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WE WELCOME YOU TO THE 14TH

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SESSION OF THE 23RD YEAR OF THE

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COURSE IN DEMYSTIFYING MEDICINE

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CONDUCTED AT THE NATIONAL

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INSTITUTES OF HEALTH IN

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BETHESDA, MARYLAND.

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THE PROGRAM FOR THIS YEAR AND

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THE PREVIOUS YEAR WAS VIRTUAL,

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BUT WE MAY BE MOVING NOW INTO A

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MORE HYBRID MODE IN 2024.

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WE CERTAINLY HOPE SO.

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THE PURPOSE OF THIS COURSE IS TO

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BRIDGE, BRIDGE EXCITING

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DEVELOPMENTS IN BIOLOGY AND

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ENGINEERING WITH MEDICINE.

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AND THE RAPID DEVELOPMENTS IN

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BIOLOGICAL SCIENCE, ENGINEERING

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SCIENCE, METHODOLOGIES, HAS

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CREATED AN ENORMOUS GAP BETWEEN

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WHAT IS USED AND PRACTICED IN

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THE DIAGNOSIS AND TREATMENT OF

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HUMAN DISEASE.

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SO THE LOGO FOR OUR COURSE SHOWN

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IN THE UPPER RIGHT IS THE WORLD

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FAMOUS BROOKLYN BRIDGE, WHICH WE

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HAVE SHOWN 412 TIMES FOR

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SESSIONS IN THIS COURSE, A LONG

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TIME.

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TODAY, THE INDIVIDUALS ON THE

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CATWALK REPRESENT A UNIQUE KIND

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OF BRIDGING, ALL CONCERNS

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DIABETES.

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WE'LL GET TO THAT IN A MOMENT.

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BUT WE HAVE THE BRIDGING BETWEEN

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A CHANGE IN CAREER FROM A

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LEADING DEVELOPMENTAL BIOLOGIST

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INTO A PATHOBIOLOGICALLY -- CELL

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BIOLOGIST.

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AND A YOUNG WOMAN WHO HAS TYPE .

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AND HAS MADE ENORMOUS PROGRESS

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IN HER LIFE, WHICH SHE'S GOING

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TO SHARE WITH US.

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SO OUR CONCERN IS THAT MUCH OF

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THE PROGRESS IN THE MORE BASIC

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SCIENCES AND IN MEDICINE

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CONSTITUTE LIKE SILOS OF

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INFORMATION.

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THEY BECOME SO SPECIALIZED THAT

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THERE'S LIMITED BRIDGING BETWEEN

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THEM.

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SO THE PURPOSE OF THIS COURSE IS

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ESSENTIALLY TO CONVERT SILOS OF

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KNOWLEDGE AND EXPERIENCE INTO

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BRIDGES FOR THE BETTERMENT OF AN

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UNDERSTANDING OF BIOLOGY AND

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MEDICINE.

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SO THE SPEAKERS HAVE NO

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FINANCIAL RELATIONSHIPS.

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THE CME CREDIT IS 45394.

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THE PHONE NUMBTODAY THE TOPIC IT

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PROGRESS IN DIABETES.

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NOW IT'S BEEN OVER 100 YEARS

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SINCE THE DISCOVERY OF INSULIN.

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AND YET THE CURE OF DIABETES AND

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THE TREATMENT REMAINS

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CHALLENGING.

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AT THE SAME TIME, BOTH THE

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FREQUENCY OF TYPE 1 AND TYPE

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2 DIABETES GLOBALLY CONTINUES T.

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MANY QUESTIONS ARISE, AND SOME

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THAT I WILL MENTION HERE ARE

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ONES THAT WILL BE THE TOPIC OF

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TODAY'S PRESENTATIONS.

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IS METICULOUS CONTROL OF BLOOD

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SUGAR POSSIBLE, THEREBY

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PREVENTING MANY OF THE LONG-TERM

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COMPLICATIONS OF DIABETES, SUCH

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AS CARDIOVASCULAR DISEASE,

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INFECTION, CANCER, BLINDNESS,

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NEUROPATHY, NEPHROPATHY, AND

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OTHERS.

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WHAT'S THE PATHOGENESIS OF TYPE

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1 DIABETES?

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CAN PANCREATIC BETA CELL BIOLOGY

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BE USED AS TREATMENT TO PROVIDE

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ESSENTIALLY IN VIVO FUNCTION IN

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MAN?

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AND HOW CAN DIABETICS "LIVE

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WITH" THEIR DISEASE AND FUNCTION

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NORMALLY?

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THESE ARE THE BIG TOPICS TO BE

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PRESENTED TODAY BY OUR SPEAKERS

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SO LET ME INTRODUCE THEM TO YOU.

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SO THE FIRST SPEAKER IS COURTNEY

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DUCKWORTH.

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WHO GRADUATED FROM THE

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UNIVERSITY OF VIRGINIA,

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RECEIVING HER MEDICAL DEGREE IN

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2022.

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AND SHE IS PRESENTLY A FIRST

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YEAR PEDIATRIC RESIDENT AT

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BOSTON CHILDREN'S HOSPITAL.

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IN 2003, COURTNEY WAS DIAGNOSED

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WITH TYPE 1 DIABETES.

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IN A FRIGHTENING CLINICAL

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SITUATION.

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FROM 2015 TO '17, SHE WAS AT THE

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NATIONAL INSTITUTES OF HEALTH AS

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A POSTBAC, AN IRTA RESEARCH

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FELLOW.

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AND THERE, SHE WORKED WITH AARON

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SIPUS AND OTHERS PRIMARILY ON

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STUDIES IN VIVO OF BROWN FAT

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METABOLISM.

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IN 2018, SHE WAS A RESEARCH

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ASSISTANT IN GENETICS AND

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METABOLISM AT THE CHILDREN'S

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NATIONAL HEALTH SYSTEM.

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NOW ASIDE FROM THIS CHEVY -- ASE

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FROM THIS HEAVY ACADEMIC

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RESPONSIBILITY, COURTNEY DOES

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NOT LET GRASS GROW UNDER HER

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FEET.

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SHE IS A FIGURE SKATING COACH.

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SHE WAS A FIGURE SKATING

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CHEERLEADER WITH THE WASHINGTON

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CAPITALS, THE PROFESSIONAL

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HOCKEY TEAM.

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SHE IS A MARATHON RUNNER.

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HAS RUN THE BOSTON MARATHON AT

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LEAST TWICE, AND SHE'S A FITNESS

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AND DANCE INSTRUCTOR, AND

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PROBABLY A FEW OTHER THINGS.

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BUT MOST NOTABLY, FOR TODAY'S

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PRESENTATION, SHE'S AN AUTHOR.

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AND HER BOOK ENTITLED "THE

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MARATHON WE LIVE:  TRAINING FOR

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A PERSONAL BEST IN LIFE WITH

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TYPE 1 DIABETES," IS, IN MY

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VIEW, A CLASSIC THAT PEOPLE

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SHOULD READ TO UNDERSTAND WHAT

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REALLY CAN BE DONE IN THE WAY OF

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TREATMENT AND MANAGEMENT OF THIS

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DISEASE.

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NOW OUR SECOND SPEAKER WHO WILL

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BE WITH US THROUGH THE COURTESY

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OF MAKING A VIDEO AS A

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LAST-MINUTE CONFLICT PREVENTED

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HIM FROM BEING IN PERSON WITH

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US, IS DOUG MELTON.

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NOW DOUG RECEIVED A BACHELO

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BACHELOR'S DEGREE IN BIOLOGY

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FROM THE UNIVERSITY OF ILLINOIS

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AND A SECOND DEGREE IN

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PHILOSOPHY AND SCIENCE AT

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CAMBRIDGE, AND THEN A PH.D. IN

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MOLECULAR BIOLOGY AT TRINITY

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COLLEGE THERE IN THE FAMOUS

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MEDICAL RESEARCH COUNCIL

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LABORATORY OF MOLECULAR BIOLOGY.

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AFTER THAT TRAINING, THERE WAS

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NO POSTDOC FOR DOUG.

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HE WAS RECRUITED AT WH HARVARD N

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1981 AND LEFT IN 2022, WHERE HE

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WAS THE XANDER UNIVERSITY

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PROFESSOR AND HOWARD HUGHES

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INVESTIGATOR AND CO-DIRECTOR OF

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THE HARVARD STEM CELL INSTITUTE.

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IN 2022, HE MOVED TO THE VERTEX

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FAPHARMACEUTIC COMPANY, AND HE

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WILL EXPLAIN THE REASONS FOR

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THIS CHANGE.

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DOUG HAS RECEIVED NUMEROUS

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AWARDS, INCLUDING ELECTION TO

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THE NATIONAL ACADEMY OF MEDIC 

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MEDICINE.

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IN HIS EARLIER CAREER AT

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HARVARD, HE WAS A LEADING

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DEVELOPMENTAL BIOLOGIST, AND

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THEN RATHER DRAMATICALLY CHANGED

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HIS FOCUS TO DEVELOP TREATMENT

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FOR DIABETES BY INSULIN

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PRODUCING PANCREATIC BETA CELL

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TRANSPLANTS, MAINLY FROM STEM

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CELLS.

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USING IPS CELLS FROM TYPE

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1 JUVENILE DIABETICS, HE STUDIED

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THE BASIS OF AUTOIMMUNITY AND

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HIS LABORATORY HAS ALSO DONE

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ELEGANT STUDIES IN TYPE

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2 DIABETES.

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SO WE WILL BEGIN WITH

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DR. DUCKWORTH, AND COURTNEY,

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IT'S A PLEASURE TO HAVE YOU WITH

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US.

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>>THANK YOU FOR THAT KIND

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INTRODUCTION, WIN.

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THANK YOU, EVERYONE, FOR YOUR

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TIME TODAY, AND FOR ATTENDING

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THIS LECTURE IN DEMYSTIFYING

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MEDICINE.

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AS WIN SAID, MY NAME IS COURTNEY

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DUCKWORTH.

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I'M CURRENTLY A RESIDENT

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PHYSICIAN AT BOSTON CHILDREN'S

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HOSPITAL AND BOSTON MEDICAL

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CENTER, CALLING IN FROM THE CALL

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ROOM HERE AT THE BRIGHAM AND

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WOMEN'S NICU.

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TODAY WE'RE GOING TO BE TALKING

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ABOUT HOW IN MANY WAYS DIABETES

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IS ONE OF THE GREAT MARATHONS OF

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LIFE.

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I HAVE NO FINANCIAL DISCLOSURES

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OR CONFLICTS OF INTEREST WITH

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THE MATERIAL IN THIS

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PRESENTATION.

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AND PRIOR TO MEDICAL SCHOOL, I

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WAS A POSTBAC RESEARCH FELLOW AT

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THE NIH AND BEFORE CONTINUING

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THIS PRESENTATION, I FIRST HAVE

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TO THANK EVERYONE WHO BROUGHT ME

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THERE, INCLUDING DR. CHEN, MY

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P.I., DR. CYPESS, DR. BRYCHTA,

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MY COLLEAGUES DR. LEITNE R &
B

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ASKIN AS WELL AS THE COUNTLESS

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MENTORS I MEANT ALONG THE WAY

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INCLUDES DRS. ARIAS AND DRS.

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COLLINS AND COUNTLESS OTHERS.

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MY INTRODUCTION TO MEDICINE CAME

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IN THE FORM OF DIAGNOSIS WITH

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TYPE 1 DIABETES AT THE AGE OF

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10.

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I'VE LIVED WITH THIS DISEASE NOW

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FOR ABOUT TWO DECADES,

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EXPERIENCING THE COMPLEXITIES OF

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THIS CHRONIC ILLNESS, THE

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PHYSICAL AS WELL AS PSYCHOSOCIAL

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IMPACTS, AS WELL AS THE

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INCREDIBLE CHANGES IN DIABETES

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TECHNOLOGY THAT HAVE HAPPENED IN

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THIS PERIOD OF TIME.

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WHEN I WAS FIRST DIAGNOSED, I

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WAS USING MPH AND REGULAR

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INSULIN.

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I HAVE ALSO EXPERIENCED A NUMBER

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OF MULTIPLE DAILY INJECTION

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THERAPIES TO INSULIN PUMPS, NOW

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CGMs AND ON THE HORIZON ARE

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INSULIN-PRODUCING CELL

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TRANSPLANTS, LARGELY LY A PART F

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DR. MELTON'S WORK WHICH WE'LL

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HEAR ABOUT LATER IN HIS

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PRESENTATION.

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I HOPE TO CONTRIBUTE MY

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PERSPECTIVE AS BOTH A PATIENT

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AND AS A PHYSICIAN AS WE DISCUSS

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THE FOLLOWING OBJECTIVES.

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FIRST, GAINING AN UNDERSTANDING

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OF THE MULTIFACETED NATURE OF

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MANAGING TYPE 1 DIABETES.

262
00:11:42,720 --> 00:11:45,320
APPRECIATING HOW ADVANCEMENTS IN

263
00:11:45,320 --> 00:11:46,280
TREATMENT IMPROVE DIABETES

264
00:11:46,280 --> 00:11:50,440
MANAGEMENT AND QUALITY OF LIFE.

265
00:11:50,440 --> 00:11:51,640
RECOGNIZING EXPANDING HEALTHCARE

266
00:11:51,640 --> 00:11:52,640
DISPARITIES IN THE CONTEXT OF

267
00:11:52,640 --> 00:11:58,520
NEW DIABETES TREATMENTS.

268
00:11:58,520 --> 00:12:00,320
FIRST TOUCHING ON

269
00:12:00,320 --> 00:12:01,360
PATHOPHYSIOLOGY AND PREVALENCE

270
00:12:01,360 --> 00:12:02,600
OF TYPE 1 DIABETES, AS MANY

271
00:12:02,600 --> 00:12:03,680
PEOPLE IN THIS AUDIENCE ARE

272
00:12:03,680 --> 00:12:05,200
FAMILIAR WITH, TYPE 1 DIABETES

273
00:12:05,200 --> 00:12:07,600
IS AN AUTOIMMUNE CONDITION

274
00:12:07,600 --> 00:12:09,240
CHARACTERIZED BY T-CELL MEDIATED

275
00:12:09,240 --> 00:12:12,120
ATTACK ON PANCREATIC BETA CELLS

276
00:12:12,120 --> 00:12:13,840
LEADING TO LACK OF INSULIN

277
00:12:13,840 --> 00:12:16,600
SECRETION.

278
00:12:16,600 --> 00:12:17,280
CURRENTLY 8.8 MILLION PEOPLE IN

279
00:12:17,280 --> 00:12:19,480
THE WORLD ARE ESTIMATED TO HAVE

280
00:12:19,480 --> 00:12:21,960
TYPE 1 DIABETES, WITH 1.5 BEING

281
00:12:21,960 --> 00:12:24,280
IN THE U.S. ALONE.

282
00:12:24,280 --> 00:12:25,400
OVERALL, TYPE 1 DIABETES

283
00:12:25,400 --> 00:12:27,640
ACCOUNTS FOR ABOUT 5 TO 10% OF

284
00:12:27,640 --> 00:12:30,880
ALL DIABETES CASES.

285
00:12:30,880 --> 00:12:32,600
THERE'S AN ESTIMATED INCREASE OF

286
00:12:32,600 --> 00:12:35,880
ABOUT 2 TO 3% IN INCIDENCE PER

287
00:12:35,880 --> 00:12:37,760
YEAR, AND WHILE THERE'S MANY

288
00:12:37,760 --> 00:12:39,960
THEORIES BEHIND THIS, ONE

289
00:12:39,960 --> 00:12:41,240
UNDOUBTED THEORY IS THAT THERE'S

290
00:12:41,240 --> 00:12:44,120
BETTER PUBLIC EDUCATION AROUND

291
00:12:44,120 --> 00:12:44,960
DIABETES AND DIAGNOSIS IN

292
00:12:44,960 --> 00:12:45,760
GENERAL.

293
00:12:45,760 --> 00:12:47,040
THERE'S ALSO AN INCREASE IN

294
00:12:47,040 --> 00:12:48,200
PREVALENCE AS TREATMENTS

295
00:12:48,200 --> 00:12:49,960
CONTINUE TO PROGRESS.

296
00:12:49,960 --> 00:12:52,200
AND WHILE TYPE 1 DIABETES IS

297
00:12:52,200 --> 00:12:54,320
TRADITIONALLY THOUGHT TO BE A

298
00:12:54,320 --> 00:12:56,480
DISEASE OF CHILDHOOD, ABOUT 50%

299
00:12:56,480 --> 00:12:58,400
OF NEW CASES ARE DIAGNOSED IN

300
00:12:58,400 --> 00:13:03,080
ADULTHOOD.

301
00:13:03,080 --> 00:13:04,800
DIABETES HAS FAR REACHING

302
00:13:04,800 --> 00:13:06,480
PHYSICAL, PSYCHOSOCIAL AND

303
00:13:06,480 --> 00:13:10,320
FINANCIAL IMPACTS.

304
00:13:10,320 --> 00:13:11,320
PHYSICALLY FOR EVERY TWO PEOPLE

305
00:13:11,320 --> 00:13:14,480
WITH TYPE 1 ALIVE TODAY, ONE IS

306
00:13:14,480 --> 00:13:17,520
LOST TO DIRECT CAUSES.

307
00:13:17,520 --> 00:13:20,080
ABOUT 22 HEALTHY LIFE YEARS ARE

308
00:13:20,080 --> 00:13:22,200
LOST IF DIAGNOSED IN CHILDHOOD

309
00:13:22,200 --> 00:13:24,320
IN THE UNITED STATES, WHICH IS A

310
00:13:24,320 --> 00:13:28,240
LITTLE BIT HIGHER THAN THAT OF

311
00:13:28,240 --> 00:13:29,640
OTHER COMPARABLE HIGH INCOME

312
00:13:29,640 --> 00:13:33,640
COUNTRIES.

313
00:13:33,640 --> 00:13:34,280
PSYCHOLOGICALLY, DIABETES IS A

314
00:13:34,280 --> 00:13:35,480
VERY INTERESTING CONDITION IN

315
00:13:35,480 --> 00:13:37,560
THAT SO MUCH OF THE OUTCOMES OF

316
00:13:37,560 --> 00:13:39,280
THIS DISEASE DEPEND ON

317
00:13:39,280 --> 00:13:41,440
INDIVIDUAL ACTION.

318
00:13:41,440 --> 00:13:42,720
EVERYTHING YOU DO OR DON'T DO

319
00:13:42,720 --> 00:13:44,240
CAN AFFECT YOUR GLUCOSE LEVELS,

320
00:13:44,240 --> 00:13:47,440
WHICH IS AN INCREDIBLE AMOUNT OF

321
00:13:47,440 --> 00:13:48,320
PRESSURE.

322
00:13:48,320 --> 00:13:49,760
PERHAPS NOT SURPRISINGLY, PEOPLE

323
00:13:49,760 --> 00:13:51,200
WITH DIABETES ARE TWO TO THREE

324
00:13:51,200 --> 00:13:53,760
TIMES MORE LIKELY TO DEVELOP

325
00:13:53,760 --> 00:13:54,760
DEPRESSION.

326
00:13:54,760 --> 00:13:56,000
ABOUT 20% MORE LIKELY TO

327
00:13:56,000 --> 00:13:58,600
EXPERIENCE ANXIETY.

328
00:13:58,600 --> 00:14:00,360
AND WOMEN WITH TYPE 1 ARE ABOUT

329
00:14:00,360 --> 00:14:02,000
TWICE AS LIKELY TO DEVELOP AN

330
00:14:02,000 --> 00:14:05,280
EATING DISORDER.

331
00:14:05,280 --> 00:14:06,920
AND IMPORTANTLY, PHYSICAL HEALTH

332
00:14:06,920 --> 00:14:08,760
AND MENTAL HEALTH ARE A

333
00:14:08,760 --> 00:14:11,080
BIDIRECTIONAL RELATIONSHIP, AND

334
00:14:11,080 --> 00:14:16,080
FOR MENTAL HPOOR MENTAL HEALTH N

335
00:14:16,080 --> 00:14:17,960
NEGATIVELY AFFECT GLUCOSE LEVELS

336
00:14:17,960 --> 00:14:19,800
AND VICE VERSA.

337
00:14:19,800 --> 00:14:21,120
FINANCIALLY, PEOPLE WITH

338
00:14:21,120 --> 00:14:23,240
DIABETES ARE ESTIMATED TO SPEND

339
00:14:23,240 --> 00:14:26,800
AN ADDITIONAL $9,600 A YEAR

340
00:14:26,800 --> 00:14:29,320
DIRECTLY DUE TO DIABETES

341
00:14:29,320 --> 00:14:30,800
TREATMENTS.

342
00:14:30,800 --> 00:14:33,600
AND ABOUT 5.5 DAYS OF WORK ARE

343
00:14:33,600 --> 00:14:35,680
MISSED A YEAR ON AVERAGE, AND IN

344
00:14:35,680 --> 00:14:37,200
TOTAL, IT'S ESTIMATED THAT ABOUT

345
00:14:37,200 --> 00:14:38,640
14 DAYS OF PRODUCTIVITY AT WORK

346
00:14:38,640 --> 00:14:40,840
ARE MISSED, AND THIS CAN BE DUE

347
00:14:40,840 --> 00:14:43,440
TO THE TIME IT TAKES TO CARE FOR

348
00:14:43,440 --> 00:14:45,000
DIABETES, AS WELL AS THE MENTAL

349
00:14:45,000 --> 00:14:46,760
ENERGY IT TAKES TO CONTROL THIS

350
00:14:46,760 --> 00:14:52,240
DISEASE AS WELL.

351
00:14:52,240 --> 00:14:54,080
ILLUSTRATING THIS BURDEN OF

352
00:14:54,080 --> 00:14:58,080
DISEASE ON AN INDIVIDUAL LEVEL,

353
00:14:58,080 --> 00:14:59,680
MY CRASH COURSE IN MEDICINE

354
00:14:59,680 --> 00:15:01,320
BEGAN OCTOBER 27TH, 2003, WHEN I

355
00:15:01,320 --> 00:15:05,480
WAS DIAGNOSED WITH DIABETES, AND

356
00:15:05,480 --> 00:15:08,080
ENDED OCTOBER 30TH, 2003, WHEN I

357
00:15:08,080 --> 00:15:10,400
LEFT THE HOSPITAL AT CHILDREN'S

358
00:15:10,400 --> 00:15:11,000
NATIONAL.

359
00:15:11,000 --> 00:15:13,600
PRIOR TO DIAGNOSIS, I WOULD HAVE

360
00:15:13,600 --> 00:15:14,880
DESCRIBED MY LIFE AS A

361
00:15:14,880 --> 00:15:17,080
COMBINATION OF VARIOUS

362
00:15:17,080 --> 00:15:18,480
ACTIVITIES, MOSTLY SCHOOL,

363
00:15:18,480 --> 00:15:21,560
FRIENDS, AND FIGURE SKATING.

364
00:15:21,560 --> 00:15:23,320
AND AFTER DIAGNOSIS, I WOULD

365
00:15:23,320 --> 00:15:24,840
STILL DESCRIBE MY LIFE AS A

366
00:15:24,840 --> 00:15:27,000
COMBINATION OF THESE ACTIVITIES.

367
00:15:27,000 --> 00:15:30,200
JUST NOW WITH MULTIPLE

368
00:15:30,200 --> 00:15:34,000
INJECTIONS, FINGER STICKS, AND

369
00:15:34,000 --> 00:15:36,760
CARB COUNTING AS WELL AS AN A

370
00:15:36,760 --> 00:15:37,960
CONSTANT INTERNAL DIALOGUE OF

371
00:15:37,960 --> 00:15:40,600
WHAT MY GLUCOSE LEVELS WERE

372
00:15:40,600 --> 00:15:41,440
DOING AT ANY TIME PRIOR TO DO

373
00:15:41,440 --> 00:15:47,120
THE BEING A TIINGTHE ACTIVITIES.

374
00:15:47,120 --> 00:15:48,800
THE FIRST YEAR WAS ESPECIALLY

375
00:15:48,800 --> 00:15:50,160
DIFFICULT BECAUSE THE LEARNING

376
00:15:50,160 --> 00:15:51,720
CURVE WAS VERY DEEP.

377
00:15:51,720 --> 00:15:53,200
MY FAMILY AND I BARELY KNEW WHAT

378
00:15:53,200 --> 00:15:56,120
A CARB WAS MUCH LESS HOW TO

379
00:15:56,120 --> 00:15:57,320
COUNT THEM.

380
00:15:57,320 --> 00:15:58,880
WE FOUND THERE WAS A LOT OF

381
00:15:58,880 --> 00:16:01,560
SOCIAL STIGMA BEHIND THE WORD

382
00:16:01,560 --> 00:16:03,520
"DIABETES."

383
00:16:03,520 --> 00:16:05,640
THIS SLIDE IS BUSY ON PURPOSE,

384
00:16:05,640 --> 00:16:06,840
REPRESENTING ALL OF THE

385
00:16:06,840 --> 00:16:08,400
ADDITIONAL ACTIVITY THAT WERE

386
00:16:08,400 --> 00:16:10,880
NOW ADDED TO MY DAY, SUCH AS

387
00:16:10,880 --> 00:16:13,440
TESTING GLUCOSE ANYWHERE BETWEEN

388
00:16:13,440 --> 00:16:16,560
6 TO 14 TIMES A DAY, TAKING

389
00:16:16,560 --> 00:16:18,640
ANYWHERE FROM 6 TO 8 SHOTS, AS

390
00:16:18,640 --> 00:16:20,120
WELL AS SOME OF THE

391
00:16:20,120 --> 00:16:21,880
INCONVENIENCES THAT COULD HAPPEN

392
00:16:21,880 --> 00:16:23,480
AT ANY TIME OF THE DAY, SUCH AS

393
00:16:23,480 --> 00:16:26,000
GETTING AN EPISODE OF

394
00:16:26,000 --> 00:16:26,880
HYPOGLYCEMIA, AND HAVING TO GO

395
00:16:26,880 --> 00:16:29,360
TO THE NURSE'S OFFICE, AS WELL

396
00:16:29,360 --> 00:16:32,680
AS THE VERY METICULOUS CARB

397
00:16:32,680 --> 00:16:33,960
COUNTING AS WELL AS THE TIMING

398
00:16:33,960 --> 00:16:40,760
OF CARBOHYDRATES IN MY DAY.

399
00:16:40,760 --> 00:16:41,120
ON

400
00:16:41,120 --> 00:16:42,240
AVERAGE, IT'S ESTIMATED THAT

401
00:16:42,240 --> 00:16:43,560
DIABETES CARE TASKS ALONE TAKE

402
00:16:43,560 --> 00:16:45,440
ABOUT AN HOUR AND 15 MINUTES A

403
00:16:45,440 --> 00:16:47,080
DAY.

404
00:16:47,080 --> 00:16:49,440
AND IF SOMEONE WITH DIABETES

405
00:16:49,440 --> 00:16:51,560
WERE TO PERFORM ALL RECOMMENDED

406
00:16:51,560 --> 00:16:52,840
HEALTHCARE TASKS SUCH AS GOING

407
00:16:52,840 --> 00:16:55,840
TO THE DOCTOR, DOING THEIR FOOT

408
00:16:55,840 --> 00:16:57,520
EXAM, FOR EXAMPLE, YOU KNOW,

409
00:16:57,520 --> 00:16:58,960
CHANGING OUT THEIR INSULIN, ALL

410
00:16:58,960 --> 00:17:00,760
OF THESE TASKS THAT CAN ADD UP,

411
00:17:00,760 --> 00:17:02,600
IT CAN TAKE UPWARDS OF FIVE

412
00:17:02,600 --> 00:17:08,320
HOURS A DAY.

413
00:17:08,320 --> 00:17:09,520
WITH DIABETES TREATMENT, I

414
00:17:09,520 --> 00:17:11,040
LEARNED A FEW UNDERLYING

415
00:17:11,040 --> 00:17:13,440
PRINCIPLES EARLY ON.

416
00:17:13,440 --> 00:17:15,400
FIRST, THAT FOLLOWING DIRECTIONS

417
00:17:15,400 --> 00:17:16,840
PERFECTLY DIDN'T NECESSARILY

418
00:17:16,840 --> 00:17:19,480
MAKE FOR PERFECT RESULTS.

419
00:17:19,480 --> 00:17:22,560
DIABETES THRIVES ON CONSISTENCY.

420
00:17:22,560 --> 00:17:24,040
AND PEOPLE'S ACTIVITIES CHANGE

421
00:17:24,040 --> 00:17:25,600
FROM DAY TO DAY, ESPECIALLY WHEN

422
00:17:25,600 --> 00:17:26,920
YOU'RE VERY YOUNG AND YOU DON'T

423
00:17:26,920 --> 00:17:29,800
HAVE ANY AGENCY OVER YOUR

424
00:17:29,800 --> 00:17:31,080
SCHEDULE, AND DIABETES ALSO

425
00:17:31,080 --> 00:17:32,120
DEPENDS ON THE CONDITIONS WITHIN

426
00:17:32,120 --> 00:17:34,040
YOUR OWN BODY, WHICH ALSO CHANGE

427
00:17:34,040 --> 00:17:35,400
FROM DAY TO DAY, ESPECIALLY WHEN

428
00:17:35,400 --> 00:17:37,480
YOU'RE YOUNG AND YOUR BODY IS

429
00:17:37,480 --> 00:17:40,920
GROWING VERY RAPIDLY.

430
00:17:40,920 --> 00:17:42,720
SECOND, I LEARNED THAT LOW BLOOD

431
00:17:42,720 --> 00:17:44,560
SUGAR KILLS YOU IN MINUTES, HIGH

432
00:17:44,560 --> 00:17:45,200
BLOOD PRESSURE KILLS YOU IN

433
00:17:45,200 --> 00:17:45,920
YEARS.

434
00:17:45,920 --> 00:17:47,600
OFTENTIMES, IT FELT SAFER TO RUN

435
00:17:47,600 --> 00:17:49,200
MY BLOOD SUGARS A LITTLE HIGHER

436
00:17:49,200 --> 00:17:51,000
AND BE ABLE TO PARTICIPATE IN

437
00:17:51,000 --> 00:17:52,800
ACTIVITIES WITH MY PEERS.

438
00:17:52,800 --> 00:17:54,760
IT WAS EXTREMELY SCARY TO HAVE

439
00:17:54,760 --> 00:17:56,320
LOW BLOOD SUGAR, ESPECIALLY WHEN

440
00:17:56,320 --> 00:17:58,160
I DIDN'T KNOW HOW RAPIDLY IT WAS

441
00:17:58,160 --> 00:18:00,320
DROPPING, AND ALSO WHEN I WAS IN

442
00:18:00,320 --> 00:18:02,280
ENVIRONMENTS WHERE I FELT THAT

443
00:18:02,280 --> 00:18:04,080
PEOPLE WERE NOT EDUCATED ON

444
00:18:04,080 --> 00:18:05,280
DIABETES AND THAT I WAS TAKING

445
00:18:05,280 --> 00:18:09,880
CARE OF IT BY MYSELF.

446
00:18:09,880 --> 00:18:11,280
HOWEVER, I KNEW BEING IN RANGE

447
00:18:11,280 --> 00:18:14,440
HELPED ME LIVE TO MY FULLEST

448
00:18:14,440 --> 00:18:14,720
POTENTIAL.

449
00:18:14,720 --> 00:18:16,760
WHEN MY BLOOD SUGAR WAS LOW I

450
00:18:16,760 --> 00:18:18,520
FELT SHAKY AND LIGHT-HEADED AND

451
00:18:18,520 --> 00:18:19,520
OFTEN COULDN'T PARTICIPATE IN

452
00:18:19,520 --> 00:18:20,440
THE ACTIVITIES I WAS SUPPOSED TO

453
00:18:20,440 --> 00:18:21,240
BE DOING.

454
00:18:21,240 --> 00:18:22,640
HOWEVER, WHEN MY BLOOD SUGAR WAS

455
00:18:22,640 --> 00:18:25,280
HIGH, I WOULD FEEL SLEEPY, AND

456
00:18:25,280 --> 00:18:27,000
LIKE I COULD LOSE MY FOCUS VERY

457
00:18:27,000 --> 00:18:28,680
EASILY.

458
00:18:28,680 --> 00:18:30,280
AND I KNEW THAT BEING SOMEWHERE

459
00:18:30,280 --> 00:18:33,960
IN THE MIDDLE HELPED ME TO LIVE

460
00:18:33,960 --> 00:18:37,440
MY LIFE TO MY FULLEST POTENTIAL.

461
00:18:37,440 --> 00:18:41,080
AND FINALLY, DIABETES IS A TEAM

462
00:18:41,080 --> 00:18:41,800
SPORT.

463
00:18:41,800 --> 00:18:42,920
ESPECIALLY WHEN YOU'RE YOUNG, SO

464
00:18:42,920 --> 00:18:44,560
MUCH OF CARRYING OUT DAILY

465
00:18:44,560 --> 00:18:46,640
MANAGEMENT TASKS DEPENDS ON THE

466
00:18:46,640 --> 00:18:48,400
ADULTS AROUND YOU.

467
00:18:48,400 --> 00:18:50,280
MY MOM WOULD WAKE UP EVERY NIGHT

468
00:18:50,280 --> 00:18:51,880
TO TEST MY GLUCOSE TO MAKE SURE

469
00:18:51,880 --> 00:18:53,640
THAT I WOULD WAKE UP THE NEXT

470
00:18:53,640 --> 00:18:55,400
MORNING, AND I ALSO HAD AN

471
00:18:55,400 --> 00:18:57,280
EXCELLENT CARE TEAM AT

472
00:18:57,280 --> 00:19:00,760
CHILDREN'S NATIONAL, INCLUDING

473
00:19:00,760 --> 00:19:02,120
DR. COGAN, WHO ALWAYS GOT TO

474
00:19:02,120 --> 00:19:03,960
KNOW ME AS A PERSON BEFORE WE

475
00:19:03,960 --> 00:19:05,840
TRIED TO TACKLE THE PROBLEMS OF

476
00:19:05,840 --> 00:19:11,480
DIABETES TOGETHER.

477
00:19:11,480 --> 00:19:13,040
IN MY FIRST 10 YEARS OF LIVING

478
00:19:13,040 --> 00:19:15,680
WITH TYPE 1 DIABETES, AGAIN, I

479
00:19:15,680 --> 00:19:17,920
EXPERIENCED A NUMBER OF

480
00:19:17,920 --> 00:19:21,960
DIFFERENT TREATMENTS, BUT FACED

481
00:19:21,960 --> 00:19:22,920
SIMILAR CHALLENGES.

482
00:19:22,920 --> 00:19:26,640
AGAIN, GOING FROM MPH AND

483
00:19:26,640 --> 00:19:31,880
REGULAR INSULIN TO BASAL/BOLUS

484
00:19:31,880 --> 00:19:34,040
REGIMES, AND INSULIN PUMP IN

485
00:19:34,040 --> 00:19:34,280
2013.

486
00:19:34,280 --> 00:19:35,400
DURING THIS TIME, I HAD ALSO

487
00:19:35,400 --> 00:19:37,720
BECOME A COLLEGE STUDENT AT

488
00:19:37,720 --> 00:19:39,600
WILLIAM AND MARY, AND I DID

489
00:19:39,600 --> 00:19:41,080
PRETTY WELL AS A PRE-MED, AND

490
00:19:41,080 --> 00:19:43,160
GAVE MORE HEALTHCARE LITERACY.

491
00:19:43,160 --> 00:19:46,680
AND THESE BETTER

492
00:19:46,680 --> 00:19:47,880
TREATMENTS AND INCREASE IN

493
00:19:47,880 --> 00:19:49,120
HEALTHCARE LITERACY, I FOUND IT

494
00:19:49,120 --> 00:19:50,680
WAS EXTREMELY CHALLENGING TO

495
00:19:50,680 --> 00:19:52,720
MEET THE GOALS SET FORTH BY THE

496
00:19:52,720 --> 00:19:54,880
AMERICAN DIABETES ASSOCIATION

497
00:19:54,880 --> 00:19:56,640
AND THE GLYCEMIC GOALS I KNEW I

498
00:19:56,640 --> 00:20:01,520
WAS CAPABLE.

499
00:20:01,520 --> 00:20:04,120
CURRENTLY THE ADA RECOMMENDS

500
00:20:04,120 --> 00:20:06,520
THAT A1Cs BE BELOW 7% FOR BOTH

501
00:20:06,520 --> 00:20:07,920
YOUTH AND ADULTS.

502
00:20:07,920 --> 00:20:09,840
HOWEVER, THIS IS A FAIRLY NEW

503
00:20:09,840 --> 00:20:12,080
RECOMMENDATION, AND PREVIOUSLY,

504
00:20:12,080 --> 00:20:15,360
A1Cs WERE RECOMMENDED TO BE

505
00:20:15,360 --> 00:20:18,680
BELOW 7.5% FOR YOUTH AND YOUNG

506
00:20:18,680 --> 00:20:21,280
ADULTS.

507
00:20:21,280 --> 00:20:23,080
IN 2015, WE CAN SEE IN THIS

508
00:20:23,080 --> 00:20:25,200
FIGURE ON THE RIGHT THAT EVEN

509
00:20:25,200 --> 00:20:29,520
WITH THE 7.5%, ABOUT 86% OF

510
00:20:29,520 --> 00:20:31,360
TEENS AND YOUNG ADULTS WERE NOT

511
00:20:31,360 --> 00:20:32,280
MEETING THIS RECOMMENDATION,

512
00:20:32,280 --> 00:20:33,440
MEANING THAT I WAS IN THE VAST

513
00:20:33,440 --> 00:20:38,240
MAJORITY.

514
00:20:38,240 --> 00:20:40,120
DURING THIS TIME, I HAD ALSO

515
00:20:40,120 --> 00:20:42,080
TAKEN ON AN EXTRA CHALLENGE IN

516
00:20:42,080 --> 00:20:44,160
THE FORM OF RUNNING MARATHONS

517
00:20:44,160 --> 00:20:46,240
WHEN A FRIEND AND I DISCOVERED

518
00:20:46,240 --> 00:20:48,760
THAT WE BOTH SHARED RUNNING A

519
00:20:48,760 --> 00:20:52,480
MARATHON ON OUR BUCKET LIST.

520
00:20:52,480 --> 00:20:54,120
IN MY VERY FIRST MARATHON

521
00:20:54,120 --> 00:20:55,320
WITHOUT EVER HAVING TRAINED FOR

522
00:20:55,320 --> 00:20:56,680
SPEED, I WAS ABOUT 3 MINUTES

523
00:20:56,680 --> 00:20:58,160
AWAY FROM QUALIFYING FOR THE

524
00:20:58,160 --> 00:20:59,160
BOSTON MARATHON.

525
00:20:59,160 --> 00:21:01,760
SO NATURALLY, MY GOAL CHANGED

526
00:21:01,760 --> 00:21:04,280
FROM RUN A MARATHON TO RUN THE

527
00:21:04,280 --> 00:21:07,600
BOSTON MARATHON.

528
00:21:07,600 --> 00:21:10,400
AND ABOUT A YEAR LATER, A VERY

529
00:21:10,400 --> 00:21:11,520
STRATEGIC TRAINING AND A COUPLE

530
00:21:11,520 --> 00:21:14,600
OF MARATHONS, I WAS ABLE TO

531
00:21:14,600 --> 00:21:16,120
QUALIFY.

532
00:21:16,120 --> 00:21:17,640
AND I THOUGHT TO MYSELF, IF I

533
00:21:17,640 --> 00:21:20,360
CAN TRAIN TO BECOME A BETTER

534
00:21:20,360 --> 00:21:21,560
RUNNER IN THE SPAN OF JUST ONE

535
00:21:21,560 --> 00:21:23,280
YEAR AND EVEN QUALIFY FOR THE

536
00:21:23,280 --> 00:21:25,200
BOSTON MARATHON, SURELY I CAN

537
00:21:25,200 --> 00:21:26,880
TRAIN TO BE BETTER IN A DISEASE

538
00:21:26,880 --> 00:21:30,440
THAT I'VE HAD FOR OVER A DECADE.

539
00:21:30,440 --> 00:21:32,280
AND THIS LED TO THE THOUGHT,

540
00:21:32,280 --> 00:21:33,960
WHAT IF I APPROACHED DIABETES

541
00:21:33,960 --> 00:21:35,760
CARE LIKE I APPROACHED TRAINING

542
00:21:35,760 --> 00:21:38,920
FOR MARATHONS?

543
00:21:38,920 --> 00:21:40,360
THIS WOULD BECOME THE FRAMEWORK

544
00:21:40,360 --> 00:21:42,320
FOR MY BOOK, "THE MARATHON WE

545
00:21:42,320 --> 00:21:44,040
LIVE," AND IT'S HOW WE TALK

546
00:21:44,040 --> 00:21:45,800
ABOUT THE MULTIFACETED NATURE OF

547
00:21:45,800 --> 00:21:46,720
DIABETES CARE FOR THE REST OF

548
00:21:46,720 --> 00:21:51,160
THIS TALK.

549
00:21:51,160 --> 00:21:52,480
OVERALL, MY MARATHON TRAINING

550
00:21:52,480 --> 00:21:54,120
STRATEGY CONSISTED OF FOUR

551
00:21:54,120 --> 00:21:54,680
PARTS.

552
00:21:54,680 --> 00:21:56,080
KNOWING WHAT YOU'RE TRAINING FOR

553
00:21:56,080 --> 00:21:57,720
AND WHY YOU'RE TRAINING,

554
00:21:57,720 --> 00:22:00,560
LEARNING HOW TO TRAIN, FORMING

555
00:22:00,560 --> 00:22:02,680
STRATEGIES, AND BUILDING

556
00:22:02,680 --> 00:22:05,720
ENDURANCE.

557
00:22:05,720 --> 00:22:06,720
FIRST, KNOWING WHAT YOU'RE

558
00:22:06,720 --> 00:22:07,720
TRAINING FOR.

559
00:22:07,720 --> 00:22:09,480
IN RUNNING, IT'S EXCEEDINGLY

560
00:22:09,480 --> 00:22:10,760
DIFFICULT TO CONVINCE YOURSELF

561
00:22:10,760 --> 00:22:12,320
TO GET UP AND RUN 20 MILES FOR

562
00:22:12,320 --> 00:22:13,240
NO GOOD REASON.

563
00:22:13,240 --> 00:22:15,400
YOU HAVE TO HAVE A LONG-TERM

564
00:22:15,400 --> 00:22:17,800
EVENT IN MIND.

565
00:22:17,800 --> 00:22:19,200
AND YOU HAVE TO HAVE A TARGET.

566
00:22:19,200 --> 00:22:20,400
LIKEWISE IN DIABETES, WE HAVE TO

567
00:22:20,400 --> 00:22:23,920
KNOW WHAT WE'RE TRAINING FOR.

568
00:22:23,920 --> 00:22:25,360
ANECDOTALLY AS A PHYSICIAN AND A

569
00:22:25,360 --> 00:22:28,640
PATIENT, I'VE NOTICED THAT

570
00:22:28,640 --> 00:22:29,960
CONVERSATIONS AROUND GLYCEMIC

571
00:22:29,960 --> 00:22:32,880
GOALS OFTEN GO OVERLOOKED.

572
00:22:32,880 --> 00:22:33,840
AGAIN, A1C GOALS ARE RECOMMENDED

573
00:22:33,840 --> 00:22:36,920
TO BE BELOW 7%, WITH POST

574
00:22:36,920 --> 00:22:38,560
PRANDIAL GLUCOSE LEVELS BEING

575
00:22:38,560 --> 00:22:41,320
BELOW 180, AND FOR THOSE WHO USE

576
00:22:41,320 --> 00:22:42,880
CONTINUOUS GLUCOSE MONITOR OR

577
00:22:42,880 --> 00:22:45,680
CGM TECHNOLOGY, TIME AND RANGE

578
00:22:45,680 --> 00:22:48,040
IS RECOMMENDED TO BE AT LEAST

579
00:22:48,040 --> 00:22:53,880
70%, WITH 4% BELOW TARGET.

580
00:22:53,880 --> 00:22:55,240
IN THIS GRAPH HERE FROM DIABETES

581
00:22:55,240 --> 00:22:56,960
CARE ON THE RIGHT, WE CAN SEE

582
00:22:56,960 --> 00:22:59,040
TIME AND RANGE REPRESENTED IN

583
00:22:59,040 --> 00:23:00,960
THE GREEN HERE.

584
00:23:00,960 --> 00:23:03,160
TIME ABOVE RANGE REPRESENTED IN

585
00:23:03,160 --> 00:23:05,160
THE YELLOW, AND TIME BELOW RANGE

586
00:23:05,160 --> 00:23:10,320
REPRESENTED IN THE RED.

587
00:23:10,320 --> 00:23:11,840
NEXT YOU HAVE TO KNOW WHY YOU'RE

588
00:23:11,840 --> 00:23:14,280
TRAINING, WHAT ARE YOUR BENEF 

589
00:23:14,280 --> 00:23:14,600
BENEFITS.

590
00:23:14,600 --> 00:23:18,200
IN RUNNING, MY LONG TERM BIG

591
00:23:18,200 --> 00:23:20,240
PICTURE BENEFITS WERE CROSSING

592
00:23:20,240 --> 00:23:21,760
AN ITEM OFF MY BUCKET LIST,

593
00:23:21,760 --> 00:23:23,600
WHILE THERE WERE ALSO DAY TO DAY

594
00:23:23,600 --> 00:23:24,800
BENEFITS, AND THIS COULD BE

595
00:23:24,800 --> 00:23:25,800
ANYTHING FROM EXPLORING A NEW

596
00:23:25,800 --> 00:23:28,400
PART OF TOWN ON A RUN TO HAVING

597
00:23:28,400 --> 00:23:30,000
BANANA AND PEANUT BUTTER AFTER A

598
00:23:30,000 --> 00:23:31,440
RUN.

599
00:23:31,440 --> 00:23:34,320
LIKEWISE, IN DIABETES, WE GAIN

600
00:23:34,320 --> 00:23:37,400
BOTH LONG TERM AND SHORT TERM

601
00:23:37,400 --> 00:23:37,720
BENEFITS.

602
00:23:37,720 --> 00:23:41,000
LONG TERM, WE GAIN PROTECTION

603
00:23:41,000 --> 00:23:43,880
FROM RETINOPATHY, NEUROPATHY,

604
00:23:43,880 --> 00:23:46,040
NEPHROPATHY, AS WELL AS MACRO

605
00:23:46,040 --> 00:23:46,720
VASCULAR EVENTS.

606
00:23:46,720 --> 00:23:48,240
HOWEVER, THIS LONG TERM

607
00:23:48,240 --> 00:23:49,680
PROTECTION CAN SEEM VAGUE,

608
00:23:49,680 --> 00:23:51,760
ESPECIALLY FOR YOUNG PEOPLE WHO

609
00:23:51,760 --> 00:23:54,560
PROBABLY FEEL RELATIVELY

610
00:23:54,560 --> 00:23:56,040
INVINCIBLE, AND PROBABLY HAVE AN

611
00:23:56,040 --> 00:24:00,000
EASIER TIME RELATING TO THESE

612
00:24:00,000 --> 00:24:01,600
DAY TO DAY BENEFITS THAT THEY

613
00:24:01,600 --> 00:24:04,240
GET FROM BETTER GLUCOSE CONTROL.

614
00:24:04,240 --> 00:24:07,120
THIS INCLUDES INCREASED ENERGY,

615
00:24:07,120 --> 00:24:09,480
FOCUS, SATIETY, IMMUNITY, MENTAL

616
00:24:09,480 --> 00:24:11,720
HEALTH, AND SOCIAL RELATIONSHIPS

617
00:24:11,720 --> 00:24:17,880
WITH THEIR PEERS.

618
00:24:17,880 --> 00:24:19,080
NEXT, YOU HAVE TO KNOW HOW TO

619
00:24:19,080 --> 00:24:20,840
TRAIN FOR THE TASK AT HAND.

620
00:24:20,840 --> 00:24:22,480
WHAT ARE YOUR TOOLS AND WHAT ARE

621
00:24:22,480 --> 00:24:25,080
THE SKILLS THAT YOU'RE TRYING TO

622
00:24:25,080 --> 00:24:26,000
DEVELOP?

623
00:24:26,000 --> 00:24:27,520
IN RUNNING, TRAINING FOR A

624
00:24:27,520 --> 00:24:28,960
50-YARD DASH IS GOING TO LOOK A

625
00:24:28,960 --> 00:24:29,800
LOT DIFFERENT THAN TRAINING FOR

626
00:24:29,800 --> 00:24:32,440
A MARATHON.

627
00:24:32,440 --> 00:24:34,280
LIKEWISE, IN DIABETES, WE HAVE

628
00:24:34,280 --> 00:24:35,640
TO KNOW EXACTLY WHAT WE'RE

629
00:24:35,640 --> 00:24:38,640
TRYING TO ACCOMPLISH.

630
00:24:38,640 --> 00:24:40,120
QUITE SIMPLY, THIS IS REALLY

631
00:24:40,120 --> 00:24:41,720
JUST TWO THINGS:  SENSING

632
00:24:41,720 --> 00:24:42,640
GLUCOSE CHANGES AND STAYING

633
00:24:42,640 --> 00:24:46,000
WITHIN A RELATIVELY TIGHT RANGE.

634
00:24:46,000 --> 00:24:49,520
AND WE HAVE MULTIPLE TOOLS TO DO

635
00:24:49,520 --> 00:24:54,120
BOTH OF THESE THINGS.

636
00:24:54,120 --> 00:24:57,040
FOR SENSING GLUCOSE CHANGES WE

637
00:24:57,040 --> 00:24:59,800
USE GLUCOSE MONITORS AS WELL AS

638
00:24:59,800 --> 00:25:00,960
CONTINUOUS GLUCOSE MONITORS, AND

639
00:25:00,960 --> 00:25:02,120
TO STAY WITHIN A TIGHT RANGE, WE

640
00:25:02,120 --> 00:25:04,840
CAN USE INSULIN, NUTRITION, AND

641
00:25:04,840 --> 00:25:06,720
EXERCISE, WITH THE CAVEAT THAT

642
00:25:06,720 --> 00:25:09,160
WHILE EXERCISE CAN BE GREAT FOR

643
00:25:09,160 --> 00:25:10,640
INCREASING INSULIN SENSITIVITY,

644
00:25:10,640 --> 00:25:13,240
IT CAN BE REALLY HARD TO CONTROL

645
00:25:13,240 --> 00:25:15,360
GLUCOSE LEVELS DURING EXERCISE.

646
00:25:15,360 --> 00:25:17,560
AND IN FACT, PHYSICAL ACTIVITY

647
00:25:17,560 --> 00:25:20,480
HAS NOT SHOWN TO BE ASSOCIATED

648
00:25:20,480 --> 00:25:26,720
WITH LOWER A1C LEVELS.

649
00:25:26,720 --> 00:25:28,080
EACH OF THESE TOOLS COME WITH

650
00:25:28,080 --> 00:25:31,520
THEIR OWN SET OF SKILLS THAT

651
00:25:31,520 --> 00:25:34,120
NECESSITATE THE NEED FOR

652
00:25:34,120 --> 00:25:36,200
CONTINUOUS EDUCATION AND VERY

653
00:25:36,200 --> 00:25:38,400
STRATEGIC PRACTICE.

654
00:25:38,400 --> 00:25:39,960
FOR EXAMPLE, USING INSULIN TO

655
00:25:39,960 --> 00:25:41,760
ITS UTMOST EFFECT REQUIRES THAT

656
00:25:41,760 --> 00:25:44,480
ONE KNOWS HOW TO DOSE THEIR

657
00:25:44,480 --> 00:25:46,640
INSULIN CORRECTLY, AS WELL AS

658
00:25:46,640 --> 00:25:49,000
TIME THEIR INSULIN CORRECTLY,

659
00:25:49,000 --> 00:25:51,280
ADMINISTER SAFELY, AND STORE

660
00:25:51,280 --> 00:25:56,200
EFFECTIVELY.

661
00:25:56,200 --> 00:25:59,400
NEXT, WE FORM STRATEGIES.

662
00:25:59,400 --> 00:26:01,640
IN RUNNING, YOU MIGHT SIT DOWN

663
00:26:01,640 --> 00:26:03,760
16 WEEKS BEFORE A RACE AND PLAN

664
00:26:03,760 --> 00:26:06,080
OUT EVERY SINGLE WORKOUT THAT

665
00:26:06,080 --> 00:26:08,200
YOU DO WITH THE REALIZATION THAT

666
00:26:08,200 --> 00:26:10,200
THIS IS EXTREMELY FLEXIBLE.

667
00:26:10,200 --> 00:26:12,400
YOU HAVE TO TRY YOUR STRATEGIES,

668
00:26:12,400 --> 00:26:14,600
SEE IF THEY'RE WORKING, AND THEN

669
00:26:14,600 --> 00:26:20,080
ADAPT ALONG THE WAY.

670
00:26:20,080 --> 00:26:22,160
LIKEWISE IN TYPE 1 DIABETES,

671
00:26:22,160 --> 00:26:24,120
EVERY DAY YOU'RE YOUR OWN

672
00:26:24,120 --> 00:26:26,080
SCIENTIFIC EXPERIMENT AND WE'RE

673
00:26:26,080 --> 00:26:27,200
CONSTANTLY DESIGNING STRATEGIES

674
00:26:27,200 --> 00:26:28,160
FOR INDIVIDUAL SITUATIONS,

675
00:26:28,160 --> 00:26:29,920
WHETHER THIS IS HAVING BETTER

676
00:26:29,920 --> 00:26:31,800
GLYCEMIC CONTROL AT BEDTIME, OR

677
00:26:31,800 --> 00:26:34,160
IF THIS IS DEVELOPING SKILLS

678
00:26:34,160 --> 00:26:36,800
SUCH AS LEARNING HOW TO DOSE

679
00:26:36,800 --> 00:26:40,120
INSULIN CORRECTLY.

680
00:26:40,120 --> 00:26:43,480
IN MEDICINE, WE OFTEN TALK ABOUT

681
00:26:43,480 --> 00:26:46,560
THE PDSA CYCLE, PLAN, DO, STUDY

682
00:26:46,560 --> 00:26:48,200
ACT, WHEN WE TALK ABOUT QUALITY

683
00:26:48,200 --> 00:26:54,560
IMPROVEMENT, WHICH IS A

684
00:26:54,560 --> 00:26:56,320
RECENT -- FIRST WE PROACTIVELY

685
00:26:56,320 --> 00:26:59,120
DECIDE THE ACTIONS THAT WILL

686
00:26:59,120 --> 00:27:00,360
TARGET A CERTAIN AREA OF

687
00:27:00,360 --> 00:27:04,080
IMPROVEMENT.

688
00:27:04,080 --> 00:27:05,280
WE PERFORM THESE ACTIONS AND

689
00:27:05,280 --> 00:27:07,760
COLLECT OUR DATA.

690
00:27:07,760 --> 00:27:10,640
WE ANALYZE OUR DATA.

691
00:27:10,640 --> 00:27:13,360
AND FINALLY, WE IDENTIFY AREAS

692
00:27:13,360 --> 00:27:16,440
FOR IMPROVEMENT AND BEGIN A NEW

693
00:27:16,440 --> 00:27:18,560
CYCLE.

694
00:27:18,560 --> 00:27:20,000
AND STUDYING OUR DATA AS WELL AS

695
00:27:20,000 --> 00:27:21,600
ACTING ON OUR DATA AND

696
00:27:21,600 --> 00:27:22,760
IDENTIFYING AREAS FOR

697
00:27:22,760 --> 00:27:24,240
IMPROVEMENT IS WHERE OUR SECOND

698
00:27:24,240 --> 00:27:27,080
LEARNING OBJECTIVE COMES IN.

699
00:27:27,080 --> 00:27:28,480
APPRECIATING THE CHANGES THAT

700
00:27:28,480 --> 00:27:30,920
HAVE COME ABOUT WITH BETTER

701
00:27:30,920 --> 00:27:32,520
DIABETES TECHNOLOGY TO HELP US

702
00:27:32,520 --> 00:27:37,040
IN BOTH OF THESE DOMAINS.

703
00:27:37,040 --> 00:27:39,480
LARGELY, THIS IS DUE TO

704
00:27:39,480 --> 00:27:41,200
CONTINUOUS GLUCOSE MONITORS.

705
00:27:41,200 --> 00:27:42,640
CGMs TAKE A READING OF THE

706
00:27:42,640 --> 00:27:44,160
GLUCOSE IN THE INTERSTITIAL

707
00:27:44,160 --> 00:27:46,560
FLUID EVERY FIVE MINUTES.

708
00:27:46,560 --> 00:27:49,600
THIS GIVES US 284 ADDITIONAL

709
00:27:49,600 --> 00:27:50,760
DATA POINTS A DAY.

710
00:27:50,760 --> 00:27:53,000
AND SO WE CAN SEE THE EFFECTS OF

711
00:27:53,000 --> 00:27:56,080
OUR STRATEGIES IN REALTIME AND

712
00:27:56,080 --> 00:27:58,320
ADAPT AS NEEDED.

713
00:27:58,320 --> 00:28:00,800
BELOW, THIS IS ONE OF MY GLUCOSE

714
00:28:00,800 --> 00:28:01,240
READOUTS.

715
00:28:01,240 --> 00:28:03,680
IN A TWO-WEEK PERIOD OF TIME.

716
00:28:03,680 --> 00:28:06,600
SO LOOKING AT OUR DATA, WE CAN

717
00:28:06,600 --> 00:28:08,800
SEE THAT WHILE 86% OF THE TIME I

718
00:28:08,800 --> 00:28:11,960
WAS IN RANGE FOR THESE TWO

719
00:28:11,960 --> 00:28:13,760
WEEKS, WHICH IS QUITE GOOD, 7%

720
00:28:13,760 --> 00:28:15,960
OF THE TIME I WAS SPENDING BELOW

721
00:28:15,960 --> 00:28:17,240
RANGE, WHICH IS ABOVE THE

722
00:28:17,240 --> 00:28:18,760
RECOMMENDED 4% FROM THE ADA.

723
00:28:18,760 --> 00:28:20,840
SO THAT'S A POTENTIAL AREA FOR

724
00:28:20,840 --> 00:28:21,600
IMPROVEMENT.

725
00:28:21,600 --> 00:28:23,160
LOOKING AT THIS GRAPH ON THE

726
00:28:23,160 --> 00:28:24,880
BOTTOM, WE CAN SEE THE TIMES OF

727
00:28:24,880 --> 00:28:26,360
THE DAY WHERE I WAS TENDING TO

728
00:28:26,360 --> 00:28:28,400
GO LOW.

729
00:28:28,400 --> 00:28:29,840
ONE BEING AFTER DINNER, FOR

730
00:28:29,840 --> 00:28:30,600
EXAMPLE.

731
00:28:30,600 --> 00:28:33,200
AND I CAN BACKTRACK AND ASK

732
00:28:33,200 --> 00:28:34,840
MYSELF QUESTIONS ABOUT WHY THAT

733
00:28:34,840 --> 00:28:36,640
MIGHT HAPPEN SUCH AS TAKING TOO

734
00:28:36,640 --> 00:28:38,480
MUCH INSULIN AND DINNER AND THEN

735
00:28:38,480 --> 00:28:40,560
BREAKING THAT DOWN EVEN FURTHER

736
00:28:40,560 --> 00:28:43,160
INTO INSULIN DOSE AND INSULIN TO

737
00:28:43,160 --> 00:28:46,480
CARB RATIO AND TRYING TO CHANGE

738
00:28:46,480 --> 00:28:48,120
THAT, AND THEN LOOKING AT THE

739
00:28:48,120 --> 00:28:50,160
DATA THAT I HAVE FROM THE NEXT

740
00:28:50,160 --> 00:28:51,600
TWO WEEKS AFTER IMPLEMENTING A

741
00:28:51,600 --> 00:28:52,560
CHANGE.

742
00:28:52,560 --> 00:28:56,800
OR EVEN SOONER.

743
00:28:56,800 --> 00:28:58,280
OVERALL, CGM TECHNOLOGY HAS BEEN

744
00:28:58,280 --> 00:29:01,880
SHOWN TO INCREASE TIME IN RANGE.

745
00:29:01,880 --> 00:29:03,200
FOR YOUTH UNDER 26 YEARS OLD,

746
00:29:03,200 --> 00:29:08,800
THIS CAN BE AS MUCH AS 0.7 TO 1%

747
00:29:08,800 --> 00:29:13,480
IMPROVEMENT IN A1C LEVELS.

748
00:29:13,480 --> 00:29:15,120
CGM TECHNOLOGY HAS ALSO BEEN

749
00:29:15,120 --> 00:29:18,640
SHOWN TO DECREASE EPISODES OF

750
00:29:18,640 --> 00:29:20,600
DKA, AS WELL AS HYPOGLYCEMIC

751
00:29:20,600 --> 00:29:21,520
EVENTS, WHICH ARE SOME OF THE

752
00:29:21,520 --> 00:29:23,200
LEADING CAUSES OF MORBIDITY AND

753
00:29:23,200 --> 00:29:29,040
MORTALITY WI FOR PEOPLE WITH TY.

754
00:29:29,040 --> 00:29:32,000
CGMs HAVE ALSO BEEN SHOWN TO

755
00:29:32,000 --> 00:29:33,840
PROVIDE PSYCHOSOCIAL BENEFITS.

756
00:29:33,840 --> 00:29:36,280
THIS INCLUDES INCREASED EFFICACY

757
00:29:36,280 --> 00:29:38,880
AND CARE, CONFIDENCE THAT YOU

758
00:29:38,880 --> 00:29:43,400
CAN HAVE GREAT GLYCEMIC CONTROL,

759
00:29:43,400 --> 00:29:45,360
AND THAT FOLLOWING THROUGH ON

760
00:29:45,360 --> 00:29:47,920
THE ACTIONS IN MANAGEMENT

761
00:29:47,920 --> 00:29:48,880
PRODUCES THE RESULTS THAT YOU

762
00:29:48,880 --> 00:29:51,800
WANT.

763
00:29:51,800 --> 00:29:53,320
IT'S ALSO BEEN SHOWN TO DECREASE

764
00:29:53,320 --> 00:29:54,920
LEVELS OF ANXIETY AND DEPRESSION

765
00:29:54,920 --> 00:29:58,160
FOR PEOPLE WITH DIABETES,

766
00:29:58,160 --> 00:30:00,040
INCREASED RESTFUL SLEEP, PROVIDE

767
00:30:00,040 --> 00:30:02,200
GREATER PARTICIPATION IN PEER

768
00:30:02,200 --> 00:30:03,640
ACTIVITIES, AND INCREASED

769
00:30:03,640 --> 00:30:05,480
COMFORT WITH NON-GUARDIAN

770
00:30:05,480 --> 00:30:11,720
CAREGIVERS.

771
00:30:11,720 --> 00:30:14,840
THIS BRINGS US TO OUR THIRD

772
00:30:14,840 --> 00:30:16,680
LEARNING OBJECTIVE, WHICH IS

773
00:30:16,680 --> 00:30:19,680
APPRECIATING THE DISPARITIES IN

774
00:30:19,680 --> 00:30:21,160
THE CONTEXT OF NEW TREATMENTS.

775
00:30:21,160 --> 00:30:22,480
THIS CONVERSATION IS ESPECIALLY

776
00:30:22,480 --> 00:30:24,000
IMPORTANT, ESPECIALLY WITH

777
00:30:24,000 --> 00:30:27,840
RECENT IMPROVEMENTS IN ACCESS TO

778
00:30:27,840 --> 00:30:28,160
INSULIN.

779
00:30:28,160 --> 00:30:29,920
IT'S IMPORTANT THAT WE CARRY OUT

780
00:30:29,920 --> 00:30:31,360
THIS CONVERSATION IN ALL ASPECTS

781
00:30:31,360 --> 00:30:33,880
OF DIABETES CARE.

782
00:30:33,880 --> 00:30:35,360
CURRENTLY ABOUT 30% OF PEOPLE

783
00:30:35,360 --> 00:30:37,360
WITH TYPE 1 HAVE ACCESS TO

784
00:30:37,360 --> 00:30:38,640
CGMs, MEANING THAT THE VAST

785
00:30:38,640 --> 00:30:41,520
MAJORITY DO NOT.

786
00:30:41,520 --> 00:30:44,640
THOSE WHO PERHAPS NEED CGMs

787
00:30:44,640 --> 00:30:46,680
THE MOST INCLUDING ADOLESCENTS,

788
00:30:46,680 --> 00:30:48,840
MINORITY GROUPS, AND THOSE OF

789
00:30:48,840 --> 00:30:50,880
LOWER SOCIOECONOMIC STATUS WHO

790
00:30:50,880 --> 00:30:53,120
ON AVERAGE TEND TO HAVE HIGHER

791
00:30:53,120 --> 00:30:54,440
A1C LEVELS AND INCREASED RATES

792
00:30:54,440 --> 00:30:57,360
OF DKA AND HYPOGLYCEMIA ARE ALSO

793
00:30:57,360 --> 00:30:59,320
THOSE WHO HAVE THE LOWEST RATES

794
00:30:59,320 --> 00:31:02,560
OF CGM USE.

795
00:31:02,560 --> 00:31:04,720
CURRENTLY THE NUMBER ONE BARRIER

796
00:31:04,720 --> 00:31:06,720
TO CGM USE IS COST AND INSURANCE

797
00:31:06,720 --> 00:31:09,200
COVERAGE.

798
00:31:09,200 --> 00:31:11,040
NOT ALL STATES' MEDICAID

799
00:31:11,040 --> 00:31:12,680
CURRENTLY COVER CGMs, AND FOR

800
00:31:12,680 --> 00:31:15,080
THOSE WHO DO, THERE'S OFTEN AN

801
00:31:15,080 --> 00:31:16,320
EXTENSIVE PROCESS TO PROVE

802
00:31:16,320 --> 00:31:19,920
MEDICAL NEED.

803
00:31:19,920 --> 00:31:22,680
FOR THOSE WHO DO HAVE INSURANCE

804
00:31:22,680 --> 00:31:24,640
LIVING 133% ABOVE POVERTY LEVEL,

805
00:31:24,640 --> 00:31:26,400
THEY OFTEN PAY HUNDREDS OF

806
00:31:26,400 --> 00:31:26,880
DOLLARS OUT OF POCKET.

807
00:31:26,880 --> 00:31:30,200
THIS CAN BE ANYWHERE FROM 200 TO

808
00:31:30,200 --> 00:31:31,520
$500 A MONTH.

809
00:31:31,520 --> 00:31:33,280
WHICH IS SIMPLY NOT POSSIBLE FOR

810
00:31:33,280 --> 00:31:36,800
MOST FAMILIES.

811
00:31:36,800 --> 00:31:39,160
HOWEVER, STUDIES HAVE SHOWN OVER

812
00:31:39,160 --> 00:31:40,600
AND OVER AGAIN

813
00:31:40,600 --> 00:31:41,560
COST-EFFECTIVENESS EVEN WHEN

814
00:31:41,560 --> 00:31:43,800
ACCOUNTING FOR ONLY A FEW COST

815
00:31:43,800 --> 00:31:45,960
SAVING VARIABLES, SUCH AS

816
00:31:45,960 --> 00:31:49,040
ADMISSION TO THE HOSPITAL FROM

817
00:31:49,040 --> 00:31:50,880
DKA, BUT THEY'RE NOT COUNTING

818
00:31:50,880 --> 00:31:52,120
ALL OF THE COST SAVING

819
00:31:52,120 --> 00:31:54,640
VARIABLES.

820
00:31:54,640 --> 00:31:57,920
THERE'S ALSO ADDITIONAL BARRIERS

821
00:31:57,920 --> 00:31:59,680
TO CGM ACCESS IN THE FORM OF THE

822
00:31:59,680 --> 00:32:02,160
WAY THAT PROVIDERS OFFER CGMs

823
00:32:02,160 --> 00:32:03,960
TO PATIENTS.

824
00:32:03,960 --> 00:32:06,240
AS WELL AS THE WAY THAT CGMs

825
00:32:06,240 --> 00:32:08,320
ARE PERCEIVED BY INDIVIDUAL

826
00:32:08,320 --> 00:32:09,520
PATIENTS, WHICH IS A CURRENT

827
00:32:09,520 --> 00:32:12,800
AREA OF STUDY HERE AT BOSTON

828
00:32:12,800 --> 00:32:14,960
CHILDREN'S THAT WE'RE TRYING TO

829
00:32:14,960 --> 00:32:21,200
ELUCIDATE FURTHER.

830
00:32:21,200 --> 00:32:22,440
FINALLY, THE LAST STEP OF

831
00:32:22,440 --> 00:32:25,360
MARATHON TRAINING IS BUILDING

832
00:32:25,360 --> 00:32:26,360
ENDURANCE.

833
00:32:26,360 --> 00:32:28,520
AND THIS IS NOT NECESSARILY JUST

834
00:32:28,520 --> 00:32:30,840
PHYSICAL ENDURANCE BUT ALSO THE

835
00:32:30,840 --> 00:32:33,120
MENTAL ENDURANCE TO KEEP GOING.

836
00:32:33,120 --> 00:32:35,080
WHEN YOU'RE TRAINING FOR A

837
00:32:35,080 --> 00:32:36,160
MARATHON, THERE ARE MANY DAYS

838
00:32:36,160 --> 00:32:37,840
WHERE YOU WAKE UP AND YOU SIMPLY

839
00:32:37,840 --> 00:32:40,360
DON'T WANT TO RUN.

840
00:32:40,360 --> 00:32:42,000
IT'S DARK OUTSIDE, IT'S COLD,

841
00:32:42,000 --> 00:32:43,760
ESPECIALLY HERE IN BOSTON, AND

842
00:32:43,760 --> 00:32:47,960
YOU JUST NEED TO FIND STRATEGIES

843
00:32:47,960 --> 00:32:49,880
TO KEEP GOING ONE MORE DAY.

844
00:32:49,880 --> 00:32:52,720
THERE'S MANY WAYS THAT WE CAN DO

845
00:32:52,720 --> 00:32:56,440
THIS.

846
00:32:56,440 --> 00:32:58,080
IN DIABETES, SIMILARLY, WE CAN

847
00:32:58,080 --> 00:33:03,560
FACE BURNOUT, BUT WE CAN EMPLOY

848
00:33:03,560 --> 00:33:06,440
STRATEGIES TO, AGAIN, KEEP GOING

849
00:33:06,440 --> 00:33:08,040
AND JUST TAKE IT ONE DAY AT A

850
00:33:08,040 --> 00:33:09,840
TIME.

851
00:33:09,840 --> 00:33:12,160
ONE STRATEGY IS LEANING IN TO

852
00:33:12,160 --> 00:33:15,520
THE SUPPORT FROM THOSE O ON THE

853
00:33:15,520 --> 00:33:16,840
SIDELINES.

854
00:33:16,840 --> 00:33:18,560
IF YOU'RE SUPPORTING SOMEONE

855
00:33:18,560 --> 00:33:21,320
WITH TYPE 1, IT REALLY HELPS TO

856
00:33:21,320 --> 00:33:22,400
LISTEN, ENCOURAGE, LEND

857
00:33:22,400 --> 00:33:24,840
PERSPECTIVE, ADVOCATE, AND OFFER

858
00:33:24,840 --> 00:33:27,360
INSPIRATION, WHICH CAN COME FROM

859
00:33:27,360 --> 00:33:30,840
ANYONE AT ANY TIME.

860
00:33:30,840 --> 00:33:32,640
NEXT, WE CAN SHARE THE RACE WITH

861
00:33:32,640 --> 00:33:34,440
OTHER PEOPLE WHO ARE IN A

862
00:33:34,440 --> 00:33:38,080
SIMILAR SITUATION.

863
00:33:38,080 --> 00:33:40,080
HAVING CAMARADERIE IS INCREDIBLY

864
00:33:40,080 --> 00:33:41,400
HELPFUL IN BOTH SHARING

865
00:33:41,400 --> 00:33:42,280
CHALLENGES AND FINDING

866
00:33:42,280 --> 00:33:43,720
SOLUTIONS.

867
00:33:43,720 --> 00:33:45,040
AND THIS MEANS GETTING INVOLVED

868
00:33:45,040 --> 00:33:46,960
IN THE DIABETES COMMUNITY AND

869
00:33:46,960 --> 00:33:48,720
GIVING BACK, WHICH WILL CIRCLE

870
00:33:48,720 --> 00:33:52,440
AROU -- WHICHWE'LL CIRCLE AROUNN

871
00:33:52,440 --> 00:33:53,160
A SECOND.

872
00:33:53,160 --> 00:33:54,760
AND FINALLY, AGAIN, TRYING TO

873
00:33:54,760 --> 00:33:57,000
BUILD MENTAL STRENGTH, WHICH IS

874
00:33:57,000 --> 00:33:59,920
JUST AS MUCH A SKILL AS BUILDING

875
00:33:59,920 --> 00:34:00,560
PHYSICAL STRENGTH AND SOMETHING

876
00:34:00,560 --> 00:34:04,000
THAT NEEDS TO BE PRACTICED DAI 

877
00:34:04,000 --> 00:34:04,640
DAILY.

878
00:34:04,640 --> 00:34:06,680
THIS INCLUDES PRACTICING A

879
00:34:06,680 --> 00:34:08,120
PROBLEM-SOLVING MINDSET, AS WELL

880
00:34:08,120 --> 00:34:09,880
AS GRATITUDE, ESPECIALLY IN THE

881
00:34:09,880 --> 00:34:11,720
CONTEXT OF THE INCREDIBLE

882
00:34:11,720 --> 00:34:13,120
CHANGES THAT HAVE NOT ONLY

883
00:34:13,120 --> 00:34:16,040
HAPPENED IN THE LAST 20 YEARS,

884
00:34:16,040 --> 00:34:17,760
BUT AS WIN ALLUDED TO AT THE

885
00:34:17,760 --> 00:34:19,040
BEGINNING OF THIS LECTURE, HAVE

886
00:34:19,040 --> 00:34:20,400
HAPPENED IN THE PAST HUNDRED

887
00:34:20,400 --> 00:34:20,920
YEARS.

888
00:34:20,920 --> 00:34:23,440
AND THE FACT THAT WE'RE ABLE TO

889
00:34:23,440 --> 00:34:24,640
MANAGE DIABETES AT ALL AND LIVE

890
00:34:24,640 --> 00:34:26,080
WITH THIS DISEASE IS AN

891
00:34:26,080 --> 00:34:29,680
INCREDIBLE BLESSING.

892
00:34:29,680 --> 00:34:31,080
ALSO REMEMBERING OUR WINS, EVEN

893
00:34:31,080 --> 00:34:33,960
THE SMALL ONES.

894
00:34:33,960 --> 00:34:35,920
TRANSIENCE.

895
00:34:35,920 --> 00:34:39,080
THAT GOOD OR BAD, SITUATIONS ARE

896
00:34:39,080 --> 00:34:39,880
NOT PERMANENT.

897
00:34:39,880 --> 00:34:42,440
KINDNESS TO OUR FUTURE SELVES,

898
00:34:42,440 --> 00:34:45,040
ALL THE BENEFIT THAT WE'RE

899
00:34:45,040 --> 00:34:47,280
RECEIVING BY WORKING SO HARD,

900
00:34:47,280 --> 00:34:50,200
AND JUST TRYING TO BE 1% BETTER

901
00:34:50,200 --> 00:34:52,120
EVERY SINGLE DAY, NOT TRYING TO

902
00:34:52,120 --> 00:34:58,080
CHANGE TOO MUCH TOO SOON.

903
00:34:58,080 --> 00:35:03,080
GIVING BACK IS ESPECIALLY

904
00:35:03,080 --> 00:35:03,400
IMPORTANT.

905
00:35:03,400 --> 00:35:04,960
I FIND THAT A LOT OF PEOPLE IN

906
00:35:04,960 --> 00:35:06,600
THE DIABETES COMMUNITY WANT TO

907
00:35:06,600 --> 00:35:07,800
FIND MEANING IN THEIR

908
00:35:07,800 --> 00:35:09,000
EXPERIENCES, AND I BELIEVE

909
00:35:09,000 --> 00:35:12,160
THAT'S WHY SO MANY PEOPLE WITH

910
00:35:12,160 --> 00:35:15,640
DIABETES BECOME PART OF

911
00:35:15,640 --> 00:35:20,560
HEALTHCARE PROFESSIONS.

912
00:35:20,560 --> 00:35:22,000
FINALLY, IF THIS LIFE WITH

913
00:35:22,000 --> 00:35:23,960
DIABETES IS A MARATHON, WE CAN

914
00:35:23,960 --> 00:35:27,040
CREATE A BETTER RACE THROUGH

915
00:35:27,040 --> 00:35:28,560
INNOVATION, PATIENT CARE, AND

916
00:35:28,560 --> 00:35:30,240
ADVOCACY.

917
00:35:30,240 --> 00:35:32,080
INNOVATION TO CONTINUE TO FIND

918
00:35:32,080 --> 00:35:35,040
BETTER TREATMENTS, AND IMPROVE

919
00:35:35,040 --> 00:35:36,680
QUALITY OF LIFE, PATIENT CARE,

920
00:35:36,680 --> 00:35:38,120
ALWAYS GETTING TO KNOW A PATIENT

921
00:35:38,120 --> 00:35:40,920
AND THEIR VALUES BEFORE THEIR

922
00:35:40,920 --> 00:35:44,160
ILLNESS, AND FINALLY, ADVOCACY.

923
00:35:44,160 --> 00:35:45,600
SHARING DATA AND STORIES, SO

924
00:35:45,600 --> 00:35:47,080
THAT WE WORK IN A HEALTHCARE

925
00:35:47,080 --> 00:35:49,000
SYSTEM WHERE INNOVATION AND

926
00:35:49,000 --> 00:35:50,400
PATIENT CARE CAN BE USED TO

927
00:35:50,400 --> 00:35:52,560
THEIR UTMOST EFFECT.

928
00:35:52,560 --> 00:35:53,560
AND THANK YOU TO EVERYONE IN

929
00:35:53,560 --> 00:35:55,640
THIS AUDIENCE WHO ARE WORKING IN

930
00:35:55,640 --> 00:35:58,520
THESE DOMAINS TO CREATE A BETTER

931
00:35:58,520 --> 00:36:00,560
RACE FOR THOSE LIVING WITH

932
00:36:00,560 --> 00:36:01,520
DIABETES TODAY AND THOSE WHO

933
00:36:01,520 --> 00:36:04,400
LIVE WITH IT IN THE FUTURE.

934
00:36:04,400 --> 00:36:08,880
HERE ARE MY REFERENCES.

935
00:36:08,880 --> 00:36:10,640
AND THANK YOU SO MUCH AGAIN FOR

936
00:36:10,640 --> 00:36:13,040
YOUR ATTENTION AND FOR ATTENDING

937
00:36:13,040 --> 00:36:14,720
THIS LECTURE.

938
00:36:14,720 --> 00:36:16,560
IF YOU HAVE ANY REMAINING

939
00:36:16,560 --> 00:36:17,440
QUESTIONS AFTER THE END OF THIS

940
00:36:17,440 --> 00:36:19,840
TALK, I CAN BE REACHED AT

941
00:36:19,840 --> 00:36:23,120
COURTNEY.DUCKWORTH AT

942
00:36:23,120 --> 00:36:23,640
CHILDREN'S.HARVARD.EDU.

943
00:36:23,640 --> 00:36:24,360
THANK YOU.

944
00:36:24,360 --> 00:36:26,120
>>THANK YOU, THANK YOU
VERY

945
00:36:26,120 --> 00:36:30,520
MUCH, COURTNEY, FOR REALLY AN

946
00:36:30,520 --> 00:36:34,760
EXCELLENT, INSPIRING AND

947
00:36:34,760 --> 00:36:35,080
INFORMATIVE.

948
00:36:35,080 --> 00:36:36,080
NOW WE'RE GOING TO MOVE TO THE

949
00:36:36,080 --> 00:36:38,680
OTHER SIDE OF THE BRIDGE.

950
00:36:38,680 --> 00:36:41,760
AND WELCOME DOUG MELTON, WHO

951
00:36:41,760 --> 00:36:45,600
WILL BE WITH US IN A MOMENT.

952
00:36:45,600 --> 00:36:47,360
AS SOON AS THE ELECTRONICS ARE

953
00:36:47,360 --> 00:36:50,640
CONNECTED, FOR HIS VIDEO

954
00:36:50,640 --> 00:36:51,120
PRESENTATION.

955
00:36:51,120 --> 00:36:52,320
>>HELLO.

956
00:36:52,320 --> 00:36:54,080
MY NAME IS DOUG MELTON, AND I'M

957
00:36:54,080 --> 00:36:55,560
HAPPY TO TALK TO YOU THIS

958
00:36:55,560 --> 00:36:56,840
AFTERNOON ABOUT TYPE 1 DIABETES

959
00:36:56,840 --> 00:36:58,760
AND STEM CELLS.

960
00:36:58,760 --> 00:37:00,880
I'M ESPECIALLY GRATEFUL TO

961
00:37:00,880 --> 00:37:04,920
DR. WIN ARIAS AND DRS. COURTNEY

962
00:37:04,920 --> 00:37:07,320
DUCKWORTH, WHO ARE JOINING ME IN

963
00:37:07,320 --> 00:37:08,560
TODAY'S PRESENTATION ON

964
00:37:08,560 --> 00:37:10,480
DEMYSTIFYING MEDICINE.

965
00:37:10,480 --> 00:37:12,000
I'LL SHARE MY SCREEN AND THEN

966
00:37:12,000 --> 00:37:13,840
SPEAK FOR ABOUT A HALF AN HOUR

967
00:37:13,840 --> 00:37:17,440
ABOUT THIS PROJECT.

968
00:37:17,440 --> 00:37:20,640
SO WHAT YOU CAN SEE HERE THEN IN

969
00:37:20,640 --> 00:37:23,600
MY FIRST SLIDE IS I'M GOING TO

970
00:37:23,600 --> 00:37:24,920
TALK TO YOU TODAY ABOUT CELLS AS

971
00:37:24,920 --> 00:37:26,800
LIVING MEDICINES, A NEW APPROACH

972
00:37:26,800 --> 00:37:27,920
TO TREAT TYPE 1 DIABETES.

973
00:37:27,920 --> 00:37:31,200
AS IT SAYS HERE ON THIS SLIDE,

974
00:37:31,200 --> 00:37:33,200
I'M NOW A FELLOW, A RESEARCH

975
00:37:33,200 --> 00:37:34,480
FELLOW AT VERTEX

976
00:37:34,480 --> 00:37:35,200
PHARMACEUTICALS.

977
00:37:35,200 --> 00:37:36,800
I'M ON LEAVE FROM HARVARD

978
00:37:36,800 --> 00:37:37,120
UNIVERSITY.

979
00:37:37,120 --> 00:37:39,080
BUT I'M A FULL TIME EMPLOYEE OF

980
00:37:39,080 --> 00:37:40,480
VERTEX, AND, THEREFORE, I WANT

981
00:37:40,480 --> 00:37:43,360
TO SHOW THIS DISCLAIMER.

982
00:37:43,360 --> 00:37:45,120
WHAT YOU SEE HERE IS THAT I AM

983
00:37:45,120 --> 00:37:47,680
AN EMPLOYEE, I OWN SOME STOCK,

984
00:37:47,680 --> 00:37:49,320
AND THIS WILL BE RELEVANT AT THE

985
00:37:49,320 --> 00:37:51,520
END, NOT THE BEGINNING, OF MY

986
00:37:51,520 --> 00:37:51,720
TALK.

987
00:37:51,720 --> 00:37:53,200
THE BEGINNING OF MY TALK, I'M

988
00:37:53,200 --> 00:37:56,200
GOING TO FOCUS ENTIRELY ON WORK

989
00:37:56,200 --> 00:37:59,160
DONE FOR MANY YEARS AT HARVARD

990
00:37:59,160 --> 00:38:01,800
UNIVERSITY, AND THIS IS A

991
00:38:01,800 --> 00:38:02,680
RESEARCH PROJECT AND IT WON'T BE

992
00:38:02,680 --> 00:38:04,440
UNTIL THE END WHERE I'LL MAKE

993
00:38:04,440 --> 00:38:05,680
CLEAR THINGS THAT HAVE BEEN DONE

994
00:38:05,680 --> 00:38:10,040
AT VERTEX.

995
00:38:10,040 --> 00:38:12,880
SO IF I CAN ADVANCE THE SLIDES

996
00:38:12,880 --> 00:38:14,520
HERE.

997
00:38:14,520 --> 00:38:15,960
I DON'T PROBABLY NEED TO REMIND

998
00:38:15,960 --> 00:38:17,600
THIS AUDIENCE THAT FOR MORE THAN

999
00:38:17,600 --> 00:38:21,640
100 YEARS NOW, DIABETES,

1000
00:38:21,640 --> 00:38:23,440
PARTICULARLY TYPE 1 DIABETES AND

1001
00:38:23,440 --> 00:38:24,280
AUTOIMMUNE DISEASE, HAS BEEN

1002
00:38:24,280 --> 00:38:25,360
TREATED BY THE INJECTION OF

1003
00:38:25,360 --> 00:38:27,240
INSULIN.

1004
00:38:27,240 --> 00:38:29,080
THIS REQUIRES PATIENTS MOB TORE

1005
00:38:29,080 --> 00:38:32,360
TMONITORTHEIR BLOOD SUGARS.

1006
00:38:32,360 --> 00:38:33,920
AS SHOWN HERE, IT'S BEING

1007
00:38:33,920 --> 00:38:35,560
MONITORED IN TWO WAY, ONE WITH A

1008
00:38:35,560 --> 00:38:36,800
FINGER PRICK AND A LITTLE DROP

1009
00:38:36,800 --> 00:38:38,320
OF BLOOD TO MEASURE ON THEIR

1010
00:38:38,320 --> 00:38:39,720
MONITOR, OR WITH A CONTINUOUS

1011
00:38:39,720 --> 00:38:40,880
GLUCOSE MONITOR SHOWN AT THE

1012
00:38:40,880 --> 00:38:41,480
BOTTOM RIGHT.

1013
00:38:41,480 --> 00:38:44,840
AND THEN INSULIN IN RESPONSE TO

1014
00:38:44,840 --> 00:38:46,240
THOSE BLOOD GLUCOSE MEASUREMENTS

1015
00:38:46,240 --> 00:38:51,600
IS INJECTED WITH SYRINGES RE ATE

1016
00:38:51,600 --> 00:38:53,440
BOTTOM LEFT OR AN INSULIN PUMP.

1017
00:38:53,440 --> 00:38:55,760
WHAT I WANT TO POINT OUT HERE IS

1018
00:38:55,760 --> 00:38:57,520
THAT WHILE THERE HAVE BEEN VAST

1019
00:38:57,520 --> 00:38:59,040
IMPROVEMENTS IN MEASURING BLOOD

1020
00:38:59,040 --> 00:39:00,360
GLUCOSE LEVELS AND PROVIDING

1021
00:39:00,360 --> 00:39:02,560
INSULIN BY MECHANICAL MEANS,

1022
00:39:02,560 --> 00:39:03,200
FUNDAMENTALLY, IT'S BEEN THE

1023
00:39:03,200 --> 00:39:04,440
SAME APPROACH FOR MORE THAN A

1024
00:39:04,440 --> 00:39:06,520
HUNDRED YEARS.

1025
00:39:06,520 --> 00:39:08,600
NAMELY, FIGURE OUT YOUR BLOOD

1026
00:39:08,600 --> 00:39:10,000
SUGAR, ADJUST YOUR MEALS AND

1027
00:39:10,000 --> 00:39:12,360
YOUR EXERCISE, AND THEN INJECT A

1028
00:39:12,360 --> 00:39:13,640
BOLUS OF INSULIN TO TRY TO

1029
00:39:13,640 --> 00:39:15,280
CONTROL YOUR BLOOD SUGARS AND

1030
00:39:15,280 --> 00:39:18,240
KEEP THEM WITHIN A NORMAL RANGE.

1031
00:39:18,240 --> 00:39:20,680
BY RANGE, I MEAN A RANGE OF

1032
00:39:20,680 --> 00:39:23,720
BLOOD GLUCOSE LEVEL IN THE

1033
00:39:23,720 --> 00:39:25,680
BLOOD, BECAUSE TOO LOW BLOOD

1034
00:39:25,680 --> 00:39:27,640
GLUCOSE WILL LEAD TO PROBLEMS AS

1035
00:39:27,640 --> 00:39:30,080
WELL AS TOO HIGH, SO THERE'S

1036
00:39:30,080 --> 00:39:33,040
HYPOGLYCEMIA, WHICH CAN LEAD TO

1037
00:39:33,040 --> 00:39:35,120
UNCONSCIOUSNESS AND OTHER SEVERE

1038
00:39:35,120 --> 00:39:36,760
PROBLEMS, AND TO HIGH BLOOD

1039
00:39:36,760 --> 00:39:37,760
SUGARS, WHICH LEADS TO THE

1040
00:39:37,760 --> 00:39:39,280
COMPLICATIONS THAT ARE WELL

1041
00:39:39,280 --> 00:39:40,480
DOCUMENTED IN THE TREATMENT OF

1042
00:39:40,480 --> 00:39:45,520
DIABETES.

1043
00:39:45,520 --> 00:39:46,600
I'M GOING TO PRESENT TODAY AN

1044
00:39:46,600 --> 00:39:47,840
IDEA THAT THERE MAY BE A BETTER

1045
00:39:47,840 --> 00:39:49,160
WAY TO DO THIS, NAMELY, REPLACE

1046
00:39:49,160 --> 00:39:53,080
THE MISSING BETA CELLS.

1047
00:39:53,080 --> 00:39:55,080
YOU CAN SEE HERE THAT BETA CELLS

1048
00:39:55,080 --> 00:39:57,200
READ BLOOD GLUCOSE EVERY

1049
00:39:57,200 --> 00:39:58,080
MILLISECOND, AND THEY RELEASE

1050
00:39:58,080 --> 00:40:00,480
JUST THE RIGHT AMOUNT OF INSULIN

1051
00:40:00,480 --> 00:40:01,760
TO CONTROL GLUCOSE UPTAKE.

1052
00:40:01,760 --> 00:40:03,920
AND I PUT THOSE SIMPLE FACTS

1053
00:40:03,920 --> 00:40:05,280
THERE TO CONTRAST THEM WITH

1054
00:40:05,280 --> 00:40:07,480
WHAT'S DONE BY TRYING TO ADJUST

1055
00:40:07,480 --> 00:40:08,560
BLOOD GLUCOSE LEVELS

1056
00:40:08,560 --> 00:40:09,960
MECHANICALLY.

1057
00:40:09,960 --> 00:40:12,080
BLOOD GLUCOSE MONITORS IN THE

1058
00:40:12,080 --> 00:40:17,880
BEST CASES READ INTERSTITIAL

1059
00:40:17,880 --> 00:40:19,040
BLOOD GLUCOSE LEVELS ABOUT EVERY

1060
00:40:19,040 --> 00:40:22,040
FIVE MINUTES, WHICH WOULD MEAN

1061
00:40:22,040 --> 00:40:24,680
5,000 TIMES OR ABOUT 3,000 TIMES

1062
00:40:24,680 --> 00:40:26,520
LESS FREQUENTLY THAN A BETA

1063
00:40:26,520 --> 00:40:27,960
CELL.

1064
00:40:27,960 --> 00:40:29,600
SIMILARLY, AN INSULIN PUMP

1065
00:40:29,600 --> 00:40:31,080
INJECTS A LARGE AMOUNT OF

1066
00:40:31,080 --> 00:40:33,800
INSULIN TO CONTROL GLUCOSE

1067
00:40:33,800 --> 00:40:36,080
UPTAKE, WHEREAS THE BETA CELL

1068
00:40:36,080 --> 00:40:37,720
SQUEAKS OUT OR SECRETES JUST THE

1069
00:40:37,720 --> 00:40:39,360
RIGHT AMOUNT CONSTANTLY TO

1070
00:40:39,360 --> 00:40:41,440
CONTROL BLOOD GLUCOSE LEVELS.

1071
00:40:41,440 --> 00:40:43,080
SO THIS MAKES IT PRETTY OBVIOUS

1072
00:40:43,080 --> 00:40:44,400
THAT WHAT ONE WOULD WANT TO DO

1073
00:40:44,400 --> 00:40:46,720
MAYBE IS TO TRY A DIFFERENT

1074
00:40:46,720 --> 00:40:48,120
APPROACH, AND WHILE THIS SLIDE

1075
00:40:48,120 --> 00:40:49,800
MIGHT SEEM RATHER SIMPLE-MINDED,

1076
00:40:49,800 --> 00:40:51,200
IT IS ADMITTEDLY HOW I THINK

1077
00:40:51,200 --> 00:40:54,040
ABOUT THE PROBLEM.

1078
00:40:54,040 --> 00:40:55,800
THE CHALLENGES FOR TYPE

1079
00:40:55,800 --> 00:40:56,720
1 DIABETES ARE TWOFOLD.

1080
00:40:56,720 --> 00:40:58,240
THERE'S THE LOSS OF BETA CELLS

1081
00:40:58,240 --> 00:41:00,000
MAKING THE PATIENT

1082
00:41:00,000 --> 00:41:00,880
INSULIN-DEPENDENT, AND THERE'S

1083
00:41:00,880 --> 00:41:02,720
AN AUTOIMMUNE ATTACK, WHICH IS

1084
00:41:02,720 --> 00:41:04,480
THE PRIMARY CAUSE OF THE LOSS OF

1085
00:41:04,480 --> 00:41:06,120
THE BETA CELLS.

1086
00:41:06,120 --> 00:41:07,760
AND SO ONE WAY TO THINK ABOUT

1087
00:41:07,760 --> 00:41:10,400
THIS IS COULD WE DISCOVER AND

1088
00:41:10,400 --> 00:41:12,440
DEVELOP REPLACEMENT BETA CELLS?

1089
00:41:12,440 --> 00:41:13,800
I'M GOING TO FOCUS MOST OF MY

1090
00:41:13,800 --> 00:41:15,160
TALK ON THAT TODAY.

1091
00:41:15,160 --> 00:41:18,000
AND THEN SECONDLY, IF ONE IS

1092
00:41:18,000 --> 00:41:20,080
ABLE TO SOLVE THE FIRST HALF OF

1093
00:41:20,080 --> 00:41:22,480
THE PROBLEM, WHAT WOULD WE DO

1094
00:41:22,480 --> 00:41:23,880
ABOUT AUTOIMMUNE ATTACK OF BETA

1095
00:41:23,880 --> 00:41:24,560
CELLS?

1096
00:41:24,560 --> 00:41:26,080
HERE I'LL TALK ABOUT AN APPROACH

1097
00:41:26,080 --> 00:41:29,920
TO MODULATE THE IMMUNE ATTACK TO

1098
00:41:29,920 --> 00:41:31,360
REDUCE TOLERANCE TO THE STEM

1099
00:41:31,360 --> 00:41:32,680
CELL DERIVED ISLETS.

1100
00:41:32,680 --> 00:41:35,040
AS A DISCLAIMER AT THE

1101
00:41:35,040 --> 00:41:36,680
BEGINNING, I'LL TELL YOU WE'VE

1102
00:41:36,680 --> 00:41:38,080
COME QUITE A LONG WAY ON NUMBER

1103
00:41:38,080 --> 00:41:39,880
ONE AND WE'RE JUST STARTING ON

1104
00:41:39,880 --> 00:41:40,320
NUMBER TWO.

1105
00:41:40,320 --> 00:41:43,120
SO OUR APPROACH TO THE FIRST

1106
00:41:43,120 --> 00:41:45,120
PROBLEM, THE ABSENCE OF

1107
00:41:45,120 --> 00:41:46,800
PANCREATIC INSULIN PRODUCING

1108
00:41:46,800 --> 00:41:49,200
BETA CELLS, WAS TO TRY TO

1109
00:41:49,200 --> 00:41:50,320
RECAPITULATE WHAT HAPPENS IN

1110
00:41:50,320 --> 00:41:52,720
NORMAL DEVELOPMENT, AND TO DO

1111
00:41:52,720 --> 00:41:56,080
THAT IN VITRO, USING EMBRYONIC

1112
00:41:56,080 --> 00:41:57,760
OR PLURIPOTENT STEM CELLS.

1113
00:41:57,760 --> 00:42:01,920
AS MANY WELL KNOW, EMBRY OH TICK

1114
00:42:01,920 --> 00:42:06,000
OR PLUR POTENT STEM CELLS SHOWN

1115
00:42:06,000 --> 00:42:08,200
HERE, INFORM IN PRINCIPLE ANY

1116
00:42:08,200 --> 00:42:10,080
CELL TYPE IN THE BODY, AND SO IT

1117
00:42:10,080 --> 00:42:11,480
SEEMED OBVIOUS THAT WHAT ONE

1118
00:42:11,480 --> 00:42:13,120
WOULD TRY TO DO IS TO INSTRUCT

1119
00:42:13,120 --> 00:42:15,880
THOSE CELLS TO BECOME FULLY

1120
00:42:15,880 --> 00:42:17,360
FUNCTIONAL PANCREATIC BETA CELLS

1121
00:42:17,360 --> 00:42:21,560
SHOWN HERE ON THE FAR RIGHT IN

1122
00:42:21,560 --> 00:42:22,800
PURPLE, AS A BETA.

1123
00:42:22,800 --> 00:42:25,120
SO THE IDEA HERE IS TO REPEAT

1124
00:42:25,120 --> 00:42:28,960
WHAT HAPPENS IN NORMAL

1125
00:42:28,960 --> 00:42:30,440
DEVELOPMENT BUT OF COURSE DO IT

1126
00:42:30,440 --> 00:42:32,360
IN HUMAN CELLS OUTSIDE THE BODY.

1127
00:42:32,360 --> 00:42:33,560
AND I MIGHT NOTE THAT MY LAB

1128
00:42:33,560 --> 00:42:39,160
MAKES FUN OF ME BECAUSE THIS

1129
00:42:39,160 --> 00:42:41,000
SKITTLE DIAGRAM AS IT'S KNOWN

1130
00:42:41,000 --> 00:42:43,000
HAS BEEN SHOWN FOR MANY YEARS.

1131
00:42:43,000 --> 00:42:45,200
WE FIRST TELL THE CELLS HOW TO

1132
00:42:45,200 --> 00:42:48,720
BECOME DEFINITIVE ENDODERM, DE,

1133
00:42:48,720 --> 00:42:51,200
THEN TELL THEM -- THEN

1134
00:42:51,200 --> 00:42:52,640
PANCREATIC PROGENITORS OF TWO

1135
00:42:52,640 --> 00:42:54,640
FORMS, THEN FINALLY AN ENDOCRINE

1136
00:42:54,640 --> 00:42:57,120
PROGENITOR SHOWN HERE AS EN, AND

1137
00:42:57,120 --> 00:42:58,720
LASTLY, THE PANCREATIC BETA

1138
00:42:58,720 --> 00:43:01,680
CELL.

1139
00:43:01,680 --> 00:43:03,400
A COUPLE THINGS I'D LIKE TO SAY

1140
00:43:03,400 --> 00:43:03,600
HERE.

1141
00:43:03,600 --> 00:43:06,560
FIRST OF ALL, YOU CAN SEE THAT

1142
00:43:06,560 --> 00:43:08,240
THIS TAKES MANY DAYS, SEVERAL

1143
00:43:08,240 --> 00:43:09,440
WEEKS, IN ORDER TO DO THIS, AND

1144
00:43:09,440 --> 00:43:11,520
THERE ARE DIFFERENT FACTORS

1145
00:43:11,520 --> 00:43:14,880
ADDED AT EACH STAGE.

1146
00:43:14,880 --> 00:43:16,320
SO IN SOME SENSE, I COULD

1147
00:43:16,320 --> 00:43:17,880
SUMMARIZE IT BY SAYING ONE HAD

1148
00:43:17,880 --> 00:43:19,520
TO JUST FIGURE OUT WHICH FACTORS

1149
00:43:19,520 --> 00:43:21,200
TO ADD AT WHICH CONCENTRATION AT

1150
00:43:21,200 --> 00:43:23,840
WHAT TIME IN ORDER TO ACHIEVE

1151
00:43:23,840 --> 00:43:26,200
THIS GOAL, AND NAIVELY, I

1152
00:43:26,200 --> 00:43:27,560
THOUGHT WHEN WE BEGAN THIS, THIS

1153
00:43:27,560 --> 00:43:29,520
WOULD BE RELATIVELY

1154
00:43:29,520 --> 00:43:30,800
STRAIGHTFORWARD.

1155
00:43:30,800 --> 00:43:32,360
IT TURNED OUT TO BE MUCH MORE

1156
00:43:32,360 --> 00:43:33,720
DIFFICULT THAN I THOUGHT IT WAS,

1157
00:43:33,720 --> 00:43:35,120
OR THOUGHT IT WOULD BE.

1158
00:43:35,120 --> 00:43:36,680
I THINK IT'S FAIR TO SAY THAT

1159
00:43:36,680 --> 00:43:39,400
IT'S NOT SO COMPLICATED TO TURN

1160
00:43:39,400 --> 00:43:44,640
PLPLURIPOTENT STEM CELLS INTO

1161
00:43:44,640 --> 00:43:45,440
NEURONS.

1162
00:43:45,440 --> 00:43:46,640
THE PARTICULAR TYPE OF NEURON

1163
00:43:46,640 --> 00:43:48,280
ONE WANTS TO MAKE, BECAUSE, OF

1164
00:43:48,280 --> 00:43:50,080
COURSE, SPECIFIC ADJUSTMENTS.

1165
00:43:50,080 --> 00:43:52,680
IT'S ALSO BEEN DEMONSTRATED TO

1166
00:43:52,680 --> 00:44:03,040
MAKE CARDIOMYOCYTES.

1167
00:44:03,600 --> 00:44:04,760
IT JUST REQUIRES MANY MORE

1168
00:44:04,760 --> 00:44:05,160
SIGNALS.

1169
00:44:05,160 --> 00:44:06,840
AND THIS SLIDE HERE SUMMARIZES

1170
00:44:06,840 --> 00:44:10,800
MORE THAN 15 YEARS OF RESULTS

1171
00:44:10,800 --> 00:44:12,600
WITH ABOUT 50 STUDENTS AND

1172
00:44:12,600 --> 00:44:13,640
POSTDOCS, WHO I'M GLAD TO SAY

1173
00:44:13,640 --> 00:44:14,840
JOINED IN ON THIS PROJECT TO

1174
00:44:14,840 --> 00:44:17,080
HELP MAKE THIS POSSIBLE.

1175
00:44:17,080 --> 00:44:19,720
ON THE BOTTOM LEFT, YOU SEE WHAT

1176
00:44:19,720 --> 00:44:22,560
OUR TARGET GOAL WAS, IS ORGAN

1177
00:44:22,560 --> 00:44:26,840
DONOR ISLETS, AND THEY'RE

1178
00:44:26,840 --> 00:44:28,960
STAINED WITH TWO MARKERS,

1179
00:44:28,960 --> 00:44:29,920
INSULIN, THE GOAL BEING STAINED

1180
00:44:29,920 --> 00:44:32,840
IN THE CYTOPLASM AS GREEN AND

1181
00:44:32,840 --> 00:44:36,440
THE RED IMPORTANT TRANSCRIPTION

1182
00:44:36,440 --> 00:44:38,640
FACTOR IN RED STAINING IN THE

1183
00:44:38,640 --> 00:44:38,960
NUCLEUS.

1184
00:44:38,960 --> 00:44:41,600
ON THE RIGHT, WHERE IT SAYS

1185
00:44:41,600 --> 00:44:43,400
SC-BETA, THAT'S FOR STEM CELL

1186
00:44:43,400 --> 00:44:44,680
DERIVED ISLETS FOR BETA CELLS,

1187
00:44:44,680 --> 00:44:47,480
YOU SEE WHAT AT THIS LEVEL A

1188
00:44:47,480 --> 00:44:49,320
RESOLUTION LOOKS TO BE

1189
00:44:49,320 --> 00:44:50,520
INDISTINGUISHABLE FROM THE ORGAN

1190
00:44:50,520 --> 00:44:51,280
DONOR ISLETS.

1191
00:44:51,280 --> 00:44:52,480
THE IMPORTANT TRANSCRIPTION

1192
00:44:52,480 --> 00:44:53,720
FACTOR IS EXPRESSED IN THE

1193
00:44:53,720 --> 00:44:55,880
NUCLEUS AND THE INSULIN IN THE

1194
00:44:55,880 --> 00:44:56,480
CYTOPLASM.

1195
00:44:56,480 --> 00:44:58,400
YOU MIGHT SAY A BIT MORE THIS

1196
00:44:58,400 --> 00:44:59,320
TRANSCRIPTION FACTOR IS KNOWN TO

1197
00:44:59,320 --> 00:45:00,840
BE ABSOLUTELY REQUIRED FOR BETA

1198
00:45:00,840 --> 00:45:02,600
CELL DEVELOPMENT, INDEED IT'S

1199
00:45:02,600 --> 00:45:04,040
REQUIRED FOR PANCREATIC

1200
00:45:04,040 --> 00:45:05,560
DEVELOPMENT, AND THAT'S WHY WE

1201
00:45:05,560 --> 00:45:08,880
USED IT AS ONE OF THE MARKERS TO

1202
00:45:08,880 --> 00:45:10,720
TELL US GOING ALONG EACH STAGE

1203
00:45:10,720 --> 00:45:15,440
HERE, HOW FAR WE WERE GETTING.

1204
00:45:15,440 --> 00:45:17,880
NOW THE RESULT OF THIS WAS WE

1205
00:45:17,880 --> 00:45:19,960
MADE THESE CELLS, THESE CLUSTERS

1206
00:45:19,960 --> 00:45:22,160
OF CELLS IN A SPINNER FLASK IN

1207
00:45:22,160 --> 00:45:24,600
THREE DIMENSIONS, AND WE WERE

1208
00:45:24,600 --> 00:45:26,760
ABLE TO MAKE CLUSTERS THAT ARE

1209
00:45:26,760 --> 00:45:30,520
NOT ONLY HOMO GENIUS IN CELL

1210
00:45:30,520 --> 00:45:31,560
COMPOSITION BUT THEY WERE THE

1211
00:45:31,560 --> 00:45:33,160
SAME SIZE AT HUMAN ISLETS.

1212
00:45:33,160 --> 00:45:35,600
SO HERE YOU SEE A CONFOCAL IMAGE

1213
00:45:35,600 --> 00:45:36,760
THROUGH A SLICE OF THE CLUSTERS,

1214
00:45:36,760 --> 00:45:38,480
AND THIS IS A TYPICAL EXAMPLE OF

1215
00:45:38,480 --> 00:45:39,960
WHAT WE WERE ABLE TO ACHIEVE AT

1216
00:45:39,960 --> 00:45:44,120
THE BEGINNING, WHICH IS ABOUT

1217
00:45:44,120 --> 00:45:45,120
16 1/2% IT SHOWS HERE OF THE

1218
00:45:45,120 --> 00:45:47,440
CELLS WHE WERE THE CELLS WE WAN,

1219
00:45:47,440 --> 00:45:49,200
THAT IS, THE PANCREATIC BETA

1220
00:45:49,200 --> 00:45:49,560
CELLS.

1221
00:45:49,560 --> 00:45:50,520
I'LL SHOW YOU IN A FEW MINUTES

1222
00:45:50,520 --> 00:45:53,160
THAT THE OTHER CELLS ARE OTHER

1223
00:45:53,160 --> 00:45:54,240
ENDOCRINE CELLS AND SOME CELLS

1224
00:45:54,240 --> 00:45:56,080
WE DIDN'T WANT, BUT OUR GOAL

1225
00:45:56,080 --> 00:45:58,280
INITIALLY WAS TO MAKE INSULIN

1226
00:45:58,280 --> 00:46:01,760
PRODUCING CELLS SHOWN HERE BY C

1227
00:46:01,760 --> 00:46:04,120
PEPTIDE PROTEIN AND THE

1228
00:46:04,120 --> 00:46:06,560
TRANSCRIPTION FACTOR NKX6.1,

1229
00:46:06,560 --> 00:46:08,680
WHICH IS SPECIALIZED IN THE BETA

1230
00:46:08,680 --> 00:46:13,920
CELL IN HUMANS.

1231
00:46:13,920 --> 00:46:15,160
I COULD SHOW YOU A LOT OF

1232
00:46:15,160 --> 00:46:16,240
MOLECULAR DETAIL AND WE'LL COME

1233
00:46:16,240 --> 00:46:18,200
TO THAT LATER.

1234
00:46:18,200 --> 00:46:21,080
BUT THE QUESTION WOULD BE USING

1235
00:46:21,080 --> 00:46:22,400
MOLECULAR AND CELL BIOLOGY AND

1236
00:46:22,400 --> 00:46:24,920
HISTOLOGY, DID WE REALLY MAKE A

1237
00:46:24,920 --> 00:46:25,480
FUNCTIONAL BETA CELL.

1238
00:46:25,480 --> 00:46:26,720
AND INSTEAD OF JUST SHOWING YOU

1239
00:46:26,720 --> 00:46:30,200
A LOT OF TRANSCRIPTIONAL DATA, I

1240
00:46:30,200 --> 00:46:31,760
LIKE THIS KIND OF OLD-FASHIONED

1241
00:46:31,760 --> 00:46:33,880
METHOD WHICH IS A TRANSMISSION

1242
00:46:33,880 --> 00:46:34,280
EM PICTURE.

1243
00:46:34,280 --> 00:46:37,280
FOR THOSE WHO HAVE STUDIED CELL

1244
00:46:37,280 --> 00:46:38,480
BIOLOGY, YOU'LL REMEMBER THAT

1245
00:46:38,480 --> 00:46:41,680
THE BETA CELL IS WELL-KNOWN,

1246
00:46:41,680 --> 00:46:44,120
CONTAINING VACUOLES THAT HAVE

1247
00:46:44,120 --> 00:46:45,560
CRYSTALLIZED INSULIN IN THEM.

1248
00:46:45,560 --> 00:46:46,800
YOU SEE THAT HERE ON THE UPPER

1249
00:46:46,800 --> 00:46:49,120
RIGHT, WHERE YOU SEE A SINGLE

1250
00:46:49,120 --> 00:46:51,880
VACUOLE WITH A CRYSTALLIZED

1251
00:46:51,880 --> 00:46:53,280
INSULIN COMPLEX.

1252
00:46:53,280 --> 00:46:56,240
IT'S A ZINC KRAIS CRIST TALLIZED

1253
00:46:56,240 --> 00:46:58,000
WITH MANY MOLECULES OF

1254
00:46:58,000 --> 00:46:58,560
CRYSTALLINE.

1255
00:46:58,560 --> 00:47:00,640
ON THE BOTTOM YOU SEE OUR STEM

1256
00:47:00,640 --> 00:47:03,960
CELL DERIVED BETA SELL, LOOKS TO

1257
00:47:03,960 --> 00:47:05,760
BE INDISTINGUISHABLE, AGAIN,

1258
00:47:05,760 --> 00:47:06,720
VACUOLES WITH CRYSTALLIZED

1259
00:47:06,720 --> 00:47:07,160
INSULIN.

1260
00:47:07,160 --> 00:47:08,680
MY POINT IN SHOWING THIS SLIDE

1261
00:47:08,680 --> 00:47:10,680
IS THAT IN ORDER FOR A CELL TO

1262
00:47:10,680 --> 00:47:14,280
MAKE THESE STRUCTURES, THE

1263
00:47:14,280 --> 00:47:15,280
PLURIPOTENT STEM CELL HAD TO

1264
00:47:15,280 --> 00:47:17,280
TURN ON AND TURN OFF THOUSANDS

1265
00:47:17,280 --> 00:47:19,280
OF GENES TO GET TO THIS POINT.

1266
00:47:19,280 --> 00:47:21,280
AND YOU CAN'T MAKE THESE

1267
00:47:21,280 --> 00:47:22,920
STRUCTURES IF YOU ARE ONLY HALF

1268
00:47:22,920 --> 00:47:25,360
OF A BETA CELL, OR IF YOU'RE A

1269
00:47:25,360 --> 00:47:26,560
MIXED UP CELL MAKING OTHER KINDS

1270
00:47:26,560 --> 00:47:29,880
OF THINGS.

1271
00:47:29,880 --> 00:47:31,560
WELL, IN ADDITION TO, LET'S SAY,

1272
00:47:31,560 --> 00:47:33,880
THE ANATOMY, THE HISTOLOGY OF

1273
00:47:33,880 --> 00:47:36,640
THE CELLS, LET'S HAVE A LOOK AT

1274
00:47:36,640 --> 00:47:36,920
FUNCTION.

1275
00:47:36,920 --> 00:47:38,120
THIS IS ONE OF THE FIRST

1276
00:47:38,120 --> 00:47:39,480
EXAMPLES THAT LED US TO BELIEVE

1277
00:47:39,480 --> 00:47:43,480
THAT WE WERE SUCCESSFUL, AND

1278
00:47:43,480 --> 00:47:46,600
THAT IS, WE SHOW THAT IN VITRO,

1279
00:47:46,600 --> 00:47:49,440
WE COULD OBTAIN SEQUENTIAL HUMAN

1280
00:47:49,440 --> 00:47:50,520
INSULIN SECRETION FOLLOWING

1281
00:47:50,520 --> 00:47:52,080
GLUCOSE CHALLENGES.

1282
00:47:52,080 --> 00:47:54,720
I'LL EXPLAIN THIS BY FOCUSING ON

1283
00:47:54,720 --> 00:47:59,160
THE GRAPH HERE ON THE LEFT, THIS

1284
00:47:59,160 --> 00:47:59,440
HISTOGRAM.

1285
00:47:59,440 --> 00:48:00,960
ON THE Y AXIS IS THE AMOUNT OF

1286
00:48:00,960 --> 00:48:02,600
HUMAN INSULIN BEING SECRETED AND

1287
00:48:02,600 --> 00:48:06,000
ON THE X AXIS ARE THREE

1288
00:48:06,000 --> 00:48:07,400
SEQUENTIAL CHALLENGES WITH

1289
00:48:07,400 --> 00:48:08,880
GLUCOSE.

1290
00:48:08,880 --> 00:48:10,120
I SOMETIMES LIKE TO JOKE AND

1291
00:48:10,120 --> 00:48:12,080
DESCRIBE THIS AS LIKE BREAKFAST,

1292
00:48:12,080 --> 00:48:14,480
LUNCH AND DINNER.

1293
00:48:14,480 --> 00:48:15,840
THERE'S 2 MILLIMOLAR OF GLUCOSE

1294
00:48:15,840 --> 00:48:18,360
FOLLOWED BY 20.

1295
00:48:18,360 --> 00:48:19,880
2 MILLIMOLAR, 20.

1296
00:48:19,880 --> 00:48:20,320
2 MILLIMOLAR, 20.

1297
00:48:20,320 --> 00:48:22,200
AND THEN DEPOLARIZATION OF THE

1298
00:48:22,200 --> 00:48:24,080
MEMBRANE WITH POTASSIUM

1299
00:48:24,080 --> 00:48:24,520
CHLORIDE.

1300
00:48:24,520 --> 00:48:27,040
YOU SEE IN EACH SEQUENTIAL

1301
00:48:27,040 --> 00:48:28,040
TREATMENT, WE'RE OBSERVING AN

1302
00:48:28,040 --> 00:48:29,120
INCREASE IN INSULIN SECRETION,

1303
00:48:29,120 --> 00:48:31,840
WHICH IS WHAT WOULD HAPPEN IN A

1304
00:48:31,840 --> 00:48:33,400
PATIENT'S PANCREAS IF THEY DID

1305
00:48:33,400 --> 00:48:37,680
NOT HAVE TYPE 1 DIABETES.

1306
00:48:37,680 --> 00:48:38,560
SO A CONTROL PATIENT.

1307
00:48:38,560 --> 00:48:40,400
IN THE MIDDLE OF IS A CONTROL

1308
00:48:40,400 --> 00:48:41,120
DIFFERENTIATION.

1309
00:48:41,120 --> 00:48:42,240
I WON'T TALK MUCH ABOUT THIS BUT

1310
00:48:42,240 --> 00:48:43,200
THESE WERE THE CELLS THAT HAD

1311
00:48:43,200 --> 00:48:44,720
BEEN WORKED ON BY OTHERS, AND

1312
00:48:44,720 --> 00:48:46,640
THE MAIN POINT BEING THAT THOSE

1313
00:48:46,640 --> 00:48:47,920
PROGENITOR CELLS WERE NOT

1314
00:48:47,920 --> 00:48:50,680
CAPABLE OF THIS KIND OF

1315
00:48:50,680 --> 00:48:52,880
SEQUENTIAL SECRETION OF INSULIN.

1316
00:48:52,880 --> 00:48:55,520
ON THE FAR RIGHT ARE ISLETS

1317
00:48:55,520 --> 00:48:56,960
KNOWN TO BE ABLE TO CONTROL

1318
00:48:56,960 --> 00:48:59,120
BLOOD SUGARS WHEN TRANSPLANTED

1319
00:48:59,120 --> 00:49:01,920
INTO TYPE 1 DIABETICS ALONG WITH

1320
00:49:01,920 --> 00:49:03,040
IMMUNOSUPPRESSION, AND YOU SEE

1321
00:49:03,040 --> 00:49:04,520
HERE AGAIN THE SEQUENTIAL

1322
00:49:04,520 --> 00:49:05,600
SECRETION OF INSULIN.

1323
00:49:05,600 --> 00:49:08,600
THIS WAS A GOOD PREPARATION OF

1324
00:49:08,600 --> 00:49:10,160
THE CAT VAIRK ISLETS BUT THEY

1325
00:49:10,160 --> 00:49:11,600
VARY QUITE A BIT AS YOU WOULD

1326
00:49:11,600 --> 00:49:13,080
EXPECT, SINCE THEY HAVE TO COME

1327
00:49:13,080 --> 00:49:16,400
FROM A CADAVER AND HAVE TO BE

1328
00:49:16,400 --> 00:49:19,960
ENZYMATICALLY OBTAINED BY -- THE

1329
00:49:19,960 --> 00:49:22,240
PANCREAS THROUGH A COMPLEX

1330
00:49:22,240 --> 00:49:24,760
PROCEDURE.

1331
00:49:24,760 --> 00:49:26,320
HERE IS A SLIDE I LIKE TO SHOW

1332
00:49:26,320 --> 00:49:27,200
FOR A COUPLE OF REASONS.

1333
00:49:27,200 --> 00:49:31,800
ONE IS IT SHOWS THE TOTAL MASS

1334
00:49:31,800 --> 00:49:34,160
OR VOLUME OF ISLETS FOUND IN A

1335
00:49:34,160 --> 00:49:38,400
PERSON WITH TYPE 1 DIABETES.

1336
00:49:38,400 --> 00:49:40,040
SAID ANOTHER WAY, THESE ARE

1337
00:49:40,040 --> 00:49:41,040
HUMAN ISLETS MADE FROM STEM

1338
00:49:41,040 --> 00:49:41,840
CELLS.

1339
00:49:41,840 --> 00:49:42,960
THE ISLETS HAVE BEEN STAINED

1340
00:49:42,960 --> 00:49:44,680
DARK BLUE FOR INSULIN, SO IT

1341
00:49:44,680 --> 00:49:47,000
LOOKS AS IF EVERY CELL IN THOSE

1342
00:49:47,000 --> 00:49:48,440
DOTS IS AN INSULIN CELL.

1343
00:49:48,440 --> 00:49:50,200
THAT'S NOT TRUE AS I SHOWED YOU

1344
00:49:50,200 --> 00:49:51,200
BEFORE, ONLY A PORTION OF THOSE

1345
00:49:51,200 --> 00:49:53,600
CELLS ARE, BUT THIS STAIN IS SO

1346
00:49:53,600 --> 00:49:55,880
STRONG, THE INSULIN SIZE

1347
00:49:55,880 --> 00:49:57,880
CLUSTERS ALL LOOK DARK BLUE.

1348
00:49:57,880 --> 00:50:00,440
EACH DOT THERE CONTAINS ABOUT

1349
00:50:00,440 --> 00:50:03,040
5 TO 10,000 CELLS, AND THE TOTAL

1350
00:50:03,040 --> 00:50:05,920
NUMBER OF BETA CELLS IN THAT

1351
00:50:05,920 --> 00:50:09,040
VIAL IS WHAT IT WOULD TAKE TO

1352
00:50:09,040 --> 00:50:10,200
TREAT EFFECTIVELY A TYPE

1353
00:50:10,200 --> 00:50:12,800
1 DIABETIC BY OUR CALCULATIONS.

1354
00:50:12,800 --> 00:50:14,160
AND SO THIS IS JUST TO GIVE YOU

1355
00:50:14,160 --> 00:50:15,800
AN IDEA OF THIS SIZE OF THE

1356
00:50:15,800 --> 00:50:17,600
CELLS YOU COULD SAY WHICH CAUSE

1357
00:50:17,600 --> 00:50:19,000
SO MUCH TROUBLE.

1358
00:50:19,000 --> 00:50:20,400
I HAVEN'T TALKED TODAY A LOT

1359
00:50:20,400 --> 00:50:22,440
ABOUT HOW MUCH TROUBLE THEY

1360
00:50:22,440 --> 00:50:23,960
CAUSE, YOU'LL HEAR MORE ABOUT

1361
00:50:23,960 --> 00:50:26,040
THAT FROM DR. DUCKWORTH, BUT LET

1362
00:50:26,040 --> 00:50:31,720
ME JUST SAY THAT FROM WHAT I

1363
00:50:31,720 --> 00:50:34,720
UNDERSTAND THIS YEAR IN 2023,

1364
00:50:34,720 --> 00:50:37,200
ABOUT $30 BILLION WILL BE SPENT

1365
00:50:37,200 --> 00:50:38,520
INJECTING INSULIN AND

1366
00:50:38,520 --> 00:50:41,880
CONTROLLING BLOOD GLUCOSE REALLY

1367
00:50:41,880 --> 00:50:43,080
BECAUSE OF THE DEFICIENCY IN

1368
00:50:43,080 --> 00:50:43,400
THOSE CELLS.

1369
00:50:43,400 --> 00:50:45,000
SO THAT'S REALLY TAKING IT FROM

1370
00:50:45,000 --> 00:50:47,920
A KIND OF DEVELOPMENTAL BIOLOGY

1371
00:50:47,920 --> 00:50:49,000
PERSPECTIVE TO THE EFFECT IT HAS

1372
00:50:49,000 --> 00:50:54,720
ON PATIENTS.

1373
00:50:54,720 --> 00:50:56,600
SO WE'VE BEEN ABLE TO MAKE STEM

1374
00:50:56,600 --> 00:50:58,240
CELL DERIVED ISLETS.

1375
00:50:58,240 --> 00:50:59,440
WE'RE GOING TO SPEND THE NEXT

1376
00:50:59,440 --> 00:51:01,080
FEW MINUTES ON WHAT'S NEXT.

1377
00:51:01,080 --> 00:51:02,520
AGAIN I WANT TO EMPHASIZE THE

1378
00:51:02,520 --> 00:51:03,440
EXPERIMENTS I'VE SHOWN YOU THUS

1379
00:51:03,440 --> 00:51:04,840
FAR AND WHAT I'LL SHOW YOU NOW

1380
00:51:04,840 --> 00:51:06,280
WERE DONE WITH A RESEARCH GRADE

1381
00:51:06,280 --> 00:51:07,520
CELL LINE DONE AT HARVARD.

1382
00:51:07,520 --> 00:51:09,360
THESE ARE NOT THE CELLS THAT

1383
00:51:09,360 --> 00:51:11,560
I'LL DESCRIBE LATER THAT VERTEX

1384
00:51:11,560 --> 00:51:15,960
USES IN THEIR CLINICAL TRIALS.

1385
00:51:15,960 --> 00:51:17,440
SO SORRY.

1386
00:51:17,440 --> 00:51:19,080
WHAT I WANT TO TALK ABOUT THEN

1387
00:51:19,080 --> 00:51:20,040
IS, COULD WE GET COMPLETE

1388
00:51:20,040 --> 00:51:22,360
CONTROL OR MASTERY OVER THE CELL

1389
00:51:22,360 --> 00:51:25,240
COMPOSITION OF THESE IN VITRO

1390
00:51:25,240 --> 00:51:27,560
DERIVED CELLS, AND THEN WHAT ARE

1391
00:51:27,560 --> 00:51:28,680
WE GOING TO DO ABOUT WHAT I SEE

1392
00:51:28,680 --> 00:51:30,560
AS THE NEED TO ELIMINATE THIS

1393
00:51:30,560 --> 00:51:32,640
REQUIREMENT SO FAR OF SYSTEMIC

1394
00:51:32,640 --> 00:51:34,880
IMMUNE SUPPRESSION.

1395
00:51:34,880 --> 00:51:36,520
I'LL COME BACK TO THE IMMUNE

1396
00:51:36,520 --> 00:51:40,480
SUPPRESSION PROBLEM IN A MOMENT.

1397
00:51:40,480 --> 00:51:41,440
SO FIRST THING WE DID, AND I'M

1398
00:51:41,440 --> 00:51:42,920
GOING TO SHOW THIS BECAUSE IT

1399
00:51:42,920 --> 00:51:45,480
DIDN'T PRODUCE THE RESULT I

1400
00:51:45,480 --> 00:51:47,760
WANTED, WAS TO SAY BECAUSE WE

1401
00:51:47,760 --> 00:51:50,720
MAKE THESE CELLS IN VITRO, COULD

1402
00:51:50,720 --> 00:51:52,920
WE DO A DEEP DIVE INTO ALL OF

1403
00:51:52,920 --> 00:51:55,560
THE TRANS KRIPTIONAL CHANGES AND

1404
00:51:55,560 --> 00:51:57,960
THE CHROMATIN CHANGES THAT OCCUR

1405
00:51:57,960 --> 00:52:00,640
FROM THE DEVELOPMENT OF A

1406
00:52:00,640 --> 00:52:01,360
PLURIPOTENT STEM CELL SHOWN HERE

1407
00:52:01,360 --> 00:52:02,840
ON THE LEFT ALL THE WAY TO A

1408
00:52:02,840 --> 00:52:05,080
STEM CELL DERIVED BETA CELL, AND

1409
00:52:05,080 --> 00:52:08,120
COMPARE THAT TO WHAT I CALL

1410
00:52:08,120 --> 00:52:11,520
PRIMARY OR CADAVERIC ALPHA AND

1411
00:52:11,520 --> 00:52:15,920
BETA CELLS, ALPHA CELLS BEING

1412
00:52:15,920 --> 00:52:17,720
THOSE PRODUCING GLUCAGON AND THE

1413
00:52:17,720 --> 00:52:19,800
BETA CELLS PRODUCING INSULIN.

1414
00:52:19,800 --> 00:52:23,160
SO WE PREPARED MANY TIMES THIS

1415
00:52:23,160 --> 00:52:25,200
IN VITRO DIFFERENTIATION, AND

1416
00:52:25,200 --> 00:52:27,400
THEN STUDIED CHROMATIN CHANGES

1417
00:52:27,400 --> 00:52:30,520
LOOKING AT CHANGES IN HISTONE

1418
00:52:30,520 --> 00:52:34,880
MODIFICATIONS USING ATTACK SEQ,

1419
00:52:34,880 --> 00:52:37,000
LOOKING AT DNA METHYLATION, AND

1420
00:52:37,000 --> 00:52:38,480
THEN WE DID TRANSCRIPTIONAL

1421
00:52:38,480 --> 00:52:40,720
CHANGES USING SINGLE CELL

1422
00:52:40,720 --> 00:52:41,040
SEQUENCING.

1423
00:52:41,040 --> 00:52:41,880
THAT'S QUITE COMMON NOW.

1424
00:52:41,880 --> 00:52:43,080
WHEN WE DID THIS, IT WAS JUST AT

1425
00:52:43,080 --> 00:52:44,640
THE BEGINNING OF THIS SO WE USE

1426
00:52:44,640 --> 00:52:47,400
THE A TECHNIQUE CALLED SINGLE

1427
00:52:47,400 --> 00:52:48,920
CELL SEQUENCING, AND WE DID THIS

1428
00:52:48,920 --> 00:52:52,720
FOR A COUPLE OF REASONS.

1429
00:52:52,720 --> 00:52:53,840
ONE IS I THINK IT'S IMPORTANT TO

1430
00:52:53,840 --> 00:52:55,880
KNOW AS MUCH AS ONE CAN ABOUT --

1431
00:52:55,880 --> 00:52:57,080
YOU COULD CALL IT THE DRUG

1432
00:52:57,080 --> 00:52:58,000
PRODUCT OF THE THING WE WANT AT

1433
00:52:58,000 --> 00:52:58,840
THE END.

1434
00:52:58,840 --> 00:53:00,720
BUT FRANKLY, THE MAIN REASON WE

1435
00:53:00,720 --> 00:53:04,600
DID IT WAS I WAS HOPING THAT WE

1436
00:53:04,600 --> 00:53:06,400
WOULD DISCOVER SIGNALING

1437
00:53:06,400 --> 00:53:07,760
MOLECULES OR RECEPTORS AT

1438
00:53:07,760 --> 00:53:09,600
VARIOUS STAGES, WHICH WOULD GIVE

1439
00:53:09,600 --> 00:53:11,960
US GREATER CONTROL OVER THE

1440
00:53:11,960 --> 00:53:12,600
PROCESS.

1441
00:53:12,600 --> 00:53:14,880
THIS WAS A VERY DIFFICULT,

1442
00:53:14,880 --> 00:53:17,880
EXPENSIVE AND TIME-CONSUMING

1443
00:53:17,880 --> 00:53:19,040
EXPERIMENT, AND FRANKLY IT

1444
00:53:19,040 --> 00:53:20,760
PRODUCED INTEREST IN INFORMATION

1445
00:53:20,760 --> 00:53:22,520
BUT IT DID NOT PRODUCE WHAT I

1446
00:53:22,520 --> 00:53:23,640
WANTED, WHICH WAS SON IMPORTANT

1447
00:53:23,640 --> 00:53:27,720
NEW CLUES ABOUT HOW TO BETTER

1448
00:53:27,720 --> 00:53:29,000
CONTROL THE PROCESS.

1449
00:53:29,000 --> 00:53:30,560
LET'S LOOK AT THE POSITIVE AND

1450
00:53:30,560 --> 00:53:32,440
SEE WHAT WE DID LEARN FROM IT.

1451
00:53:32,440 --> 00:53:33,240
FIRST IMPORTANT THING WE LEARNED

1452
00:53:33,240 --> 00:53:35,160
BY DOING SINGLE CELL SEQUENCING

1453
00:53:35,160 --> 00:53:38,560
IS THAT THERE WERE THE CELLS WE

1454
00:53:38,560 --> 00:53:40,200
WANTED, BUT THERE WERE ALSO

1455
00:53:40,200 --> 00:53:41,080
SURPRISING CELLS WHICH WE DIDN'T

1456
00:53:41,080 --> 00:53:41,600
WANT.

1457
00:53:41,600 --> 00:53:43,320
SO LET ME DESCRIBE THIS

1458
00:53:43,320 --> 00:53:44,480
PRESENTATION HERE TO YOU NOW.

1459
00:53:44,480 --> 00:53:47,360
THIS IS AT THE END OF OUR

1460
00:53:47,360 --> 00:53:50,000
PROCESS, WHAT WE CALLED STAGE 6,

1461
00:53:50,000 --> 00:53:52,200
AND WE'RE LOOKING AT 37,000

1462
00:53:52,200 --> 00:53:53,840
CELLS IN THOSE CLUSTERS THAT I

1463
00:53:53,840 --> 00:53:57,760
SHOWED YOU ALREADY.

1464
00:53:57,760 --> 00:54:02,080
THIS IS A SO-CALLED TSNE PLOT,

1465
00:54:02,080 --> 00:54:03,000
STATISTICAL REPRESENTATION OF

1466
00:54:03,000 --> 00:54:04,960
THE DATA, AND THE CELLS WE

1467
00:54:04,960 --> 00:54:06,760
WANTED ARE SHOWN HERE IN PURPLE.

1468
00:54:06,760 --> 00:54:08,000
THEY'RE IN THE MIDDLE.

1469
00:54:08,000 --> 00:54:10,480
I LIKE TO SHOW THIS PLOT BECAUSE

1470
00:54:10,480 --> 00:54:12,600
YOU CAN SHOW THESE PLOTS KIND OF

1471
00:54:12,600 --> 00:54:14,000
BY MANIPULATING THE PRESENTATION

1472
00:54:14,000 --> 00:54:15,200
IN A NUMBER OF WAYS.

1473
00:54:15,200 --> 00:54:16,360
I LIKE THIS ONE BECAUSE I THINK

1474
00:54:16,360 --> 00:54:18,600
IT LOOKS LIKE A LOBSTER, AND

1475
00:54:18,600 --> 00:54:19,840
SINCE I LIVE IN BOSTON AND I

1476
00:54:19,840 --> 00:54:21,560
LIKE LOBSTER, I CHOSE THIS WAY

1477
00:54:21,560 --> 00:54:24,000
TO SHOW YOU THE DATA.

1478
00:54:24,000 --> 00:54:26,160
HERE YOU SEE IN PURR PULL THE

1479
00:54:26,160 --> 00:54:27,880
CELLS WE WANTED.

1480
00:54:27,880 --> 00:54:29,000
THEY'RE STEM CELL DERIVED BETA

1481
00:54:29,000 --> 00:54:29,560
CELLS.

1482
00:54:29,560 --> 00:54:31,120
IN RED ARE OTHER CELLS WE DIDN'T

1483
00:54:31,120 --> 00:54:32,240
AIM FOR BUT WE WERE HAPPY TO

1484
00:54:32,240 --> 00:54:32,520
FIND.

1485
00:54:32,520 --> 00:54:34,120
THESE ARE STEM CELL DERIVED

1486
00:54:34,120 --> 00:54:36,520
ALPHA CELLS.

1487
00:54:36,520 --> 00:54:39,480
THE CELLS THAT MAKE GLUCAGON, AS

1488
00:54:39,480 --> 00:54:43,000
I'VE SAID THE -- REGULATORY

1489
00:54:43,000 --> 00:54:43,240
HORMONE.

1490
00:54:43,240 --> 00:54:44,400
BEFORE I GET TO THE SURPRISE,

1491
00:54:44,400 --> 00:54:45,760
THE BROWN CELLS WERE

1492
00:54:45,760 --> 00:54:47,320
PROGENITORS, WE WEREN'T

1493
00:54:47,320 --> 00:54:48,480
SURPRISED TO LEARN THAT NOT ALL

1494
00:54:48,480 --> 00:54:50,760
OF THE CELLS RECEIVED THE

1495
00:54:50,760 --> 00:54:53,240
INSTRUCTIONS THE WAY WE WANTED.

1496
00:54:53,240 --> 00:54:55,600
AND THEN THERE WERE SOME

1497
00:54:55,600 --> 00:54:56,680
NON-ENDOCRINE CELLS, CELLS WHICH

1498
00:54:56,680 --> 00:54:57,640
DIDN'T BECOME ENDOCRINE.

1499
00:54:57,640 --> 00:54:59,760
THE BIG SURPRISE WERE THESE BLUE

1500
00:54:59,760 --> 00:55:01,920
CELLS HERE ON THE BOTTOM RIGHT,

1501
00:55:01,920 --> 00:55:03,760
ENTEAR A CHROMAFFIN CELLS.

1502
00:55:03,760 --> 00:55:05,440
THESE SECRETE SA SEROTONIN IN TE

1503
00:55:05,440 --> 00:55:05,760
GUT.

1504
00:55:05,760 --> 00:55:06,600
THEY'RE NORMALLY FOUND IN THE

1505
00:55:06,600 --> 00:55:09,120
GUT BUT THEY ARE NOT FOUND IN

1506
00:55:09,120 --> 00:55:12,400
ADULT PANCREATIC ISLETS.

1507
00:55:12,400 --> 00:55:13,760
THERE ARE A COUPLE OF

1508
00:55:13,760 --> 00:55:14,640
PUBLICATIONS SUGGESTING, WITH

1509
00:55:14,640 --> 00:55:17,160
EVIDENCE, THAT THOSE CELLS ARE

1510
00:55:17,160 --> 00:55:18,640
FOUND DURING FETAL DEVELOPMENT

1511
00:55:18,640 --> 00:55:21,240
IN THE PANCREAS, BUT EVERYONE

1512
00:55:21,240 --> 00:55:23,040
AGREES THEY ARE NOT FOUND IN THE

1513
00:55:23,040 --> 00:55:24,560
ADULT ISLET AND THEY'RE NOT A

1514
00:55:24,560 --> 00:55:25,880
CELL WE REALLY WANT TO HAVE IN

1515
00:55:25,880 --> 00:55:26,800
OUR END PRODUCT.

1516
00:55:26,800 --> 00:55:29,280
ON THE BOTTOM, IT SHOWS YOU THE

1517
00:55:29,280 --> 00:55:33,080
KIND OF POPULATION RATIOS.

1518
00:55:33,080 --> 00:55:34,400
YOU MIGHT REMEMBER AT THE

1519
00:55:34,400 --> 00:55:36,840
BEGINNING THERE WAS ABOUT 16%

1520
00:55:36,840 --> 00:55:37,960
BETA CELLS, THAT'S PROBABLY

1521
00:55:37,960 --> 00:55:39,360
CLOSE TO WHAT WE GOT HERE AS WE

1522
00:55:39,360 --> 00:55:41,160
WERE IMPROVING THE PROTOCOL, SO

1523
00:55:41,160 --> 00:55:42,200
IT'S THESE PURPLE AND RED CELLS

1524
00:55:42,200 --> 00:55:43,960
THAT ARE THE ONES WE WANT WHICH

1525
00:55:43,960 --> 00:55:46,400
MAKE UP MORE THAN, SAY, 50% OF

1526
00:55:46,400 --> 00:55:47,320
THE TOTAL.

1527
00:55:47,320 --> 00:55:49,240
BUT THESE ENTERIC CHROMAFFIN

1528
00:55:49,240 --> 00:55:51,880
CELLS AND THE OTHER ONES ARE

1529
00:55:51,880 --> 00:55:52,880
ONES WE DON'T WANT.

1530
00:55:52,880 --> 00:55:53,720
SO ONE OTHER THING WE LEARNED

1531
00:55:53,720 --> 00:55:55,760
FROM THIS KIND OF SINGLE CELL

1532
00:55:55,760 --> 00:55:57,840
ANALYSIS, WHICH I SUPPOSE WE

1533
00:55:57,840 --> 00:55:58,680
COULD HAVE THOUGHT OF AHEAD OF

1534
00:55:58,680 --> 00:56:00,760
TIME BUT FRANKLY WE DIDN'T, IT

1535
00:56:00,760 --> 00:56:02,120
WAS KIND OF AN INTERESTING

1536
00:56:02,120 --> 00:56:05,400
OUTCOME OF THE RESULTS, WAS THAT

1537
00:56:05,400 --> 00:56:07,280
WHEN WE LOOKED AT ALL OF THE

1538
00:56:07,280 --> 00:56:08,560
GENES EXPRESSED, WE FOUND THAT

1539
00:56:08,560 --> 00:56:10,440
THE CELLS WERE EXPRESSING ALL OF

1540
00:56:10,440 --> 00:56:11,920
THE GENES FOR THE CIRCADIAN

1541
00:56:11,920 --> 00:56:12,280
CLOCK.

1542
00:56:12,280 --> 00:56:15,040
THAT IS, ALL OF THE CELLS HAD

1543
00:56:15,040 --> 00:56:17,560
THEIR CIRCADIAN CLOCK GENES ON

1544
00:56:17,560 --> 00:56:20,080
AND WERE ON A CIRCADIAN RHYTHM.

1545
00:56:20,080 --> 00:56:22,000
BUT WHAT WE NOTICED, OF COURSE,

1546
00:56:22,000 --> 00:56:23,360
WAS -- AND NOT SURPRISINGLY --

1547
00:56:23,360 --> 00:56:25,520
THEY WERE NOT ALL KIND OF

1548
00:56:25,520 --> 00:56:27,200
STARTING AT THE SAME TIME.

1549
00:56:27,200 --> 00:56:31,120
THEY WERE ALL KIND OF MARCHI

1550
00:56:31,120 --> 00:56:32,760
MARCHING -- SOMETHING LIKE AT A

1551
00:56:32,760 --> 00:56:34,520
FOOTBALL GAME, YOU THINK OF A

1552
00:56:34,520 --> 00:56:36,880
HALF TIME, THE MARCHING BAND,

1553
00:56:36,880 --> 00:56:37,520
EVERYONE STARTS AT THE SAME TIME

1554
00:56:37,520 --> 00:56:40,080
AND THEN MARCHES AND PLAYS IN

1555
00:56:40,080 --> 00:56:40,400
STEP.

1556
00:56:40,400 --> 00:56:41,560
WELL IN THIS CASE, IT WOULD BE

1557
00:56:41,560 --> 00:56:42,960
LIKE IF ALL THE FOOTBALL

1558
00:56:42,960 --> 00:56:44,200
PLAYERS -- SORRY, IF ALL OF THE

1559
00:56:44,200 --> 00:56:45,960
BAND MEMBERS WERE LISTENING TO

1560
00:56:45,960 --> 00:56:47,320
MUSIC THAT STARTED AT A

1561
00:56:47,320 --> 00:56:48,840
DIFFERENT TIME, WHILE THEY WERE

1562
00:56:48,840 --> 00:56:50,520
MARCHING, THEY WERE COMPLETELY

1563
00:56:50,520 --> 00:56:51,760
UNSYNCHRONIZED.

1564
00:56:51,760 --> 00:56:53,360
I DON'T KNOW IF THAT HELPS

1565
00:56:53,360 --> 00:56:54,400
DESCRIBE THIS EXPERIMENT, BUT

1566
00:56:54,400 --> 00:56:55,400
THAT'S SORT OF ONE WAY TO THINK

1567
00:56:55,400 --> 00:56:58,800
ABOUT IT.

1568
00:56:58,800 --> 00:57:00,560
SO WHAT WE LOOKED AT THEN, IF I

1569
00:57:00,560 --> 00:57:01,640
CAN DRAWL YOUR ATTENTION TO THE

1570
00:57:01,640 --> 00:57:03,480
BOTTOM LEFT, IS GLUCOSE

1571
00:57:03,480 --> 00:57:06,440
STIMULATED INSULIN SECRETION,

1572
00:57:06,440 --> 00:57:07,840
AND IN GREY BARS ARE WHAT I

1573
00:57:07,840 --> 00:57:10,680
SHOWED YOU EARLIER, WHICH IS

1574
00:57:10,680 --> 00:57:14,720
OVER SEVERAL DAYS, THESE CELLS

1575
00:57:14,720 --> 00:57:18,080
ARE SECRETE INSULIN RESPONSE TO

1576
00:57:18,080 --> 00:57:20,040
GLUCOSE WITH THAT STIMULATION

1577
00:57:20,040 --> 00:57:21,560
INDENTION OF ABOUT 1 OR 2.

1578
00:57:21,560 --> 00:57:23,520
BUT IF WE SYNCHRONIZE THE CELLS

1579
00:57:23,520 --> 00:57:26,760
AS SHOWN HERE IN RED, AND WE DID

1580
00:57:26,760 --> 00:57:28,440
THAT BY GIVING THEM SHOCKS AND

1581
00:57:28,440 --> 00:57:30,200
ALLOWING THEM TO RECOVER OVER A

1582
00:57:30,200 --> 00:57:32,160
THREE-DAY PERIOD, WE DID THIS

1583
00:57:32,160 --> 00:57:36,720
THREE TIMES, GIVE THEM EITHER

1584
00:57:36,720 --> 00:57:38,320
ARGININE, INSULIN OR GLUCOSE FOR

1585
00:57:38,320 --> 00:57:39,840
12 HOURS AND THEN TAKE IT AWAY,

1586
00:57:39,840 --> 00:57:42,080
THIS IS ALL TO KIND OF GET THEM

1587
00:57:42,080 --> 00:57:42,600
SYNCHRONIZED.

1588
00:57:42,600 --> 00:57:44,320
YOU SEE THE MUCH BETTER RESPONSE

1589
00:57:44,320 --> 00:57:46,080
HERE IN GLUCOSE STIMULATED

1590
00:57:46,080 --> 00:57:47,720
INSULIN SECRETION IN RED.

1591
00:57:47,720 --> 00:57:50,960
YOU SEE THE GSIS, AS IT'S

1592
00:57:50,960 --> 00:57:52,920
CALLED, GO FROM ABOUT 1 1/2 TO

1593
00:57:52,920 --> 00:57:54,600
ABOUT 3 1/2 HERE.

1594
00:57:54,600 --> 00:57:56,600
THIS IS VERY REMINISCENT OF WHAT

1595
00:57:56,600 --> 00:57:58,480
YOU SEE IN CADAVERIC ISLETS.

1596
00:57:58,480 --> 00:58:01,240
SO YOU SEE HERE CADAVERIC

1597
00:58:01,240 --> 00:58:02,720
ISLETS, WHICH HAVE OF COURSE

1598
00:58:02,720 --> 00:58:04,000
GROWN UP AND BEEN IN A PERSON

1599
00:58:04,000 --> 00:58:07,760
THAT HAD DAILY CYCLE, CIRCADIAN

1600
00:58:07,760 --> 00:58:08,040
CYCLE.

1601
00:58:08,040 --> 00:58:10,640
AND SO THIS IS, I THINK, A

1602
00:58:10,640 --> 00:58:11,440
GRATIFYING RESULT THAT WE CAN

1603
00:58:11,440 --> 00:58:13,040
TAKE THE STEM CELL DERIVED

1604
00:58:13,040 --> 00:58:14,880
ISLETS AND MAKE THEM WORK EVEN

1605
00:58:14,880 --> 00:58:16,600
BETTER IN VITRO BY SYNCHRONIZING

1606
00:58:16,600 --> 00:58:21,160
THEIR CIRCADIAN RHYTHM.

1607
00:58:21,160 --> 00:58:23,960
SO HERE'S THE CHALLENGE WE HAVE

1608
00:58:23,960 --> 00:58:25,960
NOW.

1609
00:58:25,960 --> 00:58:28,360
WE ARE ABLE TO TAKE EMBRYONIC

1610
00:58:28,360 --> 00:58:29,720
STEM CELLS AND TELL THEM TO

1611
00:58:29,720 --> 00:58:32,040
BECOME ISLET-LIKE STRUCTURES BUT

1612
00:58:32,040 --> 00:58:33,240
THEY DON'T HAVE ALL OF THE CELLS

1613
00:58:33,240 --> 00:58:34,560
WE WANT, THEY HAVE SOME CELLS WE

1614
00:58:34,560 --> 00:58:36,800
DON'T WANT, AND SO COULD WE GAIN

1615
00:58:36,800 --> 00:58:38,000
COMPLETE CONTROL OVER THE

1616
00:58:38,000 --> 00:58:40,080
COMPOSITION?

1617
00:58:40,080 --> 00:58:42,320
THE WAY I'M GOING TO DESCRIBE

1618
00:58:42,320 --> 00:58:46,920
DOING THAT IS TO USE GENETIC

1619
00:58:46,920 --> 00:58:47,240
MODIFICATION.

1620
00:58:47,240 --> 00:58:48,800
SO WHAT I'M SHOWING YOU HERE IN

1621
00:58:48,800 --> 00:58:50,280
THIS LITTLE CARTOON IS I WANT TO

1622
00:58:50,280 --> 00:58:53,120
USE GENETIC MODIFICATION WHICH

1623
00:58:53,120 --> 00:58:56,840
WOULD PREVENT THE FORMATION OF

1624
00:58:56,840 --> 00:58:58,080
ENTERIC -- CELLS, PREVENT THE

1625
00:58:58,080 --> 00:58:59,960
FORMATION OF THE NON-ENDOCRINE

1626
00:58:59,960 --> 00:59:01,440
CELLS, THE CELLS YOU COULD SAY

1627
00:59:01,440 --> 00:59:02,960
DIDN'T GET WITH THE PROGRAM, AND

1628
00:59:02,960 --> 00:59:04,800
THEN MAKE ONLY THESE THREE CELL

1629
00:59:04,800 --> 00:59:05,000
TYPES.

1630
00:59:05,000 --> 00:59:07,480
THAT WOULD BE THE IDEAL GOAL.

1631
00:59:07,480 --> 00:59:09,400
INSULIN PRODUCING CELLS,

1632
00:59:09,400 --> 00:59:12,400
GLUCAGON PRODUCING CELLS, AND

1633
00:59:12,400 --> 00:59:14,240
SOMATOSTATIN PRODUCING CELLS.

1634
00:59:14,240 --> 00:59:15,680
THEN WITH THIS LITTLE CARTOON

1635
00:59:15,680 --> 00:59:17,840
HERE, WE'RE ALSO TAKING ON THE

1636
00:59:17,840 --> 00:59:20,440
IDEA WITH THESE LIKE SHIELDS

1637
00:59:20,440 --> 00:59:23,640
THAT COULD WE MAKE CELLS WHICH

1638
00:59:23,640 --> 00:59:26,360
DID NOT -- WERE NOT EASILY

1639
00:59:26,360 --> 00:59:27,720
REMOVED BY THE PATIENT'S IMMUNE

1640
00:59:27,720 --> 00:59:29,320
SYSTEM.

1641
00:59:29,320 --> 00:59:30,400
SO LET ME PAUSE THERE AND TALK

1642
00:59:30,400 --> 00:59:31,920
ABOUT SOMETHING I HAVEN'T REALLY

1643
00:59:31,920 --> 00:59:32,440
EMPHASIZED.

1644
00:59:32,440 --> 00:59:34,520
I MENTIONED THAT TYPE 1 DIABETES

1645
00:59:34,520 --> 00:59:36,920
IS AN AUTOIMMUNE DISEASE, WHICH

1646
00:59:36,920 --> 00:59:39,440
MEANS THAT THE PATIENT'S IMMUNE

1647
00:59:39,440 --> 00:59:41,000
SYSTEM RECOGNIZES THEIR VERY OWN

1648
00:59:41,000 --> 00:59:43,200
BETA CELLS AND KILLS THEM.

1649
00:59:43,200 --> 00:59:44,080
ELIMINATES THEM.

1650
00:59:44,080 --> 00:59:46,280
IT DOESN'T ELIMINATE THE ALPHA

1651
00:59:46,280 --> 00:59:49,640
OR DELTA OR OTHER ISLET-LIKE

1652
00:59:49,640 --> 00:59:52,240
CELLS, JUST THE BETA CELLS.

1653
00:59:52,240 --> 00:59:55,320
BUT IN THIS CASE, WE ARE

1654
00:59:55,320 --> 00:59:57,800
PRODUCING ALLO CELLS, CELLS FROM

1655
00:59:57,800 --> 01:00:00,840
AN EMBRYONIC STEM CELLS OR

1656
01:00:00,840 --> 01:00:01,600
PLURIPOTENT STEM CELLS AND,

1657
01:00:01,600 --> 01:00:02,920
THEREFORE, THEY ARE NON-CELL, SO

1658
01:00:02,920 --> 01:00:05,280
ALL OF THE CELLS WOULD BE KILLED

1659
01:00:05,280 --> 01:00:08,040
IN A PATIENT'S -- A PATIENT

1660
01:00:08,040 --> 01:00:09,600
RECEIVING A TRANSPLANT BECAUSE

1661
01:00:09,600 --> 01:00:10,800
THEIR IMMUNE SYSTEM WOULD

1662
01:00:10,800 --> 01:00:13,560
RECOGNIZE THEM AS FOREIGN.

1663
01:00:13,560 --> 01:00:15,520
ANOTHER WAY TO EMPHASIZE THAT IS

1664
01:00:15,520 --> 01:00:16,560
THE PATIENTS WE'RE AIMING FOR

1665
01:00:16,560 --> 01:00:19,800
HERE NOT ONLY WOULD SEE OUR DRUG

1666
01:00:19,800 --> 01:00:23,200
PRODUCT AS FOREIGN BECAUSE

1667
01:00:23,200 --> 01:00:25,960
THEY'RE ALLO CELLS BUT THEY ALSO

1668
01:00:25,960 --> 01:00:27,400
HAVE AUTOIMMUNITY BECAUSE

1669
01:00:27,400 --> 01:00:28,920
THEY'RE PARTICULARLY INCLINED TO

1670
01:00:28,920 --> 01:00:30,000
RECOGNIZE THE BETA CELL.

1671
01:00:30,000 --> 01:00:31,280
SO BACK TO THESE EXPERIMENTS I'M

1672
01:00:31,280 --> 01:00:32,720
GOING TO DESCRIBE, WHAT WE WOULD

1673
01:00:32,720 --> 01:00:34,200
LIKE TO DO IS TO SAY COULD WE

1674
01:00:34,200 --> 01:00:36,400
MODIFY THE GENES IN OUR STARTING

1675
01:00:36,400 --> 01:00:38,080
MATERIAL SUCH THAT AS THEY GO

1676
01:00:38,080 --> 01:00:40,680
THROUGH THE DIFFERENTIATION

1677
01:00:40,680 --> 01:00:42,800
PROCESS, THERE ARE DOORS BEING

1678
01:00:42,800 --> 01:00:47,080
CLOSED, THEY CANNOT BECOME

1679
01:00:47,080 --> 01:00:49,120
ENTEROCHROMAFFIN CELLS OR

1680
01:00:49,120 --> 01:00:49,640
NON-ENDOCRINE CELLS.

1681
01:00:49,640 --> 01:00:50,640
THEY CAN ONLY, AS THEY'RE

1682
01:00:50,640 --> 01:00:52,640
WALKING DOWN THE HALL THE ONLY

1683
01:00:52,640 --> 01:00:54,400
DOORS OPEN TO THEM ARE TO BECOME

1684
01:00:54,400 --> 01:00:56,440
DELTA CELLS THAT MAKE

1685
01:00:56,440 --> 01:00:57,200
SOMATOSTATIN, ALPHA CELLS THAT

1686
01:00:57,200 --> 01:00:59,800
MAKE GLUCAGON OR BETA CELLS THAT

1687
01:00:59,800 --> 01:01:00,640
MAKE INSULIN.

1688
01:01:00,640 --> 01:01:01,840
THAT'S SORT OF LOGIC OF WHAT

1689
01:01:01,840 --> 01:01:04,360
WE'RE TRYING TO DO.

1690
01:01:04,360 --> 01:01:05,680
IN ADDITION, WE WANT AS I SAID

1691
01:01:05,680 --> 01:01:08,240
TO MODIFY GENES WHICH ARE NOT

1692
01:01:08,240 --> 01:01:10,640
REQUIRED FOR THE FORMATION OF

1693
01:01:10,640 --> 01:01:12,840
ENDOCRINE CELLS, BUT INSTEAD

1694
01:01:12,840 --> 01:01:14,480
MIGHT BE GENES THAT ALLOW THE

1695
01:01:14,480 --> 01:01:16,960
CELLS TO BE RECOGNIZED AS

1696
01:01:16,960 --> 01:01:18,920
FOREIGN AND, THEREFORE, KILLED

1697
01:01:18,920 --> 01:01:20,120
OFF BY THE PATIENT'S IMMUNE

1698
01:01:20,120 --> 01:01:20,960
SYSTEM.

1699
01:01:20,960 --> 01:01:23,840
COULD WE MAKE KIND OF OPAQUE OR

1700
01:01:23,840 --> 01:01:25,600
HIDDEN CELLS THAT EVADE IMMUNE

1701
01:01:25,600 --> 01:01:29,120
ATTACK?

1702
01:01:29,120 --> 01:01:30,800
SO I'M GOING TO DESCRIBE IN SOME

1703
01:01:30,800 --> 01:01:32,080
DETAIL HOW WE'VE GONE ABOUT

1704
01:01:32,080 --> 01:01:32,800
THIS.

1705
01:01:32,800 --> 01:01:35,080
THIS WORK HASN'T YET BEEN

1706
01:01:35,080 --> 01:01:36,280
PUBLISHED.

1707
01:01:36,280 --> 01:01:37,880
AND IT'S TAKEN US A LONG TIME TO

1708
01:01:37,880 --> 01:01:39,680
FIGURE OUT HOW TO DO THIS, WHICH

1709
01:01:39,680 --> 01:01:41,120
IS WHY I THOUGHT IT MIGHT BE

1710
01:01:41,120 --> 01:01:42,240
INTERESTING TO DESCRIBE IT.

1711
01:01:42,240 --> 01:01:43,960
ONE OF THE ADVANTAGES WE HAVE

1712
01:01:43,960 --> 01:01:46,240
HERE IS THAT WE GROW HUNDREDS OF

1713
01:01:46,240 --> 01:01:48,160
MILLIONS OF CELLS IN THESE

1714
01:01:48,160 --> 01:01:50,360
SPINNER FLASKS.

1715
01:01:50,360 --> 01:01:51,960
THIS DIAGRAM HERE, THIS CARTOON

1716
01:01:51,960 --> 01:01:54,960
IS INTENDED TO SHOW A KIND OF

1717
01:01:54,960 --> 01:01:58,200
THREE-DIMENSIONAL SPAIN SPINNER.

1718
01:01:58,200 --> 01:01:59,440
BECAUSE WE GROW HUNDREDS OF

1719
01:01:59,440 --> 01:02:00,440
MILLIONS OF CELLS, WE COULD

1720
01:02:00,440 --> 01:02:01,760
KNOCK OUT GENES ONE AT A TIME,

1721
01:02:01,760 --> 01:02:04,880
THAT IS KNOCKING OUT ONE GENE

1722
01:02:04,880 --> 01:02:06,280
PER CELL, AND THEN LOOK FOR THE

1723
01:02:06,280 --> 01:02:07,480
PHENOTYPE, THAT IS, DOES IT

1724
01:02:07,480 --> 01:02:10,800
AFFECT THE COMPOSITION AND THE

1725
01:02:10,800 --> 01:02:13,400
ABILITY OF THE CELL TO AVOID

1726
01:02:13,400 --> 01:02:14,120
IMMUNE ATTACK?

1727
01:02:14,120 --> 01:02:16,320
THIS SLIDE SHOWS HOW WE DO THAT.

1728
01:02:16,320 --> 01:02:18,360
WE INFECT THE STARTING MATERIAL,

1729
01:02:18,360 --> 01:02:20,520
THE PLURIPOTENT STEM CELLS, WITH

1730
01:02:20,520 --> 01:02:22,320
A LENTIVIRAL LIBRARY CONTAINING

1731
01:02:22,320 --> 01:02:24,680
CRISPR AND GUIDE RNAs.

1732
01:02:24,680 --> 01:02:26,760
IT ALSO CONTAINS A DRUG

1733
01:02:26,760 --> 01:02:29,400
SELECTION, SO AS SHOWN HERE WITH

1734
01:02:29,400 --> 01:02:31,080
THE ASTERISK, WE INFECT THE

1735
01:02:31,080 --> 01:02:33,480
CELLS AT A LOW MULTIPLICITY OF

1736
01:02:33,480 --> 01:02:35,440
INFECTION THEN SELECT WITH

1737
01:02:35,440 --> 01:02:37,360
PUREMYCIN SO THE ONLY CELLS THAT

1738
01:02:37,360 --> 01:02:38,240
SURVIVE ARE THOSE THAT HAVE

1739
01:02:38,240 --> 01:02:42,480
RECEIVED A GENE MODIFYING VIRUS.

1740
01:02:42,480 --> 01:02:44,880
WE ALLOW THE CELLS TO RECOVER,

1741
01:02:44,880 --> 01:02:46,360
WE THEN SEED THEM FOR

1742
01:02:46,360 --> 01:02:47,320
DIFFERENTIATION AND GO THROUGH

1743
01:02:47,320 --> 01:02:49,120
THAT SIX-STAGE PROTOCOL I

1744
01:02:49,120 --> 01:02:50,240
DESCRIBED AND HERE THE COLOR

1745
01:02:50,240 --> 01:02:51,440
CODING IS RELEVANT TO WHAT I'M

1746
01:02:51,440 --> 01:02:54,600
GOING TO SHOW YOU SO WE'RE NOW

1747
01:02:54,600 --> 01:02:56,560
LOOKING SOME 40 DAYS LATER.

1748
01:02:56,560 --> 01:02:57,880
PURPLE WERE THE BETA CELLS, THE

1749
01:02:57,880 --> 01:03:00,040
CELLS THAT WE WANT, RED ARE THE

1750
01:03:00,040 --> 01:03:01,120
ALPHA CELLS, THE CELLS WE WANT,

1751
01:03:01,120 --> 01:03:03,840
BLUE ARE THE ENTEROCHROMAFFIN

1752
01:03:03,840 --> 01:03:05,480
CELLS, THE CELLS WE DO NOT WANT

1753
01:03:05,480 --> 01:03:07,400
AND THEN GREEN HERE IS JUST

1754
01:03:07,400 --> 01:03:08,520
TRIPLE NEGATIVE MEANING IT'S

1755
01:03:08,520 --> 01:03:09,960
CELLS THAT DIDN'T RESPOND AT ALL

1756
01:03:09,960 --> 01:03:14,960
OR BECAME SOMETHING DIFFERENT.

1757
01:03:14,960 --> 01:03:17,480
WE THEN DISASSOCIATE THE

1758
01:03:17,480 --> 01:03:18,680
CLUSTER, STAIN FOR THESE

1759
01:03:18,680 --> 01:03:19,840
MARKERS, SORT OUT THE

1760
01:03:19,840 --> 01:03:22,400
POPULATIONS, UNDUE THE FIXATION,

1761
01:03:22,400 --> 01:03:24,720
AND THEN SEQUENCE THE GUIDE DNA

1762
01:03:24,720 --> 01:03:25,760
TO TELL US WHICH GENE WAS

1763
01:03:25,760 --> 01:03:26,600
KNOCKED OUT.

1764
01:03:26,600 --> 01:03:31,040
SO AT THE END, WE HAVE FOUR CELL

1765
01:03:31,040 --> 01:03:33,560
POPULATIONS, BETA, ALPHA,

1766
01:03:33,560 --> 01:03:34,680
ENTEROCHROMAFFIN AND TRIPLE

1767
01:03:34,680 --> 01:03:35,560
NEGATIVE, AND WE'RE LOOKING TO

1768
01:03:35,560 --> 01:03:38,280
SEE WHAT SURVIVED ALL OF THIS

1769
01:03:38,280 --> 01:03:39,280
PROCESS.

1770
01:03:39,280 --> 01:03:40,280
ONE OF THE THINGS I LIKE ABOUT

1771
01:03:40,280 --> 01:03:42,040
THIS APPROACH IS THAT WHEN WE

1772
01:03:42,040 --> 01:03:44,200
KNOCK OUT GENES THAT ARE

1773
01:03:44,200 --> 01:03:46,560
HOUSEKEEPING GENES LIKE FOR DNA

1774
01:03:46,560 --> 01:03:53,000
PRELIMINPOLYMERASE, YOU NEED THE

1775
01:03:53,000 --> 01:03:54,000
HOUSEKEEPING GENES TO GROW, BUT

1776
01:03:54,000 --> 01:03:55,000
WE'RE NOT INTERESTED IN THOSE

1777
01:03:55,000 --> 01:03:55,560
GENES ANYWAY.

1778
01:03:55,560 --> 01:03:58,120
WE'RE NOT TRYING TO KNOCK OUT

1779
01:03:58,120 --> 01:04:00,320
HOUSEKEEPING GENES THAT CELLS

1780
01:04:00,320 --> 01:04:01,600
NEED FOR LIVING.

1781
01:04:01,600 --> 01:04:03,360
WE'RE ONLY INTERESTED IN THOSE

1782
01:04:03,360 --> 01:04:06,280
THAT AFFECT DIFFERENTIATION AND

1783
01:04:06,280 --> 01:04:07,280
FUNCTION.

1784
01:04:07,280 --> 01:04:08,400
SO IN OTHER WORDS, WE GET RID OF

1785
01:04:08,400 --> 01:04:09,920
A LOT OF UNINTERESTING GENES

1786
01:04:09,920 --> 01:04:12,600
FROM THE POINT OF VIEW OF OUR

1787
01:04:12,600 --> 01:04:13,600
GOAL.

1788
01:04:13,600 --> 01:04:17,240
HERE'S HOW WE DID IT, THESE

1789
01:04:17,240 --> 01:04:17,840
GENETIC SCREENS.

1790
01:04:17,840 --> 01:04:19,240
I'M SHOWING YOU LOTS OF DETAIL

1791
01:04:19,240 --> 01:04:20,600
HERE MOSTLY TO CONVINCE YOU THAT

1792
01:04:20,600 --> 01:04:22,440
THE RESULTS I SHOW YOU ARE

1793
01:04:22,440 --> 01:04:25,280
LIKELY TO BE IMPORTANT AND

1794
01:04:25,280 --> 01:04:26,200
ACCURATE.

1795
01:04:26,200 --> 01:04:30,280
WE USE A LIN TEE VIRAL LIBRARY

1796
01:04:30,280 --> 01:04:31,760
PROVIDED BY THE BROAD INSTITUTE

1797
01:04:31,760 --> 01:04:35,960
WHICH EXPRESSES CAS # ALONG WITH

1798
01:04:35,960 --> 01:04:37,360
THE GUIDES.

1799
01:04:37,360 --> 01:04:39,080
THE PRIMARY GENOME-WIDE SCREEN

1800
01:04:39,080 --> 01:04:44,000
WAS DONE THREE TIMES, USING

1801
01:04:44,000 --> 01:04:47,960
19,000 TARGETS, THAT IS, FOUR

1802
01:04:47,960 --> 01:04:50,760
GUIDE RNAs FOR A TOTAL OF

1803
01:04:50,760 --> 01:04:51,840
80,000 GUIDE RNAs.

1804
01:04:51,840 --> 01:04:54,440
WE HAD A THOUSAND NON-TARGETING

1805
01:04:54,440 --> 01:04:56,800
CONTROLS AND WE DID THIS THREE

1806
01:04:56,800 --> 01:04:58,880
TIMES TO IDENTIFY TOP CANDIDATES

1807
01:04:58,880 --> 01:04:59,760
FOR RESCREENING.

1808
01:04:59,760 --> 01:05:03,320
WE THEN DID THE RESCREENING

1809
01:05:03,320 --> 01:05:04,960
AIMING AT 800 GENES WE FOUND IN

1810
01:05:04,960 --> 01:05:08,640
THE FIRST THREE DIFFERENTIA

1811
01:05:08,640 --> 01:05:09,680
DIFFERENTIATIONS, AGAIN USING

1812
01:05:09,680 --> 01:05:13,200
MULTIPLE TARGETS, GUIDES, SORRY,

1813
01:05:13,200 --> 01:05:14,520
MULTIPLE GUIDES FOR EACH GENE,

1814
01:05:14,520 --> 01:05:17,800
AND IMPORTANTLY, WE DID THIS 18

1815
01:05:17,800 --> 01:05:18,560
DIFFERENT TIMES.

1816
01:05:18,560 --> 01:05:19,960
SO THIS IS A VERY EXTENSIVE

1817
01:05:19,960 --> 01:05:22,480
EXPERIMENT THAT ALLOWED US TO

1818
01:05:22,480 --> 01:05:24,440
IDENTIFY 200 GENETIC

1819
01:05:24,440 --> 01:05:26,760
PERTURBATIONS WITH STATISTICALLY

1820
01:05:26,760 --> 01:05:27,600
SIGNIFICANT EFFECTS.

1821
01:05:27,600 --> 01:05:29,680
THE REASON WE HAD TO DO IT THIS

1822
01:05:29,680 --> 01:05:32,200
WAY, I'LL POINT OUT, IS THAT

1823
01:05:32,200 --> 01:05:34,360
WE'RE NOT USING MONOCLONAL CELL

1824
01:05:34,360 --> 01:05:35,560
LINES AT THIS POINT, WE'RE

1825
01:05:35,560 --> 01:05:39,320
LOOKING AT POPULATIONS, SO WE

1826
01:05:39,320 --> 01:05:41,000
HAD TO HAVE STATISTICALLY

1827
01:05:41,000 --> 01:05:41,760
SIGNIFICANT RESULTS IN ORDER TO

1828
01:05:41,760 --> 01:05:42,960
DRAW ANY CONCLUSIONS.

1829
01:05:42,960 --> 01:05:44,680
AND WHAT YOU SEE HERE THEN IS

1830
01:05:44,680 --> 01:05:46,880
TWO WAYS OF SHOWING YOU THE

1831
01:05:46,880 --> 01:05:49,320
CONCLUSIONS WE WERE ABLE TO

1832
01:05:49,320 --> 01:05:49,920
ACHIEVE.

1833
01:05:49,920 --> 01:05:52,160
I'M SHOWING YOU THE DATA IN TWO

1834
01:05:52,160 --> 01:05:53,000
DIFFERENT FORMS.

1835
01:05:53,000 --> 01:05:54,720
THESE ARE CONTROLS IN SOME WAYS.

1836
01:05:54,720 --> 01:05:56,480
LET'S LOOK AT THE TOP LEFT.

1837
01:05:56,480 --> 01:05:57,920
I'D ALREADY MENTIONED EARLIER ON

1838
01:05:57,920 --> 01:06:01,720
IN MY TALK THIS PANCREATIC DUO

1839
01:06:01,720 --> 01:06:02,840
DEENL HOMEOBOX GENE NUMBER 1,

1840
01:06:02,840 --> 01:06:04,120
AND YOU SEE THAT WHEN WE KNOCKED

1841
01:06:04,120 --> 01:06:06,840
IT OUT, EACH DOT HERE REPRESENTS

1842
01:06:06,840 --> 01:06:09,240
A KNOCKOUT, IT REDUCES THE

1843
01:06:09,240 --> 01:06:11,960
PROBABILITY THAT THE CELLS COULD

1844
01:06:11,960 --> 01:06:12,440
BECOME BETA CELLS.

1845
01:06:12,440 --> 01:06:14,360
SO YOU SEE THESE WERE

1846
01:06:14,360 --> 01:06:16,760
STATISTICALLY INSIGNIFICANT,

1847
01:06:16,760 --> 01:06:18,280
DOWN HERE IS PDX.

1848
01:06:18,280 --> 01:06:19,240
THESE CELLS ARE MORE LIKELY TO

1849
01:06:19,240 --> 01:06:22,320
BE ABLE TO BECOME ALPHA OR

1850
01:06:22,320 --> 01:06:23,400
ENTEROCHROMAFFIN BUT NOT BETA.

1851
01:06:23,400 --> 01:06:26,560
AND THIS JUST SHOWS FOUR GENES

1852
01:06:26,560 --> 01:06:27,360
IN TWO DIFFERENT WAYS.

1853
01:06:27,360 --> 01:06:31,120
THIS SHOWS YOU BY KIND OF A BAR

1854
01:06:31,120 --> 01:06:33,120
PLOT, AND HERE IS A CIRCULAR

1855
01:06:33,120 --> 01:06:35,640
DIAGRAM, WHERE YOU SEE THE X IS

1856
01:06:35,640 --> 01:06:37,480
OPPOSITE PRO BETA, MEANING THAT

1857
01:06:37,480 --> 01:06:39,560
IF YOU KNOCK OUT PDX, YOU'RE

1858
01:06:39,560 --> 01:06:41,040
MUCH LESS LIKELY TO BECOME A

1859
01:06:41,040 --> 01:06:43,440
BETA CELL.

1860
01:06:43,440 --> 01:06:44,480
I'LL JUST SHOW ONE OTHER EXAMPLE

1861
01:06:44,480 --> 01:06:45,320
HERE.

1862
01:06:45,320 --> 01:06:46,600
ARX HAD BEEN SHOWN BY MANY

1863
01:06:46,600 --> 01:06:48,880
OTHERS IN MICE TO BE REQUIRED

1864
01:06:48,880 --> 01:06:51,440
FOR ALPHA CELLS, AND WHEN WE

1865
01:06:51,440 --> 01:06:53,400
KNOCKED THIS GENE OUT, WE SEE

1866
01:06:53,400 --> 01:06:55,600
AGAIN YOU'RE NOT -- YOU'RE MUCH

1867
01:06:55,600 --> 01:06:58,160
LESS LIKELY TO BECOME A GLUCAGON

1868
01:06:58,160 --> 01:06:59,800
PRODUCING CELL THAN YOU ARE

1869
01:06:59,800 --> 01:07:02,680
OTHER CELL TYPES.

1870
01:07:02,680 --> 01:07:03,960
I DON'T HAVE A SLIDE TO SHOW YOU

1871
01:07:03,960 --> 01:07:05,400
BUT I CAN TELL YOU THERE ARE A

1872
01:07:05,400 --> 01:07:06,240
NUMBER OF GENES THAT MAKE YOU

1873
01:07:06,240 --> 01:07:08,040
MUCH MORE LIKELY TO BECOME BETA

1874
01:07:08,040 --> 01:07:09,440
CELLS, LIKE THIS ONE.

1875
01:07:09,440 --> 01:07:10,600
AND ONE OF THE ONES WE'RE

1876
01:07:10,600 --> 01:07:12,080
PARTICULARLY INTERESTED IN IS A

1877
01:07:12,080 --> 01:07:15,760
GENE CALLED F BOX L14, WHICH IS

1878
01:07:15,760 --> 01:07:17,400
IN THE UBIQUITIN PATHWAY, AND

1879
01:07:17,400 --> 01:07:19,280
WHAT WE THINK IS GOING ON THERE,

1880
01:07:19,280 --> 01:07:21,120
WE'RE NOW TRYING TO PROVE THAT

1881
01:07:21,120 --> 01:07:24,280
WITH MONOCLONAL CELL LINES, IS

1882
01:07:24,280 --> 01:07:26,600
THAT THAT PROTEIN, THAT ENZYME

1883
01:07:26,600 --> 01:07:30,520
IS REQUIRED TO MARK CELLS FOR

1884
01:07:30,520 --> 01:07:32,840
DEGRADATION, AND IF WE DEGRADE

1885
01:07:32,840 --> 01:07:33,960
THEM, THEN THE CELLS ARE MORE

1886
01:07:33,960 --> 01:07:37,240
LIKELY TO BECOME BETA CELL,

1887
01:07:37,240 --> 01:07:38,760
MEANING THE PROTEINS IT PROBABLY

1888
01:07:38,760 --> 01:07:40,520
MARKS ARE INCLINED TO MAKE THE

1889
01:07:40,520 --> 01:07:42,320
CELLS BECOME ENTEROCHROMAFFIN

1890
01:07:42,320 --> 01:07:44,480
CELLS WHICH WE DON'T WANT.

1891
01:07:44,480 --> 01:07:46,200
SO THE POINT OF THIS SLIDE IS TO

1892
01:07:46,200 --> 01:07:48,000
SHOW YOU THAT A GENETIC SCREEN

1893
01:07:48,000 --> 01:07:50,360
CAN GIVE US CLUES NOW ABOUT WHAT

1894
01:07:50,360 --> 01:07:53,920
MODIFICATIONS WE COULD MAKE TO

1895
01:07:53,920 --> 01:07:55,480
ACHIEVE THE GOAL OF MAKING

1896
01:07:55,480 --> 01:07:57,560
PRIMARILY IF NOT EXCLUSIVELY

1897
01:07:57,560 --> 01:07:59,320
ALPHA CELLS, BETA CELLS, AND

1898
01:07:59,320 --> 01:08:00,400
DELTA CELLS.

1899
01:08:00,400 --> 01:08:02,880
INSULIN PRODUCING GLUCAGON

1900
01:08:02,880 --> 01:08:04,960
PRODUCING, AND SOMATOSTATIN

1901
01:08:04,960 --> 01:08:07,040
CELLS.

1902
01:08:07,040 --> 01:08:08,720
I DIDN'T TELL YOU WHY WE WOULD

1903
01:08:08,720 --> 01:08:11,240
WANT TO MAKE THE DELTA CELLS,

1904
01:08:11,240 --> 01:08:12,440
THE SOMATOSTATIN PRODUCING CELLS

1905
01:08:12,440 --> 01:08:13,720
BUT THE MAIN REASON FOR THAT IS

1906
01:08:13,720 --> 01:08:15,080
EXPERIMENTS IN MICE SHOW THAT

1907
01:08:15,080 --> 01:08:18,000
KNOCKING OUT DELTA CELLS MAKES

1908
01:08:18,000 --> 01:08:19,720
THE ALPHA AND BETA CELLS WORK A

1909
01:08:19,720 --> 01:08:22,480
LITTLE LESS WELL.

1910
01:08:22,480 --> 01:08:24,280
LAST THING, AND I'M ALMOST DONE

1911
01:08:24,280 --> 01:08:26,080
HERE, IS TO TELL BUT THIS

1912
01:08:26,080 --> 01:08:29,000
CHALLENGE OF ALLO INJECTION.

1913
01:08:29,000 --> 01:08:30,840
I'M NOT AN IMMUNOLOGIST SO I'M

1914
01:08:30,840 --> 01:08:33,800
GOING TO GIVE YOU -- WHAT I

1915
01:08:33,800 --> 01:08:35,880
WOULD SAY IS KIND OF MY

1916
01:08:35,880 --> 01:08:38,080
UNDERGRADUATE VIEW OF WHAT WE

1917
01:08:38,080 --> 01:08:42,520
CAN ACLEAVE.

1918
01:08:42,520 --> 01:08:42,800
 ACHIEVE.

1919
01:08:42,800 --> 01:08:44,840
SHOWN HERE IN PURPLE COULD BE

1920
01:08:44,840 --> 01:08:46,040
DEGRADED BY A NUMBER OF CELL

1921
01:08:46,040 --> 01:08:47,040
TYPES AND I WON'T GO THROUGH

1922
01:08:47,040 --> 01:08:48,400
THESE IN DETAIL, MAINLY I JUST

1923
01:08:48,400 --> 01:08:50,080
WANT TO SHOW YOU HOW COMPLICATED

1924
01:08:50,080 --> 01:08:52,080
IT IS.

1925
01:08:52,080 --> 01:08:54,280
THAT THESE CELLS COULD BE KILLED

1926
01:08:54,280 --> 01:08:57,120
BY CYTOACTIVE T-CELLS,

1927
01:08:57,120 --> 01:08:58,640
CD8 POSITIVE T-CELLS, BY NATURAL

1928
01:08:58,640 --> 01:09:01,280
KILLER CELLS, BY COMPLEMENT

1929
01:09:01,280 --> 01:09:04,400
FIXATION, BY CYTOKINES, BY

1930
01:09:04,400 --> 01:09:05,840
MACROPHAGE ENGULFMENT.

1931
01:09:05,840 --> 01:09:07,200
AND THE POINT OF THIS SLIDE IS

1932
01:09:07,200 --> 01:09:08,360
THAT THERE'S A LOT KNOWN FROM

1933
01:09:08,360 --> 01:09:10,760
THE WORK OF IMMUNOLOGISTS AND

1934
01:09:10,760 --> 01:09:12,200
OTHERS ABOUT THE MOLECULAR

1935
01:09:12,200 --> 01:09:15,240
SIGNALS INVOLVED IN THERE, AND

1936
01:09:15,240 --> 01:09:16,520
SO WE ARE THINKING THAT WE CAN

1937
01:09:16,520 --> 01:09:18,720
KNOCK THOSE GENES OUT OR ADD

1938
01:09:18,720 --> 01:09:21,880
GENES TWHA WOULD PR THAT WOULD S

1939
01:09:21,880 --> 01:09:22,920
KIND OF IMMUNE ATTACK.

1940
01:09:22,920 --> 01:09:24,920
I'M NOT GOING INTO DETAIL HERE

1941
01:09:24,920 --> 01:09:25,840
BECAUSE WE HAVEN'T ACHIEVED THAT

1942
01:09:25,840 --> 01:09:26,240
GOAL.

1943
01:09:26,240 --> 01:09:27,480
I'M GOING TO SHOW YOU ONE

1944
01:09:27,480 --> 01:09:28,280
EXAMPLE, MORE TO JUST SHOW YOU

1945
01:09:28,280 --> 01:09:30,560
WHAT THE CHALLENGE AHEAD IS.

1946
01:09:30,560 --> 01:09:31,680
AND HERE IS THE ONE EXAMPLE I

1947
01:09:31,680 --> 01:09:33,720
WANTED TO DESCRIBE.

1948
01:09:33,720 --> 01:09:35,520
THE STEM CELL DERIVED ISLETS IN

1949
01:09:35,520 --> 01:09:36,920
THIS CASE WERE GENETICALLY

1950
01:09:36,920 --> 01:09:41,520
MODIFIED TO EXPRESS IL10, TGF

1951
01:09:41,520 --> 01:09:43,640
BETA AND A MODIFIED IL2.

1952
01:09:43,640 --> 01:09:44,800
WHAT WE SHOW HERE AND IF YOU

1953
01:09:44,800 --> 01:09:46,160
LOOK AT THE BOTTOM RIGHT IS IF

1954
01:09:46,160 --> 01:09:50,720
WE TAKE UNMODIFIED CELLS, WHILED

1955
01:09:50,720 --> 01:09:52,640
TYPE CELLS AND PUT THEM INTO A

1956
01:09:52,640 --> 01:09:53,800
HUMANIZED MOUSE WHICH WE THEN

1957
01:09:53,800 --> 01:09:58,640
CAN INJECT WITH HUMAN PBMCs OR

1958
01:09:58,640 --> 01:09:59,680
FROM XENOREJECTION IN THE MOUSE

1959
01:09:59,680 --> 01:10:01,280
THAT THESE GENETICALLY MODIFIED

1960
01:10:01,280 --> 01:10:02,760
CELLS CAN SURVIVE FOR UP TO NINE

1961
01:10:02,760 --> 01:10:03,320
WEEKS.

1962
01:10:03,320 --> 01:10:04,920
I DON'T WANT TO IMPLY THAT THIS

1963
01:10:04,920 --> 01:10:06,440
IS THE SOLUTION TO THE PROBLEM.

1964
01:10:06,440 --> 01:10:09,160
I SIMPLY WANT TO SAY THAT BY

1965
01:10:09,160 --> 01:10:10,280
GENETICALLY MODIFYING THE CELLS,

1966
01:10:10,280 --> 01:10:12,760
I THINK WE CAN INCREASE THEIR

1967
01:10:12,760 --> 01:10:15,200
SURVIVAL IN PATIENTS.

1968
01:10:15,200 --> 01:10:16,920
NOW LET ME FINISH WITH THIS

1969
01:10:16,920 --> 01:10:19,680
QUESTION OF PATIENTS.

1970
01:10:19,680 --> 01:10:23,280
WHAT I'VE TOLL YOU A TOLD YOU SS

1971
01:10:23,280 --> 01:10:24,880
ABOUT RESEARCH WORK DONE IN LAB.

1972
01:10:24,880 --> 01:10:27,480
I WANT TO FINISH UP BY SAYING

1973
01:10:27,480 --> 01:10:29,880
WHAT ARE THE CHALLENGES OF GOING

1974
01:10:29,880 --> 01:10:31,400
FROM THESE KIND OF RESEARCH

1975
01:10:31,400 --> 01:10:32,400
DERIVED CELLS TO ACTUALLY A

1976
01:10:32,400 --> 01:10:33,800
CLINICAL TRIAL AND EVENTUALLY, I

1977
01:10:33,800 --> 01:10:35,040
HOPE, TREATING PATIENTS.

1978
01:10:35,040 --> 01:10:36,720
THIS REQUIRES LOTS OF THINGS

1979
01:10:36,720 --> 01:10:40,320
WHICH WE CANNOT AND ONE CANNOT

1980
01:10:40,320 --> 01:10:42,240
GENERALLY SPEAKING DO IN A

1981
01:10:42,240 --> 01:10:43,680
UNIVERSITY ENVIRONMENT.

1982
01:10:43,680 --> 01:10:45,360
SO WHERE I TEACH AT HARVARD

1983
01:10:45,360 --> 01:10:46,720
COLLEGE AND THE HARVARD MEDICAL

1984
01:10:46,720 --> 01:10:49,000
SCHOOL, WE COULD WORK ON

1985
01:10:49,000 --> 01:10:50,520
REPRODUCIBILITY, WHICH WE DID,

1986
01:10:50,520 --> 01:10:54,960
BUT SCALING, GETTING CLINICALLY

1987
01:10:54,960 --> 01:10:56,160
COMPLIANT CELLS, DEALING WITH

1988
01:10:56,160 --> 01:10:57,720
REGULATORY ISSUES, DESIGNING AND

1989
01:10:57,720 --> 01:10:59,640
EXECUTING A CLINICAL TRIAL,

1990
01:10:59,640 --> 01:11:00,880
FINDING PATIENT ELIGIBILITY FOR

1991
01:11:00,880 --> 01:11:04,160
THIS AND OF COURSE THE FINANCES

1992
01:11:04,160 --> 01:11:06,080
ARE REALLY BEYOND OF SCOPE OF

1993
01:11:06,080 --> 01:11:06,880
WHAT ONE DOES AT THE UNIVERSITY.

1994
01:11:06,880 --> 01:11:09,080
SO THIS LITTLE SLIDE HERE SHOWS

1995
01:11:09,080 --> 01:11:12,560
MY PATH OR MY LAB'S PATH TO A

1996
01:11:12,560 --> 01:11:13,720
CLINICAL TRIAL, WE BEGAN THE

1997
01:11:13,720 --> 01:11:16,480
WORK I DESCRIBED FOR YOU IN

1998
01:11:16,480 --> 01:11:19,440
ABOUT 1998 AT HARVARD.

1999
01:11:19,440 --> 01:11:20,520
WE THEN DETERMINED ONCE WE WERE

2000
01:11:20,520 --> 01:11:23,000
ABLE TO MAKE STEM CELL DERIVED

2001
01:11:23,000 --> 01:11:24,600
ISLETS AND PATENTED THAT

2002
01:11:24,600 --> 01:11:25,760
PROTOCOL, THAT THE THINGS I JUST

2003
01:11:25,760 --> 01:11:27,280
DESCRIBED WOULD BE BETTER DONE

2004
01:11:27,280 --> 01:11:28,600
OUTSIDE OF THE UNIVERSITY OR

2005
01:11:28,600 --> 01:11:32,440
ENABLED OUTSIDE OF THE

2006
01:11:32,440 --> 01:11:34,400
UNIVERSITY, SO WE STARTED A

2007
01:11:34,400 --> 01:11:37,160
COMPANY IN 2015 CALLED SEMMA

2008
01:11:37,160 --> 01:11:37,880
THERAPEUTICS, AND IT INDUSTRIAL

2009
01:11:37,880 --> 01:11:39,480
IZED THE PROTOCOL, USED

2010
01:11:39,480 --> 01:11:40,680
CLINICALLY COMPLIANT CELLS,

2011
01:11:40,680 --> 01:11:43,200
DEMONSTRATED EFFICACY IN A MORE

2012
01:11:43,200 --> 01:11:45,680
ANIMAL MODELS THAN WE HAD DONE,

2013
01:11:45,680 --> 01:11:49,280
STUDIED THESE CELLS IN A DEVICE

2014
01:11:49,280 --> 01:11:51,560
IN PIGS, AND THAT COMPANY WAS

2015
01:11:51,560 --> 01:11:53,440
ACQUIRED A FEW YEARS AGO BY

2016
01:11:53,440 --> 01:11:54,760
VERTEX PHARMACEUTICALS, AND I'M

2017
01:11:54,760 --> 01:11:57,000
NOW GOING TO SWITCH TO

2018
01:11:57,000 --> 01:11:59,280
DESCRIBING WHAT VERTEX HAS DONE.

2019
01:11:59,280 --> 01:12:01,440
SO A CLINICAL TRIAL WITH STEM

2020
01:12:01,440 --> 01:12:04,640
CELL DERIVED ISLETS BEGAN IN

2021
01:12:04,640 --> 01:12:07,040
2021, BY VERTEX PHARMACEUTICALS.

2022
01:12:07,040 --> 01:12:10,040
SO HERE'S WHAT WAS DONE.

2023
01:12:10,040 --> 01:12:11,160
THEY USE ADD MODIFIED VERSION OF

2024
01:12:11,160 --> 01:12:12,960
THE PROTOCOL WITH A DIFFERENT

2025
01:12:12,960 --> 01:12:16,000
CELL LINE TO MAKE THESE STEM

2026
01:12:16,000 --> 01:12:18,120
CELL DERIVED ISLETS AND THEN

2027
01:12:18,120 --> 01:12:19,880
FOLLOWED WHAT HAD BEEN DONE WITH

2028
01:12:19,880 --> 01:12:20,880
CADAVERIC ISLETS BY TRANSPORTING

2029
01:12:20,880 --> 01:12:23,520
THEM TO THE PORTAL VEIN,

2030
01:12:23,520 --> 01:12:26,560
IMPORTANTLY HERE ALONG WITH

2031
01:12:26,560 --> 01:12:27,400
NONSTEROIDAL IMMUNOSUPPRESSANTS.

2032
01:12:27,400 --> 01:12:28,640
I THINK I'VE SAID IT CLEARLY

2033
01:12:28,640 --> 01:12:31,480
ENOUGH ALREADY, THAT THESE ARE

2034
01:12:31,480 --> 01:12:33,000
ALLO CELLS WHICH WOULD BE

2035
01:12:33,000 --> 01:12:33,960
REJECTED BY THE PATIENT SO THE

2036
01:12:33,960 --> 01:12:36,480
STEM CELL DERIVED ISLETS ARE

2037
01:12:36,480 --> 01:12:39,440
PROVIDED WITH NONSTEROIDAL

2038
01:12:39,440 --> 01:12:39,880
IMMUNOSUPPRESSANTS.

2039
01:12:39,880 --> 01:12:41,640
AND I'M ALLOWED TO SHOW THESE

2040
01:12:41,640 --> 01:12:43,400
DATA, WHICH HAVE BEEN MADE

2041
01:12:43,400 --> 01:12:44,920
PUBLIC, AND THERE'S LOTS OF DATA

2042
01:12:44,920 --> 01:12:47,240
HERE ON THIS SLIDE BUT IT WOULD

2043
01:12:47,240 --> 01:12:49,080
BE PRETTY EASY FOR ME TO AT THE

2044
01:12:49,080 --> 01:12:54,640
ME TODESCRIBE WHY I'M EXCITED AT

2045
01:12:54,640 --> 01:12:54,840
THIS.

2046
01:12:54,840 --> 01:12:56,480
WE CALCULATED HOW MANY STEM CELL

2047
01:12:56,480 --> 01:12:57,480
DERIVED ISLETS A PATIENT WOULD

2048
01:12:57,480 --> 01:13:00,280
NEED AND THE FDA WISELY

2049
01:13:00,280 --> 01:13:01,520
SUGGESTED THAT INITIALLY WE JUST

2050
01:13:01,520 --> 01:13:02,600
USE HALF OF THAT DOSE.

2051
01:13:02,600 --> 01:13:03,800
SO I'M SHOWING YOU HERE ON THE

2052
01:13:03,800 --> 01:13:05,680
LEFT, LET'S LOOK AT THE

2053
01:13:05,680 --> 01:13:08,040
PATIENTS' BLOOD GLUCOSE LEVELS,

2054
01:13:08,040 --> 01:13:11,640
25 DAYS BEFORE TRANSPLANTATION.

2055
01:13:11,640 --> 01:13:13,720
MEASURED BY A CONTINUOUS GLUCOSE

2056
01:13:13,720 --> 01:13:14,600
MONITOR.

2057
01:13:14,600 --> 01:13:16,320
AND THE DETAIL HERE ISN'T SO

2058
01:13:16,320 --> 01:13:17,640
IMPORTANT TO LOOK AT ALL THE

2059
01:13:17,640 --> 01:13:20,160
NUMBERS, BUT JUST TO SAY LOOK IN

2060
01:13:20,160 --> 01:13:23,360
THE GREY REGION, WHICH IS WHAT A

2061
01:13:23,360 --> 01:13:24,240
NON-DIABETIC'S BLOOD GLUCOSE

2062
01:13:24,240 --> 01:13:25,640
LEVELS WOULD BE, A SO-CALLED

2063
01:13:25,640 --> 01:13:26,520
TIME IN RANGE.

2064
01:13:26,520 --> 01:13:28,800
AND YOU SEE THIS POOR PATIENT

2065
01:13:28,800 --> 01:13:30,840
SUFFERS FROM MANY PERIODS OF

2066
01:13:30,840 --> 01:13:33,360
TIME WHERE THEY HAD HIGH BLOOD

2067
01:13:33,360 --> 01:13:34,800
SUGARS AND IMPORTANTLY THEY ALSO

2068
01:13:34,800 --> 01:13:37,120
HAD VERY LOW AND DANGEROUS LOW

2069
01:13:37,120 --> 01:13:38,280
BLOOD SUGAR SHOWN HERE AT THE

2070
01:13:38,280 --> 01:13:43,040
BOTTOM AN IN SORT OF ORANGE AND

2071
01:13:43,040 --> 01:13:45,320
PURPLE.

2072
01:13:45,320 --> 01:13:49,280
270 DAYS, OR 240 TO 270 DAYS

2073
01:13:49,280 --> 01:13:51,040
AFTER RECEIVING HALF A DOSE OF

2074
01:13:51,040 --> 01:13:52,480
STEM CELL DERIVED ISLETS, LOOK

2075
01:13:52,480 --> 01:13:53,840
AT HOW GOOD THIS LOOK.

2076
01:13:53,840 --> 01:13:54,160
S.

2077
01:13:54,160 --> 01:13:57,320
THEIR TIME IN RANGE IS 99.9%,

2078
01:13:57,320 --> 01:13:58,880
THEIR DAILY INSULIN REQUIREMENTS

2079
01:13:58,880 --> 01:14:00,320
WENT FROM 34 UNITS OF INSULIN

2080
01:14:00,320 --> 01:14:01,840
EVERY DAY TO ZERO.

2081
01:14:01,840 --> 01:14:04,200
AND THEIR HEMOGLOBIN A1C, A

2082
01:14:04,200 --> 01:14:06,200
MEASUREMENT OF BLOOD GLUCOSE

2083
01:14:06,200 --> 01:14:08,040
CONTROL, WENT FROM 8.6 TO

2084
01:14:08,040 --> 01:14:10,120
ESSENTIALLY NORMAL.

2085
01:14:10,120 --> 01:14:11,880
THIS IS FRANKLY A RESULT BETTER

2086
01:14:11,880 --> 01:14:13,400
THAN I COULD HAVE HOPED FOR,

2087
01:14:13,400 --> 01:14:16,640
WITH JUST HALF A DOSE, AND IN MY

2088
01:14:16,640 --> 01:14:18,080
VIEW IS A VERY EXCITING RESULT

2089
01:14:18,080 --> 01:14:20,600
SHOWING FOR THE FIRST TIME THAT

2090
01:14:20,600 --> 01:14:23,640
STEM CELL DERIVED ISLETS CAN

2091
01:14:23,640 --> 01:14:25,920
CONTROL A PATIENT'S BLOOD

2092
01:14:25,920 --> 01:14:27,480
SUGARS, ALBEIT IN THE PRESENCE

2093
01:14:27,480 --> 01:14:28,320
OF IMMUNOSUPPRESSION BUT

2094
01:14:28,320 --> 01:14:29,760
NEVERTHELESS THESE STEM CELL

2095
01:14:29,760 --> 01:14:33,040
DERIVED ISLETS WORKED AS WELL AS

2096
01:14:33,040 --> 01:14:33,600
CADAVERIC ISLETS.

2097
01:14:33,600 --> 01:14:35,360
AS IT'S NOT SURPRISING, THIS

2098
01:14:35,360 --> 01:14:36,760
RESULT ISN'T ALWAYS THE CASE.

2099
01:14:36,760 --> 01:14:38,160
THE SECOND PATIENT WITH HALF A

2100
01:14:38,160 --> 01:14:42,640
DOSE HAD AN IMPROVEMENT, 25

2101
01:14:42,640 --> 01:14:45,800
UNITS TO 18, 35% HIGH RANGE TO

2102
01:14:45,800 --> 01:14:49,040
MORE THAN 50%, A LOWERING OF THE

2103
01:14:49,040 --> 01:14:50,960
HEMOGLOBIN A1C, BUT CLEARLY NOT

2104
01:14:50,960 --> 01:14:52,280
AS GOOD A RESULT AS THE FIRST

2105
01:14:52,280 --> 01:14:52,720
PATIENT.

2106
01:14:52,720 --> 01:14:54,440
THERE ARE MORE PATIENTS NOW THAT

2107
01:14:54,440 --> 01:14:56,760
HAVE BEEN PROVIDED WITH STEM

2108
01:14:56,760 --> 01:14:57,880
CELL DERIVED ISLETS AND THOSE

2109
01:14:57,880 --> 01:14:58,880
RESULTS WILL READ OUT IN THE

2110
01:14:58,880 --> 01:15:01,080
NEXT FEW MONTHS.

2111
01:15:01,080 --> 01:15:02,520
BUT IN MY VIEW, I WOULD JUST SAY

2112
01:15:02,520 --> 01:15:03,800
THAT THE FIRST RESULTS WERE

2113
01:15:03,800 --> 01:15:06,120
MAYBE EVEN BETTER THAN I COULD

2114
01:15:06,120 --> 01:15:07,960
HAVE HOPED FOR, AND I FEEL LIKE

2115
01:15:07,960 --> 01:15:09,280
THIS SHOWS WE'RE ON THE RIGHT

2116
01:15:09,280 --> 01:15:10,680
TRACK FOR FINDING A NEW

2117
01:15:10,680 --> 01:15:14,520
TREATMENT FOR TYPE 1 DIABETES.

2118
01:15:14,520 --> 01:15:19,200
SO I'LL CONCLUDE T CONCLUDE THEG

2119
01:15:19,200 --> 01:15:20,840
WHERE I THINK WE ARE.

2120
01:15:20,840 --> 01:15:22,480
THIS IS AN INVESTIGATION TALL

2121
01:15:22,480 --> 01:15:24,000
AFROACH USING STEM CELL DERIVED

2122
01:15:24,000 --> 01:15:26,640
ISLETS FOR TRANSPLANTATION INTO

2123
01:15:26,640 --> 01:15:27,360
TYPE 1 DIABETICS.

2124
01:15:27,360 --> 01:15:29,600
IF I GO BACK TO MY SIMPLE MINDED

2125
01:15:29,600 --> 01:15:31,080
DIVISION OF THE PROBLEM CAN WE

2126
01:15:31,080 --> 01:15:32,280
MAKE THE ISLETS, THERE ARE

2127
01:15:32,280 --> 01:15:32,880
IMPROVEMENTS WHICH CAN BE MADE

2128
01:15:32,880 --> 01:15:35,320
ON THAT, BUT I THINK WE'VE

2129
01:15:35,320 --> 01:15:36,760
SOLVED IN PRINCIPLE THE FIRST

2130
01:15:36,760 --> 01:15:38,520
HALF OF THE PROBLEM.

2131
01:15:38,520 --> 01:15:39,920
WE'RE NOW DOSING WITH

2132
01:15:39,920 --> 01:15:40,680
IMMUNOSUPPRESSION AND THAT'S

2133
01:15:40,680 --> 01:15:42,760
GOING WELL.

2134
01:15:42,760 --> 01:15:45,160
I DIDN'T HAVE TIME TODAY TO TELL

2135
01:15:45,160 --> 01:15:47,960
YOU ABOUT AN ENS CAPS LAITION

2136
01:15:47,960 --> 01:15:50,000
DEVICE DEVELOPED AT SEMMA AND

2137
01:15:50,000 --> 01:15:51,400
VERTEX AND THAT'S NOW BEEN

2138
01:15:51,400 --> 01:15:53,160
APPROVED FOR A CLINICAL TRIAL

2139
01:15:53,160 --> 01:15:54,440
WHICH IS ONGOING BUT AT THE END

2140
01:15:54,440 --> 01:15:56,720
I DESCRIBED FOR YOU MY VIEW THAT

2141
01:15:56,720 --> 01:15:58,360
MAYBE EVENTUALLY, WE CAN GET TO

2142
01:15:58,360 --> 01:16:00,000
NAKED OR GENETICALLY MODIFIED

2143
01:16:00,000 --> 01:16:01,560
CELLS, WHICH WOULD NOT BE PUT IN

2144
01:16:01,560 --> 01:16:03,240
A DEVICE.

2145
01:16:03,240 --> 01:16:06,160
SO TO BE OPTIMISTIC ABOUT THE

2146
01:16:06,160 --> 01:16:09,200
FUTURE, I LIKE TO THINK ABOUT A

2147
01:16:09,200 --> 01:16:11,160
TIME WHEN A POOR YOUNG GIRL OR

2148
01:16:11,160 --> 01:16:15,120
BOY IS DIAGNOSED WITH TYPE

2149
01:16:15,120 --> 01:16:16,240
1 DIABETES AND THEY'RE TALKING

2150
01:16:16,240 --> 01:16:17,960
TO THEIR ENDOCRINOLOGIST, SHE

2151
01:16:17,960 --> 01:16:19,440
SAYS TO THEM, WELL, THIS IS NOT

2152
01:16:19,440 --> 01:16:21,440
A GOOD DISEASE TO HAVE, BUT IT'S

2153
01:16:21,440 --> 01:16:24,000
POSSIBLE THAT WE CAN INJECT YOU

2154
01:16:24,000 --> 01:16:25,760
OR TRANSPLANT YOU WITH STEM CELL

2155
01:16:25,760 --> 01:16:27,280
DERIVED ISLETS, WHICH WON'T BE

2156
01:16:27,280 --> 01:16:29,240
REJECTED BY YOUR OWN IMMUNE

2157
01:16:29,240 --> 01:16:31,240
SYSTEM, AND WHICH WILL CONTROL

2158
01:16:31,240 --> 01:16:32,320
YOUR BLOOD SUGARS.

2159
01:16:32,320 --> 01:16:35,240
SO AS LONG AS YOU RECEIVE THESE

2160
01:16:35,240 --> 01:16:38,000
ISLETS, YOUR BLOOD SUGARS AND

2161
01:16:38,000 --> 01:16:40,840
YOUR METABOLISM WILL BE

2162
01:16:40,840 --> 01:16:41,800
CONTROLLED.

2163
01:16:41,800 --> 01:16:43,440
I FINISH BY SHOWING A PICTURE OF

2164
01:16:43,440 --> 01:16:46,400
THE LUCKY TEAM I'VE HAD TO WORK

2165
01:16:46,400 --> 01:16:47,480
WITH ME ON THIS PROBLEM OVER A

2166
01:16:47,480 --> 01:16:48,680
NUMBER OF YEARS AND I'D ALSO

2167
01:16:48,680 --> 01:16:50,760
LIKE TO THANK THE FUNDING

2168
01:16:50,760 --> 01:16:53,720
AGENCIES AND OUR COLLABORATORS.

2169
01:16:53,720 --> 01:16:54,920
IN BLACK ON THE LEFT ARE THE

2170
01:16:54,920 --> 01:16:56,000
PEOPLE WHO ARE STILL IN MY

2171
01:16:56,000 --> 01:16:57,440
HARVARD LAB, ALTHOUGH IT IS

2172
01:16:57,440 --> 01:16:58,640
CLOSING DOWN.

2173
01:16:58,640 --> 01:17:01,280
IN BLUE ARE THE COLLABORATORS

2174
01:17:01,280 --> 01:17:02,920
WE'VE ENJOYED WORKING WITH FOR

2175
01:17:02,920 --> 01:17:07,400
MANY YEARS, AND IN BLACK AT THE

2176
01:17:07,400 --> 01:17:09,080
BOTTOM ARE THE FUNDING AGENCIES

2177
01:17:09,080 --> 01:17:16,920
INCLUDING THE NIH, JDRF, PICOWER

2178
01:17:16,920 --> 01:17:19,680
FOUNDATION, HARVARD STEM CELL

2179
01:17:19,680 --> 01:17:22,640
INSTITUTE, IN GREEN, SEMMA

2180
01:17:22,640 --> 01:17:24,560
ACQUIRED BY VERTEX, WHERE I NOW

2181
01:17:24,560 --> 01:17:26,120
WORK AS A RESEARCH FELLOW.

2182
01:17:26,120 --> 01:17:28,960
SO THANK YOU FOR YOUR ATTENTION,

2183
01:17:28,960 --> 01:17:30,280
AND I HOPE THE REST OF THE

2184
01:17:30,280 --> 01:17:33,920
DISCUSSION GOES WELL.

2185
01:17:33,920 --> 01:17:39,040
>>THANK YOU VERY MUCH,
DOUG,

2186
01:17:39,040 --> 01:17:41,200
AND WE GREATLY APPRECIATE YOUR

2187
01:17:41,200 --> 01:17:47,320
TAKING THE TIME TO PREPARE THIS

2188
01:17:47,320 --> 01:17:50,520
VIDEO, GIVEN THE CIRCUMSTANCES

2189
01:17:50,520 --> 01:17:51,960
THAT YOU COULD UNFORTUNATELY NOT

2190
01:17:51,960 --> 01:17:52,680
BE WITH US.

2191
01:17:52,680 --> 01:17:54,920
WE HAVE A VARIETY OF QUESTIONS

2192
01:17:54,920 --> 01:17:56,080
HERE.

2193
01:17:56,080 --> 01:18:03,600
AND SO I'M GOING TO DIRECT THE

2194
01:18:03,600 --> 01:18:14,040
FIRST GROUP TO COURTNEY.

2195
01:18:21,960 --> 01:18:28,560
SO COURTNEY, WE HAVE A QUESTION

2196
01:18:28,560 --> 01:18:31,440
FROM JIM TAYLOR WHO SAYS HIS

2197
01:18:31,440 --> 01:18:35,360
WIFE WAS ON METFORMIN FOR MANY

2198
01:18:35,360 --> 01:18:37,840
YEARS TO LOWER HER BLOOD SUGAR.

2199
01:18:37,840 --> 01:18:39,960
WHEN HER BLOOD SUGAR STARTED

2200
01:18:39,960 --> 01:18:45,280
MEASURING LESS THAN 100, SHE WAS

2201
01:18:45,280 --> 01:18:46,960
REMOVED FROM METFORMIN AND HER

2202
01:18:46,960 --> 01:18:49,080
BLOOD SUGAR LEVELS HAVE REMAINED

2203
01:18:49,080 --> 01:18:51,440
STABLE WITHIN THE NORMAL LIMITS.

2204
01:18:51,440 --> 01:18:56,720
IS THIS A COMMON PHENOMENA?

2205
01:18:56,720 --> 01:18:57,920
AND SHOULD SHE STILL BE

2206
01:18:57,920 --> 01:19:00,720
CONSIDERED AS A DIABETIC?

2207
01:19:00,720 --> 01:19:01,720
WHAT MIGHT HAVE HAPPENED TO

2208
01:19:01,720 --> 01:19:05,240
CAUSE HER TO NO LONGER NEED

2209
01:19:05,240 --> 01:19:07,080
MEDICATION?

2210
01:19:07,080 --> 01:19:08,080
WEL

2211
01:19:08,080 --> 01:19:11,200
>>THAT'S AN EXCELLENT
QUESTION.

2212
01:19:11,200 --> 01:19:14,200
METFORMIN HAS A LOT OF WONDERFUL

2213
01:19:14,200 --> 01:19:16,840
BENEFITS FOR PEOPLE WITH INSULIN

2214
01:19:16,840 --> 01:19:17,680
RESISTANCE.

2215
01:19:17,680 --> 01:19:20,240
INCLUDING LOWERING THAT INSULIN

2216
01:19:20,240 --> 01:19:21,720
RESISTANCE AND YOU CAN DO THAT A

2217
01:19:21,720 --> 01:19:22,280
NUMBER OF WAYS.

2218
01:19:22,280 --> 01:19:24,360
YOU CAN DO THAT THROUGH

2219
01:19:24,360 --> 01:19:25,760
MEDICATION, LIFESTYLE IS ALSO AN

2220
01:19:25,760 --> 01:19:27,640
EXCELLENT CHOICE, SO I'D BE

2221
01:19:27,640 --> 01:19:31,840
CURIOUS TO LEARN WHAT LIFESTYLE

2222
01:19:31,840 --> 01:19:34,880
INTERVENTIONS THAT SHE

2223
01:19:34,880 --> 01:19:35,640
UNDERTOOK, WHETHER IT WAS

2224
01:19:35,640 --> 01:19:37,320
CHANGING DIET, CHANGING EXERCISE

2225
01:19:37,320 --> 01:19:38,840
OR SOMETHING ELSE IN HER LIFE

2226
01:19:38,840 --> 01:19:40,040
THAT COULD HAVE ALSO LOWERED

2227
01:19:40,040 --> 01:19:41,800
THAT INSULIN RESISTANCE.

2228
01:19:41,800 --> 01:19:44,120
AS FAR AS THE DIAGNOSIS OF

2229
01:19:44,120 --> 01:19:46,720
DIABETES, AN A1C OF 6.5 OR

2230
01:19:46,720 --> 01:19:47,960
HIGHER IS JUST ONE CRITERIA THAT

2231
01:19:47,960 --> 01:19:50,360
CAN BE USED FOR DIAGNOSIS.

2232
01:19:50,360 --> 01:19:52,640
SO WHILE THERE IS A SPECTRUM OF

2233
01:19:52,640 --> 01:19:54,000
INSULIN SENSITIVITY, USUALLY THE

2234
01:19:54,000 --> 01:19:55,040
CUTOFFS ARE PRETTY BLACK AND

2235
01:19:55,040 --> 01:19:56,280
WHITE AS TO WHETHER OR NOT

2236
01:19:56,280 --> 01:19:58,240
SOMEONE IS CONSIDERED DIABETIC

2237
01:19:58,240 --> 01:20:01,080
OR PREDIABETIC OR SOMEONE WHO

2238
01:20:01,080 --> 01:20:02,480
DOES NOT HAVE DIABETES AT ALL

2239
01:20:02,480 --> 01:20:07,120
AND HAS NORMAL GLUCOSE LEVELS.

2240
01:20:07,120 --> 01:20:08,840
>>WE HAVE A SERIES OF
SOMEWHAT

2241
01:20:08,840 --> 01:20:09,920
PERSONAL QUESTIONS, SO --

2242
01:20:09,920 --> 01:20:11,160
>>THAT'S FINE.

2243
01:20:11,160 --> 01:20:14,560
>>OKAY.

2244
01:20:14,560 --> 01:20:16,800
SO, ONE, WHAT IS THE MOST

2245
01:20:16,800 --> 01:20:18,440
DIFFICULT DECISION YOU HAD TO

2246
01:20:18,440 --> 01:20:21,080
MAKE IN THE LAST 20 YEARS SINCE

2247
01:20:21,080 --> 01:20:23,280
YOU WERE DIAGNOSED WITH TYPE

2248
01:20:23,280 --> 01:20:26,440
1 DIABETES?

2249
01:20:26,440 --> 01:20:27,560
AND SORT OF A SECOND PART, DO

2250
01:20:27,560 --> 01:20:29,280
YOU THINK THAT RUNNING LONG

2251
01:20:29,280 --> 01:20:31,680
DISTANCES IS BETTER THAN OTHER

2252
01:20:31,680 --> 01:20:34,200
FORMS OF EXERCISE TO CONTROL

2253
01:20:34,200 --> 01:20:36,080
BLOOD SUGAR?

2254
01:20:36,080 --> 01:20:38,120
>>BOTH GOOD QUESTIONS.

2255
01:20:38,120 --> 01:20:39,800
IN REGARDS TO THE FIRST

2256
01:20:39,800 --> 01:20:42,120
QUESTION, IS THIS A DECISION

2257
01:20:42,120 --> 01:20:43,560
REGARDING DIABETES MANAGEMENT

2258
01:20:43,560 --> 01:20:47,920
SPECIFICALLY?

2259
01:20:47,920 --> 01:20:50,360
>>I'M SORRY.

2260
01:20:50,360 --> 01:20:51,640
>>THE QUESTION REGARDING

2261
01:20:51,640 --> 01:20:52,760
DIABETES MANAGEMENT

2262
01:20:52,760 --> 01:20:54,680
SPECIFICALLY, THE MOST DIFFICULT

2263
01:20:54,680 --> 01:20:57,040
DECISION WITHIN MANAGEMENT?

2264
01:20:57,040 --> 01:21:00,040
>>IT JUST SAID WHAT IS
THE MOST

2265
01:21:00,040 --> 01:21:01,240
DIFFICULT DECISION YOU HAD TO

2266
01:21:01,240 --> 01:21:04,920
MAKE IN YOUR LIFE IN THE PAST 20

2267
01:21:04,920 --> 01:21:06,880
YEARS SINCE YOU WERE DIAGNOSED

2268
01:21:06,880 --> 01:21:11,640
WITH TYPE 1 DIABETES.

2269
01:21:11,640 --> 01:21:13,040
>>WOW, WHAT A GOOD
QUESTION.

2270
01:21:13,040 --> 01:21:16,320
I DON'T KNOW IF THERE'S ANY ONE

2271
01:21:16,320 --> 01:21:19,040
SPECIFIC DECISION THAT COMES TO

2272
01:21:19,040 --> 01:21:19,920
MIND.

2273
01:21:19,920 --> 01:21:22,200
I THINK RECENT DECISIONS ARE

2274
01:21:22,200 --> 01:21:25,240
EASIER TO REMEMBER.

2275
01:21:25,240 --> 01:21:29,000
AND CERTAINLY AS A RESIDENT,

2276
01:21:29,000 --> 01:21:31,480
KNOWING THAT SOMETIMES YOUR OWN

2277
01:21:31,480 --> 01:21:32,720
HEALTHCARE CAN GET PUT ON THE

2278
01:21:32,720 --> 01:21:36,880
BACK BURNER, WHICH IS AN

2279
01:21:36,880 --> 01:21:37,760
UNFORTUNATE TRUTH WHEN YOU

2280
01:21:37,760 --> 01:21:39,920
DECIDE TO PURSUE A CAREER IN

2281
01:21:39,920 --> 01:21:41,400
MEDICINE, HAS DEFINITELY BEEN A

2282
01:21:41,400 --> 01:21:43,240
DIFFICULT DECISION AND ONE THAT

2283
01:21:43,240 --> 01:21:45,960
HAS TAKEN A LITTLE BIT MORE

2284
01:21:45,960 --> 01:21:47,520
STRATEGIZING.

2285
01:21:47,520 --> 01:21:48,240
ESPECIALLY AS A FIRST YEAR

2286
01:21:48,240 --> 01:21:48,720
RESIDENT.

2287
01:21:48,720 --> 01:21:50,760
AGAIN WITH LITTLE AUTONOMY

2288
01:21:50,760 --> 01:21:53,840
SOMETIMES IN MY OWN SCHEDULE.

2289
01:21:53,840 --> 01:21:58,760
BUT I THINK IT'S A WORTHWHILE

2290
01:21:58,760 --> 01:21:59,600
DECISION.

2291
01:21:59,600 --> 01:22:00,680
IT'S DIFFICULT BUT WORTHWHILE.

2292
01:22:00,680 --> 01:22:02,680
>>FOLKS HAVE ASKED
WHETHER

2293
01:22:02,680 --> 01:22:03,680
DIABETES IS PRESENT IN YOUR

2294
01:22:03,680 --> 01:22:05,440
FAMILY.

2295
01:22:05,440 --> 01:22:09,480
>>IT'S NOT, NOT TO MY
KNOWLE 

2296
01:22:09,480 --> 01:22:10,280
KNOWLEDGE.

2297
01:22:10,280 --> 01:22:11,280
WHICH DOESN'T MEAN THAT IT

2298
01:22:11,280 --> 01:22:13,880
WASN'T PRESENT IN PREVIOUS

2299
01:22:13,880 --> 01:22:16,520
GENERATIONS AND JUST WENT

2300
01:22:16,520 --> 01:22:17,720
UNDIAGNOSED BUT NO CASES I KNOW

2301
01:22:17,720 --> 01:22:23,160
OF SPECIFICALLY, NO.

2302
01:22:23,160 --> 01:22:27,640
>>SO TURNING A WHRIT BIT
MORE E

2303
01:22:27,640 --> 01:22:29,160
TO THE SCIENCE OF IT, WHAT'S

2304
01:22:29,160 --> 01:22:31,240
YOUR FEELING ABOUT THE

2305
01:22:31,240 --> 01:22:39,360
UNDERLYING AUTOIMMUNE PROCESS?

2306
01:22:39,360 --> 01:22:42,400
DOLL YOU THINK IT'S POSSIBLE TO

2307
01:22:42,400 --> 01:22:46,320
DETECT EVIDENCE OF THAT PROCESS

2308
01:22:46,320 --> 01:22:52,720
BEFORE THERE IS ANY

2309
01:22:52,720 --> 01:22:56,360
MANIFESTATION OF HYPOINSULIN?

2310
01:22:56,360 --> 01:22:57,160
>>I DO.

2311
01:22:57,160 --> 01:22:58,200
THERE'S A LOT OF THEORIES ABOUT

2312
01:22:58,200 --> 01:23:00,320
THE TRIGGERS FOR AUTOIMMUNITY

2313
01:23:00,320 --> 01:23:01,840
AND A LOT OF GOOD TRIALS RIGHT

2314
01:23:01,840 --> 01:23:04,720
NOW LOOKING AT SPECIFIC

2315
01:23:04,720 --> 01:23:06,880
ANTIBODIES THAT CAN BE PICKED UP

2316
01:23:06,880 --> 01:23:08,080
YEARS BEFORE A DIAGNOSIS.

2317
01:23:08,080 --> 01:23:10,480
I KNOW FOR EXAMPLE WHEN I WAS

2318
01:23:10,480 --> 01:23:14,040
YOUNGER AND MY FAMILY WENT TO A

2319
01:23:14,040 --> 01:23:15,840
DIABETES CAMP, THERE WAS THE

2320
01:23:15,840 --> 01:23:17,200
OPTION FOR SIBLINGS TO BE TESTED

2321
01:23:17,200 --> 01:23:18,880
FOR THESE ANTIBODIES.

2322
01:23:18,880 --> 01:23:20,080
MY SISTER CHOSE TO NOT BE TESTED

2323
01:23:20,080 --> 01:23:23,160
SO I THINK THAT THIS IS ALSO

2324
01:23:23,160 --> 01:23:24,440
HIGHLY PERSONAL, WHETHER OR NOT

2325
01:23:24,440 --> 01:23:25,760
SOMEONE CHOOSES TO KNOW THAT

2326
01:23:25,760 --> 01:23:28,920
THEY'RE PREDISPOSED OR NOT.

2327
01:23:28,920 --> 01:23:33,400
>>THERE HAVE BEEN A
SERIES OF

2328
01:23:33,400 --> 01:23:35,160
PAPERS IN THE PAST, I DON'T

2329
01:23:35,160 --> 01:23:37,920
KNOW, SIX MONTHS OR A YEAR, MORE

2330
01:23:37,920 --> 01:23:39,920
FROM SORT OF THE TECHNICAL

2331
01:23:39,920 --> 01:23:42,760
STANDPOINT OF DEVELOPMENTS OF

2332
01:23:42,760 --> 01:23:44,440
DIFFERENT WAYS OF MONITORING

2333
01:23:44,440 --> 01:23:48,080
BLOOD SUGAR.

2334
01:23:48,080 --> 01:23:50,600
SOME ACTUALLY SUGGESTING A KIND

2335
01:23:50,600 --> 01:23:54,520
OF AI APPROACH OR A COMPUTER

2336
01:23:54,520 --> 01:23:55,920
BASED APPROACH.

2337
01:23:55,920 --> 01:23:56,920
DO YOU HAVE COMMENTS ABOUT

2338
01:23:56,920 --> 01:24:00,440
THOSE?

2339
01:24:00,440 --> 01:24:04,040
>>COMPUTER AI APPROACH AS
IN

2340
01:24:04,040 --> 01:24:05,160
CLOSED LOOP TECHNOLOGY OR ALONG

2341
01:24:05,160 --> 01:24:06,680
THE LINES OF CLOSED LOOP

2342
01:24:06,680 --> 01:24:08,840
TECHNOLOGY?

2343
01:24:08,840 --> 01:24:11,360
>>WELL, THE QUESTION IS
WHAT

2344
01:24:11,360 --> 01:24:13,440
ABOUT THE RECENT METHODS FOR

2345
01:24:13,440 --> 01:24:15,520
MONITORING BLOOD GLUCOSE?

2346
01:24:15,520 --> 01:24:17,240
IS THERE ROOM FOR IMPROVEMENT

2347
01:24:17,240 --> 01:24:19,040
THERE?

2348
01:24:19,040 --> 01:24:21,320
>>OH, ABSOLUTELY.

2349
01:24:21,320 --> 01:24:23,480
EVEN WITHIN THE -- GOODNESS, I

2350
01:24:23,480 --> 01:24:25,160
GUESS IT'S BEEN SEVEN YEARS NOW

2351
01:24:25,160 --> 01:24:27,320
SINCE THE FDA-APPROVED CGMs AS

2352
01:24:27,320 --> 01:24:30,080
A REPLACEMENT FOR BLOOD GLUCOSE

2353
01:24:30,080 --> 01:24:30,400
MONITORING.

2354
01:24:30,400 --> 01:24:34,120
AND EVEN IN THAT TIME, CGMs

2355
01:24:34,120 --> 01:24:34,760
HAVE BECOME INCREASINGLY

2356
01:24:34,760 --> 01:24:35,800
ACCURATE.

2357
01:24:35,800 --> 01:24:36,840
HOWEVER, THEY'RE STILL NOT

2358
01:24:36,840 --> 01:24:37,800
PERFECT.

2359
01:24:37,800 --> 01:24:40,000
THEY ONLY LAST FOR ABOUT 10 DAYS

2360
01:24:40,000 --> 01:24:43,520
ON AVERAGE, 10 TO 14 DAYS, AND

2361
01:24:43,520 --> 01:24:45,680
WHILE ACCURACY IS INCREASING,

2362
01:24:45,680 --> 01:24:47,000
IT'S STILL NOT PERFECT AND THERE

2363
01:24:47,000 --> 01:24:49,080
ARE A NUMBER OF VARIABLES THAT

2364
01:24:49,080 --> 01:24:51,920
CAN AFFECT A READING, ONE BEING

2365
01:24:51,920 --> 01:24:53,480
PRESSURE THAT'S APPLIED TO THE

2366
01:24:53,480 --> 01:24:55,040
OUTSIDE OF THE SENSOR THAT CAN

2367
01:24:55,040 --> 01:24:56,240
AFFECT MEASUREMENTS AS WELL AS

2368
01:24:56,240 --> 01:24:58,640
CERTAIN MEDICATIONS.

2369
01:24:58,640 --> 01:25:00,840
AS FAR AS TECHNOLOGY IN THE

2370
01:25:00,840 --> 01:25:04,040
FUTURE, THERE'S ALSO BEEN WORK

2371
01:25:04,040 --> 01:25:05,720
ON CONTINUOUS MONITORS THAT ARE

2372
01:25:05,720 --> 01:25:06,720
IMPLANTED THAT NEED TO SCAN AND

2373
01:25:06,720 --> 01:25:09,360
LAST FOR LONGER PERIODS OF TIME.

2374
01:25:09,360 --> 01:25:11,000
I'M NOT PERSONALLY AS FAMILIAR

2375
01:25:11,000 --> 01:25:13,280
WITH THOSE YET.

2376
01:25:13,280 --> 01:25:15,360
AND THEN THERE'S ALSO A LOT OF

2377
01:25:15,360 --> 01:25:17,600
WORK BEING DONE WITH THE WAY

2378
01:25:17,600 --> 01:25:19,400
THAT THE CONTINUOUS GLUCOSE

2379
01:25:19,400 --> 01:25:20,400
MONITORS CAN TALK IN A SENSE

2380
01:25:20,400 --> 01:25:23,600
WITH THE INSULIN PUMPS AND THE

2381
01:25:23,600 --> 01:25:24,880
INSULIN PUMPS CAN EITHER GIVE

2382
01:25:24,880 --> 01:25:26,760
MORE OR LESS INSULIN DEPENDING

2383
01:25:26,760 --> 01:25:31,600
ON THOSE READINGS.

2384
01:25:31,600 --> 01:25:36,520
>>IT'S APROPOS THE
INFORMATION

2385
01:25:36,520 --> 01:25:38,120
YOU PROVIDED WAS RATHER

2386
01:25:38,120 --> 01:25:44,320
DEVASTATING AS TO WHAT THE

2387
01:25:44,320 --> 01:25:45,840
DEFICITS ARE IN OUR HEALTHCARE

2388
01:25:45,840 --> 01:25:49,800
SYSTEM, WHICH ARE PRIMARILY OR

2389
01:25:49,800 --> 01:25:55,600
TO A GREATER EXTENT FELT BY

2390
01:25:55,600 --> 01:25:57,600
PEOPLE WHO ARE NOT VERY WELL

2391
01:25:57,600 --> 01:26:00,560
INFORMED AND ARE AT THE LOWER

2392
01:26:00,560 --> 01:26:06,040
END OF THE SOCIOECONOMIC SCALE.

2393
01:26:06,040 --> 01:26:07,680
SO I'M CURIOUS, WHAT ABOUT IN

2394
01:26:07,680 --> 01:26:10,960
OTHER COUNTRIES, WHERE THE

2395
01:26:10,960 --> 01:26:14,200
SYSTEM IS MORE BASED ON SINGLE

2396
01:26:14,200 --> 01:26:17,320
INSURANCE OR NATIONAL HEALTH, DO

2397
01:26:17,320 --> 01:26:19,000
COUNTRIES LIKE THE UNITED

2398
01:26:19,000 --> 01:26:21,920
KINGDOM, CANADA, THE

2399
01:26:21,920 --> 01:26:29,800
NETHERLANDS, DO THEY PROVIDE

2400
01:26:29,800 --> 01:26:32,800
GLUCOSE MONITORS AND INJECTORS

2401
01:26:32,800 --> 01:26:34,640
AS PART OF THEIR HEALTH POLICY,

2402
01:26:34,640 --> 01:26:36,200
DO YOU KNOW?

2403
01:26:36,200 --> 01:26:39,120
>>IN THE FEW PAPERS THAT
I'VE

2404
01:26:39,120 --> 01:26:41,000
READ, IT SEEMS LIKE THERE'S

2405
01:26:41,000 --> 01:26:42,840
BETTER COVERAGE AND FEWER

2406
01:26:42,840 --> 01:26:45,400
DISPARITIES BETWEEN DIFFERENT

2407
01:26:45,400 --> 01:26:46,560
SOCIOECONOMIC GROUPS, SO AS

2408
01:26:46,560 --> 01:26:48,200
WHERE THE U.S. MIGHT HAVE A

2409
01:26:48,200 --> 01:26:53,400
DIFFERENCE IN A1C OF AROUND --

2410
01:26:53,400 --> 01:26:56,000
BETWEEN THE HIGHEST AND LOWEST

2411
01:26:56,000 --> 01:26:58,000
SOCIOECONOMIC GROUPS, THAT

2412
01:26:58,000 --> 01:26:58,840
DIFFERENCE DOESN'T EXIST IN

2413
01:26:58,840 --> 01:27:00,400
COUNTRIES WITH SINGLE PAYOR

2414
01:27:00,400 --> 01:27:03,040
SYSTEMS TYPICALLY IN WHAT I'VE

2415
01:27:03,040 --> 01:27:05,120
READ SO FAR.

2416
01:27:05,120 --> 01:27:09,560
>>CAN ANYONE, FOR
EXAMPLE, WHO

2417
01:27:09,560 --> 01:27:11,960
BECOMES A DIABETIC IN ANY --

2418
01:27:11,960 --> 01:27:13,240
TYPE 1, DIABETES, LET'S SAY, IN

2419
01:27:13,240 --> 01:27:16,720
ANY OF THOSE COUNTRIES, CAN THEY

2420
01:27:16,720 --> 01:27:21,320
AUTOMATICALLY APPLY FOR AND

2421
01:27:21,320 --> 01:27:24,480
RECEIVE GLUCOSE MONITORS AND

2422
01:27:24,480 --> 01:27:30,800
INSULIN INJECTORS, OR  OR DOES T

2423
01:27:30,800 --> 01:27:32,680
STILL REQUIRE SOME PRIVATE

2424
01:27:32,680 --> 01:27:33,360
INSURANCE OPERATION, DO YOU

2425
01:27:33,360 --> 01:27:33,560
KNOW?

2426
01:27:33,560 --> 01:27:36,440
>>I DON'T KNOW ABOUT ALL

2427
01:27:36,440 --> 01:27:39,120
COMPARABLE HIGH INCOME

2428
01:27:39,120 --> 01:27:41,120
COUNTRIES, BUT GERMANY COMES TO

2429
01:27:41,120 --> 01:27:43,080
MIND AS ONE THAT DOES COVER

2430
01:27:43,080 --> 01:27:43,480
PRETTY WELL.

2431
01:27:43,480 --> 01:27:45,600
AND I THINK THE UK AND FRANCE

2432
01:27:45,600 --> 01:27:48,760
ALSO COVER PRETTY WELL.

2433
01:27:48,760 --> 01:27:50,160
BUT I WOULD HAVE TO READ A

2434
01:27:50,160 --> 01:27:53,040
LITTLE BIT MORE ABOUT OTHER

2435
01:27:53,040 --> 01:27:54,360
COUNTRIES TO GIVE A MORE

2436
01:27:54,360 --> 01:27:57,160
THOROUGH ANSWER TO THAT QUEST 

2437
01:27:57,160 --> 01:27:59,040
QUESTION.

2438
01:27:59,040 --> 01:28:01,640
>>IN THE UNITED STATES,
IS THIS

2439
01:28:01,640 --> 01:28:04,800
EQUIPMENT AND TREATMENT

2440
01:28:04,800 --> 01:28:06,800
AVAILABLE THROUGH MEDICARE AND

2441
01:28:06,800 --> 01:28:08,600
MEDICAID PATIENTS?

2442
01:28:08,600 --> 01:28:12,240
>>IT'S COVERED UNDER
MEDICAID

2443
01:28:12,240 --> 01:28:13,200
IN MOST STATES BUT NOT ALL

2444
01:28:13,200 --> 01:28:13,520
STATES.

2445
01:28:13,520 --> 01:28:15,040
I THINK THAT A LOT OF STATES

2446
01:28:15,040 --> 01:28:18,880
HAVE GOTTEN ON BOARD AND THEY DO

2447
01:28:18,880 --> 01:28:20,400
UNDERSTAND THAT THIS IS BECOMING

2448
01:28:20,400 --> 01:28:22,080
A MEDICAL NECESSITY FOR PEOPLE

2449
01:28:22,080 --> 01:28:24,520
WITH DIABETES AND WITHOUT IT,

2450
01:28:24,520 --> 01:28:25,800
YOU'RE EFFECTIVELY LIVING IN THE

2451
01:28:25,800 --> 01:28:28,040
80s OR THE 90s, AS FAR AS

2452
01:28:28,040 --> 01:28:31,560
DIABETES TREATMENTS GO.

2453
01:28:31,560 --> 01:28:32,400
HOWEVER, THERE'S A LONG WAY TO

2454
01:28:32,400 --> 01:28:32,760
GO.

2455
01:28:32,760 --> 01:28:34,560
THE PROCESS TO PROVE MEDICAL

2456
01:28:34,560 --> 01:28:35,720
NECESSITY CAN MAKE YOU JUMP

2457
01:28:35,720 --> 01:28:38,000
THROUGH A LOT OF HOOPS AND I

2458
01:28:38,000 --> 01:28:40,600
THINK THAT FOR MANY PEOPLE, THAT

2459
01:28:40,600 --> 01:28:43,440
CAN PROVIDE A LARGE OBSTACLE

2460
01:28:43,440 --> 01:28:44,120
ESPECIALLY FOR THOSE WITH LOWER

2461
01:28:44,120 --> 01:28:47,640
LEVELS OF HEALTHCARE LITERACY.

2462
01:28:47,640 --> 01:28:49,520
>>LET'S PUSH THIS JUST A
LITTLE

2463
01:28:49,520 --> 01:28:50,080
BIT FURTHER.

2464
01:28:50,080 --> 01:28:54,480
IS THIS A PART OF A FEDERAL

2465
01:28:54,480 --> 01:28:56,320
MANDATE AS IT WERE OR IS THIS

2466
01:28:56,320 --> 01:29:00,680
SOMETHING THAT IS DECIDED AT THE

2467
01:29:00,680 --> 01:29:02,400
INDIVIDUAL STATE LEVEL, WHETHER

2468
01:29:02,400 --> 01:29:06,360
A PERSON CAN RECEIVE MONITORING

2469
01:29:06,360 --> 01:29:09,280
AND INSULIN INJECTORS?

2470
01:29:09,280 --> 01:29:11,080
>>FROM WHAT I GATHER,
IT'S

2471
01:29:11,080 --> 01:29:13,680
MOSTLY DEPENDENT STATE TO STATE.

2472
01:29:13,680 --> 01:29:17,360
>>IT'S A STATE --
PREDOMINANTLY

2473
01:29:17,360 --> 01:29:17,920
A STATE ISSUE?

2474
01:29:17,920 --> 01:29:19,680
>>PREDOMINANTLY A STATE
ISSUE,

2475
01:29:19,680 --> 01:29:23,720
FROM WHAT I CAN TELL.

2476
01:29:23,720 --> 01:29:24,480
>>ALL RIGHT.

2477
01:29:24,480 --> 01:29:27,680
HERE'S AN INTERESTING QUESTION.

2478
01:29:27,680 --> 01:29:29,080
WHAT IS THE BEST ADVICE FROM

2479
01:29:29,080 --> 01:29:32,120
YOUR BOOK?

2480
01:29:32,120 --> 01:29:34,000
YOU COVERED ALL OF IT, I DON'T

2481
01:29:34,000 --> 01:29:35,200
KNOW WHY SOMEONE WANTS TO KNOW

2482
01:29:35,200 --> 01:29:39,160
THE ABSOLUTE BEST, BUT I GUESS

2483
01:29:39,160 --> 01:29:40,680
THE ADVICE IS TO READ THE BOOK,

2484
01:29:40,680 --> 01:29:41,920
RIGHT?

2485
01:29:41,920 --> 01:29:43,160
>>WELL, THERE'S NOTHING
BETTER

2486
01:29:43,160 --> 01:29:47,080
THAN READING THE ENTIRE BOOK,

2487
01:29:47,080 --> 01:29:47,640
BUT GOODNESS.

2488
01:29:47,640 --> 01:29:50,240
I THINK THE BIGGEST REVELATION

2489
01:29:50,240 --> 01:29:52,320
FOR ME, AT LEAST WHEN I WAS

2490
01:29:52,320 --> 01:29:53,440
DOING THE RESEARCH FOR THE BOOK

2491
01:29:53,440 --> 01:29:55,440
AND WRITING THE BOOK, WAS THAT

2492
01:29:55,440 --> 01:29:57,680
THE STRUGGLES I WAS FACING WERE

2493
01:29:57,680 --> 01:30:01,560
NOT UNCOMMON AND I THINK THAT

2494
01:30:01,560 --> 01:30:02,880
OFTENTIMES THE LOUDEST VOICES IN

2495
01:30:02,880 --> 01:30:03,880
THE DIABETES COMMUNITY ARE FROM

2496
01:30:03,880 --> 01:30:06,040
THOSE WHO TEND TO DO VERY WELL,

2497
01:30:06,040 --> 01:30:09,120
AND IT CREATES THIS PICTURE THAT

2498
01:30:09,120 --> 01:30:10,120
EVERYONE WITH DIABETES IS DOING

2499
01:30:10,120 --> 01:30:12,160
WELL, AND I THINK THAT CAN

2500
01:30:12,160 --> 01:30:14,080
REALLY DECREASE MENTAL HEALTH OF

2501
01:30:14,080 --> 01:30:16,800
PEOPLE WHO ARE LIVING WITH

2502
01:30:16,800 --> 01:30:17,640
DIABETES AND STRUGGLING.

2503
01:30:17,640 --> 01:30:19,360
AND I THINK THAT NORMALIZING

2504
01:30:19,360 --> 01:30:22,280
THOSE STRUGGLES IS VERY

2505
01:30:22,280 --> 01:30:23,480
IMPORTANT IN TALKING ABOUT THE

2506
01:30:23,480 --> 01:30:27,760
ISSUES VERY OPENLY CAN REALLY

2507
01:30:27,760 --> 01:30:29,320
NOT ONLY BUILD CAMARADERIE BUT

2508
01:30:29,320 --> 01:30:30,440
ALSO BUILD HOPE IN THAT YOU

2509
01:30:30,440 --> 01:30:33,680
DON'T HAVE TO EITHER BE,

2510
01:30:33,680 --> 01:30:35,280
QUOTE-UNQUOTE, LIKE A PERFECT

2511
01:30:35,280 --> 01:30:37,000
DIABETIC OR LIKE A BAD DIABETIC,

2512
01:30:37,000 --> 01:30:38,680
THERE'S NO SUCH THING AS EITHER

2513
01:30:38,680 --> 01:30:39,160
ONE OF THOSE.

2514
01:30:39,160 --> 01:30:41,440
IT IS ALL JUST A CONTINUOUS

2515
01:30:41,440 --> 01:30:43,760
PROCESS OF IMPROVEMENT AND I

2516
01:30:43,760 --> 01:30:45,440
THINK THAT FRAMING IT IN THAT

2517
01:30:45,440 --> 01:30:53,400
LENS WAS VERY HELPFUL.

2518
01:30:53,400 --> 01:30:57,040
>>SO YOU ALLUDED TO IN
YOUR

2519
01:30:57,040 --> 01:31:01,720
REALLY ELEGANT DESCRIPTION OF

2520
01:31:01,720 --> 01:31:07,080
HOW A PATIENT CAN RELATE TO THE

2521
01:31:07,080 --> 01:31:09,480
DISEASE AND ONE OF THE

2522
01:31:09,480 --> 01:31:10,560
APPROACHES, THE STANDARDS, THE

2523
01:31:10,560 --> 01:31:13,080
GOALS YOU SET FOR YOURSELF, SO

2524
01:31:13,080 --> 01:31:14,160
THIS PROMPTS THE QUESTION FROM

2525
01:31:14,160 --> 01:31:21,560
YOUR UNDERSTANDING, HOW

2526
01:31:21,560 --> 01:31:23,920
METICULOUS DOES REGULATION OF

2527
01:31:23,920 --> 01:31:27,400
BLOOD GLUCOSE HAVE TO BE?

2528
01:31:27,400 --> 01:31:29,600
IDEALLY, I GUESS IT SHOULD BE

2529
01:31:29,600 --> 01:31:32,400
MAYBE A STEM CELL MEDIATED THING

2530
01:31:32,400 --> 01:31:35,160
THAT'S NORMAL, BUT WITHIN THE

2531
01:31:35,160 --> 01:31:40,480
RANGE OF WHAT WE CURRENTLY DEAL

2532
01:31:40,480 --> 01:31:44,960
WITH, DO YOU STRUGGLE TO KEEP IT

2533
01:31:44,960 --> 01:31:48,760
WITHIN A NORMAL RANGE OR IS IT A

2534
01:31:48,760 --> 01:31:50,360
LITTLE BIT OF VARIATION GIVEN

2535
01:31:50,360 --> 01:31:52,200
YOUR ACTIVITIES AND GIVEN YOUR

2536
01:31:52,200 --> 01:31:57,360
OTHER THINGS PERMISSIBLE, AND IF

2537
01:31:57,360 --> 01:32:01,880
ISTHAT GOOD FOR YOU, IS IT BAD R

2538
01:32:01,880 --> 01:32:05,040
YOU, DO WE KNOW WHETHER MODEST

2539
01:32:05,040 --> 01:32:06,720
CHANGES IN THE BLOOD GLUCOSE

2540
01:32:06,720 --> 01:32:08,200
CURVE PERHAPS WITH SOME

2541
01:32:08,200 --> 01:32:09,840
FREQUENCY HAVE ANY DELETERIOUS

2542
01:32:09,840 --> 01:32:11,360
HEALTH EFFECTS?

2543
01:32:11,360 --> 01:32:15,320
>>I THINK IN AN IDEAL
WORLD, WE

2544
01:32:15,320 --> 01:32:17,360
WOULD BE ABLE TO MIMIC WHAT THE

2545
01:32:17,360 --> 01:32:18,760
BODY DOES PERFECTLY, WHICH IS

2546
01:32:18,760 --> 01:32:19,280
IMPOSSIBLE.

2547
01:32:19,280 --> 01:32:25,520
THE BODY IS SMARTER THAN ANY

2548
01:32:25,520 --> 01:32:28,840
REGIMEN COULD EVER HOPE TO MIM 

2549
01:32:28,840 --> 01:32:33,000
MIMIC.

2550
01:32:33,000 --> 01:32:34,200
ALSO THE GOALS FOR EACH PERSON

2551
01:32:34,200 --> 01:32:36,320
HAVE TO BE INDIVIDUALIZED.

2552
01:32:36,320 --> 01:32:38,240
SO WHILE WE DO HAVE THESE

2553
01:32:38,240 --> 01:32:40,840
CUTOFFS OF AN A1C LESS THAN 7%,

2554
01:32:40,840 --> 01:32:41,880
THAT'S NOT NECESSARILY THE GOAL

2555
01:32:41,880 --> 01:32:42,440
FOR EVERY PERSON.

2556
01:32:42,440 --> 01:32:44,200
FOR EXAMPLE, WHEN PEOPLE ARE

2557
01:32:44,200 --> 01:32:45,360
OLDER AND THEY'RE LIVING WITH

2558
01:32:45,360 --> 01:32:46,680
DIABETES, IT IS PERMISSIBLE

2559
01:32:46,680 --> 01:32:48,480
SOMETIMES TO HAVE A HIGHER A1C

2560
01:32:48,480 --> 01:32:50,520
LEVEL BECAUSE EPISODES OF

2561
01:32:50,520 --> 01:32:52,160
HYPOGLYCEMIA CAN LEAD TO REALLY

2562
01:32:52,160 --> 01:32:54,720
TRAGIC EVENTS.

2563
01:32:54,720 --> 01:32:55,600
LIKEWISE IF YOU'RE DEALING WITH

2564
01:32:55,600 --> 01:32:58,560
SOMEONE WHO'S INCREDIBLY YOUNG,

2565
01:32:58,560 --> 01:33:00,960
SOMETIMES A HIGHER A1C MIGHT BE

2566
01:33:00,960 --> 01:33:02,720
MORE PERMISSIBLE IN THE SETTING

2567
01:33:02,720 --> 01:33:04,480
OF THEM GOING TO SCHOOL AND NOT

2568
01:33:04,480 --> 01:33:07,080
WANTING TO RISK LOW BLOOD

2569
01:33:07,080 --> 01:33:10,400
SUGARS, SO AGAIN IT DEPENDS ON

2570
01:33:10,400 --> 01:33:10,920
EACH INDIVIDUAL AND

2571
01:33:10,920 --> 01:33:16,480
CONVERSATIONS WITH THEIR DOCTORS

2572
01:33:16,480 --> 01:33:20,360
IDEALLY WE RANGE FOR A RANGE IN

2573
01:33:20,360 --> 01:33:23,160
DIABETES FROM 170 TO 180, 180

2574
01:33:23,160 --> 01:33:25,520
MOSTLY AFTER MEALS AND SOMEWHERE

2575
01:33:25,520 --> 01:33:29,320
IN BETWEEN WITH AS FEW

2576
01:33:29,320 --> 01:33:29,920
VARIATIONS AS POSSIBLE, WHICH

2577
01:33:29,920 --> 01:33:35,600
CAN BE KIND OF DIFFICULT, AS

2578
01:33:35,600 --> 01:33:37,800
FAR AS TIME IN RANGE AND KIND OF

2579
01:33:37,800 --> 01:33:41,240
THE LEVELS THAT YOU SWING IN

2580
01:33:41,240 --> 01:33:45,760
BETWEEN, YOU SHOULD BE ABOUT --

2581
01:33:45,760 --> 01:33:47,320
GOODNESS, I'M FORGETTING THE

2582
01:33:47,320 --> 01:33:48,600
RIGHT WORD FOR IT, I WOULD HAVE

2583
01:33:48,600 --> 01:33:52,680
TO LOOK AT MY MONITOR, BUT

2584
01:33:52,680 --> 01:33:54,040
STANDARD DEVIATION, STANDARD

2585
01:33:54,040 --> 01:33:54,800
DEVIATION.

2586
01:33:54,800 --> 01:33:55,920
YOUR STANDARD DEVIATION SHOULD

2587
01:33:55,920 --> 01:33:57,200
BE ABOUT A THIRD OF YOUR AVERAGE

2588
01:33:57,200 --> 01:34:00,760
GLUCOSE.

2589
01:34:00,760 --> 01:34:04,000
>>WHY ARE ADOLESCENTS ON
THE

2590
01:34:04,000 --> 01:34:08,960
LIST OF NOT TAKING FULL

2591
01:34:08,960 --> 01:34:12,360
ADVANTAGE OF THE BEST THERAPIES?

2592
01:34:12,360 --> 01:34:15,000
IS THAT ADOLESCENCE OR IS

2593
01:34:15,000 --> 01:34:17,720
THAT -- WHAT'S YOUR --

2594
01:34:17,720 --> 01:34:21,720
>>I HAVE A LOT OF
THEORIES.

2595
01:34:21,720 --> 01:34:23,480
IT DEPENDS ON THE ADOLESCENT.

2596
01:34:23,480 --> 01:34:26,200
I THINK IT'S IMPORTANT TO

2597
01:34:26,200 --> 01:34:28,160
RECOGNIZE THAT AT THIS AGE,

2598
01:34:28,160 --> 01:34:30,040
DEVELOPMENTALLY WHAT'S VERY

2599
01:34:30,040 --> 01:34:31,480
IMPORTANT FOR ADOLESCENTS IS

2600
01:34:31,480 --> 01:34:33,440
FITTING IN WITH YOUR PEERS.

2601
01:34:33,440 --> 01:34:35,520
THAT'S PERHAPS THEIR NUMBER ONE,

2602
01:34:35,520 --> 01:34:36,960
TWO AND THREE PRIORITY WHEN IT

2603
01:34:36,960 --> 01:34:38,520
COMES TO CONSIDERING DIABETES

2604
01:34:38,520 --> 01:34:39,160
TREATMENTS.

2605
01:34:39,160 --> 01:34:40,560
THEY JUST WANT TO BE ABLE TO FIT

2606
01:34:40,560 --> 01:34:41,760
IN AND DO WHATEVER THEIR PEERS

2607
01:34:41,760 --> 01:34:42,880
ARE DOING.

2608
01:34:42,880 --> 01:34:45,080
AND BY WEARING A CGM, YOU HAVE

2609
01:34:45,080 --> 01:34:46,640
SOMETHING EXTRA ON YOUR BODY, SO

2610
01:34:46,640 --> 01:34:47,960
ALREADY YOU'RE SETTING YOURSELF

2611
01:34:47,960 --> 01:34:49,520
APART FROM YOUR PEERS, SAME WITH

2612
01:34:49,520 --> 01:34:52,240
AN INSULIN PUMP.

2613
01:34:52,240 --> 01:34:54,840
WHEN I WAS IN HIGH SCHOOL, I WAS

2614
01:34:54,840 --> 01:34:56,160
SUPPOSED TO TRY PUMP AND I PUT

2615
01:34:56,160 --> 01:34:57,920
IT ON MY BODY, I TRIED TO

2616
01:34:57,920 --> 01:34:59,680
SITUATE IT, I TRIED TO PUT IT IN

2617
01:34:59,680 --> 01:35:02,400
MY POCKET, I TRIED TO STUFF IT

2618
01:35:02,400 --> 01:35:03,520
INTO MY CLOTHES IN VARIOUS

2619
01:35:03,520 --> 01:35:05,720
PLACES AND BECAUSE IT LOOKED SO

2620
01:35:05,720 --> 01:35:07,680
DIFFERENT, I COULD NOT DO IT IN

2621
01:35:07,680 --> 01:35:11,840
HIGH SCHOOL, AND IN COLLEGE, I

2622
01:35:11,840 --> 01:35:13,480
FELT LIKE IT WAS MORE

2623
01:35:13,480 --> 01:35:14,560
ACCEPTABLE, PEOPLE DIDN'T

2624
01:35:14,560 --> 01:35:16,560
QUESTION AS MUCH WHAT IT WAS,

2625
01:35:16,560 --> 01:35:21,640
AND I WAS FINALLY ABLE TO START,

2626
01:35:21,640 --> 01:35:23,720
BUT AS FAR AS BEING ABLE TO FIT

2627
01:35:23,720 --> 01:35:25,240
IN WITH YOUR PEERS, I THINK

2628
01:35:25,240 --> 01:35:26,920
IMPORTANCE CAN BE IMPORTANT AND

2629
01:35:26,920 --> 01:35:29,440
THAT'S ALSO A BARRIER TO

2630
01:35:29,440 --> 01:35:35,120
TECHNOLOGY.

2631
01:35:35,120 --> 01:35:39,400
>>THERE IS LITERATURE,
QUITE A

2632
01:35:39,400 --> 01:35:45,160
BIT ACTUALLY, ON THE EFFECT OF

2633
01:35:45,160 --> 01:35:47,200
MARIJUANA ON INTERMEDIARY

2634
01:35:47,200 --> 01:35:48,280
METABOLISM, PARTICULARLY

2635
01:35:48,280 --> 01:35:52,360
CARBOHYDRATE METABOLISM.

2636
01:35:52,360 --> 01:35:55,320
IS THERE ANY SPINOFF ON THIS IN

2637
01:35:55,320 --> 01:35:57,400
TERMS OF ITS EFFECT IN A

2638
01:35:57,400 --> 01:35:58,520
DIABETIC PATIENT?

2639
01:35:58,520 --> 01:36:04,960
HAS THAT BEEN STUDIED OR IS IT

2640
01:36:04,960 --> 01:36:06,120
NOT A SIGNIFICANT FACTOR AS FAR

2641
01:36:06,120 --> 01:36:07,280
AS YOU KNOW?

2642
01:36:07,280 --> 01:36:09,000
>>OH, I THINK IT SHOULD

2643
01:36:09,000 --> 01:36:10,360
ABSOLUTELY BE STUDIED MORE,

2644
01:36:10,360 --> 01:36:11,880
ESPECIALLY AS MARIJUANA BECOMES

2645
01:36:11,880 --> 01:36:15,120
MORE LEGALIZED ACROSS THE UNITED

2646
01:36:15,120 --> 01:36:17,080
STATES.

2647
01:36:17,080 --> 01:36:19,840
I THINK THERE NEEDS TO BE MORE

2648
01:36:19,840 --> 01:36:24,200
REGULATED STUDIES ON THIS, AND

2649
01:36:24,200 --> 01:36:26,920
PERHAPS LESS STIGMA AROUND THIS

2650
01:36:26,920 --> 01:36:30,240
CONVERSATION.

2651
01:36:30,240 --> 01:36:30,920
THINGS THAT ARE IMPORTANT TO

2652
01:36:30,920 --> 01:36:34,440
TALK ABOUT PATIENTS DO INCLUDE

2653
01:36:34,440 --> 01:36:36,120
YOUR TYPICAL SEX, DRUGS AND ROCK

2654
01:36:36,120 --> 01:36:37,720
AND ROLL AND THESE THINGS CANNOT

2655
01:36:37,720 --> 01:36:41,480
HAVE ANY SORT OF BARRIERS TO

2656
01:36:41,480 --> 01:36:42,480
STUDYING BECAUSE YOU HAVE TO

2657
01:36:42,480 --> 01:36:44,000
GIVE THE RIGHT ANTICIPATORY

2658
01:36:44,000 --> 01:36:45,560
GUIDANCE TO PATIENTS IN THOSE

2659
01:36:45,560 --> 01:36:46,520
SITUATIONS, ESPECIALLY IF THEY

2660
01:36:46,520 --> 01:36:47,960
CHANGE METABOLISM, CAN BE

2661
01:36:47,960 --> 01:36:49,160
DANGEROUS FOR PEOPLE WITH

2662
01:36:49,160 --> 01:36:50,560
DIABETES.

2663
01:36:50,560 --> 01:36:51,760
SO HAVING THOSE CONVERSATIONS

2664
01:36:51,760 --> 01:36:54,640
AND HAVING THE DATA TO BACK IT

2665
01:36:54,640 --> 01:36:56,080
UP AND KNOW WHAT TO TELL

2666
01:36:56,080 --> 01:36:58,520
PATIENTS TO EXPECT WOULD BE

2667
01:36:58,520 --> 01:37:00,000
INCREDIBLY HELPFUL IN GUIDING

2668
01:37:00,000 --> 01:37:02,920
THOSE CONVERSATIONS.

2669
01:37:02,920 --> 01:37:04,040
>>VERY GOOD.

2670
01:37:04,040 --> 01:37:07,560
WELL, WE HAVE A SERIES OF

2671
01:37:07,560 --> 01:37:13,680
QUESTIONS THAT ARE SORT OF

2672
01:37:13,680 --> 01:37:15,160
PRIMARILY DIRECTED TO DOUG.

2673
01:37:15,160 --> 01:37:16,920
BUT LET ME RUN A FEW OF THEM BY

2674
01:37:16,920 --> 01:37:18,000
AND SEE, MAYBE YOU HAVE SOME

2675
01:37:18,000 --> 01:37:19,520
COMMENTS ABOUT IT.

2676
01:37:19,520 --> 01:37:23,920
SO HERE IS ONE.

2677
01:37:23,920 --> 01:37:28,760
FROM MARK SAYING, TO DR. MELTON,

2678
01:37:28,760 --> 01:37:30,520
YOU ARE INDUCING TOLERANCE BY

2679
01:37:30,520 --> 01:37:33,240
KNOCKING OUT GENES THAT WOULD

2680
01:37:33,240 --> 01:37:36,040
ORDINARILY ELICIT AN IMMUNE

2681
01:37:36,040 --> 01:37:36,600
RESPONSE.

2682
01:37:36,600 --> 01:37:39,200
WHY ISN'T THAT DONE FOR ORGAN

2683
01:37:39,200 --> 01:37:42,600
TRANSPLANT PATIENTS IN GENERAL?

2684
01:37:42,600 --> 01:37:47,440
DOES THIS HAVE SOME BROAD

2685
01:37:47,440 --> 01:37:48,480
APPLICATION TO THE WHOLE

2686
01:37:48,480 --> 01:37:50,840
QUESTION OF AUTOIMMUNITY?

2687
01:37:50,840 --> 01:37:54,560
OR IS IT SOMEWHAT RESTRICTED TO

2688
01:37:54,560 --> 01:37:58,480
INSULIN?

2689
01:37:58,480 --> 01:38:00,080
>>THAT'S AN EXCELLENT
QUESTION.

2690
01:38:00,080 --> 01:38:03,280
AND I SEE WHY THEY'RE ASKING.

2691
01:38:03,280 --> 01:38:06,320
I THINK THAT, YOU KNOW, MAYBE

2692
01:38:06,320 --> 01:38:08,960
THIS COULD EVENTUALLY CROSS OVER

2693
01:38:08,960 --> 01:38:10,160
INTO ORGAN TRANSPLANTATION.

2694
01:38:10,160 --> 01:38:11,480
OF COURSE I DON'T KNOW AS MUCH

2695
01:38:11,480 --> 01:38:12,720
ABOUT CELL BIOLOGY AS DOUG AND

2696
01:38:12,720 --> 01:38:14,360
HE WOULD BE ABLE TO GIVE A MORE

2697
01:38:14,360 --> 01:38:15,360
THOROUGH ANSWER, BUT WOULDN'T

2698
01:38:15,360 --> 01:38:17,680
THAT BE EXCITING IF IT WERE ABLE

2699
01:38:17,680 --> 01:38:20,680
TO BETTER BOTH FIELDS.

2700
01:38:20,680 --> 01:38:22,640
>>WELL, IT IS OF INTEREST
THAT,

2701
01:38:22,640 --> 01:38:27,680
YOU KNOW, ISLET CELL

2702
01:38:27,680 --> 01:38:29,720
TRANSPLANTATION IS IN AND OF

2703
01:38:29,720 --> 01:38:32,920
ITSELF NOT A NEW PHENOMENON.

2704
01:38:32,920 --> 01:38:37,640
IT WAS ACTUALLY ATTEMPTED, I

2705
01:38:37,640 --> 01:38:41,520
NING IN THINK IN THE 80s, AND TE

2706
01:38:41,520 --> 01:38:43,480
WAS QUITE A FLURRY OF ACTIVITY,

2707
01:38:43,480 --> 01:38:45,480
GRANT SUPPORT AND SO FORTH FOR

2708
01:38:45,480 --> 01:38:45,920
IT.

2709
01:38:45,920 --> 01:38:48,520
ONE OF THE GREAT PROBLEMS WAS

2710
01:38:48,520 --> 01:38:50,600
THE ISLETS WERE ADMINISTERED

2711
01:38:50,600 --> 01:38:53,480
EITHER BY INJECTION INTO THE

2712
01:38:53,480 --> 01:38:58,160
PORTAL VEIN OR IN SOME FORM OF

2713
01:38:58,160 --> 01:38:59,600
ENCAPSULATED MATERIAL THAT WAS

2714
01:38:59,600 --> 01:39:03,800
PLACED USUALLY IN THE ABDOMINAL

2715
01:39:03,800 --> 01:39:07,960
CAVITY.

2716
01:39:07,960 --> 01:39:11,960
BUT THOSE CELLS DON'T LAST VERY

2717
01:39:11,960 --> 01:39:16,760
LONG AND THEY'RE EITHER ATTACKED

2718
01:39:16,760 --> 01:39:18,760
IMMUNOLOGICALLY OR PERHAPS

2719
01:39:18,760 --> 01:39:21,520
THEY'RE BEREFT OF THEIR BLOOD

2720
01:39:21,520 --> 01:39:23,040
SUPPLY, I DON'T KNOW, BUT AT ANY

2721
01:39:23,040 --> 01:39:24,640
RATE, THAT WHOLE OPERATION USING

2722
01:39:24,640 --> 01:39:27,680
THOSE KINDS OF ISLET CELL

2723
01:39:27,680 --> 01:39:31,320
PREPARATIONS HAS, I THINK,

2724
01:39:31,320 --> 01:39:31,840
COMPLETELY ENDED.

2725
01:39:31,840 --> 01:39:33,320
I DON'T BELIEVE IT'S SUPPORTED

2726
01:39:33,320 --> 01:39:38,160
ANYMORE.

2727
01:39:38,160 --> 01:39:41,560
SO WHAT DOUG IS PROPOSING IS

2728
01:39:41,560 --> 01:39:47,800
USING THOSE SAME METHODS FOR

2729
01:39:47,800 --> 01:39:48,800
ADMINISTRATION, AND IT'S TOO BAD

2730
01:39:48,800 --> 01:39:51,240
HE'S NOT WITH US SO HE CAN

2731
01:39:51,240 --> 01:39:54,280
COMMENT ABOUT WHETHER THERE ARE

2732
01:39:54,280 --> 01:39:56,040
SOME DEVELOPMENTS THAT

2733
01:39:56,040 --> 01:39:59,800
FACILITATE THAT FORM OF

2734
01:39:59,800 --> 01:40:01,120
ADMINISTRATION ASIDE FROM THE

2735
01:40:01,120 --> 01:40:02,480
NATURE OF THE CELLS THEMSELVES

2736
01:40:02,480 --> 01:40:03,720
AND THEIR ORIGIN.

2737
01:40:03,720 --> 01:40:07,160
SO WE'LL FORWARD THAT QUESTION

2738
01:40:07,160 --> 01:40:13,040
TO HIM ALONG WITH A GOOD MANY

2739
01:40:13,040 --> 01:40:18,200
OTHERS IN THE ANIMALS, HOW LONG

2740
01:40:18,200 --> 01:40:19,280
CAN THESE CELLS WORK?

2741
01:40:19,280 --> 01:40:23,600
IS IT REALLY NECESSARY TO HAVE

2742
01:40:23,600 --> 01:40:26,040
IMMUNOSUPPRESSION?

2743
01:40:26,040 --> 01:40:28,720
WELL, CAN YOU INDUCE TOLERANCE?

2744
01:40:28,720 --> 01:40:31,080
ALL THE BASIC QUESTIONS OF

2745
01:40:31,080 --> 01:40:33,600
IMMUNOLOGY HAVE POPPED UP, AND

2746
01:40:33,600 --> 01:40:34,960
WE'LL REFER THEM TO HIM UNLESS

2747
01:40:34,960 --> 01:40:36,560
YOU WANT TO MAKE SOME COMMENT

2748
01:40:36,560 --> 01:40:38,280
ABOUT IT.

2749
01:40:38,280 --> 01:40:39,840
>>NO, REFERRAL SOUNDS
GREAT.

2750
01:40:39,840 --> 01:40:42,600
WE CAN REFER TO DOUG.

2751
01:40:42,600 --> 01:40:44,320
>>I THINK WE'D BOTH BE
VERY

2752
01:40:44,320 --> 01:40:45,600
INTERESTED IN HIS REPLY.

2753
01:40:45,600 --> 01:40:46,600
>>MM-HMM.

2754
01:40:46,600 --> 01:40:49,600
>>SO LISTEN, I WANT TO
THANK

2755
01:40:49,600 --> 01:40:51,760
YOU ON BEHALF OF -- I TOLD YOU

2756
01:40:51,760 --> 01:40:57,480
THIS PROGRAM GOES GLOBALLY, AND

2757
01:40:57,480 --> 01:40:58,760
WE FREQUENTLY HAVE PEOPLE IN

2758
01:40:58,760 --> 01:41:00,280
SOMETHING LIKE 38 DIFFERENT

2759
01:41:00,280 --> 01:41:03,720
COUNTRIES.

2760
01:41:03,720 --> 01:41:06,920
SO HOPEFULLY YOU'LL RECEIVE SOME

2761
01:41:06,920 --> 01:41:08,240
RESPONSES WHERE YOU'LL BE ABLE

2762
01:41:08,240 --> 01:41:11,720
TO HELP PEOPLE.

2763
01:41:11,720 --> 01:41:13,840
BUT IT'S REALLY BEEN A PLEASURE,

2764
01:41:13,840 --> 01:41:16,280
AND WE ALL CONGRATULATE YOU ON

2765
01:41:16,280 --> 01:41:21,240
YOUR SUCCESSES AND LOOK FORWARD

2766
01:41:21,240 --> 01:41:22,360
TO EVEN BRIGHTER DAYS.

2767
01:41:22,360 --> 01:41:24,080
>>WELL THANK YOU AGAIN SO
MUCH

2768
01:41:24,080 --> 01:41:26,880
FOR HAVING ME AND FOR EVERYONE

2769
01:41:26,880 --> 01:41:29,400
WHO JOINED THE VIDEOCAST TODAY.

2770
01:41:29,400 --> 01:41:30,600
WE REALLY APPRECIATE IT.

2771
01:41:30,600 --> 01:41:31,400
>>OKAY.

2772
01:41:31,400 --> 01:41:36,360
SO I GUESS YOU GO BACK TO WORK,

2773
01:41:36,360 --> 01:41:39,160
AND CONTINUE YOUR GOOD WORK.

2774
01:41:39,160 --> 01:41:39,320
BYE.

2775
01:41:39,320 --> 00:00:00,000
>>THANK YOU, WIN.