIS IS RESEARCH
ETHICS CLASS SO FOR RESEARCH
PURPOSES, AND DURING THE
INFORMED CONSENT PROCESS THERE'S
A CHECK BOX IT SAYS WE MIGHT
FIND IMPORTANT MEDICAL
INFORMATION ONCE SEQUENCING YOUR
GENOME WOULD YOU WANT TO KNOW IT
YES OR NO. SHE SAYS NO. BUT
DURING THEIR ANALYSIS THE
RESEARCHERS FIND EVIDENCE OF
HIGH GENETIC RISK FOR NON POLYP
FORMING COLON CANCER WHICH IS
THE KIND OF THING IF YOU DON'T
CATCH IT IT'S PRETTY UNIFORMLY
FATAL BUT IF YOU DO KNOW YOU
HAVE GENETIC RISK THERE ARE
ENHANCED SCREENING TECHNIQUES
THAT YOU CAN USE AND YOU CAN
CATCH IT EARLY AND IT'S CURABLE
AND SO LIKE KNOWING THAT YOU
HAVE THIS GENETIC RISK IS REALLY
IMPORTANT. IT'S LITERALLY A
MATTER OF LIFE AND DEATH. AND
SO THE QUESTION IS, SHE CHECKED
THE NO BOX, SHE SAID SHE DIDN'T
WANT THIS KIND OF SECONDARY
INFORMATION. SHOULD THEY
DISCLOSE THE FINDING? SHOULD
THE RESEARCHERS DISCLOSE THE
FINDING EVEN THOUGH SHE SAID NO?
THIS IS THE CLASSIC CASE IN THE
RIGHT NOT TO KNOW. LET ME GIVE
A LITTLE BIT OF SETUP AND THEN
GIVE YOUR THOUGHTS ON THAT KIND
OF SITUATION EARLY ON IN THE
GENOMIC FINDINGS RESEARCH
DEBATE, THIS WAS ACTUALLY AN
AREA WHERE WE THOUGHT WE HAD
CONSENSUS, WE SHOULD ONLY -- THE
IDEA IS WE SHOULD ONLY BE
RETURNING FINDINGS WHEN THEY'RE
DESIRED BY THE PARTICIPANT,
THERE'S AN ONLY, SUCH -- TO THE
EXTENT THERE'S AN OBLIGATION
ONLY TO OFFER INDIVIDUAL
FINDINGS TO RESEARCH SUBJECTS
AND LET THEM KNOW THAT THEY CAN
SAY NO, SOLICIT THEIR PREFERENCE
AND ONLY GIVE IT TO THEM WHEN
THERE'S SORT OF OPT IN WHEN
SOMEONE HAS POSITIVELY INDICATED
THAT THEY WANT THESE KINDS OF
FINDINGS. THEN THE ACMG
PRODUCED THESE RECOMMENDATIONS
ALTHOUGH CONTROVERSIAL WHERE
THEY PRODUCED THIS LIST AND I
SHOULD STRESS THE LIST THAT I
REFERENCED EARLIER, THESE ARE
ALL THINGS THAT ARE ASSOCIATED
WITH SERIOUS DISEASE WHERE
THERE'S SOMETHING YOU CAN DO
ABOUT IT AND WHERE THE EVIDENCE
BASE IS RELATIVELY STRONG. SO
NOT HUNTINGTON'S DISEASE, NOT
ALZHEIMER'S WHERE THERE'S
NOTHING YOU CAN DO ABOUT IT.
BUT IN THESE RECOMMENDATIONS
THEY CONTROVERSIALLY ARGUED THAT
THIS SHOULD JUST BE THE DEFAULT.
THAT WE SHOULD BE RETURNING
THESE THINGS TO PEOPLE AND NOT
BE ASKING ABOUT THEIR
PREFERENCES. THE WORLD
EXPLODED. IT WAS LIKE EVERY
MEETING I WENT TO, EVERY
CONFERENCE I WENT TO FOR THREE
YEARS PEOPLE DEVOLVED INTO
SHOUTING MATCHES AND TEARS, IT
WAS VERY DRAMATIC. EVENTUALLY
THE ACMG WALKED BACK THEIR
RECOMMENDATIONS, SORT OF WALKED
BACK THEIR RECOMMENDATIONS AND
SO THERE'S THIS DEBATE OF THE
RIGHT NOT TO KNOW PROPONENTS
ARGUE IF YOU RETURN INFORMATION
WITHOUT PEOPLE'S BUY IN, WITHOUT
THEIR PERMISSION IT'S A
VIOLATION OF THEIR AUTONOMY AND
THEY WOULD SAY TO THAT FIRST
CASE THAT I STARTED WITH THAT
AUTONOMY CONCERNS SHOULD TAKE
PRIORITY OVER BENEFICENCE. THAT
PERSON SAID NO, HER COLON CANCER
RISK WE SHOULDN'T RETURN THAT TO
HER. I'M A SKEPTIC I THINK I
SAID THAT ALREADY. I CAN READ
MY WHOLE ARGUMENT IF YOU WANT.
THE EARLY LITERATURE IS MUCH,
MUCH LESS STRIDENT ABOUT THE
STRENGTH OF SOMEONE'S RIGHT NOT
TO KNOW. PEOPLE MAKE ARGUMENTS
ABOUT THE RIGHT NO -- THE
CONSTITUTIONALLY PROTECTED RIGHT
TO REFUSE TREATMENT. TO REFUSE
INFORMATION. I THINK THAT'S
WRONG FOR BOTH LEGAL AND
CONCEPTUAL REASONS. I GOT SOME
EMPIRICAL DATA THAT SHOW HOW
EASY IT IS TO SHIFT PEOPLE'S
PREFERENCES ABOUT THIS.
DEPENDING ON HOW YOU WORD THINGS
I THINK THERE ARE CONCEPTS LIKE
MORAL DISTRESS AND GENETIC
EXCEPTIONALISM THAT WEIGH IN
FAVOR OF BEING SKEPTICAL ABOUT
THE RIGHT NOT TO KNOW AND FOR A
VARIETY OF REASONS I THINK IF WE
REALLY ENSHRINED AS A POLICY
THIS STRONG CONCEPTION OF THE
RIGHT NOT TO KNOW WE DO MORE
HARM THAN GOOD THE MAIN ARGUMENT
I WOULD MAKE IS FROM SOME
DIDN'T -- AN EMPIRICAL PROJECT
THEY DID A FEW YEARS AGO.
WHERE WE ASKED PEOPLE WHO SAID
NO WHO CHECKED THE NO BOX THAT
WE WENT BACK TO THEM JUST TO
GIVE THEM A LITTLE MORE
INFORMATION AND SAID PLEASE MAKE
ANOTHER DECISION AND ABOUT HALF
OF THEM SAID NO A SECOND TIME.
WE CALLED THEM STRONG REFUSERS.
BUT ABOUT HALF OF THEM SAID YES.
AND WE CALLED THEM WEAK REFUSERS
SO THEY SAID NO INITIALLY AND
THEN SAID YES LATER. AND THE
BIG THING IS THAT THOSE STRONG
REFUSERS REMEMBERED WHAT THEY
SAID BEFORE. THEY REMEMBERED
THAT THEY SAID NO AND THEY SAID
NO A SECOND TIME BUT THE WEAK
REFUSERS, 75% OF THEM
MISREMEMBERED. THEY CLEARLY
MADE A MISTAKE AND THOUGHT THEY
HAD AFREEWAYED TO RECEIVE
SECONDARY FINDINGS.
IF YOU ENSHRINE THIS IDEA THAT
WE HAVE TO ASK EVERYONE FOR
THEIR PREFERENCES ABOUT WHETHER
OR NOT THEY WANT TO KNOW
SECONDARY FINDINGS, SOME OF THEM
ARE GOING TO MAKE A MISTAKE AND
THIS RAISES FOR ME AT LEAST A
NORMATIVE QUESTION OF WHETHER WE
SHOULD CONSTRUCT RIGHT NOT TO
KNOW POLICY TO ACCOMMODATE THIS
TINY GROUP OF PEOPLE WHO ARE
REFUSERS AND DON'T WANT TO KNOW
GIVEN THE SIGNIFICANT HARMS TO
PATIENTS OR PARTICIPANTS THAT
MIGHT MAKE A MISTAKE AND
MISREPORT THEIR PREFERENCES ON A
CONSENT FORM OR WHOSE INTERESTS
ARE MORE IMPORTANT THE WEAK OR
THE STRONG REFUSERS, THE PEOPLE
WHO REALLY DON'T WANT TO KNOW,
IMPOSING INFORMATION ON THEM
THAT DON'T WANT TO KNOW OR THOSE
WHO DO WANT TO KNOW THIS
POTENTIALLY LIFE SAVING
INFORMATION BUT JUST HAVE
CHECKED THE WRONG BOX. I'D
ARGUE THAT WE SHOULD PROTECT THE
WEAK REFUSERS BUT AGAIN
REASONABLE PEOPLE CAN DISAGREE
AND THIS IS, SORRY, I HAVE BEEN
PLAGUE AROUND WITH THIS IDEA WE
WROTE A COUPLE FELLOWS AND I
WROTE A LAW REVIEW ARTICLE A
COUPLE YEARS AGO ABOUT CHOICE
MASKING NUDGES. PEOPLE CAN HAVE
A CHOICE BUT WE CAN HIDE THAT
CHOICE FROM THEM. SO THEY'D
HAVE TO RAISE THEIR HAND. THE
STRONG REFUSERS WOULD HAVE TO
SAY YOU KNOW, I DON'T WANT TO
KNOW THIS INFORMATION. THERE'D
BE NO QUESTION, THERE'D BE NO
INFORMATION IN THE CONSENT FORM
EXCEPT FOR INFORMATION ABOUT HOW
TO CONTACT PEOPLE WITH
QUESTIONS. THERE'D BE NO
PROMPTING. I AM ATTRACTED TO
THIS IDEA I ACKNOWLEDGE IN THE
RESEARCH ETHICS AND BIOETHICS
COMMUNITY THE IDEA OF CHOICE
MASKING NUDGES COULD BE
CONTROVERSIAL DEPENDING ON THE
CONTEXT BUT I THINK IT'S AN
INTERESTING CONCEPT TO PLAY
WITH. ALL RIGHT. I AM NEARLY
OUT OF TIME. LET ME JUST GIVE
YOU MY BOTTOM LINE, WELL, LET ME
GIVE YOU MY E-MAIL AND THEN
WE'LL, SORRY, I PUSHED THE WRONG
BUTTON. I THINK THAT WE
SHOULDN'T EXPLICITLY SOLICIT
PREFERENCES ABOUT CONSENT ABOUT
THE RIGHT NOT TO KNOW IF PEOPLE
RAISE THEIR HAND AND SAY I DON'T
WANT TO KNOW WE CAN HONOR THAT
AND THAT'S THE EXTENT OF WHAT WE
NEED TO SOLICIT WITH THE
EXCEPTION THAT WHEN THERE ARE
PEOPLE FOR WHOM THE GENETIC
FINDINGS MIGHT NOT BE CLINICALLY
ACTIONABLE, IT'S OKAY? THOSE
CASES TO SOLICIT PREFERENCES BUT
THAT'S AN EXCEPTION I THINK TO
MY GENERAL RULE. SO I THINK I'M
RIGHT ON TIME I THINK WE HAVE
TEN MINUTES AND I WOULD LOVE ALL
OF YOUR QUESTIONS. THANK YOU.
>> AUDIENCE: (APPLAUSE).
>> THANK YOU, BEN AND AS USUAL,
FOLKS CAN GO TO THE MICS AND
THOSE OF YOU WHO ARE WATCHING
ONLINE, FEEL FREE TO POST
QUESTIONS IN THE DISCUSSION
BOARD, LOOKS LIKE DANIEL IS
GETTING UP FOR A QUESTION.
>> HEY, BEN MY QUESTION IS THE
DUTY TO RES CUES. MAYBE IT'S
GONE STRONGER AS GENOMICS HAS
BECOME LESS DANGEROUS OR CHEAPER
OR MORE UBIQUITOUS THE BAR FOR
WHAT TO -- WHAT SECONDARY
RESULTS TO RETURN HAS GOTTEN
LOWER AS IT'S BECOME EASIER TO,
LIKE, DO ALL THIS GENOMICS. SO
I'M WONDERING, LIKE, IF SORT OF
TRENDS CONTINUE AND GENOMICS
BECOMES SO CHEAP AND UBIQUITOUS
THAT THE DUTY OF RESCUE BECOMES
SO STRONG THAT WE HAVE A DUTY TO
RETURN RESULTS THAT ARE LESS
CLINICALLY RELEVANT OR, LIKE THE
THREAT IS LESS DANGEROUS LIKE,
DISEASES THAT AREN'T QUITE AS
HARMFUL EVEN TO THE PINT THAT
FOR RESULTS THAT ARE NOT
CLINICALLY RELEVANT AT ALL FF
FUTURE BALDNESS OR RELATION TO
PARENTS, THAT SORT OF THING.
>> RIGHT, SO THAT'S A GOOD
QUESTION. AND I HAVE WRITTEN A
PAPER ABOUT THIS GENERALLY SO
ONE OF THE TRICKY THINGS IS THAT
WE'RE STILL SORT OF IN THE EARLY
PHASES OF THE GENOMIC ERA. AND
IT HASN'T FULLY BEEN INTEGRATED
INTO CLINICAL CARE YET. SO
EARLY IN THE GENOMIC ERA IT WAS
REALLY HARD TO GENERATE THESE
FINDINGS IT WAS HARD TO RETURN
THEM AND SO THE IMPOSING THE
DUTY TO RESCUE IN THOSE CASES
WAS A PRETTY BIG ASK WE'RE NOW
IN THIS MOMENT WHERE IT'S
GETTING EASIER AND EASIER. THE
VALUE OF THESE FINDINGS IS
INCREASING EVERYDAY. BUT YET
WE'RE NOT STILL FULLY
INCORPORATED INTO CLINICAL CARE
AND SO IN THIS MOMENT, I THINK
THE DUTY TO RESCUE IS GOING TO
BE HIGHEST BECAUSE RESEARCHERS
HAVE MORE OF A UNIQUE
OPPORTUNITY. PEOPLE AREN'T
GETTING THIS TESTING IN CLINICAL
CARE. BUT THEY SOMETIMES ARE
GETTING IT IN RESEARCH AND SO
THERE'S MORE OF A UNIQUE
OPPORTUNITY TO HELP PEOPLE.
IMAGINE A WORLD TEN, TWENTY
YEARS FROM NOW WHERE EVERYONE
GETS SEQUENCED AT BIRTH AND YOUR
SEQUENCE DATA IS JUST
INCORPORATED INTO YOUR MEDICAL
RECORD AND CONSTANTLY ANALYZED
BY YOUR DOCTORS OR AI OR
WHATEVER. I THINK IN THAT
MOMENT THE DUTY TO RESCUE IS
GOING TO GO AWAY BECAUSE
RESEARCHERS WON'T BE ANY SORT OF
UNIQUE POSITION TO HELP PEOPLE.
SO I THINK NOW OR SOON WE'RE
GOING TO BE IN THE HACKS
MAXIMAL DUTY TO RESCUE MOMENT.
BUT IT WILL HAVE A WAY AS IT
GETS MORE AND MORE INCORPORATED
INTO CLINICAL CARE.
>> AUDIENCE: THANKS.
>> ALEX.
>> AUDIENCE: HI, BEN, CAN YOU
ALL HEAR ME? OKAY. GREAT. SO
MY QUESTION IS, ONCE MAYBE
TECHNOLOGY GETS MORE ADVANCED
AND IT'S NOT AS MUCH OF A BURDEN
TO REPORT SECONDARY FINDINGS,
BECAUSE THAT SEEMS LIKE THE MAIN
IMPEDIMENT IS IT'S A HUGE BURDEN
TO TRACK THOSE PEOPLE DOWN BUT
IF THAT BECAME ALMOST SEAMLESS
IN THE FUTURE DO YOU THINK THERE
WOULD STILL BE A GOOD ARGUMENT
FOR SECONDARY FINDINGS NOT BEING
RETURNED IF IT, SAY IT WERE EASY
TO DO IT?
>> BEN: I THINK PEOPLE ADOPT OUR
ARGUMENT THAT THERE SHOULD BE AN
INSTITUTIONAL OBLIGATION I DON'T
THINK IT'S GOING TO BE THAT HARD
TO SET UP THESE PROGRAMS AND
JULIE'S GOING TO TALK ABOUT THIS
IN A MINUTE ABOUT THE NIH
PROGRAM. SO I THINK YOUR
INSTINCT IS RIGHT. AS IT GETS
EASIER AND EASIER TO RETURN
FINDINGS AND PARTICULARLY AS WE
GET BETTER AND BETTER AT SETTING
UP RESOURCES ON THE
INSTITUTIONAL LEVEL THAT ARE
REALLY GOOD AT THIS, THAT THE
ARGUMENTS THAT PEOPLE WANT TO
MAKE ABOUT HOW THIS IS HARD,
THIS IS TOO MUCH BURDEN, THIS
WILL SLOW MY RESEARCH DOWN THOSE
ARE GOING TO BE INCREASINGLY
UNTENABLE AND I'D ARGUE THEY
ALREADY SORT OF ARE. EXCEPT IN
PRETTY RARE CASES SO I THINK
YOU'RE RIGHT. WE SHOULD BE
PRETTY SKEPTICAL OF THOSE KINDS
OF ARGUMENTS.
>> AUDIENCE: M-HM. THANKS.
>> GO AHEAD, JULIE.
>> AUDIENCE: SO I'M GOING TO
REFERENCE THE FIRST QUESTION, I
REFLECT ON THIS A LOT BUT
HEARING HOW YOU LAY OUT HOW THE
THINKING HAS EVOLVED 2010 IS
KIND OF A BENCHMARK FOR ME TOO
I'M JUST CURIOUS ABOUT YOUR TAKE
ON THE EXTENT TO WHICH KIND OF
POSITIONS HAVE EVOLVED ON THIS
ISSUE AND HOW MUCH OF THAT HAS
BEEN INFORMED BY KIND OF
EMPIRICAL RESEARCH AND HOW MUCH
DO YOU THINK JUST THE FACT THAT
THE TECHNOLOGY HAS EVOLVED AT
JUST SUCH AN ENORMOUSLY RAPID
PACE CONTRIBUTES TO THAT. DO
YOU KIND OF UNDERSTAND WHAT I'M
SAYING?
>> BEN: I THINK IT'S BOTH. IT'S
CERTAINLY BOTH. BUT I THINK THE
BIGGEST BARRIER EARLY ON, AT
LEAST FROM THE CONVERSATIONS I
WAS SEEING, WAS THIS CONCERN
ABOUT THE PSYCHOSOCIAL HARMS,
THE IDEA THAT GENETIC --
RETURNING UNPLEASANT UNFORTUNATE
GENETIC INFORMATION TO PEOPLE
WOULD CREATE TERRIBLE ANXIETY OR
DEPRESSION OR THEY'D BE
STIGMATIZED OR DISCRIMINATED
AGAINST ECONOMICALLY OR IN THEIR
JOB OR HEALTH CARE, INSURANCE,
AND I THINK THAT THOSE WORRIES
WERE VERY UNDERSTANDABLE BUT
THEY WERE THEORETICAL, THEY WERE
SPECULATIVE AND WE KNEW HAVE
FIFTEEN MORE YEARS OF EXPERIENCE
WHERE PEOPLE HAVE BEEN ACTIVELY
STUDYING THOSE.
AND WE JUST HAVEN'T FOUND
ACCEPTANCE EXCEPT IN DISCREET
CASES WHERE THOSE KINDS OF
PSYCHOSOCIAL AND ECONOMIC HARMS
ARE REALLY MANIFESTING. ONCE
THAT WENT AWAY AND AS IT GOT
EASIER AND TECHNOLOGY IMPROVED
AND THE VALUE OF THE FINDINGS
INCREASED AS WE KNEW MORE AND
MORE, BUT AS THAT COST BENEFIT
RATIO SHIFTED, I THINK IT JUST
BECAME MORE AND MORE SORT OF
LIKE A NO-BRAINER. WE SHOULD BE
RETURNING THESE THINGS TO
PEOPLE. THERE'S NOT THAT MUCH
RISK OF HARM. IT DO CAN DO A
LOT OF GOOD AND IT GOETZ EASIER
AND EASIER.
MY PAIN POINT IS THIS IS AN
IMPORTANT THING TO DO AND WE
SHOULD DO IT. BUT IT'S OKAY TO
DRAW CONTOURS AROUND. IT'S OKAY
TO LIMIT IT TO SOME DEGREE.
THOSE LIMITS MIGHT CHANGE AS THE
SITUATION AND TECHNOLOGY DEVOLVE
BUT IT'S OKAY TO SAY THIS IS
RESEARCH, IT'S NOT CLINICAL CARE
WE DON'T HAVE TO PROVIDE THE
SAME THINGS BUT WE SHOULD REALLY
BE TRAYING TO HELP PEOPLE WITH
THESE POTENTIALLY LIFE SAVING
FINDINGS WHEN WE CAN.
>> WE HAVE TWO QUESTIONS OUT
FROM OUT IN THE WORLD. ONE FROM
ANITA.
THANK YOU FOR THIS INTERESTING
DISCUSSION, IN TERMS OF THE
RIGHT NOT TO KNOW, AND IF
AUTONOMY IS GREATER THAN
BENEFICENCE HOW DOES THIS FIT
WITH THE CLINICIAN'S HIPPOCRATIC
OATH TO FIRST DO NO HARM I CAN'T
IMAGINE KNOWING A PERSON'S LIFE
COULD BE SAVED IF THEY HAD A
PARTICULAR TREATMENT AND NOT
TELLING THEM ABOUT IT TO MAKE
THE DECISION.
>> BEN. IT'S A GREAT QUESTION
AND INVOKING THE IDEA OF MORAL
DISTRESS.
THE IDEA THAT YOU KNOW THE RIGHT
THING AS A PROVIDER, YOU KNOW
THE RIGHT THING TO DO. BUT FOR
VARIOUS REASONS ARE CONSTRAINED.
YOU KNOW YOU CAN SAVE A PERSON'S
LIFE BUT BECAUSE THEY CHECKED A
BOX YOU'RE NOT ALLOWED TO AND
THAT'S ONE OF THE REASONS WHY I
THINK WE SHOULDN'T ASK THEM TO
CHECK BOX ON SOMETHING THIS
IMPORTANT BECAUSE THERE'S SO
MUCH LITERATURE ABOUT HOW PEOPLE
DON'T UNDERSTAND CONSENT FORMS
AND DON'T READ THEM AND MAKE
MISTAKES AND I THINK THAT
WORRYING ABOUT THAT PERSON WHOSE
LIFE CAN BE SAVED IS MORE
IMPORTANT THAN WORRYING ABOUT
THE PERSON WHO DOESN'T WANT TO
KNOW THIS INFORMATION AND MAYBE
HAS GOOD REASONS TO.
BUT PARTICULARLY AS I'VE ARGUED
IF THEY CAN RAISE THEIR HAND AND
SAY I DON'T WANT TO KNOW LET'S
PUT THE OBLIGATION ON THEM TO DO
THAT AND PROTECT THE PERSON WHO
MIGHT CHECK THE WRONG BOX AND
THE PROVIDER WHO MIGHT FEEL
REALLY TROUBLED ABOUT NOT SAVING
THAT PERSON'S LIFE.
>> EXACTLY. GREAT, WE HAVE ONE
MORE QUESTION. IT'LL BE QUICK
IF POSSIBLE ANSWER. IF, SO,
THIS IS FROM KIM. THANK YOU FOR
BRINGING THE CLARITY TO A
COMPLEX TOPIC. IF RESEARCHERS
ORG THAT RESULTS SHOULD NOT BE
RETURNED, IF THERE IS NO
ACTIONABLE OPTION, THEN ONE CAN
ARGUE THAT RESEARCH SHOULDN'T BE
DONE IN THAT GEOGRAPHIC LOCATION
AT ALL, HOW DO WE THINK ABOUT
THAT VIEW?
>> BEN: SO THAT'S INTERESTING.
AND PEOPLE -- TO BE CLEAR I'M
NOT ARGUING YOU SHOULDN'T RETURN
THAT BUT THE PEOPLE THAT MAKE
THAT KIND OF ARGUMENT, I MEAN,
THERE ARE GOOD REASONS WHY WE
HAVE TO DO RESEARCH IN A WIDE
VARIETY OF REGIONS. AND I WOULD
HATE IT, IF THE RESEARCH IS
DESIGNED TO PRODUCE
GENERALIZABLE KNOWLEDGE THAT
COULD REALLY HELP THAT REGION I
WOULD HATE TO SHUT DOWN RESEARCH
JUST BECAUSE OF THE SECONDARY
FINDINGS ARGUMENT BUT I THINK
THIS PERSON IS HIGHLIGHTING A
TENSION THAT MAKING AN ARGUMENT
THAT REALLY SUGGESTS WE
SHOULDN'T BE RETURNING THINGS
JUST BECAUSE IT'S NOT ACTIONABLE
IN THAT COMMUNITY, ON THAT DAY,
THINGS CHANGE, THINGS CAN
EVOLVE, PEOPLE HAVE MORE
RESOURCES AND MORE, IT'S FAIRLY
PATERNALISTIC AND MYOPIC TO
ASSUME THAT JUST BECAUSE THERE'S
NOT THE FACILITIES TO HELP
SOMEONE TREAT THAT CONDITION NOW
THAT THEY COULDN'T ACCESS IT
SOON OR IN THE MEDIUM OR
LONG-TERM SO I AGREE THAT IT'S
NOT A VERY STRONG ARGUMENT TO
MAKE TO SAY THAT WE SHOULDN'T BE
RETURNING JUST BECAUSE IT'S NOT
ACTIONABLE.
>> GREAT. THANK YOU, BEN.
>> BEN: THANK YOU SO MUCH.
>> RIGHT ON TIME, THANK YOU VERY
MUCH. SO, NEXT, IT'S MY GREAT
PLEASURE TO INTRODUCE DR. JULIE
SAP AND AS BEN SAID SHE'S GOING
TO REALLY TALK TO US A BIT ABOUT
THE PRACTICAL ASPECTS OF ALL OF
THIS. SHE IS A GENETIC
COUNSELOR AND AT THE CENTER FOR
PRECISION HEALTH RESEARCH AT
NHGRI AND HER RESEARCH FOCUS ON
EFFORTS INVESTIGATE THE CLINICAL
UTILITY OF GENOMIC TECHNOLOGIES
AND TO DEVELOP BEST PRACTICES
FOR RETURN OF RESULTS SO THE
PERFECT PERSON TO FOLLOW BEN.
THANK YOU, JULIE. SNUL.
>> THANK YOU SO MUCH FOR THAT
INTRODUCTION AND THANK YOU,
EVERYBODY, IT'S ALWAYS GREAT TO
FOLLOW BEN. I THINK THAT I --
IT'S ALWAYS GREAT AGAIN TO HEAR
SOME OF THE ETHICAL ARGUMENTS.
YOU KNOW, ONE OF MY FIRST
DISCLAIMERS HERE IS OF COURSE
LIKE MOST PEOPLE I THINK THAT
ARE TALKING, AS A FEDERAL
GOVERNMENT EMPLOYEE THESE ARE MY
OWN WORDS AND MY OWN OPINIONS.
BUT YOU KNOW I THINK THE OTHER
THING I WOULD WANT TO SHARE WITH
YOU GUYS IS I'M A TRAINED AS A
COUNSELOR BUT MOST OF MY
RESEARCH IS IN THIS FIELD OF
IMPLEMENTATION SCIENCE WHERE I
AM REALLY VERY FOCUSED ON KIND
OF PRACTICAL, PRAGMATIC
OUTCOMES. AND KIND OF THE, YOU
KNOW, WHERE THE RUBBER MEETS THE
ROAD WHEN WE START TO THINK
ABOUT THESE IDEAS AND HOW WE
OPERATIONALIZE THEM FOR PATIENTS
AND IN OUR WORK. IN THIS, YOU
KNOW, KIND OF MESSY ENVIRONMENT
WHERE WE'RE DOING THIS CLINICAL
RESEARCH WITH PEOPLE. SO, I
THINK YOU SHOULD JUST KNOW THAT
AGAIN, I HAVE THIS REALLY
PRAGMATIC APPROACH AND I AM
SITUATED AS A CLINICIAN AND I
ALSO DON'T REALLY HOLD WITH THIS
VIEW THAT GENETIC DATA IN ALMOST
ALL CASES IS REALLY DIFFERENT
FROM OTHER KINDS OF HEALTH DATA
AND SO THAT'S THAT IDEA OF
GENETIC EXCEPTIONALISM THAT BEN
MENTIONED. I JUST DON'T THINK
THAT THAT'S SOMETHING THAT WE
NEED TO SPEND A TON OF TIME
THINKING ABOUT AND I DON'T
REALLY HOLD WITH THAT VIEW TOO
MUCH. SO IN TERMS OF AN OUTLINE
HERE THERE'S TWO MAJOR BUCKETS
OF THINGS THAT I WANT TO TALK
ABOUT WHICH IS HOW RESEARCH
PARTICIPANTS THINK ABOUT OR FEEL
ABOUT GETTING GENOMIC DATA AS A
RESULT OF RESEARCH PARTICIPATION
AND THEN OF COURSE WHAT ARE THE
OUTCOMES? WHAT HAPPENS TO
PEOPLE ONCE THEY LEARN THIS KIND
OF INFORMATION? I THINK WHAT I
WILL DO IS REFINE THIS A LITTLE
BIT. AND FOCUS IN ON HOW
PEOPLE, JUST GENERALLY THINK
ABOUT AND REACT TO OPTIONS FOR
LEARNING GENETIC DATA AND THE
REASON I THINK IT'S IMPORTANT TO
THINK BEYOND RESEARCH
PARTICIPANT WHEN IS --
PARTICIPANTS WHEN WE THINK ABOUT
THIS ANY PERSON CAN ENTER A
RESEARCH STUDY AND WE KNOW THERE
ARE RESEARCH STUDIES THAT ARE
RECRUITING PEOPLE FROM THE
GENERAL POPULATION TO
PARTICIPATE IN GENOMIC RESEARCH.
SO WE NEED TO THINK ABOUT -- I
THINK THE VIEWS OF THE GENERAL
PUBLIC ARE IMPORTANT TO THINK
ABOUT HERE AND AS BEN MENTIONED
MOST OF WHAT I'M GOING TO BE
TALKING ABOUT IS OUR, YOU KNOW,
WHAT WE UNDERSTAND ABOUT WHAT
HAPPENS TO PEOPLE ONCE THEY
LEARN ABOUT ACTIONABLE GENOMIC
DATA? AND SO, YOU KNOW, WHEN WE
THINK ABOUT ATTITUDES TOWARDS
THE RETURN OF RESULTS THERE HAVE
BEEN MANY, MUCH INK HAS BEEN
SPILLED ON THIS TOPIC AND I WILL
CIRCLE BACK TO THAT IN A MINUTE
BUT AS GENOMIC INTERROGATION
TECHNIQUES BECAME MORE
UBIQUITOUS AND MUCH LESS
EXPENSIVE THERE'S BEEN JUST A
LOCK OF WO-- LOT OF WORK DONE O
TRYING TO SOLICIT PREFERENCES OF
PEOPLE.
OF DIFFERENT GROUPS OF PEOPLE
TOWARDS GENOMIC DATA AND SO, YOU
KNOW, THERE'S WORK THAT'S BEEN
DONE WITH ASKING RESEARCH
PARTICIPANTS, WHAT KIND OF DATA
THEY WILL LIKE, THE GENERAL
PUBLIC, AND THEN OF COURSE, YOU
KNOW, SPECIFIC GROUPS. LIKE
PARENTS OF PEDIATRIC, SICK
CHILDREN BASICALLY, PATIENTS WHO
ARE PRESENTING WITH PARTICULAR,
YOU KNOW, DISEASE WHERE GENOMIC
INTERROGATION MIGHT BE HELPFUL.
AND THEN, AGAIN, SOME SUB
STUDIES OF EVEN MORE FINE
GRAINED PARTICIPANT ATTRIBUTES.
AND WHEN WE LOOK AT THIS BODY OF
LITERATURE, THERE IS AN
OVERWHELMING PREFERENCE FOR
RETURN OF RESULTS AND SO, AGAIN,
I THINK SOME OF THIS IS JUST
FURTHER SUBSTANTIATING THIS
ARGUMENT THAT, YOU KNOW, IF YOU
ASK PEOPLE WHAT THEY WANT, MANY
PEOPLE, THE FIST FIRST THING
THAT WILL COME TO MIND IS I
DON'T ACTUALLY WANT TO KNOW THIS
INFORMATION. ACROSS ALL OF
THESE STUDIES, IN, YOU KNOW, UP
TO 100% OF PEOPLE WHO
PARTICIPATE IN THIS KIND OF
WORK, SAY THAT THEY WANT
EVERYTHING THAT YOU CAN TELL ME.
IN GENERAL, WITH INCREASE
ACTIONABILITY, THERE IS AN
INCREASING PREFERENCE FOR
RETURN. SO MORE PEOPLE, IF YOU
GIVE THEM AN ARRAY OF CHOICES,
WOULD YOU LIKE TO KNOW ABOUT
THINGS LIKE YOUR ANCESTRY OR THE
BALDNESS EXAMPLE THAT WAS A
REALLY GOOD ONE OR A NON
TREATABLE DISEASE, PEOPLE HAVE
LESS INTEREST IN LEARNING SOME
OF THAT STUFF AND MORE INTEREST
IN LEARNING ABOUT ACTUAL RESULTS
THAT MAY MAKE A DIFFERENCE IN
THEIR HEALTH. BUT, YOU KNOW,
THIS IS NOT THE ONLY BOUNDARY
THAT PEOPLE WILL SICITE MANY
PEOPLE WILL SAY I WANT YOU TO
TELL ME EVEN IF IT'S NORMAL. I
EVEN WANT A NEGATIVE FINDINGS.
AND THEN PEOPLE ALSO WILL DESIRE
THEIR RAW SEQUENCE DATA. FOR
RESEARCH STUDIES EVEN IF THEY
DON'T HAVE THE EXPERTISE TO
INTERPRET THIS DATA THEY WANT TO
HAVE, YOU KNOW, EVERYTHING THAT
YOU COULD POSSIBLY TELL ME IS
WHAT MANY PEOPLE SAY. PEOPLE
ARE ALSO VERY INTERESTED AND
ROET MOTIVATED TO LEARN ABOUT
RESEARCH RESULTS THAT
RESEARCHERS THINK ARE
INTERESTING.
THEY'LL SAY IF YOU THINK IT'S
INTERESTING YOU SHOULD
DEFINITELY SHARE IT WITH ME EVEN
IF IT MIGHT BE INTERESTING FOR
SOME VERY ESOTERIC REASON THAT
HAS TO DO WITH SOME BIOCHEMICAL
FUNCTION THAT A NORMAL PERSON
MIGHT NOT REALLY CARE ABOUT.
PEOPLE STILL REALLY WANT THAT
KIND OF INFORMATION. AND A
VERY, VERY SMALL MINORITY OF
PEOPLE WILL SAY THAT THEY WANT
NONE OF THEIR GENETIC DATA BACK
OR THAT THEY ONLY WANT PRIMARY
DATA BACK AND WHAT I MEAN BY
PRIMARY DATA ARE GENETIC RESULTS
THAT RELATES SPECIFICALLY TO THE
REASON WHY THE SEQUENCING WAS
DONE IN THE FIRST PLACE. SO I
JOINED A RESEARCH STUDY BECAUSE
MY CHILD HAS AUTISM I ONLY WANT
RESULTS RELATED TO AUTISM THAT'S
IT. DON'T TELL ME ANYTHING ELSE
AND WHEN YOU ASK PEOPLE WHY THEY
WANT THIS INFORMATION THE MOST
SALIENT REASON OR THE PRIMARY
REASON IS THAT PEOPLE FIND THIS
TO BE VERY EMPOWERING. YOU
KNOW, THIS IDEA, AGAIN, THAT
KNOWLEDGE IS POWER, THAT THERE'S
SOMETHING THAT THEY COULD DO
WITH THE INFORMATION. RELATED
TO THAT MANY PEOPLE WILL TALK
ABOUT HOW, WELL THERE'S A
POTENTIAL FOR ME TO PREVENT
DISEASE IN MYSELF OR IN MY
FAMILY MEMBERS. WHICH IS,
AGAIN, RELATED TO THIS IDEA
THAT, YOU KNOW, PERHAPS THIS
COULD BE BENEFICIAL TO ME AND MY
RELATIVES. AND ALSO PEOPLE ARE
CURIOUS WHICH IS NOT ROCKET
SCIENCE. WE HAVE 23ANDME AND
ALL OF THESE DIRECT TO CONSU
CONSUMERS. THEY FEEL THEY COULD
KNOW THEMSELVES BETTER IN SOME
WAYS BY HAVING ACCESS TO THEIR
DNA. AND AGAIN I THINK THAT
RELATES TO THIS OTHER IDEA THAT
PEOPLE FIND THIS A WAY TO BE
THAT THEY CAN KIND OF EXPLORE
ATTRIBUTES ABOUT THEMSELVES THAT
MAYBE A CLINICIAN WOULDN'T PUT
AS, THE MOST HIGH PRIORITY ITEM,
LIKE ANCESTRY BUT HAS A LOT OF
PERSONAL UTILITY TO A PERSON.
SO THESE ARE ALL REASONS WHY
PEOPLE SAY THAT THEY WANT THIS
INFORMATION. AND THEY SAY THAT
THEY WANT ALL OF THIS
INFORMATION OR THEY WANT THEIR
GENETIC RESULTS EVEN AS THEY
CITE SOME OF THESE CONCERNS.
LIKE WHO IS GOING TO MAINTAIN MY
GENOMIC DATA AND HOW MIGHT IT BE
USED IN THE FUTURE. IS THERE A
BURDEN TO WHAT I MIGHT -- WHAT'S
THE BURDEN ASSOCIATED WITH THE
KNOWLEDGE THAT YOU'RE GOING TO
IMPART UPON ME. IS IT GOING TO
RESULT IN SOME SORT OF POOR
OUTCOME FOR MYSELF? PEOPLE ARE
ABLE TO KIND OF WEIGH AND THINK
ABOUT THESE RISKS, BUT THEY
CERTAINLY DO NOT OVERRIDE THIS
PREFERENCE OR RETURN. SO,
AGAIN, I THINK PEOPLE CAN
MANIPULATE THESE CONCEPTS IN
THEIR MINDS AND YET STILL COME
DOWN ON THE SIDE OF, YOU KNOW,
THIS IS SOMETHING THAT I REALLY,
REALLY WANT AND, AGAIN, I THINK
THIS REALLY SPEAKS TO THIS IDEA
THAT PEOPLE BELIEVE THAT THEIR
GENOMIC DATA ARE THEIR DATA.
THEY WANT TO CONTROL IT THEY
WANT TO KNOW WHO IS LOOKING AT
IT. WHEN YOU TALK TO RESEARCH
PARTICIPANTS THEY WILL SAY
THINGS LIKE NO ONE CARES AS MUCH
ABOUT MY SEQUENCE DATA AS I DO.
YOU KNOW, YOU MIGHT BE LOOKING
AT IT FOR THIS ONE REASON. BUT
I AM -- IF YOU GIVE IT TO ME
THEN I CAN REVISIT IT AND THINK
ABOUT IT OVER TIME AND TALK WITH
MY DOCTORS MOVING FORWARD. AND
SO, YOU KNOW, I AM UNCOMFORTABLE
WITH THIS IDEA OF SOMEONE ELSE
DETERMINING YOU KNOW, WHAT'S IN
MY BEST INTEREST. IN TERMS OF
MAKING DECISIONS FOR ME ABOUT
WHAT KIND OF STUFF I SHOULD
LEARN FROM RESEARCH SEQUENCING.
AND THEN I THINK AGAIN THE
CONVERSE OF THE RIGHT NOT TO
KNOW IT'S THE RIGHT TO KNOW.
IT'S MY DATA, I SHOULD HAVE A
AUTONOMY AND CONTROL OVER IT AND
PEOPLE LOOK AT THE TYPES OF DATA
AS GIVEN TO PEOPLE IS VIEWED AS
PATERNALISTIC GENERALLY BY
PEOPLE WHO ARE ASKED TO THINK
ABOUT WHAT KIND OF GENETIC DATA
THEY MIGHT WANT TO GET FROM
RESEARCH. SO WHEN YOU ASK
PEOPLE, YOU KNOW, OKAY, WE'VE
ESTABLISHED THAT YOU WANT TO
KNOW THIS INFORMATION, WHAT ARE
YOUR PREFERENCES FOR RETURNING,
YOU KNOW, FOR LEARNING THIS
INFORMATION? AND SO PEOPLE WILL
SAY AFTER BROAD CONSENT, SO THEY
WANT TO BE INFORMED ABOUT WHAT
KIND OF GENOMIC DATA ARE GOING
TO BE GENERATED AND THEY ALSO
REALLY WANT TO UNDERSTAND WHAT'S
THE PLAN TO GET THIS BACK TO ME
ARE YOU GOING TO CALL ME? ARE
YOU GOING TO SEND ME A LETTER
AND I THINK MANY PEOPLE HAVE
ARGUED AND WE HAVE A LOT OF GOOD
DATA TO SUGGEST THAT WHEN YOU
STICK TO A PLAN TO RETURN
RESULTS IT IS A GREAT WAY TO
FOSTER ONGOING PARTICIPANT
ENGAGEMENT. AND YOU KNOW WE
KNOW THAT HAVING PARTICIPANTS
ACTIVELY ENGAGED IN RESEARCH IS
JUST A HUGE PART OF THE WHOLE
ENTERPRISE. AND THEN THERE'S
SOME, YOU KNOW, DATA TO SUGGEST
THAT PEOPLE PREFER THINGS LIKE
FACE-TO-FACE GENETIC COUNSELING
FOR RETURN OF RESULTS BUT I
THINK THERE'S A LOT OF ROOM FOR
INNOVATION HERE AS WELL. AND
I'M GOING TO COME BACK TO THE
IDEA OF CONSENT A LITTLE BIT --
A LITTLE BIT LATER. I'M GOING
TO AGAIN CITE BEN'S WORK HERE.
BECAUSE WE CAN LOOK AT PEOPLE
WHO REFUSE TO GET GENETIC DATA
AND SO, AGAIN, I WILL JUST
EMPHASIZE THAT THESE PEOPLE ARE
IN THE MINORITY. AND I THINK
ANOTHER REALLY IMPORTANT THING
TO BE AWARE OF WHEN WE'RE
LOOKING AT THIS LITERATURE IS
THAT A LOT OF SIT HYPOTHETICAL
OR ANALOG SO YOU WOULD ASK A
GROUP OF RESEARCH PARTICIPANTS
IF WE WERE ABLE TO IMPLEMENT
GENOMIC SEQUENCING IN OUR STUDY
WHAT CHOICES WOULD YOU MAKE OR
IF YOU WERE OFFERED THESE
CHOICES WHICH SOUND BEST TO YOU?
THERE'S THE BODY OF LITERATURE
THAT'S FOCUSED ON PEOPLE WHO ARE
ACTUALLY MAKING THESE DECISIONS
IS MUCH SMALLER COMPARED TO THE
GROUP OF PEOPLE WHO ARE -- THE
LITERATURE THAT'S ON PEOPLE WHO
ARE ACTUALLY MAKING SOME OF
THESE CHOICES. AND AS BEN
POINTED OUT, THIS REFUSAL MAY
NOT BE DURABLE AND SO, AGAIN,
THERE'S SOME DATA TO SUGGEST
THAT PEOPLE CAN CHANGE THEIR
MINDS ON THIS OVER TIME AND BY
KIND OF HAPPENSTANCE I HAVE
TALKED TO SOME OF THESE PEOPLE,
THESE REFUSERS AND RETURNED
SECONDARY FINDINGS TO THEM. AND
THEY ARE FINE. IT'S ANECDOTAL
DATA BUT THEY WERE FINE. AND I
THINK ONE THING THAT IS AN
INTERESTING POINT THAT I WILL
MENTION HERE BECAUSE YOU MIGHT
BE ASKING YOURSELF, WELL, IF
THEY REFUSED, HOW DID YOU COME
TO TALK TO THEM? AND THIS IS
ANOTHER PRACTICAL ARGUMENT
AGAINST THINGS LIKE CHECK BOXES.
THERE'S A LOT OF POSSIBILITIES
FOR DATA INTEGRITY ISSUES TO
COME INTO PLAY. SO IF SOMEONE
CHECKS THE BOX NO, ON A PAPER
CONSENT FORM THEN THAT CHOICE
NEEDS TO BE CARRIED FORWARD WITH
FIDELITY INTO WHATEVER YOUR KIND
OF RESEARCH DATABASE IS AND SO I
JUST THINK IT INTRODUCES A LOT
OF POTENTIAL FOR KIND OF
BIDIRECTIONAL ERROR. WHERE YOU
DO FIND YOURSELF IN A POSITION
WHERE, YOU KNOW, MAYBE WE
WEREN'T REALLY SUPPOSED TO BE
ANALYZING THIS SEQUENCE DATA
THIS PERSON BECAUSE THEY CHECKED
THE BOX FOR NO BUT WE DID
ANALYZE THE DATA AND WE'RE
EXACTLY IN THE BOX OF THE SECOND
CASE THAT BEN MENTIONED WHERE WE
KNOW SOMETHING ABOUT SOMEBODY.
THEY SAID NO, HOW DO WE GO BACK
AND TALK TO THEM BECAUSE NOW WE
KNOW THIS INFORMATION. AND I
THINK IT'S A DIFFERENT SITUATION
WHERE YOU DON'T ACTUALLY SEEK IS
DATA FROM THE SEQUENCE DATA THAT
YOU GENERATE. YOU DON'T SEEK
THESE FINDINGS. IT'S A BIT OF A
TANGENT BUT THINKING ABOUT HOW
WE CAT SGEGORIZE PEOPLE'S CHOIC
IS ANOTHER OPPORTUNITY TO
INTRODUCE ERROR. SO I THINK
WHEN WE THINK ABOUT, YOU KNOW,
THIS WHOLE TOPIC, WE ARE STILL
IN A SITUATION WHERE WE KNOW
MUCH MORE ABOUT PEOPLE'S
ATTITUDES ABOUT GENOMIC DATA.
AND WHETHER OR NOT RESEARCH, HOW
RESEARCH PARTICIPANTS FEEL ABOUT
GETTING THESE KINDS OF DATA.
COMPARED TO WHAT THE OUTCOMES
ARE. AND SO I'M GOING TO KIND
OF TRANSITION A LITTLE BIT INTO
TALKING ABOUT OUTCOMES BECAUSE I
THINK WE NEED TO SHIFT THIS
RATIO, AGAIN, A LOT OF INK HAS
BEEN SPILLED OVER WHAT OUGHT WE
TO DO AND WHY OUGHT WE TO DO IT
AND LESS HAS BEEN ON THIS AREA
OF WELL, WHAT HAPPENS WHEN WE
MAKE DECISIONS. WHAT ARE THE
OUTCOMES ASSOCIATED WITH SOME OF
THOSE DECISIONS? AND I THINK
THIS IS A POINT TO REVISIT ONE
OF, YOU KNOW, REVISIT CONSENT IN
ONE WAY WHICH IS, YOU KNOW, OVER
THE YEARS I'VE TALKED -- I'VE
CONSENTED MANY PEOPLE FOR
GENOMIC SEQUENCING WITH RETURN
OF SECONDARY FINDINGS AND I
ALWAYS LIKE IT WHEN PEOPLE
DECLINE PARTICIPATION IN
RESEARCH STUDIES. YOU REALLY
SHOULDN'T IDEALLY HAVE 100% OF
YOUR PROSPECTIVE PARTICIPANTS
SIGNING THAT CONSENT FORM.
RIGHT? IT'S GREAT IF MOST
EVERYBODY DOES BUT I THINK IT'S
A REALLY GREAT, I DON'T KNOW, I
LIKE IT WHEN PEOPLE DECLINE
BECAUSE TO ME IT'S AN INTERNAL
CHECK THAT I'M DOING IT RIGHT.
BECAUSE NOT EVERYONE WHO I TALK
TO COULD POSSIBLY WANT TO BE IN
MY STUDY EVEN WITH THE SELECTED
POPULATION THAT COME THROUGH TO
HAVE THAT CONVERSATION WITH ME
AND I THINK THE CASES IN WHICH
I'VE TALKED TO PEOPLE AND THEY
ARE CONCERNED ABOUT RECEIVING
THESE FINDINGS KIND OF AGAIN GO
ALONG WITH WHAT SOME OF THE
THINGS THAT BEN WAS SAYING ABOUT
THESE, LIKE, SPECIFIC INSTANCES.
YOU KNOW, I'VE HAD A COUPLE OF
PEOPLE IN THE MILITARY AND HAVE
BEEN REALLY CONCERNED ABOUT
WHERE THEIR GENOMIC DATA ARE
GOING AND HOW THAT WILL AFFECT
THEIR POTENTIAL FITNESS AND
CONCERNS THAT THAT WILL
DISCHARGE THAT'S A REALLY
SPECIFIC AND IMPORTANT CASE THAT
IS IMPORTANT TO TALK ABOUT. IN
ANOTHER CASE I'VE WORKED WITH
SOME FAMILIES WHERE THERE ARE
SOME PROGRAMS WHERE THERE'S
CARRIER SCREENING FOR GENETIC
CONDITIONS THAT ARE REALLY MORE
COMMON IN A CERTAIN POPULATION.
AND SO THERE ARE KIND OF
COMMUNITY GENETIC SCREENING
INITIATIVES THAT ARE, AGAIN,
COMMUNITY LED, COMMUNITY
ORGANIZED, AND ONE OF THE
FEATURES OF SOME OF THOSE
PROGRAMS IS THAT PEOPLE WHO
PARTICIPATE IN THE PROGRAM DON'T
LEARN THEIR INDIVIDUAL RESULTS
BECAUSE THE PURPOSE OF THE
PROGRAM IS TO HELP MAKE SURE
THAT A POTENTIAL PARTNER DOESN'T
CARRY THE SAME PATHOGENIC
VARIANT FOR A SPECIFIC CONDITION
THAT THEY MIGHT SO IT REDUCES
THE PROBABILITY THAT THEY WOULD
HAVE AN AFFECTED CHILD THE
PARTNERSHIP IS ANALYZED AND THE
POTENTIAL FOR THE PERSPECTIVE
PARTNERSHIP TO HAVE AN INCREASED
RISK TO HAVE A CHILD WITH ONE OF
THESE CONDITIONS IS KIND OF
LOOKED AT ON A COMMUNITY LEVEL
BUT INDIVIDUAL RESULTS ARE NOT
RETURNED BECAUSE THAT WOULD BE
STIGMATIZING. THIS IS SUCH A
SPECIFIC SITUATION THAT IT'S
GREAT. THAT PEOPLE HAVE, AGAIN,
BROUGHT THIS UP AND I THINK
THAT'S SOMETHING THAT ABSOLUTELY
SHOULD BE ACCOMMODATED. AND
THEN, YOU KNOW, IN OTHER
INSTANCES I'VE HAD PEOPLE TALK
ABOUT HOW, YOU KNOW, THEY JUST
FEEL UNCOMFORTABLE WITH GENETIC
DATA. BECAUSE THEY THOUGHT
ABOUT WHAT DOES THAT MEAN FOR
CHOICES THAT PEOPLE MIGHT MAKE
IN A REPRODUCTIVE SETTING.
RIGHT? I THINK THESE ARE ALL
REALLY SPECIFIC EXAMPLES THAT
ARE WORTH EXPLORING BUT
HOPEFULLY YOU CAN KIND OF TELL
FROM WHAT I'M SAYING AND WHAT
BEN WAS SAYING IS THESE ARE
SUPER, SUPER SPECIFIC AND AGAIN
WE REALLY NEED TO THINK ABOUT
THIS IDEA THAT WE HAVE A HUGE
AMOUNT OF DATA TO SUGGEST THAT
BY AND LARGE PEOPLE WANT US TO
TELL THEM THESE KINDS OF THINGS.
SO I JUST WANT TO TAKE A STEP
BACK BEFORE WE START TALKING
ABOUT OUTCOMES AND, AGAIN, SOME
PRACTICAL CONSIDERATIONS. IN
RETURNING THESE KINDS OF
FINDINGS, TO JUST TAKE A MOMENT
TO FIND THEM. I HAVE THE COMIC
ALSO JUST LIKE BEN AND WHAT'S
INTERESTING ABOUT THIS AND THE
COMIC THAT BEN PUT UP ALSO IS
THAT, YOU KNOW, I THINK THAT
WHEN YOU TALK TO A PERSON IN THE
GENERAL PUBLIC ABOUT LIKE
GENETIC DATA, YOU KNOW, I THINK
THAT WHAT THEY ARE HOPING FOR
AND WHAT MIGHT HAPPEN IN THE
FUTURE IS THAT AT SOME POINT
WE'RE GOING TO GO TO THE DOCTOR,
THEY'LL DO A FINGER STICK AND
PUT A DROP OF BLOOD IN A MACHINE
IN THE BACK AND COME OUT WITH A
RESULTS REPORT AND PRESCRIBE TO
YOU WAYS TO CHANGE YOUR LIFE OR
CHANGE YOUR HEALTH CARE TO MAKE
YOU HEALTHIER. RIGHT? SO
THEY'RE GOING TO TALK TO YOU
ABOUT HOW YOU'RE MORE LIKELY TO
HAVE DIABETES OR PEOPLE
SHOULDN'T HAVE GLUTEN. I THINK
PEOPLE THINK ABOUT THAT WHEN
THINK THINK ABOUT THE UTILITY OF
GENETIC INFORMATION IN A HEALTH
SETT
SETTING.
AND I THINK THAT'S A CONTEXT
THAT I THINK ABOUT IN TALKING
WITH PEOPLE ABOUT EXACTLY WHAT
IT IS THAT WE FIND. BECAUSE
WE'RE STILL AT THE POINT WHERE
THE KINDS OF FINDINGS THAT WE
WOULD PROPOSE TO RETURN TO
PEOPLE THROUGH AN OPPORTUNISTIC
SCREENING PROGRAM ARE MUCH MORE
DELIMITED AND THEY TAKE A LOT
MORE EFFORT TO PRODUCE THAN
JUST, AGAIN, PUTTING A DROP OF
BLOOD IN THE MACHINE IN THE
BACK. RIGHT? AND SO, YOU KNOW,
I THINK IT'S IMPORTANT TO
DISCUSS THIS IDEA THAT WHEN WE
ARE RETURNING RESEARCH RESULTS
IT'S NOT A POPULATION SCREENING.
I DO THINK THAT THE GOAL THAT
WE'RE ALL TRYING TO GET TO AS
BEN MENTIONED IS TO INCORPORATE
GENOMIC DATA INTO OUR HEALTH
CARE MORE BROADLY BUT THERE ARE
A LOT OF THINGS WE CAN LEARN
FROM MOMENT IN TIME WHEN WE ARE
GIVING THIS INFORMATION BACK TO
PEOPLE WHO ARE IN A CERTAIN
PLACE AND TIME, RIGHT? IF YOU
HAVE THE -- IF YOU ARE JOINING A
RESEARCH STUDY WHERE GENOMIC
SEQUENCING IS PART OF IT YOU
MIGHT HAVE THE OPPORTUNITY TO
HAVE YOUR, YOU KNOW, SOME OF
THESE FINDINGS RETURNED TO YOU
AS OPPOSED TO, YOU KNOW, WHAT IF
WE WERE TO IMPLEMENT THIS ON THE
OVULATION LEVEL. AND, AGAIN, I
THINK IT'S ALSO IMPORTANT TO
THINK ABOUT THE FACT THAT WHAT
WE'RE REALLY DOING HERE IN MOST
INSTANCES IS REPURPOSING THIS
LIST OF VARIANTS THAT WAS
PUBLISHED NOT VARIANTS, GENES,
BUT SPECIFIC VARIANTS THAT HAVE
SPECIFIC ATTRIBUTES IN SPECIFIC
GENES BY THE AMERICAN COLLEGE OF
AMERICAN GENETICS AND GENOMICS
AND THIS LIST WAS DEVELOPED
BECAUSE -- IT WAS DEVELOPED FOR
CLINICAL LABORATORIES, RIGHT?
SO MANY, MANY MORE PEOPLE ARE
HAVING CLINICAL GENOME
SEQUENCING. AND THE -- THIS
LIST AND THIS POLICY WAS
DEVELOPED FOR, YOU KNOW, HOW
SHOULD CLINICAL LABORATORIES
ESSENTIALLY HANDLE THE PROBLEM
FROM BEN'S CASE, RIGHT? THEY
WERE ASKED TO ANALYZE GENOMIC
DATA TO TRY TO UNDERSTAND WHY
SOMEONE MIGHT HAVE, YOU KNOW,
AUTISM OR A SEIZURE DISORDER OR
SOMETHING LIKE THAT BUT THEY ARE
IN A POSITION TO KNOW MUCH MORE.
HOW SHOULD THEY HANDLE THAT AND
THE CONSENSUS WAS THAT WELL,
THEY SHOULD LOOK FOR THESE
THINGS AND THEY SHOULD RETURN
THEM TO PEOPLE WHEN PEOPLE
EXPRESS A PREFERENCE TO LEARN
THIS INFORMATION. AND SO I
THINK, YOU KNOW, THE KEY
ATTRIBUTE OF ALL OF THESE
SECONDARY FINDINGS THAT WE'RE
TALKING ABOUT IS THAT THEY ARE
ACTIONABLE AS BEN MENTIONED SO
IF YOU WERE TO KNOW ABOUT THIS,
THERE WAS -- THERE'S SOMETHING
YOU COULD DO ABOUT IT. AND I
THINK ANOTHER THING THAT'S
IMPORTANT TO KNOW IS THAT, YOU
KNOW, MOST OF THE FIND -- MOST
OF THE DISORDERS ON THE LIST
ARE -- HAVE AUTOSOMAL DOMINANT
INHERITANCE, THAT MEANS IF YOU
AS THE PATIENT ARE FOUND TO HAVE
ONE OF THESE VARIANTS ALL OF
YOUR FIRST DEGREE RELATIVES ARE
AT 50% RISK TO SHARE THAT WITH
YOU AND PRESUMABLY THAT RISK
STATUS AND THAT'S FOR A
TREATABLE OR PREVENTABLE DISEASE
FOR WHICH POTENTIALLY LIFE
SAVING TREATMENT IS AVAILABLE
AND AGAIN I THINK THIS IS AN
AREA WHERE WE REALLY NEED TO
THINK ABOUT IS THIS REALLY
SECONDARY? WHEN WE ARE IN --
WHEN THE ACMG LIST AND THE ACMG
GUIDELINES WERE WRITTEN FOR
CLINICAL LABORATORIES WHEN
THERE'S SOMEONE ORDERING THE
TEST FOR A CLINICAL REASON AND
THERE'S AN INTERPRETING
LABORATORY WHOSE MAIN EXPERTISE
IS TRYING TO UNDERSTAND GENETIC
ETIOLOGIES OF SPECIFIC CLINICAL
ENTITIES IN RESEARCH. YOU KNOW,
THE ORDERING CLINICIAN IS MAYBE
NOT GOING TO BE A GENETICIST AND
THEY MAY NOT REALLY BE ORDERING,
YOU KNOW, A GENOME INTERROGATION
TEST FOR THE SAME REASONS THAT
SOMEONE IN THE CLINICAL WORLD
MIGHT BE. SO THIS IS JUST A
COUPLE OF CAVEATS TO KIND OF
THINK ABOUT AND KICK AROUND.
BUT, YOU KNOW, IF THINGS GO
ACCORDING TO PLAN, IDEALLY WHAT
WE WOULD SEE IS A SECONDARY
FINDINGS PARADIGM WHERE THIS
FINDING IS DISCLOSED AND
RECOMMENDATIONS ARE MADE TO THE
RECIPIENT. AND THERE ARE TWO
MAJOR RECOMMENDATIONS THAT OUGHT
TO BE MADE TO PEOPLE WHO ARE IN
THIS POSITION. THE POINTER
DOESN'T WORK. THAT'S RIGHT. I
WONDER IF -- BUT THIS DOES,
RIGHT? YOU GUYS CAN SEE THIS?
GREAT. SO THE FIRST THING IS
THAT THE PERSON SHOULD UNDERGO
SOME DISEASE SPECIFIC
EVALUATIONS. BECAUSE NOW THEY
KNOW THAT THEY HAVE A GENETIC
RISK FACTOR AND SO THEY SHOULD
MEET WITH AN EXPERT TO YOU KNOW,
BEGIN SURVEILLANCE OR, YOU KNOW,
SEE IF THEY ALREADY HAVE SIGNS
OF THIS DISEASE. BECAUSE THEY
HAVE THIS RISK FACTOR. AND OF
COURSE THE HOPE THERE WOULD BE
THAT IF THEY ARE FOUND TO HAVE
FEATURES, THEY, YOU KNOW, COULD
ENGAGE IN EARLIER DIAGNOSIS OR
PREVENTION OR TREATMENT BUT IF
THEY DON'T THEY COULD
PARTICIPATE THIS THE KIND OF
ONGOING SURVEILLANCE THAT WOULD
ALLOW INTERVENTION AT A TIME
WHEN IT IS MOST LIKELY TO HAVE
THE BEST OUTCOME. BUT THEN THIS
GETS TO THE SECOND
RECOMMENDATION. WHAT I
MENTIONED ABOUT THESE GENES THAT
ARE ON THIS LIST IS THAT THEY'RE
DOMINANT. SO, AGAIN, IF ANY
PERSON IS FOUND TO HAVE ONE OF
THESE FINDINGS, AN IMPORTANT
SECONDARY BENEFIT MIGHT BE TO
FAMILY MEMBERS. AND SO THE
SECOND GENERAL RECOMMENDATION
THAT PEOPLE ARE GIVEN IS TO TELL
PEOPLE IN YOUR FAMILY ABOUT THIS
VARIANT. NOT ONLY WOULD IT --
COULD IT BE, KNEW IT'S NOT
MOVING, SIT MOVING NOW? MAYBE
IT DOESN'T MATTER.
SO NOT ONLY SHOULD YOU SHARE
THIS INFORMATION WITH YOUR
FAMILY SO THAT THEY CAN GET
TESTED, WE CALL THAT CASCADE
TESTING IS WHEN YOU HAVE GENETIC
TESTING TO SEE IF YOU HAVE A
KNOWN FAMILIAL VARIANT AND IF
YOU'RE POSITIVE YOU CAN ENTER
THIS VIRTUOUS CYCLE OF, YOU
KNOW, INCREASING YOUR
SURVEILLANCE THAT COULD
POTENTIALLY SAVE YOUR LIFE BUT
ALSO, OFTENTIMES, YOU KNOW,
THESE ARE FINDINGS THAT PEOPLE
ARE NOT NECESSARILY EXPECTING
AND YOU CAN BETTER INTERPRET THE
CLINICAL MEANING OF THE FINDING
IF YOU UNDERSTAND MORE ABOUT THE
FAMILY AS WELL. YOU KNOW, SO I
THINK IT'S IMPORTANT TO THINK
THAT, YOU KNOW, THIS IS KIND OF
HOW WE HOPE THINGS GO. AND WHAT
WE DID A COUPLE YEARS AGO WAS
TURN TO THE LITERATURE TO SEE
KIND OF WHAT IS THE EVIDENCE
BASE FOR ANY OF THE THINGS THAT
I JUST MENTIONED. AND SO WE DID
A SYSTEMATIC REVIEW WHERE WE
LOOKED IN THE LITERATURE WHERE
THE UNIT OF ANALYSIS WAS
INDIVIDUAL RECIPIENTS OF
SECONDARY FINDINGS ON THE ACMG
LIST. AND SO WE WERE ONLY ABLE
TO FIND ABOUT 700 REPORTS OF
THESE KINDS OF FINDINGS BEING
RETURNED TO PEOPLE AND THAT WAS
A BIT SURPRISING TO ME BECAUSE,
YOU KNOW, THE FIRST ITERATION OF
THIS LIST WAS PUBLISHED IN 2013.
AND SO LCALMOST TEN YEARS AFTER
THE LIST WAS PUBLISHED WE STILL
DIDN'T FIND A TON OF REPORTS
ABOUT THIS BUT WE LOOKED AT WHAT
IS KNOWN IN THE LITERATURE ABOUT
HOW THESE FINDINGS ARE RETURNED
AND WHAT OUTCOMES HAPPEN AFTER
RECEIPT. AND I THINK THE ONE
IMPORTANT FINDING THAT STOOD OUT
TO US IMMEDIATELY WAS THAT 97%
OF THESE REPORTS WERE
PARTICIPANTS IN RESEARCH STUDIES
SO REALLY A TINY FRACTION ARE
PEOPLE WHO ARE GETTING THESE
KINDS OF RESULTS IN A CLINICAL
WAY MEANING THE WAY THE LIST WAS
INTENDED TO BE OPERATIONALIZED.
THAT'S -- HAS INTERESTING
IMPLICATIONS WHEN WE THINK ABOUT
MAYBE LIKE POPULATION SCREENING.
AND KIND OF CLINICAL EFFORTS BUT
IT'S GOOD FOR US HERE BECAUSE
MOST OF THESE PEOPLE ARE
RESEARCH PARTICIPANTS AND THAT'S
WHAT WE'RE TALKING ABOUT IS
RETURNING THESE RESULT TO
RESEARCH PARTICIPANTS. THERE'S
BEEN A LOT OF HAND WAVING ABOUT
WHAT DO PEOPLE DO? WHAT ARE
ADVERSE PSYCHOLOGICAL OUTCOMES
WHEN PEOPLE LEARN THIS
INFORMATION AND WE FOUND AN
ARRAY IN STUDIES THAT EVALUATED
HOW PEOPLE APPROACH THESE
RESULTS FROM AN EMOTIONAL
PERSPECTIVE, PEOPLE WILL SAY
THINGS LIKE THEY WERE SURPRISE,
RELIEVED, SAD, BUT HARDLY ANYONE
SAYS THEY REGRET THEIR CHOICE TO
LEARN THIS INFORMATION. I THINK
THIS DOVETAILS WITH THE RIGHT
NOT TO KNOW. WHEN GIVEN THIS
OPTION, VERY, VERY FEW PEOPLE
WILL SAY THAT THEY REGRET
LEARNING THIS INFORMATION. WHEN
WE FOLLOW PEOPLE OVER TIME,
LEVELS OF DEPRESSION AND ANXIETY
FROM BEFORE TO RESULTS
DISCLOSURE TO AFTER RESULTS
DISCLOSURE REMAIN UNCHANGED
ALTHOUGH THERE'S NOT A TON OF
DATA ON THIS AND SOME PEOPLE
EVEN FORGET THAT THEY'VE -- THAT
THESE DATA HAVE BEEN SHARED WITH
THEM. AND I'VE EXPERIENCED THAT
PERSONALLY. HIGH NUMBERS OF
PEOPLE REPORT SHARING THEIR
RESULTS WITH THEIR FAMILY.
ESPECIALLY TO CLOSE RELATIVES
AND WE ALSO SAW THAT DISCLOSURE
TO PRIMARY CARE DOCTORS AND THEN
SPECIALISTS WAS COMMON BUT
CERTAINLY NOT UNIVERSAL. AND I
THINK THIS IS AN IMPORTANT POINT
WHEN WE THINK ABOUT, AGAIN, THAT
PARADIGM AND I WILL COME BACK TO
THAT IN A MINUTE. WE LOOKED FOR
PRECISION MEDICINE SURVEILLANCE
OUTCOMES AND WHAT I MEAN BY THAT
IS, YOU KNOW, MOST OF US WILL
UNDERGO SCREENING TESTS BASED ON
ATTRIBUTES THAT HAVE NOTHING TO
DO WITH OUR DNA, RIGHT? YOU'RE
A WOMAN OVER 40, YOU HAVE
MAMMOGRAMS, YOU'RE A MAN OVER 50
YOU GET YOUR PSA TESTED RIGHT?
A PRECISION MEDICINE APPROACH IS
YOU'RE A WOMAN OVER 40 AND YOU
HAVE A VARIANT IN YOUR GENE THAT
PUTS YOU AT A HIGHER RISK FOR
OVARIAN CANCER SO ADHERENCE
ACROSS THE RANGE OF STUDY WHERE
IS ADHERENCE WAS EXAMINED WAS
GENERALLY PRETTY GOOD. AND
PEOPLE DID REFER PEOPLE TO, YOU
KNOW, SPECIALISTS, MANY PEOPLE
WERE FOLLOWED BY SPECIALISTS
AFTER THEY RECEIVED THEIR
RESULTS. AND IN STUDIES WHERE
COST WAS EXAMINED, THE COSTS
WERE LOWER THAN EXPECTED, AND
AGAIN, IF YOU LOOK ACROSS THIS
BODY OF LITERATURE AND I WILL
PUT A FEW CASES IN IN A MINUTE
YOU CAN FIND REPORTS OF LIFE
SAVING TREATMENT AFTER PEOPLE
LEARN THIS KIND OF INFORMATION.
THIS COULD INCLUDE, YOU KNOW,
NOT TAKING MEDICINES THAT
AVOID -- THAT INCREASE YOUR QT
INTERVAL. IT HAS TO DO WITH
YOUR HEART RATE AND RHYTHM.
TARGETED THERAPY FOR HYPER KOE
LEST TEAR ROW LIAM YA. AND
PROPHYLACTIC SURGERIES WHICH WE
KNOW REDUCE CAN SIR RISK.
IF WE OVERLAY OUR FINDINGS TO
THIS IDEAL PARADIGM THE BLUE
CIRCLES HERE ARE PROPORTIONATE
TO THE NUMBER OF CASES WHERE
THERE'S DATA TO SUPPORT A
DIFFERENT -- DIFFERENT PARTS OF
THIS PROCESS AND I THINK WHAT
YOU WILL NOTICE IMMEDIATELY IS
THAT THE PROPORTION OF DATA THAT
ARE IN THE LITERATURE ABOUT HOW
WE DO THIS AND WHAT WE SHOULD
TELL PEOPLE IS QUITE -- IS VERY
LARGE COMPARED TO, AGAIN,
OUTCOME DATA. AND WHEN WE THINK
ABOUT OUTCOME DATA SPECIFICALLY
THERE STILL IS NOT A TON OF DATA
IN THE LITERATURE ABOUT WHAT ARE
THE SPECIFIC HEALTH OUTCOMES,
ARE WE REALLY MOVING THE NEEDLE
ON PEOPLE'S HEALTH? AND ANOTHER
WAY TO THINK ABOUT THIS IS WHAT
IS THE CLINICAL UTILITY OF
SHARING THIS KIND OF INFORMATION
WITH PEOPLE? SO, AGAIN, THERE
ARE REPORTS IN THE LITERATURE
I'M GOING TO GIVE SOME CASE
EXAMPLES BUT THIS IS REALLY AN
OPPORTUNITY WHERE WE CAN IMPROVE
THE KNOWLEDGE BASE ABOUT WHAT
HAPPENS TO PEOPLE AFTER THEY
LEARN THIS KIND OF INFORMATION.
AND SO I AM GOING TO WRAP UP BY
TALKING ABOUT A COUPLE OF
DIFFERENT THINGS THAT WE DO HERE
AT NIH. WHILE ALSO
ACKNOWLEDGING THAT THERE ARE
LOTS OF OTHER GROUPS WHO ARE
WORKING ON DEVELOPING THESE BEST
PRACTICES FOR RETURN OF RESULTS
AND OUTCOMES RESEARCH, EMERGE
AND ALL OF US AND THE GUY SINGER
MY CODE INITIATIVE ARE THINGS
THAT COME TO MIND.
AND WE'RE LEARNING MORE AND MORE
DATA ABOUT ADHERENCE AND WHETHER
OR NOT PEOPLE ARE SHARING THIS
INFORMATION AND WHAT ARE THE
MOST EFFICIENT WAY TO SHARE
INFORMATION ACROSS HEALTH CARE
SYSTEMS MIGHT BE. BUT I'M GOING
TO TALK A LITTLE BIT ABOUT TWO
DIFFERENT PROGRAMS ONE -- AND OF
COURSE IT'S THE FEDERAL
GOVERNMENT SO WE HAVE ACRONYMS
FOR BOTH OF THEM. GSRP IS THE
GENOMIC SERVICES RESEARCH
PROGRAM AND SGFS IS OUR
SECONDARY GENOMICS FINDING
SERVICE I WILL START WITH GSRP
AND THIS IS A STUDY THAT'S
CURRENTLY UNDERWAY SPECIFICALLY
FOR PEOPLE WHO HAVE RECEIVED
SECONDARY FINDINGS.
SO WE ARE, YOU KNOW, ACTIVELY
RECRUITING PEOPLE FOR THIS
STUDY. WE HAVE ABOUT 300 PEOPLE
ENROLLED SO FAR. AND SO WE ARE
BROADLY RECRUITING PEOPLE ACROSS
MANY DIFFERENT RECRUITMENT
MECHANISMS TO ASCERTAIN
SECONDARY FINDINGS RECIPIENTS
AND WE'RE EVALUATING ADHERENCE
TO MEDICAL RECOMMEND --
RECOMMENDATIONS AND
COMMUNICATIONS OUTCOMES.
WE DO QUITE A BIT OF GENOTYPING
OF PEOPLE IN THE FAMILY. WE
WILL OFFER CASCADE TESTING TO
RELATIVES AND THAT IS BECAUSE WE
WANT TO REALLY UNDERSTAND THE
PREVALENCE OF THE PHENOTYPE
THAT'S ASSOCIATED WITH THE
VARIANT. ANOTHER WAY OF
THINKING ABOUT THAT IS YOUR
GENES SAY YOU SHOULD HAVE FILL
IN THE BLANK CONDITION. WHAT DO
YOU ACTUALLY HAVE? AND I THINK
THIS IS IMPORTANT FROM KIND OF A
POPULATION GENETICS PERSPECTIVE
BECAUSE ALTHOUGH THE RISKS THAT
WE QUOTE TO PEOPLE WHEN WE
RETURN THESE KINDS OF FINDINGS
TO THEM COME FROM A SELECTED
POPULATION. RIGHT? SO WE KNOW
THAT THE RISK TO DEVELOP OVARIAN
CANCER, IF YOU HAVE A BRCA 2
VARIANT IS 45% ACROSS THE
LIFETIME THAT DATA POINT COMES
FROM YEARS AND YEARS OF STUDY OF
PEOPLE WHO HAVE HEREDITARY
BREAST AND OVARIAN CANCER SO
THERE'S A SELECTION BIAS HERE
AND SO IT'S REALLY IMPORTANT TO
UNDERSTAND, YOU KNOW, WHAT MIGHT
BE THE ACTUAL, WHAT'S THE ACTUAL
PREVALENCE OF DISEASE IN PEOPLE
WHO GET THIS KIND OF
INFORMATION? SO I A COUPLE
CASES TO SHARE WITH YOU OF
PEOPLE THAT WE HAVE SEEN HERE AT
THE NIH THIS IS A PED AGREE, I
DON'T KNOW PEOPLE HAVE SEEN A
DIAGRAM LIKE THIS BUT SQUARES
ARE MEN AND CIRCLES ARE WOMEN
AND PROBAND, THAT'S THE WORD WE
USE IN GENETICS FOR THE FIRST
PERSON THAT COME TO CLINICAL
ATTENTION IS A 43-YEAR-OLD WOMAN
WHO LEARNED ABOUT A PATHOGENIC
VARIANT AND THIS VARIANT IS
ASSOCIATED WITH IF A FILIAL
HYPER CHOLESTEROL EEM YA AND SHE
FOUND OUT ABOUT THIS BECAUSE
SHED A ANCESTRY TESTING THAT SHE
BOUGHT.
MANY OF THESE COMPANIES WILL PUT
THEIR OFFERINGS ON SALE AROUND
THANKSGIVING AND THAT'S WHAT
HAPPENED TO HER SO YOU CAN
CHOOSE -- YOU CAN CHECK THE BOX
FOR DO I WANT TO RECEIVE HEALTH
DATA IN ADDITION TO KNOWING HOW
SCOTTISH OR IRISH I AM AND SHE
WAS LIKE, YEAH, IT'S ON
SALMONELLA SALE, I WILL ASK FOR
THAT AND HAVE AND I KNOW IT'S
REALLY HARD TO READ HERE AND
WE'LL SEE IF THE CURSOR
COOPERATES BUT YOU CAN SEE THAT,
YOU KNOW, I ACTUALLY DON'T THINK
SHE NEEDED A GENETIC TEST TO
TELL ME THIS BECAUSE SHE HAS A
BROTHER WHO HAD HIGH CHOLESTEROL
AT AGE SEVEN. MANY PATERNAL
RELATIVES WHO HAVE HAD HEART
ATTACKS AND BYPASS SURGERY IN
THEIR 40S AND 5ED 0S AND FOUR
OF HER SIX CHILDREN WERE ALSO
REPORTED TO HAVING HIGH
CHOLESTEROL SO THIS SCREAMS
HYPER COALESCE ROLL EEM YA TO
ME.
BUT WHEN SHE ENROLLED SHE --
THIS HAD NOT BEEN ASCERTAINED
AND WE BROUGHT HERE HER TO THE
NIH AND THIS IS A GREAT EXAMPLE
OF HOW SHARING THIS INFORMATION
WITH PEOPLE AND, AGAIN, WE DID A
LOT FOR THIS PERSON. BECAUSE ON
OUR PROTOCOL WE HAVE THE ABILITY
TO BRING THEM TO NIH FOR
PHENOTYPING BUT A HOME CLINICIAN
COULD HAVE DONE THIS TOO.
GENOMIC ASCERTAINMENT CAN
OVERCOME BARRIER TO CLINICAL
CARE AND SO THIS IS A CT SCANNER
FOR HEART AND SHE HAD THE
CORONARY ARTERIES OF A WOMAN IN
HER UPPER 70S.
SO SHE HAD SOME EVIDENCE OF
CORONARY ARTERY CALCIFICATION
ALREADY AND WE STARTED TWO OF
HER FOUR CHILDREN ON TREATMENT
FOR HIGH CHOLESTEROL AND
HOPEFULLY THAT WILL LOWER THEIR
RISKS OF CORONARY ARTERY
DISEASE. SO, AGAIN, I THINK
THIS IS JUST A CONCRETE EXAMPLE
OF HOW THIS CAN MOVE THE NEEDLE
FOR PEOPLE BECAUSE EVEN THOUGH I
WOULD ARGUE THAT YOU DIDN'T NEED
A GENETIC TEST RESULT TO
RECOGNIZE THIS CLINICAL ENTITY
IN THIS PARTICULAR FAMILY, IT
TOOK HAVING THOSE GENOMIC DATA
TO MAKE THAT RECOGNITION.
HERE'S ANOTHER PATIENT WHO WE
HAVE ENROLLED. THIS IS A
36-YEAR-OLD, WHEN THIS WOMAN, WE
MET HER WHEN SHE WAS 40 BUT WHEN
SHE WAS 46 SHE JOINED KIND OF A
BIOBANK STUDY THAT WAS RUN OUT
OF A HISTORICALLY BLACK COLLEGE
AND UNIVERSITY AND SHE WAS
MOTIVATED BY CURIOSITY BUT ALSO
DIDN'T KNOW MUCH ABOUT HER DAD'S
SIDE OF THE FAMILY AND THOUGHT
IT WAS IMPORTANT FOR MINORITIES
TO BE REPRESENTED IN GENETIC
RESEARCH AND THROUGH THAT
PARTICIPATION IN THAT STUDY SHE
LEARNED ABOUT A BRCA 2
PATHOGENIC VARIANT. THIS
INCREASES YOUR RISK OF BREAST
AND OVARIAN CANCER. SHE MET
WITH A COUNSELOR AND DID
SCREENINGS AND ALSO HER PRIMARY
CARE PROVIDER RECOGNIZED THIS
AND URGED HER TO HAVE MAMMOGRAMS
AND SHE ACTUALLY WAS DIAGNOSED
WITH BREAST CANCER AT AGE 39 ON
HER VERY, VERY FIRST MAMMOGRAM.
BUT HAVING THIS FINDING ALLOWED
HER TO REALLY MOTIVATED HER TO
FIND OUT MUCH MORE ABOUT HER
DAD'S SIDE OF THE FAMILY AND SO
THROUGH THIS SHE WAS ABLE TO
RECONNECT WITH FOLKS ON HER
DAD'S SIDE OF THE FAMILY AND
LEARNED ABOUT THIS REALLY
STRIKING HISTORY OF BREAST
CANCER AND PANCREATIC CANCER
WHICH IS ALSO ASSOCIATED WITH
THIS VARIANT ON HER PATERNAL
SIDE OF THE FAMILY. SO, AGAIN,
ANOTHER EXAMPLE OF, YOU KNOW,
SOME OUTCOMES THAT CAN COME FROM
SHARING THIS INFORMATION WITH
PEOPLE. BOTH OF THESE FAMILIES
HAVE BEEN ON DIFFERENT EPISODES
OF THE PODCAST DNA TODAY SO IF
YOU'RE INTERESTED YOU CAN FIND
THEM THERE. AND THEN I'M GOING
TO WRAP UP JUST BY TALKING ABOUT
SGFS. WHICH IS AGAIN, THE
CLINICAL SERVICE THAT BEN ELUDED
TO THAT REONE -- WE RUN TO HELP
RETURN THESE FINDINGS TO
RESEARCH PARTICIPANTS.
IN 2010 WAS THE FIRST TIME OUR
GROUP STARTED USING EXOME AND
GENOME SEQUENCING TO UNDERSTAND
THE CAUSES OF SOME RARE
PEDIATRIC ONSET CONDITIONS AND I
REALLY REMEMBER AT THE TIME
WRITING THE CONSENT FORM. FOR
THAT STUDY. AND REALLY THINKING
ABOUT -- MY POSITION HAS
OBVIOUSLY REALLY CHANGED BECAUSE
I THOUGHT, WELL, WE CAN'T
POSSIBLY TELL THESE PEOPLE
ANYTHING OTHER THAN THE CAUSE
FOR THEIR KID'S CONDITION.
BECAUSE THAT JUST SEEMS SO --
SEEMS LIKE SO MUCH TO BURDEN
THEM WITH. RIGHT? BUT, AGAIN,
MY THINKING HAS REALLY, REALLY
CHANGED HERE. AND I THINK WHAT
I WILL SAY IS THAT, YOU KNOW,
THROUGH THINGS LIKE SGFS WHAT
WE'RE REALLY DOING HERE IS
OPERATIONALIZING THIS
INSTITUTIONAL DUTY HERE AT THE
NIH TO RETURN THESE KINDS OF
RESULTS AND SO THIS IS A
CLINICAL SERVICE THAT'S
AVAILABLE TO INTRAMURAL
INVESTIGATORS WHERE WE SCREEN
SEQUENCE DATA THAT'S BEEN
GENERATED THROUGH A RESEARCH
PROTOCOL SO WE DON'T SEQUENCE
THE PEOPLE. THEY SEND US THEIR
SEQUENCE DATA AND WE LOOK FOR
THESE FINDINGS AND THEN WE HELP
RESEARCH TEAMS TO CLINICALLY
VALIDATE AND RETURN THESE
FINDINGS TO PEOPLE AND SO I DO
THIS. SO I PROVIDE GENETIC
COUNSELING FOR THESE PEOPLE AND
WE GET A FAMILY AND PERSONAL
HISTORY AND THEN MAKE A LOCAL
REFERRAL. AND I THINK AGAIN,
THE MAJOR QUESTION I GET WHEN
PEOPLE ARE APPLYING TO USE THIS
SERVICE IS, WELL, AGAIN, BECAUSE
THE RECOMMENDATION IS TO DO THIS
PROSPECTIVELY, HOW SHOULD I
WRITE THIS CONSENT FORM AND CAN
YOU GIVE OUR TEAM TRAINING ON
CONSENT AND CONCEPT --
CONSENTING PEOPLE TO THIS IS
REALLY NOT HARD.
AGAIN, THINKING ABOUT THE BUILD
UP TO THIS POINT, MOST PEOPLE
REALLY WANT THIS INFORMATION,
MOST PEOPLE THINK THAT GENOMIC
DATA ARE IMPORTANT. AND I DON'T
KNOW THAT WE NECESSARILY NEED TO
THINK ABOUT CONSENTING FOR
RECEIPT OF GENETIC TEST RESULTS
THAT ARE DIFFERENT FROM HEALTH
DATA JUST THINK TO YOURSELF IF
YOU HAVE EVER HAD A DOCTOR ORDER
LIKE A LIPID PANEL OR HEPATIC
PANEL, HAVE THEY EVER SPENT A
LONG TIME TALKING WITH YOU
ABOUT, LIKE, SO HERE'S WHAT
WE'RE GOING FIND AND WE MIGHT
FIND THIS ALSO. I THINK IT'S
JUST KIND OF IMPLIED, RIGHT?
AND SO, TO WRAP UP WHAT I WILL
SAY HERE IS THAT YOU KNOW THIS
HAS BEEN, THERE HAVE BEEN SOME
IMPLEMENTATION CHALLENGES HERE
AND I THINK THESE ARE IMPORTANT
THINGS TO THINK ABOUT. THERE
ARE SOME INDIVIDUAL ATTRIBUTES
ABOUT PARTICIPANTS THAT CAN MAKE
THIS PROCESS OF RETURNING
RESEARCH GENETIC RESULTS
CHALLENGING. THINGS LIKE THEIR
AGE OR THEIR WELLNESS THAT THESE
PEOPLE COME FROM A FRAIL
POPULATION AND BEN MENTIONED
THIS EARLIER AND THEN FINDING
LOCAL REFERRALS FOR RESEARCH
PARTICIPANTS EVEN IN THE U.S. IS
NOT EASY. THERE'S NOT A
CARDIOVASCULAR GENETICIST WITHIN
A 200 MILE RADIUS OF PEOPLE
LIVING IN PLACES LIKE IDAHO AND
NORTH DAKOTA BUT I THINK THE
MAJOR CONCERN HERE IS RECON
CONTACTING PEOPLE AND SO, YOU
KNOW, I THINK THE BIGGEST LESSON
LEARNED HERE MIGHT BE TO JUST,
THE WAY YOU CAN MAKE THIS
MOVE -- GO SMOOTHLY IS TO
MAINTAIN CONTACT WITH YOUR
RESEARCH PARTICIPANTS SO YOU'RE
ABLE TO GET TO THEM LATER IN
TIME. SO JUST SOME VERY BRIEF
ANECDOTAL DATA OF WHAT WE FOUND
IN SGFS, CLINICAL GENETIC
TESTING I THINK IS UNCOMMON. SO
ANOTHER BENEFIT OF DOING THIS
WHOLE THING IS THAT MANY PEOPLE
LIKE THE FAMILY WITH FAMILIAL
HYPER COLEST EEM YA HAVE SIGNS
OF WHAT'S GOING ON AND NOT
GETTING DIAGNOSTIC TESTING. IF
WE LOOK ACROSS THE PEOPLE AT
SGFS, ABOUT 25% REPORT A
DIAGNOSIS BUT NO GENETIC
TESTING. IF THEY'VE GOT A
CLINICAL DIAGNOSIS, MAYBE, YOU
KNOW, I THINK -- IT'S IMPORTANT
TO KIND OF HAVE THE MOLECULAR
BACKGROUND FOR THAT. AND ABOUT
50% OF PEOPLE WHO WE TALK TO
REPORT A CONSISTENT PERSONAL OR
FAMILY HISTORY THAT'S CONSISTENT
WITH THE VARIANT WITHOUT A
CLINICAL DIAGNOSIS OR GENETIC
TESTING SO IN CONCLUSION I THINK
I'VE -- I HOPE I CONVINCED YOU
THAT MOST PEOPLE WANT THIS
INFORMATION. AND THAT
THERE'S -- THE POTENTIAL FOR
SOME REALLY GOOD OUTCOMES THAT
RESULT WHEN WE DO THIS, BUT WE
NEED TO STUDY THIS MORE. AND,
AGAIN, I THINK WE DO HAVE THE
POTENTIAL TO IMPROVE OUTCOMES
FOR PARTICIPANTS BUT THE
BIGGEST, AGAIN, LESSON LEARNED
FOR ME IS THIS REQUIRES ONGOING
INVESTMENT ON THE PART OF
INSTITUTIONS. WHO, YOU KNOW R
THINKING ABOUT THIS
INSTITUTIONAL DUTY TO DO THIS
BUT ALSO, YOU KNOW,
PARTICIPANTS, WE DO PUT A BURDEN
ON THEM TO FOLLOW UP WITH THE,
YOU KNOW, RECOMMENDATIONS THAT
WE MAKE. BUT ALSO ON INDIVIDUAL
RESEARCHERS TO MAINTAIN CONTACT
WITH THEIR PARTICIPANTS TO
FACILITATE THIS BUT, AGAIN, I
THINK THIS HAS THE POTENTIAL TO
CLOSE GAPS IN CLINICAL CARE AND
I THINK WE'RE HIGHLIGHTING SOME
REAL SYSTEMIC CHALLENGES AND
ALLEVIATING SOME OF THOSE. A
LOT OF PEOPLE HAVE CONTRIBUTED
TO THE WORK I PRESENTED TODAY
AND I AM VERY GRATEFUL TO THEM
AND YOU CAN FIND ALL MY
REFERENCES HERE AND I AM IN THE
GLOBAL I DON'T HAVE A SLIDE WITH
MY E-MAIL. GREAT.
>> HI, EVERYONE, QUESTION TO THE
MIC PLEASE, I HAVE A QUESTION DO
YOU HAVE PEOPLE RUNNING TO YOUR
SERVICE? IT SEEMS THIS IS A
REAL, YOU KNOW, OPPORTUNITY IF
I'M AN INVESTIGATOR IN THE
CLINICAL CENTER AND NOT A
GENETICIST AND CONNECTING
INFORMATION IT SEEMS I WOULD
SEND ALL MY PATIENT TO YOU.
>> JULIE. THAT'S A GREAT
QUESTION AND WE'RE NOT THE ONLY
SERVICE THAT CAN DO SOME OF
THIS. SO THE NIAD, THE -- THEY
HAVE A CENTRALIZED SEQUENCING
CORE AND WILL DO ALL OF THESE
THINGS IF YOU SEND ALL THE
THINGS I TALKED ABOUT THEY ARE
THE ONES WHO SEQUENCE YOUR
PATIENTS. BUT, YOU KNOW, I
THINK IT IS NOT AS HEAVILY
UTILIZED AS I COULD HAVE
ANTICIPATED. AND I THINK THAT'S
BECAUSE MANY PEOPLE JUST REALLY
WISH THIS WASN'T A PROBLEM. I
JUST -- MANY PEOPLE JUST REALLY
ARE TRYING TO STRUCTURE
PROTOCOLS IN SUCH A WAY THAT
THEY CAN MAKE AN ARGUMENT WHERE
THEY DON'T HAVE TO DO IT. AND I
HAVE SOME HYPOTHESES ABOUT THAT
BUT I THINK -- I MEAN, IT'S
INCONVENIENT THAT THESE FINDINGS
EXIST BUT IT CAN BE REALLY
BENEFICIAL TO PEOPLE.
>> BUT I WOULD SAY BACK TO THAT
THAT YOU, RIGHT, YOUR TEAM HAS
THE INFRASTRUCTURE TO TAKE CARE
OF IT, RIGHT? SO IF I WAS AN
INVESTIGATOR AND I DIDN'T HAVE
THAT RESOURCE I COULD UNDERSTAND
WHY I WOULD WANT TO AVOID IT.
>> JULIE: I THINK INFRASTRUCTURE
IS A HUGE THING. IT IS
COMPLETELY UNREALISTIC. I MADE
THE ARGUMENT THAT YOU DO NOT
NEED ANY SPECIAL EXPERTISE TO
CONSENT PEOPLE TO THIS IDEA. I
REALLY THINK A CHATBOT CAN DO
THIS AND I'M VERY EXCITED BY
RESEARCH THAT'S EMERGING FOR HOW
WE CAN MEET THE CONSENT NEEDS
AND MY MAIN THOUGHT WITH BEN'S
CASE THAT HE PRESENTED WAS, YOU
KNOW, HOW CONFIDENT IS THE TEAM
IN THE ROBUSTNESS OF THE CONSENT
PROCESS THAT THEY WERE CONFIDENT
THAT THAT PERSON'S CHOICE WOULD
BE DURABLE. THAT'S KIND OF A
BIT OF A TAN JEPT -- TANGENT BUT
EXPERTISE IS HELPFUL.
>> I WANT TO FOLLOW UP ON OTHER
THINGS. I DON'T HAVE QUESTIONS
YET BUT COME UP TO THE MIC. I
REALLY LIKED YOUR COMMENT ABOUT
TICKING THE BOX. -- THERE'S A
CONTENT FORM. SOMEONE PUT FILLS
OUT A CONSENT FORM.
AND YOU HAVE SOME DATA. AND SO
THIS IS MY GENERAL PITCH TO
EVERYONE. DON'T USE CONSENT
FORMS TO COLLECT IMPORTANT
INFORMATION RELATED TO THE
IMPLEMENTATION OF YOUR PROTOCOL.
RIGHT? BECAUSE YOU'RE GOING TO
END UP IN SITUATIONS WHICH JUST
SOUNDS LIKE YOU HAD AT LEAST
ONCE WHERE SOMEONE TICKED THE
BOX, NO, I DON'T WANT IT AND THE
DATA GOT TO YOU AND YOU HAVE THE
PARTICIPANT IN FRONT OF YOU, NOW
WHAT DO I DO? SO JUST A PITCH,
YOU KNOW, I KNOW THAT'S CONTRARY
TO OUR CURRENT BOILERPLATE BUT,
OR MAKE SURE YOU'RE COLLECTING
IT ELSEWHERE. NOT JUST ON --
>> JULIE: AND THE COROLLARY TO
THAT IS PLEASE LET US KNOW IF
YOU MOVE. MROOET PLEASE KEEP US
POSTED ABOUT YOUR HEALTH CARE.
IF YOU REALLY WANT TO KNOW
YOU'VE GOT TO TALK TO PEOPLE
ONCE A YEAR. AT LEAST. SEND
THEM A HOLIDAY CARD. THERE'S
LOTS OF WAYS TO DO THIS.
>> GREAT. ONE QUICK QUESTION
AND I WILL GET TO BRITTANY JUST
TO CLARIFY FOR ALL OF -- SO THE
QUESTION FROM SARA IS FOR
CLINICAL TESTING IS CONSENT
REQUIRED PRIOR TO TESTING BEING
DONE. WE'VE BEEN TALKING ABOUT
IT IN THE RESEARCH SETTING IN
THE CLINICAL SETTING --
>> JULIE: ABSOLUTELY. EVERY
LABORATORY IS GOING TO HAVE A
CONSENT FORM IN THEIR CONSENT
FORM THEY'RE GOING TO REQUIRE
THE CLINICAL PERSON TO CHECK THE
BOX ABOUT WHETHER OR NOT THEY
WANT SECONDARY FINDINGS AND IT
GETS TRANSMITTED ALONG WITH THE
SAMPLE.
>> AUDIENCE: I WAS WONDERING IF
PEOPLE MIGHT NOT WANT SECONDARY
FINDINGS BECAUSE IT'S JUST TOO
ABSTRACT AT THAT TIME. SO IF I
WAS ASKED LIKE DO YOU WANT SOME
GENETIC INFORMATION THAT WE
MIGHT FIND I'D PROBABLY BE LIKE
I DON'T THINK SO BUT THEN IF IT
WAS THE CASE OF SOMEBODY WHO HAS
THAT, WHAT WAS IT COLORECTAL
CANCER INDICATOR AND IT'S LIKE
THIS IS SOMETHING THAT COULD
KILL YOU UNLESS YOU KNOW THIS,
WOULD THERE BE A WAY TO REACH
OUT TO THEM AND SAY WE FOUND
SOMETHING AND WE KNOW YOU DIDN'T
WANT INFORMATION BUT THIS MIGHT
SAVE YOUR LIFE.
>> JULIE: I THINK THAT'S THE
LYNCHPIN OF THE CONSENT PROCESS
WHERE, AGAIN, I KNOW I USED THE
EXAMPLE OF HAS YOUR DOCTOR SAT
DOWN AND SAID ON YOUR LIPID
PANEL I SEE YOUR HDL AND HERE IS
WHAT I MIND FIND. NO. WHEN WE
CONSENT FOR THIS IT DOES NOT
MEAN COMPLICATED. WE SAY WE
WILL DO SOME SEQUENCING AND
SOMETIMES WE FIND OUT A
PREDECISION POSITION TO A
TREATABLE DISZ DISEASE WHEN WE
FIND SOMETHING LIKE THAT IT
MAKES US UNCOMFORTABLE TO KNOW
THAT ABOUT YOU AND NOT SHARE IT
WITH YOU.
IF WE FIND SOMETHING THAT YOU'RE
AT AN INCREASED RISK FOR
SOMETHING TREATABLE OR
PREVENTABLE WE WILL SHARE THAT
WITH YOU, WHAT DO YOU THINK?
RIGHT? SO I THINK IT HAS TO BE
CONCRETE AND EXAMPLES AND I
THINK, AGAIN, I OFTEN GIVE
EXAMPLES OF HYPER KOE LEST RAL
EEM YA OR HEART DISEASE OR
CANCER AS OPPOSED TO ALZHEIMER'S
DISEASE, PARKINSON'S DISEASE. I
THINK YOU'RE RIGHT, I, YEAH,
THERE'S CERTAINLY CONTEXTUAL
ELEMENT TO THIS FOR SURE.
>> AND I THINK IT KIND OF BRINGS
US BACK TO DANIEL'S COMMENT
EARLIER ABOUT, YOU KNOW, THE
SORT OF ONE DAY WE MIGHT ALL
WANT OF THIS INFORMATION
REGARDLESS IF IT'S A
PREDISPOSITION OR AN AUTOSOMAL
DOMINANT OR NO TREATMENT
AVAILABLE. WE CHANGED OUR MINDS
BEFORE AND WE MIGHT CHANGE OUR
MINDS, YOU KNOW, AGAIN.
>> JULIE: ABSOLUTELY WHICH IS
WHERE I THINK OUTCOME RESEARCH
IS SO IMPORTANT BECAUSE WE FIND
THAT JUST BECAUSE YOU TELL
PEOPLE THIS AND I DIDN'T REALLY
GET INTO IT THAT MUCH BUT JUST
BECAUSE YOU TELL THEM DOESN'T
MEAN THEY ACTUALLY -- IT SAVES
THEIR LIVES THERE'S SO MANY
BARRIERS.
>> RIGHT. AND, EXACTLY.
>> JULIE: BUT THAT'S LIKE OTHER
HEALTH CARE DATA. EVERY SMOKER
HAS BEEN TOLD BY EVERY DOCTOR TO
QUIT SMOKING. SO --
>> SO THIS IS A REALLY IMPORTANT
QUESTION. WHAT IS ACMG FINDINGS
MEAN?
>> JULIE. I AM SO GLAD THEY
ASKED -- IT IS SUCH A WORD SALAD
WHAT ON EARTH ARE WE TALKING
ABOUT. THE AMERICAN COLLEGE OF
AMERICAN GENETICS AND GENOMICS
IT'S THE ACCREDITING BODY FOR
GENOMIC PROFESSIONALS IN THE
U.S.
AND THE LIST IS A SET OF GENE
WHERE IS THIS BODY HAS SAID IF
YOU FIND A PATHOGENIC AND THAT
MEANS DISEASE CAUSING VARIANT,
IN ONE OF THESE GENES, YOU
SHOULD TELL SOMEONE ABOUT THAT.
BECAUSE IT HAS THESE ATTRIBUTES
THAT WE'VE BEEN TALKING ABOUT.
THAT IT'S TREATABLE, IT'S
PREVENTABLE. THE DISEASE, AND
IMPORTANTLY, WE KNOW A LOT ABOUT
THE GENETICS OF THAT CONDITION.
RIGHT? SO THESE AREN'T
HYPOTHETICAL, YOU KNOW, MAYBE
THERE'S AN ASSOCIATION BETWEEN
THIS VARIANT AND, YOU KNOW,
GLUTEN INSENSITIVITY. YOU KNOW,
THERE'S REALLY ROCK SOLID
EVIDENCE TO SUGGEST THAT IF YOU
HAVE THIS VARIANT, YOU COULD, IT
COULD SAVE YOUR LIFE TO DO
SOMETHING ABOUT IT, BASICALLY.
>> I WILL POST A LINK TO THE
ACMG AND THE MOST RECENT
PUBLICATION SO FOLKS WHO WANT TO
LEARN MORE CAN DO SO. THANK
YOU, NICE TO HAVE YOU AND SHARE
YOUR KNOWLEDGE. WE EVER AT --
WE ARE AT THE TIME OF OUR BREAK
SO PLEASE RETURN AT 10:35 WHERE
AS I MENTIONED WE WILL BE JOINED
BY KATRINA WHO WILL TALK ABOUT
CONDUCTING RESEARCH WITH
INDIGENOUS COMMUNITIES. SO SEE
YOU BACK SOON. (BREAK).
FOCUSES ON PERSONALIZING
MEDICINE, PHARMCO YESACOGENOMIC
THE ETHICAL IMBRING OCCASION OF
GENOMIC RESEARCH OF THE
INDIGENOUS DMIENS.
SO WITH THAT, I'M GOING TO HAND
IT OTHER TO YOU DR. CLAW. IT'S
ALL YOURS.
>> HI, THERE, THANK YOU VERY
MUCH, CAN EVERYONE HEAR ME OKAY?
>> WE CAN, WE CAN'T SEE THE
SLIDES. CAN YOU SHARE THEM.
>> I WILL. ON MY END I HEARD A
LITTLE BIT OF BREAKING UP SO IF
I BREAK UP JUST SEND ME A CHAT
AND I WILL TRY TO PAUSE. BUT
GREAT, DOES EVERYONE SEE MY
SLIDES?
>> WE DO.
>> OKAY, GREAT. WELL THANK YOU
SO MUCH FOR THAT INTRODUCTION,
HOLLY. AND HI, EVERYONE. (IN
DIALECT). THANK YOU SO MUCH FOR
INVITING ME, THIS IS ALWAYS A
FUN TIME OF THE YEAR WHEN I GET
TO THE NIH AND FOLKS TAKING THIS
COURSE. SO I WANTED TO START
OFF BY ACKNOWLEDGING THE
TRADITIONAL HOMELANDS OF WHERE I
DO MY RESEARCH AT THE UNIVERSITY
OF -- OR, UNIVERSITY OF
COLORADO. WE ALSO HAVE A
DOWNTOWN CAMPUS SHOWN HERE BUT
THESE ARE THE TRADITIONAL
HOMELANDS OF THE APACHE,
COMANCHE AND ALSO HOME TO MANY
OTHER INDIGENOUS PEOPLES TODAY.
SO TODAY I HOPE TO RELAY THE
IMPORTANCE OF THINKING ABOUT
DIVERSITY, EQUITY AND EQUALITY
AND HEALTH CARE RESEARCH AND
HEALTH RESEARCH AND WHY IT'S
IMPERATIVE TO ENGAGE COMMUNITIES
IN YOUR RESEARCH. FIRST OFF, I
WILL CONTEXTUALIZE MY
EXPERIENCES WITH SOME OF THE --
MY JOURNEY IN ACADEMIA AND
MOTIVATIONS FOR DOING THE WORK
THAT I DO, AS WELL HOW I'M
MOVING TOWARDS COMMUNITY BASED
RESEARCH IN MY WORK. SO TO
START OFF, I GREW UP ON THE
NAVAJO NATION WHICH IS SHOWN
HERE IN THE MIDDLE OF THE FOUR
CORNERS OF -- SO THE NAVAJO
NATION SPANS ACROSS ARIZONA, NEW
MEXICO AND UTAH WE HAVE ALMOST
500,000 ENROLLED MEMBERS IN THE
NAVAJO TRIBE AND IT'S THE
LARGEST TRIBAL LAND BASE AS
WELL. SO THIS BLACK BLOB HERE
IS ABOUT THE SIZE OF WEST
VIRGINIA. SO I GREW UP HERE AND
WENT TO HIGH SCHOOL HERE AND ALL
OF MY FAMILY STILL LIVE ON THE
NAVAJO NATION. BUT I ALSO DID
MY POSTDOC AND MY PH.D. AT
UNIVERSITY OF WASHINGTON. SO I
SPENT QUITE A FEW YEARS THERE AS
I GOT MY PH.D. IN GENOME
SCIENCES AND THEN I DID A
POSTDOC WITH THE NORTHWEST
ALASKA PHARMACOGENOMICS RESEARCH
NETWORK IN WHICH I HAD ADVISORS
BOTH IN PHARMACEUTICS AND
BIOETHICS BUT WHAT WAS REALLY
GREAT ABOUT THE NWAPGRN IS THEY
HAD A REALLY DIVERSE TEAM BUT
THEY WORKED WITH TRIBAL
COMMUNITIES AND WERE AT ITS CORE
THEY WERE TRYING TO DO COMMUNITY
ENGAGED RESEARCH AS WELL AS
THINKING ABOUT THE ETHICAL AND
SOCIAL IMPLICATIONS OF THAT
RESEARCH IN THOSE COMMUNITIES.
SO IN 2019, I MOVED BACK TO MY
BELOVED SOUTHWEST AND STARTED MY
OWN RESEARCH PROGRAM AT THE
UNIVERSITY OF COLORADO. SO I
HAVE ALWAYS WANTED TO WORK WITH
MY OWN TRIBE AND OTHER
INDIGENOUS PEOPLES AND IT'S ALSO
AN IDEAL FOR MANY NATIVE ELDERS
AND FAMILIES. THEY ALWAYS TELL
YOU GO AND GET YOUR EDUCATION
AND THEN COME BACK AND HELP YOUR
PEOPLE. SO I HOPE THAT THE WORK
THAT I'M DOING NOW IS AFFECTING
SOME OF THE WORK THAT I DO WITH
MY OWN COMMUNITY AS WELL AS
OTHER TRIBAL NATIONS. BUT,
GROWING UP I DID NOT KNOW WHAT
RESEARCH WAS. AND IT WASN'T
UNTIL I CONDUCTED MY OWN
RESEARCH IN HIGH SCHOOL THAT I
REALIZED WHAT IT WAS AND HOW FAR
IT COULD TAKE ME IN MY CAREER.
AND IT WASN'T UNTIL I WAS
PROBABLY A LATE UNDERGRADUATE
WHEN I REALIZED THIS COULD BE A
CAREER FOR ME. BUT IT WAS
REALLY BECAUSE OF THE
INFLUENTIAL ATTENTIVE AND
SUPPORTIVE MENTORS AND COMMUNITY
AND FAMILY AND MANY DIVERSITY
PROGRAMS THAT I WAS A PART OF IS
THAT IS WHY I'M HERE TODAY AND
SOME OF THESE MENTORS WERE
SCIENTISTS BUT ALSO OTHERS WERE
MEMBERS OF MY FAMILY AND SAW MY
POTENTIAL AND GUIDED ME AND SAW
ME ONWARD I WHOLEHEARTEDLY THAT
SCIENCE IS NOT A SOLITARY EFFORT
BUT ONE INFORMED BY YOUR
COMMUNITIES. AS I WANTED TO
THINK MORE ABOUT GENOMIC
RESEARCH AND MOVE MY RESEARCH
BEYOND GENETIC FINDINGS, I FOUND
THAT THERE WAS A DISCONNECT
BETWEEN GENOMIC RESEARCH AND
INDIGENOUS COMMUNITIES. I THINK
MANY PEOPLE THINK THAT NATIVE
AMERICANS ARE ANTISCIENCE. BUT
REALLY WE JUST WANT RESEARCH TO
BE DONE ON OUR OWN TERMS WE HAVE
OUR OWN WORDS FOR DNA SO IN
NAVAJO WE HAVE OUR OWN WAYS OF
KEEP TRACKING OF OUR GENEALOGY
AND SOCIAL RELATIONSHIPS AND
HISTORIES AND FAMILY TRAITS. WE
HAVE COMPLEX RELATIONSHIPS WITH
OUR ENVIRONMENT AND ECOLOGIES
AND REALLY WE JUST WANT OUR
FAMILIES AND FUTURE GENERATIONS
TO BE HEALTHY TOO. SOMETHING
THAT MANY OTHER COMMUNITIES ALSO
FEEL. BUT WHEN THE GENOMIC
REVELATION -- REVOLUTION STARTED
GAINING MOMENTUM, INDIGENOUS
PEOPLES WERE HESITANT TO
PARTICIPATE BECAUSE OF PAST
ABUSE, RESEARCH MISCONDUCT AND
HELICOPTER SCIENCE. THIS IS ONE
EXAMPLE OF THE HAVASUPAI TRIBAL
MEMBERS LEARNING THAT THEIR DNA
SAMPLES WERE USED FOR -- TO
STUDY SCHIZOPHRENIA AND HUMAN
MIGRATION RESEARCH, THINGS THAT
THEY HAD NOT AGREED TO INITIALLY
SO BACK IN 2010 THIS WAS SETTLED
OUTSIDE OF COURT AND THE TRIBAL
MEMBERS WERE ABLE TO RECEIVE
THEIR SAMPLES BACK BUT THIS HAS
REALLY AFFECTED THAT COMMUNITY.
THAT COMMUNITY IS STILL VERY,
VERY DISTRUSTFUL OF RESEARCHERS
COMING INTO THEIR COMMUNITY AND
TAKING SAMPLES AND NOT COMING
BACK.SO WITHIN MY OWN TRIBAL
COMMUNITY, GENETIC RESEARCH IS
ACTUALLY NOT EVEN ALLOWED.
SO IN -- BACK IN 2002 RIGHT
AROUND THE TIME I WAS STARTING
COLLEGE, A MORATORIUM OR A BAN
ON GENETIC RESEARCH WAS PUT IN
PLACE ON THE NAVAJO NATION. AND
THIS WAS BECAUSE AT THAT TIME
THERE WAS A LOT GOING ON WITH
THE -- WITH DIFFERENT PROJECTS
TRYING TO OBTAIN SAMPLES FROM
INDIGENOUS PEOPLES BUT FOR THE
NAVAJO PEOPLE THEY CONSULTED
WITH THEIR TRIBAL LEADERS, AND
ALSO NAVAJO PEOPLE WITH TRAINING
AND THEY REALIZED THAT THE
NAVAJO NATION LACKED POLICIES
FOR GENETIC RESEARCH PROTOCOLS
AND OVER 20 YEARS LATER THIS
MORATORIUM IS STILL IN PLACE.
SO I THINK THAT IT'S -- I THINK
IT'S IRONIC, SOMETIMES THAT
MY -- I RECEIVED MY PH.D. IN
GENETICS BUT I'M NOT ABLE TO
CONDUCT ANY GENETIC RESEARCH
WITH MY OWN TRIBAL COMMUNITY BUT
I THINK IT'S PRECISELY BECAUSE
OF THIS LACK OF NAVAJO AND OTHER
INDIGENOUS GENETICISTS THAT I
PURSUED THIS PATH. WE LOOKED AT
THE LITERATURE, WE DID A
LITERATURE REVIEW AND WE LOOKED
AT STUDIES THAT HAD BEEN
CONDUCTED IN NAVAJO PEOPLE.
THESE ARE JUST A SNAPSHOT OF
SOME OF THE STUDIES AND JUST
FROM THE TITLES YOU KNOW THEY'RE
A LITTLE BIT, MIGHT HAVE SOME
ISSUES SO ONE OF THEM WAS
INBREEDING COEFFICIENTS IN THE
NAVAJO POPULATION. ANOTHER WAS
A STUDY OF BLOOD GROUPS AMONG
AMERICAN INDIANS IN
THE-AND-A-HALF ROW BUT FOR THIS
STUDY OF THE BLOOD GROUPS A LOT
OF THOSE SAMPLES WERE COLLECTED
FROM CHILDREN IN BOARDING
SCHOOLS IN THE NAVAJO NATION.
AND THEN THIS OTHER STUDY ON
COLORECTAL CANCER THE STUDY
PUBLISHED VERY DETAIL DETAILE
PEDIGREES AND SINCE THESE ARE
ICE -- ISOLATED COMMUNITIES
THERE WERE ISSUES.
AND WE RECEIVED PUBLICATIONS
FROM THE EARLY 1900S AND FEW
STUDIES MADE MENTION OBTAINING
TRIBAL IRB APPROVAL AND WHILE
STANDARDS HAVE CHANGED THIS
REFLECTS THE TREND OF HOW FEW
STUDIES INVOLVED COMMUNITIES AND
RESPECTED TRIBAL SOVEREIGNTY.
SO MORE BROADLY IN NATIVE
AMERICAN COMMUNITIES THESE ARE
THE CONCERNS OF PARTICIPATION
AND RESEARCH. THERE ARE MANY
CULTURAL AND ETHICAL CONCERNS.
THERE'S ALWAYS CONCERNS ABOUT
THE LACK OF ADEQUATE COMMUNITY
CONSULTATIONS. AND SPECIFICALLY
WHEN WE'RE IN THE GENOMIC ERA
THERE'S CONCERNS ABOUT LONG-TERM
DATA STORAGE AND BUY LOW C-- BI
SAMPLE STEWARDSHIP.
I WANTED TO FOCUS ON QUESTIONS
OF MY COMMUNITY BACK WHEN I
STARTED MY POSTDOC PERSONALIZED
MEDICINE WAS A BUZZWORD IN THE
COMMUNITY AND I THINK STILL IS I
DECIDED TO FOCUS ON
PHARMACOGENOMICS BECAUSE I
THOUGHT OF THAT AS SORT OF THE
FOUNDATION OF PRECISION MEDICINE
AND A LOT OF PEOPLE THOUGHT THIS
WAS ONE OF THE LOW-HANGING
FRUITS OF HOW YOU COULD USE
GENETICS INFORM DRUG DOSAGE AND
DRUG, WHAT PRESCRIPTIONS THAT
YOU USE. ALSO I WAS DRAWN TO
THIS AREA BECAUSE OF TRADITIONAL
MEDICINES USED IN OUR COMMUNITY
TODAY AND HAVE INFORMED A LOT OF
THE PHARMACEUTICAL DRUGS THAT
HAVE BEEN CREATED IN MODERN
TIMES. BUT OF COURSE AS YOU GO
THROUGH THE STEM FIELDS THERE
ARE DEFINITELY UNEQUAL --
INEQUALITIES THAT YOU EXPERIENCE
ESPECIALLY COMING FROM A TRIBAL
COMMUNITY AND THEN BEING IN A
LARGER INSTITUTION SOME OF THESE
INCLUDED SOME SACRIFICES OF
BEING AWAY FROM HOME. LOSING
SOME OF MY LANGUAGE AND NOT
BEING ABLE TO BE A PART OF OUR
TRADITIONAL EVENTS AND
CEREMONIAL EVENTS BACK HOME.
THERE'S A LOT OF SELF-DOUBT AND
IMPOSTER SYNDROME, LONELINESS
AND ALSO AS I STARTED GETTING
INTO MY POST-DOCTORAL POSITION
AND FACULTY POSITIONS I REALIZED
THERE WERE NOT EQUAL NETWORKS.
I DID NOT HAVE THOSE ESTABLISHED
NETWORKS THAT A LOT OF FOLKS
HAVE. IF YOU HAVE FAMILY MIGHT
BE WHO IS HAD GONE THROUGH
HIGHER EDUCATION TRAINING
BEFORE. SO A PART OF MY
MOTIVATIONS FOR MY RESEARCH
PROGRAM IS REALLY SUPPORTING
EQUITY AND INCLUSION OF DIVERSE
POPULATIONS IN GENOMIC RESEARCH.
ALSO ADDRESSING HEALTH AND
HEALTH CARE DISPARITIES AND THEN
ENHANCING ETHICAL RESEARCH WITH
INDIGENOUS AND OTHER
UNDERREPRESENTED COMMUNITIES AND
I LIKE TO SHOW THIS FIGURE HERE
BECAUSE THIS IS THE -- ONE OF
THE GWAS MONITORS. DAILY I
THINK THIS WAS FROM TO YEARS AGO
SO I HAVE TO UPDATE THIS BUT IT
HASN'T REALLY CHANGED.
SO IF YOU LOOK AT THIS GWAS
DIVERSITY MONITOR YOU WILL SEE
REALTIME HOW MANY STUDIES ARE
INVOLVING OTHER POPULATIONS. BY
FAR ABOUT 95% ARE EUROPEAN
DISSENT POPULATION WHO IS ARE
INVOLVED IN THESE LARGE-SCALE
GENOME PROJECTS.
AND THE REST OF THE 4-5% ARE ALL
OF THE OTHER WORLD POPULATION.
INDIGENOUS PEOPLES AREN'T ON
HERE BUT THEY'RE ABOUT .04%
REPRESENTATION. SO THAT'S WHY I
HAVE MY LAB. AND IT'S
SPECIFICALLY FOCUSED ON WORKING
WITH INDIGENOUS PEOPLES. ONE
PART OF MY LAB DOES
PHARMACOGENOMICS RESEARCH SO WE
STUDY THE CYTOCHROME ENZYMES AND
WORK WITH TRIBAL PARTNER TO
DETERMINE WHAT THEY'RE
INTERESTED IN.
SO ONE OF THE AREAS THAT BECAME
INTERESTING TO TRIBAL PARTNERS
WERE LOOKING AT NICOTINE
METABOLISM AND HOW WE CAN USE
THAT TO CREATE PERSONALIZED
PHARMACOTHERAPY FOR PEOPLE WHO
WANTED TO STOP SMOKING THE OTHER
ASPECT OF MY WET LAB WE'RE
TRYING TO UNDERSTAND WHAT THESE
VARIANTS DO IN CELL CULTURES AND
THEN A PART OF MY BACKGROUND IS
IN EVOLUTIONARY GENOMICS SO I'M
REALLY INTERESTED IN SEEING HOW
THESE ENZYMES HAVE CHANGED OVER
TIME. AND THEN THE OTHER PART
OF MY WORK SORT OF AROSE OUT OF
MY EFFORTS TO DO COMMUNITY
ENGAGED RESEARCH WITH
COMMUNITIES. SOMETIMES
COMMUNITIES WERE NOT READY TO
JUMP INTO A FULL BLOWN RESEARCH
STUDY. SO WE STEPPED BACK AND
THEN WE DECIDED TO DO LOOK USING
QUALITATIVE AND MIXED METHODS
RESEARCH WE DECIDED TO ACTUALLY
TAKE A LOOK AT WHAT'S THE
LANDSCAPE LIKE IN THE
COMMUNITIES? SO THIS IS ONE OF
THE PROJECTS THAT I'M DOING WITH
THE NAVAJO NATION. WHERE WE ARE
ACTUALLY SERVING PEOPLE ABOUT
WHAT DO THEY THINK ABOUT GENETIC
RESEARCH, WHAT DO THEY THINK
ABOUT THE MORATORIUM, WHAT ARE
BIG CONCERNS IN THEIR
COMMUNITIES, DO SO I DO THIS
RESEARCH WITH VARIOUS
COMMUNITIES.
WHO REALLY WANT TO TAKE A STEP
BACK AND TALK BEFORE YOU JUMP
INTO THE ACTUAL RESEARCH. THE
OTHER PART OF MY WORK IS LOOKING
AT ANCIENT DNA ETHICS AND THEN
ALSO MENTORING INDIGENOUS
TRAINEES THROUGH THE SING
PROGRAM AS WELL AS THE PRIME
PROGRAM SO I'M EXTREMELY
THANKFUL TO ALL OF MY TRAINEES,
COLLABORATORS AND TRIBAL PARTNER
WHO IS REALLY MOVED THIS
RESEARCH FORWARD. THE OTHER BIG
PART OF MY LABORATORY IS
BRINGING MY CULTURE INTO THE
LAB. SO THIS IS AN ACTUAL
PICTURE OF MY LAB BACK IN 2020
WHEN I WAS ABLE TO MOVE INTO THE
SPACE BUT WE HAD A TRADITIONAL
CEREMONY TO OPEN UP THE LAB
BEFORE ANY SAMPLES WERE BROUGHT
IN I ALSO HAVE INDIGENOUS
TRAINEES WHO WORK IN MY LAB AND
OFTEN CONTACT ME FOR TRAINING
OPPORTUNITIES. BUT I WANTED TO
SWITCH GEARS INTO THIS IDEA
ABOUT INDIGENOUS SCIENCE. SO,
INDIGENOUS PEOPLE HAVE ALWAYS
BEEN SCIENTISTS. FROM BUNCH
PRACTICES IN SOME INDIGENOUS
COMMUNITIES, A LOT OF THE
VEGETABLES THAT WE HAVE TODAY
ARE -- WERE OR RELIGIONALLY
DOMESTICATED BY INDIGENOUS
PEOPLES AND EVEN THOUGH THERE
WAS NOT THE UNDERSTANDING OF
GENETICS AS WE HAVE IT, NOW
THERE IS -- THERE WAS DEFINITELY
AN UNDERSTANDING OF HOW YOU WERE
ABLE TO MAINTAIN BALANCE WITH
THE ENVIRONMENT BUT ALSO
CULTIVATE DOMESTIC PRODUCTS OR
PRODUCTS THAT PEOPLE COULD EAT
AND USE. SO WITHIN INDIGENOUS
SCIENCE THERE ARE MULTIPLE WAYS
OF KNOWING. SOMETIMES PEOPLE
CALL THIS TRADITION AL KNOWLEDG,
OR INDIGENOUS KNOWLEDGE, OFTEN
THESE ARE PASSED ON THROUGH ORAL
OR WRITTEN KNOWLEDGE A LOT OF
TYPES IT'S ORALLY TRANSMITTED.
CEREMONIAL PRACTICES AND BELIEFS
AND ALSO A GENERAL KNOWLEDGE
PASSED ON FROM OUR ANCESTORS SO
RECENTLY, WELL, NOT SO RECENTLY,
IT'S FIVE YEARS AGO BUT WE, A
COLLEAGUE AND I PUBLISHED AN
INDIGENOUS SCIENCE SPECIAL ISSUE
IN HUMAN BIOLOGY WHERE WE
HIGHLIGHT MULTIPLE INDIGENOUS
AUTHOR WHO IS ARE INCORPORATING
INDIGENOUS SCIENCE.
INTO THEIR RESEARCH PROTOCOLS.
SO TAKE A LOOK, I THINK IT'S
FREELY AVAILABLE IF PEOPLE ARE
INTERESTED. BUT MOVING INTO THE
WORK THAT I DO, SO WITHIN THE
UNITED STATES, THERE ARE OVER
574 FEDERALLY RECOGNIZED TRIBES
ABOUT 70-80% OF THE TRIBAL
MEMBERS LIVE IN CITIES AND NOT
THE COMMUNITIES. SO A LOT OF
MAJOR CITIES, WASHINGTON DC,
DENVER, PHOENIX, A LOT OF THESE
PEOPLE HAVE NATIVE SCHEMES JUST
TO GO BACK TO SOME OF THE
ETHICAL.
REGULATIONS IN PLACE SO I'M SURE
MANY OF YOU HAVE HEARD OF THE
COMMON RULE. SO THE COMMON RULE
UPHOLDS TRIBAL SOVEREIGNTY SO
WHAT DOES THAT MEAN? THAT MEANS
THAT THE TRIBAL SOVEREIGNTY IS
EXTENDS TO RECOGNIZE AMERICAN
INDIAN ALASKAN NATIVE TRIBES BUT
THE COMMON RULE UPHOLDS THE
RIGHT OF AUTHORITY OF U.S. TRIBE
TO APPROVE OR DISAPPROVE OF
RESEARCH IN THEIR COMMUNITY. SO
IT IS A LEGAL THING WHERE YOU DO
HAVE TO CONSULT WITH TRIBAL
COMMUNITIES IF YOU'RE PLANNING
TO DO RESEARCH WITH THEM. SO
WITHIN MY FIELD, PERSONALIZED
AND PRECISION MEDICINE THIS IS A
FIELD THAT TRIES TO USE GENETIC
INFORMATION, ENVIRONMENT AND
LIFESTYLE TO AID IN THE
DIAGNOSIS, PREVENTION AND
TREATMENT OF DISEASES AND I AM
SURE MANY OF YOU HAVE HEARD OF,
OOPS. OF SOME OF THESE EFFORTS,
THE ALL OF US IS ONE OF THE MOST
WELL-KNOWN EFFORTS, THE
PRECISION INITIATIVE WHICH WAS
ANNOUNCED BY -- PRESIDENT BARACK
OBAMA A COUPLE YEARS AGO AND NOW
THERE ARE OTHER BIOBANKS THAT
ARE TRYING TO DO SOMETHING
SIMILAR WHERE THEY'RE COLLECTING
SAMPLES AND HOPING TO USE THIS
INFORMATION COUPLED WITH
ELECTRONIC HEALTH MEDICAL
RECORDS AND VERY DETAILED
SURVEYS TO MAKE THIS INFORMATION
AVAILABLE TO RESEARCHERS WHO
WANT TO STUDY DIFFERENT DISEASES
AND HEALTH CONDITIONS. SO
WITHIN PHARMACOGENOMICS, THIS
FIELD AIMS TO ESTABLISH HOW
GENES AFFECT A PERSON'S RESPONSE
TO DRUGS. AND PHARMACOGENOMICS
GUIDES THE SELECTION OF THE BEST
DRUG AND DOSE OF AN INDIVIDUAL
AND IT'S PREDICTED TO REDUCE THE
COST OF ADVERSE DRUG REACTIONS
WHICH IS ACTUALLY QUITE
EXPENSIVE IN THE RIGHT NOW IN
HEALTH CARE. SO IF I GO TO THIS
CARTOON AND TAKE A DIVERSE
POPULATION HERE, SOMETIMES IF
YOU TREAT A CERTAIN POPULATION
WITH A PARTICULAR MEDICATION THE
VAST MAJORITY WILL HAVE A
FAVORABLE RESPONSE SO YOU'RE
ABLE TO TREAT THESE PEOPLE IN
BLUE WITH A CONVENTIONAL DRUG OR
DOSE. BUT THERE ARE OTHER
PEOPLE WHO, BECAUSE OF THEIR
GENETIC PROFILE, MIGHT NOT
RESPOND OR THEY MIGHT HAVE AN
ADVERSE EFFECT AND WITH THESE
PEOPLE WHO ARE IN RED AND
PURPLE, YOU WILL WANT TO TREAT
WITH AN ALTERNATIVE DRUG OR DOSE
BUT GETTING TO THIS POPULATION
IN THE PINK AND RED IS ACTUALLY
A REALLY HARD PROCESS BECAUSE
YOU HAVE TO HAVE GENETIC
INFORMATION AVAILABLE. YOU HAVE
TO HAVE EVIDENCE BEHIND THE DRUG
GENE PAIRS AND THEN YOU HAVE TO
HAVE A WAY TO IMPLEMENT THIS IN
THE COMMUNITY. SO THAT'S
ACTUALLY ONE OF THE HARDEST
THINGS THAT WE'RE -- FOLKS ARE
TRAINED TO DO IN PRECISION
HEALTH SO ONE OF THE ENZYMES
THAT I -- A FAMILY OF ENZYMES
THAT I STUDY ARE THE CYTOCHROME
Q450 ANN EN -- ENZYMES.
THERE ARE 57 ENZYMES IN THE
HUMAN BODY THAT ARE INVOLVED IN
SOME TYPE OF DRUG METABOLISM
ABOUT 75% OF THE DRUGS THAT
PEOPLE TAKE TODAY ARE ME TABIZED
IN THIS GENE FAMILY.
AND INSERTIONS AND DELETIONS ARE
A BIG PART OF WHY WE SEE SOME
GENETIC VARIANCE IN HOW PEOPLE
RESPOND TO MEDICATIONS AND THEN
INTERESTINGLY THERE ARE ALSO
COPY NUMBER OF VARIATIONS.
SO WITH ONE OF THE MORE COMMON
ENZYMES WE SEE A LOT OF NOON
ALLELE I DIDN'T CARE HOMOLOGOUS
RECOMBINATION OCCURRING WHERE
YOU MIGHT GET HYBRIDS. SO
THEY'RE A REALLY INTERESTING
FAMILY TO STUDY SO IN TERMS OF
THE ACTUAL GENES SO THIS IS JUST
AN EXAMPLE OF 2D 6 I AM NOT
GOING TO GO TOO IN DEPTH BUT
IT'S A GENE CARTOON AND WITH
EACH, OR DIFFERENT ENZYMES, WITH
DIFFERENT VARIANTS, THESE NUKE
LOW TIDE CHANGES WILL CAUSE AN
IMMUNO ACID CHANGE AND A CHANGE
IN ENZYME ACTIVITY.
THIS ONE DOESN'T REALLY CHANGE
IT BUT IF WE GO BACK TO THIS
STAR TEN VARIANT IT DECREASES
ENZYME FUNCTION WHICH HAS
IMPLICATIONS FOR THE DOSAGE OF
THE MEDICATIONS,S OR THE
MEDICINES THAT ARE METABOLIZED
BY THIS ENZYME.
SO JUST A BIG PICTURE. AND THEN
WHEN WE THINK ABOUT THE
APPLICABILITY OF PHARMACOGENETIC
INFORMATION I WANTED TO GO TO
THIS STUDY THAT WAS PUBLISHED A
COUPLE YEARS AGO WHERE THEY DID
USE THE PHARMACOGENETIC
ALGORITHM BASED ON TWO GENES. D
4C 1 AND CYP 2C 9 AND THEY
LOOKED AT THE GENE IS THAT THE
US THE AND COMPARED TO IT TO
CLINICAL CARE.
FOR ONE OF THE GROUPS THEY FOUND
THAT THERE WAS A BENEFIT FOR
GENOTYPE GUIDE WARFARIN DOSING
AND WARFARIN IS A BLOOD THINNER
COMMONLY PRESCRIBED, ALSO KNOWN
AS COUMADIN. THEY FOUND THIS
PHENOTYPE WAS BENEFICIAL FOR
PEOPLE. AND THEN FOR COAG THAT
FOUND NO DIFFERENCE.
WHY DO YOU THINK WE HAVE THESE
CONFLICTING RESULTS? WELL, WHEN
YOU LOOK AT THE COMPOSITION OF
THE COHORTS, THE EU PAC WAS
PRIMARILY EUROPEAN DECENT COAGO
HAD REPRESENTATION. AND IN THIS
GENE, AFRICAN AMERICANS HAVE
LOW
LOWER FREQUENCY OF THE TWO
VARIETIES PUT IN THIS ALGORITHM.
AND NONE OF THE OTHER CYP 2C 9
WERE CONSIDERED IN THIS
ALGORITHM.
IT WAS EXCLUDING POTENTIALLY
IMPORTANT VARIANTS FOR A
SPECIFIC SUB GROUP AND SO THIS
IS A PART OF THE REASON WHY IT'S
SO IMPORTANT THAT WE LOOK AT
CHARACTERIZE VARIATION IN
DIFFERENT POPULATIONS.
POTENTIALLY, CLINICALLY THERE'S
THE POTENTIAL FOR PHENOTYPIC
CLASSIFICATION, THIS WILL END UP
CONTRIBUTING TO DISPARITIES AND
THEN THERE'S MISSED
OPPORTUNITIES FOR OPTIMIZING
CARE FOR PEOPLE. AND THE OTHER
PART MARK FOR IDENTIF OF MY WOR.
IT'S INTERESTING TO LOOK AT WHY
WE HAVE THE VARIATION THAT WE
DO. THIS IS LOOKING AT
POPULATIONS IN OCEANIA SO
LOOKING AT POLL NEESHA, MICRO
NEESHA IN DIFFERENT GEOGRAPHIC
REGIONS AND ETHNIC GROUPS.
BUT IT'S ANY -- THESE -- FOR
THIS CYP 2C 19 FOR METABOLIZER
STATUS IT VARIES FROM 71% IN
CERTAIN GROUPS TO 8 OR 7% IN
OTHER GROUPS.
AND A LOT OF THIS IS DRIVEN BY
THE FOUNDER EFFECT SO SMALL
POPULATIONS KEEPING -- OR -- IN
SMALL POPULATIONS SOME OF THE
VARIANTS -- THERE'LL BE A LOSS
OF GENETIC VARIANT THAT OCCURS
FROM A NEW POPULATION BEING
ESTABLISHED FROM A SMALLER
NUMBER OF PEOPLE OR SELECTIVE
PRESSURES. THERE MIGHT BE
THINGS IN THE ENVIRONMENT THAT
ARE BEING SELECTED POOR. THERE
MIGHT BE GEOGRAPHIC BARRIERS AS
WELL AND GENETIC DRIFT IS WHEN
NON-RANDOM DRIFT OCCURS DUE TO
SMALL POPULATION SIZE I THINK WE
SEE THIS ALL OVER THE WORLD WITH
THESE SUBSET OF ENZYMES AND IT'S
REALLY INTERESTING FROM MY
PERSPECTIVE TO LOOK AT WHY WE
SEE THESE CHANGES. IS THERE A
SELECTIVE ADVANTAGE OR IS THERE
ARCHAIC GENOMES THAT ARE
INVOLVED SO ONE OF THE --
ANOTHER PAPER THAT I'M NOT GOING
TO TALK ABOUT TODAY, WE LOOKED
AT THESE VARIANTS IN NEANDERTHAL
INDIVIDUALS AND WE WERE ABLE TO
SEE THAT SOME OF THAT VARIATION
IS SHARED FROM A LONG TIME AGO.
WHY IS THIS VARIATION STAYING IN
THE POPULATION? SO THIS IS JUST
AN EXAMPLE. BUT IN ALL, I THINK
THAT A LOT OF THE WORK THAT I
HAVE DONE AND HAVE BEEN DOING
WITH COMMUNITIES IS -- WAS
REALLY A CALL TO ACTION TO ME.
THERE IS A DEFINITE BIAS IN WHO
WAS REPRESENTED IN GENOMIC AND
PHARMACOGENOMIC RESEARCH. THERE
IS A SHOCKING LACK OF INDIGENOUS
PH.D.S OR PRINCIPLE
INVESTIGATORS IN THE BIOMEDICAL
SCIENCES. CURRENTLY, THERE ARE
VERY FEW PRINCIPLE INVESTIGATORS
WHO HAVE RESEARCH LABS, MUCH
LESS WET LABS AND ARE ABLE TO DO
SOME OF THIS WORK WITH TRIBAL
COMMUNITIES. SO IT REALLY
BECAME A CALL OR A REALIZATION
THAT WE -- I HAVE TO TRY TO
INCREASE THE NUMBER OF
INDIGENOUS CALLERS IN THE
GENOMIC WORKFORCE AND THEN ONE
WAY TO DO THIS IS WORING WITH
COMMUNITIES AS PARTNERS BUT ALSO
INVOLVING MORE OF THE
COMMUNITIES IN RESEARCH IN THE
ACTUAL -- START OR DOING THE
RESEARCH. SO NOW I'M GOING
SWITCH GEARS INTO SOME OF THE
ETHICAL RESEARCH APPROACHES THAT
I THINK OF AS I DO MY RESEARCH
AND I DO THIS -- I GO THROUGH
THIS PROCESS WITH EVERY PROJECT
THAT I DO AND THROUGHOUT THE
RESEARCH PROJECT I ALSO CHECK
MYSELF AND THINK ABOUT THESE
QUESTIONS. AM I DOING THIS?
SHOULD I HAVE DONE THIS? HOW
CAN I DO IT BETTER? SO I THINK
WHEN WE THINK ABOUT WHAT MEANS
TO BE AN ETHICAL RESEARCHER,
WHAT SITUATES OUR ETHICAL NORMS
AND BELIEFS?
I THINK THE NOTIONS OF GOOD AND
BAD VARY ACROSS COMMUNITIES.
BIOETHICS IS A STUDY OF ETHICS
IN MEDICINE AND RESEARCH AND
OFTEN GUIDELINES AND BEST
PRACTICES ARE NEED TO ENSURE
THAT MINIMUM STANDARDS ARE
IMPLEMENTED. SO I WON'T TALK A
LOT ABOUT THIS WORK. SO I DO
RESEARCH WITH CONTEMPORARY
INDIGENOUS PEOPLES. I ALSO DO
RESEARCH INVOLVING ANCESTORS.
SOME OF THE PAPER THAT I SHARED
WILL GIVE YOU MORE IDEAS ABOUT
WHAT IT MEANS BUT EITHER --
WHETHER I'M WORKING WITH
CONTEMPORARY INDIGENOUS PEOPLES
OR ANCESTORS A LOT OF THE
QUESTIONS THAT I THINK OF -- AND
HOW I APPROACH MY RESEARCH ARE
THE SAME. SO I REALLY LOVE THIS
QUOTE BY DR. KIM. IF YOU'RE
GOING TO WORK WITH INDIGENOUS
COMMUNITIES, YOU HAVE -- ON
GENETICS YOU HAVE TO BE WILLING
TO MAKE LIFELONG RELATIONSHIPS
SO CBPR IS COMMUNITY BASED
PARTICIPATORY RESEARCH. IT'S A
COLLABORATIVE APPROACH TO
RESEARCH THAT INVOLVES ALL
COMMUNITY PARTNERS IN THE
RESEARCH PROCESS. AND IT
RECOGNIZES THE STRENGTHS THAT
EACH BRINGS. SO COMMUNITY
RESEARCH BEGINS WITH A RESEARCH
TOPIC OF IMPORTANCE TO THE
COMMUNITY. WITH THE AIM OF
COMBINING KNOWLEDGE AND ACTION
FOR SOCIAL CHANGE TO IMPROVE
COMMUNITY HEALTH AND ELIMINATE
HEALTH DISPARITIES. SORRY, I
KEEP PRESSING THE WRONG BUTTON.
SO I THINK ONE THING THAT I
WOULD LOVE EVERYONE TO THINK
ABOUT IS WHAT WOULD YOUR STUDY
LOOK LIKE? WHEN COMMUNITY'S
INVOLVED OR WHAT DOES YOUR STUDY
LOOK LIKE AND THIS CAN BE
WHATEVER YOU'RE STUDYING IF IT'S
PUBLIC HEALTH, IF IT'S
QUALITATIVE OR IF YOU'RE DOING
GENETIC RESEARCH HOW DO YOU
INVOLVE YOUR COMMUNITY MEMBERS?
SO RECENTLY, THERE HAVE BEEN
MANY COMMUNITIES, THAT AFFECT
RESEARCH GUIDELINES THAT HAVE
COME OUT. THESE -- THIS IS A
LITTLE BIT OLDER BUT THESE ARE A
COUPLE THAT I LIKE TO HIGHLIGHT
AFTERNOON R H 3 AFRICA HAS A
FRAMEWORK. WE HAVE A GOOD
EXAMPLE OF GUIDELINES THAT WERE
PRODUCED, CREATED AND MADE BY
MARY INDIVIDUALS SO IT BRINGS
DOWN WHAT GENOMIC RESEARCH LOOKS
LIKE FROM THE MAY OR RI
PERSPECTIVE.
AND THEN THIS OTHER PUBLICATION
MY COLLEAGUES AND I PUBLISHED
BACK IN 2018. IN THIS FRAMEWORK
WE LAY OUT ETHICAL PRINCIPLES,
SIX PRINCIPLES THAT ANYONE CAN
USE IN THEIR RESEARCH. AND I
WILL GO THROUGH THIS A LITTLE
BIT MORE AFTER I HIGHLIGHT SOME
OF THE OTHER UPCOMING STUDIES
AND THEN RECENTLY THERE'S BEEN A
LOT OF WORK DONE PARTICULARLY IN
GENOMIC RESEARCH AND PRECISION
MEDICINE. ONE OF THE PRINCIPLES
THAT CAME OUT WHERE THE CARE
PRINCIPLES SO THIS IS SELECTION,
OWNERSHIP, AND APPLICATION OF
DATA AND SPECIMENS. SO THE CARE
PRINCIPLES FOR INDIGENOUS DATA
GOVERNANCE, THAT'S A REALLY
GREAT PAPER TO READ AND THERE IS
A -- I'M NOT SURE IF FOLKS HAVE
HEARD OF THE FAIR PRINCIPLES
ABOUT DATA STEWARDSHIP BUT
THERE'S A PAPER THAT LINKS THE
CARE AND FAIR PRINCIPLES
TOGETHER WHICH I FIND REALLY
GREAT AND THERE'S OTHER STUDIES
THAT THINK OF DNA ON LOAN. OR
IN RELATION TO DATA STEWARDSHIP
THERE LAURA ARBOR'S GROUP IN
CANADA BUT I ALSO WANTED TO
HIGHLIGHT THE PAPER THAT MY
COLLEAGUES AND I WERE ABLE TO
PUT TOGETHER.
WITH THIS PAPER WE LIKE TO START
FROM THE MIDDLE. SO
UNDERSTANDING TRIBAL SOVEREIGNTY
AND RESEARCH REGULATIONS WITH
THE COMMUNITIES THAT YOU'RE
WORKING WITH BEFORE STARTING AND
THEN GOING OUTWARDS TO ENGAGING
THE COMMUNITY. AND THEN MAKING
SURE THAT YOU'RE CULTURALLY
COMPETENT AND THEN IMPROVING
TRANSPARENCY IN EVERYTHING THAT
YOU'RE DOING. NOT JUST IN THE
STARTING STUDY BUT IN INFORMED
CONSENT. SO INVOLVING MEMBERS
OF THE COMMUNITY AND THEN
DISTRIBUTING KNOWLEDGE IN
DIFFERENT WAYS. AND THEN
THROUGHOUT WE HAVE THESE
PRINCIPLES OF RESPECT, EQUITY,
BENEFICENCE AND RECIPROCITY. SO
WITH THIS, I'M JUST GOING TO
START FROM THE BEGINNING AND
TELL PEOPLE HOW I APPROACH THIS
RESEARCH. SO IN ACKNOWLEDGES
SOVEREIGNTY AND RESEARCH
RELATIONS, WE'RE ASKING THAT
BOTH TRIBAL GROUPS AND
INDIVIDUALS CONSENT ALSO IF
YOU'RE WORKING WITH URBAN
POPULATIONS IT BECOMES A LITTLE
HARDER BECAUSE OFTEN THERE'S NOT
A SINGLE ENTITY THAT CAN APPROVE
OR DISAPPROVE OF A STUDY. FOR
EXAMPLE I'M GOING TO HIGHLIGHT
THE PHARMACOGENOMICS RESEARCH
NETWORK. SO WITHIN THIS
PARTNERSHIP THEY HAVE THREE
TRIBAL PARTNERS LISTED HERE AND
THEN WITH THE OVERSIGHT APPROVAL
PROCESS FOR EVERY STUDY THAT WAS
DONE AS A PART OF THIS LARGER
GRANT THEY WENT THROUGH THE
ALASKA AREA IRB AND THEN THE
OVERSIGHT COMMITTEE OF THE
FOUNDATION AND THEN FOR THE YK
HEALTH CORPORATION THEY WENT
THROUGH MULTIPLE LEVELS OF
REVIEW AND THIS IS FOR THE STUDY
BUT ALSO FOR ANY PUBLICATIONS
AND PRESENTATIONS THAT HAPPENED.
AND THEN SAME WITH THE TRIBE IN
MONTANA THERE WERE MULTIPLE
LEVELS OF REVIEW FROM THE
COMMUNITY BEFORE THIS GOT
APPROVED OR STARTED AND THEN FOR
COMMUNITY ENGAGEMENT THIS IS
REALLY TALKING ABOUT BUILDING
LONG-TERM RELATIONSHIPS. AND
HAVING SOME TYPE OF ENGAGEMENT
PLANNED. ONE REALLY GOOD WAY TO
DO THIS IS TO HAVE COMMUNITY
ADVISORY GROUPS. SO, AND ALL --
MOST OF THE STUDIES THAT I DO, I
HAVE A COMMUNITY ADVISORY GROUP.
THIS CAN BE ANYWHERE FROM FIVE
PEOPLE TO ONE OF MY GROUPS. WE
HAVE 30 COMMUNITY MEMBERS IN THE
ADVISORY GROUP. SO I THINK IT
JUST DEPENDS ON WHAT LEVEL OF
INTEREST AND IF YOU'RE ABLE TO
ORGANIZE FOLKS BUT OFTEN THE
COMMUNITY ADVISORY GROUP
MEETINGS ARE THE BEST PART OF MY
JOB. BECAUSE I GET TO CONNECT
WITH COMMUNITIES, LEARN, AND
TALK ABOUT RESEARCH TOGETHER.
SO THE OTHER CULTURAL
COMPETENCY, SO INTEGRATING
CULTURAL AND TRADITIONAL
KNOWLEDGE. TAKING THE VIEWS AND
PERSPECTIVES OF TRIBAL MEMBERS
INTO CONSIDERATION. AND THEN
ALSO HAVING REVIEWED BY THE IRB
AND COMMUNITY RESEARCHERS. SO
WITH ONE OF THE PROJECTS THAT I
WAS LUCKY ENOUGH TO BE A PART OF
WAS WITH THE SOUTH CENTRAL
FOUNDATION BEFORE WE -- WE MOVED
FORWARD WITH DOING AN IN-DEPTH
ANALYSIS OF THE CYP GENE ONE OF
THE THINGS WE DID FIRST WAS
EXPLORING THE PERCEPTIONS BEFORE
EMBARKING ON THIS PROJECT SO WE
DID A QUALITATIVE STUDY ON
PATIENTS, PROVIDERS AND LEADERS
REGARDING FARM COY --
PHARMACOGENETICS USED IN TOBACCO
CESSATION RESEARCH. A LOT OF
THOSE WANTED COLLABORATION WITH
EXISTING TRIBAL PROGRAMS AND
WANTED THEIR RESULTS BACK.
SO THIS IS ONE WAY WE CAN DO
THIS BEFORE EMBARKING ON A
PROJECT. TRANSPARENCY, JUST
MAKING SURE THAT THE CONSENT AND
THE PROCESS ARE SHARED AND
DETAILED MAKING SURE STORAGE OF
DATA IS ADDRESSED AND MADE CLEAR
TO THE COMMUNITY AND ALSO FUTURE
USE OF DATA AND SAMPLES SO THIS
WAS AN EXAMPLE OF SOME OF THE
LANGUAGE USED IN AN INFORMED
CONSENT THAT WAS ACTUALLY USED.
IT'S ANONYMISED HERE BUT IT SAYS
CLEARLY THAT YOUR SAMPLES BELONG
TO YOU AND WILL BE STORED.
SAMPLES WILL BE SENT TO THIS
PLACE FOR ANALYSIS. IT'S VERY
CLEAR WHAT HAPPENS TO THE AMPLE
-- SAMPLE AND IT TELLS THEM HOW
LONG YOU KEEP THE SAMPLES. AND
WHAT WILL HAPPEN AFTER. AND
CAPACITY BUILDING, MAKING SURE
THAT YOU'RE TRYING TO INCLUDE
OTHERS AND DIVERSIFYING THE
WORKFORCE, DOING COLLABORATIVE
ANALYSIS AND THEN ALSO SHARING
COAUTHORSHIP WITH COMMUNITY
MEMBERS AS WELL AS RESEARCHERS.
ONE WAY I LIKE TO DO THIS AND I
AM A LONG TIME FACULTY MEMBER
WITH THE SUMMER INTERNSHIP FOR
INDIGENOUS PEOPLES IN GENOMICS
AT THAT WORKSHOP WE'RE ABLE TO
DO HANDS-ON TRAINING IN
GENOMICS. WE TALK ABOUT
DIFFERENT ELSI ISSUES. WE TALK
ABOUT DIFFERENT KNOWLEDGE IN
DECOLONIZING SCIENCE AND THIS
WORKSHOP HAS BEEN AROUND SINCE
2011 AND MANY OF MY TRIBAL
RESEARCH PARTNERS HAVE ATTENDED
SING BECAUSE IT WAS A GREAT WAY
TO HAVE THEM LEARN MORE ABOUT
GENOMICS BUT ALSO ENGAGE IN
DISCUSSION WITH OTHER TRIBAL
COMMUNITY MEMBERS. SO OFTEN WE
HAVE ABOUT 20 PEOPLE WHO ATTEND
EVERY YEAR AND THESE INDIVIDUALS
ARE ALL HAVE DIFFERENT TRIBAL
INDIGENOUS COMMUNITIES AROUND
THE U.S. AND AROUND THE WORLD SO
IT'S A REALLY GREAT WAY TO
SUPPORT CAPACITY BUILDING AND
THEN ALSO INFORM PEOPLE OF WHAT
WE'RE DOING. AND SING HAS
ACTUALLY CROSSED INTERNATIONAL
WATERS NOW SO THERE'S AN SING IN
NEW ZEALAND, THERE'S AN SING
AUSTRALIA CANADA. THOUGH I
THINK IT GOES UNDER A DIFFERENT
NAME.
FROM THE ORIGINAL SING IN THE U
SA ALL THOSE OTHER GROUPS HAVE
USED SING IN THEIR OWN WAY AND
CREATED THEIR OWN SHOPS FOR
CAPACITY BUILDING. AND THEN
THINKING ABOUT KNOWLEDGE AND
DISTRIBUTING KNOWLEDGE. ONLY
VERY FEW PEOPLE I FOUND FROM THE
COMMUNITY ACTUALLY READ YOUR --
THE ACADEMIC PUBLICATION SO IT'S
IMPORTANT TO MAKE IT AVAILABLE
IN DIFFERENT AREA. AS PART OF
MY RESEARCH, OUR RESEARCH TEAM
HAS PRESENTED AT TRIBAL
COMMUNITY MEETINGS. WE HAVE
DONE FORMS ON THE LOCAL NAVAJO
RADIO STATION. AND ALSO I KNOW
OTHER COLLEAGUES HAVE CREATED
PAMPHLETS.
AND PUT THINGS ON SOCIAL MEDIA
TO MAKE IT MORE EASILY D
DIGESTIBLE. THESE ARE SOME
IDEAS ON HOW PEOPLE CAN WORK
WITH COMMUNITIES SO THAT THE
KNOWLEDGE IS SHARED AND PEOPLE
ARE EXCITED ABOUT THE RESEARCH
AND DON'T FEEL LIKE THEY'RE JUST
BEING USED AS A PART OF THE
RESEARCH PROCESS. SO IN
PHARMACOGENOMICS SPECIFICALLY I
THINK SPECIFICALLY THAT THE
FUTURE OF PHARMACOGENOMICS IS
BROUGHT. WE HAVE A LOT OF
DIFFERENT INITIATIVES HAPPENING.
ONE OF WHICH I'M SUPER PRUDE
PROUD OF HERE IS THE CONSORTIUM.
THE FIRST INSTITUTE LED BY
INDIGENOUS SCIENTISTS AND THEY
ARE ABLE TO STORE DATA, STORE
BIOSPECIMENS ON TRIBAL LANDS.
SO IF YOU'RE INTERESTED HERE IS
THE DIRECTOR. THE OTHER
INITIATIVE THAT I HAVE BEEN
WORKING WITH IS DR. ERICA AT THE
UNIVERSITY OF MONTANA. SHE HAS
THE PRECISION MEDICINE PROJECT
WHERE THEY ARE TARGETING RURAL
AND INDIGENOUS COMMUNITIES AND
TRYING TO IMPLEMENT PRECISION
MEDICINE IN THOSE COMMUNITIES.
AND ALSO I WORK WITH IN
COMMUNITIES. I WORK WITH
COMMUNITIES IN BRITISH COLUMBIA,
IN ARIZONA, ACROSS THE UNITED
STATES. SO I AM REALLY EXCITED
TO CONTINUE THIS WORK. I WANTED
TO END WITH THE NEXT STEPS IN
PRECISION PHARMACOGENETICS. SO
MY COLLEAGUES AND I WROTE THIS
ARTICLE IN HOW TO IMPLEMENT
PHARMCO YES THEMMICS IN THE
INDIGENOUS COMMUNITIES.
SO THIS IS ONE OF OUR FIGURES WE
THOUGHT THAT THIS WAS A GOOD WAY
OF THINKING ABOUT ALL OF THE
DIFFERENT COMPONENTS TO TAKING A
HOLISTIC HEALING APPROACH. SO
IN THE MIDDLE WE SHARE ALL OF
THE KEY PEOPLE AND STAKEHOLDERS
WHO ARE INVOLVED. NOT ONLY IN
COMMUNITIES BUT RESEARCHERS,
FUNDERS, TRIBAL HEALTH,
TRADITIONAL HEALERS AND RESEARCH
PARTICIPANTS. AND THEN WE
THOUGHT THAT INCREASING
KNOWLEDGE, PHARMACOGENETIC
KNOWLEDGE OF USING AMERICAN
INDIAN ALASKAN NATIVE VARIATION
WAS SUPER IMPORTANT BECAUSE
UNTIL WE KNOW THIS VARIATION,
WE'RE NOT ABLE TO IMPLEMENT IT
CLINICALLY AND THAT WAS THE
OTHER AREA THAT WE THOUGHT WAS
REALLY IMPORTANT IN THINKING
ABOUT CLINICAL IMPLEMENTATION
WHICH IS RELATED TO CLINICAL
DECISION SUPPORT SYSTEMS.
PHARMACOGENETIC TESTING AND ALSO
EDUCATION AND RESOURCES FOR
PHYSICIANS WHO ARE WORKING WITH
NATIVE PARTICIPANTS OR NATIVE
PATIENTS. AND THEN LASTLY
TRADITIONAL KNOWLEDGE AND
PRACTICES. SO THIS WAS BACK A
COUPLE YEARS AGO THE TRIBAL
HEALTH RESEARCH OFFICE PUT
TOGETHER A SUMMIT. AND IT WAS
HELD AT UNIVERSITY OF COLORADO
BUT THIS REPORT IS AVAILABLE
ONLINE BUT ONE OF THE QUOTES
THAT I LIKED IS THAT IT IS
IMPORTANT FOR RESEARCHERS TO
UNDERSTAND THAT THERE IS AN
INTERSECTION BETWEEN HEALTH,
RESEARCH AND SPIRITUALITY IN
AMERICAN INDIAN ALASKAN NATIVE
HEALTH AND SO THIS GOES BACK TO
WHAT I SAID INITIALLY THAT A LOT
OF OUR COMMUNITY MEMBERS ARE
STILL USING TRADITIONAL HERBS
AND TRADITIONAL CEREMONIES
WHENEVER SOMETHING BAD HAPPENS
SO IF THERE'S A DIAGNOSIS FOR A
DISEASE, THEY OFTEN GO TO THE
TRADITIONAL PEOPLE FIRST. AND
THEN THEY GO TO THE WESTERN
TREATMENT OPTION. SO, AND
IT'S -- THERE'S A SEPARATION
THAT DOESN'T NEED TO BE A
SEPARATION BUT WE CAN DO IT
TOGETHER AND ONE OF THE THINGS
IN PHARMACOGENETICS WE HAVE ALL
OF THESE GUIDELINES THAT WE HAVE
TO ESTABLISH A PERSON'S DOSE TO
TREATMENT A PERSON'S DEPRESSION.
THAT'S JUST TREATING ONE SYMPTOM
WHEREAS IN ORDER TO TREAT THE
WHOLE PERSON WE NEED TO TAKE IN
THE WHOLE COMMUNITY ENVIRONMENT
THAT THE PERSON LIVES IN. SO,
WITH THAT, I WILL LEAVE YOU WITH
A COUPLE THOUGHTS. WE NEED TO
SHIFT TO COMMUNITY BASED
RESEARCH AND HOLISTIC HEALING TO
ENSURE THAT PEOPLE ARE HEALTHY
TO THE BEST THAT THEY CAN BE.
AND THEN WE HAVE TO ENSURE THAT
INDIGENOUS COMMUNITIES GOVERN
AND BENEFIT FROM RESEARCH AND
WITH THAT, I WILL THANK YOU. I
WANT TO THANK MY LAB MEMBERS,
CURRENT AND PAST. AND ALSO I
WANT TO THANK MY TRIBAL PARTNERS
WHO HAVE BEEN AMAZING AND
SUPPORTIVE ALL OF THIS WOULD NOT
BE DONE WITHOUT THEIR INPUT AND
THEN ALSO MY MANY COLLABORATORS
ACROSS THE WORLD AND THE U.S.
BUT THANK YOU, EVERYONE AND I'M
HAPPY TO TAKE QUESTIONS.
>> THANK YOU SO MUCH, KATRINA.
ALWAYS GREAT TO HAVE YOU AND
YOUR PERSPECTIVE AND HAVE YOU
SHARE YOUR DEPTH OF KNOWLEDGE
WITH US. LET ME SEE, SO WE HAVE
BOTH A COUPLE OF PEOPLE, WELL,
MORE THAN A COUPLE BUT SOME
PEOPLE HERE IN THE AUDIENCE THAT
ARE GOING TO GO TO THE MICS IF
THEY HAVE ANY QUESTIONS. AND
THEN I HAVE FOLKS WHO ARE COMING
IN FROM VIDEO AND I'M CHECKING
TO SEE IF THEY HAVE ANY
QUESTIONS FOR YOU.
>> SORRY, I'M NOT ABLE TO HEAR
ANYTHING.
>> OH, YOU CAN'T HEAR ANYTHING,
IS THAT SOMETHING ON YOUR END UP
THERE? CAN YOU NOT HERE US AT
ALL, KATRINA? HM, THAT'S --
WEIRD BECAUSE WE DIDN'T DO
ANYTHING OTHER THAN TURN THE
SLIDES OFF. MAYBE ONCE ALEX IS
IN I CAN TRANSLATE TO YOU TO ASK
THE QUESTION? SO IF YOU COULD
ASK KATRINA ABOUT, SO, WE'VE
BEEN TALKING TODAY -- WE'VE BEEN
TALKING TODAY ABOUT GENOMICS AND
I'M WONDERING IF IN HER WORK SHE
HAS FOUND WHETHER, I'M ASSUMING
THESE PRINCIPLES WOULD APPLY TO
ANY RESEARCH THAT'S BEING
CONDUCTED IN INDIGENOUS
COMMUNITIES OR WHETHER THERE'S
ANY ADDITIONAL FEEDBACK SHE
WOULD HAVE ON THAT. HERE IS MY
QUESTION. WE'VE BEEN TALKING
CERTAINLY FROM YOUR PERSPECTIVE
FROM PHARMACOGENOMICS MORE
GENERALLY AND WE'VE BEEN TALKING
ABOUT THAT ALL DAY. BUT I'M
WONDERING IF, I MEAN, IT SEEMS
TO ME THAT ALL OF THE PRINCIPLES
AND APPROACHES AND THE -- WOULD
APPLY TO ANY RESEARCHER WHO THE
IS PLANNING TO ENGAGE IN A
RESEARCH EFFORT.
>> THAT'S RIGHT THINK IT IS NOT
ONLY INDIGENOUS COMMUNITIES I
THINK OTHER COMMUNITIES, WE CAN
USE THESE SAME PRINCIPLES.
>> SO OTHER COMMUNITIES THAT
MIGHT BE UNDERSERVED OR, I
THINK, I REALLY LIKE THE OF NOT
THINKING OF THESE AS SEPARATE
REALMS.
THERE IS SCIENCE AND CULTURAL
CONDITIONS ON THE OTHER AND THAT
SEEMS LIKE A UNIVERSAL LESSON
THAT THERE ARE ALL SORTS OF WAYS
THAT IF YOU GO IN WITH ONE
PERSPECTIVE AND SORT OF DISMISS
THE OTHER, IT WOULDN'T BE
SURPRISING IF YOU WOULDN'T BE
WELCOME INTO THAT COMMUNITY.
>> M-HM.
>> IN THINKING MORE ABOUT THE
WORK THAT YOU'RE DOING, ARE
THERE PARTICULAR TOPICS THAT YOU
FIND ARE, YOU KNOW, MORE
CONTROVERSIAL THAN OTHERS WHEN
ENGAGING IN INDIGENOUS
COMMUNITIES OR IS IT A MATTER OF
SORT OF MEETING THEM WHERE THEY
ARE AND ENGAGING THEM FROM THAT
POIN
POINT?
>> YEAH, I THINK THAT'S
INITIALLY ONE OF THE QUESTIONS
THAT I ALWAYS GET. AND FROM
FOLKS IS ABOUT TRIBAL MEMBERSHIP
AND TRIBAL ENROLLMENT IN HOW
GENETICS COULD PLAY A ROLE BUT I
THINK IT'S -- I DON'T THINK THAT
GENETICS CAN HELP WITH THAT
BECAUSE A LOT OF TRIBAL
ENROLLMENT RULES ARE
TRIBE-SPECIFIC TOO. SO IT
ALWAYS INVOLVES A CONVERSATION
OF WHAT CAN GENETICS ACTUALLY
DO. WE CAN'T DISTINGUISH
BETWEEN PEOPLE AT A TRIBAL LEVEL
AND WOULD WE EVEN WANT TO ALSO.
I THINK THE OTHER, ONE OF THE
WAYS IT'S -- GENETICS CAN BE
USED IN TRIBAL ENROLLMENT IS
LIKE A PATERNITY TEST THAT IS
THE ONLY -- GENETIC TEST I'VE
USE SEEN BEING USED BUT THAT'S A
SORT OF CONTROVERSIAL -- BE A
CONTENTIOUS TOPIC THAT I DON'T
DO ANY RESEARCH IN THAT AREA.
SO I TRY TO AVOID THAT IF
POSSIBLE. THE OTHER THING, I
THINK THE OTHER TOPICS ARE
REALLY DRIVEN BY THE TRIBAL
COMMUNITIES INVOLVED. SOMETIMES
IT'S ALSO THAT I HAVE TO TAKE A
STEP BACK AND SAY THAT, WELL,
THIS TECHNICALLY ISN'T A
GENETICS -- GENETICS RESEARCH
PROBABLY WON'T HELP THIS AS MUCH
AS PREVENTION RESEARCH OR HAVE
ADEQUATE HEALTH CARE. THAT'S
ONE OF THE THINGS I THINK OF
WHEN LIKE A LOT OF PEOPLE, ARE
INTERESTED IN TYPE TWO DIABETES
BECAUSE IT AFFECTS SO MANY OF
THEIR COMMUNITY MEMBERS BUT I
DON'T KNOW IF A GENETIC APPROACH
WOULD BE APPROPRIATE, LIKE,
USING A LOT OF FUNDS TO STUDY
TYPE TWO DIABETES IN GENETIC --
IN THE GENETICS ASPECT WHEN I
CAN SEE THAT THERE ARE -- PEOPLE
ARE LIVING IN FOOD DESERTS, THEY
DON'T HAVE ADEQUATE ACCESS TO
HEALTHY FOODS, THEY DON'T HAVE A
LOT OF OTHER RESOURCES THAT ARE
NOT GENETICS BUT OTHER
PREVENTION MECHANISMS. THAT ARE
MORE APPROPRIATE FOR WHEN YOU'RE
THINKING ABOUT THOSE TOPICS SO I
THINK I'M ALWAYS TRYING TO SEE
HOW, WOULD GENETICS REALLY PLAY
A ROLE? AND JUST THINKING ABOUT
WHAT WOULD BE BEST FROM MY
PERSPECTIVE, THAT'S ALWAYS WHY
AND WHEN I DO THESE STUDIES TRY
TO AT LEAST HAVE OTHER TYPES OF
MEASUREMENTS THAT CAN BE USEFUL
IN THE FUTURE TOO IF WE DO DO
SOME TYPE OF GENETICS.
>> YEAH, JUST ANOTHER REMINDER
ABOUT CONTEXT. RIGHT? IN TERMS
OF, YOU KNOW, THE -- THE
LIMITATIONS OF THE GENETIC
INFORMATION. WE HAVE A QUESTION
HERE.
>> I WAS WONDERING IF YOU CAN
SAY MORE ABOUT THE DISCUSSIONS
WITHIN THE NAVAJO NATION ABOUT
THE BAN ON GENETICS RESEARCH AND
IF IT'S JUST KIND OF THE RISKS
SEEM TO BE MORE THAN THE
BENEFITS FOR PEOPLE WITHIN THE
NATION. AND ALSO IF THAT
EXTENDS TO CLINICAL GENETICS OR
JUST RESEARCH.
>> YEAH. THAT'S A GREAT
QUESTION. SO THE MORATORIUM
ONLY EXTENDS TO INDIVIDUALS ON
THE JURISDICTION OF THE NAVAJO
NATION SO TECHNICALLY IF YOU
WERE OFF THE NAVAJO NATION YOU
COULD PARTICIPATE IN A STUDY.
AND IT'S ONLY ON RESEARCH.
CLINICAL USE OF GENETICS FOR
CLINICAL TESTING CAN BE DONE.
IT'S OFTEN NOT DONE ON THE
NAVAJO NATION ANYWAYS BUT THEY
USUALLY HAVE TO REFER PEOPLE
OUTSIDE THE RESERVATION FOR
CLINICAL TESTING IF IT'S BEING
USED FOR CLINICAL CARE I THINK
THAT'S COMPLETELY ALLOWABLE.
AND SO BACK WHEN THE MORATORIUM
WAS PUT IN PLACE, THERE'S A
REALLY GREAT VIDEO THAT CAME OUT
AROUND THE TIME CALLED THE GIFT
OF LIFE. IT'S, I DON'T KNOW IF
IT'S AVAILABLE ONLINE BUT --
>> WE'LL LOOK FOR IT.
>> IT'S A REALLY GREAT VIDEO
THAT CONTEXTUALIZES ALL OF THE
CONCERNS AT THE TIME. I THINK
ALSO THESE PERCEPTIONS HAVE
CHANGED SO WE PUBLISHED A PAPER
IN 2019 WHERE WE DID A SURVEY IN
THE NAVAJO COMMUNITY. WE
SURVEYED OVER 700 NAVAJO PEOPLE
AND WE ASKED THEM QUESTIONS LIKE
WHAT -- DID YOU KNOW MORATORIUM
WAS -- EXISTED? AND THEN ONE OF
THE LAST QUESTIONS WAS DO YOU
THINK THAT WE SHOULD LIFT OR
REMOVE THE MORATORIUM AND ALSO
WE ASKED THEM ABOUT DIFFERENT
CONCERNS THAT THEY HAD IN THE
COMMUNITY. SO, ONE OF THEM ,
THE RESOUNDING RESULTS WAS OVER
75% OF PEOPLE DID NOT KNOW THE
MORATORIUM WAS IN PLACE BACK IN
2019 WHEN WE CONDUCTED THE
SURVEY. AND ABOUT 50-60% WERE
NOT SURE WHAT TO DO. THEY FELT
LIKE THEY WEREN'T INFORMED
ENOUGH TO KNOW WHETHER THEY
SHOULD SUPPORT LIFTING THE
MORATORIUM OR NOT. AND ONE OF
THE BIG THINGS THAT CAME OUT OF
THAT WAS THAT PEOPLE SAID WE
WANT MORE INFORMATION ON
GENETICS AND HOW IT COULD AFFECT
THE NAVAJO COMMUNITY. WE WANT,
IF THIS WAS -- GENETIC RESEARCH
WAS TO GO FORWARD WE WANT IT TO
PRIORITIZE SOME OF THE HEALTH
ISSUES IN OUR COMMUNITY. AND
THEN WE WANT TO BE INVOLVED AND
SO THAT SURVEY LED TO MY
COLLEAGUES AND I CREATING
ANOTHER, OR SUBMITTING ANOTHER
GRANT. IT'S A PILOT GRANT AND
AS A PART OF THAT GRANT WE
PROPOSE TO DEVELOP ALL OF THESE
GENETIC LITERACY PROJECTS FOR
THE NAVAJO NATION SO WE'RE
EXCITED THAT NEXT YEAR WE, AS A
PART OF THAT WE'RE ALSO --
PROPOSED A -- TO HOST A BIG
CONFERENCE SO NEXT YEAR WE WILL
BE HOSTING THE NAVAJO GENETICS
CONFERENCE IN MAY OF 2025.
WHERE WE WILL SHARE ALL OF THE
EDUCATIONAL PRODUCTS THAT WE
HAVE CREATED. ONE IS A NAVAJO
GENETICS GLOSSARY OF OVER 250
GENETICS TERMS, TRANSLATED INTO
THE NAVAJO LANGUAGE. THAT WILL
BE A BOOK THAT WE PUBLISH.
ANOTHER IS FIVE DIGITAL STORIES
THAT WE WILL SHARE HOPEFULLY
BEFORE THEN. AND THEN WE'RE
ALSO CREATING A CULTURAL
FRAMEWORK FOR THINKING ABOUT
GENETIC RESEARCH WITHIN THE
NAVAJO COMMUNITY. WE'RE REALLY
EXCITED ABOUT THIS CONFERENCE
NEXT YEAR IF ANYONE'S INTERESTED
PLEASE LET ME KNOW WE SHOULD
HAVE A WEBSITE UP IN A COUPLE
MONTHS. OR THIS YEAR. BUT --
THANK YOU FOR THAT QUESTION.
>> WELL, YEAH, AND THANK YOU,
AGAIN, KATRINA, IT'S ALWAYS A
PLEASURE TO HAVE YOU AND ENJOY
THE REST OF YOUR DAY.
>> THANK YOU. BYE, EVERYONE.
>> THANK YOU. AND WE WILL
RECONVENE NEXT WEEK WHERE WE
WILL HAVE JILL FISHER WHO WILL
BE JOINING US FROM THE
UNIVERSITY OF NORTH CAROLINA AND
I'M VERY EXCITED. WE'RE GOING
TO HAVE A PANEL OF PARTICIPANTS
WHO PREVIOUSLY ENROLLED IN
RESEARCH PROJECTS HERE AT THE
CLINICAL CENTER TO SHARE THEIR
STORIES.