>>HI, I'M DAN KASTNER.
I AM THE SCIENTIFIC DIRECTOR
EMERITUS AND A SENIOR
INVESTIGATOR IN THE NATIONAL
HUMAN GENOME RESEARCH INSTITUTE
AND IT IS MY ENORMOUS PLEASURE
TO WELCOME YOU TO THIS, THE 14TH
INSTALLMENT OF THE 23RD SEASON
OF DEMYSTIFYING MEDICINE AT THE
NIH.
THIS IS A COURSE SERIES THAT WE
PUT ON, WE MEANING MY
COMODERATOR, DR. WIN ARIAS, WHO
IS A SENIOR SCIENTIST EMERITUS
AT THE NIH, AND THE FOUNDER OF
THIS COURSE, AND MYSELF, WE PUT
TOGETHER THIS COURSE TO BRIDGE
THE EXCITING DEVELOPMENTS IN
BIOLOGY AND ENGINEERING WITH
MEDICINE.
AND BRIDGING IS TRULY IN WHAT WE
ARE INTERESTED IN DOING,
BRINGING TOGETHER EXPERTS IN A
PARTICULAR FIELD OF INTEREST TO
HIGHLIGHT SOME OF THE IMPORTANT
ACCOMPLISHMENTS IN THAT FIELD
AND TO EXCITE THE VIEWER WITH
THE NEW OPPORTUNITIES FOR
ADVANCEMENT IN THAT FIELD.
AND JUST LIKE THE TWO MEN ON
THIS ICONIC PHOTO OF THE
CONSTRUCTION OF THE BROOKLYN
BRIDGE IN THE UPPER RIGHT,
PROUDLY ONE OF THEM FROM MA
MANHATTAN, THE OTHER FROM
BROOKLYN, HAVING A CONVERSATION
ABOUT SOME OF THE MATTERS OF THE
TIMES IN THE 1870s, BUT NOW WE
ARE IN THE 21ST CENTURY AND WE
HAVE A COUPLE OF NEW
INTERLOCUTORS TO DISCUSS THE
LATEST DEVELOPMENTS IN A
PARTICULAR FIELD.
THE TITLE OF THE
PRESENTATION IS: OUT OF AFRICA,
GENOMIC AND ENVIRONMENTAL
DETERMINANTS OF GLOBAL HEALTH.
AND WE HAVE TWO STELLAR SPEAKERS
THIS AFTERNOON.
THE FIRST OF THEM IS DR. CHARLES
ROTIMI.
THE GOOD DR. ROTIMI IS
SCIENTIFIC DIRECTOR OF THE
DIVISION OF INTRAMURAL RESEARCH
AT THE NATIONAL HUMAN GENOME
RESEARCH INSTITUTE, AND HE WAS
THE FOUNDING DIRECTOR OF THE
CENTER FOR RESEARCH ON GENOMICS
AND GLOBAL HEALTH AT THE NIH.
HE'S ALSO AN NIH DISTINGUISHED
INVESTIGATOR.
HE CURRENTLY IS THE PRESIDENT OF
THE AMERICAN SOCIETY OF HUMAN
GENETICS, AND HE IS THE FOUNDING
AND PAST PRESIDENT OF THE
AFRICAN SOCIETY OF HUMAN
GENETICS.
HE GOT HIS BACHELOR'S DEGREE AT
THE UNIVERSITY OF BENIN IN
NIGERIA.
HIS MASTER'S DEGREE IN HEALTH
SCIENCE ADMINISTRATION FROM THE
UNIVERSITY OF MISSISSIPPI, AND
HIS DOCTORAL DEGREE IN
EPIDEMIOLOGY FROM THE UNIVERSITY
OF ALABAMA AT BIRMINGHAM.
HE'S THE RECIPIENT OF A NUMBER
OF AWARDS AND PRIZES, INCLUDING
THE CURT STERN AWARD OF THE
AMERICAN SOCIETY OF HUMAN
GENETICS, AND HE'S A MEMBER OF
THE NATIONAL ACADEMY OF
MEDICINE.
HIS RESEARCH GROUP CURRENTLY
DEVELOPS ANALYTIC TOOLS FOR
GENETICS IN ADMIXED POPULATIONS.
HIS GROUP HAS PLAYED A LEADING
ROLE IN THE DEVELOPMENT OF
GENOMIC RESOURCES FOR THE STUDY
OF AFRICAN ANCESTRY POPULATIONS,
INCLUDING THE HAPMAP,
1000 GENOMES AND AFRICAN GENOME
VARIATION PROJECTS.
IN ADDITION, HIS GROUP HAS MADE
MAJOR CONTRIBUTIONS IN THE
GENETICS AND GENOMICS OF
DIABETES, HYPERTENSION AND
CARDIOVASCULAR DISEASE.
AND HE'S BEEN A LEADER OF THE
HUMAN H HEREDITY AND HEALTH IN
AFRICA, H3AFRICA INITIATIVE, TO
DEVELOP A PAN-CONTINENTAL
NETWORK OF LABS TO STUDY THE
GENETIC AND ENVIRONMENTAL BASIS
OF DISEASE IN AFRICANS.
IF WE CAN HAVE THE NEXT SLIDE,
WE WILL TURN TO OUR SECOND
SPEAKER IN THIS TALK, SERIES OF
TALKS ABOUT THE GENOMIC AND
ENVIRONMENTAL DETERMINANTS OF
GLOBAL HEALTH.
AND OUR SECOND SPEAKER IS THE
GOOD DR. CLEMENT ADEBAMOWO, FROM
THE UNIVERSITY OF MARYLAND.
HE IS A PROFESSOR OF
EPIDEMIOLOGY AND PUBLIC HEALTH,
AND DIRECTOR FOR GLOBAL HEALTH
CANCER RESEARCH, AND ASSOCIATE
DIRECTOR FOR DIVERSITY, EQUITY
AND INCLUSION AT THE MARLENE AND
STEWART GREENBAUM CANCER CENTER
AT THE UNIVERSITY OF MARYLAND.
HE'S THE PRINCIPAL INVESTIGATOR
ON AN NIH-FUNDED TRAINING
PROGRAM IN NON-COMMUNICABLE
DISEASES RESEARCH IN NIGERIA,
AND DIRECTOR OF THE
FOGARTY-FUNDED WEST AFRICAN
BIOETHICS TRAINING PROGRAM.
HE GOT HIS MEDICAL DEGREE WITH
HONORS AT THE UNIVERSITY OF JOS
IN NIGERIA.
HE HAD TRAINING IN SURGICAL
ONCOLOGY IN IBADAN, ALSO IN
NIGERIA, AND HAS A DOCTOR OF
SCIENCES DEGREE IN NUTRITION AND
EPIDEMIOLOGY -- NUTRITION
EPIDEMIOLOGY AND BIOSTATISTICS
FROM HARVARD.
HIS RESEARCH GROUP WORKS ON THE
EPIDEMIOLOGY OF CANCER IN
AFRICAN POPULATIONS, AND IN
PARTICULAR, WORKS ON THE
INTEGRATIVE EPIDEMIOLOGY OF
PERSISTENT HIGH RISK HPV
INFECTION, HOST GERMLINE AND
SOMATIC GENOMICS AND EP
GENOMICS, AND THE VAGINAL
MICROENVIRONMENT INCLUDING
CYTOKINES AND THE MICROBIOME,
AND THE RISK OF CERVICAL CANCER,
AND ALSO WORKS ON THE GENOMIC,
MICROBIOME AND ENVIRONMENTAL
RISK FOR BREAST CANCER IN
AFRICA.
SO WITHOUT FURTHER ADO, I'M
GOING TO TURN THINGS OVER TO THE
GOOD DOCTOR ROTIMI, WHO WILL GET
US STARTED BEFORE WE TURN TO OUR
SECOND SPEAKER.
DR. ROTIMI, PLEASE, TAKE IT
AWAY.
>>THANK YOU.
SO AGAIN, THANK YOU FOR THAT
WONDERFUL INTRODUCTION.
I JUST WANT TO SAY THAT MY GOAL
HERE TODAY IS TO PROVIDE INSIGHT
INTO THE IMPORTANT ROLE OF
AFRICA, THAT GEOGRAPHICAL AREA
OF THE WORLD WE CALL AFRICA
TODAY, IN TERMS OF HUMAN
GENETICS, ALSO HUMAN HISTORY,
AND TO BRING US HOME, ALL OF US,
IF WE TRACE OUR ANCESTRY FAR
ENOUGH, WE'RE GOING TO END UP
SOMEWHERE IN AFRICA.
AND THAT IS MY ROLE TODAY, AND
BEFORE MY GOOD FRIEND CLEMENT
TALKS TO YOU SPECIFICALLY ABOUT
HIS RESEARCH.
SO I DON'T HAVE ANY DISCLOSURE,
AS HAS BEEN SAID.
I HAVE A LEARNING OBJECTIVE.
AGAIN, UNDERSTANDING HOW THE
GEOGRAPHICAL REGION OF AFRICA
HAS SHIFTED REVOLUTIONARY
HISTORY OF HUMANS AND ALSO THE
IMPACT ON OUR HEALTH AND
DISEASE, THROUGH THE LENS OF
FOSSIL RECORDS AND GENOMICS.
SO THE FIRST INSIGHT HERE, IF I
CAN GET A POINTER, SO THE
HISTORY STARTED A LONG, LONG
TIME AGO AGAIN IN THAT
GEOGRAPHICAL AREA CALLED AFRICA.
OUR INITIAL SPLIT FROM OUR
CLOSEST RELATIVE ABOUT 6 TO
7 MILLION YEARS AGO, AND SINCE
THEN, WE HAVE BEEN EVOLVING AND
TRAVELING ACROSS AFRICA, AND
THEN AS YOU WILL SEE LATER, SOME
OF US VENTURED OUT OF AFRICA.
SO THIS REMARKABLE SIMILARITY
BETWEEN US AND OUR CLOSEST
RELATIVE, THE APES, ARE THAT LED
CHARLES DARWIN, IN 1871, TO
PREDICT THAT AFRICA WAS THE
LIKELY PLACE WHERE THE HUMAN
LINEAGE BRANCHED OFF FROM OTHER
ANIMALS, THAT IS, THE PLACE
WHERE THE COMMON ANCESTORS OF
CHIMPANZEES, HUMANS AND GORILLAS
ONCE LIVED.
NOW I'LL TELL YOU WHAT IS EVEN
MORE REMARKABLE ABOUT THAT
PREDICTION IN A MINUTE.
SO MOST OF THE RECORDS AND
HISTORY THAT HAVE BEEN WRITTEN
ABOUT HUMAN MIGRATION INSIDE AND
OUT OF AFRICA -- THE SOUTHEAST
AFRICA IS WHERE WE STARTED THE
HUMAN STORY, WHERE PEOPLE
MIGRATED TO DIFFERENT PARTS OF
THE WORLD, BUT AS I WILL SHOW
YOU IN A MINUTE, THERE HAS BEEN
SOME REVISION OF THAT HISTORY A
LITTLE BIT.
THIS IS WHEN I VISITED, I HAD
THIS WONDERFUL PICTURE TAKEN.
AGAIN, LOOKING AT LUCY,
3.2 MILLION YEARS OLD IN THAT
AREA DISCOVERED IN 1974, AGAIN
GIVING US A VERY LONG HISTORY OF
HUMANS IN THAT PART OF THE
WORLD.
SO RECENTLY, THIS IS THE STORY I
WAS TELLING YOU ABOUT, THERE WAS
A DISCOVERY IN MOROCCO THAT
CHANGED THE STORY OF THINKING
THAT EVERYTHING STARTED FROM
SOUTHERN AND EASTERN PARTS OF
AFRICA TO A PAN-AFRICAN
UNDERSTANDING OF HUMAN EVOLUTION
ACROSS AFRICA.
SO THIS RECENT DISCOVERY REALLY
CHANGED THE PICTURE, AND WHAT I
WILL SAY IS THAT WE ARE GOING TO
CONTINUE TO MAKE DISCOVERIES, SO
IT IS SUFFICIENT TO THINK THAT
IT IS TRULY A PAN AFRICAN STORY
TO HUMAN MIGRATION OF HUMAN
ORIGIN AFTER WE MIGRATED OUT OF
AFRICA AND POPULATED THE REST OF
THE WORLD.
SO IN TERMS OF GENOMIC EVIDENCE,
THIS PAPER THAT WAS WRITTEN IN
2017 ACTUALLY SUMMARIZES IT
QUITE NICELY.
AS YOU WILL SEE, A LONG HISTORY
IN THAT PART OF THE WORLD IN
AFRICA, UNTIL SOME OF US
MIGRATED OUT ABOUT 100,000 YEARS
AGO TO POPULATE THE REST OF THE
WORLD, AND WHAT IS REMARKABLE IS
THAT GENOMICS AND GENETICS
INFORMATION ENCODED IN OUR DNA
IS KNOWN TO CONFIRM THIS, AND
THIS IS WHAT I WAS SAYING IN
TERMS OF CHARLES DARWIN, THAT IT
WAS TRULY REMARKABLE THAT JUST
BY APPEARANCE AND LOOK, HE WAS
ABLE TO MAKE A PREDICTION IN
1871 THAT IS NOW FULLY SUPPORTED
BY GENOMIC DATA IN SEQUENCING
DNA GENOTYPING OF THOUSANDS OF
HUMAN BEINGS AROUND THE WORLD
AND IN AFRICA.
ONE OF THE REALLY INTERESTING
STORIES THAT WE COULDN'T HAVE
UNDERSTOOD UNTIL VERY RECENT AND
WITH THE HELP OF GENOMICS IS
THAT -- THAT WE ACTUALLY SHARE
DNA WITH DINOSAURS AND OTHERS
THAT WE DON'T HAVE THE
INFORMATION ON YET, AND THAT IS
TRULY REMARKABLE BECAUSE THERE
WAS NO WAY WE COULD HAVE
UNDERSTOOD THAT LOOKING AT
FOSSIL RECORDS.
SO GENOMICS HAVE PROVIDED
INSIGHTS, SO I'M NOT SURPRISED
THAT THE NOBEL PRIZE OF MEDICINE
THIS YEAR WAS INDEED GIVEN TO
THIS ASPECT OF GENOMIC SCIENCE,
AND -- DNA.
SO GIVEN THIS LONG HISTORY OF
HUMANS IN AFRICA, ACROSS AFRICA,
IT IS INDEED REMARKABLE THAT WE
SPENT OVER 99% OF OUR HISTORY,
OF OUR EVOLUTIONARY HISTORY, ON
THAT CONTINENT AFTER THE
CHIMPANZEE HUMAN DIVER JAN'S.
DIVERGENCE.SO THAT IS TRULY REMD
I WILL SHOW YOU WHAT IS SO
IMPORTANT.
SO THIS LONG HISTORY HAS INDEED
GENERATED SEVERAL IMPORTANT
CULTURAL AND GENETIC
CHARACTERISTICS IN AFRICAN
PEOPLE AND DIFFERENT PEOPLE
ACROSS THE WORLD.
SO AFRICANS HAVE OVER 200
LANGUAGES.
AND THAT'S ABOUT ONE-THIRD OF
THE LANGUAGES THAT EXIST IN THE
WORLD.
JUST THINK ABOUT THAT FOR A
MINUTE.
AND IN NIGERIA, WHERE I WAS
BORN, IS ONE OF THE MOST
LINGUISTICALLY DIVERSE COUNTRIES
IN THE WORLD, WITH OVER 500
LANGUAGES SPOKEN.
IN FACT, I WAS JOKING WITH
CLEMENT, WHO'S ALSO FROM
NIGERIA, AND GROWING UP,
20 KILOMETERS FROM EACH OTHER,
YOU RUN INTO A DIFFERENT
LANGUAGE GROUP.
SO IT'S ABSOLUTELY REMARKABLE.
SO AFRICAN POPULATIONS DISPLAY,
AGAIN, BASED ON THIS HISTORY AND
CONTINUOUS MIGRATION AND
VARIATION AND SHARING OF DNA,
DISPLAY CONSIDERABLE PHENOTYPIC
VARIATION IN TERMS OF SKIN
COLOR, HAIR TEXTURE, HEAD SHAPE
AND WE ARE TRYING TO TAKE
ADVANTAGE OF THIS.
SO IT IS NOT SURPRISING THAT
PEOPLE WHO LIVE CLOSE TO THE
EQUATOR ARE DARKER IN
COMPLEXIONS.
THIS IS TO PREVENT SUNBURN, SKIN
CANCER AND PHOTOLYSIS OF FOLATE
AND DAMAGE TO SWEAT GLANDS.
SO THIS I IS A VERY IMPORTANT
EVOLUTIONARY DEVELOPMENT, IN
THAT PART OF THE WORLD.
SO IN TERMS OF GENETICS, IT IS
IMPORTANT FOR US TO RECOGNIZE
AND SHARE THIS STORY THAT GIVEN
OUR COMMON HOME, AFRICA, CREATOR
OF HUMANITY, WE SHARE A LOT OF
GENETIC INHERITANCE.
BECAUSE WE WERE THERE BEFORE WE
MOVED TO DIFFERENT PARTS OF THE
WORLD.
THESE ARE SHARED BY ALL PEOPLE
AROUND THE WORLD.
AGAIN, IT'S A VERY IMPORTANT
MESSAGE THAT WE DON'T TELL WELL
ENOUGH, AND THAT IS WHY WHEN YOU
LEARN OF THE GENOME OF A LOT OF
DIFFERENT PEOPLE FROM DIFFERENT
PARTS OF THE WORLD, THEY ARE
REMARKABLY SIMILAR TO THE POINT
THAT THEY ARE ALMOST BORING,
ALTHOUGH THERE ARE STILL SOME
DIFFERENCES WHICH MEDICINE AND
SCIENCE ARE TRYING TO TAKE
ADVANTAGE OF TO UNDERSTAND.
SO WHY IS IT THAT WHEN YOU LOOK
AT AFRICAN POPULATION, AND
THEN -- OR POPULATIONS FROM
OTHER PARTS OF THE WORLD, THE
VARIATION YOU SEE IN THE OTHER
PARTS OF THE WORLD SEEMS TO BE
ALMOST A SUBSET OF WHAT YOU SEE
IN AFRICA, AND THAT IS BECAUSE
OF THIS ORIGINAL MIGRATION AND
BOTTLENECK EFFECT.
THOSE ADVENTUROUS MEMBERS THAT
EMIGRATED OUT OF AFRICA ONLY
TOOK A SUBSET OF THE VARIATION
THAT EXISTED THEN, AND,
THEREFORE, AFRICA IS THE ONLY
PLACE YOU CAN TRULY STUDY THIS.
AND I'LL SAY A LITTLE MORE ABOUT
THIS.
THIS IS WHY I THINK IT'S
TREMENDOUSLY IMPORTANT FOR US TO
SYSTEMATICALLY SAMPLE AFRICA,
THE NO JUST FOR ANOT JUST FOR AT
FOR THE WORLD BECAUSE WHAT WE
WILL LEARN WILL BENEFIT
EVERYBODY.
SO USING THE DATA FROM THE
HAPMAP WHICH CLEMENT AND MYSELF
HAHAVE BROUGHT TO FRUITION IN
NIGERIA AND ALSO KENYA AND THE
1000 GENOME, WE'VE BEEN ABLE TO
SHOW VERY WELL THAT THIS
DIVERSITY THAT WE'VE BEEN
TALKING ABOUT IN TERMS OF
AFRICAN POPULATION AND
EVOLUTIONARY HISTORY IS INDEED
TRUE, WE HAVE EVIDENCE OF IT IN
GENOMES.
AFRICAN POPULATIONS HAVE THE
HIGHEST NUMBER OF VARIABLE SIZE
BY GENOME.
LOSS OF FUNCTION VARIANTS,
AFRICAN POPULATION TENDS TO
DISPLAY THE LARGEST NUMBER OF
VARIATION THAT YOU SEE AGAIN
VERY, VERY CONSISTENT WITH THAT
EVOLUTIONARY STORY.
SO WHAT DO WE SEE WHEN WE LOOK
AT GENOMES OF AFRICAN PEOPLE?
YOU SEE MORE HAPLOTYPES.
MORE LEVELS OF LINKAGES TO --
PHYSICALLY STRUGGLE -- WHETHER
THEY'VE BEEN BROKEN DOWN SO YOU
DO SEE YOU HAVE LOWER LEVEL OF
LINKAGE DISEQUILIBRIUM, BECAUSE
OF VERY LONG HISTORY, THESE HAVE
HAD MORE TIME TO RECOMBINE.
MORE DIVERGENT PATTERNS OF
LINKAGE DISEQUILIBRIUM AND MORE
COMPLEX PATTERNS OF POPULATION
SUBSTRUCTURE.
SO I USE THIS TO TRY TO EXPLAIN
THIS IN A VERY SIMPLE WAY.
WHEN YOU TAKE THE GENOMES OF
THESE YORUBA AND COMPARE THEM TO
THESE MAASAI, SO YOU SEE THE
DIVERSITY, AND THAT IS WHY IT IS
CRITICALLY IMPORTANT THAT WHEN
WE LOOK AT PEOPLE IN TERMS OF
COMPLEXION OR SOCIAL
DEFINITION -- THAT WE MAY INDEED
NOT BE FULLY APPRECIATING THE
DIVERSITY THAT EXISTS WITHIN
THESE POPULATIONS THAT WE ARE
GROUPING TOGETHER.
AND I WILL SHOW YOU MORE
EXAMPLES OF THAT.
SO IN THE CONTEXT OF
PHARMACOGENOMICS, THIS IS REALLY
AN EXAMPLE OF TALKING ABOUT HUGE
DIVERSITY IN AFRICAN POPULATION.
SO WHEN YOU LOOK AT ADVERSE
REACTION TO A DRUG FOR THE
TREATMENT OF HIV, THERE'S AN HLA
THAT HELPS US TO IDENTIFY
INDIVIDUALS WHO WOULD HAVE
SENSITIVITY TO THIS DRUG.
NOW, WHAT IS REMARKABLE ABOUT
THIS IS THAT THE FREQUENCY OF
THIS HLA VARIES ACROSS THE WORLD
TREMENDOUSLY.
NOW WHEN YOU LOOK AT TWO AFRICAN
POPULATIONS, THE MAASAI AND
YORUBA, YOU SEE TREMENDOUS
DIFFERENCE IN THE ALLELE
FREQUENCY.
WHICH YOU WOULD EXPECT IN GIVING
THE HISTORY OF WEST AFRICA AND
POPULATIONS IN AMERICA.
SO THE POINT I'D LIKE TO MAKE
HERE IS THAT WHEN YOU USE A
CONCEPT OF AFRICANS OR BLACK,
YOU'RE RADICALLY -- IT CAN LEAD
US TO DECISIONS IN TERMS OF THE
PRACTICE OF MEDICINE.
SO WE HAVE TO RECOGNIZE THIS
DIVERSITY ACROSS THE POPULATION,
ESPECIALLY AFRICAN POPULATIONS.
SO IN SCIENCE, AS DR. KASTNER
SAYS, IN MY LAB WE ARE BEGINNING
TO TAKE ADVANTAGE OF THIS
DIVERSITY THAT WE SEE IN AFRICAN
POPULATIONS TO UNDERSTAND THE
GENETIC BASIS OF LOGICAL COMPLEX
DISEASE, AND THE EXAMPLE HERE IS
THAT WE'VE BEEN ABLE TO USE TO
LOCALIZE WHAT WE THINK IS THE
CAUSAL VARIANT, GET CLOSER TO
THE CAUSAL VARIANTS, SO I'LL
HIGHLIGHT AND GO MORE
SPECIFICALLY, WITH URIC ACID,
BUT WITH THIS PARTICULAR GENE,
WE ARE ABLE TO FINE MAP WHAT WAS
DISCOVERED IN THE EUROPEAN
POPULATION OF 250KB TO UNDER
50KB USING AFRICAN -- THE
DIVERSITY THAT WE SEE IN AFRICAN
POPULATION.
SO QUITE REMARKABLE.
NOW THIS IS A MORE SPECIFIC AM
AND A TRUE FIRST DEMONSTRATION
OF HOW THE FINE GRAIN --
STRUCTURE IN AFRICAN POPULATION
HAPLOS IN THE GENETICS OF TYPE .
SO WHEN YOU LOOK AT THIS REGION
FOR TCF7L2, YOU SEE WHEN YOU
LOOK AT THE EUROPEAN POPULATION,
CHINESE POPULATION COMPARED TO
KENYA, YOU SEE THE AFRICAN
POPULATION, THIS REGION HAS BEEN
BROKEN DOWN MULTIPLE, MULTIPLE
TIMES TO THE POINT THAT THE
RELATIONSHIP IN AFRICAN
POPULATION IS VERY, VERY, VERY
SMALL AND IN RELATIONSHIP
EUROPEAN POPULATION IS QUITE
HIGH, THEREFORE YOU'RE NOT
REALLY ABLE TO IDENTIFY THE TRUE
CAUSAL VARIANT.
SO USING THE AFRICAN FINE GRAIN
HAPLOTYPE STRUCTURE, WE'RE ABLE
TO BETTER LOCALIZE THE
PARTICULAR VARIANTS IN THIS GENE
TO A SINGLE SNP, SO THAT IS HOW
POWERFUL USING AFRICAN GENOME
AND THE HISTORY AND LONGER
EVOLUTIONARY HISTORY.
THIS IS ANOTHER REMARKABLE
EXAMPLE FROM THE LAB, AND THAT
IS ONE OF THE AREAS WHERE WE
HAVE BEEN VERY SUCCESSFUL IN
GENOMICS IS USING WHAT WE CALL
GENOME WIDE ASSOCIATION STUDY,
WHICH IS BASICALLY AN AGNOSTIC
WAY OF SEARCHING THE GENOME TO
SEE WHERE YOU SEE A SIGNAL FOR A
SPECIFIC TRAIT, IN THIS CASE,
TYPE 2 DIABETES.
IN EUROPEAN POPULATION, WHICH WE
HAVE DONE MOST OF THE WORK, WE
HAVE BEEN ABLE TO IDENTIFY OVER
400 VARIANTS, BUT THE REASON I
WANT TO SHOW TO YOU HERE TODAY,
THIS STUDY CALLED AADM THAT WE
HAVE BEEN DOING IN GHANA,
NIGERIA AND KENYA, WE WERE ABLE
TO STILL MAKE NOVEL DISCOVERIES
FOR TYPE 2 DIABETES IN THIS GE
GENE, ZRANB3.
THIS WAS REMARKABLE FOR US
BECAUSE THIS GENE -- THE REASON
IS QUITE SIMPLE, IT IS
AFRICAN-SPECIFIC, IN NON-AFRICAN
POPULATIONS, BUT WE DIDN'T KNOW
ANYTHING ABOUT ZRANB3 IN THE
CONTEXT OF TYPE 2 DIABETES SO WE
WENT TO MODEL IN THIS CASE WITH
ZEBRAFISH.
WHEN WE KNOCKED DOWN ZRANB3, WE
OBSERVED A MASSIVE REDUCTION IN
BETA CELLS.
SO THIS IS THE CONTROLS, AND
THESE ARE THE -- WHERE WE KNOCK
DOWN ZRANB3.
THE -- REDUCED TREMENDOUSLY.
THIS IS INDICATION FOR TYPE
2 DIABETES.
THEN WHEN WE WENT TO MAMMALIAN
CELL LINES AND SUPPRESSED, WE
WERE ABLE TO FULLY APPRECIATE
THE CONSEQUENCE OF THIS GENE IN
THE CONTEXT OF TYPE 2 DIABETES
BECAUSE THESE CELLS WERE UNABLE
TO RESPOND IN A HIGH GLUCOSE
ENVIRONMENT IN TERMS OF INSULIN
PRODUCTION.
SO THAT WAS REALLY SORT OF AN
AHA MOMENT IN THIS EXPERIMENT.
THE SAME STORY HERE IN TERMS O
OF -- AGAIN MAKING NOVEL
DISCOVERY IS SIGNAL 4D IN
RELATION TO BODY MASS INDEX.
WHAT WAS REMARKABLE IS THAT
CARRIERS OF THE C ALLELE OF THIS
VARIANT WEIGH ABOUT 6 POUNDS
HEAVIER AND THAT IS TREMENDOUS
IN TERMS OF POPULATION EFFECT.
AND WE WERE ABLE TO SHOW THAT
INDIVIDUALS, WHETHER THEY'RE MEN
OR WOMEN WHO WERE OBESE WERE
EXPRESSING -- 4D SEMA4D AT A LEL
THAT IS MUCH HIGHER, NOT PICKED
UP IN EUROPEAN POPULATION.
NOW THIS IS ONE OF THE MOST
EXCITING WORK I THINK COMING OUT
OF OUR LAB, AND THAT IS HOW WE
USE GENOMIC DATA, SEQUENCE DATA
FROM DIFFERENT PARTS OF THE
WORLD TO ANSWER SOME VERY OLD
QUESTIONS IN TERMS OF SICKLE
CELL.
WE WERE ABLE TO RESOLVE A
40-YEAR-OLD DEBATE ABOUT THE
ORIGIN OF THE SICKLE ALLELE.
THIS HAS BEEN GOING ON, AROSE
MULTIPLE TIMES IN ONE PLACE.
WE SHOW USING OUR DATA THAT IT'S
ACTUALLY ORIGINATED IN ONE
PLACE, AND WE WERE ABLE TO DATE
THAT MUTATION TO ABOUT 7300
YEARS AGO IN AN AREA IN THE
SAHARA, TODAY A DESERT, BUT IT
WAS INDEED VERY GREEN AND WET AT
THAT POINT, SO YOU CAN SEE HOW
IT CAN INDEED SUPPORT MOSQUITO
LIFE IN THAT PART OF THE WORLD.
AND THEN WE WERE ABLE TO
SIMPLIFY THE HAPLOTYPE BASED
CLASSIFICATIONS, AND THEN WE
IDENTIFIED 27 LINKED VARIANTS
THAT WE BELIEVE MAY INFLUENCE
DISEASE SEVERITY.
THIS WAS ABSOLUTELY AN EXCITING
DISCOVERY.
WE RECEIVED INTERNATIONAL
RECOGNITION, PARTICULARLY LIKE
THIS HEADING FROM "THE NEW YORK
TIMES," HOW ONE CHILD'S SICKLE
CELL MUTATION HELPED PROTECT THE
WORLD FROM MALARIA.
THAT IS INDEED THE STORY, AND WE
WERE VERY EXCITED ABOUT THIS
DISCOVERY.
SO GIVEN EVERYTHING THAT I'VE
SAID TO YOU SO FAR, IT IS INDEED
A LITTLE TROUBLING TO KNOW THAT
WE HAVE REALLY DONE GOOD WORK
SAMPLING DIFFERENT AFER CAP AFRN
POPULATIONS SO WHEN YOU COMPARE
A NUMBER OF AFRICAN GWAS
STUDIES, GENOME WIDE ASSOCIATION
STUDIES THAT HAVE BEEN DONE IN
AFRICAN POPULATIONS, YOU'LL SEE
UP TO 1%, AND COMPARED TO CLOSE
TO 96% IN THE EUROPEAN
POPULATION.
THIS IS WHERE SOMETIMES THE
SCIENTIFIC PROCESS IS NOT VERY
RATIONAL IN THE SENSE THAT GIVEN
THE HISTORY, GIVEN THAT AFRICA
IS THE CRATER OF HUMANITY AND
THAT'S WHERE WE HAVE MOST OF THE
VARIATION, YOU WOULD THINK THAT
AS THEY WILL START AND MOVE TO
DIFFERENT PARTS OF THE WORLD,
BUT AGAIN, THAT IS NOT A STORY
OF SCIENCE, AT LEAST SCIENCE --
AND FOR US, WE WERE VERY WORRIED
AND CONCERNED ABOUT THIS BECAUSE
WE WANTED TO MAKE SURE THAT
TOMORROW'S MEDICINE IS INDEED IN
THE FUTURE TO ALL HUMANITY.
WE WERE ABLE TO CONDUCT A LARGE
STUDY THAT WAS TALKED ABOUT IN
MY INTRODUCTION EARLIER.
THIS IS A REMARKABLE STUDY
FUNDED BY THE NIH AND THE
WELLCOME TRUST IN THE U.K., AND
MONEY HAS GONE TO DIFFERENT
AFRICAN INSTITUTIONS AND
INVESTIGATORS TO THE POINT WHERE
THETHEY HAVE ENROLLED OVER 100,0
AFRICANS INTO THIS STUDY AND WE
HAVE TRAINED A LARGE NUMBER OF
AFRICAN SCIENTISTS WHO A.
SO THE STORY I BRING TO YOU HERE
IS IN A RECENT PUBLICATION IN
TWEB 20.
ONE OF THE INTERESTING STORIES
THAT ALMOST ALWAYS HAPPENS IS
WHEN YOU SEQUENCE AFRICAN
POPULATION, YOU ALMOST ALWAYS
DISCOVER NOVEL VARIANTS.
IN THIS CASE, WE DISCOVERED OVER
3 MILLION NOVEL VARIANTS.
AND WE WERE ABLE TO IDENTIFY
62 NEW LOCI ON THAT VERY STRONG
SELECTION, INCLUDING DATA FROM
BACTERIAL, VIRAL, DEFENSE
AGAINST NEMOTODES, HEMO STASIS
AND PIGMENTATION.
BECAUSE SOME OF THESE PATHOGENIC
VARIANTS ARE IN NORTH AMERICA,
EUROPE, CARRIED BY A NUMBER OF
AFRICANS, SO IT STARTED TO BRING
TO QUESTION, SOME OF THESE
PATHOGENIC VARIANTS MAY NOT BE
AS PATHOGENIC, CALLING FOR MORE
STUDIES TO BE DONE.
WE ALSO INFORMED HUMAN
HISTORIMENT WE CONTINUED TO
INFORM HUMAN HISTORY.
ONE OF THE LARGEST MIGRATIONS IN
AFRICA IS THE BANTU MIGRATION.
WHICH STARTED AROUND THE AREAS
OF -- AROUND CAMEROON, AND THERE
HAVE BEEN DIFFERENT MIGRATION
ROUTES THAT HAVE BEEN SUGGESTED,
BUT WE BELIEVE USING OUR DATA,
THAT THE WAREHOUSE SO TO SAY IS
SWSOMEWHERE IN ZAMBIA, NOT IN ET
AFRICA LIKE WE TALKED ABOUT.
SO THIS AGAIN IS A VERY
IMPORTANT DISCOVERY, AND THIS IS
FOR ME ONE OF THE MOST
FASCINATING STORY FROM THIS
WORLD, BECAUSE -- THERE'S A
GROUP IN NIGERIA, ALMOST THE
MIDDLE OF NIGERIA, THAT SHOWED A
VERY HIGH LEVEL OF NILO-IS A
HA-IS-SAHARANANCESTRY.
WE'RE ABLE TO DATE THIS TO ABOUT
1850 YEARS AGO, SO THE QUESTION
IS HOW DOES THIS VARIATION --
MOI DELVE NIGERIA.
SO WE CONTINUE TO -- THE POINT
HERE IS WE NEED TO SAMPLE MORE
AFRICAN POPULATIONS.
SO NOW I'M GOING TO MOVE INTO
THE OTHER ASPECTS OF AFRICAN
ANCESTRY POPULATION THAT I THINK
IS CRITICALLY IMPORTANT.
HERE I SAY THAT AFRICAN
POPULATIONS, YOU KNOW, REALLY
PROVIDE SCIENTISTS A UNIQUE
HUMAN LABORATORY TO STUDY HOW
OLD GENES INTERACT WITH NEW
ENVIRONMENT IN THE EVOLUTION OF
COMPLEX TRAITS.
BECAUSE AFRICAN POPULATION ARE
NOW SPRAYED ALL OVER THE WORLD,
HISTORY IN TERMS OF SLAVE TRADE,
AND NOW IN NORTH AMERICA, IN
BRAZIL AND DIFFERENT PARTS OF
THE WORLD, AND THEY SHARE A
DIFFERENT LEVEL OF EUROPEAN,
NATIVE AMERICAN AND AFRICAN
GENETIC BACKGROUND, AND WE CAN
TAKE ADVANTAGE OF THIS USING
STRATEGY LIKE ADD MIXTURE
MAPPING AND I'LL TALK ABOUT THAT
IN THE NEXT SLIDE.
SO ONE OTHER STORY HERE WHICH IS
REALLY IMPORTANT IS THAT WHEN
YOU LOOK AT PEOPLE WHO
SELF-IDENTIFY AT AFRICAN
AMERICAN, THERE'S HUGE VARIATION
IN TERMS OF THE AFRICAN GENETIC
POOL.
RANGING FROM .6 TO 99.7%.
SO -- AND THE AVERAGE IS ABOUT
80%.
SO THIS IS WHERE AVERAGE BECOMES
NOT VERY USEFUL OR HELPFUL IN
THIS REGARD.
SO YOU SEE THIS PERSON HERE,
AGAIN ALMOST COMPLETELY WHAT WE
CALL EUROPEAN ANCESTRY, AND THIS
ALMOST COMPLETELY AFRICAN
ANCESTRY.
SO AGAIN, -- IN TERMS OF HOW WE
CLASSIFY PEOPLE.
BUT THE ADMIXTURE MAPPING HERE
IS REALLY TAKING ADVANTAGE OF
THE FACT THAT IN THE CONTEXT OF
AFRICAN AMERICAN, SO MOSTLY
AFRICAN AND EUROPEAN POPULATION
TOGETHER AND OVER TIME, THE
RECOMBINATION -- DIFFERENT
FRAGMENTS OF THE GENOME NOW
CONTAIN DIFFERENT INFORMATION
FROM THE TWO ANCESTRAL
POPULATIONS AND WE TAKE
ADVANTAGE OF THAT IN MAPPING
GENES.
AND WE ALSO DEVELOP -- TAKEN
ADVANTAGE OF -- THE STORY I WANT
TO TELL YOU TODAY IS REALLY
ABOUT KIDNEY DISEASE.
AFRICAN AMERICAN -- ABOUT 18% OF
U.S. POPULATION, BUT ABOUT 32%
OF KIDNEY FAILURE, AFRICAN
AMERICANS ARE FOUR TIMES MORE
LIKELY TO DEVELOP KIDNEY FAILURE
THAN THEIR EUROPEAN COUNTERPART.
SO THERE'S THE HYPOTHESIS THAT
IF INDEED THIS DISPARITY IS DUE
TO GENETICS, THEN THE SIGNAL IN
OUR GENOME SHOULD TRACK THE WEST
AFRICAN PART OF THAT ANCESTRY.
AND IT WAS INDEED, YOU KNOW,
SHOWN BY THE GROUP FROM NIH, DRR
COLLEAGUES IN HOPKINS, PICKING
UP A VERY STRONG SIGNAL IN 2022,
WHICH WAS PREVIOUSLY THOUGHT OF
AS MHY9 LOCUS, BUT SUBSEQUENT
SEQUENCING DATA SHOW THAT --
GENE THAT WAS A STRONG LINKA
LINKAGE -- SO WHAT IS IMPORTANT
ABOUT THIS DISCOVERY?
IT IS VERY RARE FOR US TO SEE
RISK -- ALL RATIO THAT IS THIS
HIGH IN COMPLEX TRAITS.
THERE WAS ABOUT 10 FOR FSGS AND
OVER 7 FOR END STAGE KIDNEY
DISEASE.
REMARKABLY, THIS VARIANCE IS
ABOUT 40% -- ABOUT 20% AMONG
AFRICAN AMERICANS, NOW THIS
DIDN'T MAKE ANY EVOLUTIONARY
SENSE BECAUSE IF SOMETHING IS
THIS -- TO SURVIVAL, THEN --
SHOULD BE TRYING TO ELIMINATE
IT.
IT TURNS OUT THAT IT'S
ABSOLUTELY PROTECTIVE, BEGINS
THE SO CALLED AFRICAN SLEEPING
SICKNESS.
SO THAT IS REALLY A WONDERFUL
STORE HE'LL.
WHAT IS TRULY REMARKABLE IN THIS
CASE IS THE FACT THAT 1 IN
5 PEOPLE WITH TWO COPIES OF THE
APOL1 RISK VARIANT WILL DEVELOP
KIDNEY DISEASE.
AND OVER 70% OF NON-DIABETIC
KIDNEY FAILURE IN AFRICAN
AMERICANS IS DUE TO
APOL1 VARIANTS.
4 IN 10 AFRICAN AMERICANS ON
DIALYSIS HAVE TWO COPIES OF THIS
APOL1 VARIANT.
SO YOU SEE HOW IT CAN REALLY
INCREASE THE DISPARITY IN TERMS
OF KIDNEY FAILURE.
AND MORE IMPORTANTLY, IT'S ALSO
ALREADY HAVING CLINICAL UTILITY
IN THE SENSE THAT IF YOU ARE
ABOUT TO DONATE YOUR KIDNEY, IT
IS IMPORTANT TO BE SCREENED FOR
THIS VARIANCE BECAUSE THE
LIKELIHOOD OF THE KIDNEY FAILING
IS QUITE HIGH, AND IF YOU'RE
ALSO A KIDNEY RECIPIENT, IT
WOULD BE GOOD FOR YOU TO KNOW
THE STATUS OF YOUR DONOR,
BECAUSE, AGAIN, THE LIKELIHOOD
OF THE KIDNEY YOU ARE RECEIVING
FAIL SOMETHING ALSO QUITE HIGH.
NOW, THIS IS THE WONDERFUL STORY
ABOUT HUMANITY.
WE LIKE TO TRAVEL, WE LIKE TO
VISIT DIFFERENT PLACES, AND MORE
IMPORTANTLY, WE LIKE TO SHARE
DNA.
AS A RESULT OF THIS SHARING,
THIS PARTICULAR RISK VARIANT FOR
KIDNEY DISEASE HAS SPREAD ALL
OVER THE WORLD TO THE POINT NOW
WHERE YOU CAN -- USE -- TO
IDENTIFY WHO IS AT RISK.
AGAIN GIVING US CAUTIONARY TALES
ABOUT HOW WE CLASSIFY PEOPLE OR
LOOK AT PEOPLE ESPECIALLY IN THE
CONTEXT OF MEDICINE, WHICH IS A
SAMPLE SIZE OF 1, IT IS YOU AND
YOUR DOCTOR.
SO AGAIN, VERY, VERY IMPORTANT
DISCOVERY, AND I THINK THIS
MIGHT BE MY LAST SLIDE HERE, TO
REALLY TELL YOU ABOUT
INTERACTIONS IN TERMS OF
DIFFERENT ME TABULATE --
TRIGLYCERIDES.
WHICH IS THE BAY OWE MARKER FOR
BIOMARKER FOR HEARTDISEASE, STRB
WE'RE ALWAYS WONDERING WHAT'S
GOING ON WITH TRIGLYCERIDES
BECAUSE WHEN WE MEASURE THEM IN
EUROPEANS, EAST AFRICANS AND
WEST AFRICANS, THEY ARE
REMARKABLY SIMILAR DESPITE
DIFFERENT LEVEL OF PHYSICAL
ACTIVITY AND WOULD DEMAX INDEX,
REMARKABLY -- ACTUALLY HAVE
ALMOST WHAT I WOULD CALL
EXCELLENT TRIGLYCERIDE LEVELS.
AND THAT IS NOT WHAT WE OBSERVE
IN EAST AFRICANS AND IT'S ALSO
NOT WHAT WE OBSERVE IN
EUROPEANS.
SO WE WANTED TO STUDY THIS A
LITTLE MORE.
SO WE PUT TOGETHER A VERY LARGE
STUDY COMBINING -- OF 32,000
PEOPLE FROM DIFFERENT PARTS OF
THE WORLD IN DIFFERENT
ENVIRONMENTAL SETTINGS.
AND ONE OF THE THINGS THAT WE
OBSERVE CLEARLY IS THAT FOR SOME
OF THESE -- WE FOUND VERY CLEAR
ANCESTRY PATTERNS TO THE POINT
WHERE WE DIDN'T SEE A LOT OF
ENVIRONMENTAL INFLUENCE.
BUT THAT STORY WAS VERY
DIFFERENT FOR WHEN WE LOOK AT
THE RELATIONSHIP BETWEEN
TRIGLYCERIDES AND TYPE
2 DIABETES, WHERE WE SAW THAT
IN -- WHERE WE SAW THE STRONGEST
EVIDENCE OF EVIDENCE IN RURAL
WEST AFRICAN COMMUNITIES, WHICH
AGAIN SHOWS THAT THERE IS REALLY
STRONG ENVIRONMENTAL CONTEXT, WE
ARE GOING TO STUDY THAT MORE.
SO I WANT TO LEAVE YOU WITH THIS
MESSAGE.
THIS IS FROM MY -- FRIENDS WHO
WROTE THIS REVIEW PAPER AND
ARTICLE, AND REALLY SAID THIS
VERY WELL.
THE GENETICS OF AFRICAN
POPULATIONS REVEALS AN OTHERWISE
MISSING LAYER OF HUMAN VARIATION
THAT AROSE BETWEEN 100,000 YEARS
AND 5 MILLION YEARS AGO.
BOTH THE VAST NUMBER OF THESE
ANCIENT VARIANTS AND THE
SELECTIVE PRESSURES THAT THEY
SURVIVED YIELD INSIGHTS INTO
GENES RESPONSIBLE FOR COMPLEX
TRAITS IN ALL, IN ALL
POPULATIONS.
THIS IS WHY I THINK STUDYING
AFRICAN POPULATIONS AND IN A
VERY SYSTEMATIC WAY IS A GLOBAL
BENEFIT AND IS SCIENTIFIC AND
SOCIAL -- IT'S AN EQUITY ISSUE
THAT WE NEED TO DO AND STUDY
VERY WELL FOR THE BENEFIT OF
AFRICANS AND FOR THE BENEFIT OF
THE GLOBAL POPULATIONS.
SO THANK YOU, QUITE A BIT OF
DATA FROM MY LAB ARE FROM THESE
INDIVIDUALS.
I'M JUST THE CHAIR LEADER, AND
I'M GLAD TO TAKE QUESTIONS AFTER
CLEMENT FINISHES HIS TALK.
SO I'M GOING TO STOP SHARING NOW
AND I THANK YOU FOR LISTENING.
>>I'M CLEMENT ADEBAMOWO.
AS DAN KASTNER HAS PREVIOUSLY
INTRODUCED, I WORK NOW AT THE
UNIVERSITY OF MARYLAND, WHERE I
CONTINUE TO TEACH AND DO
RESEARCH.
I'M EXTREMELY EXCITED TO FOLLOW
UP ON THE BRILLIANT PRESENTATION
THAT DR. ROTIMI JUST GAVE ON THE
VALUE AND THE OUTCOMES OF
CONDUCTING GENOMIC RESEARCH IN
AFRICAN POPULATIONS.
SO I'VE TITLED MY PRESENTATION
"INTO AFRICA," IN CONTRAST WITH
HIS TALK, WHICH IS FOCUSED ON
OUT OF AFRICA.
AND THE REASON WHY I'VE DONE
THIS IS TO SAY THAT WE'RE AT A
BIT OF A CROSS ROAD AND WE NEED
TO BE THINKING ABOUT HOW NEXT WE
SHOULD ENGAGE AFRICAN
POPULATIONS AND AFRICAN
SCIENTIFIC COMMUNITY IN
ADVANCING GENOMIC RESEARCH AND
GENOMIC MEDICINE IN AFRICAN
POPULATIONS.
SO AFRICAN POPULATIONS ARE NOT
ONLY PARTICIPATING IN
EPIDEMIOLOGICAL STUDIES THAT
THEY MAY NOT DERIVE MEDIUM AND
SHORT TERM BENEFITS FROM, BUT
THEY ARE ENGAGED IN STUDIES THAT
DELIVER ON THE PROMISE OF
GENOMICS FOR MEDICINE AND PUBLIC
HEALTH.
SO I HAVE NO CONFLICTS TO
DISCLOSE.
I HOPE THAT BY THE TIME I FINISH
MY PRESENTATION, YOU WILL HAVE
HAD THE OPPORTUNITY TO
APPRECIATE THE OPPORTUNITIES AND
CHALLENGES FOR GENOMIC MEDICINE
IN AFRICAN POPULATIONS,
UNDERSTAND THE CLINICAL PRACTICE
AND HEALTH RESEARCH ECOSYSTEMS
IN THESE AFRICAN COUNTRIES, AND
THE IMPLICATIONS OF THE
ECOSYSTEMS FOR THE
IMPLEMENTATION AND UPTAKE OF
GENOMICS INTO CLINICAL MEDICAL
PRACTICE AND PUBLIC HEALTH.
SO I WILL NOT GO ABOUT THE
TERRAIN DR. ROTIMI HAS GIVEN A
VERY GOOD SUMMARY OF THE
CONTRIBUTIONS OF RESEARCH IN
AFRICA THROUGH GLOBAL GEE DMOA S
DATA AND PUBLIC GOOD.
SO WE KNOW MANY OF THIS ALREADY,
AND MANY OF THESE GOODS OCCURRED
BECAUSE OF SEVERAL RESEARCH
PROJECTS.
SOME OF THESE ARE CONSORTIUM
PROJECTS LIKE THE INTERNATIONAL
HAPLOTYPE MAPPING PROJECTS, THE
THOUSAND GENOMES, HUMAN HEREDITY
FOR HEALTH IN AFRICA, TCGA,
PRIMED CONSORTIUM, WHICH IN THE
DIFFERENT WAYS HAVE ENABLED THE
AVAILABILITY OF TREMENDOUS
AMOUNT OF GENOMIC DATA FROM
AFRICA TO BE AVAILABLE IN PUBLIC
DATABASES.
AND THEN THERE ARE NUMEROUS
INVESTIGATOR-LED GENOMIC
RESEARCH THAT HAVE ALSO
CONTRIBUTED TO WHAT WE KNOW AND
WHAT IS AVAILABLE.
YET DESPITE THIS PROGRESS AND
CONTRIBUTIONS FROM AFRICAN
SCIENTISTS AND POPULATIONS, AND
AS DR. ROTIMI'S PRESENTATION HAS
DEMONSTRATED, GIVEN REALLY
INTRIGUING AND INTERESTING
FINDINGS THAT LEAD TO NEW
BIOMARKER DISCOVERIES, NEW
UNDERSTANDING OF DISEASE
MECHANISMS IN AFRICAN AND GLOBAL
POPULATIONS, THERE IS AN
UNFORTUNATELY LIMITED AMOUNT OF
GENOMIC RESEARCH TO BE DONE IN
AFRICAN POPULATIONS.
WHAT IS EVEN MORE CHALLENGING AS
WE GO FORWARD IS THAT THE
PROPORTION OF GENOMIC RESEARCH
BEING DONE IN AFRICAN
POPULATIONS MAY ACTUALLY NOW BE
EITHER STATIC OR BE DECLINING,
AND PART OF THE REASON FOR THAT
IS MANY OF THOSE CONSORTIA
PROJECTS THAT HAVE BEEN
INCREDIBLY HELPFUL ARE COMING TO
AN END, AND RESEARCHERS IN OTHER
PARTS OF THE WORLD CONTINUE TO
GENERATE AND DUMP HUGE AMOUNTS
OF GENOMIC DATA FROM DIVERSE
POPULATIONS.
SO WE SEE A SITUATION WHERE THE
POTENTIAL FOR DISCOVERY AND
DELIVERY OF THE BENEFITS OF
GENOMIC MEDICINE AND PUBLIC
HEALTH APPEAR TO CERTAIN DEGREE
TO BE -- FROM AFRICAN
POPULATIONS.
TO COUNTER THIS, THERE HAVE BEEN
SEVERAL PROPOSALS.
PERHAPS THE MOST WELL-KNOWN AND
PARADIGMACTIC EXAMPLE OF THESE
PROPOSALS IS THE ONE FROM
AMBROSE -- OF THE SEQUENCING OF
3 MILLION AFRICAN GENOMES TO
BUILD A REPRESENTATIVE HUMAN
REFERENCE GENOME AND ESTABLISH A
PAN-AFRICAN BIOBANK OF CLINICAL
INFORMATION AND SAMPLES.
SO ON THE ONE HAND THEREFORE, WE
HAVE THE CHALLENGE OF GENERATING
MORE GENOMIC DATA FROM AFRICAN
POPULATIONS, MAKING THEM
PUBLICLY AVAILABLE SUCH THAT
THEY CAN CONTRIBUTE TO DISCOVERY
IN AFTER CAN POPULATIONS AND IN
THE REST OF THE WORLD.
A DIFFERENT BUT RELATED CONCERN
IS THE LIMITED APPLICATION TO
DATE OF GENOMIC MEDICINE IN
AFRICAN POPULATIONS.
BECAUSE THESE POPULATIONS HAVE
CONTRIBUTED AS YOU HE HEARD FROM
DR. ROTIMI'S PRESENTATION, IT IS
REASONABLE THAT WE WILL SEE
COMMUNITIES AND PATIENTS WITH
EXPECTATIONS OF DOWNSTREAM
BENEFITS FROM GENOMIC RESEARCH
THAT HAVE BEEN DONE IN THEIR
COUNTRIES AND IN THEIR
ENVIRONMENTS.
AND RESEARCHERS, WHEN WE ENGAGE
THESE COMMUNITIES, TYPICALLY
ASSURE THE COMMUNITIES THAT THEY
WILL AT SOME POINT BENEFIT FROM
THE OUTCOMES OF THESE GENOMIC
RESEARCH PROJECTS.
BUT WHAT WE SEE IS THAT THERE
HAS BEEN LESS ATTENTION TO
DISSEMINATION OF THE BENEFITS OF
GENOMIC RESEARCH.
AND THIS IS PARTLY BECAUSE OF
THE SHARED COMPLEXITY, THE
INVESTMENT AND INFRASTRUCTURE
THAT IS REQUIRED TO TRANSLATE
THE FINDINGS FROM GENOMIC
RESEARCH TO CLINICAL OR
CLINICALLY ACTIONABLE
INTERVENTIONS, AND THAT'S WHY WE
EMPHASIZE THE ROLE OF THE
ECOSYSTEM IN WHICH PATIENTS AND
COMMUNITIES IN THIS ENVIRONMENT
EXISTS, BECAUSE IT IS BEYOND THE
ABILITY OF THE TYPICAL RESEAR
RESEARCHERS AND THEIR FUNDING TO
BE RESPONSIBLE FOR THE CONTINUUM
OF DISCOVERY TO CLINICAL
ACTIONABILITY.
PARTICULARLY BECAUSE THOSE KINDS
OF INTERVENTIONS HAVE A MORE
LOCAL BENEFIT THAN DISCOVERIES
THAT CAN FWELL NEW BIOMARKERS OF
DISEASE IN DEVELOPED COUNTRIES.
SO WE ASK OURSELVES, HOW ON THE
ONE HAND DO WE SOLVE THE PROBLEM
OF GENERATING MORE AND MORE
DIVERSE GENOMIC DATA FROM
AFRICAN POPULATIONS WHILE
SIMULTANEOUSLY DELIVERING THE
BENEFITS OF GENOMIC RESEARCH TO
THESE POPULATIONS.
SO IN THE PAST SEVERAL YEARS,
THE RESEARCH COMMUNITY HAS
CONFRONTED THIS KIND OF PROBLEM
AND DEVELOP A WHOLE FIELD CALLED
IMPLEMENTATION SCIENCE TO SPEED
UP THE DELIVERY OF
EVIDENCE-BASED INTERVENTIONS
INTO POPULATIONS.
THE FIELD OF IMPLEMENTATION
SCIENCE ENABLES US TO IDENTIFY
THE BARRIERS AND THE FACILIT
FACILITATORS AND THE
DETERMINANTS OF THE ADOPTION AND
THE SUSTENANCE OF EVIDENCE-BASED
INTERVENTION IN ANY HEALTHCARE
SYSTEM.
SO WHAT WE'RE PROPOSING IS TO
CONSIDER GENOMIC RESEARCH THAT
INCREASES THE NUMBER AND
DIVERSITY OF GENOMIC DATA FROM
AFRICA AND THE IMPLEMENTATION OF
PROVEN GENOMIC MEDICAL
INTERVENTIONS IN THE CLINICAL
AND PUBLIC HEALTH PRACTICE IN
AFRICA AS EVIDENCE-BASED
INTERVENTIONS, AND IF WE
CONCEPTUALIZE THE PROBLEM IN
THIS FASHION, THEN WE ARE ABLE
TO BORROW FROM THE FIELD OF
IMPLEMENTATION AND DISSEMINATION
SCIENCE, AND USE THE TOOLS OF
THIS SCIENCE TO ADVANCE THE
GENOMIC RESEARCH AND CLINICAL
PRACTICE, NOT JUST IN AFRICA,
BUT IN OTHER LOW AND MIDDLE
INCOME COUNTRIES, AND SOME AREAS
IN HIGH INCOME COUNTRIES THAT
ARE RELATIVELY UNDERSERVED.
BY
THE CURRENT SYSTEMS IN THOSE
ENVIRONMENTS.
SO AS EVIDENCE-BASED
INTERVENTIONS, THEREFORE, WE CAN
USE, FOR EXAMPLE, INTERVENTION
MAPPING IN ORDER TO CONDUCT A
SYSTEMATIC EVALUATION FOR THE
IMPLEMENTATION AND DISSEMINATION
OF RESEARCH THAT INCREASES THE
NUMBER AND DIVERSITY OF GENOMIC
DATA FROM AFRICAN POPULATIONS
AND IMPLEMENT GENOMIC MEDICINE
IN CLINICAL AND PUBLIC HEALTH
PRACTICE IN AFRICA BY TAKING
CONSIDERATION OF THE
DETERMINANTS AND THE MECHANISMS
AND STRATEGIES THAT WE NEED TO
IMPLEMENT TO EFFECT THE NEEDED
CHANGE.
INTERVENTION MAPPING ENABLES US
TO DESIGN AND IMPLEMENT MULTIPLE
OR MULTILEVEL INTERVENTIONS AND
IMPLEMENTATION STRATEGIES THAT
ENHANCE THE ADOPTION,
IMPLEMENTATION AND SUSTENANCE OF
THESE EBIs.
SO WE'RE NOT DEALING WITH THE
CHALLENGE IN THE TRADITIONAL WAY
OF JUST GRANTS AND CONTRACTS,
BUT WE'RE STEPPING BACK TO SAY
WHAT DO WE NEED TO DO TO ENHANCE
THE ADOPTION AND MAINTENANCE OF
BOTH GENOMIC RESEARCH AND
GENOMIC MEDICINE IN AFRICA?
SO IF WE TAKE THE INTERVENTION
MAPPING CONCEPT FURTHER,
INTERVENTION MAPPING HAS SIX
DOMAINS.
AND THESE DOMAINS, WHILE THEY
MAY APPEAR LINEAR, ARE ACTUALLY
ITERATIVE, SO ONE STEP FITS ON
THE OTHER, INFORMS THE OTHER,
AND YOU CAN GO BACK AND FORTH
AND BUILD AS YOU BETTER
UNDERSTAND THE LANDSCAPE.
SO WE NEED FIRST TO UNDERSTAND
WHAT THE NEEDS ARE, WHAT NEEDS
TO BE DONE AND FOR WHOM.
IN THIS CASE, FOR GENOMIC
RESEARCH, WE WANT TO INCREASE
THE NUMBER AND DIVERSITY OF
AFRICAN GENOMIC DATA IN GLOBAL
DATABASES.
THAT DEFINES THE EBI THAT WE
WANT TO IMPLEMENT.
THIS DOES NOT MEAN IT'S
EXCLUSIVE, BUT FOR THE
INTERVENTION MAPPING PROCESS, WE
HAVE TO DEFINE THE PROBLEM.
AND FOR GENOMIC MEDICINE, WHAT
WE WANT TO SEE IS THE
INTEGRATION OF GENOMIC MEDICAL
PRACTICE INTO CLINICAL AND
PUBLIC HEALTH.
NOW, IF WE SUCCEED IN DOING
THESE TWO THINGS, WE WILL BE
ABLE TO REGULARLY GENERATE HIGH
QUALITY GENOMIC DATA FROM AFRICA
WITHOUT THE NEED FOR THE
CONSORTIA PROJECTS AN AND THIS L
CREATE A SUSTAINABLE PATH SUCH
THAT THE INSTITUTIONS, THE
PERSONNEL AND THE COMMUNITIES,
THE STRUCTURES AND THE
GOVERNMENTS AND NON-GOVERNMENT
COMPLEMENTS CAN WORK TOGETHER
AND BRING THE BENEFIT OF GENOMIC
MEDICINE TO THESE POPULATIONS.
SO OF COURSE WE NEED TO CREATE
MA TRTRICES OF THE CHANGE WE WAT
TO SEE BY COMBINING PERFORMANCE
OBJECTIVES WITH THEIR
DETERMINANTS.
SO WE NEED FUNDING, BUT WHAT
KIND OF FUNDING?
HOW SHALL IT BE STRUCTURED?
WE NEED INFRASTRUCTURE.
WHAT TYPES OF INFRASTRUCTURE CAN
BE SUSTAINABLY INTRODUCED INTO
LOW AND MIDDLE INCOME COUNTRIES
THAT WILL CONTINUE TO SS SSH THE
POPULATION BEYOND THE RESEARCH
PROJECTS.
HOW DO WE CREATE CLINICAL AND
LABORATORY INFRASTRUCTURE TO
GENERATE AND CREATE VALIDATED
GENOMIC MEDICAL PRACTICE?
THEN IT'S NOT EVERY GENOMIC
INTERVENTION OR GENOMIC RESEARCH
PROJECT THAT IS GOING TO BE
FEASIBLE IN ALL COMMUNITIES,
SOCIETIES AND ENVIRONMENTS.
SO WE NEED TO SELECT WHAT
INTERVENTIONS WE BELIEVE WILL BE
MOST USEFUL, AND MATCH THEM WITH
THE APPLICATIONS THAT WILL
SATISFY OUR PARAMETERS FOR
SUCCESS.
WHAT TYPE OF FUNDING?
IS IT AN R03 KIND OF FUNDING?
AN R21?
A U01?
ARE THOSE TYPES OF FUNDING
REALLY SUITABLE FOR THE
ENVIRONMENTS THAT WE'RE TALKING
ABOUT?
OR WE NEED TO, IN FACT, STEP
BACK AND UNDERSTAND THAT THOSE
FUNDING MECHANISMS AND THE
PROCESSES THAT SUPPORT THEM HAVE
BEEN DEVELOPED FOR A PARTICULAR
SOCIOECONOMIC CULTURAL AND
GOVERNMENTAL ENVIRONMENT AND
PERHAPS MAY NOT BE A GOOD FIT
WHEN WE APPLY THEM TO DIFFERENT
ENVIRONMENTS.
THEN WE NEED TO INTEGRATE ALL
THESE METHODS AND APPLICATIONS
INTO ORGANIZED PROGRAMS THAT CAN
OPERATIONALIZE IN SHORT, MEDIUM
AND LONG TERM FASHION.
ONCE WE HAVE ALL OUR DUCKS IN A
ROW, THEN WE BORROW FURTHER FROM
THE IMPLEMENTATION AND
DISSEMINATION SCIENCE FIELD TO
DO IMPLEMENTATION MAPPING, AND
INCLUDE WITHIN OUR WORK
EVALUATIONS OF THE EFFECTS AND
PROCESSES THAT WE ARE
IMPLEMENTING.
THE OUTCOMES AND THE PROCESSES
LEADING TO THOSE OUTCOMES.
HOW WELL ARE THEY WORKING, WHAT
DO WE NEED TO CHANGE?
SO IN ORDER TO GIVE US A BETTER
APPRECIATION OF THE CHALLENGES
AND PERHAPS THE OPPORTUNITIES IN
THESE ENVIRONMENTS, I WANT US TO
WALK IN THE SHOES OF A RECENTLY
DIAGNOSED BREAST CANCER PATIENT
WHO IS A PUBLIC ADVOCATE AS
SHARED ON FACEBOOK A RECENT
POSTING OF TWO OR THREE DAYS AGO
IS WHAT I'M SHOWING IN THE
PICTURE, AND OF COURSE CONSENTED
TO PARTICIPATE IN THIS PROGRAM
AND WE RECORDED OUR
CONVERSATIONS, WHICH I HAVE
EDITED.
SHE'S THE MOTHER OF TWO GIRLS
AND SHE HAS FIVE SISTERS.
SHE'S 40 YEARS OLD.
AND HAS HAD THE OPPORTUNITY TO
WORK IN SUCH RESEARCH PROGRAMS.
SO LET'S HEAR SOME OF THE
SNIPPETS FROM OUR TWO TO
THREE-HOUR-LONG CONVERSATION.
SO ONE OF THE CHALLENGES, OF
COURSE, THAT SHE EXPERIENCED IS
DIAGNOSTIC DELAY.
SO HOW LONG DID IT TAKE BETWEEN
WHEN YOU NOTICED THE DISCOMFORT
AND WHEN YOU FINALLY HAD A
DIAGNOSTIC CONFIRMATION?
>>THAT WAS FROM DECEMBER TO
JULY.
>>SO THAT'S ABOUT EIGHT MONTHS.
THEN SHE HIGHLIGHTED THE
CHALLENGE THAT SHE FACED FROM
HEALTHCARE PROFESSIONALS AND THE
LEVEL OF KNOWLEDGE THEY HAD
ABOUT HER DIAGNOSIS OF BREAST
CANCER AND TREATMENT.
>>I WENT TO THE HOSPITAL TO
COMPLAIN.
I WAS TOLD THAT I WAS --
PSYCHOLOGICAL, THAT THERE'S
NOTHING, THAT MAYBE IT'S MY
PERIOD OR CHANGE OF HORMONE OR
SOMETHING.
I WAS LIKE, THIS THING HAS NEVER
BEEN HAPPENING TO ME.
IT KEPT COMING, IT'S NOT
SOMETHING THAT JUST HAPPENED
MAYBE ONCE IN A WEEK OR ONCE IN
TWO WEEKS.
AFTER LIKE TWO MONTHS, I NOTI
NOTICED -- THERE WERE SO MANY
DIFFERENT COMPETING OPINIONS, SO
TO SAY.
THE NURSE THAT WAS TO TAKE MY
VITALS WAS TO TAKE MY VITALS AND
SEND ME TO THE ROOM WHERE I WAS
TO WAIT.
WHEN I GIVE HER MY FILE SHE SAID
OKAY WHAT ARE YOU HERE FOR, I
SAID I'M HERE FOR MY VITAL -- I
NEED TO PRAY AND I WANT TO
ASK -- REMOVE CANCER FROM MY
BODY WITHOUT ME DOING ANYTHING.
>>OF COURSE WITH FIVE SISTERS
AND A DIAGNOSIS OF BREAST
CANCER, WE WERE INTERESTED IN
KNOWING HOW THE FAMILY RECEIVED
THE DIAGNOSIS AND POTENTIAL
IMPLICATION THAT IT HAS FOR
THEIR RISK OF BREAST CANCER.
>>YOU SAID THAT YOU'RE FROM A
FAMILY OF SIX GIRLS.
YOU HAVE FIVE SISTERS?
>>YES.
YES, SIR.
>>AND IS THERE ANY FAMILY
HISTORY OF BREAST CANCER OR ARE
YOU AWARE OR DID YOU KNOW PEOPLE
BEFORE YOUR DIAGNOSIS AND
OUTSIDE OF YOUR WORK, YOU KNOW,
WHO HAD BREAST CANCER?
>>NONE THAT I KNOW.
>>SO YOU HAVE NO PREVIOUS
INTERACTION OR KNOWLEDGE OF THIS
DISEASE UNTIL YOU STARTED
WALKING IN THE LAB?
-- CAUSED THE DIAGNOSIS WITH
YOUR SISTERS AND THE CONCERN
THAT THERE MAY BE A GENETIC
BASIS FOR THE DISEASE AND WHAT
THAT IMPLIES FOR THEM?
>>I'VE TRIED TO.
-- IN DENIAL, DON'T WANT TO
ACCEPT -- WHEN I TOLD THEM ABOUT
MY DIAGNOSIS AND THAT I'M GOING
FOR MASTECTOMY, THEY DIDN'T
AGREE.
THEY DIDN'T EVEN WANT ME TO
START ON THE TO TOPIC, YOU KNOWO
TELL THEM TO EVEN CHECK
THEMSELVES WHEN I -- WHENEVER --
YOU'RE GOING TO REMOVE YOUR
BREAST, IN FACT, SOME DAYS THEY
WOULD CALL ME AND, YOU KNOW, --
THIS SURGERY WILL NOT HOLD.
SO AT THE END OF THE DAY, WHEN I
WANT TO BRING UP THE TOPIC THAT
PLEASE, EVEN IF IT'S JUST
SELF-EXAMINATION, DO IT.
NOBODY IS WILLING TO, YOU KNOW,
LISTEN TO ME.
SO IT'S BEEN LIKE A CHALLENGE,
BUT --
>>THEN BECAUSE SHE HAD WALKED
ON PROJECTS THAT INCLUDED
GENOMIC EPIDEMIOLOGY OF BREAST
CANCER, WE WANTED TO KNOW ABOUT
GENOMIC TESTING FOR BREAST
CANCER.
>>DID YOU DO ANY GENOMIC TEST?
>>I TRIED TO DO A GENOMIC TEST,
BUT I FOUND OUT THAT THERE WAS
NO PLACE TO DO THAT IN NIGERIA,
SO THE PEOPLE -- TAKING MY
SAMPLE ABROAD.
>>WHICH -- WAS THIS?
>>THAT WAS BRCA.
>>YOU TALKED ABOUT THE BRCA
TEST AND THAT IT WAS YOUR
INITIATIVE TO CONSIDER IT.
DID YOU DISCUSS IT WITH YOUR
CARE PROVIDERS?
>>OF COURSE I DID.
WHEN I OPTED TO DO THE -- REMOVE
BOTH BREASTS AND THEY TOLD ME
THAT IF I DO THE BRCA, IT
WILL -- GIVE THEM A BASIS TO DO
THE DOUBLE MASTECTOMY BUT IF I
DON'T DO IT THEY DON'T HAVE ANY
BASIS, BUT LIKE I SAID EARLIER,
IT COST --
>>WAS THERE ANY TIME THAT YOU
WERE REFERRED TO, SAY, A GENETIC
COUNSELOR?
>>NOT AT ALL.
>>ARE YOU AWARE OF THAT SERVICE
IN ANY HOSPITAL IN NIGERIA?
>>NO, SIR.
>>THROUGHOUT THE PERIOD THAT
YOU ARE GOING THROUGH THIS
TREATMENT, DID YOU HAVE ANY
OPPORTUNITY TO PARTICIPATE IN
ANY RESEARCH, WHETHER IT'S
EPIDEMIOLOGY OR CLINICAL TRIALS?
>>NO, SIR.
>>I NOTE THAT YOU ARE FANNING
YOURSELF A LOT.
>> --
>>OKAY.
THESE ARE ALL THE CHALLENGES.
SO THAT L
>>SO THAT LAST CONVERSATION WAS
ABOUT POWER OUTAGE WHICH AFFECTS
PEOPLE'S LIVES, AFFECTS ACCESS
TO CARE, AND YOU KNOW, THE
MATERIALS AND RESOURCES,
RADIOTHERAPY AND THINGS LIKE
THAT, THAT PATIENTS LIKE THIS
NEED.
THEN I SPOKE TO HER ABOUT THE
COST AND THIS WAS QUITE
CHALLENGING.
SO HERE ARE THE EXPENSES THAT
SHE HAS INCURRED FOR HER CARE.
EVEN THOUGH THERE IS HEALTH
INSURANCE, ONCE SHE RECEIVED THE
DIAGNOSIS OF CANCER, THE HEALTH
INSURANCE COMPANY INFORMED HER
THAT THEY DON'T COVER ANY
TREATMENT FOR ANY TYPE OF
CANCER.
SO SHE HAD TO USE HER SAVINGS,
RESOURCES, FAMILY RESOURCES, TO
GET ALL OF THIS OUT OF POCKET
COSTS FOR HER TREATMENT.
THE BRCA TEST THAT SHE ALLUDED
TO, SHE HAS NOT DONE THAT.
BUT IT WOULD HAVE COST HER
$2,000 TO DO.
SO FOR PATIENTS LIKE THIS, IN
AFRICA, AND AS WE ALL KNOW, THE
FIELD OF CANCER AND CANCER CARE
IS PERHAPS MOST ACCESSIBLE IN
TERMS OF INTEGRATION OF GENOMIC
RESEARCH AND MEDICINE.
HOW DO WE INCREASE THE NUMBER
AND DIVERSITY OF GENOMIC DATA
DERIVED FROM PATIENTS LIKE THIS
WHILE SIMULTANEOUSLY DELIVERING
TO THEM THE BENEFITS OF GENOMIC
RESEARCH?
THOSE WHO ARE -- MAY HAVE
NOTICED THAT QUITE A FEW OF THE
THINGS THAT ARE LISTED AS
INTERVENTIONS THAT THE PATIENT
HAS SPENT MONEY ON, PERHAPS
COULD BE AVOIDED.
YOU ALSO HEARD HER TALK ABOUT
THE LIMITED KNOWLEDGE AMONG
HEALTHCARE PROVIDERS, SO WE NEED
TO CONTINUE TO BUILD TRAINING
PROGRAMS, NOT JUST ON GENOMICS,
BUT ON DISEASE-SPECIFIC TOPICS,
AND WE WANT TO MAKE SURE THAT WE
ALIGN THE GOALS OF TH THESE
TRAINING PROGRAMS WITH THE LOCAL
AND GLOBAL PUBLIC HEALTH
PRIORITIES SO THAT WE CAN ENSURE
SUCCESSFUL IMPLEMENTATION OF
WHAT WE DEFINED AS OUR EBIs.
THAT WAY, WE'LL BE SURE THAT THE
TRAINING PROGRAMS SERVE THE NEED
OF THE POPULATION.
THEN THE GENOMIC RESEARCH ITSELF
NEEDS TO BE BUILT IN WAYS THAT
DELIVER SHORT AND MEDIUM TERM
HEALTH BENEFIT TO THE POPULA
POPULATION, AND AS I PREVIOUSLY
ALLUDED, SOME OF THE CURRENT
METHODS THAT WE'RE USING TO
CONDUCT GENOMIC RESEARCH, NOT
THE METHODS WHICH OF COURSE THE
SCIENTISTS ARE TYPICALLY
TOPNOTCH, BUT THE PROCESSES, THE
GRANT MECHANISMS, THE FUNDING,
THE ADMINISTRATION OF THE
GRANTS, THE SIZE OF THE GRANTS,
THE DURATION, MAY REALLY NOT BE
THE MOST APPROPRIATE FOR SUPP
SUPPORTING SUSTAINED LONG TERM
ROBUST GENOMIC RESEARCH THAT
DELIVERS GENOMIC MEDICINE
BENEFITS IN CLINICAL PRACTICE
AND PUBLIC HEALTH TO LOW AND
MIDDLE INCOME POPULATIONS.
AND WE DO HAVE AGENCY, WE HAVE A
ROLE, IN LOOKING AT THIS PICTURE
AND ASKING WHAT IS WRONG, WHAT
IS WRONG WITH THIS PICTURE?
HOW SHALL WE ARRANGE THE
COMPONENTS, THE DIFFERENT
STAKEHOLDERS?
RECOGNIZING THEIR AGENCY.
DIFFERENT COUNTRIES NEED TO
ENGAGE THEIR GOVERNMENTS IN
MULTIPLE LEVELS, AND UNLESS WE
HAVE, ONE, THE RECOGNITION OF
THE AGENCY, OF THE INDIVIDUALS
AND INSTITUTIONS, AND ENGAGEMENT
OF THOSE INDIVIDUALS AND
INSTITUTIONS, WE ARE NOT LIKELY
TO BE ABLE TO BUILD THE KIND OF
SUSTAINABLE PROGRAMS THAT WILL
HELP TO CONTINUOUSLY GENERATE
HIGH QUALITY GENOMIC RESEARCH,
AND DELIVER THE BENEFITS OF
GENOMIC MEDICINE FOR THE
POPULATIONS IN LOW AND MIDDLE
INCOME COUNTRIES.
THIS IS THE CHALLENGE, THIS IS
THE PRIORITY.
THIS IS THE CONUNDRUM THAT WE
FACE AS SOME OF THE CONSORTIA
PROJECTS COME TO AN END, AND NOW
WE'RE TRYING TO FIGURE OUT WHAT
OUR NEXT STEPS SHOULD BE.
SO THANK YOU VERY MUCH FOR THE
OPPORTUNITY AND FOR LISTENING
TO -- I'VE NOT PRESENTED ANY
DATA AND -- YOU HAVE HAD
DR. ROTIMI PRESENT
EXTRAORDINARILY COMPELLING
EVIDENCE FOR WHY GENOMIC
RESEARCH IN AFRICAN POPULATIONS
IS NECESSARY, IS COMPELLING, AND
LIKELY TO YIELD HIGHLY IMPACTFUL
OUTCOMES.
THANK YOU.
>>WELL, THANK YOU SO, SO MUCH,
DR. ADEBAMOWO.
THAT WAS REALLY A VERY, VERY
MOVING PRESENTATION, I MUST SAY,
AND DR. ROTIMI, THANK YOU AS
WELL.
WE ARE OVERFLOWING WITH
QUESTIONS ACTUALLY FOR THE TWO
OF YOU.
SO WE'LL HAVE TO SEND OUT FOR
PIZZA PROBABLY IN ORDER TO GET
THROUGH ALL OF THESE QUESTIONS.
THIS AFTERNOON.
BUT IN ANY CASE, WE HAVE REALLY
LOTS OF THINGS TO TALK ABOUT.
SO MAYBE, CLEMENT, WE CAN START
WITH JUST ONE OF THE QUESTIONS
THAT COMES IN FROM THE AUDIENCE,
HAVING TO DO WITH JUST THE SORT
OF ALONG THE LINES OF WHAT YOU
WERE DISCUSSING, THE FACT THAT,
REALLY, THERE'S A REAL
DISCONNECT BETWEEN WHAT WE'RE
DOING IN THE DEVELOPED WORLD
WITH REGARD TO SOME OF THESE
GENETIC STUDIES, AND WHAT IS
BEING DONE AND CAN BE DONE AND
NEEDS TO BE DONE IN AFRICA.
SO THE QUESTION HAS TO DO WITH
THE FOUNDATION OF PHENOTYPING.
SO YOU KNOW, IN A COUNTRY LIKE
THE UNITED STATES, WHEN WE
ASSEMBLE THE GENOTYPES FROM A
THOUSAND INDIVIDUALS, OF COURSE
THERE'S A LOT OF PHENOTYPIC
INFORMATION THAT SORT OF COMES
JUST BY ENROLLING THOSE
INDIVIDUALS, BECAUSE THEIR
MEDICAL RECORDS ALREADY CONTAIN
A LOT OF PHENOTYPIC INFORMATION.
HOW IS THIS BEING HANDLED IN
GENOMIC STUDIES IN AFRICA, WHERE
THERE'S NOT NEARLY AS MUCH
PHENOTYPIC DATA, THE QUESTIONER
IS HYPOTHESIZING, AS WHAT WOULD
BE AVAILABLE IN THE U.S. OR SOME
OTHER DEVELOPED COUNTRY?
>>THANK YOU VERY MUCH FOR THAT
QUESTION.
I THINK IT'S HIGHLY INSIGHTFUL
AND RECOGNIZES THE BIG CHALLE
CHALLENGE, WHICH I THINK WE ARE
ABLE TO COMPREHEND FROM THE
EXPERIENCE OF THE PATIENT WHO
VOLUNTEERED TO SHARE HER BREAST
CANCER JOURNEY WITH US.
SO IT TURNS OUT THAT IN MOST
CASES, WHEN WE'RE DOING GENOMIC
RESEARCH IN AFRICA, THE
INVESTIGATORS ALSO HAVE TO BE
RESPONSIBLE FOR GENERATING THE
HIGH QUALITY PHENOTYPIC DATA
THAT NEEDS TO ACCOMPANY THE
GENOMIC DATA, AND THE
IMPLICATION OF THIS, OF COURSE,
IS THAT THE OVERALL COST AND
LABEL OF GENOMIC RESEARCH,
QUOTE-UNQUOTE, INCREASES
SUBSTANTIALLY.
AND THAT IS WHY I'VE ARGUED THAT
WE NEED A NEW PARADIGM THAT
ENSURES THAT WE ENGAGE ALL THE
STAKEHOLDERS BECAUSE THE CURRENT
METHOD IS NOT SUSTAINABLE.
THE INSTITUTIONS HAVE TO HAVE
THE RESOURCES AND GENERATE SOME
MINIMAL PHENOTYPIC DATA OF
SUFFICIENT QUALITY SO THAT WHEN
WE SAY THIS PERSON HAS BREAST
CANCER, THE PERSON DOES INDEED
HAVE BREAST CANCER, AND THOSE
WHO HAVE WALKED IN THESE
ENVIRONMENTS WILL READILY ATTEST
TO THE AMOUNT OF TIME AND
RESOURCES, THAT CHARACTERIZATION
OF PHENOTYPE, TAKES.
AND THIS FEEDS INTO THE ATTITUDE
OF BOTH THE STUDY PARTICIPANTS
AND THE LOCAL INVESTIGATORS IN
MERE YADZ OF WAYS, INCLUDING
ISSUES RELATED TO DATA SHARING,
COLLABORATIONS, AND
INTERNATIONAL TRANSFER OF
BIOLOGICAL SAMPLES.
SO THERE ARE CHALLENGES THERE.
THE GROUPS THAT HAVE BEEN
SUCCESSFUL HAVE CONFRONTED THOSE
CHALLENGES HEAD-ON, AND IT NEEDS
TO BE BETTER UNDERSTOOD SO THAT
IT CAN FEED INTO THE RESEARCH
ECOSYSTEM.
THAT'S WHY I HAVE CHOSEN TO BE
CALLING THIS THE ECOSYSTEM,
BECAUSE IT GOES BEYOND THE ONE
INVESTIGATOR AND THE ONE STUDY.
IT'S REALLY, YOU KNOW, WHAT TO
SUPPLY, CONSUMABLES IN THE
HOSPITAL, THE HOSPITAL JUST
FUNCTIONING IN ORDER TO LINK THE
STUDY PARTICIPANTS WITH SUITABLE
RESEARCH PROJECTS.
EXCELLENT QUESTION.
>>WELL, AND MAYBE TO FOLLOW UP
ON MY QUESTION, I'M JUST SORT OF
PUTTING WORDS IN THE MOUTH OF
THE INTERROGATOR, BUT YOU KNOW,
IT WOULD SEEM THAT MAYBE IN
AFRICA, THERE WOULD BE SOME BIAS
IN TERMS OF WHAT POPULATIONS ARE
SAMPLED FOR GENOMIC TESTING JUST
BY VIRTUE OF THEIR PHYSICAL
LOCATION AND BY VIRTUE OF THE
HEALTHCARE SYSTEM THAT THEY LIVE
IN, YOU KNOW, THOSE WHO LIVE IN,
PERHAPS, CITIES OR IN APLACE
WHERE THERE'S AT LEAST SOME MORE
ADVANCED HEALTHCARE SYSTEM WOULD
BE MORE LIKELY, I WOULD THINK,
TO BE ENROLLED IN THE GENOMIC
STUDIES THAN THOSE WHO MIGHT
LIVE IN A RURAL AREA WHERE THEY
DON'T HAVE ACCESS TO GOOD
HEALTHCARE.
>>YOU'RE RIGHT, BUT I THINK THE
WAY TO PUT IT IS THAT THERE IS
POTENTIAL BIAS, BECAUSE LIKE IN
ANY EPIDEMIOLOGIC STUDY, WE
CAN -- IF WE UNDERSTAND THE
STUDY AND THE DESIGN WELL ENOUGH
AND THE ENVIRONMENT, WE CAN
DESIGN OUR STUDY TO ADDRESS MANY
OF THESE BIASES BY USING
SAMPLING FRAMES THAT -- YOU
KNOW, BASED ON AN APPRECIATION
OF SOME OF THE VARIATIONS THAT
YOU'RE MENTIONING IN TERMS OF
WHO GETS TO COME TO THE HOSPITAL
AND EVEN AMONG THOSE WHO COME TO
THE HOSPITAL, WHO GETS SEEN BY
THE PHYSICIANS AND WHO GETS
INVESTIGATED.
AND SO WE UNDERSTAND AND FOR
PERHAPS INTERNATIONAL
INVESTIGATORS, THIS IS WHERE
HAVING A HIGH LEVEL OF LOCAL
INPUT AND KNOWLEDGE BECOMES
CRITICAL, OTHERWISE AS YOU
MENTION, THE RESULTS OF THE
RESEARCH WOULD BE QUITE BIASED.
AND, OF COURSE, THERE ARE OTHER
WAYS OF DEALING WITH THOSE
BIASES, AND I THINK
INVESTIGATORS SHOULD PAY
ATTENTION TO THOSE AND MAKE SURE
THAT TH THE ENTIRE METHOD OF
PARTICIPANT ENGAGEMENT,
RECRUITMENT, AND SAMPLING IS
SUFFICIENTLY WELL DESCRIBED FOR
READERS TO APPRECIATE THE
OUTCOMES AND THE FACTORS THAT
MAY INFLUENCE THE OUTCOMES OF
SPECIFIC STUDIES.
>>OKAY, SO I JUST WANTED TO ADD
A LITTLE BIT TO THAT BECAUSE
THAT'S SUCH A POWERFUL QUESTION.
IN THE SENSE THAT IN POPULATION
GENETICS, FOR A VERY LONG TIME,
WIWE KEPT ANALYZING SAMPLE FROM
SOME VERY SPECIFIC AFRICAN
COUNTRIES.
ONE OF THE MAIN REASONS BEHIND
THAT WAS THERE WERE QUITE A FEW
COUNTRIES THAT WE COULDN'T GO TO
BECAUSE THERE WAS WAR GOING ON.
WAR THAT LASTED 15, 25 YEARS, SO
WHAT YOU KEPT SEEING WAS
UNDERSTANDING OF VARIATION AND
EVOLUTION FROM THE VERY
CONVENIENT SET OF SAMPLES THAT
WERE DRIVEN BY THE FACT THAT
SCIENTISTS COULD GO TO THOSE
PLACES AND SAMPLE.
YOU KNOW, SO EVEN BEFORE
CLINICAL MEDICINE, YOU HAVE THIS
POPULATION GENETIC BIAS, OTHERS
BEGINNING TO CHANGE SLOWLY, BUT
IT'S STILL THERE.
AND THAT PEOPLE ARE ANALYZING
SAMPLES THAT WE CONVENIENTLY
COLLECTED BECAUSE THERE ARE SOME
AREAS WE JUST COULDN'T GO TO.
>>YES, AND OF COURSE READING
THE NEWS, THERE ARE AREAS EVEN
NOW, OF COURSE IT'S NOT JUST
RESTRICTED TO AFRICA.
>>NO, IT'S NOT.
WE'RE TALKING ABOUT AFRICA.
>>YES.
ABSOLUTELY.
WELL, SO NOW WE HAVE ANOTHER
PERSON FROM THE AUDIENCE WHO HAS
A QUESTION, I THINK IT'S FOR DR.
SO THE QUESTION HAS TO DO WITH
THE THE FACT THAT THERE HAS BEEN
SELECTION, AND I GUESS IT'S IN
EAST AFRICA, FOR THE VARIANT OF
APOL1, THAT IS PROTECTIVE FOR
AFRICAN SLEEPING SICKNESS, AND
THAT VARIANT APPARENTLY CONFERS
AT LEAST IN THE AFRICAN AMERICAN
POPULATION RISK FOR END STAGE
RENAL DISEASE.
SO THE QUESTIONER IS ASKING,
WELL, WHAT HAPPENS IN AFRICA
ITSELF?
IS THERE A HIGH FREQUENCY OF END
STAGE RENAL DISEASE IN THOSE
PARTS OF EAST AFRICA WHERE THE
SELECTION IS OPERATIVE?
>>ABSOLUTELY.
AS PART OF THE HISTORY OF AFR
AFRICA, THERE WAS MAJOR FUNDING
TO LOOK AT KIDNEY DISEASE IN
PLACES LIKE NIGERIA AND GHANA.
AND MY GHANA COLLEAGUES ARE JUST
FLOORED BY THIS STORY THAT HAS
BEEN IN THE BACKGROUND FOR SO
LONG, BUT WE COULDN'T PUT AN END
TO IT.
SO THERE IS INDEED VERY HIGH
RATES OF KIDNEY DISEASE IN
PLACES LIKE GHANA, WHERE THERE
HAS BEEN SYSTEMATICALLY
DOCUMENTED TO THE POINT WHERE
THEY'RE ABOUT TO DO A CLINICAL
TRIAL NOW, LOCALLY, I HOPE IT
WORKS OUT, THIS SMALL MOLECULE
HAS NOW BEEN DISCOVERED THAT
WILL BLOCK THE APOL1, YOU KNOW,
AND WE ARE THINKING THAT MAY BE
EFFECTIVE AGAINST THE KIDNEY
DISEASE, BUT THAT IS SOMETHING
THAT IS JUST ABOUT TO START.
THE ANSWER TO THAT QUESTION IS
YES, THERE IS QUITE A HIGH RATE
OF KIDNEY DISEASE IN THAT PART
OF THE WORLD.
IT'S REALLY THOSE AREAS THAT
HAVE BEEN ENDEMIC -- INFECTION,
AND THAT'S -- IT'S NOT THE
CHARACTERISTICS OF BEING
AFRICAN.
IT'S THE CHARACTERISTICS OF
BEING -- HAVING LIVED IN AN
ENENVIRONMENT THAT WAS ENDEMIC
TO -- INFECTION AND THAT'S WHY
THERE'S VERY LITTLE -- IN AFRICA
OR NORTHERN AFRICA, BUT FROM
WEST TO SOME PARTS OF EAST
AFRICA, YOU DO HAVE A VERY HIGH
RATE.
SO NO LESS IN --
>>YES, INDEED.
AND SO I TAKE IT THAT AT THIS
POINT PROBABLY THERE'S NOT
TESTING THAT'S AVAILABLE TO SEE
WHETHER OR NOT YOU HAVE THE
VARIANT.
THAT WOULDN'T BE WIDELY
AVAILABLE.
>>I WOULDN'T SAY WIDELY, BUT
IT'S THERE.
IT'S AVAILABLE.
HOWEVER, I WON'T SAY WIDELY
BECAUSE AS PART OF THE HISTORY
OF AFRICA WORK -- TYPING THESE
VARIANTS, SO THERE'S OPPORTUNITY
TO ACTUALLY UNDERSTAND YOUR
STATUS.
SO IT GETTING BETTER AND THE
POINT THEY'RE MAKING, IT IS NOT
REALLY CONSTITUTED IN A WAY
THAT'S PART OF THE CLINICAL
CARE, THAT IF YOU WALK INTO THE
HOSPITAL, YOU CAN GET TESTED,
YOU KNOW, WITHOUT NECESSARILY
HAVING TO FALL UNDER A
PARTICULAR RESEARCH UMBRELLA.
SO THAT'S SOME OF THE
CHALLENGES.
BUT IT IS THERE, YOU CAN DO IT.
AND IF YOU TALK WITH THE RIGHT
PEOPLE, YOU GO TO THE RIGHT
PLACES, YOU CAN GET IT DONE,
YES.
>>SO I'LL PUT ON MY
VENTRILOQUIST HAT AGAIN AND PUT
WORDS IN THE MOUTH OF THE
QUESTIONER.
ARE THERE OTHER PARTS OF THE
WORLD WHERE TRIPANOCIMIASIS OR
ARE THERE OTHER PARTS IN AFRICA
THAT IT'S SEEN?
LIKE WITH MALARIA, YOU MIGHT SEE
SELECTIVE PRESSURES FOR CERTAIN
VARIANTS IN OTHER PARTS OF THE
WORLD BESIDES AFRICA, IS
TRIPANOCIMIASIS COMMON IN OTHER
PLACES WHERE I MIGHT ALSO SEE
EITHER THE SAME APOL1 VARIANT
BEING SELECTED FOR OR MAYBE SOME
OTHER VARIANT THAT WOULD GET
SELECTED FOR JUST LIKE MALARIA
SELECTS FOR ALL SORTS OF
ERYTHROCYTE VARIANTS?
>>THAT'S AN EXCELLENT QUESTION.
I DON'T THINK WE'VE ACTUALLY
LOOKED, BUT GIVEN THE WAY -- I
WOULD SAY THOSE ENVIRONMENTS
WHERE LIKE IN SOUTH ASIA, PLACES
LIKE THAT, THAT I WOULDN'T BE
SURPRISED, BUT I DON'T THINK
THERE'S ANY SYSTEMATIC
EVALUATION IN THAT PROCESS.
WHAT HAS BEEN SYSTEMATICALLY
DOCUMENTED IS THE SPREAD OF THIS
VARIANT THAT ORIGINATED FROM
SOME PARTS OF AFRICA OVER THE
WORLD.
WHETHER THERE'S A SELECTION
PRESSURE THAT HAS OCCURRED IN
OTHER PARTS OF THE WORLD, RILEY
DON'T KNOW THAT, BUT THAT'S AN
EXCELLENT QUESTION AND I'M GOING
TO TRY TO SEE IF THERE'S
ANYTHING PUBLISHED ON IT YET.
>>WELL, AND THEN HOLDING YOU
GUYS TO THE TITLE OF YOUR
PRESENTATION, GENOMIC AND
ENVIRONMENTAL DETERMINANTS OF
GLOBAL HEALTH, SO NOW I'M GOING
TO REALLY PUT YOUR FEET TO THE
FIRE HERE.
AND ASK THE QUESTION,
WELL, SO ARE THERE SPECIFIC
ENVIRONMENTAL FACTORS THAT IF
YOU HAVE THE VARIANT, YOU'RE
MORE LIKELY TO GET KIDNEY
DISEASE?
IN OTHER WORDS, IF YOU'RE
EXPOSED TO SOMETHING OR YOU HAVE
HIGH BLOOD PRESSURE, YOU HAVE
DIABETES OR, YOU KNOW, SOMETHING
LIKE THAT, YOU KNOW, THAT WOULD
SORT OF HAVE A MULTIPLIER EFFECT
ON THE RISK?
>>ABSOLUTELY.
I THINK IN MY TALK, I SAID
HYPERTENSIVE END STAGE KIDNEY
DISEASE, THE EFFECT OF THIS
VARIANT IS REALLY IN CONTEST OF
REPETITION OF KIDNEY DISEASE.
FOR WHATEVER REASON, IT'S NOT
BEEN DOCUMENTED AMONG KIDNEY
DISEASE THAT COMES FROM TYPE
2 DIABETES.
SO YES, THERE IS ENVIRONMENTAL
CONTEST WITHIN THAT, AND IT IS
ALSO TRUE THAT NOT EVERYBODY
THAT CARRIES THESE VARIANTS DIE
FROM KIDNEY DISEASE.
AND THEREFORE, THERE MUST BE
SOME FINE GENETIC BACKGROUND OR
ENVIRONMENT THAT MAY BE
PROTECTING SOME PEOPLE AND
PUTTING SOME PEOPLE AT REAL
EARLY RISK IN TERMS OF
DEVELOPING KIDNEY FAILURE.
SO ALL OF THOALS ARE
SYSTEMATICALLY STUDIED AND I
THINK THERE ARE DATA BEING
COLLECTED ON THEM.
>>ALL RIGHT.
WELL, THANK YOU.
SO NOW, I HAVE A QUESTION THAT I
THINK IS PROBABLY DIRECTED AT
BOTH OF YOU.
THAT IS FROM -- I GUESS IT WOULD
BE A DREAMER, A DREAMER
QUESTIONER.
AND SO THE DREAMER WANTS TO KNOW
WHETHER OR NOT THERE IS AN
ALL-OF-US PROGRAM, LIKE WHAT WE
HAVE IN THE UNITED STATES, IS
THERE AN ALL-OF-US PROGRAM THAT
IS EITHER ABOUT TO BE UNDERTAKEN
OR CONTEMPLATED FOR THE AFRICAN
POPULATION?
>>THE CLOSEST TO THAT IS THE
RECENT FUNDING BY THE WELLCOME
TRUST OF WHAT IS CALLED
POPULATION COHORT ACROSS AFRICA.
AND THAT JUST STARTED.
IT'S NOWHERE NEAR ALL-OF-US TYPE
SIZE, BUT IT JUST STARTED SO
THAT'S A VERY GOOD ONE.
AND HISTORY AFRICA HAS INDEED --
OVER 100,000 AFRICANS FROM
DIFFERENT PARTS OF SPECIFICALLY
SUB-SAHARAN AFRICA FOR THE MOST
PART, AND THOSE ARE GOOD
EXAMPLES OF WHAT YOU MAY CALL
SOMETHING RESEMBLING THE
ALL-OF-US BUT THEY ARE REALLY
NOT OF THAT SIZE.
AND I THINK THERE NEEDS TO BE,
YOU KNOW, SOME WAY TO GET TO
THAT LEVEL, BUT TO GET TO THAT
LEVEL, -- THAT CLEMENT PRESENTED
IN HIS PRESENTATION, THE THINGS
WE NEED TO UNDERSTAND, SO
CLEMENT, TO YOU DO YOU WANT TO E
INTO THAT?
>>SO THANK YOU VERY MUCH.
THAT'S AN EXCELLENT QUESTION,
AND WHAT I WAS TRYING TO PUT OUT
THERE TO ADDRESS, I THINK, THE
RATIONALE FOR ASKING THAT
QUESTION, IS THE IDEA THAT BY
BRINGING GENOMICS TO CLINICAL
PRACTICE AND PUBLIC HEALTH, WE
CAN BEGIN TO HAVE A SYSTEM THAT
GENERATES GENOMICS DATA AND
MAKES IT AVAILABLE FOR RESEARCH
SEPARATE FROM AND IN ADDITION TO
FOCUSED INTERVENTIONS LIKE
H3 AFRICA AND CONSORTIA PROJECTS
LIKE, YOU KNOW, ALL-OF-US.
AFRICA'S POPULATION IS ABOUT
1.3 BILLION PEOPLE, AND THERE
ARE THOUSANDS OF ETHNIC GROUPS.
SOME OF THOSE ETHNIC GROUPS AND
POPULATIONS AS THEY'VE
INTERACTED WITH THE ENVIRONMENT
ARE GOING TO PROVIDE US WITH
OPPORTUNITIES TO LEARN UNIQUE
INSIGHTS INTO HUMAN POPULATION,
HUMAN HISTORY, DISEASE GENE
ASSOCIATION AND DRUG RESPONSE.
SO HOW DO WE BRING ABOUT A
SYSTEM THAT SYSTEMATICALLY
GENERATES GENOMICS DATA FROM
AFRICAN POPULATIONS AT THE LEVEL
THAT THE WORLD NEEDS?
WITHOUT FURTHER DELAY?
AND THAT'S THE CHALLENGE THAT
NOT JUST AFRICANS BUT THE WORLD
FACES.
AS DR. ROTIMI'S PRESENTATION
SHOWS.
FOR EXAMPLE, -- B WHICH WAS NOT
IDENTIFIED IN ANY OTHER
POPULATION, THAT DISCOVERY IS
NOT ONLY OF BENEFIT TO AFRICANS
BECAUSE IT LEADS OR YIELDS
INSIGHT INTO MECHANISM,
MECHANISM THAT CAN BE EXPLOITED
FOR BIOMARKER OR DRUGS, DRUG
DISCOVERY, WHICH WILL BE A VALUE
TO ANY POPULATION.
SO THERE IS NO ALL-OF-US KIND OF
PROJECT, AND WE NEED TO BE
THINKING ABOUT WHAT OTHER WAY
CAN WE GET THIS GOING?
BECAUSE IT'S AN URGENT TASK THAT
WE NEED TO DO.
SO SMALL GRANTS INTEGRATED INTO
HEALTHCARE SYSTEMS FOCUSED ON
THE DISEASES THAT WILL GIVE US
THE BIGGER BANG FOR THE BUCK IN
TERMS OF DISCOVERY AND
UNDERSTANDING OF DISEASE.
I APPRECIATE FULLY THAT THOSE
KINDS OF APPROACHES, THEY HAVE
THEIR DOWN SIDES, COMPARED TO
AGNOSTIC METHODS THAT CAN LEAD
TO REALLY UNEXPECTED FINDINGS,
BUT WE HAVE TO START SOMEWHERE.
>>YES.
WELL, THANK YOU VERY MUCH FOR
THAT.
SO NOW WE HAVE A PRACTICAL
QUESTION.
WE'VE HAD A DREAMER AND WHATNOT
BUT NOW A PRACTICAL QUESTIONER
WHO IS FOLLOWING UP ON SOME OF
YOUR COMMENTS, CLEMENT,
ACTUALLY, AND THIS PERSON IS
STATING THAT IT SEEMS LIKE IT'S
REALLY IN ALL OF OUR INTERESTS
AROUND THE WORLD TO SUPPORT
GENOMIC INVESTIGATION INTO
AFRICAN POPULATIONS.
WHAT CAN WE AS THE SCIENTIFIC
COMMUNITY OF THE UNITED STATES
DO TO FACILITATE THAT?
>>THAT'S A VERY INTERESTING AND
VERY POWERFUL QUESTION, AND I'M
SURE CHARLES WILL HAVE SOMETHING
TO SAY BECAUSE OF HIS ROLE IN
MOTIVATING SOME OF THE THINGS
THAT WE HAVE DONE AND WE HAVE
ACHIEVED, INCLUDING H3 AFRICA,
AND HIS CURRENT POSITION TO A
CERTAIN DEGREE AS THE POLICY
MAKER IN THE NIH THAT CAN
INFLUENCE NIH AS ONE
INSTITUTION.
BUT GOING BEYOND NIH, AND
HOPEFULLY I WILL HAVE THE
OPPORTUNITY AS OTHERS DEFINITELY
WILL TO ELABORATE MORE ON THE
MECHANISMS THAT WE CAN BUILD
APPLYING THE IMPLEMENTATION
MAPPING STRATEGY WHICH IS A
SUBSET OF THE INTERVENTION
MAPPING STRATEGY THAT I
DESCRIBED, AND SOME OF THE IDEAS
INCLUDE IDENTIFYING AND -- IN A
LONG TERM FASHION, OFTENTIMES
BEYOND THE TYPICAL TIMELINE OF
AN NIH R OR U GRANT KIND OF
AWARD, ANOTHER WHICH I WAS
DISCUSSING JUST BEFORE WE
STARTED IS INSTITUTIONAL SUPPORT
AND MENTORING PROGRAMS THAT GO
BEYOND JUST SINGLE PROJECTS, BUT
HELP INSTITUTIONS TO GRADUALLY
SHIFT THE LANDSCAPE OF CLINICAL
AND PUBLIC HEALTH PRACTICE.
WE ALSO NEED TO BE STRONG
ADVOCATES, I MEAN, THERE'S A
TENDENCY FOR PEOPLE SOMETIMES TO
BE EXHAUSTED, BUT THE WORK THAT
HAS BEEN DONE HAS YIELDED
TREMENDOUS BENEFIT, AND IT IS
JUST THE BEGINNING, BECAUSE ALL
OF THESE PEOPLE ARE BUSY AND
WE'RE GOING TO SEE A WHOLE
SERIES OF PUBLICATIONS FROM SOME
OF THE PROJECTS.
AND I HOPE THAT THOSE
PUBLICATIONS WILL ENCOURAGE EVEN
MORE INTERNATIONAL INVESTIGATORS
TO OVERCOME THE CHALLENGES OF
INTERNATIONAL RESEARCH.
THOSE CHALLENGES ARE NO NOT
TRIVIAL, AND ENGAGE IN A DEEP
AND SUSTAINED FASHION.
AND BY SO DOING, I'M SURE WE
WILL ALL BENEFIT FROM THE
OUTCOMES OF THOSE PROJECTS, AND
CHARLES, YOU MAY HAVE ONE OR TWO
THINGS TO ADD.
>>YEAH, I THINK THAT IS A VERY
POWERFUL QUESTION, AND WHEN I
GAVE MY PRECEDEN PRESIDENTIAL A,
THAT WAS -- ALSO THE SYMPOSIUM I
ATTENDED WITH FRANCIS COLLINS,
THAT WAS PART OF THE -- I WAS
TREMENDOUSLY PLEASED THAT A LOT
OF SCIENTISTS AROUND THE WORLD,
ESPECIALLY YOUNG SCIENTISTS,
WERE ASKING WHAT CAN I DO, HOW
CAN I JOIN, HOW CAN I MAKE
THINGS BETTER?
AND WE ARE TRYING TO CAPITALIZE
ON THAT.
ONE OF THE THINGS FIRST I WILL
SAY IS THIS.
IIF YOU HAVE OPPORTUNITY TO
COLLABORATE OR TO INITIATE
SOMETHING WITH AN AFRICAN
INVESTIGATOR OR IN DEVELOPING
PARTS OF THE WORLD, PERIOD, YOU
SHOULD ASSURE THAT YOUR
COLLABORATION IS FAIR, AND THAT
YOU RESPECT WHAT THOSE
INVESTIGATORS CAN BRING, AND TO
DEVELOP A STRATEGY THAT ENABLES
BOTH PARTIES TO HAVE A WIN-WIN
SITUATION.
I THINK WE ARE WAY PAST THE
SITUATION WHERE YOU COME IN, YOU
DETECT WHAT HAS TO BE DONE, AND
YOU LEAVE.
I THINK WE REALLY NEED TO DO A
LOT OF SOUL SEARCHING AND SAY
ARE WE DOING THE BEST SCIENCE
THAT WE CAN DO FOR THE PEOPLE
WHERE WE ARE GETTING THESE
RESOURCES FROM?
AND TO CONTINUE TO ANSWER THE
QUESTION, ARE YOU TRAINING
PEOPLE WHO CAN INDEED GO BACK
HOME, AND NOT ALWAYS DEPEND ON
THE FISH THAT YOU CATCH.
SO IT'S REALLY SORT OF A
DIFFERENT WAY OF MINDSET OF
LOOKING AT THINGS.
THE OTHER THING I WILL SAY IS,
AS PART OF WHAT WE'RE DOING, WE
ARE ALSO TRYING TO DEVELOP WHAT
WE ARE CALLING GENOMIC CENTERS
OF EXCELLENCE.
WHICH WE ARE HOPING, YOU KNOW,
TO ESTABLISH ACROSS THE AFRICAN
CONTINENT, TO HELP SITUATE SOME
OF THE THINGS CLEMENT IS TALKING
ABOUT IN TERMS OF LINING GENOMIC
CENTERS TO LIN CAL FACILITIES,
TO HOSPITALS, AND TO PUBLIC
HEALTH STRATEGY SO THAT AS THEY
ARE GENERATING GENETIC AND
GENOMIC INFORMATION, YOU ARE
IMMEDIATELY THINKING OF
TRANSLATION.
YOU ARE IMMEDIATELY THINKING OF
HOW CAN IT BENEFIT PEOPLE?
SO WE ARE WORKING ON THAT AS
PART OF THE MAYBE SPINOFF, IF WE
USE THAT PHRASE, OF HISTORY OF
AFRICA TO INDEED BEGIN TO CREATE
WONDERFUL EXAMPLES OF CENTERS
THAT CAN -- JUST LIKE WE HAVE
THE BROAD IN BOSTON, AND SANGER
IN UK, WE WANT TO CREATE SIMILAR
STRUCTURES WHERE YOU HAVE DIRECT
TIES TO HOSPITALS, TO PUBLIC
HEALTH STRATEGY, SO THAT WHEN
YOU'RE FINDING THINGS, YOU ARE
DEVELOPING STRATEGY TO BRING TO
THE CLINIC, TO BRING TO THE
PATIENT, AND THAT'S WHERE WE
ARE, AND WE'LL CONTINUE TO DO
THAT.
SO M ENGAGE, ENGAGE AND ENGAGE.
IF YOU KNOW, AND IF YOU DON'T
KNOW, SEND ME AN EMAIL, I CAN
DIRECT YOU TO SOMEBODY WHO YOU
CAN COLLABORATE WITH OR
COOPERATE WITH.
EVERY LITTLE BIT HELPS.
>>OKAY.
ALL RIGHT.
WELL, THANK YOU FOR THAT.
SO HERE'S ONE THAT IS NEAR AND
DEAR TO MY HEART, I GUESS.
BUT IT COMES FROM ONE OF OUR
LISTENERS.
AFRICAN AMERICANS SEEM TO HAVE
AN INCREASED FREQUENCY AND
SEVERITY OF AUTOIMMUNE DISEASE.
WHAT IS KNOWN ABOUT AUTOIMMUNE
DISEASE IN AFRICA ITSELF?
>>CLEMENT?
>>EXCELLENT QUESTION.
THAT REFLECTS ON COMMENTS THAT
HAVE BEEN MADE EARLIER.
AND ALSO FEED INTO SOME OF THE
MATERIALS I PRESENTED.
PHENOTYPING IS A HUGE CHALLENGE.
DIAGNOSING MANY OF THESE
CLINICAL CONDITIONS, ADEQUATELY
CHARACTERIZING BEYOND JUST THE
MOST MINIMAL EVALUATION
CONTINUES TO CHALLENGE MANY
AFRICAN HEALTH INSTITUTIONS, AND
IN ORDER TO BE ABLE TO ANSWER
QUESTIONS LIKE YOURS AND
QUESTIONS THAT MANY OTHERS HAVE,
WE NEED A MULTI-STAKEHOLDER,
MULTILEVEL INTERVENTION.
INDIVIDUAL RESEARCH PROJECTS ANN
ONLY DO SO MUCH, BUT COUNTRY
LEADERS, INSTITUTIONAL LEADERS,
PROFESSIONAL LEADERS, NEED TO
BUILD UP THE CAPABILITIES THAT
EXIST WITHIN THEIR COUNTRIES TO
IMPROVE DIAGNOSIS AND ACCESS TO
CARE.
BECAUSE THESE THINGS ARE
LACKING, WE OFTEN GET
INFORMATION SUGGESTING THIS
DISEASE IS NOT AS PREVALENT OR
THIS DISEASE HAS THIS UNIQUE
AFRICAN PATTERN OR THIS DISEASE
DOES NOT EXIST, BUT MANY TIMES,
THOSE KINDS OF REPORTS ARE A
REFLECTION OF THE UNDERLYING
WEAKNESSES WITHIN THE HEALTHCARE
INFRASTRUCTURE.
SO I'M NOT A SPECIALIST IN THIS
AREA, BUT I CAN EXPECT THAT IF
YOU WERE TO DIG INTO THE
LITERATURE, YOU WILL PROBABLY
NOT FIND SUFFICIENT HIGH QUALITY
INFORMATION ABOUT THE TRUE
NATURE OF THE PATTERN OF SOME OF
THE DISEASES THAT WE ARE TALKING
ABOUT.
SO WE NEED TO GO BEYOND THE
TRADITIONAL METHODS AND LOOK AT
BROADER TERMS OF ENGAGEMENT IN
ORDER NOT JUST TO ANSWER THIS TE
SPECIFIC QUESTIONS BUT OTHERS
GOING FORWARD.
THANK YOU.
>>ALL RIGHT.
WELL, THANK YOU.
SO HERE'S ONE THAT COMES FROM A
DIFFERENT ORIENTATION, PERHAPS.
THE QUESTIONER IS ASKING, I HAVE
HEARD THAT MENTHOL CIGARETTES
WERE BANNED, AT LEAST IN PART,
BECAUSE OF THEIR SIGNIFICANT USE
AMONG THE AFRICAN AMERICAN
POPULATION.
IS THERE A GENETIC OR GENOMIC
BASIS FOR THIS WILL PREFERENCE
FOR MENTHOL CIGARETTES?
CHARLES, YOU'RE MUTED.
>>YES.
THE ANSWER IS YES.
THERE IS A IS A GEOGRAPHIC HAPE
THAT WAS DISCOVERED BY A GROUP
FROM NIH AND HOPKINS AGAIN THAT
SHOWED IT'S ABOUT -- IN AFRICAN
AMERICANS, AND IT ACTUALLY
ENHANCES MENTHOL CIGARETTE.
THE REASON PEOPLE PREFER MENTHOL
CIGARETTES IS IT IS SOOTHING,
AND FOR WHATEVER REASON, OVER
THE YEARS, WE HAVE INDEED KNOWN
IN TERMS OF -- DATA THAT ABOUT
80% OF AFRICAN AMERICANS WHO
SMOKE PREFER MENTHOL CIGARETTES.
WE DIDN'T KNOW THE REASON BEHIND
THAT.
AND MORE RECENTLY, DISCOVERY OF
THIS HAPLOTYPE THAT REALLY
DRIVES PREFERENCE FOR MENTHOL
CIGARETTES CLOSE TO EIGHT FOLD
REALLY PROVIDE SOME INSIGHTS AND
VERY STRONG EVIDENCE FOR
INSTITUTIONS LIKE -- TO SAY WE
HAVE TO DO SOMETHING LIKE THIS
IF WE TRULY WANT TO REDUCE
SMOKING IN THIS POPULATION.
SO AS TO THE PERSON ASKING THE
QUESTION, THE ANSWER IS INDEED
YES.
>>AND I PRESUME THAT THAT --
MAYBE, I DON'T KNOW, I'M PUTTING
WORDS IN PEOPLE'S MOUTHS ALL THE
TIME NOW, BUT MAYBE IT WOULD
HAVE SOME EFFECT ON YOUR TASTE
FOR CERTAIN KINDS OF FOODS OR
SOMETHING LIKE THAT.
>>ABSOLUTELY.
ABSOLUTELY.
SO THE EVOLUTIONARY STORY BEHIND
THIS NEEDS TO BE TOLD.
IT MAY INDEED -- MAY NOT HAVE
ANYTHING TO DO WITH MENTHOL IN
TERMS OF SELECTION ON THAT.
IT MAY HAVE BEEN DRIVEN BY OTHER
PHENOMENON.
FOR EXAMPLE, WE KNOW THAT THERE
ARE NEW VARIANTS FOR BITTER
TASTE, FOR EXAMPLE, BECAUSE --
FROM POISON AND THINGS LIKE
THAT.
SO THE EVOLUTIONARY STORY BEHIND
THIS HAPLOTYPE NEEDS TO BE
STUDIED, LOOKED AT MORE, YES.
>>OKAY.
VERY GOOD.
SO WE'RE GETTING KIND OF CLOSE
TO THE FINISHING TIME.
THIS QUESTION MAY BE ONE THAT
CLEMENT WOULD WANT TO AT LEAST
TAKE A CRACK AT FIRST.
THE GUT MICROBIOME IS NOW KNOWN
TO PLAY AN IMPORTANT ROLE IN THE
DEVELOPMENT OF THE IMMUNE
SYSTEM.
ARE THERE ANY DATA SUGGESTING
THAT DIETARY DIFFERENCES IN
AFRICAN DIASPORA POPULATIONS
MIGHT AFFECT THE IMMUNE SYSTEM
IN THIS WAY?
>>THANK YOU VERY MUCH.
SO THAT'S A VERY INTERESTING
QUESTION.
YOU'RE RIGHT, THE GUT MICROBIOME
PLAYS A MAJOR ROLE, MUCH MORE
THAN WE ARE AWARE OF, IN MANY
ASPECTS OF HUMAN PHYSIOLOGY AND
DISEASE.
BUT THERE HAVE BEEN VERY FEW GUT
MICROBIOME STUDIES IN AFRICA, SO
WE AGAIN ARE UNABLE TO REALLY
ANSWER THAT QUESTION BECAUSE WE
NEED TO DO MORE RESEARCH USING
THE WHOLE WIDE RANGE OF TOOLS IN
THAT ENVIRONMENT AND CONTRIBUTE
THE DATA AND THE RESULTS TO THE
PUBLIC DOMAIN SO THAT IT CAN BE
OF GLOBAL BENEFIT, SO THE
QUESTIONER HAS HIT UPON A VERY
IMPORTANT COMPONENT OF CURRENT
GENOMIC METHODS, WHICH IS
DIFFERENT FROM, YOU KNOW, WHAT
WE'VE BEEN LOOKING AT IN TERMS
OF THE HUMAN GENOME AND ALL
THAT, BUT NOW EXPANDING TO THIS
INNOVATIVE AREAS OF MICROBIOME,
ME THAT GENOMICS AND SIMILAR
AREAS.
SO MORE WORK NEEDS TO BE DONE, I
THINK IS THE APPROPRIATE
RESPONSE THERE.
CHARLES, LOOKS LIKE YOU'RE
WARMING UP TO SAY SOMETHING.
>>I WAS GOING TO SAY AS PART OF
OUR TYPE 2 DIABETES STUDY, IN
NIGERIA, WE ARE INDEED
COLLECTING TWO SAMPLES TO DO,
YOU KNOW, THE MICROBIOME.
AND WE HAVE ANALYZED IT, WE
CONTINUE TO ANALYZE IT.
SOME OF THE EARLY EVIDENCE SHOWS
VERY CLEARLY THAT THE MICROBIOME
ENVIRONMENT IN TYPE 2 DIABETES
AND CONTROLS ARE VERY DIFFERENT.
AND THAT BACKGROUND MAY INDEED
BE DUE TO THE DISEASE ITSELF OR
THE MEDICATION THAT THEY ARE
TAKEN.
SO THE CHALLENGE HERE FOR US,
AND THAT'S THE AREA WE'RE TRYING
TO GO INTO NOW, IS HOW DO WE DO
IT IN SUCH A WAY THAT WE ARE
ABLE TO IDENTIFY TYPE 2 DIABETIC
PATIENTS BEFORE THEY GO ON
MEDICINE.
AND COLLECT -- SAMPLES AND --
MICROBIOME COMPARE TO THE
CONTROLS, THEN YOU CAN ACTUALLY
MAKE A STATEMENT THAT IT'S
INDEED DUE TO THE DIABETES
CONDITION -- MEDICATION ON THEIR
OWN.
SO THAT IS ONGOING WORK IN OUR
LAB THAT WE ARE DOING, THE
COLLABORATION WITH CLEMENT, OF
COURSE, YOU KNOW, SO THE INITIAL
EVIDENCE SEEMS TO SUPPORT THE
IDEA THAT THE MICROBIOME IS
INDEED CRITICALLY IMPORTANT FOR
SOMEONE WITH THESE CONDITIONS
LIKE TYPE 2 DIABETES AND OBESITY
THAT WE ARE STUDYING.
>>THERE'S GOING TO BE AN
ELEMENT OF SORTING OUT WHAT'S
THE CART AND WHAT'S THE HORSE.
>>EXACTLY.
>>IN THIS PROCESS.
ALL RIGHT.
WELL, WE'RE DOWN TO OUR LAST
THREE MINUTES OR SO.
I DO HAVE ANOTHER QUESTION
THAT'S COME IN ABOUT --
DEFICIENCY AND WHETHER IT WOULD
BE USEFUL FOR TRACING THE
GENOMIC HISTORY OF AFRICAN
DIASPORA POPULATIONS.
>>YEAH, YEAH, YEAH, I WAS -- I
WAS GOING TO BE SURPRISED THAT
QUESTION DIDN'T COME.
>>THERE IT IS.
>>YEAH, YEAH, YEAH.
BUT WHAT -- IT'S AN IMPORTANT
QUESTION, AND I DON'T THINK IT
WILL BE A VE VERY USEFUL IN TERF
MIGRATION.
WHAT IS VERY USEFUL FOR IS
IDENTIFYING THOSE AREAS THAT DID
SOME FARM BEING PRACTICES IN
ANIMALS, HAVING ACCESS TO MILK
AND THINGS LIKE THAT, OVER A
VERY LONG PERIOD OF TIME, BUT
THE STORY IS NOT
STRAIGHTFORWARD.
THERE ARE AREAS WHERE WE
EXPERIENCE THAT REALLY DON'T
HAVE THAT HISTORY.
SO I THINK IT AN ONGOING STORY,
AND THERE ARE VARIANTS THAT HAVE
BEEN SELECTED THAT ARE DIFFERENT
IN EUROPE OR IN AFRICA, SOUTH
AMERICA, SO THE STORY IS
ACTUALLY QUITE AN INTERESTING
ONE, SO THERE HAS BEEN SELECTION
PRESSURE THAT RESULTED IN
DIFFERENT VARIANTS IN DIFFERENT
PARTS OF THE WORLD.
AND I WON'T BE SURPRISED IF THE
SAME STORY IS TRUE ACROSS AFR
AFRICA.
>>ALL RIGHT.
WELL, AT THIS POINT WE'RE DOWN
TO OUR FINAL MINUTE, AND I THINK
THAT I WILL CALL THINGS TO A
CLOSE IN THAT FINAL MINUTE BY
THANKING THE TWO OF YOU.
CHARLES AND CLEMENT, THIS HAS
BEEN JUST A REALLY SPECTACULAR
COUPLE OF HOURS HEARING YOU
PRESENT YOUR WORK, PRESENT SOME
OF THE CHALLENGES OF THE FIELD
AND TALK TO US A LITTLE BIT
ABOUT WHAT WE REALLY NEED TO DO,
IT HAS REALLY BEEN FANTASTIC.
AND I WANT TO THANK THE BOTH OF
YOU SO, SO MUCH FOR TAKING THE
TIME WITH US THIS AFTERNOON.
I DO HAVE SOME ADDITIONAL
QUESTIONS THAT WE DIDN'T GET TO
THAT I WILL PASS ON TO YOU A
LITTLE BIT LATER.
I DO WANT TO REMIND THOSE WHO
ARE WATCHING THIS FOR POSSIBLE
CME CREDIT THAT THE NUMBER, THE
PHONE NUMBER TO TEXT TO IS
443-541-5052, AND YOU HAVE TO
TEXT THE 45391 CODE IN ORDER TO
GET CREDIT.
BUT AGAIN, CLEMENT AND CHARLES,
THANK YOU SO MUCH FOR REALLY A
WONDERFUL COUPLE OF HOURS, AND I
WISH YOU BOTH A GOOD NIGHT.
>>THANK YOU VERY MUCH, AND
>>BYE-BYE.