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>>WELCOME, EVERYONE, TO THE

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ASSAY GUIDANCE WORKSHOP ON 3D

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TISSUE MODELS FOR ANTIVIRAL DRUG

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DEVELOPMENT.

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I AM THE EDITOR-IN-CHIEF OF THE

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ASSAY GUIDANCE MANUAL AND THE

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LEAD OF THE ASSAY GUIDANCE

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MANUAL PROGRAM HERE AT THE

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NATIONAL CENTER FOR ADVANCING

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TRANSLATIONAL SCIENCES.

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AT THE NATIONAL INSTITUTES OF

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HEALTH.

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WE ARE EXTREMELY EXCITED TO HAVE

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YOU ALL JOIN US TODAY IN THIS

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EXCITING WORKSHOP THAT WILL RUN

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FOR TWO DAYS, TODAY, JUNE 7, AND

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TOMORROW, JUNE 8 AS WELL.

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SO THIS WORKSHOP WAS ORGANIZED

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BY THE NATIONAL CENTER FOR

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ADVANCING TRANSLATIONAL SCIENCES

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AS WELL AS THE BILL AND MELINDA

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GATES FOUNDATION, AS WELL AS THE

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NATIONAL INSTITUTES OF ALLERGY

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AND INFECTIOUS DISEASES.

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AND WE'RE GOING TO START THE

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PROGRAM TODAY BY INTRODUCTORY

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COMMENTS BY LEADERSHIP FROM

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THESE THREE INSTITUTES.

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WE'LL START WITH DR. JONI

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RUTTER, WHO'S THE ACTING

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DIRECTOR OF THE NATIONAL CENTER

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FOR ADVANCING TRANSLATIONAL

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SCIENCES AT THE NATIONAL

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INSTITUTES OF HEALTH.

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WE'RE REALLY EXCITED TO HAVE YOU

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HERE, JONI.

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WELCOME.

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THANK YOU SO MUCH FOR BEING

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HERE.

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WE'RE LOOKING FORWARD TO HEARING

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YOUR COMMENTS.

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THE FLOOR IS YOURS.

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>> OKAY.

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THANK YOU SO MUCH, IT'S REALLY A

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PLEASURE TO BE HERE.

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HELLO, EVERYONE, AND WELCOME TO

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THE MEETING.

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AGAIN, MY NAME IS JONI RUTTER,

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ACTING DIRECTOR OF NCATS.

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BEFORE I BEGIN, I WANT TO THANK

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SEVERAL OF OUR PARTNERS FOR THE

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FORESIGHT AND VISION FOR THIS

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MEETING.

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AND THOSE INCLUDE

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REPRESENTATIVES FROM EACH OF

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THOSE ORGANIZATIONS THAT YOU SEE

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LISTED THERE ON THAT SLIDE.

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RUDOLPHO, MINDY, ANNE, TIM AND

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MARK ALL FROM NIAID WHO'VE

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REALLY HELPED FROM THEIR

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PERSPECTIVE BRING IMPORTANT

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CONTRIBUTIONS TO THIS MEETING.

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I'D LIKE TO ALSO THANK TIM

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DUNCAN AND ROBERT JORDAN FROM

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THE BILL AND MELINDA GATES

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FOUNDATION FOR THEIR SUPPORT AS

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WELL AND THEN ALSO CAL, MARK,

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STEPHANIE, MATT, EMILY, ALL FROM

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NCATS, CONTRIBUTING THEIR

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PERSPECTIVES, AND THEN

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ESPECIALLY AS YOU'VE HEARD

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SERENE AND ABIGAIL WHO HAVE BEEN

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VERY MUCH HELPING US ORK STATE

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THIS ENTIRE EFFORT.

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SO THANK YOU TO ESPECIALLY

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ABIGAIL AND SERENE FOR PULLING

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THIS MEETING TOGETHER AND ALL

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THE OTHER PARTNERS AND

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CONTRIBUTORS WHO HAVE HELPED

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BRING THIS MEETING AND THE

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AGENDA WHICH IS INCREDIBLY

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FANTASTIC TO THE FORE HERE.

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THIS MEETING SEEKS TO GUIDE THE

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DEVELOPMENT OF STANDARDIZED 3D

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CELLULAR ASSAYS WITH THE HOPE OF

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HELPING THE COMMUNITY TO

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SUCCESSFULLY AND MORE

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EFFICIENTLY DEVELOP, TEST,

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VALIDATE AND DEPLOY THERAPEUTICS

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FOR FUTURE PANDEMIC THREATS.

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AND THEREFORE ALSO PROVIDE PROOF

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OF CONCEPT FOR THESE MODELS THAT

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CAN DO THE SAME FOR OTHER PUBLIC

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HEALTH MATTERS.

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AND RIGHT NOW, THESE 3D MODELS

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ARE SOPHISTICATED TOOLS IN THE

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TOOLBOX, BUT CAN THEY BE MORE?

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CAN THEY BE PARADIGM-SHIFTING IN

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A SPACE OF THERAPEUTICS

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DEVELOPMENT THAT IS IN DIRE NEED

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OF TRANSFORMATION?

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SO OUR MISSION AT NCATS IS TO

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CATALYZE THE GENERATION OF

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INNOVATIVE METHODS AND

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TECHNOLOGIES THAT WILL ENHANCE

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THE DEVELOPMENT, TESTING AND

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IMPLEMENTATION OF PLATFORM

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DIAGNOSTICS AND THERAPEUTICS

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ACROSS A WIDE RANGE OF HUMAN

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DISEASES AND CONDITIONS, AND

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ALWAYS WITH AN EYE TOWARDS

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TURNING PROMISING RESEARCH

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DISCOVERIES INTO HEALTH

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SOLUTIONS.

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AND OUR STRATEGY AT NCATS IS

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TWOFOLD.

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EVERY PROJECT WE TAKE ON

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ADVANCES THE SCIENCE OF THE

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PARTICULAR PROJECT AT HAND, BUT

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IT ALSO SEEKS TO IDENTIFY AND

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ADDRESS COSTLY AND

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TIME-CONSUMING BOTTLENECKS THAT

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SLOW DOWN OR PREVENT THE

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TRANSLATION OF RESEARCH.

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AND SO WE SEEK TO INCREASE THE

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PACE OF RESEARCH BY TESTING AND

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DEVELOPING THERAPEUTIC SO THAT

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WE CAN ADVANCE ON THE SCALE OF

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MANY DISEASES AT A TIME, NOT

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JUST ONE DISEASE AT A TIME.

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AND OUR ULTIMATE DRIVING HOPE IS

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TO GET MORE TREATMENTS TO ALL

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PEOPLE MORE QUICKLY.

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AND LOTS OF TIMES THAT'S REALLY

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THROUGH ENABLING AND DE-RISKING

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PLATFORM-BASED TECHNOLOGIES FOR

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THERAPEUTIC DEVELOPMENT.

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LIKE 3D TISSUE MODELS THAT WE'RE

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TALKING ABOUT OVER THE NEXT

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COUPLE OF DAYS.

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SO IMAGINE IF THE 3D MODELS ARE

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SUCCESSFUL AT INCREASING OUR

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ABILITY TO ADDRESS TOXICOLOGICAL

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ISSUES OR EFFICACY PREDICTIONS,

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FOR EXAMPLE, THEN WE CAN HASTEN

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NEEDED NEW DRUG DEVELOPMENT

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APPROACHES THAT WOULD OTHERWISE

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TAKE DECADES.

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OR WE COULD ENSURE THAT THERE

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ARE PROVEN OFF THE SHELF HUMAN

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CELL-BASED MODELS FOR DRUG

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REPURPOSING EFFORTS IN TIME OF

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URGENCY WHERE AN ANIMAL MODEL,

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FOR EXAMPLE, MAY NOT BE

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ULTIMATELY AS HELPFUL AS HUMAN

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CELL-BASED MODELS OR WHERE THEY

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MAY BE A LITTLE BIT MORE

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LIMITING BECAUSE OF MULTIPLE

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CO-MORBIDITY TYPES OF

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CONDITIONS.

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SO THESE ARE THE IMPORTANT KINDS

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OF THINGS WE'LL BE TALKING ABOUT

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OVER THE NEXT COUPLE OF DAYS.

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NOW IN 2019, THERE WAS A DRUG

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DISCOVERY TODAY ARTICLE THAT

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PURPORTED THE POTENTIAL OF 3D

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MODELS COULD REDUCE R & D
DRUG

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COSTS BY UPWARDS OF 26%.

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WHERE IMPROVEMENTS IN CLINICAL

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TRIAL SUCCESS PREDICTION RATES

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WOULD REALLY BE THE MAIN DRIVERS

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OF WHERE THOSE ANTICIPATED COSTS

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COULD FIND -- WE COULD FIND COST

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SAVINGS.

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AND WE KNOW ABOUT 85 TO 90% OF

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DRUG CANDIDATE ARE -- THEY FAIL

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BECAUSE OF DRUG EFFICACY

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CONCERNS OR SAFETY CONCERNS, AND

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THAT'S WHERE THOSE COST SAVINGS

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ARE LURKING, AND IF THAT'S THE

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MAJOR DRIVE OF R & D COSTS,
THEN

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BETTER PREDICTIVE MODELS COULD

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HELP CHIP AWAY AT THOSE COSTS SO

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WE NEED TO FIND WAYS TO GET THEM

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INCULCATED INTO THE

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TRANSLATIONAL DRUG DEVELOPMENT

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IN THE GENERAL ECOSYSTEM FOR

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DRUG DEVELOPMENT.

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IN ADDITION TO TALKING ABOUT

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2019 IN THAT ARTICLE, THEY ALSO

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SUGGESTED THE TECHNOLOGY WILL

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HELP TO MAKE QUICKER AND MORE

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PRECISE DECISIONS DURING THESE

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PRE-CLINICAL STAGES OF DRUG

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DEVELOPMENT.

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SO THE PROMISE OF 3D MODELS IS

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REALLY -- THERE IS STILL A LONG

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ROAD AHEAD TO UNDERSTAND WHETHER

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THAT PROMISE WILL BECOME A

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REALITY AND THIS MEETING NEEDS

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TO HELP FOCUS AND SHAPE THE PATH

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FORWARD IN THE CRITICAL AREA OF

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ANTIVIRAL DRUG DEVELOPMENT.

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IN TERMS OF REGULATORY ADOPTION,

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THERE ARE BIG QUALIFICATION

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CHALLENGES THAT 3D MODELS NEED

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TO MEET BEFORE WIDER ADOPTION

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WILL ULTIMATELY BE SEEN.

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WE NEED TO GET HIGHER HUMAN

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RELEVANCE AND DISEASE RELEVANCE

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EARLIER IN THE DRUG DEVELOPMENT

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PIPELINE FOR THOSE TO REALLY

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MANIFEST AND TAKE EFFECT, AND

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ANTIVIRAL DRUG DEVELOPMENT IS A

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RIPE AREA FOR THIS TO BE DONE SO

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THERE'S NO TIME LIKE THE PRESENT

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AND CERTAINLY THIS PARTICULAR

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MEETING WILL HELP TO ADDRESS

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THAT.

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AND I WANT TO HIGHLIGHT THREE

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KEY AREAS THAT I HOPE WILL BE

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DISCUSSED DURING OUR NEXT TWO

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DAYS TOGETHER.

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FIRST ARE SOME HIGH LEEFL

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OUTSTANDING QUESTIONS AND BIG

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CHALLENGES THAT ARE STILL AT

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PLAY.

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WE NEED TO ESTABLISH AND BEGIN

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TO QUANTIFY THE CLINICAL

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PREDICTABILITY OF 3D TISSUE

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MODELS.

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HOW GOOD ARE THEY IN

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RECAPITULATING DISEASES OF

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INTEREST?

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WHAT IS THE PHYSIOLOGICAL

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COMPLEXITY NEEDED IN A TISSUE

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MODEL TO BEST PREDICT THE

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CLINICAL RESPONSES?

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HOW IMPORTANT ARE THE IMMUNE

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COMPONENTS OR ENDOTHELIAL

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COMPONENTS IN THESE MODELS?

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AND ASSESSING WHETHER THE TISSUE

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HAS THE APPROPRIATE SET OF

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BIOMARKERS, WHETHER THOSE

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BIOMARKERS BE FOR PREDICTIVE

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PURPOSES OR SAFETY PURPOSES OR

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MONITORING PURPOSES.

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ASSESSING THOSE BIOMARKERS FOR

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EVALUATING AND ACCURATELY

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DISTINGUISHING NORMAL AND

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DISEASE STATES AND HOW THOSE

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BIOMARKERS CAN BE USED IN TERMS

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OF CONTEXT OF USE FOR THOSE 3D

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MODELS IS GOING TO BE IMPORTANT.

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WHAT'S THE BIOLOGY AND THE

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PATHOLOGY THAT THESE MODELS WILL

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REPORT ON.

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AND THEN VALIDATING THAT THEY

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CAN PREDICT PHARMACOLOGICAL

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RESPONSES OR THERAPEUTICS IN

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HUMANS FROM BOTH A SAFETY AND

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TOX STANDPOINT AS WELL AS AN

263
00:08:23,120 --> 00:08:24,680
EFFICACY STANDPOINT, THESE ARE

264
00:08:24,680 --> 00:08:25,760
ALL OPEN QUESTIONS THAT ARE

265
00:08:25,760 --> 00:08:28,280
LIKELY TO BE MODEL AND

266
00:08:28,280 --> 00:08:28,720
QUESTION-DEPENDENT.

267
00:08:28,720 --> 00:08:30,920
SO WE NEED TO DEVELOP MULTIPLE

268
00:08:30,920 --> 00:08:32,760
MODELS TO REFLECT A VARIETY OF

269
00:08:32,760 --> 00:08:33,960
DIFFERENT, FOR EXAMPLE,

270
00:08:33,960 --> 00:08:35,800
CARDIOVASCULAR OR HEPATIC OR

271
00:08:35,800 --> 00:08:38,440
NEURONAL OR IMMUNE TOXICITIES,

272
00:08:38,440 --> 00:08:39,760
FOR EXAMPLE, OR FOCUS ON AREAS

273
00:08:39,760 --> 00:08:42,800
WHERE NO PHYSIOLOGICALLY OR

274
00:08:42,800 --> 00:08:43,680
PHARMACOLOGICALLY RELEVANT

275
00:08:43,680 --> 00:08:45,320
MODELS ARE AVAILABLE.

276
00:08:45,320 --> 00:08:48,600
AND THESE ARE AREAS SUCH AS RARE

277
00:08:48,600 --> 00:08:49,600
DISEASES OR RARE CANCERS OR EVEN

278
00:08:49,600 --> 00:08:53,080
IP FORECASTTIOUS            EVEN

279
00:08:53,080 --> 00:08:53,880
INFECTIOUS DISEASES WE'LL BE

280
00:08:53,880 --> 00:08:54,640
TALKING ABOUT.

281
00:08:54,640 --> 00:08:55,840
THE SECOND ISSUE IS WITH THESE

282
00:08:55,840 --> 00:08:56,920
MAJOR GAPS STILL IN THE FIELD,

283
00:08:56,920 --> 00:08:59,000
HOW CAN WE IMPROVE UPON THEM?

284
00:08:59,000 --> 00:09:01,320
SO TECHNOLOGICAL ROBUSTNESS AND

285
00:09:01,320 --> 00:09:02,720
REPRODUCIBILITY FOR SCREENING

286
00:09:02,720 --> 00:09:04,240
ASSAYS IS ONE OF THE KEY

287
00:09:04,240 --> 00:09:04,560
CHALLENGES.

288
00:09:04,560 --> 00:09:06,200
AND AS WE ACHIEVE HIGHER

289
00:09:06,200 --> 00:09:09,520
COMPLEXITY IN OUR 3D MODELS, HOW

290
00:09:09,520 --> 00:09:13,120
CAN WE REGAIN GROUND IN

291
00:09:13,120 --> 00:09:15,320
IDENTIFYING A SORT OF MEDIUM TO

292
00:09:15,320 --> 00:09:16,920
HIGH THROUGHPUT ASSAYS FOR

293
00:09:16,920 --> 00:09:18,600
SCREENING FOR THESE TYPES OF 3D

294
00:09:18,600 --> 00:09:19,040
MODELS.

295
00:09:19,040 --> 00:09:20,840
AS YOU INCREASE COMPLEXITY IN

296
00:09:20,840 --> 00:09:22,720
THE 3D MODELS, YOU TEND TO LOSE

297
00:09:22,720 --> 00:09:24,680
THAT HIGH-THROUGHPUT APPROACHES

298
00:09:24,680 --> 00:09:26,480
FOR ASSAYS, SO HOW CAN WE REGAIN

299
00:09:26,480 --> 00:09:28,640
SOME OF THAT MEDIUM OR

300
00:09:28,640 --> 00:09:29,000
HIGH-THROUGHPUT.

301
00:09:29,000 --> 00:09:30,600
HOW CAN WE PERSONALIZE TISSUE

302
00:09:30,600 --> 00:09:31,800
MODELS SO THAT WE CAN ENSURE

303
00:09:31,800 --> 00:09:34,240
THAT MODELS REPRESENT DISEASE

304
00:09:34,240 --> 00:09:35,880
AND POPULATION HETEROGENEITY TO

305
00:09:35,880 --> 00:09:38,160
BETION ENSURE       

306
00:09:38,160 --> 00:09:39,560
BEST ENSURE THE RESULTS ARE

307
00:09:39,560 --> 00:09:40,000
GENERALIZABLE.

308
00:09:40,000 --> 00:09:41,640
THEN HOW DO WE INTEGRATE THOSE

309
00:09:41,640 --> 00:09:43,520
TISSUE MODELS EARLIER IN THE

310
00:09:43,520 --> 00:09:44,520
DRUG DISCOVERY PIPELINE?

311
00:09:44,520 --> 00:09:45,720
THIS IS HUGELY CRITICAL.

312
00:09:45,720 --> 00:09:46,920
I THINK ONE OF THE KEY ASPECTS

313
00:09:46,920 --> 00:09:49,600
OF THIS IS UNDERSTANDING HOW

314
00:09:49,600 --> 00:09:51,400
HUMAN RELEVANCE OF TOXICITY IN

315
00:09:51,400 --> 00:09:53,440
ANIMAL STUDIES, BY DOING

316
00:09:53,440 --> 00:09:55,440
COMPARATIVE MEDICINE RESEARCH IN

317
00:09:55,440 --> 00:09:58,280
3D ANIMAL MODELS COMPARED TO 3D

318
00:09:58,280 --> 00:10:00,880
HUMAN MODELS OF KNOWN COMPOUNDS,

319
00:10:00,880 --> 00:10:04,080
FOR EXAMPLE, THAT DIDN'T SHOW

320
00:10:04,080 --> 00:10:06,440
THAT -- THAT SHOWED FAILURE IN

321
00:10:06,440 --> 00:10:07,800
THE HUMAN CONTEXT BUT ACTUALLY

322
00:10:07,800 --> 00:10:09,000
DIDN'T SHOW FAILURE IN THE

323
00:10:09,000 --> 00:10:10,120
ANIMAL CONTEXT, THAT'S GOING TO

324
00:10:10,120 --> 00:10:11,760
BE IMPORTANT TO GO

325
00:10:11,760 --> 00:10:12,720
RETROSPECTIVELY TO UNDERSTAND

326
00:10:12,720 --> 00:10:14,920
WHY THAT IS AND IN WHAT AREAS

327
00:10:14,920 --> 00:10:16,320
THOSE TEND TO HAPPEN.

328
00:10:16,320 --> 00:10:18,400
SO THOSE KINDS OF RETROSPECTIVE

329
00:10:18,400 --> 00:10:19,400
EXPERIMENTS ARE GOING TO BE

330
00:10:19,400 --> 00:10:20,720
IMPORTANT FOR GAINING CONFIDENCE

331
00:10:20,720 --> 00:10:23,000
IN HUMAN CELL-BASED MODELS GOING

332
00:10:23,000 --> 00:10:23,440
FORWARD.

333
00:10:23,440 --> 00:10:25,280
AND THEN WORKING WITH REGULATORY

334
00:10:25,280 --> 00:10:26,920
AGENCIES TO DEVELOP GUIDELINES,

335
00:10:26,920 --> 00:10:28,240
WHAT NEEDS TO BE DONE FOR THESE

336
00:10:28,240 --> 00:10:30,680
MODELS TO BE BROADLY ADAPTED BY

337
00:10:30,680 --> 00:10:32,840
PHARMA AND BY REGULATORY

338
00:10:32,840 --> 00:10:34,600
AGENCIES FOR IND FILING, WHAT'S

339
00:10:34,600 --> 00:10:36,320
GOING TO BE NEEDED FOR THE

340
00:10:36,320 --> 00:10:37,240
REGULATORY PACKAGES SUBMITTED.

341
00:10:37,240 --> 00:10:38,320
THESE ARE OTHER ISSUES THAT NEED

342
00:10:38,320 --> 00:10:39,400
TO BE UNDERSTOOD.

343
00:10:39,400 --> 00:10:41,040
AND THEN OF COURSE BACK TO

344
00:10:41,040 --> 00:10:43,680
BIOMARKERS, DEVELOPING THE

345
00:10:43,680 --> 00:10:45,400
QUANTITATIVE ASSAYS THAT

346
00:10:45,400 --> 00:10:46,960
BIOMARKERS CAN HELP SUPPORT FOR

347
00:10:46,960 --> 00:10:48,720
CLINICAL END POINTS IN 3D MODELS

348
00:10:48,720 --> 00:10:49,800
ARE ANOTHER, OF COURSE, KEY

349
00:10:49,800 --> 00:10:53,280
AREA.

350
00:10:53,280 --> 00:10:54,280
LASTLY, WHAT ARE THE BIGGEST

351
00:10:54,280 --> 00:10:55,720
OPPORTUNITIES FOR THE ANTIVIRAL

352
00:10:55,720 --> 00:10:56,680
DRUG DEVELOPMENT SPACE, AND

353
00:10:56,680 --> 00:10:57,800
THAT'S GOING TO BE THE FOCUS OF

354
00:10:57,800 --> 00:10:58,640
THIS CONVERSATION OVER THE NEXT

355
00:10:58,640 --> 00:11:00,840
COUPLE OF DAYS, BUT HOW CAN 3D

356
00:11:00,840 --> 00:11:02,160
MODELS HELP US PREPARE BETTER

357
00:11:02,160 --> 00:11:03,440
FOR THE CURRENT AND THE NEXT

358
00:11:03,440 --> 00:11:04,120
PANDEMIC.

359
00:11:04,120 --> 00:11:05,000
THAT'S A KEY QUESTION.

360
00:11:05,000 --> 00:11:07,520
SO THERE ARE MANY SCIENTIFIC

361
00:11:07,520 --> 00:11:08,480
TECHNOLOGICAL AND REGULATORY

362
00:11:08,480 --> 00:11:09,600
CHALLENGES THAT STILL REMAIN,

363
00:11:09,600 --> 00:11:12,320
BUT THE 3D MODEL AND THE FIELD

364
00:11:12,320 --> 00:11:16,160
THAT IS REALLY SORT OF COME ON

365
00:11:16,160 --> 00:11:18,360
THE SCENE IN FULL FORCE HAS

366
00:11:18,360 --> 00:11:20,200
SHOWN REMARKABLE

367
00:11:20,200 --> 00:11:21,160
PREDIBILITIABILITY DURING COVID

368
00:11:21,160 --> 00:11:23,160
AND THE 3D MODELS HAVE A BIG

369
00:11:23,160 --> 00:11:25,560
PLACE IN ADVANCING OUR DRUG

370
00:11:25,560 --> 00:11:26,200
DEVELOPMENT GAIN.

371
00:11:26,200 --> 00:11:30,680
SO THE UTION VISION FOR        T

372
00:11:30,680 --> 00:11:32,320
DRIVE UTILITY AND ADOPTION OF

373
00:11:32,320 --> 00:11:34,640
THESE 3D MODELS, WORK TOWARDS

374
00:11:34,640 --> 00:11:35,840
THE HARMONIZATION OF REGULATORY

375
00:11:35,840 --> 00:11:37,080
USE AND STANDARDIZATION OF

376
00:11:37,080 --> 00:11:38,440
PLATFORMS AND THEN CHART A PATH

377
00:11:38,440 --> 00:11:41,960
FORWARD THAT WILL EP ABLE US   O

378
00:11:41,960 --> 00:11:43,000
BETTER BE PREPARED FOR TREATING

379
00:11:43,000 --> 00:11:44,600
NOT JUST THE CURRENT COVID

380
00:11:44,600 --> 00:11:45,360
PANDEMIC, BUT TO BE MORE

381
00:11:45,360 --> 00:11:47,680
PREPARED FOR ANY FUTURE PUBLIC

382
00:11:47,680 --> 00:11:48,320
HEALTH CRISES.

383
00:11:48,320 --> 00:11:49,840
SO WITH THAT, I WANT TO THANK

384
00:11:49,840 --> 00:11:51,160
AGAIN ALL OF THE SPEAKERS FOR

385
00:11:51,160 --> 00:11:53,000
JOINING US TODAY.

386
00:11:53,000 --> 00:11:55,400
IT'S A LITANY OF REALLY BIG

387
00:11:55,400 --> 00:11:56,840
QUESTIONS AND BIG TOPICS TO

388
00:11:56,840 --> 00:11:58,720
DISCUSS, BUT I KNOW THAT THIS

389
00:11:58,720 --> 00:12:00,000
GROUP WILL PULL TOGETHER AND

390
00:12:00,000 --> 00:12:01,000
IDENTIFY A REALLY GOOD PATH

391
00:12:01,000 --> 00:12:01,200
FORWARD.

392
00:12:01,200 --> 00:12:02,520
SO I LOOK FORWARD TO A VERY

393
00:12:02,520 --> 00:12:04,400
PRODUCTIVE MEETING, AND WITH

394
00:12:04,400 --> 00:12:07,560
THAT, SARINE, I'LL TURN IT BACK

395
00:12:07,560 --> 00:12:09,200
TO YOU TO USHER FORWARD TO THE

396
00:12:09,200 --> 00:12:09,800
NEXT SPEAKERS.

397
00:12:09,800 --> 00:12:11,280
>> THANK YOU VERY MUCH,
JONI,

398
00:12:11,280 --> 00:12:12,360
FOR LAYING DOWN THE CHALLENGES

399
00:12:12,360 --> 00:12:14,320
AND THE VISION SO CLEARLY.

400
00:12:14,320 --> 00:12:16,200
WE APPRECIATE IT.

401
00:12:16,200 --> 00:12:16,920
OKAY.

402
00:12:16,920 --> 00:12:19,360
SO OUR NEXT INTRODUCTORY SPEAKER

403
00:12:19,360 --> 00:12:22,560
IS DR. ROBERT JORDAN, WHO IS A

404
00:12:22,560 --> 00:12:24,720
SENIOR PROGRAM OFFICER FROM THE

405
00:12:24,720 --> 00:12:26,240
BILL AND MELINDA GATES

406
00:12:26,240 --> 00:12:27,560
FOUNDATION.

407
00:12:27,560 --> 00:12:28,680
WELCOME, ROB.

408
00:12:28,680 --> 00:12:34,720
THE FLOOR IS YOURS.

409
00:12:34,720 --> 00:12:36,560
>> GREAT.

410
00:12:36,560 --> 00:12:37,000
THANKS, SARINE.

411
00:12:37,000 --> 00:12:47,200
COULD YOU ACTIVATE MY CAMERA?

412
00:12:47,200 --> 00:12:55,200
IT SAYS THE HOST HAS STOPPED IT.

413
00:12:55,200 --> 00:12:55,520
GREAT.

414
00:12:55,520 --> 00:12:56,120
THANK YOU VERY MUCH.

415
00:12:56,120 --> 00:12:58,400
>> THANK YOU.

416
00:12:58,400 --> 00:13:01,200
>> THANKS, IS   SARINE,
FOR THAT

417
00:13:01,200 --> 00:13:02,760
INTRODUCTION, AND JONI FOR THE

418
00:13:02,760 --> 00:13:03,840
REALLY NICE INTRODUCTORY

419
00:13:03,840 --> 00:13:04,360
COMMENTS.

420
00:13:04,360 --> 00:13:06,600
I THOUGHT TODAY AS AN

421
00:13:06,600 --> 00:13:07,640
INTRODUCTION, I WANTED TO TALK A

422
00:13:07,640 --> 00:13:11,240
LITTLE BIT ABOUT THE BILL AND

423
00:13:11,240 --> 00:13:12,680
MELINDA GATES FOUNDATION, WHO WE

424
00:13:12,680 --> 00:13:16,400
ARE, WHAT WE DO, AND HOW WE'RE

425
00:13:16,400 --> 00:13:17,440
THINKING ABOUT CULTURES IN THE

426
00:13:17,440 --> 00:13:19,280
DRUG DEVELOPMENT AND DISCOVERY

427
00:13:19,280 --> 00:13:19,600
PROCESS.

428
00:13:19,600 --> 00:13:21,000
I PUT TOGETHER A FEW SLIDE THAT

429
00:13:21,000 --> 00:13:31,160
I'D LIKE TO SHARE.

430
00:13:31,160 --> 00:13:32,160
TO HELP DESCRIBE SOME OF THE

431
00:13:32,160 --> 00:13:33,480
WORK THAT WE'RE DOING IN THE

432
00:13:33,480 --> 00:13:36,400
SPACE.

433
00:13:36,400 --> 00:13:38,720
SO THE DRIVING PHILOSOPHY AT THE

434
00:13:38,720 --> 00:13:40,800
FOUNDATION IS THAT ALL LIVES

435
00:13:40,800 --> 00:13:42,800
HAVE EQUAL VALUE, AND THAT WE

436
00:13:42,800 --> 00:13:47,880
WANT TO DEVELOP PROGRAMS THAT

437
00:13:47,880 --> 00:13:48,440
WILL ENABLE EVERYONE IN THE

438
00:13:48,440 --> 00:13:49,880
WORLD TO LIVE HEALTHY AND

439
00:13:49,880 --> 00:13:53,480
PRODUCTIVE LIVES.

440
00:13:53,480 --> 00:13:55,040
SO WE HAVE REALLY FOUR MAJOR

441
00:13:55,040 --> 00:13:56,880
MISSIONS WE'RE WORKING ON AT THE

442
00:13:56,880 --> 00:13:57,520
FOUNDATION.

443
00:13:57,520 --> 00:13:58,720
FOCUSED ON CHILDREN AND YOUNG

444
00:13:58,720 --> 00:14:00,800
PEOPLE, TO HELP THEM SURVIVE AND

445
00:14:00,800 --> 00:14:02,560
THRIVE, EMPOWER THE POOREST,

446
00:14:02,560 --> 00:14:03,960
ESPECIALLY WOMEN AND GIRLS, TO

447
00:14:03,960 --> 00:14:05,840
HELP TRANSFORM THEIR LIVES.

448
00:14:05,840 --> 00:14:08,240
WE'RE WORKING ON DEVELOPING

449
00:14:08,240 --> 00:14:09,560
THERAPEUTICS, VACCINES,

450
00:14:09,560 --> 00:14:12,080
BIOLOGICS TO TREAT INFECTIOUS

451
00:14:12,080 --> 00:14:13,280
DISEASES, ESPECIALLY THOSE THAT

452
00:14:13,280 --> 00:14:15,800
AFFECT THE POOREST PEOPLE IN THE

453
00:14:15,800 --> 00:14:17,360
WORLD, AS WELL AS INSPIRE PEOPLE

454
00:14:17,360 --> 00:14:19,400
AT THE LOCAL LEVEL TO TAKE

455
00:14:19,400 --> 00:14:21,720
ACTION TO CHANGE, TO CHANGE

456
00:14:21,720 --> 00:14:23,240
LIVES, AND HOW WE DO THIS IS

457
00:14:23,240 --> 00:14:24,840
THROUGH GRANTEES AND PARTNERS,

458
00:14:24,840 --> 00:14:28,600
WHICH ARE THE CENTER OF OUR

459
00:14:28,600 --> 00:14:28,920
WORK.

460
00:14:28,920 --> 00:14:30,480
WE LIKE TO WORK TOGETHER WITH

461
00:14:30,480 --> 00:14:31,440
OUR GRANTEES AND PARTNERS TO

462
00:14:31,440 --> 00:14:33,520
TAKE RISKS, TO PUSH BOUNDARIES,

463
00:14:33,520 --> 00:14:34,920
TO DEVELOP NEW SCIENCE AND ALSO

464
00:14:34,920 --> 00:14:38,160
TO HARNESS THE POWER OF SCIENCE

465
00:14:38,160 --> 00:14:39,960
AND TECHNOLOGY TO DEVELOP

466
00:14:39,960 --> 00:14:40,960
THERAPEUTIC AND OTHER PROGRAMS.

467
00:14:40,960 --> 00:14:43,040
SO THIS WORK DOESN'T HAPPEN IN A

468
00:14:43,040 --> 00:14:44,160
VACUUM OBVIOUSLY, WE LIKE TO

469
00:14:44,160 --> 00:14:45,800
WORK WITH OTHER GOVERNMENTS,

470
00:14:45,800 --> 00:14:48,960
PRIVATE ORGANIZATIONS,

471
00:14:48,960 --> 00:14:50,600
COMMUNITIES, NON-PROFITS AND

472
00:14:50,600 --> 00:14:51,680
INDIVIDUALS TO HELP PROGRESS OUR

473
00:14:51,680 --> 00:14:52,440
PROGRAMS.

474
00:14:52,440 --> 00:14:54,080
ONE OF THE THINGS THAT WE ARE

475
00:14:54,080 --> 00:14:56,160
FOCUSED ON AT THE FOUNDATION IS

476
00:14:56,160 --> 00:14:57,920
GLOBAL HEALTH EQUITY, AND WHAT

477
00:14:57,920 --> 00:15:01,640
WE'VE SEEN IN THE PAST AND MOST

478
00:15:01,640 --> 00:15:02,840
RECENTLY, FOR EXAMPLE, WITH

479
00:15:02,840 --> 00:15:03,920
COVID VACCINES IS WHILE WE ARE

480
00:15:03,920 --> 00:15:06,240
ABLE TO DEVELOP PHENOMENAL

481
00:15:06,240 --> 00:15:08,200
THERAPEUTICS, THEY DON'T ALWAYS

482
00:15:08,200 --> 00:15:11,240
GET TO PEOPLE WHO NEED IT THE

483
00:15:11,240 --> 00:15:12,560
MOST OR GET TO PEOPLE AROUND THE

484
00:15:12,560 --> 00:15:14,120
WORLD IN AN EQUITABLE FASHION.

485
00:15:14,120 --> 00:15:16,840
FOR EXAMPLE, THE MRNA VACCINES

486
00:15:16,840 --> 00:15:19,000
THAT WERE DEVELOPED WHICH ARE

487
00:15:19,000 --> 00:15:20,800
HIGHLY EFFECTIVE AT REDUCING

488
00:15:20,800 --> 00:15:24,720
DISEASE SEVERITY FROM SARS-COV-2

489
00:15:24,720 --> 00:15:28,000
INFECTION AND PREVENTING

490
00:15:28,000 --> 00:15:28,640
INFECTION WERE PRIMARILY

491
00:15:28,640 --> 00:15:29,840
DISTRIBUTED IN HIGH INCOME

492
00:15:29,840 --> 00:15:31,080
COUNTRIES, BUT SIGNIFICANTLY

493
00:15:31,080 --> 00:15:33,200
LAGGED IN THEIR DISTRIBUTION IN

494
00:15:33,200 --> 00:15:35,640
LOW AND MIDDLE INCOME COUNTRIES.

495
00:15:35,640 --> 00:15:38,360
AND SO IN ALL OUR WORK, WE LOOK

496
00:15:38,360 --> 00:15:41,000
FOR GLOBAL SOLUTIONS, PRODUCTS

497
00:15:41,000 --> 00:15:45,360
THAT ARE SUITABLE FOR USE

498
00:15:45,360 --> 00:15:46,680
EVERYWHERE ACROSS THE GLOBE THAT

499
00:15:46,680 --> 00:15:48,880
CAN BE REGISTERED IN A TIMELY

500
00:15:48,880 --> 00:15:49,960
FASHION SO THEY CAN GET TO THE

501
00:15:49,960 --> 00:15:52,160
PEOPLE WHO NEED THEM MOST, AND

502
00:15:52,160 --> 00:15:54,160
WE WANT TO AVOID PRODUCT

503
00:15:54,160 --> 00:15:55,120
NATIONALISM AND WE WANT

504
00:15:55,120 --> 00:15:56,640
ESSENTIALLY TO HAVE EQUAL ACCESS

505
00:15:56,640 --> 00:15:59,400
TO ALL OF THESE THERAPEUTICS.

506
00:15:59,400 --> 00:16:02,240
SO IN ALL OF OUR GRANTS AND OUR

507
00:16:02,240 --> 00:16:03,200
PARTNERSHIPS, WE HAVE THESE

508
00:16:03,200 --> 00:16:05,280
GLOBAL ACCESS PROVISIONS THAT WE

509
00:16:05,280 --> 00:16:07,280
WANT TO FOLLOW TO MAKE SURE THAT

510
00:16:07,280 --> 00:16:10,440
PRODUCTS DEVELOPED CAN BE USED

511
00:16:10,440 --> 00:16:12,720
ACROSS THE GLOBE.

512
00:16:12,720 --> 00:16:14,040
SO SOME OF THE WORK WE'VE DONE

513
00:16:14,040 --> 00:16:18,160
IN THE COVID-19 SPACE AND SOME

514
00:16:18,160 --> 00:16:19,840
OF THE LESSONS WE'VE LEARNED,

515
00:16:19,840 --> 00:16:22,360
FIRST WE REALIZED THAT WE WERE

516
00:16:22,360 --> 00:16:23,120
UNPREPARED, GIVEN THAT THERE WAS

517
00:16:23,120 --> 00:16:25,000
A LACK OF INVESTMENT IN

518
00:16:25,000 --> 00:16:26,840
DEVELOPMENT OF ANTIVIRALS,

519
00:16:26,840 --> 00:16:29,000
ESPECIALLY THOSE TARGETING MANY

520
00:16:29,000 --> 00:16:30,800
OF THE READILY TRANSMISSIBLE

521
00:16:30,800 --> 00:16:31,760
VIRAL FAMILIES.

522
00:16:31,760 --> 00:16:33,480
WE DIDN'T HAVE ANY STRONG

523
00:16:33,480 --> 00:16:36,800
THERAPEUTICS AVAILABLE WHEN

524
00:16:36,800 --> 00:16:40,600
SARS-COV-2 PANDEMIC STARTED.

525
00:16:40,600 --> 00:16:47,160
WE ALSO FOUND AND WE SPENT A

526
00:16:47,160 --> 00:16:51,320
LONG -- INVESTMENT TO REPURPOSE

527
00:16:51,320 --> 00:16:52,960
COMPOUNDS FOR SARS-COV-2.

528
00:16:52,960 --> 00:16:55,280
WHILE THERE WERE SOME FOR SEVERE

529
00:16:55,280 --> 00:16:57,000
AND LATE DISEASE CONTEXT, THERE

530
00:16:57,000 --> 00:16:58,360
WAS VERY FEW THAT COULD BE

531
00:16:58,360 --> 00:17:00,400
REPURPOSED EFFECTIVELY TO TREAT

532
00:17:00,400 --> 00:17:02,480
MILD TO MODERATE DISEASE OR TO

533
00:17:02,480 --> 00:17:04,120
PREVENT A TRANSMISSION IN

534
00:17:04,120 --> 00:17:05,640
POPULATIONS.

535
00:17:05,640 --> 00:17:06,760
SO WE REALIZE THAT THERE'S A

536
00:17:06,760 --> 00:17:09,840
NEED TO FOCUS UPSTREAM IN THE

537
00:17:09,840 --> 00:17:11,440
COURSE OF DISEASE AND DEVELOP

538
00:17:11,440 --> 00:17:13,680
THERAPEUTICS THAT CAN BE READILY

539
00:17:13,680 --> 00:17:14,960
DEPLOYED IN THE EVENT OF AN

540
00:17:14,960 --> 00:17:17,720
OUTBREAK SITUATION.

541
00:17:17,720 --> 00:17:18,920
SO A LOT OF THE WORK THAT WE'RE

542
00:17:18,920 --> 00:17:20,200
FOCUSED ON MOVING FORWARD IS TO

543
00:17:20,200 --> 00:17:23,160
TRY TO DEVELOP ANTIVIRAL

544
00:17:23,160 --> 00:17:24,920
THERAPEUTICS THAT WOULD BE PHASE

545
00:17:24,920 --> 00:17:27,560
2 READY OR CLINIC-READY IN CASE

546
00:17:27,560 --> 00:17:29,960
OF AN OUTBREAK OF A NEW PANDEMIC

547
00:17:29,960 --> 00:17:30,280
THREAT AGENT.

548
00:17:30,280 --> 00:17:31,680
AND THE VIRUS FAMILIES THAT WE

549
00:17:31,680 --> 00:17:34,400
WERE INTERESTED IN LOOKING AT

550
00:17:34,400 --> 00:17:45,280
ARE CORONAVIRUS WITH A MIX     O

551
00:17:45,280 --> 00:17:46,240
DEVELOP VIRAL AND HOST TARGETS

552
00:17:46,240 --> 00:17:48,520
WOULD BE DIRECTLY APPLICABLE TO

553
00:17:48,520 --> 00:17:50,400
VIRUS REPLICATION, OR

554
00:17:50,400 --> 00:17:51,600
STIMULATING HOST INNATE

555
00:17:51,600 --> 00:17:53,480
RESPONSES TO PREVENT INFECTION.

556
00:17:53,480 --> 00:17:57,280
AND WE'RE ALSO EXPLORING SOME

557
00:17:57,280 --> 00:17:59,320
OTHER MODALITIES THAT COULD BE

558
00:17:59,320 --> 00:18:05,280
CONSIDERED PROGRAMMABLE, SUCH AS

559
00:18:05,280 --> 00:18:06,920
SIRNAs OR CRISPR TECHNOLOGIES.

560
00:18:06,920 --> 00:18:08,120
WE'RE ALSO IN OTHER ASPECTS OF

561
00:18:08,120 --> 00:18:10,520
THE FOUNDATION LOOKING AT NEW

562
00:18:10,520 --> 00:18:13,360
VACCINES AND BIOLOGICS AS WELL.

563
00:18:13,360 --> 00:18:19,280
AND SO WHAT WE LIKE TO DO IS TO

564
00:18:19,280 --> 00:18:22,320
SUPPORT EARLY SCIENCE AND TOOLS

565
00:18:22,320 --> 00:18:24,960
AVAILABLE ACROSS THE GLOBE FOR

566
00:18:24,960 --> 00:18:28,360
RESEARCHERS TO ENGAGE IN --

567
00:18:28,360 --> 00:18:29,560
PHARMA, BIOTECH, NON-PROFITS,

568
00:18:29,560 --> 00:18:30,760
AND WE HAVE A COMMITMENT TO DATA

569
00:18:30,760 --> 00:18:33,960
SHARING SO THE WORK WE SUPPORT

570
00:18:33,960 --> 00:18:35,240
SHOULD BE AVAILABLE TO

571
00:18:35,240 --> 00:18:36,760
RESEARCHERS ACROSS THE GLOBE.

572
00:18:36,760 --> 00:18:40,800
AND WE ALSO LIKE TO PARTNER WITH

573
00:18:40,800 --> 00:18:43,560
OTHER GOVERNMENT AGENCIES,

574
00:18:43,560 --> 00:18:44,640
ACADEMIC INSTITUTIONS,

575
00:18:44,640 --> 00:18:46,520
COMMERCIAL AND PHILANTHROPIC

576
00:18:46,520 --> 00:18:48,040
FUNDERS TO SUPPORT THIS WORK,

577
00:18:48,040 --> 00:18:51,160
AND FOR EXAMPLE, WE'VE PARTNERED

578
00:18:51,160 --> 00:18:57,680
WITH NOVANORTIS FOUNDATION TO

579
00:18:57,680 --> 00:18:59,720
PUT TOGETHER AN INITIATIVE TO

580
00:18:59,720 --> 00:19:01,360
SUPPORT SMALL MOLECULE DRUG

581
00:19:01,360 --> 00:19:03,040
DEVELOPMENT FOR PANDEMIC THREAT

582
00:19:03,040 --> 00:19:04,440
PATHOGENS.

583
00:19:04,440 --> 00:19:06,640
SO HOW DO WE VIEW ORGANOIDS IN

584
00:19:06,640 --> 00:19:09,680
THIS PROCESS FOR ANTIVIRAL

585
00:19:09,680 --> 00:19:10,160
DISCOVERY?

586
00:19:10,160 --> 00:19:12,640
WE THINK THAT THE ORGANOIDS

587
00:19:12,640 --> 00:19:14,960
REPRESENT A GOOD MODEL SYSTEM

588
00:19:14,960 --> 00:19:17,560
FOR COMPLEX BIOLOGY, AN

589
00:19:17,560 --> 00:19:18,640
INTERMEDIARY BETWEEN THE WHOLE

590
00:19:18,640 --> 00:19:21,040
ANIMAL, PRIMARY TISSUES AND CELL

591
00:19:21,040 --> 00:19:21,640
CULTURAL.

592
00:19:21,640 --> 00:19:25,880
THEY'RE RELATIVELY EASY TO USE,

593
00:19:25,880 --> 00:19:27,080
OBVIOUSLY TECHNICALLY DIFFICULT

594
00:19:27,080 --> 00:19:29,160
TO PUT TOGETHER BUT MORE EASY TO

595
00:19:29,160 --> 00:19:31,480
USE RELATIVE TO PRIMARY TISSUES

596
00:19:31,480 --> 00:19:32,360
AND ANIMALS.

597
00:19:32,360 --> 00:19:34,520
WE FEEL THAT THERE COULD BE A

598
00:19:34,520 --> 00:19:36,080
BETTER TRANSLATION OF THE DATA

599
00:19:36,080 --> 00:19:38,600
GENERATED IN THESE 3D CULTURES

600
00:19:38,600 --> 00:19:40,560
TO HUMAN STUDIES.

601
00:19:40,560 --> 00:19:42,080
IT ALSO HELPS REMOVE SOME OF THE

602
00:19:42,080 --> 00:19:43,320
ETHICAL ISSUES SURROUNDING USE

603
00:19:43,320 --> 00:19:49,000
OF ANIMALS, AND THERE COULD BE

604
00:19:49,000 --> 00:19:50,960
BETTER TRANSLATION OF THE DATA,

605
00:19:50,960 --> 00:19:53,240
GIVEN THAT THERE'S LARGER SAMPLE

606
00:19:53,240 --> 00:19:56,720
SIZES TO IMPROVE STATISTICS FOR

607
00:19:56,720 --> 00:19:57,280
THERAPEUTIC EVALUATION.

608
00:19:57,280 --> 00:19:58,600
SO THESE ARE SOME OF THE IDEAS

609
00:19:58,600 --> 00:20:00,960
THAT WE'RE THINKING WITH IN ABON

610
00:20:00,960 --> 00:20:03,600
TERMS OF THESE 3D CULTURES AND

611
00:20:03,600 --> 00:20:05,120
HOW THEY CAN BE USED IN THE

612
00:20:05,120 --> 00:20:05,920
DISCOVERY PROCESS.

613
00:20:05,920 --> 00:20:07,120
THIS SLIDE SHOWS THE EVOLUTION

614
00:20:07,120 --> 00:20:11,480
OF SOME OF THE ORGANOID OR 3D

615
00:20:11,480 --> 00:20:12,560
CULTURE SYSTEMS OVER TIME.

616
00:20:12,560 --> 00:20:16,280
ON THE RIGHT-HAND SIDE, THERE

617
00:20:16,280 --> 00:20:19,240
ARE EXAMPLES OF ORGANOIDS USE IN

618
00:20:19,240 --> 00:20:21,480
SARS-COV-2 RESEARCH IN DRUG

619
00:20:21,480 --> 00:20:23,920
SCREENING TO IDENTIFY NOVEL

620
00:20:23,920 --> 00:20:25,600
ANTIVIRALS THAT WEREN'T

621
00:20:25,600 --> 00:20:28,320
DISCOVERED IN 2D CULTURES THAT

622
00:20:28,320 --> 00:20:32,360
WOULD BE -- COULD BE

623
00:20:32,360 --> 00:20:33,800
EFFECTIVE -- POTENTIALLY

624
00:20:33,800 --> 00:20:36,400
EFFECTIVE ANTIVIRALS TO TREAT

625
00:20:36,400 --> 00:20:41,960
SARS-COV-2 INFECTIONS, TO STUDY

626
00:20:41,960 --> 00:20:43,120
NEUROTROPISM, 3D CULTURE MODELS

627
00:20:43,120 --> 00:20:44,960
THAT COULD ALSO INCLUDE IMMUNE

628
00:20:44,960 --> 00:20:46,240
COMPONENTS TO UNDERSTAND THE

629
00:20:46,240 --> 00:20:49,480
IMMUNE RESPONSE TO INFECTION, AS

630
00:20:49,480 --> 00:20:51,800
WELL AS JUST STUDIES TO LOOK AT

631
00:20:51,800 --> 00:20:55,880
RECEPTOR USAGE TO UNDERSTAND

632
00:20:55,880 --> 00:20:56,640
PATHOGENESIS OF INFECTION.

633
00:20:56,640 --> 00:20:58,400
SO THERE ARE A LOT OF

634
00:20:58,400 --> 00:21:00,000
APPLICATIONS FOR 3D CULTURES IN

635
00:21:00,000 --> 00:21:02,320
THE ANTIVIRAL DRUG DISCOVERY AND

636
00:21:02,320 --> 00:21:03,640
DEVELOPMENT SPACE.

637
00:21:03,640 --> 00:21:09,000
THE ORGANOIDS, WE HAVE AN

638
00:21:09,000 --> 00:21:09,960
ORGANOID CONSORTIUM AT THE

639
00:21:09,960 --> 00:21:10,640
FOUNDATION THAT'S ACTUALLY

640
00:21:10,640 --> 00:21:12,840
LOOKING AT THE USE OF 3D

641
00:21:12,840 --> 00:21:13,920
CULTURES IN A NUMBER OF

642
00:21:13,920 --> 00:21:15,440
DIFFERENT THERAPEUTIC AREAS WE

643
00:21:15,440 --> 00:21:17,640
ARE INTERESTED IN, AND WE'RE

644
00:21:17,640 --> 00:21:19,600
FOCUSED ON STANDARDIZING AND

645
00:21:19,600 --> 00:21:21,160
BENCHMARKING THESE MODELS,

646
00:21:21,160 --> 00:21:23,640
MAKING PROTOCOLS SCALABLE AND

647
00:21:23,640 --> 00:21:25,000
REPRODUCIBLE SO THAT THEY CAN BE

648
00:21:25,000 --> 00:21:27,680
USED BY OTHER INVESTIGATORS,

649
00:21:27,680 --> 00:21:29,440
DEVELOPING ORGANOID OR 3D

650
00:21:29,440 --> 00:21:32,640
CULTURE MODELS AND CONTAINMENT

651
00:21:32,640 --> 00:21:36,040
LABORATORIES FOR PATHOGEN WORK,

652
00:21:36,040 --> 00:21:37,680
AS ALSO UNDERSTANDING MICRO

653
00:21:37,680 --> 00:21:39,080
ENENVIRONMENT ENGAGEMENT AND

654
00:21:39,080 --> 00:21:40,920
STANDARDIZATION TO VERIFY AND

655
00:21:40,920 --> 00:21:42,680
VALIDATE SOME OF THESE MODEL

656
00:21:42,680 --> 00:21:43,120
SYSTEMS.

657
00:21:43,120 --> 00:21:44,800
SOME OF THE AREAS IN GLOBAL

658
00:21:44,800 --> 00:21:46,080
HEALTH WE'RE INTERESTED IN ARE

659
00:21:46,080 --> 00:21:47,400
OBVIOUSLY ANTIVIRALS, WE'RE

660
00:21:47,400 --> 00:21:49,560
INTERESTED IN NON-HORMONAL

661
00:21:49,560 --> 00:21:50,320
CONTRACEPTIVES, UNDERSTANDING

662
00:21:50,320 --> 00:21:52,200
THE IMPACT OF MICROBIOME IN

663
00:21:52,200 --> 00:21:54,040
SPECIFIC AREAS IN THE GUT AND

664
00:21:54,040 --> 00:22:02,480
THE VA   VAGINAL ORGANOID MODELN

665
00:22:02,480 --> 00:22:06,760
BE USED TO CULTIVATE MICROBIOTA,

666
00:22:06,760 --> 00:22:08,200
VACCINE PRODUCTION, AS WELL AS

667
00:22:08,200 --> 00:22:09,840
STANDARD TOXICOLOGY FOR DRUG

668
00:22:09,840 --> 00:22:11,680
DISCOVERY AND DEVELOPMENT ACROSS

669
00:22:11,680 --> 00:22:14,840
THESE DIFFERENT THERAPEUTIC

670
00:22:14,840 --> 00:22:17,280
AREAS.

671
00:22:17,280 --> 00:22:19,120
SO WE HAVE A NUMBER OF QUESTIONS

672
00:22:19,120 --> 00:22:20,280
AND I'M SURE WE'RE GOING TO

673
00:22:20,280 --> 00:22:21,440
EXPLORE MANY OF THESE QUESTIONS

674
00:22:21,440 --> 00:22:23,120
IN THE NEXT TWO DAYS WITH SOME

675
00:22:23,120 --> 00:22:26,640
REALLY FANTASTIC TALKS.

676
00:22:26,640 --> 00:22:28,760
WHERE HAVE ORGANOIDS BEEN MOST

677
00:22:28,760 --> 00:22:30,080
SUCCESSFUL IN THE DRUG DISCOVERY

678
00:22:30,080 --> 00:22:32,800
PROCESS AND FOR WHAT PURPOSE FOR

679
00:22:32,800 --> 00:22:36,280
UNDERSTANDING THE COMPLEX

680
00:22:36,280 --> 00:22:37,280
BIOLOGY, IDENTIFYING NEW TARGETS

681
00:22:37,280 --> 00:22:43,280
AND NEW BIOLOGY THRALD BE THAT E

682
00:22:43,280 --> 00:22:44,920
UNAVAILABLE IN 2D CULTURE

683
00:22:44,920 --> 00:22:46,040
SYSTEMS, ARE THESE BETTER

684
00:22:46,040 --> 00:22:47,760
TRANSLATION FROM THE IN VITRO TO

685
00:22:47,760 --> 00:22:51,600
THE HUMAN SYSTEMS.

686
00:22:51,600 --> 00:22:53,560
AND WHAT GAPS REMAIN IN

687
00:22:53,560 --> 00:22:55,880
REALIZING THE IMPACT OF THESE 3D

688
00:22:55,880 --> 00:22:58,280
CULTURE SYSTEMS AND HOW CAN WE

689
00:22:58,280 --> 00:22:59,800
STANDARDIZE THESE SYSTEMS FOR

690
00:22:59,800 --> 00:23:06,040
DRUG DISCOVERY AND DEVELOPMENT?

691
00:23:06,040 --> 00:23:08,120
AND WHAT WILL IT TAKE TO EXPAND

692
00:23:08,120 --> 00:23:09,760
ACCESS TO AND UTILIZATION OF

693
00:23:09,760 --> 00:23:11,240
THESE MODELS IN DRUG DISCOVERY,

694
00:23:11,240 --> 00:23:12,480
WHERE WOULD THE HIGHEST VALUE BE

695
00:23:12,480 --> 00:23:14,440
IN TERMS OF FUTURE FOR INCREASED

696
00:23:14,440 --> 00:23:15,000
UTILIZATION?

697
00:23:15,000 --> 00:23:16,320
SO THESE ARE A NUMBER OF

698
00:23:16,320 --> 00:23:17,200
QUESTIONS I'M SURE WE'RE GOING

699
00:23:17,200 --> 00:23:18,200
TO BE TALKING ABOUT MANY OF

700
00:23:18,200 --> 00:23:21,320
THESE IN THE TALKS TO FOLLOW.

701
00:23:21,320 --> 00:23:23,440
SO WITH THAT, I'LL TURN IT BACK

702
00:23:23,440 --> 00:23:26,840
TO SARINE.

703
00:23:26,840 --> 00:23:28,440
>> THANK YOU SO MUCH,
ROBERT,

704
00:23:28,440 --> 00:23:31,520
FOR THAT WONDERFUL COMMENTS.

705
00:23:31,520 --> 00:23:32,160
OKAY.

706
00:23:32,160 --> 00:23:37,640
SO THE NEXT SPEAKER FOR

707
00:23:37,640 --> 00:23:40,960
INTRODUCTORY COMMENTS IS

708
00:23:40,960 --> 00:23:46,960
DR. EMILYER     EMILY ERBELDINGE

709
00:23:46,960 --> 00:23:47,840
NATIONAL INSTITUTES OF ALLERGY

710
00:23:47,840 --> 00:23:50,760
AND INFECTIOUS DISEASES PART OF

711
00:23:50,760 --> 00:23:51,280
THE NATIONAL INSTITUTES OF

712
00:23:51,280 --> 00:23:52,640
HEALTH.

713
00:23:52,640 --> 00:23:55,280
EMILY, THE FLOOR IS YOURS.

714
00:23:55,280 --> 00:23:57,000
>> THANK YOU.

715
00:23:57,000 --> 00:24:03,240
I'M JUST SHARING MY SLIDES AND

716
00:24:03,240 --> 00:24:04,000
I -- HERE WE GO.

717
00:24:04,000 --> 00:24:05,400
SO THANK YOU FOR INVITING ME TO

718
00:24:05,400 --> 00:24:05,760
PRESENT.

719
00:24:05,760 --> 00:24:07,720
I WAS ASKED TO TALK A LITTLE BIT

720
00:24:07,720 --> 00:24:09,240
ABOUT -- TO REFLECT A LITTLE BIT

721
00:24:09,240 --> 00:24:13,200
BACK ON THE LESSONS LEARNED AT

722
00:24:13,200 --> 00:24:14,400
NIAID FROM THE PANDEMIC THAT

723
00:24:14,400 --> 00:24:15,600
WE'RE STILL EXPERIENCING AND A

724
00:24:15,600 --> 00:24:16,360
PATH FORWARD.

725
00:24:16,360 --> 00:24:19,640
IN PARTICULAR, WITH A FOCUS ON

726
00:24:19,640 --> 00:24:21,720
OUR PROTOTYPE PATHOGEN PLAN FOR

727
00:24:21,720 --> 00:24:23,360
ADDRESSING FUTURE PANDEMICS,

728
00:24:23,360 --> 00:24:26,960
READINESS FOR FUTURE PANDEMICS,

729
00:24:26,960 --> 00:24:28,840
WHICH MIGHT OFFER PERSPECTIVE

730
00:24:28,840 --> 00:24:30,240
FOR YOUR DELIBERATIONS OVER THE

731
00:24:30,240 --> 00:24:32,760
NEXT COUPLE DAYS.

732
00:24:32,760 --> 00:24:34,800
SO AT NIAID AND MORE BROADLY IT

733
00:24:34,800 --> 00:24:41,760
WAS RECOGNIZED THAT THERE WERE

734
00:24:41,760 --> 00:24:44,600
NUMEROUS CORONAVIRUS OUTBREAKS

735
00:24:44,600 --> 00:24:47,320
OCCURRING ABOUT EVERY 10 YEARS,

736
00:24:47,320 --> 00:24:51,600
WITH SARS AND THEN MERS, AND WE

737
00:24:51,600 --> 00:24:53,240
NEEDED TO BE PREPARED FOR A

738
00:24:53,240 --> 00:24:54,080
BIGGER CORONAVIRUS WHICH

739
00:24:54,080 --> 00:24:55,160
ACTUALLY HAPPENED IN LATE 2019

740
00:24:55,160 --> 00:24:58,440
AND CONTINUES TO THE PRESENT.

741
00:24:58,440 --> 00:25:00,480
SO IT WASN'T MAGIC, THE RAPID

742
00:25:00,480 --> 00:25:03,840
DEVELOPMENT OF VACCINES WASN'T

743
00:25:03,840 --> 00:25:04,080
MAGICAL.

744
00:25:04,080 --> 00:25:07,240
THERE WAS A LOT OF SCIENTIFIC

745
00:25:07,240 --> 00:25:08,760
EFFORT AND INVESTMENT THAT WENT

746
00:25:08,760 --> 00:25:10,280
IN A MULTIDISCIPLINARY

747
00:25:10,280 --> 00:25:11,800
INVESTMENTS IN STRUCTURAL

748
00:25:11,800 --> 00:25:13,560
BIOLOGY FOR CORONAVIRUS BECAUSE

749
00:25:13,560 --> 00:25:16,720
PEOPLE RECOGNIZED THAT THIS TYPE

750
00:25:16,720 --> 00:25:18,600
OF VIRUS HAD PANDEMIC POTENTIAL

751
00:25:18,600 --> 00:25:21,880
AND THE THREAT WAS THERE FOR AN

752
00:25:21,880 --> 00:25:23,200
UNPRECEDENTED PANDEMIC.

753
00:25:23,200 --> 00:25:25,040
SO I'M JUST GOING TO TELL YOU A

754
00:25:25,040 --> 00:25:26,480
LITTLE BIT ABOUT THIS STORY

755
00:25:26,480 --> 00:25:28,480
WHICH HAPPENED WITHIN NIAID AT

756
00:25:28,480 --> 00:25:32,160
THE VRC ALONG WITH EXTRAMURAL

757
00:25:32,160 --> 00:25:34,120
INVESTIGATORS.

758
00:25:34,120 --> 00:25:35,840
BACK MORE THAN 10 YEARS AGO, IT

759
00:25:35,840 --> 00:25:38,920
WAS RECOGNIZED BY BARNEY GRAHAM,

760
00:25:38,920 --> 00:25:41,120
WHO'S NOW RETIRED FROM THE VRC,

761
00:25:41,120 --> 00:25:45,400
THAT STRUCTURAL BIOLOGY DEFINING

762
00:25:45,400 --> 00:25:48,240
PARTICULARLY WITH RSV ENTRY

763
00:25:48,240 --> 00:25:51,840
PROTEINS, IF YOU COULD STABILIZE

764
00:25:51,840 --> 00:25:56,640
AN ENTRY PROTEIN IN ITS

765
00:25:56,640 --> 00:25:57,760
PRE-FUSION STRUCTURE USING

766
00:25:57,760 --> 00:26:01,240
VARIOUS TOOLS, YOU COULD IMPROVE

767
00:26:01,240 --> 00:26:04,080
ON ITS IMMUNOGENICITY AND THAT

768
00:26:04,080 --> 00:26:05,520
COULD PROVIDE A BASIS FOR A

769
00:26:05,520 --> 00:26:09,480
BETTER VACCINE FNLT SO THERE WAS

770
00:26:09,480 --> 00:26:11,520
SO THIS WAS ALSO APPLIED TO THE

771
00:26:11,520 --> 00:26:13,080
CORONAVIRUS SPIKE PROTEIN OF

772
00:26:13,080 --> 00:26:15,360
MERS, AND THIS WAS BACK 10 YEARS

773
00:26:15,360 --> 00:26:21,280
AGO, SO INTRODUCING A FEW

774
00:26:21,280 --> 00:26:22,640
MUTATIONS AT A CERTAIN PART OF

775
00:26:22,640 --> 00:26:24,120
THE SPIKE PROTEIN, YOU COULD

776
00:26:24,120 --> 00:26:26,200
STABILIZE IT IN ITS PRE-FUSION

777
00:26:26,200 --> 00:26:28,800
COMPLEX AND RATHER THAN

778
00:26:28,800 --> 00:26:32,760
INFUSING -- USING AS AN ANTIGEN

779
00:26:32,760 --> 00:26:34,200
VARIOUS CONFIRMATIONS OF THE

780
00:26:34,200 --> 00:26:36,800
PROTEIN, YOU COULD GENERATE A

781
00:26:36,800 --> 00:26:39,880
VERY PRECISE, BETTER ANTIBODIES,

782
00:26:39,880 --> 00:26:43,360
MORE PRECISELY TARGETED TO THE

783
00:26:43,360 --> 00:26:47,960
SPIKE PROTEIN THAT WOULD BE MORE

784
00:26:47,960 --> 00:26:48,960
IMMUNOGENIC THAN IF IT WASN'T

785
00:26:48,960 --> 00:26:52,000
HELD IN ITS PREFUSION

786
00:26:52,000 --> 00:26:52,440
CONFORMATION.

787
00:26:52,440 --> 00:26:54,400
SO VACCINES WERE IN THE EARLY

788
00:26:54,400 --> 00:26:55,280
STAGES OF DEVELOPMENT.

789
00:26:55,280 --> 00:26:57,240
IT WAS ALSO TESTED ON A SEASONAL

790
00:26:57,240 --> 00:26:58,800
CORONAVIRUS WHICH ALSO HAD A

791
00:26:58,800 --> 00:27:02,600
SPIKE PROTEIN, THE

792
00:27:02,600 --> 00:27:03,480
OC43 CORONAVIRUS AND IT WAS

793
00:27:03,480 --> 00:27:04,600
HYPOTHESIZED THAT THAT COULD BE

794
00:27:04,600 --> 00:27:07,960
A GENERALIZABLE SOLUTION TO

795
00:27:07,960 --> 00:27:11,360
DEVELOP A VACCINE FOR ANY

796
00:27:11,360 --> 00:27:11,880
CORONAVIRUS.

797
00:27:11,880 --> 00:27:14,400
SO AGAIN, ALL THE CORONAVIRUS

798
00:27:14,400 --> 00:27:15,720
HAVE THESE SPIKE PROTEINS,

799
00:27:15,720 --> 00:27:17,920
PUTTING SPECIFIC MUTATIONS AND

800
00:27:17,920 --> 00:27:20,680
SUBSTITUTING PROLINES IN A FEW

801
00:27:20,680 --> 00:27:24,720
SITES LED TO A STABLE PRE-FUSION

802
00:27:24,720 --> 00:27:28,640
FORM THAT PROVIDED THE BASIS FOR

803
00:27:28,640 --> 00:27:29,320
FIVE OF THE SIX VACCINES THAT

804
00:27:29,320 --> 00:27:34,000
WERE SUPPORTED IN DEVELOPMENT

805
00:27:34,000 --> 00:27:39,480
FOR THE SARS-COV-2 PANDEMIC.

806
00:27:39,480 --> 00:27:41,880
SO THIS SHORTENED TREMENDOUSLY

807
00:27:41,880 --> 00:27:43,000
THE STORY LINE WE HEAR IN THE

808
00:27:43,000 --> 00:27:44,960
PRESS IS SORT OF THAT IT WAS THE

809
00:27:44,960 --> 00:27:47,680
MIRACLE OF MRNA VACCINE PLATFORM

810
00:27:47,680 --> 00:27:49,960
THAT LED US TO BE SO RAPID IN

811
00:27:49,960 --> 00:27:50,960
OUR VACCINE DEVELOPMENT.

812
00:27:50,960 --> 00:27:52,280
BUT REALLY IT WAS YEARS AND

813
00:27:52,280 --> 00:27:54,800
YEARS OF THESE MULTIDISCIPLINARY

814
00:27:54,800 --> 00:27:57,720
TEAMS DEFINING THE STRUCTURE,

815
00:27:57,720 --> 00:27:58,760
TESTING DIFFERENT SUBSTITUTIONS

816
00:27:58,760 --> 00:28:01,560
TO PUT THE PROTEIN, THE ENTRY

817
00:28:01,560 --> 00:28:04,320
PROTEIN OF SARS, WELL, SARS

818
00:28:04,320 --> 00:28:07,040
1 ORIGINALLY BUT THEN OTHER

819
00:28:07,040 --> 00:28:09,120
CORONAVIRUS, TO GENERATE -- TO

820
00:28:09,120 --> 00:28:11,280
USE THAT STABILIZED PRE-FUSION

821
00:28:11,280 --> 00:28:12,960
PROTEIN TO GENERATE AN IMMUNE

822
00:28:12,960 --> 00:28:13,440
RESPONSE.

823
00:28:13,440 --> 00:28:16,440
AND THAT ALLOWED -- THOSE YEARS

824
00:28:16,440 --> 00:28:18,760
OF BASIC SCIENCE WORK AND

825
00:28:18,760 --> 00:28:19,720
TRANSLATIONAL -- EARLY

826
00:28:19,720 --> 00:28:23,000
TRANSLATIONAL WORK LED TO THE

827
00:28:23,000 --> 00:28:24,760
CORONAVIRUS VACCINE BEING

828
00:28:24,760 --> 00:28:26,160
DEVELOPED IN SUCH RAPID TIME,

829
00:28:26,160 --> 00:28:28,720
ALONG WITH THE ADVENT OF THE

830
00:28:28,720 --> 00:28:31,960
MRNA PLATFORM.

831
00:28:31,960 --> 00:28:34,360
SO THIS IS SORT OF THIS IDEA AND

832
00:28:34,360 --> 00:28:37,560
THE SUCCESS OF THIS, YOU KNOW,

833
00:28:37,560 --> 00:28:39,320
EARLY BASIC SCIENCE DISCOVERY,

834
00:28:39,320 --> 00:28:43,000
EARLY PRODUCT DEVELOPMENT AS DES

835
00:28:43,000 --> 00:28:45,240
SORT OF BEEN DEVELOPED INTO, I

836
00:28:45,240 --> 00:28:47,840
GUESS YOU'D SAY, AN APPROACH TO

837
00:28:47,840 --> 00:28:49,040
PANDEMIC PREPAREDNESS THAT NIAID

838
00:28:49,040 --> 00:28:51,760
HAS NOW ENDORSED AS A STRATEGIC

839
00:28:51,760 --> 00:28:54,520
PLAN FOR PREPARING -- FOR

840
00:28:54,520 --> 00:28:56,040
RESEARCH THAT WOULD PREPARE US

841
00:28:56,040 --> 00:28:58,000
FOR FUTURE PANDEMICS.

842
00:28:58,000 --> 00:28:59,200
THE IDEA GOES SOMETHING LIKE

843
00:28:59,200 --> 00:29:00,520
THIS, IF YOU THINK ABOUT VIRUSES

844
00:29:00,520 --> 00:29:02,160
THAT ARE OUT THERE THAT COULD

845
00:29:02,160 --> 00:29:03,360
SPILL FROM ANIMAL RESERVOIRS

846
00:29:03,360 --> 00:29:06,120
INTO THANK    HUMANS, IT SEEMS E

847
00:29:06,120 --> 00:29:07,520
NUMBER IS INFINITE AND THE

848
00:29:07,520 --> 00:29:09,280
THREAT IS INFINITE BUT IF YOU

849
00:29:09,280 --> 00:29:10,720
BREAK THAT DOWN INTO 20 VIRAL

850
00:29:10,720 --> 00:29:13,000
FAMILIES THAT ARE RESPONSIBLE

851
00:29:13,000 --> 00:29:14,520
FOR HUMAN DISEASE AND IF YOU

852
00:29:14,520 --> 00:29:17,000
BREAK THAT DOWN FURTHER TO THE

853
00:29:17,000 --> 00:29:19,640
RNA VIRUSES THAT ARE LIKELY TO

854
00:29:19,640 --> 00:29:21,960
CAUSE SPILLOVER EVENTS BECAUSE

855
00:29:21,960 --> 00:29:24,040
OF THEIR HIGH MUTATION RATE,

856
00:29:24,040 --> 00:29:25,200
REALLY THERE'S LESS THAN 10

857
00:29:25,200 --> 00:29:26,320
VIRAL FAMILIES THAT PROBABLY

858
00:29:26,320 --> 00:29:29,640
HAVE PANDEMIC POTENTIAL.

859
00:29:29,640 --> 00:29:31,800
IF YOU COULD REPLICATE THE

860
00:29:31,800 --> 00:29:36,920
STEPS, THE EARLY SCIENCE STEPS

861
00:29:36,920 --> 00:29:39,000
IN SCIENCE THAT LED TO THE RAPID

862
00:29:39,000 --> 00:29:40,280
DEVELOPMENT OF THE MRNA VACCINES

863
00:29:40,280 --> 00:29:43,960
AND THE OTHER GENE-ENCODED

864
00:29:43,960 --> 00:29:45,240
VACCINES, IF YOU REPLICATE THOSE

865
00:29:45,240 --> 00:29:52,840
STEPS WITH DEFINING AN ANTIGENIC

866
00:29:52,840 --> 00:29:56,760
TARGET TESTING ANIMALS AND ALSO

867
00:29:56,760 --> 00:29:58,600
TESTING MONOCLONAL ANTIBODIES

868
00:29:58,600 --> 00:30:00,360
TESTING THAT SPECIFIC STRUCK

869
00:30:00,360 --> 00:30:02,760
TOOR FOR VIRAL ENTRY, YOU MIGHT

870
00:30:02,760 --> 00:30:04,280
BE WAY FARTHER ALONG SHOULD

871
00:30:04,280 --> 00:30:06,600
ANOTHER VIRUS IN THAT FAMILY

872
00:30:06,600 --> 00:30:09,120
BECOME -- CAUSE AN OUTBREAK THAT

873
00:30:09,120 --> 00:30:10,720
MIGHT LEAD TO AN EPIDEMIC OR

874
00:30:10,720 --> 00:30:13,360
EVEN A PANDEMIC.

875
00:30:13,360 --> 00:30:15,160
SO THIS, WE'RE CALLING THE

876
00:30:15,160 --> 00:30:16,640
PROTOTYPE PATHOGEN APPROACH TO

877
00:30:16,640 --> 00:30:18,520
ACCELERATE MEDICAL

878
00:30:18,520 --> 00:30:20,440
COUNTERMEASURES, VACCINES AND

879
00:30:20,440 --> 00:30:21,440
ALSO MONOCLONAL ANTIBODIES, SO

880
00:30:21,440 --> 00:30:22,720
CHOOSING THESE PROTOTYPE

881
00:30:22,720 --> 00:30:24,080
PATHOGENS WITHIN THE VIRAL

882
00:30:24,080 --> 00:30:26,480
FAMILIES HAS BECOME A FOCUS OF

883
00:30:26,480 --> 00:30:27,400
OUR THINKING OVER THE PAST

884
00:30:27,400 --> 00:30:31,000
SEVERAL MONTHS.

885
00:30:31,000 --> 00:30:32,400
SO OUTLINED ON THE SLIDE

886
00:30:32,400 --> 00:30:33,920
REPRESENTED ARE THE VIRAL

887
00:30:33,920 --> 00:30:35,880
FAMILIES OF CONCERN.

888
00:30:35,880 --> 00:30:37,520
THEY'RE ALL RNA VIRUSES BECAUSE

889
00:30:37,520 --> 00:30:38,640
WE KNOW THESE ARE THE VIRUSES

890
00:30:38,640 --> 00:30:40,600
THAT HAVE HIGH MUTATIONAL RATES

891
00:30:40,600 --> 00:30:42,920
AND, THEREFORE, WITH A LOT OF

892
00:30:42,920 --> 00:30:43,880
MISTAKES, MIGHT LEAD TO

893
00:30:43,880 --> 00:30:46,320
SOMETHING THAT BECOMES MORE

894
00:30:46,320 --> 00:30:48,360
TRANSMISSIBLE SOMETIMES OR MORE

895
00:30:48,360 --> 00:30:50,000
LIKELY TO BE PATHOGENIC IN

896
00:30:50,000 --> 00:30:51,640
HUMANS AND WHEN HUMANS COME INTO

897
00:30:51,640 --> 00:30:54,160
PROXIMITY WITH THEIR ZOONOTIC

898
00:30:54,160 --> 00:30:56,240
RESERVOIR, MORE LIKELY TO CAUSE

899
00:30:56,240 --> 00:30:57,640
DISEASE, POTENTIALLY CAUSE AN

900
00:30:57,640 --> 00:30:59,520
OUTBREAK AND MAYBE EVEN CAUSE A

901
00:30:59,520 --> 00:31:02,360
PANDEMIC.

902
00:31:02,360 --> 00:31:08,280
SO CORONAVIRUS AND ORTHO

903
00:31:08,280 --> 00:31:09,800
MYXOVIRADE HAVE BEEN OF CORNER

904
00:31:09,800 --> 00:31:12,120
FOR A WHILE BUT THERE ARE OTHER

905
00:31:12,120 --> 00:31:14,720
VIRUSES THAT ARE LESS UNDERSTOOD

906
00:31:14,720 --> 00:31:16,360
THAT HAVE FEWER VIRGINIA BEACH

907
00:31:16,360 --> 00:31:18,120
INVESTMENTS BUT PROBABLY STILL

908
00:31:18,120 --> 00:31:19,960
HAVE EPIDEMIC AND MAYBE EVEN

909
00:31:19,960 --> 00:31:20,640
PANDEMIC POTENTIAL.

910
00:31:20,640 --> 00:31:23,480
SO OUR RESEARCH STRATEGY OVER

911
00:31:23,480 --> 00:31:24,920
UPCOMING YEARS, BOTH INTRAMURAL

912
00:31:24,920 --> 00:31:26,760
AND EXTRAMURAL AT NIAID FOR

913
00:31:26,760 --> 00:31:27,960
PANDEMIC PREPAREDNESS, IS TO

914
00:31:27,960 --> 00:31:29,480
FOCUS ON THESE OTHER VIRAL

915
00:31:29,480 --> 00:31:31,240
FAMILIES.

916
00:31:31,240 --> 00:31:36,840
SO WE HAVE PROPOSED, WE HAVEN'T

917
00:31:36,840 --> 00:31:38,600
EVEN GOTTEN FUNDING TO FUND

918
00:31:38,600 --> 00:31:40,080
THESE CENTERS THAT WOULD DEVELOP

919
00:31:40,080 --> 00:31:42,640
VACCINES AND MONOCLONAL

920
00:31:42,640 --> 00:31:46,480
ANTIBODIES FOR PANDEMIC

921
00:31:46,480 --> 00:31:48,320
PREPAREDNESS, WE HAVE PROPOSED A

922
00:31:48,320 --> 00:31:54,640
FUND FOR MULTIDISCIPLINARY TEAMS

923
00:31:54,640 --> 00:31:55,960
EARLY WORKING ON CORONAVIRUS

924
00:31:55,960 --> 00:31:58,480
THAT LED TO RAPID DEVELOPMENT OF

925
00:31:58,480 --> 00:32:00,560
VACCINES AND THEN ALSO

926
00:32:00,560 --> 00:32:02,520
MONOCLONAL ANTIBODIES, AND THEN

927
00:32:02,520 --> 00:32:04,040
WE HOPE THAT THIS APPROACH

928
00:32:04,040 --> 00:32:06,880
GENERALLY CAN ALSO TRANSLATE

929
00:32:06,880 --> 00:32:09,000
INTO PROGRESS IN IDENTIFYING

930
00:32:09,000 --> 00:32:11,040
TARGETS FOR ANTIVIRAL -- OTHER

931
00:32:11,040 --> 00:32:13,360
TYPES OF ANTIVIRALS SUCH AS

932
00:32:13,360 --> 00:32:16,200
SMALL MOLECULE THERAPEUTICS.

933
00:32:16,200 --> 00:32:18,600
SO WE PROPOSE TO DEVELOP CENTERS

934
00:32:18,600 --> 00:32:21,760
THAT FOCUS ON BASIC VEERLOLOGY,

935
00:32:21,760 --> 00:32:23,120
STRUCTURAL BIOLOGY, ANTIGEN

936
00:32:23,120 --> 00:32:24,640
MAPPING, ET CETERA, ANIMAL

937
00:32:24,640 --> 00:32:27,760
MODELS AND REPLACEMENT MODELS

938
00:32:27,760 --> 00:32:30,960
FOR -- MODELS THAT WOULD REPLACE

939
00:32:30,960 --> 00:32:32,960
ANIMALS, AS WELL AS IND-ENABLING

940
00:32:32,960 --> 00:32:35,200
RESEARCH TO FOCUS ON PROTOTYPE

941
00:32:35,200 --> 00:32:38,280
PATHOGENS FROM EACH OF THESE

942
00:32:38,280 --> 00:32:39,840
FAMILIES AND IDEALLY THEY WOULD

943
00:32:39,840 --> 00:32:41,640
FOCUS ON MORE THAN ONE.

944
00:32:41,640 --> 00:32:44,720
SO FOR THE FUTURE, WE BELIEVE

945
00:32:44,720 --> 00:32:46,400
THAT THAT WOULD PROVIDE A PATH

946
00:32:46,400 --> 00:32:49,680
TOWARDS BEING PREPARED FOR

947
00:32:49,680 --> 00:32:55,120
POTENTIALLY ANY ZOO NO     ZOON-

948
00:32:55,120 --> 00:32:57,000
THAT MIGHT LEAD TO A PANDEMIC.

949
00:32:57,000 --> 00:32:58,560
SO I WAS ASKED TO SUMMARIZE SOME

950
00:32:58,560 --> 00:33:00,400
OF THE LESSONS WE'VE LEARNED TO

951
00:33:00,400 --> 00:33:01,720
DATE FROM THE COVID-19 PANDEMIC.

952
00:33:01,720 --> 00:33:02,920
WE'RE STILL LEARNING, OF COURSE,

953
00:33:02,920 --> 00:33:04,560
REALLY THE FIRE IS STILL

954
00:33:04,560 --> 00:33:06,000
SMOLDERING, THIS ISN'T DONE SO

955
00:33:06,000 --> 00:33:08,600
IT FEELS A LITTLE BIT ODD TO

956
00:33:08,600 --> 00:33:10,880
REFLECT AS THOUGH IT WERE DONE,

957
00:33:10,880 --> 00:33:12,520
BUT SOME LESSONS LEARNED, YEARS

958
00:33:12,520 --> 00:33:14,400
OF VIROLOGY AND IP MU NOLG AND

959
00:33:14,400 --> 00:33:15,600
STRUCTURAL BIOLOGY PREPARED THE

960
00:33:15,600 --> 00:33:18,320
WAY FOR RAPID VACCINE

961
00:33:18,320 --> 00:33:29,000
DEVELOPMENT AND IF IT WAS A

962
00:33:29,000 --> 00:33:31,240
DIFFERENT VIRAL FAMILY, WE COULD

963
00:33:31,240 --> 00:33:34,400
NOT HAVE RESPONDED AS RAPIDLY OR

964
00:33:34,400 --> 00:33:35,200
EFFECTIVE, DUE TO THE KNOWLEDGE

965
00:33:35,200 --> 00:33:38,800
WE HAD FOR CORONAVIRUS WHEN THE

966
00:33:38,800 --> 00:33:40,400
SARS-COV-2 PANDEMIC STARTED.

967
00:33:40,400 --> 00:33:43,160
THE RECENT EMERGENCE OF MRNA AS

968
00:33:43,160 --> 00:33:45,240
AN IMMUNOGENIC PLATFORM WAS KEY

969
00:33:45,240 --> 00:33:47,440
TO RAPIDLY MANUFACTURING A

970
00:33:47,440 --> 00:33:48,840
VACCINE AND KEY TO THE CLINICAL

971
00:33:48,840 --> 00:33:50,680
RESPONSE, BUT IT WASN'T A

972
00:33:50,680 --> 00:33:51,360
MIRACLE.

973
00:33:51,360 --> 00:33:54,880
WE ONLY KNEW WHAT TARGET TO

974
00:33:54,880 --> 00:33:56,920
ENCODE IN THE MRNA BECAUSE OF

975
00:33:56,920 --> 00:33:59,920
YEARS OF BASIC SCIENCE AND

976
00:33:59,920 --> 00:34:00,760
TRANSLATIONAL SCIENCE AND WORK

977
00:34:00,760 --> 00:34:05,240
THAT WAS DONE TO BUILD UP TO

978
00:34:05,240 --> 00:34:05,560
THAT POINT.

979
00:34:05,560 --> 00:34:06,440
SO WE PROPOSE THAT THE WORLD

980
00:34:06,440 --> 00:34:08,200
NEEDS A MORE SYSTEMATIC APPROACH

981
00:34:08,200 --> 00:34:09,400
TO PANDEMIC PREPAREDNESS, AND

982
00:34:09,400 --> 00:34:12,240
THIS MIGHT INVOLVE FOCUSING ON

983
00:34:12,240 --> 00:34:13,360
PROTOTYPE PATHOGENS WITHIN EACH

984
00:34:13,360 --> 00:34:15,200
OF THESE VIRAL FAMILIES WITH

985
00:34:15,200 --> 00:34:17,400
PANDEMIC POTENTIAL.

986
00:34:17,400 --> 00:34:18,920
SO IN ADDITION TO FOCUSING ON

987
00:34:18,920 --> 00:34:21,760
VACCINE DEVELOPMENT, MONOCLONAL

988
00:34:21,760 --> 00:34:24,280
ANTIBODY DEVELOPMENT WHICH HAVE

989
00:34:24,280 --> 00:34:25,160
SOME SCIENTIFIC SIMILARITIES

990
00:34:25,160 --> 00:34:26,120
EARLY IN THE DEVELOPMENT STAGE,

991
00:34:26,120 --> 00:34:29,640
WE ALSO ARE TRYING TO FOCUS ON

992
00:34:29,640 --> 00:34:32,600
ANTIVIRAL DEVELOPMENT IN THE

993
00:34:32,600 --> 00:34:34,240
SAME WAY, SO RECENTLY WE

994
00:34:34,240 --> 00:34:37,920
ANNOUNCED FUNDING FOR ANTIVIRAL

995
00:34:37,920 --> 00:34:40,160
DISCOVERY CENTERS.

996
00:34:40,160 --> 00:34:41,360
THESE ARE LARGE COOPERATIVE

997
00:34:41,360 --> 00:34:43,560
AGREEMENTS FUNDED THROUGH THE

998
00:34:43,560 --> 00:34:46,920
AMERICAN PANDEMIC PREPAREDNESS

999
00:34:46,920 --> 00:34:47,360
PROGRAM.

1000
00:34:47,360 --> 00:34:48,560
THESE ARE LARGE

1001
00:34:48,560 --> 00:34:49,320
MULTIDISCIPLINARY TEAMS THAT

1002
00:34:49,320 --> 00:34:51,080
WILL FOCUS ON THE SAME THINGS

1003
00:34:51,080 --> 00:34:52,840
THAT PROVIDED A FOUNDATION FOR

1004
00:34:52,840 --> 00:34:55,240
RAPID DEVELOPMENT OF THE

1005
00:34:55,240 --> 00:34:58,680
SARS-COV-2 VACCINE, STRUCTURAL

1006
00:34:58,680 --> 00:35:07,040
BIOLOGISTS, ME  , MEDICINAL CHE,

1007
00:35:07,040 --> 00:35:09,480
IN VITRO TESTING, ANIMAL MODEL

1008
00:35:09,480 --> 00:35:10,000
DEVELOPMENT.

1009
00:35:10,000 --> 00:35:12,520
THEY WILL FOCUS ON SARS-COV-2

1010
00:35:12,520 --> 00:35:15,160
AND OTHER CORONAVIRUS BUT ALL OF

1011
00:35:15,160 --> 00:35:17,320
THEM WILL HAVE ONE ADDITIONAL

1012
00:35:17,320 --> 00:35:18,320
VIRAL FAMILY WITHIN THESE GROUPS

1013
00:35:18,320 --> 00:35:21,240
THAT MIGHT HAVE PANDEMIC

1014
00:35:21,240 --> 00:35:22,440
POTENTIAL, BECAUSE WE RECOGNIZE

1015
00:35:22,440 --> 00:35:25,440
THAT SOME THERAPEUTICS MIGHT

1016
00:35:25,440 --> 00:35:27,200
HAVE EFFECTIVENESS ACROSS VIRAL

1017
00:35:27,200 --> 00:35:30,040
FAMILIES.

1018
00:35:30,040 --> 00:35:32,760
SO THAT'S OUR PLAN.

1019
00:35:32,760 --> 00:35:34,240
AND I'M HAPPY TO TAKE QUESTIONS

1020
00:35:34,240 --> 00:35:36,680
IF HE   THERE'S TIME.

1021
00:35:36,680 --> 00:35:43,720
THANK YOU.

1022
00:35:43,720 --> 00:35:45,000
>> THANK YOU VERY MUCH,
EMILY.

1023
00:35:45,000 --> 00:35:46,760
I APPRECIATE THOSE WONDERFUL

1024
00:35:46,760 --> 00:35:47,400
COMMENTS THERE.

1025
00:35:47,400 --> 00:35:48,760
THERE IS ACTUALLY ONE QUESTION

1026
00:35:48,760 --> 00:35:50,040
FOR YOU SO I'LL JUST READ IT FOR

1027
00:35:50,040 --> 00:35:50,360
YOU.

1028
00:35:50,360 --> 00:35:52,200
SO THE QUESTION SAYS, IT HAS

1029
00:35:52,200 --> 00:35:54,720
BEEN SHOWN THAT THE IMMUNE

1030
00:35:54,720 --> 00:35:56,400
REPERTOIRE HAS AN IMPACT ON THE

1031
00:35:56,400 --> 00:35:58,560
EFFICACY OF MRNA VACCINES.

1032
00:35:58,560 --> 00:36:00,760
IS THE SAME TRUE FOR OTHER TYPES

1033
00:36:00,760 --> 00:36:03,040
OF VACCINES?

1034
00:36:03,040 --> 00:36:08,520
>> PROBABLY.

1035
00:36:08,520 --> 00:36:10,800
THE IMMUNE REPERTOIRE, I DON'T

1036
00:36:10,800 --> 00:36:12,160
KNOW SPECIFICALLY WHAT ASPECT OF

1037
00:36:12,160 --> 00:36:14,320
THE IMMUNE RESPONSE THE

1038
00:36:14,320 --> 00:36:15,960
QUESTIONER IS FOCUSED ON, BUT I

1039
00:36:15,960 --> 00:36:19,680
THINK WE KNOW THAT THE

1040
00:36:19,680 --> 00:36:21,400
NON-REPLICATING VIRAL VECTOR

1041
00:36:21,400 --> 00:36:22,640
VACCINES PROBABLY STIMULATE A

1042
00:36:22,640 --> 00:36:25,360
BETTER T-CELL RESPONSE AND

1043
00:36:25,360 --> 00:36:27,320
LESS -- AND PROTECT EVEN THOUGH

1044
00:36:27,320 --> 00:36:31,280
THEY ARE STIMULATING --

1045
00:36:31,280 --> 00:36:34,000
GENERATING A LOWER AMOUNT OF

1046
00:36:34,000 --> 00:36:35,760
HUMERAL ANTIBODIES, SO

1047
00:36:35,760 --> 00:36:37,040
NEUTRALIZING ANTIBODIES, SO IT

1048
00:36:37,040 --> 00:36:38,840
MUST BE, SO YES, OTHER THAN MRNA

1049
00:36:38,840 --> 00:36:40,440
VACCINES, THERE IS A DIFFERENCE

1050
00:36:40,440 --> 00:36:43,640
IN THE IMMUNE REP   REPERTOIRE S

1051
00:36:43,640 --> 00:36:43,920
STIMULATED.

1052
00:36:43,920 --> 00:36:45,080
>> THANK YOU VERY MUCH,
EMILY.

1053
00:36:45,080 --> 00:36:48,320
APPRECIATE YOUR TIME.

1054
00:36:48,320 --> 00:36:48,720
OKAY.

1055
00:36:48,720 --> 00:36:52,760
SO WITH THE NEXT FEW MINUTES,

1056
00:36:52,760 --> 00:36:56,320
I'M GOING TO GO OVER THE MISSION

1057
00:36:56,320 --> 00:37:01,000
OF THE ASSAY GUIDANCE PROGRAM

1058
00:37:01,000 --> 00:37:02,320
AND I'LL TALK MORE ABOUT THE

1059
00:37:02,320 --> 00:37:03,320
WORKSHOP OBJECTIVES.

1060
00:37:03,320 --> 00:37:12,840
SO LET ME SHARE MY SLIDES.

1061
00:37:12,840 --> 00:37:15,120
SO AS I SAID EARLIER, I'M THE

1062
00:37:15,120 --> 00:37:16,240
EDITOR-IN-CHIEF OF THE ASSAY

1063
00:37:16,240 --> 00:37:18,480
GUIDANCE MANUAL AND THE LEAD OF

1064
00:37:18,480 --> 00:37:19,840
THE TRANSLATIONAL SCIENCE

1065
00:37:19,840 --> 00:37:23,680
RESOURCES PROGRAM HERE AT NCATS.

1066
00:37:23,680 --> 00:37:25,160
SO BASICALLY WHY WE ARE DOING

1067
00:37:25,160 --> 00:37:28,040
WHAT WE DO IN OUR PROGRAM IS

1068
00:37:28,040 --> 00:37:32,320
BECAUSE THERE IS A CRISIS OF EAR

1069
00:37:32,320 --> 00:37:34,040
IRREPRODUCIBILITY IN BASIC AND

1070
00:37:34,040 --> 00:37:34,800
PRE-CLINICAL RESEARCH THAT MANY

1071
00:37:34,800 --> 00:37:36,800
OF YOU ARE I'M SURE AWARE.

1072
00:37:36,800 --> 00:37:38,520
A PUBLICATION IN 2015 SHOWED

1073
00:37:38,520 --> 00:37:40,720
THAT THE CUMULATIVE PREVALENCE

1074
00:37:40,720 --> 00:37:43,040
OF EAR REPRODUCIBLE PRE-CLINICAL

1075
00:37:43,040 --> 00:37:46,400
RESEARCH EXCEEDS 50%, AND THIS

1076
00:37:46,400 --> 00:37:51,080
ACTUALLY RESULTS IN

1077
00:37:51,080 --> 00:37:51,720
APPROXIMATELY $28 BILLION U.S.

1078
00:37:51,720 --> 00:37:53,320
SPENT ON PRE-CLINICAL RESEARCH

1079
00:37:53,320 --> 00:37:55,520
THAT IS NOT REPRODUCIBLE.

1080
00:37:55,520 --> 00:37:58,880
AND THE CATEGORIES OF

1081
00:37:58,880 --> 00:37:59,640
PRE-CLINICAL EAR REPRO

1082
00:37:59,640 --> 00:38:00,960
QUEUESIBILITY INCLUDE BIOLOGICAL

1083
00:38:00,960 --> 00:38:01,840
REAGENTS AND REFERENCE

1084
00:38:01,840 --> 00:38:03,520
MATERIALS, STUDY DESIGN, DATA

1085
00:38:03,520 --> 00:38:05,440
ANAL   

1086
00:38:05,440 --> 00:38:06,840
ANALYSIS AND REPORTING AND DATA

1087
00:38:06,840 --> 00:38:07,960
AND LABORATORY PROTOCOLS.

1088
00:38:07,960 --> 00:38:09,200
THE ASSAY GUIDANCE MANUAL

1089
00:38:09,200 --> 00:38:11,560
PROGRAM THAT I LEAD IS A DISEASE

1090
00:38:11,560 --> 00:38:13,440
AGNOSTIC PROGRAM THAT ADDRESSES

1091
00:38:13,440 --> 00:38:18,120
THIS CRISIS OF IRREPRODUCIBILITY

1092
00:38:18,120 --> 00:38:19,240
IN BASIC AND PRE-CLINICAL

1093
00:38:19,240 --> 00:38:20,760
RESEARCH AND WE DO SO BY SETTING

1094
00:38:20,760 --> 00:38:24,040
STANDARDS FOR RI CORE     RIGORN

1095
00:38:24,040 --> 00:38:24,640
TRANSLATIONAL SCIENCE.

1096
00:38:24,640 --> 00:38:26,240
WHAT WE ACTUALLY DO IS WE

1097
00:38:26,240 --> 00:38:29,720
PROVIDE MULTIPLE RESOURCES WITH

1098
00:38:29,720 --> 00:38:31,360
THE OVERALL GOAL OF HELPING

1099
00:38:31,360 --> 00:38:33,240
SCIENTISTS LIKE YOU DESIGN AND

1100
00:38:33,240 --> 00:38:35,120
IMPLEMENT ROBUST ASSAYS IN EARLY

1101
00:38:35,120 --> 00:38:37,200
TRANSLATION RESEARCH.

1102
00:38:37,200 --> 00:38:38,200
THE MAIN COMPONENT OF OUR

1103
00:38:38,200 --> 00:38:39,600
PROGRAM IS THE ASSAY GUIDANCE

1104
00:38:39,600 --> 00:38:41,600
MANUAL, WHICH IS A FREE AND

1105
00:38:41,600 --> 00:38:43,560
PUBLICLY AVAILABLE RESOURCE AND

1106
00:38:43,560 --> 00:38:48,320
IS ACCESSIBLE AS AN EBOOK ON THE

1107
00:38:48,320 --> 00:38:49,600
NATIONAL LIBRARY OF MEDICINE

1108
00:38:49,600 --> 00:38:51,120
NCBI BOOKSHELF.

1109
00:38:51,120 --> 00:38:52,960
THIS EBOOK IS DYNAMIC WITH

1110
00:38:52,960 --> 00:38:54,400
CONTINUED RENEWAL AND EXPANSION

1111
00:38:54,400 --> 00:38:56,120
OF CONTENT, AND IT IS WIDELY

1112
00:38:56,120 --> 00:38:59,120
ACCESSED AS WE GOT MORE THAN

1113
00:38:59,120 --> 00:39:02,480
40,000 VIEWS PER MONTH IN 2022.

1114
00:39:02,480 --> 00:39:06,760
AND IT IS ACTUALLY ACCESSED BY

1115
00:39:06,760 --> 00:39:08,560
SCIENTIST FROM PHARMA, BIOTECH,

1116
00:39:08,560 --> 00:39:10,240
GOVERNMENT AND ACADEMIA ALIKE.

1117
00:39:10,240 --> 00:39:13,000
WE ALSO RUN WORKSHOPS AS PART OF

1118
00:39:13,000 --> 00:39:17,840
OUR PROGRAM, AND THIS IS ONE

1119
00:39:17,840 --> 00:39:22,160
TOPIC-FOCUSED WORKSOP THAT WE WE

1120
00:39:22,160 --> 00:39:22,840
ARE RUNNING.

1121
00:39:22,840 --> 00:39:24,680
SO WHAT I'D LIKE TO DO NEXT IS

1122
00:39:24,680 --> 00:39:26,320
GO OVER HIGH LEVEL GOALS OR

1123
00:39:26,320 --> 00:39:27,200
OBJECTIVE FS THIS WORKSHOP.

1124
00:39:27,200 --> 00:39:28,520
SO THE HIGH LEVEL GOALS OF THIS

1125
00:39:28,520 --> 00:39:30,920
WORKSHOP IS TO HELP SCIENTISTS

1126
00:39:30,920 --> 00:39:34,200
ESTABLISH ROBUST REPRODUCIBLE

1127
00:39:34,200 --> 00:39:35,320
SCALABLE CONSISTENT ADVANCED

1128
00:39:35,320 --> 00:39:36,920
TISSUE MODELS TO STUDY PANDEMIC

1129
00:39:36,920 --> 00:39:38,800
THREAT VIRUSES.

1130
00:39:38,800 --> 00:39:40,360
WE'D LIKE TO PROVIDE YOU ALL

1131
00:39:40,360 --> 00:39:41,640
WITH PRACTICAL APPROACHES AND

1132
00:39:41,640 --> 00:39:43,320
BEST PRACTICES FOR DEVELOPING

1133
00:39:43,320 --> 00:39:44,080
STANDARDIZED ASSAYS WITH THE

1134
00:39:44,080 --> 00:39:47,800
HOPE OF HELPING YOU TO

1135
00:39:47,800 --> 00:39:49,760
SUCCESSFULLY DEVELOP

1136
00:39:49,760 --> 00:39:52,840
THERAPEUTICS FOR FUTURE PANDEMIC

1137
00:39:52,840 --> 00:39:53,840
THREATS, AND WE WOULD REALLY

1138
00:39:53,840 --> 00:39:55,440
LIKE TO GENERATE A ROAD MAP TO

1139
00:39:55,440 --> 00:39:57,080
HELP SCIENTISTS DEVELOP ROBUST

1140
00:39:57,080 --> 00:39:59,280
AND REPRODUCIBLE 3D TISSUE

1141
00:39:59,280 --> 00:40:02,440
MODELS TO STUDY VIRUSES.

1142
00:40:02,440 --> 00:40:03,960
THE SPECIFIC ABTTIVES OF THIS

1143
00:40:03,960 --> 00:40:06,720
WORKSHOP INCLUDES INTRODUCE

1144
00:40:06,720 --> 00:40:09,480
PARTICIPANTS TO THE AVAILABLE 3D

1145
00:40:09,480 --> 00:40:10,640
TISSUE MODELS AND DISCUSS

1146
00:40:10,640 --> 00:40:12,280
CHALLENGES IN BUILDING THESE

1147
00:40:12,280 --> 00:40:13,480
MODELS AS WELL AS THEIR UTILITY

1148
00:40:13,480 --> 00:40:19,960
AND LIMITATIONS, AND MOST OF

1149
00:40:19,960 --> 00:40:20,800
THIS FIRST OBJECTIVE WILL BE

1150
00:40:20,800 --> 00:40:27,640
COVERED IN TODAY'S SESSION, ONE

1151
00:40:27,640 --> 00:40:28,680
IN THE AFTERNOON.

1152
00:40:28,680 --> 00:40:30,160
WE'D ALSO LIKE TO PROVIDE CASE

1153
00:40:30,160 --> 00:40:31,640
STUDIES ON HOW THESE AVAILABLE

1154
00:40:31,640 --> 00:40:33,520
3D TISSUE MODELS HAVE BEEN

1155
00:40:33,520 --> 00:40:35,280
UTILIZED IN ANTIVIRAL DRUG

1156
00:40:35,280 --> 00:40:36,280
DISCOVERY AND DEVELOPMENT AS

1157
00:40:36,280 --> 00:40:37,360
WELL AS TOOLS FOR UNDERSTANDING

1158
00:40:37,360 --> 00:40:39,320
AND MODELING INFECTIOUS

1159
00:40:39,320 --> 00:40:41,080
DISEASES, INCLUDING STUDYING

1160
00:40:41,080 --> 00:40:45,320
VIRAL INFECTION AND

1161
00:40:45,320 --> 00:40:52,520
PATHOGENESIS, AND THIS OBJECTIV 

1162
00:40:52,520 --> 00:40:53,640
OBJECTIVE -- MOST OF THESE WILL

1163
00:40:53,640 --> 00:40:55,400
BE COVERED IN SESSION TWO

1164
00:40:55,400 --> 00:40:57,160
TOMORROW, AND WE'D ALSO LIKE TO

1165
00:40:57,160 --> 00:40:58,360
PROVIDE GUIDELINES AND

1166
00:40:58,360 --> 00:41:00,160
CONSIDERATIONS FOR DEVELOPING

1167
00:41:00,160 --> 00:41:02,400
ROBUST AND REPRODUCIBLE 3D

1168
00:41:02,400 --> 00:41:03,160
TISSUE MODELS THAT CAN BE US

1169
00:41:03,160 --> 00:41:04,480
OOOD FOR TESTING THERAPEUTICS.

1170
00:41:04,480 --> 00:41:05,880
WE'D LIKE TO DISCUSS CHALLENGES

1171
00:41:05,880 --> 00:41:08,280
IN AFFORDABILITY, ACCESSIBILITY,

1172
00:41:08,280 --> 00:41:09,200
TRANSFERABILITY AND

1173
00:41:09,200 --> 00:41:10,680
REPRODUCIBILITY OF THESE 3D

1174
00:41:10,680 --> 00:41:13,000
TISSUE MODELS, AND ALSO DISCUSS

1175
00:41:13,000 --> 00:41:17,280
THE ADVANTAGES VERSUS THE

1176
00:41:17,280 --> 00:41:20,440
DISADVANTAGES OF THESE 3D MODELS

1177
00:41:20,440 --> 00:41:23,040
WILL BE COVERED IN SESSION ONE,

1178
00:41:23,040 --> 00:41:24,080
TWO AS WELL AS SESSION THREE.

1179
00:41:24,080 --> 00:41:24,600
OKAY.

1180
00:41:24,600 --> 00:41:25,920
I ALWAYS ASK FOLKS TO CONNECT

1181
00:41:25,920 --> 00:41:28,320
WITH US TO STAY TUNED ABOUT ANY

1182
00:41:28,320 --> 00:41:30,200
UPCOMING WORKSHOPS AND SYMPOSIA

1183
00:41:30,200 --> 00:41:32,600
WE HAVE IN OUR PROGRAM, AS WE

1184
00:41:32,600 --> 00:41:34,400
HAVE ONE COMING UP IN OCTOBER,

1185
00:41:34,400 --> 00:41:36,960
THIS IS AN IN-PERSON WORKSHOP ON

1186
00:41:36,960 --> 00:41:38,400
ASSAY GUIDANCE FOR

1187
00:41:38,400 --> 00:41:39,800
HIGH-THROUGHPUT SCREENING AND

1188
00:41:39,800 --> 00:41:40,360
LEAD DISCOVERY.

1189
00:41:40,360 --> 00:41:44,840
IT WILL BE RUN IN NIH MAIN

1190
00:41:44,840 --> 00:41:45,840
CAMPUS, AND THERE IS MULTIPLE

1191
00:41:45,840 --> 00:41:46,920
WAYS CAN YOU CONNECT WITH US.

1192
00:41:46,920 --> 00:41:48,920
WE ARE ON TWITTER AND OUR

1193
00:41:48,920 --> 00:41:52,360
TWITTER HANDLE IS@ASSAYGUIDANCE.

1194
00:41:52,360 --> 00:41:54,160
WE HAVE A LINKEDIN GROUP THAT

1195
00:41:54,160 --> 00:41:56,280
YOU CAN JOIN HERE, AS WELL AS

1196
00:41:56,280 --> 00:41:59,800
YOU CAN SEE ALL OUR EVENTS AT

1197
00:41:59,800 --> 00:42:04,080
NCATS EVENTS WEBSITE, AND NCATS

1198
00:42:04,080 --> 00:42:07,200
AGM WEBSITE AS WELL.

1199
00:42:07,200 --> 00:42:09,840
SO BACK TO THE MAIN EVENT,

1200
00:42:09,840 --> 00:42:11,240
TODAY'S AGENDA HERE THAT I'M

1201
00:42:11,240 --> 00:42:14,520
SHARING.

1202
00:42:14,520 --> 00:42:16,400
SO AFTER THIS, WE'LL HAVE THE

1203
00:42:16,400 --> 00:42:20,520
KEYNOTE SPEECH BY DR. SIMON

1204
00:42:20,520 --> 00:42:20,880
FUNNELL.

1205
00:42:20,880 --> 00:42:22,720
WE'RE REALLY EXCITED TO HEAR HIM

1206
00:42:22,720 --> 00:42:23,400
SPEAK TODAY.

1207
00:42:23,400 --> 00:42:24,840
AND THEN WE'LL HAVE A LUNCH

1208
00:42:24,840 --> 00:42:27,880
AFTER HIS KEYNOTE, AND THEN THIS

1209
00:42:27,880 --> 00:42:29,520
AFTERNOON WE'LL HAVE THE FIRST

1210
00:42:29,520 --> 00:42:31,480
SESSION, WHICH IS ON 3D TISSUE

1211
00:42:31,480 --> 00:42:34,560
MODELS, UTILITY AND LIMITATIONS,

1212
00:42:34,560 --> 00:42:37,600
AND WE WILL CONCLUDE THE DAY

1213
00:42:37,600 --> 00:42:39,920
TODAY AROUND 4:15.

1214
00:42:39,920 --> 00:42:45,720
I DO WANT TO SAY THAT, PLEASE

1215
00:42:45,720 --> 00:42:46,800
FEEL FREE TO ASK ANY QUESTIONS

1216
00:42:46,800 --> 00:42:50,280
YOU HAVE THROUGHOUT THE TALKS

1217
00:42:50,280 --> 00:42:58,040
USING THE Q & A CHAT BOX

1218
00:42:58,040 --> 00:42:58,960
FUNCTION, AND THE SPEAKERS WILL

1219
00:42:58,960 --> 00:43:02,760
GET TO YOUR QUESTIONS AT THE END

1220
00:43:02,760 --> 00:43:04,600
OF THEIR -- FOR EXAMPLE, THE

1221
00:43:04,600 --> 00:43:05,960
KEYNOTE SPEAKER WILL GET TO YOUR

1222
00:43:05,960 --> 00:43:07,240
QUESTIONS AT THE END OF HIS

1223
00:43:07,240 --> 00:43:08,440
SPEECH, AND THEN FOR THE

1224
00:43:08,440 --> 00:43:11,200
SESSIONS, WE WILL HAVE A Q &
A

1225
00:43:11,200 --> 00:43:12,520
DISCUSSION SESSION AFTER ALL THE

1226
00:43:12,520 --> 00:43:17,240
TALKS HAVE COMPLETED, BUT FEEL

1227
00:43:17,240 --> 00:43:18,360
FREE TO ASK YOUR QUESTIONS AND

1228
00:43:18,360 --> 00:43:21,480
IF YOU WOULD LIKE TO DIRECT YOUR

1229
00:43:21,480 --> 00:43:23,080
QUESTIONS TO A PARTICULAR

1230
00:43:23,080 --> 00:43:24,000
SPEAKER, MAKE SURE YOU ADD THE

1231
00:43:24,000 --> 00:43:25,080
NAME OF THE SPEAKER WHEN YOU

1232
00:43:25,080 --> 00:43:26,680
TYPE IN THE QUESTION IN THE Q
&

1233
00:43:26,680 --> 00:43:35,040
A BOX.

1234
00:43:35,040 --> 00:43:35,480
OKAY.

1235
00:43:35,480 --> 00:43:37,240
I'M EXTREMELY EXCITED TO

1236
00:43:37,240 --> 00:43:39,320
INTRODUCE OUR KEYNOTE SPEAKER,

1237
00:43:39,320 --> 00:43:41,800
DR. SIMON FUNNELL, A SCIENTIFIC

1238
00:43:41,800 --> 00:43:43,880
LEADER BASED AT UK HEALTH

1239
00:43:43,880 --> 00:43:45,840
SECURITY AGENCY.

1240
00:43:45,840 --> 00:43:49,680
HE ALSO HAS A POSITION AT THE

1241
00:43:49,680 --> 00:43:50,960
QUANTUM INSTITUTE IN NORWICH,

1242
00:43:50,960 --> 00:43:54,200
ALSO A FACULTY MEMBER AT THE

1243
00:43:54,200 --> 00:43:54,920
UNIVERSITY OF TEXAS MEDICAL

1244
00:43:54,920 --> 00:43:57,480
BRANCH AND HAS BEEN SECONDED

1245
00:43:57,480 --> 00:43:59,200
PART-TIME TO THE R & D

1246
00:43:59,200 --> 00:44:01,160
BLUEPRINTING AT THE WORLD HEALTH

1247
00:44:01,160 --> 00:44:03,360
ORGANIZATION IN GENEVA SINCE

1248
00:44:03,360 --> 00:44:05,680
FEBRUARY 2020.

1249
00:44:05,680 --> 00:44:08,840
DR. FUNNELL HAS 36 YEARS OF

1250
00:44:08,840 --> 00:44:10,040
WORKING EXPERIENCE AND HAS

1251
00:44:10,040 --> 00:44:11,680
STUDIED AND PUBLISHED PAPERS ON

1252
00:44:11,680 --> 00:44:13,400
A WIDE RANGE OF SELECT AGENTS.

1253
00:44:13,400 --> 00:44:14,320
HE'S EXPERIENCED WITH WORKING

1254
00:44:14,320 --> 00:44:18,160
WITH OTHER DANGEROUS PATHOGENS,

1255
00:44:18,160 --> 00:44:19,440
ASSISTED THE U.K. HEALTH

1256
00:44:19,440 --> 00:44:21,080
SECURITY AGENCY TO PIVOT THEIR

1257
00:44:21,080 --> 00:44:25,240
RESOURCES SO THE SARS-COV-2

1258
00:44:25,240 --> 00:44:26,680
RESPONSE AND ASSURED THAT THE

1259
00:44:26,680 --> 00:44:28,080
U.K. HEALTH SECURITY AGENCY WAS

1260
00:44:28,080 --> 00:44:31,440
AND CONTINUES TO BE REACTIVE TO

1261
00:44:31,440 --> 00:44:32,680
THE DYNAMIC SITUATION PRESENTED

1262
00:44:32,680 --> 00:44:39,640
TO US ALL.

1263
00:44:39,640 --> 00:44:41,800
YOU AM SUPER EXCITED TO HAVE YOU

1264
00:44:41,800 --> 00:44:42,920
WITH US HERE TODAY, SIMON, AND

1265
00:44:42,920 --> 00:44:44,200
WE ARE REALLY EXCITED TO HEAR

1266
00:44:44,200 --> 00:44:45,120
YOUR TALK.

1267
00:44:45,120 --> 00:44:46,840
LIKE I SAID EARLIER, PLEASE FEEL

1268
00:44:46,840 --> 00:44:48,720
TBREE TO ASK ANY QUESTIONS YOU

1269
00:44:48,720 --> 00:44:50,800
HAVE FOR DR. FUNNELL THROUGH THE

1270
00:44:50,800 --> 00:44:52,760
Q & A CHAT BOX AND HE WILL
GET

1271
00:44:52,760 --> 00:44:53,680
TO THESE QUESTIONS AT THE END OF

1272
00:44:53,680 --> 00:44:56,800
THE TALK.

1273
00:44:56,800 --> 00:44:58,760
THANK YOU SO MUCH, SIMON, AGAIN,

1274
00:44:58,760 --> 00:45:00,000
AND THE FLOOR IS YOURS.

1275
00:45:00,000 --> 00:45:01,200
>> THANK YOU VERY MUCH,
SARINE,

1276
00:45:01,200 --> 00:45:02,280
FOR THAT INTRODUCTION.

1277
00:45:02,280 --> 00:45:06,080
AND THANK YOU ALSO TO ALL THE

1278
00:45:06,080 --> 00:45:07,040
ORGANIZERS FOR INVITING ME TO

1279
00:45:07,040 --> 00:45:10,440
SPEAK TO YOU TODAY ABOUT

1280
00:45:10,440 --> 00:45:11,840
SARS-COV-2, HOW IT'S THE START

1281
00:45:11,840 --> 00:45:14,280
OF A NEW SCIENTIFIC RENAISSANCE

1282
00:45:14,280 --> 00:45:22,000
IN BIOLOGICAL SCIENCE.

1283
00:45:22,000 --> 00:45:23,800
CAN I CHECK THAT THAT'S IN

1284
00:45:23,800 --> 00:45:27,200
PRESENTATION MODE?

1285
00:45:27,200 --> 00:45:27,920
>> IT IS NOT.

1286
00:45:27,920 --> 00:45:31,760
>> IT IS NOT.

1287
00:45:31,760 --> 00:45:33,200
THERE WE GO.

1288
00:45:33,200 --> 00:45:33,720
>> GREAT.

1289
00:45:33,720 --> 00:45:36,680
THANK YOU VERY MUCH.

1290
00:45:36,680 --> 00:45:38,480
SO AS YOU'VE MENTIONED, I HAD

1291
00:45:38,480 --> 00:45:39,880
THREE POSITIONS, THANK YOU,

1292
00:45:39,880 --> 00:45:42,120
SARINE, FOR INTRODUCING ME IN

1293
00:45:42,120 --> 00:45:44,000
THAT WAY.

1294
00:45:44,000 --> 00:45:45,200
I HAVE FIVE COMPONENTS OF THE

1295
00:45:45,200 --> 00:45:46,760
TALK I'D LIKE TO GIVE TODAY.

1296
00:45:46,760 --> 00:45:49,720
FIRST I'D LIKE TO TALK ABOUT WHY

1297
00:45:49,720 --> 00:45:52,560
I THINK WE'RE IN THE MIDDLE OF A

1298
00:45:52,560 --> 00:45:53,400
21ST CENTURY SCIENTIFIC

1299
00:45:53,400 --> 00:45:54,400
RENAISSANCE, THEN I'D LIKE TO

1300
00:45:54,400 --> 00:45:55,560
TALK ABOUT ASPECTS OF INFECTION

1301
00:45:55,560 --> 00:45:56,800
MORE GENERALLY, AND THEN I'LL

1302
00:45:56,800 --> 00:45:58,680
TALK ABOUT MODEL SUITABILITY,

1303
00:45:58,680 --> 00:46:01,400
WHAT ARE THE THREE MAJOR COMPLEX

1304
00:46:01,400 --> 00:46:02,680
REQUIREMENTS OF AN INFECTIOUS

1305
00:46:02,680 --> 00:46:05,120
DISEASE MODEL.

1306
00:46:05,120 --> 00:46:07,000
THEN I'LL GIVE SOME EXAMPLES,

1307
00:46:07,000 --> 00:46:08,840
BOTH OLD AND NEW, AND THEN TALK

1308
00:46:08,840 --> 00:46:11,800
ABOUT SUPPLY AND DEMAND ISSUES.

1309
00:46:11,800 --> 00:46:13,640
SO TO BEGIN WITH, WHY DO I SAY

1310
00:46:13,640 --> 00:46:16,520
THAT WE'RE IN THE 21ST CENTURY

1311
00:46:16,520 --> 00:46:17,040
SCIENTIFIC RENAISSANCE?

1312
00:46:17,040 --> 00:46:19,240
I'VE HAD A LOOK AT DICTIONARY

1313
00:46:19,240 --> 00:46:21,400
DEFINITIONS OF RENAISSANCE, AND

1314
00:46:21,400 --> 00:46:22,600
TRADITIONALLY, IT'S BEEN IN

1315
00:46:22,600 --> 00:46:27,400
REFERENCE TO THE 15TH, 16TH

1316
00:46:27,400 --> 00:46:29,840
CENTURIES IN TERMS OF GROWTH OF

1317
00:46:29,840 --> 00:46:31,360
ACTIVITY IN ARTS AND LITERATURE.

1318
00:46:31,360 --> 00:46:33,120
AND I'VE LOOKED AT SOME OF THE

1319
00:46:33,120 --> 00:46:35,200
USAGE OF THE WORD, AND I'D LIKE

1320
00:46:35,200 --> 00:46:37,280
TO PROPOSE A NEW DEFINITION TO

1321
00:46:37,280 --> 00:46:39,040
THE WORD RENAISSANCE.

1322
00:46:39,040 --> 00:46:40,120
I BELIEVE THAT WE'RE IN THE

1323
00:46:40,120 --> 00:46:43,640
MIDDLE OF A GLOBAL -- DURING THE

1324
00:46:43,640 --> 00:46:45,640
GLOBAL SARS-COV-2 OUTBREAK THERE

1325
00:46:45,640 --> 00:46:47,000
WAS SUCH ENORMOUS GROWTH IN

1326
00:46:47,000 --> 00:46:47,920
SCIENTIFIC RESEARCH,

1327
00:46:47,920 --> 00:46:48,880
COLLABORATION AND ACTIVITIES, I

1328
00:46:48,880 --> 00:46:50,160
THINK THAT CONSTITUTES A

1329
00:46:50,160 --> 00:46:52,040
SCIENTIFIC RENAISSANCE.

1330
00:46:52,040 --> 00:46:54,760
AND AN EXAMPLE OF ITS USE COULD

1331
00:46:54,760 --> 00:46:57,160
BE, "I AM PARTICIPATING IN A

1332
00:46:57,160 --> 00:46:57,720
21ST CENTURY SCIENTIFIC

1333
00:46:57,720 --> 00:47:00,000
RENAISSANCE IN WHICH SCIENTISTS,

1334
00:47:00,000 --> 00:47:01,240
DEVELOPERS AND FUNDERS ARE

1335
00:47:01,240 --> 00:47:03,400
COLLABORATING USING THE POWERS

1336
00:47:03,400 --> 00:47:08,120
OF MICRO PHYSIOLOGICAL SYSTEMS."

1337
00:47:08,120 --> 00:47:09,560
TO EXPAND ON THIS IDEA THAT WE

1338
00:47:09,560 --> 00:47:11,200
ARE IN THE MIDDLE OF A

1339
00:47:11,200 --> 00:47:11,960
SCIENTIFIC RENAISSANCE, JUST

1340
00:47:11,960 --> 00:47:14,480
LOOK AT WHAT'S HAPPENED IN TERMS

1341
00:47:14,480 --> 00:47:15,880
OF GLOBAL SOCIETY.

1342
00:47:15,880 --> 00:47:17,720
THERE'S BEEN GLOBAL TRAVEL BANS,

1343
00:47:17,720 --> 00:47:19,520
LOCKDOWNS AND AWARENESS IN THE

1344
00:47:19,520 --> 00:47:21,120
GLOBAL POPULATION THAT HAS

1345
00:47:21,120 --> 00:47:23,000
REALLY FOCUSED ATTENTION ON

1346
00:47:23,000 --> 00:47:24,640
BIOLOGICAL SCIENCE.

1347
00:47:24,640 --> 00:47:26,360
WE'VE HAD GLOBAL PUBLIC

1348
00:47:26,360 --> 00:47:28,360
ENGAGEMENT AND PERSONAL

1349
00:47:28,360 --> 00:47:31,840
PROTECTIVE EQUIPMENT AND

1350
00:47:31,840 --> 00:47:32,280
LOCKDOWNS.

1351
00:47:32,280 --> 00:47:33,800
WIRELESS BANKING HAS TRANSFORMED

1352
00:47:33,800 --> 00:47:35,160
THE WAY THAT WE DO BUSINESS, AND

1353
00:47:35,160 --> 00:47:37,200
THAT DOESN'T APPEAR TO BE

1354
00:47:37,200 --> 00:47:37,480
CHANGING.

1355
00:47:37,480 --> 00:47:39,400
REMOTE WORKING HAS BECOME THE

1356
00:47:39,400 --> 00:47:40,720
NORM, EVEN THOUGH WE'RE NOW

1357
00:47:40,720 --> 00:47:43,000
APPEARING TO GO BACK TO

1358
00:47:43,000 --> 00:47:44,120
NORMALITY, THERE'S FAR LESS

1359
00:47:44,120 --> 00:47:45,440
COMMUTING THAN THERE EVER WAS.

1360
00:47:45,440 --> 00:47:48,600
WE'VE ALSO SEEN AN EPIDEMIC OF

1361
00:47:48,600 --> 00:47:50,280
DISINFORMATION, WHICH AT FIRST

1362
00:47:50,280 --> 00:48:00,080
SEEMED TO BE EAR   EAR RESIST T.

1363
00:48:00,080 --> 00:48:02,560
THEY NOW REALIZE THAT THEY HAVE

1364
00:48:02,560 --> 00:48:06,760
TO GO TO SCIENTIFIC INFORMATION

1365
00:48:06,760 --> 00:48:08,280
TO FORM THEIR JUDGMENTS AND NOT

1366
00:48:08,280 --> 00:48:11,080
RELY ON SOCIAL MEDIA.

1367
00:48:11,080 --> 00:48:12,720
SO THE IMPORTANCE OF BIOLOGICAL

1368
00:48:12,720 --> 00:48:19,080
SCIENCE HAS REALLY BLOSSOMED AND

1369
00:48:19,080 --> 00:48:20,840
SO HAS THE IMPORTANCE OF

1370
00:48:20,840 --> 00:48:22,320
BIOLOGICAL SCIENTISTS.

1371
00:48:22,320 --> 00:48:23,240
POLITICIANS HAVE HAD TO RESPOND

1372
00:48:23,240 --> 00:48:25,520
TO PUBLIC CONCERNS ABOUT SARS

1373
00:48:25,520 --> 00:48:28,360
COV-2 AND NOW WE SEE POLITICIANS

1374
00:48:28,360 --> 00:48:30,240
WITH A THIRST FOR DATA-DRIVEN

1375
00:48:30,240 --> 00:48:31,760
DECISIONS AND THAT'S BECOME

1376
00:48:31,760 --> 00:48:32,560
INCREASINGLY IMPORTANT FOR

1377
00:48:32,560 --> 00:48:35,920
POLITICIANS.

1378
00:48:35,920 --> 00:48:37,000
WE'VE SEEN GLOBAL DATA SHARING

1379
00:48:37,000 --> 00:48:39,520
ON AN UNPRECEDENTED LEVEL AND

1380
00:48:39,520 --> 00:48:41,280
WE'VE SEEN LIVE DATA SHARING

1381
00:48:41,280 --> 00:48:43,600
THREE TIMES A WEEK COORDINATED

1382
00:48:43,600 --> 00:48:48,160
BY THE WHO AND IN SOME TELECOMS

1383
00:48:48,160 --> 00:48:50,360
OVER 1 1/2 THOUSAND PARTICIPANTS

1384
00:48:50,360 --> 00:48:52,240
IN CONSORTIUMS WHICH HAVE BEEN

1385
00:48:52,240 --> 00:48:53,000
HAPPENING QUITE FREQUENTLY.

1386
00:48:53,000 --> 00:48:54,520
THIS REALLY IS UNPRECEDENTED

1387
00:48:54,520 --> 00:48:59,880
COLLABORATION.

1388
00:48:59,880 --> 00:49:01,080
I THINK WE ALL UNDERSTAND THESE

1389
00:49:01,080 --> 00:49:03,160
COMPLEX PROBLEMS WE FACE FROM

1390
00:49:03,160 --> 00:49:08,400
DISEASES LIKE SARS-COV-2 REALLY

1391
00:49:08,400 --> 00:49:10,480
DO NEED CROSS WORKING NOT JUST

1392
00:49:10,480 --> 00:49:11,480
BETWEEN COUNTRIES BUT BETWEEN

1393
00:49:11,480 --> 00:49:12,880
THE FACULTIES OF SCIENCE WHICH

1394
00:49:12,880 --> 00:49:14,080
WE SEEM TO BE BRINGING TOGETHER

1395
00:49:14,080 --> 00:49:16,480
VERY EFFECTIVELY IN THESE TYPES

1396
00:49:16,480 --> 00:49:16,960
OF FORUMS.

1397
00:49:16,960 --> 00:49:18,360
AS WE'VE JUST HEARD FROM ALL THE

1398
00:49:18,360 --> 00:49:19,880
PREVIOUS SPEAKERS, WE'VE SEEN

1399
00:49:19,880 --> 00:49:22,040
SOME AMAZING DEVELOPMENTS IN 3D

1400
00:49:22,040 --> 00:49:23,160
MODELING TECHNOLOGY AND

1401
00:49:23,160 --> 00:49:25,160
ADVANCES.

1402
00:49:25,160 --> 00:49:27,000
AND AS A RESULT OF THAT, WE ARE

1403
00:49:27,000 --> 00:49:28,960
NOW BEGINNING TO SEE LEGISLATIVE

1404
00:49:28,960 --> 00:49:30,680
CHANGES WHICH ARE HAPPENING AS

1405
00:49:30,680 --> 00:49:34,640
WE SPEAK, WHICH ARE GOING TO

1406
00:49:34,640 --> 00:49:37,160
ENABLE US TO ACCEPT DATA

1407
00:49:37,160 --> 00:49:38,360
GENERATED IN THESE TYPES OF

1408
00:49:38,360 --> 00:49:38,720
SYSTEMS.

1409
00:49:38,720 --> 00:49:40,120
I THINK THAT'S WHY I THINK WE'RE

1410
00:49:40,120 --> 00:49:42,080
IN THE MIDDLE OF A SCIENTIFIC

1411
00:49:42,080 --> 00:49:45,960
RENAISSANCE.

1412
00:49:45,960 --> 00:49:47,680
SO MOVING ON, I'D LIKE TO TALK

1413
00:49:47,680 --> 00:49:50,200
ABOUT ASPECTS OF INFECTION IN

1414
00:49:50,200 --> 00:49:52,520
RESPECT TO MY EXPERIENCE IN THE

1415
00:49:52,520 --> 00:49:53,400
LAST 36 YEARS.

1416
00:49:53,400 --> 00:49:54,600
I THINK BROADLY, YOU CAN TALK

1417
00:49:54,600 --> 00:49:57,760
ABOUT A PATHOGEN AND BREAK DOWN

1418
00:49:57,760 --> 00:49:59,200
THE STEPS THAT A PATHOGEN

1419
00:49:59,200 --> 00:50:00,480
INTERACTS WITH A HOST WITH,

1420
00:50:00,480 --> 00:50:01,840
WHICH LEADS TO DISEASE.

1421
00:50:01,840 --> 00:50:04,240
AND THE VERY FIRST OF THOSE IS

1422
00:50:04,240 --> 00:50:04,520
CONTACT.

1423
00:50:04,520 --> 00:50:06,320
AND I KNOW IN THE INTRODUCTORY

1424
00:50:06,320 --> 00:50:07,640
SPEAKERS, WE'VE BEEN HEARING

1425
00:50:07,640 --> 00:50:12,200
ABOUT HOW THAT    THAT WAS THE T

1426
00:50:12,200 --> 00:50:13,760
FOR MANY YEARS AND INDEED THAT'S

1427
00:50:13,760 --> 00:50:14,960
AN EFFECTIVE APPROACH.

1428
00:50:14,960 --> 00:50:16,240
ONE AN ORGANISM HAS HAD COULD BE

1429
00:50:16,240 --> 00:50:19,840
TACT WITH A            CONTACT

1430
00:50:19,840 --> 00:50:22,280
WITH A HOST IT NORMALLY FORMS A

1431
00:50:22,280 --> 00:50:26,080
MORE SECURE ATTACHMENT.

1432
00:50:26,080 --> 00:50:27,400
FOLLOWING ATTACHMENT, AN EVEN

1433
00:50:27,400 --> 00:50:28,280
MORE SECURE ADHESION.

1434
00:50:28,280 --> 00:50:31,440
WE OFTEN SEE PATHOGENS MIMICKING

1435
00:50:31,440 --> 00:50:35,080
THE HOST AND IN THE CASE OF

1436
00:50:35,080 --> 00:50:36,600
VIRUSES, WHICH I'VE PUT IN

1437
00:50:36,600 --> 00:50:37,680
ITALICS, WE THEN SEE INNOVATION

1438
00:50:37,680 --> 00:50:40,960
OF THE HOST CELL, TRANSCRIPTION

1439
00:50:40,960 --> 00:50:43,480
OF THE PATHOGEN GENETIC

1440
00:50:43,480 --> 00:50:46,200
MATERIAL, PIRACY OF THE HOST,

1441
00:50:46,200 --> 00:50:47,560
THEN INTERFERENCE WITH THE HOST

1442
00:50:47,560 --> 00:50:49,840
MACHINERY AND IMMUNE RESPONSE.

1443
00:50:49,840 --> 00:50:52,680
AND IF IT EFFECTIVE, WE THEN SEE

1444
00:50:52,680 --> 00:50:54,640
PATHOGEN ASSEMBLY WITHIN THE

1445
00:50:54,640 --> 00:50:56,840
HOST CELL, WHICH LEADS TO

1446
00:50:56,840 --> 00:50:59,080
REPRODUCTION OF THE PATHOGEN,

1447
00:50:59,080 --> 00:51:00,640
AND THEN WHICH COULD LEAD TO

1448
00:51:00,640 --> 00:51:01,840
DISSEMINATION OF THE PATHOGEN TO

1449
00:51:01,840 --> 00:51:05,680
OTHER HOSTS, OR CONTINUATION OF

1450
00:51:05,680 --> 00:51:09,080
DISEASE IN THE ORIGINAL HOST.

1451
00:51:09,080 --> 00:51:10,160
AND I THINK BREAKING IT DOWN

1452
00:51:10,160 --> 00:51:11,480
INTO THOSE STEPS HELPS US TO

1453
00:51:11,480 --> 00:51:14,000
THINK ABOUT WAYS IN WHICH A HOST

1454
00:51:14,000 --> 00:51:17,360
RESPONDS TO INFECTION.

1455
00:51:17,360 --> 00:51:18,920
SO HERE I'VE TRIED TO BREAK DOWN

1456
00:51:18,920 --> 00:51:20,440
SOME OF THE KEY HOST RESPONSES

1457
00:51:20,440 --> 00:51:23,520
TO THOSE PROCESSES THAT A

1458
00:51:23,520 --> 00:51:25,720
PATHOGEN REPRESENTS.

1459
00:51:25,720 --> 00:51:27,680
THE FIRST OF THOSE IS AVOIDANCE.

1460
00:51:27,680 --> 00:51:33,160
WE ALL KNOW HOW TO AVOID

1461
00:51:33,160 --> 00:51:34,440
SARS-COV-2, WE ISOLATE AND PUT

1462
00:51:34,440 --> 00:51:35,760
IN PERSONAL PROTECTIVE

1463
00:51:35,760 --> 00:51:36,960
EQUIPMENT, BUT THERE'S ALSO --

1464
00:51:36,960 --> 00:51:44,520
WE HAVE AN INNATE INTEGMEN,

1465
00:51:44,520 --> 00:51:46,360
WHICH AVOID THE PATHOGEN MAKING

1466
00:51:46,360 --> 00:51:49,520
ATTACHMENT TO OUR HOST CELLS.

1467
00:51:49,520 --> 00:51:52,520
AND PART OF THAT, I WOULD

1468
00:51:52,520 --> 00:51:55,000
INCLUDE THE MUCOSAL MUCUS FLOW

1469
00:51:55,000 --> 00:51:57,320
WHICH IS INCREDIBLY COMPLEX.

1470
00:51:57,320 --> 00:52:00,480
IF WE THINK ABOUT THE HUMAN

1471
00:52:00,480 --> 00:52:02,440
AIRWAY, WE HAVE WITHIN OUR LUNGS

1472
00:52:02,440 --> 00:52:04,760
WHAT WE CALL A MUCOCILIARY

1473
00:52:04,760 --> 00:52:05,080
ESCALATOR.

1474
00:52:05,080 --> 00:52:08,680
THE WALLS OF OUR TRACHEA AND

1475
00:52:08,680 --> 00:52:18,200
BRONCHI ARE LINED WITH CILIATED

1476
00:52:18,200 --> 00:52:20,760
EPITHELIUM AT TWO HUP BEATS PER

1477
00:52:20,760 --> 00:52:21,040
SECOND.

1478
00:52:21,040 --> 00:52:23,120
TOGETHER THERE'S AN ORCHESTRATED

1479
00:52:23,120 --> 00:52:25,520
MOVEMENT OF MUCUS UP TO OUR

1480
00:52:25,520 --> 00:52:29,160
THROAT, WHERE WE CAN EITHER

1481
00:52:29,160 --> 00:52:30,280
EXPECTORATE, SWALLOW OR

1482
00:52:30,280 --> 00:52:32,880
ELIMINATE THE PATHOGEN FROM OUR

1483
00:52:32,880 --> 00:52:37,800
RESPIRATORY ALVEOLI.

1484
00:52:37,800 --> 00:52:42,400
WHAT'S INTERESTING ABOUT THESE

1485
00:52:42,400 --> 00:52:44,080
CELLS, IT HAS MASSIVE METABOLIC

1486
00:52:44,080 --> 00:52:45,440
IMPACT ON THOSE CELLS AND IT'S

1487
00:52:45,440 --> 00:52:47,080
INTERESTING THAT THOSE ARE THE

1488
00:52:47,080 --> 00:52:57,080
CELLS THAT SARS-COV-2 TARGETS.

1489
00:52:57,080 --> 00:53:02,320
WHEN WHEN I SAY INTEGUMEN, THE

1490
00:53:02,320 --> 00:53:04,760
SKIN HAS EPITHELIAL CELLS,

1491
00:53:04,760 --> 00:53:06,480
ENDOTHELIAL CELLS, DENDRITIC

1492
00:53:06,480 --> 00:53:07,680
CELLS, HAIRS, THE FOLLICLES OF

1493
00:53:07,680 --> 00:53:10,000
THE HAIRS, AND WE HAVE SENSORY

1494
00:53:10,000 --> 00:53:12,160
CONNECTIONS TO THE HAIR,

1495
00:53:12,160 --> 00:53:13,160
MUSCULAR CONNECTIONS TO THE

1496
00:53:13,160 --> 00:53:16,440
HAIR, SEBACEOUS GLANDS, SWEAT

1497
00:53:16,440 --> 00:53:17,880
GLANDS, VENOUS AND ARTERIAL

1498
00:53:17,880 --> 00:53:19,720
BLOOD SUPPLY, ADIPOSE TISSUE,

1499
00:53:19,720 --> 00:53:23,000
AND ON TOP OF ALL OF THAT

1500
00:53:23,000 --> 00:53:25,280
COMPLEXITY, THE IMMUNE SYSTEM

1501
00:53:25,280 --> 00:53:26,520
AND IMMUNE DUCTS.

1502
00:53:26,520 --> 00:53:29,440
BUT THE SKIN ISN'T JUST ON THE

1503
00:53:29,440 --> 00:53:30,440
OUTSIDE OF US.

1504
00:53:30,440 --> 00:53:35,800
WE HAVE RESPIRATORY EPITHELIA,

1505
00:53:35,800 --> 00:53:36,960
GASTROINTESTINAL, REPRO DUCK

1506
00:53:36,960 --> 00:53:41,040
TRI, URINARY, AUDITORY, OCULAR,

1507
00:53:41,040 --> 00:53:42,680
MUCOSAL SURFACES WHICH HAVE NOT

1508
00:53:42,680 --> 00:53:45,760
ONLY UNIQUE EPITHELIAL SURFACES,

1509
00:53:45,760 --> 00:53:48,040
EVEN IN THE GASTROINTESTINAL

1510
00:53:48,040 --> 00:53:50,360
TRACT, THERE ARE DIFFERENT PATHS

1511
00:53:50,360 --> 00:53:52,000
OF THE GASTROINTESTINAL TRACT

1512
00:53:52,000 --> 00:53:54,400
WHICH HAVE VASTLY DIFFERENT

1513
00:53:54,400 --> 00:53:55,080
DIFFERENTIATION IN THE

1514
00:53:55,080 --> 00:54:01,160
EPITHELIUM.

1515
00:54:01,160 --> 00:54:02,040
AND ANOTHER PART OF THE HOST

1516
00:54:02,040 --> 00:54:04,000
DEFENSE IS THE MICROBIOTA.

1517
00:54:04,000 --> 00:54:05,240
I KNOW THAT WAS MENTIONED

1518
00:54:05,240 --> 00:54:06,640
EARLIER, BUT THE MICROBIOME IS

1519
00:54:06,640 --> 00:54:09,040
VERY EFFECTIVE AT COMPETING OR

1520
00:54:09,040 --> 00:54:10,680
DESTROYING POTENTIALLY INVADING

1521
00:54:10,680 --> 00:54:11,560
PATHOGENS.

1522
00:54:11,560 --> 00:54:15,200
AND I THINK WHEN WE TALK ABOUT

1523
00:54:15,200 --> 00:54:16,920
HOST DEFENSES, WE OFTEN DON'T

1524
00:54:16,920 --> 00:54:18,120
THINK ABOUT THE MICROBIOME.

1525
00:54:18,120 --> 00:54:20,240
AND I'D LIKE TO PROPOSE TO YOU

1526
00:54:20,240 --> 00:54:22,040
THAT IN THE CONTEXT OF THE

1527
00:54:22,040 --> 00:54:24,040
MICROBIOME, HEALTH IS A

1528
00:54:24,040 --> 00:54:25,800
CONDITION OF SYMBIOSIS BETWEEN

1529
00:54:25,800 --> 00:54:27,960
THE HOST AND ITS DIVERSE

1530
00:54:27,960 --> 00:54:29,640
MICROBIOME, AND THAT DYSBIOSIS

1531
00:54:29,640 --> 00:54:31,040
IS A CONDITION IN WHICH THE HOST

1532
00:54:31,040 --> 00:54:33,440
IS COMPROMISED BY DISTURBANCE IN

1533
00:54:33,440 --> 00:54:35,080
ITS NORMAL MICROBIOME, LEADING

1534
00:54:35,080 --> 00:54:37,920
TO AN UNHEALTHY CONDITION,

1535
00:54:37,920 --> 00:54:39,000
ILLNESS OR EVEN DEATH.

1536
00:54:39,000 --> 00:54:40,640
AND I'M NOT EXAGGERATING WHEN I

1537
00:54:40,640 --> 00:54:42,280
SAY THAT, BECAUSE LET'S TAKE,

1538
00:54:42,280 --> 00:54:44,200
FOR EXAMPLE, A HEALTHY SYMBIOSIS

1539
00:54:44,200 --> 00:54:46,240
IN WHICH YOU INTRODUCE

1540
00:54:46,240 --> 00:54:50,400
ANTIBIOTICS FOR A VALID REASON.

1541
00:54:50,400 --> 00:54:53,560
A BROAD SPECTRUM ANTIBIOTIC WILL

1542
00:54:53,560 --> 00:54:54,880
REDUCE MICROBIOME DIVERSITY IN A

1543
00:54:54,880 --> 00:54:56,640
HOST, LEADING THEN TO THE

1544
00:54:56,640 --> 00:54:59,360
SUSCEPTIBILITY TO PATHOGENIC OR

1545
00:54:59,360 --> 00:55:00,680
PARASITIC ORGANISM SUCH AS

1546
00:55:00,680 --> 00:55:03,280
C. DIFFICILE.

1547
00:55:03,280 --> 00:55:05,680
C. DIFFICILE CAN THEN INVADE AND

1548
00:55:05,680 --> 00:55:07,560
CAUSE A LIFE-THREATENING

1549
00:55:07,560 --> 00:55:09,120
DISEASE, AND IN FACT, FURTHER

1550
00:55:09,120 --> 00:55:11,520
ANTIBIOTICS MAY ACTUALLY

1551
00:55:11,520 --> 00:55:13,160
EXACERBATE THE INFECTION AND

1552
00:55:13,160 --> 00:55:14,560
ACCENTUATE THE DYSBIOSIS AND

1553
00:55:14,560 --> 00:55:19,720
PROVIDE AN EVEN STRONGER BIAS

1554
00:55:19,720 --> 00:55:21,680
FOR C. DIFFICILE TO TAKE HOLD.

1555
00:55:21,680 --> 00:55:28,800
AS WE SEE, FECAL GAVAGE CAN

1556
00:55:28,800 --> 00:55:30,520
ACTUALLY SAVE LIVES, WHEN DOING

1557
00:55:30,520 --> 00:55:32,720
IT FROM HEALTHY VOLUNTEERS AND

1558
00:55:32,720 --> 00:55:33,840
SUCCESSFULLY SAVING LIVES AS

1559
00:55:33,840 --> 00:55:36,240
MANY CENTERS GLOBALLY HAVE BEEN

1560
00:55:36,240 --> 00:55:36,400
DOG.

1561
00:55:36,400 --> 00:55:37,880
IN FACT THIS THERAPY, AS CRUDE

1562
00:55:37,880 --> 00:55:39,600
AS IT IS, HAS BEEN ACCEPTED BY

1563
00:55:39,600 --> 00:55:40,360
REGULATORY AUTHORITIES IN THE

1564
00:55:40,360 --> 00:55:41,360
U.K. AND WE'RE NOW THINKING

1565
00:55:41,360 --> 00:55:44,320
ABOUT USING IT FOR DISEASES SUCH

1566
00:55:44,320 --> 00:55:47,640
AS M.E., AND WE'RE THINKING

1567
00:55:47,640 --> 00:55:48,920
ABOUT IT IN TERMS OF AGING AND

1568
00:55:48,920 --> 00:55:50,560
TRYING TO PROMOTE HEALTHY AGING

1569
00:55:50,560 --> 00:55:54,720
IN A DICE     A DYSBIOSIS SITUA.

1570
00:55:54,720 --> 00:55:56,680
EVEN PRE-TERM INFANTS GIVEN

1571
00:55:56,680 --> 00:56:00,960
MATERNAL FLORA MICROBIOME

1572
00:56:00,960 --> 00:56:02,240
INOCULUM, IT'S A LIFE SAVING

1573
00:56:02,240 --> 00:56:05,000
TREATMENT AND HAS BEEN SHOWN

1574
00:56:05,000 --> 00:56:06,960
HIGHLY SIGNIFICANTLY TO REDUCE

1575
00:56:06,960 --> 00:56:07,640
PRE-TERM INFANT DEATHS.

1576
00:56:07,640 --> 00:56:10,240
SO THE IMPACT OF A DRUG NEEDS TO

1577
00:56:10,240 --> 00:56:12,960
CONSIDER BOTH THE HOST AND ITS

1578
00:56:12,960 --> 00:56:17,320
MICROBIOME SYMBIOSIS.

1579
00:56:17,320 --> 00:56:19,200
SO THOSE ELEMENTS I'VE JUST BEEN

1580
00:56:19,200 --> 00:56:20,320
TALKING ABOUT ARE REALLY VERY

1581
00:56:20,320 --> 00:56:22,360
MUCH DIRECTED AT THE FIRST THREE

1582
00:56:22,360 --> 00:56:24,760
STEPS IN THE HOST -- IN THE

1583
00:56:24,760 --> 00:56:26,120
PATHOGEN INTERACTION WITH THE

1584
00:56:26,120 --> 00:56:28,040
HOST, NAMELY CONTACT, ATTACHMENT

1585
00:56:28,040 --> 00:56:32,680
AND ADHESION.

1586
00:56:32,680 --> 00:56:36,040
BUT TO ADDRESS LATER STAGES IN A

1587
00:56:36,040 --> 00:56:37,240
HOST PATHOGEN INTERACTION, WE

1588
00:56:37,240 --> 00:56:38,800
NEED TO BECOME -- WE NEED TO

1589
00:56:38,800 --> 00:56:41,440
MOVE AWAY FROM INNATE INTO THE

1590
00:56:41,440 --> 00:56:42,480
ADAPTIVE PROCESSES.

1591
00:56:42,480 --> 00:56:44,600
I'VE TALKED ABOUT AVOIDANCE

1592
00:56:44,600 --> 00:56:46,560
WHICH IS BEHAVIORAL, I'VE TALKED

1593
00:56:46,560 --> 00:56:49,720
ABOUT PHYSICAL BARRIERS SUCH AS

1594
00:56:49,720 --> 00:56:51,560
EPITHELIUM AND CLEARANCE SUCH AS

1595
00:56:51,560 --> 00:56:53,120
THE MUCOUS ESCALATOR,

1596
00:56:53,120 --> 00:56:55,160
COMPETITION BY THE MICROBIOME.

1597
00:56:55,160 --> 00:56:57,360
BUT THE INNATE IMMUNE SYSTEM CAN

1598
00:56:57,360 --> 00:57:01,320
CAUSE AN ALARM TO BE INITIATED

1599
00:57:01,320 --> 00:57:06,680
AND THOSE ARE BY EXAMPLE TOLL

1600
00:57:06,680 --> 00:57:11,240
LIKE RECEPTORS, NATURAL KILLER

1601
00:57:11,240 --> 00:57:13,520
CELLS OR T-CELLS, BUT AS WE

1602
00:57:13,520 --> 00:57:15,200
BECOME MORE ADAPTIVE, WE CAN

1603
00:57:15,200 --> 00:57:17,280
HAVE POLICING FOR MACROPHAGES

1604
00:57:17,280 --> 00:57:18,480
LOOKING FOR THE ANTIGEN AND THEN

1605
00:57:18,480 --> 00:57:20,760
WE HAVE THE T-CELL IMMUNE

1606
00:57:20,760 --> 00:57:22,320
RESPONSE AND DENDRITIC AND NK

1607
00:57:22,320 --> 00:57:24,600
CELLS HAVE ALSO A ROLE IN

1608
00:57:24,600 --> 00:57:25,600
POLICING.

1609
00:57:25,600 --> 00:57:28,120
AS WE BECOME MORE ADAPTIVE,

1610
00:57:28,120 --> 00:57:30,080
SPECIFIC CHEMICAL INHIBITION CAN

1611
00:57:30,080 --> 00:57:32,720
OCCUR FROM ANTIBODIES THAT ARE

1612
00:57:32,720 --> 00:57:34,160
GENERATED BY VACCINE OR PREVIOUS

1613
00:57:34,160 --> 00:57:34,520
INFECTION.

1614
00:57:34,520 --> 00:57:36,120
AND WE SEE DETECTION OF A

1615
00:57:36,120 --> 00:57:38,200
PATHOGEN BY AN ANTIBODY BINDING

1616
00:57:38,200 --> 00:57:40,680
TO THE SURFACE OF EITHER A

1617
00:57:40,680 --> 00:57:42,120
BACTERIA OR VIRUS, AND THEN

1618
00:57:42,120 --> 00:57:43,440
CREATING A FLAG BY THE FC

1619
00:57:43,440 --> 00:57:45,640
PORTION OF THE ANTIBODY, WHICH

1620
00:57:45,640 --> 00:57:47,080
THEN ENCOURAGES OTHER ELEMENTS

1621
00:57:47,080 --> 00:57:49,320
OF THE IMMUNE SYSTEM TO KICK IN.

1622
00:57:49,320 --> 00:57:51,280
WE ALSO SEE A SEEK AND DESTROY

1623
00:57:51,280 --> 00:57:53,120
FUNCTION FROM OUR ADAPTIVE

1624
00:57:53,120 --> 00:57:54,920
IMMUNE RESPONSE, WHERE

1625
00:57:54,920 --> 00:57:58,000
ANTIBODIES CAN MEDIATE KILLING

1626
00:57:58,000 --> 00:58:00,040
BY COMPLEMENT, NATURAL KILLER

1627
00:58:00,040 --> 00:58:01,640
CELLS, DENDRITIC CELLS, AND IN

1628
00:58:01,640 --> 00:58:03,000
FACT T-CELLS AND OTHER ELEMENTS

1629
00:58:03,000 --> 00:58:08,040
OF THE ADAPTIVE IMMUNE RESPONSE.

1630
00:58:08,040 --> 00:58:10,120
SO WE CAN SEE THAT IMMUNITY

1631
00:58:10,120 --> 00:58:11,120
PROVIDES US PROTECTION TO SOME

1632
00:58:11,120 --> 00:58:13,640
OF THE OTHER STEPS IN A

1633
00:58:13,640 --> 00:58:14,600
PATHOGEN-HOST INTERACTION,

1634
00:58:14,600 --> 00:58:16,640
INCLUDING INNOVATION AND

1635
00:58:16,640 --> 00:58:17,560
REPRODUCTION OF THE PATHOGEN AND

1636
00:58:17,560 --> 00:58:19,440
IT MAY EVEN PRESENT

1637
00:58:19,440 --> 00:58:20,720
DISSEMINATION OF THE PATHOGEN.

1638
00:58:20,720 --> 00:58:22,880
AND SO WE SEE THAT A MODEL THAT

1639
00:58:22,880 --> 00:58:24,760
NEEDS TO -- THAT REFLECTS THAT

1640
00:58:24,760 --> 00:58:26,640
INTERACTION HAS TO BE EXTREMELY

1641
00:58:26,640 --> 00:58:32,120
COMPLEX.

1642
00:58:32,120 --> 00:58:36,160
BUT WE STILL HAVE A GAP IN THAT

1643
00:58:36,160 --> 00:58:37,000
PATHOGEN INTERACTION.

1644
00:58:37,000 --> 00:58:39,320
THE GAP BEING INNOVATION,

1645
00:58:39,320 --> 00:58:40,120
TRANSCRIPTION, PIRACY,

1646
00:58:40,120 --> 00:58:41,200
INTERFERENCE WITH THE HOST AND

1647
00:58:41,200 --> 00:58:42,600
EVEN ASSEMBLY OF THE VIRUS.

1648
00:58:42,600 --> 00:58:43,920
DRUGS CAN BE VERY EFFECTIVE AT

1649
00:58:43,920 --> 00:58:44,440
DOING THAT.

1650
00:58:44,440 --> 00:58:47,760
BUT WHEN I SAY THERAPEUTICS,

1651
00:58:47,760 --> 00:58:49,160
THAT'S ALSO INCLUDING SMALL

1652
00:58:49,160 --> 00:58:51,800
MOLECULES SUCH AS ANTIBODIES OR

1653
00:58:51,800 --> 00:58:53,080
NANOBODIES WHICH OVERLAP INTO

1654
00:58:53,080 --> 00:58:55,840
OUR ADAPTIVE IMMUNE SYSTEM.

1655
00:58:55,840 --> 00:58:58,240
SO IF WE'RE GOING TO MODEL A

1656
00:58:58,240 --> 00:58:59,680
THERAPEUTIC WHICH HAS THAT TYPE

1657
00:58:59,680 --> 00:59:03,080
OF COMPLEXITY, WE HAVE TO HAVE A

1658
00:59:03,080 --> 00:59:07,320
MODEL THAT'S SUITABLE TO DO SO.

1659
00:59:07,320 --> 00:59:08,760
SO WHEN I TALK ABOUT MODEL

1660
00:59:08,760 --> 00:59:10,160
SUITABILITY, I WANT TO BEGIN BY

1661
00:59:10,160 --> 00:59:11,360
TALKING ABOUT THE INTERACTION OF

1662
00:59:11,360 --> 00:59:15,960
A SELECT AGENT WITH THE HOST

1663
00:59:15,960 --> 00:59:16,520
CELL.

1664
00:59:16,520 --> 00:59:17,920
WHEN WE TALK ABOUT SELECT

1665
00:59:17,920 --> 00:59:20,440
AGENTS, THAT DOES INCLUDE

1666
00:59:20,440 --> 00:59:21,640
EUKARYOTES, PRO CARE YOATS,

1667
00:59:21,640 --> 00:59:22,760
VIRUSES, WHICH IS THE SUBJECT OF

1668
00:59:22,760 --> 00:59:24,280
TODAY'S AND TOMORROW'S TALKS,

1669
00:59:24,280 --> 00:59:27,320
BUT ALSO TOXINS.

1670
00:59:27,320 --> 00:59:31,120
WHEN WE TALK ABOUT ANTIBIOTICS,

1671
00:59:31,120 --> 00:59:33,000
WE NATURALLY THINK ABOUT

1672
00:59:33,000 --> 00:59:36,720
ANTIBIOTICS TARGETING THE

1673
00:59:36,720 --> 00:59:38,320
PROKARYOTES, BUT THEY ACT

1674
00:59:38,320 --> 00:59:42,840
DIRECTLY ON THE SELECT AGENT.

1675
00:59:42,840 --> 00:59:45,960
SO THOSE DRUGS TARGET THE

1676
00:59:45,960 --> 00:59:47,320
REPRODUCTIVE PROCESSES OR

1677
00:59:47,320 --> 00:59:48,640
VULNERABILITIES OF BOTH YOU'RE

1678
00:59:48,640 --> 00:59:52,120
CARE YOTS AND PROKARYOTICS

1679
00:59:52,120 --> 00:59:53,640
DIRECTLY AND THAT KILLS THEM OR

1680
00:59:53,640 --> 00:59:58,280
STOPS REPRODUCTION DIRECTLY.

1681
00:59:58,280 --> 00:59:59,600
BUT WHEN WE TALK ABOUT AN

1682
00:59:59,600 --> 01:00:10,120
ANTIVIRAL DRUG, S, IT NEEDS TO

1683
01:00:10,960 --> 01:00:12,120
TARGET THE REPLICATED MECHANISMS

1684
01:00:12,120 --> 01:00:14,000
AND IT NEEDS A HIGH FIDELITY

1685
01:00:14,000 --> 01:00:15,400
HUMAN HOST MODEL.

1686
01:00:15,400 --> 01:00:17,280
IT MAY BE THAT SOME CANCER CELL

1687
01:00:17,280 --> 01:00:18,640
LINES OR OTHER CELL LINES MAY

1688
01:00:18,640 --> 01:00:24,400
NOT PROIF THIS       PROVIDE THF

1689
01:00:24,400 --> 01:00:29,840
METABOLIC COMPLEXITY AND THIS IS

1690
01:00:29,840 --> 01:00:31,280
WHERE 3D MODELS MAY OFFER THE

1691
01:00:31,280 --> 01:00:32,080
COMPLEXITY THAT IS REQUIRED

1692
01:00:32,080 --> 01:00:34,440
BECAUSE YOU CAN THEN USE DRUGS

1693
01:00:34,440 --> 01:00:36,080
THAT TARGET THE CORRECT

1694
01:00:36,080 --> 01:00:37,400
MECHANISMS WITHIN THE HOST CELL

1695
01:00:37,400 --> 01:00:46,120
FOR WHICH THE VIRUS IS RELIANT.

1696
01:00:46,120 --> 01:00:47,680
I NO VACCINES AREN'T TOPIC TODAY

1697
01:00:47,680 --> 01:00:49,120
BUT WE NEED TO CONSIDER THE HOST

1698
01:00:49,120 --> 01:00:51,720
IMMUNE SYSTEM IS ABSOLUTELY

1699
01:00:51,720 --> 01:00:54,240
PIVOTAL FOR THE ACTION OF A

1700
01:00:54,240 --> 01:00:55,440
VACCINE, A VACCINE THAT CAN ONLY

1701
01:00:55,440 --> 01:00:57,200
WORK IF THE HOST IMMUNE SYSTEM

1702
01:00:57,200 --> 01:00:58,080
RESPONDS TO IT AND IT'S ONLY

1703
01:00:58,080 --> 01:00:59,320
THROUGH THE HOST IMMUNE RESPONSE

1704
01:00:59,320 --> 01:01:01,680
THAT YOU CAN SEE INHIBITION OF

1705
01:01:01,680 --> 01:01:08,040
REPRODUCTION OR KILLING.

1706
01:01:08,040 --> 01:01:11,080
SOME THERAPEUTIC DRUGS ACTUALLY

1707
01:01:11,080 --> 01:01:13,480
HAVE AN IMMUNE FUNCTION, AND WE

1708
01:01:13,480 --> 01:01:16,760
CAN SEE HERE IN THE DIAGRAM THAT

1709
01:01:16,760 --> 01:01:17,880
THOSE THERAPEUTIC DRUGS ARE

1710
01:01:17,880 --> 01:01:20,840
ACCESSING THE HOST IMMUNE SYSTEM

1711
01:01:20,840 --> 01:01:22,400
TO GENERATE THEIR EFFECT ON THE

1712
01:01:22,400 --> 01:01:24,120
HUMAN HOST.

1713
01:01:24,120 --> 01:01:27,200
SO THERAPEUTIC MONOCLONALS AND

1714
01:01:27,200 --> 01:01:28,680
NANOPARTICLES MAY ACT DIRECTLY

1715
01:01:28,680 --> 01:01:32,000
OR INDIRECTLY ON THE HOST IMMUNE

1716
01:01:32,000 --> 01:01:33,640
SYSTEM.

1717
01:01:33,640 --> 01:01:38,000
AN EXAMPLE IS A MONOCLONAL

1718
01:01:38,000 --> 01:01:39,000
ANTIBODY MAY ACTUALLY PROVIDE A

1719
01:01:39,000 --> 01:01:41,280
LINK TO A NATURAL KILLER CELL TO

1720
01:01:41,280 --> 01:01:46,280
TARGET BY THE FC PORTION.

1721
01:01:46,280 --> 01:01:48,840
WHAT I WANTED TO DO IS BUILD ON

1722
01:01:48,840 --> 01:01:50,480
SOME OF THE POINTS THAT WERE

1723
01:01:50,480 --> 01:01:52,200
RAISED IN THE INTRODUCTORY TALKS

1724
01:01:52,200 --> 01:01:55,480
AND PROVIDE A QUALITATIVE

1725
01:01:55,480 --> 01:01:58,000
ASSESSMENT OF IN VITRO MODELS

1726
01:01:58,000 --> 01:02:00,160
ENGAGED IN IN VIVO ALTERNATIVES.

1727
01:02:00,160 --> 01:02:01,600
WHEN WE TALK ABOUT A HUMAN

1728
01:02:01,600 --> 01:02:03,000
POPULATION, A HUMAN POPULATION

1729
01:02:03,000 --> 01:02:04,800
HAS VAST GENETIC DIVERSITY, BUT

1730
01:02:04,800 --> 01:02:06,760
WITHIN THAT GENETIC DIVERSITY,

1731
01:02:06,760 --> 01:02:09,600
EACH PERSON HAS WITHIN THEM MANY

1732
01:02:09,600 --> 01:02:11,800
BODY SYSTEMS AND I'VE LISTED 11

1733
01:02:11,800 --> 01:02:16,400
OF THESE BODY SYSTEMS.

1734
01:02:16,400 --> 01:02:17,800
AND THAT COMPLEXITY OF THE HOST

1735
01:02:17,800 --> 01:02:19,240
POPULATION IS ACTIVELY REFLECTED

1736
01:02:19,240 --> 01:02:22,400
IN HUMAN CLINICAL TRIALS, AND IN

1737
01:02:22,400 --> 01:02:23,840
HUMAN CHALLENGE STUDIES, AND

1738
01:02:23,840 --> 01:02:25,920
IT'S FAIRLY WELL REFLECTED IN

1739
01:02:25,920 --> 01:02:28,840
ANIMAL MODELS.

1740
01:02:28,840 --> 01:02:30,600
BUT IN VERO CELLS, FOR EXAMPLE,

1741
01:02:30,600 --> 01:02:31,720
MANY OF THOSE BODY SYSTEMS ARE

1742
01:02:31,720 --> 01:02:36,760
NOT U.S. RT POOED        SUPPORT

1743
01:02:36,760 --> 01:02:38,680
YOU COULD SAY THE URINARY TRACT

1744
01:02:38,680 --> 01:02:42,520
IS SUPPORTED BECAUSE THERE ARE

1745
01:02:42,520 --> 01:02:43,640
CELLS, MONKEY KIDNEY CELLS THAT

1746
01:02:43,640 --> 01:02:45,240
ARE NOT FULLY DIFFERENTIATED IN

1747
01:02:45,240 --> 01:02:47,240
TERMS OF A MONKEY KIDNEY, SO

1748
01:02:47,240 --> 01:02:52,680
GIVE IT A PLUS OR MINUS.

1749
01:02:52,680 --> 01:02:55,520
MICROPHYSIOLOGICAL SYSTEMS HAVE

1750
01:02:55,520 --> 01:02:56,400
REVOLUTIONIZED IN VITRO

1751
01:02:56,400 --> 01:02:58,080
TECHNOLOGY AND IT MAY BE THAT

1752
01:02:58,080 --> 01:02:59,600
THESE COMPLEX IN VITRO SYSTEMS

1753
01:02:59,600 --> 01:03:04,840
CAN ADD SOME SYSTEM

1754
01:03:04,840 --> 01:03:07,080
REPRESENTATION BECAUSE YOU CAN

1755
01:03:07,080 --> 01:03:09,120
GET MORE THAN ONE TISSUE TYPE

1756
01:03:09,120 --> 01:03:09,640
INTO ONE CHIP.

1757
01:03:09,640 --> 01:03:12,160
SO FOR EXAMPLE, IN A SINGLE

1758
01:03:12,160 --> 01:03:12,800
MICROPHYSIOLOGICAL SYSTEM, YOU

1759
01:03:12,800 --> 01:03:15,320
MIGHT HAVE BOTH RESPIRATORY AND

1760
01:03:15,320 --> 01:03:16,720
CIRCULATORY CELLS REPRESENTED IN

1761
01:03:16,720 --> 01:03:18,640
ONE CHIP, AND IF YOU

1762
01:03:18,640 --> 01:03:20,160
INTERCONNECT TWO CHIPS, YOU

1763
01:03:20,160 --> 01:03:22,880
MIGHT, FOR EXAMPLE, BE ABLE TO

1764
01:03:22,880 --> 01:03:25,720
GET NEURAL, RESPIRATORY AND

1765
01:03:25,720 --> 01:03:26,400
CIRCULATORY REPRESENTATION.

1766
01:03:26,400 --> 01:03:28,240
SO WE CAN SEE WE'RE GETTING

1767
01:03:28,240 --> 01:03:30,880
BETTER BODY SYSTEMS

1768
01:03:30,880 --> 01:03:32,320
REPRESENTATION IN THE

1769
01:03:32,320 --> 01:03:36,440
MICROPHYSIOLOGICAL SYSTEMS.

1770
01:03:36,440 --> 01:03:38,000
IF I START ASSIGNING SINGLE

1771
01:03:38,000 --> 01:03:39,080
SCORE POINTS TO EACH TIP AND

1772
01:03:39,080 --> 01:03:40,520
BUILDING UP A QUALITATIVE

1773
01:03:40,520 --> 01:03:42,000
ASSESSMENT, BUT WHEN WE TALK

1774
01:03:42,000 --> 01:03:46,200
ABOUT PROTECTION IN HUMAN

1775
01:03:46,200 --> 01:03:46,840
POPULATION, AS I REFERRED TO

1776
01:03:46,840 --> 01:03:49,240
EARLIER, WE HAVE BEHAVIORAL

1777
01:03:49,240 --> 01:03:50,360
PROTECTION THROUGH AVOIDANCE, WE

1778
01:03:50,360 --> 01:03:52,800
HAVE PHYSICAL PROTECTION FROM

1779
01:03:52,800 --> 01:03:54,920
THE SKIN, INNATE PROTECTION FROM

1780
01:03:54,920 --> 01:03:57,880
IMMUNE SYSTEM, AND ACQUIRED

1781
01:03:57,880 --> 01:03:58,240
IMMUNITY.

1782
01:03:58,240 --> 01:04:00,240
AND YOU CAN SEE HUMAN CLINICAL

1783
01:04:00,240 --> 01:04:02,360
TRIALS ACCURATELY REPRESENT

1784
01:04:02,360 --> 01:04:03,480
HUMAN POPULATIONS.

1785
01:04:03,480 --> 01:04:06,400
BUT HUMAN CHALLENGE DOES NOT

1786
01:04:06,400 --> 01:04:08,960
HAVE THAT BEHAVIORAL AVOIDANCE

1787
01:04:08,960 --> 01:04:10,800
THAT THE HUMAN POPULATION HAS,

1788
01:04:10,800 --> 01:04:12,560
BECAUSE THE SUBJECTS ARE BEING

1789
01:04:12,560 --> 01:04:14,840
DELIBERATELY INFECTED IN THE SAY

1790
01:04:14,840 --> 01:04:16,800
WAY ANIMAL MODEL IS, SO WE'RE

1791
01:04:16,800 --> 01:04:19,000
USING A SCORE THERE FOR BOTH

1792
01:04:19,000 --> 01:04:19,880
HUMAN CHALLENGE AND ANIMAL

1793
01:04:19,880 --> 01:04:20,840
MODELS.

1794
01:04:20,840 --> 01:04:23,040
IN IN VITRO SYSTEM, ONCE AGAIN,

1795
01:04:23,040 --> 01:04:25,240
VERO CELLS MAY REPRESENT INNATE

1796
01:04:25,240 --> 01:04:28,520
PROTECTION, BUT THEY DO HAVE

1797
01:04:28,520 --> 01:04:31,160
COMPROMISED INTERFERON

1798
01:04:31,160 --> 01:04:33,080
CHROMOSOME, WHEREAS IN OUR

1799
01:04:33,080 --> 01:04:34,320
MICROPHYSIOLOGICAL SYSTEM, WE'RE

1800
01:04:34,320 --> 01:04:37,160
USING CELLS THAT HAVE GOOD

1801
01:04:37,160 --> 01:04:38,560
INNATE PROTECTION AND GOOD

1802
01:04:38,560 --> 01:04:42,080
PHYSICAL PROTECTION.

1803
01:04:42,080 --> 01:04:44,280
SO YOU CAN SEE THE SCORES ARE

1804
01:04:44,280 --> 01:04:46,000
SLIGHTLY BUILDING UP THERE ON

1805
01:04:46,000 --> 01:04:46,600
MICROPHYSIOLOGICAL SYSTEMS IN

1806
01:04:46,600 --> 01:04:50,400
TERMS OF THIS ARBITRARY

1807
01:04:50,400 --> 01:04:50,960
SCORECARD.

1808
01:04:50,960 --> 01:04:52,440
I WANT TO NOW EXTEND THAT

1809
01:04:52,440 --> 01:04:54,120
SCORECARD TO TALK ABOUT

1810
01:04:54,120 --> 01:04:54,640
SCIENTIFIC VARIABLES.

1811
01:04:54,640 --> 01:04:56,440
WHEN WE TALK ABOUT HUMAN

1812
01:04:56,440 --> 01:04:59,120
POPULATIONS, WE HAVE NO IDEA

1813
01:04:59,120 --> 01:05:02,000
ABOUT PREVIOUS EXPOSURE, AND

1814
01:05:02,000 --> 01:05:03,400
IT'S VERY DIFFICULT TO ESTABLISH

1815
01:05:03,400 --> 01:05:07,560
THAT IN HUMAN CLINICAL TRIALS.

1816
01:05:07,560 --> 01:05:08,760
CERTAINLY IF YOU HAVE A

1817
01:05:08,760 --> 01:05:10,080
VOLUNTEER FOR HUMAN CHALLENGE,

1818
01:05:10,080 --> 01:05:11,160
IT'S NOW BECOMING VERY DIFFICULT

1819
01:05:11,160 --> 01:05:12,880
TO KNOW WHETHER OR NOT ANY

1820
01:05:12,880 --> 01:05:17,080
VOLUNTEER HAS HAD PREVIOUS

1821
01:05:17,080 --> 01:05:21,000
INFECTION WITH SARS-COV-2 OR

1822
01:05:21,000 --> 01:05:22,560
CROSS-REACTING CORONAVIRUS,

1823
01:05:22,560 --> 01:05:24,520
BECAUSE SEROLOGY MAY NOT GIVE

1824
01:05:24,520 --> 01:05:27,360
YOU THAT READOUT OF DEEP BONE

1825
01:05:27,360 --> 01:05:33,920
MARROW MEMORY IN THE T-CELLS.

1826
01:05:33,920 --> 01:05:35,800
WE WON'T KNOW THE EXPOSURE ROUTE

1827
01:05:35,800 --> 01:05:40,160
OR THE DOSE THAT PEOPLE HAD

1828
01:05:40,160 --> 01:05:42,120
RECEIVED OF A PATHOGEN IN A

1829
01:05:42,120 --> 01:05:45,840
HUMAN CLINICAL TRIAL, AND WE

1830
01:05:45,840 --> 01:05:47,280
DON'T KNOW THAT IN THE HUMAN

1831
01:05:47,280 --> 01:05:47,760
POPULATION.

1832
01:05:47,760 --> 01:05:49,120
IN THE HUMAN CHALLENGE, WE DO

1833
01:05:49,120 --> 01:05:52,320
KNOW THAT BECAUSE WE GIVE

1834
01:05:52,320 --> 01:05:54,040
THEM -- NOT WE, BUT WHOEVER DOES

1835
01:05:54,040 --> 01:05:57,120
THAT WOULD GIVE A KNOWN DOSE BY

1836
01:05:57,120 --> 01:05:58,520
A KNOWN ROUTE, AND THAT'S TRUE

1837
01:05:58,520 --> 01:06:00,840
FOR ANIMAL MODELS, WHERE WE CAN

1838
01:06:00,840 --> 01:06:03,240
VERY CAREFULLY ADMINISTER EXACT

1839
01:06:03,240 --> 01:06:05,200
DOSES WITH A KNOWN ROUTE.

1840
01:06:05,200 --> 01:06:09,200
AND WE CAN COULD THAT IN IN

1841
01:06:09,200 --> 01:06:10,680
VITRO SYSTEMS SO ALL THE YESES

1842
01:06:10,680 --> 01:06:19,960
GET A GREEN BOX FOR EXTRA POINT.

1843
01:06:19,960 --> 01:06:23,040
PREVIOUS EXPOSURE -- WELL

1844
01:06:23,040 --> 01:06:24,000
VALIDATED BREEDING FACILITY AND

1845
01:06:24,000 --> 01:06:25,560
OF COURSE OUR CELL CULTURES WILL

1846
01:06:25,560 --> 01:06:29,040
BE EXPOSURE -- AS WELL.

1847
01:06:29,040 --> 01:06:30,840
IN TERMS OF EXISTING IMMUNITY,

1848
01:06:30,840 --> 01:06:31,800
I'VE SAID BEFORE IT'S VERY

1849
01:06:31,800 --> 01:06:33,840
DIFFICULT TO KNOW WHAT LEVELS OF

1850
01:06:33,840 --> 01:06:35,640
IMMUNITY VOLUNTEERS OR TRIAL

1851
01:06:35,640 --> 01:06:38,360
PARTICIPANTS HAVE, BUT OF COURSE

1852
01:06:38,360 --> 01:06:40,760
ANIMALS OR TISSUE CULTURE WILL

1853
01:06:40,760 --> 01:06:45,240
NOT HAVE ANY EXISTING IMMUNITY.

1854
01:06:45,240 --> 01:06:46,680
THERE IS GREAT GENETIC

1855
01:06:46,680 --> 01:06:47,520
VARIABILITY AS DISCUSSED EARLIER

1856
01:06:47,520 --> 01:06:49,520
IN POPULATIONS AND IN CLINICAL

1857
01:06:49,520 --> 01:06:51,800
TRIALS, THAT CAN BE WELL

1858
01:06:51,800 --> 01:06:53,120
REPRESENTED, AND IN A HUMAN

1859
01:06:53,120 --> 01:06:54,320
CHALLENGE, THAT CAN ALSO BE

1860
01:06:54,320 --> 01:06:56,600
REPRESENTED.

1861
01:06:56,600 --> 01:06:57,960
OBVIOUSLY IN ANIMAL MODEL, THEY

1862
01:06:57,960 --> 01:07:04,400
TEND TO BE INNATE IN BRED

1863
01:07:04,400 --> 01:07:07,040
ANIMALS BUT OF COURSE YOU CAN

1864
01:07:07,040 --> 01:07:08,760
SUES DIFFERENT HAPLOTYPES WITHIN

1865
01:07:08,760 --> 01:07:13,120
ANIMAL MODELS TO REPLICATE

1866
01:07:13,120 --> 01:07:15,000
WHAT'S HAPPENING IN THE HUMAN

1867
01:07:15,000 --> 01:07:15,520
CHALLENGE.

1868
01:07:15,520 --> 01:07:19,880
OBVIOUSLY WE COULD TAKE

1869
01:07:19,880 --> 01:07:21,760
REPRESENTATIVES AND GET

1870
01:07:21,760 --> 01:07:23,200
DONATIONS FROM DIFFERENT GENETIC

1871
01:07:23,200 --> 01:07:24,840
GROUPS SO THOSE COULD BE YESES.

1872
01:07:24,840 --> 01:07:26,480
IN TERMS OF UNDERLYING

1873
01:07:26,480 --> 01:07:31,280
CONDITIONS, IN HUMAN CLINICAL

1874
01:07:31,280 --> 01:07:33,040
TRIALS, THERE CAN BE MANY

1875
01:07:33,040 --> 01:07:35,000
UNDERLYING CONDITIONS BUT IN A

1876
01:07:35,000 --> 01:07:36,400
HUMAN CLINICAL TRIAL, THERE

1877
01:07:36,400 --> 01:07:37,520
WON'T BE ANY BECAUSE WE CAN

1878
01:07:37,520 --> 01:07:39,480
SELECT THOSE CLINICAL UNDERLYING

1879
01:07:39,480 --> 01:07:40,360
CONDITIONS OUT AND THAT'S THE

1880
01:07:40,360 --> 01:07:43,000
SAME IN ANIMAL MODELS AND

1881
01:07:43,000 --> 01:07:45,280
MICROPHYSIOLOGICAL SYSTEMS,

1882
01:07:45,280 --> 01:07:47,480
BECAUSE IN VERO CELLS, THERE IS

1883
01:07:47,480 --> 01:07:48,360
EFFECTIVELY AN UNDERLYING

1884
01:07:48,360 --> 01:07:50,080
CONDITION BECAUSE THERE IS NO

1885
01:07:50,080 --> 01:07:53,480
INTERFERON PRODUCTION.

1886
01:07:53,480 --> 01:07:55,000
IN TERMS OF RISK OF HARM, THAT

1887
01:07:55,000 --> 01:07:57,960
WAS MENTIONED EARLIER IN A HUMAN

1888
01:07:57,960 --> 01:08:01,480
POPULATION, THERE'S LOW RISK OF

1889
01:08:01,480 --> 01:08:01,800
HARM.

1890
01:08:01,800 --> 01:08:03,560
IN A HUMAN CLINICAL TRIAL,

1891
01:08:03,560 --> 01:08:05,280
THERE'S MODERATE RISK OF HARM

1892
01:08:05,280 --> 01:08:06,960
BECAUSE THAT PLACEBO IS NOT

1893
01:08:06,960 --> 01:08:07,800
PROVIDING PROTECTION OF THE

1894
01:08:07,800 --> 01:08:08,600
VACCINE UNLESS YOU MITIGATE

1895
01:08:08,600 --> 01:08:08,920
THAT.

1896
01:08:08,920 --> 01:08:10,440
AND CERTAINLY IF YOU WANT TO DO

1897
01:08:10,440 --> 01:08:11,880
A HUMAN CHALLENGE WITH A SELECT

1898
01:08:11,880 --> 01:08:13,040
AGENT, THERE'S A HIGH RISK OF

1899
01:08:13,040 --> 01:08:14,040
HARM HERE.

1900
01:08:14,040 --> 01:08:16,680
IN TERMS OF ANIMALS, THERE'S A

1901
01:08:16,680 --> 01:08:20,640
MODERATE RISK OF HARM, BOTH ET

1902
01:08:20,640 --> 01:08:24,520
CAL AND IN TERMS OF SUFFERING,

1903
01:08:24,520 --> 01:08:26,960
BUT IN TERMS OF IN VITRO AND

1904
01:08:26,960 --> 01:08:27,840
MICROPHYSIOLOGICAL SYSTEMS, THE

1905
01:08:27,840 --> 01:08:30,560
RISK OF HARM IS EXTREMELY LOW,

1906
01:08:30,560 --> 01:08:32,960
HANDLED IN A CATEGORY

1907
01:08:32,960 --> 01:08:33,400
3 LABORATORY.

1908
01:08:33,400 --> 01:08:34,960
AND OF COURSE ANIMAL MODELS ARE

1909
01:08:34,960 --> 01:08:38,160
NOT HUMAN, AND VERO CELLS AREN'T

1910
01:08:38,160 --> 01:08:39,880
HUMAN EITHER, BUT

1911
01:08:39,880 --> 01:08:40,760
MICROPHYSIOLOGICAL SYSTEMS GIVE

1912
01:08:40,760 --> 01:08:41,800
YOU A HUMAN REPRESENTATION IN

1913
01:08:41,800 --> 01:08:45,760
THE WAY THAT THE OTHER IN VITRO

1914
01:08:45,760 --> 01:08:46,320
SYSTEMS DON'T.

1915
01:08:46,320 --> 01:08:48,040
SO IF I ADD ALL OF THESE

1916
01:08:48,040 --> 01:08:48,720
QUALITATIVE POINTS TOGETHER, YOU

1917
01:08:48,720 --> 01:08:51,240
CAN SEE THAT THE

1918
01:08:51,240 --> 01:08:52,120
MICROPHYSIOLOGICALS' SCORE HAS

1919
01:08:52,120 --> 01:08:54,280
ACTUALLY CREPT UP QUITE WELL.

1920
01:08:54,280 --> 01:08:56,160
AND I HAVEN'T DONE THIS YET, BUT

1921
01:08:56,160 --> 01:08:59,760
IF WE ADD IN ACQUIRED IMMUNITY

1922
01:08:59,760 --> 01:09:02,520
INTO MICROPHYSIOLOGICAL SYSTEMS,

1923
01:09:02,520 --> 01:09:04,040
I THINK THEIR QUALITATIVE SCORE

1924
01:09:04,040 --> 01:09:06,320
WILL POSSIBLY REACH OR EXCEED

1925
01:09:06,320 --> 01:09:08,400
THAT OF THESE OTHER TYPES OF

1926
01:09:08,400 --> 01:09:12,560
HUMAN CLINICAL TRIAL.

1927
01:09:12,560 --> 01:09:13,880
SO NOW I WANT TO TALK ABOUT

1928
01:09:13,880 --> 01:09:14,320
TOXICOLOGY.

1929
01:09:14,320 --> 01:09:15,560
I KNOW IT WAS MENTIONED EARLIER

1930
01:09:15,560 --> 01:09:16,800
AS WELL.

1931
01:09:16,800 --> 01:09:19,120
TOXICOLOGY IS IN SOME RESPECTS A

1932
01:09:19,120 --> 01:09:21,320
FAIRLY SIMPLE SCIENTIFIC ASPECT

1933
01:09:21,320 --> 01:09:23,280
OF BIOLOGICAL SCIENCE, BECAUSE

1934
01:09:23,280 --> 01:09:25,440
IT INVOLVES CELL CULTURE, CELL

1935
01:09:25,440 --> 01:09:29,080
BIOLOGY, MOLECULAR BIOLOGY,

1936
01:09:29,080 --> 01:09:30,640
THERE'S BEAUTIFUL ROBOTICS AND

1937
01:09:30,640 --> 01:09:35,440
MICRO FLUIDICS NA HAVE     THATN

1938
01:09:35,440 --> 01:09:36,960
ADVANCED IN THE LAST DECADE, AND

1939
01:09:36,960 --> 01:09:39,120
THOSE PK AND PD STUDIES ARE VERY

1940
01:09:39,120 --> 01:09:40,240
PRECISE AND ACCURATE.

1941
01:09:40,240 --> 01:09:42,640
AND ACTUALLY HAVE BEEN VERY

1942
01:09:42,640 --> 01:09:46,800
ILLUMINATING FOR REGULATORS.

1943
01:09:46,800 --> 01:09:48,200
BUT WHEN WE TALK ABOUT CANCER

1944
01:09:48,200 --> 01:09:49,560
RESEARCH, THERE'S ANOTHER ORDER

1945
01:09:49,560 --> 01:09:51,200
OF COMPLEXITY IN THOSE STUDIES.

1946
01:09:51,200 --> 01:09:54,360
BECAUSE NOW YOU INCLUDE

1947
01:09:54,360 --> 01:10:03,000
IMMUNOHISTO PATHOLOGY, HUMAN

1948
01:10:03,000 --> 01:10:07,920
IN SITU HYBRIDIZATION,

1949
01:10:07,920 --> 01:10:10,960
BIOLUMINESCENCE, POSSIBLY

1950
01:10:10,960 --> 01:10:12,720
TRANSCRIPTOMICS AND PROTEOMICS.

1951
01:10:12,720 --> 01:10:14,200
BUT CANCER RESEARCH IS ALSO

1952
01:10:14,200 --> 01:10:16,640
PERHAPS LESS COMPLICATED THAN

1953
01:10:16,640 --> 01:10:18,000
VIROLOGY, BECAUSE VIROLOGY HAS

1954
01:10:18,000 --> 01:10:19,920
ALL OF THE COMPONENTS OF CANCER

1955
01:10:19,920 --> 01:10:21,560
RESEARCH ON TOP OF THE

1956
01:10:21,560 --> 01:10:29,080
REQUIREMENTS TO HANDLE BSL LEVEL

1957
01:10:29,080 --> 01:10:31,640
3 PATHOGENS AND IT REQUIRES

1958
01:10:31,640 --> 01:10:32,600
ILLUMINATION AND TITRATION OF

1959
01:10:32,600 --> 01:10:34,120
THOSE PATHOGENS, SEROLOGY

1960
01:10:34,120 --> 01:10:36,280
AGAINST THE PATHOGEN AND

1961
01:10:36,280 --> 01:10:37,200
IMMUNOLOGY AGAINST THE PATHOGEN

1962
01:10:37,200 --> 01:10:38,160
OF INTEREST.

1963
01:10:38,160 --> 01:10:39,840
BUT IT DOES HAVE MANY OF THE

1964
01:10:39,840 --> 01:10:41,480
FEATURES OF THE TWO OTHER

1965
01:10:41,480 --> 01:10:48,920
FACULTIES OF BIOLOGICAL SCIENCE.

1966
01:10:48,920 --> 01:10:50,440
I WAS SURPRISED AT THIS AND I

1967
01:10:50,440 --> 01:10:52,720
WANTED TO DRAW TO EVERYBODY'S

1968
01:10:52,720 --> 01:10:55,480
ATTENTION, THAT THERE IS

1969
01:10:55,480 --> 01:10:56,800
REGULATORY ADAPTATION OCCURRING

1970
01:10:56,800 --> 01:11:00,480
AS WE SPEAK IN THE FDA

1971
01:11:00,480 --> 01:11:05,080
MODERNIZATION ACT OF 2021, HERE

1972
01:11:05,080 --> 01:11:06,400
ON THE LEFT-HAND SIDE, THE

1973
01:11:06,400 --> 01:11:07,680
PHRASE THEY WANT TO USE

1974
01:11:07,680 --> 01:11:08,920
ALTERNATIVE TESTING METHODS TO

1975
01:11:08,920 --> 01:11:10,440
ANIMAL TESTING TO INVESTIGATE

1976
01:11:10,440 --> 01:11:11,440
THE SAFETY AND EFFECTIVENESS OF

1977
01:11:11,440 --> 01:11:13,080
A DRUG AND FOR OTHER PURPOSES.

1978
01:11:13,080 --> 01:11:16,320
AND THIS HAS BEEN SUPPORTED BY

1979
01:11:16,320 --> 01:11:17,680
JIM CORBETT AND MANY OTHER

1980
01:11:17,680 --> 01:11:18,520
PEOPLE, SUGGESTING THAT SOME OF

1981
01:11:18,520 --> 01:11:22,040
THE AP MALL     ANIMAL STUDIES E

1982
01:11:22,040 --> 01:11:23,360
OCCURRED HAVE LED TO THE WRONG

1983
01:11:23,360 --> 01:11:24,360
CONCLUSION WHEN IT COMES TO

1984
01:11:24,360 --> 01:11:24,840
HUMANS.

1985
01:11:24,840 --> 01:11:27,400
SO WHAT WE'RE SEEING HERE IS A

1986
01:11:27,400 --> 01:11:30,000
PARADIGM SHIFT IN REGULATORY

1987
01:11:30,000 --> 01:11:31,640
ACCEPTANCE OF MICROPHYSIOLOGICAL

1988
01:11:31,640 --> 01:11:32,320
SYSTEMS.

1989
01:11:32,320 --> 01:11:39,560
INTO AND I CAN      I   I CASSIS

1990
01:11:39,560 --> 01:11:40,640
IN TOXICOLOGY AND CANCER

1991
01:11:40,640 --> 01:11:42,080
RESEARCH WILL SPREAD THROUGH

1992
01:11:42,080 --> 01:11:44,680
INTO MICROBIOLOGY AND IMMUNOLOGY

1993
01:11:44,680 --> 01:11:46,320
QUITE RAPIDLY, BECAUSE THAT

1994
01:11:46,320 --> 01:11:47,120
CROSS-CUTTING ADVANCES ARE GOING

1995
01:11:47,120 --> 01:11:50,280
TO IMMEDIATELY HAVE AN IMPACT ON

1996
01:11:50,280 --> 01:11:51,560
REGULATORS AND FUNDERS AND

1997
01:11:51,560 --> 01:11:58,680
DEVELOPERS.

1998
01:11:58,680 --> 01:12:02,280
I'VE TRIED TO DRAW A SIMPLE

1999
01:12:02,280 --> 01:12:02,720
REPRESENTATION OF

2000
01:12:02,720 --> 01:12:03,400
MICROPHYSIOLOGICAL SYSTEMS AND

2001
01:12:03,400 --> 01:12:04,400
THE ADVANTAGES THEY OFFER AS

2002
01:12:04,400 --> 01:12:05,880
WELL.

2003
01:12:05,880 --> 01:12:08,960
BECAUSE FOR EXAMPLE, A

2004
01:12:08,960 --> 01:12:09,920
TWO-TISSUE MICROPHYSIOLOGICAL

2005
01:12:09,920 --> 01:12:12,240
SYSTEM HAS TWO CHAMBERS, WE CAN

2006
01:12:12,240 --> 01:12:16,720
MODEL SYSTEMIC DOSING OF

2007
01:12:16,720 --> 01:12:17,480
ANTIVIRALS, DRUGS AND

2008
01:12:17,480 --> 01:12:18,800
ANTIBIOTICS INTO THE VASCULAR

2009
01:12:18,800 --> 01:12:20,880
COMPONENT AND THEN INTRODUCE THE

2010
01:12:20,880 --> 01:12:22,840
SELECT AGENT INTO THE ORGAN CELL

2011
01:12:22,840 --> 01:12:24,160
CHANNEL OF WHICH MIGHT BE THE

2012
01:12:24,160 --> 01:12:26,680
BRAIN, KIDNEY OR OTHER ORGAN.

2013
01:12:26,680 --> 01:12:29,840
SO HERE WE'RE ASSIMILATING

2014
01:12:29,840 --> 01:12:30,600
SYSTEMIC DOSING.

2015
01:12:30,600 --> 01:12:32,480
BUT IN THE SAME CHIP, WE MIGHT

2016
01:12:32,480 --> 01:12:34,200
HAVE A MODEL MUCOSAL INFECTION

2017
01:12:34,200 --> 01:12:36,520
OR DOSING BY APPLYING ANTIVIRAL

2018
01:12:36,520 --> 01:12:37,960
DRUG, ANTIBIOTIC OR EVEN IMMUNE

2019
01:12:37,960 --> 01:12:40,000
CELLS INTO THE MUCOSAL SURFACE,

2020
01:12:40,000 --> 01:12:41,560
ALONG WITH A SELECT AGENT.

2021
01:12:41,560 --> 01:12:44,040
SO WE HAVE IMMEDIATELY USED IT

2022
01:12:44,040 --> 01:12:45,600
FOR MORE THAN ONE PURPOSE

2023
01:12:45,600 --> 01:12:48,480
WITHOUT CHANGING ANYTHING, THE

2024
01:12:48,480 --> 01:12:50,080
ROUTE OF ENTRY OF THE DRUG

2025
01:12:50,080 --> 01:12:51,640
ANTIVIRAL OR IMMUNE CELLS.

2026
01:12:51,640 --> 01:12:53,920
BUT WE CAN ALSO MODEL

2027
01:12:53,920 --> 01:12:57,080
COMBINATIONS OF THE TWO, PERHAPS

2028
01:12:57,080 --> 01:12:58,320
INTRAVENOUS ANTIVIRAL DRUG

2029
01:12:58,320 --> 01:12:59,520
ADMINISTRATION, AS WELL AS

2030
01:12:59,520 --> 01:13:02,360
MUCOSAL ANTIBODY OR IMMUNE CELL

2031
01:13:02,360 --> 01:13:03,880
ADDITION, AS WELL AS THE SELECT

2032
01:13:03,880 --> 01:13:04,600
AGENT.

2033
01:13:04,600 --> 01:13:11,400
AND CULMINATIONS THERE.

2034
01:13:11,400 --> 01:13:12,720
NOW I WANT TO TALK ABOUT SOME

2035
01:13:12,720 --> 01:13:14,480
OLD EXAMPLES AND IN THE EARLY

2036
01:13:14,480 --> 01:13:18,840
90s, WHEN I WAS DOING MY PH.D.

2037
01:13:18,840 --> 01:13:23,680
ON B. PERTUSSIS, MECHANISMS OF

2038
01:13:23,680 --> 01:13:25,400
COLONIZATION OF MAMMALIAN

2039
01:13:25,400 --> 01:13:26,920
TISSUES BY BOARD AT THE LA

2040
01:13:26,920 --> 01:13:30,040
PERTUSSIS.

2041
01:13:30,040 --> 01:13:32,000
IT DOES STICK VERY WELL TO VERO

2042
01:13:32,000 --> 01:13:36,160
CELLS BUT IT DOES SO USING

2043
01:13:36,160 --> 01:13:37,360
COMPONENTS OTHER THAN THE

2044
01:13:37,360 --> 01:13:46,160
SPECIFIC ADHESION.

2045
01:13:46,160 --> 01:13:51,520
YOU CAN SEE THIS COMPLEX

2046
01:13:51,520 --> 01:13:53,160
CILIATED EPITHELIUM SO CRITICAL

2047
01:13:53,160 --> 01:13:56,000
TO THE FIRST STEPS OF CONTACT

2048
01:13:56,000 --> 01:14:00,160
BETWEEN BORDETELLA PER   PERTUSD

2049
01:14:00,160 --> 01:14:04,400
THE CELL.

2050
01:14:04,400 --> 01:14:09,920
 -- INITIALLY HAS AN ADD   ADHEN

2051
01:14:09,920 --> 01:14:13,080
EVENT WHICH OCCURS FROM THE END

2052
01:14:13,080 --> 01:14:15,240
OF THE -- TO THE CILIATED

2053
01:14:15,240 --> 01:14:15,800
EPITHELIUM.

2054
01:14:15,800 --> 01:14:19,960
AND THEN THIS LEADS TO BETTER

2055
01:14:19,960 --> 01:14:21,840
ADHESION OF THE ORGANISM

2056
01:14:21,840 --> 01:14:23,240
FOLLOWING THAT INITIAL

2057
01:14:23,240 --> 01:14:24,320
ATTACHMENT THROUGH OTHER

2058
01:14:24,320 --> 01:14:26,760
MECHANISMS.

2059
01:14:26,760 --> 01:14:31,120
SO THIS LOVELY CILIATED

2060
01:14:31,120 --> 01:14:32,640
EPITHELIAL TISSUE MODEL WAS ABLE

2061
01:14:32,640 --> 01:14:34,400
TO DEMONSTRATE MANY OF THE

2062
01:14:34,400 --> 01:14:36,120
PATHOGEN INTERACTIONS WITH

2063
01:14:36,120 --> 01:14:36,600
BORDETELLA PERTUSSIS.

2064
01:14:36,600 --> 01:14:41,320
SO IN TERMS OF CON TAJT      COS

2065
01:14:41,320 --> 01:14:42,840
INITIAL INHALATION FROM AN

2066
01:14:42,840 --> 01:14:45,440
AEROSOL FROM A CHILD WITH

2067
01:14:45,440 --> 01:14:48,080
WHOOPING COUGH, AND ADD HEE SIN

2068
01:14:48,080 --> 01:14:49,800
SPECIFIC FOR HUMAN CILIA AT THE

2069
01:14:49,800 --> 01:14:56,040
TIP OF FIMBRIA, OTHER SURFACE

2070
01:14:56,040 --> 01:14:57,920
ADHESIVES OF BORDETELLA

2071
01:14:57,920 --> 01:14:59,240
PERTUSSIS CAN ADHERE VERY

2072
01:14:59,240 --> 01:15:00,480
EFFECTIVELY TO THE SURFACE OF

2073
01:15:00,480 --> 01:15:02,280
THE CELL, AND THEN START

2074
01:15:02,280 --> 01:15:05,120
INTERFERING WITH THE HOST BY

2075
01:15:05,120 --> 01:15:07,080
DISRUPTING THE CILIATED

2076
01:15:07,080 --> 01:15:12,800
EPITHELIUM THROUGH TOXINS.

2077
01:15:12,800 --> 01:15:15,440
THEN WHEN WE SEE DISSEMINATION

2078
01:15:15,440 --> 01:15:19,560
OF DISEASE, IT'S THROUGH AN

2079
01:15:19,560 --> 01:15:20,680
EXTREME COUGH, IF YOU'VE EVER

2080
01:15:20,680 --> 01:15:23,640
SEE IT, IT'S VERY DISTRESSING,

2081
01:15:23,640 --> 01:15:26,920
WHICH   

2082
01:15:26,920 --> 01:15:28,320
PERTUSSIS TOXIN, WHICH CAN LEAD

2083
01:15:28,320 --> 01:15:29,320
TO DISSEMINATION TO THE NEXT

2084
01:15:29,320 --> 01:15:29,640
HOST.

2085
01:15:29,640 --> 01:15:31,280
EVEN WHEN SOMEONE HAS ELIMINATED

2086
01:15:31,280 --> 01:15:32,680
THE ORGANISM FROM THEIR SYSTEM,

2087
01:15:32,680 --> 01:15:34,240
THE DISEASE CONTINUES FOR A LONG

2088
01:15:34,240 --> 01:15:35,520
TIME, AND THAT'S DUE TO THE

2089
01:15:35,520 --> 01:15:39,680
TOXIN REMAINING IN CELLS AND

2090
01:15:39,680 --> 01:15:42,000
CAUSING THAT HORRIBLE PAROXYSMAL

2091
01:15:42,000 --> 01:15:42,320
COUGH.

2092
01:15:42,320 --> 01:15:44,520
SO YOU SEE THE BEAUTY OF THAT

2093
01:15:44,520 --> 01:15:46,480
CILIATED EPITHELIUM IS ABLE TO

2094
01:15:46,480 --> 01:15:49,000
REFLECT THOSE COMPLEX PROCESSES

2095
01:15:49,000 --> 01:15:54,920
LISTED ON THE LEFT-HAND SIDE.

2096
01:15:54,920 --> 01:15:57,840
BETWEEN THE 1960s AND 1980s,

2097
01:15:57,840 --> 01:16:01,240
THE WIDELY ACCEPTED BORDETELLA

2098
01:16:01,240 --> 01:16:02,440
PERTUSSIS WAS -- VACCINE WHICH

2099
01:16:02,440 --> 01:16:03,800
WAS INDEED VERY COMPLEX BECAUSE

2100
01:16:03,800 --> 01:16:07,600
IT WAS BASICALLY A FORMALDEHYDE

2101
01:16:07,600 --> 01:16:09,480
SOUP OF BORDETELLA PERTUSSIS.

2102
01:16:09,480 --> 01:16:14,920
IN THE 80s AND EARLY 90s,

2103
01:16:14,920 --> 01:16:17,280
THAT VACCINE WAS REPLACED BY ONE

2104
01:16:17,280 --> 01:16:19,640
THAT HAD A SINGLE, DOUBLE OR

2105
01:16:19,640 --> 01:16:20,520
TRIPLE ANTIGEN COMPONENTS, WHICH

2106
01:16:20,520 --> 01:16:21,960
IS ACTUALLY A VERY SIMPLE

2107
01:16:21,960 --> 01:16:22,680
VACCINE.

2108
01:16:22,680 --> 01:16:26,200
BUT DUE TO VACCINE ESCAPE IN THE

2109
01:16:26,200 --> 01:16:27,600
21ST CENTURY, WE'VE HAD TO

2110
01:16:27,600 --> 01:16:28,600
INCREASE THE NUMBER OF

2111
01:16:28,600 --> 01:16:29,920
COMPONENTS IN EACH VACCINE SO

2112
01:16:29,920 --> 01:16:32,760
THEY'RE MUCH MORE COMPLEX, LESS

2113
01:16:32,760 --> 01:16:33,080
SIMPLE.

2114
01:16:33,080 --> 01:16:34,720
BUT AS WE SPEAK, NOW IN

2115
01:16:34,720 --> 01:16:37,320
DEVELOPMENT, THERE IS NOW A LIVE

2116
01:16:37,320 --> 01:16:40,200
ATTENUATED B. PERTUSSIS VACCINE

2117
01:16:40,200 --> 01:16:41,760
ONGOING ASSESSMENT, AND OF

2118
01:16:41,760 --> 01:16:44,000
COURSE THIS VACCINE IS VERY

2119
01:16:44,000 --> 01:16:46,640
COMPLEX IN THE SAME WAY THAT WE

2120
01:16:46,640 --> 01:16:48,840
HAD IN THE 60s AND 80s, SO

2121
01:16:48,840 --> 01:16:50,480
WE'VE GONE FULL LOOP FROM A VERY

2122
01:16:50,480 --> 01:16:51,800
COMPLEX VACCINE, FROM A SIMPLE,

2123
01:16:51,800 --> 01:16:52,960
BACK TO A VERY COMPLEX.

2124
01:16:52,960 --> 01:16:54,920
BUT WHEN WE LOOK AT THE ANIMAL

2125
01:16:54,920 --> 01:16:57,000
MODELS AVAILABLE TO MIMIC

2126
01:16:57,000 --> 01:16:58,880
BORDETELLA PERTUSSIS, THERE'S

2127
01:16:58,880 --> 01:17:00,760
ONLY THE BOONS THAT ACTUALLY

2128
01:17:00,760 --> 01:17:03,400
COUGH WHEN THEY'RE INFECTED.

2129
01:17:03,400 --> 01:17:05,960
AND SO AT THE MOMENT WE'RE NOW

2130
01:17:05,960 --> 01:17:07,400
SEEING HUMAN CHALLENGE MODEL

2131
01:17:07,400 --> 01:17:09,920
BEING UTILIZED THE ASSESSMENT OF

2132
01:17:09,920 --> 01:17:13,000
A LIVE AT10 WAITED BORDETELLA

2133
01:17:13,000 --> 01:17:14,760
PERTUSSIS IN 2022, AND I REALLY

2134
01:17:14,760 --> 01:17:16,280
THINK THE HUMAN

2135
01:17:16,280 --> 01:17:16,920
MICROPHYSIOLOGICAL SYSTEMS COULD

2136
01:17:16,920 --> 01:17:18,360
HAVE ASSISTED IN THIS PROCESS IF

2137
01:17:18,360 --> 01:17:20,080
WE HAD THIS WONDERFUL TECHNOLOGY

2138
01:17:20,080 --> 01:17:24,560
WHEN I STARTED MY PH.D.

2139
01:17:24,560 --> 01:17:26,160
SORE LET'S TAKE ANOTHER EXAMPLE,

2140
01:17:26,160 --> 01:17:27,880
POX VIRUSES AND HOW TOPICAL IS

2141
01:17:27,880 --> 01:17:30,160
THAT?

2142
01:17:30,160 --> 01:17:33,120
ANTIVIRAL DRUGS FOR SMALLPOX

2143
01:17:33,120 --> 01:17:34,160
WERE DEVELOPED USING MONKEYPOX

2144
01:17:34,160 --> 01:17:36,960
AND THEY CAN BE USED AGAINST

2145
01:17:36,960 --> 01:17:37,280
MONKEYPOX.

2146
01:17:37,280 --> 01:17:40,360
AND WE TAKE TWO KRUTION     DRUE

2147
01:17:40,360 --> 01:17:42,760
BEEN APPROVED BY THE FDA, WE CAN

2148
01:17:42,760 --> 01:17:45,360
SEE THEY WERE APPROVED IN 2018

2149
01:17:45,360 --> 01:17:46,880
AND 2021 RESPECTIVELY.

2150
01:17:46,880 --> 01:17:48,720
NOW THE ISSUE WITH SMALLPOX IS

2151
01:17:48,720 --> 01:17:51,720
THAT IT'S A HUMAN-SPECIFIC VIRAL

2152
01:17:51,720 --> 01:17:54,120
PATHOGEN, SO IT WASN'T EASY TO

2153
01:17:54,120 --> 01:17:55,440
MODEL THAT IN ORDER TO DEVELOP

2154
01:17:55,440 --> 01:17:57,720
THESE DRUGS AND ACTUALLY THE

2155
01:17:57,720 --> 01:17:58,400
VACCINES.

2156
01:17:58,400 --> 01:18:00,920
SO MONKEYPOX WAS USED AS A

2157
01:18:00,920 --> 01:18:02,360
SURROGATE FOR SMALLPOX IN

2158
01:18:02,360 --> 01:18:04,840
NON-HUMAN PRIMATE, AND INDEED IN

2159
01:18:04,840 --> 01:18:06,480
U.K. AND MANY OTHER PLACE,

2160
01:18:06,480 --> 01:18:10,840
VACCINES WERE TESTED IN NHP

2161
01:18:10,840 --> 01:18:14,800
MODELS USING MONKEYPOX.

2162
01:18:14,800 --> 01:18:16,320
BUT ONE OF THE OTHER ISSUES WAS

2163
01:18:16,320 --> 01:18:20,680
THAT THE FAR KA COKINETICS OF

2164
01:18:20,680 --> 01:18:23,440
TEMBAXA IN NHPs WAS VERY

2165
01:18:23,440 --> 01:18:24,960
DIFFERENT FROM THAT IN HUMANS.

2166
01:18:24,960 --> 01:18:27,040
THAT WASN'T AN EXPECTED OUTCOME.

2167
01:18:27,040 --> 01:18:30,520
THAT LED TO -- FDA APPROVAL

2168
01:18:30,520 --> 01:18:31,640
GRANTING AND BECAUSE THEY HAD TO

2169
01:18:31,640 --> 01:18:32,920
FIND ANOTHER WAY OF ASSESSING

2170
01:18:32,920 --> 01:18:39,160
IT, AND IN FACT, VACCINIA CAN

2171
01:18:39,160 --> 01:18:41,160
ALSO BE USED AS A SURROGATE FOR

2172
01:18:41,160 --> 01:18:43,120
SMALLPOX IN HUMANS.

2173
01:18:43,120 --> 01:18:44,760
MAYBE THERE'S A LESSON TO BE

2174
01:18:44,760 --> 01:18:50,120
LEARNED THERE BECAUSE MAYBE 3D

2175
01:18:50,120 --> 01:18:51,840
MICROPHYSIOLOGICAL SYSTEMS COULD

2176
01:18:51,840 --> 01:18:53,840
HAVE BEEN USED IF WE HAD THOSE

2177
01:18:53,840 --> 01:18:55,160
TOOLS 15 YEARS AGO WHEN DRUG

2178
01:18:55,160 --> 01:18:57,120
DEVELOPMENT WAS ONGOING.

2179
01:18:57,120 --> 01:19:00,280
WHEN WE TALK ABOUT EBOLA, THERE

2180
01:19:00,280 --> 01:19:02,280
ARE MANY FILOVIRUSES APART FROM

2181
01:19:02,280 --> 01:19:04,440
EBOLA AND SOME OF THEM DON'T

2182
01:19:04,440 --> 01:19:06,320
INFECT NHPs, SO THIS

2183
01:19:06,320 --> 01:19:11,000
REPRESENTS A BLIND ALLEY FOR

2184
01:19:11,000 --> 01:19:16,200
THOSE PARTICULAR FILOVIRUS

2185
01:19:16,200 --> 01:19:16,480
FAMILY.

2186
01:19:16,480 --> 01:19:18,560
WE NOW KNOW EBOLA CAN SEQUESTER

2187
01:19:18,560 --> 01:19:20,520
IN EYE, BRAIN AND REPRODUCTIVE

2188
01:19:20,520 --> 01:19:21,040
TISSUES.

2189
01:19:21,040 --> 01:19:23,160
HOW CAN WE STUDY CLEARANCE FROM

2190
01:19:23,160 --> 01:19:24,800
THESE IMMUNE PRIVILEGE SITES

2191
01:19:24,800 --> 01:19:28,080
WITHOUT ACTUALLY GOING INTO

2192
01:19:28,080 --> 01:19:30,080
INDEMIC AREAS, EVEN IF YOU CAN

2193
01:19:30,080 --> 01:19:30,920
DO THAT?

2194
01:19:30,920 --> 01:19:32,480
IT'S EXTREMELY DIFFICULT TO TAKE

2195
01:19:32,480 --> 01:19:35,080
SAMPLES FROM THOSE IMMUNE

2196
01:19:35,080 --> 01:19:35,960
PRIVILEGED SITES.

2197
01:19:35,960 --> 01:19:38,480
AND HOW DO WE TEST COMBINATIONS

2198
01:19:38,480 --> 01:19:43,160
OF ANTIVIRALS OUTSIDE OF

2199
01:19:43,160 --> 01:19:43,600
OUTBREAKS?

2200
01:19:43,600 --> 01:19:45,760
ONCE AGAIN, HUMAN

2201
01:19:45,760 --> 01:19:46,560
MICROPHYSIOLOGICAL SYSTEMS COULD

2202
01:19:46,560 --> 01:19:49,320
ASSIST.

2203
01:19:49,320 --> 01:19:51,080
AND WHAT ABOUT HEPATITIS?

2204
01:19:51,080 --> 01:19:56,640
THIS IS ALSO A VERY TOUGH

2205
01:19:56,640 --> 01:19:58,840
TOPICAL TOPIC BECAUSE WE'RE

2206
01:19:58,840 --> 01:20:00,120
SEEING SEVERE CASES IN VERY

2207
01:20:00,120 --> 01:20:01,240
YOUNG CHILDREN.

2208
01:20:01,240 --> 01:20:02,960
IN THE U.K., THERE ARE MANY

2209
01:20:02,960 --> 01:20:04,280
THEORIES ABOUT WHY THIS IS

2210
01:20:04,280 --> 01:20:04,680
OCCURRING.

2211
01:20:04,680 --> 01:20:07,320
AT THE MOMENT, IT COULD BE DO TO

2212
01:20:07,320 --> 01:20:09,880
A NEW ADENOVIRUS OR COULD BE A

2213
01:20:09,880 --> 01:20:11,840
NEW VARIANT OF ADENOVIRUS OR IT

2214
01:20:11,840 --> 01:20:13,120
COULD BE SOMETHING TO DO WITH A

2215
01:20:13,120 --> 01:20:14,760
NEW VARIANT OF SARS-COV-2 OR

2216
01:20:14,760 --> 01:20:16,760
COULD BE RELATED TO CO-INFECTION

2217
01:20:16,760 --> 01:20:17,600
WITH SARS-COV-2.

2218
01:20:17,600 --> 01:20:22,000
AND THERE ARE MANY QUESTIONS

2219
01:20:22,000 --> 01:20:23,520
REMAINING ABOUT WHY THERE ARE SO

2220
01:20:23,520 --> 01:20:26,680
MANY GLOBAL CASES OF JUVENILE

2221
01:20:26,680 --> 01:20:27,800
HEPATITIS, AND IN SOME CASES

2222
01:20:27,800 --> 01:20:28,680
REQUIRING LIVER TRANSPLANT,

2223
01:20:28,680 --> 01:20:32,400
WHICH IS A LIFE-CHANGING IMPACT.

2224
01:20:32,400 --> 01:20:34,240
AND MAYBE HUMAN

2225
01:20:34,240 --> 01:20:36,080
MICROPHYSIOLOGICALS COULD HAVE

2226
01:20:36,080 --> 01:20:38,080
ASSISTED IN THIS INITIAL

2227
01:20:38,080 --> 01:20:38,960
OUTBREAK INVESTIGATION, BUT I

2228
01:20:38,960 --> 01:20:43,440
WOULD SAY THAT IT COULD

2229
01:20:43,440 --> 01:20:44,320
CONTINUE, MICROPHYSIOLOGICAL

2230
01:20:44,320 --> 01:20:45,160
SYSTEMS COULD ASSIST IN

2231
01:20:45,160 --> 01:20:46,080
ANSWERING SOME OF THESE

2232
01:20:46,080 --> 01:20:47,360
QUESTIONS WHICH ARE VERY TOPICAL

2233
01:20:47,360 --> 01:20:51,880
EVEN AS I SPEAK.

2234
01:20:51,880 --> 01:20:53,320
SO LET'S TALK ABOUT DISEASE X

2235
01:20:53,320 --> 01:20:55,360
BECAUSE THAT ONE IS QUITE A

2236
01:20:55,360 --> 01:20:56,120
TOPICAL SUBJECT.

2237
01:20:56,120 --> 01:20:58,200
DISEASE X IS THE UNKNOWN AGENT

2238
01:20:58,200 --> 01:21:00,720
WHICH WE CAN PREDICT MIGHT BE

2239
01:21:00,720 --> 01:21:03,880
THE CASE AND I KNOW SOME OF THE

2240
01:21:03,880 --> 01:21:05,000
INTRODUCTORY SPEAKERS HAVE

2241
01:21:05,000 --> 01:21:06,080
SPOKEN ABOUT DISEASE X.

2242
01:21:06,080 --> 01:21:08,160
BUT LET'S TAKE SCENARIO H WITHIN

2243
01:21:08,160 --> 01:21:09,360
THE DISEASE X SCENARIO.

2244
01:21:09,360 --> 01:21:11,160
LET'S SAY THAT THE SCENARIO H IS

2245
01:21:11,160 --> 01:21:14,080
A VIRUS WHICH ONLY AFFECTS HUMAN

2246
01:21:14,080 --> 01:21:18,640
LIVER.

2247
01:21:18,640 --> 01:21:20,520
AND FOR EXAMPLE THAT'S FATAL.

2248
01:21:20,520 --> 01:21:23,080
NO ANIMAL MODEL IS POSSIBLE

2249
01:21:23,080 --> 01:21:24,800
WITHOUT GENETIC TRANSFORMATION

2250
01:21:24,800 --> 01:21:26,640
AND WITHOUT A 100-DAY CHALLENGE,

2251
01:21:26,640 --> 01:21:27,960
WE'RE NOT GOING TO BE ABLE TO DO

2252
01:21:27,960 --> 01:21:28,720
THAT FAST ENOUGH.

2253
01:21:28,720 --> 01:21:33,000
A HUMAN INFECTION WITH DISEASE X

2254
01:21:33,000 --> 01:21:34,280
SCENARIO H WOULD NOT BE

2255
01:21:34,280 --> 01:21:35,840
ETHICALLY JUSTIFIED SO WE'RE

2256
01:21:35,840 --> 01:21:37,640
HEAVILY RELIANT ON GENETICS IN

2257
01:21:37,640 --> 01:21:41,640
THE INITIAL STAGES OF A

2258
01:21:41,640 --> 01:21:42,400
CHALLENGE.

2259
01:21:42,400 --> 01:21:44,360
HOW COULD WE TEST DRUGS,

2260
01:21:44,360 --> 01:21:45,320
THERAPEUTICS AND VACCINES FOR

2261
01:21:45,320 --> 01:21:47,000
SUCH A DISEASE H SCENARIO H?

2262
01:21:47,000 --> 01:21:49,080
HERE, I THINK MICROPHYSIOLOGICAL

2263
01:21:49,080 --> 01:21:49,920
SYSTEMS COULD COME INTO THEIR

2264
01:21:49,920 --> 01:21:52,000
OWN AND ASSIST QUITE

2265
01:21:52,000 --> 01:21:52,400
DRAMATICALLY.

2266
01:21:52,400 --> 01:21:54,320
AND I THINK WE NEED TO GET THEM

2267
01:21:54,320 --> 01:21:55,640
READY FOR THAT SCENARIO, BECAUSE

2268
01:21:55,640 --> 01:21:56,720
IT'S THE WORST CASE.

2269
01:21:56,720 --> 01:21:59,360
IF WE'RE READY FOR THE WORST

2270
01:21:59,360 --> 01:22:02,520
CASE, WE'RE READY FOR ANYTHING.

2271
01:22:02,520 --> 01:22:06,200
SO NOW LET ME TALK ABOUT VERO

2272
01:22:06,200 --> 01:22:08,000
CELLS, AS MANY OF YOU WILL KNOW

2273
01:22:08,000 --> 01:22:10,960
THEY'RE THE VIROLOGIST'S

2274
01:22:10,960 --> 01:22:11,720
FAVORITE BECAUSE THEY'RE

2275
01:22:11,720 --> 01:22:13,360
AVAILABLE GLOBALLY, THEY GROW

2276
01:22:13,360 --> 01:22:16,640
MANY VIRUSES VERY EASILY,

2277
01:22:16,640 --> 01:22:19,040
INCLUDING SARS-COV-2 AND THEY'RE

2278
01:22:19,040 --> 01:22:25,480
WIDELY USED FOR VIRAL

2279
01:22:25,480 --> 01:22:25,800
PROPAGATION.

2280
01:22:25,800 --> 01:22:27,120
THEY DO HAVE AS MENTIONED

2281
01:22:27,120 --> 01:22:28,960
EARLIER A DELUSION IN CHROMOSOME

2282
01:22:28,960 --> 01:22:30,160
12, WHICH RESULTS IN THE LOSS OF

2283
01:22:30,160 --> 01:22:32,360
ABILITY TO PRODUCE TYPE

2284
01:22:32,360 --> 01:22:34,560
1 INTERFERON.

2285
01:22:34,560 --> 01:22:35,880
THERE'S ALSO A LOSS OF SOME

2286
01:22:35,880 --> 01:22:37,080
ELEMENTS OF REGULATION AND

2287
01:22:37,080 --> 01:22:38,600
THAT'S WHY THEY GROW SO WELL,

2288
01:22:38,600 --> 01:22:40,240
AND THAT'S REPRESENTED IN OTHER

2289
01:22:40,240 --> 01:22:41,800
DELETIONS IN THE CHROMOSOME

2290
01:22:41,800 --> 01:22:48,680
WHICH YOU'LL READ ABOUT IN 2014.

2291
01:22:48,680 --> 01:22:50,200
THAT'S NOT ONLY FROM KIDNEY

2292
01:22:50,200 --> 01:22:53,480
ORIGIN BUT ALSO FROM A GREY

2293
01:22:53,480 --> 01:22:56,120
MONKEY.

2294
01:22:56,120 --> 01:22:58,960
AND I CAN'T HELP MENTIONING MY

2295
01:22:58,960 --> 01:23:00,720
OWN ARTICLE WHICH I PUBLISHED

2296
01:23:00,720 --> 01:23:02,360
WITH THE ASSISTANCE OF MANY

2297
01:23:02,360 --> 01:23:05,760
PEOPLE WHO MAY ALSO BE ON THE

2298
01:23:05,760 --> 01:23:07,600
LINE TODAY, WHICH WAS A

2299
01:23:07,600 --> 01:23:09,240
CAUTIONARY PERSPECTIVE ABOUT

2300
01:23:09,240 --> 01:23:11,760
ISOLATION OF SARS-COV-2 2 AND

2301
01:23:11,760 --> 01:23:13,720
THE URGE FOR PEOPLE TO CHECK

2302
01:23:13,720 --> 01:23:17,040
ANYTHING THEY GROW IN VERO CELLS

2303
01:23:17,040 --> 01:23:19,280
BECAUSE WE CAN SEE GENETIC

2304
01:23:19,280 --> 01:23:20,400
DIVERGENCE WITHIN THESE CELLS

2305
01:23:20,400 --> 01:23:24,160
THAT DON'T HAVE INTERFERON

2306
01:23:24,160 --> 01:23:28,200
PRODUCTION.

2307
01:23:28,200 --> 01:23:30,720
IF YOU DO USE A STOCK WHICH IS

2308
01:23:30,720 --> 01:23:34,400
COMPROMISED, IT WILL RESULT IN

2309
01:23:34,400 --> 01:23:37,800
REDUCED PATHOGENICITY IN AN

2310
01:23:37,800 --> 01:23:43,800
ANIMAL MODEL, LOSS OF INTERFERON

2311
01:23:43,800 --> 01:23:44,360
CLEAVAGE SITE.

2312
01:23:44,360 --> 01:23:45,360
THESE ARE TABLE FROM THE PAPER

2313
01:23:45,360 --> 01:23:47,080
WHICH YOU CAN LOOK AT LATER.

2314
01:23:47,080 --> 01:23:49,200
IT'S NOT JUST ABOUT THE SPIKE.

2315
01:23:49,200 --> 01:23:50,480
THERE ARE OTHER CHANGES THAT

2316
01:23:50,480 --> 01:23:56,320
OCCUR IN SOME CULTURES.

2317
01:23:56,320 --> 01:24:05,520
IN THIS PARTICULAR, WE SAW IT I 

2318
01:24:05,520 --> 01:24:07,360
IN -- WE STILL DON'T REALLY KNOW

2319
01:24:07,360 --> 01:24:13,280
ABOUT.

2320
01:24:13,280 --> 01:24:15,040
ALSO WANT TO MENTION A PAPER

2321
01:24:15,040 --> 01:24:17,440
WHICH WE PRODUCED ABOUT

2322
01:24:17,440 --> 01:24:21,920
HYDROXYCHLOROQUINE WHICH IS

2323
01:24:21,920 --> 01:24:24,320
REALLY -- THAT IS THAT VERO CELL

2324
01:24:24,320 --> 01:24:26,040
DATA WE HAD ON HAND AT THE

2325
01:24:26,040 --> 01:24:27,400
BEGINNING OF THE OUTBREAK SEEMED

2326
01:24:27,400 --> 01:24:31,080
TO SUGGEST THAT

2327
01:24:31,080 --> 01:24:34,680
HYDROXYCHLOROQUINE HAD ANTIVIRAL

2328
01:24:34,680 --> 01:24:35,720
AND SYMPTOMATIC IMPACT IN THE

2329
01:24:35,720 --> 01:24:37,800
VERO CELL MODEL OF INFECTION.

2330
01:24:37,800 --> 01:24:39,960
BUT AS A RESULT OF COLLABORATION

2331
01:24:39,960 --> 01:24:45,360
WITH THE WHO, WHEN WE ASKED

2332
01:24:45,360 --> 01:24:46,760
DIFFERENT AUTHORITIES IF THEY

2333
01:24:46,760 --> 01:24:48,040
HAD HYDROXYCHLOROQUINE DATA,

2334
01:24:48,040 --> 01:24:49,280
EACH LABORATORY HAD A LITTLE BIT

2335
01:24:49,280 --> 01:24:50,600
OF INFORMATION AND WHEN YOU

2336
01:24:50,600 --> 01:24:51,800
PIECED IT TOGETHER, EACH PIECE

2337
01:24:51,800 --> 01:24:53,840
OF THE JIGSAW SEEMED TO SUGGEST

2338
01:24:53,840 --> 01:24:55,720
THERE WAS NO ANTIVIRAL

2339
01:24:55,720 --> 01:24:57,800
SYMPTOMATIC RELIEF IN ANY ANIMAL

2340
01:24:57,800 --> 01:24:58,880
MODEL AVAILABLE AT THE TIME.

2341
01:24:58,880 --> 01:25:01,400
BUT THE MOST INTERESTING THING

2342
01:25:01,400 --> 01:25:04,680
FOR THIS AUDIENCE TODAY IS THAT

2343
01:25:04,680 --> 01:25:06,000
TWO INDEPENDENT LABORATORIES

2344
01:25:06,000 --> 01:25:07,440
USING MICROPHYSIOLOGICAL SYSTEMS

2345
01:25:07,440 --> 01:25:10,040
ALSO SUPPORTED THE IN VIVO

2346
01:25:10,040 --> 01:25:13,000
OUTCOMES, WHICH IS THAT

2347
01:25:13,000 --> 01:25:14,320
HYDROXYCHLOROQUINE HAD NO

2348
01:25:14,320 --> 01:25:17,360
ANTIVIRAL OR SYMPTOMATIC IMPACT.

2349
01:25:17,360 --> 01:25:21,600
AND THIS PAPER POSSIBLY ASSISTED

2350
01:25:21,600 --> 01:25:24,160
IN THE LACK OF UTILIZATION OF

2351
01:25:24,160 --> 01:25:24,920
HYDROXYCHLOROQUINE FROM THAT

2352
01:25:24,920 --> 01:25:28,320
POINT ON WARDS.

2353
01:25:28,320 --> 01:25:29,640
SO MICROPHYSIOLOGICAL SYSTEMS OF

2354
01:25:29,640 --> 01:25:32,360
COURSE HAVE ALREADY PROVEN THEIR

2355
01:25:32,360 --> 01:25:35,240
WORTH, NOT ONLY FOR HYDROXYCOLOR

2356
01:25:35,240 --> 01:25:37,600
QUICK BUT ALSO FOR IMATINIB,

2357
01:25:37,600 --> 01:25:39,600
WHICH HAS A VERY SIMILAR STORY.

2358
01:25:39,600 --> 01:25:41,000
I KNOW WE'RE TALKING ABOUT

2359
01:25:41,000 --> 01:25:44,200
ANTIVIRALS, BUT LET ME TALK

2360
01:25:44,200 --> 01:25:48,560
ABOUT HUME RORL    ORAL IMMUNITE

2361
01:25:48,560 --> 01:25:53,840
CONTEXT OF SARS-COV-2.

2362
01:25:53,840 --> 01:25:57,120
THAT CARTOON OF VIRUS ENTRY AND

2363
01:25:57,120 --> 01:25:58,000
DISSEMINATION ILLUSTRATES SOME

2364
01:25:58,000 --> 01:26:01,840
OF THE KIT CAL PARTS OF VIRUS

2365
01:26:01,840 --> 01:26:02,440
REPLICATION.

2366
01:26:02,440 --> 01:26:03,920
WHEN WE TALK ABOUT HUMAN

2367
01:26:03,920 --> 01:26:05,200
ANTIBODIES, WE OFTEN TALK ABOUT

2368
01:26:05,200 --> 01:26:07,440
THE FIRST TWO OF FIVE

2369
01:26:07,440 --> 01:26:08,520
CONSEQUENCES OF ANTIBODY

2370
01:26:08,520 --> 01:26:12,000
BINDING, WHICH IS INHIBITION OF

2371
01:26:12,000 --> 01:26:13,520
BINDING OF THE VIRUS TO THE

2372
01:26:13,520 --> 01:26:14,840
SURFACE OF THE HOST CELL BUT

2373
01:26:14,840 --> 01:26:20,120
ALSO INHIBITION OF FUSION OF THE

2374
01:26:20,120 --> 01:26:22,680
VIRUS WHICH SUGGESTS UP TAKE

2375
01:26:22,680 --> 01:26:24,200
INTO THE CELL.

2376
01:26:24,200 --> 01:26:28,760
AND THOSE TWO STEPS ARE VERY

2377
01:26:28,760 --> 01:26:30,560
WELL REPRESENTED IN A

2378
01:26:30,560 --> 01:26:32,400
NEUTRALIZATION ASSAY, AND WE'VE

2379
01:26:32,400 --> 01:26:34,680
BEEN PRODUCING MICRO

2380
01:26:34,680 --> 01:26:35,440
NEUTRALIZATION ASSAY AGAINST ALL

2381
01:26:35,440 --> 01:26:37,320
THE VARIANTS OF CONSENT SINCE

2382
01:26:37,320 --> 01:26:39,040
VERY EARLY ON IN THE OUTBREAK.

2383
01:26:39,040 --> 01:26:40,720
AND AS WE CAN SEE OVER TIME,

2384
01:26:40,720 --> 01:26:44,760
WHEN WE LOOK AT THE VARIANTS OF

2385
01:26:44,760 --> 01:26:46,400
CONCERN COMPARED TO VICTORIA,

2386
01:26:46,400 --> 01:26:49,560
OMICRON WAS PREDICTED TO HAVE

2387
01:26:49,560 --> 01:26:52,520
VERY LITTLE NEUTRALIZATION

2388
01:26:52,520 --> 01:26:56,920
CAPABILITY IN TERMS OF HUMORAL

2389
01:26:56,920 --> 01:26:57,240
IMMUNITY.

2390
01:26:57,240 --> 01:26:58,440
AS THE OTHER SPEAKERS HAVE

2391
01:26:58,440 --> 01:26:59,400
MENTIONED, IT WASN'T JUST ABOUT

2392
01:26:59,400 --> 01:27:03,920
APT BO DIES.    

2393
01:27:03,920 --> 01:27:04,360
ANTIS.

2394
01:27:04,360 --> 01:27:06,960
WHEN WE ACTUALLY USED OMICRON TO

2395
01:27:06,960 --> 01:27:09,240
INFECT HAMSTERS, IT PRODUCED A

2396
01:27:09,240 --> 01:27:10,600
VERY MILD FORM WHICH YOU CAN SEE

2397
01:27:10,600 --> 01:27:12,640
ON THE LEFT.

2398
01:27:12,640 --> 01:27:16,360
WE SAW SOME -- SIGNS AND WE DID

2399
01:27:16,360 --> 01:27:19,680
SEE A LEVELING OUT RATHER THAN

2400
01:27:19,680 --> 01:27:20,520
REDUCTION IN WEIGHT.

2401
01:27:20,520 --> 01:27:21,920
BUT WHEN WE TOOK HAMSTERS THAT

2402
01:27:21,920 --> 01:27:25,760
HAD ACTUALLY RECOVERED FROM

2403
01:27:25,760 --> 01:27:26,760
VICTORIA, THE SEROLOGY WOULD

2404
01:27:26,760 --> 01:27:30,160
HAVE PREDICTED THAT THAT HUMORAL

2405
01:27:30,160 --> 01:27:32,240
RESPONSE WOULD NOT HAVE -- OUT,

2406
01:27:32,240 --> 01:27:33,960
BUT IN FACT CONVALESCENT

2407
01:27:33,960 --> 01:27:35,600
HAMSTERS WERE ACTUALLY VERY WELL

2408
01:27:35,600 --> 01:27:39,000
PROTECTED AGAINST OMICRON.

2409
01:27:39,000 --> 01:27:41,760
SO WHY WOULD CONVALESCENT

2410
01:27:41,760 --> 01:27:43,840
HAMSTERS BE CROSS-PROTECTED WHEN

2411
01:27:43,840 --> 01:27:45,240
THE NEUTRALIZATION ASSAYS

2412
01:27:45,240 --> 01:27:46,240
PREDICTED THAT THEY WOULDN'T BE?

2413
01:27:46,240 --> 01:27:48,840
AND IT COULD BE THAT THE HAMSTER

2414
01:27:48,840 --> 01:27:49,840
ANTIBODIES WERE MUCH STRONGER

2415
01:27:49,840 --> 01:27:51,360
AND MORE LASTING THAN IN HUMANS,

2416
01:27:51,360 --> 01:27:54,200
BUT IT'S MORE LIKELY THAT THE

2417
01:27:54,200 --> 01:27:55,400
HUMAN -- THE HAMSTER INFECTION

2418
01:27:55,400 --> 01:27:56,760
MODEL INCLUDES T-CELL IMMUNITY

2419
01:27:56,760 --> 01:27:59,320
AND THE CD4 AND CD8 CELL

2420
01:27:59,320 --> 01:28:01,200
COMPONENTS OF THE IMMUNE

2421
01:28:01,200 --> 01:28:03,080
RESPONSE WAS RESPONSIBLE IN PART

2422
01:28:03,080 --> 01:28:04,560
FOR THAT CROSS-PROTECTION.

2423
01:28:04,560 --> 01:28:07,760
IN ADDITION, THE HAMSTER MODEL

2424
01:28:07,760 --> 01:28:10,720
INCLUDES ANTIBODIES, INDUCING A

2425
01:28:10,720 --> 01:28:11,600
COMPLEMENT CASCADE, WHICH MAY

2426
01:28:11,600 --> 01:28:14,000
NOT BE ACCURATELY REFLECTED IN A

2427
01:28:14,000 --> 01:28:15,760
MICRO NEUTRALIZATION ASSAY.

2428
01:28:15,760 --> 01:28:17,960
AND ANOTHER ALTERNATIVE

2429
01:28:17,960 --> 01:28:19,680
CONTRIBUTOR COULD BE THAT THE

2430
01:28:19,680 --> 01:28:21,320
HAMSTER INCLUDES ANTIBODY

2431
01:28:21,320 --> 01:28:23,080
TARGETED CELLULAR COMPONENTS.

2432
01:28:23,080 --> 01:28:27,120
BY THAT, I MEAN ANTIBODIES

2433
01:28:27,120 --> 01:28:28,920
BRIDGING FC RECEPTORS TO

2434
01:28:28,920 --> 01:28:31,080
DENDRITIC AND MACROPHAGE CELLS,

2435
01:28:31,080 --> 01:28:33,280
AND ALSO CYTOTOXIC KILLER CELLS

2436
01:28:33,280 --> 01:28:36,880
BEING FLAGGED, SUCH AS NATURAL

2437
01:28:36,880 --> 01:28:38,520
KILLER CELLS TO THE SURFACE OF

2438
01:28:38,520 --> 01:28:41,600
INFECTED CELLS.

2439
01:28:41,600 --> 01:28:44,400
SO WHEN WE TALK ABOUT MODELS OF

2440
01:28:44,400 --> 01:28:46,280
THE INTERACTION BETWEEN HOST AND

2441
01:28:46,280 --> 01:28:47,760
PATHOGEN IN AN IMMUNE CONTEXT,

2442
01:28:47,760 --> 01:28:49,240
WE SHOULD BE THINKING ABOUT HOW

2443
01:28:49,240 --> 01:28:51,200
WE CAN INCLUDE CELLULAR IMMUNITY

2444
01:28:51,200 --> 01:28:53,840
INTO THESE MODELS, AND YOU CAN

2445
01:28:53,840 --> 01:28:55,160
SEE HERE, CELLULAR IMMUNITY HAS

2446
01:28:55,160 --> 01:28:57,080
QUITE A DIVERSE ARRAY OF

2447
01:28:57,080 --> 01:29:01,040
CHARACTERS AS ILLUSTRATED IN

2448
01:29:01,040 --> 01:29:07,280
THIS FROM THE BBC WEBSITE.

2449
01:29:07,280 --> 01:29:09,360
SO THE THREE OTHER ELEMENTS OF

2450
01:29:09,360 --> 01:29:10,560
ANTIBODY BINDING CONSEQUENCES

2451
01:29:10,560 --> 01:29:14,160
ARE THAT AN ANTIBODY CAN

2452
01:29:14,160 --> 01:29:17,560
ACTUALLY PRODUCE A COMPLEMENT

2453
01:29:17,560 --> 01:29:21,400
CASCADE OR VIRAL OPSONO

2454
01:29:21,400 --> 01:29:22,480
PHAGOCYTOSIS BY FLAGGING --

2455
01:29:22,480 --> 01:29:23,200
EXCUSE ME

2456
01:29:23,200 --> 01:29:25,240
[KNOWN   

2457
01:29:25,240 --> 01:29:27,840
[PHONE RINGING]

2458
01:29:27,840 --> 01:29:33,200
 -- BY FLAGGING VIRAL OPSONO

2459
01:29:33,200 --> 01:29:35,080
PHAGOCYTOSIS AND ALSO BY

2460
01:29:35,080 --> 01:29:36,960
FLAGGING CELLULAR ELEMENTS OF

2461
01:29:36,960 --> 01:29:38,120
THE IMMUNE SYSTEM SUCH AS

2462
01:29:38,120 --> 01:29:40,720
NATURAL KILLER CELLS,

2463
01:29:40,720 --> 01:29:44,560
MACROPHAGES OR LOCAL DENDRITIC

2464
01:29:44,560 --> 01:29:49,720
CELLS BY THE SE COMPONENTS.

2465
01:29:49,720 --> 01:29:51,680
BUT IN THAT DATA THAT I'VE JUST

2466
01:29:51,680 --> 01:29:54,200
SHOWN, LET'S NOT FORGET ZETA.

2467
01:29:54,200 --> 01:29:56,480
I KNOW IT'S GONE, BUT IT DOESN'T

2468
01:29:56,480 --> 01:29:57,760
APPEAR TO BE DETECTED ANYWHERE,

2469
01:29:57,760 --> 01:30:00,440
BUT THE STORY ABOUT ZETA IS VERY

2470
01:30:00,440 --> 01:30:01,960
INTERESTING BECAUSE UNLIKE

2471
01:30:01,960 --> 01:30:05,040
OMICRON, IT ONLY HAD ONE CHANGE

2472
01:30:05,040 --> 01:30:06,560
IN THE SPIKE AND OMICRON HAD

2473
01:30:06,560 --> 01:30:09,080
MANY CHANGES IN ITS SPIKE.

2474
01:30:09,080 --> 01:30:14,000
BUT ZETA HAD A CHANGE IN OH --

2475
01:30:14,000 --> 01:30:15,200
MAYBE THERE'S CHANGES IN OTHER

2476
01:30:15,200 --> 01:30:16,760
ASPECTS OF THE VIRUS WERE

2477
01:30:16,760 --> 01:30:19,680
RESPONSIBLE FOR THE ESCAPE IN

2478
01:30:19,680 --> 01:30:21,000
THE MICRO NEUTRALIZATION ASSAY.

2479
01:30:21,000 --> 01:30:21,880
MAYBE WE NEED TO INVESTIGATE

2480
01:30:21,880 --> 01:30:23,840
THIS IN A MICROPHYSIOLOGICAL

2481
01:30:23,840 --> 01:30:24,600
SYSTEM TO UNDERSTAND WHAT WAS

2482
01:30:24,600 --> 01:30:32,280
HAPPENING THERE.

2483
01:30:32,280 --> 01:30:37,440
WHEN WE LOOK AT A PSEUDOVIRUS

2484
01:30:37,440 --> 01:30:38,920
ASSAY, WE DON'T SEE THAT TYPE OF

2485
01:30:38,920 --> 01:30:40,040
REDUCTION IN SIGNAL AND THAT MAY

2486
01:30:40,040 --> 01:30:42,920
BE BECAUSE THE

2487
01:30:42,920 --> 01:30:44,520
PSEUDONEUTRALIZATION ASSAYS ARE

2488
01:30:44,520 --> 01:30:45,840
ONLY FOCUSED ON THE SPIKE

2489
01:30:45,840 --> 01:30:49,760
PROTEIN.

2490
01:30:49,760 --> 01:30:52,280
WHEN WE TALK ABOUT RESEARCH AND

2491
01:30:52,280 --> 01:30:53,960
DEVELOPMENT, IN THE CONTEXT OF

2492
01:30:53,960 --> 01:30:57,000
SCIENTIFIC SERVICES, I'M

2493
01:30:57,000 --> 01:30:58,520
STARTING TO USE THIS DIAGRAM TO

2494
01:30:58,520 --> 01:30:59,480
EXPLAIN TO PEOPLE THE DIFFERENCE

2495
01:30:59,480 --> 01:31:03,320
BETWEEN RESEARCH AND DEVELOPMENT

2496
01:31:03,320 --> 01:31:04,120
IN THIS CONTEXT.

2497
01:31:04,120 --> 01:31:05,520
I KNOW IN TERMS OF RESEARCH, WE

2498
01:31:05,520 --> 01:31:08,040
TEND TO HAVE HYPOTHESIS TESTING

2499
01:31:08,040 --> 01:31:10,480
WHERE WE MOVE FROM AN UNKNOWN

2500
01:31:10,480 --> 01:31:11,320
SITUATION TO A KNOWN SITUATION

2501
01:31:11,320 --> 01:31:14,400
BY USING A SCIENTIFIC SERVICE TO

2502
01:31:14,400 --> 01:31:15,280
ANSWER A SPECIFIC QUESTION.

2503
01:31:15,280 --> 01:31:16,480
THE KNOWLEDGE THAT WE GAIN FROM

2504
01:31:16,480 --> 01:31:18,880
THAT GIVES US APPLIED KNOWLEDGE,

2505
01:31:18,880 --> 01:31:21,800
AND THAT IN ITSELF IS A SIGN OF

2506
01:31:21,800 --> 01:31:23,160
SCIENTIFIC SERVICE.

2507
01:31:23,160 --> 01:31:25,320
BUT MAKING SURE THAT OUR

2508
01:31:25,320 --> 01:31:28,800
SCIENTIFIC SERVICES REMAIN ON

2509
01:31:28,800 --> 01:31:29,720
TARGET IS AN IMPORTANT COMPONENT

2510
01:31:29,720 --> 01:31:32,000
OF A SCIENTIFIC SERVICE, AND A

2511
01:31:32,000 --> 01:31:33,400
QUALITY MANAGEMENT SYSTEM WILL

2512
01:31:33,400 --> 01:31:35,400
DETECT WHETHER OUR SCIENTIFIC

2513
01:31:35,400 --> 01:31:38,640
SERVICES ARE OFF TARGET OR NOT.

2514
01:31:38,640 --> 01:31:40,840
AND IF THEY ARE, WE THEN NEED TO

2515
01:31:40,840 --> 01:31:43,360
APPLY DEVELOPMENT TO RE-TARGET

2516
01:31:43,360 --> 01:31:47,280
OUR SCIENTIFIC SERVICES IN ORDER

2517
01:31:47,280 --> 01:31:48,880
TO IMPROVE OUR SERVICE TO ENSURE

2518
01:31:48,880 --> 01:31:50,200
WE SEE THE WHOLE PICTURE, NOT

2519
01:31:50,200 --> 01:31:51,120
THE TIP OF THE ICEBERG.

2520
01:31:51,120 --> 01:31:52,560
THIS IS EXACTLY WHAT HAPPENED

2521
01:31:52,560 --> 01:31:55,080
WITH SARS-COV-2 DURING OWRL

2522
01:31:55,080 --> 01:31:56,720
RESPONSE TO THE PANDEMIC,

2523
01:31:56,720 --> 01:31:59,560
BECAUSE OF THE EMERGENCE OF

2524
01:31:59,560 --> 01:32:00,320
VARIANTS OF CONCERN.

2525
01:32:00,320 --> 01:32:02,520
WHEN WE TALK ABOUT AN ANIMAL

2526
01:32:02,520 --> 01:32:03,720
MODEL WE HAD AVAILABLE, THESE

2527
01:32:03,720 --> 01:32:10,480
WERE VERY WELL ILLUSTRATED IN

2528
01:32:10,480 --> 01:32:12,360
MANY COLLABORATORS, WE SAW THERE

2529
01:32:12,360 --> 01:32:13,720
WAS FOR EACH VARIANT OF CONCERN,

2530
01:32:13,720 --> 01:32:16,080
THERE WAS A SLIGHTLY DIFFERENT

2531
01:32:16,080 --> 01:32:19,480
PROFILE OF INFECTIVITY BETWEEN

2532
01:32:19,480 --> 01:32:21,440
HAMSTERS, PRIMATES, FERRETS AND

2533
01:32:21,440 --> 01:32:28,040
SMALL ANIMALS.

2534
01:32:28,040 --> 01:32:31,360
BUT THIS HOST RANGE VAIR    VARS

2535
01:32:31,360 --> 01:32:32,480
SOMETHING WE JUST CAN'T DEAL

2536
01:32:32,480 --> 01:32:34,760
WITH IN TERMS OF ANIMAL MODELS.

2537
01:32:34,760 --> 01:32:37,080
SO ASSAYS NEED TO BE FUTURE

2538
01:32:37,080 --> 01:32:38,800
PROOFED, AND IF SARS-COV-2 IS

2539
01:32:38,800 --> 01:32:40,680
EVOLVING INTO HUMAN-ONLY FORM,

2540
01:32:40,680 --> 01:32:42,440
MAYBE THESE ANIMAL MODELS WILL

2541
01:32:42,440 --> 01:32:46,360
EFFICIENTLY BECOME REDUNDANT.

2542
01:32:46,360 --> 01:32:48,040
UNLESS WE USE RECOMBINANT

2543
01:32:48,040 --> 01:32:48,480
ANIMALS.

2544
01:32:48,480 --> 01:32:50,080
BUT THIS IS NOT THE LONG TERM

2545
01:32:50,080 --> 01:32:51,920
ANSWER, AND I THINK THE

2546
01:32:51,920 --> 01:32:52,840
MICROPHYSIOLOGICAL SYSTEMS MAY

2547
01:32:52,840 --> 01:32:57,320
OFFER A FUTURE PATHWAY TO NOT

2548
01:32:57,320 --> 01:32:58,920
ONLY VARIANTS OF CONCERN BUT

2549
01:32:58,920 --> 01:33:02,880
OTHER HUMAN SPECIFIC PATHOGENS.

2550
01:33:02,880 --> 01:33:08,680
AS WE CAN SEE IN THIS PICTURE

2551
01:33:08,680 --> 01:33:16,560
FROM LONGLONG.

2552
01:33:16,560 --> 01:33:17,640
SO IN THE LAST FEW MINUTES, I

2553
01:33:17,640 --> 01:33:19,080
JUST WANTED TO TALK ABOUT SUPPLY

2554
01:33:19,080 --> 01:33:19,640
AND DEMAND.

2555
01:33:19,640 --> 01:33:23,040
WE DO NEED A PLAN.

2556
01:33:23,040 --> 01:33:25,000
FOR SMALL ANIMAL STUDIES, THAT'S

2557
01:33:25,000 --> 01:33:27,280
FINE, BUT TRANSGENICS TOOK A LOT

2558
01:33:27,280 --> 01:33:28,680
OF MONEY AND THEY TOOK TIME TO

2559
01:33:28,680 --> 01:33:29,720
DEVELOP, AND ACTUALLY WHEN WE

2560
01:33:29,720 --> 01:33:31,960
DID HAVE SOME OF THEM, THEY WERE

2561
01:33:31,960 --> 01:33:33,160
EXTREMELY SEVERE FORM OF

2562
01:33:33,160 --> 01:33:34,520
INFECTION WHICH DIDN'T REPRESENT

2563
01:33:34,520 --> 01:33:37,760
A NORMAL FORM OF INFECTION.

2564
01:33:37,760 --> 01:33:39,520
FOR NON-HUMAN PRIMATE, IT'S NOT

2565
01:33:39,520 --> 01:33:44,360
OKAY TO LOOK AT EACH VARIANT

2566
01:33:44,360 --> 01:33:45,760
CONCERN FOR EFFECTORS OF

2567
01:33:45,760 --> 01:33:47,080
VACCINES AND DRUGS BECAUSE

2568
01:33:47,080 --> 01:33:48,160
THERE'S SIMPLY NOT ENOUGH

2569
01:33:48,160 --> 01:33:49,240
ANIMALS AND WE CAN'T COPE WITH

2570
01:33:49,240 --> 01:33:50,440
ALL THE VARIANTS OF CONCERN,

2571
01:33:50,440 --> 01:33:52,120
EVEN IF WE WANTED TO, AND IT MAY

2572
01:33:52,120 --> 01:33:54,640
BE THAT IT WILL DRIFT AWAY FROM

2573
01:33:54,640 --> 01:33:58,560
HAVING SPECIFICITY TO NHPs.

2574
01:33:58,560 --> 01:34:00,520
SO IN MICROPHYSIOLOGICAL SYSTEM,

2575
01:34:00,520 --> 01:34:01,840
THEY CAN BE USED FOR CELL LINES

2576
01:34:01,840 --> 01:34:02,960
BUT THEY'RE NOT REPRESENTATIVE

2577
01:34:02,960 --> 01:34:05,560
OF COMPLEX TISSUES BUT COULD USE

2578
01:34:05,560 --> 01:34:07,120
HUMAN PRIMARY TISSUE BUT THERE'S

2579
01:34:07,120 --> 01:34:08,200
VARIANCE IN ETHICAL CONCERNS AND

2580
01:34:08,200 --> 01:34:09,600
WE NEED TO HAVE SOMETHING THAT'S

2581
01:34:09,600 --> 01:34:11,160
RELIABLE AND REPRODUCIBLE OVER

2582
01:34:11,160 --> 01:34:13,000
TIME.

2583
01:34:13,000 --> 01:34:15,840
SO MAYBE POTENTIAL PLEUR OWE

2584
01:34:15,840 --> 01:34:17,400
POTENT STEM CELLS IN THE FUTURE

2585
01:34:17,400 --> 01:34:19,080
AND IF SO WE NEED TO THINK OF A

2586
01:34:19,080 --> 01:34:21,000
GLOBAL SUPPLY AND ALTHOUGH THAT

2587
01:34:21,000 --> 01:34:24,400
MIGHT BE EXPENSIVE IN THE FIRST

2588
01:34:24,400 --> 01:34:25,440
INSTANCE, DEMAND AND SCALE WILL

2589
01:34:25,440 --> 01:34:26,440
REDUCE THAT COST.

2590
01:34:26,440 --> 01:34:30,280
SO IN CONCLUSION, WELCOME TO THE

2591
01:34:30,280 --> 01:34:30,800
21ST CENTURY SCIENTIFIC

2592
01:34:30,800 --> 01:34:31,360
RENAISSANCE.

2593
01:34:31,360 --> 01:34:32,360
THE GLOBAL COMMUNITY IS NOW

2594
01:34:32,360 --> 01:34:33,480
LISTENING TO US.

2595
01:34:33,480 --> 01:34:35,640
WE'RE NOW SHARING DATA AND

2596
01:34:35,640 --> 01:34:37,720
TECHNOLOGY IN A WAY WHICH WE

2597
01:34:37,720 --> 01:34:38,720
COULDN'T HAVE ANTICIPATED AND

2598
01:34:38,720 --> 01:34:42,560
THIS IS NOW THE NEW NORM.

2599
01:34:42,560 --> 01:34:44,720
I THINK THE HUMAN

2600
01:34:44,720 --> 01:34:47,080
MICROPHYSIOLOGICAL SYSTEMS

2601
01:34:47,080 --> 01:34:48,560
OFFERING A POTENTIAL TO ANIMALS

2602
01:34:48,560 --> 01:34:50,960
IN THE LONG TERM, BUT WE NEED TO

2603
01:34:50,960 --> 01:34:54,560
FIT THOSE ANTIVIRAL DRUG TESTING

2604
01:34:54,560 --> 01:34:59,160
REQUIREMENTS, BUT THOSE THAT

2605
01:34:59,160 --> 01:35:01,560
TICK THE BOXES FOR ANTIVIRAL

2606
01:35:01,560 --> 01:35:03,760
DRUG TESTING SHOULD ALSO BE

2607
01:35:03,760 --> 01:35:04,720
FIT-FOR-PURPOSES FOR VACCINES

2608
01:35:04,720 --> 01:35:06,280
AND THERAPEUTICS, WHICH COULD BE

2609
01:35:06,280 --> 01:35:07,360
INCORPORATED INTO DRUGS.

2610
01:35:07,360 --> 01:35:10,640
SO LET'S MAKE SURE THAT THE

2611
01:35:10,640 --> 01:35:11,720
MODELS WE CHOOSE ARE APPLICABLE

2612
01:35:11,720 --> 01:35:13,360
TO VACCINE AND THERAPEUTIC

2613
01:35:13,360 --> 01:35:13,920
TESTING.

2614
01:35:13,920 --> 01:35:18,080
INTO AND    AND ONCE WE HAVE TH,

2615
01:35:18,080 --> 01:35:19,960
THAT COULD BE USED FOR ALL

2616
01:35:19,960 --> 01:35:21,680
SELECT AGENTS ONCE WE ADDRESS

2617
01:35:21,680 --> 01:35:24,000
ISSUES AROUND CONTAINMENT, WHICH

2618
01:35:24,000 --> 01:35:25,600
ARE QUITE FORMIDABLE, BUT WE

2619
01:35:25,600 --> 01:35:27,600
NEED A GLOBAL SUPPLY AND DEMAND

2620
01:35:27,600 --> 01:35:32,280
PLAN.

2621
01:35:32,280 --> 01:35:33,480
SO WITH THAT, I'D LIKE TO THANK

2622
01:35:33,480 --> 01:35:35,040
YOU FOR YOUR ATTENTION AND OPEN

2623
01:35:35,040 --> 01:35:39,320
UP FOR QUESTIONS.

2624
01:35:39,320 --> 01:35:41,040
>> THANK YOU SO MUCH,
SIMON, FOR

2625
01:35:41,040 --> 01:35:42,240
THIS WONDERFUL TALK.

2626
01:35:42,240 --> 01:35:43,560
I SEE ONE QUESTION IN THE Q
& A

2627
01:35:43,560 --> 01:35:47,280
BOX SO I'LL DIRECT THAT TO YOU.

2628
01:35:47,280 --> 01:35:48,480
SO THE QUESTION SAYS, THE FDA

2629
01:35:48,480 --> 01:35:50,280
HAS THE ANIMAL RULE FOR

2630
01:35:50,280 --> 01:35:52,400
APPROVING DRUGS BASED ON ANIMAL

2631
01:35:52,400 --> 01:35:52,760
STUDIES.

2632
01:35:52,760 --> 01:35:54,720
IS THERE ANY MOVEMENT ON THE

2633
01:35:54,720 --> 01:35:56,800
PART OF THE FDA OR OTHER

2634
01:35:56,800 --> 01:35:59,560
REGULATORY AGENCIES AROUND THE

2635
01:35:59,560 --> 01:36:03,440
WORLD TO THE ESTABLISHMENT OF A

2636
01:36:03,440 --> 01:36:04,560
"CHIP RULE"?

2637
01:36:04,560 --> 01:36:09,680
>> YES, I THINK IN ONE OF
MY

2638
01:36:09,680 --> 01:36:12,760
SLIDES, I ACTUALLY HAD A SCREEN

2639
01:36:12,760 --> 01:36:15,160
SHOT OF A BILL THAT'S PASSING

2640
01:36:15,160 --> 01:36:16,840
THROUGH AT THE MOMENT IN THE

2641
01:36:16,840 --> 01:36:20,120
U.S. IN TERMS OF ACCEPTANCE TO

2642
01:36:20,120 --> 01:36:30,640
MICROPHYSIOLOGICAL SYSTEM DATA.

2643
01:36:31,440 --> 01:36:32,720
I THINK IT'S IMPORTANT WHEN WE

2644
01:36:32,720 --> 01:36:34,680
TALK ABOUT THE ANIMAL RULE THAT

2645
01:36:34,680 --> 01:36:35,960
IF THERE'S ONGOING INFECTION,

2646
01:36:35,960 --> 01:36:37,840
THEN THE ANIMAL RULE CANNOT

2647
01:36:37,840 --> 01:36:39,400
APPLY BECAUSE YOU CAN'T ACTUALLY

2648
01:36:39,400 --> 01:36:44,720
GO AND DO A CLINICAL TRIAL.

2649
01:36:44,720 --> 01:36:46,920
BUT I THINK WE'RE AT A MOMENT IN

2650
01:36:46,920 --> 01:36:49,520
TIME WHERE MICROPHYSIOLOGICAL

2651
01:36:49,520 --> 01:36:51,120
SYSTEMS ARE BEGINNING TO BE

2652
01:36:51,120 --> 01:36:55,240
ACCEPTED AND THAT'S WHY I'M

2653
01:36:55,240 --> 01:36:57,120
HERE.

2654
01:36:57,120 --> 01:36:58,400
>> THANK YOU, SIMON.

2655
01:36:58,400 --> 01:36:59,360
THERE'S MULTIPLE OTHER QUESTIONS

2656
01:36:59,360 --> 01:36:59,960
COMING IN.

2657
01:36:59,960 --> 01:37:05,840
SO WE'LL TAKE ONE FROM MARK,

2658
01:37:05,840 --> 01:37:07,240
WHO'S ASKING, CAN YOU COMMENT ON

2659
01:37:07,240 --> 01:37:11,640
THE VALUE OR NOT OF ANIMAL --

2660
01:37:11,640 --> 01:37:14,040
MPS TO SUPPORT THE DEVELOPMENT

2661
01:37:14,040 --> 01:37:15,160
OF ANTIVIRAL DRUGS?

2662
01:37:15,160 --> 01:37:18,880
>> YES, I THINK THERE ARE

2663
01:37:18,880 --> 01:37:20,280
EXISTING DATASETS THAT HAVE BEEN

2664
01:37:20,280 --> 01:37:24,120
GENERATED IN NON-HUMAN PRIMATES.

2665
01:37:24,120 --> 01:37:24,560
HISTORICALLY.

2666
01:37:24,560 --> 01:37:26,080
AND WE HAVE DATASETS THAT HAVE

2667
01:37:26,080 --> 01:37:29,560
BEEN PRODUCED IN HUMAN

2668
01:37:29,560 --> 01:37:32,760
MICROPHYSIOLOGICAL SYSTEMS, AND

2669
01:37:32,760 --> 01:37:34,720
IT MAY BE IMPORTANT TO LINK

2670
01:37:34,720 --> 01:37:38,880
HISTORIC DATASETS THAT HAVE BEEN

2671
01:37:38,880 --> 01:37:43,240
GENERATED IN NHPs IN HUMANS --

2672
01:37:43,240 --> 01:37:43,920
MICROPHYSIOLOGICAL SYSTEM DATA

2673
01:37:43,920 --> 01:37:46,640
IN HUMANS, MICROPHYSIOLOGICAL

2674
01:37:46,640 --> 01:37:48,720
SYSTEM DATA IN ANIMALS AND THE

2675
01:37:48,720 --> 01:37:50,120
ANIMAL DATA AND HUMAN DATA AND

2676
01:37:50,120 --> 01:37:51,760
IT MAY BE THAT WE CAN LINK ALL

2677
01:37:51,760 --> 01:37:54,280
THOSE FOUR DAY IT SETS.

2678
01:37:54,280 --> 01:37:54,560
 DATASETS.

2679
01:37:54,560 --> 01:37:56,840
SO YES, THERE IS VALUE IN

2680
01:37:56,840 --> 01:37:57,720
DEVELOPING THOSE IN ORDER TO

2681
01:37:57,720 --> 01:37:59,000
ACCESS THE EXISTING DATASETS

2682
01:37:59,000 --> 01:38:03,280
THAT ARE IN ANIMALS AND HUMANS.

2683
01:38:03,280 --> 01:38:06,360
>> THANK YOU, SIMON.

2684
01:38:06,360 --> 01:38:08,600
NEXT QUESTION IS, IS IT ONLY

2685
01:38:08,600 --> 01:38:11,160
CHIP-BASED MODELS THAT WILL BE

2686
01:38:11,160 --> 01:38:12,800
CONSIDERED OR CO-CULTURED

2687
01:38:12,800 --> 01:38:17,480
WITHOUT A CHIP?

2688
01:38:17,480 --> 01:38:18,800
>> I THINK IN SOME OF THE

2689
01:38:18,800 --> 01:38:19,560
PRELIMINARY TALKS, WE HEARD

2690
01:38:19,560 --> 01:38:22,040
ABOUT SCALE, AND CAN YOU HAVE

2691
01:38:22,040 --> 01:38:24,080
THE MOST SOPHISTICATED -- YOU

2692
01:38:24,080 --> 01:38:27,000
CAN HAVE THE MOST SOPHISTICATED

2693
01:38:27,000 --> 01:38:31,080
SYSTEM ON THE PLANET BUT WITHOUT

2694
01:38:31,080 --> 01:38:32,920
SCALE, WE CAN'T ACTUALLY APPLY

2695
01:38:32,920 --> 01:38:33,560
IT.

2696
01:38:33,560 --> 01:38:36,320
WE NEED THE ACTUAL NUMBERS TO

2697
01:38:36,320 --> 01:38:39,240
GET STATISTICAL SIGNIFICANCE.

2698
01:38:39,240 --> 01:38:40,760
SO I WOULDN'T ELIMINATE ANY

2699
01:38:40,760 --> 01:38:42,320
APPROACH, I THINK, AS LONG AS

2700
01:38:42,320 --> 01:38:46,040
IT'S SCIENTIFICALLY JUSTIFIABLE

2701
01:38:46,040 --> 01:38:48,200
AND ADDRESSES THE REQUIREMENTS

2702
01:38:48,200 --> 01:38:49,960
OF THE DRUG WHICH MAY VARY FROM

2703
01:38:49,960 --> 01:38:54,040
ONE DRUG TO ANOTHER, THEN I

2704
01:38:54,040 --> 01:38:58,200
DON'T THINK THAT'S IMPORTANT.

2705
01:38:58,200 --> 01:38:59,600
I THINK IT'S MORE IMPORTANT TO

2706
01:38:59,600 --> 01:39:02,440
MAKE SURE WE HAVE A MODEL THAT'S

2707
01:39:02,440 --> 01:39:03,520
REPRODUCIBLE AND RELIABLE AND

2708
01:39:03,520 --> 01:39:04,640
CAN COPE WITH THE NUMBERS THAT

2709
01:39:04,640 --> 01:39:07,040
ARE REQUIRED TO ACHIEVE

2710
01:39:07,040 --> 01:39:07,920
STATISTICAL SIGNIFICANCE.

2711
01:39:07,920 --> 01:39:13,600
SO I'M NOT ELIMINATING ANY

2712
01:39:13,600 --> 01:39:15,960
APPROACH.

2713
01:39:15,960 --> 01:39:16,600
>> MAKE SENSE.

2714
01:39:16,600 --> 01:39:17,520
THANK YOU, SIMON.

2715
01:39:17,520 --> 01:39:18,600
WE HAVE MORE QUESTIONS COMING

2716
01:39:18,600 --> 01:39:18,800
IN.

2717
01:39:18,800 --> 01:39:20,800
THE NEXT QUESTION IS, WHAT IS

2718
01:39:20,800 --> 01:39:22,600
THE IMPORTANCE OF PROVIDING A

2719
01:39:22,600 --> 01:39:26,280
TRUE BLOOD AND LYMPHATIC CIRCUIT

2720
01:39:26,280 --> 01:39:28,880
USING WHOLE BLOOD TO PERFUSE THE

2721
01:39:28,880 --> 01:39:29,600
MPS SYSTEM?

2722
01:39:29,600 --> 01:39:33,600
>> I'VE GOT TO SAY, THAT
SOUNDS

2723
01:39:33,600 --> 01:39:34,360
ATTRACTIVE.

2724
01:39:34,360 --> 01:39:36,480
BUT I KNOW FROM PREVIOUS

2725
01:39:36,480 --> 01:39:38,320
EXPERIENCE FROM OTHER STUDIES

2726
01:39:38,320 --> 01:39:40,480
THAT THAT CAN BE COMPLICATED

2727
01:39:40,480 --> 01:39:43,560
BECAUSE IF, FOR EXAMPLE, SOMEONE

2728
01:39:43,560 --> 01:39:45,880
IS RECEIVING ANTIVIRAL DRUG AND

2729
01:39:45,880 --> 01:39:49,040
YOU TAKE A SAMPLE OF THE WHOLE

2730
01:39:49,040 --> 01:39:50,440
BLOOD, THEN THEY WILL HAVE THAT

2731
01:39:50,440 --> 01:39:52,320
ANTIVIRAL DRUG IN THEIR BLOOD

2732
01:39:52,320 --> 01:39:56,800
EQUALLY IF THEY'VE HAD -- IF

2733
01:39:56,800 --> 01:39:58,120
THEY HAVE AN UNDERLYING

2734
01:39:58,120 --> 01:39:59,560
CONDITION SUCH AS A COMPLEMENT

2735
01:39:59,560 --> 01:40:00,920
DEFICIENCY, THEN THAT MODEL WILL

2736
01:40:00,920 --> 01:40:03,360
REFLECT THAT.

2737
01:40:03,360 --> 01:40:04,680
AND SO THE ANSWER TO THAT

2738
01:40:04,680 --> 01:40:05,440
QUESTION IS, WHAT IS THE

2739
01:40:05,440 --> 01:40:06,760
QUESTION THAT YOU'RE ANSWERING?

2740
01:40:06,760 --> 01:40:10,120
AND IF IT'S IS THE INDIVIDUAL

2741
01:40:10,120 --> 01:40:11,320
PROTECTED, THEN MAYBE A WHOLE

2742
01:40:11,320 --> 01:40:13,120
BLOOD SAMPLE WOULD GIVE YOU THAT

2743
01:40:13,120 --> 01:40:13,320
ANSWER.

2744
01:40:13,320 --> 01:40:14,320
BUT IF YOU WANT TO TEST WHETHER

2745
01:40:14,320 --> 01:40:17,560
A DRUG HAS AN IMPACT ON A

2746
01:40:17,560 --> 01:40:18,440
HEALTHY IMMUNE SYSTEM, YOU MAY

2747
01:40:18,440 --> 01:40:20,120
HAVE TO HAVE A HEALTHY IMMUNE

2748
01:40:20,120 --> 01:40:21,600
SYSTEM WHICH YOU CAN APPLY THAT

2749
01:40:21,600 --> 01:40:25,600
DRUG OR THERAPEUTIC TO.

2750
01:40:25,600 --> 01:40:27,440
SO I THINK IN ANSWER TO THAT

2751
01:40:27,440 --> 01:40:28,880
QUESTION, I THINK IT SOUNDS

2752
01:40:28,880 --> 01:40:30,000
ATTRACTIVE, BUT I'M ALSO AWARE

2753
01:40:30,000 --> 01:40:31,440
THAT RED BLOOD CELLS REPRESENT

2754
01:40:31,440 --> 01:40:34,120
QUITE A TECHNICAL CHALLENGE IN

2755
01:40:34,120 --> 01:40:36,160
SOME SYSTEMS, BUT THAT CHALLENGE

2756
01:40:36,160 --> 01:40:39,280
CAN BE OVERCOME.

2757
01:40:39,280 --> 01:40:40,000
>> UNDERSTOOD.

2758
01:40:40,000 --> 01:40:40,880
THANK YOU, SIMON.

2759
01:40:40,880 --> 01:40:43,960
THREE MORE QUESTIONS AND WE HAVM

2760
01:40:43,960 --> 01:40:45,720
LIVE IF THAT'S OKAY WITH YOU.

2761
01:40:45,720 --> 01:40:46,680
>> THAT'S FINE.

2762
01:40:46,680 --> 01:40:49,760
WITH  BUT PLEASE READ THEM BACKI

2763
01:40:49,760 --> 01:40:51,600
CAN'T SEE THEM.

2764
01:40:51,600 --> 01:40:52,080
>> ALL RIGHT.

2765
01:40:52,080 --> 01:40:53,960
SO THE NEXT QUESTION IS, WHAT

2766
01:40:53,960 --> 01:40:57,840
STRATEGIES DO YOU PROPOSE FOR

2767
01:40:57,840 --> 01:41:01,720
INCORPORATING ADAPTIVE IMMUNITY?

2768
01:41:01,720 --> 01:41:02,800
>> OKAY.

2769
01:41:02,800 --> 01:41:03,640
THAT'S A VERY CHALLENGING

2770
01:41:03,640 --> 01:41:07,840
QUESTION.

2771
01:41:07,840 --> 01:41:09,480
BUT I'M AWARE THAT THERE ARE

2772
01:41:09,480 --> 01:41:12,880
SYSTEMS OUT THERE THAT CAN USE

2773
01:41:12,880 --> 01:41:18,640
VERY SMALL VOLUMES OF BLOOD TO

2774
01:41:18,640 --> 01:41:21,720
ASSESS T-CELLS.

2775
01:41:21,720 --> 01:41:24,320
AND I THINK THAT USING MICRO

2776
01:41:24,320 --> 01:41:25,840
FLUIDICS, THERE MUST BE A WAY TO

2777
01:41:25,840 --> 01:41:29,920
GET A SMALL VOLUME OF WHOLE

2778
01:41:29,920 --> 01:41:32,520
BLOOD INTO THE ENDOTHELIAL

2779
01:41:32,520 --> 01:41:36,360
CHANNEL OF A SYSTEM WHICH HAS AN

2780
01:41:36,360 --> 01:41:42,280
ENDOTHELIAL AND MUCOSAL SURFACE.

2781
01:41:42,280 --> 01:41:44,560
I'M NOT A MICRO FLUIDICS EXPERT

2782
01:41:44,560 --> 01:41:46,320
BUT I CAN SEE PEOPLE ARE DOING

2783
01:41:46,320 --> 01:41:48,080
THAT FOR OTHER PURPOSES, SO I

2784
01:41:48,080 --> 01:41:49,280
THINK WHERE THERE'S A NEED,

2785
01:41:49,280 --> 01:41:51,480
THERE WILL BE A SOLUTION.

2786
01:41:51,480 --> 01:41:53,480
AND SO I DON'T HAVE A GENERIC

2787
01:41:53,480 --> 01:41:57,480
ANSWER TO THAT, BUT I DO THINK

2788
01:41:57,480 --> 01:41:59,200
THAT SMALL VOLUMES CAN BE

2789
01:41:59,200 --> 01:42:01,400
INTRODUCED EITHER INTO THE

2790
01:42:01,400 --> 01:42:03,720
ENDOTHELIAL CHANNEL OR IF IT'S

2791
01:42:03,720 --> 01:42:05,800
IN AN ORGAN, IT MAY BE

2792
01:42:05,800 --> 01:42:06,440
INTRODUCING CELLS.

2793
01:42:06,440 --> 01:42:07,400
BECAUSE ACTUALLY WHEN YOU THINK

2794
01:42:07,400 --> 01:42:09,720
ABOUT A MICRO NEUTRALIZATION

2795
01:42:09,720 --> 01:42:11,880
ASSAY, ALL THAT'S HAPPENING IS

2796
01:42:11,880 --> 01:42:13,240
THE ANTIBODIES BEING MIXED WITH

2797
01:42:13,240 --> 01:42:16,400
THE VIRUS ARE BEING -- ON TO THE

2798
01:42:16,400 --> 01:42:16,840
VERO CELL.

2799
01:42:16,840 --> 01:42:18,040
THAT'S PRETTY SIMPLE.

2800
01:42:18,040 --> 01:42:21,760
BUT IF WE CAN GET A COMPLEX

2801
01:42:21,760 --> 01:42:25,240
TISSUE MODEL AT A CONTROLLED

2802
01:42:25,240 --> 01:42:26,680
RATE, MAYBE FLOW CYTOMETRY CAN

2803
01:42:26,680 --> 01:42:28,520
GIVE US THE NUMBERS SO WE CAN

2804
01:42:28,520 --> 01:42:31,160
STANDARDIZE THE NUMBERS GOING

2805
01:42:31,160 --> 01:42:33,000
IN, AND MAYBE THAT CAN BE A WAY

2806
01:42:33,000 --> 01:42:36,040
TO ACTUALLY ASSESS ANTIBODIES

2807
01:42:36,040 --> 01:42:39,200
AND CELLULAR IMMUNITY AT THE

2808
01:42:39,200 --> 01:42:40,360
SAME TIME.

2809
01:42:40,360 --> 01:42:41,760
>> THANK YOU, SIMON.

2810
01:42:41,760 --> 01:42:43,000
AND HOPEFULLY WE CAN ANSWER SOME

2811
01:42:43,000 --> 01:42:44,920
OF THESE QUESTIONS BETWEEN TODAY

2812
01:42:44,920 --> 01:42:46,880
AND TOMORROW WITH ALL THE

2813
01:42:46,880 --> 01:42:48,240
SPEAKERS, THE TALKS, THE

2814
01:42:48,240 --> 01:42:49,080
FANTASTIC TALKS THAT WE HAVE.

2815
01:42:49,080 --> 01:42:49,960
ALL RIGHT.

2816
01:42:49,960 --> 01:42:52,280
MORE QUESTIONS FOR YOU, SIMON.

2817
01:42:52,280 --> 01:42:55,240
SO I'VE GOT ONE THAT SAYS, HI,

2818
01:42:55,240 --> 01:42:55,440
SIMON.

2819
01:42:55,440 --> 01:42:56,520
THANK YOU FOR THE VERY NICE

2820
01:42:56,520 --> 01:42:57,520
TALK.

2821
01:42:57,520 --> 01:43:01,480
CAN YOU EXPAND ON WHAT MODEL

2822
01:43:01,480 --> 01:43:03,640
COMPONENTS ARE NECESSARY FOR

2823
01:43:03,640 --> 01:43:04,960
MICROPHYSIOLOGICAL SYSTEMS BEING

2824
01:43:04,960 --> 01:43:10,120
USED FOR VACCINE DEVELOPMENT?

2825
01:43:10,120 --> 01:43:11,760
>> AT THE MOMENT, LET ME
TALK

2826
01:43:11,760 --> 01:43:14,600
ABOUT SARS-COV-2 2, THERE IS A

2827
01:43:14,600 --> 01:43:16,120
HEAVY RELIANCE ON HUMAN

2828
01:43:16,120 --> 01:43:18,720
IMMUNITY.

2829
01:43:18,720 --> 01:43:22,120
BECAUSE THAT'S SEEN AS A GOOD

2830
01:43:22,120 --> 01:43:23,560
CORRELATE, A CO-CORRELATE OF

2831
01:43:23,560 --> 01:43:24,240
PROTECTION, BECAUSE IT WOULD BE

2832
01:43:24,240 --> 01:43:27,160
VERY ODD FOR A VACCINE TO INDUCE

2833
01:43:27,160 --> 01:43:28,880
HUMAN IMMUNITY WITHOUT CELLULAR

2834
01:43:28,880 --> 01:43:29,160
IMMUNITY.

2835
01:43:29,160 --> 01:43:30,520
AND PART OF THAT IS BECAUSE IT'S

2836
01:43:30,520 --> 01:43:32,640
ACTUALLY VERY DIFFICULT TO TAKE

2837
01:43:32,640 --> 01:43:36,440
THE SAMPLES THAT ARE REQUIRED TO

2838
01:43:36,440 --> 01:43:37,440
ACTUALLY CONDUCT CELLULAR

2839
01:43:37,440 --> 01:43:40,960
IMMUNITY ASSESSMENT, BUT JUST

2840
01:43:40,960 --> 01:43:42,240
BECAUSE IT'S DIFFICULT DOESN'T

2841
01:43:42,240 --> 01:43:43,240
MEAN WE CAN'T DO IT.

2842
01:43:43,240 --> 01:43:45,400
I THINK THERE IS A -- FOR

2843
01:43:45,400 --> 01:43:47,600
CELLULAR IMMUNITY TO BE ANALYZED

2844
01:43:47,600 --> 01:43:48,480
BUT FIRST YOU'VE GOT TO THINK

2845
01:43:48,480 --> 01:43:50,120
ABOUT HOW DO YOU TAKE A BLOOD

2846
01:43:50,120 --> 01:43:52,080
SAMPLE FROM SOMEONE IN AN

2847
01:43:52,080 --> 01:43:54,600
ENDEMIC COUNTRY, AND ANALYZE IT?

2848
01:43:54,600 --> 01:43:57,240
YOU CAN EITHER SHIP IT BACK TO A

2849
01:43:57,240 --> 01:44:00,080
HUB IN A CENTRAL REGION, OR YOU

2850
01:44:00,080 --> 01:44:02,160
CAN TAKE THE TECHNOLOGY TO THE

2851
01:44:02,160 --> 01:44:05,000
ENDEMIC SITE.

2852
01:44:05,000 --> 01:44:08,720
THE SECOND OPTION IS OBVIOUSLY

2853
01:44:08,720 --> 01:44:10,680
THE OPTION WHICH WHO WOULD

2854
01:44:10,680 --> 01:44:12,280
PROMOTE, THEY WANT TO INCREASE

2855
01:44:12,280 --> 01:44:14,640
THE ABILITY OF ENDEMIC COUNTRIES

2856
01:44:14,640 --> 01:44:16,240
TO ANALYZE THEIR OWN SAMPLES.

2857
01:44:16,240 --> 01:44:18,120
WE HAVE FACED CHALLENGES NOW IN

2858
01:44:18,120 --> 01:44:21,280
TERMS OF -- PROTOCOL IN SHIPPING

2859
01:44:21,280 --> 01:44:22,480
SAMPLES OUT OF THIRD WORLD

2860
01:44:22,480 --> 01:44:24,160
COUNTRIES INTO FIRST WORLD

2861
01:44:24,160 --> 01:44:24,800
COUNTRIES.

2862
01:44:24,800 --> 01:44:26,320
SO WHAT WE NEED TO DO IS PIONEER

2863
01:44:26,320 --> 01:44:28,480
THE TECHNOLOGY OF HOW TO DO THIS

2864
01:44:28,480 --> 01:44:30,160
AT HOME, THEN LEARN HOW TO

2865
01:44:30,160 --> 01:44:32,040
MINIATURIZE IT AND MAKE IT

2866
01:44:32,040 --> 01:44:32,680
FIELD-ACCESSIBLE.

2867
01:44:32,680 --> 01:44:34,320
AND THAT'S A SEQUENTIAL PROCESS

2868
01:44:34,320 --> 01:44:35,760
AND IT'S NOT GOING TO HAPPEN

2869
01:44:35,760 --> 01:44:40,000
OVERNIGHT.

2870
01:44:40,000 --> 01:44:42,080
SO THE ANSWER IS, I DON'T HAVE

2871
01:44:42,080 --> 01:44:46,160
THE ANSWER YET, BUT I THINK THAT

2872
01:44:46,160 --> 01:44:47,880
THERE'S MOMENTUM CERTAINLY IN

2873
01:44:47,880 --> 01:44:49,400
THE TALKS I SEE LINED UP IN THE

2874
01:44:49,400 --> 01:44:50,200
NEXT TWO DAYS.

2875
01:44:50,200 --> 01:44:54,000
MAYBE SOME OF THE ANSWERS YOU'RE

2876
01:44:54,000 --> 01:44:55,560
SEARCHING FOR WILL ACTUALLY BE

2877
01:44:55,560 --> 01:44:56,720
ANSWERED IN THE COURSE OF THE

2878
01:44:56,720 --> 01:44:57,720
PRESENTATIONS, AND IF THEY'RE

2879
01:44:57,720 --> 01:44:58,840
NOT, IT'S SOMETHING I'M GOING TO

2880
01:44:58,840 --> 01:45:04,400
BE LOOKING AT IN THE VERY NEAR

2881
01:45:04,400 --> 01:45:04,640
FUTURE.

2882
01:45:04,640 --> 01:45:05,880
>> FANTASTIC.

2883
01:45:05,880 --> 01:45:06,880
THANK YOU, SIMON.

2884
01:45:06,880 --> 01:45:09,320
SO THIS IS AMY FROM NIAID AGAIN.

2885
01:45:09,320 --> 01:45:11,160
THIS IS THE PERSON THAT ASKED

2886
01:45:11,160 --> 01:45:13,360
ABOUT THE STRATEGIES THAT YOU'RE

2887
01:45:13,360 --> 01:45:14,680
PROPOSING FOR INCORPORATING

2888
01:45:14,680 --> 01:45:16,400
ADAPTIVE IMMUNITY, AND SHE'S

2889
01:45:16,400 --> 01:45:19,360
EXPANDING AND SAYING, I'M

2890
01:45:19,360 --> 01:45:21,560
CONCERNED ABOUT THE BARRIER OF

2891
01:45:21,560 --> 01:45:22,600
NHC MATCHING.

2892
01:45:22,600 --> 01:45:26,160
>> YES, I KNOW, WE'VE
TALKED

2893
01:45:26,160 --> 01:45:28,800
ABOUT THAT, AND WHEN WE TALK

2894
01:45:28,800 --> 01:45:31,440
ABOUT NHC MATCHING, I THINK IF

2895
01:45:31,440 --> 01:45:33,840
YOU TALK ABOUT DELAYED TYPE

2896
01:45:33,840 --> 01:45:35,120
HYPERSENSITIVITY, THAT TAKES

2897
01:45:35,120 --> 01:45:37,960
SOME TIME TO KICK IN, AND

2898
01:45:37,960 --> 01:45:39,400
CERTAINLY WITH REJECTION, IT

2899
01:45:39,400 --> 01:45:41,360
DOESN'T HAPPEN IN THE COURSE OF

2900
01:45:41,360 --> 01:45:47,280
SEVERAL HOURS -- TAKES QUITE A

2901
01:45:47,280 --> 01:45:49,440
BIT OF TIME AND SOME OF THESE

2902
01:45:49,440 --> 01:45:50,960
ASSAYS COULD TAKE AN HOUR TO BE

2903
01:45:50,960 --> 01:45:51,320
CONDUCTED.

2904
01:45:51,320 --> 01:45:53,520
SO ALTHOUGH THEY WOULD OBVIOUSLY

2905
01:45:53,520 --> 01:45:57,000
BE SOMETHING LIKE THAT BEING

2906
01:45:57,000 --> 01:45:59,320
INITIATED IN THE CASE OF A

2907
01:45:59,320 --> 01:45:59,880
MISMATCH.

2908
01:45:59,880 --> 01:46:00,960
I THINK THAT SOME OF THE ASSAYS

2909
01:46:00,960 --> 01:46:04,240
THAT WE'RE LOOKING AT WOULD

2910
01:46:04,240 --> 01:46:07,040
BE -- TO BE CONDUCTED WITHIN A

2911
01:46:07,040 --> 01:46:08,400
FEW HOURS OR EVEN OVERNIGHT, IN

2912
01:46:08,400 --> 01:46:11,200
WHICH CASE THE --

2913
01:46:11,200 --> 01:46:11,840
HYPERSENSITIVITY WILL NOT HAVE

2914
01:46:11,840 --> 01:46:13,200
HAD TIME TO INTERFERE WITH THE

2915
01:46:13,200 --> 01:46:14,480
ASSAY, BUT IT'S SOMETHING WE ARE

2916
01:46:14,480 --> 01:46:19,440
ALL THINKING ABOUT.

2917
01:46:19,440 --> 01:46:20,520
>> THANK YOU, SIMON.

2918
01:46:20,520 --> 01:46:23,480
TWO MORE QUESTIONS.

2919
01:46:23,480 --> 01:46:26,320
ONE MORE SAYS TO DATE, WHAT IS

2920
01:46:26,320 --> 01:46:28,720
THE MOST COMPLEX MPS IN TERMS OF

2921
01:46:28,720 --> 01:46:32,880
ITS DIVERSITY OF IMMUNE CELLS

2922
01:46:32,880 --> 01:46:34,200
INCORPORATION, AND WHAT IMMUNE

2923
01:46:34,200 --> 01:46:39,000
CELL TYPES ARE USED FOR YOU --

2924
01:46:39,000 --> 01:46:40,080
THINK SHOULD BE INITIALLY

2925
01:46:40,080 --> 01:46:42,840
COMBINED FOR TESTING?

2926
01:46:42,840 --> 01:46:50,920
>> I THINK I CAN'T ANSWER
THAT

2927
01:46:50,920 --> 01:46:58,160
QUESTION, I THINK SOME PEOPLE

2928
01:46:58,160 --> 01:46:59,160
HAVE ACTUALLY ANSWERED THAT

2929
01:46:59,160 --> 01:47:01,840
QUESTION, SO I THINK I'D HAVE

2930
01:47:01,840 --> 01:47:02,760
THE RIGHT TO DEFER THAT

2931
01:47:02,760 --> 01:47:03,200
QUESTION.

2932
01:47:03,200 --> 01:47:04,800
I KNOW NATURAL KILLER KELCE ARE

2933
01:47:04,800 --> 01:47:07,320
OBVIOUSLY VERY IMPORTANT, BUT --

2934
01:47:07,320 --> 01:47:08,640
AND THERE ARE MANY T-CELLS THAT

2935
01:47:08,640 --> 01:47:11,160
MAY BE INVOLVED AND

2936
01:47:11,160 --> 01:47:12,240
UNFORTUNATELY WE DON'T REALLY

2937
01:47:12,240 --> 01:47:13,360
KNOW WHICH ONES ARE YET.

2938
01:47:13,360 --> 01:47:18,280
WE'RE GETTING HINTS FROM IB IN

2939
01:47:18,280 --> 01:47:20,240
VITRO ANALYSIS FLOW CYTOMETRY.

2940
01:47:20,240 --> 01:47:22,880
BUT UNTIL WE HAVE MODELS TO

2941
01:47:22,880 --> 01:47:25,120
ANALYZE IT, WE WON'T HAVE THE

2942
01:47:25,120 --> 01:47:25,520
ANSWERS TO THAT.

2943
01:47:25,520 --> 01:47:29,360
>> THANK YOU, SIGH   
SIMON.

2944
01:47:29,360 --> 01:47:31,760
I INVITE ANYONE ON THE PANEL

2945
01:47:31,760 --> 01:47:35,120
TODAY TO TYPE ANSWERS AS WELL.

2946
01:47:35,120 --> 01:47:37,200
I KNOW THERE'S MULTIPLE PEOPLE

2947
01:47:37,200 --> 01:47:39,600
ON THE PANEL RIGHT NOW THAT

2948
01:47:39,600 --> 01:47:40,920
MIGHT HAVE ADDITIONS TO THE

2949
01:47:40,920 --> 01:47:43,640
ANSWER AS WELL.

2950
01:47:43,640 --> 01:47:44,720
SO FEEL FREE TO TYPE IN YOUR

2951
01:47:44,720 --> 01:47:45,040
ANSWERS.

2952
01:47:45,040 --> 01:47:45,720
ONE MORE QUESTION.

2953
01:47:45,720 --> 01:47:48,440
A PAPER IN THE JOURNAL OF

2954
01:47:48,440 --> 01:47:50,480
INFECTIOUS DISEASES EXPLORED

2955
01:47:50,480 --> 01:47:51,280
NOROVIRUS INFECTION MECHANISMS

2956
01:47:51,280 --> 01:47:56,560
BY USING STEM CELL DERIVED

2957
01:47:56,560 --> 01:47:57,320
INTESTINAL -- TO SIMULATE

2958
01:47:57,320 --> 01:47:58,160
INFECTION.

2959
01:47:58,160 --> 01:47:59,600
HOWEVER, IT WAS FOUND ONLY

2960
01:47:59,600 --> 01:48:01,480
CERTAIN NOROVIRUS GENOTYPES WERE

2961
01:48:01,480 --> 01:48:03,880
ABLE TO INTBECT THE --.

2962
01:48:03,880 --> 01:48:05,520
ARE YOU FAMILIAR WITH OTHER

2963
01:48:05,520 --> 01:48:07,480
SCENARIOS IN WHICH STEM CELL

2964
01:48:07,480 --> 01:48:09,360
DERIVED MODEL SYSTEMS

2965
01:48:09,360 --> 01:48:14,520
ENCOUNTERED SIMILAR LIMITATIONS?

2966
01:48:14,520 --> 01:48:16,480
>> I'M NOT FAMILIAR WITH
OTHER

2967
01:48:16,480 --> 01:48:18,000
SCENARIOS THAT HAVE FAILED, BUT

2968
01:48:18,000 --> 01:48:22,200
I AM AWARE THAT IF WE KEEP USING

2969
01:48:22,200 --> 01:48:25,920
VOLUNTEERS TO SUPPLY OUR SEEDS

2970
01:48:25,920 --> 01:48:28,120
CULTURES FOR MICROPHYSIOLOGICAL

2971
01:48:28,120 --> 01:48:29,080
SYSTEMS, WE'RE GOING TO GET A

2972
01:48:29,080 --> 01:48:31,840
LOT OF VARIANTS, AND IT MAY BE

2973
01:48:31,840 --> 01:48:33,560
THAT FOR SEARCH IN ORGANISMS, WE

2974
01:48:33,560 --> 01:48:35,240
NEED TO MAKE SURE THE

2975
01:48:35,240 --> 01:48:36,760
APPROPRIATE BIOMARKERS ARE

2976
01:48:36,760 --> 01:48:37,640
REPRESENTED IN THE MODEL THAT WE

2977
01:48:37,640 --> 01:48:38,160
USE.

2978
01:48:38,160 --> 01:48:43,400
IT MAY BE THAT -- X CELL Y IS

2979
01:48:43,400 --> 01:48:44,200
APPROPRIATE BUT WE'RE GOING TO

2980
01:48:44,200 --> 01:48:48,800
HAVE TO CHANGE THE CELLS.

2981
01:48:48,800 --> 01:48:50,440
BUT WE NEED TO ENSURE THAT THE

2982
01:48:50,440 --> 01:48:52,200
MODEL IS SUITABLE FOR THE

2983
01:48:52,200 --> 01:48:56,240
QUESTION THAT WE'RE ASKING.

2984
01:48:56,240 --> 01:48:58,400
FOR YEARS NOW, WE'VE BEEN USING

2985
01:48:58,400 --> 01:48:59,160
VERO CELLS.

2986
01:48:59,160 --> 01:49:02,800
AND I DON'T THINK THEY'RE A VERY

2987
01:49:02,800 --> 01:49:05,400
GOOD MODEL OF SARS-COV-2

2988
01:49:05,400 --> 01:49:06,320
INFECTION, AS YOU MAY HAVE

2989
01:49:06,320 --> 01:49:08,040
GATHERED.

2990
01:49:08,040 --> 01:49:09,000
BUT WHETHER OR NOT VERO CELLS

2991
01:49:09,000 --> 01:49:11,200
ARE APPROPRIATE FOR VIRUS X WILL

2992
01:49:11,200 --> 01:49:12,320
DEPEND ON THE RESULT THAT WE

2993
01:49:12,320 --> 01:49:14,360
ACHIEVE AND WHAT BIOMARKERS ARE

2994
01:49:14,360 --> 01:49:16,160
REQUIRED FOR VIRUS X.

2995
01:49:16,160 --> 01:49:17,640
BUT I THINK IN THE SAME WAY THAT

2996
01:49:17,640 --> 01:49:20,600
YOU WOULDN'T USE YOUR STANDARD

2997
01:49:20,600 --> 01:49:22,160
SCIENTIFIC TECHNIQUE TO APPLY TO

2998
01:49:22,160 --> 01:49:23,640
ANY VIRUS, YOU'D WANT TO MAKE

2999
01:49:23,640 --> 01:49:25,120
SURE THAT THE SCIENTIFIC

3000
01:49:25,120 --> 01:49:27,640
TECHNIQUES OR SERVICES YOU HAVE

3001
01:49:27,640 --> 01:49:29,480
ARE APPROPRIATE FOR USE.

3002
01:49:29,480 --> 01:49:30,560
AND THAT'S PART OF THE

3003
01:49:30,560 --> 01:49:31,120
VALIDATION OF THE MODEL.

3004
01:49:31,120 --> 01:49:34,280
AND IT MAY BE THAT WE NEED TO

3005
01:49:34,280 --> 01:49:36,120
VALIDATE A GENERIC MODEL FOR

3006
01:49:36,120 --> 01:49:37,560
SUITABILITY TO THE LIST OF

3007
01:49:37,560 --> 01:49:39,880
PRIORITY PATHOGENS THAT WAS

3008
01:49:39,880 --> 01:49:42,360
LISTED EARLIER ON BY EMILY.

3009
01:49:42,360 --> 01:49:45,120
AND IT MAY BE THAT FOR THE

3010
01:49:45,120 --> 01:49:47,840
PRIORITY PATHOGENS, MODEL X WILL

3011
01:49:47,840 --> 01:49:51,000
BE APPROPRIATE FOR THOSE BUT NOT

3012
01:49:51,000 --> 01:49:54,000
FOR MODEL -- NOT FOR VIRUS Y,

3013
01:49:54,000 --> 01:49:56,400
AND IT MAY BE THAT SPECIFIC

3014
01:49:56,400 --> 01:49:58,800
VIRUSES HAVE SPECIFIC BIOMARKER

3015
01:49:58,800 --> 01:49:59,880
REQUIREMENTS THAT HAVE TO BE

3016
01:49:59,880 --> 01:50:00,080
PRINT.

3017
01:50:00,080 --> 01:50:04,560
AND IT MAY BE THAT             

3018
01:50:04,560 --> 01:50:04,800
PRESENT.

3019
01:50:04,800 --> 01:50:06,000
IT MAY BE THE FIRST TIME YOU TRY

3020
01:50:06,000 --> 01:50:07,440
IT WHEN YOU GROW IN THE CELLS

3021
01:50:07,440 --> 01:50:09,400
FOR A COUPLE OF WEEKS, MAYBE YOU

3022
01:50:09,400 --> 01:50:11,320
HAVEN'T GOT THE RIGHT BIOMARKERS

3023
01:50:11,320 --> 01:50:12,800
BUT MAYBE YOU'RE MISSING A VITAL

3024
01:50:12,800 --> 01:50:17,720
COMPONENT IN THE DIFFERENTIATION

3025
01:50:17,720 --> 01:50:19,680
MEDIA THAT SIMPLY NEEDS

3026
01:50:19,680 --> 01:50:20,360
MODIFICATION AND IT MAY BE

3027
01:50:20,360 --> 01:50:21,640
THROUGH A QUALITY MEASUREMENT

3028
01:50:21,640 --> 01:50:23,000
SYSTEM, THOSE FAILURES ARE

3029
01:50:23,000 --> 01:50:24,040
EXTREMELY IMPORTANT TO PUBLISH,

3030
01:50:24,040 --> 01:50:25,920
BECAUSE IT MAY BE THAT WE SAY,

3031
01:50:25,920 --> 01:50:28,000
WELL, WE NEED TO GO BACK AND SEE

3032
01:50:28,000 --> 01:50:29,840
WHY THAT'S FAIL AND SHARE THAT

3033
01:50:29,840 --> 01:50:31,400
LEARNING WITH THE COMMUNITY SO

3034
01:50:31,400 --> 01:50:36,640
THAT WE ALL KNOW THAT THE

3035
01:50:36,640 --> 01:50:38,400
BIOMARKER REQUIREMENT FOR THE

3036
01:50:38,400 --> 01:50:41,560
NOROVIRUS HAS TO BE INDUCED BY

3037
01:50:41,560 --> 01:50:42,680
THIS MEDIA -- WE CAN IMMEDIATELY

3038
01:50:42,680 --> 01:50:43,960
FIND THAT OUT OURSELVES AS A

3039
01:50:43,960 --> 01:50:44,880
COMMUNITY AND SHARE THAT.

3040
01:50:44,880 --> 01:50:48,800
>> FANTASTIC.

3041
01:50:48,800 --> 01:50:50,160
>> IT'S THROUGH FAILURE WE
CAN

3042
01:50:50,160 --> 01:50:51,440
LEARN, SO FAILURE IS PART OF THE

3043
01:50:51,440 --> 01:50:53,200
NATURAL PROCESS OF IMPROVEMENT.

3044
01:50:53,200 --> 01:50:54,400
>> THANK YOU, SIMON.

3045
01:50:54,400 --> 01:51:00,400
WE WILL HAVE A TALK TOMORROW ON

3046
01:51:00,400 --> 01:51:03,600
NOROVIRUS SO WE MAY GET MORE

3047
01:51:03,600 --> 01:51:04,680
ANSWERS FROM FOLKS THAT ARE

3048
01:51:04,680 --> 01:51:06,000
INTERESTED TO LEARN MORE.

3049
01:51:06,000 --> 01:51:06,200
OKAY.

3050
01:51:06,200 --> 01:51:07,320
I'M GOING TO STOP HERE.

3051
01:51:07,320 --> 01:51:09,240
YOU DO HAVE MORE QUESTIONS,

3052
01:51:09,240 --> 01:51:09,440
SIMON.

3053
01:51:09,440 --> 01:51:13,880
SO FEEL FREE TO, AFTER WE --

3054
01:51:13,880 --> 01:51:15,480
DURING THE LUNCH BREAK, IF YOU

3055
01:51:15,480 --> 01:51:17,280
CAN STAY A LITTLE LONGER AND

3056
01:51:17,280 --> 01:51:19,000
MAYBE ANSWER SOME OF THESE

3057
01:51:19,000 --> 01:51:21,960
QUESTIONS AND TYPE IN THE

3058
01:51:21,960 --> 01:51:22,400
ANSWERS.

3059
01:51:22,400 --> 01:51:23,720
ALSO I INVITE EVERYONE ON THE

3060
01:51:23,720 --> 01:51:26,240
PANEL IF THEY WOULD LIKE TO ADD

3061
01:51:26,240 --> 01:51:27,960
ANYTHING TO THE ANSWERS, FEEL

3062
01:51:27,960 --> 01:51:29,400
FREE TO TYPE IN YOUR ANSWERS AS

3063
01:51:29,400 --> 01:51:29,760
WELL.

3064
01:51:29,760 --> 01:51:31,520
AND THEN PLEASE, THE AUDIENCE,

3065
01:51:31,520 --> 01:51:32,240
KEEP ASKING QUESTIONS.

3066
01:51:32,240 --> 01:51:33,240
THIS IS GREAT.

3067
01:51:33,240 --> 01:51:34,560
WE'D LOVE TO GET YOUR QUESTIONS,

3068
01:51:34,560 --> 01:51:37,160
WE'D LIKE TO HAVE NICE

3069
01:51:37,160 --> 01:51:38,480
DISCUSSIONS DURING THIS MEETING.

3070
01:51:38,480 --> 01:51:39,600
OKAY.

3071
01:51:39,600 --> 01:51:41,240
SIMON, THANK YOU SO MUCH FOR

3072
01:51:41,240 --> 01:51:43,480
SUCH A WONDERFUL PRESENTATION,

3073
01:51:43,480 --> 01:51:45,280
SO ENGAGING, SO MANY QUESTIONS.

3074
01:51:45,280 --> 01:51:48,200
WE'RE REALLY HAPPY YOU WERE

3075
01:51:48,200 --> 01:51:50,400
HERE, AND WE APPRECIATE YOUR

3076
01:51:50,400 --> 01:51:51,400
TIME DURING THIS.

3077
01:51:51,400 --> 01:51:58,800
ALL RIGHT.

3078
01:51:58,800 --> 01:51:59,920
SO I'M GOING TO -- WE'RE GOING

3079
01:51:59,920 --> 01:52:02,200
TO GO FOR A LUNCH BREAK NOW, AND

3080
01:52:02,200 --> 01:52:08,000
WE ARE GOING TO RECONVENE AT

3081
01:52:08,000 --> 01:52:09,320
1:20 FOR SESSION 1 ON 3D TISSUE

3082
01:52:09,320 --> 01:52:11,200
MODELS, UTILITY AND LIMITATIONS.

3083
01:52:11,200 --> 01:52:14,880
HOPEFULLY YOU'RE ENJOYING TODAY

3084
01:52:14,880 --> 01:52:17,960
AND YOU ARE GOING TO ENJOY

3085
01:52:17,960 --> 01:52:18,400
SESSION 1.

3086
01:52:18,400 --> 01:52:20,600
SO HAVE A GREAT LUNCH BREAK, AND

3087
01:52:20,600 --> 01:52:23,520
LET'S RECONVENE AT 1:20.

3088
01:52:23,520 --> 01:52:25,320
I'M GOING TO PULL UP THE AGENDA

3089
01:52:25,320 --> 01:52:27,480
HERE SO PEOPLE ARE AWARE.

3090
01:52:27,480 --> 01:52:31,400
SO 1:20 P.M., SESSION 1 ON 3D

3091
01:52:31,400 --> 01:52:33,600
TISSUE MODELS:  UTILITY AND

3092
01:52:33,600 --> 01:52:33,920
LIMITATIONS.

3093
01:52:33,920 --> 01:52:38,240
THANK YOU.

3094
01:52:38,240 --> 01:52:39,800
>>WELCOME BACK, EVERYONE.

3095
01:52:39,800 --> 01:52:41,320
NEXT WE ARE GOING TO HAVE

3096
01:52:41,320 --> 01:52:43,320
SESSION 1 WHICH IS ON 3D TISSUE

3097
01:52:43,320 --> 01:52:44,600
MODELS AND THEIR UTILITY AND

3098
01:52:44,600 --> 01:52:45,040
LIMITATIONS.

3099
01:52:45,040 --> 01:52:47,160
THIS SESSION IS CHAIRED BY

3100
01:52:47,160 --> 01:52:50,760
DR. MARK FERRER, CURRENTLY THE

3101
01:52:50,760 --> 01:52:52,920
DIRECTOR OF THE 3D TISSUE

3102
01:52:52,920 --> 01:52:53,920
BIOPRINTING LABORATORY AT THE

3103
01:52:53,920 --> 01:52:55,640
NATIONAL CENTER OF ADVANCING

3104
01:52:55,640 --> 01:52:57,000
TRANSLATIONAL SCIENCES AT NIH,

3105
01:52:57,000 --> 01:52:59,240
WHICH IS A MULTIDISCIPLINARY

3106
01:52:59,240 --> 01:53:00,920
GROUP ESTABLISHED IN 2018 WITH

3107
01:53:00,920 --> 01:53:03,320
THE GOAL OF CREATING, VALIDATING

3108
01:53:03,320 --> 01:53:06,080
AND USING 3D BIOENGINEERED

3109
01:53:06,080 --> 01:53:08,040
TISSUES FOR DISEASE MODELING AND

3110
01:53:08,040 --> 01:53:10,760
PREDICTIVE DRUG DISCOVERY AND

3111
01:53:10,760 --> 01:53:11,080
DEVELOPMENT.

3112
01:53:11,080 --> 01:53:12,400
THANK YOU FOR BEING HERE, MARK,

3113
01:53:12,400 --> 01:53:14,640
AND I'LL PASS THE BATON TO YOU.

3114
01:53:14,640 --> 01:53:18,200
>> THANKS SO MUCH, IS A   
SARI.

3115
01:53:18,200 --> 01:53:20,160
WELCOME, EVERYONE, BACK TO

3116
01:53:20,160 --> 01:53:20,560
SESSION 1.

3117
01:53:20,560 --> 01:53:23,120
I WANT TO THANK THE SPEAKERS FOR

3118
01:53:23,120 --> 01:53:24,840
MAKING THE TIME TO TELL US ABOUT

3119
01:53:24,840 --> 01:53:28,440
THEIR RESEARCH, ESPECIALLY

3120
01:53:28,440 --> 01:53:29,680
CHRISTINE AND HANS FROM EUROPE,

3121
01:53:29,680 --> 01:53:33,400
WE KNOW IT'S LATE OVER THERE.

3122
01:53:33,400 --> 01:53:35,440
AS SARINE MENTIONED AT THE

3123
01:53:35,440 --> 01:53:36,560
BEGINNING, THE OBJECTIVE OF THIS

3124
01:53:36,560 --> 01:53:38,440
SESSION WAS TO REALLY GIVE AN

3125
01:53:38,440 --> 01:53:39,520
OVERVIEW NOT SPECIFICALLY FOR

3126
01:53:39,520 --> 01:53:41,840
VIRUSES BUT IN GENERAL OF WHAT

3127
01:53:41,840 --> 01:53:45,440
TISSUE MODELS ARE AVAILABLE AND

3128
01:53:45,440 --> 01:53:46,320
DISCUSS THE CHALLENGES IN

3129
01:53:46,320 --> 01:53:50,680
BUILDING THESE MODELS AS WELL AS

3130
01:53:50,680 --> 01:53:54,160
IMPLEMENTING THEIR USE FOR DRUG

3131
01:53:54,160 --> 01:53:57,120
SCREENING AND DEVELOPMENT AND

3132
01:53:57,120 --> 01:53:58,560
REALLY THE GOOD AND THE BAD.

3133
01:53:58,560 --> 01:54:02,280
SO HOPEFULLY WE'LL HAVE TIME TO

3134
01:54:02,280 --> 01:54:06,600
GO THROUGH THE TALKS, REMINDER

3135
01:54:06,600 --> 01:54:08,040
BECAUSE IT'S 20 MINUTES, SO WHAT

3136
01:54:08,040 --> 01:54:09,840
I'LL DO IS I'M GOING TO TURN MY

3137
01:54:09,840 --> 01:54:13,080
CAMERA OFF AND THEN TWO MINUTES

3138
01:54:13,080 --> 01:54:14,840
BEFORE THE 20 MINUTES, I'LL TURN

3139
01:54:14,840 --> 01:54:18,120
IT ON SO THAT WILL BE THE SIGN

3140
01:54:18,120 --> 01:54:19,440
THAT THE -- THE SIGNAL THAT YOU

3141
01:54:19,440 --> 01:54:20,880
HAVE 2 MINUTES LEFT.

3142
01:54:20,880 --> 01:54:23,840
AND THEN AGAIN, AS SARINE

3143
01:54:23,840 --> 01:54:25,040
MENTIONED, WE'RE GOING TO GO

3144
01:54:25,040 --> 01:54:27,400
FROM ONE SPEAKER TO THE OTHER

3145
01:54:27,400 --> 01:54:28,440
AND THEM WE'RE GOING TO HAVE

3146
01:54:28,440 --> 01:54:32,680
HALF AN HOUR AT THE END FOR

3147
01:54:32,680 --> 01:54:34,200
QUESTIONS AND DISCUSSIONS.

3148
01:54:34,200 --> 01:54:35,760
IF YOU HAVE ANY QUESTIONS ALONG

3149
01:54:35,760 --> 01:54:39,640
THE WAY, YOU CAN PUT THEM IN

3150
01:54:39,640 --> 01:54:43,280
QUESTIONS AND ANSWERS BOX, AND

3151
01:54:43,280 --> 01:54:44,600
THE SPEAKERS ARE WELCOME TO

3152
01:54:44,600 --> 01:54:48,960
PROVIDE ANSWERS IN WRITING OR WE

3153
01:54:48,960 --> 01:54:50,920
CAN ADDRESS THEM AT THE END AS

3154
01:54:50,920 --> 01:54:51,160
WELL.

3155
01:54:51,160 --> 01:54:53,920
SO WITHOUT FURTHER ADO, IT IS MY

3156
01:54:53,920 --> 01:54:55,840
PLEASURE TO INTRODUCE THE FIRST

3157
01:54:55,840 --> 01:54:58,720
SPEAKER OF THIS SESSION,

3158
01:54:58,720 --> 01:55:00,760
DR. CHRISTINE MUMMERY, PROFESSOR

3159
01:55:00,760 --> 01:55:02,640
OF DEVELOPMENTAL BIOLOGY IN THE

3160
01:55:02,640 --> 01:55:07,400
DEPARTMENT OF ANATOMY AT LEIDEN

3161
01:55:07,400 --> 01:55:08,800
UNIVERSITY MEDICAL CENTER, WHERE

3162
01:55:08,800 --> 01:55:13,480
SHE ALSO HEADS THE FACILITY.

3163
01:55:13,480 --> 01:55:16,440
SHE'S A MEMBER OF THE ROYAL

3164
01:55:16,440 --> 01:55:19,160
ACADEMY OF SCIENCE AND PAST

3165
01:55:19,160 --> 01:55:20,680
PRESIDENT OF SOCIETY OF STEM

3166
01:55:20,680 --> 01:55:21,360
CELL RESEARCH.

3167
01:55:21,360 --> 01:55:24,960
SHE'S GOING TO TELL US ABOUT HER

3168
01:55:24,960 --> 01:55:26,360
RESEARCH IN CARDIOVASCULAR

3169
01:55:26,360 --> 01:55:26,920
DISEASES.

3170
01:55:26,920 --> 01:55:31,120
CHRISTINE, THE FLOOR IS YOURS.

3171
01:55:31,120 --> 01:55:37,560
>> THANK YOU.

3172
01:55:37,560 --> 01:55:39,080
CAN YOU SEE MY SCREEN?

3173
01:55:39,080 --> 01:55:40,720
>> YEAH, YOU HAVE TO MAKE
IT

3174
01:55:40,720 --> 01:55:41,600
PRESENTATION MODE BUT OTHERWISE

3175
01:55:41,600 --> 01:55:47,840
WE SEE IT.

3176
01:55:47,840 --> 01:55:48,120
>> PERFECT.

3177
01:55:48,120 --> 01:55:52,520
>> OKAY, THANK YOU.

3178
01:55:52,520 --> 01:55:54,480
SO I WAS ASKED TO TALK ABOUT

3179
01:55:54,480 --> 01:55:55,680
CARDIOVASCULAR DISEASE MODEL,

3180
01:55:55,680 --> 01:55:57,560
AND TOWARDS STANDARDIZATION OF

3181
01:55:57,560 --> 01:55:59,200
HOW WE MIGHT USE THEM.

3182
01:55:59,200 --> 01:56:03,120
AND IN THE CONTEXT OF VIRUS,

3183
01:56:03,120 --> 01:56:05,760
IT'S QUITE IMPORTANT TO DISCUSS

3184
01:56:05,760 --> 01:56:06,600
THE LIMITATIONS.

3185
01:56:06,600 --> 01:56:09,920
SO I'M GOING TO DISCUSS THAT A

3186
01:56:09,920 --> 01:56:11,000
LITTLE BIT, AND HERE IS A SORT

3187
01:56:11,000 --> 01:56:13,960
OF OVERVIEW OF WHAT WE CAN DO

3188
01:56:13,960 --> 01:56:15,040
WITH PLURIPOTENT STEM CELLS.

3189
01:56:15,040 --> 01:56:17,240
SO WE CAN MAKE THEM FORM ALL

3190
01:56:17,240 --> 01:56:18,320
DERIVATIVES OF THE BODY, AND IN

3191
01:56:18,320 --> 01:56:20,240
MANY CASES, WE CAN DO THAT NOW

3192
01:56:20,240 --> 01:56:26,520
IN VITRO VERY SUCCESSFULLY, BUT

3193
01:56:26,520 --> 01:56:28,080
WE ALL KNOW THE LIMITATIONS OF

3194
01:56:28,080 --> 01:56:29,280
THIS MODEL ARE THAT THE CELLS

3195
01:56:29,280 --> 01:56:30,800
ARE ALL IMMATURE.

3196
01:56:30,800 --> 01:56:32,240
AND THIS IN THE CONTEXT OF,

3197
01:56:32,240 --> 01:56:35,160
LET'S SAY, COVID RESEARCH HAS

3198
01:56:35,160 --> 01:56:37,240
NOT BEEN PARTICULARLY BENEFICIAL

3199
01:56:37,240 --> 01:56:38,920
BECAUSE IF I WOULD TAKE THE

3200
01:56:38,920 --> 01:56:40,960
HEART AS AN EXAMPLE,

3201
01:56:40,960 --> 01:56:43,000
CARDIOMYOCYTES FROM IPS CELLS,

3202
01:56:43,000 --> 01:56:45,600
FOR EXAMPLE, EXPRESS ACE

3203
01:56:45,600 --> 01:56:46,800
2 RECEPTORS, BUT THEY'RE NOT

3204
01:56:46,800 --> 01:56:50,120
REALLY EXPRESSED VERY HIGHLY IN

3205
01:56:50,120 --> 01:56:50,720
THE ADULT HEART.

3206
01:56:50,720 --> 01:56:52,680
SO WE HAVE TO BE VERY CAREFUL IN

3207
01:56:52,680 --> 01:56:55,520
INTERPRETING SOME OF THIS DATA.

3208
01:56:55,520 --> 01:56:56,520
SO LET ME TELL YOU SOMETHING

3209
01:56:56,520 --> 01:56:58,080
ABOUT HOW WE'VE BEEN OVERCOMING

3210
01:56:58,080 --> 01:57:01,440
THIS LIMITATION AND ARE TRYING

3211
01:57:01,440 --> 01:57:03,320
TO MAKE MATURE CARDIOMYOCYTES

3212
01:57:03,320 --> 01:57:06,120
THAT WE CAN MOVE FORWARD IN

3213
01:57:06,120 --> 01:57:07,240
MODELING DISEASE, AND I'LL GIVE

3214
01:57:07,240 --> 01:57:12,800
YOU SOME EXAMPLES.

3215
01:57:12,800 --> 01:57:14,560
SO WHAT DO I MEAN ABOUT IMMATURE

3216
01:57:14,560 --> 01:57:15,000
CELLS?

3217
01:57:15,000 --> 01:57:20,120
THIS IS BEATING CELLS -- THE

3218
01:57:20,120 --> 01:57:22,000
BEATING MEANS THEY ARE IMMATURE

3219
01:57:22,000 --> 01:57:23,400
BECAUSE AN ADULT HEART CELL

3220
01:57:23,400 --> 01:57:25,440
WOULD NOT BEAT BY ITSELF, IT

3221
01:57:25,440 --> 01:57:26,680
WOULD NEED A PACEMAKER.

3222
01:57:26,680 --> 01:57:28,200
HERE ARE NO PACEMAKERS SO WE

3223
01:57:28,200 --> 01:57:29,000
KNOW IT'S IMMATURE.

3224
01:57:29,000 --> 01:57:30,840
IT LACKS A 3D ENVIRONMENT, AND

3225
01:57:30,840 --> 01:57:33,440
IT LACKS OTHER CARDIAC-SPECIFIC

3226
01:57:33,440 --> 01:57:33,720
CELL TYPES.

3227
01:57:33,720 --> 01:57:37,280
SO WE ASKED THE QUESTION, WOULD

3228
01:57:37,280 --> 01:57:38,640
IT BE POSSIBLE TO ADD THESE

3229
01:57:38,640 --> 01:57:40,720
CELLS IN IN A 3D ENVIRONMENT AND

3230
01:57:40,720 --> 01:57:41,760
CREATE SOMETHING THAT LOOKED

3231
01:57:41,760 --> 01:57:43,320
MORE LIKE HEART TISSUE.

3232
01:57:43,320 --> 01:57:46,720
AND JUST TO BRIEFLY SHOW YOU THE

3233
01:57:46,720 --> 01:57:48,120
HEART, THIS IS THE MYOCARDIUM

3234
01:57:48,120 --> 01:57:49,760
HERE, LINED WITH AN ENDO CARD

3235
01:57:49,760 --> 01:57:50,560
YUM.

3236
01:57:50,560 --> 01:57:52,080
THERE'S AN OUTER LAYER OF EP

3237
01:57:52,080 --> 01:58:00,480
CARD YUM THAT          EP --

3238
01:58:00,480 --> 01:58:01,760
FORM ABOUT 70% OF THE CELLS IN

3239
01:58:01,760 --> 01:58:03,640
THE HEART.

3240
01:58:03,640 --> 01:58:04,880
EVERY CARDIOMYOCYTE TOUCHES A

3241
01:58:04,880 --> 01:58:07,160
BLOOD VESSEL SO IT TOUCHES AN

3242
01:58:07,160 --> 01:58:07,600
ENDOTHELIAL CELL.

3243
01:58:07,600 --> 01:58:09,560
SO WE THOUGHT WE MIGHT MAKE A

3244
01:58:09,560 --> 01:58:11,440
MODEL IN WHICH WE INCLUDED THE

3245
01:58:11,440 --> 01:58:13,400
ENDOTHELIAL CELLS, CARDIAC

3246
01:58:13,400 --> 01:58:14,360
FIBROBLASTS, SO REMEMBER EVERY

3247
01:58:14,360 --> 01:58:16,560
TISSUE HAS ITS OWN TYPE OF

3248
01:58:16,560 --> 01:58:18,560
STROMA CELLS, IT'S OWN TYPE OF

3249
01:58:18,560 --> 01:58:21,720
END THEEL YELL CELLS, ITS OWN

3250
01:58:21,720 --> 01:58:23,160
TYPE OF FIBROBLASTS THAT WE

3251
01:58:23,160 --> 01:58:26,200
WOULD DERIVE FROM EPICARDIAL

3252
01:58:26,200 --> 01:58:27,720
CELLS AND THE CARDIOMYOCYTES.

3253
01:58:27,720 --> 01:58:28,800
THE FIRST THING WE NEEDED TO DO

3254
01:58:28,800 --> 01:58:30,600
WAS TO ACTUALLY GET THE

3255
01:58:30,600 --> 01:58:32,560
DIFFERENTIATION PROTOCOLS VERY

3256
01:58:32,560 --> 01:58:34,720
ROBUST, SO WE WANTED TO USE ONE

3257
01:58:34,720 --> 01:58:38,120
BASAL MEDIUM TO DERIVE THESE

3258
01:58:38,120 --> 01:58:40,560
CELL TYPES AND WHERE POSSIBLE

3259
01:58:40,560 --> 01:58:42,000
MOVE AWAY FROM GROWTH FACTORS.

3260
01:58:42,000 --> 01:58:43,760
THIS WOULD REDUCE LOT TO LOT

3261
01:58:43,760 --> 01:58:45,160
VARIABILITY, WOULD ENABLE

3262
01:58:45,160 --> 01:58:49,000
UPSCALING AND REDUCE COSTS.

3263
01:58:49,000 --> 01:58:49,880
ESSENTIALLY THAT'S WHAT WE'VE

3264
01:58:49,880 --> 01:58:50,960
WORKED ON FOR THE LAST SEVERAL

3265
01:58:50,960 --> 01:58:52,480
YEARS, WE HAVE MANY OF THESE

3266
01:58:52,480 --> 01:58:53,720
PROTOCOLS HIGHLY DEFINED, SOME

3267
01:58:53,720 --> 01:58:57,000
BASED ON SMALL MOLECULES.

3268
01:58:57,000 --> 01:59:00,280
WE CAN NOW DERIVE ENDOTHELIAL

3269
01:59:00,280 --> 01:59:02,600
CELLS, CARDIOMYOCYTES AND

3270
01:59:02,600 --> 01:59:03,600
CARDIOFIBROBLASTS FROM A COMMON

3271
01:59:03,600 --> 01:59:05,080
PROGENITOR THAT WE GET FROM IPS

3272
01:59:05,080 --> 01:59:05,440
CELLS.

3273
01:59:05,440 --> 01:59:07,520
WE CAN NOW CRYOPRESERVE THESE IN

3274
01:59:07,520 --> 01:59:08,240
LARGE BATCHES.

3275
01:59:08,240 --> 01:59:10,440
WE CAN CARRY OUT QA AND QC

3276
01:59:10,440 --> 01:59:12,520
BEFORE FREEZING, AND THESE ARE

3277
01:59:12,520 --> 01:59:15,160
READY TO USE IN ASSAYS AFTER

3278
01:59:15,160 --> 01:59:19,200
THAW, SO THIS MAKES IT A GREAT

3279
01:59:19,200 --> 01:59:23,920
ADVANTAGE FOR DOING ASSAYS.

3280
01:59:23,920 --> 01:59:25,240
SO WHAT DO WE MEAN BY

3281
01:59:25,240 --> 01:59:25,680
MATURATION?

3282
01:59:25,680 --> 01:59:28,200
HOW WOULD WE RECOGNIZE IF IT

3283
01:59:28,200 --> 01:59:30,280
OCCURRED IN OUR CARDIOMYOCYTES?

3284
01:59:30,280 --> 01:59:31,720
IT'S VERY SIMPLE, WE WOULD LOOK

3285
01:59:31,720 --> 01:59:34,600
AT GENE EXPRESSION, LOOKING AT

3286
01:59:34,600 --> 01:59:39,680
WHETHER SUPPLIES         

3287
01:59:39,680 --> 01:59:42,320
WHETHER SPLICE, STRUCTURE,

3288
01:59:42,320 --> 01:59:43,200
CONTRACTION, ELECTROPHYSIOLOGY

3289
01:59:43,200 --> 01:59:46,560
AND METABOLISM, THEY WILL ALL

3290
01:59:46,560 --> 01:59:48,520
DIFFER FROM WHAT WE WOULD SEE IN

3291
01:59:48,520 --> 01:59:50,160
A PLURIPOTENT STEM CELL.

3292
01:59:50,160 --> 01:59:52,360
THESE ARE CARRIED OUT TO TRY TO

3293
01:59:52,360 --> 01:59:54,400
MATURE CARDIOMYOCYTES, ENGINEER

3294
01:59:54,400 --> 01:59:57,040
HEART TISSUES, 3D STRETCHING

3295
01:59:57,040 --> 01:59:59,920
SORT OF STRUCTURES, CHANGING THE

3296
01:59:59,920 --> 02:00:01,360
CULTURE REAGENTS, USING ECK PO

3297
02:00:01,360 --> 02:00:02,560
TICK GENE EXPRESSION, USING

3298
02:00:02,560 --> 02:00:05,040
SOMETHING CALLED A BIOWIRE, 3D

3299
02:00:05,040 --> 02:00:06,800
PRINTING, ALIGNING THE CELLS.

3300
02:00:06,800 --> 02:00:11,520
THEY ALL WORK TO A CERTAIN

3301
02:00:11,520 --> 02:00:12,840
EXPECT BUT WE WANTED A VERY

3302
02:00:12,840 --> 02:00:14,040
SIMPLE LOW TECH METHOD.

3303
02:00:14,040 --> 02:00:15,640
SO WE DECIDED TO MAKE SIMPLE

3304
02:00:15,640 --> 02:00:19,080
MICRO TISSUES.

3305
02:00:19,080 --> 02:00:21,360
SO WE'RE USING THESE

3306
02:00:21,360 --> 02:00:22,320
PREDIFFERENTIATED CELLS, WE CAN

3307
02:00:22,320 --> 02:00:28,120
DO THESE ASSAYS ISOGENICLY.

3308
02:00:28,120 --> 02:00:29,960
WE PUT THEM TOGETHER AS 5,000

3309
02:00:29,960 --> 02:00:33,600
CELLS IN THESE RATIOS, SO 70%

3310
02:00:33,600 --> 02:00:34,560
CARDIOMYOCYTES, 15% OF EACH OF

3311
02:00:34,560 --> 02:00:36,560
THE OTHER CELLS, AND PUT THEM IN

3312
02:00:36,560 --> 02:00:38,080
MULTI-WELL PLATES AND WE GET

3313
02:00:38,080 --> 02:00:44,440
THESE BEATING HEART CELLS.

3314
02:00:44,440 --> 02:00:45,840
THESE MINI HEARTS, YOU COULD

3315
02:00:45,840 --> 02:00:49,240
SAY, IN A METAPHOR.

3316
02:00:49,240 --> 02:00:50,320
IT'S VERY LOW TECH.

3317
02:00:50,320 --> 02:00:52,520
SO WITHOUT SHOWING YOU ALL THE

3318
02:00:52,520 --> 02:00:53,960
DATA, THIS IS WHAT OUR MICRO

3319
02:00:53,960 --> 02:00:54,480
TISSUES LOOK LIKE.

3320
02:00:54,480 --> 02:00:58,440
WE SEE THE CARDIOFIBROBLASTS,

3321
02:00:58,440 --> 02:00:59,760
THE ENDOTHELIAL CELLS ARE LINED

3322
02:00:59,760 --> 02:01:03,560
UP IN THESE TWO STRUCTURES.

3323
02:01:03,560 --> 02:01:06,320
WE CAN COUPLE THEM INTO ORGAN ON

3324
02:01:06,320 --> 02:01:08,720
CHIP MODELS AND CREATE A LUMEN

3325
02:01:08,720 --> 02:01:11,240
THAT'S FULLY VASCULARIZED AND

3326
02:01:11,240 --> 02:01:13,640
THE CARDIOMYOCYTES ARE MARKED

3327
02:01:13,640 --> 02:01:14,280
HERE IN GREEN.

3328
02:01:14,280 --> 02:01:16,720
WE SHOW THESE HAVE STRUCTURAL

3329
02:01:16,720 --> 02:01:17,680
MATURITY, ELECTRICAL AND

3330
02:01:17,680 --> 02:01:19,320
MECHANICAL MATURITY AND

3331
02:01:19,320 --> 02:01:20,760
METABOLIC MATURITY.

3332
02:01:20,760 --> 02:01:23,240
THE FEATURES ACTUALLY OF AN

3333
02:01:23,240 --> 02:01:24,840
EARLY POSTNATAL CARDIOMYOCYTE,

3334
02:01:24,840 --> 02:01:28,280
SO THEY'RE NOT FULLY ADULTS AND

3335
02:01:28,280 --> 02:01:31,720
CERTAINLY NOT OLD, WITH YOU    E

3336
02:01:31,720 --> 02:01:32,360
POSTNATAL.

3337
02:01:32,360 --> 02:01:34,960
USING JUST 5,000    5,000 CELLSR

3338
02:01:34,960 --> 02:01:37,680
TISSUE, WE CAN REDUCE THE COST

3339
02:01:37,680 --> 02:01:42,080
TO  

3340
02:01:42,080 --> 02:01:43,400
IN THE RANGE OF WHAT PHARMA

3341
02:01:43,400 --> 02:01:45,160
WOULD LIKE TO HAVE FOR DRUG

3342
02:01:45,160 --> 02:01:45,480
ASSAYS.

3343
02:01:45,480 --> 02:01:47,760
AND WE CAN DO MULTI-LINEAGE

3344
02:01:47,760 --> 02:01:50,480
CARDIAC DISEASE MODELING.

3345
02:01:50,480 --> 02:01:52,480
WHAT I MEAN BY THAT IS WE CAN

3346
02:01:52,480 --> 02:01:53,960
REPLACE ANY ONE OF THOSE THREE

3347
02:01:53,960 --> 02:01:58,680
CELL TYPES, THE GUY WROA      G,

3348
02:01:58,680 --> 02:02:01,440
ENDOTHELIAL CELLS OR RM -- FROM

3349
02:02:01,440 --> 02:02:02,520
CONTAINING A MUTATION.

3350
02:02:02,520 --> 02:02:04,520
SO IT ALLOWS US TO IDENTIFY

3351
02:02:04,520 --> 02:02:05,800
WHICH CELL IS CONTRIBUTING TO A

3352
02:02:05,800 --> 02:02:06,120
PHENOTYPE.

3353
02:02:06,120 --> 02:02:08,000
I'LL GIVE YOU ONE QUICK EXAMPLE

3354
02:02:08,000 --> 02:02:11,960
HERE OF THESE TRI--LINEAGE

3355
02:02:11,960 --> 02:02:12,560
MODELS.

3356
02:02:12,560 --> 02:02:14,760
IT'S AN EXAMPLE OF A DISEASE

3357
02:02:14,760 --> 02:02:20,040
CALLED ARRHYTHMOGENIC

3358
02:02:20,040 --> 02:02:20,400
CARDIOMYOPATHY.

3359
02:02:20,400 --> 02:02:24,840
IT'S CAUSED BY MUTATIONS OF THE

3360
02:02:24,840 --> 02:02:26,480
DESMOSOMAL PROTEIN PKP26789.

3361
02:02:26,480 --> 02:02:28,040
IT'S CHARACTERIZED BY

3362
02:02:28,040 --> 02:02:29,640
ARRHYTHMIAS AND FIBRO-FATTY

3363
02:02:29,640 --> 02:02:30,360
REPLACEMENT OF THE MIGHT OWE

3364
02:02:30,360 --> 02:02:31,400
CARD YUM.

3365
02:02:31,400 --> 02:02:34,480
THE CELL OF ORIGIN IS UNKNOWN,

3366
02:02:34,480 --> 02:02:36,080
POSTULATED THAT CARDIAC

3367
02:02:36,080 --> 02:02:37,080
FIBROBLASTS MAY ALSO PLAY A

3368
02:02:37,080 --> 02:02:37,480
ROLE.

3369
02:02:37,480 --> 02:02:39,720
SO WHAT WE DID WAS TO REPLACE

3370
02:02:39,720 --> 02:02:41,440
THE CARDIAC FIBROBLASTS IN THE

3371
02:02:41,440 --> 02:02:43,640
MICRO TISSUES WITH THESE ACM

3372
02:02:43,640 --> 02:02:46,920
MUTANT CARDIAC FIBROBLASTS

3373
02:02:46,920 --> 02:02:47,440
ISOGENICLY.

3374
02:02:47,440 --> 02:02:48,760
SO TO CUT A LONG STORY SHORT,

3375
02:02:48,760 --> 02:02:50,520
THIS IS AN EXAMPLE OF WHAT THESE

3376
02:02:50,520 --> 02:02:53,240
MICRO TISSUES LOOK LIKE AND

3377
02:02:53,240 --> 02:02:56,760
WHAT'S SHOWN HERE IS THE

3378
02:02:56,760 --> 02:02:58,040
STAINING FOR THE JUNCTIONS.

3379
02:02:58,040 --> 02:02:59,840
YOU CAN SEE THE CONTROL HERE ON

3380
02:02:59,840 --> 02:03:04,520
THE LEFT, THERE'S A GREAT DEAL

3381
02:03:04,520 --> 02:03:08,320
OF FORMATION, AND YOU SEE IN THE

3382
02:03:08,320 --> 02:03:11,280
MUTANT CELLS THE CARDIAC

3383
02:03:11,280 --> 02:03:13,000
FIBROBLASTS FORM FEWER GAP

3384
02:03:13,000 --> 02:03:15,400
JUNCTIONS AND THIS IS CAUSED BY

3385
02:03:15,400 --> 02:03:17,720
THE ABSENCE OF PKP2.

3386
02:03:17,720 --> 02:03:19,080
BUT MOST IMPORTANTLY, WHEN WE

3387
02:03:19,080 --> 02:03:21,040
START PACING THESE CELLS, SO

3388
02:03:21,040 --> 02:03:23,760
YOUR HEART NORMALLY BEATS AT

3389
02:03:23,760 --> 02:03:24,760
1 HERTZ 60 TIMES A MINUTE, YOU

3390
02:03:24,760 --> 02:03:26,720
CAN SEE THE CONTROL MICRO

3391
02:03:26,720 --> 02:03:27,920
TISSUES HERE FOLLOWING THIS

3392
02:03:27,920 --> 02:03:29,360
PACING VERY NICELY.

3393
02:03:29,360 --> 02:03:31,320
IT'S NOT TOO BAD FOR THE ONES

3394
02:03:31,320 --> 02:03:32,720
CONTAINING THE MUTANT

3395
02:03:32,720 --> 02:03:34,480
FIBROBLASTS BUT IF WE GO TO

3396
02:03:34,480 --> 02:03:35,520
2 HERTZ, YOU SEE THEY'RE HAVING

3397
02:03:35,520 --> 02:03:37,000
DIFFICULTY FOLLOWING THE PACING

3398
02:03:37,000 --> 02:03:37,320
SIGNALS.

3399
02:03:37,320 --> 02:03:39,400
AND WHEN WE GO TO 3 HERTZ, WHICH

3400
02:03:39,400 --> 02:03:42,800
IS ABOUT WHEN YOU MIGHT BE

3401
02:03:42,800 --> 02:03:44,000
RUNNING A MARATHON OR SOMETHING,

3402
02:03:44,000 --> 02:03:47,920
YOU CAN SEE HERE THESE VERY

3403
02:03:47,920 --> 02:03:48,920
PROMINENT ARRHYTHMIAS.

3404
02:03:48,920 --> 02:03:50,440
SO THIS IS TELLING US THAT

3405
02:03:50,440 --> 02:03:52,320
ACTUALLY THE CARDIAC FIBROBLASTS

3406
02:03:52,320 --> 02:03:54,960
ARE ONE OF THE CULPRITS IN THIS

3407
02:03:54,960 --> 02:03:56,480
DISEASE, SO THE CARDIOMYOCYTES

3408
02:03:56,480 --> 02:03:58,200
ARE NORMAL, YET WE'RE GETTING

3409
02:03:58,200 --> 02:03:59,560
THESE ARRHYTHMIAS.

3410
02:03:59,560 --> 02:04:02,440
ANOTHER QUICK EXAMPLE.

3411
02:04:02,440 --> 02:04:13,280
MANY OF YOU KNOW THAT      KNOWT

3412
02:04:17,640 --> 02:04:19,000
DOXORUBICIN IS USED FOR AS YOE

3413
02:04:19,000 --> 02:04:20,520
CAR SOMA IN CHILDREN AND BREAST

3414
02:04:20,520 --> 02:04:21,200
CANCER.

3415
02:04:21,200 --> 02:04:23,360
THE PROBLEM IS MANY PATIENTS

3416
02:04:23,360 --> 02:04:26,000
DEVELOP IRREVERSIBLE HEART

3417
02:04:26,000 --> 02:04:26,640
FAILURE 2 TO 10 YEARS AFTER

3418
02:04:26,640 --> 02:04:27,560
TREATMENT AND THE ONLY THING

3419
02:04:27,560 --> 02:04:28,640
THAT CAN BE DONE FOR THESE

3420
02:04:28,640 --> 02:04:30,720
PATIENTS IS HEART REPLACEMENT.

3421
02:04:30,720 --> 02:04:33,440
SO WHAT WE CAN SEE HERE ON THE

3422
02:04:33,440 --> 02:04:37,040
TOP IS VECTORROLOGY SHOWING THE

3423
02:04:37,040 --> 02:04:38,560
CONTRACTION OF A SINGLE MICRO

3424
02:04:38,560 --> 02:04:40,240
TISSUE HERE, YOU CAN SEE IN THE

3425
02:04:40,240 --> 02:04:41,840
GRAPH ON THE RIGHT, THE

3426
02:04:41,840 --> 02:04:44,240
CONTRACTION FOLLOWED BY THE

3427
02:04:44,240 --> 02:04:45,600
RELAXATION, QUANTIFIED IN THIS

3428
02:04:45,600 --> 02:04:47,000
PLOT HERE.

3429
02:04:47,000 --> 02:04:47,760
AND AT THE BOTTOM.

3430
02:04:47,760 --> 02:04:50,680
YOU CAN SEE WHAT DOXORUBICIN

3431
02:04:50,680 --> 02:04:50,880
DOES.

3432
02:04:50,880 --> 02:04:52,640
IT REDUCES THE AMOUNT OF

3433
02:04:52,640 --> 02:04:55,640
CONTRACTION SIG   SIGNIFICANTLY.

3434
02:04:55,640 --> 02:04:59,480
NOW A COLLEAGUE OF MINE IN

3435
02:04:59,480 --> 02:05:01,360
LEIDEN IS A BRILLIANT MEDICINAL

3436
02:05:01,360 --> 02:05:03,520
CHEMIST AND HE FIGURED OUT THAT

3437
02:05:03,520 --> 02:05:05,600
DOXORUBICIN ACTUALLY HAD TWO

3438
02:05:05,600 --> 02:05:06,200
PARTICULAR BIOLOGICAL EFFECTS.

3439
02:05:06,200 --> 02:05:09,560
IT CAN CAUSE DNA DAMAGE, AND IT

3440
02:05:09,560 --> 02:05:11,040
CAUSES HISTONE EVICTION.

3441
02:05:11,040 --> 02:05:12,920
AND IT'S THE DNA DAMAGE THAT

3442
02:05:12,920 --> 02:05:15,120
ACTUALLY CAUSES THE DAMAGE TO

3443
02:05:15,120 --> 02:05:17,200
THE HEART AND THE HISTONE

3444
02:05:17,200 --> 02:05:19,400
EVICTION IS THE ACTIVITY

3445
02:05:19,400 --> 02:05:20,480
RESPONSIBLE FOR KILLING THE

3446
02:05:20,480 --> 02:05:21,880
TUMOR.

3447
02:05:21,880 --> 02:05:24,880
SO HE DESIGNED VARIANTS OF

3448
02:05:24,880 --> 02:05:26,520
DOXORUBICIN WHICH ONLY HAVE THE

3449
02:05:26,520 --> 02:05:29,440
HISTONE EVICTION PART AND NOT

3450
02:05:29,440 --> 02:05:30,200
THE DNA DAMAGE.

3451
02:05:30,200 --> 02:05:31,840
AND THIS KILLED THE TUMORS, AND

3452
02:05:31,840 --> 02:05:35,560
WHAT WE SAW VERY NICELY IN THIS

3453
02:05:35,560 --> 02:05:37,000
MODEL OF THE MICRO TISSUES, HERE

3454
02:05:37,000 --> 02:05:38,520
YOU CAN SEE THE AMPLITUDE OF

3455
02:05:38,520 --> 02:05:39,600
CONTRACTION OF THE CONTROLS,

3456
02:05:39,600 --> 02:05:42,360
HERE YOU SEE WITH DOXORUBICIN,

3457
02:05:42,360 --> 02:05:50,560
BUT WHEN WE ADD THIS VARIANT,

3458
02:05:50,560 --> 02:05:55,160
ACLARUBICIN, THERE'S NO EFFECT

3459
02:05:55,160 --> 02:05:56,240
ON THE CONTRACTION.

3460
02:05:56,240 --> 02:05:57,760
WE'RE DISCUSSING WITH THE

3461
02:05:57,760 --> 02:05:59,320
AUTHORITIES IF THEY WOULD FIND

3462
02:05:59,320 --> 02:06:00,200
THIS ACCEPTABLE AS AN OPTION

3463
02:06:00,200 --> 02:06:01,600
INSTEAD OF A SECOND ANIMAL MODEL

3464
02:06:01,600 --> 02:06:02,360
TO THE MASS.

3465
02:06:02,360 --> 02:06:03,680
THEY DON'T ACTUALLY FIND IT

3466
02:06:03,680 --> 02:06:04,760
ACCEPTABLE, BUT THEY FOUND IT

3467
02:06:04,760 --> 02:06:11,560
VERY INTERESTING TO LOOK AT.

3468
02:06:11,560 --> 02:06:12,640
A THIRD EXAMPLE IS HOW WE CAN

3469
02:06:12,640 --> 02:06:14,200
NOW USE THIS FOR HIGH-THROUGHPUT

3470
02:06:14,200 --> 02:06:14,440
SCREENING.

3471
02:06:14,440 --> 02:06:15,920
AS I SAID, THESE TISSUES ARE

3472
02:06:15,920 --> 02:06:19,000
VERY EASY TO MAKE, WE CAN DO IT

3473
02:06:19,000 --> 02:06:20,640
WITH ROBOTICS NOW, PUT THEM IN

3474
02:06:20,640 --> 02:06:23,360
THESE LARGE WELL PLATES, A WE

3475
02:06:23,360 --> 02:06:24,560
CAN LOOK AT CALCIUM SIGNALING.

3476
02:06:24,560 --> 02:06:26,880
SO YOU CAN SEE THAT HERE, WE

3477
02:06:26,880 --> 02:06:30,880
LOADED THEM WITH A CALCIUM DYE,

3478
02:06:30,880 --> 02:06:32,040
YOU CAN SEE THEM FLASHING AND

3479
02:06:32,040 --> 02:06:33,800
YOU CAN SEE IN A HIGH-THROUGHPUT

3480
02:06:33,800 --> 02:06:36,600
SYSTEM WHERE THE DRUGS MIGHT

3481
02:06:36,600 --> 02:06:38,000
HAVE THIS EFFECT.

3482
02:06:38,000 --> 02:06:40,560
SO THIS IS WHAT WE WOULD SEE IF

3483
02:06:40,560 --> 02:06:41,640
THERE'S ARRHYTHMIAS AND THIS IS

3484
02:06:41,640 --> 02:06:43,040
WHAT WE WOULD SEE IF IT WAS

3485
02:06:43,040 --> 02:06:44,680
OKAY.

3486
02:06:44,680 --> 02:06:47,640
SO LOOKING AT YET ANOTHER

3487
02:06:47,640 --> 02:06:53,320
DISEASE, THIS IS CALLED CPVT.

3488
02:06:53,320 --> 02:06:55,200
IT ALSO CAUSES ARRHYTHMIAS BUT

3489
02:06:55,200 --> 02:06:59,480
IT'S CAUSED BY MUTATIONS IN A

3490
02:06:59,480 --> 02:07:01,080
RECEPTOR THAT REGULATES CALCIUM

3491
02:07:01,080 --> 02:07:01,680
HANDLING.

3492
02:07:01,680 --> 02:07:02,960
YOU CAN SEE HERE IN THAT SYSTEM

3493
02:07:02,960 --> 02:07:09,200
I JUST SHOWED YOU, THAT THERE'S

3494
02:07:09,200 --> 02:07:10,080
REGULAR CALCIUM BEATS.

3495
02:07:10,080 --> 02:07:12,560
IF WE GIVE THE CPV T-CELLS A

3496
02:07:12,560 --> 02:07:14,880
TRIGGER, YOU CAN SEE THESE

3497
02:07:14,880 --> 02:07:16,520
ARRHYTHMIAS REVEALED.

3498
02:07:16,520 --> 02:07:18,480
AND IF WE ADD A DRUG THAT WORKS

3499
02:07:18,480 --> 02:07:19,720
IN SOME PATIENTS BUT NOT OTHERS,

3500
02:07:19,720 --> 02:07:21,200
WE CAN SEE WE GET THIS RESCUE.

3501
02:07:21,200 --> 02:07:23,000
NOW IT'S BEEN VERY HARD IN ANY

3502
02:07:23,000 --> 02:07:26,480
OTHER MODELS TO ACTUALLY SEE THE

3503
02:07:26,480 --> 02:07:30,200
EFFECTS OF FLECANYDE.

3504
02:07:30,200 --> 02:07:31,520
WE HOPE NOW AND IN THE FUTURE WE

3505
02:07:31,520 --> 02:07:34,360
CAN DO POPULATION STUDIES AND

3506
02:07:34,360 --> 02:07:35,880
FIGURE OUT WHICH PATIENT IS

3507
02:07:35,880 --> 02:07:37,720
LAKELY TO RESPOND AND DO SCREENS

3508
02:07:37,720 --> 02:07:39,600
OF LIBRARIES TO SEE WHICH DRUGS

3509
02:07:39,600 --> 02:07:45,840
MIGHT BE EFFECTIVE.

3510
02:07:45,840 --> 02:07:48,240
MOVING NOW TO VASCULAR DISEASE,

3511
02:07:48,240 --> 02:07:49,360
VASCULAR DISEASE IS OFTEN CAUSED

3512
02:07:49,360 --> 02:07:50,960
BY A FAILURE TO HAVE PROPER

3513
02:07:50,960 --> 02:07:51,640
DIALOGUE BETWEEN THE CELLS THAT

3514
02:07:51,640 --> 02:07:53,280
MAKE UP THE VESSEL WALL.

3515
02:07:53,280 --> 02:07:55,920
SO THAT'S THE VEST COLLAR SMOOTH

3516
02:07:55,920 --> 02:07:57,880
MUSCLE CELLS, ENDOTHELIAL CELLS

3517
02:07:57,880 --> 02:08:00,240
AND PERHAPS THE IMMUNE SYSTEM IN

3518
02:08:00,240 --> 02:08:00,840
THE STROMA.

3519
02:08:00,840 --> 02:08:02,240
SO MUTATIONS IN ANY OF THESE

3520
02:08:02,240 --> 02:08:03,560
SIGNALING PATHWAYS BETWEEN THESE

3521
02:08:03,560 --> 02:08:08,360
CELLS CAUSE A VARIETY OF RARE

3522
02:08:08,360 --> 02:08:10,320
VASCULAR DISEASES.

3523
02:08:10,320 --> 02:08:11,200
TOGETHER, THERE ARE ACTUALLY

3524
02:08:11,200 --> 02:08:13,600
QUITE A LOT OF PEOPLE WITH THESE

3525
02:08:13,600 --> 02:08:14,800
CONDITIONS.

3526
02:08:14,800 --> 02:08:16,480
WE'RE PARTICULARLY INTERESTED IN

3527
02:08:16,480 --> 02:08:21,600
ONE CALLED HEREDITARY

3528
02:08:21,600 --> 02:08:22,800
HEMORRHAGIC TELANGIECTASIA.

3529
02:08:22,800 --> 02:08:23,960
THIS IS CAUSED BY DISTRACTION OF

3530
02:08:23,960 --> 02:08:25,400
A DIALOGUE BETWEEN THE

3531
02:08:25,400 --> 02:08:26,200
ENDOTHELIAL CELLS AND THE

3532
02:08:26,200 --> 02:08:27,600
PARASITES.

3533
02:08:27,600 --> 02:08:29,360
SO LOOKING TOWARDS

3534
02:08:29,360 --> 02:08:30,360
STANDARDIZATION, THIS IS VERY

3535
02:08:30,360 --> 02:08:34,400
IMPORTANT, SO WE CAN GET

3536
02:08:34,400 --> 02:08:35,920
CD31 POSITIVE ENDOTHELIAL CELLS

3537
02:08:35,920 --> 02:08:37,680
FROM IPS CELLS QUITE HAPPILY.

3538
02:08:37,680 --> 02:08:41,840
THEY SAY PROPERLY WITH THE RIGHT

3539
02:08:41,840 --> 02:08:48,320
MARKER SO HERE IN PECAM1 VON

3540
02:08:48,320 --> 02:08:50,920
WILLEBRAND FACTOR, AND WE CAN

3541
02:08:50,920 --> 02:08:53,560
STANDARDIZE THESE IN QA AND QC

3542
02:08:53,560 --> 02:08:55,080
BY QUANTIFYING FUNCTIONAL

3543
02:08:55,080 --> 02:08:57,160
PARAMETERS.

3544
02:08:57,160 --> 02:08:58,160
I'LL JUST SHOW YOU AN EXAMPLE OF

3545
02:08:58,160 --> 02:08:59,880
WHAT THAT MEANS AND HOW WE CAN

3546
02:08:59,880 --> 02:09:01,000
MONITOR BATCH TO BATCH

3547
02:09:01,000 --> 02:09:02,080
VARIABILITY.

3548
02:09:02,080 --> 02:09:04,360
SO WE USE SOMETHING CALLED

3549
02:09:04,360 --> 02:09:05,920
ELECTRICAL CELL-SUBSTRATE IMPEE

3550
02:09:05,920 --> 02:09:08,280
DANCE SENSING, ECIS, AND IT

3551
02:09:08,280 --> 02:09:09,880
MEASURES THE BARRIER FUNCTION OF

3552
02:09:09,880 --> 02:09:12,040
THE EPITHELIAL LAYER.

3553
02:09:12,040 --> 02:09:13,760
SO BASICALLY WHAT YOU DO IS YOU

3554
02:09:13,760 --> 02:09:15,960
MEASURE THE RESISTANCE, YOU

3555
02:09:15,960 --> 02:09:18,920
CREATE A WOUND IN THAT

3556
02:09:18,920 --> 02:09:21,520
EPITHELIAL LAYER BY TURNING UP

3557
02:09:21,520 --> 02:09:24,800
THE GAIN ON SOME ELECTRODES, IT

3558
02:09:24,800 --> 02:09:26,160
BYRNES A HOLE YOU AND GET

3559
02:09:26,160 --> 02:09:27,120
MIGRATION OF THE CELLS BACK INTO

3560
02:09:27,120 --> 02:09:27,880
THAT WOUND.

3561
02:09:27,880 --> 02:09:32,360
YOU DO THIS IN COMPLETE MEDIUM,

3562
02:09:32,360 --> 02:09:34,120
SERUM-FREE MEDIUM OR MEDIUM IN

3563
02:09:34,120 --> 02:09:34,360
VEGF.

3564
02:09:34,360 --> 02:09:37,960
SO THIS IS THE MIGRATION SHOWN

3565
02:09:37,960 --> 02:09:40,440
AND THE IMPEE DANCE.

3566
02:09:40,440 --> 02:09:40,800
 IMPEDANCE.

3567
02:09:40,800 --> 02:09:42,240
NOW JUST WATCH THAT SHAPE.

3568
02:09:42,240 --> 02:09:43,440
I'M NOT GOING TO GO INTO THE

3569
02:09:43,440 --> 02:09:44,840
DETAILS TOO MUCH, BUT THIS IS

3570
02:09:44,840 --> 02:09:46,280
INDEPENDENT BIOLOGICAL

3571
02:09:46,280 --> 02:09:47,480
EXPERIMENTS WITH THE SAME BATCH

3572
02:09:47,480 --> 02:09:50,640
OF IPS ENDOTHELIAL CELLS.

3573
02:09:50,640 --> 02:09:52,160
SO BASICALLY WHAT YOU SEE IS THE

3574
02:09:52,160 --> 02:09:54,400
SHAPE IN ALL CASES IS THE SAME,

3575
02:09:54,400 --> 02:09:56,200
SO THE RESISTANCE IN ALL THREE

3576
02:09:56,200 --> 02:09:57,200
BATCHES IS THE SAME.

3577
02:09:57,200 --> 02:10:00,480
SO THAT'S GOOD.

3578
02:10:00,480 --> 02:10:01,120
WITHIN ONE PATCH.

3579
02:10:01,120 --> 02:10:03,200
SO      BAMP.

3580
02:10:03,200 --> 02:10:03,960
SO THERE'S NOTHING TECHNICALLY

3581
02:10:03,960 --> 02:10:04,960
WRONG WITH THE ASSAY.

3582
02:10:04,960 --> 02:10:06,800
IF WE TAKE INDEPENDENT BATCHES

3583
02:10:06,800 --> 02:10:08,200
OF THESE CELLS ISOLATED FROM THE

3584
02:10:08,200 --> 02:10:13,400
SAME CONTROL LINE, WE CAN'T NO

3585
02:10:13,400 --> 02:10:14,040
DIFFERENCES AT ALL.

3586
02:10:14,040 --> 02:10:15,360
SO THE BATCH TO BATCH

3587
02:10:15,360 --> 02:10:17,240
VARIABILITY IS LOOKING EXTREMELY

3588
02:10:17,240 --> 02:10:17,760
GOOD.

3589
02:10:17,760 --> 02:10:21,600
WHEN WE GO TO LINE TO LINE

3590
02:10:21,600 --> 02:10:22,560
DIFFERENCES, THAT'S WHEN WE'RE

3591
02:10:22,560 --> 02:10:23,320
SEEING A DIFFERENCE.

3592
02:10:23,320 --> 02:10:24,520
YOU CAN SEE HERE WITH THREE

3593
02:10:24,520 --> 02:10:26,920
DIFFERENT LINES, THERE ARE TWO

3594
02:10:26,920 --> 02:10:28,120
LOOKING QUITE SIMILAR, ONE

3595
02:10:28,120 --> 02:10:29,920
SLIGHTLY DIFFERENT IN THE

3596
02:10:29,920 --> 02:10:33,160
RESISTANCE IT'S SHOWING US IN

3597
02:10:33,160 --> 02:10:35,720
THE TIER ASSAY, TRANS EPITHELIAL

3598
02:10:35,720 --> 02:10:36,360
RESISTANCE ASSAY.

3599
02:10:36,360 --> 02:10:38,640
SO THAT MEANS WE HAVE TO BE VERY

3600
02:10:38,640 --> 02:10:40,400
SURE TO TAKE THE RIGHT CONTROL

3601
02:10:40,400 --> 02:10:43,800
BELONGING TO EACH LINE BEFORE WE

3602
02:10:43,800 --> 02:10:44,800
CAN MAKE CONCLUSIONS.

3603
02:10:44,800 --> 02:10:47,040
SO HAVING DONE THAT SORT OF QA

3604
02:10:47,040 --> 02:10:48,840
AND QC IN THESE VERY LARGE

3605
02:10:48,840 --> 02:10:50,880
BATCH, WE CAN PUT THEM IN AN

3606
02:10:50,880 --> 02:10:53,200
ORGANOID CHIP FORMAT.

3607
02:10:53,200 --> 02:10:57,480
THIS IS USING COMMERCIALLY

3608
02:10:57,480 --> 02:10:58,760
AVAILABLE BIOCHIP CHIP.

3609
02:10:58,760 --> 02:11:00,320
YOU HAVE A GEL CHANNEL IN THE

3610
02:11:00,320 --> 02:11:03,360
MIDDLE OF THESE MICRO FLUIDIC

3611
02:11:03,360 --> 02:11:04,040
DEVICE, GEL CHANNEL CONTAINING

3612
02:11:04,040 --> 02:11:04,480
THE CELLS.

3613
02:11:04,480 --> 02:11:06,160
THERE ARE TWO MEDIA CHANNELS ON

3614
02:11:06,160 --> 02:11:06,640
EITHER SIDE.

3615
02:11:06,640 --> 02:11:08,600
THEY COME IN MULTIPLEX FORMS.

3616
02:11:08,600 --> 02:11:10,920
WE PUT A SUSPENSION OF

3617
02:11:10,920 --> 02:11:13,000
ENDOTHELIAL CELLS AND PARASITES

3618
02:11:13,000 --> 02:11:18,920
IN THE MIDDLE CHANNEL, AND THESE

3619
02:11:18,920 --> 02:11:20,240
ENDOTHELIAL AND SMOOTH MUSCLE

3620
02:11:20,240 --> 02:11:23,560
CELLS ORGANIZE THEMSELVES INTO A

3621
02:11:23,560 --> 02:11:23,840
VASCULATURE.

3622
02:11:23,840 --> 02:11:25,200
IF THIS FILM COULD RUN, YOU

3623
02:11:25,200 --> 02:11:25,840
COULD SEE IT.

3624
02:11:25,840 --> 02:11:28,880
BUT IT SELF-ORGANIZES HERE, AND

3625
02:11:28,880 --> 02:11:33,400
YOU CAN ACTUALLY SEE THESE

3626
02:11:33,400 --> 02:11:35,480
FORMING LEUM NIEZED VESSELS VERY

3627
02:11:35,480 --> 02:11:35,720
NICELY.

3628
02:11:35,720 --> 02:11:38,400
HERE IN PURPLE YOU CAN SEE THE

3629
02:11:38,400 --> 02:11:40,160
EPITHELIAL CELLS AND BEAUTIFUL

3630
02:11:40,160 --> 02:11:41,080
LUMEN FORMED INSIDE.

3631
02:11:41,080 --> 02:11:42,920
THESE ARE THE EPITHELIAL CELLS

3632
02:11:42,920 --> 02:11:43,880
IN PURPLE AND THE GREEN CELLS

3633
02:11:43,880 --> 02:11:45,160
ARE THE SMOOTH MUSCLE CELLS.

3634
02:11:45,160 --> 02:11:47,800
THIS IS IN A CONTROL SITUATION

3635
02:11:47,800 --> 02:11:50,200
SO VERY TIGHT CONTACT BETWEEN

3636
02:11:50,200 --> 02:11:51,560
THESE SMOOTH MUSCLE CELLS AND

3637
02:11:51,560 --> 02:11:52,840
THE ENDOTHELIAL CELLS.

3638
02:11:52,840 --> 02:11:55,040
NOW, IN THIS DISEASE CALLED HHT,

3639
02:11:55,040 --> 02:11:56,560
WHICH I SAID WAS ONE OF OUR

3640
02:11:56,560 --> 02:12:01,400
FAVORITE DISEASES, THERE ARE

3641
02:12:01,400 --> 02:12:02,680
MUTATIONS IN THE SIGNALING

3642
02:12:02,680 --> 02:12:02,920
PATHWAY.

3643
02:12:02,920 --> 02:12:04,360
THESE PATIENTS HAVE VERY WEAK

3644
02:12:04,360 --> 02:12:05,760
BLOOD VESSELS, THEY HEMORRHAGE

3645
02:12:05,760 --> 02:12:08,600
VERY EASILY, THEY HAVE

3646
02:12:08,600 --> 02:12:10,240
PARTICULARLY CHRONIC NOSE

3647
02:12:10,240 --> 02:12:11,520
BLEEDS, SO MAYBE FIVE TO 10

3648
02:12:11,520 --> 02:12:13,200
TIMES A DAY, SOMETIMES UP TO

3649
02:12:13,200 --> 02:12:15,160
HALF A LITER A TIME.

3650
02:12:15,160 --> 02:12:16,040
THEY'RE COMPLETELY MISERABLE.

3651
02:12:16,040 --> 02:12:17,680
SO WHAT WE'RE LOOKING FOR IS

3652
02:12:17,680 --> 02:12:20,080
WAYS TO STABILIZE THESE VESSELS.

3653
02:12:20,080 --> 02:12:21,280
THE FIRST QUESTION IS, COULD WE

3654
02:12:21,280 --> 02:12:23,680
CREATE A MODEL TO MIMIC THIS?

3655
02:12:23,680 --> 02:12:25,640
AND BASICALLY WHAT WE'VE DONE IS

3656
02:12:25,640 --> 02:12:28,640
SHOWN IN THE NEXT SLIDE.

3657
02:12:28,640 --> 02:12:30,160
WE CAN CREATE THIS MODEL.

3658
02:12:30,160 --> 02:12:32,480
SO IN THE TOP, YOU SEE AGAIN

3659
02:12:32,480 --> 02:12:33,760
THIS CONTROL, THE PURPLE ON THE

3660
02:12:33,760 --> 02:12:35,520
RIGHT IS THE ENDOTHELIAL CELLS,

3661
02:12:35,520 --> 02:12:37,680
THE GREEN OF THE SMOOTH MUSCLE

3662
02:12:37,680 --> 02:12:38,120
CELLS.

3663
02:12:38,120 --> 02:12:41,720
BUT WHEN WE HAVE THE CELLS

3664
02:12:41,720 --> 02:12:44,680
FORMED FROM IPS CELLS FROM AN

3665
02:12:44,680 --> 02:12:46,360
HHT PATIENT, WHAT WE FIND IS

3666
02:12:46,360 --> 02:12:48,760
THESE SMOOTH MUSCLE CELLS

3667
02:12:48,760 --> 02:12:51,560
INTERACT VERY POORLY WITH THE

3668
02:12:51,560 --> 02:12:54,960
ENDOTHELIAL CELLS, AND THAT

3669
02:12:54,960 --> 02:12:56,400
STABILITY IS LIKELY THE REASON

3670
02:12:56,400 --> 02:12:58,680
THAT THESE VESSELS HEMORRHAGE

3671
02:12:58,680 --> 02:13:00,120
EASILY.

3672
02:13:00,120 --> 02:13:05,560
AND WHEN WE LOOK AT THE FLOW OF

3673
02:13:05,560 --> 02:13:07,080
DEXTRAN THROUGH THESE LEUM

3674
02:13:07,080 --> 02:13:11,480
NIEZED VESSELS ON THE TOP, IT

3675
02:13:11,480 --> 02:13:12,720
RETAINED WITHIN THESE VESSEL

3676
02:13:12,720 --> 02:13:15,640
STRUCTURES WITH    BUT THE HHT-D

3677
02:13:15,640 --> 02:13:17,000
VESSELS ARE LEAKING, JUST AS

3678
02:13:17,000 --> 02:13:20,440
THEY ARE IN PATIENTS.

3679
02:13:20,440 --> 02:13:22,760
WE'RE USING THIS ASSAY TO SCREEN

3680
02:13:22,760 --> 02:13:23,520
FOR REPURPOSED DRUGS AT THE

3681
02:13:23,520 --> 02:13:26,160
PRESENT TIME AND WE'VE GOT -- ON

3682
02:13:26,160 --> 02:13:29,520
THE BASIS OF THIS ASSAY, WE NOW

3683
02:13:29,520 --> 02:13:32,800
HAVE TWO DRUGS IN CLINICAL

3684
02:13:32,800 --> 02:13:34,560
TRIAL.

3685
02:13:34,560 --> 02:13:36,440
SO JUST TO SUMMARIZE BECAUSE

3686
02:13:36,440 --> 02:13:40,680
TIME FLIES, THIS IS -- WHAT I'VE

3687
02:13:40,680 --> 02:13:42,280
SHOWED YOU IS A LOW-TECH

3688
02:13:42,280 --> 02:13:44,080
SCALABLE AND INEXPENSIVE MODEL

3689
02:13:44,080 --> 02:13:45,800
TO STUDY CARDIAC DISEASE AND

3690
02:13:45,800 --> 02:13:52,040
TOXICITY BASED ON MATURE

3691
02:13:52,040 --> 02:13:53,160
CARDIOMYOCYTES, SO I THINK IF WE

3692
02:13:53,160 --> 02:13:54,440
MOVE NOW TO LOOKING MORE AT THE

3693
02:13:54,440 --> 02:13:56,560
EFFECT OF VIRUSES, WE MAY SEE

3694
02:13:56,560 --> 02:13:58,280
THE OUTCOME WE EXPECT.

3695
02:13:58,280 --> 02:14:00,040
THE MULTICELL TYPE MODEL ALLOWS

3696
02:14:00,040 --> 02:14:01,000
IDENTIFICATION OF CELLULAR

3697
02:14:01,000 --> 02:14:03,640
TARGET IN CARDIAC DISEASE.

3698
02:14:03,640 --> 02:14:05,480
THE 3D ORGANS ON CHIP UNDER FLOW

3699
02:14:05,480 --> 02:14:07,800
THAT I SHOWED YOU CAPTURE SMALL

3700
02:14:07,800 --> 02:14:10,000
VESSEL DISEASE MODEL PHENOTYPES.

3701
02:14:10,000 --> 02:14:12,600
AND WE DO NOT SEE THIS IN 2D

3702
02:14:12,600 --> 02:14:13,920
BECAUSE IN 2D, THERE ARE NO

3703
02:14:13,920 --> 02:14:15,440
LUMEN.

3704
02:14:15,440 --> 02:14:18,960
AND MANY IPS AND ORGANOID MODELS

3705
02:14:18,960 --> 02:14:20,160
ON WHICH THEY'RE BASED ARE READY

3706
02:14:20,160 --> 02:14:22,920
TO GO FOR EXAMINING EFFECT OF

3707
02:14:22,920 --> 02:14:24,120
VIRUSES, DRUG REPURPOSES AND

3708
02:14:24,120 --> 02:14:25,520
SCREENING OF THERAPEUTIC DRUGS.

3709
02:14:25,520 --> 02:14:26,840
SO THESE ARE THE PEOPLE IN THE

3710
02:14:26,840 --> 02:14:31,840
LAB WHO HAVE BEEN DRIVING THIS

3711
02:14:31,840 --> 02:14:36,880
WORK, JUNIOR PIs, THESE ARE

3712
02:14:36,880 --> 02:14:38,400
PH.D. STUDENTS AND POSTDOCS

3713
02:14:38,400 --> 02:14:39,280
INVOLVED IN THE WORK AND THESE

3714
02:14:39,280 --> 02:14:41,040
ARE SOME OF OUR MANY

3715
02:14:41,040 --> 02:14:41,600
COLLABORATOR.

3716
02:14:41,600 --> 02:14:43,120
THANK YOU.

3717
02:14:43,120 --> 02:14:44,440
AND OF COURSE OUR FUNDERS AT THE

3718
02:14:44,440 --> 02:14:46,880
BOTTOM.

3719
02:14:46,880 --> 02:14:51,240
>> THANK YOU SO MUCH,
CHRISTINE.

3720
02:14:51,240 --> 02:14:54,160
I LOVE YOUR LOW TECH MODEL.

3721
02:14:54,160 --> 02:14:56,360
REALLY NICE WORK.

3722
02:14:56,360 --> 02:14:57,320
AGAIN REMIND EVERYONE THAT IF

3723
02:14:57,320 --> 02:14:59,200
YOU HAVE QUESTIONS FOR THE

3724
02:14:59,200 --> 02:15:02,280
SPEAKERS, TO TYPE THEM ON THE

3725
02:15:02,280 --> 02:15:04,760
QUESTION AND ANSWER BOX AND

3726
02:15:04,760 --> 02:15:07,960
WE'LL ADDRESS THEM, THE SPEAKERS

3727
02:15:07,960 --> 02:15:09,800
CAN ADDRESS THEM DURING -- LIKE

3728
02:15:09,800 --> 02:15:13,080
BY TYPING, OR WE CAN ADDRESS

3729
02:15:13,080 --> 02:15:13,960
THEM AT THE END.

3730
02:15:13,960 --> 02:15:16,440
SO NOW WE'RE GOING TO MOVE ON TO

3731
02:15:16,440 --> 02:15:17,600
THE NEXT SPEAKER, AND IT'S A

3732
02:15:17,600 --> 02:15:22,840
PLEASURE FOR ME TO INTRODUCE DRI

3733
02:15:22,840 --> 02:15:25,480
BELIEVE RECENTLY MOVED TO ROACH

3734
02:15:25,480 --> 02:15:35,280
AND IS        ROCHE

3735
02:15:35,280 --> 02:15:36,560
IN SWITZERLAND, BEFORE HE WAS

3736
02:15:36,560 --> 02:15:41,520
DIRECTOR AND PRINCIPAL

3737
02:15:41,520 --> 02:15:44,600
INVESTIGATOR IN THE NETHERLANDS,

3738
02:15:44,600 --> 02:15:48,440
ALSO INVESTIGATING DIRECTOR OF

3739
02:15:48,440 --> 02:15:52,120
RESEARCH AT THE CENTER FOR

3740
02:15:52,120 --> 02:15:53,760
PROCEED TRICK ONCOLOGY.

3741
02:15:53,760 --> 02:15:59,000
HE'SAND BEEN DOING PIONEERING

3742
02:15:59,000 --> 02:16:02,080
WORK IN ORGANOIDS, PARTICULARLY

3743
02:16:02,080 --> 02:16:06,680
INTESTINAL TRACT ORGANOIDS.

3744
02:16:06,680 --> 02:16:10,160
TODAY HE'S GOING TO BE TALKING,

3745
02:16:10,160 --> 02:16:12,440
THE TITLE OF THE PRESENTATION IS

3746
02:16:12,440 --> 02:16:17,160
HUMAN TISSUE STEM CELL DERIVED

3747
02:16:17,160 --> 02:16:18,400
ORGANOIDS MODEL VIRAL INFECTION.

3748
02:16:18,400 --> 02:16:19,280
HANS, THE FLOOR IS YOURS.

3749
02:16:19,280 --> 02:16:24,920
>> THANKS VERY MUCH.

3750
02:16:24,920 --> 02:16:28,680
, MARC, FOR THE INTRODUCTION AND

3751
02:16:28,680 --> 02:16:35,760
INVITATION TO SPEAK.

3752
02:16:35,760 --> 02:16:36,880
I'LL GIVE YOU A BRIEF

3753
02:16:36,880 --> 02:16:38,160
INTRODUCTION TO THE TYPES OF

3754
02:16:38,160 --> 02:16:39,160
ORGANOIDS THAT MY LAB HAS

3755
02:16:39,160 --> 02:16:42,760
DEVELOPED ABOUT 12 YEARS AGO AND

3756
02:16:42,760 --> 02:16:43,960
THEN I'LL GIVE YOU SOME EXAMPLES

3757
02:16:43,960 --> 02:16:46,800
OF HOW WE HAVE BEEN USING THIS

3758
02:16:46,800 --> 02:16:48,360
TECHNOLOGY TO MODEL VARIOUS

3759
02:16:48,360 --> 02:16:50,080
VIRAL INFECTIONS.

3760
02:16:50,080 --> 02:16:54,160
WHAT YOU SEE HERE IS THE INSIDES

3761
02:16:54,160 --> 02:16:55,560
OF THE HUMAN SMALL INTESTINE.

3762
02:16:55,560 --> 02:16:57,600
FOOD PASSES BY FROM LEFT TO

3763
02:16:57,600 --> 02:16:58,080
RIGHT.

3764
02:16:58,080 --> 02:16:58,960
THIS STRUCTURE HERE IS CALLED

3765
02:16:58,960 --> 02:17:00,040
THE VILLUS.

3766
02:17:00,040 --> 02:17:01,880
THERE'S ABOUT MAYBE 8 TO 10

3767
02:17:01,880 --> 02:17:02,720
CRYPTS THAT SURROUND THE BASE OF

3768
02:17:02,720 --> 02:17:05,720
THE VILLUS AND THESE

3769
02:17:05,720 --> 02:17:06,720
STRUCTURES -- WHEN WE WERE

3770
02:17:06,720 --> 02:17:08,040
STUDYING THE PATHWAY A LONG TIME

3771
02:17:08,040 --> 02:17:09,360
AGO BECAUSE THE STEM CELL

3772
02:17:09,360 --> 02:17:10,520
PROCESS THAT YOU SEE HERE, THE

3773
02:17:10,520 --> 02:17:13,520
CELERY NEWELL PROCESS           

3774
02:17:13,520 --> 02:17:15,040
CELL RENEWAL PROCESS IS PROBABLY

3775
02:17:15,040 --> 02:17:17,120
THE FASTEST IN THE HUMAN BODY.

3776
02:17:17,120 --> 02:17:18,520
THEY PRODUCE DAUGHTER CELLS

3777
02:17:18,520 --> 02:17:19,400
EVERY DAY.

3778
02:17:19,400 --> 02:17:20,720
THOSE DAUGHTER CELLS TAKE ABOUT

3779
02:17:20,720 --> 02:17:22,880
TWO DAYS WHILE THEY DIVIDE THREE

3780
02:17:22,880 --> 02:17:25,080
OR FOUR TIMES TO EXIT THE

3781
02:17:25,080 --> 02:17:26,640
CRYPTS, THEY THEN MATURE INTO

3782
02:17:26,640 --> 02:17:28,400
SOMETHING LIKE 10 DIFFERENT CELL

3783
02:17:28,400 --> 02:17:29,880
TYPES THAT YOU NEED FOR

3784
02:17:29,880 --> 02:17:33,200
DIGESTING FOOD AND TAKING OF

3785
02:17:33,200 --> 02:17:33,640
NUTRIENTS.

3786
02:17:33,640 --> 02:17:34,600
THEY WILL THEN CONTINUE TO MOVE

3787
02:17:34,600 --> 02:17:37,760
UP AS FULLY DIFFERENTIATED CELLS

3788
02:17:37,760 --> 02:17:39,440
FIVE DAYS IN THE MOWRT, THEY

3789
02:17:39,440 --> 02:17:42,160
REACH THE TIPS OF THE VILLI AND

3790
02:17:42,160 --> 02:17:42,800
GO UP.

3791
02:17:42,800 --> 02:17:44,600
NOW THIS IS PROBABLY THE FASTEST

3792
02:17:44,600 --> 02:17:47,480
CELERY NEWELL       

3793
02:17:47,480 --> 02:17:49,960
CELL SL RENEWAL PROCESS IN THE

3794
02:17:49,960 --> 02:17:52,880
MAMMALIAN BODY.

3795
02:17:52,880 --> 02:17:54,840
WE KNEW -- WAS A KEY TO DRIVE

3796
02:17:54,840 --> 02:17:57,520
THIS, AND THIS ALLOWED US TO

3797
02:17:57,520 --> 02:17:59,640
FINALLY IDENTIFY A MARKER FOR

3798
02:17:59,640 --> 02:18:07,320
THE STEM CELLS LGR5 IN MICE

3799
02:18:07,320 --> 02:18:13,440
WHERE WE COULD INSERT -- IN THE

3800
02:18:13,440 --> 02:18:15,520
LGR5 LOCUS, WE COULD EASILY SORT

3801
02:18:15,520 --> 02:18:16,200
OUT OF STEM CELLS.

3802
02:18:16,200 --> 02:18:18,480
WE NOTED LOTS OF UNEXPECTED

3803
02:18:18,480 --> 02:18:22,400
THINGS, THERE WERE MULTIPLE DOG

3804
02:18:22,400 --> 02:18:25,160
MASKS AROUND THE CELLS, THAT

3805
02:18:25,160 --> 02:18:27,200
THEY RARELY DIVIDE.

3806
02:18:27,200 --> 02:18:28,600
THESE STEM CELLS LIKE STEM CELLS

3807
02:18:28,600 --> 02:18:31,160
OF THE STOMACH OR THE HAIR

3808
02:18:31,160 --> 02:18:32,240
FOLLICLE, FOR INSTANCE,

3809
02:18:32,240 --> 02:18:34,320
CONSTANTLY DIVIDE, AND BASED ON

3810
02:18:34,320 --> 02:18:40,040
THIS OBSERVATION, TOSHIRO SATO

3811
02:18:40,040 --> 02:18:44,480
AND -- WE CAME UP WITH -- ONE WE

3812
02:18:44,480 --> 02:18:47,440
LATER TO FIND LIGAND OF LGR5 OF

3813
02:18:47,440 --> 02:18:52,280
OUR STEM CELL FACTOR, WE DO

3814
02:18:52,280 --> 02:19:02,800
THESE STEM CELLS IN MAT RIGEL IN

3815
02:19:03,400 --> 02:19:04,960
3D.

3816
02:19:04,960 --> 02:19:07,920
MUCH TO OUR SURPRISE, WE SAW

3817
02:19:07,920 --> 02:19:09,320
FORMATION OF THESE VERY

3818
02:19:09,320 --> 02:19:11,200
IRREGULAR STRUCTURES THAT UPON

3819
02:19:11,200 --> 02:19:12,400
CLOSE EXAMINATION TURN OUT TO BE

3820
02:19:12,400 --> 02:19:13,920
SMALL COPIES OF THE GUT

3821
02:19:13,920 --> 02:19:14,560
EPITHELIUM.

3822
02:19:14,560 --> 02:19:16,520
SO A SINGLE STEM CELL KNOWS HOW

3823
02:19:16,520 --> 02:19:19,480
TO BUILD THESE 3D STRUCTURES

3824
02:19:19,480 --> 02:19:20,840
WITH ALL OF THE DIFFERENTIATED

3825
02:19:20,840 --> 02:19:25,640
CELL TYPES, LINING THE CENTRAL

3826
02:19:25,640 --> 02:19:26,600
LUMEN WITH CRYPTS, AT THE BASE

3827
02:19:26,600 --> 02:19:27,800
OF THE CRYPTS ARE MULTIPLE STEM

3828
02:19:27,800 --> 02:19:29,360
CELLS AND THE OTHER CELLS THAT

3829
02:19:29,360 --> 02:19:30,000
RESIDE THERE.

3830
02:19:30,000 --> 02:19:31,400
SO REALLY REMARKABLE THAT THEY

3831
02:19:31,400 --> 02:19:35,880
CAN BUILD THIS, EVEN MORE

3832
02:19:35,880 --> 02:19:37,000
REMARKABLE THAT THEY CAN KEEP

3833
02:19:37,000 --> 02:19:38,840
GROWING AS THESE INTESTINAL

3834
02:19:38,840 --> 02:19:40,400
ORGANOIDS FOR MANY, MANY YEARS

3835
02:19:40,400 --> 02:19:41,720
AND WE'VE NEVER SEEN MUTATIONS

3836
02:19:41,720 --> 02:19:43,120
WHEN YOU TRANSPLANT THEM, THEY

3837
02:19:43,120 --> 02:19:46,960
ARE REALLY NORMAL TISSUE.

3838
02:19:46,960 --> 02:19:49,280
WE THEN REALIZED THIS PROTOCOL

3839
02:19:49,280 --> 02:19:51,000
WAS APPLICABLE TO PROBABLY ALL

3840
02:19:51,000 --> 02:19:52,760
EPITHELIA OF THE MAMMALIAN BODY.

3841
02:19:52,760 --> 02:19:53,840
YOU SEE A WHOLE LIST HERE.

3842
02:19:53,840 --> 02:19:55,280
WE HAVE PUBLISHED MULTIPLE

3843
02:19:55,280 --> 02:19:56,360
PROTOCOLS BUT I'M SURE MANY OF

3844
02:19:56,360 --> 02:19:57,920
THEM CAN STILL BE IMPROVED AND

3845
02:19:57,920 --> 02:19:58,520
THERE'S MULTIPLE OTHER PAPERS

3846
02:19:58,520 --> 02:19:59,560
THAT HAVE COME UP WITH

3847
02:19:59,560 --> 02:20:00,640
ADDITIONAL PROTOCOLS.

3848
02:20:00,640 --> 02:20:02,920
VERY BRIEFLY, YOU START YOUR

3849
02:20:02,920 --> 02:20:04,560
CULTURE NOT FROM A STEM CELL,

3850
02:20:04,560 --> 02:20:06,320
YOU JUST GET A SMALL PIECE OF

3851
02:20:06,320 --> 02:20:07,200
TISSUE.

3852
02:20:07,200 --> 02:20:08,520
THERE'S ALWAYS STEM CELL

3853
02:20:08,520 --> 02:20:09,880
ACTIVITY, BIOPSY OR SURGICAL

3854
02:20:09,880 --> 02:20:11,200
RESECTION OR FOR KIDNEY, FOR

3855
02:20:11,200 --> 02:20:14,000
INSTANCE, WE CAN JUST SPIN SOME

3856
02:20:14,000 --> 02:20:19,120
CELLS OUT OF URINE AND GROW THEM

3857
02:20:19,120 --> 02:20:23,920
HAD, YOU PUT THEM IN MAT RIGEL,

3858
02:20:23,920 --> 02:20:29,400
YOU ADD GROWTH FACTORS, KINASE

3859
02:20:29,400 --> 02:20:32,040
RECEPTORS, AND OFTEN YOU NEED

3860
02:20:32,040 --> 02:20:33,960
TO -- AND IF YOU FIND THE RIGHT

3861
02:20:33,960 --> 02:20:35,080
OPTIMIZED CULTURE CONDITION,

3862
02:20:35,080 --> 02:20:36,280
TYPICALLY YOU CAN GROW THIS

3863
02:20:36,280 --> 02:20:40,800
PIECE OF TISSUE PROBABLY

3864
02:20:40,800 --> 02:20:41,560
FOREVER.

3865
02:20:41,560 --> 02:20:43,080
VERY DIFFERENT FROM THE IPS

3866
02:20:43,080 --> 02:20:43,360
ORGANOIDS.

3867
02:20:43,360 --> 02:20:44,800
FROM THE MOMENT YOU PUT THEM IN

3868
02:20:44,800 --> 02:20:45,800
CULTURE, THEY'RE FULLY

3869
02:20:45,800 --> 02:20:47,880
SPECIFIED, THEY ACTUALLY PRODUCE

3870
02:20:47,880 --> 02:20:49,840
FULLY MATURE CELL TYPES BUT

3871
02:20:49,840 --> 02:20:51,480
THEY'RE VERY DONE, SO YOU CAN'T

3872
02:20:51,480 --> 02:20:52,800
TURN THEM INTO ANYTHING ELSE.

3873
02:20:52,800 --> 02:20:54,480
THEY'RE JUST GROW THE AREA OF

3874
02:20:54,480 --> 02:20:58,360
THE ORGAN OF INTEREST, THEY JUST

3875
02:20:58,360 --> 02:20:59,560
GROW THERE FOREVER IN THE FORM

3876
02:20:59,560 --> 02:21:00,760
OF ORGANOIDS.

3877
02:21:00,760 --> 02:21:02,640
ALSO WE CAN ONLY GROW EPITHELIAL

3878
02:21:02,640 --> 02:21:03,720
ELEMENTS FROM THESE TYPES OF

3879
02:21:03,720 --> 02:21:05,040
ORGANOIDS SO WE DON'T GET BONE,

3880
02:21:05,040 --> 02:21:06,680
WE DON'T GET MUSCLE, WE DON'T

3881
02:21:06,680 --> 02:21:10,960
GET BRAIN.

3882
02:21:10,960 --> 02:21:14,680
BUT RESPIRATORY AND INTESTINAL

3883
02:21:14,680 --> 02:21:16,320
VIRUSES TYPICALLY GO FOR

3884
02:21:16,320 --> 02:21:17,840
EPITHELIAL CELLS, ALL THESE

3885
02:21:17,840 --> 02:21:20,040
OTHER ORGANS ESSENTIALLY IN THE

3886
02:21:20,040 --> 02:21:23,440
EPITHELIAL CELL LAYERS OF THESE

3887
02:21:23,440 --> 02:21:24,200
ORGANS.

3888
02:21:24,200 --> 02:21:27,040
WHAT YOU CAN SEE HERE, STRAIGHT

3889
02:21:27,040 --> 02:21:28,280
FROM -- YOU CAN GROW CANCER

3890
02:21:28,280 --> 02:21:29,560
CELLS FROM A PATIENT, YOU CAN

3891
02:21:29,560 --> 02:21:33,160
GROW CELL FROM CYSTIC FIBROSIS

3892
02:21:33,160 --> 02:21:35,040
PATIENTS, LUNG, KIDNEY, STOMACH

3893
02:21:35,040 --> 02:21:36,520
AND RECAPITULATE PHENOTYPE AND

3894
02:21:36,520 --> 02:21:39,520
IT WILL REMAIN YOU THE EXAMPLES

3895
02:21:39,520 --> 02:21:40,960
OF INFECTIOUS DISEASE ORGANOIDS.

3896
02:21:40,960 --> 02:21:42,560
THIS IS AN ORGANOID THAT WE HAVE

3897
02:21:42,560 --> 02:21:43,960
WORKED VERY HARD AND VERY LONG

3898
02:21:43,960 --> 02:21:52,280
TO GET GROWING, HUILI HU IN

3899
02:21:52,280 --> 02:21:54,280
CHINA MANAGED TO COME UP WITH A

3900
02:21:54,280 --> 02:21:56,560
COMPLICATED COCKTAIL, EIGHT

3901
02:21:56,560 --> 02:21:57,760
GROWTH FACTORS.

3902
02:21:57,760 --> 02:22:00,840
IF WE HIT THE PROTOCOL RIGHT,PI

3903
02:22:00,840 --> 02:22:02,040
SME OF LIVER TISSUE WILL

3904
02:22:02,040 --> 02:22:04,640
GROW FOR LONG PERIODS OF TIME,

3905
02:22:04,640 --> 02:22:07,040
AND IT CONSISTS ENTIRELY OF

3906
02:22:07,040 --> 02:22:09,000
FULLY MATURE HEPATOCYTES THAT

3907
02:22:09,000 --> 02:22:09,440
OCCASIONALLY DIVIDE.

3908
02:22:09,440 --> 02:22:12,160
THEY'RE NOT THE FASTEST GROWER,

3909
02:22:12,160 --> 02:22:13,920
THEY PROBABLY GROW ABOUT THREE

3910
02:22:13,920 --> 02:22:17,560
FOLD HER WEEK, THESE CELLS ARE

3911
02:22:17,560 --> 02:22:19,080
FULLY MATURE HEPATOCYTES

3912
02:22:19,080 --> 02:22:20,600
DIRECTLY COMPARABLE TO PRIMARY

3913
02:22:20,600 --> 02:22:23,000
HE  

3914
02:22:23,000 --> 02:22:25,640
HEPATOCYTES, SO CITE DIFFERENT

3915
02:22:25,640 --> 02:22:28,160
FROM -- ONE THING HERE, ANOTHER

3916
02:22:28,160 --> 02:22:31,080
CHINESE POSTDOC IN THE LAB,

3917
02:22:31,080 --> 02:22:32,520
BECAUSE WE CAN GROW THESE

3918
02:22:32,520 --> 02:22:34,080
ORGANOIDS FOR SUCH A LONG TIME,

3919
02:22:34,080 --> 02:22:35,480
WE CAN NOW STUDY CHRONIC

3920
02:22:35,480 --> 02:22:39,080
INFECTION BY VIRUSES AND THIS IS

3921
02:22:39,080 --> 02:22:41,280
HBV, THE CORE ANTIGEN OF HBV IS

3922
02:22:41,280 --> 02:22:43,240
MODELED HERE, AND THIS IS AFTER

3923
02:22:43,240 --> 02:22:47,160
32 DAYS IN CULTURE, AFTER

3924
02:22:47,160 --> 02:22:48,160
INFECTION, THEY CAN KEEP IT FOR

3925
02:22:48,160 --> 02:22:48,520
MONTHS.

3926
02:22:48,520 --> 02:22:50,240
YOU CAN SEE HIGH LEVELS OF THE

3927
02:22:50,240 --> 02:22:52,200
CORE ANTIGEN HERE IN GREEN, SO

3928
02:22:52,200 --> 02:22:55,720
THE VIRUS IS THERE, WE CAN SEE

3929
02:22:55,720 --> 02:23:02,400
FOR THE CC DNA -- AND THEY

3930
02:23:02,400 --> 02:23:03,480
SECRETE LIVE VIRAL PARTICLES AS

3931
02:23:03,480 --> 02:23:08,520
YOU CAN SEE IN THESE CURVES.

3932
02:23:08,520 --> 02:23:10,680
SO WE'RE WORKING TO MAKE

3933
02:23:10,680 --> 02:23:12,680
DISCOVERIES IN THIS MODEL SYSTEM

3934
02:23:12,680 --> 02:23:14,440
BUT IT SHOWS SOMETHING VERY HARD

3935
02:23:14,440 --> 02:23:16,840
TO STUDY PRIOR TO ORGANOID

3936
02:23:16,840 --> 02:23:18,560
TECHNOLOGY IF ONE GROWS IT AND

3937
02:23:18,560 --> 02:23:20,120
INFECTS IT WITH A VIRUS, ONE CAN

3938
02:23:20,120 --> 02:23:21,400
BUILD A CHRONIC MODEL FOR

3939
02:23:21,400 --> 02:23:23,560
INFECTION.

3940
02:23:23,560 --> 02:23:28,200
SO THIS IS CERVICAL ORGANOIDS,

3941
02:23:28,200 --> 02:23:34,760
SO LIVE CELLS TO GROW THESE

3942
02:23:34,760 --> 02:23:37,280
ORGANOIDS, AND SHE INFECTS WITH

3943
02:23:37,280 --> 02:23:44,280
HSV VIRUS, YOU CAN SEE HOW

3944
02:23:44,280 --> 02:23:45,480
RAPIDLY -- I THINK THIS MOVIE

3945
02:23:45,480 --> 02:23:49,320
RUNS OVER TWO DAYS OR SO -- HOW

3946
02:23:49,320 --> 02:23:50,720
RAPIDLY FIRST OF ALL THE VIRUS

3947
02:23:50,720 --> 02:23:52,040
PROPAGATES AND ALSO HOW IT KILLS

3948
02:23:52,040 --> 02:23:53,560
THE EPITHELIAL ORGANOIDS.

3949
02:23:53,560 --> 02:23:55,200
THESE ORGANOIDS DON'T HAVE

3950
02:23:55,200 --> 02:23:56,840
LUMENS, THEY COME FROM A

3951
02:23:56,840 --> 02:23:58,040
STRATIFIED EPITHELIUM, SO

3952
02:23:58,040 --> 02:24:00,800
TYPICALLY YOU SEE A VERY SORT OF

3953
02:24:00,800 --> 02:24:04,280
LIKE A -- LAKE LUMEN SKIN, THE

3954
02:24:04,280 --> 02:24:06,600
MOST MATURE CELLS ARE IN THE

3955
02:24:06,600 --> 02:24:09,240
INSIDE, AND THE BASAL CELLS WITH

3956
02:24:09,240 --> 02:24:11,200
THE PROLIFERATIVE LAYER IS ON

3957
02:24:11,200 --> 02:24:12,040
THE OUTSIDE.

3958
02:24:12,040 --> 02:24:14,560
EVERY ORGANOID YOU SEE HERE

3959
02:24:14,560 --> 02:24:17,440
INDIVIDUAL CELLS, WE STAINED FOR

3960
02:24:17,440 --> 02:24:20,360
THESE CILIA, THE BEATING CILIA

3961
02:24:20,360 --> 02:24:21,680
OF THE CILIATED CELLS, IN

3962
02:24:21,680 --> 02:24:24,120
BETWEEN THE OTHER CELL TYPES OF

3963
02:24:24,120 --> 02:24:27,040
THE BRONCHUS, AND HERE YOU CAN

3964
02:24:27,040 --> 02:24:28,800
ACTUALLY SEE, IT WAS VERY

3965
02:24:28,800 --> 02:24:34,720
SURPRISING WITH NORMAN SACS GROW

3966
02:24:34,720 --> 02:24:36,240
THESE ORGANOIDS ORIGINALLY, THE

3967
02:24:36,240 --> 02:24:38,640
SLIME THAT'S PRODUCED BY THE

3968
02:24:38,640 --> 02:24:39,960
GLOBUS CELLS -- IT'S MOVING AND

3969
02:24:39,960 --> 02:24:41,680
IT'S BECAUSE OF THE CILIATED

3970
02:24:41,680 --> 02:24:42,800
CELLS THAT ARE ALSO PRESENCE,

3971
02:24:42,800 --> 02:24:44,240
YOU CAN SEE THE CILIA NICELY

3972
02:24:44,240 --> 02:24:46,520
BEAT AND YOU MIGHT ALSO OBSERVE

3973
02:24:46,520 --> 02:24:48,480
THAT THEY BEAT IN A CONCERTED

3974
02:24:48,480 --> 02:24:49,880
WAY, SO THEY BASICALLY BEAT THE

3975
02:24:49,880 --> 02:24:51,680
WAY THEY SHOULD BEAT IN THE

3976
02:24:51,680 --> 02:24:53,920
AIRWAY SO THEY BASICALLY

3977
02:24:53,920 --> 02:24:55,040
SYNCHRONIZE WHAT THEY DO, AND

3978
02:24:55,040 --> 02:24:57,120
THIS MAKES THAT THE MUCUS IN THE

3979
02:24:57,120 --> 02:25:01,160
CENTER OF THESE ORGANOIDS SPIN.

3980
02:25:01,160 --> 02:25:03,360
THESE, WE'VE USED FOR A NUMBER

3981
02:25:03,360 --> 02:25:06,320
OF VIRUSES.

3982
02:25:06,320 --> 02:25:09,280
THIS IS JUST MAKING A MOVIE OF

3983
02:25:09,280 --> 02:25:11,000
AN ORGANOID WITH NO INFECTION.

3984
02:25:11,000 --> 02:25:13,520
OUR COLLABORATORS IN HONG KONG

3985
02:25:13,520 --> 02:25:15,840
HAVE USED THESE ORGANOIDS TO

3986
02:25:15,840 --> 02:25:18,240
STUDY INFLUENZA VIRUSES A NUMBER

3987
02:25:18,240 --> 02:25:19,440
OF YEARS AGO.

3988
02:25:19,440 --> 02:25:20,760
THE PAPER IS VERY POPULAR NOW

3989
02:25:20,760 --> 02:25:22,720
WITH THE SARS AND SARS-COV-2

3990
02:25:22,720 --> 02:25:23,440
STUDIES.

3991
02:25:23,440 --> 02:25:25,040
AND IT TURNS OUT THAT ONE CAN

3992
02:25:25,040 --> 02:25:29,720
USE THESE ORGANOIDS TO DEFINE

3993
02:25:29,720 --> 02:25:32,480
PATHOGENIC EFFECTS OF NEW

3994
02:25:32,480 --> 02:25:34,360
INFLUENZA STRAINS, PARTICULARLY

3995
02:25:34,360 --> 02:25:37,480
THE ONES THAT JUMP FROM PIG OR

3996
02:25:37,480 --> 02:25:38,920
BIRDS FROM HUMANS CAN BE VERY

3997
02:25:38,920 --> 02:25:39,160
DANGEROUS.

3998
02:25:39,160 --> 02:25:41,560
IN THE PAST WHEN THEY USED THIS

3999
02:25:41,560 --> 02:25:42,520
PLATFORM, THEY COULD ACTUALLY

4000
02:25:42,520 --> 02:25:45,800
SEE THIS IN CULTURES.

4001
02:25:45,800 --> 02:25:48,520
SO NOW IF WE ADD THE RSV VIRUS

4002
02:25:48,520 --> 02:25:59,080
ON THE NEXT MOVIE, HERE YOU SEE

4003
02:26:04,480 --> 02:26:06,440
THE ORGANOID AND SOMEHOW THEY

4004
02:26:06,440 --> 02:26:08,640
BECOME EXTREMELY MOTILE AND THEY

4005
02:26:08,640 --> 02:26:10,080
ACTUALLY BECOME CANNIBAL, THEY

4006
02:26:10,080 --> 02:26:13,160
EAT HEALTHY -- EAT AND AFFECT

4007
02:26:13,160 --> 02:26:13,920
HEALTHY ORGANOIDS.

4008
02:26:13,920 --> 02:26:15,000
YOU CAN SEE HERE.

4009
02:26:15,000 --> 02:26:24,520
THERE'S ANOTHER MOVIE HERE.

4010
02:26:24,520 --> 02:26:26,040
THIS ONE HERE.

4011
02:26:26,040 --> 02:26:29,240
YOU SEE THE FIRST IN RED, THE

4012
02:26:29,240 --> 02:26:35,760
FIRST RSV INFECTED ORGANOIDS, WE

4013
02:26:35,760 --> 02:26:37,520
ALSO SEE HUMAN LUNGS, THE

4014
02:26:37,520 --> 02:26:39,080
AFFECTED EPITHELIAL CELLS,

4015
02:26:39,080 --> 02:26:42,120
ORGANOIDS CONSIST ENTIRELY OF

4016
02:26:42,120 --> 02:26:43,120
EPITHELIAL CELLS, THEY VERY

4017
02:26:43,120 --> 02:26:45,600
RAPIDLY UNDERGO VMT AND WE

4018
02:26:45,600 --> 02:26:46,960
OBSERVE NOW IN THE LUNGS OF

4019
02:26:46,960 --> 02:26:49,560
INFECTED PATIENTS THAT THESE

4020
02:26:49,560 --> 02:26:50,800
CELLS HELP SPREAD THE VIRUS.

4021
02:26:50,800 --> 02:26:52,840
THE VIRUS HIDES INSIDE THESE

4022
02:26:52,840 --> 02:26:53,720
CELLS, WE BELIEVE, AND THEY

4023
02:26:53,720 --> 02:26:55,240
TRAVEL THROUGH THE AIRWAYS.

4024
02:26:55,240 --> 02:26:58,200
ANOTHER THING YOU CAN DO IS NOW

4025
02:26:58,200 --> 02:27:00,720
COINCUBATE WITH NEW CELLS AND

4026
02:27:00,720 --> 02:27:03,560
THESE ARE LYMPHOCYTE, NOTHING

4027
02:27:03,560 --> 02:27:04,880
MUCH HAPPENS WHEN WE DON'T

4028
02:27:04,880 --> 02:27:06,400
INFECT AND ON THE RIGHT, WE

4029
02:27:06,400 --> 02:27:07,520
TRACE INDIVIDUAL CELLS AND THEY

4030
02:27:07,520 --> 02:27:09,120
DON'T DO MUCH AS YOU CAN SEE.

4031
02:27:09,120 --> 02:27:11,000
BUT IF YOU INFECT THEM AGAIN BUT

4032
02:27:11,000 --> 02:27:13,600
NOW WITH A GREEN RSV VIRUS, YOU

4033
02:27:13,600 --> 02:27:15,160
CAN SEE THE MOMENT THEY GET

4034
02:27:15,160 --> 02:27:16,720
INFECTED, THE ORGANOIDS BECOME

4035
02:27:16,720 --> 02:27:20,000
EXTREMELY INTERESTING FOR THE

4036
02:27:20,000 --> 02:27:24,120
IMMUNE CELLS, THEY SE SECRETE

4037
02:27:24,120 --> 02:27:26,320
CERTAIN CHEMOKINES, THAT THEY

4038
02:27:26,320 --> 02:27:27,840
ATTRACT THE LYMPHOCYTES.

4039
02:27:27,840 --> 02:27:31,240
SO ONE CAN BUILD VIRAL -- IN

4040
02:27:31,240 --> 02:27:33,880
THESE ORGANOIDS BUT ON TOP OF

4041
02:27:33,880 --> 02:27:36,600
THAT, ONE CAN -- IMMUNE CELLS.

4042
02:27:36,600 --> 02:27:38,560
FINALLY, A SLIGHTLY LONGER STORY

4043
02:27:38,560 --> 02:27:40,320
THAT WILL BE PUBLISHED AT THE

4044
02:27:40,320 --> 02:27:42,840
BEGINNING OF THE PANDEMIC, WHEN

4045
02:27:42,840 --> 02:27:44,280
OUR INSTITUTE CLOSED DOWN, I

4046
02:27:44,280 --> 02:27:46,320
SHOULD SAY THAT ALL OF THIS

4047
02:27:46,320 --> 02:27:47,040
ACTUALLY COMES FROM THE

4048
02:27:47,040 --> 02:27:48,960
INSTITUTE WHERE I STILL ADVISE

4049
02:27:48,960 --> 02:27:50,800
MY ACADEMIC LAB.

4050
02:27:50,800 --> 02:27:54,640
NOT FROM -- SO HERE YOU SEE ACE

4051
02:27:54,640 --> 02:27:55,600
2 EXPRESSION IN THE GUT.

4052
02:27:55,600 --> 02:27:57,200
WE REALIZE THAT ACE 2, WHEN IT

4053
02:27:57,200 --> 02:28:00,000
WAS PUBLISHED TO BE THE RECEPTOR

4054
02:28:00,000 --> 02:28:01,760
FOR SARS-COV-2 2 IS EXTREMELY

4055
02:28:01,760 --> 02:28:03,920
HIGHLY EXPRESSED IN THE SMALL

4056
02:28:03,920 --> 02:28:04,240
INTESTINES.

4057
02:28:04,240 --> 02:28:05,360
THESE ARE VILLI OF THE SMALL

4058
02:28:05,360 --> 02:28:07,040
INTESTINE THAT YOU SAW EARLIER

4059
02:28:07,040 --> 02:28:08,440
IN THE ANIMATION.

4060
02:28:08,440 --> 02:28:09,840
MUCH HIGHER ACTUALLY THAN IN THE

4061
02:28:09,840 --> 02:28:10,840
RESPIRATORY TRACT, AND THERE'S

4062
02:28:10,840 --> 02:28:12,080
ALSO SOME INDICATIONS THAT THE

4063
02:28:12,080 --> 02:28:14,960
VIRUS NOT ONLY HIT LUNGS, THERE

4064
02:28:14,960 --> 02:28:18,160
ARE GI ESTIMATES, QUITE COMMON.

4065
02:28:18,160 --> 02:28:20,320
NAUSEA, STOMACH ACHES, DIARRHEA,

4066
02:28:20,320 --> 02:28:23,520
AND ALSO WHEN THE FIRST PCR

4067
02:28:23,520 --> 02:28:27,600
ASSAYS BECAME AVAILABLE FOR SARS

4068
02:28:27,600 --> 02:28:30,960
COV-2, PEOPLE DETECT VIRAL RNA

4069
02:28:30,960 --> 02:28:31,280
IN STOOL.

4070
02:28:31,280 --> 02:28:33,160
CAN BE PRODUCED IN THE LUNG BUT

4071
02:28:33,160 --> 02:28:37,280
ALSO IN THE GUT.

4072
02:28:37,280 --> 02:28:41,680
SO WE GOT -- INFECTION OF EVERY

4073
02:28:41,680 --> 02:28:45,920
ORGANOID, CROW INTO EXPERTS,

4074
02:28:45,920 --> 02:28:49,240
MART LAMERS, BART HAAGMANS.

4075
02:28:49,240 --> 02:28:52,160
WE GET A -- INCREASE OF LIVE

4076
02:28:52,160 --> 02:28:53,760
VIRUS PARTICLES, WE ALSO GET A

4077
02:28:53,760 --> 02:28:56,560
FOUR LOG INCREASE IN VIRAL RNA.

4078
02:28:56,560 --> 02:28:57,760
MUCH HIGHER THAN IN ANY OTHER

4079
02:28:57,760 --> 02:29:00,400
TISSUE THAT WE HAVE TESTED, ALSO

4080
02:29:00,400 --> 02:29:02,000
MUCH HIGHER, MUCH MORE

4081
02:29:02,000 --> 02:29:03,800
REPLICATION THAN IN THE AIRWAYS.

4082
02:29:03,800 --> 02:29:06,200
AND IF YOU FOLLOW THIS -- WE

4083
02:29:06,200 --> 02:29:07,840
STAIN IN WHITE FOR THE NUCLEAR

4084
02:29:07,840 --> 02:29:12,440
PROTEIN OF SARS-COV-2 2, SO SARS

4085
02:29:12,440 --> 02:29:14,240
ONE INFECTED ORGANOID AFTER 24

4086
02:29:14,240 --> 02:29:14,440
HOURS.

4087
02:29:14,440 --> 02:29:16,040
WE KNOW THE VIRUS HAS TO ENTER

4088
02:29:16,040 --> 02:29:19,440
FROM THE LUMEN, ACE 2 IS A

4089
02:29:19,440 --> 02:29:20,600
LUMINAL PROTEIN, I'LL GET INTO

4090
02:29:20,600 --> 02:29:24,320
THAT A LITTLE BIT LATER, AND

4091
02:29:24,320 --> 02:29:26,560
ALSO ARE AS EXPECTED THE VIRUS

4092
02:29:26,560 --> 02:29:29,040
ENTERS THE CELL FROM THE LUMEN,

4093
02:29:29,040 --> 02:29:30,560
ONCE IT'S REPLICATED, IT'S

4094
02:29:30,560 --> 02:29:31,720
RELEASED AGAIN INTO THE LUMEN OF

4095
02:29:31,720 --> 02:29:35,600
THE GUT, AND THE SAME THING WILL

4096
02:29:35,600 --> 02:29:36,800
HAPPEN IN THE RESPIRATORY TRACT.

4097
02:29:36,800 --> 02:29:38,320
IF WE WAIT THREE DAYS OR SO, WE

4098
02:29:38,320 --> 02:29:42,400
NOW SEE THAT IN AN AFFECTED

4099
02:29:42,400 --> 02:29:43,680
ORGANOID, ALMOST EVERY CELL IS

4100
02:29:43,680 --> 02:29:45,440
EFFECTED BUT THE NEARBY

4101
02:29:45,440 --> 02:29:50,080
ORGANOIDS DO NOT GET AIIVETTED ,

4102
02:29:50,080 --> 02:29:51,720
IT GETS EXTRUDED INTO THE LUMENS

4103
02:29:51,720 --> 02:29:53,560
AND CANNOT ESCAPE TO AFFECT

4104
02:29:53,560 --> 02:29:54,240
ANOTHER ORGANOID.

4105
02:29:54,240 --> 02:29:54,800
SO THIS WORKS.

4106
02:29:54,800 --> 02:29:59,160
WE DID A LOT OF SINGLE CELL

4107
02:29:59,160 --> 02:30:02,120
SEQUENCING AND THINGS WITH

4108
02:30:02,120 --> 02:30:03,880
INTERFERON, THE VIRUS BLOCKS

4109
02:30:03,880 --> 02:30:04,560
INTERFERON RESPONSES.

4110
02:30:04,560 --> 02:30:06,360
THAT WAS NOT TOO INTERESTING.

4111
02:30:06,360 --> 02:30:07,920
WE THEN WENT ON TO STUDY HOSTS

4112
02:30:07,920 --> 02:30:09,320
THAT THE VIRUS IS USING.

4113
02:30:09,320 --> 02:30:11,320
OBVIOUSLY IT HAS SO FEW GENES

4114
02:30:11,320 --> 02:30:13,600
ITSELF THAT IT MUST RELY HEAVILY

4115
02:30:13,600 --> 02:30:15,680
ON HOST GENES.

4116
02:30:15,680 --> 02:30:20,160
THE FIRST THING IS KNOCK OUT --

4117
02:30:20,160 --> 02:30:22,120
THESE ARE CLONAL ORGANOIDS SO WE

4118
02:30:22,120 --> 02:30:23,600
CONFIRM BY SEQUENCING THESE TWO

4119
02:30:23,600 --> 02:30:25,920
INDEPENDENT CLONES, WE HAVE A

4120
02:30:25,920 --> 02:30:28,720
NUMBER OF THESE WILD TYPE THAT

4121
02:30:28,720 --> 02:30:31,440
GETS HARD LIE AFFECTED WITH

4122
02:30:31,440 --> 02:30:33,600
SARS-COV-2, THE ACE 2 MUTANTS AS

4123
02:30:33,600 --> 02:30:34,800
EXPECTED DO NOT GET AFFECTED.

4124
02:30:34,800 --> 02:30:36,440
SO IT'S A GOOD CONTROL FOR WHAT

4125
02:30:36,440 --> 02:30:37,760
WE'RE TRYING TO DO HERE.

4126
02:30:37,760 --> 02:30:39,840
SARS, THE ORIGINAL VIRUS, IS

4127
02:30:39,840 --> 02:30:41,280
ALSO KNOWN TO USE ACE 2 AND

4128
02:30:41,280 --> 02:30:43,680
INDEED IT DOES NOT AFFECT WHEN

4129
02:30:43,680 --> 02:30:45,840
ACE 2 IS KNOCKED OUT.

4130
02:30:45,840 --> 02:30:51,000
MERS, A THIRD MEMBER OF THIS

4131
02:30:51,000 --> 02:30:51,880
CORONA DOESN'T CARE ABOUT THE

4132
02:30:51,880 --> 02:30:53,280
ABSENCE OF ACE 2 IN BLUE HERE

4133
02:30:53,280 --> 02:30:55,280
AND IT'S KNOWN TO USE ANOTHER

4134
02:30:55,280 --> 02:30:57,200
RECEPTOR, DPP4, AND INDEED WHEN

4135
02:30:57,200 --> 02:31:02,920
WE KNOCK OUT D PSM  PP46789 NOWS

4136
02:31:02,920 --> 02:31:05,880
CANNOT INFECT BUT SARS-COV-2

4137
02:31:05,880 --> 02:31:10,240
2 CAN.

4138
02:31:10,240 --> 02:31:11,240
DPP4 -- WE CONFIRMED THAT FOR

4139
02:31:11,240 --> 02:31:12,200
THE GUT.

4140
02:31:12,200 --> 02:31:13,760
WHEN WE LOOK AT PUBLISHED

4141
02:31:13,760 --> 02:31:16,040
LITERATURE THERE ARE A NUMBER OF

4142
02:31:16,040 --> 02:31:16,720
GENOME-WIDE CRISPR SCREENS

4143
02:31:16,720 --> 02:31:18,000
REPORTED THAT HAVE COME UP WITH

4144
02:31:18,000 --> 02:31:19,440
DOZENS OF HUMAN GENES THAT WOULD

4145
02:31:19,440 --> 02:31:20,640
BE ESSENTIAL FOR VIRAL

4146
02:31:20,640 --> 02:31:21,080
REPLICATION.

4147
02:31:21,080 --> 02:31:23,720
WE KNOCKED OUT MOST OF THESE.

4148
02:31:23,720 --> 02:31:25,120
AGAIN, CLONAL, WE CONFIRM THAT

4149
02:31:25,120 --> 02:31:29,080
THEY CREATE NO ALLELES OF THESE

4150
02:31:29,080 --> 02:31:31,080
OR HOMOZYGOUS OF THESE GENES,

4151
02:31:31,080 --> 02:31:32,800
AND MUCH TO OUR SURPRISE, THE

4152
02:31:32,800 --> 02:31:35,120
ONLY GENE THAT WE CAN CONFIRM ON

4153
02:31:35,120 --> 02:31:38,480
TOP OF -- IN ADDITION TO ACE

4154
02:31:38,480 --> 02:31:42,760
2 IS TMPRSS2, SO THAT'S THE

4155
02:31:42,760 --> 02:31:44,800
SURFACE PROTEASE THAT CLEAVES

4156
02:31:44,800 --> 02:31:46,440
THE SPIKE PROTEIN AND ALLOWS THE

4157
02:31:46,440 --> 02:31:48,000
VIRUS THEN TO FUSE ITS ENVELOPE

4158
02:31:48,000 --> 02:31:49,760
WITH THE HOST MEMBRANE, BUT NONE

4159
02:31:49,760 --> 02:31:51,400
OF THESE OTHER GENES ACTUALLY

4160
02:31:51,400 --> 02:31:58,040
GAVE US ANY INHI    INHIBITION Y

4161
02:31:58,040 --> 02:32:06,360
ANY INHIBITION.

4162
02:32:06,360 --> 02:32:09,960
ANOTHER OBSERVATION IS THAT

4163
02:32:09,960 --> 02:32:12,600
CHLOROQUINE, PROBABLY ALL OF

4164
02:32:12,600 --> 02:32:15,240
KNOW CHLOROQUINE,

4165
02:32:15,240 --> 02:32:16,560
HYDROXYCHLOROQUINE WERE VERY

4166
02:32:16,560 --> 02:32:17,840
POPULAR IN THE FIRST YEAR OR SO

4167
02:32:17,840 --> 02:32:21,960
OF THE PANDEMIC FOR SARS-COV-2

4168
02:32:21,960 --> 02:32:22,640
PATIENTS.

4169
02:32:22,640 --> 02:32:24,960
INDEED WE CAN REPRODUCE THAT IN

4170
02:32:24,960 --> 02:32:27,680
VERO E6 CELLS, AFRICAN MONKEY

4171
02:32:27,680 --> 02:32:28,800
CELLS FROM THE KIDNEY, THAT WHEN

4172
02:32:28,800 --> 02:32:30,640
YOU LOOK AT THEM LOOK MORE LIKE

4173
02:32:30,640 --> 02:32:31,000
FIBROBLASTS.

4174
02:32:31,000 --> 02:32:33,160
YOU TYPICALLY HAVE TO TRANSFECT

4175
02:32:33,160 --> 02:32:34,640
IN ACE 2 TO MAKE THEM RECEPTIVE

4176
02:32:34,640 --> 02:32:36,240
TO THE VIRUS.

4177
02:32:36,240 --> 02:32:39,600
BUT WHEN YOU DO THAT, YOU THEN

4178
02:32:39,600 --> 02:32:42,240
EFFECT WITH THE VIRUS AND ADD

4179
02:32:42,240 --> 02:32:43,760
CHLOROQUINE, CHLOROQUINE NICELY

4180
02:32:43,760 --> 02:32:46,960
BLOCKS INFECTION WITH AN IC50 OF

4181
02:32:46,960 --> 02:32:48,560
ONE MICROMOLAR AND 10

4182
02:32:48,560 --> 02:32:50,560
MICROMOLAR, VIRAL REPLICATION IS

4183
02:32:50,560 --> 02:32:51,880
ENTIRELY DEAD.

4184
02:32:51,880 --> 02:32:54,960
IF YOU NOTE THE SAME AMOUNT OF

4185
02:32:54,960 --> 02:32:55,800
CHLOROQUINE OR

4186
02:32:55,800 --> 02:32:57,120
HYDROXYCHLOROQUINE AND ADD TO AN

4187
02:32:57,120 --> 02:32:58,200
ORGANOID CULTURE, WE SEE NO

4188
02:32:58,200 --> 02:33:00,000
EFFECT WHATSOEVER, SO GREEN IS

4189
02:33:00,000 --> 02:33:04,360
THE WILD TYPE, BLUE IS THE

4190
02:33:04,360 --> 02:33:05,840
CHLOROQUINE-TREATED ORGANOID, SO

4191
02:33:05,840 --> 02:33:08,320
10 MICROMOLAR, NO EFFECT, IN

4192
02:33:08,320 --> 02:33:09,920
VERY SICK CELLS YOU HAVE FULL

4193
02:33:09,920 --> 02:33:10,200
BLOCKADE.

4194
02:33:10,200 --> 02:33:12,000
HOW TO EXPLAIN THIS, THERE ARE

4195
02:33:12,000 --> 02:33:14,400
OTHER PAPERS THAT SHOW THE SAME

4196
02:33:14,400 --> 02:33:15,360
PHENOMENA.

4197
02:33:15,360 --> 02:33:16,720
WHAT WE THINK IS HAPPENING IN

4198
02:33:16,720 --> 02:33:18,480
THESE NON-PRIMARY EPITHELIAL

4199
02:33:18,480 --> 02:33:21,200
CELLS THAT ARE OFTEN USED IN

4200
02:33:21,200 --> 02:33:22,320
VIROLOGY LABS IS THAT THE VIRUS

4201
02:33:22,320 --> 02:33:23,840
WILL BIND TO ACE 2 IF IT'S

4202
02:33:23,840 --> 02:33:24,360
PRESENT.

4203
02:33:24,360 --> 02:33:28,960
IT THEN GETS ENDO CYTOSED INTO

4204
02:33:28,960 --> 02:33:31,160
THE CELL AND FINALLY WHEN THE

4205
02:33:31,160 --> 02:33:32,240
RNA GENOME NEEDS TO BE RELEASED

4206
02:33:32,240 --> 02:33:35,760
FROM THIS PARTICLE HERE, THIS

4207
02:33:35,760 --> 02:33:37,160
INVOLVES THE CATH EP SINS THAT I

4208
02:33:37,160 --> 02:33:37,920
JUST SHOWED.

4209
02:33:37,920 --> 02:33:41,680
OF COURSE ENDO CYTOSIS IS

4210
02:33:41,680 --> 02:33:43,080
HIGHLY -- TO CHLOROQUINE AND

4211
02:33:43,080 --> 02:33:48,440
WOULD ALSO BE HIGHLY SENSITIVE

4212
02:33:48,440 --> 02:33:50,400
TO -- YOU HAVE AIRWAYS OR

4213
02:33:50,400 --> 02:33:53,240
INTESTINAL TRACT BUT ALSO

4214
02:33:53,240 --> 02:33:55,200
ORGANOIDS AND INTESTINAL TRACT

4215
02:33:55,200 --> 02:33:56,640
ORGANOIDS IS THERE'S A REAL

4216
02:33:56,640 --> 02:33:58,280
APICAL DOMAIN WHERE NATURALLY

4217
02:33:58,280 --> 02:33:59,800
ACE 2 IS EXPRESSED SO THE VIRUS

4218
02:33:59,800 --> 02:34:01,560
BINDS.

4219
02:34:01,560 --> 02:34:02,640
NATURALLY ALSO MOST -- CAN BE

4220
02:34:02,640 --> 02:34:04,720
KNOCKED OUT ALL -- THEY DO

4221
02:34:04,720 --> 02:34:09,320
NOTHING, IT'S ONLY TMPRSS2 THAT

4222
02:34:09,320 --> 02:34:12,040
HAS THAT EFFECT, THAT ACTUALLY

4223
02:34:12,040 --> 02:34:14,080
CLEAVE AND -- THE VIRAL ENVELOPE

4224
02:34:14,080 --> 02:34:15,240
DIRECTLY FUSES WITH THE HOST

4225
02:34:15,240 --> 02:34:17,720
MEMBRANE, THE VIRUS INFECTS ITS

4226
02:34:17,720 --> 02:34:19,160
RNA GENOME INTO THE HOST CELL

4227
02:34:19,160 --> 02:34:20,360
AND INFECTION IS STARTED.

4228
02:34:20,360 --> 02:34:24,400
THERE'S NO ENDO CYTOSIS UPON

4229
02:34:24,400 --> 02:34:25,720
INFECTION OF THE PRIMARY

4230
02:34:25,720 --> 02:34:28,240
EPITHELIAL CELL AND NO

4231
02:34:28,240 --> 02:34:29,680
SENSITIVITY TO HYDROXYCOLOR KIN.

4232
02:34:29,680 --> 02:34:32,280
SO LESSON TO BE LEARNED HERE IS

4233
02:34:32,280 --> 02:34:35,120
IT MAY BE GOOD TO INVOLVE

4234
02:34:35,120 --> 02:34:36,560
ORGANOIDS IN ADDITION TO THE

4235
02:34:36,560 --> 02:34:37,640
MORE EASY TO WORK WITH CELL

4236
02:34:37,640 --> 02:34:40,400
LINES IF I WANT TO STEP FROM

4237
02:34:40,400 --> 02:34:42,040
OBSERVATION IN THE LAB INTO THE

4238
02:34:42,040 --> 02:34:42,520
CLINIC.

4239
02:34:42,520 --> 02:34:44,840
AND WITH THAT, I THINK I NAMED

4240
02:34:44,840 --> 02:34:46,280
THE IMPORTANT INVESTIGATORS

4241
02:34:46,280 --> 02:34:47,680
ALREADY, COLLABORATORS ALREADY,

4242
02:34:47,680 --> 02:34:51,440
AND OF COURSE       

4243
02:34:51,440 --> 02:34:52,480
THAT ENDS MY TALK, I THANK YOU

4244
02:34:52,480 --> 02:34:53,960
VERY MUCH FOR YOUR ATTENTION AND

4245
02:34:53,960 --> 02:34:55,040
I'LL STOP HERE AND GIVE THE

4246
02:34:55,040 --> 02:34:56,440
FLOOR BACK TO MARC.

4247
02:34:56,440 --> 02:34:58,200
>> THANKS, HANS.

4248
02:34:58,200 --> 02:34:58,720
BEAUTIFUL PRESENTATION.

4249
02:34:58,720 --> 02:35:01,080
I THINK WE ACTUALLY HAVE TIME --

4250
02:35:01,080 --> 02:35:02,560
WE'RE AHEAD OF SCHEDULE.

4251
02:35:02,560 --> 02:35:05,960
THERE'S A QUESTION ON THE CHAT

4252
02:35:05,960 --> 02:35:08,800
FOR YOU THAT SAYS THE VIDEO OF

4253
02:35:08,800 --> 02:35:12,200
THE RSV TOMATO-INFECTED 3D

4254
02:35:12,200 --> 02:35:14,840
ORGANOIDS LOOKS REALLY NICE.

4255
02:35:14,840 --> 02:35:17,040
WHICH MODEL OF MICROSCOPE DO YOU

4256
02:35:17,040 --> 02:35:20,280
USE FOR LIGHT IMAGING?

4257
02:35:20,280 --> 02:35:22,400
I GUESS WE KNOW SOME OF THESE

4258
02:35:22,400 --> 02:35:29,200
ORGANOIDS ARE HARD TO IMAGE.

4259
02:35:29,200 --> 02:35:33,760
RAPID LOW ENERGY CON FOCALS BUT

4260
02:35:33,760 --> 02:35:37,600
I DON'T KNOW HOW THIS MOVIE WAS

4261
02:35:37,600 --> 02:35:38,840
MADE.

4262
02:35:38,840 --> 02:35:39,560
>> GREAT.

4263
02:35:39,560 --> 02:35:40,560
THANKS SO MUCH, HANS.

4264
02:35:40,560 --> 02:35:41,200
APPRECIATE IT.

4265
02:35:41,200 --> 02:35:42,400
HANS, I BELIEVE YOU WON'T BE

4266
02:35:42,400 --> 02:35:44,600
ABLE TO BE IN THE QUESTION AND

4267
02:35:44,600 --> 02:35:45,400
ANSWERS, I DON'T KNOW HOW LONG

4268
02:35:45,400 --> 02:35:45,800
YOU CAN STAY.

4269
02:35:45,800 --> 02:35:46,920
>> I HAVE TO APOLOGIZE.

4270
02:35:46,920 --> 02:35:48,320
I HAVE TO STEP OUT IN A FEW

4271
02:35:48,320 --> 02:35:48,560
MINUTES.

4272
02:35:48,560 --> 02:35:49,200
>> YEAH.

4273
02:35:49,200 --> 02:35:50,720
SO THERE'S A FEW QUESTIONS YOU

4274
02:35:50,720 --> 02:35:53,360
CAN TAKE IF YOU HAVE TIME

4275
02:35:53,360 --> 02:35:54,240
OFFLINE.

4276
02:35:54,240 --> 02:35:59,800
BUT WE'LL CONTINUE NOW, AND THE

4277
02:35:59,800 --> 02:36:01,920
NEXT SPEAKER IS PROFESSOR LINDA

4278
02:36:01,920 --> 02:36:03,440
GRIFFITH.

4279
02:36:03,440 --> 02:36:06,560
SHE IS MIT SCHOOL OF ENGINEERING

4280
02:36:06,560 --> 02:36:07,920
TEACHING INNOVATION PROFESSOR OF

4281
02:36:07,920 --> 02:36:09,760
BIOLOGICAL AND MECHANICAL

4282
02:36:09,760 --> 02:36:12,480
ENGINEERING, AND DIRECTOR OF THE

4283
02:36:12,480 --> 02:36:14,680
CENTER FOR GYNEPATHOLOGY

4284
02:36:14,680 --> 02:36:16,200
RESEARCH AT MIT, WHICH IS AN

4285
02:36:16,200 --> 02:36:17,400
INSTITUTE THAT FOSTERS BOTH

4286
02:36:17,400 --> 02:36:19,920
BASIC AND CLINICAL RESEARCH IN

4287
02:36:19,920 --> 02:36:21,240
PATHOLOGIES OF THE FEMALE

4288
02:36:21,240 --> 02:36:23,000
REPRODUCTIVE TRACT.

4289
02:36:23,000 --> 02:36:26,480
AND SHE'S A MEMBER OF THE

4290
02:36:26,480 --> 02:36:27,800
NATIONAL ACADEMY OF ENGINEERS,

4291
02:36:27,800 --> 02:36:29,680
NATIONAL ACADEMY OF MEDICINE,

4292
02:36:29,680 --> 02:36:31,480
NATIONAL ACADEMY OF INVENTORS, A

4293
02:36:31,480 --> 02:36:33,480
IF LOW OF THE AMERICAN ACADEMY

4294
02:36:33,480 --> 02:36:35,320
OF ARTS AND SCIENCE.

4295
02:36:35,320 --> 02:36:38,160
SHE WAS A RECIPIENT OF THE

4296
02:36:38,160 --> 02:36:42,120
MACARTHUR FOUNDATION FELLOWSHIP.

4297
02:36:42,120 --> 02:36:43,880
AND THE GRIFFITH LAB HAS BEEN A

4298
02:36:43,880 --> 02:36:45,280
PIONEER IN USING TISSUE

4299
02:36:45,280 --> 02:36:49,880
ENGINEERING AND BIOMATERIALS

4300
02:36:49,880 --> 02:36:51,840
TECHNOLOGIES FOR REGENERATIVE

4301
02:36:51,840 --> 02:36:53,200
MEDICINE, DRUG DEVELOPMENT AND

4302
02:36:53,200 --> 02:36:54,240
UNDERSTANDING DISEASE

4303
02:36:54,240 --> 02:36:58,440
PATHOPHYSIOLOGY.

4304
02:36:58,440 --> 02:37:05,680
LINDA, THE FLOOR IS YOURS.

4305
02:37:05,680 --> 02:37:12,320
>> THANK YOU.

4306
02:37:12,320 --> 02:37:19,840
LET ME SHARE MY SCREEN.

4307
02:37:19,840 --> 02:37:22,720
SO I'M GOING TO SHARE WITH YOU A

4308
02:37:22,720 --> 02:37:25,120
VERY USEFUL TOOL, SO THERE'S ONE

4309
02:37:25,120 --> 02:37:27,640
MAIN THEME OF MY WORK, BUT I'M

4310
02:37:27,640 --> 02:37:30,440
GOING TO PUT AROUND THE

4311
02:37:30,440 --> 02:37:31,640
PRESENTATION THAT THE CONTEXT

4312
02:37:31,640 --> 02:37:34,400
FOR WHICH WE DEVELOPED THIS

4313
02:37:34,400 --> 02:37:34,720
TOOL.

4314
02:37:34,720 --> 02:37:38,680
SO BY WAY OF INTRODUCTION, JUST

4315
02:37:38,680 --> 02:37:40,520
BIG CONTEXT FOR MY LAB, WE'VE

4316
02:37:40,520 --> 02:37:43,920
BEEN INVOLVES IN ORGANS ON A

4317
02:37:43,920 --> 02:37:47,480
CHIP WORK SINCE THE BEGINNING OF

4318
02:37:47,480 --> 02:37:48,400
THE 1990s DEVELOPING VARIOUS

4319
02:37:48,400 --> 02:37:51,160
KINDS OF MODELS, AND AN

4320
02:37:51,160 --> 02:37:52,240
OVERARCHING CHALLENGE THAT WE

4321
02:37:52,240 --> 02:37:55,200
ADDRESS IN OUR WORK IS THE NEED

4322
02:37:55,200 --> 02:38:00,360
TO USE DEVICES THAT DO NOT

4323
02:38:00,360 --> 02:38:01,080
ABSORB LIPOPHILIC COMPOUNDS.

4324
02:38:01,080 --> 02:38:02,400
SO I'M SHOWING YOU A PROJECT WE

4325
02:38:02,400 --> 02:38:04,600
DID WITH DARPA SPONSORSHIP TO

4326
02:38:04,600 --> 02:38:05,880
PUT 10 ORGANS TOGETHER ON A CHIP

4327
02:38:05,880 --> 02:38:10,280
FOR A MONTH, AND THE REASON TO

4328
02:38:10,280 --> 02:38:11,840
SHOW THIS CHIP IS NOT THAT CUTE

4329
02:38:11,840 --> 02:38:13,520
AND ATTRACTIVE, BUT IT IS VERY,

4330
02:38:13,520 --> 02:38:16,200
VERY GOOD FOR PHARMACOKINETICS.

4331
02:38:16,200 --> 02:38:17,760
AND MY MAIN RESEARCH INTERESTS

4332
02:38:17,760 --> 02:38:20,760
ARE IN INFLAMMATION, SO RELEVANT

4333
02:38:20,760 --> 02:38:21,440
TO VIRUSES.

4334
02:38:21,440 --> 02:38:22,640
SO THE TOOLS I'M GOING TO TALK

4335
02:38:22,640 --> 02:38:25,160
ABOUT TODAY ARE MAINLY VALUABLE,

4336
02:38:25,160 --> 02:38:28,120
I THINK IN THIS COMMUNITY,

4337
02:38:28,120 --> 02:38:29,640
BECAUSE WE CAN CAPTURE

4338
02:38:29,640 --> 02:38:30,600
INFLAMMATORY EVENTS THAT ARE

4339
02:38:30,600 --> 02:38:32,600
REGULATED BY A LOT OF THINGS,

4340
02:38:32,600 --> 02:38:34,040
INCLUDING STEROID HORMONES,

4341
02:38:34,040 --> 02:38:35,760
WHICH ABSORB INTO PDMS.

4342
02:38:35,760 --> 02:38:37,440
SO AFTER THE BIG DARPA PROJECT,

4343
02:38:37,440 --> 02:38:39,600
WE'VE GONE ON TO DO A NUMBER OF

4344
02:38:39,600 --> 02:38:42,680
PROJECTS WITH THAT PLATFORM,

4345
02:38:42,680 --> 02:38:45,080
MAINLY MARTIN TRAPECAR, POSTDOC

4346
02:38:45,080 --> 02:38:46,680
LOOKING AT INFLAMMATION BETWEEN

4347
02:38:46,680 --> 02:38:48,320
THE GUT, LIVER AND BRAIN AND HOW

4348
02:38:48,320 --> 02:38:50,120
THAT'S MODULATED WITH SHORT

4349
02:38:50,120 --> 02:38:51,440
CHAIN FATTY ACIDS.

4350
02:38:51,440 --> 02:38:54,040
AGAIN, THAT PLATFORM IS NOT

4351
02:38:54,040 --> 02:38:55,440
HIGH-THROUGHPUT, IT'S NOT

4352
02:38:55,440 --> 02:38:58,160
INCREDIBLY PORTABLE TO OTHER

4353
02:38:58,160 --> 02:38:59,280
LABS, ALTHOUGH OTHER LABS HAVE

4354
02:38:59,280 --> 02:39:00,720
USED IT, BUT IT DOES HAVE THE

4355
02:39:00,720 --> 02:39:04,520
VALUE OF CAPTURING COMPLEX

4356
02:39:04,520 --> 02:39:06,400
ORGAN-ORGAN CROSSTALK AND

4357
02:39:06,400 --> 02:39:07,400
INFLAMMATION SO IT DOES HAVE

4358
02:39:07,400 --> 02:39:08,120
RELEVANCE FOR INFECTION.

4359
02:39:08,120 --> 02:39:10,000
NOW ALL OF THIS WORK SPARCED US

4360
02:39:10,000 --> 02:39:13,280
IN RECENT YEARS TO DO TWO BIG

4361
02:39:13,280 --> 02:39:14,520
THINGS, AND THAT IS TO DEVELOP

4362
02:39:14,520 --> 02:39:17,240
BETTER MODELS OF THE FISH    TIS

4363
02:39:17,240 --> 02:39:18,960
THEMSELVES USING ORGANOIDS, SO

4364
02:39:18,960 --> 02:39:20,720
IT'S GREAT TO HAVE HANS AHEAD OF

4365
02:39:20,720 --> 02:39:24,000
ME, AND SECONDLY, TO PUSH REALLY

4366
02:39:24,000 --> 02:39:27,520
HARD TO MAKE BETTER DEVICES,

4367
02:39:27,520 --> 02:39:28,720
PARTICULARLY ONES THAT ARE

4368
02:39:28,720 --> 02:39:29,360
VASCULARIZED.

4369
02:39:29,360 --> 02:39:31,120
AND WE DO THIS IN THE CONTEXT OF

4370
02:39:31,120 --> 02:39:34,960
A DISEASE CALLED ENDOMETRIOSIS,

4371
02:39:34,960 --> 02:39:36,600
WHICH IS A COMPLEX INFLAMMATORY

4372
02:39:36,600 --> 02:39:38,320
DISEASE CHARACTERIZED BY ECTOPIC

4373
02:39:38,320 --> 02:39:40,320
GROWTH OF ENDOMETRIUM, WHICH IS

4374
02:39:40,320 --> 02:39:41,520
THE LINING OF THE UTERUS, SO YOU

4375
02:39:41,520 --> 02:39:44,240
CAN SEE HERE THESE LESIONS, THEY

4376
02:39:44,240 --> 02:39:46,320
CAN BECOME VERY INVASIVE, INVADE

4377
02:39:46,320 --> 02:39:47,360
THROUGH THE DIAPHRAGM AND GET TO

4378
02:39:47,360 --> 02:39:48,400
THE LUNGS.

4379
02:39:48,400 --> 02:39:50,800
THEY'RE BEAUTIFUL CYSTIC-LIKE

4380
02:39:50,800 --> 02:39:51,920
STRUCTURES, SINGLE EPITHELIUM,

4381
02:39:51,920 --> 02:39:55,040
JUST LIKE IN THE END   ENDOMETR.

4382
02:39:55,040 --> 02:39:58,240
WHY IT CAN IB   INVADE A MUSCLES

4383
02:39:58,240 --> 02:39:59,320
ANYBODY'S GUESS RIGHT NOW, BUT

4384
02:39:59,320 --> 02:40:01,160
IT DOES FORM THE CONTEXT FOR THE

4385
02:40:01,160 --> 02:40:01,840
ORGANOID WORK WE DO.

4386
02:40:01,840 --> 02:40:04,480
WHEN WE CAME IN THE FIELD, A

4387
02:40:04,480 --> 02:40:08,200
CONTRIBUTION WE MADE WAS TO

4388
02:40:08,200 --> 02:40:10,400
START EFFORTS TO DO MOLECULAR

4389
02:40:10,400 --> 02:40:11,200
STRATIFICATION OF THE DISEASE ON

4390
02:40:11,200 --> 02:40:13,600
THE BASIS OF INFLAMMATORY AND

4391
02:40:13,600 --> 02:40:14,440
INNOVATION SIGNATURES.

4392
02:40:14,440 --> 02:40:16,520
THERE'S NOT GREAT GENETICS FOR

4393
02:40:16,520 --> 02:40:18,280
THIS DISEASE, UNLIKE CANCER,

4394
02:40:18,280 --> 02:40:19,920
THERE AREN'T SOMATIC MUTATIONS,

4395
02:40:19,920 --> 02:40:22,680
SO WE HAVE BEEN INVESTIGATING

4396
02:40:22,680 --> 02:40:27,320
THE INFLAMMATION SIGNATURES IN

4397
02:40:27,320 --> 02:40:33,280
THE EU TO PICK     TOPIC TISSUE.

4398
02:40:33,280 --> 02:40:36,560
ALL OF THEM HAVE FEATURES OF THE

4399
02:40:36,560 --> 02:40:38,080
EPITHELIAL, STROH MOLE AND

4400
02:40:38,080 --> 02:40:39,600
IMMUNE INTERACTIONS THAT ARE

4401
02:40:39,600 --> 02:40:39,960
ARRANGED.

4402
02:40:39,960 --> 02:40:41,280
I WANT TO FOCUS MORE ON THE

4403
02:40:41,280 --> 02:40:44,000
TOOLS BUT THIS IS REALLY

4404
02:40:44,000 --> 02:40:47,240
IMPORTANT CONTEXT.

4405
02:40:47,240 --> 02:40:48,600
A FIRST THING WE DID WAS A STUDY

4406
02:40:48,600 --> 02:40:50,320
IN ABOUT A HUNDRED WOMEN, WE

4407
02:40:50,320 --> 02:40:52,440
SHOWED THAT PERITONEAL FLUID HAD

4408
02:40:52,440 --> 02:40:54,280
SIGNATURES THAT ALLOWED A

4409
02:40:54,280 --> 02:40:56,360
MOLECULAR CLASSIFICATION OF

4410
02:40:56,360 --> 02:40:58,440
ABOUT A THIRD OF THE PATIENTS

4411
02:40:58,440 --> 02:41:03,280
WHO HAD ALL THE SURGICAL DISEASE

4412
02:41:03,280 --> 02:41:04,280
STAGES, AND WE USED THIS

4413
02:41:04,280 --> 02:41:05,720
MOLECULAR SIGNATURES WITH

4414
02:41:05,720 --> 02:41:07,000
BIOINFORMATICS TO PREDICT THAT A

4415
02:41:07,000 --> 02:41:08,560
CERTAIN KIND OF MACROPHAGE WAS

4416
02:41:08,560 --> 02:41:12,480
MAKING THESE CYTOKINES AND THAT

4417
02:41:12,480 --> 02:41:13,880
JUN KINASE WAS REGULATING IT.

4418
02:41:13,880 --> 02:41:15,200
FIRST TIME THERE WAS A REAL DRUG

4419
02:41:15,200 --> 02:41:16,840
TARGET THAT WASN'T A HORMONE.

4420
02:41:16,840 --> 02:41:18,480
JUN KINASE WAS ALSO IMPLICATED

4421
02:41:18,480 --> 02:41:21,360
IN AN INNOVATION STUDY WE DID,

4422
02:41:21,360 --> 02:41:23,440
COMBINING IN VITRO MODELS AND IN

4423
02:41:23,440 --> 02:41:25,160
VIVO SAMPLE, SO WE BECAME VERY

4424
02:41:25,160 --> 02:41:26,600
INTERESTED IN THIS AS A DRUG

4425
02:41:26,600 --> 02:41:27,800
TARGET AND WE LEARNED THAT THERE

4426
02:41:27,800 --> 02:41:30,640
HAD BEEN A CLINICAL TRIAL THAT

4427
02:41:30,640 --> 02:41:32,680
HAD FAILED BASED ON GREAT

4428
02:41:32,680 --> 02:41:34,760
PRE-CLINICAL DATA.

4429
02:41:34,760 --> 02:41:36,640
SO IN TALKING TO PHARMA, THEY

4430
02:41:36,640 --> 02:41:37,840
SAID WE NEED BETTER MODELS.

4431
02:41:37,840 --> 02:41:39,280
SO THIS IS REALLY WHERE I WANT

4432
02:41:39,280 --> 02:41:39,800
TO FOCUS.

4433
02:41:39,800 --> 02:41:42,320
SO TOGETHER WITH OUR WONDERFUL

4434
02:41:42,320 --> 02:41:43,120
CLINICAL COLLABORATORS, WE GET

4435
02:41:43,120 --> 02:41:45,360
SAMPLES FROM PATIENTS, AND BUILD

4436
02:41:45,360 --> 02:41:48,560
TISSUE BANKS, AND THESE ARE WELL

4437
02:41:48,560 --> 02:41:50,000
CLINICALLY PHENOTYPED PATIENTS.

4438
02:41:50,000 --> 02:41:52,360
AND OF COURSE THEN WE WANT TO

4439
02:41:52,360 --> 02:41:52,960
RECONSTRUCT AVATARS OF THE

4440
02:41:52,960 --> 02:41:55,240
PATIENTS THAT MAY LET US TEST

4441
02:41:55,240 --> 02:41:59,720
COMPLEX DISEASE MECHANISMS.

4442
02:41:59,720 --> 02:42:01,160
SO I'M GOING TO FOCUS HERE ON

4443
02:42:01,160 --> 02:42:02,880
BIDDING MODELS OF THE AIN'T

4444
02:42:02,880 --> 02:42:04,440
ACTIONS BETWEEN EPITHELIA,

4445
02:42:04,440 --> 02:42:06,480
STROMA AND IMMUNE CELLS AND

4446
02:42:06,480 --> 02:42:07,920
LATER VASCULAR TISSUE.

4447
02:42:07,920 --> 02:42:11,440
NOW EVERYTHING THAT HANS CLEVERS

4448
02:42:11,440 --> 02:42:12,720
JUST SPOKE ABOUT HAS BEEN

4449
02:42:12,720 --> 02:42:14,200
ENORMOUSLY ENABLING FOR LABS ALL

4450
02:42:14,200 --> 02:42:17,440
OVER THE WORLD WHO USE ANY KIND

4451
02:42:17,440 --> 02:42:20,280
OF MUCOSAL BARRIER TISSUES.

4452
02:42:20,280 --> 02:42:21,600
SHOWN BY TWO DIFFERENT GROUPS WE

4453
02:42:21,600 --> 02:42:24,440
WORKED WITH, THE TURCO, ET AL.

4454
02:42:24,440 --> 02:42:26,080
INVESTIGATORS, AND ALL THE

4455
02:42:26,080 --> 02:42:27,080
ENDOMETRIUM LABS AROUND THE

4456
02:42:27,080 --> 02:42:28,040
WORLD USE VERSIONS OF THESE.

4457
02:42:28,040 --> 02:42:29,240
NOW A HUGE PROBLEM AND SOMETHING

4458
02:42:29,240 --> 02:42:31,440
I WANT TO FOCUS ON, I THINK IS

4459
02:42:31,440 --> 02:42:33,280
USEFUL TO THE COMMUNITY, IS THAT

4460
02:42:33,280 --> 02:42:35,400
ALL OF THESE ORGANOIDS ARE

4461
02:42:35,400 --> 02:42:40,720
GENERALLY GROWN IN MAT RIGEL.

4462
02:42:40,720 --> 02:42:44,560
MOST GROW THEM IN -- CULTURE,

4463
02:42:44,560 --> 02:42:45,880
BUT ESPECIALLY FOR US BECAUSE

4464
02:42:45,880 --> 02:42:47,760
WE'RE TRYING TO BUILD COMPLEX

4465
02:42:47,760 --> 02:42:49,800
TISSUES, THE INTERACTIONS WITH

4466
02:42:49,800 --> 02:42:51,000
STROMAL AND IMMUNE CELLS ARE NOT

4467
02:42:51,000 --> 02:42:53,560
SO FAVORABLE.

4468
02:42:53,560 --> 02:42:55,000
IT ALSO HARD TO PUT IN DEVICES

4469
02:42:55,000 --> 02:42:56,320
AND DO ALL THE THINGS WE WANT TO

4470
02:42:56,320 --> 02:42:57,200
DO WITH TISSUE ENGINEERING.

4471
02:42:57,200 --> 02:42:59,280
SO WE UNDERTOOK A FAIRLY

4472
02:42:59,280 --> 02:43:01,960
COMPREHENSIVE EFFORT TO BUILD

4473
02:43:01,960 --> 02:43:02,680
SYNTHETIC HYDROGELS THAT COULD

4474
02:43:02,680 --> 02:43:05,440
BE USED FOR TISSUE ENGINEERING

4475
02:43:05,440 --> 02:43:07,200
OF THE MUCOSAL BARRIER

4476
02:43:07,200 --> 02:43:07,960
STRUCTURES AND THESE OF COURSE

4477
02:43:07,960 --> 02:43:09,680
ARE VERY IMPORTANT IN VIRUSES TO

4478
02:43:09,680 --> 02:43:10,880
INCLUDE IMMUNE CELLS PAUSE THE

4479
02:43:10,880 --> 02:43:12,080
INTERACTIONS WITH IMMUNE CELLS

4480
02:43:12,080 --> 02:43:13,320
OF COURSE ARE GOING TO DICTATE

4481
02:43:13,320 --> 02:43:17,280
WHAT HAPPENS.

4482
02:43:17,280 --> 02:43:19,680
WE INTRODUCED AN APPROACH

4483
02:43:19,680 --> 02:43:20,640
DECADES AGO USED ALL OVER THE

4484
02:43:20,640 --> 02:43:22,600
WORLD BUT WE CUSTOMIZED IT IN

4485
02:43:22,600 --> 02:43:23,800
VERY SPECIAL WAYS.

4486
02:43:23,800 --> 02:43:26,000
AT THE HEART OF THIS IS MULTIARM

4487
02:43:26,000 --> 02:43:29,400
PEGS MODIFIED WITH SMALL

4488
02:43:29,400 --> 02:43:33,320
PEPTIDES, WE TYPICALLY -- THESE

4489
02:43:33,320 --> 02:43:35,960
CAN BE BLADE INTO A GEL BY A.

4490
02:43:35,960 --> 02:43:38,480
PH CHANGE VERY SAFELY AROUND

4491
02:43:38,480 --> 02:43:38,920
CELLS.

4492
02:43:38,920 --> 02:43:40,120
WHAT WE DID THAT WAS SPECIAL AND

4493
02:43:40,120 --> 02:43:41,600
DRIVEN HUGELY BY OUR DESIRE TO

4494
02:43:41,600 --> 02:43:44,280
HAVE A MATRIX THAT    THAT WOULT

4495
02:43:44,280 --> 02:43:46,240
NOT ONLY EPITHELIA BUT STROMA,

4496
02:43:46,240 --> 02:43:48,520
IMMUNE CELLS, VASCULAR CELLS, ET

4497
02:43:48,520 --> 02:43:51,720
CETERA, IS TO THINK ABOUT FIRST

4498
02:43:51,720 --> 02:43:52,680
THE INTERACTION CELLS WOULD HAVE

4499
02:43:52,680 --> 02:43:54,280
WHEN THEY'RE NAKED AND FIRST PUT

4500
02:43:54,280 --> 02:43:58,720
INTO THE GEL, THEY NEED TO

4501
02:43:58,720 --> 02:44:01,440
INTERACT WITH INTIGRINS TO

4502
02:44:01,440 --> 02:44:01,680
SURVIVE.

4503
02:44:01,680 --> 02:44:02,760
ONE OF THOSE THINGS THE DO

4504
02:44:02,760 --> 02:44:03,960
OBVIOUSLY IS TO DEPOSIT THEIR

4505
02:44:03,960 --> 02:44:06,040
OWN MATRIX AND REMODEL THEIR

4506
02:44:06,040 --> 02:44:06,680
MICROENVIRONMENT.

4507
02:44:06,680 --> 02:44:10,160
SO WE INCLUDE IN OUR GEL TWO

4508
02:44:10,160 --> 02:44:13,920
SPECIAL PEPTIDES THAT INTERACT.

4509
02:44:13,920 --> 02:44:15,560
I NOTE WE HAVE A DIFFERENT FORM

4510
02:44:15,560 --> 02:44:19,400
OF AN RGD INTERGREN.

4511
02:44:19,400 --> 02:44:22,560
A LOT OF FOLKS USE -- MOST CELLS

4512
02:44:22,560 --> 02:44:24,400
DOCTOR NORMAL CELLS DON'T HAVE

4513
02:44:24,400 --> 02:44:26,520
ALPHA B BETA 3 SO WE USE A

4514
02:44:26,520 --> 02:44:30,320
LIGAND THAT INTERACTS WITH OTHER

4515
02:44:30,320 --> 02:44:30,960
RGD INTERGRENS.

4516
02:44:30,960 --> 02:44:32,520
THEN WE ALSO HAVE PEPTIDES THAT

4517
02:44:32,520 --> 02:44:35,680
BIND TO EXTRACELLULAR MATRIX.

4518
02:44:35,680 --> 02:44:36,880
THAT CELLS THEMSELVES DEPOSIT.

4519
02:44:36,880 --> 02:44:39,080
SO WHERE THERE ARE FIBROBLASTS,

4520
02:44:39,080 --> 02:44:42,440
THE PROVISIONAL MATRIX OF

4521
02:44:42,440 --> 02:44:43,800
IVERMECTIN AS SHOWN HERE IS

4522
02:44:43,800 --> 02:44:46,400
STABILIZED SO CELLS CAN MAKE

4523
02:44:46,400 --> 02:44:48,280
MORE INTERACTIONS THROUGH THEIR

4524
02:44:48,280 --> 02:44:49,880
OWN DPOSTIVE MATRIX AND WHERE

4525
02:44:49,880 --> 02:44:51,680
THERE ARE EPITHELIAL CELLS THAT

4526
02:44:51,680 --> 02:44:52,960
DEPOSIT BASEMENT MEMBRANE, THAT

4527
02:44:52,960 --> 02:44:55,040
IS ALSO SEQUESTERED BY BINDING

4528
02:44:55,040 --> 02:44:55,920
PEPTIDES IN THE MATRIX.

4529
02:44:55,920 --> 02:45:00,160
AND WE FOUND THAT THOSE

4530
02:45:00,160 --> 02:45:01,120
FACILITATE THE ABILITY OF CELLS

4531
02:45:01,120 --> 02:45:02,720
TO BUILD THEIR OWN MICRO

4532
02:45:02,720 --> 02:45:03,760
ENVIRONMENTS AND FUNCTION AS

4533
02:45:03,760 --> 02:45:06,520
THEY WOULD IN THE TISSUE.

4534
02:45:06,520 --> 02:45:08,040
NOW IN THE LAB, EVEN THOUGH I'M

4535
02:45:08,040 --> 02:45:09,800
INCREDIBLY INTERESTED IN THE

4536
02:45:09,800 --> 02:45:13,400
ENDOMETRIUM, WE ALSO STUDY THE

4537
02:45:13,400 --> 02:45:14,520
GUT, AND DEVELOP TISSUE

4538
02:45:14,520 --> 02:45:15,440
ENGINEERING APPROACHES FOR THAT

4539
02:45:15,440 --> 02:45:16,480
AND A THERE'S SOME GOOD REASONS

4540
02:45:16,480 --> 02:45:17,440
FOR THAT.

4541
02:45:17,440 --> 02:45:18,560
MANY SCIENTIFIC REASONS BUT ALSO

4542
02:45:18,560 --> 02:45:21,280
SOME VERY PRACTICAL ONES.

4543
02:45:21,280 --> 02:45:23,360
THE PERSON WHO REALLY PUSHED THE

4544
02:45:23,360 --> 02:45:26,200
ORGANOID SIDE OF THIS INTO

4545
02:45:26,200 --> 02:45:31,240
EXISTENCE IS VICTOR

4546
02:45:31,240 --> 02:45:31,920
HERNANDEZ-GORDILLA WHO DID A

4547
02:45:31,920 --> 02:45:33,000
SCREAN GUIDED BY WHAT WAS KNOWN

4548
02:45:33,000 --> 02:45:34,560
ABOUT SOME OF THE ADHESIVE

4549
02:45:34,560 --> 02:45:36,360
INTERACTIONS AND THINGS GOING ON

4550
02:45:36,360 --> 02:45:38,560
IN THE STEM CELL NICHE OBVIOUSLY

4551
02:45:38,560 --> 02:45:40,880
IN WORK THAT HANS HAD PUBLISHED.

4552
02:45:40,880 --> 02:45:42,720
IN DOING THE SCREEN, HE LOOKED

4553
02:45:42,720 --> 02:45:45,120
AT A LOT OF DIFFERENT LIGANDS,

4554
02:45:45,120 --> 02:45:45,600
BIOPHYSICAL PROPERTIES,

4555
02:45:45,600 --> 02:45:46,800
BIOCHEMICAL PROPERTIES AND

4556
02:45:46,800 --> 02:45:48,760
IDENTIFIED A COMPLETELY TOTALLY

4557
02:45:48,760 --> 02:45:52,600
SYNTHETIC MATRIX SO THERE'S NO

4558
02:45:52,600 --> 02:45:53,560
LAMININ OR ANYTHING ADDED TO

4559
02:45:53,560 --> 02:45:56,960
THIS THAT ALLOWS CLONAL GROWTH

4560
02:45:56,960 --> 02:45:58,600
FROM EITHER THE UPPER OR LOWER

4561
02:45:58,600 --> 02:46:00,480
GI TRACT OVER TIME, AND IT'S NOT

4562
02:46:00,480 --> 02:46:05,120
AS EFFICIENT AS MAT RIGEL IN THE

4563
02:46:05,120 --> 02:46:06,560
ORIGINAL -- BUT IT DOES ALLOW

4564
02:46:06,560 --> 02:46:07,680
THE CLONAL GROWTH AND ALL THESE

4565
02:46:07,680 --> 02:46:08,960
OTHER FEATURES.

4566
02:46:08,960 --> 02:46:13,120
IT REQUIRES HAVING A PARTICULAR

4567
02:46:13,120 --> 02:46:14,360
LIGAND IN THE MATRIX AND SHOWN

4568
02:46:14,360 --> 02:46:15,320
HERE, IF YOU MAKE A

4569
02:46:15,320 --> 02:46:18,600
SUBSTITUTION, WE DON'T GET

4570
02:46:18,600 --> 02:46:19,680
ORGANOIDS.

4571
02:46:19,680 --> 02:46:20,920
STWA TO SHOW YOU THE IMPORTANCE

4572
02:46:20,920 --> 02:46:22,760
OF THIS FOR CELL-CELL

4573
02:46:22,760 --> 02:46:23,440
INTERACTION, I'M GOING TO COME

4574
02:46:23,440 --> 02:46:26,600
BACK TO THE ENT ME TREE UM.

4575
02:46:26,600 --> 02:46:27,560
IT FASCINATING BECAUSE IT GOES

4576
02:46:27,560 --> 02:46:29,240
THROUGH THESE ENORMOUS GROWTH

4577
02:46:29,240 --> 02:46:34,960
AND REGENERATION CYCLES EVERY 28

4578
02:46:34,960 --> 02:46:37,120
DAYS DRIVEN BY FIRST

4579
02:46:37,120 --> 02:46:39,080
PROLIFERATION UNDER THE PUSH OF

4580
02:46:39,080 --> 02:46:41,720
ESTROGEN, SO ESTROGEN DERIVES

4581
02:46:41,720 --> 02:46:42,680
ABOUT A COUNCILMEMBER GROWTH OF

4582
02:46:42,680 --> 02:46:43,960
THE TISSUE, THEN THERE'S

4583
02:46:43,960 --> 02:46:45,520
OVULATION AND PROGESTERONE COMES

4584
02:46:45,520 --> 02:46:47,040
IN AND CAUSES MATURATION OF THE

4585
02:46:47,040 --> 02:46:49,000
TISSUE SUCH THAT THE FIBROBLASTS

4586
02:46:49,000 --> 02:46:50,360
BECOME EPITHELIAL-LIKE OR AT

4587
02:46:50,360 --> 02:46:57,440
LEAST A SUBPOPULATION BECOMES

4588
02:46:57,440 --> 02:47:03,160
ACUTELY ?EA SENT.

4589
02:47:03,160 --> 02:47:08,120
SO WE WANT TO RECAPITULATE THIS.

4590
02:47:08,120 --> 02:47:09,320
WE KNOW MEN AND WOMEN DO NOT

4591
02:47:09,320 --> 02:47:11,120
HAVE EQUAL RESPONSES TO

4592
02:47:11,120 --> 02:47:12,480
INFECTION AND IMMUNITY, AND THIS

4593
02:47:12,480 --> 02:47:14,680
IS ACTUALLY A HUGE TOPIC WE

4594
02:47:14,680 --> 02:47:15,680
STARTED A DISCUSSION GROUP IN

4595
02:47:15,680 --> 02:47:17,520
THE BOSTON AREA AROUND THAT.

4596
02:47:17,520 --> 02:47:21,320
SO FOR PURPOSES OF THIS TALK,

4597
02:47:21,320 --> 02:47:24,400
PROGESTERONE INDUCES SOMETHING

4598
02:47:24,400 --> 02:47:30,000
CALLED A DECIDUALIZATION

4599
02:47:30,000 --> 02:47:30,400
RESPONSE.

4600
02:47:30,400 --> 02:47:32,040
YOU CAN SEE THEY BECOME PLUMP

4601
02:47:32,040 --> 02:47:33,440
LIKE EPITHELIA.

4602
02:47:33,440 --> 02:47:37,200
IT'S A VERY EASY ASSAY IN VITRO.

4603
02:47:37,200 --> 02:47:40,120
MANY UTERINE DISORDERS BEYOND

4604
02:47:40,120 --> 02:47:41,680
ENDOMETRIOSIS ARE CHARACTERIZED

4605
02:47:41,680 --> 02:47:43,080
BY PROGESTERONE RESISTANCE AND

4606
02:47:43,080 --> 02:47:44,400
CELLS THAT WILL NOT MAKE

4607
02:47:44,400 --> 02:47:45,720
PROLACTIN IN RESPONSE TO

4608
02:47:45,720 --> 02:47:46,040
PROGESTERONE.

4609
02:47:46,040 --> 02:47:49,040
SO IF WE CO-CULTURE NOW OUR

4610
02:47:49,040 --> 02:47:51,320
EPITHELIAL ORGANOIDS FROM

4611
02:47:51,320 --> 02:47:52,800
PATIENT END ME TREE A, THESE ARE

4612
02:47:52,800 --> 02:47:54,120
HEALTHY PATIENTS WITH STROMA, WE

4613
02:47:54,120 --> 02:47:55,120
CAN TAKE THEM THROUGH A

4614
02:47:55,120 --> 02:47:57,000
SIMULATED CYCLE AND THIS IS JUST

4615
02:47:57,000 --> 02:48:01,160
SHOWING MORPHOLOGY.

4616
02:48:01,160 --> 02:48:02,440
THEY WILL MAKE PROLACTIN.

4617
02:48:02,440 --> 02:48:04,240
IF WE ADD AN INFLAMMATION QUEUE

4618
02:48:04,240 --> 02:48:07,040
SUCH AS IL-1 BETA, THESE CELLS

4619
02:48:07,040 --> 02:48:07,920
BECOME INFLAMED-LOOKING.

4620
02:48:07,920 --> 02:48:09,680
THERE'S A FLATTENING OF THE

4621
02:48:09,680 --> 02:48:13,480
EPITHELIA, THE STROMA BECOME

4622
02:48:13,480 --> 02:48:14,240
ACTIVATED, AND OF COURSE WHAT WE

4623
02:48:14,240 --> 02:48:18,280
FIND IS IF WE GIVE PROGESTERONE

4624
02:48:18,280 --> 02:48:19,720
IN THE CULTURE, YOU GET

4625
02:48:19,720 --> 02:48:21,880
PROLACTIN BUT NOT WHEN YOU GIVE

4626
02:48:21,880 --> 02:48:22,960
IL-1 BETA.

4627
02:48:22,960 --> 02:48:23,760
IMPORTANTLY, THE MATRIX ITSELF

4628
02:48:23,760 --> 02:48:27,960
CAN BE USED TO MODULATE THE

4629
02:48:27,960 --> 02:48:29,800
BIOPHYSICAL PROPERTIES WITHOUT A

4630
02:48:29,800 --> 02:48:31,320
CHEMICAL QUEUE FOR INFLA NATION,

4631
02:48:31,320 --> 02:48:33,400
WE GET FEATURES OF LESION-LIKE

4632
02:48:33,400 --> 02:48:33,800
BEHAVIOR.

4633
02:48:33,800 --> 02:48:36,040
SO THIS IS AN ACTUAL PATIENT

4634
02:48:36,040 --> 02:48:37,880
LESION BY WHOLE SHEET

4635
02:48:37,880 --> 02:48:38,840
MICROSCOPY, YOU CAN SEE IT

4636
02:48:38,840 --> 02:48:40,640
INVADING IN THIS CASE INTO THE

4637
02:48:40,640 --> 02:48:42,280
MUSCLE, THE MYOMETRIUM, AND THIS

4638
02:48:42,280 --> 02:48:46,440
IS A SOFT MATRIX, IT HAS THE

4639
02:48:46,440 --> 02:48:48,280
PROPERTIES OF ENDOMETRIUM.

4640
02:48:48,280 --> 02:48:49,240
HERE'S THE MECHANICAL PROPERTIES

4641
02:48:49,240 --> 02:48:52,320
OF THE TISSUES HERE AND OF OUR

4642
02:48:52,320 --> 02:48:52,560
MATRICES.

4643
02:48:52,560 --> 02:48:56,480
SO IN THE SOFT PEG MATRIX, THE

4644
02:48:56,480 --> 02:48:58,880
EPITHELIAL STROMAL COCULTURES

4645
02:48:58,880 --> 02:49:02,200
LOOK BEAUTIFUL, BUT IN THE STIFF

4646
02:49:02,200 --> 02:49:03,720
MATRICES, THEY ACTUALLY TAKE ON

4647
02:49:03,720 --> 02:49:04,800
AN INFLAMMATORY PHENOTYPE.

4648
02:49:04,800 --> 02:49:06,640
NOW I WANT TO ILLUSTRATE WHY WE

4649
02:49:06,640 --> 02:49:08,080
ARE VERY EXCITED ABOUT THIS, AND

4650
02:49:08,080 --> 02:49:09,480
WE'VE SHARED THIS MATRIX WITH

4651
02:49:09,480 --> 02:49:11,120
MANY LABS NOW WHO ARE USING IT

4652
02:49:11,120 --> 02:49:14,960
FOR VARIOUS THINGS, BUT REALLY A

4653
02:49:14,960 --> 02:49:17,160
WONDERFUL COLLABORATION IS WITH

4654
02:49:17,160 --> 02:49:22,320
HILLARY CRITCHLEY, PROFESSOR OF

4655
02:49:22,320 --> 02:49:24,040
OGBYN IN EDINBURGH, SHE IS

4656
02:49:24,040 --> 02:49:26,120
PROBABLY THE WORLD EXPERT ON

4657
02:49:26,120 --> 02:49:28,320
HEAVY MENSTRUAL BLEEDING SO SHE

4658
02:49:28,320 --> 02:49:30,600
TREATS A LOT OF PATIENTS IN HER

4659
02:49:30,600 --> 02:49:34,320
CLINIC WITH SELECTED

4660
02:49:34,320 --> 02:49:35,520
PROGESTERONE RECEPTOR MOD LAY

4661
02:49:35,520 --> 02:49:36,280
FOR.

4662
02:49:36,280 --> 02:49:38,000
PROGESTERONE IS A PERFECT

4663
02:49:38,000 --> 02:49:41,840
AGONIST FOR IT.

4664
02:49:41,840 --> 02:49:44,720
AND MIFEPRISTONE, ABORTION

4665
02:49:44,720 --> 02:49:48,400
DWRUG, IS AN ANTAGONIST, AND IN

4666
02:49:48,400 --> 02:49:50,280
THE U.S., WE DO NOT HAVE

4667
02:49:50,280 --> 02:49:54,040
APPROVAL TO USE THIS DRUG FOR

4668
02:49:54,040 --> 02:49:55,960
HMB, IN PART BECAUSE THERE'S

4669
02:49:55,960 --> 02:49:59,800
THESE WEIRD FOR MOLGS THAT SHOWT

4670
02:49:59,800 --> 02:50:01,480
SHOW UP IN THE ENDOMETRIUM AND

4671
02:50:01,480 --> 02:50:02,440
THERE'S CONCERN ABOUT POTENTIAL

4672
02:50:02,440 --> 02:50:03,360
CONTRIBUTIONS TO ENDOMETRIAL CAN

4673
02:50:03,360 --> 02:50:05,840
SE WHICH IS ON          

4674
02:50:05,840 --> 02:50:07,160
CANCER, WHICH IS ON THE RISE.

4675
02:50:07,160 --> 02:50:08,880
THERE'S INDICATIONS THAT IT

4676
02:50:08,880 --> 02:50:11,200
CAUSES DOWN REGULATION OF BOTH

4677
02:50:11,200 --> 02:50:12,400
PROLIFERATION AND DESYDIZATION,

4678
02:50:12,400 --> 02:50:14,120
GIVING RISE TO THESE WEIRD

4679
02:50:14,120 --> 02:50:15,640
PHENOTYPES.

4680
02:50:15,640 --> 02:50:20,040
SO THE CRITCHLEY LAB HAS ACCESS

4681
02:50:20,040 --> 02:50:21,360
TO PATIENTS AND THEY DID A

4682
02:50:21,360 --> 02:50:22,480
BEAUTIFUL STUDY IN PATIENTS WHO

4683
02:50:22,480 --> 02:50:24,640
WERE TAKING THE DRUG AND TOOK

4684
02:50:24,640 --> 02:50:25,640
ENDOMETRIAL BIOPSIES BEFORE,

4685
02:50:25,640 --> 02:50:28,240
DURING AND AFTER TREATMENT WITH

4686
02:50:28,240 --> 02:50:30,120
THE DRUG, FROM THE ENDOMETRIAL

4687
02:50:30,120 --> 02:50:32,400
BIOPSIES, DID A LOT OF MOLECULAR

4688
02:50:32,400 --> 02:50:36,880
OMICS AND THEN ALSO MAKE TISSUE

4689
02:50:36,880 --> 02:50:38,520
BANKS SO THAT YOU COULD GROW THE

4690
02:50:38,520 --> 02:50:40,720
ORGANOIDS AND STROMA TOGETHER.

4691
02:50:40,720 --> 02:50:44,760
SO ALEX TSOLOVA, THE GRADUATE

4692
02:50:44,760 --> 02:50:46,080
STUDENT SHOWN BEAMING BECAUSE

4693
02:50:46,080 --> 02:50:48,480
SHE WON AN AWARD IN MARCH THIS

4694
02:50:48,480 --> 02:50:50,440
YEAR AND SHE JUST DEFENDED HER

4695
02:50:50,440 --> 02:50:54,720
THESIS AND THIS IS A PAPER IN

4696
02:50:54,720 --> 02:50:55,480
PREPARATION, SHE ASKED THE

4697
02:50:55,480 --> 02:50:57,240
QUESTION ABOUT CELL-CELL MATRIX

4698
02:50:57,240 --> 02:51:00,280
AND THE MECHANISM OF ACTION OF

4699
02:51:00,280 --> 02:51:01,360
SPRM SINCE SHE FIRST SHOWED YOU

4700
02:51:01,360 --> 02:51:03,240
HAVE TO HAVE THE CELLS

4701
02:51:03,240 --> 02:51:03,920
CO-CULTURED TOGETHER TO GET

4702
02:51:03,920 --> 02:51:05,640
ANYTHING LIKE AN IN VIVO

4703
02:51:05,640 --> 02:51:06,280
RESPONSE.

4704
02:51:06,280 --> 02:51:08,080
SO SHE'S GOT THE IN VIVO OMICS

4705
02:51:08,080 --> 02:51:09,560
DATA AND NOW SHE CAN COMPARE HER

4706
02:51:09,560 --> 02:51:10,160
CULTURES.

4707
02:51:10,160 --> 02:51:11,360
BUT A CRUCIAL FEATURE, I'LL JUST

4708
02:51:11,360 --> 02:51:13,760
SHOW YOU THE DATA HERE, IS

4709
02:51:13,760 --> 02:51:15,800
COMPARING MATRIGEL AND PEG FOR

4710
02:51:15,800 --> 02:51:16,720
THESE CO-CULTURES.

4711
02:51:16,720 --> 02:51:17,800
SO I'M GOING TO WALK YOU THROUGH

4712
02:51:17,800 --> 02:51:19,000
THIS BECAUSE IT'S REALLY

4713
02:51:19,000 --> 02:51:19,440
COMPLICATED.

4714
02:51:19,440 --> 02:51:24,800
WHAT SHE DID IS REVERSE PHASE

4715
02:51:24,800 --> 02:51:29,400
PROTEIN ARRAY OF -- REVERSE

4716
02:51:29,400 --> 02:51:31,600
PHASE ANTIBODY ARRAY WITH 100

4717
02:51:31,600 --> 02:51:32,680
ANTIBODIES CHOSEN FROM THE IN

4718
02:51:32,680 --> 02:51:33,880
VIVO OMICS DATA.

4719
02:51:33,880 --> 02:51:38,120
THAT DATA SHOWED THAT THE

4720
02:51:38,120 --> 02:51:39,560
SPRMs DOWNREGULATED A HUGE SET

4721
02:51:39,560 --> 02:51:42,840
OF GENES ASSOCIATED WITH CELL

4722
02:51:42,840 --> 02:51:43,520
PROLIFERATION.

4723
02:51:43,520 --> 02:51:45,480
SO FIRST LET'S LOOK AT PEG-GROWN

4724
02:51:45,480 --> 02:51:48,320
CELLS HERE.

4725
02:51:48,320 --> 02:51:51,040
ESTROGEN, THE RED GENES ARE ALL

4726
02:51:51,040 --> 02:51:51,920
PROLIFERATION GENES AND I'LL

4727
02:51:51,920 --> 02:51:53,000
JUST FOCUS ON THOSE FOR NOW.

4728
02:51:53,000 --> 02:51:54,760
YOU CAN SEE THAT ESTROGEN

4729
02:51:54,760 --> 02:51:56,280
UPREGULATES THOSE GENES AS YOU

4730
02:51:56,280 --> 02:52:01,080
WOULD EXPECT IN VIVO, AND THE

4731
02:52:01,080 --> 02:52:03,080
SPRM IN THE PEG SYNTHETIC

4732
02:52:03,080 --> 02:52:04,280
CO-CULTURE COMPLETELY

4733
02:52:04,280 --> 02:52:04,680
DOWNREGULATES THEM.

4734
02:52:04,680 --> 02:52:07,560
SO THIS IS SIMILAR TO WHAT WE

4735
02:52:07,560 --> 02:52:12,040
SEE IN VIVO FROM THOSE PATIENTS.

4736
02:52:12,040 --> 02:52:13,120
MATRIGEL IS ALL OVER THE MAP.

4737
02:52:13,120 --> 02:52:14,000
IT'S REALLY A MESS.

4738
02:52:14,000 --> 02:52:16,800
IT DOES NOT RECAPITULATE THE IN

4739
02:52:16,800 --> 02:52:17,440
VIVO.

4740
02:52:17,440 --> 02:52:19,920
SHE'S FOLLOWED UP WITH IHC AND

4741
02:52:19,920 --> 02:52:21,040
VARIOUS OTHER THINGS TO VALIDATE

4742
02:52:21,040 --> 02:52:21,560
THESE FINDINGS.

4743
02:52:21,560 --> 02:52:24,360
SO THIS IS AN AMAZING OUTCOME.

4744
02:52:24,360 --> 02:52:26,600
THE TAKE-HOME MESSAGE FROM THIS,

4745
02:52:26,600 --> 02:52:27,680
THEN I JUST HAVE A COUPLE MORE

4746
02:52:27,680 --> 02:52:28,440
SLIDES HOW WE'RE TAKING THIS

4747
02:52:28,440 --> 02:52:31,640
INTO A BIOREACTOR, IS THAT THE

4748
02:52:31,640 --> 02:52:33,680
SYNTHETIC MATRIX IS A LOW NOISE

4749
02:52:33,680 --> 02:52:35,120
MICROENVIRONMENT IN WHICH HE CAN

4750
02:52:35,120 --> 02:52:37,200
LISTEN TO THE CROSSTALK BETWEEN

4751
02:52:37,200 --> 02:52:37,960
THE DIFFERENT CELL TYPES.

4752
02:52:37,960 --> 02:52:39,400
NOW I DIDN'T SHOW IMMUNE CELLS

4753
02:52:39,400 --> 02:52:40,600
BUT THERE'S A SEPARATE

4754
02:52:40,600 --> 02:52:44,200
PUBLICATION WE HAVE RECENTLY

4755
02:52:44,200 --> 02:52:46,520
APPLYING TO PANCREATIC ORGANOID

4756
02:52:46,520 --> 02:52:47,800
STROMA IMMUNE CROSSTALK WHERE

4757
02:52:47,800 --> 02:52:48,800
THERE'S A LOT OF DETAILS.

4758
02:52:48,800 --> 02:52:52,080
SO IT'S LIKE YOU'RE CAPTURING

4759
02:52:52,080 --> 02:52:53,480
THE CELLS TALKING TO EACH OTHER

4760
02:52:53,480 --> 02:52:54,920
WITH NO BACKGROUND NOISE, LIKE

4761
02:52:54,920 --> 02:52:58,800
YOU'RE IN A QUIET QA FAY.

4762
02:52:58,800 --> 02:52:59,800
 CAFE.

4763
02:52:59,800 --> 02:53:02,640
BUT MATRIGEL, IF YOU'RE TRYING

4764
02:53:02,640 --> 02:53:03,960
TO CAPTURE WHAT THE CELLS ARE

4765
02:53:03,960 --> 02:53:05,720
SAYING, IT'S LIKE YOU'RE ON THE

4766
02:53:05,720 --> 02:53:07,000
RUNWAY AT LOGAN AIRPORT AND JETS

4767
02:53:07,000 --> 02:53:08,240
ARE TAKING OFF, THEY CAN'T TALK

4768
02:53:08,240 --> 02:53:09,240
TO EACH OTHER VERY WELL.

4769
02:53:09,240 --> 02:53:10,640
SO THAT'S THE TAKEHOME.

4770
02:53:10,640 --> 02:53:12,320
WE'RE TRYING TO COMMERCIALIZE IT

4771
02:53:12,320 --> 02:53:14,120
IN THE ERA OF COVID, THERE'S

4772
02:53:14,120 --> 02:53:16,120
BEEN A LOT OF LAWYER DRAMA, SO

4773
02:53:16,120 --> 02:53:17,120
HOPEFULLY WE'LL BE ABLE TO GET

4774
02:53:17,120 --> 02:53:19,520
THIS OUT TO MORE LABS THAN THE

4775
02:53:19,520 --> 02:53:20,360
LABS WE'RE CURRENTLY

4776
02:53:20,360 --> 02:53:20,920
COLLABORATING WITH.

4777
02:53:20,920 --> 02:53:23,800
I'M GOING TO END BY SAYING OF

4778
02:53:23,800 --> 02:53:25,320
COURSE WE'RE TAKING THIS BACK IN

4779
02:53:25,320 --> 02:53:26,840
VIVO TO LOOK AT INTERACTIONS

4780
02:53:26,840 --> 02:53:30,000
BETWEEN THESE LESIONS AND BLOOD

4781
02:53:30,000 --> 02:53:32,960
VESSELS, AND I WAS THRILLED TO

4782
02:53:32,960 --> 02:53:36,120
SEE CHRISTINE MIMMERY SHOW THE

4783
02:53:36,120 --> 02:53:37,440
IMMUNE CHIP, AN IMPORTANT

4784
02:53:37,440 --> 02:53:38,760
FEATURE OF THESE KINDS OF

4785
02:53:38,760 --> 02:53:42,200
VESSELS IS YOU CAN ADD I MEUP AE

4786
02:53:42,200 --> 02:53:44,360
CELLS AND LOOK AT TRAFFICKING.

4787
02:53:44,360 --> 02:53:48,320
THIS IS JUST A GRAPHIC, THE

4788
02:53:48,320 --> 02:53:49,960
FIRST EXPERIMENT, OUR STUDENT

4789
02:53:49,960 --> 02:53:51,360
ELLEN DID IN THE AIM CHIPS.

4790
02:53:51,360 --> 02:53:52,360
BUT WHAT WE'VE BEEN DOING, ALL

4791
02:53:52,360 --> 02:53:55,440
OF THESE RELY ON USING FIBRIN

4792
02:53:55,440 --> 02:53:57,040
FOR FORMING THE BLOOD VESSELS.

4793
02:53:57,040 --> 02:53:58,760
IT BEEN HARD TO GET A SYNTHETIC

4794
02:53:58,760 --> 02:53:59,160
MATRIX.

4795
02:53:59,160 --> 02:54:00,760
WE'VE BEEN WORKING WITH ROGER'S

4796
02:54:00,760 --> 02:54:02,640
LAB TO BUILD OUR LESION MODEL,

4797
02:54:02,640 --> 02:54:05,400
AND FOR NOW, THERE'S SOME PDMS

4798
02:54:05,400 --> 02:54:07,000
DEVICES HE USED FOR TUMORS, AND

4799
02:54:07,000 --> 02:54:10,720
WHAT WE'VE BEEN ABLE TO SHOW IS

4800
02:54:10,720 --> 02:54:13,880
GROWTH OF VESSELS FROM A

4801
02:54:13,880 --> 02:54:17,200
PREFORMED VESSEL EMBEDDED

4802
02:54:17,200 --> 02:54:19,160
FIBRIN, THIS IS A PROTO LESION

4803
02:54:19,160 --> 02:54:20,680
IN PEG BECAUSE OUR LESIONS HAVE

4804
02:54:20,680 --> 02:54:24,080
TO BE GROWN IN BEG.

4805
02:54:24,080 --> 02:54:25,080
 PEG.

4806
02:54:25,080 --> 02:54:27,120
FIBRIN DOES NOT WORK WELL FOR

4807
02:54:27,120 --> 02:54:29,000
OUR EPITHELIAL STROMAL

4808
02:54:29,000 --> 02:54:29,680
CO-CULTURES.

4809
02:54:29,680 --> 02:54:30,960
HOWEVER, WE HAVE A MANUFACTURING

4810
02:54:30,960 --> 02:54:32,840
PROCESS NOW IN PLACE TO TAKE

4811
02:54:32,840 --> 02:54:35,240
THESE CHIPS AND PUT THEM INTO

4812
02:54:35,240 --> 02:54:36,120
THERMOPLASTICS, INCLUDING

4813
02:54:36,120 --> 02:54:36,760
EMBEDDED PUMPS.

4814
02:54:36,760 --> 02:54:39,480
I'M NOT SHOWING THAT BECAUSE OF

4815
02:54:39,480 --> 02:54:40,720
SOME I.P. ISSUES, BUT THIS IS

4816
02:54:40,720 --> 02:54:41,400
WHERE WE'RE GOING.

4817
02:54:41,400 --> 02:54:42,440
SO THESE KINDS OF SYSTEMS COULD

4818
02:54:42,440 --> 02:54:44,320
BE VALUABLE FOR LOOKING AT VIRUS

4819
02:54:44,320 --> 02:54:47,480
INFECTION BECAUSE THEY SHOULD BE

4820
02:54:47,480 --> 02:54:48,880
AMENABLE TO CONTROLLING BOTH THE

4821
02:54:48,880 --> 02:54:50,880
BIOCHEMICAL AND THE BIOPHYSICAL

4822
02:54:50,880 --> 02:54:51,560
MICROENVIRONMENT, AND THERE'S A

4823
02:54:51,560 --> 02:54:53,480
LOT OF PEOPLE WHO CONTRIBUTED TO

4824
02:54:53,480 --> 02:54:57,600
THIS, ESPECIALLY DAVE TREMPER ON

4825
02:54:57,600 --> 02:55:03,360
THE DEVICE SIDE, HEAVY LIFTING

4826
02:55:03,360 --> 02:55:05,560
ONCOORGANOID CULTURE, HILLARY'S

4827
02:55:05,560 --> 02:55:07,600
LAB, ALEKS AND OUR FABULOUS

4828
02:55:07,600 --> 02:55:08,800
CLINICAL COLLABORATORS FOR THE

4829
02:55:08,800 --> 02:55:10,720
SAMPLES.

4830
02:55:10,720 --> 02:55:12,760
>> THIS IS GREAT.

4831
02:55:12,760 --> 02:55:13,760
THANKS SO MUCH, LINDA.

4832
02:55:13,760 --> 02:55:16,600
IT IS INTERESTING, THE SAME --

4833
02:55:16,600 --> 02:55:17,800
CHRISTINE AND YOU STARTING WITH

4834
02:55:17,800 --> 02:55:19,000
ORGANOIDS AND MICRO TISSUES AND

4835
02:55:19,000 --> 02:55:23,120
THEN AT THE END MOVING INTO THIS

4836
02:55:23,120 --> 02:55:24,880
VASCULARIZED BED TISSUE CHIP

4837
02:55:24,880 --> 02:55:26,880
PLATFORMS TO SORT OF MOVE THEM

4838
02:55:26,880 --> 02:55:29,360
INTO A MORE LIKE PERFUSE SYSTEM.

4839
02:55:29,360 --> 02:55:32,000
IT SEEMS TO BE LIKE A TREND OF

4840
02:55:32,000 --> 02:55:37,040
BLENDING TECHNOLOGIES INSTEADING

4841
02:55:37,040 --> 02:55:38,360
STUDYING SEPARATE BUT THEN

4842
02:55:38,360 --> 02:55:39,440
PUTTING THEM TOGETHER WHICH I

4843
02:55:39,440 --> 02:55:40,840
THINK IS FASCINATING AND

4844
02:55:40,840 --> 02:55:41,760
HOPEFULLY SOMETHING WE CAN

4845
02:55:41,760 --> 02:55:43,400
DISCUSS MORE AT THE END.

4846
02:55:43,400 --> 02:55:44,600
THANK YOU SO MUCH, LINDA.

4847
02:55:44,600 --> 02:55:46,840
>> THANK YOU.

4848
02:55:46,840 --> 02:55:49,640
>> WE'RE GOING TO MOVE TO
THE

4849
02:55:49,640 --> 02:55:51,680
NEXT SPEAKER, AND IT'S PROFESSOR

4850
02:55:51,680 --> 02:55:55,400
ANTHONY ATALA, WHO IS ES THE

4851
02:55:55,400 --> 02:55:56,840
LINK PROFESSOR AND DIRECTOR OF

4852
02:55:56,840 --> 02:55:58,040
THE WAKE FOREST INSTITUTE FOR

4853
02:55:58,040 --> 02:56:02,200
REGENERATIVE MEDICINE AND THE

4854
02:56:02,200 --> 02:56:03,240
BOYCE PROFESSOR AND CHAIR OF THE

4855
02:56:03,240 --> 02:56:04,680
DEPARTMENT OF UROLOGY AT WAKE

4856
02:56:04,680 --> 02:56:06,240
FOREST UNIVERSITY.

4857
02:56:06,240 --> 02:56:07,520
DR. ATALA IS A MEMBER OF THE

4858
02:56:07,520 --> 02:56:08,560
NATIONAL ACADEMY OF MEDICINE AND

4859
02:56:08,560 --> 02:56:10,520
THE NATIONAL ACADEMY OF

4860
02:56:10,520 --> 02:56:13,000
INVENTORS, AND HE'S RECIPIENT OF

4861
02:56:13,000 --> 02:56:14,440
THE U.S. CONGRESS FUNDED

4862
02:56:14,440 --> 02:56:15,760
COLUMBUS FOUNDATION AWARD AND

4863
02:56:15,760 --> 02:56:17,960
THE EDISON SCIENCE AND MEDICAL

4864
02:56:17,960 --> 02:56:19,680
AWARD, AND R & D INNOVATOR
OF

4865
02:56:19,680 --> 02:56:23,440
THE YEAR AWARD AND SMITHSONIAN

4866
02:56:23,440 --> 02:56:24,640
INGENUITY AWARD AMONG SOME

4867
02:56:24,640 --> 02:56:27,560
OTHERS.

4868
02:56:27,560 --> 02:56:30,440
AND DR. ATALA HAS BEEN A PIONEER

4869
02:56:30,440 --> 02:56:32,320
IN THE FIELD OF TISSUE

4870
02:56:32,320 --> 02:56:36,200
ENGINEERING, BIOPRINTING AND

4871
02:56:36,200 --> 02:56:37,640
ESPECIALLY GROWING TISSUES AND

4872
02:56:37,640 --> 02:56:38,840
ORGANS FOR PATIENTS AND

4873
02:56:38,840 --> 02:56:39,800
PHYSIOLOGICAL MODELING.

4874
02:56:39,800 --> 02:56:43,880
SO TONY, THE FLOOR IS YOURS.

4875
02:56:43,880 --> 02:56:45,040
>> THANK YOU, MARK.

4876
02:56:45,040 --> 02:56:45,960
IT'S GREAT TO BE WITH YOU AND

4877
02:56:45,960 --> 02:56:49,800
GREAT TO BE WITH THIS PANEL.

4878
02:56:49,800 --> 02:56:50,640
THANK YOU FOR PUTTING THIS

4879
02:56:50,640 --> 02:56:51,600
TOGETHER ALONG WITH YOUR TEAM.

4880
02:56:51,600 --> 02:56:52,840
WHAT I THOUGHT I WOULD DO TODAY

4881
02:56:52,840 --> 02:56:54,280
IS REALLY GIVE YOU AN OVERVIEW

4882
02:56:54,280 --> 02:56:56,360
OF SOME OF THE WORK WE'RE DOING

4883
02:56:56,360 --> 02:57:00,600
IN THE AREA OF THE BODY ON A

4884
02:57:00,600 --> 02:57:01,040
CHIP.

4885
02:57:01,040 --> 02:57:02,360
OUR AREA OF EXPERTISE OVER THE

4886
02:57:02,360 --> 02:57:04,080
LAST SEVERAL DECADES HAS BEEN

4887
02:57:04,080 --> 02:57:05,200
REGENERATIVE MEDICINE, BASICALLY

4888
02:57:05,200 --> 02:57:08,320
MAKING TISSUES FOR PATIENTS, AND

4889
02:57:08,320 --> 02:57:09,320
OF COURSE AS YOU CAN IMAGINE,

4890
02:57:09,320 --> 02:57:10,880
WE'RE MAKING TISSUES FOR

4891
02:57:10,880 --> 02:57:11,960
PATIENTS, WE HAVE TO GO THROUGH

4892
02:57:11,960 --> 02:57:16,480
THIS WHOLE APPROACH OF CELL IS

4893
02:57:16,480 --> 02:57:19,160
HARVESTING, CELL PROCURING,

4894
02:57:19,160 --> 02:57:20,720
EXPANSION OF CELLS OUTSIDE THE

4895
02:57:20,720 --> 02:57:22,480
BODY, MIXING THAT WITH BIOFEERLS

4896
02:57:22,480 --> 02:57:23,440
SO       

4897
02:57:23,440 --> 02:57:24,560
BIOMATERIALS SO WE CAN PUT THEM

4898
02:57:24,560 --> 02:57:25,080
INTO PATIENTS.

4899
02:57:25,080 --> 02:57:26,840
SO REALLY THE STRATEGY FOR US

4900
02:57:26,840 --> 02:57:29,400
REALLY EARLY ON WAS HOW DO WE

4901
02:57:29,400 --> 02:57:30,400
MINIATURIZE THE SYSTEMS THAT WE

4902
02:57:30,400 --> 02:57:33,040
ARE DOING IN REGEN MED.

4903
02:57:33,040 --> 02:57:34,720
WE PUT A WHITE PAPER OUT ON THIS

4904
02:57:34,720 --> 02:57:37,560
INITIALLY BACK IN THE EARLY

4905
02:57:37,560 --> 02:57:37,880
2000s.

4906
02:57:37,880 --> 02:57:41,280
THE STRATEGY HERE WAS TO GO

4907
02:57:41,280 --> 02:57:42,720
AFTER THE SYSTEM IN A COMBINED

4908
02:57:42,720 --> 02:57:44,240
WAY, AND THAT WAS MADE POSSIBLE

4909
02:57:44,240 --> 02:57:48,960
BY A GRANT FUNDED BY DTRA, THE

4910
02:57:48,960 --> 02:57:50,040
DEFENSE THREAT REDUCTION AGENCY

4911
02:57:50,040 --> 02:57:52,200
THAT THEY ANNOUNCED IN 2012 WITH

4912
02:57:52,200 --> 02:57:54,400
OUR PARTNERS IN SEVERAL CENTERS

4913
02:57:54,400 --> 02:57:55,080
IN THE U.S.

4914
02:57:55,080 --> 02:57:56,040
REALLY THE MAIN GOAL OF OUR

4915
02:57:56,040 --> 02:57:57,920
PROGRAM WAS TO CREATE THESE

4916
02:57:57,920 --> 02:57:59,880
MICRO CHIP TECHNOLOGIES BUT TO

4917
02:57:59,880 --> 02:58:01,640
DO SO WITH BIOPRINTED HUMAN

4918
02:58:01,640 --> 02:58:03,920
TISSUES AS MUCH AS POSSIBLE, SO

4919
02:58:03,920 --> 02:58:05,560
WE STARTED PRINTERS THAT WE

4920
02:58:05,560 --> 02:58:07,000
DESIGNED OVER A 20-YEAR PERIOD

4921
02:58:07,000 --> 02:58:08,720
TO CREATE TISSUES AND ORGANS.

4922
02:58:08,720 --> 02:58:10,160
THESE PRINTERS WERE ABLE TO

4923
02:58:10,160 --> 02:58:12,480
STANDARDIZE THE SYSTEM AND ALLOW

4924
02:58:12,480 --> 02:58:14,880
THESE STRUCTURES TO BE PRINTED

4925
02:58:14,880 --> 02:58:16,080
IN THE RELIABLE MANNER THAT CAN

4926
02:58:16,080 --> 02:58:19,480
BE EXPANDED OVER TIME.

4927
02:58:19,480 --> 02:58:20,520
BASICALLY AS WE ALL KNOW WE'RE

4928
02:58:20,520 --> 02:58:21,760
PREACHING TO THE CHOIR HERE BUT

4929
02:58:21,760 --> 02:58:23,960
JUST TO REMIND EVERYBODY WHY

4930
02:58:23,960 --> 02:58:25,760
THIS, WHY DTRA CAME OUT WITH

4931
02:58:25,760 --> 02:58:26,560
THIS PROGRAM, MAINLY BECAUSE AS

4932
02:58:26,560 --> 02:58:29,200
YOU KNOW, DRUG DEVELOPMENT IS

4933
02:58:29,200 --> 02:58:30,920
CHALLENGING, AND IT TAKES TENS

4934
02:58:30,920 --> 02:58:33,560
OF MILLIONS OF DOLLARS TO GET A

4935
02:58:33,560 --> 02:58:35,080
TARGET TO PHASE 1 HUMAN CLINICAL

4936
02:58:35,080 --> 02:58:36,680
TRIAL, BUT UNFORTUNATELY 90% OF

4937
02:58:36,680 --> 02:58:38,600
THE DRUGS THAT REACH PHASE

4938
02:58:38,600 --> 02:58:39,680
1 CLINICAL TRIALS END UP

4939
02:58:39,680 --> 02:58:39,920
FAILING.

4940
02:58:39,920 --> 02:58:41,280
AND THAT REALLY HAS TO DOITH

4941
02:58:41,280 --> 02:58:43,600
THE SYSTEMS THAT ARE BEING USED,

4942
02:58:43,600 --> 02:58:43,800
RIGHT?

4943
02:58:43,800 --> 02:58:47,680
BASICALLY TO   2D CULTURES ARE T

4944
02:58:47,680 --> 02:58:49,640
REALLY 3D TISSUES AND ANIMALS

4945
02:58:49,640 --> 02:58:51,800
ARE NOT ALWAYS PREDICTIVE OF

4946
02:58:51,800 --> 02:58:52,800
HUMAN OUTCOMES.

4947
02:58:52,800 --> 02:58:53,760
THEREFORE, WITH THIS PROGRAM

4948
02:58:53,760 --> 02:58:57,520
THAT WE FIRST DEVELOPED WITH

4949
02:58:57,520 --> 02:58:59,000
DTRA, THE EX VIVO CONSOLE OF

4950
02:58:59,000 --> 02:59:05,040
HUMAN ORGANOIDS AND WE ASSIGNEDD

4951
02:59:05,040 --> 02:59:07,120
ORGANOIDS THE SAME -- WE USE THE

4952
02:59:07,120 --> 02:59:08,120
NORMAL HUMAN CELL TYPES THAT ARE

4953
02:59:08,120 --> 02:59:10,080
PRESENT IN THE ORGAN IN THE SAME

4954
02:59:10,080 --> 02:59:11,640
PROPORTION, SO THE LIVER HAS

4955
02:59:11,640 --> 02:59:13,040
FIVE DIFFERENT CELL TYPES, EACH

4956
02:59:13,040 --> 02:59:15,880
CELL TYPE HAS A ROLE THAT PLAYS

4957
02:59:15,880 --> 02:59:17,280
INTO THE FUNCTIONALITY, SO THESE

4958
02:59:17,280 --> 02:59:18,080
ARE INCORPORATED.

4959
02:59:18,080 --> 02:59:20,560
WE ALSO INCORPORATE THE

4960
02:59:20,560 --> 02:59:21,680
EXTRACELLULAR MATRIX WHENEVER

4961
02:59:21,680 --> 02:59:23,320
POSSIBLE, WHERE WE TAKE AN OR

4962
02:59:23,320 --> 02:59:26,720
GAL THAT WE DECELLULARRIZE, WE

4963
02:59:26,720 --> 02:59:30,560
THEN CREATE A POWDER TO CREATE

4964
02:59:30,560 --> 02:59:32,160
THE ORGANOIDS, SO BASICALLY ALL

4965
02:59:32,160 --> 02:59:33,480
THE ELEMENTS PRESENT IN THE

4966
02:59:33,480 --> 02:59:36,760
ORGAN, ALL THE CELLS AND THE

4967
02:59:36,760 --> 02:59:37,400
EXTRACELLULAR MATRIX.

4968
02:59:37,400 --> 02:59:38,280
WE EVEN CONTROL FOR THE

4969
02:59:38,280 --> 02:59:40,040
STIFFNESS BECAUSE THAT ALSO

4970
02:59:40,040 --> 02:59:43,880
INFLUENCES THE LOCAL

4971
02:59:43,880 --> 02:59:45,080
MICROENVIRONMENT.

4972
02:59:45,080 --> 02:59:46,040
THE OUTCOME IS STRUCTURES THAT

4973
02:59:46,040 --> 02:59:48,240
REALLY HAVE A HIGH FIDELITY TO

4974
02:59:48,240 --> 02:59:49,480
THE HUMAN, FOR EXAMPLE, WITH THE

4975
02:59:49,480 --> 02:59:51,640
LIVER AS YOU CAN EVEN SEE

4976
02:59:51,640 --> 02:59:53,480
PRIMITIVE BILIARY SYSTEMS THAT

4977
02:59:53,480 --> 02:59:56,760
YOU SEE HERE.

4978
02:59:56,760 --> 02:59:58,640
WHEN YOU LOOK AT THESE, THEY CAN

4979
02:59:58,640 --> 02:59:59,440
PRESERVE THEIR FUNCTION LONG

4980
02:59:59,440 --> 02:59:59,760
TERM.

4981
02:59:59,760 --> 03:00:01,600
THIS IS LOOKING AT THE LIVER,

4982
03:00:01,600 --> 03:00:04,560
ORGANOIDS LOOKING AT -- ALBUMEN

4983
03:00:04,560 --> 03:00:04,960
SECRETION.

4984
03:00:04,960 --> 03:00:06,520
FOR EXAMPLE, WHEN WE PUT THESE

4985
03:00:06,520 --> 03:00:08,160
INTO LIVERS WITH DRUGS LIKE

4986
03:00:08,160 --> 03:00:09,600
VALIUM, WE SEE IT GETS BROKEN

4987
03:00:09,600 --> 03:00:11,200
DOWN INTO ITS NORMAL METABOLITES

4988
03:00:11,200 --> 03:00:13,080
WITH THE UPREGULATION OF THE

4989
03:00:13,080 --> 03:00:14,400
RIGHT -- AS YOU WOULD EXPECT IN

4990
03:00:14,400 --> 03:00:14,920
A HUMAN.

4991
03:00:14,920 --> 03:00:18,240
SAME MANNER, WE CREATE THE

4992
03:00:18,240 --> 03:00:19,440
MINIATURE HEART ORGANS IN THE

4993
03:00:19,440 --> 03:00:21,280
SAME MANNER USING ALL THE MAJOR

4994
03:00:21,280 --> 03:00:22,600
HEART CELL TYPES IN THE SAME

4995
03:00:22,600 --> 03:00:22,920
PROPORTION.

4996
03:00:22,920 --> 03:00:25,000
WE CAN SLOW THEM DOWN OR SPEED

4997
03:00:25,000 --> 03:00:27,840
THEM UP FROM THEIR 60 BEATS PER

4998
03:00:27,840 --> 03:00:31,000
MINUTE BASED ON DIFFERENT DRUGS

4999
03:00:31,000 --> 03:00:32,320
AND THE HUMAN DOSE-RELEVANT

5000
03:00:32,320 --> 03:00:32,600
RESPONSE.

5001
03:00:32,600 --> 03:00:34,320
WE CAN ALSO CREATE MINIATURE

5002
03:00:34,320 --> 03:00:35,960
HEART ATTACKS, SO CREATE MODEL

5003
03:00:35,960 --> 03:00:37,240
SYSTEMS THAT ARE ABLE TO HELP US

5004
03:00:37,240 --> 03:00:39,000
OUT WHEN WE'RE LOOKING AT DRUG

5005
03:00:39,000 --> 03:00:40,200
DEVELOPMENT OR MODEL SYSTEMS.

5006
03:00:40,200 --> 03:00:41,840
WE CAN CREATE THESE MINIATURE

5007
03:00:41,840 --> 03:00:42,360
BRAINS.

5008
03:00:42,360 --> 03:00:43,600
SAME THING WITH THESE MINIATURE

5009
03:00:43,600 --> 03:00:45,480
BRAINS, WE USE ALL THE SIX MAJOR

5010
03:00:45,480 --> 03:00:46,880
TYPES THAT ARE PRESENT IN THE

5011
03:00:46,880 --> 03:00:48,960
BRAIN IN THE SAME PROPORTION,

5012
03:00:48,960 --> 03:00:50,680
AND BY DOING SO, WE'RE ABLE TO

5013
03:00:50,680 --> 03:00:55,520
CREATE AN   AN ENTIRELY NATIVE N

5014
03:00:55,520 --> 03:00:57,160
BLOOD BRAIN BARRIER, THAT IS, A

5015
03:00:57,160 --> 03:00:58,360
BARRIER CREATED BY THE CELLS

5016
03:00:58,360 --> 03:00:58,800
THEMSELVES.

5017
03:00:58,800 --> 03:01:02,520
WE'RE NOT USING TRANS MEMBRANES

5018
03:01:02,520 --> 03:01:04,280
OR SILICONE MEMBRANES FOR THIS.

5019
03:01:04,280 --> 03:01:06,560
BLOOD BRAIN BARRIER IS CREATED

5020
03:01:06,560 --> 03:01:07,880
ENTIRELY BY THE MINIATURE BRAIN

5021
03:01:07,880 --> 03:01:08,960
ORGANOIDS THAT YOU SEE HERE,

5022
03:01:08,960 --> 03:01:11,280
WHERE WE CAN CREATE ALSO MIMIC

5023
03:01:11,280 --> 03:01:12,800
STROKES, FOR EXAMPLE, AND THEN

5024
03:01:12,800 --> 03:01:14,560
GO AFTER TREATMENT MODALITIES.

5025
03:01:14,560 --> 03:01:16,320
SAME THING FOR THE LUNG, THIS IS

5026
03:01:16,320 --> 03:01:17,720
A NICE SLIDE BECAUSE IT SHOWS

5027
03:01:17,720 --> 03:01:19,480
WHAT A 2D CULTURE SYSTEM LOOKS

5028
03:01:19,480 --> 03:01:20,840
LIKE ON THE TOP RIGHT, WHAT A

5029
03:01:20,840 --> 03:01:27,240
NATIVE LUK LOOKS LIKE ON       E

5030
03:01:27,240 --> 03:01:28,000
BOTTOM RIGHT.

5031
03:01:28,000 --> 03:01:30,520
WE CAN SEE THEN WE CAN START

5032
03:01:30,520 --> 03:01:31,080
DOING INFECTIVITY.

5033
03:01:31,080 --> 03:01:33,120
FOR EXAMPLE, WE TOOK STRAINS OF

5034
03:01:33,120 --> 03:01:35,240
PSEUDOMONAS THAT WERE SHOWN TO

5035
03:01:35,240 --> 03:01:36,880
BE DIFFERENTIAL IN TERMS OF

5036
03:01:36,880 --> 03:01:38,080
THEIR AGGRESSIVENESS IN HUMANS

5037
03:01:38,080 --> 03:01:39,640
AND WE WERE ABLE TO TEST THAT IN

5038
03:01:39,640 --> 03:01:41,880
THE ORGANOID SYSTEM REPLICATING

5039
03:01:41,880 --> 03:01:44,960
BASICALLY THE INFECTIVITY

5040
03:01:44,960 --> 03:01:45,720
AGGRESSIVENESS THAT WE WOULD SEE

5041
03:01:45,720 --> 03:01:49,400
IN A HUMAN MODEL, SHOWING -- TO

5042
03:01:49,400 --> 03:01:50,080
THE HUMANS.

5043
03:01:50,080 --> 03:01:52,080
THIS IS LOOKING AT RSV, WHERE WE

5044
03:01:52,080 --> 03:01:54,680
CAN ACTUALLY INCORPORATE

5045
03:01:54,680 --> 03:01:55,000
NEUTROPHILS.

5046
03:01:55,000 --> 03:01:59,040
ON THE LEFT YOU CAN SEE THE

5047
03:01:59,040 --> 03:02:00,280
MODEL -- BUT ON THE TOP RIGHT,

5048
03:02:00,280 --> 03:02:04,080
YOU SEE WHAT HAPPENS WHEN WE

5049
03:02:04,080 --> 03:02:05,960
INFECT THE LUNG ORGANOIDS WITH

5050
03:02:05,960 --> 03:02:07,920
RSV, SHOWING MIGRATION OF THE

5051
03:02:07,920 --> 03:02:09,800
NEUTROPHILS TO THE EPITHELIAL

5052
03:02:09,800 --> 03:02:10,880
MEMBRANE WITH DISRUPTION OF

5053
03:02:10,880 --> 03:02:12,080
CILIA, AND YOU CAN SEE THE

5054
03:02:12,080 --> 03:02:14,600
INCORPORATION OF THE NEUTROPHILS

5055
03:02:14,600 --> 03:02:16,240
WITH THE IMMUNOFLUORESCENCE THAT

5056
03:02:16,240 --> 03:02:18,200
YOU SEE HERE.

5057
03:02:18,200 --> 03:02:24,000
WE CAN ALSO LOOK AT ZIKA VIRUS,

5058
03:02:24,000 --> 03:02:24,440
FOR EXAMPLE.

5059
03:02:24,440 --> 03:02:26,200
THIS WAS DONE IN TESTICULAR

5060
03:02:26,200 --> 03:02:27,720
TISSUE, SHOWING HOW WE CAN

5061
03:02:27,720 --> 03:02:29,120
ACTUALLY INFECT THESE WITH THE

5062
03:02:29,120 --> 03:02:32,200
ZIKA VIRUS AND LOOK AT THE

5063
03:02:32,200 --> 03:02:33,080
NATURAL HISTORY OF THE VIRUS

5064
03:02:33,080 --> 03:02:35,480
OVER TIME.

5065
03:02:35,480 --> 03:02:37,240
WE ALSO LOOKED AT COVID.

5066
03:02:37,240 --> 03:02:38,560
AS YOU CAN SEE HERE WITH THE

5067
03:02:38,560 --> 03:02:42,080
COVID INFECTION, WE CAN SHOW

5068
03:02:42,080 --> 03:02:45,000
THAT THE LUNG IS POSITIVE FOR

5069
03:02:45,000 --> 03:02:49,360
ACE 2, AND THEN YOU CAN SEE THE

5070
03:02:49,360 --> 03:02:51,000
SARS SPIKE PROTEIN WITHIN THE

5071
03:02:51,000 --> 03:02:54,560
ORGANOIDS AND YOU CAN SEE THE

5072
03:02:54,560 --> 03:02:56,920
EXPANSION OF THE VIRUS AS YOU

5073
03:02:56,920 --> 03:02:59,120
WOULD SEE WITH HEIGHTENED

5074
03:02:59,120 --> 03:03:01,440
REPLICATION AT DAY #  3 TO 4-RBS

5075
03:03:01,440 --> 03:03:05,680
WHICH IS WHAT YOU              H

5076
03:03:05,680 --> 03:03:08,320
YOU WOULD SEE IN HUMANS.

5077
03:03:08,320 --> 03:03:10,200
 -- MAXIMIZED AT DAY 4 ALSO WHAT

5078
03:03:10,200 --> 03:03:11,840
YOU WOULD SEE IN A HUMAN MODEL.

5079
03:03:11,840 --> 03:03:15,320
SO THESE REALLY DO RESPOND TO

5080
03:03:15,320 --> 03:03:16,440
THESE MODELS VERY WELL.

5081
03:03:16,440 --> 03:03:17,920
WE'RE NOT LOOKING AT THE TRAN

5082
03:03:17,920 --> 03:03:23,000
SCRIP TOE MINK ANALYSIS         

5083
03:03:23,000 --> 03:03:24,160
TRANSCRIPTOMIC ANALYSIS OF

5084
03:03:24,160 --> 03:03:26,040
DRUGGABLE TARGETS, LOOKING AT

5085
03:03:26,040 --> 03:03:26,920
POTENTIAL DRUG TARGETS FOR THE

5086
03:03:26,920 --> 03:03:27,400
FUTURE.

5087
03:03:27,400 --> 03:03:29,040
AND ALSO LOOKING AT, FOR

5088
03:03:29,040 --> 03:03:30,760
EXAMPLE, WE DID USE OUR SYSTEM

5089
03:03:30,760 --> 03:03:33,160
TO TEST ANTIVIRAL AGENTS DURING

5090
03:03:33,160 --> 03:03:35,000
THE COVID PANDEMIC, AND ONE OF

5091
03:03:35,000 --> 03:03:40,240
THESE AISHTS IS NOW IN ENTRY

5092
03:03:40,240 --> 03:03:41,120
PHASE 2 CLINICAL TRIALS SHOWING

5093
03:03:41,120 --> 03:03:43,320
THIS AGENT WAS EFFECTIVE AGAINST

5094
03:03:43,320 --> 03:03:44,640
THE SARS-COV-2 VIRUS.

5095
03:03:44,640 --> 03:03:46,400
NOW WHAT DO THEY ACTUALLY LOOK

5096
03:03:46,400 --> 03:03:46,600
LIKE?

5097
03:03:46,600 --> 03:03:48,360
THIS IS AN ACTUAL PRINTED CHIP.

5098
03:03:48,360 --> 03:03:50,320
SO WE PRINT BOTH THE CHIP AND

5099
03:03:50,320 --> 03:03:52,720
THE ORGANOIDS TOGETHER, AND THIS

5100
03:03:52,720 --> 03:03:55,480
PARTICULAR ONE, WE HAVE LIVER,

5101
03:03:55,480 --> 03:03:57,560
KIDNEY AND OVARY ALL PRINTED

5102
03:03:57,560 --> 03:03:57,880
TOGETHER.

5103
03:03:57,880 --> 03:03:59,320
SO THE WHOLE STRUCTURE WAS

5104
03:03:59,320 --> 03:04:01,720
PRINTED HERE, THE CHIP AND THE

5105
03:04:01,720 --> 03:04:02,040
CELLS.

5106
03:04:02,040 --> 03:04:03,560
THE ONLY THING THAT WAS NOT

5107
03:04:03,560 --> 03:04:04,760
PRINTED WAS THE TUBING AND THE

5108
03:04:04,760 --> 03:04:05,400
GLASS SLIDE.

5109
03:04:05,400 --> 03:04:06,960
BUT EVERYTHING ELSE WAS PRINTED.

5110
03:04:06,960 --> 03:04:11,440
AND YOU CAN SEE HERE THAT WE CAN

5111
03:04:11,440 --> 03:04:12,240
PUT SIX TOGETHER.

5112
03:04:12,240 --> 03:04:13,440
IN THIS PARTICULAR ONE, WE HAVE

5113
03:04:13,440 --> 03:04:15,120
LIVER, HEART, INTESTINE, LUNG,

5114
03:04:15,120 --> 03:04:17,680
BLOOD VESSELS AND TESTES, WE CAN

5115
03:04:17,680 --> 03:04:18,840
HOOK UP 12 OF THESE TOGETHER IN

5116
03:04:18,840 --> 03:04:19,520
THE SAME SYSTEM.

5117
03:04:19,520 --> 03:04:21,280
AND WE'RE STARTING TO SEE NOW

5118
03:04:21,280 --> 03:04:22,280
THINGS THAT WE COULDN'T SEE

5119
03:04:22,280 --> 03:04:23,920
BEFORE.

5120
03:04:23,920 --> 03:04:27,080
SO FOR EXAMPLE, BLEOMYCIN IS

5121
03:04:27,080 --> 03:04:29,360
KNOWN TO BE TOXIC TO THE LUNG.

5122
03:04:29,360 --> 03:04:30,560
AND THAT'S BEEN KNOWN FOR

5123
03:04:30,560 --> 03:04:31,560
DECADES.

5124
03:04:31,560 --> 03:04:35,160
AND SO TO OUR SURPRISE, WHEN WE

5125
03:04:35,160 --> 03:04:36,720
PUT IT IN OUR SYSTEM, THE HEART

5126
03:04:36,720 --> 03:04:38,040
STOPPED BEATING AND WE COULDN'T

5127
03:04:38,040 --> 03:04:39,760
FIGURE OUT WHY THE HEART STOPPED

5128
03:04:39,760 --> 03:04:40,520
BEATING BECAUSE THERE'S NOTHING

5129
03:04:40,520 --> 03:04:42,040
IN THE LITERATURE TO SUGGEST

5130
03:04:42,040 --> 03:04:45,680
THAT THESE ORGANOIDS WOULD STOP

5131
03:04:45,680 --> 03:04:47,440
THE HEART -- THESE HEART

5132
03:04:47,440 --> 03:04:48,520
ORGANOIDS WOULD BE AFFECTED.

5133
03:04:48,520 --> 03:04:50,080
SO WE PUT A NEW BATCH IN.

5134
03:04:50,080 --> 03:04:51,680
SAME CHALLENGE, THEY AGAIN

5135
03:04:51,680 --> 03:04:53,000
WERE -- THEY STOPPED BEATING, SO

5136
03:04:53,000 --> 03:04:54,960
WE THOUGHT MAYBE IT WAS A LIVER

5137
03:04:54,960 --> 03:04:55,280
METABOLITE.

5138
03:04:55,280 --> 03:04:56,720
WE PULLED THE LIVER OUT, THEY

5139
03:04:56,720 --> 03:04:58,480
STILL STOPPED BEATING.

5140
03:04:58,480 --> 03:05:00,000
TURNS OUT THAT WHEN THE LUNG

5141
03:05:00,000 --> 03:05:02,320
STARTS TO BE TOXIC FROM THE

5142
03:05:02,320 --> 03:05:03,520
BLEOMYCIN, THAT THERE'S

5143
03:05:03,520 --> 03:05:05,360
SECRETION OF INTERLEUKINS AND

5144
03:05:05,360 --> 03:05:07,960
THE INTERLEUKINS, IN FACT, CAN

5145
03:05:07,960 --> 03:05:11,160
BE CARDIOTOXIC, SO THE FACT IS

5146
03:05:11,160 --> 03:05:13,000
THAT WITH SUBCLINICALLY, THIS IS

5147
03:05:13,000 --> 03:05:16,200
PROBABLY OCCURRING, WE DON'T SEE

5148
03:05:16,200 --> 03:05:17,200
IT BECAUSE BY THE TIME WE PULL

5149
03:05:17,200 --> 03:05:18,800
THE DRUG, THIS CHEMOTHERAPY

5150
03:05:18,800 --> 03:05:20,120
AGENT THAT IS COMMONLY USED, BY

5151
03:05:20,120 --> 03:05:21,480
THE TIME WE PULL IT FROM THE

5152
03:05:21,480 --> 03:05:23,640
PATIENT, YOU PROBABLY DO HAVE

5153
03:05:23,640 --> 03:05:24,520
CARDIAC SUBCLINICAL TOXICITY

5154
03:05:24,520 --> 03:05:25,160
GOING ON.

5155
03:05:25,160 --> 03:05:26,880
WE'RE NOW STARTING TO SEE THINGS

5156
03:05:26,880 --> 03:05:30,840
THAT BEFORE WERE NOT POSSIBLE TO

5157
03:05:30,840 --> 03:05:31,520
SEE.

5158
03:05:31,520 --> 03:05:32,720
HOW DOES THE SYSTEM WORK

5159
03:05:32,720 --> 03:05:33,920
ACTUALLY IN TERMS OF DRUGS?

5160
03:05:33,920 --> 03:05:36,320
SO WE TOOK ABOUT 40 DRUGS THAT

5161
03:05:36,320 --> 03:05:37,840
WERE RECALLED BY THE FDA.

5162
03:05:37,840 --> 03:05:40,040
I'M GOING TO GIVE YOU A COUPLE

5163
03:05:40,040 --> 03:05:41,160
EXAMPLES HERE, WHERE THERE ARE

5164
03:05:41,160 --> 03:05:43,200
DRASTIC DIFFERENCES.

5165
03:05:43,200 --> 03:05:46,600
THIS IS HISMANAL, ANTIHISTAMINE

5166
03:05:46,600 --> 03:05:48,120
THAT HAD BEEN USED IN THE

5167
03:05:48,120 --> 03:05:48,960
MARKETPLACE FOR 11 YEARS.

5168
03:05:48,960 --> 03:05:50,840
THE DRUG HAD BEEN TESTED IN THEY

5169
03:05:50,840 --> 03:05:54,600
WILL LINES, NO TOXICITY, ANIMAL

5170
03:05:54,600 --> 03:05:55,880
MODELS, NO TOXICITY.

5171
03:05:55,880 --> 03:05:58,840
HUMAN CLINICAL TRIALS, NO

5172
03:05:58,840 --> 03:05:59,840
TOXICITY.

5173
03:05:59,840 --> 03:06:01,040
GETS RELEASED INTO THE

5174
03:06:01,040 --> 03:06:01,800
MARKETPLACE, 11 YEARS LATER,

5175
03:06:01,800 --> 03:06:02,880
THEY FINALLY CONNECT THE DOTS

5176
03:06:02,880 --> 03:06:04,640
FOR THIS OVER THE COUNTER DRUG

5177
03:06:04,640 --> 03:06:05,960
TO SHOW THIS WAS ACTUALLY

5178
03:06:05,960 --> 03:06:11,120
CAUSING HEART BLOCK.

5179
03:06:11,120 --> 03:06:12,840
THE DRUG WAS RECALLED BY THE

5180
03:06:12,840 --> 03:06:15,280
FDA, WE TRUSTED THE DRUG, IN TWO

5181
03:06:15,280 --> 03:06:16,600
WEEKS WE KNEW THE DRUG WAS TOXIC

5182
03:06:16,600 --> 03:06:20,160
TO THE HEART, SAME RESPONSE IN

5183
03:06:20,160 --> 03:06:20,360
HUMAN.

5184
03:06:20,360 --> 03:06:22,600
THIS IS MORE OF A TRAGIC STORY.

5185
03:06:22,600 --> 03:06:25,120
THIS IS REZULIN, AN ANTIDIABETIC

5186
03:06:25,120 --> 03:06:26,200
ON THE MARKETPLACE FOR THREE

5187
03:06:26,200 --> 03:06:26,520
YEARS.

5188
03:06:26,520 --> 03:06:30,040
SAME, HAD BEEN TESTED IN CELL

5189
03:06:30,040 --> 03:06:33,200
LINES, ANIMAL MODEL, PHASE 1,

5190
03:06:33,200 --> 03:06:33,920
2 AND 3 HUMAN CLINICAL TRIALS,

5191
03:06:33,920 --> 03:06:35,160
ON THE MARKET FOR THREE YEARS

5192
03:06:35,160 --> 03:06:38,760
AND BASICALLY WHAT WE SAW WAS A

5193
03:06:38,760 --> 03:06:40,320
MAJOR CHALLENGE WITH 63 DEATHS

5194
03:06:40,320 --> 03:06:42,960
DUE TO LIVER FAILURE WITHIN

5195
03:06:42,960 --> 03:06:46,760
THREE YEARS.

5196
03:06:46,760 --> 03:06:49,360
SO WE WERE ABLE TO GET THE DRUG

5197
03:06:49,360 --> 03:06:54,840
TESTED IN OUR SYSTEM, SAME HUMAN

5198
03:06:54,840 --> 03:06:55,520
DRUG DOSE-RESPONSE.

5199
03:06:55,520 --> 03:06:58,680
SO THE SYSTEM IS FAIRLY USEFUL

5200
03:06:58,680 --> 03:06:59,760
WHEN LOOKING AT THESE DRUGS.

5201
03:06:59,760 --> 03:07:04,600
WE'RE NOW USING THIS FOR CANCER.

5202
03:07:04,600 --> 03:07:06,120
WE HAVE ABOUT 12 DIFFERENT

5203
03:07:06,120 --> 03:07:06,760
CLINICAL TRIALS GOING ON WHERE

5204
03:07:06,760 --> 03:07:07,920
WE TAKE TISSUES FROM PATIENTS

5205
03:07:07,920 --> 03:07:10,400
HERE AT WAKE FOREST WITH TUMORS,

5206
03:07:10,400 --> 03:07:12,320
WE CREATE A TUMOR IN A CHIP, WE

5207
03:07:12,320 --> 03:07:14,520
CAN THEN USE CHEMOTHERAPY AGENTS

5208
03:07:14,520 --> 03:07:16,320
TO LOOK AT PREDICTIVE MODELING

5209
03:07:16,320 --> 03:07:17,160
OF WHAT WOULD BE THE BEST

5210
03:07:17,160 --> 03:07:18,760
TREATMENT FOR THE PATIENTS IN

5211
03:07:18,760 --> 03:07:19,760
THE FUTURE.

5212
03:07:19,760 --> 03:07:22,520
SO THIS IS ACTUALLY ACTIVELY

5213
03:07:22,520 --> 03:07:22,840
ONGOING.

5214
03:07:22,840 --> 03:07:23,840
WE HAVE SEVERAL PROGRAMS RIGHT

5215
03:07:23,840 --> 03:07:25,240
NOW, WE HAVE A PROGRAM FROM

5216
03:07:25,240 --> 03:07:27,120
BARDA LOOKING AT CHEMICAL

5217
03:07:27,120 --> 03:07:29,520
AGENTS, A PROGRAM FROM DTRA

5218
03:07:29,520 --> 03:07:31,920
LOOKING AT NERVE AGENTS AND A

5219
03:07:31,920 --> 03:07:32,840
RECENT PROGRAM, WE'RE GOING TO

5220
03:07:32,840 --> 03:07:33,800
BE LOOKING AT VIRUSES.

5221
03:07:33,800 --> 03:07:35,000
SO BASICALLY HERE WHAT WE DO IS

5222
03:07:35,000 --> 03:07:37,640
WE ARE LOOKING AT A SELECTION OF

5223
03:07:37,640 --> 03:07:38,480
RELEVANT ORGAN TISSUE

5224
03:07:38,480 --> 03:07:38,920
EQUIVALENTS.

5225
03:07:38,920 --> 03:07:40,880
WE CAN EXPOSE THEM TO THE

5226
03:07:40,880 --> 03:07:42,640
VIRUSES OF INTEREST.

5227
03:07:42,640 --> 03:07:45,160
WE CAN THEN ANALYZE FOR

5228
03:07:45,160 --> 03:07:47,320
BIOMARKERS AND THEN WE CAN LOOK

5229
03:07:47,320 --> 03:07:49,880
AT A WIDE RANGE OF DOSES AND

5230
03:07:49,880 --> 03:07:51,720
RESPONSES FROM MILD TO SEVERE,

5231
03:07:51,720 --> 03:07:53,720
AND THEN BASICALLY WE'RE LOOKING

5232
03:07:53,720 --> 03:07:56,200
AT ALL THE OMICS.

5233
03:07:56,200 --> 03:07:58,080
SO CURRENTLY FOR EXAMPLE FOR

5234
03:07:58,080 --> 03:07:59,600
CHEMICAL PROGRAM AND SAME THING

5235
03:07:59,600 --> 03:08:01,000
FOR VIRAL PROGRAM, WE'LL BE

5236
03:08:01,000 --> 03:08:04,000
LOOKING AT TRANSCRIPTOMICS,

5237
03:08:04,000 --> 03:08:05,640
PROTEOMICS, METABOLOMICS.

5238
03:08:05,640 --> 03:08:07,600
WE LIKE TO SAY THERE ARE NO

5239
03:08:07,600 --> 03:08:08,360
OMICS LEFT BEHIND.

5240
03:08:08,360 --> 03:08:09,480
BUT THIS IS BASICALLY BEING DONE

5241
03:08:09,480 --> 03:08:11,880
SO WE CAN APPLY THESE CAPABILITY

5242
03:08:11,880 --> 03:08:13,400
TO GENERATE HIGH QUALITY AND

5243
03:08:13,400 --> 03:08:15,040
REPRODUCIBLE DATASETS FOR

5244
03:08:15,040 --> 03:08:16,760
DOWNSTREAM INTEGRATED

5245
03:08:16,760 --> 03:08:18,200
BIOINFORMATIC AND STATISTICAL

5246
03:08:18,200 --> 03:08:19,600
ANALYSIS SO WE CAN THEN IN THE

5247
03:08:19,600 --> 03:08:23,120
FUTURE TAKE A KNOWN VIRUS, LOOK

5248
03:08:23,120 --> 03:08:26,280
AT HOW THE VIRUS REPLICATE, LOOK

5249
03:08:26,280 --> 03:08:28,360
INTO BIG DATA, LOOK AT THE

5250
03:08:28,360 --> 03:08:29,880
BIOMARKERS, USE ARTIFICIAL

5251
03:08:29,880 --> 03:08:30,560
INTELLIGENCE AND MACHINE

5252
03:08:30,560 --> 03:08:33,400
LEARNING, SO WE CAN LOOK AT

5253
03:08:33,400 --> 03:08:36,000
EXPOSURE AND PROGNOSTIC

5254
03:08:36,000 --> 03:08:38,680
BIOMARKERS, LOOK AT PROPHYLAX  S

5255
03:08:38,680 --> 03:08:39,280
AND THERAPEUTICS.

5256
03:08:39,280 --> 03:08:42,920
WE'RE USING THIS SYSTEM FOR

5257
03:08:42,920 --> 03:08:44,680
IDENTIFYING AND CREATING NEW

5258
03:08:44,680 --> 03:08:45,000
COMPOUNDS.

5259
03:08:45,000 --> 03:08:46,520
WE ARE NOW APPROACHING THROUGH

5260
03:08:46,520 --> 03:08:48,160
THE PATHWAY OF CLINICAL

5261
03:08:48,160 --> 03:08:49,920
TRANSLATION.

5262
03:08:49,920 --> 03:08:52,000
AND OF COURSE WITH THE SYSTEMS,

5263
03:08:52,000 --> 03:08:53,120
THERE'S STILL WORK TO BE DONE.

5264
03:08:53,120 --> 03:08:56,360
WE HAVE TO LOOK AT RELIABLE CELL

5265
03:08:56,360 --> 03:08:59,320
SOURCING, WE HAVE TO LOOK AT

5266
03:08:59,320 --> 03:08:59,960
INFECTIVITY STANDARDS,

5267
03:08:59,960 --> 03:09:01,760
REPRODUCIBILITY, AND GENETIC

5268
03:09:01,760 --> 03:09:02,520
VARIABILITY SO THERE'S STILL A

5269
03:09:02,520 --> 03:09:03,720
LOT OF WORK THAT NEEDS TO BE

5270
03:09:03,720 --> 03:09:06,200
DONE, BUT CERTAINLY IT'S A

5271
03:09:06,200 --> 03:09:07,760
SYSTEM THAT CAN LEND ITSELF TO

5272
03:09:07,760 --> 03:09:08,600
BEING USEFUL.

5273
03:09:08,600 --> 03:09:11,040
WE DO HAVE THIS CONSORTIUM

5274
03:09:11,040 --> 03:09:13,000
THAT'S LOOKING AT DEVELOPING

5275
03:09:13,000 --> 03:09:15,040
THIS AI MACHINE LEARNING

5276
03:09:15,040 --> 03:09:16,200
CAPABILITIES TO ACCELERATE DRUG

5277
03:09:16,200 --> 03:09:18,120
SCREENING AND DISCOVERY, AND

5278
03:09:18,120 --> 03:09:19,560
LOOKING -- OUR FOUNDING MEMBER

5279
03:09:19,560 --> 03:09:23,720
WAS ORACLE, SO THEY CAN -- TO

5280
03:09:23,720 --> 03:09:24,920
HELP MANAGE ASPECTS RELATED TO

5281
03:09:24,920 --> 03:09:26,880
THE A.I. FOR FUTURE BIOMARKER

5282
03:09:26,880 --> 03:09:28,080
AND DRUG DEVELOPMENT.

5283
03:09:28,080 --> 03:09:30,960
SO WE HAVE A LARGE PORTFOLIO OF

5284
03:09:30,960 --> 03:09:32,160
TISSUES AND ORGANOIDS SO WE CAN

5285
03:09:32,160 --> 03:09:35,400
PUT INTO THESE CHIPS.

5286
03:09:35,400 --> 03:09:36,960
WHAT WE NOW CALL THE BODY IN A

5287
03:09:36,960 --> 03:09:38,160
CHIP.

5288
03:09:38,160 --> 03:09:39,240
AND BASICALLY A LOT OF

5289
03:09:39,240 --> 03:09:40,880
PUBLICATIONS THAT HAVE COME OUT

5290
03:09:40,880 --> 03:09:42,640
OF OUR TEAM HERE AT THE WAKE

5291
03:09:42,640 --> 03:09:43,720
FOREST INSTITUTE FOR

5292
03:09:43,720 --> 03:09:44,280
REGENERATIVE MEDICINE, JUST

5293
03:09:44,280 --> 03:09:47,440
REALLY A TERRIFIC TEAM.

5294
03:09:47,440 --> 03:09:48,640
AND I'D LIKE TO THANK YOU ALL

5295
03:09:48,640 --> 03:09:51,280
FOR YOUR ATTENTION AND THANK YOU

5296
03:09:51,280 --> 03:09:53,960
AGAIN FOR HAVING ME.

5297
03:09:53,960 --> 03:09:55,520
>> THANKS SO MUCH, TONY,
FOR THE

5298
03:09:55,520 --> 03:10:03,120
VERY NICE OVERVIEW.

5299
03:10:03,120 --> 03:10:04,800
THINK THE BREAK WAS AT 2:40.

5300
03:10:04,800 --> 03:10:05,960
I THINK IF ALL THE SPEAKERS CAN

5301
03:10:05,960 --> 03:10:08,640
STAY FOR THE QUESTION AND ANSWER

5302
03:10:08,640 --> 03:10:14,800
SESSION, WHICH IS GOING TO BE, I

5303
03:10:14,800 --> 03:10:17,840
BELIEVE, AT 3:40, I THINK I

5304
03:10:17,840 --> 03:10:22,800
WOULD RATHER TAKE THE BREAK NOW

5305
03:10:22,800 --> 03:10:24,280
UNTIL 3:00, AND THEN WE'LL

5306
03:10:24,280 --> 03:10:26,680
RESUME THE SESSION AT 3:00 AND

5307
03:10:26,680 --> 03:10:28,880
THEN HAVE THE QUESTION AND

5308
03:10:28,880 --> 03:10:32,720
ANSWER SESSION AT 3:40.

5309
03:10:32,720 --> 03:10:34,720
IS THAT OKAY WITH EVERYONE?

5310
03:10:34,720 --> 03:10:36,440
SARINE, ARE YOU OKAY WITH THAT?

5311
03:10:36,440 --> 03:10:38,400
>> THAT'S PERFECT, IF
EVERYONE

5312
03:10:38,400 --> 03:10:39,720
IS OKAY WITH THAT, WE SHOULD

5313
03:10:39,720 --> 03:10:40,320
STICK TO THE SCHEDULE.

5314
03:10:40,320 --> 03:10:41,720
>> ALL RIGHT.

5315
03:10:41,720 --> 03:10:44,320
THANK YOU, ALL THE SPEAKERS, AND

5316
03:10:44,320 --> 03:10:45,760
WE'LL RESUME AT 3:00.

5317
03:10:45,760 --> 03:10:46,840
>> 3:00.

5318
03:10:46,840 --> 03:10:50,240
>> SEE YOU IN A BIT.

5319
03:10:50,240 --> 03:10:51,560
AND KEEP ADDING QUESTIONS TO THE

5320
03:10:51,560 --> 03:10:52,760
BOX.

5321
03:10:52,760 --> 03:11:03,120
WHILE YOU'RE ON BREAK.

5322
03:11:50,840 --> 03:11:57,280
THANK YOU FOR THE INTRODUCTION.

5323
03:11:57,280 --> 03:12:00,880
I'M JASON, POSTDOC FROM MIT.

5324
03:12:00,880 --> 03:12:04,840
TODAY I'M GOING TO REPRESENT MY

5325
03:12:04,840 --> 03:12:09,640
SUPERVISOR, ROGER KAMM, TO SHARE

5326
03:12:09,640 --> 03:12:12,160
VASCULOGENESIS AND ANGIOGENESIS

5327
03:12:12,160 --> 03:12:12,920
MODELS.

5328
03:12:12,920 --> 03:12:14,480
FOCUSING ON THE NEUROLOGICAL

5329
03:12:14,480 --> 03:12:16,760
DISEASE, CANCERS, AND ALSO LAST

5330
03:12:16,760 --> 03:12:20,480
PART OF MY TALK, I'M GOING TO

5331
03:12:20,480 --> 03:12:23,120
SHOW ROBUST STRATEGIES TO FORM

5332
03:12:23,120 --> 03:12:23,840
MICROVASCULAR NETWORKS,

5333
03:12:23,840 --> 03:12:29,840
HOPEFULLY IT WILL BE BENEFICIAL

5334
03:12:29,840 --> 03:12:30,560
FOR ANTIVIRAL DRUG DEVELOPMENT

5335
03:12:30,560 --> 03:12:32,040
AS WELL.

5336
03:12:32,040 --> 03:12:34,040
SO AS WE KNOW,

5337
03:12:34,040 --> 03:12:36,680
MICROPHYSIOLOGICAL SYSTEMS

5338
03:12:36,680 --> 03:12:39,720
ACTUALLY ATTRACT MORE AND MORE

5339
03:12:39,720 --> 03:12:42,480
ATTENTION RECENTLY BECAUSE OF

5340
03:12:42,480 --> 03:12:45,520
PARTIALLY TO RECALCULATE -- THE

5341
03:12:45,520 --> 03:12:47,720
ORGANIZE FORM AND FUNCTIONS

5342
03:12:47,720 --> 03:12:50,240
THROUGHOUT THE CELLS MODIFY

5343
03:12:50,240 --> 03:12:55,920
SCREENING DRUGS TO MIMIC DISEASE

5344
03:12:55,920 --> 03:12:58,000
MODELS, TISSUES, ORGANS ACTUALLY

5345
03:12:58,000 --> 03:12:59,520
FOCUSING ON THE CIRCULATION

5346
03:12:59,520 --> 03:13:04,120
SYSTEM AND AS WE ALL KNOW THAT

5347
03:13:04,120 --> 03:13:06,640
BLOOD OR NUTRIENTS IN CELLS

5348
03:13:06,640 --> 03:13:07,640
TRANSPORT THROUGH THE

5349
03:13:07,640 --> 03:13:08,600
CIRCULATION SYSTEM AND THEY ARE

5350
03:13:08,600 --> 03:13:09,600
VERY IMPORTANT FOR ALMOST ALL

5351
03:13:09,600 --> 03:13:14,520
THE OR   ORGANS.

5352
03:13:14,520 --> 03:13:16,480
PARTICULARLY WE ARE INTERESTED

5353
03:13:16,480 --> 03:13:19,200
IN THE CAPILLARY, ENGINEERING OF

5354
03:13:19,200 --> 03:13:19,800
CAPILLARIES.

5355
03:13:19,800 --> 03:13:20,720
THEY HAVE THREE FEATURES.

5356
03:13:20,720 --> 03:13:22,480
ONE IS THEY ARE PERFUSABLE AS I

5357
03:13:22,480 --> 03:13:25,000
JUST MENTIONED, THE CELLS GET

5358
03:13:25,000 --> 03:13:26,640
TRANSPORTED THROUGH THE

5359
03:13:26,640 --> 03:13:28,400
CAPILLARIES.

5360
03:13:28,400 --> 03:13:29,480
THE SECOND FEATURE IS THEY HAVE

5361
03:13:29,480 --> 03:13:30,480
SMALL DIAMETER.

5362
03:13:30,480 --> 03:13:36,640
SOMETIMES THEY HAVE ONLY SINGLE

5363
03:13:36,640 --> 03:13:40,240
CELL CAN CUT THROUGH ONE

5364
03:13:40,240 --> 03:13:41,400
CAPILLARY, THE THIRD FEATURE IS

5365
03:13:41,400 --> 03:13:43,920
THEY ARE PERMEABLE, SO THEY CAN

5366
03:13:43,920 --> 03:13:46,720
TRANSPORT ACROSS THE ENDOTHELIUM

5367
03:13:46,720 --> 03:13:50,360
FROM THE LUMINAL SIDE TO THE

5368
03:13:50,360 --> 03:13:53,560
STROMAL SIDE.

5369
03:13:53,560 --> 03:13:58,480
SO TO MIMIC CAPILLARIES BY

5370
03:13:58,480 --> 03:14:02,000
PROFESSOR MIMMERY AND ALSO

5371
03:14:02,000 --> 03:14:06,240
PROFESSOR GRIFFIN, SO AT THE LAB

5372
03:14:06,240 --> 03:14:11,600
WE ACTUALLY USE MICRO -- TO

5373
03:14:11,600 --> 03:14:15,680
ENGINEER CAPILLARY-LIKE

5374
03:14:15,680 --> 03:14:21,560
STRUCTURES, SO -- DESIGNS, MOST

5375
03:14:21,560 --> 03:14:26,120
OF THEM SIMILAR TO THIS A --

5376
03:14:26,120 --> 03:14:27,560
THREE CHANNELS.

5377
03:14:27,560 --> 03:14:30,320
IN THE CENTER THIS IS A GEL

5378
03:14:30,320 --> 03:14:32,480
CHANNEL, LEFT SIDE THEY HAVE

5379
03:14:32,480 --> 03:14:34,560
MEDIA CHANNEL.

5380
03:14:34,560 --> 03:14:36,000
ENDOTHELIAL CELLS AND STROMAL

5381
03:14:36,000 --> 03:14:42,880
CELLS INTO THE -- IN HYDROGEL

5382
03:14:42,880 --> 03:14:44,960
PRECURSOR AND WE INJECT IT --

5383
03:14:44,960 --> 03:14:46,600
WE'RE GOING TO ADD THE MEDIA

5384
03:14:46,600 --> 03:14:56,240
INTO THE DEVICE SO -- SO BE SINK

5385
03:14:56,240 --> 03:14:58,120
GEL CELL ARE GOING TO MIGRATE,

5386
03:14:58,120 --> 03:14:59,520
PROLIFERATE, MAKE CONNECTIONS

5387
03:14:59,520 --> 03:15:00,720
AND EVENTUALLY THEY ARE GOING TO

5388
03:15:00,720 --> 03:15:04,960
FORM A NETWORK SO -- SHOWN IN

5389
03:15:04,960 --> 03:15:06,720
GREEN SO WE CALL IT

5390
03:15:06,720 --> 03:15:09,000
MICROVASCULAR NETWORKS AND ALL

5391
03:15:09,000 --> 03:15:12,600
THESE DEVICES HAVE LIKE

5392
03:15:12,600 --> 03:15:15,560
COMMERCIALLY AVAILABLE FROM AIM

5393
03:15:15,560 --> 03:15:21,480
BIOTECH.

5394
03:15:21,480 --> 03:15:24,880
SO OUR DEVICE TECHNIQUE ACTUALLY

5395
03:15:24,880 --> 03:15:26,880
PREPARED WITH ASSAYS, WE CAN

5396
03:15:26,880 --> 03:15:29,360
TAKE FLUORESCENT IMAGING OR USE

5397
03:15:29,360 --> 03:15:30,360
TEM TO SEE THE STRUCTURE.

5398
03:15:30,360 --> 03:15:33,080
WE CAN ALSO ATTRACT MORE

5399
03:15:33,080 --> 03:15:35,560
INFLAMMATION SUCH AS GENOMIC

5400
03:15:35,560 --> 03:15:38,760
RNA, DNA SEQUENCING, COMPARED

5401
03:15:38,760 --> 03:15:42,040
WITH OUR DEVICE, WE CAN SORT

5402
03:15:42,040 --> 03:15:43,240
CELLS, ALSO COLLECT MEDIA TO SEE

5403
03:15:43,240 --> 03:15:50,000
HOW THE PROTEINS ARE SECRETED BY

5404
03:15:50,000 --> 03:15:54,080
THE CELLS, DO SOME FUNCTIONAL

5405
03:15:54,080 --> 03:15:59,560
ANALYSIS SUCH AS MICRO

5406
03:15:59,560 --> 03:16:02,320
VASCULATURE -- TO SEE TUMOR

5407
03:16:02,320 --> 03:16:02,920
CELL -- ET CETERA.

5408
03:16:02,920 --> 03:16:05,680
SO I'M GOING TO SHOW ALL THOSE

5409
03:16:05,680 --> 03:16:07,120
ASSAYS AND APPLICATIONS USING

5410
03:16:07,120 --> 03:16:08,320
THE FOLLOWING EXAMPLES.

5411
03:16:08,320 --> 03:16:11,720
SO AS I MENTIONED THAT THE

5412
03:16:11,720 --> 03:16:14,000
CAPILLARIES, ONE OF THE FEATURES

5413
03:16:14,000 --> 03:16:15,520
IS -- IN OUR SYSTEM WE CAN

5414
03:16:15,520 --> 03:16:19,120
ACTUALLY DETECT THE

5415
03:16:19,120 --> 03:16:21,400
PERFUSABILITY BY ADDING

5416
03:16:21,400 --> 03:16:23,720
FLUORESCENT MOLECULES SUCH AS

5417
03:16:23,720 --> 03:16:25,920
DEX TRAN THROUGH THE MEDIA

5418
03:16:25,920 --> 03:16:31,560
CHANNEL.

5419
03:16:31,560 --> 03:16:32,400
ACTUALLY SEE THE TRANSPORT

5420
03:16:32,400 --> 03:16:37,680
THROUGH THE LUMEN AND THE

5421
03:16:37,680 --> 03:16:40,840
VASCULAR IMAGE -- WE CALL SUCH A

5422
03:16:40,840 --> 03:16:43,000
STRUCTURE AS THEY ARE PERFUSABLE

5423
03:16:43,000 --> 03:16:49,240
MICROVASCULAR NETWORKS.

5424
03:16:49,240 --> 03:16:50,800
ANOTHER FEATURE OF THE CAPILLARY

5425
03:16:50,800 --> 03:16:53,080
IS THEY ARE PERMEABLE, SO IF WE

5426
03:16:53,080 --> 03:16:55,920
PERFUSE SMALL MOLECULES -- VERY

5427
03:16:55,920 --> 03:16:59,200
SMALL AND THEN WE TOOK TWO

5428
03:16:59,200 --> 03:17:00,200
IMAGES AT DIFFERENT TIMES, WE

5429
03:17:00,200 --> 03:17:04,120
SEE ACTUALLY HOWL RAPID THE --

5430
03:17:04,120 --> 03:17:05,880
ACROSS THE ENDOTHELIUM GET INTO

5431
03:17:05,880 --> 03:17:08,840
THE STROMA, YOU SEE THE STROMA

5432
03:17:08,840 --> 03:17:11,920
REGIONS HAVE HIGHER FLUORESCENT

5433
03:17:11,920 --> 03:17:12,560
SIGNALS.

5434
03:17:12,560 --> 03:17:19,680
WE PERFUSE -- SO THE MOLECULES

5435
03:17:19,680 --> 03:17:22,600
CAN GET THROUGH THE TIGHT

5436
03:17:22,600 --> 03:17:27,560
JUNCTIONS,  -- CAN SEE THERE ARE

5437
03:17:27,560 --> 03:17:31,800
NO SIGNIFICANT FLUORESCENT

5438
03:17:31,800 --> 03:17:33,880
SIGNALS ACROSS THE LUMEN TO THE

5439
03:17:33,880 --> 03:17:35,720
STROMAL SITE.

5440
03:17:35,720 --> 03:17:37,080
SO IF YOU QUANTIFY THOSE

5441
03:17:37,080 --> 03:17:38,200
FLUORESCENT SIGNALS, WE CAN

5442
03:17:38,200 --> 03:17:40,760
ACTUALLY MEASURE THE PERM   

5443
03:17:40,760 --> 03:17:41,520
PERMEABILITY OF THE VESSELS.

5444
03:17:41,520 --> 03:17:44,160
SO WHAT I WANT TO SHOW HERE IS

5445
03:17:44,160 --> 03:17:46,080
THE GREEN ONES ARE THE ONES IN

5446
03:17:46,080 --> 03:17:48,960
VIVO USING OUR IN VITRO SYSTEM.

5447
03:17:48,960 --> 03:17:51,600
SO JUST TO -- THE IMPRESSION

5448
03:17:51,600 --> 03:17:55,640
THAT OUR MODEL IS REALLY -- HAS

5449
03:17:55,640 --> 03:17:56,960
SIMILAR PERMEABILITY COMPARED TO

5450
03:17:56,960 --> 03:17:58,800
THE ONES MEASURED IN VIVO.

5451
03:17:58,800 --> 03:18:02,240
COMPARED TO THE TRADITIONAL

5452
03:18:02,240 --> 03:18:03,840
2D -- METHOD TO MEASURE THE

5453
03:18:03,840 --> 03:18:04,960
PERMEABILITY, THEY HAVE MORE --

5454
03:18:04,960 --> 03:18:08,760
THEY ARE BETTER, THEY HAVE A

5455
03:18:08,760 --> 03:18:09,120
LOWER MOBILITY.

5456
03:18:09,120 --> 03:18:11,200
SO THOSE ARE FROM USING THOSE

5457
03:18:11,200 --> 03:18:14,120
FLUORESCENT SIGNAL BASED ON

5458
03:18:14,120 --> 03:18:15,760
PERMEABILITY, WE ALSO SEE SOME

5459
03:18:15,760 --> 03:18:18,200
STRUCTURE FROM OUR MUTUAL MODELS

5460
03:18:18,200 --> 03:18:19,720
VERY SIMILAR TO THE ONES IN VIVO

5461
03:18:19,720 --> 03:18:23,320
THAT YOU CAN SEE THOSE TIGHT

5462
03:18:23,320 --> 03:18:27,680
JUNCTIONS, VERY TINY CONNECTION

5463
03:18:27,680 --> 03:18:29,360
AND ALSO YOU CAN SEE THE

5464
03:18:29,360 --> 03:18:33,720
VESICLES DURING THE ACTIVE

5465
03:18:33,720 --> 03:18:34,240
TRANSPORTATION.

5466
03:18:34,240 --> 03:18:37,520
SO WE GET THE IMPRESSION INDEED

5467
03:18:37,520 --> 03:18:38,960
OUR -- MAY MAKE IN VIVO

5468
03:18:38,960 --> 03:18:40,040
CAPILLARY WELL.

5469
03:18:40,040 --> 03:18:42,560
NOT ONLY WE CAN PERFUSE THOSE

5470
03:18:42,560 --> 03:18:44,520
MOLECULES BUT PERFUSE OTHER

5471
03:18:44,520 --> 03:18:46,280
PARTICLES, SO AS FROM HERE, RED

5472
03:18:46,280 --> 03:18:48,360
AND WE CAN ALSO USE SIMILAR

5473
03:18:48,360 --> 03:18:50,920
STRATEGY TO SEE THE PERMEABILITY

5474
03:18:50,920 --> 03:18:52,120
OF NANOPARTICLES TO COMPARE

5475
03:18:52,120 --> 03:19:00,600
WHETHER THEY ARE MODIFIED OR

5476
03:19:00,600 --> 03:19:01,480
WITHOUT MODIFICATION, CAN

5477
03:19:01,480 --> 03:19:06,080
REGULATE THE STRATEGIES TO

5478
03:19:06,080 --> 03:19:07,720
IMPROVE THE DRUG -- SO NEXT I'M

5479
03:19:07,720 --> 03:19:12,760
GOING TO TALK ABOUT THE BBB

5480
03:19:12,760 --> 03:19:14,120
SYSTEM, BLOOD BRAIN BARRIER,

5481
03:19:14,120 --> 03:19:15,720
QUITE A UNIQUE STRUCTURE, THEY

5482
03:19:15,720 --> 03:19:18,680
HAVE VERY TIGHT JUNCTION AND

5483
03:19:18,680 --> 03:19:23,160
ALSO THEY HAVE VERY HIGH

5484
03:19:23,160 --> 03:19:24,240
SELECTIVITY, ALL THE MOLECULES

5485
03:19:24,240 --> 03:19:26,000
CAN CUT THROUGH THE ENDOTHELIUM

5486
03:19:26,000 --> 03:19:29,520
AND INTO THE BRAIN SO YOU DON'T

5487
03:19:29,520 --> 03:19:31,080
WANT EVERYTHING GETTING -- THE

5488
03:19:31,080 --> 03:19:32,880
BRAIN TO MESS UP ANYTHING, SO

5489
03:19:32,880 --> 03:19:37,600
THEY HAVE SOME UNIQUE TRANSPORT

5490
03:19:37,600 --> 03:19:39,240
CHANNELS THAT HELP THE MOLECULES

5491
03:19:39,240 --> 03:19:39,600
TRANSPORTATION.

5492
03:19:39,600 --> 03:19:43,400
TO MIMIC SUCH -- STRUCTURE, THE

5493
03:19:43,400 --> 03:19:47,880
LAB ACTUALLY DEVELOPED A MODEL

5494
03:19:47,880 --> 03:19:50,400
USING -- ONE IS LIKE A HUMAN

5495
03:19:50,400 --> 03:19:52,800
DERIVED ENDOTHELIAL CELLS PAIRED

5496
03:19:52,800 --> 03:19:58,360
WITH THE BRAIN PERICYTES AND

5497
03:19:58,360 --> 03:20:00,000
ASTROCYTES, SO TWO DAYS THEY

5498
03:20:00,000 --> 03:20:03,160
FORM THE MICROVASCULAR NETWORKS,

5499
03:20:03,160 --> 03:20:09,640
SO WHAT WE FOUND IS -- CULTURE

5500
03:20:09,640 --> 03:20:11,800
CONDITIONS, THEY HAVE GOOD --

5501
03:20:11,800 --> 03:20:13,600
COMPARED TO THE MOUSE BRAIN

5502
03:20:13,600 --> 03:20:19,920
MEASURED IN VIVO.

5503
03:20:19,920 --> 03:20:24,400
SO -- STROMAL CELLS, THE

5504
03:20:24,400 --> 03:20:28,320
PERMEABILITY -- THIS TELLS US

5505
03:20:28,320 --> 03:20:29,880
TO -- WE NEED ALL THOSE STROMAL

5506
03:20:29,880 --> 03:20:30,320
CELLS.

5507
03:20:30,320 --> 03:20:33,280
SO NOT ONLY WE TEST THE

5508
03:20:33,280 --> 03:20:35,760
FUNCTION, WE ALSO TEST THE

5509
03:20:35,760 --> 03:20:37,960
TRANSCRIPTOME RESULTS OF USING

5510
03:20:37,960 --> 03:20:42,640
OUR MODELS, SO WE COMPARE THE 2D

5511
03:20:42,640 --> 03:20:49,040
AND 3D USING HUMAN BRAIN --

5512
03:20:49,040 --> 03:20:53,160
ENDOTHELIAL CELLS PAIRED WITH

5513
03:20:53,160 --> 03:20:54,600
PERICYTE AS MENTIONED.

5514
03:20:54,600 --> 03:20:57,760
SO THE RESULT 3D BETTER THAN 2D

5515
03:20:57,760 --> 03:21:00,280
AND ALSO WHEN WE HAVE

5516
03:21:00,280 --> 03:21:03,240
TRI-CULTURE, WE HAVE THE

5517
03:21:03,240 --> 03:21:05,120
PERICYTES OUTSIDE, THEN

5518
03:21:05,120 --> 03:21:06,400
ENDOTHELIAL CELLS EXPRESS HIGHER

5519
03:21:06,400 --> 03:21:08,360
LEVELS OF THOSE TIGHT JUNCTION

5520
03:21:08,360 --> 03:21:13,720
PROTEINS ANDS ARE      AND ALSOS

5521
03:21:13,720 --> 03:21:17,800
AS AN EXAMPLE THAT -- SYSTEM

5522
03:21:17,800 --> 03:21:20,680
MIMIC BETTER THE -- SYSTEM IN

5523
03:21:20,680 --> 03:21:24,560
VIVO.

5524
03:21:24,560 --> 03:21:27,960
SO NOW BESIDES PROFUSE MOLECULES

5525
03:21:27,960 --> 03:21:30,360
ACTUALLY PERFUSE TUMORS BETWEEN

5526
03:21:30,360 --> 03:21:30,880
CELLS AS WELL.

5527
03:21:30,880 --> 03:21:33,000
SO HERE ARE SOME EXAMPLES OF

5528
03:21:33,000 --> 03:21:37,120
PERFUSED TUMOR CELLS, THEY WERE

5529
03:21:37,120 --> 03:21:40,640
GREEN -- MICRO VASCULATURE, WE

5530
03:21:40,640 --> 03:21:44,160
CAN SEE HOW THE TUMOR CELLS

5531
03:21:44,160 --> 03:21:45,360
EXTRAVASATED.

5532
03:21:45,360 --> 03:21:47,800
ACTUALLY MAKE A HOLE FROM -- IN

5533
03:21:47,800 --> 03:21:53,160
THE VESSELS AND THEN IN THIS WAY

5534
03:21:53,160 --> 03:21:55,640
THEY'RE -- MULTIPLE TYPES OF

5535
03:21:55,640 --> 03:21:57,080
CELLS, TUMOR CELLS, NEUTROPHILS

5536
03:21:57,080 --> 03:21:58,960
TO SEE HOW THOSE TWO CELLS

5537
03:21:58,960 --> 03:22:01,360
INTERACT WITH EACH OTHER.

5538
03:22:01,360 --> 03:22:06,160
SO USING COMBINED THE BB SYSTEM

5539
03:22:06,160 --> 03:22:08,120
AND ALSO TUMOR CELL MODEL, WE

5540
03:22:08,120 --> 03:22:14,720
ALSO STUDIED -- THEY PREFER

5541
03:22:14,720 --> 03:22:16,680
TO -- FOUND METASTASIZE WHEN

5542
03:22:16,680 --> 03:22:19,400
COCULTURED WITH TUMOR AND

5543
03:22:19,400 --> 03:22:20,280
ASTROCYTES ALONE THEY CREATE

5544
03:22:20,280 --> 03:22:24,120
HIGHER LEVEL OF CCL2, AND THOSE

5545
03:22:24,120 --> 03:22:27,280
ATTRACT TUMOR CELLS EXPRESSING

5546
03:22:27,280 --> 03:22:31,440
CCR2 TO WE ACTUALLY USE

5547
03:22:31,440 --> 03:22:34,040
ANTI-CCL2 TO BLOCK THE SECRETION

5548
03:22:34,040 --> 03:22:39,960
AND ALSO -- FROM THE TUMOR SITE

5549
03:22:39,960 --> 03:22:42,800
AND -- WE CAN REDUCE

5550
03:22:42,800 --> 03:22:43,600
EXTRAVASATION OF THE TUMOR

5551
03:22:43,600 --> 03:22:43,920
CELLS.

5552
03:22:43,920 --> 03:22:45,120
SO THIS IS AN EXAMPLE OF HOW TO

5553
03:22:45,120 --> 03:22:47,720
USE OUR MODEL SYSTEM, OUR --

5554
03:22:47,720 --> 03:22:51,120
SYSTEM TO STUDY TUMORS IN

5555
03:22:51,120 --> 03:22:51,840
EXTRAVASATION.

5556
03:22:51,840 --> 03:22:54,520
WE ALSO DEVELOP SOME SOLID

5557
03:22:54,520 --> 03:22:58,240
TUMOR -- MODEL, SO SIMILAR LE WE

5558
03:22:58,240 --> 03:23:04,440
HAVE A THREE-CHANNEL DEVICE, THE

5559
03:23:04,440 --> 03:23:05,640
MISSION OF THE DEVICE IS

5560
03:23:05,640 --> 03:23:07,080
ACTUALLY LARGER SO IN THIS WAY,

5561
03:23:07,080 --> 03:23:09,840
WE CAN EMBED A LARGER TUMOR --

5562
03:23:09,840 --> 03:23:13,440
INTO    

5563
03:23:13,440 --> 03:23:15,720
SPHEROID INTO THE DEVICE SO WE

5564
03:23:15,720 --> 03:23:17,920
CAN ACTUALLY TEST THE

5565
03:23:17,920 --> 03:23:20,760
PERMEABILITY OF THE VESSELS AT A

5566
03:23:20,760 --> 03:23:23,560
DIFFERENT DISTANCE FROM THE

5567
03:23:23,560 --> 03:23:24,040
TUMOR.

5568
03:23:24,040 --> 03:23:25,560
THESE ARE CLOSE, THESE ARE FAR

5569
03:23:25,560 --> 03:23:26,000
AWAY FROM IT.

5570
03:23:26,000 --> 03:23:28,520
WE CAN ALSO USE THIS MODEL TO

5571
03:23:28,520 --> 03:23:32,160
SEE -- TO TEST DRUG

5572
03:23:32,160 --> 03:23:32,680
TRANSPORTATION.

5573
03:23:32,680 --> 03:23:36,840
OR WE CAN ALSO USE THIS

5574
03:23:36,840 --> 03:23:38,960
VASCULARIZED TUMOR MODEL TO TEST

5575
03:23:38,960 --> 03:23:46,680
FOR KA.-T-CELL       CAR-T-CELL.

5576
03:23:46,680 --> 03:23:48,320
WHITE COLOR, WE CAN ACTUALLY SEE

5577
03:23:48,320 --> 03:23:49,960
HOW THOSE T-CELLS INTERACT WITH

5578
03:23:49,960 --> 03:23:51,080
THE TUMOR CELLS, WHICH IS SHOWN

5579
03:23:51,080 --> 03:23:55,560
IN RED, AND EVENTUALLY THEY CAN

5580
03:23:55,560 --> 03:23:58,720
SCAN THE DEAD CELLS TO SEE

5581
03:23:58,720 --> 03:24:04,400
CAR-T-CELL KILLING -- T-CELL

5582
03:24:04,400 --> 03:24:05,960
RESPONSE.

5583
03:24:05,960 --> 03:24:07,560
SO OTHER DEVICES THAT WE

5584
03:24:07,560 --> 03:24:09,880
ACTUALLY STUDIED THE

5585
03:24:09,880 --> 03:24:10,960
ANGIOGENESIS OF THE BLOOD

5586
03:24:10,960 --> 03:24:12,920
VESSELS ACROSS THE POROUS

5587
03:24:12,920 --> 03:24:13,400
MEMBRANES.

5588
03:24:13,400 --> 03:24:19,840
SO THERE IS A -- ON THE LEFT

5589
03:24:19,840 --> 03:24:21,040
SIDE -- THE NETWORKS FOR

5590
03:24:21,040 --> 03:24:23,680
TREATING THE DEVICE WITH OTHER

5591
03:24:23,680 --> 03:24:24,920
CYTOKINES OF THOSE -- ON THE

5592
03:24:24,920 --> 03:24:29,560
LEFT SIDE, SO THOSE ENDOTHELIAL

5593
03:24:29,560 --> 03:24:30,400
CELLS -- ANGIOGENESIS THROUGH

5594
03:24:30,400 --> 03:24:33,600
THOSE POROUS MEMBRANES ACROSS --

5595
03:24:33,600 --> 03:24:35,240
SO IN THIS WAY JUST ONE EXAMPLE

5596
03:24:35,240 --> 03:24:40,200
TO SHOW YOU OTHER DEVICES FROM

5597
03:24:40,200 --> 03:24:42,800
THE LAB THAT CAN BE USED --

5598
03:24:42,800 --> 03:24:43,040
STUDIES.

5599
03:24:43,040 --> 03:24:48,800
WE ALSO HAVE ANGIOGENESIS USING

5600
03:24:48,800 --> 03:24:51,320
LYMPHATIC ENDOTHELIAL CELLS.

5601
03:24:51,320 --> 03:24:54,840
SO INSTEAD OF PUTTING THEM INTO

5602
03:24:54,840 --> 03:24:56,560
THE GEL CHANNEL AND THE MEDIA

5603
03:24:56,560 --> 03:24:57,920
CHANNEL ON THE LEFT AND ON THE

5604
03:24:57,920 --> 03:25:02,600
RIGHT SIDE WE'RE GOING TO ADD DI

5605
03:25:02,600 --> 03:25:05,200
FLOW WE CAN SEE HOW THOSE

5606
03:25:05,200 --> 03:25:07,760
LYMPHATIC ENDOTHELIAL CELLS

5607
03:25:07,760 --> 03:25:08,840
ANGIOGENESIS -- STIMULUS, THAT

5608
03:25:08,840 --> 03:25:11,800
MAY MAKE THIS RELEVANT FOR

5609
03:25:11,800 --> 03:25:14,640
INFECTING -- ANG GENESIS.

5610
03:25:14,640 --> 03:25:15,640
 ANGIOGENESIS.

5611
03:25:15,640 --> 03:25:18,880
WE ALSO DEVELOPED THIS MICRO

5612
03:25:18,880 --> 03:25:21,080
PUMP WE CALL A MICROHEART, SO WE

5613
03:25:21,080 --> 03:25:24,280
CAN CONNECT TO THE DEVICE,

5614
03:25:24,280 --> 03:25:25,040
IMMUNE CELLS, TUMOR CELLS, TO

5615
03:25:25,040 --> 03:25:35,400
SEE HOW THEY RESPOND.

5616
03:25:38,960 --> 03:25:39,560
VASCULARIZED ALZHEIMER'S DISEASE

5617
03:25:39,560 --> 03:25:40,640
MODEL.

5618
03:25:40,640 --> 03:25:42,480
SO I'M GOING TO TALK ABOUT THOSE

5619
03:25:42,480 --> 03:25:47,760
TWO ROBUST -- TO FORM

5620
03:25:47,760 --> 03:25:49,480
MICROVASCULAR NETWORKS AND

5621
03:25:49,480 --> 03:25:52,360
ALSO -- SPHRAT      -- STRATEGI.

5622
03:25:52,360 --> 03:25:56,200
SO FOR THE -- AND OTHER LABS

5623
03:25:56,200 --> 03:25:58,480
WHICH WE USE PRIMARY CELLS, AND

5624
03:25:58,480 --> 03:26:00,040
WE KNOW PRIMARY CELLS HAVE BATCH

5625
03:26:00,040 --> 03:26:01,240
TO BATCH VARIATIONS.

5626
03:26:01,240 --> 03:26:06,280
IN THESE STUDIES, THEY ACTUALLY

5627
03:26:06,280 --> 03:26:09,320
COMPARED DIFFERENT LUNG

5628
03:26:09,320 --> 03:26:11,960
FIBROBLAST, SAME HUMAN UMBILICAL

5629
03:26:11,960 --> 03:26:15,320
VEIN ENDOTHELIAL CELLS TO FORM

5630
03:26:15,320 --> 03:26:17,960
MICROVASCULAR NETWORKS.

5631
03:26:17,960 --> 03:26:20,680
 -- THEY ARE TOTALLY DIFFERENT.

5632
03:26:20,680 --> 03:26:25,840
SO THIS INDEED TELLS US THOSE

5633
03:26:25,840 --> 03:26:27,240
PRIMARY CELLS SIGNIFICANT AND

5634
03:26:27,240 --> 03:26:28,880
EVEN THOUGH YOU FIND A GOOD PAIR

5635
03:26:28,880 --> 03:26:32,160
OF STROMAL CELLS AND IND THEEL

5636
03:26:32,160 --> 03:26:33,600
YAL CELLS, THEY STILL HAVE -- IN

5637
03:26:33,600 --> 03:26:34,080
THEM.

5638
03:26:34,080 --> 03:26:41,480
SO WE TOOK ADVANTAGE OF -- USING

5639
03:26:41,480 --> 03:26:44,120
HTERT -- INTO THE ENDOTHELIAL

5640
03:26:44,120 --> 03:26:48,040
CELLS, FIBROBLASTS TO MAKE THEM

5641
03:26:48,040 --> 03:26:52,760
SIMILAR TO A CELL LINE -- THEY

5642
03:26:52,760 --> 03:26:54,600
CAN FORM MICROVASCULAR NETWORK

5643
03:26:54,600 --> 03:26:55,920
SIMILAR TO THE PRIMARY CELLS IN

5644
03:26:55,920 --> 03:26:57,760
TERMS OF THEIR MORPHOLOGY, AND

5645
03:26:57,760 --> 03:27:00,400
SINCE THEY ARE IMMORTGAGIZED, WE

5646
03:27:00,400 --> 03:27:01,680
CAN PASSAGE THEM OVER 20 TIMES,

5647
03:27:01,680 --> 03:27:04,880
THEY ARE STILL GOOD FOR MICRO

5648
03:27:04,880 --> 03:27:07,080
MICROVASCULAR NETWORK FORMATION,

5649
03:27:07,080 --> 03:27:10,920
NOT ONLY WE TRIED THIS IN HUMAN

5650
03:27:10,920 --> 03:27:13,520
ALSO -- DERMAL ENDOTHELIAL CELLS

5651
03:27:13,520 --> 03:27:17,000
TO MIMIC THE SKIN MODEL, SO ALL

5652
03:27:17,000 --> 03:27:19,520
THIS TELLS YOU -- THIS IS --

5653
03:27:19,520 --> 03:27:21,840
CELLS ARE GOOD SOURCES FOR

5654
03:27:21,840 --> 03:27:25,440
MICROVASCULAR NETWORK FORMATION.

5655
03:27:25,440 --> 03:27:27,280
AND ALSO THEY ARE SIMILAR TO A

5656
03:27:27,280 --> 03:27:29,600
CELL LINE SO IF THEY ARE VERY

5657
03:27:29,600 --> 03:27:35,560
EASY TO -- CRISPR TECHNIQUE AND

5658
03:27:35,560 --> 03:27:40,200
ALSO YOU CAN -- SHOWN HERE TO

5659
03:27:40,200 --> 03:27:42,400
SEE HOW THOSE MICRO VASCULATURE

5660
03:27:42,400 --> 03:27:44,920
RESPONDS TO THE TUMOR CELLS WHEN

5661
03:27:44,920 --> 03:27:45,800
THEY PERFUSE THEM TO THE

5662
03:27:45,800 --> 03:27:46,240
VESSELS.

5663
03:27:46,240 --> 03:27:49,160
WE CAN SIMILARLY TEST THE TUMOR

5664
03:27:49,160 --> 03:27:52,360
CELL EXTRAVASATIONS, AND ALSO

5665
03:27:52,360 --> 03:27:55,200
USE THOSE -- CELLS FOR THE SOLID

5666
03:27:55,200 --> 03:27:59,000
TUMOR MODELS AS I JUST

5667
03:27:59,000 --> 03:28:02,520
INTRODUCED PREVIOUS.

5668
03:28:02,520 --> 03:28:09,880
SO ANOTHER CHALLENGE WHEN WE TRY

5669
03:28:09,880 --> 03:28:13,480
TO GENERATE MICRO VASCULATURE

5670
03:28:13,480 --> 03:28:14,680
IS -- OUR LAB AND OTHER

5671
03:28:14,680 --> 03:28:16,320
PUBLISHED DATA FROM OTHER LABS

5672
03:28:16,320 --> 03:28:18,280
THAT MOST OF THE PERFUSIBLE

5673
03:28:18,280 --> 03:28:19,720
NETWORK, THEY TEND TO HAVE

5674
03:28:19,720 --> 03:28:21,880
LARGER DIAMETER VESSELS.

5675
03:28:21,880 --> 03:28:23,640
SO BUT COMPARED TO THE ONES IN

5676
03:28:23,640 --> 03:28:27,160
VIVO, THOSE VESSELS -- ACTUALLY

5677
03:28:27,160 --> 03:28:30,600
THEY ARE VERY SMALL.

5678
03:28:30,600 --> 03:28:33,040
 -- AS SHOWN HERE THEY CAN BE --

5679
03:28:33,040 --> 03:28:37,280
BUT HOW TO -- ENGINEERING THOSE

5680
03:28:37,280 --> 03:28:40,680
SMALL VESSELS THEY ARE

5681
03:28:40,680 --> 03:28:41,800
PERFUSABLE IS CHALLENGING.

5682
03:28:41,800 --> 03:28:45,480
SO FROM ALL THE STUDY AND

5683
03:28:45,480 --> 03:28:47,680
ALSO -- STUDIES FROM OTHERS WE

5684
03:28:47,680 --> 03:28:49,880
FOUND THAT MANIPULATING THE

5685
03:28:49,880 --> 03:28:50,760
ENDOTHELIAL CELL CONCENTRATION

5686
03:28:50,760 --> 03:28:53,720
WE CAN ACTUALLY GET DIFFERENT

5687
03:28:53,720 --> 03:28:54,800
MORPHOLOGY OF THE VESSELS.

5688
03:28:54,800 --> 03:28:56,560
SO FOR EXAMPLE IF WE USE A

5689
03:28:56,560 --> 03:28:59,960
HIGHER CONCENTRATION OF

5690
03:28:59,960 --> 03:29:01,920
ENDOTHELIAL CELLS -- THEY ARE

5691
03:29:01,920 --> 03:29:02,480
PERFUSIBLE.

5692
03:29:02,480 --> 03:29:04,840
BUT IF WE USE A LOWER -- THEY

5693
03:29:04,840 --> 03:29:09,440
ACTUALLY CAN FORM THE VESSELS

5694
03:29:09,440 --> 03:29:10,320
VERY SMALL.

5695
03:29:10,320 --> 03:29:14,160
MOST PERFUSABLE -- THEY ARE

5696
03:29:14,160 --> 03:29:16,360
PERFUSE ABLE BECAUSE THEY HAVE

5697
03:29:16,360 --> 03:29:18,000
LARGE DIAMETER OPENINGS

5698
03:29:18,000 --> 03:29:21,080
CONNECTING TO THE MEDIA CHANNEL

5699
03:29:21,080 --> 03:29:23,920
TO ALLOW DEXTRAN TO FLOW THROUGH

5700
03:29:23,920 --> 03:29:25,200
THE NETWORKS.

5701
03:29:25,200 --> 03:29:26,840
THESE OPENINGS, THEY ARE CLOSED,

5702
03:29:26,840 --> 03:29:29,280
SO HOW ABOUT WE COMBINE THESE

5703
03:29:29,280 --> 03:29:30,440
TWO CONDITIONS SO WE CAN FORM A

5704
03:29:30,440 --> 03:29:32,440
LARGER DIAMETER VESSELS AT THE

5705
03:29:32,440 --> 03:29:36,400
REGION BETWEEN THE MICRO -- TO

5706
03:29:36,400 --> 03:29:38,360
COME BACK TO THE MEDIA CHANNEL

5707
03:29:38,360 --> 03:29:40,080
BUT AT THE CENTER WE HAVE VERY

5708
03:29:40,080 --> 03:29:41,640
SMALL, TINY VESSELS.

5709
03:29:41,640 --> 03:29:45,120
SO WE DEVELOPED -- FIRST WE SEE

5710
03:29:45,120 --> 03:29:48,040
THE HIGHER DENSITY OF

5711
03:29:48,040 --> 03:29:49,160
ENDOTHELIAL CELLS INTO THE

5712
03:29:49,160 --> 03:29:51,680
DEVICE AND HAS CAREFULLY

5713
03:29:51,680 --> 03:29:53,960
ASPIRATED THE -- BECAUSE OF THE

5714
03:29:53,960 --> 03:29:56,720
SURFACE TENSION PROVIDED BY THE

5715
03:29:56,720 --> 03:29:58,640
MICRO POST, THOSE HIGHER DENSITY

5716
03:29:58,640 --> 03:30:01,720
OF THE ENDOTHELIAL CELLS -- IN

5717
03:30:01,720 --> 03:30:02,760
THIS REGION AND THEY ARE GOING

5718
03:30:02,760 --> 03:30:09,520
TO FORM A LARGER DIAMETER VESSEL

5719
03:30:09,520 --> 03:30:10,720
OPENINGS.

5720
03:30:10,720 --> 03:30:12,800
LOWER -- WITH FIBROBLASTS INTO

5721
03:30:12,800 --> 03:30:14,560
THE CHANNEL AGAIN, SO IN THE

5722
03:30:14,560 --> 03:30:16,640
CENTER THEY HAVE ENDOTHELIAL

5723
03:30:16,640 --> 03:30:18,280
CELL -- THEY'RE GOING TO FORM A

5724
03:30:18,280 --> 03:30:19,680
VERY SMALL DIAMETER VESSELS, SO

5725
03:30:19,680 --> 03:30:23,960
IN THIS WAY, WE CAN GENERATE

5726
03:30:23,960 --> 03:30:26,040
MICRO VASCULATURE THAT HAS VERY

5727
03:30:26,040 --> 03:30:28,000
TINY SMALL DIAMETERS IN THE

5728
03:30:28,000 --> 03:30:29,320
CENTER CONNECTING TO A LARGER

5729
03:30:29,320 --> 03:30:33,040
OPENINGS ON THE SIDE.

5730
03:30:33,040 --> 03:30:37,960
AND I JUST SHOW VERY CROWDED

5731
03:30:37,960 --> 03:30:40,160
IMAGE HERE, THIS IS ACTUALLY --

5732
03:30:40,160 --> 03:30:44,960
IN MY DEVICE AND THOSE IMAGES

5733
03:30:44,960 --> 03:30:47,440
ARE -- AND ALL OF THOSE --

5734
03:30:47,440 --> 03:30:48,560
PERFUSIBLE AND WITH LARGER

5735
03:30:48,560 --> 03:30:49,880
OPENINGS ON THE SIDE AND SMALLER

5736
03:30:49,880 --> 03:30:50,760
VESSELS IN THE CENTER.

5737
03:30:50,760 --> 03:30:53,240
SO JUST TO GIVE YOU THE

5738
03:30:53,240 --> 03:30:54,880
IMPRESSION THESE TWO METHODS

5739
03:30:54,880 --> 03:30:56,240
REALLY ROBUST AND HOPEFULLY CAN

5740
03:30:56,240 --> 03:31:01,800
BE CONVINCING FOR THE COMMUNITY.

5741
03:31:01,800 --> 03:31:06,320
THIS TWO EPITHELIUM METHOD --

5742
03:31:06,320 --> 03:31:09,120
PATIENT DERIVED CELLS ORDER MALL

5743
03:31:09,120 --> 03:31:11,320
FIBROBLASTS TO MAKE THE SKIN

5744
03:31:11,320 --> 03:31:17,640
MODEL OR BRAIN -- OR USING --

5745
03:31:17,640 --> 03:31:19,080
ENDOTHELIAL CELLS.

5746
03:31:19,080 --> 03:31:26,840
SO AS A SUMMARY, -- ALSO I SHOW

5747
03:31:26,840 --> 03:31:30,240
USING MODELS COMPARED WITH OTHER

5748
03:31:30,240 --> 03:31:32,280
TECHNIQUES AND TO SEE HOW IT CAN

5749
03:31:32,280 --> 03:31:35,280
BE USEFUL -- NEUROLOGICAL

5750
03:31:35,280 --> 03:31:39,520
DISEASE OR CANCER STUDY, LAST I

5751
03:31:39,520 --> 03:31:41,800
SHOWED TWO STRATEGIES WHY TO

5752
03:31:41,800 --> 03:31:44,120
USE -- AS CELL SOURCES AND THEN

5753
03:31:44,120 --> 03:31:45,640
INTRODUCE THIS TWO-STEP METHOD

5754
03:31:45,640 --> 03:31:47,280
TO GENERATE THE VERY SMALL

5755
03:31:47,280 --> 03:31:51,800
VESSELS IN THE CENTER AND

5756
03:31:51,800 --> 03:31:52,280
THEN --.

5757
03:31:52,280 --> 03:31:56,640
LAST I WOULD LIKE TO THANK MY

5758
03:31:56,640 --> 03:32:00,040
SUPERVISORS, COLLABORATORS,

5759
03:32:00,040 --> 03:32:00,800
FUNDINGS.

5760
03:32:00,800 --> 03:32:02,120
AND THANK YOU VERY MUCH FOR YOUR

5761
03:32:02,120 --> 03:32:03,240
ATTENTION.

5762
03:32:03,240 --> 03:32:04,960
>> THANKS SO MUCH, JASON.

5763
03:32:04,960 --> 03:32:06,160
THIS WAS BEAUTIFUL WORK.

5764
03:32:06,160 --> 03:32:09,560
THANKS SO MUCH FOR SHARING.

5765
03:32:09,560 --> 03:32:11,120
WE'RE GOING TO KEEP GOING, AND

5766
03:32:11,120 --> 03:32:14,600
AGAIN IF YOU HAVE ANY QUESTIONS,

5767
03:32:14,600 --> 03:32:21,360
POP THEM IN THE Q & A BOX.

5768
03:32:21,360 --> 03:32:22,960
LAST SPEAKER, NOT THE LEAST, IT

5769
03:32:22,960 --> 03:32:25,400
IS MY PLEASURE TO INTRODUCE

5770
03:32:25,400 --> 03:32:29,600
DR. JEFF BORNENSTEIN, GROUP

5771
03:32:29,600 --> 03:32:34,720
LEADER FOR SYNTHETIC BIOLOGIES

5772
03:32:34,720 --> 03:32:36,680
AND BIOINSTRUMENTATION AND

5773
03:32:36,680 --> 03:32:41,600
LABORATORY FELLOW AT DRAPER IN

5774
03:32:41,600 --> 03:32:42,360
CAMBRIDGE WHERE HE LEADS

5775
03:32:42,360 --> 03:32:43,600
PROGRAMS IN ORGAN AND DISEASE

5776
03:32:43,600 --> 03:32:46,720
MODELS FOR DRUG DISCOVERY AND

5777
03:32:46,720 --> 03:32:48,600
SAFETY TESTING, ORGAN ASSIST

5778
03:32:48,600 --> 03:32:49,720
DEVICES AND DRUG DELIVERY

5779
03:32:49,720 --> 03:32:50,040
SYSTEMS.

5780
03:32:50,040 --> 03:32:51,600
JEFF IS MEMBER OF THE NATIONAL

5781
03:32:51,600 --> 03:32:53,520
ACADEMY OF INVENTORS AND HE'S

5782
03:32:53,520 --> 03:32:55,400
BEEN DOING A LOT OF WORK WITH

5783
03:32:55,400 --> 03:32:58,120
APPLICATIONS OF MICROSYSTEMS AND

5784
03:32:58,120 --> 03:33:00,080
MICRO FABRICATION TECHNOLOGIES

5785
03:33:00,080 --> 03:33:00,840
TOWARDS MEDICINE.

5786
03:33:00,840 --> 03:33:07,760
JEFF, THE FLOOR IS YOURS.

5787
03:33:07,760 --> 03:33:18,120
>> THANK YOU, MARC.

5788
03:33:20,360 --> 03:33:21,120
IS THAT SHARING PROPERLY?

5789
03:33:21,120 --> 03:33:22,040
>> YES.

5790
03:33:22,040 --> 03:33:23,160
>> GREAT.

5791
03:33:23,160 --> 03:33:27,320
THANK YOU SO MUCH, MARC, FOR THE

5792
03:33:27,320 --> 03:33:28,400
KIND INTRODUCTION, AND THANK

5793
03:33:28,400 --> 03:33:29,720
YOU, SARINE AND THE ORGANIZERS.

5794
03:33:29,720 --> 03:33:30,800
IT'S A PLEASURE TO BE HERE AS

5795
03:33:30,800 --> 03:33:32,800
PART OF THIS GREAT PANEL TODAY.

5796
03:33:32,800 --> 03:33:34,400
I'D LIKE TO TALK TO YOU ABOUT

5797
03:33:34,400 --> 03:33:36,840
OUR WORK IN DRAPER IN ORGAN ON

5798
03:33:36,840 --> 03:33:38,480
CHIP PLATFORMS TOWARDS THREE

5799
03:33:38,480 --> 03:33:39,160
DIMENSIONS, REALLY.

5800
03:33:39,160 --> 03:33:40,360
ONE OF THEM AS HAS BEEN TALKED

5801
03:33:40,360 --> 03:33:42,520
ABOUT EARLIER IS THE HIGHER

5802
03:33:42,520 --> 03:33:43,280
THROUGHPUT ASPECT.

5803
03:33:43,280 --> 03:33:45,600
ANOTHER IS WORKING IN HIGH

5804
03:33:45,600 --> 03:33:48,080
CONTAINMENT, PARTICULARLY ACUTE

5805
03:33:48,080 --> 03:33:51,720
NEED AND SITUATION WITH REGARD

5806
03:33:51,720 --> 03:33:52,800
TO COVID-19 AND MANY OF THE

5807
03:33:52,800 --> 03:33:54,000
OTHER HIGH PRIORITY PATHOGENS

5808
03:33:54,000 --> 03:33:55,440
THAT THE GOVERNMENT IS

5809
03:33:55,440 --> 03:33:56,960
INTERESTED IN IN PURSUING

5810
03:33:56,960 --> 03:34:01,120
MEDICAL COUNTERMEASURES FOR,

5811
03:34:01,120 --> 03:34:02,640
THEN REALLY ANOTHER EXCITING

5812
03:34:02,640 --> 03:34:03,840
DIMENSION, AND THAT'S

5813
03:34:03,840 --> 03:34:05,480
PERSONALIZED MEDICINE, WHERE WE

5814
03:34:05,480 --> 03:34:06,680
CAN OBTAIN CELLS FROM PATIENT

5815
03:34:06,680 --> 03:34:07,800
POPULATIONS AND UNDERSTAND HOW

5816
03:34:07,800 --> 03:34:09,320
THESE INFECTIOUS DISEASES AND

5817
03:34:09,320 --> 03:34:12,920
POTENTIAL TREATMENTS WORK IN

5818
03:34:12,920 --> 03:34:13,840
PARTICULAR PATIENT DEMOGRAPHICS

5819
03:34:13,840 --> 03:34:16,440
AND POPULATIONS.

5820
03:34:16,440 --> 03:34:17,520
SO WITH THAT, JUST A LITTLE BIT

5821
03:34:17,520 --> 03:34:19,840
OF BACKGROUND ON THE PREDICT

5822
03:34:19,840 --> 03:34:20,480
96 TECHNOLOGY.

5823
03:34:20,480 --> 03:34:23,240
AND SO PREDICT 96 IS REALLY

5824
03:34:23,240 --> 03:34:25,240
BUILT ON A PLATFORM, ON A BACK

5825
03:34:25,240 --> 03:34:31,200
PLANE OF A STANDARD MICRO    MIR

5826
03:34:31,200 --> 03:34:32,280
PLATE.

5827
03:34:32,280 --> 03:34:33,720
THERE ARE FOUR WELLS FOR EACH

5828
03:34:33,720 --> 03:34:34,560
DEVICE.

5829
03:34:34,560 --> 03:34:39,080
SO ESSENTIALLY 96 DEVICE SYSTEM

5830
03:34:39,080 --> 03:34:42,680
BUILT ON TO THIS 3D PLATE.

5831
03:34:42,680 --> 03:34:44,240
THERE'S AN APICAL CHANNEL AND A

5832
03:34:44,240 --> 03:34:46,040
BASAL CHANNEL WITH AN

5833
03:34:46,040 --> 03:34:46,960
OVERLAPPING REGION THAT'S

5834
03:34:46,960 --> 03:34:49,800
SEPARATED BY A SEMI POROUS

5835
03:34:49,800 --> 03:34:50,880
MEMBRANE, AND THERE IS FLOW

5836
03:34:50,880 --> 03:34:52,760
THROUGH THE APICAL CHANNEL AND

5837
03:34:52,760 --> 03:34:54,720
THROUGH THE BASAL CHANNEL AND

5838
03:34:54,720 --> 03:34:56,120
CELLS CAN BE CULTURED ON ONE OR

5839
03:34:56,120 --> 03:35:01,600
BOTH SIDES OF THIS MEMBRANE.

5840
03:35:01,600 --> 03:35:05,880
SO THERE'S FOUR PORTS, TWO

5841
03:35:05,880 --> 03:35:07,960
INLETS, TWO OUTLETS, ARRANGED ON

5842
03:35:07,960 --> 03:35:08,720
THE 96 DEVICE SYSTEM.

5843
03:35:08,720 --> 03:35:11,880
WE CAN EITHER WORK WITH CULTURED

5844
03:35:11,880 --> 03:35:13,200
TISSUES AS SHOWN HERE WITH

5845
03:35:13,200 --> 03:35:14,400
MATRIX MATERIALS ON THE MEMBRANE

5846
03:35:14,400 --> 03:35:15,840
AND VARIOUS CELL TYPES, AS MANY

5847
03:35:15,840 --> 03:35:17,360
AS FOUR OR FIVE CELL TYPES, OR

5848
03:35:17,360 --> 03:35:19,440
WE CAN WORK IN OTHER

5849
03:35:19,440 --> 03:35:21,400
CONFIGURATIONS WITH ORGANOIDS OR

5850
03:35:21,400 --> 03:35:24,120
TUMORS THAT'S BEEN DISCUSSED

5851
03:35:24,120 --> 03:35:24,560
PREVIOUSLY.

5852
03:35:24,560 --> 03:35:25,880
I'D LIKE TO TOUCH ON SOME OF THE

5853
03:35:25,880 --> 03:35:27,880
POINTS THAT THIS PANEL HAS

5854
03:35:27,880 --> 03:35:28,720
TALKED ABOUT THROUGHOUT THE

5855
03:35:28,720 --> 03:35:30,080
COURSE OF THE DAY, AND REALLY

5856
03:35:30,080 --> 03:35:31,360
ONE OF THOSE IS SCALE, AND I

5857
03:35:31,360 --> 03:35:32,720
THINK THAT WAS AN IMPORTANT

5858
03:35:32,720 --> 03:35:34,200
POINT MADE EARLIER.

5859
03:35:34,200 --> 03:35:35,720
SO THE DESIRE HERE IS TO BE ABLE

5860
03:35:35,720 --> 03:35:37,360
TO STUDY MANY CONDITIONS AND

5861
03:35:37,360 --> 03:35:39,960
LOOK AT STATISTICAL REPLICATES

5862
03:35:39,960 --> 03:35:41,200
ON A SINGLE PLATE TO TRY TO

5863
03:35:41,200 --> 03:35:42,280
REDUCE SOME OF THE VARIABILITY

5864
03:35:42,280 --> 03:35:43,960
AND INCREASE THE THROUGHPUT OF

5865
03:35:43,960 --> 03:35:45,800
THESE SYSTEMS, AND SO THAT'S THE

5866
03:35:45,800 --> 03:35:47,000
GOAL HERE, AND I THINK ANOTHER

5867
03:35:47,000 --> 03:35:49,360
IS TO MAINTAIN THE FIDELITY OF

5868
03:35:49,360 --> 03:35:53,440
THE SYSTEM AND WE DO THAT WITH

5869
03:35:53,440 --> 03:35:55,320
SENSING AND FLUIDICS INTEGRATED

5870
03:35:55,320 --> 03:35:55,880
INTO THESE PLATES.

5871
03:35:55,880 --> 03:35:58,160
SO THERE'S A CLAMSHELL HERE THAT

5872
03:35:58,160 --> 03:36:00,680
PROVIDES A PUMPING TO EACH OF

5873
03:36:00,680 --> 03:36:02,880
THESE 96 DEVICES SO THE APICAL

5874
03:36:02,880 --> 03:36:04,720
CHAMBER AND THE BASAL CHAMBER OF

5875
03:36:04,720 --> 03:36:06,920
EACH OF THE 96 DEVICES IS

5876
03:36:06,920 --> 03:36:10,400
ADDRESSED SEPARATELY AND

5877
03:36:10,400 --> 03:36:11,080
INDEPENDENTLY BY THESE PUMPS

5878
03:36:11,080 --> 03:36:13,040
THAT ARE INTRODUCED FROM AN

5879
03:36:13,040 --> 03:36:14,000
OVERLYING CLAM SHELL STRUCTURE,

5880
03:36:14,000 --> 03:36:15,560
AND THEN AS WE'LL SHOW ON THE

5881
03:36:15,560 --> 03:36:17,520
NEXT SLIDE, THERE ARE READOUTS

5882
03:36:17,520 --> 03:36:17,720
HERE.

5883
03:36:17,720 --> 03:36:19,160
AND I THINK THE KEY REALLY WITH

5884
03:36:19,160 --> 03:36:21,320
THE THROUGHPUT IS NOT ONLY JUST

5885
03:36:21,320 --> 03:36:23,080
HOW MANY CONDITIONS ON A PLATE,

5886
03:36:23,080 --> 03:36:24,960
BUT HOW MANY PLATES CAN FIT INTO

5887
03:36:24,960 --> 03:36:32,160
AN INCUBATOR AND SO WE CAN SEE

5888
03:36:32,160 --> 03:36:37,440
WE'RE UPWARDS OF -- ONE OF THE

5889
03:36:37,440 --> 03:36:39,160
KEYS TO THE TECHNOLOGY IS TO BE

5890
03:36:39,160 --> 03:36:42,560
ABLE TO USE IT APPLYING STANDARD

5891
03:36:42,560 --> 03:36:44,560
TOOLS AND STRUCTURES AND IN

5892
03:36:44,560 --> 03:36:46,160
TALKING WITH THE PHARMACEUTICAL

5893
03:36:46,160 --> 03:36:48,040
LABORATORIES, THINK THE ISSUE OF

5894
03:36:48,040 --> 03:36:48,920
MAINTAINING THE FIDELITY OF

5895
03:36:48,920 --> 03:36:50,880
THESE MODELS WHILE ACHIEVING

5896
03:36:50,880 --> 03:36:51,760
HIGH-THROUGHPUT IS REALLY

5897
03:36:51,760 --> 03:36:52,080
CRITICAL.

5898
03:36:52,080 --> 03:36:55,920
ONE OF THE OTHER POINTS WE HEARD

5899
03:36:55,920 --> 03:37:00,240
EARLIER WAS THAT SOME OF THE

5900
03:37:00,240 --> 03:37:05,360
IMMORTALIZED SUS TEMS ARE   SYSE

5901
03:37:05,360 --> 03:37:06,200
LACKING -- I THINK THE OTHER

5902
03:37:06,200 --> 03:37:07,080
SIDE OF THAT CHALLENGE, THOUGH,

5903
03:37:07,080 --> 03:37:09,920
IS THAT SYSTEMS LIKE VERO

5904
03:37:09,920 --> 03:37:12,120
E6 PRESENT KIND OF A CHALLENGE

5905
03:37:12,120 --> 03:37:14,320
FROM THE ORGAN ON A CHIP

5906
03:37:14,320 --> 03:37:15,520
STANDPOINT BECAUSE OF THEIR

5907
03:37:15,520 --> 03:37:17,160
ROBUSTNESS AND STATISTICAL POWER

5908
03:37:17,160 --> 03:37:18,720
AND THROUGHPUT, EVEN THOUGH THEY

5909
03:37:18,720 --> 03:37:23,920
LACK IF DEALT AND        FIDELIE

5910
03:37:23,920 --> 03:37:24,600
POWER IN SOME CASES.

5911
03:37:24,600 --> 03:37:26,800
SO I THINK THE CHALLENGE IS TO

5912
03:37:26,800 --> 03:37:28,200
ACHIEVE HIGHER FIDELITY BUT TO

5913
03:37:28,200 --> 03:37:29,520
MAINTAIN THE THROUGHPUT,

5914
03:37:29,520 --> 03:37:30,840
USABILITY AND TO SUPPORT THE

5915
03:37:30,840 --> 03:37:32,200
WORKFLOW IN THE PHARMACEUTICAL

5916
03:37:32,200 --> 03:37:34,880
INDUSTRY WITH AN ORGAN ON A CHIP

5917
03:37:34,880 --> 03:37:35,200
SYSTEM.

5918
03:37:35,200 --> 03:37:36,720
SO YOU CAN SEE WE BUILT IN NOT

5919
03:37:36,720 --> 03:37:38,680
ONLY THE PUMPS BUT THE

5920
03:37:38,680 --> 03:37:40,760
INTEGRATED BARRIER FUNCTION AND

5921
03:37:40,760 --> 03:37:42,880
CURRENTLY WITH BARDA WORKING ON

5922
03:37:42,880 --> 03:37:44,080
CHEMICAL SENATOR INTEGRATION AS

5923
03:37:44,080 --> 03:37:44,280
WELL.

5924
03:37:44,280 --> 03:37:47,800
ONE OF                   SENSORS

5925
03:37:47,800 --> 03:37:48,280
WELL.

5926
03:37:48,280 --> 03:37:49,560
ONE OF THE PROBLEMS WITH

5927
03:37:49,560 --> 03:37:51,360
TRANSWELL SYSTEMS IS THAT THE

5928
03:37:51,360 --> 03:37:52,800
MEMBRANE IS TYPICALLY NOT FLAT

5929
03:37:52,800 --> 03:37:56,760
AND THE SYSTEMS MUST BE REMOVED

5930
03:37:56,760 --> 03:38:02,320
MECHANICALLY IN ORDER TO DO

5931
03:38:02,320 --> 03:38:06,040
BIRESOLUTION, HERE WE HAVE MUCH

5932
03:38:06,040 --> 03:38:08,440
SMALLER MEDIA VOLUME, LESS USE

5933
03:38:08,440 --> 03:38:10,200
OF REAGENTS IN DRUGS AND

5934
03:38:10,200 --> 03:38:11,960
COMPATIBILITY WITH IN SITU HIGH

5935
03:38:11,960 --> 03:38:12,720
CONTENT IMAGING.

5936
03:38:12,720 --> 03:38:14,360
SO ALL OF THOSE FEATURES COME

5937
03:38:14,360 --> 03:38:16,000
TOGETHER IN THE

5938
03:38:16,000 --> 03:38:16,640
PREDICT96 SYSTEM.

5939
03:38:16,640 --> 03:38:18,720
IF WE THINK ABOUT THE DIFFERENT

5940
03:38:18,720 --> 03:38:20,160
ORGAN MODEL, WE'VE WORKED IN

5941
03:38:20,160 --> 03:38:21,480
MANY DIFFERENT ORGAN MODELS AS

5942
03:38:21,480 --> 03:38:23,000
MANY OF THE OTHER SPEAKERS HAVE

5943
03:38:23,000 --> 03:38:25,080
TALKED ABOUT TODAY, THE BLOOD

5944
03:38:25,080 --> 03:38:27,160
BRAIN BARRIER WORK WE'RE DOING,

5945
03:38:27,160 --> 03:38:29,240
WE'RE WORKING AND HAVE WORKED

5946
03:38:29,240 --> 03:38:30,320
WITH PHARMACEUTICAL COMPANIES ON

5947
03:38:30,320 --> 03:38:33,600
MANY OF THESE MODEL, THE

5948
03:38:33,600 --> 03:38:35,160
LIVER/KIDNEY VASCULAR SYSTEM,

5949
03:38:35,160 --> 03:38:36,240
THE ONE WE'LL FOCUS ON TODAY IS

5950
03:38:36,240 --> 03:38:41,600
THE AIRWAY FOR THE RESPIRATORY

5951
03:38:41,600 --> 03:38:42,240
DISEASE APPLICATION.

5952
03:38:42,240 --> 03:38:44,000
MANY ARE PUBLICLY ACKNOWLEDGED

5953
03:38:44,000 --> 03:38:46,720
COLLABORATIONS WITH COMPANIES

5954
03:38:46,720 --> 03:38:49,720
LIKE COLGATE-PAL MO LIVE,

5955
03:38:49,720 --> 03:38:50,240
BRISTOL-MYERS SQUIBB.

5956
03:38:50,240 --> 03:38:51,560
SOME ARE NOT PUBLICLY

5957
03:38:51,560 --> 03:38:52,520
ACKNOWLEDGED BUT MANY OF THE TOP

5958
03:38:52,520 --> 03:38:53,720
PHARMA COMPANIES.

5959
03:38:53,720 --> 03:38:55,040
THEN THE ONE WE'LL TALK A LITTLE

5960
03:38:55,040 --> 03:38:58,760
MORE ABOUT HERE IS THE PROGRAM

5961
03:38:58,760 --> 03:39:01,280
LOOKING AT INFLUENZA, LOOKING AT

5962
03:39:01,280 --> 03:39:02,800
MEDICAL COUNTERMEASURES FROM THE

5963
03:39:02,800 --> 03:39:05,000
EMERGING FIELD OF PROGRAMMABLE

5964
03:39:05,000 --> 03:39:05,880
GENE MODULATORS.

5965
03:39:05,880 --> 03:39:07,080
THAT'S A PROGRAM WE'VE BEEN

5966
03:39:07,080 --> 03:39:08,040
INVOLVED WITH THAT'S HELPED

5967
03:39:08,040 --> 03:39:10,360
SUPPORT THE DEVELOPMENT OF THE

5968
03:39:10,360 --> 03:39:11,560
AIRWAY MODEL.

5969
03:39:11,560 --> 03:39:13,320
SO HERE'S A CLOSER LOOK AT THAT

5970
03:39:13,320 --> 03:39:15,280
AIRWAY MODEL, AND AGAIN, IT IS

5971
03:39:15,280 --> 03:39:21,480
THIS PREDICT 96 PLATFORM WITH 9L

5972
03:39:21,480 --> 03:39:22,520
PLANE.

5973
03:39:22,520 --> 03:39:24,040
THE ONLY DIFFERENCE IS THE

5974
03:39:24,040 --> 03:39:25,480
APICAL CHAMBER DOES NOT HAVE

5975
03:39:25,480 --> 03:39:26,680
PUMPING OR FLUID.

5976
03:39:26,680 --> 03:39:28,640
IT'S AT AN AIR-LIQUID INTERFACE

5977
03:39:28,640 --> 03:39:31,040
SO WE'RE PUMPING THE BASAL

5978
03:39:31,040 --> 03:39:32,560
CHAMBER WHICH SUPPORTS EXCELLENT

5979
03:39:32,560 --> 03:39:33,680
TISSUE DEVELOPMENT OVER THE

5980
03:39:33,680 --> 03:39:35,320
COURSE OF ROUGHLY 21 DAYS WITH

5981
03:39:35,320 --> 03:39:38,160
HIGH BARRIER FUNCTION, MUCOUS

5982
03:39:38,160 --> 03:39:39,400
FORMATION, CILIARY BEADING AND

5983
03:39:39,400 --> 03:39:43,400
MANY OF           BEATING, MANY

5984
03:39:43,400 --> 03:39:44,600
OF THE CELL TYPES PRESENT THAT

5985
03:39:44,600 --> 03:39:46,240
ARE CRITICAL, GOBLET CELLS AND

5986
03:39:46,240 --> 03:39:47,560
OTHER CELLS, THE CLUB CELLS, SO

5987
03:39:47,560 --> 03:39:49,600
WE FORMED THIS TISSUE, THIS IS A

5988
03:39:49,600 --> 03:39:52,040
SIDE VIEW OF IT, IN A SCHEMATIC

5989
03:39:52,040 --> 03:39:54,000
FORM AND THEN A HIGH RESOLUTION

5990
03:39:54,000 --> 03:39:57,920
IMAGING AND WE CAN SEE THE

5991
03:39:57,920 --> 03:39:58,920
PSEUDOSTRATIFIED EPITHELIUM

5992
03:39:58,920 --> 03:39:59,800
THAT'S ESTABLISHED IN THIS

5993
03:39:59,800 --> 03:40:00,480
SYSTEM.

5994
03:40:00,480 --> 03:40:02,200
SO THIS IS PUBLISHED IN

5995
03:40:02,200 --> 03:40:03,160
SCIENTIFIC REPORTS, THE LEADER

5996
03:40:03,160 --> 03:40:06,560
OF THIS PROGRAM IS ASHLEY GARD,

5997
03:40:06,560 --> 03:40:08,000
WHO I WOULD LIKE TO ACKNOWLEDGE

5998
03:40:08,000 --> 03:40:10,080
HERE FROM OUR DRAPER TEAM.

5999
03:40:10,080 --> 03:40:11,560
ONE OF THE THINGS I MENTIONED AT

6000
03:40:11,560 --> 03:40:13,600
THE BEGINNING IS GETTING CELLS

6001
03:40:13,600 --> 03:40:15,880
FROM PATIENT DEMOGRAPHICS.

6002
03:40:15,880 --> 03:40:17,280
SO AN EXCITING ASPECT HERE THAT

6003
03:40:17,280 --> 03:40:19,480
WE'VE BEEN PURSUING FIRST WITH

6004
03:40:19,480 --> 03:40:22,240
DARPA FUNDING AND ALSO WITH OUR

6005
03:40:22,240 --> 03:40:23,280
SARS-COV-2 RESEARCH IS OBTAINING

6006
03:40:23,280 --> 03:40:24,640
OF CELLS FROM LIVING DONORS.

6007
03:40:24,640 --> 03:40:26,080
THIS IS WORK IN COLLABORATION

6008
03:40:26,080 --> 03:40:28,360
WITH THE MASSACHUSETTS GENERAL

6009
03:40:28,360 --> 03:40:34,720
HOSPITAL, DR. BEN MEDOFF AND DRY

6010
03:40:34,720 --> 03:40:36,560
CRITICAL CARE UNIT, AND THEY DO

6011
03:40:36,560 --> 03:40:37,560
THESE BRONCHOSCOPIES WHERE THEY

6012
03:40:37,560 --> 03:40:38,600
BRUSH AND THEN COLLECT CELLS

6013
03:40:38,600 --> 03:40:41,560
FROM THE AIRWAY, VARIOUS REGIONS

6014
03:40:41,560 --> 03:40:42,440
OF THE AIRWAY.

6015
03:40:42,440 --> 03:40:43,560
THEY DO SORTING AND THEN THEY

6016
03:40:43,560 --> 03:40:44,760
PROVIDE US WITH THESE

6017
03:40:44,760 --> 03:40:46,200
POPULATIONS AND WE CAN EXPAND

6018
03:40:46,200 --> 03:40:47,720
THEM AND DEVELOP THEM INTO THE

6019
03:40:47,720 --> 03:40:48,240
TISSUES.

6020
03:40:48,240 --> 03:40:50,280
AND AS I'LL TALK ABOUT LATER, WE

6021
03:40:50,280 --> 03:40:54,680
LOOK AT THE VARIOUS DEMOGRAPHIC

6022
03:40:54,680 --> 03:40:56,360
POPULATIONS AND HOW THEY WILL

6023
03:40:56,360 --> 03:40:57,240
INFLUENCE THE RESULTS THAT WE

6024
03:40:57,240 --> 03:40:58,520
OBTAIN WITH THESE INFECTIOUS

6025
03:40:58,520 --> 03:40:59,520
DISEASE MODELS.

6026
03:40:59,520 --> 03:41:01,600
AND WE GET SOME BEAUTIFUL TISSUE

6027
03:41:01,600 --> 03:41:02,920
FORMATION IN THESE SYSTEMS.

6028
03:41:02,920 --> 03:41:06,320
ONE OF THE INTERESTING THINGS TO

6029
03:41:06,320 --> 03:41:08,040
LOOK AT IS IN PLATE AFTER PLATE,

6030
03:41:08,040 --> 03:41:10,040
WE SEE VIVID DIFFERENCES BETWEEN

6031
03:41:10,040 --> 03:41:12,200
DIFFERENT DONORS, LIVING DONORS

6032
03:41:12,200 --> 03:41:14,360
BASED ON VARIOUS

6033
03:41:14,360 --> 03:41:14,800
CHARACTERISTICS.

6034
03:41:14,800 --> 03:41:16,200
THOSE DIFFERENCES ARE IN THE

6035
03:41:16,200 --> 03:41:20,520
PERCENT OF SILL    CILIATED CELE

6036
03:41:20,520 --> 03:41:21,720
MUCOCILIARY BEATING AND MANY OF

6037
03:41:21,720 --> 03:41:22,920
THE OTHER ASPECTS OF THE

6038
03:41:22,920 --> 03:41:23,720
TISSUES, THE BARRIER QUALITY

6039
03:41:23,720 --> 03:41:26,240
THAT MAY BE INFLUENCED BY

6040
03:41:26,240 --> 03:41:28,400
BACKGROUND, GENDER, ETHNIC

6041
03:41:28,400 --> 03:41:30,160
BACKGROUND, IN PARTICULAR

6042
03:41:30,160 --> 03:41:31,120
COMORBIDITIES IS ONE OF THE MOST

6043
03:41:31,120 --> 03:41:33,640
INTERESTING ASPECTS HERE, CAN WE

6044
03:41:33,640 --> 03:41:37,040
UNDERSTAND WHAT DIABETES OR

6045
03:41:37,040 --> 03:41:39,760
ASTHMA, CHRONIC LUNG DISEASES,

6046
03:41:39,760 --> 03:41:41,080
WHAT INFLUENCE THAT MAY HAVE ON

6047
03:41:41,080 --> 03:41:42,840
THE PROGRESSION OF AN INFECTION

6048
03:41:42,840 --> 03:41:44,360
SUCH AS SARS-COV-2.

6049
03:41:44,360 --> 03:41:46,360
SO THAT IS ANOARL THING THAT

6050
03:41:46,360 --> 03:41:49,280
WE'RE LOOKING AT VERY

6051
03:41:49,280 --> 03:41:49,720
RIGOROUSLY.

6052
03:41:49,720 --> 03:41:52,360
SO I MENTIONED THE DARPA PREPARE

6053
03:41:52,360 --> 03:41:52,880
PROGRAM.

6054
03:41:52,880 --> 03:41:54,800
THAT'S AN INFLUENZA-FOCUSED

6055
03:41:54,800 --> 03:41:56,040
PROGRAM, AND WE'VE EVALUATED

6056
03:41:56,040 --> 03:41:58,640
MANY OF THE KEY INFLUENZA

6057
03:41:58,640 --> 03:42:02,480
STRAINS THAT THE PANDEMIC

6058
03:42:02,480 --> 03:42:10,040
STRAINS, HONG KONG 68 AND H1N1.

6059
03:42:10,040 --> 03:42:12,120
THIS IS PCR DATA AND WE CAN SEE

6060
03:42:12,120 --> 03:42:14,080
SEVERAL LOGS OF APPLICATION OVER

6061
03:42:14,080 --> 03:42:16,040
48 HOURS, AND WE CAN KNOCK DOWN

6062
03:42:16,040 --> 03:42:18,160
THAT VIRAL REPLICATION WITH A

6063
03:42:18,160 --> 03:42:19,440
DOSE-RESPONSE CURVE WITH THE

6064
03:42:19,440 --> 03:42:21,080
TAMIFLU AND WE CAN DO THAT WITH

6065
03:42:21,080 --> 03:42:22,400
DIFFERENT DONORS AND WE SEE

6066
03:42:22,400 --> 03:42:23,480
DIFFERENT RESULTS FOR THE

6067
03:42:23,480 --> 03:42:26,440
DIFFERENT DONORS.

6068
03:42:26,440 --> 03:42:27,880
SO COVID-19 HAS BEEN OUR MAIN

6069
03:42:27,880 --> 03:42:28,760
FOCUS RECENTLY.

6070
03:42:28,760 --> 03:42:30,240
I'D LIKE TO SPEND THE REST OF

6071
03:42:30,240 --> 03:42:32,120
THE TALK ON THAT ASPECT.

6072
03:42:32,120 --> 03:42:35,720
AND CERTAINLY THIS "NEW YORK

6073
03:42:35,720 --> 03:42:40,760
TIMES" ARTICLE ARTICULATES THE

6074
03:42:40,760 --> 03:42:42,320
COVID-19 VACCINE DEVELOPMENT,

6075
03:42:42,320 --> 03:42:43,400
THAT WAS DISCUSSED EARLIER AS

6076
03:42:43,400 --> 03:42:44,280
WELL AT THE BEGINNING OF THE

6077
03:42:44,280 --> 03:42:45,720
DAY, HAS BEEN A VERY POWERFUL

6078
03:42:45,720 --> 03:42:47,000
AND COMPELLING EXAMPLE OF HOW

6079
03:42:47,000 --> 03:42:48,880
THESE TECHNOLOGIES CAN COME

6080
03:42:48,880 --> 03:42:50,840
TOGETHER QUICKLY WITH SAFE AND

6081
03:42:50,840 --> 03:42:51,720
EFFICACIOUS VACCINES.

6082
03:42:51,720 --> 03:42:54,120
HOWEVER, I THINK A LOT OF PEOPLE

6083
03:42:54,120 --> 03:42:56,560
IN THE MICROPHYSIOLOGICAL

6084
03:42:56,560 --> 03:42:59,600
SYSTEMS DMEUNT,     COMMUNITY, G

6085
03:42:59,600 --> 03:43:00,800
ABOUT COVID-19 THERAPEUTICS, ARE

6086
03:43:00,800 --> 03:43:02,440
SEEING AN OPPORTUNITY TO ADDRESS

6087
03:43:02,440 --> 03:43:03,960
ESSENTIALLY A GAP, AND THAT GAP

6088
03:43:03,960 --> 03:43:05,440
AS MANY OF THE SPEAKERS, ALL OF

6089
03:43:05,440 --> 03:43:07,120
THE SPEAKERS HAVE TALKED ABOUT,

6090
03:43:07,120 --> 03:43:08,440
IS IN THE PRE-CLINICAL

6091
03:43:08,440 --> 03:43:09,200
DEVELOPMENT.

6092
03:43:09,200 --> 03:43:10,840
IT'S IN THE LIMITATIONS OF

6093
03:43:10,840 --> 03:43:12,400
ANIMAL MODELS, IT'S IN THE

6094
03:43:12,400 --> 03:43:15,320
LIMITATIONS OF THESE SIMPLIFIED

6095
03:43:15,320 --> 03:43:16,320
IMMORTGAGIZED CELL CULTURE

6096
03:43:16,320 --> 03:43:18,160
SYSTEMS AND MICROPHYSIOLOGICAL

6097
03:43:18,160 --> 03:43:20,320
SYSTEMS HAVE THIS TREMENDOUS

6098
03:43:20,320 --> 03:43:22,880
OPPORTUNITY TO IMPACT AN AREA

6099
03:43:22,880 --> 03:43:25,280
LIKE THE SARS-COV-2 PANDEMIC AND

6100
03:43:25,280 --> 03:43:27,360
HOW ONE MIGHT IDENTIFY

6101
03:43:27,360 --> 03:43:29,320
THERAPEUTICS THAT ARE HIGHLY

6102
03:43:29,320 --> 03:43:30,920
EFFECTIVE FROM THESE SYSTEMS,

6103
03:43:30,920 --> 03:43:33,040
MUCH MORE RAPIDLY, INEXPENSIVELY

6104
03:43:33,040 --> 03:43:35,680
AND MUCH MORE ACCURATELY THAN

6105
03:43:35,680 --> 03:43:37,000
EXISTING PRE-CLINICAL MODELS.

6106
03:43:37,000 --> 03:43:40,240
SO WITH THAT, THAT'S ANOTHER

6107
03:43:40,240 --> 03:43:41,800
AXIS OF WHAT WE'VE TALKING ABOUT

6108
03:43:41,800 --> 03:43:42,560
HERE.

6109
03:43:42,560 --> 03:43:43,520
WE'VE TALKED ABOUT THE

6110
03:43:43,520 --> 03:43:44,200
HIGH-THROUGHPUT, WE'VE TALKED

6111
03:43:44,200 --> 03:43:45,520
ABOUT THE PERSONALIZED MEDICINE.

6112
03:43:45,520 --> 03:43:48,040
THE OTHER KEY ASPECT IS THE HIGH

6113
03:43:48,040 --> 03:43:48,880
CONTAINMENT OPERATION, AND I

6114
03:43:48,880 --> 03:43:50,320
THINK THEY ALL GO TOGETHER

6115
03:43:50,320 --> 03:43:51,120
ESSENTIALLY, AND ONE OF THE

6116
03:43:51,120 --> 03:43:52,520
THINGS WE'VE SEEN IS THAT MANY

6117
03:43:52,520 --> 03:43:54,360
OF THE EFFORTS WITH ORGANS ON

6118
03:43:54,360 --> 03:43:57,120
CHIPS, SOME OF THE THOSE NOTABLE

6119
03:43:57,120 --> 03:43:58,440
EFFORTS, HAS BEEN LIMITED TO

6120
03:43:58,440 --> 03:43:59,560
PSEUDOVIRUS AND VIRAL ENTRY, AND

6121
03:43:59,560 --> 03:44:01,560
WE KNOW THAT IN THAT CASE, THE

6122
03:44:01,560 --> 03:44:03,360
DYNAMIC RANGE IS VERY LIMITED,

6123
03:44:03,360 --> 03:44:05,400
AND MANY OF THE MECHANISMS OF

6124
03:44:05,400 --> 03:44:07,200
REPLICATION ARE NOT REFLECTED BY

6125
03:44:07,200 --> 03:44:09,240
JUST LOOKING AT A PSEUDOVIRUS,

6126
03:44:09,240 --> 03:44:12,000
AND SO OUR AIM EARLY ON IN THE

6127
03:44:12,000 --> 03:44:14,200
PANDEMIC WAS TO ESTABLISH A

6128
03:44:14,200 --> 03:44:21,400
CAPABILITY IN A BSL-3 LABORATORY

6129
03:44:21,400 --> 03:44:24,120
TO LOOK AT THE VIRUS AND ITS

6130
03:44:24,120 --> 03:44:25,440
REPLICATION, BOTH ACROSS STRAINS

6131
03:44:25,440 --> 03:44:27,640
BUT THEN WHAT HAPPENS WHEN WE

6132
03:44:27,640 --> 03:44:28,280
INTRODUCE THERAPEUTIC

6133
03:44:28,280 --> 03:44:30,280
CANDIDATES.

6134
03:44:30,280 --> 03:44:31,920
SO WE'VE LEASED SPACE AT THE

6135
03:44:31,920 --> 03:44:33,880
TUFTS UNIVERSITY AND BIOSAFETY

6136
03:44:33,880 --> 03:44:38,600
LABORATORY WEST OF HERE.

6137
03:44:38,600 --> 03:44:40,080
THESE ARE PEOPLE WITH DECADES OF

6138
03:44:40,080 --> 03:44:42,200
EXPERIENCE IN BSL-3 OPERATIONS.

6139
03:44:42,200 --> 03:44:44,920
IT WASN'T IN SARS-COV-2

6140
03:44:44,920 --> 03:44:46,320
OBVIOUSLY EARLY IN THE PANDEMIC,

6141
03:44:46,320 --> 03:44:47,760
IT WAS IN TUBERCULOSIS AND

6142
03:44:47,760 --> 03:44:50,280
RABIES AND OTHER

6143
03:44:50,280 --> 03:44:51,480
BSL-3 PATHOGENS, BUT THIS

6144
03:44:51,480 --> 03:44:54,960
EXPERTISE CAME TOGETHER WITH THE

6145
03:44:54,960 --> 03:44:56,080
TECHNOLOGY, WORKING TOGETHER IN

6146
03:44:56,080 --> 03:44:56,520
THIS FACILITY.

6147
03:44:56,520 --> 03:44:58,280
A LOT OF THE WORK HAS BEEN DONE

6148
03:44:58,280 --> 03:44:59,040
ON THE WASHINGTON STRAIN BUT

6149
03:44:59,040 --> 03:45:01,120
WE'RE ACQUIRING DELTA AND

6150
03:45:01,120 --> 03:45:02,400
OMICRON AS WELL, AND YOU CAN SEE

6151
03:45:02,400 --> 03:45:03,840
HERE THE LIST OF INFECTIONS

6152
03:45:03,840 --> 03:45:07,880
WE'VE BEEN WORKING WITH IN THE

6153
03:45:07,880 --> 03:45:09,320
BSL-2 AND BSL-3 LABORATORIES.

6154
03:45:09,320 --> 03:45:12,240
SO WITH THAT, WE WERE ABLE TO

6155
03:45:12,240 --> 03:45:13,800
DEMONSTRATE ROBUST VIRAL

6156
03:45:13,800 --> 03:45:18,840
REPLICATION OF SARS-COV-2 IN OUR

6157
03:45:18,840 --> 03:45:19,480
PREDICT 96 SYSTEM.

6158
03:45:19,480 --> 03:45:20,880
WE KNOW IT'S BEEN CHALLENGING,

6159
03:45:20,880 --> 03:45:21,680
WE'VE SEEN DISCUSSIONS IN THE

6160
03:45:21,680 --> 03:45:23,080
FIELD ABOUT HOW THIS IS

6161
03:45:23,080 --> 03:45:24,160
EXTREMELY CHALLENGING AND SOME

6162
03:45:24,160 --> 03:45:26,600
OF THOSE CHALLENGES MAY BE

6163
03:45:26,600 --> 03:45:27,680
ASSOCIATED WITH THE TRANS WELL

6164
03:45:27,680 --> 03:45:29,120
SYSTEMS OR WITH OTHER SYSTEMS,

6165
03:45:29,120 --> 03:45:30,400
THEY MAY BE ASSOCIATED WITH

6166
03:45:30,400 --> 03:45:33,040
OTHER LIMITATIONS IN THE

6167
03:45:33,040 --> 03:45:34,040
PROCESSES, BUT HERE WE'VE BEEN

6168
03:45:34,040 --> 03:45:36,000
ABLE WITH MORE THAN 20 OF THESE

6169
03:45:36,000 --> 03:45:37,760
PREDICT 96 PLATES TO DEMONSTRATE

6170
03:45:37,760 --> 03:45:42,440
ROBUST VIRAL REPLICATION, WE SEE

6171
03:45:42,440 --> 03:45:46,400
VERY LOW INTRA-PLATE VARIABILITY

6172
03:45:46,400 --> 03:45:49,000
SIX DAYS WHEN WE RE-INTRODUCE

6173
03:45:49,000 --> 03:45:50,440
THE INFECTION AT DAY ZERO, THIS

6174
03:45:50,440 --> 03:45:53,720
IS WHEN THE TISSUE HAS BEEN FULL

6175
03:45:53,720 --> 03:45:55,880
LEE DEVELOPED AND THEN WE HAVE

6176
03:45:55,880 --> 03:45:57,880
READOUTS.

6177
03:45:57,880 --> 03:45:59,200
IT ALSO GIVES US OPTIONS IN

6178
03:45:59,200 --> 03:46:04,560
TERMS OF THE WORKFLOW IF WE ARE

6179
03:46:04,560 --> 03:46:05,760
LOOKING AT LARGER PANELS OF

6180
03:46:05,760 --> 03:46:07,120
COMPOUNDS THAT ARE CANDIDATES

6181
03:46:07,120 --> 03:46:09,520
FOR EVALUATION AS AN ANTIVIRAL.

6182
03:46:09,520 --> 03:46:11,560
SO PCR IS KIND OF THE GOLD

6183
03:46:11,560 --> 03:46:13,440
STANDARD, BUT A LOT OF PLAQUE

6184
03:46:13,440 --> 03:46:15,280
ASSAYS, TCIB50 IS ATTRACTIVE

6185
03:46:15,280 --> 03:46:16,400
BECAUSE IT'S VERY

6186
03:46:16,400 --> 03:46:16,760
HIGH-THROUGHPUT.

6187
03:46:16,760 --> 03:46:22,080
WE CAN ALSO DO LEUM    LUMINEX R

6188
03:46:22,080 --> 03:46:23,200
ASSAYS.

6189
03:46:23,200 --> 03:46:24,040
CERTAINLY RNA SEQ HAS BEEN DONE

6190
03:46:24,040 --> 03:46:27,320
ON A CASE-BY-CASE BASIS

6191
03:46:27,320 --> 03:46:29,400
PARTICULARLY IN THE DARPA

6192
03:46:29,400 --> 03:46:29,720
PROGRAM.

6193
03:46:29,720 --> 03:46:30,920
SO JUST GOING BACK TO THE

6194
03:46:30,920 --> 03:46:32,120
PRECISION MEDICINE ASPECT.

6195
03:46:32,120 --> 03:46:38,720
WE CAN SEE HERE'S SARS-COV-2

6196
03:46:38,720 --> 03:46:39,560
APPLICATION.

6197
03:46:39,560 --> 03:46:41,040
ACROSS MULTIPLE DONOR, WE CAN

6198
03:46:41,040 --> 03:46:41,680
LOOK AT THE CHARACTERISTICS OF

6199
03:46:41,680 --> 03:46:42,720
THESE DONORS.

6200
03:46:42,720 --> 03:46:44,960
THEIR GENDER, THEIR RACE, THEIR

6201
03:46:44,960 --> 03:46:45,560
AGE.

6202
03:46:45,560 --> 03:46:47,560
CAUSE OF DEATH IS LISTED HERE IN

6203
03:46:47,560 --> 03:46:48,960
THE CASE OF THESE CADAVER

6204
03:46:48,960 --> 03:46:49,200
SOURCES.

6205
03:46:49,200 --> 03:46:51,400
WE ALSO HAVE A SIMILAR PANEL,

6206
03:46:51,400 --> 03:46:53,160
I'M NOT SHOWING IT HERE, OF

6207
03:46:53,160 --> 03:46:55,880
LIVING DONORS FROM MASSACHUSETTS

6208
03:46:55,880 --> 03:46:56,960
GENERAL HOSPITAL, WHERE THESE

6209
03:46:56,960 --> 03:46:59,560
ARE OBTAINED FROM THE RESEARCH

6210
03:46:59,560 --> 03:47:01,320
BRONCHOSCOPIES, AND THEN THE

6211
03:47:01,320 --> 03:47:04,720
DOUBLING TIME AND OTHER

6212
03:47:04,720 --> 03:47:05,280
FEATURES.

6213
03:47:05,280 --> 03:47:06,920
THEY'RE JUST NOW GETTING INTO

6214
03:47:06,920 --> 03:47:07,760
THE THERAPEUTIC SCREENING.

6215
03:47:07,760 --> 03:47:09,880
SO WE CAN SEE ON A SINGLE

6216
03:47:09,880 --> 03:47:11,400
PREDICT 96 PLATE, WE CAN LOOK AT

6217
03:47:11,400 --> 03:47:13,280
AS MANY AS SIX OR MORE COMPOUNDS

6218
03:47:13,280 --> 03:47:16,000
AND HAVE REPLICATES AT VARIOUS

6219
03:47:16,000 --> 03:47:17,960
CONDITIONS, AND THESE CONDITIONS

6220
03:47:17,960 --> 03:47:19,600
CAN BE MULTIPLICITY OF

6221
03:47:19,600 --> 03:47:22,360
INFLATION, THEY CAN BE THE KOAS.

6222
03:47:22,360 --> 03:47:22,560
 DOSE.

6223
03:47:22,560 --> 03:47:23,880
SO WHAT WE'VE DONE IS WE'VE

6224
03:47:23,880 --> 03:47:25,080
TAKEN MANY OF THE SORT OF

6225
03:47:25,080 --> 03:47:27,040
PREDOMINANT COMPOUNDS THAT --

6226
03:47:27,040 --> 03:47:30,560
TREATMENTS THAT ARE BEING USED,

6227
03:47:30,560 --> 03:47:31,240
THE APPROVED COMPOUNDS HERE IN

6228
03:47:31,240 --> 03:47:32,720
THE UPPER ROW AND ASK OURSELVES

6229
03:47:32,720 --> 03:47:35,040
THE QUESTION, THIS IS REALLY A

6230
03:47:35,040 --> 03:47:36,760
LITMUS TEST FOR ORGAN ON CHIP

6231
03:47:36,760 --> 03:47:38,200
SYSTEMS THAT WE'VE BEEN

6232
03:47:38,200 --> 03:47:40,480
UNDERTAKING HERE, AND THAT IS IF

6233
03:47:40,480 --> 03:47:42,480
WE INTRODUCE THE APPROVED

6234
03:47:42,480 --> 03:47:44,760
TREATMENTS FOR SARS-COV-2, CAN

6235
03:47:44,760 --> 03:47:46,160
WE REPRODUCE ESSENTIALLY WHAT IS

6236
03:47:46,160 --> 03:47:49,120
SEEN CLINICALLY, AND THEN IF WE

6237
03:47:49,120 --> 03:47:51,480
LOOK AHEAD, COULD WE THEN HAVE

6238
03:47:51,480 --> 03:47:53,960
FREE   

6239
03:47:53,960 --> 03:47:55,920
PREDICTED WITHOUT GOING THROUGH

6240
03:47:55,920 --> 03:47:57,800
SCREENS OR ANIMAL MODELS OR

6241
03:47:57,800 --> 03:47:59,400
EXTENSIVE CLINICAL STUDY, COULD

6242
03:47:59,400 --> 03:48:00,720
WE PREDICT WHICH DRUGS ARE GOING

6243
03:48:00,720 --> 03:48:02,600
TO WORK BEST.

6244
03:48:02,600 --> 03:48:07,200
AND SO WE'RE LOOKING HERE AT

6245
03:48:07,200 --> 03:48:11,320
PAXLOVID, REMDESIVIR,

6246
03:48:11,320 --> 03:48:12,000
MOLNUPIRAVIR AND SOME OTHER

6247
03:48:12,000 --> 03:48:13,280
COMPOUNDS THAT ARE ESSENTIALLY

6248
03:48:13,280 --> 03:48:16,040
BEING EVALUATED.

6249
03:48:16,040 --> 03:48:16,920
CALPEPTIN AND OTHER COMPOUNDS.

6250
03:48:16,920 --> 03:48:18,920
SO JUST GOING TO THIS SLIDE HOOR

6251
03:48:18,920 --> 03:48:20,280
HERE WHERE WE ESSENTIALLY LOOK

6252
03:48:20,280 --> 03:48:22,280
AT THE RESULTS, WE THOUGHT OF

6253
03:48:22,280 --> 03:48:24,680
THOSE IN TERMS OF THE FULL

6254
03:48:24,680 --> 03:48:26,200
REDUCTION IN THE VIRAL RNA, AND

6255
03:48:26,200 --> 03:48:30,400
HERE YOU CAN SEE THE CURVES BUT

6256
03:48:30,400 --> 03:48:32,000
THESE BAR CHARTS ARE A LITTLE

6257
03:48:32,000 --> 03:48:32,880
EASIER TO VISUALIZE.

6258
03:48:32,880 --> 03:48:34,320
WHAT WE'VE DONE IS WE'VE ORDERED

6259
03:48:34,320 --> 03:48:35,600
THESE COMPOUNDS IN TERMS OF OUR

6260
03:48:35,600 --> 03:48:37,920
PREDICTION BASED ON THE PREDICT

6261
03:48:37,920 --> 03:48:40,240
96 STUDIES, AND WE CAN SEE A

6262
03:48:40,240 --> 03:48:41,720
TREMENDOUS FULL REDUCTION,

6263
03:48:41,720 --> 03:48:46,560
ESPECIALLY AT THE HIGH DOSES FOR

6264
03:48:46,560 --> 03:48:48,480
THE MAIN COMPONENT OF PAXLOVID

6265
03:48:48,480 --> 03:48:51,160
BUT EVEN AT THE MID RANGE DOSE,

6266
03:48:51,160 --> 03:48:53,680
THE REMDESIVIR IS KIND OF AN

6267
03:48:53,680 --> 03:48:54,760
INTERMEDIATE CASE WHERE AT VERY

6268
03:48:54,760 --> 03:48:58,800
HIGH DOSE, WE SEE VERY LARGE

6269
03:48:58,800 --> 03:49:00,360
REDUCTION IN THE VIRAL COPY

6270
03:49:00,360 --> 03:49:03,200
NUMBER, AND THEN THE

6271
03:49:03,200 --> 03:49:04,200
MOLNUPIRAVIR IS EASILY THE

6272
03:49:04,200 --> 03:49:05,160
WEAKEST OF THE THREE, WHERE

6273
03:49:05,160 --> 03:49:06,360
WE'VE GOT MARGINAL REDUCTION

6274
03:49:06,360 --> 03:49:08,000
EVEN AT THE HIGH DOSE, AND

6275
03:49:08,000 --> 03:49:09,600
REALLY VIRTUALLY NO EFFECT AT

6276
03:49:09,600 --> 03:49:10,520
THE LOWER DOSES.

6277
03:49:10,520 --> 03:49:12,840
AND IF WE JUST TAKE A LOOK AT

6278
03:49:12,840 --> 03:49:13,960
CLINICAL RESULTS HERE AND LOOK

6279
03:49:13,960 --> 03:49:17,200
AT THE HOSPITALIZATION, WE KNOW

6280
03:49:17,200 --> 03:49:18,840
PAXLOVID IS HIGHLY EFFICACIOUS,

6281
03:49:18,840 --> 03:49:20,800
CLEARLY THAT'S THE TREATMENT OF

6282
03:49:20,800 --> 03:49:23,720
CHOICE REDUCING HOSPITALIZATION

6283
03:49:23,720 --> 03:49:24,840
BY 89%.

6284
03:49:24,840 --> 03:49:27,240
THE REMDESIVIR REDUCES

6285
03:49:27,240 --> 03:49:28,320
HOSPITALIZATION ALMOST BY THE

6286
03:49:28,320 --> 03:49:32,960
SAME AMOUNT BUT MANY CLINICAL

6287
03:49:32,960 --> 03:49:34,160
STUDIES SUGGEST IT'S NOT QUITE

6288
03:49:34,160 --> 03:49:35,440
AS EFFICACIOUS AT PAXLOVID.

6289
03:49:35,440 --> 03:49:36,760
IT LOOKS THAT WAY FROM OUR

6290
03:49:36,760 --> 03:49:37,360
PREDICTION.

6291
03:49:37,360 --> 03:49:39,160
AND THE MOLNUPIRAVIR IN PLATE

6292
03:49:39,160 --> 03:49:41,160
AFTER PLATE SHOWS A RELATIVELY

6293
03:49:41,160 --> 03:49:44,440
WEAK RESPONSE IN OUR SYSTEM, IN

6294
03:49:44,440 --> 03:49:45,440
OUR HANDS, BUT ALSO IN TERMS OF

6295
03:49:45,440 --> 03:49:46,920
THE CLINIC, REDUCING

6296
03:49:46,920 --> 03:49:48,640
HOSPITALIZATION ONLY MARGINALLY.

6297
03:49:48,640 --> 03:49:50,000
IN ADDITION, IT DOES APPEAR TO

6298
03:49:50,000 --> 03:49:51,880
HAVE SOME SAFETY CONCERNS, BUT I

6299
03:49:51,880 --> 03:49:53,480
THINK WHAT WE'RE ESSENTIALLY

6300
03:49:53,480 --> 03:49:55,560
SHOWING HERE IS THE ABILITY OF

6301
03:49:55,560 --> 03:49:57,680
THIS PREDICT 96 SYSTEM TO GAUGE

6302
03:49:57,680 --> 03:50:00,560
THE EFFECTIVENESS IN TERMS OF

6303
03:50:00,560 --> 03:50:03,360
THE CLINIC OF THESE VARIOUS

6304
03:50:03,360 --> 03:50:04,440
COMPOUNDS IN THE SARS-COV-2

6305
03:50:04,440 --> 03:50:05,640
VIRUS, WHICH IS A CHALLENGING

6306
03:50:05,640 --> 03:50:08,280
VIRUS TO WORK WITH, AND SO WE'RE

6307
03:50:08,280 --> 03:50:11,080
VERY EXCITED OBVIOUSLY BY

6308
03:50:11,080 --> 03:50:11,880
THIS -- BY THESE RESULTS AND

6309
03:50:11,880 --> 03:50:13,400
BELIEVE THAT THE LOGICAL NEXT

6310
03:50:13,400 --> 03:50:15,560
STEP IS TO BEGIN TO LOOK AT

6311
03:50:15,560 --> 03:50:18,440
LARGER PANELS, LOOK AT DIFFERENT

6312
03:50:18,440 --> 03:50:19,760
PATIENT POPULATIONS AND LOOK AT

6313
03:50:19,760 --> 03:50:21,400
EMERGING VARIANTS WHERE WE WON'T

6314
03:50:21,400 --> 03:50:22,840
KNOW HOW WELL THESE DRUGS WORK.

6315
03:50:22,840 --> 03:50:24,560
IN FACT, SOMEONE YESTERDAY WAS

6316
03:50:24,560 --> 03:50:26,520
ASKING ME, CAN WE LOOK AT THE

6317
03:50:26,520 --> 03:50:28,480
REBOUND EFFECT IN PAXLOVID, AND

6318
03:50:28,480 --> 03:50:30,040
THAT'S A FASCINATING QUESTION.

6319
03:50:30,040 --> 03:50:32,120
SO I THINK THAT WOULD BE A NEXT

6320
03:50:32,120 --> 03:50:33,120
STEP.

6321
03:50:33,120 --> 03:50:34,520
SO JUST IN QUICK SUMMARY HERE,

6322
03:50:34,520 --> 03:50:35,920
THERE'S A CRITICAL NEED FOR

6323
03:50:35,920 --> 03:50:38,360
THESE ORGAN ON CHIP MODELS WITH

6324
03:50:38,360 --> 03:50:40,080
HIGH PRIORITY PATHOGEN RESEARCH.

6325
03:50:40,080 --> 03:50:41,840
THE HIGH-THROUGHPUT IS KEY.

6326
03:50:41,840 --> 03:50:43,800
WE'VE BEEN ABLE TO DEMONSTRATE

6327
03:50:43,800 --> 03:50:45,360
ROBUST VIRAL REPLICATION ACROSS

6328
03:50:45,360 --> 03:50:48,840
MANY, MANY PLATES IN THE

6329
03:50:48,840 --> 03:50:50,240
BSL-3 LABORATORY AND DONE SO

6330
03:50:50,240 --> 03:50:52,120
WITH CELLS FROM HUMAN PRIMARY

6331
03:50:52,120 --> 03:50:53,440
DONORS, AND WE REALLY BELIEVE

6332
03:50:53,440 --> 03:50:55,720
THAT THIS MCM SCREENING IS A

6333
03:50:55,720 --> 03:50:59,040
ROBUST AND REPRODUCIBLE

6334
03:50:59,040 --> 03:50:59,880
CAPABILITY, AND WE'D LIKE TO

6335
03:50:59,880 --> 03:51:01,880
CONTINUE WITH THAT WITH LARGER

6336
03:51:01,880 --> 03:51:03,400
PANELS AS I TALKED ABOUT ACROSS

6337
03:51:03,400 --> 03:51:05,560
THE VARIOUS DOMAINS THAT WE'RE

6338
03:51:05,560 --> 03:51:06,600
INTERESTED IN LOOKING AT.

6339
03:51:06,600 --> 03:51:10,960
SO WITH THAT, I'D REICH    LIKEK

6340
03:51:10,960 --> 03:51:12,800
EVERYONE, PARTICULARLY ASHLEY

6341
03:51:12,800 --> 03:51:14,000
GARD, THE PRINCIPAL INVESTIGATOR

6342
03:51:14,000 --> 03:51:15,200
FOR THIS WORK AND HER

6343
03:51:15,200 --> 03:51:16,840
OUTSTANDING TEAM AT DRAPER, OUR

6344
03:51:16,840 --> 03:51:19,240
COLLABORATORS AT MGH, THE

6345
03:51:19,240 --> 03:51:23,280
OUTSTANDING TEAM AT THE TUFTS,

6346
03:51:23,280 --> 03:51:25,400
OUR UMASS COLLABORATORS ON THE

6347
03:51:25,400 --> 03:51:26,800
PREPARE PROGRAM AND THE FUNDING

6348
03:51:26,800 --> 03:51:28,080
SOURCES, AND THANK YOU ALL.

6349
03:51:28,080 --> 03:51:29,760
>> THANK YOU, JEFF.

6350
03:51:29,760 --> 03:51:31,080
THIS IS AMAZING WORK THAT YOU

6351
03:51:31,080 --> 03:51:35,080
GUYS ARE DOING AND THE

6352
03:51:35,080 --> 03:51:37,200
PHARMACOLOGICAL RESULTS AND THE

6353
03:51:37,200 --> 03:51:37,840
HIGH-THROUGHPUT THAT YOU'RE

6354
03:51:37,840 --> 03:51:39,160
GETTING IN YOUR PLATFORM.

6355
03:51:39,160 --> 03:51:41,760
IT'S REALLY ENCOURAGING AND

6356
03:51:41,760 --> 03:51:45,600
REPRODUCIBILITY.

6357
03:51:45,600 --> 03:51:48,120
I THINK NOW WE ARE IN THE

6358
03:51:48,120 --> 03:51:52,720
QUESTION AND ANSWER TIME.

6359
03:51:52,720 --> 03:51:54,600
BEFORE WE GO INTO THE DISCUSSION

6360
03:51:54,600 --> 03:51:56,640
AND QUESTIONS, I WOULD LIKE TO

6361
03:51:56,640 --> 03:52:01,240
THANK THE SPEAKERS AGAIN FOR

6362
03:52:01,240 --> 03:52:03,080
TERRIFIC PRESENTATIONS, AND

6363
03:52:03,080 --> 03:52:05,720
REALLY IN MY MIND, I THINK WE

6364
03:52:05,720 --> 03:52:08,880
GOT A VERY NICE BROAD VIEW OF

6365
03:52:08,880 --> 03:52:11,640
THE DIFFERENT TISSUE MODELS,

6366
03:52:11,640 --> 03:52:15,320
ORGANOIDS, TISSUE ON A CHIP.

6367
03:52:15,320 --> 03:52:17,760
FOR THOSE OF YOU WHO ARE NEW IN

6368
03:52:17,760 --> 03:52:20,160
THIS WORLD OF 3D TISSUE MODEL,

6369
03:52:20,160 --> 03:52:21,920
YOU GOT A VERY NICE PERSPECTIVE

6370
03:52:21,920 --> 03:52:22,760
OF WHAT'S HAPPENING.

6371
03:52:22,760 --> 03:52:26,000
THE TECHNOLOGY IS ADVANCING AT A

6372
03:52:26,000 --> 03:52:32,640
VERY FAST PACE, AND I THINK --

6373
03:52:32,640 --> 03:52:34,160
ONE OF THE CHALLENGES, I THINK

6374
03:52:34,160 --> 03:52:35,360
JOHN MENTIONED AT THE BEGINNING,

6375
03:52:35,360 --> 03:52:39,520
IS HOW DO YOU MAKE THIS PROMISE

6376
03:52:39,520 --> 03:52:41,560
INTO A REALITY.

6377
03:52:41,560 --> 03:52:46,160
OF ALL THE SPEERK, I      SPEAKY

6378
03:52:46,160 --> 03:52:48,120
TWO THIRDS ARE BIOENGINEERS,

6379
03:52:48,120 --> 03:52:51,560
BIOENGINEERING LABS.

6380
03:52:51,560 --> 03:52:52,880
ONE OTHER QUESTION IS HOW DO WE

6381
03:52:52,880 --> 03:52:55,080
GET THESE TECHNOLOGIES INTO MORE

6382
03:52:55,080 --> 03:52:56,160
BIOLOGY LABS SO THERE'S MORE

6383
03:52:56,160 --> 03:53:00,000
PEOPLE REALLY DOING SCIENTIFIC

6384
03:53:00,000 --> 03:53:01,600
VALIDATION AND PHYSIOLOGICAL

6385
03:53:01,600 --> 03:53:03,040
VALIDATIONS OF THESE MODELS.

6386
03:53:03,040 --> 03:53:07,520
SO THERE'S A BUNCH OF QUESTIONS.

6387
03:53:07,520 --> 03:53:08,520
I'M GOING TO GO THROUGH THE

6388
03:53:08,520 --> 03:53:09,600
QUESTIONS IN THE BOX, BUT

6389
03:53:09,600 --> 03:53:14,000
BEFORE, I WANTED TO START WITH

6390
03:53:14,000 --> 03:53:16,520
CHRISTINE MUMMERY.

6391
03:53:16,520 --> 03:53:17,800
BECAUSE IF I UNDERSTOOD

6392
03:53:17,800 --> 03:53:19,120
CORRECTLY, YOU'RE NOT IN A

6393
03:53:19,120 --> 03:53:21,880
TISSUE ENGINEERING LAB.

6394
03:53:21,880 --> 03:53:22,960
YOU'RE A STEM CELL LAB.

6395
03:53:22,960 --> 03:53:25,040
SO MY QUESTION TO YOU IS, WHEN

6396
03:53:25,040 --> 03:53:28,960
YOU GOT INTO THESE 3D TISSUE

6397
03:53:28,960 --> 03:53:30,600
MODELS IN TERMS OF ORGANOID,

6398
03:53:30,600 --> 03:53:31,920
MICRO TISSUES AND THEN YOU'RE

6399
03:53:31,920 --> 03:53:34,000
DOING SOME WORK WITH TISSUE

6400
03:53:34,000 --> 03:53:36,840
CHIPS NOW THAT YOU SHOW, WHAT

6401
03:53:36,840 --> 03:53:37,840
WERE THE CONSIDERATIONS, WHAT

6402
03:53:37,840 --> 03:53:40,680
WERE THE DRIVERS, WHAT WERE THE

6403
03:53:40,680 --> 03:53:42,200
DECISIONS YOU HAD TO MAKE WHEN

6404
03:53:42,200 --> 03:53:44,640
YOU STARTED WORKING WITH THESE

6405
03:53:44,640 --> 03:53:45,600
COMPLEX TISSUES?

6406
03:53:45,600 --> 03:53:51,160
>> WELL, SO I'M A
PHYSICIST BY

6407
03:53:51,160 --> 03:53:54,680
TRAINING, BUT I ADOPTED STEM

6408
03:53:54,680 --> 03:53:55,520
CELL BIOLOGY VERY EARLY ON.

6409
03:53:55,520 --> 03:53:56,880
SO I TRY TO COMBINE

6410
03:53:56,880 --> 03:54:00,160
DEVELOPMENTAL BIOLOGY CONCEPTS,

6411
03:54:00,160 --> 03:54:01,760
OR WHAT DOES A CELL NEED, WITH

6412
03:54:01,760 --> 03:54:04,200
ENGINEERING CONCEPTS.

6413
03:54:04,200 --> 03:54:07,000
BECAUSE I'M IN A ENVIRONMENT

6414
03:54:07,000 --> 03:54:08,240
WHERE -- I JUST THOUGHT CHIPS

6415
03:54:08,240 --> 03:54:09,760
WERE SO COOL, BUT THEY'RE USING

6416
03:54:09,760 --> 03:54:10,520
THE WRONG CELLS.

6417
03:54:10,520 --> 03:54:13,240
SO I'M NOT A FAN OF CELLS LIKE

6418
03:54:13,240 --> 03:54:16,400
HUVEX, WHICH ARE REALLY SORT OF

6419
03:54:16,400 --> 03:54:17,480
OLD ENDOTHELIAL CELLS, THEY'RE

6420
03:54:17,480 --> 03:54:18,680
NOT REALLY REPRESENTATIVE OF

6421
03:54:18,680 --> 03:54:20,440
WHAT YOU FIND IN MOST OF THE

6422
03:54:20,440 --> 03:54:23,080
BODY.

6423
03:54:23,080 --> 03:54:25,560
AND I -- WE'RE USING THESE

6424
03:54:25,560 --> 03:54:27,120
FANTASTIC STEM CELL MODELS BUT

6425
03:54:27,120 --> 03:54:28,520
YOU JUST PUT THEM IN THE WRONG

6426
03:54:28,520 --> 03:54:29,120
SUBSTRATE.

6427
03:54:29,120 --> 03:54:31,280
SO WE GOT TOGETHER AND DECIDED

6428
03:54:31,280 --> 03:54:33,240
TO TRY AND COMBINE THESE THINGS.

6429
03:54:33,240 --> 03:54:35,560
NOW, MOST IMPORTANT WAS TO MAKE

6430
03:54:35,560 --> 03:54:37,840
THE BIOLOGY ROBUST, SO I THINK I

6431
03:54:37,840 --> 03:54:40,680
SHOWED EXAMPLES OF HOW WE DO QA

6432
03:54:40,680 --> 03:54:42,320
AND QC BEFORE WE PUT THINGS IN

6433
03:54:42,320 --> 03:54:43,720
CHIPS, BUT THEN YOU ASK WHAT

6434
03:54:43,720 --> 03:54:46,160
CHIPS DO YOU USE.

6435
03:54:46,160 --> 03:54:47,680
SO YOU WANT SOMETHING THAT'S

6436
03:54:47,680 --> 03:54:48,560
AVAILABLE, REPRODUCIBLE.

6437
03:54:48,560 --> 03:54:50,520
IF YOU GO TO A TECHNICAL

6438
03:54:50,520 --> 03:54:51,480
UNIVERSITY, THEY'LL GIVE YOU A

6439
03:54:51,480 --> 03:54:53,160
CHIP AND THERE ARE LIKE 10 OF

6440
03:54:53,160 --> 03:54:54,800
THEM, WHEN YOU SAID YOU WANT A

6441
03:54:54,800 --> 03:54:55,680
HUNDRED, THEY CHANGED THEIR

6442
03:54:55,680 --> 03:54:56,640
DESIGN.

6443
03:54:56,640 --> 03:55:00,360
SO THERE IS THIS BALANCE BETWEEN

6444
03:55:00,360 --> 03:55:01,680
INNOVATION AND REPRODUCIBILITY.

6445
03:55:01,680 --> 03:55:03,440
SO THOSE ARE THE MOST OF THE

6446
03:55:03,440 --> 03:55:05,440
QUESTIONS WE ADDRESS IN CHOOSING

6447
03:55:05,440 --> 03:55:05,960
OUR CHIPS.

6448
03:55:05,960 --> 03:55:08,600
SO WE PROBABLY HAVE FIVE OR SIX

6449
03:55:08,600 --> 03:55:10,200
DIFFERENT COMMERCIAL CHIPS WE

6450
03:55:10,200 --> 03:55:11,560
USE.

6451
03:55:11,560 --> 03:55:14,040
EACH ARE SUITED FOR DIFFERENT

6452
03:55:14,040 --> 03:55:14,960
PURPOSES.

6453
03:55:14,960 --> 03:55:16,840
SO THAT'S MOSTLY HOW THE

6454
03:55:16,840 --> 03:55:18,200
REASONING HAS GONE.

6455
03:55:18,200 --> 03:55:21,480
I THINK MOST EXCITING IS THAT WE

6456
03:55:21,480 --> 03:55:25,280
CAN SEE THINGS IN 3D UNDER FLOW

6457
03:55:25,280 --> 03:55:28,600
THAT WE NEVER SAW IN 2D.

6458
03:55:28,600 --> 03:55:33,840
AND IT'S PUTTING THINGS IN SOFT

6459
03:55:33,840 --> 03:55:35,280
SUBSTRATES HAS BEEN REALLY

6460
03:55:35,280 --> 03:55:35,680
EXTREMELY HELPFUL.

6461
03:55:35,680 --> 03:55:41,280
>> SOFFIT FOR PURPOSE,    
.

6462
03:55:41,280 --> 03:55:42,360
SIMON MENTIONED AT THE

6463
03:55:42,360 --> 03:55:43,080
BEGINNING, WHAT'S THE QUESTION

6464
03:55:43,080 --> 03:55:47,400
YOU'RE ASKING, AND REALLY VERY

6465
03:55:47,400 --> 03:55:48,960
CRITICALLY WHAT IS THE BEST

6466
03:55:48,960 --> 03:55:50,040
PLATFORM TO ANSWER THAT

6467
03:55:50,040 --> 03:55:50,360
QUESTION.

6468
03:55:50,360 --> 03:55:54,040
LIKE YOU SAID, IT MIGHT BE MANY

6469
03:55:54,040 --> 03:55:56,360
PLATFORMS, DIFFERENT THROUGH

6470
03:55:56,360 --> 03:55:56,720
PUT.

6471
03:55:56,720 --> 03:55:57,680
THANK YOU, CHRISTINE.

6472
03:55:57,680 --> 03:56:03,480
THERE'S A QUESTION IN THE CHAT

6473
03:56:03,480 --> 03:56:06,960
ABOUT FLOW, AND I'M GOING TO ASK

6474
03:56:06,960 --> 03:56:09,840
JEFF AND JASON MAYBE TO TALK A

6475
03:56:09,840 --> 03:56:16,160
LITTLE BIT ABOUT FLOW, I THINK

6476
03:56:16,160 --> 03:56:20,760
THE QUESTION IS ABOUT SOMEONE

6477
03:56:20,760 --> 03:56:21,760
MENTIONED LIKE SHEER STRESS AND

6478
03:56:21,760 --> 03:56:25,200
HOW DO YOU CONTROL -- STRESS

6479
03:56:25,200 --> 03:56:30,080
EFFECTS ON FISH EU CELL -- MEDIA

6480
03:56:30,080 --> 03:56:32,360
FLOW RATES ON EACH MODEL?

6481
03:56:32,360 --> 03:56:33,480
JEFF FIRST, THEN MAYBE JASON,

6482
03:56:33,480 --> 03:56:34,640
CAN YOU GUYS COMMENT ON THAT?

6483
03:56:34,640 --> 03:56:36,640
>> I CAN QUICKLY ANSWER
AND THEN

6484
03:56:36,640 --> 03:56:37,520
JASON PROVIDE ON HIS.

6485
03:56:37,520 --> 03:56:40,680
SO FOR OUR SYSTEM, THE SHEER CAN

6486
03:56:40,680 --> 03:56:43,160
RANGE ANYWHERE FROM ZERO UP TO

6487
03:56:43,160 --> 03:56:47,360
ABOUT 10 OR MORE DINES PER

6488
03:56:47,360 --> 03:56:47,800
SQUARE COUNCILMEMBER.

6489
03:56:47,800 --> 03:56:53,160
I         CENTIMETER.

6490
03:56:53,160 --> 03:56:56,400
WE HAVE A HIGH SHEER FORMAT THAT

6491
03:56:56,400 --> 03:56:59,160
WE CAN USE IF FOR INSTANCE WE'RE

6492
03:56:59,160 --> 03:57:00,040
STUDYING LONG COVID, I THINK

6493
03:57:00,040 --> 03:57:01,040
THAT WOULD BE A SITUATION WHERE

6494
03:57:01,040 --> 03:57:02,640
YOU'D WANT TO GO UP TO THAT 10

6495
03:57:02,640 --> 03:57:05,280
DINES PER SQUARE CENTIMETER.

6496
03:57:05,280 --> 03:57:06,800
MANY OF THE OTHER APPLICATIONS,

6497
03:57:06,800 --> 03:57:08,560
WE WORK IN A SORT OF LOW TO MID

6498
03:57:08,560 --> 03:57:10,200
RANGE SHEER THAT MAY BE

6499
03:57:10,200 --> 03:57:14,320
APPROPRIATE, MAYBE ONE DINE PER

6500
03:57:14,320 --> 03:57:16,760
SQUARE -- WHERE THERE ARE

6501
03:57:16,760 --> 03:57:17,760
SHEER-SENSITIVE CELLS BUT WE CAN

6502
03:57:17,760 --> 03:57:19,160
DIAL IT OR TUNE IT ESSENTIALLY

6503
03:57:19,160 --> 03:57:21,560
FOR THE APPROPRIATE APPLICATION.

6504
03:57:21,560 --> 03:57:27,480
>> SO FOR MINE, WE USE A
SIMILAR

6505
03:57:27,480 --> 03:57:29,120
DINE ZERO FLOW RATE, SO WHAT I

6506
03:57:29,120 --> 03:57:31,000
WANT TO COMMENT IS THE DIFFERENT

6507
03:57:31,000 --> 03:57:32,640
PUMP SYSTEM DO YOU WANT TO USE

6508
03:57:32,640 --> 03:57:40,920
IF YOU'RE CIRCULATING -- REQUIRE

6509
03:57:40,920 --> 03:57:42,560
TO MAINTAIN THE CONTINUOUS FLOW,

6510
03:57:42,560 --> 03:57:44,960
AND THAT WAY WE WILL CHOOSE THE

6511
03:57:44,960 --> 03:57:47,920
SIMPLEST WAY, JUST TO PUT -- ON

6512
03:57:47,920 --> 03:57:49,680
PATH THEAND USING THE GRADIENT

6513
03:57:49,680 --> 03:57:52,160
OF THE DIFFERENT -- WE DID TO

6514
03:57:52,160 --> 03:57:52,560
DROP FLOW.

6515
03:57:52,560 --> 03:57:57,680
SO IN THIS WAY, ALTHOUGH -- THEY

6516
03:57:57,680 --> 03:57:59,000
ARE NOT STABLE, BUT IN A SHORT

6517
03:57:59,000 --> 03:58:01,400
TIME, THEY ARE ACTUALLY QUITE

6518
03:58:01,400 --> 03:58:05,560
STABLE AND IT'S EASY TO AVOID

6519
03:58:05,560 --> 03:58:07,360
ANY -- VOLUME BY CONNECTING THE

6520
03:58:07,360 --> 03:58:09,960
PUPS   

6521
03:58:09,960 --> 03:58:13,880
PUMPS OR ANY -- MICRO FLUID

6522
03:58:13,880 --> 03:58:14,720
DEVICE ALWAYS KILLS EVERYTHING.

6523
03:58:14,720 --> 03:58:18,200
SO ANOTHER THING I WANT TO

6524
03:58:18,200 --> 03:58:19,160
MENTION, PREVIOUS PUBLICATION

6525
03:58:19,160 --> 03:58:24,800
ABOUT THE MICRO HEART.

6526
03:58:24,800 --> 03:58:27,960
ACTUALLY -- HE DEVELOPED A WAY

6527
03:58:27,960 --> 03:58:32,640
TO QUANTIFY WHAT WILL BE THE

6528
03:58:32,640 --> 03:58:36,280
FLOW RATE BY USING CONSOLE

6529
03:58:36,280 --> 03:58:37,040
SIMULATIONS MAYBE YOU WANT TO

6530
03:58:37,040 --> 03:58:38,440
USE THAT AS WELL.

6531
03:58:38,440 --> 03:58:40,000
>> TONY, ACTUALLY THAT WAS
A

6532
03:58:40,000 --> 03:58:41,760
QUESTION FOR YOU AS WELL.

6533
03:58:41,760 --> 03:58:43,280
THE QUESTION WAS, WHAT IS THE

6534
03:58:43,280 --> 03:58:46,680
CORRECT FLOW OF CIRCULATORY

6535
03:58:46,680 --> 03:58:47,680
SYSTEM THROUGH DIFFERENT ORGANS

6536
03:58:47,680 --> 03:58:49,400
AND THEIR PROPER METABOLISM IN

6537
03:58:49,400 --> 03:58:50,280
KIDNEYS OR LIVER.

6538
03:58:50,280 --> 03:58:53,000
HOW DO YOU -- WHEN YOU MAKE

6539
03:58:53,000 --> 03:58:54,440
THESE ORGANS ON A CHIP, WHEN YOU

6540
03:58:54,440 --> 03:58:55,640
HAVE DIFFERENT ORGAN, HOW DO YOU

6541
03:58:55,640 --> 03:58:59,040
ADJUST THE FLOW AND THE OTHER

6542
03:58:59,040 --> 03:59:00,440
QUESTION THAT COMES UP IS WHAT

6543
03:59:00,440 --> 03:59:05,240
MEDIAS DO YOU USE WHEN YOU HAVE

6544
03:59:05,240 --> 03:59:06,600
THESE MULTIORGAN CHIPS?

6545
03:59:06,600 --> 03:59:07,800
TONY, CAN YOU ADDRESS THIS

6546
03:59:07,800 --> 03:59:08,040
QUESTION?

6547
03:59:08,040 --> 03:59:08,880
>> YES, ABSOLUTELY.

6548
03:59:08,880 --> 03:59:11,280
THANK YOU, MARC.

6549
03:59:11,280 --> 03:59:12,040
GREAT QUESTION ACTUALLY BECAUSE

6550
03:59:12,040 --> 03:59:14,640
THIS IS AN IMPORTANT FACT.

6551
03:59:14,640 --> 03:59:16,080
WHEN YOU'RE PUTTING THESE TISSUE

6552
03:59:16,080 --> 03:59:18,840
MODELS ON THE CHIP, YOU HAVE TO

6553
03:59:18,840 --> 03:59:20,120
ACCOUNT FOR A COUPLE OF THINGS.

6554
03:59:20,120 --> 03:59:24,240
THE FIRST ONE IS THE VOLUME OF

6555
03:59:24,240 --> 03:59:24,920
THE ORGAN ITSELF.

6556
03:59:24,920 --> 03:59:26,480
SO YOU KNOW THE LIVER HAS MUCH

6557
03:59:26,480 --> 03:59:29,680
MORE VOLUME THAN THE HEART.

6558
03:59:29,680 --> 03:59:31,760
THE LUNG HAS MORE VOLUME THAN

6559
03:59:31,760 --> 03:59:32,800
THE HEART AND LESS THAN THE

6560
03:59:32,800 --> 03:59:34,240
LIVER, SO YOU HAVE TO

6561
03:59:34,240 --> 03:59:36,560
ACCOMMODATE FOR THAT IN YOUR

6562
03:59:36,560 --> 03:59:38,200
CHIP SYSTEM SO THAT YOUR BODY IN

6563
03:59:38,200 --> 03:59:42,440
A CHIP REALLY DOES REPRESENT THE

6564
03:59:42,440 --> 03:59:43,560
TRUE VOLUME IN A HUMAN.

6565
03:59:43,560 --> 03:59:46,440
YOU DON'T WANT TO HAVE 10 TIMES

6566
03:59:46,440 --> 03:59:47,480
THE HEART THAN YOU DO OF THE

6567
03:59:47,480 --> 03:59:47,680
LIVER.

6568
03:59:47,680 --> 03:59:49,120
SO THAT'S THE FIRST THING.

6569
03:59:49,120 --> 03:59:50,480
THE SECOND THING IS IN TERMS OF

6570
03:59:50,480 --> 03:59:53,880
THE FLOW, THE FLOW IS ACTUALLY

6571
03:59:53,880 --> 03:59:58,880
CONSISTENT WITH A MICROSYSTEM OF

6572
03:59:58,880 --> 04:00:00,600
WHERE WE REDUCE THE MICRO

6573
04:00:00,600 --> 04:00:01,480
FLUIDICS AND MEASURE THE FLUID

6574
04:00:01,480 --> 04:00:02,480
WITHIN THE SYSTEM.

6575
04:00:02,480 --> 04:00:04,000
DEPENDING ON HOW WE CONSTRUCT

6576
04:00:04,000 --> 04:00:05,000
THAT SYSTEM, BECAUSE AS YOU

6577
04:00:05,000 --> 04:00:06,960
KNOW, WE HAVE BEEN PRINTING THEM

6578
04:00:06,960 --> 04:00:09,360
AND WE HAVE ALSO BEEN MAKING

6579
04:00:09,360 --> 04:00:11,640
MICROPHYSIOLOGICAL SYSTEMS WITH

6580
04:00:11,640 --> 04:00:12,840
WELLS AND OTHER SYSTEMS.

6581
04:00:12,840 --> 04:00:13,840
EACH ONE IS DIFFERENT, AND YOU

6582
04:00:13,840 --> 04:00:15,040
REALLY DO HAVE TO FIGURE OUT

6583
04:00:15,040 --> 04:00:17,040
WHAT THE CONVERSION FACTOR IS IN

6584
04:00:17,040 --> 04:00:18,760
TERMS OF THE FLOW THAT GOES TO

6585
04:00:18,760 --> 04:00:19,960
THE BODY, BECAUSE IF YOU REALLY

6586
04:00:19,960 --> 04:00:22,840
THINK ABOUT IT, YOUR OWN BLOOD

6587
04:00:22,840 --> 04:00:24,480
FLOW GOES TO YOUR ENTIRE BODY,

6588
04:00:24,480 --> 04:00:26,480
YOU KNOW, EVERY HOUR BASICALLY,

6589
04:00:26,480 --> 04:00:29,920
YOU KNOW, YOU HAVE YOUR ENTIRE

6590
04:00:29,920 --> 04:00:33,360
BLOOD GO THROUGH YOUR BODY, SO O

6591
04:00:33,360 --> 04:00:34,880
YOU HAVE TO ACCOUNT FOR THE SALE

6592
04:00:34,880 --> 04:00:38,040
THING, WHICH IS ABOUT 4 TO

6593
04:00:38,040 --> 04:00:39,560
5-LITERS OF BLOOD THROUGHOUT

6594
04:00:39,560 --> 04:00:40,440
YOUR SYSTEM.

6595
04:00:40,440 --> 04:00:41,400
THE OTHER THING IS THE ABILITY

6596
04:00:41,400 --> 04:00:42,960
OF THESE STRUCTURES TO INTERACT

6597
04:00:42,960 --> 04:00:44,040
WITH EACH OTHER AND HOW ARE YOU

6598
04:00:44,040 --> 04:00:46,120
GOING TO MEL SURE THAT FLOW IN

6599
04:00:46,120 --> 04:00:47,000
TERMS OF THE MEDIA.

6600
04:00:47,000 --> 04:00:48,560
THE QUESTION WAS ABOUT OF THE

6601
04:00:48,560 --> 04:00:49,080
MEDIA.

6602
04:00:49,080 --> 04:00:51,200
ACTUALLY THAT WAS ONE OF THE

6603
04:00:51,200 --> 04:00:52,800
FIRST DIRECTIVES OF THE INITIAL

6604
04:00:52,800 --> 04:00:53,560
DTRA PROGRAM.

6605
04:00:53,560 --> 04:00:58,440
I WAS HAPPY TO SEE CLINT, HE WAS

6606
04:00:58,440 --> 04:01:00,280
ONE OF THE PEOPLE THAT ASSIGNED

6607
04:01:00,280 --> 04:01:03,960
THAT INITIAL PROGRAM WITH DTRA,

6608
04:01:03,960 --> 04:01:06,480
AND THE GOAL OF THAT PROGRAM WAS

6609
04:01:06,480 --> 04:01:07,000
COMMON MEDIA.

6610
04:01:07,000 --> 04:01:08,600
AND THAT'S WHERE WE WERE ABLE TO

6611
04:01:08,600 --> 04:01:10,320
DO, IS TO CREATE A COMMON MEDIA

6612
04:01:10,320 --> 04:01:14,440
THAT IS ABLE TO -- THAT ALLOWS

6613
04:01:14,440 --> 04:01:16,400
THE SYSTEM TO BE IN A STEADY

6614
04:01:16,400 --> 04:01:17,800
STATE IN TERMS OF EVERYTHING

6615
04:01:17,800 --> 04:01:19,160
THAT'S NEEDED WITHIN THE SYSTEM

6616
04:01:19,160 --> 04:01:22,560
AND THE SYSTEM SELF REGULATES,

6617
04:01:22,560 --> 04:01:25,040
SO WHAT HAPPENS IS INITIALLY THE

6618
04:01:25,040 --> 04:01:26,480
MEDIA GOES THROUGH AND THE

6619
04:01:26,480 --> 04:01:29,000
SYSTEM ITSELF HELPS TO REGULATE

6620
04:01:29,000 --> 04:01:30,040
THE MEDIA SO YOU HAVE SOMETHING

6621
04:01:30,040 --> 04:01:31,640
THAT IS GOOD FOR ALL THE CELL

6622
04:01:31,640 --> 04:01:32,720
TYPES WITHIN THAT SYSTEM.

6623
04:01:32,720 --> 04:01:35,160
SO THIS WAS ACTUALLY ONE OF THE

6624
04:01:35,160 --> 04:01:39,200
PRIMARY DIRECTIVES OF THE

6625
04:01:39,200 --> 04:01:43,760
DEFENSE AGENCY SYSTEM AND IT'S

6626
04:01:43,760 --> 04:01:44,600
WORK VED WELL FOR US.

6627
04:01:44,600 --> 04:01:46,960
>> THANKS, TONY.

6628
04:01:46,960 --> 04:01:50,000
IT'S ACTUALLY -- KIND OF SPLIT

6629
04:01:50,000 --> 04:01:53,480
THE QUESTION INTO TWO QUESTIONS.

6630
04:01:53,480 --> 04:01:54,600
I'LL START WITH YOU, TONY,

6631
04:01:54,600 --> 04:01:56,880
BECAUSE THE QUESTION WAS TO YOU

6632
04:01:56,880 --> 04:01:57,440
DIRECTLY.

6633
04:01:57,440 --> 04:02:00,280
ARE YOU USING HUMAN PRIMARY

6634
04:02:00,280 --> 04:02:02,800
CELLS OR ARE YOU USING IPS

6635
04:02:02,800 --> 04:02:04,000
DERIVED CELLS?

6636
04:02:04,000 --> 04:02:05,320
WE'VE SEEN IN SOME OF THE TALKS

6637
04:02:05,320 --> 04:02:06,520
THAT PEOPLE USED BOTH IN THE

6638
04:02:06,520 --> 04:02:08,920
SAME TISSUE, PRIMARY CELLS AND

6639
04:02:08,920 --> 04:02:12,200
IPS DERIVED CELLS, SO CAN YOU

6640
04:02:12,200 --> 04:02:15,040
TELL US A LITTLE BIT ABOUT HOW

6641
04:02:15,040 --> 04:02:19,320
DO YOU CHOOSE THE CELLS THAT YOU

6642
04:02:19,320 --> 04:02:25,000
USE FOR A PARTICULAR SYSTEM?

6643
04:02:25,000 --> 04:02:25,560
>> ANOTHER GREAT QUESTION.

6644
04:02:25,560 --> 04:02:29,400
SO WE REALLY TRY TO USE NORMAL

6645
04:02:29,400 --> 04:02:32,760
PRIMARY HUMAN CELLS WHEREVER

6646
04:02:32,760 --> 04:02:34,960
POSSIBLE.

6647
04:02:34,960 --> 04:02:37,800
SO FOR THE LIVER STRUCTURES, YOU

6648
04:02:37,800 --> 04:02:39,440
SAW THOSE LIVER CELL TYPES TO

6649
04:02:39,440 --> 04:02:44,120
CREATE THE TISSUES -- THERE ARE

6650
04:02:44,120 --> 04:02:45,760
SOME INSTANCES WHERE YOU HAVE TO

6651
04:02:45,760 --> 04:02:47,200
USE THE IPS.

6652
04:02:47,200 --> 04:02:49,520
WE'D RATHER NOT, BUT SOMETIMES

6653
04:02:49,520 --> 04:02:51,160
YOU HAVE TO BECAUSE THERE'S NO

6654
04:02:51,160 --> 04:02:51,800
EQUIVALENT TO THAT.

6655
04:02:51,800 --> 04:02:53,960
AND SO WHEN THAT'S THE CASE,

6656
04:02:53,960 --> 04:02:55,840
THEN WE WILL USE THE IPS CELLS.

6657
04:02:55,840 --> 04:02:59,880
BUT CERTAINLY WE DO NOT USE ANY

6658
04:02:59,880 --> 04:03:02,520
CELL -- LIKE CHRISTINE MUMMERY

6659
04:03:02,520 --> 04:03:04,400
SAID, I ENJOYED YOUR TALK,

6660
04:03:04,400 --> 04:03:05,360
CHRISTINE, LIKE SHE SAID,

6661
04:03:05,360 --> 04:03:06,440
BASICALLY YOU DON'T WANT TO BE

6662
04:03:06,440 --> 04:03:07,440
USING CELL LINES, RIGHT, YOU

6663
04:03:07,440 --> 04:03:11,840
DON'T WANT TO BE USING HUBIK

6664
04:03:11,840 --> 04:03:12,680
CELLS, THEY'RE

6665
04:03:12,680 --> 04:03:13,680
NON-REPRESENTATIVE OF THE NORMAL

6666
04:03:13,680 --> 04:03:13,880
SYSTEM.

6667
04:03:13,880 --> 04:03:15,200
SO WHEN WE CREATE THESE

6668
04:03:15,200 --> 04:03:16,400
STRUCTURES, WE REALLY WANT TO

6669
04:03:16,400 --> 04:03:18,600
USE NORMAL PRIMARY HUMAN CELLS

6670
04:03:18,600 --> 04:03:21,320
AS MUCH AS POSSIBLE.

6671
04:03:21,320 --> 04:03:24,840
>> OR IF I MAY ADD, YOU
HAVE TO

6672
04:03:24,840 --> 04:03:26,800
DO A HEAD TO HEAD COMPARISON

6673
04:03:26,800 --> 04:03:31,520
WITH YOUR IPS DERIVATIVES.

6674
04:03:31,520 --> 04:03:32,880
THAT'S HOW WE DISCOVERED, OF

6675
04:03:32,880 --> 04:03:34,880
COURSE, THAT THEY WERE IMMATURE

6676
04:03:34,880 --> 04:03:37,000
AND THAT PUTTING IN STROMA MAKES

6677
04:03:37,000 --> 04:03:39,680
THEM TO A CERTAIN EXTENT MATURE.

6678
04:03:39,680 --> 04:03:42,880
SO YOU CAN PEN CH MARK AGAIN THE

6679
04:03:42,880 --> 04:03:43,640
PRIMARY TISSUES.

6680
04:03:43,640 --> 04:03:45,280
PRIMARY TISSUES ARE SOMETIMES

6681
04:03:45,280 --> 04:03:48,160
SUBJECT TO STRESS, SO YOU GET A

6682
04:03:48,160 --> 04:03:49,520
LOT OF STRESS GENES AND YOU HAVE

6683
04:03:49,520 --> 04:03:51,440
TO TAKE CARE OF THAT.

6684
04:03:51,440 --> 04:03:55,560
BECAUSE IT'S NOT -- I MEAN, A

6685
04:03:55,560 --> 04:03:57,880
LUNG LAVAGE IS DIFFERENT BECAUSE

6686
04:03:57,880 --> 04:03:59,280
THAT'S NOT STRESS, BUT IF YOU

6687
04:03:59,280 --> 04:04:01,680
WANT TO ASSOCIATE KIDNEY OR SOME

6688
04:04:01,680 --> 04:04:03,000
OTHER TISSUES, THE STRESS GENES

6689
04:04:03,000 --> 04:04:04,080
GO ALL OVER THE PLACE.

6690
04:04:04,080 --> 04:04:06,960
SO DURING SINGLE CELL RNA SEQ,

6691
04:04:06,960 --> 04:04:08,920
THIS IS NOT NECESSARILY

6692
04:04:08,920 --> 04:04:09,680
INFORMATIVE ALL THE TIME.

6693
04:04:09,680 --> 04:04:11,240
SO I THINK THIS IS JUST USING A

6694
04:04:11,240 --> 04:04:12,520
BIT OF COMMON SENSE TO FIGURE

6695
04:04:12,520 --> 04:04:13,960
OUT WHAT'S THE BEST FOR YOUR

6696
04:04:13,960 --> 04:04:15,200
SYSTEM, WHAT'S YOUR QUESTION,

6697
04:04:15,200 --> 04:04:17,880
WHAT DO YOU WANT TO KNOW THE

6698
04:04:17,880 --> 04:04:19,280
ANSWER TO WILL GUIDE US.

6699
04:04:19,280 --> 04:04:21,880
SO IT'S CLEAR WE CAN, OF COURSE,

6700
04:04:21,880 --> 04:04:24,240
GET MANY, MANY TISSUES FROM

6701
04:04:24,240 --> 04:04:28,600
MANY, MANY PATIENTS IF WE USE

6702
04:04:28,600 --> 04:04:30,560
IPS, AND YOU HAVE THIS

6703
04:04:30,560 --> 04:04:31,760
POSSIBILITY OF ALMOST

6704
04:04:31,760 --> 04:04:33,400
NEUTRALIZING BATCH TO BATCH

6705
04:04:33,400 --> 04:04:34,720
DIFFERENCES.

6706
04:04:34,720 --> 04:04:37,240
SO THAT HAS AN UPSIDE.

6707
04:04:37,240 --> 04:04:42,600
THE DOWNSIDE, AS I SAID, RIDES

6708
04:04:42,600 --> 04:04:45,520
UP FRONT OF THE IMMATURITY OF

6709
04:04:45,520 --> 04:04:47,080
THE SYSTEM AND MANY AMOUNTS OF

6710
04:04:47,080 --> 04:04:47,440
MANIPULATION.

6711
04:04:47,440 --> 04:04:51,240
SO I THIL STIL      STILL THINKS

6712
04:04:51,240 --> 04:04:53,760
BENEFITS TO HAVING IPS OR HUMAN

6713
04:04:53,760 --> 04:04:54,200
ORGANOIDS.

6714
04:04:54,200 --> 04:04:56,080
WHAT'S NOT BEING COMBINED YET,

6715
04:04:56,080 --> 04:04:58,680
AND WE'RE GOING TO BE DOING THIS

6716
04:04:58,680 --> 04:05:02,080
WITH PEOPLE WORKING WITH HANS

6717
04:05:02,080 --> 04:05:03,600
CLEVERS IS COMBINING THE

6718
04:05:03,600 --> 04:05:09,160
ORGANOIDS WITH IPS -- WHAT YOU

6719
04:05:09,160 --> 04:05:11,800
CANNOT DO WITH THE ADULT

6720
04:05:11,800 --> 04:05:13,200
ORGANOIDS IS MAKE STROMA.

6721
04:05:13,200 --> 04:05:16,520
YOU CAN'T MAKE THE IMMUNE SYSTEM

6722
04:05:16,520 --> 04:05:19,040
ISOGENICLY -- YOU CAN GET IT FOR

6723
04:05:19,040 --> 04:05:21,440
PATIENTS BUT YOU CAN'T DO IT --

6724
04:05:21,440 --> 04:05:24,280
AND FROM IPS, CAN YOU MAKE

6725
04:05:24,280 --> 04:05:26,240
FAIRLY GOOD MONOCYTES.

6726
04:05:26,240 --> 04:05:28,760
YOU CAN MAKE THE TISSUE

6727
04:05:28,760 --> 04:05:31,520
APPROPRIATE STROMA, BUT YOU

6728
04:05:31,520 --> 04:05:33,680
CAN'T GET MATURE EPITHELIAL

6729
04:05:33,680 --> 04:05:35,320
COMPONENT THE WAY YOU CAN GET

6730
04:05:35,320 --> 04:05:37,160
THAT OF ORGANOIDS.

6731
04:05:37,160 --> 04:05:39,040
SO WHAT YOU WANT TO KNOW, YOU

6732
04:05:39,040 --> 04:05:40,440
WANT IT AS SIMPLE AS POSSIBLE TO

6733
04:05:40,440 --> 04:05:41,200
ANSWER YOUR QUESTION.

6734
04:05:41,200 --> 04:05:45,040
AS COMPLEX AS NECESSARY TO MODEL

6735
04:05:45,040 --> 04:05:47,920
YOUR DISEASE OR DRUG RESPONSE.

6736
04:05:47,920 --> 04:05:49,600
>> CHRISTINE, TO FOLLOW UP
IN

6737
04:05:49,600 --> 04:05:51,040
ONE OF THE TALKS, I FORGOT IF IT

6738
04:05:51,040 --> 04:05:52,280
WAS YOU OR SOMEONE ELSE, THE

6739
04:05:52,280 --> 04:05:54,240
WHOLE ASPECT OF CONTEXT, TISSUE

6740
04:05:54,240 --> 04:05:56,640
CONTEXT, RIGHT?

6741
04:05:56,640 --> 04:05:59,160
YOU START WITH AN IPS FROM A

6742
04:05:59,160 --> 04:06:00,360
SKIN FIBROBLAST AND THEN YOU'RE

6743
04:06:00,360 --> 04:06:04,440
TRYING TO MAKE A LONG EPITHELIAL

6744
04:06:04,440 --> 04:06:05,600
CELLS, ARE YOU LOSING THE SORT

6745
04:06:05,600 --> 04:06:09,880
OF TISSUE CONTEXT OR BY JUST

6746
04:06:09,880 --> 04:06:11,320
PUTTING OTHER CELLS, STROMA

6747
04:06:11,320 --> 04:06:15,480
CELLS, YOU WILL GAIN THAT TISSUE

6748
04:06:15,480 --> 04:06:16,760
CONTEXT THAT MIGHT DIFFERENTIATE

6749
04:06:16,760 --> 04:06:20,480
ALSO THE CELLS, ENDOTHELIAL

6750
04:06:20,480 --> 04:06:20,720
CELLS --

6751
04:06:20,720 --> 04:06:22,160
>> SO YES AND NO.

6752
04:06:22,160 --> 04:06:24,240
SO THE STROMAL CELLS LIKE THE

6753
04:06:24,240 --> 04:06:25,760
ENDOTHELIAL CELLS CAN GET FROM

6754
04:06:25,760 --> 04:06:27,040
IPS CELL USING A STANDARD

6755
04:06:27,040 --> 04:06:28,440
PROTOCOL ARE STILL PLASTIC.

6756
04:06:28,440 --> 04:06:32,440
IF YOU CO-CULTURE THEM IN AN

6757
04:06:32,440 --> 04:06:34,080
ORGANOID OR A PARTICULAR TISSUE

6758
04:06:34,080 --> 04:06:35,800
TYPE, THEY UPREGULATE

6759
04:06:35,800 --> 04:06:36,560
TRANSCRIPTION FACTORS OF THE

6760
04:06:36,560 --> 04:06:37,320
TISSUE THEY'RE IN.

6761
04:06:37,320 --> 04:06:39,320
SO THEY'RE PLASTIC ENOUGH TO

6762
04:06:39,320 --> 04:06:40,320
ADULT IDENTITY.

6763
04:06:40,320 --> 04:06:42,560
SO IN THE FIRST PLACE, WE DID IT

6764
04:06:42,560 --> 04:06:43,320
THE DIFFICULT WAY.

6765
04:06:43,320 --> 04:06:45,120
WE GOT THE PROGENITOR OF THE

6766
04:06:45,120 --> 04:06:46,320
ORGAN SO IN THIS CASE, IT WAS

6767
04:06:46,320 --> 04:06:48,720
THE CARDIAC PROGENITOR, WE MADE

6768
04:06:48,720 --> 04:06:50,600
A CARDIAC ENDOTHELIAL CELLS, AND

6769
04:06:50,600 --> 04:06:52,200
THEN WE LOOKED AT THE

6770
04:06:52,200 --> 04:06:58,120
TRANSCRIPTION PROFILE AND WE SEE

6771
04:06:58,120 --> 04:06:59,840
CARDIAC TRANSCRIPTION FACTORS IN

6772
04:06:59,840 --> 04:07:01,280
A BONA FIDE ENDOTHELIAL CELL.

6773
04:07:01,280 --> 04:07:03,160
THAT TELLS BUT TISSUE

6774
04:07:03,160 --> 04:07:04,360
SPECIFICITY AND THAT WAS AN

6775
04:07:04,360 --> 04:07:07,080
EXTRA SORT OF MESSAGE, DON'T USE

6776
04:07:07,080 --> 04:07:08,920
HUVEX, BECAUSE THEY'RE NOT TRUE

6777
04:07:08,920 --> 04:07:09,520
TISSUE-SPECIFIC CELLS.

6778
04:07:09,520 --> 04:07:11,480
ON THE OTHER HAND, IT TURNED OUT

6779
04:07:11,480 --> 04:07:13,640
THAT PLASTICITY MEANT WITH A

6780
04:07:13,640 --> 04:07:17,240
CERTAIN A COCULTURE, YOU COULD

6781
04:07:17,240 --> 04:07:18,480
RECAPITULATE SOME OF THE

6782
04:07:18,480 --> 04:07:19,680
TISSUE-SPECIFIC FEATURES AND THE

6783
04:07:19,680 --> 04:07:22,560
SAME IS TRUE OF FIBROBLASTS TO

6784
04:07:22,560 --> 04:07:26,000
SOME EXTENT.

6785
04:07:26,000 --> 04:07:26,920
SO IT DEPENDS WHAT YOU WANT TO

6786
04:07:26,920 --> 04:07:27,200
DO.

6787
04:07:27,200 --> 04:07:28,840
IF YOU JUST WANT SOMETHING THAT

6788
04:07:28,840 --> 04:07:30,040
GIVES YOU FLOW, THAT'S FINE.

6789
04:07:30,040 --> 04:07:31,680
IF YOU WANT TO DO SOMETHING

6790
04:07:31,680 --> 04:07:32,560
ABOUT -- LEARN SOMETHING ABOUT

6791
04:07:32,560 --> 04:07:35,840
THE BIOLOGY OF VASCULAR CELLS,

6792
04:07:35,840 --> 04:07:36,720
THE VASCULATURE YOU PUT IN, THEN

6793
04:07:36,720 --> 04:07:40,000
IT'S A COMPLETELY DIFFERENT

6794
04:07:40,000 --> 04:07:40,280
QUESTION.

6795
04:07:40,280 --> 04:07:41,680
>> IF I MAY ANSWER THAT,
BECAUSE

6796
04:07:41,680 --> 04:07:43,160
YOU KNOW ONE OF THE STRATEGIES

6797
04:07:43,160 --> 04:07:45,920
THAT WE HAD TO USE AS I

6798
04:07:45,920 --> 04:07:47,680
MENTIONED IS REALLY USING THE

6799
04:07:47,680 --> 04:07:51,360
EXTRACELLULAR MATRIX IN THE

6800
04:07:51,360 --> 04:07:51,800
ORGANOIDS.

6801
04:07:51,800 --> 04:07:53,240
THE REASON FOR THAT IS THAT WHEN

6802
04:07:53,240 --> 04:07:57,520
YOU'RE LOOKING AT NORMAL TISSUE,

6803
04:07:57,520 --> 04:07:58,400
WHEN YOU'RE LOOKING AT THE

6804
04:07:58,400 --> 04:07:59,160
ORGAN, THE ORGAN AT THE END OF

6805
04:07:59,160 --> 04:08:02,560
THE DAY IS BASICALLY THE CELLS,

6806
04:08:02,560 --> 04:08:04,040
AND THE EXTRACELLULAR MATRIX.

6807
04:08:04,040 --> 04:08:05,160
THAT'S WHAT IT IS, RIGHT?

6808
04:08:05,160 --> 04:08:06,920
IT'S THE CELLS AND THE GLUE THAT

6809
04:08:06,920 --> 04:08:09,760
HOLDS THE CELLS TOGETHER.

6810
04:08:09,760 --> 04:08:11,280
THE EXTRACELLULAR MATRIX PLAYS A

6811
04:08:11,280 --> 04:08:13,360
MAJOR ROLE IN THE FUNCTIONALITY

6812
04:08:13,360 --> 04:08:14,560
OF THE TISSUE, INCLUDING THE

6813
04:08:14,560 --> 04:08:15,680
STIFFNESS AS I SHOWED IN ONE OF

6814
04:08:15,680 --> 04:08:18,920
THE SLIDES.

6815
04:08:18,920 --> 04:08:20,520
SO THAT'S CRITICAL HONESTLY

6816
04:08:20,520 --> 04:08:23,760
BECAUSE FOR THE CELLS TO SE SECE

6817
04:08:23,760 --> 04:08:25,760
THEIR OWN ECM, IT TAKES TIME.

6818
04:08:25,760 --> 04:08:27,800
SO CELLS WILL SECRETE THEIR OWN

6819
04:08:27,800 --> 04:08:29,360
ECM, BUT THAT IS A TIME PROCESS

6820
04:08:29,360 --> 04:08:30,760
FOR THAT TO ACTUALLY OCCUR AND

6821
04:08:30,760 --> 04:08:33,800
TO BUILD THAT THREE DIMENSIONAL

6822
04:08:33,800 --> 04:08:34,520
ORGANIZATIONAL STRUCTURE.

6823
04:08:34,520 --> 04:08:38,280
SO THAT IS WHY VERY EARLY ON, WE

6824
04:08:38,280 --> 04:08:40,440
BASICALLY WENT TO THE STRATEGY,

6825
04:08:40,440 --> 04:08:43,760
WE JUST INK WRAIT      INCORPOR.

6826
04:08:43,760 --> 04:08:45,000
YOU'RE NOT GOING TO HAVE THESE

6827
04:08:45,000 --> 04:08:46,160
ORGANOIDS AROUND TOO LONG TO

6828
04:08:46,160 --> 04:08:48,680
ACTUALLY THEM SECRETE THAT ECM.

6829
04:08:48,680 --> 04:08:51,160
THAT'S CRITICAL, WHEN WE LOOK AT

6830
04:08:51,160 --> 04:08:51,960
THE INFECTIVITY FOR EXAMPLE OF

6831
04:08:51,960 --> 04:08:56,240
THOSE LUNG MODELS THAT I SHOWED,

6832
04:08:56,240 --> 04:08:58,280
WE USE LUNG-SPECIFIC ECM, AND WE

6833
04:08:58,280 --> 04:09:01,280
FIND THAT THAT'S CRITICAL FOR

6834
04:09:01,280 --> 04:09:04,440
THE MIGRATION OF THE NEUTROPHILS

6835
04:09:04,440 --> 04:09:05,560
THROUGH THE VIRAL RESPONSE.

6836
04:09:05,560 --> 04:09:08,480
AND THIS IS A PROGRAM THAT DAVE

6837
04:09:08,480 --> 04:09:10,880
HONE FROM DTRA HAS NOW PUT

6838
04:09:10,880 --> 04:09:13,000
TOGETHER, THIS PATNOS PROGRAM

6839
04:09:13,000 --> 04:09:14,960
FOR US TO LOOK AT VIRUSES AND

6840
04:09:14,960 --> 04:09:18,040
HOW THEY ACTUALLY PENETRATE THE

6841
04:09:18,040 --> 04:09:19,320
CELL MEMBRANES AND HOW THEY

6842
04:09:19,320 --> 04:09:20,960
ACTUALLY GET THROUGH ALL THOSE

6843
04:09:20,960 --> 04:09:23,680
CELL LAYERS, AND YOU KNOW, IT'S

6844
04:09:23,680 --> 04:09:25,880
OKAY TO GET THROUGH AN

6845
04:09:25,880 --> 04:09:26,960
EPITHELIAL CELL LAYER BUT WHEN

6846
04:09:26,960 --> 04:09:29,360
YOU DON'T HAVE ECM THERE, HOW

6847
04:09:29,360 --> 04:09:30,560
REALISTIC TO THE NATURAL

6848
04:09:30,560 --> 04:09:30,840
RESPONSE.

6849
04:09:30,840 --> 04:09:32,560
>> THAT'S WHY ALL MICRO
TISSUES

6850
04:09:32,560 --> 04:09:33,120
ARE THREE WEEKS OLD.

6851
04:09:33,120 --> 04:09:36,360
THEY HAVE TO PRODUCE THEIR OWN

6852
04:09:36,360 --> 04:09:37,160
CARDIOMYOCYTE MATRIX.

6853
04:09:37,160 --> 04:09:38,960
BUT THAT'S ALSO CONTRIBUTED BY

6854
04:09:38,960 --> 04:09:39,800
THE STROMAL CELLS.

6855
04:09:39,800 --> 04:09:41,080
>> YEAH.

6856
04:09:41,080 --> 04:09:42,280
SO I THINK IT'S SO IMPORTANT TO

6857
04:09:42,280 --> 04:09:43,280
HAVE THAT ECM.

6858
04:09:43,280 --> 04:09:43,880
IT REALLY IS.

6859
04:09:43,880 --> 04:09:45,360
>> ABSOLUTELY.

6860
04:09:45,360 --> 04:09:46,880
>> SO THERE'S A QUESTION
IN THE

6861
04:09:46,880 --> 04:09:49,280
CHAT THAT SAYS, HOW DO YOU MAKE

6862
04:09:49,280 --> 04:09:51,480
SURE THAT THE TISSUE MODELS

6863
04:09:51,480 --> 04:09:53,320
REPRESENT HUMAN PHYSIOLOGY?

6864
04:09:53,320 --> 04:09:55,280
SO IT'S TIED TO YOUR DISCUSSION

6865
04:09:55,280 --> 04:09:57,080
IN THE SENSE THAT, LIKE, WELL,

6866
04:09:57,080 --> 04:09:58,920
IF I WANT TO MAKE A LUNG TISSUE,

6867
04:09:58,920 --> 04:10:02,720
I NEED TO FIND SOME LUNG ECM

6868
04:10:02,720 --> 04:10:03,840
SOMEWHERE, WHETHER IT'S

6869
04:10:03,840 --> 04:10:05,920
COMMERCIALLY OR FIND A SOURCE,

6870
04:10:05,920 --> 04:10:09,640
AND THEN HOW -- WHAT SORT OF

6871
04:10:09,640 --> 04:10:10,840
VALIDATIONS DO WE NEED TO DO,

6872
04:10:10,840 --> 04:10:11,200
RIGHT?

6873
04:10:11,200 --> 04:10:12,600
I MEAN --

6874
04:10:12,600 --> 04:10:15,560
>> THAT'S A REALLY GOOD

6875
04:10:15,560 --> 04:10:16,240
QUESTION, BECAUSE THE QUESTION

6876
04:10:16,240 --> 04:10:18,400
IS REALLY, WHAT CAN YOU ACTUALLY

6877
04:10:18,400 --> 04:10:20,040
MEASURE IN THE HUMAN BODY THAT

6878
04:10:20,040 --> 04:10:23,200
YOU COULD TRANSLATE INTO YOUR

6879
04:10:23,200 --> 04:10:24,000
MODEL?

6880
04:10:24,000 --> 04:10:28,560
YOU CAN'T MEASURE -- IN THE

6881
04:10:28,560 --> 04:10:30,280
HUMAN BODY DB EPITHELIAL

6882
04:10:30,280 --> 04:10:30,600
RESISTANCE.

6883
04:10:30,600 --> 04:10:33,920
YOU CAN MEASURE THAT IN ISOLATED

6884
04:10:33,920 --> 04:10:34,360
EP  

6885
04:10:34,360 --> 04:10:34,680
EPITHELIUM.

6886
04:10:34,680 --> 04:10:35,880
SO IN A NUMBER OF PARAMETERS,

6887
04:10:35,880 --> 04:10:38,160
YOU CAN DO A HEAD TO HEAD

6888
04:10:38,160 --> 04:10:39,600
COMPARISON NUMERICALLY,

6889
04:10:39,600 --> 04:10:40,280
QUANTITATIVELY IT'S VERY

6890
04:10:40,280 --> 04:10:40,560
LIMITED.

6891
04:10:40,560 --> 04:10:42,360
SO FOR A HEART, YOU CAN DO THE

6892
04:10:42,360 --> 04:10:44,520
ACTION PRO TENSION.

6893
04:10:44,520 --> 04:10:44,800
 POTENTIAL.

6894
04:10:44,800 --> 04:10:46,480
CAN YOU DO IT PRIMARY.

6895
04:10:46,480 --> 04:10:49,360
IN THE HEART ITSELF AND IN THE

6896
04:10:49,360 --> 04:10:50,200
MODEL.

6897
04:10:50,200 --> 04:10:51,520
BUT WHAT ELSE?

6898
04:10:51,520 --> 04:10:53,400
SECRETED FACTORS, SO MARKER, BUT

6899
04:10:53,400 --> 04:10:55,360
YOU HAVE TO DOWNSCALE THAT OR

6900
04:10:55,360 --> 04:10:59,960
UPSCALE TO MATCH THE AMOUNT OF

6901
04:10:59,960 --> 04:11:01,440
BLOOD AND AMOUNT OF TISSUE IN

6902
04:11:01,440 --> 04:11:03,920
THE HUMAN BHO DE.

6903
04:11:03,920 --> 04:11:04,120
 BODY.

6904
04:11:04,120 --> 04:11:05,720
SO THESE ARE VERY DIFFICULT

6905
04:11:05,720 --> 04:11:07,280
CALCULATIONS.

6906
04:11:07,280 --> 04:11:09,320
PUTTING SENSORS IN THE BODY TO

6907
04:11:09,320 --> 04:11:11,000
DETECT THINGS SO THAT IT REALLY

6908
04:11:11,000 --> 04:11:12,120
IS A LOT OF WORK TO BE DONE

6909
04:11:12,120 --> 04:11:12,560
THERE.

6910
04:11:12,560 --> 04:11:14,280
SO AT THE MOMENT, WE MOSTLY GO

6911
04:11:14,280 --> 04:11:17,560
FOR SINGLE CELL RNA SEQ OR SOME

6912
04:11:17,560 --> 04:11:19,760
SORT OF GENOMICS OROMIX ASSAY TO

6913
04:11:19,760 --> 04:11:21,480
FIGURE THAT OUT.

6914
04:11:21,480 --> 04:11:23,000
SO LOOK AT THE METABOLIC PROFILE

6915
04:11:23,000 --> 04:11:24,360
OR THINGS LIKE THAT.

6916
04:11:24,360 --> 04:11:26,000
BUT IT'S QUITE LIMITED, THE

6917
04:11:26,000 --> 04:11:27,200
NUMBER OF HEAD TO HEAD

6918
04:11:27,200 --> 04:11:28,000
COMPARISONS YOU CAN DO.

6919
04:11:28,000 --> 04:11:32,000
>> AND THEN ACCESS TO THIS
HUMAN

6920
04:11:32,000 --> 04:11:35,600
DATA, RIGHT?

6921
04:11:35,600 --> 04:11:37,040
WHERE IS THIS DATA RESIDING AND

6922
04:11:37,040 --> 04:11:39,440
HOW DO YOU GET IT?

6923
04:11:39,440 --> 04:11:41,080
WHETHER IT'S PUBLIC DATABASES OR

6924
04:11:41,080 --> 04:11:42,520
WHETHER YOU HAVE COLLABORATORS

6925
04:11:42,520 --> 04:11:46,120
THAT HAVE GENERATED IT.

6926
04:11:46,120 --> 04:11:47,080
JEFF, YOU HAVE A BUNCH OF

6927
04:11:47,080 --> 04:11:50,360
QUESTIONS, IF YOU GO TO THE Q
&

6928
04:11:50,360 --> 04:11:54,400
A BOX THERE'S A BUNCH OF

6929
04:11:54,400 --> 04:11:55,320
QUESTIONS SPECIFIC TO YOUR

6930
04:11:55,320 --> 04:11:55,520
MODEL.

6931
04:11:55,520 --> 04:11:58,160
IF YOU COULD ADDRESS THOSE, TYPE

6932
04:11:58,160 --> 04:11:59,880
IN THE ANSWER, THAT WOULD BE

6933
04:11:59,880 --> 04:12:03,720
GREAT.

6934
04:12:03,720 --> 04:12:05,680
>> THANK YOU, MARK.

6935
04:12:05,680 --> 04:12:06,120
CERTAINLY.

6936
04:12:06,120 --> 04:12:08,280
I SEE ONE QUESTION FROM DAVID

6937
04:12:08,280 --> 04:12:11,160
ABOUT COMBINATION, THAT'S A

6938
04:12:11,160 --> 04:12:14,640
GREAT QUESTION LOOKING AT THE

6939
04:12:14,640 --> 04:12:15,200
COMBINATION.

6940
04:12:15,200 --> 04:12:16,320
IT'S NOT SOMETHING WE'VE TESTED

6941
04:12:16,320 --> 04:12:17,280
YET BUT SOMETHING WE COULD

6942
04:12:17,280 --> 04:12:18,480
CERTAINLY DO IN OUR SYSTEM.

6943
04:12:18,480 --> 04:12:22,640
WE COULD DO THE TWO OF THEM IN

6944
04:12:22,640 --> 04:12:23,080
ISOLATION.

6945
04:12:23,080 --> 04:12:24,960
WE DIDN'T INCLUDE THE RITONAVIR

6946
04:12:24,960 --> 04:12:28,320
BECAUSE THAT'S REALLY A

6947
04:12:28,320 --> 04:12:29,240
PHARMACOKINETIC COMPOUND THAT'S

6948
04:12:29,240 --> 04:12:30,400
ADDED TO CONTROL LIVER

6949
04:12:30,400 --> 04:12:33,800
METABOLISM, BUT I THINK WE COULD

6950
04:12:33,800 --> 04:12:35,200
CERTAINLY LOOK AT COMBINATION

6951
04:12:35,200 --> 04:12:36,200
THERAPIES IN THE SYSTEM GIVEN

6952
04:12:36,200 --> 04:12:37,720
THE THROUGH PUT AND THE SORT OF

6953
04:12:37,720 --> 04:12:41,800
STATISTICAL NATURE THAT WE HAVE

6954
04:12:41,800 --> 04:12:42,000
HERE.

6955
04:12:42,000 --> 04:12:42,600
THAT'S A GREAT QUESTION.

6956
04:12:42,600 --> 04:12:44,120
I THINK ANOTHER QUESTION WAS

6957
04:12:44,120 --> 04:12:46,160
JUST REGARDING THE MOLNUPIRAVIR,

6958
04:12:46,160 --> 04:12:47,720
WHETHER WE USED THE PARENT

6959
04:12:47,720 --> 04:12:49,120
MOLECULE OR THE PRO DRUG.

6960
04:12:49,120 --> 04:12:50,960
WE USED THE PARENT MOLECULE.

6961
04:12:50,960 --> 04:12:53,800
SO I THINK THERE'S ALWAYS

6962
04:12:53,800 --> 04:12:54,760
THESE -- THESE SORT OF GET AT

6963
04:12:54,760 --> 04:12:55,920
THE QUESTION OF THE INTRODUCTION

6964
04:12:55,920 --> 04:12:59,920
OF THE COMPOUND AND HOW WE MIMIC

6965
04:12:59,920 --> 04:13:01,160
IN VIVO WITH THAT, AND THE FACT

6966
04:13:01,160 --> 04:13:03,280
THAT WE HAVE TWO ORAL DRUGS AND

6967
04:13:03,280 --> 04:13:05,440
ONE INJECTABLE DRUG AND HOW DO

6968
04:13:05,440 --> 04:13:06,840
WE SORT OF MIMIC THAT.

6969
04:13:06,840 --> 04:13:09,880
SO THINK, TONY ATALA MADE A

6970
04:13:09,880 --> 04:13:11,440
GREAT COMMENT EARLIER ON IN HIS

6971
04:13:11,440 --> 04:13:12,880
TALK THAT WE'RE STILL -- THERE'S

6972
04:13:12,880 --> 04:13:14,280
STILL A LOT OF WORK TO BE DONE

6973
04:13:14,280 --> 04:13:15,160
WITH THESE SYSTEMS.

6974
04:13:15,160 --> 04:13:16,680
WE'RE MAKING A LOT OF PROGRESS

6975
04:13:16,680 --> 04:13:19,960
BUT ULTIMATELY RECAPITULATING

6976
04:13:19,960 --> 04:13:21,520
THE IN VIVO MICROENVIRONMENT AND

6977
04:13:21,520 --> 04:13:22,920
PUTTING THESE TOGETHER IS

6978
04:13:22,920 --> 04:13:24,760
CRITICAL, HAVING THESE VARIOUS

6979
04:13:24,760 --> 04:13:26,400
COMPONENTS, SO TOWARD THAT END,

6980
04:13:26,400 --> 04:13:27,760
WE'RE ADDING THE IMMUNE

6981
04:13:27,760 --> 04:13:30,360
COMPONENT INTO OUR LUNG MODEL IN

6982
04:13:30,360 --> 04:13:31,800
COLLABORATION WITH BARDA, AND

6983
04:13:31,800 --> 04:13:34,400
WE'RE ALSO ADDING SENSORS SO WE

6984
04:13:34,400 --> 04:13:36,000
CAN MONITOR THE MICROENVIRONMENT

6985
04:13:36,000 --> 04:13:37,600
AND COMPARE TO IN VIVO.

6986
04:13:37,600 --> 04:13:38,880
AS CHRISTINE WAS TALKING ABOUT

6987
04:13:38,880 --> 04:13:40,080
EARLIER, WITH SOME OF THESE

6988
04:13:40,080 --> 04:13:42,720
SECRETED FACTORS LIKE THE

6989
04:13:42,720 --> 04:13:43,640
REACTIVE OXYGEN SPECIES.

6990
04:13:43,640 --> 04:13:44,240
>> THANK YOU.

6991
04:13:44,240 --> 04:13:47,520
I HAVE A QUESTION FOR JASON, AND

6992
04:13:47,520 --> 04:13:50,600
IT HAS DO WITH GOING BACK TO

6993
04:13:50,600 --> 04:13:52,560
PRIMARY CELLS, IPS CELLS.

6994
04:13:52,560 --> 04:13:56,640
SO YOU SHOW US WHERE YOU TRY TO

6995
04:13:56,640 --> 04:13:59,680
IMMORTGAGIZE       

6996
04:13:59,680 --> 04:14:01,200
IMMORTALIZE YOUR CELLS TO GET

6997
04:14:01,200 --> 04:14:03,160
BETTER REPRODUCIBILITY, AND THE

6998
04:14:03,160 --> 04:14:06,800
QUESTION IS REALLY, SHOULDN'T WE

6999
04:14:06,800 --> 04:14:10,280
ACTUALLY LEARN HOW TO HANDLE

7000
04:14:10,280 --> 04:14:11,160
VARIABILITY, ESPECIALLY FROM

7001
04:14:11,160 --> 04:14:15,080
PATIENT TO PATIENT INSTEAD OF

7002
04:14:15,080 --> 04:14:17,840
TRYING TO ENGINEER CELLS SO WE

7003
04:14:17,840 --> 04:14:19,680
GET THE TECHNICAL

7004
04:14:19,680 --> 04:14:20,080
REPRODUCIBILITY?

7005
04:14:20,080 --> 04:14:21,880
HOW DO YOU GUYS HANDLE THESE

7006
04:14:21,880 --> 04:14:23,280
KIND OF DECISIONS?

7007
04:14:23,280 --> 04:14:25,720
>> SO MY UNDERSTANDING IS
KIND

7008
04:14:25,720 --> 04:14:27,120
OF LIKE -- THEY ARE JUST TOOLS.

7009
04:14:27,120 --> 04:14:30,160
FOR EXAMPLE, SOME PATIENT

7010
04:14:30,160 --> 04:14:34,360
DRUG -- AND THEN YOU FIND THE

7011
04:14:34,360 --> 04:14:36,080
SPECIFIC GENE THAT MUTATED.

7012
04:14:36,080 --> 04:14:37,840
THERE IS SPECIFIC MUTATION IN

7013
04:14:37,840 --> 04:14:38,400
ENDOTHELIAL CELLS.

7014
04:14:38,400 --> 04:14:43,400
YOU CAN ACTUALLY INDUCE THOSE

7015
04:14:43,400 --> 04:14:44,720
MUTATIONS IN THE -- CELLS AND

7016
04:14:44,720 --> 04:14:46,600
THEN YOU CAN USE THOSE AS A TOOL

7017
04:14:46,600 --> 04:14:50,440
TO STUDY FUNCTIONALLY HOW THOSE

7018
04:14:50,440 --> 04:14:53,840
MUTATIONS ACTUALLY CAUSE THOSE

7019
04:14:53,840 --> 04:14:54,680
DYSFUNCTION.

7020
04:14:54,680 --> 04:14:58,080
SO IT IS A TOOL BUT IT'S NOT

7021
04:14:58,080 --> 04:15:00,920
ALL -- IT'S NOT -- SO WE ALWAYS

7022
04:15:00,920 --> 04:15:05,280
NEED TO FIND KIND OF DIFFERENCES

7023
04:15:05,280 --> 04:15:06,840
FROM THE PATIENT AND THEN JUST

7024
04:15:06,840 --> 04:15:10,320
TO VALIDATE USING THE CELL

7025
04:15:10,320 --> 04:15:11,440
LINE -- THAT'S MY UNDERSTANDING.

7026
04:15:11,440 --> 04:15:14,920
>> SO I GUESS IT GOES BACK
TO

7027
04:15:14,920 --> 04:15:15,920
THE POINT CHRISTINE WAS MAKING,

7028
04:15:15,920 --> 04:15:17,000
IT REALLY DEPENDS ON WHAT YOU

7029
04:15:17,000 --> 04:15:19,240
WOONT TO     

7030
04:15:19,240 --> 04:15:20,480
WANT TO USE THE SYSTEM FOR AND

7031
04:15:20,480 --> 04:15:22,800
WHAT CELLS YOU USE, BECAUSE

7032
04:15:22,800 --> 04:15:29,280
JEFF, YOU SHOWED BEAUTIFUL --

7033
04:15:29,280 --> 04:15:30,760
CVs IN YOUR SYSTEM AND THAT

7034
04:15:30,760 --> 04:15:32,000
WAS FROM PATIENT TO PATIENT, YOU

7035
04:15:32,000 --> 04:15:33,240
REALLY DIDN'T SEE MUCH VARIATION

7036
04:15:33,240 --> 04:15:35,600
IN TERMS OF INFECTIVITY.

7037
04:15:35,600 --> 04:15:36,720
SO -- AND THOSE WERE PRIMARY

7038
04:15:36,720 --> 04:15:39,640
CELLS, SO IT'S PRETTY AMAZING AT

7039
04:15:39,640 --> 04:15:41,520
LEAST FOR THOSE PRIMARY CELLS,

7040
04:15:41,520 --> 04:15:44,080
EPITHELIAL CELLS HOW ROBUST THE

7041
04:15:44,080 --> 04:15:49,920
SYSTEM IS, AND REALLY

7042
04:15:49,920 --> 04:15:52,080
TECHNICALLY, PHYSIOLOGICALLY,

7043
04:15:52,080 --> 04:15:53,520
YOU SEEM TO BE READY FOR PRIME

7044
04:15:53,520 --> 04:15:56,360
TIME SCREENING.

7045
04:15:56,360 --> 04:15:58,040
>> IT IS A VERY ROBUST
SYSTEM.

7046
04:15:58,040 --> 04:15:59,000
I THINK SOME OF WHAT WOULD

7047
04:15:59,000 --> 04:16:01,960
REALLY BE INTERESTING AND WOULD

7048
04:16:01,960 --> 04:16:02,520
PROBABLY INTRODUCE MORE

7049
04:16:02,520 --> 04:16:03,840
VARIABILITY IS IF WE START TO

7050
04:16:03,840 --> 04:16:05,760
LOOK AT PARTICULAR COMORBIDITIES

7051
04:16:05,760 --> 04:16:08,080
THAT WE KNOW DRIVE DIFFERENT

7052
04:16:08,080 --> 04:16:08,720
DIFFERENTIAL RESPONSES.

7053
04:16:08,720 --> 04:16:12,000
SO IF WE START LOOKING AT

7054
04:16:12,000 --> 04:16:13,760
ASTHMATICS OR OTHER

7055
04:16:13,760 --> 04:16:14,840
COMORBIDITIES THAT MIGHT DRIVE

7056
04:16:14,840 --> 04:16:16,280
DIFFERENCES IN RESPONSE, THAT'S

7057
04:16:16,280 --> 04:16:17,280
WHAT WE MIGHT SEE.

7058
04:16:17,280 --> 04:16:21,200
I THINK WITH THE RESEARCH BRON

7059
04:16:21,200 --> 04:16:21,840
BRONCHOSCOPIES, A LOT OF THE

7060
04:16:21,840 --> 04:16:23,280
DONOR POPULATIONS ARE VERY

7061
04:16:23,280 --> 04:16:23,720
SIMILAR.

7062
04:16:23,720 --> 04:16:25,800
IT'S A SIMILAR PATIENT

7063
04:16:25,800 --> 04:16:27,640
POPULATION, USUALLY YOUNGER,

7064
04:16:27,640 --> 04:16:29,280
HEALTHIER PEOPLE THAT RESPOND TO

7065
04:16:29,280 --> 04:16:32,040
THE HOSPITAL SURVEYS OR REQUESTS

7066
04:16:32,040 --> 04:16:34,240
TO DONATE TISSUE WITH A

7067
04:16:34,240 --> 04:16:35,640
BRONCHOSCOPY, BUT I THINK

7068
04:16:35,640 --> 04:16:38,480
BROADENING THAT TO PATIENTS WITH

7069
04:16:38,480 --> 04:16:41,120
VARIOUS DISEASE PROFILES WOULD

7070
04:16:41,120 --> 04:16:43,640
REALLY BE INTERESTING.

7071
04:16:43,640 --> 04:16:45,600
>> THERE WAS A QUESTION IN
THE

7072
04:16:45,600 --> 04:16:46,920
CHAT, I THINK CHRISTINE

7073
04:16:46,920 --> 04:16:50,160
MENTIONED THAT SHE WANTED TO

7074
04:16:50,160 --> 04:16:52,800
ANSWER IT.

7075
04:16:52,800 --> 04:16:54,880
IT WAS AN INTERESTING QUESTION

7076
04:16:54,880 --> 04:16:56,080
GOES BACK TO THE ISSUE OF

7077
04:16:56,080 --> 04:16:57,320
VARIABILITY, IN THIS CASE ARE

7078
04:16:57,320 --> 04:16:59,400
THE ECM DONOR TO DONOR.

7079
04:16:59,400 --> 04:17:01,440
SO VARIABILITY IN THE ECM FROM

7080
04:17:01,440 --> 04:17:02,120
DONOR TO DONOR.

7081
04:17:02,120 --> 04:17:03,440
WE'RE NOT TALKING ABOUT CELLS

7082
04:17:03,440 --> 04:17:07,800
HERE, WE'RE TALKING ABOUT ECM.

7083
04:17:07,800 --> 04:17:11,200
AND I GUESS I DIDN'T SEE LINDA,

7084
04:17:11,200 --> 04:17:12,400
I DON'T THINK SHE WAS ABLE TO

7085
04:17:12,400 --> 04:17:15,000
MAKE IT NOW, BUT HOW THAT KIND

7086
04:17:15,000 --> 04:17:15,200
OF --

7087
04:17:15,200 --> 04:17:17,880
>> I PRESSED THE WRONG
BUTTON

7088
04:17:17,880 --> 04:17:18,400
ACTUALLY.

7089
04:17:18,400 --> 04:17:19,720
I'M QUITE HAPPY TO GIVE A GO.

7090
04:17:19,720 --> 04:17:23,120
BUT IT'S REALLY FOR -- NOT FOR

7091
04:17:23,120 --> 04:17:25,520
ME, IT'S MORE FOR ANTHONY.

7092
04:17:25,520 --> 04:17:27,800
THERE ISN'T THAT MUCH

7093
04:17:27,800 --> 04:17:29,680
VARIABILITY FROM DONOR TO DONOR

7094
04:17:29,680 --> 04:17:30,880
IN THE EXTRACELLULAR MATRIX, AND

7095
04:17:30,880 --> 04:17:32,840
IT'S NOT REALLY LOGICAL IT WOULD

7096
04:17:32,840 --> 04:17:37,440
BE HUGE, BECAUSE A NORMAL ORGAN

7097
04:17:37,440 --> 04:17:38,200
HAS TO FUNCTION.

7098
04:17:38,200 --> 04:17:40,480
OFTEN IF AN ORGAN IS FIBROTIC,

7099
04:17:40,480 --> 04:17:42,800
IT WILL VARY FROM DONOR TO DONOR

7100
04:17:42,800 --> 04:17:46,600
AND IT'S, OF COURSE, QUITE HARD

7101
04:17:46,600 --> 04:17:51,200
TO SEE HOW GUY   FIBROTIC IT IS.

7102
04:17:51,200 --> 04:17:52,720
IT WOULD DEPEND ON THE AGE OF

7103
04:17:52,720 --> 04:17:54,800
THE DONOR AND THINGS LIKE THAT.

7104
04:17:54,800 --> 04:17:55,560
>> TONY?

7105
04:17:55,560 --> 04:17:57,640
>> THANK YOU, MARC, AND
THANK

7106
04:17:57,640 --> 04:17:58,000
YOU, CHRISTINE.

7107
04:17:58,000 --> 04:17:59,080
SO BASICALLY, THE IMPORTANT

7108
04:17:59,080 --> 04:18:01,800
THING, OFTEN, IS ORGAN-SPECIFIC

7109
04:18:01,800 --> 04:18:02,280
ECM, RIGHT?

7110
04:18:02,280 --> 04:18:03,680
BECAUSE ECM FROM THE LIVER IS

7111
04:18:03,680 --> 04:18:05,560
NOT GOING TO BE THE SAME AS THE

7112
04:18:05,560 --> 04:18:08,040
EYM FROM THE LUNG.

7113
04:18:08,040 --> 04:18:08,720
CM FROM THE LUNG.

7114
04:18:08,720 --> 04:18:10,040
ONCE YOU GET DOWN TO THAT LEVEL,

7115
04:18:10,040 --> 04:18:14,080
THE WAY WE DO IT IS WE TAKE THE

7116
04:18:14,080 --> 04:18:18,480
ORGAN, WE USE -- TO WASH -- AT

7117
04:18:18,480 --> 04:18:19,960
WAY, WE'RE LEFT JUST WITH THE

7118
04:18:19,960 --> 04:18:21,400
EXTRACELLULAR MATRIX, WE MAKE

7119
04:18:21,400 --> 04:18:23,080
THE MATRIX INTO A POWDER AND WE

7120
04:18:23,080 --> 04:18:24,480
THEN RECONSTITUTE THAT POWDER TO

7121
04:18:24,480 --> 04:18:30,480
CREATE THE STRUCTURE AND THEN WE

7122
04:18:30,480 --> 04:18:32,600
MATCH THE STIFFNESS TO THE

7123
04:18:32,600 --> 04:18:33,800
NORMAL STIFFNESS THE ORGAN WOULD

7124
04:18:33,800 --> 04:18:34,080
HAVE.

7125
04:18:34,080 --> 04:18:35,760
AGAIN JUST AS A WAY TO MAKE SURE

7126
04:18:35,760 --> 04:18:37,040
WE REPLICATE AS MANY OF THE

7127
04:18:37,040 --> 04:18:39,240
PROPERTY AS POSSIBLE IN THAT

7128
04:18:39,240 --> 04:18:40,320
ORGANOID SYSTEM AS YOU WOULD SEE

7129
04:18:40,320 --> 04:18:42,720
IN A NORMAL HUMAN TISSUE AND

7130
04:18:42,720 --> 04:18:43,920
ORGAN.

7131
04:18:43,920 --> 04:18:44,840
BECAUSE EVERYTHING PLAYS A ROLE.

7132
04:18:44,840 --> 04:18:49,440
AND THERE IS NO VAST VARIABILITY

7133
04:18:49,440 --> 04:18:50,280
BETWEEN PATIENTS BECAUSE AS YOU

7134
04:18:50,280 --> 04:18:53,560
KNOW, IT DOESN'T HAVE ANY IMMUNE

7135
04:18:53,560 --> 04:18:55,000
PROPERTIES, IT'S JUST THE ECM,

7136
04:18:55,000 --> 04:18:59,920
WHICH IS MAINLY COLLAGEN, MOSTLY

7137
04:18:59,920 --> 04:19:03,320
TYPE I COLLAGEN, ALSO TYPE 2,

7138
04:19:03,320 --> 04:19:07,440
TYPE 3, SOME LAMININ.

7139
04:19:07,440 --> 04:19:09,640
BUT IT VARIES FROM ORGAN TO

7140
04:19:09,640 --> 04:19:10,000
ORGAN.

7141
04:19:10,000 --> 04:19:10,840
>> I THINK THE POINT IS
THE

7142
04:19:10,840 --> 04:19:12,280
BATCH TO BATCH VARIABILITY.

7143
04:19:12,280 --> 04:19:14,040
SO IF YOU TAKE ONE LIVER, IS

7144
04:19:14,040 --> 04:19:14,800
THIS -- THE BATCH THE SAME AS

7145
04:19:14,800 --> 04:19:15,640
THE OTHER LIVER.

7146
04:19:15,640 --> 04:19:18,960
WE KNOW WITH MATRIGEL, IT IS

7147
04:19:18,960 --> 04:19:20,160
BATCH TO BATCH VARIABILITY EVEN

7148
04:19:20,160 --> 04:19:21,080
THOUGH THEY'RE MADE IN THE SAME

7149
04:19:21,080 --> 04:19:23,960
WAY.

7150
04:19:23,960 --> 04:19:25,320
SO I THINK THIS IS THE QUESTION,

7151
04:19:25,320 --> 04:19:27,160
OF COURSE YOU GET HUGE BATCHES

7152
04:19:27,160 --> 04:19:32,840
FROM A HUMAN LIVER, BUT DO YOU

7153
04:19:32,840 --> 04:19:34,560
SEE BATCH TO BATCH DIFFERENCES?

7154
04:19:34,560 --> 04:19:36,560
>> YOU DO GET THIS HUGE
AMOUNT,

7155
04:19:36,560 --> 04:19:37,840
OF COURSE, OF THE ECM THAT

7156
04:19:37,840 --> 04:19:39,600
ALLOWS YOU TO REALLY -- TEST

7157
04:19:39,600 --> 04:19:41,920
REALLY MILLIONS OF THESE

7158
04:19:41,920 --> 04:19:43,880
ORGANOIDS.

7159
04:19:43,880 --> 04:19:49,040
 WITH THE SAME MATRIX.

7160
04:19:49,040 --> 04:19:50,120
>> I'M GOING TO GIVE AN

7161
04:19:50,120 --> 04:19:51,040
OPPORTUNITY TO THE PANELISTS

7162
04:19:51,040 --> 04:19:55,160
THAT ARE NOT THE SPEAKERS TO ASK

7163
04:19:55,160 --> 04:20:01,720
ANY QUESTIONS, IF THEY HAVE ANY?

7164
04:20:01,720 --> 04:20:03,760
SARINE, SIMON, JONI, ANY

7165
04:20:03,760 --> 04:20:11,160
PRESSING QUESTIONS?

7166
04:20:11,160 --> 04:20:13,000
>> I GUESS I'D JUST LIKE
TO

7167
04:20:13,000 --> 04:20:15,800
QUICKLY GO BACK TO THE QUESTION

7168
04:20:15,800 --> 04:20:22,720
ABOUT VARIABILITY OF DIMERS.

7169
04:20:22,720 --> 04:20:24,960
IN TERMS OF SCALE, ECM, YOU

7170
04:20:24,960 --> 04:20:26,080
MATCH THE BATCH AND BE ABLE TO

7171
04:20:26,080 --> 04:20:28,280
USE THAT, BUT I THINK AT THE

7172
04:20:28,280 --> 04:20:30,160
MOMENT, EVERYBODY IS SAYING WHAT

7173
04:20:30,160 --> 04:20:33,000
THEY WANT TO USE FRESH TISSUE,

7174
04:20:33,000 --> 04:20:36,280
FRESH PRIMARY TISSUE FROM

7175
04:20:36,280 --> 04:20:37,720
PATIENTS, BUT HOW DO WE MOVE

7176
04:20:37,720 --> 04:20:39,440
AWAY FROM THAT INTO A SYSTEM

7177
04:20:39,440 --> 04:20:42,840
WHERE ANYBODY CAN ACCESS A

7178
04:20:42,840 --> 04:20:43,960
CERTAIN LOT AND DO THE SAME

7179
04:20:43,960 --> 04:20:45,120
EXPERIMENT, NO MATTER WHERE THEY

7180
04:20:45,120 --> 04:20:47,200
ARE ON THE PLANET, AND THEN

7181
04:20:47,200 --> 04:20:49,840
WHERE THEY ARE IN TIME FROM THE

7182
04:20:49,840 --> 04:20:51,600
DATE THAT THOSE CELLS WERE

7183
04:20:51,600 --> 04:20:54,840
TAKEN.

7184
04:20:54,840 --> 04:20:56,080
AND I DON'T THINK WE'VE GOT

7185
04:20:56,080 --> 04:20:56,640
THERE YET.

7186
04:20:56,640 --> 04:21:02,320
I'VE TALKED ABOUT PLURIPOTENTIAL

7187
04:21:02,320 --> 04:21:03,840
STEM CELLS AND ALL I'VE HEARD IS

7188
04:21:03,840 --> 04:21:05,600
THAT'S PROBLEMATIC, BUT HOW DO

7189
04:21:05,600 --> 04:21:08,880
WE MOVE FORWARD FROM THIS

7190
04:21:08,880 --> 04:21:09,880
SITUATION?

7191
04:21:09,880 --> 04:21:10,920
>> SIMON, THAT'S A GREAT

7192
04:21:10,920 --> 04:21:12,040
QUESTION.

7193
04:21:12,040 --> 04:21:15,560
THAT'S THE BILLION DOLLAR

7194
04:21:15,560 --> 04:21:16,400
QUESTION.

7195
04:21:16,400 --> 04:21:17,400
BECAUSE THAT'S WHAT WE WERE

7196
04:21:17,400 --> 04:21:17,840
FACING.

7197
04:21:17,840 --> 04:21:19,040
THAT LAST SLIDE THAT I SHOWED

7198
04:21:19,040 --> 04:21:20,680
WHICH WAS BASICALLY THE

7199
04:21:20,680 --> 04:21:21,000
VARIABILITY.

7200
04:21:21,000 --> 04:21:25,920
THAT'S THE CHALLENGE.

7201
04:21:25,920 --> 04:21:27,360
I ALWAYS LIKE TO SAY, YOU KNOW,

7202
04:21:27,360 --> 04:21:29,640
HOW IS IT POSSIBLE THAT WE COULD

7203
04:21:29,640 --> 04:21:33,360
DETECT THAT TOXICITY FROM THOSE

7204
04:21:33,360 --> 04:21:36,440
DRUGS SO READILY IN OUR SYSTEM

7205
04:21:36,440 --> 04:21:40,280
WHEN IT WAS NOT POSSIBLE IN THE

7206
04:21:40,280 --> 04:21:41,400
2D MODELS, IT WAS NOT POSSIBLE

7207
04:21:41,400 --> 04:21:43,520
IN THE ANIMALS, IT WAS NOT

7208
04:21:43,520 --> 04:21:44,800
POSSIBLE IN THE HUMAN CLINICAL

7209
04:21:44,800 --> 04:21:46,040
TRIALS AND THEN 11 YEARS LATER,

7210
04:21:46,040 --> 04:21:48,760
YOU GET THIS -- YOU FINALLY FIND

7211
04:21:48,760 --> 04:21:50,560
OUT THIS DRUG IS CAUSING

7212
04:21:50,560 --> 04:21:51,960
PROBLEMS, OR THREE YEARS LATER,

7213
04:21:51,960 --> 04:21:55,120
AND SO I THINK THERE'S A LITTLE

7214
04:21:55,120 --> 04:21:56,200
BUILT OF A -- LET ME DISCUSS

7215
04:21:56,200 --> 04:22:00,160
THIS BALL ABC A LITTLE         Y

7216
04:22:00,160 --> 04:22:01,480
THEORY ON THIS IS THAT, YOU

7217
04:22:01,480 --> 04:22:05,280
KNOW, WHEN WE ARE LOOKING AT THE

7218
04:22:05,280 --> 04:22:07,480
ACTUAL DRUG TO THE ORGAN, WE ARE

7219
04:22:07,480 --> 04:22:08,920
REALLY GETTING RID OF ALL THE

7220
04:22:08,920 --> 04:22:09,360
NOISE.

7221
04:22:09,360 --> 04:22:11,320
WE'RE GETTING RID -- I SHOULD

7222
04:22:11,320 --> 04:22:12,480
SAY I SHOULD BE MORE SPECIFIC,

7223
04:22:12,480 --> 04:22:15,800
WE'RE GETTING RID OF A LOT OF

7224
04:22:15,800 --> 04:22:18,440
THE NOISE, BECAUSE WHAT HAPPENS

7225
04:22:18,440 --> 04:22:21,160
IN THE HUMAN IS WE ALL

7226
04:22:21,160 --> 04:22:21,960
METABOLIZE DRUGS DIFFERENTLY,

7227
04:22:21,960 --> 04:22:24,560
WE'RE ALL GENETICALLY DIFFERENT,

7228
04:22:24,560 --> 04:22:25,560
ALL EPIGENETICALLY DIFFERENT, WE

7229
04:22:25,560 --> 04:22:27,200
HAVE DIFFERENT DIETS, WE PROCESS

7230
04:22:27,200 --> 04:22:28,920
OUR FOODS DIFFERENT, WE HAVE

7231
04:22:28,920 --> 04:22:29,800
DIFFERENT METABOLISM RATES, AND

7232
04:22:29,800 --> 04:22:33,960
ALL THESE FACTORS GO INTO THAT

7233
04:22:33,960 --> 04:22:34,440
RESPONSE.

7234
04:22:34,440 --> 04:22:35,760
THAT IS WHY IT TOOK 11 YEARS FOR

7235
04:22:35,760 --> 04:22:37,040
THERE TO BE ENOUGH CASES WHERE

7236
04:22:37,040 --> 04:22:38,560
PEOPLE COULD CONNECT THE DOTS

7237
04:22:38,560 --> 04:22:40,000
AND SAY THIS DRUG IS CAUSING

7238
04:22:40,000 --> 04:22:41,480
HEART BLOCK, AND YET YOU PUT

7239
04:22:41,480 --> 04:22:43,280
INTO THE SYSTEM AND THERE IT IS,

7240
04:22:43,280 --> 04:22:43,880
RIGHT?

7241
04:22:43,880 --> 04:22:46,280
IT'S LIKE NINE DAY, THERE IT IS.

7242
04:22:46,280 --> 04:22:48,760
AND I THINK SO THERE ARE

7243
04:22:48,760 --> 04:22:50,880
ADVANTAGES TO GETTING RID OF ALL

7244
04:22:50,880 --> 04:22:52,840
THE NOISE BECAUSE YOU'RE REALLY

7245
04:22:52,840 --> 04:22:54,160
LOOKING AT THE EFFECT OF THE

7246
04:22:54,160 --> 04:22:56,960
DRUG AGAINST THE TISSUE AND THE

7247
04:22:56,960 --> 04:22:58,360
ORGAN AND YOU'RE GETTING RID OF

7248
04:22:58,360 --> 04:22:59,600
A LOT OF THE NOISE.

7249
04:22:59,600 --> 04:23:00,360
ON THE OTHER HAND, THERE ARE

7250
04:23:00,360 --> 04:23:01,240
MANY SITUATIONS WHERE YOU WANT

7251
04:23:01,240 --> 04:23:03,440
TO PUT THAT NOISE BACK IN,

7252
04:23:03,440 --> 04:23:03,760
RIGHT?

7253
04:23:03,760 --> 04:23:05,720
YOU WANT TO PUT THAT NOISE BACK

7254
04:23:05,720 --> 04:23:07,040
IN, LIKE THE PERSONALIZED

7255
04:23:07,040 --> 04:23:08,040
MEDICINE APPROACH LIKE THE

7256
04:23:08,040 --> 04:23:10,320
TUMORS THAT WE'RE TALKING ABOUT.

7257
04:23:10,320 --> 04:23:12,280
BECAUSE EACH TUMOR IS DIFFERENT,

7258
04:23:12,280 --> 04:23:14,040
IT'S GOING TO HAVE DIFFERENT

7259
04:23:14,040 --> 04:23:14,680
EPIGENETIC CHANGES AND WE'RE

7260
04:23:14,680 --> 04:23:15,760
GOING TO TAKE THAT TUMOR FROM

7261
04:23:15,760 --> 04:23:16,680
THAT PATIENT, WE'RE GOING TO

7262
04:23:16,680 --> 04:23:20,160
TEST THAT TUMOR AGAINST SPECIFIC

7263
04:23:20,160 --> 04:23:21,720
CHEMOTHERAPY, YOU'RE IDENTIFYING

7264
04:23:21,720 --> 04:23:23,240
THAT TUMOR WITH THEIR OWN

7265
04:23:23,240 --> 04:23:24,520
GENETIC AND EPIGENETIC CHANGES

7266
04:23:24,520 --> 04:23:25,760
AND YOU REALLY WANT THAT DATA IN

7267
04:23:25,760 --> 04:23:26,600
TERMS OF WHAT IT DOES.

7268
04:23:26,600 --> 04:23:32,520
SO I THINK WE HAVE TO MINIMIZE

7269
04:23:32,520 --> 04:23:33,520
BATCH TO BATCH VARIABILITY, WE

7270
04:23:33,520 --> 04:23:37,440
HAVE TO WORK ON BETTER AND MORE

7271
04:23:37,440 --> 04:23:39,520
RELIABLE CELL SOURCES, WE HAVE

7272
04:23:39,520 --> 04:23:41,400
TO WORK ON STANDARDIZATION OF

7273
04:23:41,400 --> 04:23:43,360
THE SYSTEMS, BUT ALSO TO KEEP IN

7274
04:23:43,360 --> 04:23:46,480
MIND WHAT THE ACTUAL END POINT

7275
04:23:46,480 --> 04:23:48,680
IS OF WHAT YOU'RE LOOKING FOR.

7276
04:23:48,680 --> 04:23:52,200
>> IF I COULD JUST JUMP IN

7277
04:23:52,200 --> 04:23:56,400
THERE, THE INTERNATIONAL -- STEM

7278
04:23:56,400 --> 04:23:57,480
CELL RESEARCH IS WORKING EXACTLY

7279
04:23:57,480 --> 04:24:00,080
ON THAT ISSUE, SO WORKING ON

7280
04:24:00,080 --> 04:24:02,280
STANDARDIZATION DOCUMENTS, HOW

7281
04:24:02,280 --> 04:24:04,240
TO STANDARDIZE STEM CELLS.

7282
04:24:04,240 --> 04:24:06,120
AND IT WAS ADULT STEM CELLS AND

7283
04:24:06,120 --> 04:24:07,800
IPS CELLS AND EMBRYONIC STEM

7284
04:24:07,800 --> 04:24:08,520
CELLS.

7285
04:24:08,520 --> 04:24:10,800
WHAT YOU NEED TO MONITOR IN

7286
04:24:10,800 --> 04:24:14,640
TERMS OF GENETIC DRIFT,

7287
04:24:14,640 --> 04:24:16,000
PROPERTIES, ALL THE KINDS OF

7288
04:24:16,000 --> 04:24:18,040
THINGS THAT PEOPLE HAVE TROUBLE

7289
04:24:18,040 --> 04:24:20,320
WITH, WHAT DO YOU HAVE TO DEFINE

7290
04:24:20,320 --> 04:24:23,080
TO ALLOW THE FIELD TO BE ABLE TO

7291
04:24:23,080 --> 04:24:24,800
DO THINGS REPRODUCIBLY FROM LAB

7292
04:24:24,800 --> 04:24:27,440
TO LAB, PERSON TO PERSON.

7293
04:24:27,440 --> 04:24:29,600
I THINK WE'RE GETTING THERE,

7294
04:24:29,600 --> 04:24:30,600
PARTICULARLY WITH COMMERCIAL

7295
04:24:30,600 --> 04:24:34,200
COMPANIES PRODUCING REAGENTS IN

7296
04:24:34,200 --> 04:24:38,400
LARGE SCALE GOING FROM GROWTH

7297
04:24:38,400 --> 04:24:42,000
FACTORS TO -- MOLECULAR BASED

7298
04:24:42,000 --> 04:24:43,160
CULTURE METHODS, THINGS LIKE

7299
04:24:43,160 --> 04:24:43,400
THAT.

7300
04:24:43,400 --> 04:24:45,040
SO IT IS GETTING THERE.

7301
04:24:45,040 --> 04:24:49,720
BUT WE WILL HAVE A CONSENSUS

7302
04:24:49,720 --> 04:24:50,520
STATEMENT DOCUMENT BEFORE THE

7303
04:24:50,520 --> 04:24:51,840
END OF THE YEAR DEFINING WHAT

7304
04:24:51,840 --> 04:24:55,320
YOU NEED TO SAY ABOUT THOSE STEM

7305
04:24:55,320 --> 04:24:56,320
CELLS.

7306
04:24:56,320 --> 04:24:59,920
AND I AGREE THAT OF COURSE THERE

7307
04:24:59,920 --> 04:25:02,440
ARE A LOT OF DIET ISSUES AND

7308
04:25:02,440 --> 04:25:03,400
LIFESTYLE ISSUES THAT IMPACT

7309
04:25:03,400 --> 04:25:05,280
CELLS, BUT AT LEAST I THINK WITH

7310
04:25:05,280 --> 04:25:07,680
SOME OF THE STEM CELL MODELS, WE

7311
04:25:07,680 --> 04:25:09,960
CAN ADDRESS THE GENETIC ISSUE,

7312
04:25:09,960 --> 04:25:11,520
PERHAPS EVEN THE EPIGENETIC

7313
04:25:11,520 --> 04:25:12,800
ISSUES AND AT LEAST GET THAT

7314
04:25:12,800 --> 04:25:13,240
STANDARD.

7315
04:25:13,240 --> 04:25:15,360
AND PARTICULARLY ADDRESS

7316
04:25:15,360 --> 04:25:17,640
VARIANTS OF UNKNOWN

7317
04:25:17,640 --> 04:25:18,720
SIGNIFICANCE, SMALL MACULAR

7318
04:25:18,720 --> 04:25:22,560
CHANGES IN THE GENOME THAT ARE

7319
04:25:22,560 --> 04:25:23,640
CAUSING PERSON TO PERSON

7320
04:25:23,640 --> 04:25:24,440
VARIABILITY.

7321
04:25:24,440 --> 04:25:28,680
BEST CASE SCENARIO, DRUGS WORK

7322
04:25:28,680 --> 04:25:31,200
NOW IN 1 IN 4 PATIENTS, THE TOP

7323
04:25:31,200 --> 04:25:33,720
10 PRESCRIBED DRUGS IN THE U.S.

7324
04:25:33,720 --> 04:25:36,600
AND THE WORST CASE, IN THOSE 10

7325
04:25:36,600 --> 04:25:40,160
TOP PRESCRIBED DRUGS, THERE ARE

7326
04:25:40,160 --> 04:25:41,040
1 IN 25 PATIENTS RESPONDING AS

7327
04:25:41,040 --> 04:25:41,760
EXPECTED.

7328
04:25:41,760 --> 04:25:42,680
THAT'S TERRIBLE.

7329
04:25:42,680 --> 04:25:44,320
THAT'S AN ENORMOUS WASTE OF

7330
04:25:44,320 --> 04:25:44,640
RESOURCES.

7331
04:25:44,640 --> 04:25:50,360
SO THERE'S A LOT OF GAIN TO BE

7332
04:25:50,360 --> 04:25:52,000
HAD, EVEN IDENTIFYING NOT JUST

7333
04:25:52,000 --> 04:25:54,040
FOR TUMORS BUT WHO'S GOING TO

7334
04:25:54,040 --> 04:25:56,240
RESPOND TO EVEN A RELATIVELY

7335
04:25:56,240 --> 04:25:59,640
EXPENSIVE DRUG, IF IT'S A DRUG

7336
04:25:59,640 --> 04:26:01,400
USED BY MILLIONS OF PEOPLE.

7337
04:26:01,400 --> 04:26:05,200
>> TECHNICALLY WE SHOULD
END

7338
04:26:05,200 --> 04:26:07,320
NOW, BUT IF THE SPEAKERS ARE

7339
04:26:07,320 --> 04:26:09,160
WILLING TO STAY A LITTLE LONGER,

7340
04:26:09,160 --> 04:26:11,240
THERE'S JUST A COUPLE OF

7341
04:26:11,240 --> 04:26:12,960
QUESTIONS THAT HAVE COME UP AND

7342
04:26:12,960 --> 04:26:15,480
SOME OF THEM ARE RELATED TO THIS

7343
04:26:15,480 --> 04:26:19,880
DISCUSSION IN TERMS OF

7344
04:26:19,880 --> 04:26:21,200
STANDARDIZATION OF MPSs AND

7345
04:26:21,200 --> 04:26:22,720
WHAT DO WE MEAN BY

7346
04:26:22,720 --> 04:26:23,200
STANDARDIZATION.

7347
04:26:23,200 --> 04:26:26,640
WE'VE TALKED ABOUT VALIDATING

7348
04:26:26,640 --> 04:26:27,960
THE TISSUES ABOUT ALL THE OMICS

7349
04:26:27,960 --> 04:26:30,600
TO MAKE SURE THEY LOOK LIKE

7350
04:26:30,600 --> 04:26:31,800
NATIVE, THAT'S A HALLMARK IN

7351
04:26:31,800 --> 04:26:32,120
ITSELF.

7352
04:26:32,120 --> 04:26:35,680
BUT THEN WE'RE TALKING PLIEK LIY

7353
04:26:35,680 --> 04:26:37,440
WAS SAYING ABOUT REMOVING THE

7354
04:26:37,440 --> 04:26:39,080
NOISE MAYBE TISSUE BY TISSUE,

7355
04:26:39,080 --> 04:26:41,800
LOOKING AT TOXIC EFFECTS,

7356
04:26:41,800 --> 04:26:44,080
LOOKING AT EFFICACY, MAYBE

7357
04:26:44,080 --> 04:26:45,200
HAVING ANOTHER LEVEL WHERE YOU

7358
04:26:45,200 --> 04:26:48,360
ACTUALLY LOOK AT MAYBE

7359
04:26:48,360 --> 04:26:50,440
METABOLISM IN A PARTICULAR DRUG.

7360
04:26:50,440 --> 04:26:56,240
SO THE QUESTION IS, IS THERE

7361
04:26:56,240 --> 04:26:59,200
GOING TO BE A STANDARDIZED MODEL

7362
04:26:59,200 --> 04:27:00,640
WHICH POTENTIALLY DECREASES

7363
04:27:00,640 --> 04:27:01,480
VARIATION AMONG DIFFERENT

7364
04:27:01,480 --> 04:27:02,600
MODELS?  I DON'T KNOW WHO WANTS

7365
04:27:02,600 --> 04:27:04,280
TO TAKE THESE QUESTIONS.

7366
04:27:04,280 --> 04:27:06,080
THE WAY I SEE THE FIELD GOING IS

7367
04:27:06,080 --> 04:27:08,840
WE HAVE MANY DIFFERENT

7368
04:27:08,840 --> 04:27:09,440
TECHNOLOGIES.

7369
04:27:09,440 --> 04:27:12,200
A LOT OF IT BECAUSE HAVE BEEN

7370
04:27:12,200 --> 04:27:13,640
MENTIONED IS REALLY DEPENDING --

7371
04:27:13,640 --> 04:27:15,280
IT'S A FIT-FOR-PURPOSE,

7372
04:27:15,280 --> 04:27:17,560
DEPENDING ON WHAT APPLICATION

7373
04:27:17,560 --> 04:27:21,280
YOU'RE LOOKING FOR, SO MAYBE I'M

7374
04:27:21,280 --> 04:27:23,920
WRONG, I DON'T SEE ONE

7375
04:27:23,920 --> 04:27:27,000
STANDARDIZED MPS MODEL, BUT

7376
04:27:27,000 --> 04:27:28,200
TONY, YOU UNMUTED YOURSELF.

7377
04:27:28,200 --> 04:27:29,320
YOU WANT TO TAKE THIS ON?

7378
04:27:29,320 --> 04:27:31,000
>> ACTUALLY, I JUST
UNMUTED JUST

7379
04:27:31,000 --> 04:27:32,560
IN CASE I WAS READY, BUT I'LL BE

7380
04:27:32,560 --> 04:27:38,680
HAPPY TO GO FIRST.

7381
04:27:38,680 --> 04:27:41,280
I THINK WHAT WE REALLY NEED DO

7382
04:27:41,280 --> 04:27:42,640
IS START LOOKING AT THE FUTURE

7383
04:27:42,640 --> 04:27:46,440
OF THE FIELD IN TERMS OF CELL

7384
04:27:46,440 --> 04:27:48,080
SOURCING AND CELL

7385
04:27:48,080 --> 04:27:49,280
STANDARDIZATION AND THE GENETIC

7386
04:27:49,280 --> 04:27:50,720
COMPONENTS OF THE CELLS.

7387
04:27:50,720 --> 04:27:51,800
THAT'S REALLY WHAT WE NEED TO

7388
04:27:51,800 --> 04:27:52,120
DO.

7389
04:27:52,120 --> 04:27:53,560
WE NEED TO START BUILDING BANKS.

7390
04:27:53,560 --> 04:27:58,160
AS YOU KNOW, IT ABSOLUTELY NO

7391
04:27:58,160 --> 04:27:58,920
DIFFERENT WHEN WE'RE TALKING

7392
04:27:58,920 --> 04:28:00,120
ABOUT A STEM CELL BANK.

7393
04:28:00,120 --> 04:28:02,200
BASICALLY IT'S NOT LIKE WE'RE

7394
04:28:02,200 --> 04:28:03,960
RE-EXPLORING THE FIELD BECAUSE

7395
04:28:03,960 --> 04:28:06,880
WE KNOW THAT IF WE HAVE A UNIQUE

7396
04:28:06,880 --> 04:28:13,320
SET OF ABOUT 7,000 STEM CELL

7397
04:28:13,320 --> 04:28:14,760
POPULATIONS, THAT WOULD PROVIDE

7398
04:28:14,760 --> 04:28:16,400
OVER 90% OF CELL POPULATION WITH

7399
04:28:16,400 --> 04:28:18,480
A PERFECT GENETIC MATCH, SO

7400
04:28:18,480 --> 04:28:21,760
THERE ARE WAYS TO DO THIS, BUT

7401
04:28:21,760 --> 04:28:22,880
THEY HAVE TO BE UNIQUE.

7402
04:28:22,880 --> 04:28:24,360
ALL THIS HAS BEEN WORKED OUT FOR

7403
04:28:24,360 --> 04:28:25,800
THE CELL BANKING INDUSTRY,

7404
04:28:25,800 --> 04:28:27,240
RIGHT, FOR THE STEM CELL

7405
04:28:27,240 --> 04:28:27,480
BANKING.

7406
04:28:27,480 --> 04:28:28,760
YOU LOOK AT BONE MARROW BANKING

7407
04:28:28,760 --> 04:28:32,680
AND YOU LOOK AT CORE BLOOD

7408
04:28:32,680 --> 04:28:34,120
BANKING, WHAT IS THAT MAGIC

7409
04:28:34,120 --> 04:28:37,720
NUMBER THAT GIVES YOU THAT

7410
04:28:37,720 --> 04:28:38,160
GENETIC VARIABILITY.

7411
04:28:38,160 --> 04:28:40,240
SO THE MAIN THING REALLY IS TO

7412
04:28:40,240 --> 04:28:43,960
ACTUALLY START ESTABLISHING SUCH

7413
04:28:43,960 --> 04:28:45,800
A BANK THAT WILL GIVE US THIS

7414
04:28:45,800 --> 04:28:46,600
GENETIC VARIABLE SO WE CAN THEN

7415
04:28:46,600 --> 04:28:47,600
START TO PICK OUT THE THINGS

7416
04:28:47,600 --> 04:28:51,840
THAT WE WANT TO LOOK AT FROM

7417
04:28:51,840 --> 04:28:52,320
THESE BANKS.

7418
04:28:52,320 --> 04:28:53,520
THEN WE HAVE THIS RESOURCE

7419
04:28:53,520 --> 04:28:57,880
THAT'S AVAILABLE TO EVERYBODY,

7420
04:28:57,880 --> 04:29:00,480
AND IT WOULD BE NICE DO IT WITH

7421
04:29:00,480 --> 04:29:03,960
CELLS WHICH ARE ALREADY, YOU

7422
04:29:03,960 --> 04:29:07,800
KNOW, MORE IN A DIFFERENTIATED

7423
04:29:07,800 --> 04:29:08,880
PATHWAY REALLY.

7424
04:29:08,880 --> 04:29:10,000
THE CHALLENGE AS YOU KNOW IS

7425
04:29:10,000 --> 04:29:13,960
GETTING TO THAT DERMAL

7426
04:29:13,960 --> 04:29:14,400
DIFFERENTIATION.

7427
04:29:14,400 --> 04:29:15,360
MANY TIMES YOU CAN ONLY DO THAT

7428
04:29:15,360 --> 04:29:17,000
WITH A PRIMARY HUMAN CELL.

7429
04:29:17,000 --> 04:29:18,320
I KNOW IT'S HARDER TO DO, BUT IF

7430
04:29:18,320 --> 04:29:20,480
YOU DON'T START NOW, THEN WE'RE

7431
04:29:20,480 --> 04:29:22,280
GOING TO BE LOOKING AT THE SAME

7432
04:29:22,280 --> 04:29:23,120
PROBLEM 20 YEARS FROM NOW.

7433
04:29:23,120 --> 04:29:25,520
SO WE MIGHT AS WELL BITE THE

7434
04:29:25,520 --> 04:29:26,720
BULLET, REALIZE WHAT WE NEED TO

7435
04:29:26,720 --> 04:29:32,120
DO, AND JUST GO AFTER IT.

7436
04:29:32,120 --> 04:29:32,960
>> AWESOME.

7437
04:29:32,960 --> 04:29:35,160
ANYBODY ELSE HAVE ANY COMMENTS?

7438
04:29:35,160 --> 04:29:38,560
>> THERE'S ALSO
ENGINEERING

7439
04:29:38,560 --> 04:29:39,320
SOURCES OF VARIABILITY THAT I

7440
04:29:39,320 --> 04:29:40,960
THINK WE NEED TO ADDRESS, AND

7441
04:29:40,960 --> 04:29:42,200
ONE OF THE CHALLENGES, I THINK,

7442
04:29:42,200 --> 04:29:44,080
IN THE ORGAN ON A CHIP FIELD HAS

7443
04:29:44,080 --> 04:29:46,000
BEEN THAT IT'S SOMETIMES VIEWED

7444
04:29:46,000 --> 04:29:49,680
AS SYNONYMOUS WITH THESE KIND OF

7445
04:29:49,680 --> 04:29:51,040
USB STICK KIND OF IMAGE, WHICH

7446
04:29:51,040 --> 04:29:53,440
IS REALLY KIND OF A SMALL SCALE,

7447
04:29:53,440 --> 04:29:55,240
IT'S VERY POWERFUL IN TERMS OF

7448
04:29:55,240 --> 04:29:56,480
THE FIDELITY OF SOME OF THESE

7449
04:29:56,480 --> 04:29:56,840
MODELS.

7450
04:29:56,840 --> 04:29:58,560
YOU CAN DO A LOT OF COMPLEX SORT

7451
04:29:58,560 --> 04:30:01,320
OF ENGINEERING IN THESE SYSTEMS,

7452
04:30:01,320 --> 04:30:03,360
BUT IT DOES REPRESENT A

7453
04:30:03,360 --> 04:30:07,560
LIMITATION RELATIVE TO THE GOLD

7454
04:30:07,560 --> 04:30:09,720
STANDARD HIGH THROUGHPUT MICRO

7455
04:30:09,720 --> 04:30:10,400
TITER PLATES THAT THE INDUSTRY

7456
04:30:10,400 --> 04:30:11,480
IS USED TO WORKING WITH.

7457
04:30:11,480 --> 04:30:13,200
WE WANT TO ELIMINATE THOSE

7458
04:30:13,200 --> 04:30:16,480
SOURCES OF ENGINEERING

7459
04:30:16,480 --> 04:30:17,280
VARIABILITY BATCH TO BATCH,

7460
04:30:17,280 --> 04:30:19,240
PLATE TO PLATE, PROVIDE THE

7461
04:30:19,240 --> 04:30:20,120
THROUGHPUT PROFESSOR GRIFFITH

7462
04:30:20,120 --> 04:30:26,080
TALKED EARLIER ABOUT THE ISSUES

7463
04:30:26,080 --> 04:30:27,760
WITH DRUG GET AWAY FROM

7464
04:30:27,760 --> 04:30:29,720
MATERIALS THAT CAUSE THESE

7465
04:30:29,720 --> 04:30:31,080
PROBLEMS, IMPLENTY SENSORS SO WE

7466
04:30:31,080 --> 04:30:32,480
KNOW WHAT'S GOING ON IN THESE

7467
04:30:32,480 --> 04:30:33,040
SYSTEMS.

7468
04:30:33,040 --> 04:30:33,760
THAT'S WITH THE ENGINEERING CAN

7469
04:30:33,760 --> 04:30:35,320
COME IN AND HELP ADDRESS SOME OF

7470
04:30:35,320 --> 04:30:36,400
THOSE PROBLEMS SO WE AREN'T

7471
04:30:36,400 --> 04:30:38,200
DEALING WITH THOSE ISSUES AS

7472
04:30:38,200 --> 04:30:39,840
WELL AS THE NATURAL BIOLOGIC

7473
04:30:39,840 --> 04:30:41,000
VARIATION.

7474
04:30:41,000 --> 04:30:42,440
>> THAT'S A GOOD POINT.

7475
04:30:42,440 --> 04:30:43,760
I THINK THE OTHER ASPECT OF HOW

7476
04:30:43,760 --> 04:30:48,760
YOU GET THESE TECHNOLOGIES

7477
04:30:48,760 --> 04:30:52,240
ARE -- SO THAT BUYOLOGIST CAN

7478
04:30:52,240 --> 04:30:54,040
USE IT AS WELL.

7479
04:30:54,040 --> 04:30:55,440
I THINK CHRISTINE HAS TO LEAVE.

7480
04:30:55,440 --> 04:30:57,200
THANK YOU SO MUCH, CHRISTINE.

7481
04:30:57,200 --> 04:30:58,280
THANKS SO MUCH FOR

7482
04:30:58,280 --> 04:30:58,720
PARTICIPATING.

7483
04:30:58,720 --> 04:30:59,480
IT'S BEEN GREAT.

7484
04:30:59,480 --> 04:31:03,680
SO THE QUESTION OF COMONETIZING

7485
04:31:03,680 --> 04:31:05,160
THE TECHNOLOGY AND GETTING TO

7486
04:31:05,160 --> 04:31:07,360
NOT ONLY THE BIOENGINEERING LABS

7487
04:31:07,360 --> 04:31:09,680
BUT BIOLOGY LABS SO THEY CAN USE

7488
04:31:09,680 --> 04:31:14,560
IT AT A REASONABLE COST.

7489
04:31:14,560 --> 04:31:17,880
SO THESE TECHNOLOGIES ARE VERY

7490
04:31:17,880 --> 04:31:18,160
EXPENSIVE.

7491
04:31:18,160 --> 04:31:19,160
SOMETIMES THAT'S A LIMITATION,

7492
04:31:19,160 --> 04:31:22,120
IF A BIOLOGY LAB WANTS TO USE

7493
04:31:22,120 --> 04:31:23,360
ONE OF THESE -- CHIPS AND THEY

7494
04:31:23,360 --> 04:31:29,200
CAN ONLY AFFORD LIKE ONE OR TWO

7495
04:31:29,200 --> 04:31:30,320
CHIPS, THERE'S SO MUCH BIOLOGY

7496
04:31:30,320 --> 04:31:34,920
YOU CAN DO.

7497
04:31:34,920 --> 04:31:36,480
I THINK THEY'RE GOING TO KICK US

7498
04:31:36,480 --> 04:31:37,400
OUT OF THE ROOM.

7499
04:31:37,400 --> 04:31:43,200
I JUST GOT A NOTE TBR   FROM AB.

7500
04:31:43,200 --> 04:31:44,120
SO SARINE, I THINK WE'RE GOING

7501
04:31:44,120 --> 04:31:44,680
TO CLOSE HERE.

7502
04:31:44,680 --> 04:31:45,880
I KNOW THERE'S A FEW MORE

7503
04:31:45,880 --> 04:31:47,200
QUESTIONS IN THE CHAT, BUT --

7504
04:31:47,200 --> 04:31:48,320
>> YEAH, NO WORRIES.

7505
04:31:48,320 --> 04:31:49,680
>> I THINK WE ARE --

7506
04:31:49,680 --> 04:31:50,360
>> THANK YOU.

7507
04:31:50,360 --> 04:31:53,600
THANK YOU SO MUCH, MARC, AND

7508
04:31:53,600 --> 04:31:55,160
THANK YOU, ALL THE SPEAKERS.

7509
04:31:55,160 --> 04:31:59,240
THIS WAS AN AMAZING SESSION, AND

7510
04:31:59,240 --> 04:32:01,160
THE DISCUSSION WAS JUST AMAZING.

7511
04:32:01,160 --> 04:32:02,600
I JUST COULDN'T -- I DON'T WANT

7512
04:32:02,600 --> 04:32:04,880
TO STOP IT, BUT WE ALL HAVE TO

7513
04:32:04,880 --> 04:32:08,920
GO.

7514
04:32:08,920 --> 04:32:09,680
SO AGAIN, MANY THANKS.

7515
04:32:09,680 --> 04:32:11,800
I KNOW THERE'S MANY QUESTIONS

7516
04:32:11,800 --> 04:32:12,320
LEFT.

7517
04:32:12,320 --> 04:32:13,880
WE TRIED TO ANSWER AS MANY

7518
04:32:13,880 --> 04:32:16,480
QUESTIONS AS POSSIBLE.

7519
04:32:16,480 --> 04:32:18,320
IF YOU SEE A QUESTION THAT YOU

7520
04:32:18,320 --> 04:32:20,880
CAN ANSWER BRIEFLY BY TYPING, GO

7521
04:32:20,880 --> 04:32:23,360
AHEAD AND DO SO.

7522
04:32:23,360 --> 04:32:24,560
APOLOGIES FOR THE PEOPLE THAT WE

7523
04:32:24,560 --> 04:32:25,800
COULDN'T ANSWER ALL THE

7524
04:32:25,800 --> 04:32:26,800
QUESTIONS, BUT I'M SO GLAD THAT

7525
04:32:26,800 --> 04:32:28,080
YOU ASKED THE QUESTIONS.

7526
04:32:28,080 --> 04:32:31,160
I HOPE YOU ENJOYED THE

7527
04:32:31,160 --> 04:32:31,680
DISCUSSION.

7528
04:32:31,680 --> 04:32:32,800
SO THANK YOU AGAIN.

7529
04:32:32,800 --> 04:32:39,120
BEFORE I WRAP TODAY'S SESSION, I

7530
04:32:39,120 --> 04:32:41,720
WOULD LIKE TO SAY THAT WE HAVE

7531
04:32:41,720 --> 04:32:47,000
TWO AWESOME SESSIONS TOMORROW,

7532
04:32:47,000 --> 04:32:48,880
AND WE WILL RECONVENE TOMORROW

7533
04:32:48,880 --> 04:32:51,720
AT 11:00 A.M., SO HOPEFULLY YOU

7534
04:32:51,720 --> 04:32:53,480
ENJOYED TODAY, YOU LEARNED A

7535
04:32:53,480 --> 04:32:55,640
LOT, AND I WILL SHARE HERE THE

7536
04:32:55,640 --> 04:32:59,000
AGENDA FOR TOMORROW QUICKLY.

7537
04:32:59,000 --> 04:33:00,400
FOR FOLKS TO KNOW WHAT'S COMING

7538
04:33:00,400 --> 04:33:06,000
TOMORROW.

7539
04:33:06,000 --> 04:33:08,640
OKAY.

7540
04:33:08,640 --> 04:33:10,360
SO TOMORROW WE WILL START AT

7541
04:33:10,360 --> 04:33:12,760
11:00, AND WE WILL HAVE THE

7542
04:33:12,760 --> 04:33:13,760
SECOND SESSION WHICH IS GOING TO

7543
04:33:13,760 --> 04:33:17,800
BE ON UTILITY OF THE EXISTING 3D

7544
04:33:17,800 --> 04:33:22,080
TISSUE MODELS FOR ANTIVIRAL DRUG

7545
04:33:22,080 --> 04:33:22,360
DEVELOPMENT.

7546
04:33:22,360 --> 04:33:24,120
AND THEN WE WILL HAVE A THIRD

7547
04:33:24,120 --> 04:33:25,360
SESSION, SESSION 3, IT WILL BE

7548
04:33:25,360 --> 04:33:27,400
ON USE OF ROBUST AND

7549
04:33:27,400 --> 04:33:28,840
REPRODUCIBLE 3D TISSUE MODELS

7550
04:33:28,840 --> 04:33:30,280
FROM DRUG DISCOVERY THROUGH

7551
04:33:30,280 --> 04:33:32,800
DEVELOPMENT, AND WE WILL WRAP UP

7552
04:33:32,800 --> 04:33:35,080
TOMORROW WITH A FINAL SESSION,

7553
04:33:35,080 --> 04:33:37,920
SESSION 4, CLOSING SESSION THAT

7554
04:33:37,920 --> 04:33:38,920
WE'LL DISCUSS SUMMARY OF

7555
04:33:38,920 --> 04:33:40,200
DISCUSSIONS AND PERSPECTIVES ON

7556
04:33:40,200 --> 04:33:43,280
THE CHALLENGES AHEAD.

7557
04:33:43,280 --> 04:33:45,680
SO AGAIN, HOPEFULLY YOU ENJOYED

7558
04:33:45,680 --> 04:33:45,920
TODAY.

7559
04:33:45,920 --> 04:33:47,480
THANK YOU FOR ALL THE SPEAKERS.

7560
04:33:47,480 --> 04:33:50,640
THIS WAS AMAZING.

7561
04:33:50,640 --> 04:33:52,120
WE WILL HOPEFULLY SEE YOU ALL

7562
04:33:52,120 --> 04:33:53,240
TOMORROW AT 11:00.

7563
04:33:53,240 --> 04:33:54,000
MANY THANKS AGAIN.

7564
04:33:54,000 --> 04:33:57,080
HAVE A WONDERFUL --

7565
04:33:57,080 --> 04:33:59,800
>> THANK YOU, TONY, JASON,
LINDA

7566
04:33:59,800 --> 04:34:01,560
AND CHRISTINE, GREAT TALKS AND

7567
04:34:01,560 --> 04:34:02,200
GREAT DISCUSSION.

7568
04:34:02,200 --> 00:00:00,000
APPRECIATE IT.