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Welcome to the Clinical
Center Grand Rounds,

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a weekly series of educational
lectures for physicians and

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health care professionals
broadcast from the Clinical

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Center at the National
Institutes of Health in

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Bethesda, MD.

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The NIH Clinical Center is the
world's largest hospital totally

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dedicated to investigational
research and leads the global

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effort in training today's
investigators and discovering

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tomorrow's cures.

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Learn more by visiting us online
at http://clinicalcenter.nih.gov

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TODAY'S LECTURE IS PART OF OUR

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CLINICAL GRAND ROUNDINGS GREAT

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TEACHER SERIES TODAY WE HONOR

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THE LEGACY OF DR. JOHN DECKER,

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WHO SERVED FROM 1983-1990.

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DURING HADIS TENURE AS DIRECTOR

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ADVANCES AT THE CLINICAL CENTER

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INCLUDED DEVELOPMENT OF THE

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POSITRON EMISSION TOMOGRAPHY

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PROGRAM, INITIATION OF THE USE

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OF MAGNETIC IMAGES AND

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MARSHALING OF SUPPORT AGE

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RESEARCH.

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I'M ESPEBLLY HONORED AND PLEASED

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TO WELCOME THE DECKER FAMILY WHO

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ARE JOINING US TODAY VIRTUALLY.

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NOW, I WOULD LIKE TO TURN THE

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PODIUM OVER TO MISS SANDRA HOYE

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ADVANCE ASSOCIATE FOR THE

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FOUNDATION FOR THE NATIONAL

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INSTITUTES OF HEALTH FOR

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REMARCOS BEHALF OF THE FNIH.

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>> THANK YOU DR. BURKLOW.

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GOOD AFTERNOON AND WELCOME, MY

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NAME IS KACCT SANDRA HOCE AND

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I'M AN ADVANCE ASSOCIATE FOR THE

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FOUNDATION FOR THE NIH.

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I AM DELIGHTED TO WELCOME YOU TO

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THE 18th ANNUAL JOHN LAWS

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DECKER MEMORIAL LECTURE

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FEATURING THE 2022 DISTINGUISHED

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CLINICAL TEACHER AWARD RECIPIENT

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DR. JONATHAN M. HERNÁNDEZ.

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DR. HERNÁNDEZ WE LOOK FORWARD TO

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YOUR PRESENTATION.

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THE FNIH IS PROUD TO HAVE BEEN A

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PARTNER OF THE IMPORTANT LECTURE

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SINCE 2003 WHEN THE NIH BEGAN

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RECOGNIZING THE LATE NIH

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CLINICAL DIRECTOR ANNUALLY

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THROUGH THE CLINICAL CENTER

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GRAND ROUNDS LECTURE SERIES.

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AT THIS TIME, FRIENDS AND FAMILY

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OF DR. DECKER WORKED WITH THE

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FNIH TO ESTABLISH THE MEMORIAL

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FUND IN HONOR OF THEIR LATE

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FATHER.

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DURING HIS LIFETIME DR. DECKER

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WAS AN OUTSTANDING TEACHER WHO

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THRIVED TO CONNECT TO SCIENTIFIC

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COMMUNICATIONS AROUND THE WORLD

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TO ACCELERATE IMPORTANT

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RESEARCH.

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THIS IS THEIR AND OUR WAY OF

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EXTENDING HIS LEGACY.

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I WANT TO THANK THE DECKER

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FAMILY FOR THEIR GENEROSITY AND

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INSPIRED VISION IN ESTABLISHING

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THE DECKER MEMORIAL FUND.

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THE FNIH IS PROUD OF OUR LONG

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LASTING COLLABORATION WITH YOU

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AND THE CLINICAL CENTER TO

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RECOGNIZE INNOVATIVE

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ACCOMPLISHMENTS IN CLINICAL

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RESEARCH AND THEIR LASTING

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IMPACT ON TRAINING THE NEXT

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GROUP OF GREAT SCIENTISTS.

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WE INVITE TO YOU EXPLORE THE

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MANY PARTNERSHIPS FORMED AND THE

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INNOVATIVE SCIENTIFIC THINKING

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THAT IS SUPPORTED THROUGH OUR

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PROGRAMS ON THE FNIH WEBSITE,

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FNIH.ORG.

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I WILL NOW TURN THINGS BACK TO

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DR. BURKLOW TO INTRODUCE THE NIH

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CLINICAL FELLOWS COMMITTEE.

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THANK YOU FOR JOINING US FOR

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THIS EVENT AND PLEASE ENJOY THE

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18th ANNUAL JOHN LAWS DECKER

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MEMORIAL LECTURE.

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>> THANK YOU MISS HOYE FOR
YOUR

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KIND REMARKS AND ESPECIALLY TO

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THE DECKER FAMILY FOR YOUR

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CONTINUED GENERATEDDOUS SUPPORT,

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IT IS MUCH APPRECIATED.

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EACH YEAR, NIH CLINICAL FELLOWS

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SEEK OUT A HIGHLY REGARDED

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TEACHER TO RECEIVE THE CLINICAL

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TEACHER AWARD.

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DR. DECKER WAS AN INSPIRING

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LEADER AND MENTOR SO IT'S VERY

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IMPORTANT THAT THE DISTINGUISHED

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CLINICAL TEACHER AWARDEE

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DELIVERED ANNUAL DECKER MEMORIAL

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LECTURE.

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BEFORE INTRODUCING TODAY'S

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SPEAKER AND THE 2022

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DISTINGUISHED CLINICAL TEACHER

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AWORRIEDEE, I WOULD LIKE TO TURN

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THE VIRTUAL PLATFORM OVER TO

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DR. MARJA BROLINSON WHO CO

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CHAIRS THE COMMITTEE TO,A NOUNS

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THE WINNER OF THE 2023 CLINICAL

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TEACHER AWARD.

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>> MY NAME IS MARJA
BROLINSON

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AND I AM THE CLINICAL FELLOWS

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COMMITTEE CO CHAIR, I WOULD LIKE

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TO THANK DR. BURKLOW FOR HIS

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ONGOING SUPPORT AND THE NIH

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CLINICAL FELLOWS AND FOR A

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STRONG COMMITMENT TO THE

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IMPORTANCE OF MENTORING AT NIH.

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I AM HOONORRED TO,A NOUNS THE

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WINNER FOR THE 2023

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DISTINGUISHED CLINICAL TEACHER

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AWARD.

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A MENTOR GUIDES PROFESSIONAL

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GROWTH BY HELPING TRAINEES

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IDENTIFY AND DEVELOP SKILLS AND

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TALENT, SET AND ACHIEVE GOALS,

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ANTICIPATE ROAD BLOCKS AND

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OVERCOME OBSTACLES.

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A CLINICAL MENTOR ALSO 'EM

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BODIES THE CHARACTERISTICS OF AN

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ETHICAL AND PASSIONAL PHYSICIAN.

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ALL OF THE INDIVIDUALS NOMINATED

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FOR THIS YEAR'S AWARD AND

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RECOGNITION AS OUTSTANDING

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CLINICAL MENTORS.

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I WOULD LIKE TO THANK ALL OF THE

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NOMINEES FOR THEIR COMMITMENT TO

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TRAINING CLINICAL INVESTIGATORS

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AT THE NIH AND THEIR OVERALL

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CONTRIBUTION TO MEDICAL

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EDUCATION.

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EACH YEAR, THE DISTINGUISHED

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CLINICAL TEACHER AWARD IS

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DECIDED BY A VOTE OF THE

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CLINICAL FELLOWS AND PRESENTED

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TO AN INDIVIDUAL WHO EXEMPLIFIES

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THE IDEA OF A MENTOR TEACHER AND

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CLINICIAN AND RESEARCHER.

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HERE ARE A FEW WORDS EXPRESSED

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ABOUT THIS YEAR'S AWARDEE.

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WITH THE UTMOST PATIENCE AND

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SINCERITY HE ALWAYS GOES ABOVE

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AND BEYOND TO TEACH THE FELLOWS

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HOWEVER MANY TIME ITS TAKES TO

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SOLIDIFY OUR KNOWLEDGE MAKING

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DIFFICULT CONCEPTS EASIER AND

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FORMING US INTO BETTER

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CLINICIANS.

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YOU CAN ALWAYS FIND HIM WITH A

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CUP OF COFFEE IN HAND, A JOKE IN

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HIS BACK POCKET AND A SMILE

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TWINKLING THROUGH HIS EYES

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BEHIND HIS MASK AS HE JUMPS

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BETWEEN FELLOWS TO HELP THEM GET

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THROUGH DIFFICULT PATIENTS.

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IF YOU LOOK CLOSE ENOUGH, YOU

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CAN FIND EXTREMELY HELPFUL

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CLINICAL PEARLS IN HIS MANY

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PUBLICATIONS.

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ONE PUBLISHED EXAMPLE IS

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HYPOCYSTITESIS AN UPPERDATEOT

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DISORDERS DIAGNOSE AND

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MANAGEMENT OF PITUITARYY

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INFLAMMATION, PLEASE JOIN ME IN

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WELCOMING OUR CLINICAL AWARD

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WINNER DR. SRIRAM, GUBBI, IN THE

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NATIONAL INSTITUTE OF DIABETES

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AND DIGESTIVE AND KIDNEY

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DISEASES.

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I WOULD NOW LIKE TO TURN THE MIC

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OVER TO DR. BURKLOW TO INTRODUCE

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TODAY'S SPEAKER AND OUR 2022

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DCTA AWARD WINNER.

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THANK YOU.

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>> THANK YOU DR. BROLINSON
AND

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MANY CONGRATULATIONS TO

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DR. GUBBI.

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I'M NOW HONORED TO INTRODUCE

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TODAY'S SPEAKER THE A RESENT OF

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THE 2022 DISTINGUISHED TEACHER

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AWARD, DR. JONATHAN M.

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HERNÁNDEZ.

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HE IS THE CHIEF OF THE SURGAL

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ONCOLOGY SECTION, HEAD OF THE

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METASTASIS BIOLOGY SECTION AT

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THE CENTER FOR CANCER RESEARCH

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AND THE NATIONAL CANCER

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EN--STRATEGIESITUTE AND

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ASSOCIATE PROFESSOR OF SURGERY

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FOR UNIFORM SERVICES, UNIVERSITY

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OF HEALTH SCIENCES.

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DR. HERNÁNDEZ EARNED HIS MEDICAL

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DEGREE FROM THE UNIVERSITY OF

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FLORIDA IN 2005 AND COMPLETEDT

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GENERAL SURGERY

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UNIVERSITY OF SOUTH FLORIDA.

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DURING HIS HESIDENCY

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DR. HERNÁNDEZ SPENT 2 YEARS AT

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THE MOFET CANCER RESEARCH CENTER

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AND INSTITUTE, FOR LIVER,

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METASTASIS, AND METASTATIC

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SPREAD TO SUPPORT THE NIH

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FUNDING.

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FOLLOWING HIS RESIDENCY HE

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COMPLETED SURGERY AND PSYCHOLOGY

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AT THE MEMORY RESPONSOR SLOAN

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KETTERRING CANCER CENTER.

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DURING FELLOWSHIP TRAINING

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DR. HERNÁNDEZ SPENT AN

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ADDITIONAL 2 YEARS IN DEDICATED

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BASIC RESEARCH STUDYING

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METASTATIC COLONIZATION WHILE A

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SCHOLAR IN THE CELL BIOLOGY

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PROGRAM OF THE SLOAN KETTERRING

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INSTITUTE AND A VISITING

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INVESTIGATOR AT THE WILD MEDICAL

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COLLEGE OF CORNELL UNIVERSITY.

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DR. HERNÁNDEZ JOINED THE

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SURGICAL ONCOLOGY PROGRAM IN

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2016 AS A TENURED TRACK

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INVESTIGATOR.

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CLINICALLY HE SPECIALIZED IN THE

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TREATMENT OF METASTATIC AND

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TUMOR AND BILE DUCTS AND

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PANCREAS AND SURGICAL MANAGEMENT

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OF COMPLEX ABDOMINAL TUMORS,

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DR. HERNÁNDEZ FOCUSED ON THE

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IMELEMENTATION OF AN EXVIEF O

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TUMOR SYSTEMS THAT ALLOW HIS

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LABORATORY TO FULLY CHARACTERIZE

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THESE IN THE OPERATING ROOM AND

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EVALUATE THERAPIES, AND THEY

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ALLOW THESE TO BUILD COMBINATION

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THERAPIES FOR TUMORS AND

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DELINEATE AND TARGET

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UNCHARACTERRIZED SINGLE AXIS FOR

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GAIN IN PATIENTS WITH COLANGIAL

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CARCINOMA AND ELUCIDATE

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MECHANISMS FOR WHICH TUMOR CELLS

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MARK THE ENVIRONMENT OF THIS

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ORGAN TO FORM LIFE THREATENING

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METASTASIS.

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00:09:17,800 --> 00:09:19,600
DR.ENER NANOG IT DES IS BOARD

258
00:09:19,600 --> 00:09:21,560
CERT TIE INDEED GENERAL SURGERY

259
00:09:21,560 --> 00:09:23,280
AND COMPLEX GENERAL SURGICAL

260
00:09:23,280 --> 00:09:24,760
ONCOLOGY BY THE AMERICAN BOARD

261
00:09:24,760 --> 00:09:26,720
OF DIRECTORS OF SURGERY.

262
00:09:26,720 --> 00:09:27,800
MEMBER OF THE AMERICAN

263
00:09:27,800 --> 00:09:30,640
ASSOCIATION FOR CANCER WERE,

264
00:09:30,640 --> 00:09:33,680
ASSOCIATE FOR SURGICAL ONCOLOGY,

265
00:09:33,680 --> 00:09:35,680
AMERICA'S PAN KRE TINSAT OLDER

266
00:09:35,680 --> 00:09:37,280
PEOPLE ASSOCIATION, SOCIETY OF

267
00:09:37,280 --> 00:09:40,480
UNIVERSITY SURGEONS AND AMERICAN

268
00:09:40,480 --> 00:09:44,040
COLLEGE OF OF SURGEONS,

269
00:09:44,040 --> 00:09:46,080
DR. HERNÁNDEZ HAS AUTHORED OVER

270
00:09:46,080 --> 00:09:47,360
100 PEER PUBLICATIONS AND

271
00:09:47,360 --> 00:09:49,280
NUMEROUS BOOK CHAPTERS AND

272
00:09:49,280 --> 00:09:50,200
AUTHORITATIVE TEXTBOOKS.

273
00:09:50,200 --> 00:09:52,600
HIS TALK TODAY IS ENTITLED THE

274
00:09:52,600 --> 00:09:54,680
DEVELOPMENT AND IMPLEMENTATION

275
00:09:54,680 --> 00:09:56,840
OF EXVIVO HUMAN TUMOR SYSTEMS

276
00:09:56,840 --> 00:09:57,680
FOR TRANSLATIONAL SCIENCE.

277
00:09:57,680 --> 00:10:05,320
PLEASE WELCOME OUR SPEAKER

278
00:10:05,320 --> 00:10:07,880
DR. JONATHAN HERNÁNDEZ.

279
00:10:07,880 --> 00:10:10,360
THANK YOU SO MUCH, TOM THANK YOU

280
00:10:10,360 --> 00:10:12,400
FOR THE INTRODUCTION, MARJA,

281
00:10:12,400 --> 00:10:15,720
THANK YOU ABOUT THE KIND WORDS

282
00:10:15,720 --> 00:10:17,120
ABOUT MENTORING AND TEACHING AND

283
00:10:17,120 --> 00:10:20,280
THE TIELT OF MY TALK IS AGAIN IS

284
00:10:20,280 --> 00:10:22,600
THE DEVELOPMENT AND

285
00:10:22,600 --> 00:10:23,840
IMPLEMENTATION OF EXVIVO HUMAN

286
00:10:23,840 --> 00:10:26,680
TUMOR SYSTEMS FOR TRANSLATIONAL

287
00:10:26,680 --> 00:10:26,880
SCIENCE.

288
00:10:26,880 --> 00:10:29,320
I WANT TO START WITH A FEW

289
00:10:29,320 --> 00:10:31,080
COMMENTS, THIS IS A HUMBLING

290
00:10:31,080 --> 00:10:32,760
AWARD TO BE HONOR WIDE, I DON'T

291
00:10:32,760 --> 00:10:33,840
NECESSARILY SEE MYSELF AS A

292
00:10:33,840 --> 00:10:35,120
MENTORSHIP SKILL OR OR A

293
00:10:35,120 --> 00:10:35,920
TEACHER, INSTEADY I SORT OF

294
00:10:35,920 --> 00:10:38,880
THINK ABOUT THE PEOPLE WHO WORK

295
00:10:38,880 --> 00:10:42,240
WITH ME AND WORKED WITH ME

296
00:10:42,240 --> 00:10:43,440
THROUGH THE YEARS AS SORT OF

297
00:10:43,440 --> 00:10:46,200
PARTNERS AND THIS HAS BEEN A

298
00:10:46,200 --> 00:10:47,960
MUTUALLY BENEFICIAL RELATIONSHIP

299
00:10:47,960 --> 00:10:52,440
AND SO I--INSTEAD OF SORT OF

300
00:10:52,440 --> 00:10:53,600
TALKING ABOUT A GIVEN TOPIC,

301
00:10:53,600 --> 00:10:55,680
WHAT I WANT TO DO IS HIGHLIGHT

302
00:10:55,680 --> 00:10:59,160
THE ACHIEVEMENTS OF MY PARTNERS,

303
00:10:59,160 --> 00:11:01,480
MY CLINICAL FELLOW PARTNERS OVER

304
00:11:01,480 --> 00:11:02,720
THE LAST SEVERAL YEARS, SO

305
00:11:02,720 --> 00:11:04,720
THAT'S WHAT I WANT TO SPEND THE

306
00:11:04,720 --> 00:11:06,240
NEXT 40 MINUTES AND SO I WILL DO

307
00:11:06,240 --> 00:11:09,400
THAT IN THE CONTEXT OF SORT OF 3

308
00:11:09,400 --> 00:11:15,480
AREAS, BUT FIRST I WILL TALK

309
00:11:15,480 --> 00:11:16,560
ABOUT EXVIVO LIVER SYSTEM AND

310
00:11:16,560 --> 00:11:17,720
SECONDLY I WILL TALK ABOUT THE

311
00:11:17,720 --> 00:11:18,760
SMART SYSTEM AND TELL WHAT YOU

312
00:11:18,760 --> 00:11:20,600
THAT IS AND LAST I WILL TALK

313
00:11:20,600 --> 00:11:22,800
ABOUT USING THE TOOLS SO THOSE

314
00:11:22,800 --> 00:11:25,360
WILL BE 2 SEPARATE ROUTES THAT I

315
00:11:25,360 --> 00:11:27,760
SHOW HOW WE UTILIZE THESE TUMOR

316
00:11:27,760 --> 00:11:28,880
SYSTEMS AND THAT'S HOW WE WILL

317
00:11:28,880 --> 00:11:29,680
DO THIS.

318
00:11:29,680 --> 00:11:32,040
SO I THINK ABOUT HUMAN TUMOR

319
00:11:32,040 --> 00:11:34,720
SETS SORT OF VERY COOL, VERY

320
00:11:34,720 --> 00:11:37,080
UNIQUE THINGS THAT HAPPEN

321
00:11:37,080 --> 00:11:37,640
UNFORTUNATELY TO PEOPLE.

322
00:11:37,640 --> 00:11:38,920
IT'S VERY HARD TO REPLICATE AND

323
00:11:38,920 --> 00:11:40,200
YOU THINK ABOUT IT WHERE WOULD

324
00:11:40,200 --> 00:11:41,920
YOU EVEN GO TO GET TUMORS, YOU

325
00:11:41,920 --> 00:11:45,200
VALID TO GO TO PATIENT WHO IS

326
00:11:45,200 --> 00:11:46,280
DEVELOP THESE, THEY'RE VERY

327
00:11:46,280 --> 00:11:51,520
COMPLICATED AND I HAD THIS IDEA

328
00:11:51,520 --> 00:11:52,520
THAT ALL THESE PRECLINICAL

329
00:11:52,520 --> 00:11:55,320
MODELS ARE AVAILABLE TO US, THEY

330
00:11:55,320 --> 00:11:56,680
DON'T--THEY DON'T REPLICATE WHAT

331
00:11:56,680 --> 00:11:58,800
WE ACTUALLY SEE AND FEEL IN

332
00:11:58,800 --> 00:12:02,080
PEOPLE WHEN WE OPERATE ON THEM

333
00:12:02,080 --> 00:12:02,360
EVERY DAY.

334
00:12:02,360 --> 00:12:05,880
DISP SO I HAD THIS IDEA THAT WE

335
00:12:05,880 --> 00:12:07,640
SHOULD INSTEAD MAYBE UTILIZE THE

336
00:12:07,640 --> 00:12:09,040
TUMORS THAT WE'RE TAKING OUT OF

337
00:12:09,040 --> 00:12:11,200
PEOPLE IN A DIFFERENT WAY, DON'T

338
00:12:11,200 --> 00:12:13,800
PUT THEM IN A FREEZER, DON'T

339
00:12:13,800 --> 00:12:14,880
JUST SEQUENCE THEM, BUT ACTUALLY

340
00:12:14,880 --> 00:12:18,200
USE THEM SO I HAD THIS IDEA THAT

341
00:12:18,200 --> 00:12:19,760
WE WOULD DO THE FOLLOWING, SO

342
00:12:19,760 --> 00:12:22,520
I'M A LIVER SURGEON, I SPEND A

343
00:12:22,520 --> 00:12:24,320
FAIR AMOUNT OF TIME DOING LIVER

344
00:12:24,320 --> 00:12:26,200
SURGERY, INSTEAD OF TAKING OFF A

345
00:12:26,200 --> 00:12:27,600
THIRD OR A QUARTER OF SOMEBODY'S

346
00:12:27,600 --> 00:12:30,840
LIVER SO I CAN TAKE OFF THE

347
00:12:30,840 --> 00:12:32,440
TUMOR, I WOULD INSTEADY TAKE

348
00:12:32,440 --> 00:12:34,320
THIS DOWN THE HALLWAY TO A

349
00:12:34,320 --> 00:12:35,440
PROFUSION MACHINE AND

350
00:12:35,440 --> 00:12:37,600
KAN--KANAUE LATE IT AND KEEP THE

351
00:12:37,600 --> 00:12:39,200
THING VIABLE AND IF I COULD DO

352
00:12:39,200 --> 00:12:42,600
THAT, THAT WOULD THEN BE AS REAL

353
00:12:42,600 --> 00:12:46,000
AS THINGS WOULD EVER BE AND

354
00:12:46,000 --> 00:12:48,520
WHATEVER QUESTIONS WE ASKED

355
00:12:48,520 --> 00:12:49,280
WOULD BE TRANSLATIONALLY

356
00:12:49,280 --> 00:12:51,320
RELEVANT AND THEN WE COULD START

357
00:12:51,320 --> 00:12:53,080
DOING REALLY COOL EXPERIMENTS

358
00:12:53,080 --> 00:12:54,720
LIKE THE FOLLOWING, WE COULD

359
00:12:54,720 --> 00:12:55,760
GIVE VARIOUS DRUGS DEPENDING ON

360
00:12:55,760 --> 00:12:57,160
WHAT WE ALREADY KNEW ABOUT THE

361
00:12:57,160 --> 00:12:58,160
TUMOR BEFORE WE OPERATED ON THE

362
00:12:58,160 --> 00:13:02,320
PASHT AND THAT COULD BE BASED ON

363
00:13:02,320 --> 00:13:04,640
MUTATIONAL STATUS OR SOME SORT

364
00:13:04,640 --> 00:13:07,640
OF TRANSCRIPT THAT THE TUMOR WAS

365
00:13:07,640 --> 00:13:09,840
EXPRESSING, OF COURSE, NOW, A

366
00:13:09,840 --> 00:13:13,480
LOT OF THINGS ARE FOCUSED ON

367
00:13:13,480 --> 00:13:14,120
IMMUNOTHERAPY AND ACTIVATING THE

368
00:13:14,120 --> 00:13:17,640
IMMUNE SYSTEM IN THE TUMOR, AND

369
00:13:17,640 --> 00:13:18,840
IT'S CERTAINLY FOCUSED DRUGS ON

370
00:13:18,840 --> 00:13:19,200
THESE EFFORTS.

371
00:13:19,200 --> 00:13:21,360
THESE ARE VERY HARD TO

372
00:13:21,360 --> 00:13:23,120
RECAPITULATE OUTSIDE OF

373
00:13:23,120 --> 00:13:26,640
PATIENTS, AND IT WILL GIVE CELL

374
00:13:26,640 --> 00:13:27,920
THERAPY INTO OUR SYSTEM AND NONE

375
00:13:27,920 --> 00:13:29,560
OF THIS WOULD HARM ANY CAUSE OF

376
00:13:29,560 --> 00:13:30,720
HARM TO THE PATIENT BECAUSE

377
00:13:30,720 --> 00:13:32,400
EVERYTHING WOULD BE OUTSIDE THE

378
00:13:32,400 --> 00:13:35,400
PATIENT AND SO THIS WAS A

379
00:13:35,400 --> 00:13:37,240
CONCEPT I SORT OF CAME WITH.

380
00:13:37,240 --> 00:13:42,480
SO I--YOU KNOW I GOT HERE IN

381
00:13:42,480 --> 00:13:44,760
FALL OF 2016 AND I AGREED TO

382
00:13:44,760 --> 00:13:48,200
TAKE SEVERAL FELLOWS IN THE LAB,

383
00:13:48,200 --> 00:13:51,360
JULY OF 2017, I TOOK 3 AGAINST

384
00:13:51,360 --> 00:13:54,040
THE ADVICE OF MANY PEOPLE.

385
00:13:54,040 --> 00:13:56,120
I COULDN'T TALK THEM OUT OF IT,

386
00:13:56,120 --> 00:13:57,160
THEY SIMPLY WOULDN'T LISTEN AND

387
00:13:57,160 --> 00:13:58,680
SO WE STARTED A PARTNERSHIP AND

388
00:13:58,680 --> 00:14:00,360
WE SAID OKAY, LET'S SEE IF WE

389
00:14:00,360 --> 00:14:05,560
CAN MAKE THIS COME TO  FRUITIONS

390
00:14:05,560 --> 00:14:07,120
AND WE CONVINCED THE POWERS THAT

391
00:14:07,120 --> 00:14:10,080
BE AT NCI THAT WE NEED A

392
00:14:10,080 --> 00:14:10,880
TRANSPLANT TRANSFUSION MACHINE,

393
00:14:10,880 --> 00:14:13,960
AT THE TIME NONE OF THIS WAS

394
00:14:13,960 --> 00:14:16,080
APPROVED IN THE FDA, WE BOUGHT

395
00:14:16,080 --> 00:14:18,080
IT WITH FROM A COMPANY IN

396
00:14:18,080 --> 00:14:19,280
EUROPE, WE DEVELOPED A BACK

397
00:14:19,280 --> 00:14:21,080
TABLE SET UP AND PLANNED

398
00:14:21,080 --> 00:14:22,240
EVERYTHING, WITH THE APPROVAL OF

399
00:14:22,240 --> 00:14:23,640
THE NCI AND PLANNED IT

400
00:14:23,640 --> 00:14:25,160
APPROPRIATELY AND SAM AND 2 OF

401
00:14:25,160 --> 00:14:26,120
THE FELLOWS THAT REALLY WORKED

402
00:14:26,120 --> 00:14:30,920
DAY AND NIGHT ON THIS ARE SAM

403
00:14:30,920 --> 00:14:32,000
ROUGH AND MIKE [INDISCERNIBLE].

404
00:14:32,000 --> 00:14:34,400
THEY WOULD SORT OF WALK THE

405
00:14:34,400 --> 00:14:36,320
LIVER DOWN THE HALL AND REALLY

406
00:14:36,320 --> 00:14:38,040
SPEND THE NIGHT NEXT TO THE

407
00:14:38,040 --> 00:14:40,000
MACHINE, THEY HAD A BET IN THE

408
00:14:40,000 --> 00:14:41,240
LAB AND THEY WOULD SPEPPED THE

409
00:14:41,240 --> 00:14:44,920
NIGHT NEXT TO THE MACHINE AND WE

410
00:14:44,920 --> 00:14:46,240
DID THIS SEVERAL TIMES SO THIS

411
00:14:46,240 --> 00:14:47,440
WAS THE FIRST PATIENT WE DID.

412
00:14:47,440 --> 00:14:50,840
YOU CAN SEE A LESION THERE, THIS

413
00:14:50,840 --> 00:14:58,280
IS A CO LANCHIAL CARCINOMA. 

414
00:14:58,280 --> 00:14:59,720
WE CANNULATED THE VASCULARRURE

415
00:14:59,720 --> 00:15:01,920
AND PUT IT ON THE MACHINE AND

416
00:15:01,920 --> 00:15:03,520
FOR OUR FIRST HUMAN RUN DIDN'T

417
00:15:03,520 --> 00:15:05,200
GO POORLY BUT CERTAINLY NOT WHAT

418
00:15:05,200 --> 00:15:07,480
WE INTENDED, THIS ONLY LASTED 11

419
00:15:07,480 --> 00:15:09,360
HOURS, OUR GOAL WAS ABOUT A WEEK

420
00:15:09,360 --> 00:15:11,760
SO WE COULD PERFORM ALL SORTS OF

421
00:15:11,760 --> 00:15:12,720
REALLY COOL EXPERIMENTS, WE DID

422
00:15:12,720 --> 00:15:14,800
THIS AGAIN ON A PATIENT, THIS

423
00:15:14,800 --> 00:15:16,840
WAS A COLORECTAL LIVER

424
00:15:16,840 --> 00:15:17,800
METASTASIS, WE GOT BETTER AT IT

425
00:15:17,800 --> 00:15:19,760
AND AT THE TIME WE WERE ABLE TO

426
00:15:19,760 --> 00:15:21,440
KEEP THIS THING VIABLE AND

427
00:15:21,440 --> 00:15:23,120
DIDN'T REALLY GET BETTER BUT WE

428
00:15:23,120 --> 00:15:25,400
WERE A BIT SLICKENER DOING THIS,

429
00:15:25,400 --> 00:15:26,920
I THINK AN IMPORTANT POINT I

430
00:15:26,920 --> 00:15:28,680
LEARNED EARLY WAS WAS THAT EVEN

431
00:15:28,680 --> 00:15:30,720
THOUGH THE LIVER WAS NOT HAPPY

432
00:15:30,720 --> 00:15:34,120
ON OUR MACHINE EARLY ON, THE

433
00:15:34,120 --> 00:15:35,080
TUMOR REMAINED VERY HAPPY AND

434
00:15:35,080 --> 00:15:37,480
THAT'S SORT OF THE PROBLEM,

435
00:15:37,480 --> 00:15:37,680
RIGHT?

436
00:15:37,680 --> 00:15:38,120
TUMORS DON'T DIE.

437
00:15:38,120 --> 00:15:43,320
AND SO THIS WAS AT LEAST

438
00:15:43,320 --> 00:15:44,080
CONCEPTUALLY, WE WERE

439
00:15:44,080 --> 00:15:46,240
ENTHUSIASTIC BY THE CONCEPT THAT

440
00:15:46,240 --> 00:15:48,440
THE TUMOR REALLY REMAINED OKAY.

441
00:15:48,440 --> 00:15:52,040
NOW, SAM AND MIKE CONVINCED ME

442
00:15:52,040 --> 00:15:56,320
WE SHOULD GO TO GONIGAN, IN THE

443
00:15:56,320 --> 00:15:57,120
NETHERLANDS WHERE THE PEOPLE

444
00:15:57,120 --> 00:15:58,880
MADE THIS MACHINE BECAUSE THEY

445
00:15:58,880 --> 00:16:00,280
ALLOWED US TO GET PIG LIVERS

446
00:16:00,280 --> 00:16:02,360
OVER AND OVER AND OVER THERE

447
00:16:02,360 --> 00:16:04,840
WITHOUT HAVING TO BURN THROUGH

448
00:16:04,840 --> 00:16:06,200
OUR LABORATORY BUDGET ON

449
00:16:06,200 --> 00:16:08,160
DISPOSABLES, SO I TELL THEM WE

450
00:16:08,160 --> 00:16:09,840
TOOK A VACATION TO THE

451
00:16:09,840 --> 00:16:11,480
NETHERLANDS, BUT THE TRUTH IS IT

452
00:16:11,480 --> 00:16:13,600
WAS NOT A VACATION BUT THEY TOOK

453
00:16:13,600 --> 00:16:16,600
TURNS SPENDING THE NIGHT IN THE

454
00:16:16,600 --> 00:16:18,080
WAREHOUSE PROFUSING LIVERS, NOW

455
00:16:18,080 --> 00:16:21,800
WE GOT BETTER AT IT BUT WE GET

456
00:16:21,800 --> 00:16:23,240
BETTER, I WILL SHOW YOU DATA

457
00:16:23,240 --> 00:16:24,880
FROM THE THIRD PERSON WE DSO

458
00:16:24,880 --> 00:16:28,000
THIS TUMOR WAS ANOTHER

459
00:16:28,000 --> 00:16:29,640
COLORECTAL LIVER METASTASIS, WE

460
00:16:29,640 --> 00:16:30,480
CANNULATED EVERYTHING, WE GOT

461
00:16:30,480 --> 00:16:32,720
BETTER AT THIS, YOU CAN SEE THE

462
00:16:32,720 --> 00:16:35,480
ARTERIAL AND VENOUS LINES, THE

463
00:16:35,480 --> 00:16:38,160
VENUS LINE WAS EXTRACTING OX

464
00:16:38,160 --> 00:16:38,440
GENERATED.

465
00:16:38,440 --> 00:16:42,600
IT MADE BILE, THE BILLIARY

466
00:16:42,600 --> 00:16:43,320
COMPOSITION LOOKED REASONABLE,

467
00:16:43,320 --> 00:16:46,680
BUT WHAT YOU CAN SEE AT ABOUT 24

468
00:16:46,680 --> 00:16:49,160
HOURS IS THE LEVELS BEGIN TO

469
00:16:49,160 --> 00:16:50,960
CLIMB AND BY 48 HOURS BY ABOUT 2

470
00:16:50,960 --> 00:16:54,800
DAYS THE LIVER LOOKED BASICALLY

471
00:16:54,800 --> 00:16:55,200
NONVIABLE.

472
00:16:55,200 --> 00:16:57,520
THE TUMOR HOWEVER, AGAIN AT THE

473
00:16:57,520 --> 00:16:59,640
END OF THE RUN, AGAIN THE

474
00:16:59,640 --> 00:17:01,160
PROBLEM WITH TUMORS THEY DON'T

475
00:17:01,160 --> 00:17:02,560
DIE, THE TUMOR STAYED QUITE

476
00:17:02,560 --> 00:17:04,120
VIABLE AND QUITE HAPPY AND I

477
00:17:04,120 --> 00:17:07,040
EVEN CONVINCED THEM FROM

478
00:17:07,040 --> 00:17:08,360
DR. ROSENBERG'S LAB TO COME

479
00:17:08,360 --> 00:17:09,960
DOWN, TAKE A PIECE OF THE LIVER

480
00:17:09,960 --> 00:17:10,800
AND DO THEIR TILL HARVEST FROM

481
00:17:10,800 --> 00:17:12,520
THIS AND THAT SEEMED TO WORK

482
00:17:12,520 --> 00:17:14,240
VERY WELL IN MY MIND SO THE TOMB

483
00:17:14,240 --> 00:17:16,720
ARE WAS HAPPY, THE TUMOR IMMUNE

484
00:17:16,720 --> 00:17:17,680
MICROENVIRONMENT WAS HAPPY, WE

485
00:17:17,680 --> 00:17:21,320
JUST WEREN'T VERY GOOD YET AT

486
00:17:21,320 --> 00:17:21,720
PROFUSING ORGANS.

487
00:17:21,720 --> 00:17:23,120
SORT OF WHAT WAS DEJECTED A

488
00:17:23,120 --> 00:17:25,400
LITTLE BIT AND THE TEAM SORT

489
00:17:25,400 --> 00:17:29,400
OF--WE HAD TO RECENTER OUR

490
00:17:29,400 --> 00:17:31,600
THINKING AND SO AS TIME WENT BY,

491
00:17:31,600 --> 00:17:33,720
I HAD NEW FELLOWS JOIN THE LAB,

492
00:17:33,720 --> 00:17:34,840
NOW PARTNERS IN ALL OF THIS AND

493
00:17:34,840 --> 00:17:37,760
WE HAD A NEW IDEA NAWE NEEDED TO

494
00:17:37,760 --> 00:17:39,000
COMPLETELY GET RID OF THE OLD

495
00:17:39,000 --> 00:17:42,720
MACHINE AND THIS WAS LED BY ALEX

496
00:17:42,720 --> 00:17:43,960
AND A POST BACKTHAT HE WANTED IN

497
00:17:43,960 --> 00:17:46,720
THE LAB VERY MUCH, ALAN LUNA AND

498
00:17:46,720 --> 00:17:48,040
WE NAMED THE SYSTEM AFTER ALAN

499
00:17:48,040 --> 00:17:50,120
AND SO A LOT OF PEOPLE HAVE

500
00:17:50,120 --> 00:17:52,800
CONTRIBUTED TO THIS, JACOB

501
00:17:52,800 --> 00:17:54,480
LANDEN CARRY RYAN, STEPHANIE AND

502
00:17:54,480 --> 00:17:55,880
LAILA, AND A LOT OF PEOPLE

503
00:17:55,880 --> 00:17:58,080
CONTRIBUTE TO THIS, BUT WE

504
00:17:58,080 --> 00:18:00,000
REDESIGNED THE SYSTEM IN

505
00:18:00,000 --> 00:18:01,160
ENTIRETYY AND SO WE'VE BASICALLY

506
00:18:01,160 --> 00:18:02,400
DECIDE THAD WE WOULD HAVE TO

507
00:18:02,400 --> 00:18:04,840
BUILD EACH OF THE ORGAN SYSTEMS

508
00:18:04,840 --> 00:18:06,480
AROUND THE LIVER IN ORDER TO

509
00:18:06,480 --> 00:18:09,040
KEEP THIS THING VIABLE AND HAPPY

510
00:18:09,040 --> 00:18:13,120
FOR A PROLONGED PERIOD OF TIME

511
00:18:13,120 --> 00:18:15,240
AND THAT INVOLVED THE ADRENAL

512
00:18:15,240 --> 00:18:16,280
GLAND, PANCREAS, HEART AND

513
00:18:16,280 --> 00:18:18,120
LUNGS, WE HAD THAT BEFORE BUT WE

514
00:18:18,120 --> 00:18:19,800
NEED TODAY TO OPTIMIZE THAT, WE

515
00:18:19,800 --> 00:18:22,280
HAD TO ADD IN A DIALYSIS

516
00:18:22,280 --> 00:18:24,200
CIRCUIT, WE WOULD ADD IN THE GUT

517
00:18:24,200 --> 00:18:27,040
SO WE WOULD ADD IN BIOSALT AND

518
00:18:27,040 --> 00:18:28,760
NUTRIENTS TO SORT OF GIVE YOU A

519
00:18:28,760 --> 00:18:31,120
TASTE OF WHAT THIS LOOKS LIKE

520
00:18:31,120 --> 00:18:34,080
YOU KNOW WE DESIGNED A

521
00:18:34,080 --> 00:18:35,360
SEMIAUTOMATED SYSTEM FROM THE

522
00:18:35,360 --> 00:18:37,080
DAYS WHEN SAM AND MIKE WERE

523
00:18:37,080 --> 00:18:39,520
SLEEPING NEXT TO THIS THING,

524
00:18:39,520 --> 00:18:40,880
MASSAGING THE LIVER EVERY COUPLE

525
00:18:40,880 --> 00:18:42,680
OF HOURS TO SORT OF TRY AND GET

526
00:18:42,680 --> 00:18:45,240
RID OF THE EDEMA, OLYMPIC

527
00:18:45,240 --> 00:18:46,200
EXPECTATIONS AND THE TEAM

528
00:18:46,200 --> 00:18:49,520
DECIDED THAT WE SHOULD HAVE A

529
00:18:49,520 --> 00:18:51,480
CENTRAL NERVOUS SYSTEM SUCH THAT

530
00:18:51,480 --> 00:18:52,560
ANY PARAMETERS THAT WERE

531
00:18:52,560 --> 00:18:54,760
BREECHED, WE WOULD AUTOMATICALLY

532
00:18:54,760 --> 00:18:56,920
INFUSE VARIOUS BASAL ACTIVE

533
00:18:56,920 --> 00:18:58,480
SUBSTANCES, NOW THIS DIDN'T

534
00:18:58,480 --> 00:18:59,600
OBVIATE THE NEED TO SLEEP NEXT

535
00:18:59,600 --> 00:19:01,600
TO THIS, I DON'T WANT TO DOWN

536
00:19:01,600 --> 00:19:03,760
GRADE THIS SORT OF LEVEL OF

537
00:19:03,760 --> 00:19:05,000
COMMITMENT THAT THE FELLOWS HAVE

538
00:19:05,000 --> 00:19:06,840
HAD OVER THE TIME, BUT WE

539
00:19:06,840 --> 00:19:09,160
DEVELOPED A CENTRAL NERVOUS

540
00:19:09,160 --> 00:19:10,920
SYSTEM TO SEMIAUTOMATE THINGS.

541
00:19:10,920 --> 00:19:13,680
WE HAD ISSUES WITH HOMOLYSIS AND

542
00:19:13,680 --> 00:19:17,440
SO, THE TEAM HACKED INTO A

543
00:19:17,440 --> 00:19:21,760
ROTOFLOW PUMP SUCH THAT WE COULD

544
00:19:21,760 --> 00:19:23,560
CONTROL THIS PUMP

545
00:19:23,560 --> 00:19:26,400
SEMIAUTOMATICALLY AND THIS WAS

546
00:19:26,400 --> 00:19:27,800
ASSOCIATED WITH FAR LESS

547
00:19:27,800 --> 00:19:28,880
HOMOLYSIS, THE DIALYSIS WAS A

548
00:19:28,880 --> 00:19:31,520
PROBLEM FOR US BECAUSE WE HAD TO

549
00:19:31,520 --> 00:19:32,680
CONTROL THE DISCIPLINARIAL SAIT

550
00:19:32,680 --> 00:19:35,000
VOLUMES AND CONTROL THINGS SO

551
00:19:35,000 --> 00:19:36,640
THE TEAM CIRCUMVENTED THESE

552
00:19:36,640 --> 00:19:38,960
PROBLEMS BY USING 2 SEPARATE

553
00:19:38,960 --> 00:19:41,600
PROMPTS 1 BEFORE AND AFTER THE

554
00:19:41,600 --> 00:19:42,560
DIALYSIS FILTER AND WE COULD

555
00:19:42,560 --> 00:19:43,800
CONTROL THE SPEED AND DETERMINE

556
00:19:43,800 --> 00:19:47,600
IF WE WANT TO PUT FLUID INTO THE

557
00:19:47,600 --> 00:19:48,640
DIALYSIS OF THE SYSTEM OR TAKE

558
00:19:48,640 --> 00:19:50,760
OFF AND YOU CAN SEE THAT THE

559
00:19:50,760 --> 00:19:53,040
URINE LOOKS LIKE URAIN BASICALLY

560
00:19:53,040 --> 00:19:54,280
SO WE EALZ REALIZED THAT

561
00:19:54,280 --> 00:19:55,360
OVERTIME AS I'M SIGHTING HERE

562
00:19:55,360 --> 00:19:58,120
TALKING TO YOU AND BREEGING MY

563
00:19:58,120 --> 00:20:00,320
DIAPHRAGM IS MOVING UP AND DOWN

564
00:20:00,320 --> 00:20:01,760
AND I'M COMPRESSING MY LIVER AND

565
00:20:01,760 --> 00:20:03,520
SO WE FELT LIKE THAT WOULD BE AN

566
00:20:03,520 --> 00:20:05,160
IMPORTANT COMPONENT OF THIS AS

567
00:20:05,160 --> 00:20:10,560
WELL, SO, WE DESIGNED AND

568
00:20:10,560 --> 00:20:11,240
IMPLEMENTED A DIAPHRAGM IF YOU

569
00:20:11,240 --> 00:20:13,920
WILL AND THIS WAS CONTROLLED BY

570
00:20:13,920 --> 00:20:15,560
A PORTABLE VENTILATURE SUCH THAT

571
00:20:15,560 --> 00:20:16,320
THE GRIEVING DYNAMICS WERE

572
00:20:16,320 --> 00:20:19,960
SIMILAR TO THAT OF A PERSON AND

573
00:20:19,960 --> 00:20:22,160
FINALLY, YOU KNOW THE TEAM

574
00:20:22,160 --> 00:20:22,760
DEVELOPED THIS GLUCOSE SENSOR

575
00:20:22,760 --> 00:20:25,320
WHICH WOULD BE THE SAME SENSOR A

576
00:20:25,320 --> 00:20:26,960
DIABETIC PATIENT WOULD HAVE

577
00:20:26,960 --> 00:20:28,720
EMBEDDED IN THEIR SKIN, WE HAD

578
00:20:28,720 --> 00:20:32,040
TO ENGINEER AN ADAPTER SUCH THAT

579
00:20:32,040 --> 00:20:33,760
WE COULD GET CONSTANT GLUCOSE

580
00:20:33,760 --> 00:20:34,720
FEEDBACKS SO WE WOULD KNOW

581
00:20:34,720 --> 00:20:37,160
WHETHER THE SYSTEM NEEDED

582
00:20:37,160 --> 00:20:42,400
INSULIN OR GLUE CODON, I WANT TO

583
00:20:42,400 --> 00:20:43,200
HIGHLIGHT THE COMPLEXITY BEFORE

584
00:20:43,200 --> 00:20:45,560
I SHOW IT TO BECAUSE IT'S TOO

585
00:20:45,560 --> 00:20:46,840
COMPLICATED TO GO THROUGH IT IN

586
00:20:46,840 --> 00:20:48,600
THE PICTURE BUT SUFFICE IT TO

587
00:20:48,600 --> 00:20:52,000
SAY THAT THIS IS YEARS OF WORK

588
00:20:52,000 --> 00:20:53,880
AND THIS IS A WORKABLE SYSTEM

589
00:20:53,880 --> 00:20:55,480
UNLIKE THE 1 WE PURCHASED.

590
00:20:55,480 --> 00:20:57,040
THIS WAS OF OUR OWN DESIGN AND

591
00:20:57,040 --> 00:20:59,280
OF OUR OWN MAKING AND I REALLY

592
00:20:59,280 --> 00:21:02,760
WANT TO CREDIT THE FELLOWS

593
00:21:02,760 --> 00:21:05,120
INVOLVED OVER THE PERIODS OF

594
00:21:05,120 --> 00:21:07,720
TIME WHO REALLY MADE THIS HAPPEN

595
00:21:07,720 --> 00:21:09,160
AND THEY MADE THIS COME TO

596
00:21:09,160 --> 00:21:12,360
FRUITION AND THEY DID THIS BY

597
00:21:12,360 --> 00:21:15,680
MANY, MANY SLEEPLESS NIGHTS.

598
00:21:15,680 --> 00:21:18,000
AND SO, I WANT TO GO THROUGH HOW

599
00:21:18,000 --> 00:21:20,120
WE OPTIMIZE IT SO WE DESIGNED IT

600
00:21:20,120 --> 00:21:22,680
AND THEN, OF COURSE, HOW ARE WE

601
00:21:22,680 --> 00:21:24,680
GOING TO OPTIMIZE THIS SO WE

602
00:21:24,680 --> 00:21:26,840
DECIDED THAT WE WOULD--SOME OF

603
00:21:26,840 --> 00:21:28,560
THE FELLOWS IN THE LAB FOUND A

604
00:21:28,560 --> 00:21:31,760
SLAUGHTER HOUSE AND SO, I HAVE

605
00:21:31,760 --> 00:21:32,480
NOT BEEN.

606
00:21:32,480 --> 00:21:34,120
THEY DON'T INVITE ME BUT THEY GO

607
00:21:34,120 --> 00:21:35,960
TO A SLAUGHTER HOUSE AND THEY GO

608
00:21:35,960 --> 00:21:37,600
UP THERE AS BEST I CAN TELL THEY

609
00:21:37,600 --> 00:21:40,160
HAVE A GREAT TIME AND THEY GO TO

610
00:21:40,160 --> 00:21:41,520
MOWPT AIRY AND GET PIGGINGS FROM

611
00:21:41,520 --> 00:21:42,800
THE LIVERS FROM THE SLAUGHTER

612
00:21:42,800 --> 00:21:43,840
HOUSE, THEY GET BLOOD AND

613
00:21:43,840 --> 00:21:45,640
SOMETIMES THEY WILL BRING BACK

614
00:21:45,640 --> 00:21:48,040
TREATS, THEY DON'T SHARE WITH ME

615
00:21:48,040 --> 00:21:49,200
NECESSARILY, BUT, AND SO THEY

616
00:21:49,200 --> 00:21:52,040
BRING BACK TREATS AND THEY COME

617
00:21:52,040 --> 00:21:54,840
BACK TO THE NIH WITH THE ORGANS

618
00:21:54,840 --> 00:21:56,720
AND WE OPTIMIZE THAT WAY.

619
00:21:56,720 --> 00:21:58,840
I'M NOT GOING TO SHOW YOU ANY

620
00:21:58,840 --> 00:21:59,880
DATA ABOUT PIG LIVERS BUT THIS

621
00:21:59,880 --> 00:22:01,080
IS A PATIENTS IN THE CLINIC

622
00:22:01,080 --> 00:22:04,720
UPPER OF ME ASSISTING

623
00:22:04,720 --> 00:22:05,840
DR. LAMBEDDEN, HE WAS TAKING OUT

624
00:22:05,840 --> 00:22:08,040
THIS LIVER AND THIS IS STEPHAN

625
00:22:08,040 --> 00:22:10,480
EXPE JACOB AND THEY'RE

626
00:22:10,480 --> 00:22:11,680
CANNULATING ON THE BACK TABLE

627
00:22:11,680 --> 00:22:13,440
AND LONG AND SHORT IS, ALL OF

628
00:22:13,440 --> 00:22:15,160
THE HARD WORK PAID OFF.  THIS IS

629
00:22:15,160 --> 00:22:18,480
A VERY RECENT PICTURE OF US AND

630
00:22:18,480 --> 00:22:21,240
WITH A PATIENT WHO THIS IS THE

631
00:22:21,240 --> 00:22:23,760
PATIENT, HER LIVER'S BACK BEHIND

632
00:22:23,760 --> 00:22:26,560
HER, THIS IS POST OPERATIVE DAY

633
00:22:26,560 --> 00:22:29,960
NUMBER--6 DAYS AFTER WE PUT HER

634
00:22:29,960 --> 00:22:32,000
LIVER ON THE SYSTEM.

635
00:22:32,000 --> 00:22:35,320
THIS IS ALAN, STEPHANIE 2 VERY

636
00:22:35,320 --> 00:22:36,520
BRIGHT POST BACKSTUDENTS AND

637
00:22:36,520 --> 00:22:39,320
JACOB, YOU SAY JACOB TAKING OUT

638
00:22:39,320 --> 00:22:40,440
THE PATIENT'S LIVER WITH ME,A

639
00:22:40,440 --> 00:22:41,560
CYSTING AND HERE'S THE PATIENT

640
00:22:41,560 --> 00:22:43,760
SO ALL OF OUR STRUGGLES AND ALL

641
00:22:43,760 --> 00:22:46,520
OF OUR EFFORTS STARTED BY SAM

642
00:22:46,520 --> 00:22:48,560
AND MIKE AND REALLY SORT OF CAME

643
00:22:48,560 --> 00:22:51,920
TO FRUITION BY A TEAM LED BY

644
00:22:51,920 --> 00:22:55,160
ALEX, JACOB AND OTHERS, REALLY

645
00:22:55,160 --> 00:23:01,560
IT WORKED AND THE LIVER LOOKED

646
00:23:01,560 --> 00:23:03,120
GOOD AND IMPORTANTLY THE TUMOR

647
00:23:03,120 --> 00:23:06,600
LOOKED GOOD AND THIS IS A

648
00:23:06,600 --> 00:23:07,360
NEUROENDOCRINE TUMOR AND I THINK

649
00:23:07,360 --> 00:23:09,440
THIS IS IMPORTANT BECAUSE AS YOU

650
00:23:09,440 --> 00:23:10,280
THINK ABOUT NEUROENDOCRINE

651
00:23:10,280 --> 00:23:14,280
TUMORS THEY ARE NOT GOOD IF ANY

652
00:23:14,280 --> 00:23:15,280
PRECLINICAL MODEL OF VALUE SO

653
00:23:15,280 --> 00:23:16,720
HAVING A SYSTEM LIKE THIS FOR

654
00:23:16,720 --> 00:23:18,080
VAR TUMORS WHERE YOU DON'T HAVE

655
00:23:18,080 --> 00:23:22,520
A MOUSE MODEL, YOU DON'T HAVE,

656
00:23:22,520 --> 00:23:24,880
YOU KNOW PATIENT DERIVED EXTEN O

657
00:23:24,880 --> 00:23:26,840
GRAPHS TO UTILIZE, THESE ARE

658
00:23:26,840 --> 00:23:28,160
TRUE OF NEUROENDOCRINE TUMORS,

659
00:23:28,160 --> 00:23:31,240
THIS BECOMES A REALLY VALUABLE

660
00:23:31,240 --> 00:23:33,080
TOOL AND BASED WHERE THERE

661
00:23:33,080 --> 00:23:35,160
AREN'T ANY OTHER OPTIONS.

662
00:23:35,160 --> 00:23:37,240
SO AGAIN, THE TEAM WE MIGHT HAVE

663
00:23:37,240 --> 00:23:39,640
HAD A BOTTLE OR 2 OF CHAMPAGNE

664
00:23:39,640 --> 00:23:41,320
TO CELEBRATE THIS 1 AND I WOULD

665
00:23:41,320 --> 00:23:43,280
SAY THAT I AM VERY HAPPY WITH

666
00:23:43,280 --> 00:23:46,840
THE WAY THE TEAM CAME TOGETHER

667
00:23:46,840 --> 00:23:57,320
AND REALLY OVERCAME A LOT OF

668
00:23:57,320 --> 00:23:57,840
OBSTACLES.

669
00:23:57,840 --> 00:23:59,640
OKAY, I DIDN'T REALLY EXPANDOT

670
00:23:59,640 --> 00:24:00,480
AMOUNT OF FRUSTRATIONS WE SAW IN

671
00:24:00,480 --> 00:24:01,720
THAT SYSTEM TO MAKE IT WORK.

672
00:24:01,720 --> 00:24:03,360
IN THE MIDDLE OF THAT I DECIDED

673
00:24:03,360 --> 00:24:05,160
WE SHOULD PIVOT AND WE HAD AN

674
00:24:05,160 --> 00:24:06,400
IDEA THAT MAYBE, YOU KNOW IF YOU

675
00:24:06,400 --> 00:24:08,600
THINK OF THE LIVER AS THE

676
00:24:08,600 --> 00:24:11,880
CADILLAC, IT'S THE TRUEST

677
00:24:11,880 --> 00:24:13,080
PRECLINICAL MODEL YOU COULD EVER

678
00:24:13,080 --> 00:24:14,800
HAVE, IT HAS THE CIRCULATORY

679
00:24:14,800 --> 00:24:16,240
SYSTEM, HAS ALL THE COMPONENTS

680
00:24:16,240 --> 00:24:20,280
BUT WHAT IF WE COULD DO THIS ON

681
00:24:20,280 --> 00:24:22,960
A SMALLER SCALE.

682
00:24:22,960 --> 00:24:24,680
AND SO THIS ALSO WAS A VERY LONG

683
00:24:24,680 --> 00:24:26,480
TIME IN THE MAKING AND

684
00:24:26,480 --> 00:24:29,880
ULTIMATELY CULMINATED IN THIS

685
00:24:29,880 --> 00:24:32,640
SORT OF IDEAL WAS SOMETHING THE

686
00:24:32,640 --> 00:24:34,960
FELLAS MADE SYSTEM CALLED SMART

687
00:24:34,960 --> 00:24:38,080
SYSTEM, THIS STANDS FOR

688
00:24:38,080 --> 00:24:39,920
SURGICALLY RESECTED MESOTHELIUM

689
00:24:39,920 --> 00:24:42,400
CONTAINING UNAFFAIRS TEAM

690
00:24:42,400 --> 00:24:42,800
LEADERRERRED TUMOR

691
00:24:42,800 --> 00:24:43,200
MICROENVIRONMENT.

692
00:24:43,200 --> 00:24:44,360
I WON'T SHOW YOU WHAT IT LOOKED

693
00:24:44,360 --> 00:24:45,560
LIKE EARLY ON BECAUSE IT'S

694
00:24:45,560 --> 00:24:50,200
LAUGHABLE TO BE HONEST BUT UNDER

695
00:24:50,200 --> 00:24:53,360
ALEX, JAMES AND STRAYA, GUPTA

696
00:24:53,360 --> 00:24:56,800
AND EMILY WITH THE HAD BEEN OF

697
00:24:56,800 --> 00:24:58,840
NEWER MEMBERS, CARRY AND RON AND

698
00:24:58,840 --> 00:25:00,480
STEPHANIE, THEY BROUGHT THIS TO

699
00:25:00,480 --> 00:25:02,920
FRUITION, AND SO WHAT THIS IS IS

700
00:25:02,920 --> 00:25:05,120
THIS LOOKS LIKE WHEN A PATIENT

701
00:25:05,120 --> 00:25:08,200
HAS METASTASIS ON THE LINING OF

702
00:25:08,200 --> 00:25:10,160
THEIR ABDOMINAL CAVITY THIS, IS

703
00:25:10,160 --> 00:25:12,960
POETIC THE PERO TONEM,

704
00:25:12,960 --> 00:25:13,600
DIAGNOSTICALLY OR

705
00:25:13,600 --> 00:25:14,360
THERAPEUTICALLY IT'S INDICATED

706
00:25:14,360 --> 00:25:16,480
WE WOULD REMOVE THIS LINING AND

707
00:25:16,480 --> 00:25:21,200
WE WOULD THEN PUT THIS ON TO

708
00:25:21,200 --> 00:25:23,120
PLATFORMS ALMOST LIKE A MODIFIED

709
00:25:23,120 --> 00:25:24,640
CHAMBER, WE DRAW THE PATIENT'S

710
00:25:24,640 --> 00:25:26,680
BLOOD BEFORE HAND AND WE COLLECT

711
00:25:26,680 --> 00:25:29,880
THEIR PLASMA, SUCH THAT THESE

712
00:25:29,880 --> 00:25:32,080
PROFUSION CHAMBERS ARE BATHED

713
00:25:32,080 --> 00:25:33,040
INOX GENERATED 8ED PLASMA FROM

714
00:25:33,040 --> 00:25:35,120
THE SAME PATIENT AND WE USED

715
00:25:35,120 --> 00:25:37,960
POINT OF CARE INSTRUMENTS TO

716
00:25:37,960 --> 00:25:39,560
MAKE SURE NORMAL PHYSIOLOGY IS

717
00:25:39,560 --> 00:25:42,480
MAINTAINED AS BEST WE CAN.

718
00:25:42,480 --> 00:25:45,160
AND THEN WE CAN CERTAINLY

719
00:25:45,160 --> 00:25:48,480
CONCEIVE OF ADDING DRUGS INTO

720
00:25:48,480 --> 00:25:50,160
THIS CIRCUIT SUCH THAT IT WOULD

721
00:25:50,160 --> 00:25:51,320
MIMIC THE PATIENT'S PLASMA

722
00:25:51,320 --> 00:25:55,040
LEVELS OF THE DRUG AND THEN WE

723
00:25:55,040 --> 00:25:56,760
CONCEIVED AFRONS AN IMPLEMENT

724
00:25:56,760 --> 00:26:02,480
THE MULTIPLE IMAGING, MULTIPLE

725
00:26:02,480 --> 00:26:03,760
INTERROGATION PILLARS, PILLARS

726
00:26:03,760 --> 00:26:06,320
OF INTERROGATION, SOME OF THESE

727
00:26:06,320 --> 00:26:08,160
ARE ADVANCED IMAGING, FLOW

728
00:26:08,160 --> 00:26:10,080
CYTOMETRY, ALL OF THE OMICs

729
00:26:10,080 --> 00:26:11,960
YOU CAN THINK OF AND THEN WE

730
00:26:11,960 --> 00:26:13,040
LOOK AT THE PROFUSATE IN THE

731
00:26:13,040 --> 00:26:15,920
PLATMA AS A WAY TO IDENTIFY

732
00:26:15,920 --> 00:26:18,280
BIOMARKERS OF RESPONSE OR NOT.

733
00:26:18,280 --> 00:26:19,560
SO THIS WAS A WAY--THIS IS TD

734
00:26:19,560 --> 00:26:23,200
WAY WE DO THIS.

735
00:26:23,200 --> 00:26:25,080
SO WE PUT A SCOPE IN SOMEBODY'S

736
00:26:25,080 --> 00:26:27,600
ABDOMEN AND WE'RE LOOKING FOR

737
00:26:27,600 --> 00:26:28,280
THESE METASTASIS AND HERE CAN

738
00:26:28,280 --> 00:26:32,280
YOU SEE WE'RE REMOVING THIS VERY

739
00:26:32,280 --> 00:26:34,280
THIN LAYER BLUNTLY AND DOING

740
00:26:34,280 --> 00:26:35,240
THIS VERY GENERALLY, ALTHOUGH I

741
00:26:35,240 --> 00:26:36,640
GUESS IT MAY NOT LOOK THAT WAY

742
00:26:36,640 --> 00:26:38,480
TO SOME BUT THEN WE'RE ABLE TO

743
00:26:38,480 --> 00:26:39,600
SORT OF CUT THIS AREA OFF AND

744
00:26:39,600 --> 00:26:41,560
TAKE THAT OUT OF THE PATIENT AND

745
00:26:41,560 --> 00:26:43,440
THEN ON THE BACK TABLE, AGAIN WE

746
00:26:43,440 --> 00:26:45,200
USE THAT SAME BACK TABLE SET UP,

747
00:26:45,200 --> 00:26:46,760
THE FELLOWS HAVE SORT OF

748
00:26:46,760 --> 00:26:49,400
DESIGNED THIS REALLY COOL WAY TO

749
00:26:49,400 --> 00:26:51,880
HOLD EVERYTHING STILL, AND THEY

750
00:26:51,880 --> 00:26:54,760
TIE AS WE DO IN SURGERY, TIE

751
00:26:54,760 --> 00:26:56,000
KNOTS DOWN AND MAKE SURE IT

752
00:26:56,000 --> 00:26:57,400
STAYS AFFIXED TO THE PLATFORM

753
00:26:57,400 --> 00:26:58,640
AND THEN WE HAVE A RUNNER THAT

754
00:26:58,640 --> 00:27:00,720
RUNS DOWN TO THE LAB AND BRINGS

755
00:27:00,720 --> 00:27:03,440
THIS INTO THEOX GENERATEDDATED

756
00:27:03,440 --> 00:27:04,280
PROFUSION CIRCUIT, THIS IS WHAT

757
00:27:04,280 --> 00:27:05,680
IT LOOKS LIKE ON THE RIGHT, CAN

758
00:27:05,680 --> 00:27:08,480
YOU SEE THERE'S AN OBVIOUS

759
00:27:08,480 --> 00:27:09,560
NODULE OR METASTASIS SURROUNDED

760
00:27:09,560 --> 00:27:16,120
BY WHAT OTHERWISE WOULD BE

761
00:27:16,120 --> 00:27:17,000
NORMAL PEROTONEUM, OKAY.

762
00:27:17,000 --> 00:27:19,840
AND SO THE MAINTENANCE OF THIS

763
00:27:19,840 --> 00:27:21,560
SYSTEM TOOK US A LONG TIME TO

764
00:27:21,560 --> 00:27:22,040
FIGURE OUT.

765
00:27:22,040 --> 00:27:24,880
BY US I DON'T MEAN ME, I MEAN IT

766
00:27:24,880 --> 00:27:26,560
TOOK THE FELLOWS, THE PARTNERS,

767
00:27:26,560 --> 00:27:27,560
MY PARTNERS A LONG TIME TO

768
00:27:27,560 --> 00:27:29,640
FIGURE THIS OUT AND SO, WHAT WE

769
00:27:29,640 --> 00:27:32,400
REALIZED EARLY ON WAS THAT WE

770
00:27:32,400 --> 00:27:34,240
WOULD NEED A SMALL CHAMBER, WE

771
00:27:34,240 --> 00:27:37,000
COULDN'T HAVE SOMETHING HUGE

772
00:27:37,000 --> 00:27:38,440
BECAUSE THE PLASMA VOLUME WAS

773
00:27:38,440 --> 00:27:38,840
TOO MUCH.

774
00:27:38,840 --> 00:27:40,000
WE WERE DRAWING TOO MUCH BLOOD

775
00:27:40,000 --> 00:27:41,560
FROM PEOPLE AND THAT'S NOT FAIR

776
00:27:41,560 --> 00:27:43,360
AND WE WEREN'T GOING TO DO THAT

777
00:27:43,360 --> 00:27:45,280
SOY REALIZED WE NEEDED TO SHRINK

778
00:27:45,280 --> 00:27:47,360
EVERYTHING DOWN AND THEN WE

779
00:27:47,360 --> 00:27:50,040
NEEDED TO HAVE THE PERSTALTIC

780
00:27:50,040 --> 00:27:51,480
PUMP BUT WE NEEDED A WAI TO

781
00:27:51,480 --> 00:27:54,600
CONTROL THE Ph ANDOX

782
00:27:54,600 --> 00:27:55,600
GENERATEDDATION, AND YOU CAN BE

783
00:27:55,600 --> 00:27:57,880
THE JUST RUN PURE OXIEN AND SO

784
00:27:57,880 --> 00:27:59,280
WE ENDED UP COMING WITH A GAS

785
00:27:59,280 --> 00:28:01,840
MIXER AND WE ENDED UP BUYING

786
00:28:01,840 --> 00:28:02,960
MULTIPLE GAS MIXERS WHICH

787
00:28:02,960 --> 00:28:10,960
ALLOWED US TO HAVE THE OX

788
00:28:10,960 --> 00:28:11,560
GENERATED--OXYGEN LEVELS, AND

789
00:28:11,560 --> 00:28:14,880
THEY REALIZED THERE WERE

790
00:28:14,880 --> 00:28:15,560
ELECTROLYTE ABNORMALITIES AS

791
00:28:15,560 --> 00:28:17,280
RESULT OF THE LOSSES SO JAIMINGS

792
00:28:17,280 --> 00:28:19,280
HOOKED UP A SYRINGE PUMP TO THE

793
00:28:19,280 --> 00:28:21,720
SYSTEM THAT SLOWLY DREVERS WATER

794
00:28:21,720 --> 00:28:25,960
AT THE RATE OF BASICALLY TO

795
00:28:25,960 --> 00:28:27,640
REPLACE EVABBARATIVE WATER AND

796
00:28:27,640 --> 00:28:28,560
TO MAINTAIN ELECTROLYTE LEVELS

797
00:28:28,560 --> 00:28:30,080
AS THEY WOULD BE IN THE PERSON

798
00:28:30,080 --> 00:28:31,960
ISSUES IN THE PATIENT.

799
00:28:31,960 --> 00:28:34,480
SO OUR FIRST QUESTION WAS OKAY,

800
00:28:34,480 --> 00:28:36,000
THIS IS COOL, BUT DOES IT

801
00:28:36,000 --> 00:28:38,920
ACTUALLY REFLECT WHAT COMES OUT

802
00:28:38,920 --> 00:28:40,040
OF THE PERSON?

803
00:28:40,040 --> 00:28:43,040
SECONDLY, CAN WE DO THIS ON ANY

804
00:28:43,040 --> 00:28:43,320
TUMOR TYPE?

805
00:28:43,320 --> 00:28:45,440
AGAIN I THINK THE IMPORTANCE

806
00:28:45,440 --> 00:28:46,480
HERE, PARTICULARLY CONSIDERING

807
00:28:46,480 --> 00:28:47,880
WHERE WE WORK IS THREEZ RARE

808
00:28:47,880 --> 00:28:49,680
TUMORS THAT DON'T HAVE A LOT OF

809
00:28:49,680 --> 00:28:51,080
GOOD ANSWERS AND DON'T HAVE A

810
00:28:51,080 --> 00:28:52,680
LOT OF OR ANY PRECLINICAL MODEL,

811
00:28:52,680 --> 00:28:55,920
THIS WOULD BE THE CASE FOR

812
00:28:55,920 --> 00:28:56,640
GASTROINTESTINAL STROMAL FOR

813
00:28:56,640 --> 00:28:58,160
EXAMPLE AND WHAT I'M SHOWING YOU

814
00:28:58,160 --> 00:29:01,560
HERE IS THAT WE'RE ABLE TO

815
00:29:01,560 --> 00:29:03,000
MAINTAIN HISTOLOGY, AND WE'RE

816
00:29:03,000 --> 00:29:06,280
ABLE TO MAINTAIN CELL NUMBERS,

817
00:29:06,280 --> 00:29:08,000
T-CELLS MACROPHAGES,

818
00:29:08,000 --> 00:29:09,120
PROLIFERATION, CONTINUES DURING

819
00:29:09,120 --> 00:29:10,000
OUR 4 DAY TIME POINT.

820
00:29:10,000 --> 00:29:13,520
WHEN YOU LOOK AT THE TUMOR

821
00:29:13,520 --> 00:29:13,960
TRANSCRIPT ORDER OF

822
00:29:13,960 --> 00:29:16,080
MICRONSICALLY WHICH IS OF COURSE

823
00:29:16,080 --> 00:29:18,760
COMMON NOW DAYS YOU SEE IS WE DO

824
00:29:18,760 --> 00:29:20,320
SEE ELEVATIONS IN HYPOXIA, AND

825
00:29:20,320 --> 00:29:21,760
YOU KNOW WE DON'T HAVE ANY RED

826
00:29:21,760 --> 00:29:24,280
CELLS IN THE SYSTEM, SO WE

827
00:29:24,280 --> 00:29:25,800
RAISED THE OXYGEN LEVELS AS HIGH

828
00:29:25,800 --> 00:29:28,200
AS WE CAN, WE DON'T ACCEPT ANY

829
00:29:28,200 --> 00:29:29,960
THICK TUMORS BECAUSE WE'RE

830
00:29:29,960 --> 00:29:31,120
RELYING ON OXYGEN DIFFUSION BUT

831
00:29:31,120 --> 00:29:34,120
OTHER THAN THAT THE TUMORS STAY

832
00:29:34,120 --> 00:29:35,760
REALLY QUITE AS THEY DID WHEN

833
00:29:35,760 --> 00:29:36,960
THEY CAME OUT OF THE PERSON'S

834
00:29:36,960 --> 00:29:38,720
BODY AS BEST WE CAN TELL.

835
00:29:38,720 --> 00:29:41,200
NOW, WITH THE SYSTEM SORT OF

836
00:29:41,200 --> 00:29:44,680
OPTIMIZED THAT 1 OF THE FELLOWS

837
00:29:44,680 --> 00:29:46,560
[INDISCERNIBLE] CAME TO US AND

838
00:29:46,560 --> 00:29:49,320
SAID, YOU KNOW YOU MIGHT AS

839
00:29:49,320 --> 00:29:50,560
WELL--YOU'RE NOT REALLY LOOKING

840
00:29:50,560 --> 00:29:52,840
AT THIS IN A WAY THAT YOU COULD.

841
00:29:52,840 --> 00:29:54,880
YOU SHOULD LEVERAGE THE

842
00:29:54,880 --> 00:29:56,480
ADVANTAGE HERE OTHERWISE YOU'RE

843
00:29:56,480 --> 00:29:59,640
SORT OF BEHAVING LIKE THOO CAVE

844
00:29:59,640 --> 00:30:00,920
PEOPLE AND ARI BA HAD THIS IDEA

845
00:30:00,920 --> 00:30:03,640
THAT WE COULD TAKE THAT PLATFORM

846
00:30:03,640 --> 00:30:06,280
OUT OF THAT PROFUSION CIRCUIT

847
00:30:06,280 --> 00:30:10,400
AND ARIBA IN CONJUNCTION WITH

848
00:30:10,400 --> 00:30:12,560
ENGINEERS REDESIGNED A WAY TO

849
00:30:12,560 --> 00:30:15,400
IMAGE THE TUMOR ON AN INVERTED

850
00:30:15,400 --> 00:30:17,800
WHITE LIGHT LASER CONFOCAL

851
00:30:17,800 --> 00:30:18,120
SCOPE.

852
00:30:18,120 --> 00:30:20,520
THIS FIRST DONE ON A MULTIPHOTON

853
00:30:20,520 --> 00:30:23,240
SCOPE AND FOW WE DO IT ON A

854
00:30:23,240 --> 00:30:24,880
WHITE LIGHT LASER SCOPE AND IT'S

855
00:30:24,880 --> 00:30:26,480
A SCREW TYPE MECHANISM SO WE CAN

856
00:30:26,480 --> 00:30:28,800
CONTROL THE DEPTH AND THEN ARIBA

857
00:30:28,800 --> 00:30:30,920
AND THE TEAM DOES IS THEY

858
00:30:30,920 --> 00:30:32,440
INCUBATE WITH ANTIBODIES TO

859
00:30:32,440 --> 00:30:34,800
HIGHLIGHT VARIOUS CELL FRACTIONS

860
00:30:34,800 --> 00:30:37,280
AND THEN THIS SITS JUST LIKE

861
00:30:37,280 --> 00:30:39,840
THIS, AND THEY'VE DESIGNED A

862
00:30:39,840 --> 00:30:43,720
STAGE INCUBATOR TO MAINTAIN

863
00:30:43,720 --> 00:30:46,400
NIZIO LOGIC PARAMETERS DURING

864
00:30:46,400 --> 00:30:47,200
THE ACTUAL VISUALIZATION, SO

865
00:30:47,200 --> 00:30:49,000
IT'S ALMOST LIKE WE'RE PUTTING A

866
00:30:49,000 --> 00:30:52,000
WINDOW INTO THE TUMORS SO WE CAN

867
00:30:52,000 --> 00:30:53,560
THEN REALIZE WHAT'S GOING ON IN

868
00:30:53,560 --> 00:30:53,840
REALTIME.

869
00:30:53,840 --> 00:30:55,240
TO THE BEST OF MY KNOWLEDGE THIS

870
00:30:55,240 --> 00:30:57,040
HAS BEEN DONE WITH ANIMALS BUT I

871
00:30:57,040 --> 00:30:58,520
DON'T KNOW IT'S EVER REALLY BEEN

872
00:30:58,520 --> 00:31:00,600
DONE WITH HUMANS ON A SCALE LIKE

873
00:31:00,600 --> 00:31:02,360
THIS, SO LET ME SHOW YOU THE

874
00:31:02,360 --> 00:31:05,480
SORT OF INFORMATION YOU GET AND

875
00:31:05,480 --> 00:31:10,920
SO HAD IS A GASTRIC CARCINOMA TO

876
00:31:10,920 --> 00:31:11,920
THE PEROTONEUM AND YOU CAN SEE

877
00:31:11,920 --> 00:31:14,040
WHAT WE'VE DONE HERE IS LABELED

878
00:31:14,040 --> 00:31:17,000
TUMOR CELLS WITH A GREEN CD44

879
00:31:17,000 --> 00:31:19,280
AND WE'VE LABELED IMMUNE CELLS

880
00:31:19,280 --> 00:31:20,000
WITH A CD45.

881
00:31:20,000 --> 00:31:20,800
COLLAGEN IS BLUE UP HERE IN THE

882
00:31:20,800 --> 00:31:22,320
TOP AND YOU CAN SEE THE ACTIVITY

883
00:31:22,320 --> 00:31:24,600
OF THESE IMMUNE CELLS NOT

884
00:31:24,600 --> 00:31:25,640
NECESSARILY KILLING ANY TUMOR

885
00:31:25,640 --> 00:31:27,840
CELLS BUT YOU CAN SEE, THE

886
00:31:27,840 --> 00:31:30,000
ACTIVITY AND I CAN TELL YOU NOT

887
00:31:30,000 --> 00:31:31,720
ALL TUMORS LOOK LIKE THIS.

888
00:31:31,720 --> 00:31:34,360
HERE'S ANOTHER EXAMPLE OF A

889
00:31:34,360 --> 00:31:35,080
MESOTHELIOMA ON THE LEFT HERE

890
00:31:35,080 --> 00:31:37,480
AND WHAT CAN YOU SEE IS THE

891
00:31:37,480 --> 00:31:40,920
TUMORS OVER HERE AND THE ACTIVE

892
00:31:40,920 --> 00:31:42,960
IMMUNE CELLS OVER HERE AND THE

893
00:31:42,960 --> 00:31:44,680
IMMUNE CELLS ARE IN RED, THIS

894
00:31:44,680 --> 00:31:47,240
WOULD BE DESCRIBED AS A COLD

895
00:31:47,240 --> 00:31:48,960
NODULE, YOU DON'T SEE MANY

896
00:31:48,960 --> 00:31:50,600
IMMUNE CELLS MIXED IN WITH THE

897
00:31:50,600 --> 00:31:51,240
TUMOR CELLS.

898
00:31:51,240 --> 00:31:52,760
NOW ON OCCASION WHAT WE SEE IS

899
00:31:52,760 --> 00:31:54,480
THIS IS A REALLY COOL VIDEO,

900
00:31:54,480 --> 00:31:57,720
OVER HERE ON THE RIGHT, I WILL

901
00:31:57,720 --> 00:32:00,240
DRAW YOUR ATTENTION TO THE GREEN

902
00:32:00,240 --> 00:32:02,800
AGAIN, A CD44 TUMOR CELL AND THE

903
00:32:02,800 --> 00:32:04,120
RED IS AN IMMUNE CELL AND YOU

904
00:32:04,120 --> 00:32:06,480
CAN SEE THIS IS AN ENDOGENOUS NO

905
00:32:06,480 --> 00:32:09,000
DRUGS ADDED AND THERE'S AN

906
00:32:09,000 --> 00:32:10,280
IMMUNE CELL THAT RUINS RIGHT UP

907
00:32:10,280 --> 00:32:11,920
AGAINST THESE TUMOR CELLS AND

908
00:32:11,920 --> 00:32:14,840
DOCKS TZ ON THIS TUMOR CELL AND

909
00:32:14,840 --> 00:32:15,240
BEGINS KILLING IT.

910
00:32:15,240 --> 00:32:17,680
AND SO THIS SORT OF STUFF, YOU

911
00:32:17,680 --> 00:32:18,800
WOULDN'T OTHERWISE KNOW THAT

912
00:32:18,800 --> 00:32:20,120
THIS SORT OF HAPPENS WITHOUT

913
00:32:20,120 --> 00:32:22,120
DRUGS ON A SORT OF CONTINUAL

914
00:32:22,120 --> 00:32:24,160
BASIS BUT IT APPEARS TO IN

915
00:32:24,160 --> 00:32:27,520
CERTAIN TUMORS AND NOT IN

916
00:32:27,520 --> 00:32:28,000
OTHERS.

917
00:32:28,000 --> 00:32:30,040
AND THIS WAS REALLY AN

918
00:32:30,040 --> 00:32:30,640
ENLIGHTENING PIECE OF

919
00:32:30,640 --> 00:32:32,560
INFORMATION AND THERE'S A LOT OF

920
00:32:32,560 --> 00:32:34,240
CONSTERNATION ABOUT WHO'S GOING

921
00:32:34,240 --> 00:32:35,240
TO RESPOND TO IMMUNOTHERAPY AND

922
00:32:35,240 --> 00:32:37,080
WHO SUBJECT AND HOW ARE WE GOING

923
00:32:37,080 --> 00:32:38,920
TO DECIDE WHO TO GIVE THIS TO

924
00:32:38,920 --> 00:32:41,080
AND NOT, AND THERE ISN'T A

925
00:32:41,080 --> 00:32:42,120
PERFECT WAY LONG AND SHORT.

926
00:32:42,120 --> 00:32:44,240
I DON'T REALLY SRO THE TIME TO

927
00:32:44,240 --> 00:32:45,480
GO THROUGH ALL THE LITERATURE

928
00:32:45,480 --> 00:32:47,680
BUT WE'RE ABLE TO ADD ANOTHER

929
00:32:47,680 --> 00:32:48,040
PARAMETER.

930
00:32:48,040 --> 00:32:49,240
NOW WHETHER IT WILL BE USEFUL OR

931
00:32:49,240 --> 00:32:50,640
NOT, I DON'T KNOW BUT WE'RE

932
00:32:50,640 --> 00:32:56,000
CLEARLY ABLE TO ADD A DYNAMIC

933
00:32:56,000 --> 00:32:57,120
METRIC, ARIBA HAS THAT

934
00:32:57,120 --> 00:32:58,760
PREVIOUSLY HAS NOT BEEN

935
00:32:58,760 --> 00:33:00,200
ACCOUNTED FOR.

936
00:33:00,200 --> 00:33:01,760
AND I THINK THAT POINT IS MADE

937
00:33:01,760 --> 00:33:04,080
BEST BY EXAMINING THESE 2 MOVIES

938
00:33:04,080 --> 00:33:04,400
SIDE BY SIDE.

939
00:33:04,400 --> 00:33:08,480
YOU CAN SEE THE 1 ON THE LEFT

940
00:33:08,480 --> 00:33:10,120
METASTATIC COLORECTAL ADEN O

941
00:33:10,120 --> 00:33:11,440
CARCINOMA, VERY ACTIVE IPT

942
00:33:11,440 --> 00:33:13,040
GREATERUNE CELLS, THOSE CELLS

943
00:33:13,040 --> 00:33:15,360
RUNNING,A ROUND IN RED, LOOK

944
00:33:15,360 --> 00:33:16,440
LIKE ANTS RUNNING AROUND OR

945
00:33:16,440 --> 00:33:17,960
SOMETHING LIKE THAT, VERY ACTIVE

946
00:33:17,960 --> 00:33:20,720
IMMUNE SYSTEM IN THIS TUMOR

947
00:33:20,720 --> 00:33:22,240
WHEREAS THIS GASTROINTESTINAL

948
00:33:22,240 --> 00:33:23,960
STROMAL TUMOR VERY QUIESCENT,

949
00:33:23,960 --> 00:33:25,400
DON'T SEE A LOST MOVEMENT, MAYBE

950
00:33:25,400 --> 00:33:29,400
A LITTLE BIT BUT REALLY NOT A

951
00:33:29,400 --> 00:33:29,720
LOT.

952
00:33:29,720 --> 00:33:31,120
NOW THE TASK IS ON US TO

953
00:33:31,120 --> 00:33:32,880
DETERMINE WHETHER THIS MEANS

954
00:33:32,880 --> 00:33:35,280
ANYTHING BUT I THINK IT WILL BE

955
00:33:35,280 --> 00:33:38,960
A VALUABLE METRIC MOVING

956
00:33:38,960 --> 00:33:40,840
FORWARD.

957
00:33:40,840 --> 00:33:42,280
ARIBA THEN ASKED THE QUESTION,

958
00:33:42,280 --> 00:33:43,000
THAT'S PRETTY INTERESTING, HOW

959
00:33:43,000 --> 00:33:44,400
LONG CAN WE DO THIS?

960
00:33:44,400 --> 00:33:46,400
HOW LONG CAN WE PUT OUR CAMERA

961
00:33:46,400 --> 00:33:50,080
INTO THIS TUMOR AND REALLY TAKE

962
00:33:50,080 --> 00:33:50,600
A LOOK?

963
00:33:50,600 --> 00:33:51,800
THE ANSWER IS WITHOUT DETRIMENT

964
00:33:51,800 --> 00:33:55,080
TO THE IMMUNE CELLS AND WE'VE

965
00:33:55,080 --> 00:33:55,960
DETERMINED DETRIMENT IN THIS

966
00:33:55,960 --> 00:33:57,080
EXPERIMENT BY LOSS OF MOVEMENT

967
00:33:57,080 --> 00:33:59,880
AND WE CAN DO IT FOR UP TO 8

968
00:33:59,880 --> 00:34:01,200
HOURS AND THAT'S REALLY COOL

969
00:34:01,200 --> 00:34:01,920
BECAUSE THAT SUGGESTS CAN YOU

970
00:34:01,920 --> 00:34:04,560
PUT A DRUG INTO THE SYSTEM AND

971
00:34:04,560 --> 00:34:06,520
REALLY WATCH BEFORE AND AFTER

972
00:34:06,520 --> 00:34:07,920
DEPENDING ON THE DRUG AND

973
00:34:07,920 --> 00:34:10,040
DEPENDING ON WHAT YOU THINK THE

974
00:34:10,040 --> 00:34:12,120
KINETICS ARE, BUT THIS ALLOWS

975
00:34:12,120 --> 00:34:13,920
YOU YOU TO LOOK BEFORE AND AFTER

976
00:34:13,920 --> 00:34:15,840
AND THAT'S REALLY QUITE COOL.

977
00:34:15,840 --> 00:34:18,640
NEXT ARIBA AND THE TEAM ASKED A

978
00:34:18,640 --> 00:34:21,640
DIFFERENT QUESTION, WHAT IF YOU

979
00:34:21,640 --> 00:34:23,480
DO THIS NOT NECESSARILY FOR A

980
00:34:23,480 --> 00:34:25,000
VERY LONG PERIOD OF TIME BUT

981
00:34:25,000 --> 00:34:27,040
WHAT IF YOU DID THIS OVER

982
00:34:27,040 --> 00:34:28,000
CONSECUTIVE DAYS SUCH THAT YOU

983
00:34:28,000 --> 00:34:29,480
COULD TAKE THE SNAPSHOTS IN A

984
00:34:29,480 --> 00:34:31,480
DIFFERENT WAY RATHER THAN 1 LONG

985
00:34:31,480 --> 00:34:32,760
CONTINUOUS MOVIE COULD YOU DO

986
00:34:32,760 --> 00:34:33,920
THIS ON VARIOUS DAYS AND THE

987
00:34:33,920 --> 00:34:36,760
ANSWER IS YES, YOU CAN, CAN YOU

988
00:34:36,760 --> 00:34:38,960
DO IT FOR 2 DAYS AND YOU CAN SEE

989
00:34:38,960 --> 00:34:40,640
WITHOUT--CAN YOU SEE THE CELLS

990
00:34:40,640 --> 00:34:44,720
STILL REMAIN HAPPY AND STILL

991
00:34:44,720 --> 00:34:45,200
MOVE.

992
00:34:45,200 --> 00:34:47,200
AGAIN RED MARKS THE IMMUNE CELLS

993
00:34:47,200 --> 00:34:48,960
WITH THE CD45 MARKER SO WHAT WE

994
00:34:48,960 --> 00:34:51,720
BEGIN TO REALIZE IS WE'VE GOT A

995
00:34:51,720 --> 00:34:54,000
VERY COOL TOOL TO BEGIN TO

996
00:34:54,000 --> 00:34:56,040
EVALUATE HUMAN TUMORS IN A WAY

997
00:34:56,040 --> 00:34:58,280
THAT IS SORT OF HARD TO DO IN A

998
00:34:58,280 --> 00:34:59,720
PERSON, HARD TO DO IN A MOUSE, I

999
00:34:59,720 --> 00:35:01,000
CAN TELL YOU BECAUSE I'VE TRIED

1000
00:35:01,000 --> 00:35:04,400
AND HARD TO DO IN AND PROBABLY

1001
00:35:04,400 --> 00:35:10,600
IMPOSSIBLE TO DO IN ANY OTHER

1002
00:35:10,600 --> 00:35:11,600
MEANINGFUL WAY.

1003
00:35:11,600 --> 00:35:13,600
SO, NEXT, YOU KNOW ARIBA AND THE

1004
00:35:13,600 --> 00:35:15,600
TEAM SAID WELL, OKAY, WE CAN

1005
00:35:15,600 --> 00:35:17,960
ONLY DO A COUPLE PARAMETERS

1006
00:35:17,960 --> 00:35:19,840
LIVE, BUT WHAT IF WE THEN BEGIN

1007
00:35:19,840 --> 00:35:22,840
TO MULTIPLEX ON TOP OF THAT

1008
00:35:22,840 --> 00:35:24,000
USING VARIOUS TECHNIQUES AND

1009
00:35:24,000 --> 00:35:25,400
THAT'S EXACTLY WHAT WAS DONE

1010
00:35:25,400 --> 00:35:26,680
HERE.

1011
00:35:26,680 --> 00:35:30,520
SO YOU CAN--YOU KNOW USE THE RED

1012
00:35:30,520 --> 00:35:32,480
AND GREEN LIVE, BUT AFTER THAT

1013
00:35:32,480 --> 00:35:34,480
WE COULD FIX IT, SECTION IT SUCH

1014
00:35:34,480 --> 00:35:35,520
THAT WE COULD ORIENT OURSELVES

1015
00:35:35,520 --> 00:35:37,640
BACK TO WHERE THE LIVE IMAGING

1016
00:35:37,640 --> 00:35:40,840
WAS AND THEN REALLY GAIN A LOT

1017
00:35:40,840 --> 00:35:42,840
OF INFORMATION AND IF--IF WE DID

1018
00:35:42,840 --> 00:35:44,000
THAT I WILL SKIP FORWARD, IF WE

1019
00:35:44,000 --> 00:35:47,400
DID THAT WE COULD REALLY BEGIN

1020
00:35:47,400 --> 00:35:49,880
TO UNDERSTAND THE WHOLE 3

1021
00:35:49,880 --> 00:35:50,560
DIMENSIONAL PICTURE, REMEMBER,

1022
00:35:50,560 --> 00:35:52,560
YOU CAN ONLY SEE WHAT RIEWR

1023
00:35:52,560 --> 00:35:54,520
LOOKING FOR BUT IN THIS

1024
00:35:54,520 --> 00:35:56,000
SCENARIO, YOU WE CAN SEE LIVE

1025
00:35:56,000 --> 00:35:57,360
ELEMENTS AND THEN WE CAN BEGIN

1026
00:35:57,360 --> 00:35:59,040
TO UNDERSTAND THE REAL

1027
00:35:59,040 --> 00:36:00,080
COMPLEXITY OF TUMORS, AFTER

1028
00:36:00,080 --> 00:36:06,120
WE'VE ACQUIRED THE DYNAMIC PARTS

1029
00:36:06,120 --> 00:36:06,640
OF THE IMAGING.

1030
00:36:06,640 --> 00:36:09,120
NOW MARTHA CAME TO THE LAB AND

1031
00:36:09,120 --> 00:36:10,720
SAID, WELL, HAVE YOU A COOL

1032
00:36:10,720 --> 00:36:12,560
SYSTEM, THAT'S TRUE, NO 1 CAN

1033
00:36:12,560 --> 00:36:14,000
DENY THIS BUT YOU HAVE A

1034
00:36:14,000 --> 00:36:16,200
LIMITATION AND THAT LIMITATION

1035
00:36:16,200 --> 00:36:19,280
IS, YOU CERTAINLY HAVE AN INTACT

1036
00:36:19,280 --> 00:36:21,160
TUMOR MICROENVIRONMENT, AND,

1037
00:36:21,160 --> 00:36:24,240
THAT'S COOL BUT HOW DO YOU MODEL

1038
00:36:24,240 --> 00:36:26,040
ANY NEW CELLS WHEN YOU COME INTO

1039
00:36:26,040 --> 00:36:28,440
THE TUMOR, AND SO EXAMPLE WOULD

1040
00:36:28,440 --> 00:36:31,040
BE HOW DO YOU MODEL, IMMUNE CELL

1041
00:36:31,040 --> 00:36:32,920
RECRUITMENT AND YOU DON'T HAVE A

1042
00:36:32,920 --> 00:36:35,240
WAY OF DOING THAT AND SO WHAT

1043
00:36:35,240 --> 00:36:36,640
MARTHA DID, MARTHA REELZED WE

1044
00:36:36,640 --> 00:36:38,480
WERE DRAWING A BUNCH OF BLOOD,

1045
00:36:38,480 --> 00:36:40,840
BLOOD FROM PATIENTS AND THEN WE

1046
00:36:40,840 --> 00:36:44,760
WERE SIMPLY THROWING AWAY THE

1047
00:36:44,760 --> 00:36:47,160
BUFFING OR THE BPMCs, AND

1048
00:36:47,160 --> 00:36:48,280
MARTHA CLICKED THEM INSTEAD OF

1049
00:36:48,280 --> 00:36:50,000
THROWING THEM AWAY AND BEGAN TO

1050
00:36:50,000 --> 00:36:52,760
LABEL THEM WITH A TRACKING DIE.

1051
00:36:52,760 --> 00:36:54,760
AND SHE DEVELOPED WITH A TEAM OF

1052
00:36:54,760 --> 00:36:56,960
ENGINEERS A WAY OF INJECTING

1053
00:36:56,960 --> 00:36:57,920
THESE LABELED CELLS, NOT INTO

1054
00:36:57,920 --> 00:37:01,760
THE TUMOR, THAT WOULD BE SORT

1055
00:37:01,760 --> 00:37:03,160
OF--I DON'T KNOW IF THAT WOULD

1056
00:37:03,160 --> 00:37:04,120
BE REALISTIC BUT MARTHA

1057
00:37:04,120 --> 00:37:07,360
DEVELOPED A WAY TO INJECT THOSE

1058
00:37:07,360 --> 00:37:12,720
CELLS INTO THE P

1059
00:37:12,720 --> 00:37:13,720
EROTONEUM AJAIZENT OR AWAY FROM

1060
00:37:13,720 --> 00:37:16,560
THE TUMOR, IT'S A FANCY SET UP

1061
00:37:16,560 --> 00:37:19,360
AND A VERY FANCY GONIOMETER WITH

1062
00:37:19,360 --> 00:37:24,280
A SENSITIVE INJECTOR AND SO

1063
00:37:24,280 --> 00:37:25,640
MARTHA DEVELOPED THIS TECHNIQUE

1064
00:37:25,640 --> 00:37:29,000
AND I'M GOING TO SHOW YOU WHAT

1065
00:37:29,000 --> 00:37:31,160
THIS LOOKS LIKE, IF THE SLIDES

1066
00:37:31,160 --> 00:37:31,600
WILL ADVANCE.

1067
00:37:31,600 --> 00:37:34,120
HERE WE GO SO WHEN MARTHA

1068
00:37:34,120 --> 00:37:35,840
INJECTS THOSE CELLS, SHE SEES

1069
00:37:35,840 --> 00:37:37,640
THEM AS SORT OF ROUND IN THE

1070
00:37:37,640 --> 00:37:39,840
BEGINNING BUT OVER A PERIOD OF

1071
00:37:39,840 --> 00:37:42,280
ABOUT 3-4 HOURS, THEY BEGIN TO

1072
00:37:42,280 --> 00:37:43,440
ELONGATE AND THEY ACTUALLY MOVE

1073
00:37:43,440 --> 00:37:47,040
ALONG FIBERS OF THE NORMAL

1074
00:37:47,040 --> 00:37:48,120
MESOTHELIUM WHICH IS REALLY COOL

1075
00:37:48,120 --> 00:37:51,720
AND THE QUESTION BECOMES, IS

1076
00:37:51,720 --> 00:37:52,600
THIS PURPOSEFUL MOVEMENT OR IS

1077
00:37:52,600 --> 00:37:54,880
IT JUST SORT OF MOVEMENT?

1078
00:37:54,880 --> 00:37:56,200
AND THE QUESTION BECOMES DOES IT

1079
00:37:56,200 --> 00:37:58,400
GET INTO THE TUMOR AND IN FACT,

1080
00:37:58,400 --> 00:38:01,040
WHAT WE'VE BEEN ABLE TO TO SHOW,

1081
00:38:01,040 --> 00:38:03,520
WHAT MARTHA'S BEEN ABLE TO SHOW

1082
00:38:03,520 --> 00:38:04,800
ALONG WITH ARIBA AND THE REST OF

1083
00:38:04,800 --> 00:38:05,800
THE TEAM, THAT THOSE OVER A

1084
00:38:05,800 --> 00:38:09,040
PERIOD OF A COUPLE OF DAYS,

1085
00:38:09,040 --> 00:38:10,320
THOSE INJECTED PBMC'S LABELED

1086
00:38:10,320 --> 00:38:11,640
FEAR IN GREEN, THEY ALSO ARE

1087
00:38:11,640 --> 00:38:13,280
IMMUNE CELLS OF COURSE SO THEY

1088
00:38:13,280 --> 00:38:17,640
HAVE A RED, GREEN, AND RED

1089
00:38:17,640 --> 00:38:17,840
LABEL.

1090
00:38:17,840 --> 00:38:20,120
THOSE ARE FOUND INSIDE THE TUMOR

1091
00:38:20,120 --> 00:38:22,800
AT THE END OF A 2 DAY RUN AND

1092
00:38:22,800 --> 00:38:24,680
THEY INTERACT WITH AN EVEN KILL

1093
00:38:24,680 --> 00:38:27,280
TUMOR CELL AND I WILL SHOW YOU

1094
00:38:27,280 --> 00:38:28,440
THAT HERE.

1095
00:38:28,440 --> 00:38:30,080
WHAT YOU CAN SEE HERE IS 1 OF

1096
00:38:30,080 --> 00:38:32,160
THOSE GREEN AND RED CELLS, HERE

1097
00:38:32,160 --> 00:38:33,840
IS A CYAN WHICH MARKETS A TUMOR

1098
00:38:33,840 --> 00:38:35,680
CELL AND YOU CAN TRACK THIS OVER

1099
00:38:35,680 --> 00:38:37,680
TIME, I'VE TAKEN IT OUT OF A

1100
00:38:37,680 --> 00:38:39,680
MOVIE FORMAT JUST TO MAKE IT

1101
00:38:39,680 --> 00:38:41,120
EASIER TO SEE AND WHAT YOU CAN

1102
00:38:41,120 --> 00:38:42,880
SEE IS THIS CELL IS NOW

1103
00:38:42,880 --> 00:38:46,880
INTIMATELY ASSOCIATE WIDE THAT

1104
00:38:46,880 --> 00:38:47,280
TUMOR CELL.

1105
00:38:47,280 --> 00:38:48,840
AND THAT WILL ULTIMATELY RESULT

1106
00:38:48,840 --> 00:38:50,600
IN THAT TUMOR CELL DYING.

1107
00:38:50,600 --> 00:38:54,520
OKAY, I'VE SHOWED YOU THE FACT

1108
00:38:54,520 --> 00:38:57,240
THAT MY PARTNERS OVER THE LAST

1109
00:38:57,240 --> 00:39:00,680
SEVERAL 4 OR 5 YEARS, HAVE

1110
00:39:00,680 --> 00:39:05,160
DEVELOPED THESE REALLY COOL

1111
00:39:05,160 --> 00:39:08,280
TOOLS TO BE ABLE TO INVESTIGATE

1112
00:39:08,280 --> 00:39:10,200
DRUGS IN AN OTHERWISE UNFETTERED

1113
00:39:10,200 --> 00:39:11,320
FLAT FORM AND NOW I WILL SHOW

1114
00:39:11,320 --> 00:39:14,840
YOU HOW WE WILL USE THESE TOOLS,

1115
00:39:14,840 --> 00:39:16,200
OKAY?

1116
00:39:16,200 --> 00:39:17,320
SO, EMILY [INDISCERNIBLE] WAS

1117
00:39:17,320 --> 00:39:19,440
HEAVILY INVOLVED IN THE SMART

1118
00:39:19,440 --> 00:39:21,440
SYSTEM AND OPTIMIZING IT BUT SHE

1119
00:39:21,440 --> 00:39:22,920
STARTED THESE EXPERIMENTS BY

1120
00:39:22,920 --> 00:39:25,040
ADDING THE TRIED AND TRUE

1121
00:39:25,040 --> 00:39:26,720
ILTWORKS THE OLD NIH IL2 AND

1122
00:39:26,720 --> 00:39:28,120
HERE WE GO, AND WHAT 'EM

1123
00:39:28,120 --> 00:39:29,640
ILLEGALS SHOWED THAT WAS THAT

1124
00:39:29,640 --> 00:39:32,160
AFTER BEING IN THE SYSTEM FOR 4

1125
00:39:32,160 --> 00:39:35,280
DAYS, YOU CAN DUMP INTERLEUKIN 2

1126
00:39:35,280 --> 00:39:38,960
ON TO THE SYSTEM AND YOU CAN SEE

1127
00:39:38,960 --> 00:39:41,200
THE IMMUNE CELLS IN THE SYSTEM

1128
00:39:41,200 --> 00:39:42,880
RESPOND BY MOVING AND INCREASING

1129
00:39:42,880 --> 00:39:44,000
THEIR VELOCITY AND THAT'S

1130
00:39:44,000 --> 00:39:45,520
ACTUALLY MAPPED OUT HERE.

1131
00:39:45,520 --> 00:39:48,680
AND SO THIS WAS OUR FIRST SORT

1132
00:39:48,680 --> 00:39:50,920
OF REAL DATA THAT YOU CAN ADD

1133
00:39:50,920 --> 00:39:53,040
DRUGS INTO THE SYSTEM AND THE

1134
00:39:53,040 --> 00:39:56,160
IMMUNE CELLS WILL RESPOND TO IT,

1135
00:39:56,160 --> 00:39:59,640
NOW EMILY, WAS INTERESTED IN

1136
00:39:59,640 --> 00:40:00,920
IMMUNOTHERAPY AND SO WE WANTED

1137
00:40:00,920 --> 00:40:03,480
TO GET A DRUG THAT WAS BEING

1138
00:40:03,480 --> 00:40:05,600
USED CLINICALLY AT THE CLINICAL

1139
00:40:05,600 --> 00:40:06,920
CENTER SO EMILY CONVINCED SOME

1140
00:40:06,920 --> 00:40:09,520
OF OUR FRIENDS FROM THE NOW

1141
00:40:09,520 --> 00:40:12,040
CENTER FOR IMMUNO ONCOLOGY TO

1142
00:40:12,040 --> 00:40:15,440
LET US TRY M7824, NOW THIS IS A

1143
00:40:15,440 --> 00:40:18,320
PBL 1 BI FUNCTIONAL TGF BETA

1144
00:40:18,320 --> 00:40:19,200
TRAPPED MOLECULE.

1145
00:40:19,200 --> 00:40:20,400
OKAY, AND WHAT WE ULTIMATELY SAW

1146
00:40:20,400 --> 00:40:23,360
WAS WHEN WE GAVE THE DRUG WE

1147
00:40:23,360 --> 00:40:25,080
COULD IN CERTAIN PATIENTS SEE, I

1148
00:40:25,080 --> 00:40:27,080
WON'T GO THROUGH THIS IN

1149
00:40:27,080 --> 00:40:29,080
ENTIRETY BUT WE COULD SEE CELL

1150
00:40:29,080 --> 00:40:31,080
KILLING, WE COULD SEE CLUSTERING

1151
00:40:31,080 --> 00:40:32,320
OF CD8 CELLS SEQUESTERED TO

1152
00:40:32,320 --> 00:40:33,720
CERTAIN AREAS, THESE ARE AREAS

1153
00:40:33,720 --> 00:40:35,560
THAT CO INSIDED WITH CELL

1154
00:40:35,560 --> 00:40:36,760
KILLING BY TUNNEL STAIN WHICH

1155
00:40:36,760 --> 00:40:39,160
WAS REALLY COOL FOR US.

1156
00:40:39,160 --> 00:40:40,760
NOW EMILY DID SIGNED, AND

1157
00:40:40,760 --> 00:40:42,080
THOUGHT ABOUT AND DESIGNED THIS

1158
00:40:42,080 --> 00:40:44,240
EXPERIMENT AND SO, WE TOOK

1159
00:40:44,240 --> 00:40:45,520
SEVERAL PATIENTS WHO ACTUALLY

1160
00:40:45,520 --> 00:40:47,400
RECEIVED THE DRUG ON A STUDY AND

1161
00:40:47,400 --> 00:40:49,080
WE ENDED UP OPERATING ON THEM.

1162
00:40:49,080 --> 00:40:51,440
AND WE USED THEIR TUMOR IN THE

1163
00:40:51,440 --> 00:40:52,560
SMART SYSTEM AND THEN WE LOOKED

1164
00:40:52,560 --> 00:40:54,120
AT WHAT HAPPENED TO THEIR TUMOR

1165
00:40:54,120 --> 00:40:54,960
BECAUSE WE ALREADY KNEW WHAT

1166
00:40:54,960 --> 00:40:56,360
HAPPENED TO THEM IN REAL LIFE.

1167
00:40:56,360 --> 00:40:58,600
AND THEN WE TOOK A SEPARATE

1168
00:40:58,600 --> 00:40:59,840
SMART COHORT, THESE ARE PATIENTS

1169
00:40:59,840 --> 00:41:02,720
WHO NEVER SAW THE DRUG, AND WE

1170
00:41:02,720 --> 00:41:04,280
GAVE THEM THE DRUG IN THE SMART

1171
00:41:04,280 --> 00:41:08,040
SYSTEM AND THEN WE LOOKED TO SEE

1172
00:41:08,040 --> 00:41:11,440
WHAT HAPPENED, JUST SO SHOW THE

1173
00:41:11,440 --> 00:41:12,360
CLINICAL RESPONDERS AND

1174
00:41:12,360 --> 00:41:12,920
NONRESPONDERS.

1175
00:41:12,920 --> 00:41:15,640
SO THE CLINICAL RESPONDERS IS AN

1176
00:41:15,640 --> 00:41:16,080
INTERESTING STORY.

1177
00:41:16,080 --> 00:41:17,800
HOW WOULD YOU GET A TUMOR THAT

1178
00:41:17,800 --> 00:41:18,920
RESPONDED TO A DRUG AND AT THE

1179
00:41:18,920 --> 00:41:21,480
END OF THE TIME WOULDN'T IT JUST

1180
00:41:21,480 --> 00:41:22,760
BE RESIDUAL CELLS, THAT WOULD BE

1181
00:41:22,760 --> 00:41:24,800
TRUE BUT AS IT TURNS OUT THAT

1182
00:41:24,800 --> 00:41:25,760
PATIENT RECEIVED TOXICITY FROM

1183
00:41:25,760 --> 00:41:26,800
THE DRUG AND SHE WOULD COME OFF

1184
00:41:26,800 --> 00:41:28,800
THE DRUG AND THE TUMOR WOULD

1185
00:41:28,800 --> 00:41:30,160
GROW AND THEN SHE WOULD DP BACK

1186
00:41:30,160 --> 00:41:31,920
ON THE DRUG AND THE TUMOR WOULD

1187
00:41:31,920 --> 00:41:33,120
SHRINK AND THEN SHE WOULD GET

1188
00:41:33,120 --> 00:41:34,840
THE DRUG AGAIN AND SO ON AND SO

1189
00:41:34,840 --> 00:41:36,000
FORTH AND I ENDED UP OPERATING

1190
00:41:36,000 --> 00:41:37,520
ON HER SO SHE WAS SOMEBODY WHO

1191
00:41:37,520 --> 00:41:39,080
HAD TUMOR WE KNEW WOULD BE

1192
00:41:39,080 --> 00:41:40,560
RESPONSIVE TO THE DRUG, SHE WAS

1193
00:41:40,560 --> 00:41:41,680
OUR TRUE POSITIVE AND THEN THERE

1194
00:41:41,680 --> 00:41:45,920
WERE PEOPLE WHO GOT THE DRUG AND

1195
00:41:45,920 --> 00:41:46,800
NOTHING APPARENTLY OSTENSIBLY

1196
00:41:46,800 --> 00:41:49,040
HAPPENED TO THE TUMOR ON RADIO

1197
00:41:49,040 --> 00:41:50,760
GRAPHS WHICH IS OUR GOLD

1198
00:41:50,760 --> 00:41:52,640
STANDARD AND WE LOOKEDDA THE

1199
00:41:52,640 --> 00:41:53,720
SINGLE PATIENT WHO RESPONDED

1200
00:41:53,720 --> 00:41:55,280
VERY WELL, IS THAT PATIENT THAT

1201
00:41:55,280 --> 00:41:56,960
INCLUDED DAY 0 HERE AND THIS IS

1202
00:41:56,960 --> 00:41:58,880
A 2 DAY EXPERIENCE, I INCLUDED

1203
00:41:58,880 --> 00:42:00,800
DAY 0 JUST TO SHOW YOU NOTHING

1204
00:42:00,800 --> 00:42:03,080
REALLY HAPPENED BETWEEN THE

1205
00:42:03,080 --> 00:42:04,160
CONTROL IN DAY ANSWER BUT WHAT

1206
00:42:04,160 --> 00:42:06,280
WE SEE IS ACTIVATED NATURAL

1207
00:42:06,280 --> 00:42:09,360
KILLER CELLS, WE SEE ACTIVATED

1208
00:42:09,360 --> 00:42:12,280
CD8 CELLS, WE SEE PROLIFERATING

1209
00:42:12,280 --> 00:42:15,680
CD45 POSITIVE IMMUNE CELLS,

1210
00:42:15,680 --> 00:42:17,680
INCREASED CASPACE 3, SO CELLS

1211
00:42:17,680 --> 00:42:19,880
ARE DYING, WE SEE DECREASED PDL

1212
00:42:19,880 --> 00:42:21,720
1 STAINING MEMBER BECAUSE THIS

1213
00:42:21,720 --> 00:42:24,480
DRUG BINDS TO PDL MASKING THE

1214
00:42:24,480 --> 00:42:25,360
EPITOPE WE WOULD GUESS SO THIS

1215
00:42:25,360 --> 00:42:27,400
IS WHAT IT LOOKS LIKE WHEN

1216
00:42:27,400 --> 00:42:28,560
SOMEBODY RESPONDS TO THE DRUG.

1217
00:42:28,560 --> 00:42:30,840
AND SO, I WILL SHOW YOU THE

1218
00:42:30,840 --> 00:42:31,800
NATURAL KILLER CELL ACTIVATION

1219
00:42:31,800 --> 00:42:34,640
AND WHEN WE LOOK AT EMILY'S TEST

1220
00:42:34,640 --> 00:42:36,440
COHORT, SOME OF THESE PATIENTS

1221
00:42:36,440 --> 00:42:38,840
LOOK VERY SIMILAR TO WHAT

1222
00:42:38,840 --> 00:42:39,960
HAPPENED TO THE PERSON WHO

1223
00:42:39,960 --> 00:42:41,040
ACTUALLY GOT THE DRUG AND

1224
00:42:41,040 --> 00:42:43,480
RESPONDED TO IT AND HERE'S THE

1225
00:42:43,480 --> 00:42:45,880
CD8 POSITIVE, AGAIN, WE SEE THAT

1226
00:42:45,880 --> 00:42:47,640
RELATIONSHIP WITH 1 OR MAYBE 2

1227
00:42:47,640 --> 00:42:49,040
OF THE PATIENTS WHERE THEY LOOK

1228
00:42:49,040 --> 00:42:52,520
LIKE THE PERSON WHO RESPONDED TO

1229
00:42:52,520 --> 00:42:53,040
THE DRUG.

1230
00:42:53,040 --> 00:42:55,280
HERE'S THE DATA FOR KI67.

1231
00:42:55,280 --> 00:42:56,360
SAME THING IS TRUE HERE, HERE'S

1232
00:42:56,360 --> 00:42:58,840
THE DAILY BASIS THEA FROM PDL 1

1233
00:42:58,840 --> 00:43:00,400
AND THE CULMINATION OF THIS

1234
00:43:00,400 --> 00:43:01,760
EXPERIMENT IS NOT TO SAY THAT,

1235
00:43:01,760 --> 00:43:04,160
YOU KNOW THIS PERSON RESPONDED

1236
00:43:04,160 --> 00:43:05,000
TO THE DRUG.

1237
00:43:05,000 --> 00:43:07,240
EMILY WOULD TELL YOU THAT THIS

1238
00:43:07,240 --> 00:43:08,600
PERSON--WE OUTTO THINK ABOUT

1239
00:43:08,600 --> 00:43:10,480
T-REGGAGING THIS PATIENT TO

1240
00:43:10,480 --> 00:43:11,440
THORS STUDY SHOULD THE DISEASE

1241
00:43:11,440 --> 00:43:13,880
COME BACK AFTER WE OPERATED ON

1242
00:43:13,880 --> 00:43:14,080
THEM.

1243
00:43:14,080 --> 00:43:17,080
AND MUCH TO MY DISPLAY MOST OF

1244
00:43:17,080 --> 00:43:18,920
THE TIME, PATIENTS WITH VERY

1245
00:43:18,920 --> 00:43:20,200
AGGRESSIVE DISEASE END UP HAVING

1246
00:43:20,200 --> 00:43:22,320
RECURRENCE OF DISEASE SO I THINK

1247
00:43:22,320 --> 00:43:26,040
OF THIS EXPERIMENT AS A VERY

1248
00:43:26,040 --> 00:43:27,040
GOOD DEMONSTRATION THAT THIS CAN

1249
00:43:27,040 --> 00:43:28,560
BE USED AS A TRIAGE TOOL TO

1250
00:43:28,560 --> 00:43:34,160
VARIOUS STUDIES IN THE CLINICAL

1251
00:43:34,160 --> 00:43:34,440
CENTER.

1252
00:43:34,440 --> 00:43:35,520
OKAY, WE'RE MOVING ALONG WIGHT A

1253
00:43:35,520 --> 00:43:38,040
BIT HERE WE'RE OKAY ON TIME BUT

1254
00:43:38,040 --> 00:43:40,000
I'M RUNNING SHORT SO I WILL SHOW

1255
00:43:40,000 --> 00:43:40,240
THIS DATA.

1256
00:43:40,240 --> 00:43:43,320
NOW WHEN I WAS A FELLOW--I WILL

1257
00:43:43,320 --> 00:43:45,040
SHOW THIS DATA BECAUSE I WANT TO

1258
00:43:45,040 --> 00:43:46,440
HIGHLIGHT THE CONTRIBUTIONS OF 2

1259
00:43:46,440 --> 00:43:47,880
PEOPLE WHO WORKED REALLY HARD ON

1260
00:43:47,880 --> 00:43:50,840
A SEPARATE PART OF THE LAB.

1261
00:43:50,840 --> 00:43:54,920
AND THEN ULTIMATELY UTILIZE THE

1262
00:43:54,920 --> 00:43:57,160
SYSTEM TO REALLY--FOR REALLY A

1263
00:43:57,160 --> 00:43:58,040
BENCH TO BEDSIDE EFFORT.

1264
00:43:58,040 --> 00:44:01,120
SO WHEN I WAS A FELLOW AT SLOAN

1265
00:44:01,120 --> 00:44:03,160
KETTERRING, 1 THING I DID WAS A

1266
00:44:03,160 --> 00:44:04,240
COLLECTED, WELL WAS THERE WAS A

1267
00:44:04,240 --> 00:44:05,960
BANK OF BILE ON PATIENTS AND WE

1268
00:44:05,960 --> 00:44:06,840
COLLECTED EXOSTUDIES OF MULTIPLE

1269
00:44:06,840 --> 00:44:08,120
ENDOCRINES FROM THIS BILE AND 1

1270
00:44:08,120 --> 00:44:10,200
OF THE THOUGHTS WAS MAYBE WE

1271
00:44:10,200 --> 00:44:12,520
COULD LEARN SOMETHING ABOUT CO

1272
00:44:12,520 --> 00:44:13,800
LANCHIAL CARCINOMA CANCER OF THE

1273
00:44:13,800 --> 00:44:14,960
BILE DUCTS AND WE LOOK AT THE

1274
00:44:14,960 --> 00:44:15,440
EXOSTUDIES OF MULTIPLE

1275
00:44:15,440 --> 00:44:16,840
ENDOCRINES AND THE PROTEIN IN

1276
00:44:16,840 --> 00:44:17,400
THE EXOSTUDIES OF MULTIPLE

1277
00:44:17,400 --> 00:44:19,560
ENDOCRINES KIND OF HARD TO DO

1278
00:44:19,560 --> 00:44:22,400
SINGLE CELL MASS SPECT TROMETRY

1279
00:44:22,400 --> 00:44:24,600
OR PROTEOMICS SPECIAL SO 1 THING

1280
00:44:24,600 --> 00:44:25,960
WE REALIZED WAS THERE A HIGH

1281
00:44:25,960 --> 00:44:27,320
LEVEL OF SOMETHING CALLED EXPORT

1282
00:44:27,320 --> 00:44:30,920
AND 7, I CAME TO THE NIH WITH

1283
00:44:30,920 --> 00:44:33,320
THIS DATA, I AWLTZ KNEW IT WAS

1284
00:44:33,320 --> 00:44:34,280
VERY INTERESTING--ALWAYS KNEW IT

1285
00:44:34,280 --> 00:44:36,480
WAS VERY INTERESTING, IT WASN'T

1286
00:44:36,480 --> 00:44:38,120
ALL PATIENTS, IT WAS MOST, ABOUT

1287
00:44:38,120 --> 00:44:39,960
A FRACTION, ABOUT A THIRD OF

1288
00:44:39,960 --> 00:44:45,520
THEM BUT WHEN IT WAS--WHEN XPO7,

1289
00:44:45,520 --> 00:44:46,760
WHEN WE LOOK AT THE STAINING

1290
00:44:46,760 --> 00:44:47,720
THIS WAS DONE AGAIN BEFORE I

1291
00:44:47,720 --> 00:44:53,240
LEFT AND BEFORE I CAME HERE,

1292
00:44:53,240 --> 00:44:56,200
WHAT WE SAW WAS THAT WAS THERE

1293
00:44:56,200 --> 00:44:57,120
CYTOPLASMIC STAIN NOTHING THE

1294
00:44:57,120 --> 00:44:58,480
CANCER CELLS WHICH WAS SORT OF

1295
00:44:58,480 --> 00:44:59,840
WEIRD AND AGAIN WHEN I TOLD YOU

1296
00:44:59,840 --> 00:45:02,080
BEFORE THAT SAM AND MIKE JOINED

1297
00:45:02,080 --> 00:45:04,280
THE LAB, MY FIRST YEAR HERE IN

1298
00:45:04,280 --> 00:45:07,560
JULY OF 2017 AND I ACTUALLY TOOK

1299
00:45:07,560 --> 00:45:09,400
3 THAT YEAR AND [INDISCERNIBLE]

1300
00:45:09,400 --> 00:45:10,960
AND I SAT THE 3 OF THEM DOWN, I

1301
00:45:10,960 --> 00:45:12,880
DON'T KNOW IF I CAN TAKE 3 OF

1302
00:45:12,880 --> 00:45:14,200
YOU, AND THEY CAME BACK TO ME

1303
00:45:14,200 --> 00:45:16,000
LATER IN THE DAY, THEY SAID NO,

1304
00:45:16,000 --> 00:45:17,680
WE WANT TO DO THIS AND I SAID,

1305
00:45:17,680 --> 00:45:19,880
WELL WHO AM I TO TALK YOU OUT OF

1306
00:45:19,880 --> 00:45:21,880
IT SO REED WORKED INCREDIBLY

1307
00:45:21,880 --> 00:45:24,240
HARD ON THIS AND THE FIRST THING

1308
00:45:24,240 --> 00:45:26,880
REED DID WAS HE GOT A TISSUE

1309
00:45:26,880 --> 00:45:29,080
MICROARRAY FROM STEVE YOU HADET

1310
00:45:29,080 --> 00:45:30,760
HERE AND STEVE STAINED THE

1311
00:45:30,760 --> 00:45:32,120
TISSUE MICROARRAY AND WE

1312
00:45:32,120 --> 00:45:34,400
VALIDATED THIS ON AN INDEPENDENT

1313
00:45:34,400 --> 00:45:35,200
COHORT, THAT THERE'S A FRACTION

1314
00:45:35,200 --> 00:45:37,280
OF THESE PATIENTS WITH CO

1315
00:45:37,280 --> 00:45:38,920
LANCHIAL CARCINOMA THAT HAVE

1316
00:45:38,920 --> 00:45:40,440
THIS EXVIVO STAIN NOTHING THE

1317
00:45:40,440 --> 00:45:43,760
CYTOPLASM AND LOW AND BEHOLD IT

1318
00:45:43,760 --> 00:45:44,960
RESULTS IN WORSE SURVIVAL AND

1319
00:45:44,960 --> 00:45:46,680
THAT IS TRUE ON A MULTIVALID AND

1320
00:45:46,680 --> 00:45:47,400
RELIABLE YABT ANALYSIS SO

1321
00:45:47,400 --> 00:45:50,600
WHATEVER THIS IS, IT'S A MARKER

1322
00:45:50,600 --> 00:45:51,080
OF AGGRESSIVE DISEASE.

1323
00:45:51,080 --> 00:45:52,280
NOW REED DID A LOT OF

1324
00:45:52,280 --> 00:45:53,920
EXPERIMENTS BUT HE FIGURED OUT

1325
00:45:53,920 --> 00:45:55,240
WAS FROM USING TUMOR

1326
00:45:55,240 --> 00:45:58,320
ORGANIZATIONS RANNOIDS WHAT HE

1327
00:45:58,320 --> 00:46:00,920
FIGURED OUT WAS THAT WHEN YOU

1328
00:46:00,920 --> 00:46:02,480
DID A NEW CLE O PLASMIC

1329
00:46:02,480 --> 00:46:03,640
SEPARATION AND AN EXPERIMENT

1330
00:46:03,640 --> 00:46:05,960
FROM THE CYTOPLASM HE PULLED

1331
00:46:05,960 --> 00:46:07,280
DOWN SOMETHING CALLED SLK, HE

1332
00:46:07,280 --> 00:46:08,760
THEN DID THE OPPOSITE EXPERIMENT

1333
00:46:08,760 --> 00:46:13,080
WHERE HE PULLED DOWN SLK AND HE

1334
00:46:13,080 --> 00:46:13,960
GOT XPO7.

1335
00:46:13,960 --> 00:46:16,200
AND WHEN YOU DO THIS

1336
00:46:16,200 --> 00:46:18,920
COMPUTATIONALLY THESE 2

1337
00:46:18,920 --> 00:46:20,880
MOLECULES FIT TOGETHER VERY

1338
00:46:20,880 --> 00:46:22,320
WELL, SO HMM, A KINASE, THAT'S

1339
00:46:22,320 --> 00:46:24,400
INTERESTING AND YOU CAN INHIBIT

1340
00:46:24,400 --> 00:46:25,720
KINASES SO WE DID THIS WITH

1341
00:46:25,720 --> 00:46:27,200
SHORT HAIR PINS IN THE BEGINNING

1342
00:46:27,200 --> 00:46:29,520
AND WE REALIZED THAT IN AN

1343
00:46:29,520 --> 00:46:31,920
ORTHOTOPIC TUMOR INJECTION MODEL

1344
00:46:31,920 --> 00:46:34,680
THAT YOU ACTUALLY INHIBIT TUMOR

1345
00:46:34,680 --> 00:46:36,360
FORMATION AND IT FORMS BUT IT'S

1346
00:46:36,360 --> 00:46:38,680
SMALL BUT REALLY COOL IS IT

1347
00:46:38,680 --> 00:46:40,960
LOOKS WAY DIFFERENT THAN A

1348
00:46:40,960 --> 00:46:42,360
FORMAL TUMOR, IT'S NOT JUST A

1349
00:46:42,360 --> 00:46:44,080
SMALL TUMOR, IT HAS A CYSTIC

1350
00:46:44,080 --> 00:46:47,520
APPEARANCE, THERE'S A LOT OF

1351
00:46:47,520 --> 00:46:48,560
DEGENERATING CELLS, THERE WASN'T

1352
00:46:48,560 --> 00:46:51,920
A LOT OF TUMOR INVADING INTO THE

1353
00:46:51,920 --> 00:46:53,080
SORT EVER NORMAL LIVER

1354
00:46:53,080 --> 00:46:57,400
ARCHITECTURE THAT WE ALWAYS SEE

1355
00:46:57,400 --> 00:46:58,320
WITH THIS DISEASE.

1356
00:46:58,320 --> 00:47:00,520
AND THEN TOSSIN JOINED THE LAB

1357
00:47:00,520 --> 00:47:02,520
SEVERAL YEARS AGO AND TOSSIN HAD

1358
00:47:02,520 --> 00:47:03,960
EXPERIENCE WITH SIGNALING AND HE

1359
00:47:03,960 --> 00:47:06,240
SAID, WELL, YOU CERTAINLY CAN'T

1360
00:47:06,240 --> 00:47:07,640
GIVE PEOPLE SHORT HAIR PINS BUT

1361
00:47:07,640 --> 00:47:10,480
CAN YOU DO IS GIVE PEOPLE KINASE

1362
00:47:10,480 --> 00:47:10,800
INHIBITORS.

1363
00:47:10,800 --> 00:47:13,080
WELL, THERE IS NO KINASE

1364
00:47:13,080 --> 00:47:15,880
INHIBITOR TO SLK SO TOSSEN

1365
00:47:15,880 --> 00:47:16,920
WORKED WITH OUR FRIENDS AT CAPER

1366
00:47:16,920 --> 00:47:19,640
AND HE CAME UP WITH SEVERAL

1367
00:47:19,640 --> 00:47:21,160
DRUGS HE THOUGHT MAYBE COULD

1368
00:47:21,160 --> 00:47:22,920
WORK AND AND HE RAN THIS EARLY

1369
00:47:22,920 --> 00:47:24,280
EXPERIMENT WHERE HE SHOWED THAT

1370
00:47:24,280 --> 00:47:27,000
1 OF THESE DRUGS, RESULT IN

1371
00:47:27,000 --> 00:47:28,480
SUBSTANTIAL TUMOR REGRESSION,

1372
00:47:28,480 --> 00:47:30,360
NOT JUST PREVENTATIVE TUMOR FROM

1373
00:47:30,360 --> 00:47:31,680
GROWING, HE LET THEM GROW AND

1374
00:47:31,680 --> 00:47:33,520
TREATED THEM AND HERE'S THE

1375
00:47:33,520 --> 00:47:37,880
WATER FALL PLOT AND HE SAW

1376
00:47:37,880 --> 00:47:39,440
SHRINKAGE OF THESE TUMORS.

1377
00:47:39,440 --> 00:47:41,120
NOW TOSSIN DID A TON OF WORK,

1378
00:47:41,120 --> 00:47:42,760
IT'S OUTSIDE THE SCOPE OF THIS

1379
00:47:42,760 --> 00:47:47,480
TALK BUT TOSSIN REALLY PROVED

1380
00:47:47,480 --> 00:47:51,040
THAT THAT DRUG TIVOZANIB BINDS

1381
00:47:51,040 --> 00:47:52,920
AND PUSHING UP THE REGION AND

1382
00:47:52,920 --> 00:47:54,160
BLOCKING THE KINASE FUNCTION.

1383
00:47:54,160 --> 00:47:55,360
HE DID THIS, I'M SHOWING YOU

1384
00:47:55,360 --> 00:47:56,600
HERE BECAUSE IT LOOKS THE

1385
00:47:56,600 --> 00:48:00,360
COOLEST BUT HE DID THIS--USING

1386
00:48:00,360 --> 00:48:02,080
AND CRYSTALLIZING SLK WITH

1387
00:48:02,080 --> 00:48:04,120
[INDISCERNIBLE] DRUGS AND

1388
00:48:04,120 --> 00:48:05,640
CRYSTALLIZED UNDER HIS WATCH, HE

1389
00:48:05,640 --> 00:48:08,160
ALSO DID A NUMBER OF

1390
00:48:08,160 --> 00:48:08,680
EXPERIMENTS, KINASE DEAD

1391
00:48:08,680 --> 00:48:10,280
CONSTRUCTS HE HAS DRUG RESIST

1392
00:48:10,280 --> 00:48:12,440
ABT CONSTRUCTS AND THE DRUG

1393
00:48:12,440 --> 00:48:14,400
COMBINED, SO HE DID A LOT OF

1394
00:48:14,400 --> 00:48:16,520
WORK TO PROVE THIS IS IN FACT,

1395
00:48:16,520 --> 00:48:17,680
HAPPENING THEN HE SAID OKAY, WE

1396
00:48:17,680 --> 00:48:20,160
NEED TO GET AHOLD OF PDXs AND

1397
00:48:20,160 --> 00:48:23,400
WE DIDN'T HAVE PDXs, THE NIH

1398
00:48:23,400 --> 00:48:25,040
DOESN'T HAVE ANY PDXs BUT WE

1399
00:48:25,040 --> 00:48:29,240
BOUGHT THEM FROM A VENDOR AND WE

1400
00:48:29,240 --> 00:48:30,960
CHECKED THISEM AND LOW AND

1401
00:48:30,960 --> 00:48:33,000
BEHOLD THEY ALL HAD EXPRESSION

1402
00:48:33,000 --> 00:48:35,120
IN THE CYTOPLASM AND WHEN WE

1403
00:48:35,120 --> 00:48:38,960
TREAT WITH THE SINGLE DRUG

1404
00:48:38,960 --> 00:48:40,440
TIVOZANIB, WE SEE QUICKLY THAT

1405
00:48:40,440 --> 00:48:42,800
IT DOESN'T GROW AT ALL, IT STAYS

1406
00:48:42,800 --> 00:48:45,240
AND SHRINKS AND THIS PDX GREW

1407
00:48:45,240 --> 00:48:46,640
QUICKER AND IT EXPERIMENT IS

1408
00:48:46,640 --> 00:48:48,280
TILL ONGOING, THEY BOTH ARE

1409
00:48:48,280 --> 00:48:49,920
REALLY, BUT THIS DRUG LOOKS LIKE

1410
00:48:49,920 --> 00:48:55,080
IT WORKS VERY WELL'RE XPO7

1411
00:48:55,080 --> 00:48:55,920
EXPRESSING FILLAGEIO CARCINOMA

1412
00:48:55,920 --> 00:48:57,520
NOW TOSSIN WANTED TO TAKE THIS A

1413
00:48:57,520 --> 00:48:58,840
STEP FURTHER.

1414
00:48:58,840 --> 00:49:00,760
I WILL TAKE IT BACK FULL CIRCLE

1415
00:49:00,760 --> 00:49:03,560
AND SHOW THAT TOSSEN THEN USED

1416
00:49:03,560 --> 00:49:05,680
THIS DATA AND TREATED 2 PATIENTS

1417
00:49:05,680 --> 00:49:06,200
IN THE SMART SYSTEM, FIRST

1418
00:49:06,200 --> 00:49:07,800
PATIENT WAS ON THE LEFT HERE

1419
00:49:07,800 --> 00:49:11,240
THIS, IS PATIENT LABELED A, THIS

1420
00:49:11,240 --> 00:49:13,960
IS AN XPO7 NEGATIVE CO LANCHIAL

1421
00:49:13,960 --> 00:49:15,640
CARCINOMA, WHEN YOU GIVE THE

1422
00:49:15,640 --> 00:49:17,560
DRUG INTO THE SYSTEM, IT'S A 4

1423
00:49:17,560 --> 00:49:19,160
DAY EXPERIMENT WHAT YOU SEE IS

1424
00:49:19,160 --> 00:49:22,920
NOT A WHOLE LOT TO BE FOUND

1425
00:49:22,920 --> 00:49:25,000
TOTALLY HONEST WE DON'T SEE A

1426
00:49:25,000 --> 00:49:28,600
MUCH INCREASE IN CASPACE 3,

1427
00:49:28,600 --> 00:49:29,360
TUNNEL STAINING DEPECTED

1428
00:49:29,360 --> 00:49:30,040
GRAPHICALLY HERE, CONTRAST THAT

1429
00:49:30,040 --> 00:49:32,720
TO THE PATIENT WHO HAD XPO7 AND

1430
00:49:32,720 --> 00:49:34,520
THE CYTOPLASM AS SHOWN BY THE

1431
00:49:34,520 --> 00:49:38,120
GROUND STAIN HERE AND WHAT

1432
00:49:38,120 --> 00:49:42,000
HAPPENED WHEN WE GAVE TIVOZANIB

1433
00:49:42,000 --> 00:49:44,600
FOR 4 DAYS YOU CAN SEE TUMOR

1434
00:49:44,600 --> 00:49:45,600
DEATH BY DAY 3 AND TUNNEL

1435
00:49:45,600 --> 00:49:47,440
STAINING AND YOU CAN SEE THAT

1436
00:49:47,440 --> 00:49:49,360
QUANTIFIED HERE AND YOU CAN SEE

1437
00:49:49,360 --> 00:49:52,040
A HUGE AMOUNT OF CELL DEATH

1438
00:49:52,040 --> 00:49:54,840
ASSOCIATED WITH THIS DRUG.

1439
00:49:54,840 --> 00:49:56,680
NOW, TOSSEN AND I THEN SAT AND

1440
00:49:56,680 --> 00:49:59,000
WE WERE VERY IMPRESSED BY ALL

1441
00:49:59,000 --> 00:49:59,680
THIS DATA.

1442
00:49:59,680 --> 00:50:00,440
WE APPROACHED THIS COMPANY AND

1443
00:50:00,440 --> 00:50:01,760
SAID WE WANT THIS DRUG TO RUN IN

1444
00:50:01,760 --> 00:50:04,120
PATIENT SAYS, THIS WOULD BE A

1445
00:50:04,120 --> 00:50:05,960
FIRST EVER CO LANCHIAL CARCINOMA

1446
00:50:05,960 --> 00:50:07,400
ANDY WOO WE WROTE THIS TRIAL

1447
00:50:07,400 --> 00:50:09,480
TOGETHER AND I'M PROUD TO SAY WE

1448
00:50:09,480 --> 00:50:10,680
HAVE NOW TREATED OUR SECOND

1449
00:50:10,680 --> 00:50:12,560
PATIENT ON STUDY, WE DON'T ARE

1450
00:50:12,560 --> 00:50:13,760
RESULTS YET, THEY ARE BEING

1451
00:50:13,760 --> 00:50:15,400
TREATED WE HAVEN'T DONE ANY

1452
00:50:15,400 --> 00:50:16,600
EVALUATION YET BUT WE'VE TREATED

1453
00:50:16,600 --> 00:50:19,360
2 PATIENTS ON STUDY, AND THIS IS

1454
00:50:19,360 --> 00:50:22,240
A TRUE BENCH TO BEDSIDE MISSION,

1455
00:50:22,240 --> 00:50:23,280
MISSION ACCOMPLISHED, NOW OF

1456
00:50:23,280 --> 00:50:25,840
COURSE IT HAS TO WORK OTHERWISE

1457
00:50:25,840 --> 00:50:27,680
IT DOESN'T MATTER BUT WE'RE HOPE

1458
00:50:27,680 --> 00:50:27,920
EMPLOY.

1459
00:50:27,920 --> 00:50:31,880
OKAY, I WANT TO END WITH AGAIN A

1460
00:50:31,880 --> 00:50:32,840
THANK YOU.

1461
00:50:32,840 --> 00:50:35,240
I MEANT TO HIGHLIGHT EVERYBODY'S

1462
00:50:35,240 --> 00:50:37,320
CONTRIBUTIONS AND I DIDN'T GET A

1463
00:50:37,320 --> 00:50:40,120
CHANCE TO GO THROUGH ALL OF THE

1464
00:50:40,120 --> 00:50:43,560
NEWER FELLOWS IN THE LAB BUT

1465
00:50:43,560 --> 00:50:44,600
CARRY RYAN'S DOING SOMETHING

1466
00:50:44,600 --> 00:50:50,720
COOL, SHE FIGURED OUT A WEB

1467
00:50:50,720 --> 00:50:52,240
CONNECTED AND THEY'RE GOING TO

1468
00:50:52,240 --> 00:50:53,200
FIGURE THAT OUT, LAILA IS,

1469
00:50:53,200 --> 00:50:54,720
WOOING ON SOMETHING NEAR AND

1470
00:50:54,720 --> 00:50:56,040
DAILY BASISSER TO MY HEART WHICH

1471
00:50:56,040 --> 00:50:57,280
IS IDENTIFYING CELLS THAT YOU

1472
00:50:57,280 --> 00:50:59,520
CANNOT OTHERWISE SEE IN

1473
00:50:59,520 --> 00:51:01,520
MICROMETASTASIS AND LARGE PIECES

1474
00:51:01,520 --> 00:51:02,920
OF LIVER, STEPHANIE GREGORY WILL

1475
00:51:02,920 --> 00:51:04,680
IS WORKING WITH ANDREW BLAKELY

1476
00:51:04,680 --> 00:51:09,240
AND WE'RE LOOKING TO SEE IF WE

1477
00:51:09,240 --> 00:51:11,320
CAN AND DECIDE WHICH DRUGS WE

1478
00:51:11,320 --> 00:51:12,520
SHOULD GIVE PATIENTS RIGHT NOW

1479
00:51:12,520 --> 00:51:14,360
IT'S A GUESS, STEPHANIE STANDS

1480
00:51:14,360 --> 00:51:15,320
TO MAKE A BIG CONTRIBUTION

1481
00:51:15,320 --> 00:51:21,120
THERE, I JUST WANT TO BE

1482
00:51:21,120 --> 00:51:23,800
EVERYBODY SORT OF CAME TOGETHER

1483
00:51:23,800 --> 00:51:25,680
AND EVERYBODY CONTRIBUTED AND IT

1484
00:51:25,680 --> 00:51:27,000
HAS TRULY BEEN MY PLEASURE OVER

1485
00:51:27,000 --> 00:51:30,080
THESE LAST 5 OR 6 YEARS TO WORK

1486
00:51:30,080 --> 00:51:40,640
WITH ALL OF THESE PARTNERS THAT

1487
00:52:01,920 --> 00:52:03,440
I'VE HAD.

1488
00:52:03,440 --> 00:52:04,720
--WORKED REALLY, REALLY HARD TO

1489
00:52:04,720 --> 00:52:05,680
DEVELOP THESE COOL IMAGING

1490
00:52:05,680 --> 00:52:08,800
THINGS YOU JUST SAW, ANDREW

1491
00:52:08,800 --> 00:52:10,760
BLAKELY AND JEREMY DAVIS ARE MY

1492
00:52:10,760 --> 00:52:11,800
SURGERY PARTNERS AND OPERATE ON

1493
00:52:11,800 --> 00:52:15,080
THESE PATIENTS WITH ME.

1494
00:52:15,080 --> 00:52:16,000
AND WE WOULDN'T--NONE OF THIS

1495
00:52:16,000 --> 00:52:17,160
WOULD BE POSSIBLE IF WE DIDN'T

1496
00:52:17,160 --> 00:52:19,160
DO A VERY GOOD JOB FOR PATIENTS

1497
00:52:19,160 --> 00:52:20,560
AND I'M VERY PROUD OF THE WAY WE

1498
00:52:20,560 --> 00:52:29,080
TREAT PATIENTS AND HOW WE TAKE

1499
00:52:29,080 --> 00:52:29,440
CARE OF THEM.

1500
00:52:29,440 --> 00:52:30,960
AND VERY PROUD OF EVERYBODY IN

1501
00:52:30,960 --> 00:52:31,880
THE OPERATING RADIO AM AND

1502
00:52:31,880 --> 00:52:33,240
EVERYBODY DOES WHAT THEY CAN AND

1503
00:52:33,240 --> 00:52:36,320
THEY TAKE CARE OF THE PATIENTS

1504
00:52:36,320 --> 00:52:38,240
AND THEY MAKE THINGS HAPPEN.

1505
00:52:38,240 --> 00:52:39,840
DR. CLIENER WE WOULD BE LOST

1506
00:52:39,840 --> 00:52:40,920
WITHOUT HIM, HE REVIEWS ALL

1507
00:52:40,920 --> 00:52:42,600
THESE SORT OF HISTOLOGY FOR US

1508
00:52:42,600 --> 00:52:45,800
ON ALL OF THESE RUNS, AND I

1509
00:52:45,800 --> 00:52:48,120
WOULD SAY PROBABLY THE PERSON I

1510
00:52:48,120 --> 00:52:49,360
DIDN'T MENTION YOU GO PROBABLY

1511
00:52:49,360 --> 00:52:51,000
DESERVES NOR CREDIT THAN I DO

1512
00:52:51,000 --> 00:52:53,280
FOR SURE AND TOM AND HIS GROUP.

1513
00:52:53,280 --> 00:52:55,520
THEY ARE THE ENGINEERS THAT HAVE

1514
00:52:55,520 --> 00:52:57,800
WORKED BEHIND THE SCENES REALLY

1515
00:52:57,800 --> 00:52:59,600
CREATE ALL OF THESE THINGS, SO

1516
00:52:59,600 --> 00:53:04,080
OUR IDEAS CAME TO FRUITION BY

1517
00:53:04,080 --> 00:53:06,600
TOM, JOHN, MARCI, RANDY, THE

1518
00:53:06,600 --> 00:53:10,440
GUYS OVER THERE AND THEY REALLY

1519
00:53:10,440 --> 00:53:12,240
HAVE DONE AN EXCELLENT JOB AND

1520
00:53:12,240 --> 00:53:14,080
CO INVEBTORS ON ALL THE PATENTS.

1521
00:53:14,080 --> 00:53:16,040
SO WITH THAT, I WOULD LIKE TO

1522
00:53:16,040 --> 00:53:26,520
END AND TAKE ANY QUESTIONS.

1523
00:53:29,760 --> 00:53:30,520
>> DR. HERNÁNDEZ, OKAY, SO
IMIE

1524
00:53:30,520 --> 00:53:32,040
FIRST OF ALL I WANT TO THANK YOU

1525
00:53:32,040 --> 00:53:35,800
FOR SHARING YOUR ABSOLUTELY

1526
00:53:35,800 --> 00:53:36,600
FASCINATING WORK AND

1527
00:53:36,600 --> 00:53:38,640
CONGRATULATIONS ON ALL YOUR

1528
00:53:38,640 --> 00:53:38,920
PROGRESS.

1529
00:53:38,920 --> 00:53:42,120
WE LOOK FORWARD TO SEEING WHAT

1530
00:53:42,120 --> 00:53:43,640
YOU WILL ACCOMPLISH IN THE

1531
00:53:43,640 --> 00:53:44,960
FUTURE, I THINK WHAT'S MOST

1532
00:53:44,960 --> 00:53:46,000
IMPORTANT AND STANDS OUT TO ME

1533
00:53:46,000 --> 00:53:49,280
IS YOU WERE SELECTED AS OUR

1534
00:53:49,280 --> 00:53:50,240
DISTINGUISHED CLINICAL TEACHER

1535
00:53:50,240 --> 00:53:52,280
AT EVERY STEP IN THE PROGRESS OF

1536
00:53:52,280 --> 00:53:54,120
YOUR RESEARCH, YOU GIVE SO MUCH

1537
00:53:54,120 --> 00:53:56,000
CREDIT TO YOUR FELLOWS WHO WOULD

1538
00:53:56,000 --> 00:53:57,760
BRING LIGHT AND INSIGHTS INTO

1539
00:53:57,760 --> 00:53:59,160
PROBLEMS THAT WERE ENCOUNTERED

1540
00:53:59,160 --> 00:54:00,120
WHILE YOU MENTORED THEIR

1541
00:54:00,120 --> 00:54:01,360
SOLUTIONS THAT THEY SUGGESTED

1542
00:54:01,360 --> 00:54:03,920
BUT, YOU KNOW IT'S NOT LOST ON

1543
00:54:03,920 --> 00:54:06,400
US THAT IT IS YOUR OWN INSIGHTS

1544
00:54:06,400 --> 00:54:09,360
AND THAT HAVE GUIDED TOWARD

1545
00:54:09,360 --> 00:54:10,320
THESE SOLUTIONS.

1546
00:54:10,320 --> 00:54:15,840
YOU'RE OBVIOUSLY A VERY HIGHLY

1547
00:54:15,840 --> 00:54:16,440
RESPECTED METROPOLITANNOR AND

1548
00:54:16,440 --> 00:54:18,040
LAUNCHED MANY CAREERS HERE FOR

1549
00:54:18,040 --> 00:54:20,120
NEW PHYSICIAN SCIENTISTS

1550
00:54:20,120 --> 00:54:21,880
SPECIFICALLY SURGEON SCIENTISTS

1551
00:54:21,880 --> 00:54:24,600
AND AGAIN CONGRATULATIONS ON

1552
00:54:24,600 --> 00:54:26,280
YOUR WELL-DESERVING OF THE

1553
00:54:26,280 --> 00:54:28,600
CLINICAL TEACHER AWARD AND SO

1554
00:54:28,600 --> 00:54:30,760
CONGRATULATIONS FOR THAT AND

1555
00:54:30,760 --> 00:54:31,200
THIS WONDERFUL TALK.

1556
00:54:31,200 --> 00:54:35,440
SO WE HAVE TIME FOR--THERE'S A

1557
00:54:35,440 --> 00:54:36,360
COUPLE QUESTIONS HERE.

1558
00:54:36,360 --> 00:54:39,560
LET'S SEE HERE, TO START, SO

1559
00:54:39,560 --> 00:54:40,800
YOUR SYSTEM LOOKEDDA THE VARIOUS

1560
00:54:40,800 --> 00:54:43,080
TUMORS IS THERE A TYPE OF

1561
00:54:43,080 --> 00:54:45,360
TUMORROR THAT APPEARS TO BE A

1562
00:54:45,360 --> 00:54:51,880
BEST CANDAD FOR BEING STUDIED IN

1563
00:54:51,880 --> 00:54:52,480
YOUR ALAN SYSTEM SPECIFICALLY?

1564
00:54:52,480 --> 00:54:53,920
>> YEAH, SO THEA WILL AN
SYSTEM

1565
00:54:53,920 --> 00:54:58,400
IS 1 THAT PROABT DOESN'T MATTER

1566
00:54:58,400 --> 00:55:00,120
AS MUCH I THINK THAT WE HAVEN'T

1567
00:55:00,120 --> 00:55:02,160
DONE IT ENOUGH TO ANSWER THAT

1568
00:55:02,160 --> 00:55:03,520
QUESTION, BUT I THINK I WILL

1569
00:55:03,520 --> 00:55:06,880
ANSWER THAT USING THE SMART

1570
00:55:06,880 --> 00:55:08,640
SYSTEM, SO, THAT SYSTEM THE MORE

1571
00:55:08,640 --> 00:55:10,760
AGGRESSIVE THE TUMOR, THE EASIER

1572
00:55:10,760 --> 00:55:11,400
IT IS.

1573
00:55:11,400 --> 00:55:13,960
AND SO, TUMORS THAT SORT OF ARE

1574
00:55:13,960 --> 00:55:17,080
SORT OF SOFT AND HAVE A LOT OF

1575
00:55:17,080 --> 00:55:18,120
NECROSIS IN THE MIDDLE, THOSE

1576
00:55:18,120 --> 00:55:28,640
TEND TO BE MORE DIFFICULT FOR

1577
00:55:35,320 --> 00:55:41,800
US--BUT THE PATIENT HAS

1578
00:55:41,800 --> 00:55:44,160
DEVELOPED AND KNEW IT WOULD BE

1579
00:55:44,160 --> 00:55:46,480
FAIRLY AGGRESSIVE AND ONCE THAT

1580
00:55:46,480 --> 00:55:49,240
HAPPENS THE TUMORS STAY FAIRLY

1581
00:55:49,240 --> 00:55:50,400
VIABLE, THE ADVANTAGE OF THE

1582
00:55:50,400 --> 00:55:52,400
ALLEN SYSTEM IS WE DON'T GO

1583
00:55:52,400 --> 00:55:54,680
ANYWHERE NEAR THE TUMOR, I USE

1584
00:55:54,680 --> 00:55:56,720
THE INFLOW AND OUTFLOW KNOWLEDGE

1585
00:55:56,720 --> 00:55:58,840
OF THE LIVER AND INFLOW AND

1586
00:55:58,840 --> 00:56:00,760
OUTFLOW VESSELS AND THAT

1587
00:56:00,760 --> 00:56:02,080
TENDINGS TO STAY FAIRLY HAPPY

1588
00:56:02,080 --> 00:56:03,080
AND YOU WOULD MENTION THE MOST

1589
00:56:03,080 --> 00:56:04,600
DIFFICULT PART OF THAT SYSTEM IS

1590
00:56:04,600 --> 00:56:06,480
KEEPING THE LIVER HAPPY, THE

1591
00:56:06,480 --> 00:56:07,680
LIVER'S NORMAL TISSUE, THE

1592
00:56:07,680 --> 00:56:08,800
NORMAL TISSUE NOT REALLY MEANT

1593
00:56:08,800 --> 00:56:11,240
TO BE LIVING LIKE THIS.

1594
00:56:11,240 --> 00:56:14,440
BUT A TOMB OAR TENDS TO DO JUST

1595
00:56:14,440 --> 00:56:14,920
FINE.

1596
00:56:14,920 --> 00:56:17,000
SO I THINK, YOU KNOW THAT THE

1597
00:56:17,000 --> 00:56:19,960
ALAN SYSTEM IS GOING TO BE--IT'S

1598
00:56:19,960 --> 00:56:21,520
GOING TO WORK FOR ANYBODY WHO

1599
00:56:21,520 --> 00:56:24,520
HAS THE METASTASIS IN THE RIGHT

1600
00:56:24,520 --> 00:56:26,680
PLACE OR IS UNDERGOING A

1601
00:56:26,680 --> 00:56:27,400
THERAPEUTIC METRICS TAFTSECTOMY

1602
00:56:27,400 --> 00:56:28,760
AND THAT'S NOT EVERYBODY I

1603
00:56:28,760 --> 00:56:30,040
OPERATE ON, IT'S A FRACTION BUT

1604
00:56:30,040 --> 00:56:31,360
TUMOR HAS TO BE IN THE RIGHT LO

1605
00:56:31,360 --> 00:56:32,440
XAIGZ AND I HAVE TO FEEL LIKE

1606
00:56:32,440 --> 00:56:33,720
IT'S THE RIGHT THING TO DO FOR

1607
00:56:33,720 --> 00:56:34,960
THE PATIENT BUT I DON'T THINK

1608
00:56:34,960 --> 00:56:36,720
THE TYPE OF TUMOR IS GOING TO--I

1609
00:56:36,720 --> 00:56:38,880
THINK IT'S ALL GOING TO WORK OUT

1610
00:56:38,880 --> 00:56:39,080
OKAY.

1611
00:56:39,080 --> 00:56:42,080
I DON'T THINK THAT'S GOING TO BE

1612
00:56:42,080 --> 00:56:44,160
DETRIMENTAL DEPENDING ON ACROSS

1613
00:56:44,160 --> 00:56:45,120
VARIOUS TUMOR TYPES, OBVIOUSLY

1614
00:56:45,120 --> 00:56:47,200
WE HAVE TO PROVE THAT BUT THAT'S

1615
00:56:47,200 --> 00:56:50,520
MY FEELING.

1616
00:56:50,520 --> 00:56:50,880
>> THANK YOU.

1617
00:56:50,880 --> 00:56:54,360
OKAY, LET'S SEE HERE 1 OTHER

1618
00:56:54,360 --> 00:56:54,640
QUESTION.

1619
00:56:54,640 --> 00:56:56,400
IT'S EXCITING HOW THE SMART

1620
00:56:56,400 --> 00:57:00,960
SYSTEM ALLOWS FOR DIRECT

1621
00:57:00,960 --> 00:57:02,160
EVALUATION TOZINIB IN THE EFFECT

1622
00:57:02,160 --> 00:57:03,680
OF PATIENTS WHO INSIGHTS HAS

1623
00:57:03,680 --> 00:57:05,080
YOUR SYSTEM REVEALED TO TUMOR

1624
00:57:05,080 --> 00:57:07,040
BIOLOGY THAT MAY OFFER THAT

1625
00:57:07,040 --> 00:57:09,280
OTHER NEXT GREAT STEPS IN

1626
00:57:09,280 --> 00:57:10,000
THERAPEUTICS?

1627
00:57:10,000 --> 00:57:11,440
>> SO WHAT I THINK, YOU
KNOW, I

1628
00:57:11,440 --> 00:57:12,880
WOULD SAY, I WILL ANSWER THAT IN

1629
00:57:12,880 --> 00:57:15,320
THE FOLLOWING WAY, SO, WHEN YOU

1630
00:57:15,320 --> 00:57:16,720
LOOK AT WHAT HAPPENS WHEN YOU

1631
00:57:16,720 --> 00:57:19,160
GIVE A DRUG THAT KILLS A LOT OF

1632
00:57:19,160 --> 00:57:20,600
TUMOR CELLS, THEY DON'T ALL DIE,

1633
00:57:20,600 --> 00:57:22,360
AND THAT'S SORT OF WHAT WE

1634
00:57:22,360 --> 00:57:25,440
OTHERWISE KNOW TO BE TRUE IN

1635
00:57:25,440 --> 00:57:25,720
PATIENTS.

1636
00:57:25,720 --> 00:57:27,200
YOU DON'T SEE THESE DRUGS MELT

1637
00:57:27,200 --> 00:57:32,360
AWAY ALL THE TUMOR AND SO, THE

1638
00:57:32,360 --> 00:57:33,920
HETEROGENERATED AITY IS REALLY,

1639
00:57:33,920 --> 00:57:36,240
REALLY CAPTURED HERE SO THIS

1640
00:57:36,240 --> 00:57:37,520
ISN'T AN ISOLATED CELL

1641
00:57:37,520 --> 00:57:39,240
POPULATION LIKE AN ORGANOID

1642
00:57:39,240 --> 00:57:40,040
POPULATION WHERE THEY'RE

1643
00:57:40,040 --> 00:57:41,680
PROBABLY ALL LIKELY TO RESPOND

1644
00:57:41,680 --> 00:57:45,760
OR NOT, THIS CAPTURES ALL THE

1645
00:57:45,760 --> 00:57:48,080
HETEROGENERATED AITY AND SO

1646
00:57:48,080 --> 00:57:49,680
THAT'S A VERY ENLIGHTENING THING

1647
00:57:49,680 --> 00:57:50,840
THAT YOU REALIZE THERE ARE

1648
00:57:50,840 --> 00:57:52,960
POCKETS OF TUMOR CELLS THAT

1649
00:57:52,960 --> 00:57:54,520
APPEAR TO NOT RESPOND AT ALL,

1650
00:57:54,520 --> 00:57:56,360
THE OTHER THING THAT'S SUPER

1651
00:57:56,360 --> 00:57:57,200
INSIGHTFUL THAT WE COME TO

1652
00:57:57,200 --> 00:57:58,560
REALIZE IS YOU SEE AREAS WHERE

1653
00:57:58,560 --> 00:58:00,000
IMMUNE CELLS ARE KILLING TUMOR

1654
00:58:00,000 --> 00:58:01,080
CELLS AND THAT IMMUNE SYSTEMUNE

1655
00:58:01,080 --> 00:58:03,560
CELL COULD HAVE WALKED RIGHT BY

1656
00:58:03,560 --> 00:58:06,400
10 TUMOR CELLS AND BE TOTALLY

1657
00:58:06,400 --> 00:58:07,560
UNBOTHERRED BY THEIR PRESENCE,

1658
00:58:07,560 --> 00:58:09,400
SO WE'RE ABLE TO VISUALIZE THESE

1659
00:58:09,400 --> 00:58:10,720
PROCESSES, NOW WE NEED TO

1660
00:58:10,720 --> 00:58:13,400
UNDERSTAND THEM AND SO WE'RE

1661
00:58:13,400 --> 00:58:14,760
WORKING ON THAT, BUT THESE SORT

1662
00:58:14,760 --> 00:58:17,240
OF THINGS THAT THIS CONCEPT THAT

1663
00:58:17,240 --> 00:58:18,280
SOMETHING WORKS OR DOESN'T,

1664
00:58:18,280 --> 00:58:20,640
BLACK AND WHITE IT'S NOT

1665
00:58:20,640 --> 00:58:21,120
REALITY.

1666
00:58:21,120 --> 00:58:23,200
REALITY IS THAT SOME OF THE

1667
00:58:23,200 --> 00:58:25,120
TUMOR IS ULTIMATELY KILLED BY

1668
00:58:25,120 --> 00:58:27,720
THESE DRUGS THAT WORK OR NOT AND

1669
00:58:27,720 --> 00:58:30,000
SOME ISN'T.

1670
00:58:30,000 --> 00:58:31,200
AND REMEMBER, THERE'S A

1671
00:58:31,200 --> 00:58:32,360
DISCREPANCY BETWEEN CLINICALLY

1672
00:58:32,360 --> 00:58:34,240
WORKING AND NOT, STUFF'S GOT TO

1673
00:58:34,240 --> 00:58:35,520
SHRINK, NORMAL TISSUE HAS TO

1674
00:58:35,520 --> 00:58:37,080
GROW IN AND IT HAS TO BE

1675
00:58:37,080 --> 00:58:38,560
MEASURABLE BUT WHAT'S HAPPENING

1676
00:58:38,560 --> 00:58:40,920
BELOW THAT IS A VERY COMPLICATED

1677
00:58:40,920 --> 00:58:43,000
THING AND I THINK IT'S SUPER

1678
00:58:43,000 --> 00:58:49,880
ENLIGHTENING TO WATCH THESE

1679
00:58:49,880 --> 00:58:50,760
THINGS.

1680
00:58:50,760 --> 00:58:51,760
>> WE'RE UP ON THE HOUR
AND

1681
00:58:51,760 --> 00:58:55,080
THAT'S ALL THE QUESTIONS WE SEE.

1682
00:58:55,080 --> 00:58:59,640
IF I GET ANY MORE QUESTIONS I

1683
00:58:59,640 --> 00:59:01,200
WILL CERTAINLY REPORT THEM TO

1684
00:59:01,200 --> 00:59:02,040
YOU FOR ANSWERINGMENT BUT AGAIN

1685
00:59:02,040 --> 00:59:05,880
I WANT TO SAY THANK YOU FOR THIS

1686
00:59:05,880 --> 00:59:07,280
ENLIGHTENING AND SUCK SETIONFUL

1687
00:59:07,280 --> 00:59:08,080
TALK AND CONGRATULATIONS AGAIN

1688
00:59:08,080 --> 00:59:09,800
FOR BEING NAMED THE

1689
00:59:09,800 --> 00:59:11,200
DISTINGUISHED CLINICAL TEACHER

1690
00:59:11,200 --> 00:59:13,320
AWARDEE, CLEARLY, A HIGHLY

1691
00:59:13,320 --> 00:59:15,280
QUALIFIED APPLICANT AND I THINK

1692
00:59:15,280 --> 00:59:16,720
OF ANYONE WHO'S MORE DESERVING

1693
00:59:16,720 --> 00:59:18,840
AND FINALLY I WANT TO THANK THE

1694
00:59:18,840 --> 00:59:20,880
DECKER FAMILY FOR SUPPORTING

1695
00:59:20,880 --> 00:59:22,880
THIS LECTURE AND FOR THE

1696
00:59:22,880 --> 00:59:23,840
GENEROUS SUPPORT THAT YOU'VE

1697
00:59:23,840 --> 00:59:26,000
GIVEN US AS WELL AS FNIH, THANK

1698
00:59:26,000 --> 00:59:27,560
YOU VERY MUCH AND EVERYBODY HAVE

1699
00:59:27,560 --> 00:59:37,960
A WONDERFUL AFTERNOON.