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WELCOME TO THE CLINICAL
CENTER GRAND ROUNDS,

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A WEEKLY SERIES OF EDUCATIONAL
LECTURES FOR PHYSICIANS AND

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HEALTH CARE PROFESSIONALS
BROADCAST FROM THE CLINICAL

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CENTER AT THE NATIONAL
INSTITUTES OF HEALTH IN

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BETHESDA, MD.

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THE NIH CLINICAL CENTER IS THE
WORLD'S LARGEST HOSPITAL TOTALLY

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DEDICATED TO INVESTIGATIONAL
RESEARCH AND LEADS THE GLOBAL

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EFFORT IN TRAINING TODAY'S
INVESTIGATORS AND DISCOVERING

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TOMORROW'S CURES.

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LEARN MORE BY VISITING US ONLINE
AT HTTP://CLINICALCENTER.NIH.GOV

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IT'S 12:00.

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I'D LIKE TO WELCOME EVERYBODY TO

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THE CLINICAL CENTER'S GRAND

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ROUNDS TODAY FOR THE GREAT

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TEACHERS LECTURE.

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IT'S MY ESTEEMED HONOR AND

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PLEASURE TO INTRODUCE YOU TO A

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PERSON WHO IS A MENTOR TO ME, A

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COLLEAGUE AND SOMETIMES MORE

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IMPORTANTLY A FRIEND.

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AND HAS HELPED ME AT NUMEROUS

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POINTS IN MY CAREER.

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INTERESTINGLY, AS I'VE KNOWN DRE

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YEARS, THERE'S BEEN A LOT OF

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TIMES WHEN OUR PATHS HAVE

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CROSSED BUT JUST DECADES APART.

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HE'S CURRENTLY THE THOMAS E. AND

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ALICE MARIE HALES DISTINGUISHED

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PROFESSOR IN TRANSPLANTATION AT

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THE UNIVERSITY OF MARYLAND

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SCHOOL OF MEDICINE.

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AS A SURGEON, HE'S UNPARALLELED.

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1200 HEART TRANSPLANTS HAVE BEEN

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DONE BY HIM.

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OVER 600 LUNG TRA TRANSPLANTS HE

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BEEN DONE BY HIM.

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HE'S THE SECOND PERSON IN THE

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WORLD TO DO AN EN BLOC

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HEART-LUNG AT THE SAME TIME.

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IN ADDITION, HE'S BEEN AN

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INNOVATOR.

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HE WAS ONE OF THE FIRST PEOPLE

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TO USE CYCLOSPORIN AS A

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IMMUNOSUPPRESSIVE MEDICATION,

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WHICH HELPED US REALLY ADVANCE

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THE FIELD OF LUNG TRANSPLANT

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SURGERY.

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FROM AN ENGINEERING STANDPOINT,

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HE IS THE INVENTOR OF THE HEART

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MATE2 VENTRICULAR ASSIST DEVICE.

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HE'S ALSO ONE OF THE FIRST

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PEOPLE TO SEND A PERSON HOME

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WITH A VENTRICULAR ASSIST

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DEVICE.

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AT EVERY STEP OF THE WAY, HE'S

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BEEN AN INNOVATOR.

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HE GRADUATED FROM SHADY SIDE

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ACADEMY IN PITTSBURGH IN 1966,

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WENT ON TO BUCKNELL AND THEN TO

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THOMAS JEFFERSON UNIVERSITY

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HOSPITAL FOR MEDICAL SCHOOL.

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THERE HE WAS INSPIRED TO BECOME

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A CARDIAC SURGEON.

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TODAY, HE TOLD THE STORY THAT HE

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USED TO GO TO DOC'S, HAVE A

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SANDWICH AND A BEER.

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SO DID I WHEN I WAS A RESIDENT.

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IT'S STILL THERE.

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FROM THERE, HE ENDED UP GOING TO

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UNIVERSITY OF PITTSBURGH MEDICAL

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CENTER, WHERE HE COMPLETED HIS

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GENERAL SURGICAL RESIDENCY AND

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BECAME FACULTY IN 1981.

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BY 1988, HE WAS A FULLY TENURED

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PROFESSOR AND TWO YEARS LATER,

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HE WAS THE HENRY T.BONSON

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PROFESSOR OF CARDIAC SURGERY.

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HANK BONSON IS A LEGEND.

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DR. GRIFFITH FILLED THOSE SHOES

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ADMIRABLY.

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FROM THERE H THERE, HE'S FUNDEDE

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NHLBI FOR ALMOST 40 YEARS.

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CURRENTLY HAS A BUDGET IN THE

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BALLPARK OF 26 TO $40 MILLION,

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DEPENDING ON WHO YOU READ.

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AND IS THE FIRST PERSON EVER TO

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PUT A HEART -- THE HEART OF A

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PIG INTO A HUMAN FOR A

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XENOTRANSPLANT.

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IN JANUARY OF 2022, WHEN I SAW

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THE NEWS, BBC, CNN, IT WAS THE

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FIRST THING ON EVERY SINGLE ONE

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OF THE NEWS FEEDS THAT I LOOK

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AT.

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I SENT MY FRIEND A TEXT,

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CONGRATULATIONS, I KNEW I WAS

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ONE OF A MILLION PEOPLE PROBABLY

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BLOWING UP HIS PHONE, BUT I GOT

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A NICE TEXT BACK.

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AND THAT MEANS A LOT TO ME.

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IT'S NOT OFTEN YOU GET TO

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INTRODUCE SOMEONE WHO IS

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EFFECTIVELY THE EQUIVALENT OF

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NEIL ARMSTRONG IN MY FIELD.

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WITHOUT ANY FURTHER ADO,

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DR. BART GRIFFITH.

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[APPLAUSE]

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>> THAT WAS RIDICULOUS.

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THANK YOU.

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I'M A MAN LOOKING FOR A JOB, I

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GUESS.

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IT'S DELIGHTFUL TO BE HERE.

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I HAD A GREAT MORNING.

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AFTER I FOUND THE RIGHT ENTRANCE

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TO COME IN.

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AND IT WAS DELIGHTFUL TO SEE THE

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STUDENTS, TO MEET WITH THE

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FACULTY, AND A TEAM FROM THE

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NHLBI AND YOUR CLINICAL DIRECTOR

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MOST IMMEDIATELY.

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THANK YOU FOR THE PRIVILEGE OF

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BEING HERE TODAY.

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I HAVE A JOB TODAY AND IT'S TO

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BASICALLY TRY TO HAVE YOU SEE

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XENOTRANSPLANTATION THROUGH MY

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EYES.

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AND THAT'S A LITTLE DIFFERENT,

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OF COURSE, BECAUSE YOU KNOW, MY

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EYES ARE MY EYES AND NOT YOURS,

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BUT IT'S IMPORTANT TO ME THAT AT

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THE END OF THE DAY, NOT THAT YOU

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NECESSARILY UNDERSTAND THE

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ACCESSORY PATHWAY AND WHY WE

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HAVE TO BLOCK IT AND WHAT

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ANTIBODY-MEDIATED REJECTION IS,

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BUT I THINK I WANT PARTICULARLY

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BECAUSE I SEE STUDENTS, I WANT

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YOU TO SEE THE RELATIVE BENEFIT

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OF RESEARCH AND THANK YOU MAPT.

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HUMANITY.

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AND WHILE IT IS TRUE, WE ARE NOT

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GOING TO SAVE LEGIONS OF

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PATIENTS WITH SEEN

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XENOTRANSPLANTATION, THE

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WALK-THROUGH THE LABORATORY INTO

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THE CLINIC HAS BEEN ONE LACED

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WITH HUMAN EMOTION AND WITH, I

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THINK, A GREAT SENSE OF

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GRATITUDE, EVEN THOUGH TWO

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PATIENTS RECEIVED HUMAN ORGANS

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AND THOSE TWO PATIENTS IN TOTAL

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LIVED FOR 100 DAYS ONLY.

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WE'RE JUST GETTING STARTED.

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I WILL TELL YOU A LITTLE ABOUT

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THAT STORY AND HOPE YOU ENJOY

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IT.

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THIS IS A ROZ CHASTE CARTOON

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THAT I'M WEIRD ENOUGH TO THINK

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IS FUNNY.

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"THE END OF NEAR, HAVE A CONE."

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I KIND OF WANTED TO USE THAT IN

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WAY TO DESCRIBE SOMETHING ELSE.

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SO THE END IS NEAR, HAVE A PIG

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HEART.

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[LAUGHTER]

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AND I DON'T MEAN THIS TO MAKE

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FUN OF PATIENTS IN ANY WAY.

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BUT MY PARTNER, DR. MOADEEN WHO

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SPENT TIME HERE AND REALLY

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SHARPENED HIS SWORD SO THAT WE

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COULD BE THINKING ABOUT THE

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ACTUAL HUMAN TRANSLATION OF THIS

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EXPERIMENT STARTED AT THE NHLBI,

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AND MANY GOOD YEARS WERE HERE,

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REALLY REFINING THE IMMUNE

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SUPPRESSIVE PROTOCOL.

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BUT I SHOW THIS BECAUSE WHAT YOU

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WILL SEE IS THAT TWO PATIENTS

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WILLINGLY UNDERWENT AN

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EXPERIMENTAL TRANSPLANT BECAUSE

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THEIR END WAS NEAR.

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IT WAS PROXIMATE.

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IT WAS WITHIN DAYS.

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BOTH OF THEM IN THE END

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PREFERRED AN ALTERNATIVE THERAPY

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WHICH WAS NOT AVAILABLE TO THEM.

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NOT BEING AVAILABLE TO THEM, AS

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OPPOSED TO GOING OUT LIKE A

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LAMB, THEY WANTED TO GO OUT A

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LITTLE BIT AS AN ASTRONAUT, AND

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THEY WANTED TO TEACH US.

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THEY WANTED TO TEACH YOU AND

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CERTAINLY ME, A LITTLE BIT ABOUT

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THIS POTENTIAL WONDERFUL

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TREATMENT THAT IS JUST KIND OF

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WAITING FOR HUMAN

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EXPERIMENTATION.

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SO WITH THAT, WE'LL TRY TO GET

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THROUGH IT.

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NOW, THIS THERAPY, IT'S KIND OF

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CUT OFF THERE, IT SAYS CHINESE

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SCIENTISTS -- TRANSPLANT OF

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HUMAN PIG LIVER.

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THIS JUST CAME OUT LAST WEEK, I

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DON'T KNOW WHETHER YOU SAW IT.

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BUT THEY DID GENETICALLY

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ENGINEERED LIVER TRANSPLANT IN A

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DECEASED PATIENT IN CHINA.

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AT THE AIR FORCE HOSPITAL IN

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CHINA.

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AND SO THIS IS HAPPENING, RIGHT?

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WE EXPECT OUR COLLEAGUES IN

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MUNICH TO GET CLOSE TO THIS

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WITHIN THE YEAR.

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I THINK WE'LL SEE OTHER CENTERS

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COME ON BOARD.

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I THINK THE TREATMENT IS GOING

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TO BE COMPELLING.

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I THINK OUR EARLY RESULTS WOULD

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SUGGEST THERE IS AT LEAST THE

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OPPORTUNITY TO LEARN AND TO DO

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BETTER AND TO PROVIDE OPTIONS

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GOING DOWN.

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THE ROAD.

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SO OUR DONOR IS A PIG HEART.

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THAT'S THE DONOR ORGAN.

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SO WHAT IS IT ABOUT THE PIG?

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WELL, THEY GROW FAST.

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WE EAT THEM.

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AND THEY CAN BE GENETICALLY

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ALTERED.

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AND SO IF YOU WERE TO DESIGN A

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PIG HEART FOR A HUMAN, YOU WOULD

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DO SOME DELETIONS, YOU WOULD ADD

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SOME GENES AND WE'RE JUST GOING

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TO BRIEFLY TALK ABOUT THAT, BUT

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IT'S THE PERFECT SIZE FOR A

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HUMAN, GENERALLY SPEAKING, AND

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THERE ARE DIFFERENCES IN HOW IT

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CONTRACTS, BUT IT CONTRACT WELL

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ENOUGH TO MASQUERADE

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BEAUTIFULLY, AS I WILL SHOW YOU,

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FOR THE HUMAN HEART.

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SO THIS IS A WILD TYPE PIG

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HEART, AND IT'S JUST GONE INTO

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THE ABDOMEN OF A BABOON.

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INCIDENTALLY, IN ONE OF THESE

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BUILDINGS HERE.

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THAT HEART, IF UNALTERED AND

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REMAINS, YOU KNOW, NOT

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GENETICALLY ALTERED, WILL TURN

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TO THIS BLACK HEART, AND IT'S

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BLACK BECAUSE ITS BLOOD VESSELS

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HAVE CLOTTED, ALMOST INSTANTLY.

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THIS IS WITHIN 15 MINUTES OF

256
00:09:22,028 --> 00:09:24,497
RELEASING THE CLAMP AND

257
00:09:24,563 --> 00:09:25,598
REPERFUSING THAT ORGAN.

258
00:09:25,665 --> 00:09:28,000
AND SO WHAT IS HAPPENING IS,

259
00:09:28,067 --> 00:09:28,734
HYPERACUTE REJECTION.

260
00:09:28,801 --> 00:09:32,705
THE BODY SENSES SOME SUGARS ON

261
00:09:32,772 --> 00:09:35,308
THAT ENDOTHELIUM THAT SHOULDN'T

262
00:09:35,374 --> 00:09:36,943
BE THERE, AND SO IT ATTACKS IT

263
00:09:37,009 --> 00:09:37,276
IMMEDIATELY.

264
00:09:37,343 --> 00:09:39,278
THESE ARE PREFORMED ANTIBODIES,

265
00:09:39,345 --> 00:09:42,648
AND THIS IS LIKE YOUR BEE STING

266
00:09:42,715 --> 00:09:44,383
ALLERGY.

267
00:09:44,450 --> 00:09:47,019
THIS IS ALL ARMS ON DECK

268
00:09:47,086 --> 00:09:48,888
BECAUSE, YOU KNOW, WE HAVE AN

269
00:09:48,955 --> 00:09:49,322
INVADER.

270
00:09:49,388 --> 00:09:50,823
AND THIS WAS THE BIG PROBLEM,

271
00:09:50,890 --> 00:09:51,090
RIGHT?

272
00:09:51,157 --> 00:09:53,159
AND SO IT WAS RECOGNIZED THAT

273
00:09:53,225 --> 00:09:54,660
SOME CHANGES COULD BE MADE,

274
00:09:54,727 --> 00:09:59,265
RIGHT, TO THE PIG HEART.

275
00:09:59,332 --> 00:10:00,800
THE PIG HEART CHANGES THAT WE

276
00:10:00,866 --> 00:10:03,536
USED ARE SHOWN HERE.

277
00:10:03,602 --> 00:10:08,774
THIS PIG HERE IS CLONED, AND IT

278
00:10:08,841 --> 00:10:10,576
HAS 10 CHANGES, AS I MENTIONED.

279
00:10:10,643 --> 00:10:16,682
FOUR OF THEM WERE ADDITIONS OF

280
00:10:16,749 --> 00:10:19,485
COAGULATION AND COMPLEMENT, AND

281
00:10:19,552 --> 00:10:21,253
THEN ONE WAS AN INFLAMMATORY

282
00:10:21,320 --> 00:10:21,587
REGULATOR.

283
00:10:21,654 --> 00:10:24,090
AND I HAD FUN TALKING TO MY

284
00:10:24,156 --> 00:10:27,693
IMMEDIATE HOST ABOUT MONOCYTE

285
00:10:27,760 --> 00:10:29,128
INHIBITION FACTOR, WHICH HE'S

286
00:10:29,195 --> 00:10:30,429
VERY INTERESTED IN, IN LUNG

287
00:10:30,496 --> 00:10:32,398
CANCER.

288
00:10:32,465 --> 00:10:35,167
WELL, WE USE A MONOCYTE

289
00:10:35,234 --> 00:10:38,104
INHIBITION FACTOR IN THE FACE OF

290
00:10:38,170 --> 00:10:40,306
CD47 TO HELP TAMP DOWN

291
00:10:40,373 --> 00:10:41,707
INFLAMMATION IN THIS PIG.

292
00:10:41,774 --> 00:10:44,110
BUT IMPORTANTLY, WE ADD

293
00:10:44,176 --> 00:10:45,544
COMPLEMENT FEATURES, RIGHT?

294
00:10:45,611 --> 00:10:48,147
AND WE ADD COAGULATION

295
00:10:48,214 --> 00:10:49,682
REGULATORS SO THAT IF A BEE

296
00:10:49,749 --> 00:10:52,084
STING GETS STARTED, IT DOESN'T

297
00:10:52,151 --> 00:10:53,719
CLOT THE BLOOD VESSELS.

298
00:10:53,786 --> 00:10:56,355
WE ALSO KNOCK OUT FOUR GENES.

299
00:10:56,422 --> 00:10:58,124
THREE OF THEM ARE THE SUGAR

300
00:10:58,190 --> 00:10:59,759
GENES THAT TURN ON THOSE BEE

301
00:10:59,825 --> 00:11:00,860
STINGS, IF YOU WISH, THAT START

302
00:11:00,926 --> 00:11:02,595
THAT WHOLE PROCESS OF TURNING

303
00:11:02,661 --> 00:11:05,998
THAT HEART INTO A USELESS

304
00:11:06,065 --> 00:11:08,634
COAGULATED BLACK ORGAN.

305
00:11:08,701 --> 00:11:12,204
THOSE ARE THE ALPHA GAU TYPE

306
00:11:12,271 --> 00:11:14,407
SUGARS.

307
00:11:14,473 --> 00:11:15,941
THEY WOULD BE A LITTLE BIT LIKE

308
00:11:16,008 --> 00:11:18,110
THE HUMAN BLOOD TYPE, RIGHT?

309
00:11:18,177 --> 00:11:18,878
A, B AND O, RIGHT?

310
00:11:18,944 --> 00:11:20,212
THOSE ARE SUGARS, RIGHT?

311
00:11:20,279 --> 00:11:22,381
AND THESE ARE THE SUGARS THAT

312
00:11:22,448 --> 00:11:25,584
WERE RECOGNIZED IMMEDIATELY.

313
00:11:25,651 --> 00:11:28,287
WE ALSO KNOCK OUT A GROWTH

314
00:11:28,354 --> 00:11:29,922
RECEPTOR, AND THE GROWTH

315
00:11:29,989 --> 00:11:31,457
RECEPTOR IS DEEMED TO BE

316
00:11:31,524 --> 00:11:32,691
NECESSARY TO BE KNOCKED OUT, I'M

317
00:11:32,758 --> 00:11:34,260
NOT SURE IT GOING TO PERSIST TO

318
00:11:34,326 --> 00:11:36,695
BE KNOCKED OUT BECAUSE I THINK

319
00:11:36,762 --> 00:11:41,734
IT WAS OVERHIGH PRESSUH OVERHYPE

320
00:11:41,801 --> 00:11:43,402
PIGS WILL GROW TO 400 POUNDS AND

321
00:11:43,469 --> 00:11:45,371
THEIR ORGANS TEND TO OVERGROW

322
00:11:45,438 --> 00:11:47,006
HUMAN SIZE SO THERE WAS CONCERN

323
00:11:47,073 --> 00:11:48,874
THE KIDNEYS WOULD GROW TOO BIG,

324
00:11:48,941 --> 00:11:50,176
THE HEART IS GOING TO GROW TOO

325
00:11:50,242 --> 00:11:50,843
BIG.

326
00:11:50,910 --> 00:11:52,144
NOT SURE THAT'S GOING TO HAPPEN.

327
00:11:52,211 --> 00:11:53,779
AND THERE'S SOME CONSEQUENCES OF

328
00:11:53,846 --> 00:11:55,414
USING THE GROWTH RECEPTOR

329
00:11:55,481 --> 00:11:57,049
KNOCKOUT BUT THESE ARE BASICALLY

330
00:11:57,116 --> 00:11:58,384
LIKE DWARFED PIGS.

331
00:11:58,451 --> 00:12:00,219
THEY MAX OUT AT ABOUT 200 POUNDS

332
00:12:00,286 --> 00:12:09,228
AS OPPOSED TO 400.

333
00:12:09,295 --> 00:12:10,863
WHEN WE LOOK AN BIOPSY TISSUE,

334
00:12:10,930 --> 00:12:11,831
WE SHOULD BE ABLE TO STAIN FOR

335
00:12:11,897 --> 00:12:12,798
THE PRESENCE OF THOSE GENES,

336
00:12:12,865 --> 00:12:14,133
THAT THOSE GENES ARE WORKING,

337
00:12:14,200 --> 00:12:15,034
RIGHT, THAT IN FACT THOSE GENES

338
00:12:15,101 --> 00:12:16,735
WE KNOCKED IN THERE ARE WORKING,

339
00:12:16,802 --> 00:12:17,103
RIGHT?

340
00:12:17,169 --> 00:12:19,605
SO THAT'S WHAT THIS PANEL ON A

341
00:12:19,672 --> 00:12:20,372
SHOWS.

342
00:12:20,439 --> 00:12:23,542
THAT'S AN IMMUNE HISTOCHEMISTRY

343
00:12:23,609 --> 00:12:26,512
STUDY OF THE FIRST HEART BIOPSY

344
00:12:26,579 --> 00:12:27,680
IN OUR FIRST PATIENT.

345
00:12:27,746 --> 00:12:29,615
ALL THE WAY TO THE LEFT, THAT'S

346
00:12:29,682 --> 00:12:30,216
DAY 30.

347
00:12:30,282 --> 00:12:32,284
THEN THERE'S NEGATIVE CONTROL,

348
00:12:32,351 --> 00:12:33,586
WHICH SHOULDN'T LIGHT UP BECAUSE

349
00:12:33,652 --> 00:12:35,454
THAT'S A WILD TYPE PIG HEART.

350
00:12:35,521 --> 00:12:38,424
AND THEN YOU'VE GOT POSTMORTEM

351
00:12:38,491 --> 00:12:41,026
TISSUE ON THE ABSOLUTE RIGHT.

352
00:12:41,093 --> 00:12:42,661
THERE IS SOME DIFFERENCE.

353
00:12:42,728 --> 00:12:49,468
IF YOU LOOK AT OUR EPCR AND OUR

354
00:12:49,535 --> 00:12:52,438
TBM, THOSE ARE REGULATORS OF

355
00:12:52,505 --> 00:12:53,372
COAGULATION.

356
00:12:53,439 --> 00:12:56,442
AND THOSE ARE ON A SEPARATE

357
00:12:56,509 --> 00:12:57,676
PROMOTER, AN

358
00:12:57,743 --> 00:12:58,711
ENDOTHELIAL-SPECIFIC PROMOTER,

359
00:12:58,777 --> 00:13:01,147
WHICH TURNS ON ONLY WHEN THE

360
00:13:01,213 --> 00:13:03,983
ENDOTHELIUM IS BEING STRESSED.

361
00:13:04,049 --> 00:13:05,417
THE NEGATIVE CONTROL DOESN'T

362
00:13:05,484 --> 00:13:07,286
SHOW IT AND THE HEART BIOPSY AT

363
00:13:07,353 --> 00:13:08,587
DAY 30 IN OUR FIRST PATIENT

364
00:13:08,654 --> 00:13:10,789
DIDN'T SHOW IT BECAUSE THAT

365
00:13:10,856 --> 00:13:11,657
HEART WASN'T STRESSED.

366
00:13:11,724 --> 00:13:12,858
LOOK AT THE POSTMORTEM.

367
00:13:12,925 --> 00:13:14,260
AT POSTMORTEM, YOU SEE IT'S

368
00:13:14,326 --> 00:13:15,060
TURNED ON.

369
00:13:15,127 --> 00:13:18,998
SO EVEN THE REGULATED TRANS GENE

370
00:13:19,064 --> 00:13:20,366
SEEMS TO BE WORKING WELL FOR US,

371
00:13:20,432 --> 00:13:22,501
AND THAT'S WHY I SHOW TO YOU.

372
00:13:22,568 --> 00:13:25,871
AND THAT IS ALSO EXEMPLIFIED IN

373
00:13:25,938 --> 00:13:27,740
THE MIDDLE COLUMN, WHERE YOU SEE

374
00:13:27,806 --> 00:13:32,211
TBM AND EPCR ELEVATED IN THE

375
00:13:32,278 --> 00:13:37,583
PRESENCE OF STRESS AT THE BIOPSY

376
00:13:37,650 --> 00:13:42,488
WHEN IT WAS SO.

377
00:13:42,555 --> 00:13:43,556
SO I THINK THAT'S PROBABLY

378
00:13:43,622 --> 00:13:44,123
ENOUGH FOR THAT SLIDE.

379
00:13:44,190 --> 00:13:45,257
THIS IS THE WORK THAT WAS DONE

380
00:13:45,324 --> 00:13:45,558
HERE.

381
00:13:45,624 --> 00:13:49,061
AND THIS IS A MODEL WHICH IS

382
00:13:49,128 --> 00:13:51,463
MORE COMMONLY DONE IN RODENTS,

383
00:13:51,530 --> 00:13:54,600
WHERE A HEART CAN BE PLACED IN

384
00:13:54,667 --> 00:13:56,635
THE ABDOMEN AND THE HEART IS

385
00:13:56,702 --> 00:13:57,136
REPERFUSED.

386
00:13:57,203 --> 00:13:58,370
WHEN STUDIES ARE DONE OF THIS

387
00:13:58,437 --> 00:13:59,471
NATURE, IT'S NOT TO SEE WHETHER

388
00:13:59,538 --> 00:14:00,873
THE HEART CAN FUNCTION WELL.

389
00:14:00,940 --> 00:14:02,608
IT'S TO SEE WHETHER THE BODY

390
00:14:02,675 --> 00:14:03,509
REJECTS IT.

391
00:14:03,576 --> 00:14:05,377
SO IT'S A GOOD WAY TO TEST

392
00:14:05,444 --> 00:14:07,546
IMMUNE SUPPRESSIVE PROTOCOLS.

393
00:14:07,613 --> 00:14:09,615
IT'S ALSO A LOT EASIER THAN

394
00:14:09,682 --> 00:14:11,383
DOING A TRUE HEART TRANSPLANT,

395
00:14:11,450 --> 00:14:13,152
BECAUSE THEN YOU DON'T HAVE THE

396
00:14:13,219 --> 00:14:15,654
CONCERN OF TAKING CARE OF AN

397
00:14:15,721 --> 00:14:18,257
ANIMAL NOW THAT'S HAD AN ACUTE

398
00:14:18,324 --> 00:14:18,824
HEART TRANSPLANT.

399
00:14:18,891 --> 00:14:21,660
SO THIS IS HOW THIS PIG HEART IS

400
00:14:21,727 --> 00:14:23,629
PLACED INTO THIS BABOON'S

401
00:14:23,696 --> 00:14:24,830
STOMACH, AND I'LL PULL THAT

402
00:14:24,897 --> 00:14:26,799
AWAY, AND YOU CAN ACTUALLY SEE

403
00:14:26,865 --> 00:14:27,299
IT PULSATING IN THERE.

404
00:14:27,366 --> 00:14:29,101
I THINK IT'S KIND OF COOL, THAT

405
00:14:29,168 --> 00:14:29,768
LITTLE MOVIE.

406
00:14:29,835 --> 00:14:31,303
AND THANK YOU, NIH, FOR HELPING

407
00:14:31,370 --> 00:14:33,706
TO PRODUCE THIS VIDEO.

408
00:14:33,772 --> 00:14:36,976
AND THIS STUDY WAS DONE IN THIS

409
00:14:37,042 --> 00:14:38,510
ANIMAL 784 DAYS AFTER THAT HEART

410
00:14:38,577 --> 00:14:41,347
WAS PLACED INTO THE ABDOMEN.

411
00:14:41,413 --> 00:14:42,681
PRETTY IMPRESSIVE, RIGHT?

412
00:14:42,748 --> 00:14:45,251
SO YOU DO THE MATH, I THINK

413
00:14:45,317 --> 00:14:46,485
THERE ARE 365 DAYS IN A YEAR, SO

414
00:14:46,552 --> 00:14:49,555
THIS WENT ON EVEN FURTHER.

415
00:14:49,622 --> 00:14:53,058
SO IT LOOKS LIKE AT LEAST THE

416
00:14:53,125 --> 00:14:54,260
IMMUNE SUPPRESSIVE PROTOCOL,

417
00:14:54,326 --> 00:14:56,128
WHICH WAS WORKED ON HERE, SEEMED

418
00:14:56,195 --> 00:14:59,932
TO BE WORKING.

419
00:14:59,999 --> 00:15:01,133
WE TOOK THAT OPPORTUNITY TO

420
00:15:01,200 --> 00:15:02,568
RECRUIT YOUR WONDERFUL

421
00:15:02,635 --> 00:15:06,372
SCIENTIST, DR. MOHADEEN TO

422
00:15:06,438 --> 00:15:07,506
MARYLAND, AND WE BECAME FAST

423
00:15:07,573 --> 00:15:07,740
FRIENDS.

424
00:15:07,806 --> 00:15:09,141
AND THE ROLE OF THE MARYLAND LAB

425
00:15:09,208 --> 00:15:10,576
WAS TO TAKE THAT HEART OUT OF

426
00:15:10,643 --> 00:15:11,977
THE ABDOMEN AND PUT IT IN THE

427
00:15:12,044 --> 00:15:13,178
CHEST AND MAKE IT A WORKING

428
00:15:13,245 --> 00:15:14,713
HEART.

429
00:15:14,780 --> 00:15:18,851
BASICALLY DO A HUMAN ESQUE-TYPE

430
00:15:18,917 --> 00:15:20,819
TRANSPLANT OF THAT BABOON WITH

431
00:15:20,886 --> 00:15:22,154
THE PIG'S HEART SO IT WOULD BE

432
00:15:22,221 --> 00:15:24,556
IN A WORKING DEMAND

433
00:15:24,623 --> 00:15:26,425
RELATIONSHIP, AND THAT WAS THE

434
00:15:26,492 --> 00:15:27,192
NECESSARY STEP BEFORE WE COULD

435
00:15:27,259 --> 00:15:31,563
BEGIN TO CONSIDER A HUMAN USE.

436
00:15:31,630 --> 00:15:32,631
THAT'S WHAT THAT HEART LOOKS

437
00:15:32,698 --> 00:15:33,098
LIKE.

438
00:15:33,165 --> 00:15:33,766
PRETTY NEAT, RIGHT?

439
00:15:33,832 --> 00:15:35,100
THIS WAS ACTUALLY THE HEART FOR

440
00:15:35,167 --> 00:15:36,268
OUR SECOND PATIENT.

441
00:15:36,335 --> 00:15:37,336
BEAUTIFUL, RIGHT?

442
00:15:37,403 --> 00:15:38,570
THAT'S BEFORE WE REMOVED IT FROM

443
00:15:38,637 --> 00:15:40,606
THE PIG.

444
00:15:40,673 --> 00:15:42,274
WE DID A BUNCH OF STUDIES, AND

445
00:15:42,341 --> 00:15:44,276
WHEN I SAY A BUNCH OF STUDIES,

446
00:15:44,343 --> 00:15:44,777
I'M EMBARRASSED.

447
00:15:44,843 --> 00:15:46,545
WHEN YOU LOOK AT THE ENDS ON THE

448
00:15:46,612 --> 00:15:49,481
RIGHT-HAND SIDE, N OF 1, N OF 2,

449
00:15:49,548 --> 00:15:52,651
N OF 4, THAT'S SILLY SCIENCE,

450
00:15:52,718 --> 00:15:53,218
RIGHT?

451
00:15:53,285 --> 00:15:56,188
BUT REMEMBER THESE ARE

452
00:15:56,255 --> 00:15:57,022
ENGINEERED PIG HEARTS THAT GO

453
00:15:57,089 --> 00:15:59,658
INTO A BABOON, AND THEN THEY'RE

454
00:15:59,725 --> 00:16:01,293
TAKEN CARE OF FOR A LONG TIME.

455
00:16:01,360 --> 00:16:02,728
WE AVERAGED OUT THE COST OF EACH

456
00:16:02,795 --> 00:16:03,962
OF THESE EXPERIMENTS TO BE IN

457
00:16:04,029 --> 00:16:07,966
THE NEIGHBORHOOD OF 500 TO

458
00:16:08,033 --> 00:16:08,233
$750,000.

459
00:16:08,300 --> 00:16:09,401
A PIECE.

460
00:16:09,468 --> 00:16:13,672
AND THEY TAKE A TON, YOU CAN'T

461
00:16:13,739 --> 00:16:15,341
DO A WHOLE BUNCH OF THEM IN A

462
00:16:15,407 --> 00:16:17,042
DAY SO IT'S ALL HANDS ON DECK TO

463
00:16:17,109 --> 00:16:18,143
GET ONE OF THESE ANIMALS

464
00:16:18,210 --> 00:16:19,144
THROUGH.

465
00:16:19,211 --> 00:16:20,979
ANYWAY, WE SETTLE ON THIS RED

466
00:16:21,046 --> 00:16:22,181
LINE OR EXCUSE ME ON THE GREEN

467
00:16:22,247 --> 00:16:25,584
LINE, WHICH IS THE 10 GENE PIG,

468
00:16:25,651 --> 00:16:26,452
BECAUSE THAT MADE THE MOST SENSE

469
00:16:26,518 --> 00:16:27,753
TO OUR SPONSOR BECAUSE THAT WAS

470
00:16:27,820 --> 00:16:28,987
THE PIG THEY WERE TRYING TO

471
00:16:29,054 --> 00:16:30,823
PRODUCE FOR UNIVERSAL NEED,

472
00:16:30,889 --> 00:16:31,924
KIDNEY, LUNG AND HEART.

473
00:16:31,990 --> 00:16:35,361
WE KIND OF LIKE THE 7 GENE PIG

474
00:16:35,427 --> 00:16:38,997
BUT WE WON'T GO INTO THAT TODAY.

475
00:16:39,064 --> 00:16:39,365
OKAY.

476
00:16:39,431 --> 00:16:41,767
DOES THE PIG HEART WORK?

477
00:16:41,834 --> 00:16:43,369
YOU'RE DARN RIGHT, IT WORKS, AND

478
00:16:43,435 --> 00:16:46,138
ON THE RIGHT-HAND SIDE, THIS IS

479
00:16:46,205 --> 00:16:46,705
MY SECOND PATIENT.

480
00:16:46,772 --> 00:16:49,108
BEFORE HE ROLLED IN FOR HIS

481
00:16:49,174 --> 00:16:49,742
TRANSPLANT.

482
00:16:49,808 --> 00:16:53,245
HE GOT SICK AS HECK.

483
00:16:53,312 --> 00:16:54,913
HIS HEART FIB RI LATED THE DAY

484
00:16:54,980 --> 00:16:56,982
BEFORE HE HAD SURGERY, HE WAS

485
00:16:57,049 --> 00:16:58,917
DEFIBRILLATED BY THAT AUTOMATIC

486
00:16:58,984 --> 00:16:59,918
DEFIBRILLATOR IN HIS CHEST.

487
00:16:59,985 --> 00:17:01,353
HIS CHEST WAS FULL OF FLUID, HIS

488
00:17:01,420 --> 00:17:02,988
LUNGS WERE FULL OF FLUID BECAUSE

489
00:17:03,055 --> 00:17:05,124
HIS HEART WAS ON ITS LAST LEG.

490
00:17:05,190 --> 00:17:06,925
SO WE HAD LOTS OF HIGH LEFT

491
00:17:06,992 --> 00:17:08,293
ATRIAL PRESSURE, PULMONARY

492
00:17:08,360 --> 00:17:08,560
EDEMA.

493
00:17:08,627 --> 00:17:10,963
HE WAS IN REAL TROUBLE.

494
00:17:11,029 --> 00:17:13,966
COMING OUT OF THE O.R. AFTER HIS

495
00:17:14,032 --> 00:17:15,567
PIG HEART TRANSPLANT, HE LOOKS

496
00:17:15,634 --> 00:17:18,203
LIKE THE IMAGE ON THE LEFT.

497
00:17:18,270 --> 00:17:19,938
SO THAT IS A PIG HEART IN HIS

498
00:17:20,005 --> 00:17:20,906
CHEST.

499
00:17:20,973 --> 00:17:22,474
THE LUNGS LOOK BETTER, RIGHT?

500
00:17:22,541 --> 00:17:23,876
YOU WOULD AGREE, RIGHT?

501
00:17:23,942 --> 00:17:25,677
YES, NOD HEAD, PLEASE.

502
00:17:25,744 --> 00:17:26,612
THANK YOU.

503
00:17:26,678 --> 00:17:28,580
SO THE HEART WORKS, YOU KNOW?

504
00:17:28,647 --> 00:17:30,115
IT A PIG HEART IN A HUMAN.

505
00:17:30,182 --> 00:17:31,083
WHO WOULD GUESS, RIGHT?

506
00:17:31,150 --> 00:17:32,618
SO IT'S A GOOD THING IT WORKED.

507
00:17:32,684 --> 00:17:34,586
AND TO SHOW YOU A LITTLE MORE

508
00:17:34,653 --> 00:17:36,688
THAT IT WORKED, THIS IS AN

509
00:17:36,755 --> 00:17:37,122
ECHOCARDIOGRAM.

510
00:17:37,189 --> 00:17:40,826
IT'S A PARTICULAR TYPE THAT

511
00:17:40,893 --> 00:17:42,461
SHOWS STRAIN, IT SHOWS

512
00:17:42,528 --> 00:17:43,328
LONGITUDAL STRAIN.

513
00:17:43,395 --> 00:17:44,997
IT BASICALLY SHOWS HOW WELL THAT

514
00:17:45,063 --> 00:17:47,366
HEART WILL CONTRACT,

515
00:17:47,433 --> 00:17:50,803
BEAT-TO-BEAT, IN A LONGITUDAL

516
00:17:50,869 --> 00:17:51,203
ARRAY.

517
00:17:51,270 --> 00:17:52,671
AND I'VE USED THE WORD BEFORE

518
00:17:52,738 --> 00:17:54,239
AND I USE IT EVERY TIME I SEE

519
00:17:54,306 --> 00:17:54,740
IT.

520
00:17:54,807 --> 00:17:57,543
THIS HEART IS A ROCK STAR.

521
00:17:57,609 --> 00:18:04,550
WORKS REALLY WELL.

522
00:18:04,616 --> 00:18:06,218
WE GOT 100 DAYS OF EXPERIENCE,

523
00:18:06,285 --> 00:18:07,853
BUT BEFORE WE DID SO, WE HAD TO

524
00:18:07,920 --> 00:18:09,488
GET PERMISSION TO GO FORWARD.

525
00:18:09,555 --> 00:18:11,990
SO WE TOOK ALL OF OUR EXPERIENCE

526
00:18:12,057 --> 00:18:16,929
IN THE LABORATORY, AND SENT TO

527
00:18:16,995 --> 00:18:18,564
THE FDA.

528
00:18:18,630 --> 00:18:19,798
AND NONE OF US THOUGHT THEY

529
00:18:19,865 --> 00:18:22,935
WOULD SAY YES.

530
00:18:23,001 --> 00:18:24,136
THEY DID.

531
00:18:24,203 --> 00:18:28,307
AND CERTAINLY MY INSTITUTION

532
00:18:28,373 --> 00:18:29,408
DIDN'T THINK -- THEY ALL WENT

533
00:18:29,475 --> 00:18:30,742
AWAY FOR THE HOLIDAY WEEKEND,

534
00:18:30,809 --> 00:18:31,977
WHICH WAS, YOU KNOW, A LONG

535
00:18:32,044 --> 00:18:33,445
CHRISTMAS AND THEN NEW YEAR'S,

536
00:18:33,512 --> 00:18:35,414
THEY CAME BACK, YOU KNOW, AFTER

537
00:18:35,481 --> 00:18:37,349
THE FIRST, AND I GOT THE FIRST

538
00:18:37,416 --> 00:18:40,752
LETTER OF APPROVAL DECEMBER 31ST

539
00:18:40,819 --> 00:18:42,287
AT 5:00 P.M.

540
00:18:42,354 --> 00:18:43,989
I REMEMBER IT BECAUSE I JUST SAT

541
00:18:44,056 --> 00:18:46,024
DOWN WITH MY WIFE WITH A GLASS

542
00:18:46,091 --> 00:18:47,426
OF CHAMPAGNE, AND THEN THERE WAS

543
00:18:47,493 --> 00:18:49,862
REASON TO DRAIN THE BOTTLE.

544
00:18:49,928 --> 00:18:51,163
BUT THEN WE GOT REALLY SCARED,

545
00:18:51,230 --> 00:18:52,464
RIGHT?

546
00:18:52,531 --> 00:18:53,699
SO ONE OF THE THINGS I MENTIONED

547
00:18:53,765 --> 00:18:56,635
TO THE STUDENTS TODAY WAS HOW

548
00:18:56,702 --> 00:18:59,905
NICE IT WAS THAT THE REGULATORY

549
00:18:59,972 --> 00:19:02,741
PROGRAM AT THE FDA NOT ONLY DID

550
00:19:02,808 --> 00:19:05,043
THEY DO A THOROUGH EVALUATION IN

551
00:19:05,110 --> 00:19:06,678
MY OPINION, THEY MADE US ANSWER

552
00:19:06,745 --> 00:19:08,347
THE QUESTIONS THAT WE FELT WE

553
00:19:08,413 --> 00:19:10,549
HAD TO ANSWER.

554
00:19:10,616 --> 00:19:11,850
AND THEN WHEN IT WAS ALL SAID

555
00:19:11,917 --> 00:19:13,919
AND DONE AND THEY'D GIVEN US

556
00:19:13,986 --> 00:19:14,786
PERMISSION, THE DAY OF THE

557
00:19:14,853 --> 00:19:16,421
INTENDED SURGERY, I GOT AN EMAIL

558
00:19:16,488 --> 00:19:17,756
IN THE MORNING -- OR THE NIGHT

559
00:19:17,823 --> 00:19:19,391
BEFORE, AND IT JUST SIMPLY SAID

560
00:19:19,458 --> 00:19:22,060
THIS, WHICH WAS, "DR. GRIFFITH,

561
00:19:22,127 --> 00:19:24,096
WE WISH YOU THE BEST OF LUCK

562
00:19:24,162 --> 00:19:24,363
TOMORROW."

563
00:19:24,429 --> 00:19:25,264
ISN'T THAT NICE?

564
00:19:25,330 --> 00:19:26,598
I MEAN, ISN'T THAT NICE?

565
00:19:26,665 --> 00:19:28,333
IT MADE ME FEEL REALLY GOOD

566
00:19:28,400 --> 00:19:30,435
THAT, YOU KNOW, WE HAD BEEN

567
00:19:30,502 --> 00:19:31,503
THROUGH THE GAUNTLET OF

568
00:19:31,570 --> 00:19:32,604
REGULATORY APPROVAL AND NOW

569
00:19:32,671 --> 00:19:34,273
THEY'RE CHEERING FOR US.

570
00:19:34,339 --> 00:19:39,945
THAT WAS PRETTY NEAT.

571
00:19:40,012 --> 00:19:41,146
PATIENT -- AS I TOLD YOU AT THE

572
00:19:41,213 --> 00:19:43,982
VERY FIRST SLIDE, IT'S YOUR LAST

573
00:19:44,049 --> 00:19:45,417
DAY, HAVE AN ICE CREAM CONE,

574
00:19:45,484 --> 00:19:46,618
WELL, HAVE A PIG HEART BECAUSE

575
00:19:46,685 --> 00:19:47,920
YOU'RE NOT GOING TO LIVE LONG IF

576
00:19:47,986 --> 00:19:49,454
YOU DON'T, AND YOU MAY LIVE

577
00:19:49,521 --> 00:19:51,423
LONGER IF YOU DO.

578
00:19:51,490 --> 00:19:53,725
AND THAT'S THE APPROACH THAT I

579
00:19:53,792 --> 00:19:55,494
TOOK WITH MY PATIENT.

580
00:19:55,561 --> 00:19:56,562
HE WAS VERY SICK.

581
00:19:56,628 --> 00:19:58,964
YOU CAN SEE THIS POUR SOUL.

582
00:19:59,031 --> 00:20:01,166
HIS LOWER LEG IS SHOWN ON THE

583
00:20:01,233 --> 00:20:04,202
LEFT PANEL WITH MY NOT VERY BIG

584
00:20:04,269 --> 00:20:05,737
HAND TRYING TO GET AROUND THE

585
00:20:05,804 --> 00:20:08,941
ENTIRETY OF IT WITH A FINGER --

586
00:20:09,007 --> 00:20:11,343
THUMB AND AN INDEX FINGER.

587
00:20:11,410 --> 00:20:13,011
HIS VENTRICLE WAS NOT SQUEEZING

588
00:20:13,078 --> 00:20:14,279
WELL AT ALL.

589
00:20:14,346 --> 00:20:17,349
THAT'S A VERY, VERY

590
00:20:17,416 --> 00:20:18,150
HYPOCONTRACTILE LEFT VENTRICLE

591
00:20:18,216 --> 00:20:19,318
AND QUITE ENLARGED.

592
00:20:19,384 --> 00:20:20,953
HE HAD BEEN HOSPITALIZED FOR

593
00:20:21,019 --> 00:20:21,720
61 DAYS.

594
00:20:21,787 --> 00:20:28,293
HIS WHITE COUNT WAS 3.2 AND IT

595
00:20:28,360 --> 00:20:29,595
HIT .1 AFTER THE PROCEDURE.

596
00:20:29,661 --> 00:20:30,862
HIS PLATELET COUNT WAS LOW AND

597
00:20:30,929 --> 00:20:32,564
IT WENT ALL THE WAY DOWN TO 10

598
00:20:32,631 --> 00:20:33,865
AFTER THE PROCEDURE.

599
00:20:33,932 --> 00:20:36,702
HE HAD THIS STRIKING SARCOPENIA,

600
00:20:36,768 --> 00:20:38,503
AND THAT MEANS LOSS OF MUSCLE

601
00:20:38,570 --> 00:20:39,004
MASS.

602
00:20:39,071 --> 00:20:41,506
SO HE WAS VERY MUCH KE KAK TICK.

603
00:20:41,573 --> 00:20:45,010
ONE WOULD NOT THINK IT WOULD BE

604
00:20:45,077 --> 00:20:49,615
SENSENSIBLE TO DO ANY KIND OF

605
00:20:49,681 --> 00:20:50,582
EXTREME SURGERY ON IT.

606
00:20:50,649 --> 00:20:52,250
BUT HE HAD NO OPTION AND WE

607
00:20:52,317 --> 00:20:53,652
FRANKLY THOUGHT WE NEEDED TO

608
00:20:53,719 --> 00:20:54,319
LEARN WHAT WOULD HAPPEN.

609
00:20:54,386 --> 00:20:56,154
WE DID PRETTY WELL OVERALL, AND

610
00:20:56,221 --> 00:20:57,723
WE WERE SITTING AROUND AFTER

611
00:20:57,789 --> 00:20:59,024
ABOUT 21 DAYS, HE WAS GETTING

612
00:20:59,091 --> 00:21:00,325
BETTER, HE WAS PUTTING ON SOME

613
00:21:00,392 --> 00:21:00,692
MUSCLE.

614
00:21:00,759 --> 00:21:01,960
WE WERE KIND OF FEELING GOOD

615
00:21:02,027 --> 00:21:04,196
ABOUT THINGS AND OUR I.D. TEAM,

616
00:21:04,262 --> 00:21:06,665
AND WE DID MULTIDISCIPLINARY

617
00:21:06,732 --> 00:21:09,501
ROUNDS EVERY DAY IN THE MORNING

618
00:21:09,568 --> 00:21:09,868
AND AT NIGHT.

619
00:21:09,935 --> 00:21:12,037
IT WAS REALLY COMING TOGETHER OF

620
00:21:12,104 --> 00:21:13,238
IN-KIND CRAZIES WHO REALLY CARED

621
00:21:13,305 --> 00:21:13,939
ABOUT THIS PATIENT.

622
00:21:14,006 --> 00:21:15,641
IT WAS A WONDERFUL OPPORTUNITY

623
00:21:15,707 --> 00:21:17,643
TO LEARN FROM THEM AND THEN FROM

624
00:21:17,709 --> 00:21:18,710
US.

625
00:21:18,777 --> 00:21:21,213
BUT THE I.D. GUY WHO WAS RATHER

626
00:21:21,279 --> 00:21:26,151
QUIET, SUBTLE, KAPIL SAHARIA, HE

627
00:21:26,218 --> 00:21:27,786
HAD SEEN THIS LITTLE BLIP HERE

628
00:21:27,853 --> 00:21:32,924
AT DAY 25 IN CELL-FREE DNA OF A

629
00:21:32,991 --> 00:21:34,259
VIRUS KNOWN TO BE PRESENT IN

630
00:21:34,326 --> 00:21:36,094
PIGS.

631
00:21:36,161 --> 00:21:38,196
AND IT WAS NOW IN MY PATIENT'S

632
00:21:38,263 --> 00:21:40,532
SERUM.

633
00:21:40,599 --> 00:21:40,899
OKAY?

634
00:21:40,966 --> 00:21:43,969
HE GOT SOME DNA FRAGMENT KNOWN

635
00:21:44,036 --> 00:21:45,837
TO BE PRESENT IN THIS VIRUS THAT

636
00:21:45,904 --> 00:21:47,272
WE SHOULDN'T HAVE BEEN

637
00:21:47,339 --> 00:21:48,006
TRANSPLANTING INTO THE PATIENT.

638
00:21:48,073 --> 00:21:49,541
WHERE DID THE PATIENT GET IT?

639
00:21:49,608 --> 00:21:50,375
WELL, IT WOULD HAVE TO COME FROM

640
00:21:50,442 --> 00:21:51,309
THE HEART.

641
00:21:51,376 --> 00:21:53,712
RIGHT?

642
00:21:53,779 --> 00:21:55,514
WE THOUGHT IT WAS CRAZY AND HE

643
00:21:55,580 --> 00:21:57,115
DIDN'T SAY ANYTHING UNTIL AFTER

644
00:21:57,182 --> 00:21:58,183
DAY 30, WHEN HE GOT ANOTHER

645
00:21:58,250 --> 00:21:59,518
SAMPLE.

646
00:21:59,584 --> 00:22:01,253
AND IT WAS GOING UP.

647
00:22:01,319 --> 00:22:03,555
SO NOW WE'RE FREAKING OUT,

648
00:22:03,622 --> 00:22:04,322
RIGHT?

649
00:22:04,389 --> 00:22:06,391
WE TRANSPLANTED A HEART THAT HAD

650
00:22:06,458 --> 00:22:08,827
PCMV, WE KNEW PCMV IS NOT A GOOD

651
00:22:08,894 --> 00:22:10,762
THING FOR HUMANS TO HAVE.

652
00:22:10,829 --> 00:22:13,165
CMV LIVES IN THE ENDOTHELIUM AND

653
00:22:13,231 --> 00:22:15,801
WHEN IT COMES OUT OF ITS

654
00:22:15,867 --> 00:22:17,869
HIBERNATION WITH REDUCED

655
00:22:17,936 --> 00:22:19,638
IMMUNITY, JUST LIKE HERPES DOES

656
00:22:19,705 --> 00:22:23,675
IN YOUR LIP, IT EXPLODES THE

657
00:22:23,742 --> 00:22:25,510
CELL OF ORIGIN, WHICH WOULD BE

658
00:22:25,577 --> 00:22:27,546
THE ENDOTHELIAL CELL, AND THAT

659
00:22:27,612 --> 00:22:29,047
WOULD BREAK DOWN CAPILLARIES.

660
00:22:29,114 --> 00:22:30,248
NOT GOOD.

661
00:22:30,315 --> 00:22:32,317
WE GAVE HIM A BUNCH OF DIFFERENT

662
00:22:32,384 --> 00:22:34,386
ANTIVIRALS AS SHOWN HERE.

663
00:22:34,453 --> 00:22:35,487
THOSE ANTIVIRALS ARE ROUGH ON

664
00:22:35,554 --> 00:22:36,054
THE BONE MARROW.

665
00:22:36,121 --> 00:22:37,122
REMEMBER WHAT I TOLD YOU?

666
00:22:37,189 --> 00:22:39,591
IN FACT, IT TOOK OFF ON DAY 45

667
00:22:39,658 --> 00:22:42,728
BECAUSE WE HAD TO CHANGE THE

668
00:22:42,794 --> 00:22:44,129
ANTIVIRAL THERAPY TO REDUCE IT

669
00:22:44,196 --> 00:22:46,331
SIMPLY BECAUSE HE WAS

670
00:22:46,398 --> 00:22:47,165
NEUTROPENIC.

671
00:22:47,232 --> 00:22:48,166
AGAIN, AND THIS GOES BACK TO

672
00:22:48,233 --> 00:22:49,367
PICKING YOUR PATIENT, RIGHT?

673
00:22:49,434 --> 00:22:51,336
IF WE'D PICKED A PATIENT WITH

674
00:22:51,403 --> 00:22:52,104
BETTER BONE MARROW, HE WOULD

675
00:22:52,170 --> 00:22:53,338
HAVE DONE BETTER, BUT WE

676
00:22:53,405 --> 00:22:54,272
WOULDN'T HAVE DONE THE PROCEDURE

677
00:22:54,339 --> 00:22:55,373
BECAUSE WE DIDN'T HAVE THAT

678
00:22:55,440 --> 00:22:55,607
PATIENT.

679
00:22:55,674 --> 00:22:57,042
SO WE DID OUR BEST WITH WHAT WE

680
00:22:57,109 --> 00:22:57,709
HAD.

681
00:22:57,776 --> 00:22:59,678
BUT THERE ARE ALWAYS LIMITS.

682
00:22:59,745 --> 00:23:00,979
IN THE END, I THINK WE KILLED

683
00:23:01,046 --> 00:23:03,048
THE VIRUS.

684
00:23:03,115 --> 00:23:05,450
AND THE PATIENT ENDED UP PASSING

685
00:23:05,517 --> 00:23:06,518
AWAY AND WE'LL TALK ABOUT THAT

686
00:23:06,585 --> 00:23:09,621
DEATH.

687
00:23:09,688 --> 00:23:11,156
THIS PATIENT AGAIN HAD A ROCK

688
00:23:11,223 --> 00:23:11,790
STAR HEART.

689
00:23:11,857 --> 00:23:14,860
IT'S SHOWN ON THE LEFT PANEL.

690
00:23:14,926 --> 00:23:16,728
DAY 19.

691
00:23:16,795 --> 00:23:20,332
DAY 49, IT LOOKS VERY DIFFERENT.

692
00:23:20,398 --> 00:23:21,433
IT'S THICKER, ISN'T IT?

693
00:23:21,500 --> 00:23:22,534
DOES IT LOOK THICKER?

694
00:23:22,601 --> 00:23:23,168
IT SHOULD.

695
00:23:23,235 --> 00:23:25,804
IT'S SQUEEZING, BUT IT'S

696
00:23:25,871 --> 00:23:26,104
THICKENING.

697
00:23:26,171 --> 00:23:27,005
AND THE PATIENT HAD SOMETHING

698
00:23:27,072 --> 00:23:29,074
THAT I'VE NEVER SEEN BEFORE IN

699
00:23:29,141 --> 00:23:31,710
CLINICAL MEDICINE, AND THAT IS

700
00:23:31,777 --> 00:23:33,145
ACUTE DIASTOLIC DYSFUNCTION.

701
00:23:33,211 --> 00:23:35,380
AND THAT MEANS THE HEART CAN'T

702
00:23:35,447 --> 00:23:36,515
RELAX TO FILL.

703
00:23:36,581 --> 00:23:37,849
JUST LIKE A BELL OWES.

704
00:23:37,916 --> 00:23:41,019
IF YOU DON'T OPEN THE BELLOWS,

705
00:23:41,086 --> 00:23:41,787
NOTHING COMES OUT.

706
00:23:41,853 --> 00:23:43,388
IF YOU CAN ONLY OPEN IT HALFWAY,

707
00:23:43,455 --> 00:23:44,856
YOU DON'T GET NEARLY AS MUCH

708
00:23:44,923 --> 00:23:45,824
STROKE OUT.

709
00:23:45,891 --> 00:23:47,692
WELL, THIS HEART CAN'T RELAX,

710
00:23:47,759 --> 00:23:48,627
AND WE'D NEVER SEEN ANYTHING

711
00:23:48,693 --> 00:23:48,994
LIKE IT.

712
00:23:49,060 --> 00:23:52,497
WE REALLY HADN'T SEEN IT IN OUR

713
00:23:52,564 --> 00:23:53,832
NON-HUMAN PRIMATE TO ANY

714
00:23:53,899 --> 00:23:54,366
GREAT DEGREE EITHER.

715
00:23:54,432 --> 00:23:55,567
WE WEREN'T REALLY SURE WHETHER

716
00:23:55,634 --> 00:23:56,868
THIS WAS AN ADVENT OF SEPSIS,

717
00:23:56,935 --> 00:23:58,837
MAYBE IT WAS A MYOCARDIAL

718
00:23:58,904 --> 00:23:59,304
DEPRESSANT FACTOR.

719
00:23:59,371 --> 00:24:00,939
SOMETHING WAS GOING ON.

720
00:24:01,006 --> 00:24:02,207
BUT WE'VE LEARNED MORE ABOUT

721
00:24:02,274 --> 00:24:04,209
WHAT IT MIGHT HAVE BEEN.

722
00:24:04,276 --> 00:24:05,844
REMEMBER I TALKED ABOUT THE

723
00:24:05,911 --> 00:24:07,479
ENDOTHELIAL CELL AND THE VIRUS.

724
00:24:07,546 --> 00:24:09,147
WE WERE STILL PERCOLATING WITH

725
00:24:09,214 --> 00:24:10,882
THIS VIRUS STORY, WE DIDN'T KNOW

726
00:24:10,949 --> 00:24:14,186
WHERE WE WERE WITH THAT.

727
00:24:14,252 --> 00:24:19,424
AT THE TIME OF HIS FIRST END

728
00:24:19,491 --> 00:24:21,393
ENDO MYOCARD YAL BIOPSY ON DAY

729
00:24:21,459 --> 00:24:22,694
33, IT WAS DONE JUST FOR

730
00:24:22,761 --> 00:24:23,562
SURVEILLANCE.

731
00:24:23,628 --> 00:24:24,596
THE CARDIOLOGIST COULDN'T WAIT

732
00:24:24,663 --> 00:24:25,964
FOR US TO TAKE A PIECE OF THIS

733
00:24:26,031 --> 00:24:26,832
MAN'S HEART SO THEY COULD LOOK

734
00:24:26,898 --> 00:24:28,033
AT IT UNDER THE MICROSCOPE.

735
00:24:28,099 --> 00:24:31,336
WE WERE INTERESTED BUT WE WERE

736
00:24:31,403 --> 00:24:32,437
CONSERVATIVE BECAUSE HE HAD NO

737
00:24:32,504 --> 00:24:33,305
PLATELET COUNT.

738
00:24:33,371 --> 00:24:35,507
AND SO WE DIDN'T WANT TO HAVE A

739
00:24:35,574 --> 00:24:36,374
RUPTURE OF THE HEART AND GET

740
00:24:36,441 --> 00:24:37,242
INTO BLEEDING DIFFICULTIES.

741
00:24:37,309 --> 00:24:38,677
SO WE JUST KIND OF HUNG OUT FOR

742
00:24:38,743 --> 00:24:41,947
A WHILE.

743
00:24:42,013 --> 00:24:42,914
THE SECOND BIOPSY -- AND BY THE

744
00:24:42,981 --> 00:24:44,449
WAY, THAT FIRST BIOPSY SHOWS A

745
00:24:44,516 --> 00:24:46,852
GREAT BIG NUCLEUS AND THAT'S AN

746
00:24:46,918 --> 00:24:47,853
ENDOTHELIAL CELL THAT'S NORMAL.

747
00:24:47,919 --> 00:24:49,054
THAT'S WHAT THEY'RE SUPPOSED TO

748
00:24:49,120 --> 00:24:51,556
LOOK LIKE ON E.M.

749
00:24:51,623 --> 00:24:53,258
THE NEXT ONE SHOWS SOME SWELLING

750
00:24:53,325 --> 00:24:53,758
OF THE CELL.

751
00:24:53,825 --> 00:24:55,393
IT'S NOT PERFECTLY NORMAL.

752
00:24:55,460 --> 00:24:59,331
AND THEN THE THIRD ENDO MYOCARD

753
00:24:59,397 --> 00:25:01,533
YAL BIOPSY SHOWS THAT WE'VE HAD

754
00:25:01,600 --> 00:25:03,602
EXPLOSION OF THE CAPILLARY BED.

755
00:25:03,668 --> 00:25:05,003
WE'VE LOST ENDOTHELIAL CELLS.

756
00:25:05,070 --> 00:25:06,037
AND WITH THAT, GUESS WHAT

757
00:25:06,104 --> 00:25:06,438
HAPPENS?

758
00:25:06,504 --> 00:25:09,908
THE HEART WILL SWELL.

759
00:25:09,975 --> 00:25:10,775
RIGHT?

760
00:25:10,842 --> 00:25:12,410
YOU DON'T HAVE A VASCULAR

761
00:25:12,477 --> 00:25:15,146
BARRIER ANYMORE.

762
00:25:15,213 --> 00:25:16,481
IT JUST LIKE LUNGS THAT GET SICK

763
00:25:16,548 --> 00:25:17,816
WITH ARDS.

764
00:25:17,883 --> 00:25:18,250
THEY LEAK.

765
00:25:18,316 --> 00:25:21,086
SO OUR HEART WAS LEAKING, AND IT

766
00:25:21,152 --> 00:25:22,387
DID SO JUST LIKE IF YOU HAD

767
00:25:22,454 --> 00:25:24,789
TURNED YOUR ANKLE ON THE CURB

768
00:25:24,856 --> 00:25:25,891
COMING OVER HERE TODAY AND YOU

769
00:25:25,957 --> 00:25:28,994
LOOKED DOWN AND WITHIN

770
00:25:29,060 --> 00:25:30,829
10 SECONDS, IT'S THE SIZE OF A

771
00:25:30,896 --> 00:25:31,263
GRAPEFRUIT, RIGHT?

772
00:25:31,329 --> 00:25:33,565
IT JUST IS REACTION.

773
00:25:33,632 --> 00:25:34,633
AND WE THOUGHT THAT MAYBE THAT'S

774
00:25:34,699 --> 00:25:36,935
WHAT WE HAD SEEN, AND WE WEREN'T

775
00:25:37,002 --> 00:25:38,370
SURE WHETHER THIS WAS FROM THE

776
00:25:38,436 --> 00:25:43,074
VIRUS OR WHAT.

777
00:25:43,141 --> 00:25:44,276
WE WROTE THAT UP, SPENT A YEAR

778
00:25:44,342 --> 00:25:45,377
AND A HALF TRYING TO GET SMART

779
00:25:45,443 --> 00:25:46,344
AND WE REALLY DIDN'T.

780
00:25:46,411 --> 00:25:47,679
WE REALLY WEREN'T SURE.

781
00:25:47,746 --> 00:25:49,547
SO WE CLEANED UP OUR PATIENT

782
00:25:49,614 --> 00:25:49,814
CRITERIA.

783
00:25:49,881 --> 00:25:52,817
WE'RE GOING TO GIVE A SECOND

784
00:25:52,884 --> 00:25:53,919
PATIENT AN OPPORTUNITY HERE AND

785
00:25:53,985 --> 00:25:55,754
WE'RE GOING TO MAKE SURE THEY

786
00:25:55,820 --> 00:25:57,122
HAVE A GOOD BONE MARROW, AND BY

787
00:25:57,188 --> 00:25:59,157
THE WAY, WE'RE GOING TO GET A

788
00:25:59,224 --> 00:26:00,458
BETTER TEST FOR THAT VIRUS THAT

789
00:26:00,525 --> 00:26:01,226
SLIPPED BY.

790
00:26:01,293 --> 00:26:02,193
WE DID BOTH THOSE THINGS.

791
00:26:02,260 --> 00:26:06,898
SO THE SECOND PATIENT WAS AN

792
00:26:06,965 --> 00:26:09,000
EX-TECHNICIAN IN THE

793
00:26:09,067 --> 00:26:10,568
HISTOPATHOLOGY DEPARTMENT OF THE

794
00:26:10,635 --> 00:26:13,038
I.D. DIVISION HERE AT THE NIH.

795
00:26:13,104 --> 00:26:14,773
HE UNDERSTOOD WHAT WE WERE

796
00:26:14,839 --> 00:26:15,340
TALKING ABOUT.

797
00:26:15,407 --> 00:26:17,976
HE UNDERSTOOD THAT HE WAS NOT

798
00:26:18,043 --> 00:26:20,578
LIKELY TO BENEFIT LONG TERM WITH

799
00:26:20,645 --> 00:26:22,013
THE PIG HEART TRANSPLANT, BUT IT

800
00:26:22,080 --> 00:26:23,648
WAS HIS ONLY OPTION FOR REASONS

801
00:26:23,715 --> 00:26:27,052
I WON'T GO INTO.

802
00:26:27,118 --> 00:26:28,353
SO HE WANTED TO GET HOME AND

803
00:26:28,420 --> 00:26:30,522
HAVE A CUP OF COFFEE WITH HIS

804
00:26:30,588 --> 00:26:32,624
WIFE ON HIS PORCH.

805
00:26:32,691 --> 00:26:33,625
THAT'S ALL HE WANTED.

806
00:26:33,692 --> 00:26:35,160
HE WAS THE GENTLEMAN THAT HAD

807
00:26:35,226 --> 00:26:36,561
THAT NASTY LOOKING X-RAY PRE-OP

808
00:26:36,628 --> 00:26:38,196
THAT I SHOWED ALREADY, AND THAT

809
00:26:38,263 --> 00:26:39,931
WAS HIS CT SCAN ALSO PREO SO WE

810
00:26:39,998 --> 00:26:41,366
WERE UP AGAINST IT THERE.

811
00:26:41,433 --> 00:26:43,068
BUT THERE HE IS ON POST-OP DAY

812
00:26:43,134 --> 00:26:44,235
TWO.

813
00:26:44,302 --> 00:26:47,038
STANDING UP WITH CHRIS WELLS,

814
00:26:47,105 --> 00:26:49,240
ONE OF OUR PHYSICAL THERAPISTS.

815
00:26:49,307 --> 00:26:49,808
PRETTY COOL.

816
00:26:49,874 --> 00:26:51,309
HE WENT ON TO PLAY CARDS AND,

817
00:26:51,376 --> 00:26:53,611
YOU KNOW, HE WAS VERY, VERY

818
00:26:53,678 --> 00:26:55,046
JIBBER JABBER AND, YOU KNOW, HE

819
00:26:55,113 --> 00:26:58,316
WAS HAPPY TO BE ALIVE.

820
00:26:58,383 --> 00:27:01,820
HE REALLY DIDN'T -- HE DIDN'T

821
00:27:01,886 --> 00:27:04,556
HAVE MUCH TO SAY NEGATIVE ABOUT

822
00:27:04,622 --> 00:27:07,292
HIS EXPERIENCE WHATSOEVER.

823
00:27:07,359 --> 00:27:10,028
I DID TELL YOU WE DID A BIOPSY,

824
00:27:10,095 --> 00:27:12,297
RIGHT?

825
00:27:12,364 --> 00:27:15,066
THAT FIRST BIOPSY, WE TOOK A

826
00:27:15,133 --> 00:27:17,102
PHOTOGRAPH OF THE MICROSCOPIC

827
00:27:17,168 --> 00:27:18,336
VIEW AND WE BROUGHT THAT UP FOR

828
00:27:18,403 --> 00:27:20,739
HIM TO READ, BECAUSE WHAT WAS

829
00:27:20,805 --> 00:27:20,905
HE?

830
00:27:20,972 --> 00:27:22,841
HE WAS A HISTOPATHOLOGY TECH,

831
00:27:22,907 --> 00:27:23,375
RIGHT?

832
00:27:23,441 --> 00:27:25,477
SO IF YOU JUST FORGIVE ME FOR

833
00:27:25,543 --> 00:27:28,313
BEING A LITTLE SH MALTSY AND

834
00:27:28,380 --> 00:27:29,381
HUMAN, I WANT YOU TO HEAR WHAT

835
00:27:29,447 --> 00:27:33,718
HE SAID, OKAY?

836
00:27:33,785 --> 00:27:34,686
BOY, WE DON'T HAVE VOLUME.

837
00:27:34,753 --> 00:27:36,888
DO YOU HAVE VOLUME, GUYS?

838
00:27:36,955 --> 00:27:44,763
IT ON HERE.

839
00:27:44,829 --> 00:27:46,965
THIS ISING IF TO BE NOT SO GOOD.

840
00:27:47,032 --> 00:27:48,166
CAN YOU CHANGE THAT UP THERE?

841
00:27:48,233 --> 00:27:49,601
I'VE GOT A FINGER UP IN THE AIR

842
00:27:49,667 --> 00:27:50,902
SO MAYBE WE CAN GET IT.

843
00:27:50,969 --> 00:27:52,003
IT WORTH LISTENING TO.

844
00:27:52,070 --> 00:27:53,405
HE'S BASICALLY SAYING, THIS IS A

845
00:27:53,471 --> 00:27:54,639
NORMAL BIOPSY.

846
00:27:54,706 --> 00:27:57,776
IT LOOKS VERY GOOD HERE.

847
00:27:57,842 --> 00:28:01,079
AND HE -- WE KEPT SAYING -- SO

848
00:28:01,146 --> 00:28:03,715
IT LOOKS NORMAL TO YOU, RIGHT?

849
00:28:03,782 --> 00:28:05,884
WELL, WE WERE DELIGHTED -- LET'S

850
00:28:05,950 --> 00:28:07,185
SEE IF IT'S GOING TO RUN.

851
00:28:07,252 --> 00:28:08,486
>> WHAT DO YOU SEE IN HERE?

852
00:28:08,553 --> 00:28:16,728
>> I SEE PERFECTLY NORMAL HEART.

853
00:28:16,795 --> 00:28:21,232
-- RIGHT THERE.

854
00:28:21,299 --> 00:28:22,934
>> SO YOU'RE HAPPY ABOUT IT?

855
00:28:23,001 --> 00:28:24,135
>> I'M VERY HAPPY ABOUT THAT.

856
00:28:24,202 --> 00:28:25,703
>> NOW I REMIND YOU, THAT MAN

857
00:28:25,770 --> 00:28:27,338
HAS A PIG'S HEART.

858
00:28:27,405 --> 00:28:28,740
I COULDN'T GET OVER IT.

859
00:28:28,807 --> 00:28:28,940
RIGHT?

860
00:28:29,007 --> 00:28:30,175
AND TO THIS DAY, I CAN'T GET

861
00:28:30,241 --> 00:28:30,809
OVER IT.

862
00:28:30,875 --> 00:28:33,545
SIT DOWN AND TALK TO HIM ABOUT

863
00:28:33,611 --> 00:28:34,846
NORMAL STUFF.

864
00:28:34,913 --> 00:28:37,282
BALL GAMES, WHATEVER, HE HAS A

865
00:28:37,348 --> 00:28:38,583
PIG'S HEART.

866
00:28:38,650 --> 00:28:41,753
ANYHOW, OKAY.

867
00:28:41,820 --> 00:28:44,355
THE ZOO KNOW CYST PIECE, THE

868
00:28:44,422 --> 00:28:45,790
TRANSFER OF VIRUS OR AN

869
00:28:45,857 --> 00:28:47,859
INFECTION FROM AN ANIMAL TO A

870
00:28:47,926 --> 00:28:48,560
HUMAN, WE'RE REALLY WORRIED

871
00:28:48,626 --> 00:28:49,627
ABOUT THAT, RIGHT?

872
00:28:49,694 --> 00:28:52,163
AND THE BIG THING WERE THESE

873
00:28:52,230 --> 00:28:54,132
PERV VIRUSES WHICH CAN GET

874
00:28:54,199 --> 00:28:55,333
INTEGRATED INTO YOUR RNA AND

875
00:28:55,400 --> 00:28:59,604
THEN YOU HAVE IT AND YOUR

876
00:28:59,671 --> 00:29:00,805
PROGENY HAS IT, YOU JUST -- YOU

877
00:29:00,872 --> 00:29:01,806
DON'T WANT THAT.

878
00:29:01,873 --> 00:29:03,341
SO THAT, WE DIDN'T SEE ANY OF,

879
00:29:03,408 --> 00:29:05,510
AND WE WERE ABLE TO COMPLETELY

880
00:29:05,577 --> 00:29:07,812
EXCLUDE ANY PRESENCE OF THAT

881
00:29:07,879 --> 00:29:12,450
PREVIOUS VIRUS PCMV, WHICH WAS

882
00:29:12,517 --> 00:29:13,551
GOOD, AND THE FDA THOUGHT THAT

883
00:29:13,618 --> 00:29:14,853
WAS REALLY NICE THAT WE WERE

884
00:29:14,919 --> 00:29:15,520
ABLE TO DO THAT.

885
00:29:15,587 --> 00:29:20,592
HERE HE IS PLAYING CARDS.

886
00:29:20,658 --> 00:29:22,327
HE DID HAVE SOME BLEEDING AFTER

887
00:29:22,393 --> 00:29:23,328
SURGERY.

888
00:29:23,394 --> 00:29:25,163
HE HAD KIND OF A SMALLISH HEART

889
00:29:25,230 --> 00:29:26,064
RELATIVE BECAUSE OF THAT

890
00:29:26,131 --> 00:29:30,768
REDUCTION IN SIZE, HI THE HEARTS

891
00:29:30,835 --> 00:29:31,970
KIND OF SMALL.

892
00:29:32,036 --> 00:29:33,171
JUST BARELY BIG ENOUGH TO GET

893
00:29:33,238 --> 00:29:33,805
THE JOB DONE.

894
00:29:33,872 --> 00:29:35,240
WE DIDN'T HAVE ANOTHER PIG TO

895
00:29:35,306 --> 00:29:38,309
OFFER BY THE WAY, SO WHY DIDN'T

896
00:29:38,376 --> 00:29:39,711
WE GIVE HIM A BIGGER ONE?

897
00:29:39,777 --> 00:29:40,712
BECAUSE WE DIDN'T HAVE A BIGGER

898
00:29:40,778 --> 00:29:42,147
ONE AND HE WAS DYING SO THAT'S

899
00:29:42,213 --> 00:29:44,415
WHY WE THOUGHT WE'D GET BY.

900
00:29:44,482 --> 00:29:47,919
THE HEART DID TAKE PRETTY GOOD

901
00:29:47,986 --> 00:29:49,888
CARE BUT WE STARTED TO LOSE

902
00:29:49,954 --> 00:29:50,755
PACING ON DAY TWO.

903
00:29:50,822 --> 00:29:53,057
WE TOOK HIM TO THE O.R. AND

904
00:29:53,124 --> 00:29:55,527
SEWED A BUNCH OF PACE WIRES, WE

905
00:29:55,593 --> 00:29:56,895
COULDN'T GET THEM IN TO GIVE US

906
00:29:56,961 --> 00:29:57,862
A TEMPORARY PACE WIRE.

907
00:29:57,929 --> 00:30:00,498
AND WE WOULD HAVE NEEDED 1SEWN

908
00:30:00,565 --> 00:30:03,234
ANYHOW, SO HE HAD SOME BLEEDING

909
00:30:03,301 --> 00:30:04,469
THAT WE DIDN'T EXPECT FROM THAT

910
00:30:04,536 --> 00:30:06,104
A FEW DAYS LATER, AGAIN FROM A

911
00:30:06,171 --> 00:30:06,971
LOW PLATELET COUNT.

912
00:30:07,038 --> 00:30:09,807
WE GAVE HIM A BUNCH OF FFP,

913
00:30:09,874 --> 00:30:12,544
FRESH FROZEN PLASMA, WHICH HAS

914
00:30:12,610 --> 00:30:13,845
HUMAN ANTIPIG ANTIBODY IN IT

915
00:30:13,912 --> 00:30:18,249
BECAUSE IT'S FROM POOLED DONOR

916
00:30:18,316 --> 00:30:18,683
SOURCES.

917
00:30:18,750 --> 00:30:20,418
WE ALL HAVE AFNT-PIG ANTIBODY,

918
00:30:20,485 --> 00:30:24,822
SO WE GAVE HIM MAYBE A SURGE OF

919
00:30:24,889 --> 00:30:26,224
THAT AND MAYBE THAT WASN'T GOING

920
00:30:26,291 --> 00:30:27,859
TO BE A GOOD IDEA.

921
00:30:27,926 --> 00:30:29,160
HIS FIRST BIOPSY I TOLD YOU HE

922
00:30:29,227 --> 00:30:29,928
WAS READING, THAT'S THE PINK

923
00:30:29,994 --> 00:30:31,563
PIECE ON THE LEFT, IT DOES LOOK

924
00:30:31,629 --> 00:30:32,430
PRETTY GOOD.

925
00:30:32,497 --> 00:30:33,698
LATER IN THE AFTERNOON WE GOT

926
00:30:33,765 --> 00:30:35,500
THE WHITE PIECE AND THAT'S THE

927
00:30:35,567 --> 00:30:36,100
IMMUNE HISTOCHEMISTRY.

928
00:30:36,167 --> 00:30:38,369
THAT SHOWS IGG AND IGM BINDING

929
00:30:38,436 --> 00:30:41,739
THAT WASN'T SUBTLE.

930
00:30:41,806 --> 00:30:45,910
THAT'S HUMAN ANTI-PIG IGG AND

931
00:30:45,977 --> 00:30:46,778
IGM.

932
00:30:46,844 --> 00:30:48,846
WHERE DID IT COME FROM?

933
00:30:48,913 --> 00:30:49,614
WAS IT FROM HIM?

934
00:30:49,681 --> 00:30:50,648
THIS WAS ONLY DAY 13.

935
00:30:50,715 --> 00:30:53,451
OR DID WE TRANSFUSE HIM WITH IT?

936
00:30:53,518 --> 00:30:54,419
DON'T KNOW.

937
00:30:54,485 --> 00:30:58,356
HE ALSO HAS COMPLEMENT C4D.

938
00:30:58,423 --> 00:31:00,658
HE HAD C3D AS WELL, BUT THAT'S

939
00:31:00,725 --> 00:31:02,627
IMPORTANT GOING FORWARD.

940
00:31:02,694 --> 00:31:05,163
HE GOT SICKER OVER TIME, AND

941
00:31:05,230 --> 00:31:07,232
AGAIN, IT LOOKED LIKE HE HAD

942
00:31:07,298 --> 00:31:09,534
PROGRESSION IN THIS PROCESS OF

943
00:31:09,601 --> 00:31:11,636
THE ANTIBODY-MEDIATED PHENOMENA

944
00:31:11,703 --> 00:31:15,240
THAT WE CALL AMR OR

945
00:31:15,306 --> 00:31:15,840
ANTIBODY-MEDIATED REJECTION.

946
00:31:15,907 --> 00:31:17,842
AND THE HISTOPATHOLOGY BEGAN TO

947
00:31:17,909 --> 00:31:19,043
LOOK MORE AND MORE LIKE THAT.

948
00:31:19,110 --> 00:31:21,579
AND THEN WE BEGAN TO THINK ABOUT

949
00:31:21,646 --> 00:31:23,314
OUR FIRST PATIENT, AND OUR FIRST

950
00:31:23,381 --> 00:31:24,182
PATIENT'S ACUTE SWELLING AND

951
00:31:24,249 --> 00:31:26,251
GUESS WHAT HAPPENED TO THIS

952
00:31:26,317 --> 00:31:27,385
GENTLEMAN?

953
00:31:27,452 --> 00:31:28,653
AMR FOCUSES ON THE SAME THING

954
00:31:28,720 --> 00:31:30,221
THAT THE VIRUS FOCUSES ON, WHICH

955
00:31:30,288 --> 00:31:32,523
IS THE ENDOTHELIAL CELL, AND SO

956
00:31:32,590 --> 00:31:34,259
WE HAD A LEAKY HEART, AND THIS

957
00:31:34,325 --> 00:31:35,994
ONE DID THE EXACT SAME THING, AS

958
00:31:36,060 --> 00:31:37,228
I WILL SHOW YOU.

959
00:31:37,295 --> 00:31:38,963
SO WE HAD TO WITHDRAW SUPPORT

960
00:31:39,030 --> 00:31:39,964
WHEN HE DIDN'T RESPOND TO ALL

961
00:31:40,031 --> 00:31:43,034
KINDS OF ADDITIONAL TREATMENTS.

962
00:31:43,101 --> 00:31:45,770
INCLUDING CAR FILL UM ZAB, WE

963
00:31:45,837 --> 00:31:49,173
STARTED A NEW ANTICOMPLEMENT

964
00:31:49,240 --> 00:31:53,044
DRUG BUT I THINK WE LOST THE

965
00:31:53,111 --> 00:31:53,711
DEAL EARLIER.

966
00:31:53,778 --> 00:31:55,013
WE COULDN'T RECOVER, SO THE KEY

967
00:31:55,079 --> 00:31:56,447
WOULD BE TO LEARN WHEN YOUR

968
00:31:56,514 --> 00:31:57,749
PATIENT MAY BE GOING INTO

969
00:31:57,815 --> 00:32:00,051
REJECTION SO YOU CAN BE SMART

970
00:32:00,118 --> 00:32:02,020
WITH THE TREATMENT OR IMPROVE

971
00:32:02,086 --> 00:32:03,354
YOUR OVERALL BASIC IMMUNE

972
00:32:03,421 --> 00:32:04,455
SUPPRESSION SO IT DOESN'T HAPPEN

973
00:32:04,522 --> 00:32:09,560
IN THE FIRST PLACE.

974
00:32:09,627 --> 00:32:11,229
WE DID THE WORK IN TERMS OF

975
00:32:11,296 --> 00:32:14,932
REPORTING OUR LITERATURE AND

976
00:32:14,999 --> 00:32:16,668
THIS WAS AFTER OUR FIRST

977
00:32:16,734 --> 00:32:18,803
PATIENT, AND THEN AFTER THE

978
00:32:18,870 --> 00:32:20,938
SECOND PATIENT, THIS VERY LONG

979
00:32:21,005 --> 00:32:23,007
THING IN LANCET.

980
00:32:23,074 --> 00:32:24,876
AND IT WAS BASICALLY NONSENSE

981
00:32:24,942 --> 00:32:26,110
BECAUSE WE SAID, WELL, WE DON'T

982
00:32:26,177 --> 00:32:29,580
KNOW WHAT HAPPENED.

983
00:32:29,647 --> 00:32:30,682
SO IT WASN'T REALLY VERY

984
00:32:30,748 --> 00:32:31,049
HELPFUL.

985
00:32:31,115 --> 00:32:32,483
BUT WITH THE SECOND PATIENT'S

986
00:32:32,550 --> 00:32:34,218
INFORMATION, I THINK WE DO

987
00:32:34,285 --> 00:32:36,054
BELIEVE THAT THIS IS AN

988
00:32:36,120 --> 00:32:37,488
ANTIBODY-MEDIATED REJECTION TO

989
00:32:37,555 --> 00:32:40,892
THESE PIG ORGANS.

990
00:32:40,958 --> 00:32:42,860
THERE ARE TWO FORMS OF THIS

991
00:32:42,927 --> 00:32:43,528
ANTIBODY-MEDIATED REJECTION THAT

992
00:32:43,594 --> 00:32:44,495
WE'VE GOT TO CHASE.

993
00:32:44,562 --> 00:32:46,664
ONE IS CALLED CDC AND THAT'S

994
00:32:46,731 --> 00:32:48,900
REALLY FROM COMPLEMENT, RIGHT?

995
00:32:48,966 --> 00:32:50,301
COMPLEMENT GETS DOWN AND PUNCHES

996
00:32:50,368 --> 00:32:52,403
HOLES IN CELLS, AND IT GET DOWN

997
00:32:52,470 --> 00:32:54,038
THERE BECAUSE IT'S STIMULATED BY

998
00:32:54,105 --> 00:32:55,807
SOME ANTIBODIES THAT THEY

999
00:32:55,873 --> 00:32:56,474
RECOGNIZE AND THE COMPLEMENT

1000
00:32:56,541 --> 00:32:58,876
GETS ON IT, SO WE'VE GOT TO

1001
00:32:58,943 --> 00:33:00,678
BLOCK COMPLEMENT BETTER.

1002
00:33:00,745 --> 00:33:03,214
ADCC IS ANOTHER FORM OF

1003
00:33:03,281 --> 00:33:04,115
ANTIBODY-MEDIATED REJECTION,

1004
00:33:04,182 --> 00:33:06,484
WHICH INCLUDES A CYTOTOXIC PIECE

1005
00:33:06,551 --> 00:33:08,486
USUALLY IN THE FORM OF SOMETHING

1006
00:33:08,553 --> 00:33:10,655
CALLED KILLER CELLS OR NK CELLS.

1007
00:33:10,722 --> 00:33:12,090
VERY IMPORTANT IN THE PROCESS.

1008
00:33:12,156 --> 00:33:14,625
AND WE DON'T LIVE IN THIS WORLD

1009
00:33:14,692 --> 00:33:15,793
WITH ALOE TRANSPLANTATION VERY

1010
00:33:15,860 --> 00:33:17,428
OFTEN, SO IT'S KIND OF NEW FOR

1011
00:33:17,495 --> 00:33:18,963
ME AS A HEART TRANSPLANTER.

1012
00:33:19,030 --> 00:33:22,400
OUR KIDNEY COLLEAGUES SEE MORE

1013
00:33:22,467 --> 00:33:24,102
OF THIS BECAUSE MORE OF THEIR

1014
00:33:24,168 --> 00:33:26,104
PATIENTS ARE SENSITIZED TO

1015
00:33:26,170 --> 00:33:28,740
DONORS THAN OURS.

1016
00:33:28,806 --> 00:33:30,808
SO THEY'RE MORE LIKELY TO SEE

1017
00:33:30,875 --> 00:33:31,409
ANTIBODY-MEDIATED REJECTION.

1018
00:33:31,476 --> 00:33:33,978
SO I HAVE A QUIZ.

1019
00:33:34,045 --> 00:33:37,482
I'M GOING TO ASK DR. CARR.

1020
00:33:37,548 --> 00:33:38,916
DR. CARR, THERE ARE FOUR ORGANS

1021
00:33:38,983 --> 00:33:42,720
THAT YOU SEE HERE.

1022
00:33:42,787 --> 00:33:45,156
TWO OF THEM ARE PIG AND TWO ARE

1023
00:33:45,223 --> 00:33:45,456
HUMAN.

1024
00:33:45,523 --> 00:33:47,225
CAN YOU PICK OUT THE BIG VERSUS

1025
00:33:47,291 --> 00:33:51,696
THE HUMAN ORGANS?

1026
00:33:51,763 --> 00:33:53,431
>> I'LL GO WITH TOP AND LEFT.

1027
00:33:53,498 --> 00:33:54,866
>> TOP AND LEFT IS A PIG.

1028
00:33:54,932 --> 00:33:57,602
AND THAT'S WHY DR. CARR IS MY

1029
00:33:57,668 --> 00:34:00,338
FRIEND, BECAUSE HE NEVER MAKES A

1030
00:34:00,405 --> 00:34:00,772
MISTAKE.

1031
00:34:00,838 --> 00:34:01,339
SO HE GOT THAT.

1032
00:34:01,406 --> 00:34:03,307
THOSE ARE PIG ORGANS, AND THE

1033
00:34:03,374 --> 00:34:05,943
TOP ORGAN CAME OUT OF A 9-MONTH

1034
00:34:06,010 --> 00:34:10,982
SURVIVOR IN THE LABORATORY OF AN

1035
00:34:11,048 --> 00:34:12,383
ORTHOTOPIC PIG TO BABOON

1036
00:34:12,450 --> 00:34:13,251
TRANSPLANT.

1037
00:34:13,317 --> 00:34:15,019
AND THAT ANIMAL WAS TAKEN FROM

1038
00:34:15,086 --> 00:34:16,754
US, WE THINK FROM A VIRAL

1039
00:34:16,821 --> 00:34:18,856
ILLNESS THAT TOOK DOWN THE WHOLE

1040
00:34:18,923 --> 00:34:19,257
COLONY.

1041
00:34:19,323 --> 00:34:22,460
THIS HEART WAS NOT KNOWN TO BE

1042
00:34:22,527 --> 00:34:23,895
REJECTING.

1043
00:34:23,961 --> 00:34:26,531
SO IF YOU ARE A 9-MONTH HEART

1044
00:34:26,597 --> 00:34:28,699
DOING WELL, AND THEY TOOK YOU

1045
00:34:28,766 --> 00:34:29,700
OUT AND THEY CUT YOU, THAT'S

1046
00:34:29,767 --> 00:34:32,003
WHAT YOU SHOULD LOOK LIKE.

1047
00:34:32,069 --> 00:34:34,639
THE OTHER THREE ARE UNITED BY

1048
00:34:34,705 --> 00:34:36,707
SOMETHING VERY STRANGE, RIGHT,

1049
00:34:36,774 --> 00:34:38,142
WHICH IS THIS ENORMOUS SWELLING.

1050
00:34:38,209 --> 00:34:39,544
YOU SEE HOW MUCH THICKER THOSE

1051
00:34:39,610 --> 00:34:40,645
OTHER THREE HEART ARE?

1052
00:34:40,711 --> 00:34:43,047
AND THOSE ARE ALL THREE HEART

1053
00:34:43,114 --> 00:34:44,582
THAT REJECTED.

1054
00:34:44,649 --> 00:34:46,684
A BABOON HEART THAT REJECTED,

1055
00:34:46,751 --> 00:34:49,754
AND OUR TWO HUMAN HEART.

1056
00:34:49,821 --> 00:34:50,521
S.

1057
00:34:50,588 --> 00:34:53,558
TO EMPHASIZE THE DEGREE OF

1058
00:34:53,624 --> 00:34:55,560
SWELLING, LARRY FOSSETT'S HEART

1059
00:34:55,626 --> 00:34:57,094
IS ON THE RIGHT, AND THAT'S OUR

1060
00:34:57,161 --> 00:34:57,628
MOST RECENT PATIENT.

1061
00:34:57,695 --> 00:34:59,831
WHEN WE TOOK IT OUT IN

1062
00:34:59,897 --> 00:35:01,399
PROCUREMENT, IT WAS 273 GRAMS.

1063
00:35:01,466 --> 00:35:05,203
THE NORMAL HUMAN HEART, MALE, IS

1064
00:35:05,269 --> 00:35:07,605
ABOUT 320 TO 340 GRAMS.

1065
00:35:07,672 --> 00:35:09,140
THIS HEART WAS, I TOLD YOU, A

1066
00:35:09,207 --> 00:35:10,141
LITTLE SMALL.

1067
00:35:10,208 --> 00:35:11,642
WE MADE UP FOR THAT BY JUST

1068
00:35:11,709 --> 00:35:13,311
PACING IT A LITTLE BIT FASTER

1069
00:35:13,377 --> 00:35:15,947
AND IT WAS MORE THAN ADEQUATE.

1070
00:35:16,013 --> 00:35:18,783
BUT AT AUTOPSY, YOU KNOW, WITHIN

1071
00:35:18,850 --> 00:35:21,419
40 DAYS OF BEING IMPLANTED, IT'S

1072
00:35:21,486 --> 00:35:22,487
NOW 480 GRAMS, AND THAT'S NOT

1073
00:35:22,553 --> 00:35:24,689
GROWTH.

1074
00:35:24,755 --> 00:35:26,023
THAT'S INFILTRATE, AND MOSTLY

1075
00:35:26,090 --> 00:35:28,226
IT'S WATER AND FIBROUS TISSUE.

1076
00:35:28,292 --> 00:35:29,227
AND THAT'S THE SAME THING THAT

1077
00:35:29,293 --> 00:35:31,062
HAPPENED TO THE OTHER ORGANS CH

1078
00:35:31,128 --> 00:35:32,930
SO WE HAVE A UNIFYING PRINCIPLE

1079
00:35:32,997 --> 00:35:36,267
OF SOMETHING BAD GOING ON, RIG

1080
00:35:36,334 --> 00:35:36,467
RIGHT?

1081
00:35:36,534 --> 00:35:37,869
AND IT AIN'T A VIRUS.

1082
00:35:37,935 --> 00:35:39,737
BECAUSE WE EXCLUDED THE VIRUS

1083
00:35:39,804 --> 00:35:40,938
FROM THE HUMAN AND THE ANIMALS

1084
00:35:41,005 --> 00:35:42,173
DIDN'T HAVE THAT, THAT ANIMAL

1085
00:35:42,240 --> 00:35:43,040
DIDN'T HAVE THE VIRUS.

1086
00:35:43,107 --> 00:35:46,410
SO WE GO TO LOOK TO SEE WHAT'S

1087
00:35:46,477 --> 00:35:48,513
GOING ON AND WE TRY TO LACK FOR

1088
00:35:48,579 --> 00:35:49,947
THIS ANTIHUMAN ANTIBODY WHICH WE

1089
00:35:50,014 --> 00:35:52,016
KNOW IS A CENTRAL CORE TO

1090
00:35:52,083 --> 00:35:52,884
ANTIBODY-MEDIATED REJECTION.

1091
00:35:52,950 --> 00:35:54,218
WE COULDN'T COME UP WITH A

1092
00:35:54,285 --> 00:35:55,553
UNIFYING PRINCIPLE BASED UPON

1093
00:35:55,620 --> 00:35:57,855
OUR PREOPERATIVE EVALUATION, I!

1094
00:35:57,922 --> 00:35:59,724
, OUR CROSSMATCH BETWEEN OUR

1095
00:35:59,790 --> 00:36:02,760
PATIENT'S SERUM AND THE PIG

1096
00:36:02,827 --> 00:36:05,730
HEARTS.

1097
00:36:05,796 --> 00:36:07,398
ALL OF US HAVE ANTI-PIG

1098
00:36:07,465 --> 00:36:07,665
ANTIBODY.

1099
00:36:07,732 --> 00:36:09,100
WE DON'T HAVE TO BE FARMERS, WE

1100
00:36:09,166 --> 00:36:10,501
DON'T HAVE TO EAT A LOT OF PIG.

1101
00:36:10,568 --> 00:36:11,969
WE CAN BE VEG TEAR YANS AND

1102
00:36:12,036 --> 00:36:13,371
STILL HAVE THESE ANTIBODIES

1103
00:36:13,437 --> 00:36:16,073
BECAUSE THE ANTIBODIES COME IN

1104
00:36:16,140 --> 00:36:18,309
THE FORM OF LEL SNIPPETS ON

1105
00:36:18,376 --> 00:36:19,977
VIRUSES AND STUFF, SO OVER TIME

1106
00:36:20,044 --> 00:36:21,279
IT ALL GETS MIXED UP OUT THERE

1107
00:36:21,345 --> 00:36:23,347
AND IT GETS INTO OUR GI TRACT

1108
00:36:23,414 --> 00:36:25,116
PROBABLY AND THAT'S HOW WE GET

1109
00:36:25,182 --> 00:36:25,416
SENSITIZED.

1110
00:36:25,483 --> 00:36:28,753
AND THERE'S MORE OR LESS OF IT,

1111
00:36:28,819 --> 00:36:30,288
I THINK IT'S MORE RANDOM THAN IT

1112
00:36:30,354 --> 00:36:32,056
IS PURPOSEFUL.

1113
00:36:32,123 --> 00:36:33,224
SO TWO PEOPLE NEXT TO EACH OTHER

1114
00:36:33,291 --> 00:36:34,358
MAY HAVE VERY DIFFERENT LEVELS

1115
00:36:34,425 --> 00:36:35,426
AND IT WOULD BE BEST FOR US TO

1116
00:36:35,493 --> 00:36:36,794
HAVE THE LOWEST LEVEL POSSIBLE

1117
00:36:36,861 --> 00:36:39,263
ON A PATIENT, RIGHT?

1118
00:36:39,330 --> 00:36:40,598
CERTAINLY AS WE BEGIN TO RAMP UP

1119
00:36:40,665 --> 00:36:42,867
OUR UNDERSTANDING, WE DON'T WANT

1120
00:36:42,934 --> 00:36:44,535
TO NECESSARILY GET UP TO THE

1121
00:36:44,602 --> 00:36:46,304
PLATE AGAINST A STRIKEOUT

1122
00:36:46,370 --> 00:36:47,505
PITCHER, RIGHT?

1123
00:36:47,572 --> 00:36:49,040
WE WOULD PREFER TO HAVE LOW

1124
00:36:49,106 --> 00:36:52,310
ANTIBODIES TO DEAL WITH.

1125
00:36:52,376 --> 00:36:54,378
THE ANTIBODIES IN THE FIRST

1126
00:36:54,445 --> 00:36:55,546
PATIENT SHOWN HERE, KIND OF

1127
00:36:55,613 --> 00:36:58,015
INTERESTING, WE GOT A SPIKE.

1128
00:36:58,082 --> 00:36:59,216
SECOND PATIENT, WE DIDN'T SEE

1129
00:36:59,283 --> 00:37:01,752
THAT SPIKE, WHICH IS

1130
00:37:01,819 --> 00:37:02,053
INTERESTING.

1131
00:37:02,119 --> 00:37:03,387
IN SPITE OF HAVINGS WHAT WE'RE

1132
00:37:03,454 --> 00:37:06,757
NOW DECLARING ANTIBODY MEDIATE D

1133
00:37:06,824 --> 00:37:07,758
REJECTION, WE COULDN'T DETECT IT

1134
00:37:07,825 --> 00:37:09,193
LOOKING AT THE HUMAN ANTIBODIES.

1135
00:37:09,260 --> 00:37:12,029
NONE OF THESE PATIENTS HAD

1136
00:37:12,096 --> 00:37:14,131
CYTOTOXICITY TO THEIR DONOR

1137
00:37:14,198 --> 00:37:14,799
ORGAN.

1138
00:37:14,865 --> 00:37:17,535
SO NOT ONLY DID THEY NOT HAVE

1139
00:37:17,602 --> 00:37:19,070
HIGH ANTIBODIES, THOSE

1140
00:37:19,136 --> 00:37:22,239
ANTIBODIES DIDN'T LYSE THE CELLS

1141
00:37:22,306 --> 00:37:24,308
OF THE PIG HEART IN CULTURE WHEN

1142
00:37:24,375 --> 00:37:27,712
WE ADDED COMPLEMENT.

1143
00:37:27,778 --> 00:37:29,814
SO THAT'S LIKE A GOLD STANDARD

1144
00:37:29,880 --> 00:37:31,349
IN ALLOTRANSPLANTATION AND YOU

1145
00:37:31,415 --> 00:37:32,883
ALWAYS TRY TO ACHIEVE THAT.

1146
00:37:32,950 --> 00:37:34,518
SO WE WERE IN GOOD HIGH GROUND

1147
00:37:34,585 --> 00:37:37,254
IN SELECTING THESE PIGS FOR

1148
00:37:37,321 --> 00:37:38,255
THESE PATIENTS, AND YET WE

1149
00:37:38,322 --> 00:37:39,624
FAILED, AND WE THINK IT WAS

1150
00:37:39,690 --> 00:37:39,890
ANTIBODY.

1151
00:37:39,957 --> 00:37:43,928
SO THERE'S MORE TO LEARN.

1152
00:37:43,995 --> 00:37:44,729
IMMUNE SUPPRESSION IS

1153
00:37:44,795 --> 00:37:46,998
COMPLICATED AND I THINK -- LET'S

1154
00:37:47,064 --> 00:37:50,635
BLOW THROUGH THAT.

1155
00:37:50,701 --> 00:37:51,936
THE IMMUNE SUPPRESSION, THE KEY

1156
00:37:52,003 --> 00:37:53,270
PART OF THIS AGAIN GOING BACK TO

1157
00:37:53,337 --> 00:37:56,540
THE NIH WORLD IS ACCESSORY

1158
00:37:56,607 --> 00:37:57,842
PATHWAY BLOCKADE, AND WE COULD

1159
00:37:57,908 --> 00:37:59,644
BLOCK IT ONE OF TWO WAYS, EITHER

1160
00:37:59,710 --> 00:38:01,512
THE LIGAND OR THE RECEPTOR OF

1161
00:38:01,579 --> 00:38:04,348
THAT, AND THAT'S -- THE RECEPTOR

1162
00:38:04,415 --> 00:38:08,085
IS CD40 AND THE LIGAND IS 154.

1163
00:38:08,152 --> 00:38:09,820
SO THE TOP DRUG IS THE MOST

1164
00:38:09,887 --> 00:38:11,689
RECENT DRUG WE USED, AND IT'S

1165
00:38:11,756 --> 00:38:13,891
BEEN USED IN HUMANS BUT NEVER IN

1166
00:38:13,958 --> 00:38:15,960
A TRANSPLANT SETTING, PER SE.

1167
00:38:16,027 --> 00:38:19,997
THE FIRST DRUG WE USED IN THE

1168
00:38:20,064 --> 00:38:20,898
LOWER PANEL HAD NEVER BEEN USED

1169
00:38:20,965 --> 00:38:23,734
IN A HUMAN, AND IT WAS GOING TO

1170
00:38:23,801 --> 00:38:25,603
BE LIKE -- IT WAS GOING TO BE

1171
00:38:25,670 --> 00:38:26,070
OUR TANK.

1172
00:38:26,137 --> 00:38:27,171
THAT'S WHAT WE WERE COUNTING ON

1173
00:38:27,238 --> 00:38:28,606
TO WORK FOR US, BECAUSE, AGAIN,

1174
00:38:28,673 --> 00:38:30,241
GOING BACK TO OUR NON-HUMAN

1175
00:38:30,307 --> 00:38:31,342
PRIMATE WORK, WE HAVE TO

1176
00:38:31,409 --> 00:38:35,479
BLOCKADE THAT.

1177
00:38:35,546 --> 00:38:37,214
AND YOU NEED A HUMAN DRUG THAT

1178
00:38:37,281 --> 00:38:38,015
WILL DO IT.

1179
00:38:38,082 --> 00:38:41,185
IN OUR BA BOB WORK, WE HAVE ONLY

1180
00:38:41,252 --> 00:38:43,254
BABOON-EFFECTIVE ANTIBODY TO TRY

1181
00:38:43,320 --> 00:38:45,356
CD40 BLOCKADE.

1182
00:38:45,423 --> 00:38:46,557
SO NOT ONLY HAD WE NOT ANY

1183
00:38:46,624 --> 00:38:47,858
EXPERIENCE WITH THESE DRUGS, WE

1184
00:38:47,925 --> 00:38:49,627
HAD TO SEND OUT THE BLOOD LEVELS

1185
00:38:49,694 --> 00:38:52,963
TO KNOW WHERE WE WERE, BECAUSE

1186
00:38:53,030 --> 00:38:54,632
WE DIDN'T HAVE PK CURVES ON ANY

1187
00:38:54,699 --> 00:38:56,267
OF THESE DRUGS AND WE WERE JUST

1188
00:38:56,333 --> 00:38:57,268
GOING BY SEAT OF PANTS IN TERMS

1189
00:38:57,334 --> 00:39:00,104
OF WHEN THE DRUG WAS TOTALLY

1190
00:39:00,171 --> 00:39:03,007
COVERING THE RECEPTORS.

1191
00:39:03,074 --> 00:39:04,575
SO IT WAS OUR BEST GUESSTIMATE.

1192
00:39:04,642 --> 00:39:05,910
DID WE DO A GOOD JOB?

1193
00:39:05,976 --> 00:39:06,877
WE'RE ALL OVER THE PLACE HERE,

1194
00:39:06,944 --> 00:39:07,244
RIGHT?

1195
00:39:07,311 --> 00:39:08,913
AND THE LITTLE DOTTED LINE ON

1196
00:39:08,979 --> 00:39:13,484
THE BOTTOM ONE WAS OUR TARGET.

1197
00:39:13,551 --> 00:39:14,685
WE HOPE TO ACHIEVE ABOVE THAT

1198
00:39:14,752 --> 00:39:16,120
DOTTED LINE, AND YOU CAN SEE

1199
00:39:16,187 --> 00:39:17,088
PROBABLY 30% OF THE TIME, WE

1200
00:39:17,154 --> 00:39:20,524
WEWERE BELOW IT.

1201
00:39:20,591 --> 00:39:22,259
THE TOP DRUG NEEDED TO BE ABOVE

1202
00:39:22,326 --> 00:39:23,360
500 AND YOU CAN SEE THERE WAS

1203
00:39:23,427 --> 00:39:24,495
SOME TIME WHEN, IN FACT, WE

1204
00:39:24,562 --> 00:39:28,532
WEREN'T THERE.

1205
00:39:28,599 --> 00:39:29,834
THIS MAY BE MORE COMPLICATED

1206
00:39:29,900 --> 00:39:32,536
THAN I CHOOSE TO GO INTO, BUT

1207
00:39:32,603 --> 00:39:34,071
I'M GOING TO TRY JUST BRIEFLY TO

1208
00:39:34,138 --> 00:39:35,673
TELL YOU THAT -- REMEMBER I SAID

1209
00:39:35,740 --> 00:39:41,212
THE WHOLE STORY ISN IS THAT ANTY

1210
00:39:41,278 --> 00:39:42,346
COMPLEMENT IS REALLY IMPORTANT.

1211
00:39:42,413 --> 00:39:43,447
BECAUSE IT'S NOT ONLY REJECTION

1212
00:39:43,514 --> 00:39:45,716
BUT IT'S ALSO THIS COMPLEMENT

1213
00:39:45,783 --> 00:39:46,751
EFFECT OF REJECTION AND THEY GO

1214
00:39:46,817 --> 00:39:47,752
HAND IN HAND.

1215
00:39:47,818 --> 00:39:49,720
WE'VE BEEN WORKING WITH A GROUP

1216
00:39:49,787 --> 00:39:55,593
FROM JOHNS HOPKINS, DR. BR

1217
00:39:55,659 --> 00:39:57,361
DR. BROADSKY'S LAB AND MICHAEL

1218
00:39:57,428 --> 00:39:58,829
COLE UP THERE, THEY HAVE A TEST,

1219
00:39:58,896 --> 00:40:00,397
A VARIANT OF SOMETHING CALLED A

1220
00:40:00,464 --> 00:40:01,699
HAM TEST WHERE YOU CAN ADD

1221
00:40:01,766 --> 00:40:05,636
COMPLEMENT TO SERUM AND YOU CAN

1222
00:40:05,703 --> 00:40:08,372
TELL WHETHER OR NOT THAT SERUM

1223
00:40:08,439 --> 00:40:10,741
IS BLOCKED.

1224
00:40:10,808 --> 00:40:13,077
YOU CAN HAVE A DRUG IN THAT

1225
00:40:13,144 --> 00:40:14,512
SERUM THAT'S BLOCKING THE

1226
00:40:14,578 --> 00:40:16,680
ACTIVATION OF THE COMPLEMENT.

1227
00:40:16,747 --> 00:40:19,183
AND IN THESE PARTICULAR

1228
00:40:19,250 --> 00:40:22,119
EXAMPLES, WE HAD BERINERT, WHICH

1229
00:40:22,186 --> 00:40:24,755
WAS OUR GO-TO ANTICOMPLEMENT

1230
00:40:24,822 --> 00:40:27,158
DRUG WITH IS A LOUSY

1231
00:40:27,224 --> 00:40:28,025
ANTICOMPLEMENT DRUG BY THE WAY

1232
00:40:28,092 --> 00:40:29,226
BUT IT'S WHAT WE HAD, AND THEN

1233
00:40:29,293 --> 00:40:33,397
WE ADDED A SECOND DRUG,

1234
00:40:33,464 --> 00:40:34,398
ECLUZIMAB, WHICH WAS A LOT

1235
00:40:34,465 --> 00:40:34,632
BETTER.

1236
00:40:34,698 --> 00:40:37,601
YOU CAN SEE BIOLUMINESCENCE HAS

1237
00:40:37,668 --> 00:40:40,871
INCREASED WHEN WE ADDED THE

1238
00:40:40,938 --> 00:40:41,972
ECLUZIMAB AS OPPOSED TO JUST

1239
00:40:42,039 --> 00:40:43,841
HAVING THE BERINERT.

1240
00:40:43,908 --> 00:40:45,509
AND THE BLUE AND KIND OF BROWN

1241
00:40:45,576 --> 00:40:47,044
LEVELS ARE TWO DIFFERENT CLASSES

1242
00:40:47,111 --> 00:40:49,346
OF CELLS THAT ARE RELATIVELY

1243
00:40:49,413 --> 00:40:51,782
MORE OR LESS SENSITIVE TO

1244
00:40:51,849 --> 00:40:55,719
COMPLEMENT KILLING.

1245
00:40:55,786 --> 00:40:56,821
SO IN THE MOST SENSITIVE, YOU

1246
00:40:56,887 --> 00:40:58,823
CAN SEE WE WERE ABLE TO MAINTAIN

1247
00:40:58,889 --> 00:41:02,626
SURVIVAL WHEN WE ADDED THE TWO

1248
00:41:02,693 --> 00:41:03,861
COMPLEMENTS TOGETHER TO BLOCK

1249
00:41:03,928 --> 00:41:09,533
THAT PATHWAY.

1250
00:41:09,600 --> 00:41:11,936
SO WE LEARNED A LOT.

1251
00:41:12,002 --> 00:41:15,673
THIS IS THE FIRST EXAMPLE IN THE

1252
00:41:15,739 --> 00:41:17,408
XENOTHERAPY WHERE WE'RE GETTING

1253
00:41:17,474 --> 00:41:19,610
FEEDBACK AS TO WHETHER OR NOT

1254
00:41:19,677 --> 00:41:21,846
WE'RE GIVING ENOUGH DRUG OR

1255
00:41:21,912 --> 00:41:23,347
ENOUGH DRUG THAT'S EFFECTIVE.

1256
00:41:23,414 --> 00:41:24,248
BECAUSE EVERYTHING ELSE WE GIVE

1257
00:41:24,315 --> 00:41:30,487
IS JUST BY SPECULATION, RIGHT?

1258
00:41:30,554 --> 00:41:31,856
CELL-FREE DNA IS A WONDERFUL

1259
00:41:31,922 --> 00:41:34,658
THING AND I KNOW IN ARE REALLY

1260
00:41:34,725 --> 00:41:37,428
GOOD RESEARCH GOING ON WITH

1261
00:41:37,494 --> 00:41:39,196
CELL-FREE DNA AND ALLO WORLD,

1262
00:41:39,263 --> 00:41:41,999
IT'S REALLY GOOD IN THE XENO

1263
00:41:42,066 --> 00:41:43,634
WORLD AS WELL.

1264
00:41:43,701 --> 00:41:45,002
THIS PARTICULAR GRAPH, I SIMPLY

1265
00:41:45,069 --> 00:41:47,071
SHOW YOU, THIS IS FROM CARIUS.

1266
00:41:47,137 --> 00:41:48,539
YOU CAN SEE THERE ARE TWO GRAPHS

1267
00:41:48,606 --> 00:41:49,640
HERE.

1268
00:41:49,707 --> 00:41:51,475
JUST LOOK AT THE GREEN AND THE

1269
00:41:51,542 --> 00:41:53,677
BROWN, BECAUSE THE GREEN IS

1270
00:41:53,744 --> 00:41:56,313
HUMAN CELL-FREE DNA WHICH IS

1271
00:41:56,380 --> 00:42:01,785
DETECTED IN THE BLOOD.

1272
00:42:01,852 --> 00:42:04,622
IN THE SAME PATIENT, YOU'RE NOW

1273
00:42:04,688 --> 00:42:06,056
SEEING PIG DNA, RIGHT?

1274
00:42:06,123 --> 00:42:08,058
HOW DID THAT PIG DNA GET THERE?

1275
00:42:08,125 --> 00:42:09,293
IT HAS TO COME FROM THE HEART,

1276
00:42:09,360 --> 00:42:09,693
RIGHT?

1277
00:42:09,760 --> 00:42:11,528
AND WHEN THE HEART IS INJURED,

1278
00:42:11,595 --> 00:42:13,464
IT GIVES UP MORE OF ITS DNA.

1279
00:42:13,530 --> 00:42:16,300
SO IT'S A SURROGATE FOR MAYBE

1280
00:42:16,367 --> 00:42:20,070
HEARTHEART ENZYME, IF YOU WISH,T

1281
00:42:20,137 --> 00:42:23,207
MORE SENSITIVE.

1282
00:42:23,274 --> 00:42:24,108
AND THERE ARE DIFFERENT SCALES

1283
00:42:24,174 --> 00:42:25,376
HERE FOR BOTH THE PORCINE AND

1284
00:42:25,442 --> 00:42:26,410
THE HUMAN, BUT IT IS INTERESTING

1285
00:42:26,477 --> 00:42:27,978
THAT WHEN THE PIG HEART GOT IN

1286
00:42:28,045 --> 00:42:29,713
TROUBLE, SO DID THE HUMAN.

1287
00:42:29,780 --> 00:42:31,048
THERE'S MORE HUMAN DNA BEING

1288
00:42:31,115 --> 00:42:32,383
RELEASED, RIGHT, SO END ORGAN

1289
00:42:32,449 --> 00:42:36,253
DAMAGE.

1290
00:42:36,320 --> 00:42:37,922
THIS WAS A EUREKA MOMENT FOR ME

1291
00:42:37,988 --> 00:42:38,255
TOO.

1292
00:42:38,322 --> 00:42:40,557
IN OUR FIRST PATIENT, WE WERE

1293
00:42:40,624 --> 00:42:42,326
MEASURING ALL THIS STUFF AND ONE

1294
00:42:42,393 --> 00:42:43,727
OF THE STUFFS THAT WE WERE

1295
00:42:43,794 --> 00:42:45,729
MEASURING WAS THE MICROBIAL

1296
00:42:45,796 --> 00:42:47,598
CELL-FREE DNA.

1297
00:42:47,665 --> 00:42:49,767
AND INSTEAD OF WAITING FOR YOUR

1298
00:42:49,833 --> 00:42:51,001
BLOOD CULTURES TO COME BACK

1299
00:42:51,068 --> 00:42:53,404
WHICH WERE SURVEILLANCE BASED,

1300
00:42:53,470 --> 00:42:54,738
RIGHT, AND THREE DAYS LATER YOU

1301
00:42:54,805 --> 00:42:56,640
GOT A NEGATIVE OR POSITIVE, ALL

1302
00:42:56,707 --> 00:42:59,109
OF A SUDDEN WITHIN BASICALLY 12

1303
00:42:59,176 --> 00:43:00,377
HOURS, WE'RE GETTING REPORTS

1304
00:43:00,444 --> 00:43:01,879
BACK THAT YOU HAVE THIS

1305
00:43:01,946 --> 00:43:03,647
BACTERIA, THIS BACTERIA AT THIS

1306
00:43:03,714 --> 00:43:07,484
LEVEL IN YOUR BLOOD.

1307
00:43:07,551 --> 00:43:09,687
USING BACTERIAL BASED CELL-FREE

1308
00:43:09,753 --> 00:43:11,355
DNA, IT IS REALLY COOL.

1309
00:43:11,422 --> 00:43:13,324
IT IS THE CELL CULTURE, THE

1310
00:43:13,390 --> 00:43:14,959
BLOOD CULTURE OF THE FUTURE, AND

1311
00:43:15,025 --> 00:43:16,694
WE WILL ALL USE THIS.

1312
00:43:16,760 --> 00:43:18,062
SOME PEOPLE ALREADY USE IT BUT I

1313
00:43:18,128 --> 00:43:19,029
HAVE NEVER SEEN IT BEFORE.

1314
00:43:19,096 --> 00:43:23,834
THAT'S HOW WE CAUGHT NOT ONLY

1315
00:43:23,901 --> 00:43:25,169
THE PRESENCE OF THESE BUGS BUT

1316
00:43:25,235 --> 00:43:26,403
ALSO THAT IMPORTANT VIRUS AS I

1317
00:43:26,470 --> 00:43:28,172
MENTIONED TO YOU EARLIER.

1318
00:43:28,238 --> 00:43:29,440
PRETTY NEAT, RIGHT?

1319
00:43:29,506 --> 00:43:31,442
SO THERE'S A LOT OF VELCRO, I

1320
00:43:31,508 --> 00:43:33,210
SAID EARLIER, A LOT OF STUFF

1321
00:43:33,277 --> 00:43:34,945
FALLING OUT OF THIS PROGRAM IN

1322
00:43:35,012 --> 00:43:35,846
XENO THAT'S GOING TO AFFECT ALL

1323
00:43:35,913 --> 00:43:37,281
OF US, BECAUSE WE'RE USING IT

1324
00:43:37,348 --> 00:43:38,816
NOW AND, HEY, MAYBE WE CAN USE

1325
00:43:38,882 --> 00:43:40,718
THAT IN ALLO OR MAYBE WE CAN USE

1326
00:43:40,784 --> 00:43:41,819
IT FOR SOMETHING ELSE.

1327
00:43:41,885 --> 00:43:45,990
IT'S REALLY IMPORTANT SCIENCE.

1328
00:43:46,056 --> 00:43:47,191
THIS LAST PATIENT, WE GOT THIS

1329
00:43:47,257 --> 00:43:47,391
BLIP.

1330
00:43:47,458 --> 00:43:49,393
I MEAN, WE'RE USED TO NOW BEING

1331
00:43:49,460 --> 00:43:51,261
SURPRISED WHAT THEY FIND.

1332
00:43:51,328 --> 00:43:53,530
WE FOUND LEGIONELLA.

1333
00:43:53,597 --> 00:43:55,265
OOPS, WHERE DID THAT COME FROM?

1334
00:43:55,332 --> 00:43:56,033
WE WENT NUTS.

1335
00:43:56,100 --> 00:43:56,800
IT WENT RIGHT AWAY.

1336
00:43:56,867 --> 00:43:58,135
WE TREATED IT, IT WENT RIGHT

1337
00:43:58,202 --> 00:43:58,335
AWAY.

1338
00:43:58,402 --> 00:44:01,739
SO IT WASN'T LIKE HE HAD

1339
00:44:01,805 --> 00:44:03,507
LEGIONELLA, HE HAD BEEN NEGATIVE

1340
00:44:03,574 --> 00:44:08,879
PRE-O -OP.

1341
00:44:08,946 --> 00:44:10,647
YOU CAN SEE IT'S WITHIN 7 DAYS.

1342
00:44:10,714 --> 00:44:12,416
THEY WENT BACK AND CULTURED

1343
00:44:12,483 --> 00:44:13,350
EVERYTHING, THEY EVEN CULTURED

1344
00:44:13,417 --> 00:44:14,818
OUR LAB WHERE THEY TOOK THE

1345
00:44:14,885 --> 00:44:15,486
HEART OUT.

1346
00:44:15,552 --> 00:44:18,355
GUESS WHERE THEY FOUND THE

1347
00:44:18,422 --> 00:44:18,989
LEGIONELLA?

1348
00:44:19,056 --> 00:44:22,059
IN HIS O.R.

1349
00:44:22,126 --> 00:44:24,728
THANOBODY COULD GO IN THE O.R.,

1350
00:44:24,795 --> 00:44:25,729
JUST ME AND SOMEBODY ELSE, WE

1351
00:44:25,796 --> 00:44:27,464
HAD TO WASH 12 TIMES, WE WORE

1352
00:44:27,531 --> 00:44:28,365
THESE SPACESUITS.

1353
00:44:28,432 --> 00:44:30,100
HOW ABOUT THAT?

1354
00:44:30,167 --> 00:44:31,101
LEGIONELLA IN THE O.R.

1355
00:44:31,168 --> 00:44:32,202
YOU'RE THE ONLY PEOPLE THAT KNOW

1356
00:44:32,269 --> 00:44:34,204
THAT PUBLICLY, BY THE WAY.

1357
00:44:34,271 --> 00:44:37,274
AND FINALLY, HOW ABOUT THESE?

1358
00:44:37,341 --> 00:44:40,544
THIS IS ANOTHER DEGREE OF

1359
00:44:40,611 --> 00:44:41,879
CELL-FREE DNA BUT THIS IS WHAT

1360
00:44:41,945 --> 00:44:46,617
THEY CALL FRAGMENTOMICS, WHERE

1361
00:44:46,683 --> 00:44:47,785
THEY CAN ACTUALLY UNDERSTAND

1362
00:44:47,851 --> 00:44:50,554
WHAT THAT REMNANT OF PIG DNA IS

1363
00:44:50,621 --> 00:44:52,189
COMING FROM, WHAT CELL OF

1364
00:44:52,256 --> 00:44:52,423
ORIGIN.

1365
00:44:52,489 --> 00:44:55,192
AND YOU CAN SEE THAT IN YELLOW

1366
00:44:55,259 --> 00:44:59,029
HERE, ON DAY 30, WE ARE SPIKING

1367
00:44:59,096 --> 00:45:00,230
ENDOTHELIAL CELL FRAGMENTS OF

1368
00:45:00,297 --> 00:45:02,866
DNA.

1369
00:45:02,933 --> 00:45:04,635
SO NOT ONLY DO YOU KNOW THAT YOU

1370
00:45:04,701 --> 00:45:06,804
GOT PIG STUFF IN THE BLOOD BAD,

1371
00:45:06,870 --> 00:45:08,138
YOU KNOW WHERE IT'S COMING FROM.

1372
00:45:08,205 --> 00:45:10,240
SO YOU MIGHT BE ABLE TO TARGET

1373
00:45:10,307 --> 00:45:12,876
WHETHER THIS IS A T-CELL

1374
00:45:12,943 --> 00:45:14,511
EFFECTIVE THING WHICH WOULD BE

1375
00:45:14,578 --> 00:45:16,814
MORE MYOCARDIAL CELL OR

1376
00:45:16,880 --> 00:45:18,048
ENDOTHELIAL CELL, WHICH WOULD BE

1377
00:45:18,115 --> 00:45:18,282
AMR.

1378
00:45:18,348 --> 00:45:19,416
SO I THINK WE'RE GOING TO BE

1379
00:45:19,483 --> 00:45:21,452
ABLE TO USE THESE JEWELS GOING

1380
00:45:21,518 --> 00:45:22,886
FORWARD IN TERMS OF OUR

1381
00:45:22,953 --> 00:45:23,220
DIAGNOSTICS.

1382
00:45:23,287 --> 00:45:25,956
THIS COULD BE A NICE BIOPROBE

1383
00:45:26,023 --> 00:45:26,824
FOR REJECTION, RIGHT?

1384
00:45:26,890 --> 00:45:29,827
WE CAN GET THIS NOW BACK IN

1385
00:45:29,893 --> 00:45:30,794
ABOUT 48 HOURS BUT I SUSPECT

1386
00:45:30,861 --> 00:45:32,429
WE'LL BE ABLE TO GET IT WITHIN

1387
00:45:32,496 --> 00:45:33,130
24.

1388
00:45:33,197 --> 00:45:34,364
PRETTY NEAT, RIGHT?

1389
00:45:34,431 --> 00:45:37,301
YEAH.

1390
00:45:37,367 --> 00:45:37,968
I THINK SO.

1391
00:45:38,035 --> 00:45:41,138
AND THEN THE LAST THING IS,

1392
00:45:41,205 --> 00:45:43,807
THERE'S THIS STUFF THAT THEY CAN

1393
00:45:43,874 --> 00:45:45,642
DO NOW WITH LOOKING AT GENES AND

1394
00:45:45,709 --> 00:45:50,147
GENE ARRAYS CALLED BULK

1395
00:45:50,214 --> 00:45:50,914
TRANSCRIPTOMICS.

1396
00:45:50,981 --> 00:45:51,949
YEAH, I CAN SAY THAT.

1397
00:45:52,015 --> 00:45:53,917
IT'S ALL ABOUT LOOKING AT OUR

1398
00:45:53,984 --> 00:45:55,119
BIOPSY IN A WAY THAT WE NEVER

1399
00:45:55,185 --> 00:45:57,354
WERE ABLE TO BEFORE, AND POOR

1400
00:45:57,421 --> 00:45:58,322
LARRY COULDN'T UNDERSTAND,

1401
00:45:58,388 --> 00:45:58,555
RIGHT?

1402
00:45:58,622 --> 00:46:00,858
HE WAS LOOKING AT THE H & E.

1403
00:46:00,924 --> 00:46:05,262
HERE'S THE GENETIC OUTPUT FROM

1404
00:46:05,329 --> 00:46:05,696
HIS BIOPSY.

1405
00:46:05,762 --> 00:46:08,432
AND THIS IS WHAT THEY CALL

1406
00:46:08,499 --> 00:46:09,500
VOLCANO GRAPHED.

1407
00:46:09,566 --> 00:46:13,036
EVERYTHING TO THE LEFT

1408
00:46:13,103 --> 00:46:15,139
DEMONSTRATES GENES THAT ARE DOWN

1409
00:46:15,205 --> 00:46:15,405
REGULATED.

1410
00:46:15,472 --> 00:46:17,341
EVERYTHING TO THE RIGHT IS

1411
00:46:17,407 --> 00:46:19,076
UPREGULATED.

1412
00:46:19,143 --> 00:46:20,777
WHEN THE A.I. SOURCE LOOKS AT

1413
00:46:20,844 --> 00:46:23,180
ALL THIS, IT SAYS, OKAY,

1414
00:46:23,247 --> 00:46:24,948
EVERYTHING IS FINE.

1415
00:46:25,015 --> 00:46:28,785
OR, UH-OH, YOU'VE GOT AN IN

1416
00:46:28,852 --> 00:46:32,623
INFECTION IN THE HEART OR YOU'VE

1417
00:46:32,689 --> 00:46:33,991
GOT REJECTION AND IT LOOKS LIKE

1418
00:46:34,057 --> 00:46:35,159
T-CELL REJECTION OR IN OUR CASE,

1419
00:46:35,225 --> 00:46:37,928
IT SAID, UH-OH, ALL OF THESE

1420
00:46:37,995 --> 00:46:42,099
GENES ARE COMPATIBLE WITH ACUTE

1421
00:46:42,166 --> 00:46:44,835
ANTIBODY-MEDIATED REJECTION.

1422
00:46:44,902 --> 00:46:46,937
SO AGAIN, IT'S ALL PART OF THE

1423
00:46:47,004 --> 00:46:48,939
PROCESS OF LEARNING, AND THEN,

1424
00:46:49,006 --> 00:46:51,241
YOU KNOW, WE CAN GET THIS BACK

1425
00:46:51,308 --> 00:46:53,977
IN 36 HOURS.

1426
00:46:54,044 --> 00:46:55,379
SO WE'RE GOING TO USE THESE

1427
00:46:55,445 --> 00:46:58,916
TOOLS TO HELP US UNDERSTAND WHAT

1428
00:46:58,982 --> 00:47:00,884
SWITCHES AND TOGGLES TO PULL TO

1429
00:47:00,951 --> 00:47:03,120
REDUCE THIS WHOLE PROCESS OF

1430
00:47:03,187 --> 00:47:03,754
ANTIBODY-MEDIATED REJECTION AS

1431
00:47:03,820 --> 00:47:04,655
WE GO FORWARD.

1432
00:47:04,721 --> 00:47:06,857
AND THIS WAS DONE BY

1433
00:47:06,924 --> 00:47:08,859
DR. ALEXANDER LOUPY, WHO IS IN

1434
00:47:08,926 --> 00:47:09,860
PARIS CURRENTLY BUT HAS SPENT A

1435
00:47:09,927 --> 00:47:11,495
LOT OF TIME IN THE U.S. HERE AND

1436
00:47:11,562 --> 00:47:12,896
ABOUT TO DO THIS.

1437
00:47:12,963 --> 00:47:14,698
IT'S A WONDERFUL GIFT TO US.

1438
00:47:14,765 --> 00:47:16,733
THIS SAME THING WAS FOUND IN THE

1439
00:47:16,800 --> 00:47:18,735
LONG TERM DECEDENT THAT

1440
00:47:18,802 --> 00:47:22,406
DR. MOMONTGOMERY DID.

1441
00:47:22,472 --> 00:47:24,942
HE DID A -- I GUESS IT WAS A

1442
00:47:25,008 --> 00:47:28,445
62-DAY DECEDENT KID NIGH

1443
00:47:28,512 --> 00:47:34,151
IMP -- KIDNEYTRANSPLANT.

1444
00:47:34,218 --> 00:47:36,019
THEY HAD THE KIDNEY ON PHORESIS

1445
00:47:36,086 --> 00:47:39,456
TO TAKE THE ANTIBODIES OUT.

1446
00:47:39,523 --> 00:47:40,991
SO WE'RE GOING TO NEED TO

1447
00:47:41,058 --> 00:47:42,793
ROAD-TEST A BETTER IMMUNE

1448
00:47:42,859 --> 00:47:43,660
SUPPRESSIVE PROTOCOL.

1449
00:47:43,727 --> 00:47:44,761
THAT'S WHY I DIDN'T SPEND A LOT

1450
00:47:44,828 --> 00:47:46,096
OF TIME ON THE OLD PROTOCOL

1451
00:47:46,163 --> 00:47:47,064
BECAUSE THIS IS WHAT WE'VE GOT

1452
00:47:47,130 --> 00:47:47,864
TO DO.

1453
00:47:47,931 --> 00:47:51,468
WE HAVE TO BRING OUR STANDARD B

1454
00:47:51,535 --> 00:47:53,870
CELLS DOWN BECAUSE B CELLS

1455
00:47:53,937 --> 00:47:56,873
BECOME PLASMA CELLS, AND PLASMA

1456
00:47:56,940 --> 00:47:58,976
CELLS MAKE ANTIBODIES.

1457
00:47:59,042 --> 00:48:00,477
WE'RE GOING TO GIVE ATG, WHICH

1458
00:48:00,544 --> 00:48:01,612
HAS BEEN PART OF THE PROCESS,

1459
00:48:01,678 --> 00:48:04,715
AND THAT'S TO HELP REGULATE THE

1460
00:48:04,781 --> 00:48:06,149
T LYMPHOCYTES AWAY.

1461
00:48:06,216 --> 00:48:07,951
WE STILL NEED TO CONTROL T

1462
00:48:08,018 --> 00:48:08,719
LYMPHOCYTES EVEN THOUGH WE

1463
00:48:08,785 --> 00:48:10,087
HAVEN'T SEEN CELL MEDIATED

1464
00:48:10,153 --> 00:48:10,354
REJECTION.

1465
00:48:10,420 --> 00:48:13,323
WE'RE GOING TO USE TAC AGAIN TO

1466
00:48:13,390 --> 00:48:16,860
HELP ATG OVER THE LONG HAUL

1467
00:48:16,927 --> 00:48:18,395
SUPPORT THE DYSREGULATION OF

1468
00:48:18,462 --> 00:48:18,629
T-CELL.

1469
00:48:18,695 --> 00:48:22,399
WE'RE GOING TO REMOVE IGG

1470
00:48:22,466 --> 00:48:24,134
PRE-OP, AND IG M & I GE, AND

1471
00:48:24,201 --> 00:48:28,772
WE'RE GOING TO USE THERMABSORB,

1472
00:48:28,839 --> 00:48:30,641
WHICH IS A COLUMN CAN HAVE THE

1473
00:48:30,707 --> 00:48:31,842
PATIENT'S BLOOD RUN THROUGH AND

1474
00:48:31,908 --> 00:48:37,247
IT SELECTIVELY REMOVES AGM, AGG.

1475
00:48:37,314 --> 00:48:39,316
IT'S PROBABLY NOT THE BEST THING

1476
00:48:39,383 --> 00:48:40,784
FOR THE PATIENT INFECTION-WISE,

1477
00:48:40,851 --> 00:48:42,953
BUT WE CAN DRIVE ANY EXISTING

1478
00:48:43,020 --> 00:48:43,954
ANTIBODIES EVEN AT LOW LEVEL

1479
00:48:44,021 --> 00:48:46,490
THAT WE THINK WERE OKAY BUT

1480
00:48:46,556 --> 00:48:49,059
WEREN'T, WE CAN DRIVE THOSE DOWN

1481
00:48:49,126 --> 00:48:50,494
TO ZERO SO WE CAN GET A REALLY

1482
00:48:50,560 --> 00:48:51,895
GOOD START WITH THIS ORGAN

1483
00:48:51,962 --> 00:48:53,163
BEFORE MAYBE REJECTION OCCURS.

1484
00:48:53,230 --> 00:48:54,364
AND WHILE WE DO THAT, WE'RE ALSO

1485
00:48:54,431 --> 00:48:55,732
GOING TO PUT DOWN PRESSURE ON

1486
00:48:55,799 --> 00:48:57,467
THE PLASMA CELL, WHICH IS THE

1487
00:48:57,534 --> 00:49:00,070
PART OF THE B CELL POPULATION

1488
00:49:00,137 --> 00:49:02,606
THAT EVOLVES TO CREATE THE

1489
00:49:02,673 --> 00:49:04,241
ANTIBODIES, SO WE'RE GOING TO

1490
00:49:04,308 --> 00:49:06,476
TAKE THE B CELLS AND WHACK THEM

1491
00:49:06,543 --> 00:49:07,911
DOWN, BUT THE PLASMA CELLS ARE

1492
00:49:07,978 --> 00:49:11,348
RESISTANT TO THAT DRUG THAT WE

1493
00:49:11,415 --> 00:49:12,382
WHACKED THE MOTHERLOAD DOWN

1494
00:49:12,449 --> 00:49:12,582
WITH.

1495
00:49:12,649 --> 00:49:14,084
SO THE PLASMA CELLS KEEP FILLING

1496
00:49:14,151 --> 00:49:15,919
UP THE WELL, EVEN THOUGH YOU'RE

1497
00:49:15,986 --> 00:49:17,387
PULLING THOSE ANTIBODIES OUT.

1498
00:49:17,454 --> 00:49:18,722
SO WE HAVE TO DO THOSE TWO

1499
00:49:18,789 --> 00:49:19,056
THINGS.

1500
00:49:19,122 --> 00:49:21,358
WE ALSO HAVE TO BE COGNIZANT OF

1501
00:49:21,425 --> 00:49:23,226
THE FACT THAT COMPLEMENT IS VERY

1502
00:49:23,293 --> 00:49:24,861
MUCH PART OF THE STORY, AND WE

1503
00:49:24,928 --> 00:49:26,730
HAD LOTS OF COMPLEMENT IN OUR

1504
00:49:26,797 --> 00:49:27,064
PATIENTS.

1505
00:49:27,130 --> 00:49:29,199
WE'VE GOT TO DO A BETTER JOB

1506
00:49:29,266 --> 00:49:31,401
BLOCKING THE COMPLEMENT, AND WE

1507
00:49:31,468 --> 00:49:35,672
HAVE A PRESCRIPTION FOR THAT.

1508
00:49:35,739 --> 00:49:36,973
WE'RE PROBABLY GOING TO STOP AT

1509
00:49:37,040 --> 00:49:38,642
THAT, BUT IF WE HAVE TO GIVE

1510
00:49:38,709 --> 00:49:44,681
BLOOD PRODUCTS, WE WILL USE

1511
00:49:44,748 --> 00:49:47,918
IDES, WHICH IS A DRUG THAT WILL

1512
00:49:47,984 --> 00:49:49,553
LYSE IGG AND WILL BASICALLY

1513
00:49:49,619 --> 00:49:55,125
ELIMINATE THE TRANSFER OF ANY

1514
00:49:55,192 --> 00:49:56,259
ANTIPIG ANTIBODY FROM AN

1515
00:49:56,326 --> 00:49:56,793
EXTERNAL SOURCE.

1516
00:49:56,860 --> 00:49:58,362
SO WE CAN KILL THAT RIGHT AWAY,

1517
00:49:58,428 --> 00:50:00,864
SO WE CAN STILL GET AWAY WITH

1518
00:50:00,931 --> 00:50:02,899
BLOOD TRANSFUSION IF WE NEED TO.

1519
00:50:02,966 --> 00:50:04,201
I THINK THAT'S PROBABLY WHERE I

1520
00:50:04,267 --> 00:50:09,339
AM WITH THAT.

1521
00:50:09,406 --> 00:50:10,941
SO LET'S GET BACK TO THE

1522
00:50:11,007 --> 00:50:11,742
HUMANITY ASPECT OF THIS, AND

1523
00:50:11,808 --> 00:50:14,845
WE'RE JUST ABOUT RIGHT ON TIME.

1524
00:50:14,911 --> 00:50:17,147
DAVE BENNETT, JR. IS SHOWN HERE

1525
00:50:17,214 --> 00:50:19,516
ON THE PATIENT'S LEFT SIDE.

1526
00:50:19,583 --> 00:50:21,051
DAVE WAS ESTRANGED FROM HIS DAD.

1527
00:50:21,118 --> 00:50:24,087
THIS WAS OUR FIRST PATIENT.

1528
00:50:24,154 --> 00:50:26,256
OUR FIRST PATIENT WAS A RASCAL.

1529
00:50:26,323 --> 00:50:27,858
HE WAS DESCRIBED FROM HIS

1530
00:50:27,924 --> 00:50:28,725
CARDIOLOGIST AS THE WORST

1531
00:50:28,792 --> 00:50:32,129
PATIENT HE EVER HAD.

1532
00:50:32,195 --> 00:50:33,497
HE WOULD NEVER DO WHAT HE WAS

1533
00:50:33,563 --> 00:50:34,698
TOLD, NEVER TAKE HIS MEDICINES

1534
00:50:34,765 --> 00:50:35,999
AND HE WOULD JUST COME INTO THE

1535
00:50:36,066 --> 00:50:37,367
EMERGENCY ROOM FOR RESCUE

1536
00:50:37,434 --> 00:50:38,235
TREATMENT.

1537
00:50:38,301 --> 00:50:40,303
THAT WAS ONE OF THE REASONS,

1538
00:50:40,370 --> 00:50:41,204
PROBABLY THE MOST IMPORTANT

1539
00:50:41,271 --> 00:50:42,839
REASON THAT WE COULDN'T GIVE HIM

1540
00:50:42,906 --> 00:50:44,741
A STANDARD ALLO TRANSPLANT,

1541
00:50:44,808 --> 00:50:48,678
BECAUSE HE JUST WOULDN'T HAVE

1542
00:50:48,745 --> 00:50:50,313
ENOUGH COMPLIANCE TO PASS OUR

1543
00:50:50,380 --> 00:50:51,415
TEST.

1544
00:50:51,481 --> 00:50:53,150
WE THOUGHT WE'D GATHER A TEAM

1545
00:50:53,216 --> 00:50:54,951
THAT COULD ENCOURAGE HIM TO TAKE

1546
00:50:55,018 --> 00:50:56,386
THE MEDS SUFFICIENT ENOUGH.

1547
00:50:56,453 --> 00:50:59,022
WE'D DO HOUSE CALLS, WHERE ELSE

1548
00:50:59,089 --> 00:51:00,090
ARE WE GOING TO GET A PATIENT.

1549
00:51:00,157 --> 00:51:01,591
SO WE FIGURED WE'D GO OUT OF OUR

1550
00:51:01,658 --> 00:51:03,126
WAY IN A WAY THAT WE COULDN'T DO

1551
00:51:03,193 --> 00:51:04,961
FOR OUR ALLO PATIENTS IN GENERAL

1552
00:51:05,028 --> 00:51:06,363
TO GIVE HIM AN OPPORTUNITY.

1553
00:51:06,430 --> 00:51:07,664
HE SAYS, DAD'S COLONEL WILL BE

1554
00:51:07,731 --> 00:51:09,433
SOMETHING I WILL NEVER FORGET

1555
00:51:09,499 --> 00:51:10,901
AND ALWAYS CHERISH.

1556
00:51:10,967 --> 00:51:12,536
HE LEFT A LEG SEES FOR US TO

1557
00:51:12,602 --> 00:51:13,503
BUILD FROM BECAUSE HE CHOSE TO

1558
00:51:13,570 --> 00:51:14,504
FIGHT FOR THE FINAL MONTHS OF

1559
00:51:14,571 --> 00:51:15,105
HIS LIFE.

1560
00:51:15,172 --> 00:51:17,307
HE PASSED AWAY FIGHTING FOR

1561
00:51:17,374 --> 00:51:18,375
SCIENCE FOR THE SAKE OF

1562
00:51:18,442 --> 00:51:18,708
HUMANITY.

1563
00:51:18,775 --> 00:51:19,976
YOU KNOW, MY DAD NEVER MADE IT

1564
00:51:20,043 --> 00:51:21,077
OUT OF THE HOSPITAL, BUT HE DID

1565
00:51:21,144 --> 00:51:22,946
MAKE IT INTO HIS ULTIMATE HOME.

1566
00:51:23,013 --> 00:51:25,115
HE FOUGHT HARD FOR THOSE ANGEL

1567
00:51:25,182 --> 00:51:25,615
WINGS.

1568
00:51:25,682 --> 00:51:27,684
AND WITH THE HEART THAT'S INSIDE

1569
00:51:27,751 --> 00:51:29,653
HIM, PIGS TRULY ARE FLYING.

1570
00:51:29,719 --> 00:51:34,090
SO HE SAYS, KEEP IT UP.

1571
00:51:34,157 --> 00:51:35,292
AND THEN I'M GOING TO LEAVE YOU

1572
00:51:35,358 --> 00:51:36,493
WITH THIS ONE.

1573
00:51:36,560 --> 00:51:37,794
AND IF THERE'S A DRY EYE, I WANT

1574
00:51:37,861 --> 00:51:38,962
TO SEE IT.

1575
00:51:39,029 --> 00:51:41,698
THIS IS OUR SECOND PATIENT.

1576
00:51:41,765 --> 00:51:44,334
AND I TOLD YOU THAT WE WERE

1577
00:51:44,401 --> 00:51:45,669
SUFFERING WITH THE SWELLING OF

1578
00:51:45,735 --> 00:51:46,736
HIS HEART TOO AND WE COULDN'T

1579
00:51:46,803 --> 00:51:48,872
REVERSE IT, SO HE WAS ON ECMO.

1580
00:51:48,939 --> 00:51:52,108
WE TREATED HIM AGGRESSIVELY FOR

1581
00:51:52,175 --> 00:51:52,976
ANTIBODY-MEDIATED REJECTION AND

1582
00:51:53,043 --> 00:51:54,411
FAILED TO REVERSE THE PROCESS

1583
00:51:54,478 --> 00:51:56,146
AFTER FIVE DAYS.

1584
00:51:56,213 --> 00:51:57,414
THE PATIENT WAS TIRED AND DIDN'T

1585
00:51:57,481 --> 00:51:59,616
WANT TO GO FORWARD.

1586
00:51:59,683 --> 00:52:00,917
WE THOUGHT MAYBE WE'D LIKE TO GO

1587
00:52:00,984 --> 00:52:02,385
10 DAYS ON ECMO TO SEE IF WE

1588
00:52:02,452 --> 00:52:04,588
COULD TURN IT AROUND, BUT WE

1589
00:52:04,654 --> 00:52:06,990
RESPECTED HIS WISHES, AND HE

1590
00:52:07,057 --> 00:52:08,258
WANTED TO GET OFF THE ECMO AND

1591
00:52:08,325 --> 00:52:09,626
WE KNEW THE MINUTE WE STOPPED

1592
00:52:09,693 --> 00:52:12,162
THE ECMO, THAT HE WOULD CEASE TO

1593
00:52:12,229 --> 00:52:14,831
BE BECAUSE HIS HEART COULDN'T

1594
00:52:14,898 --> 00:52:16,600
KEEP HIM ALIVE.

1595
00:52:16,666 --> 00:52:19,002
AND HE ASKED -- HE HAD A

1596
00:52:19,069 --> 00:52:20,637
TRACHEOSTOMY IF I REMEMBER, AND

1597
00:52:20,704 --> 00:52:24,875
SO HE ASKED FOR A CLIPBOARD, AND

1598
00:52:24,941 --> 00:52:25,842
LIKE PATIENTS, THOSE OF YOU WHO

1599
00:52:25,909 --> 00:52:26,743
HAVE BEEN TAKING CARE OF

1600
00:52:26,810 --> 00:52:27,978
PATIENTS KNOW, THEY WRITE LITTLE

1601
00:52:28,044 --> 00:52:29,412
NOTES, YOU CAN ALMOST NEVER READ

1602
00:52:29,479 --> 00:52:29,846
THEM, RIGHT?

1603
00:52:29,913 --> 00:52:31,147
AND IT TAKES FOREVER AND YOU'RE

1604
00:52:31,214 --> 00:52:32,649
GOING, OH, COME ON, COME ON,

1605
00:52:32,716 --> 00:52:33,283
I'VE GOT TO GO.

1606
00:52:33,350 --> 00:52:35,252
SO WE ALL STOOD THERE WHILE HE

1607
00:52:35,318 --> 00:52:37,320
WROTE THREE LINES.

1608
00:52:37,387 --> 00:52:37,521
RIGHT?

1609
00:52:37,587 --> 00:52:38,922
AND THE FIRST LINE, I THINK I

1610
00:52:38,989 --> 00:52:39,789
CAN READ PRETTY WELL.

1611
00:52:39,856 --> 00:52:41,558
IN FACT, I GOT THEM ALL

1612
00:52:41,625 --> 00:52:42,526
DECIPHERED NOW WITH A LOT OF

1613
00:52:42,592 --> 00:52:44,027
HELP.

1614
00:52:44,094 --> 00:52:47,397
I AM SORRY.

1615
00:52:47,464 --> 00:52:50,133
AND THEN DOT, DOT.

1616
00:52:50,200 --> 00:52:51,334
I TRIED HARD.

1617
00:52:51,401 --> 00:52:53,703
THAT'S WHAT THAT SAYS.

1618
00:52:53,770 --> 00:52:56,039
AND THEN THE LAST LINE WAS THE

1619
00:52:56,106 --> 00:52:56,473
KILLER, RIGHT?

1620
00:52:56,540 --> 00:52:58,241
NOW HE'S IN BED, YOU KNOW, ALL

1621
00:52:58,308 --> 00:52:59,342
THE NURSES ARE IN THE ROOM AND

1622
00:52:59,409 --> 00:53:01,211
THE WHOLE TEAM IS WITH HIM AND A

1623
00:53:01,278 --> 00:53:03,046
LOT OF LOVE GOES INTO THIS.

1624
00:53:03,113 --> 00:53:06,516
AND THEN HE SAYS, AND HE KIND OF

1625
00:53:06,583 --> 00:53:09,486
MOTIONS WITH HIS HAND, HE

1626
00:53:09,553 --> 00:53:10,887
STARTED WITH ME, WHICH WAS VERY

1627
00:53:10,954 --> 00:53:13,623
SAD.

1628
00:53:13,690 --> 00:53:16,226
I LOVE YOU.

1629
00:53:16,293 --> 00:53:17,761
AND THEN HE WAS AT PEACE.

1630
00:53:17,827 --> 00:53:19,729
AND HE DECIDED THAT NOW IT'S

1631
00:53:19,796 --> 00:53:21,097
OKAY, SO WE GAVE HIM A MOMENT

1632
00:53:21,164 --> 00:53:23,300
WITH HIS SPOUSE, AND WE TURNED

1633
00:53:23,366 --> 00:53:25,902
OFF THE MACHINE AND HE DIED

1634
00:53:25,969 --> 00:53:27,103
QUIETLY.

1635
00:53:27,170 --> 00:53:28,705
BUT NOT WITHOUT BEING REMEMBERED

1636
00:53:28,772 --> 00:53:30,874
FOREVER.

1637
00:53:30,941 --> 00:53:31,875
PRETTY NEAT.

1638
00:53:31,942 --> 00:53:34,077
SO THIS IS MY LAST SLIDE.

1639
00:53:34,144 --> 00:53:36,012
AND IT'S KIND OF CUTE.

1640
00:53:36,079 --> 00:53:37,747
WE ARE GROWING, AND THE DONORS

1641
00:53:37,814 --> 00:53:39,149
ARE GROWING TOO.

1642
00:53:39,215 --> 00:53:41,451
AND I THINK WE HAVE A PROCESS,

1643
00:53:41,518 --> 00:53:43,386
IF WE'RE CAREFUL WITH IT, AND

1644
00:53:43,453 --> 00:53:45,789
DELIBERATE, THAT WE CAN WORK

1645
00:53:45,855 --> 00:53:47,424
FROM ONE PATIENT TO ANOTHER TO

1646
00:53:47,490 --> 00:53:49,459
LEARN ENOUGH TO MAKE IT OF

1647
00:53:49,526 --> 00:53:53,029
VALUE, NOT JUST FOR SCIENCE BUT

1648
00:53:53,096 --> 00:53:53,997
OF VALUE TO THE PATIENT.

1649
00:53:54,064 --> 00:53:55,198
REMEMBER WHAT MAKES IT WORTH

1650
00:53:55,265 --> 00:53:57,400
THEIR WHILE IS -- OR WHAT WOULD

1651
00:53:57,467 --> 00:53:58,969
MAKE IT WORTH YOUR WHILE IS

1652
00:53:59,035 --> 00:54:00,103
RELATIVE TO YOUR RISK OF NOT

1653
00:54:00,170 --> 00:54:01,171
HAVING IT AT ALL.

1654
00:54:01,237 --> 00:54:02,772
OUR LAST PATIENT JUST WANTED A

1655
00:54:02,839 --> 00:54:04,407
CUP OF COFFEE ON HIS PORCH IN

1656
00:54:04,474 --> 00:54:06,076
THE FALL WITH HIS WIFE, ONE MORE

1657
00:54:06,142 --> 00:54:07,043
TIME.

1658
00:54:07,110 --> 00:54:08,678
I THOUGHT WE'D GET HIM THERE,

1659
00:54:08,745 --> 00:54:10,914
BUT I WAS SHORT-SIGHTED.

1660
00:54:10,981 --> 00:54:14,117
BUT WE'RE GOING TO GET TO HUMAN

1661
00:54:14,184 --> 00:54:16,353
TRIALS EVENTUALLY, BUT I THINK

1662
00:54:16,419 --> 00:54:18,188
WITH THESE EMERGENCY EXPANDED

1663
00:54:18,254 --> 00:54:19,522
USE PERMISSIONS, PERHAPS WE CAN

1664
00:54:19,589 --> 00:54:20,857
SHARPEN OUR PENCIL A LITTLE BIT

1665
00:54:20,924 --> 00:54:23,059
AND ROAD-TEST BETTER IMMUNE

1666
00:54:23,126 --> 00:54:23,994
SUPPRESSION THAT WE WOULDN'T

1667
00:54:24,060 --> 00:54:25,528
HAVE FORECASTED WAS NECESSARY

1668
00:54:25,595 --> 00:54:26,763
BASED UPON THE NON-HUMAN PRIMATE

1669
00:54:26,830 --> 00:54:28,932
WORK THAT WE HAD DONE.

1670
00:54:28,999 --> 00:54:30,367
SO IT'S VERY IMPORTANT TO ME

1671
00:54:30,433 --> 00:54:35,271
THAT I RECEIVED TEXTS FROM MY

1672
00:54:35,338 --> 00:54:36,539
FRIENDS AND FROM MY COLLEAGUES,

1673
00:54:36,606 --> 00:54:39,309
SOME OF WHOM WERE PRETTY HIGHLY

1674
00:54:39,376 --> 00:54:41,378
PLACED IN THE WORLD OF

1675
00:54:41,444 --> 00:54:44,347
IMMUNOLOGY AND TRANSPLANTATION,

1676
00:54:44,414 --> 00:54:45,382
AND THEY HAVE ALL BEEN

1677
00:54:45,448 --> 00:54:47,283
RELATIVELY ENCOURAGING.

1678
00:54:47,350 --> 00:54:48,885
AND FOR THAT, I'M VERY HUMBLED

1679
00:54:48,952 --> 00:54:50,787
AND YOUR RECEPTION TODAY AND

1680
00:54:50,854 --> 00:54:52,789
KIND ATTENTION TELLS ME YOU'RE

1681
00:54:52,856 --> 00:54:54,758
INTERESTED IN PROBABLY PART OF

1682
00:54:54,824 --> 00:54:55,725
THE CHEERING SECTION.

1683
00:54:55,792 --> 00:54:56,559
SO THANK YOU VERY MUCH.

1684
00:54:56,626 --> 00:54:56,926
THAT'S IT.

1685
00:54:56,993 --> 00:55:07,170
[APPLAUSE]

1686
00:55:08,304 --> 00:55:09,472
>> BART, AS ALWAYS, THANK YOU

1687
00:55:09,539 --> 00:55:12,742
VERY MUCH FOR INSIGHTFUL AND

1688
00:55:12,809 --> 00:55:15,011
ENCOURAGING AND

1689
00:55:15,078 --> 00:55:17,180
THOUGHT-PROVOKING IDEAS.

1690
00:55:17,247 --> 00:55:18,948
AND THE STUDENTS OUT THERE, ONE

1691
00:55:19,015 --> 00:55:19,382
LAST LITTLE THING.

1692
00:55:19,449 --> 00:55:21,084
BART IS AN AMAZING TEACHER.

1693
00:55:21,151 --> 00:55:22,385
HE'S SUCH A GOOD TEACHER OF

1694
00:55:22,452 --> 00:55:24,587
RESIDENTS AND FELLOWS THAT HE

1695
00:55:24,654 --> 00:55:26,056
WON THE TEACHING AWARD AT

1696
00:55:26,122 --> 00:55:27,691
MARYLAND SO MANY TIMES, THEY

1697
00:55:27,757 --> 00:55:29,025
WERE LIKE, WE'RE DONE.

1698
00:55:29,092 --> 00:55:31,528
LIKE THE 14-YEAR WINNER

1699
00:55:31,594 --> 00:55:32,362
CONSECUTIVELY, SO THEY HAD TO

1700
00:55:32,429 --> 00:55:33,897
STOP GIVING HIM THE AWARD, SO

1701
00:55:33,963 --> 00:55:34,664
WHAT DID THEY DO?

1702
00:55:34,731 --> 00:55:35,865
THEY NAMED IT AFTER HIM.

1703
00:55:35,932 --> 00:55:37,233
>> BUT THEN THEY GAVE TO YOU.

1704
00:55:37,300 --> 00:55:38,768
>> WELL, YEAH, THEY RAN OUT OF

1705
00:55:38,835 --> 00:55:41,504
PEOPLE.

1706
00:55:41,571 --> 00:55:44,174
BUT I'D LIKE TO OPEN THE FORUM

1707
00:55:44,240 --> 00:55:45,275
UP, WE'VE GOT A COUPLE MINUTES

1708
00:55:45,341 --> 00:55:46,042
HERE FOR QUESTIONS.

1709
00:55:46,109 --> 00:55:47,877
IF ANYBODY HAS ANY QUESTIONS,

1710
00:55:47,944 --> 00:55:50,113
PLEASE FEEL FREE TO STEP TO ONE

1711
00:55:50,180 --> 00:55:51,614
OF THE MICROPHONES TO ASK YOUR

1712
00:55:51,681 --> 00:56:01,124
QUESTIONS.

1713
00:56:01,191 --> 00:56:02,392
>> AMAZING TALK.

1714
00:56:02,459 --> 00:56:02,726
>> THANK YOU.

1715
00:56:02,792 --> 00:56:04,227
>> I'M CURIOUS ABOUT FOR GROWING

1716
00:56:04,294 --> 00:56:06,362
THE PIGS, YOU MENTI MENTIONED AT

1717
00:56:06,429 --> 00:56:06,930
THE SIZE OF THE HEART.

1718
00:56:06,996 --> 00:56:10,633
HOW DO YOU CONTROL FOR DIFFERENT

1719
00:56:10,700 --> 00:56:12,202
PATIENTS, START THINKING ABOUT

1720
00:56:12,268 --> 00:56:14,070
WHAT AGE OF THE PIG, WHAT'S THE

1721
00:56:14,137 --> 00:56:15,305
RELATIVE SIZE OF THAT PIG'S

1722
00:56:15,371 --> 00:56:19,042
HEART, AND THEN WHEN TO

1723
00:56:19,109 --> 00:56:19,342
TRANSPLANT.

1724
00:56:19,409 --> 00:56:20,610
>> IT'S FUNNY, THERE IS

1725
00:56:20,677 --> 00:56:21,611
VARIABILITY WITHIN THE PIGS,

1726
00:56:21,678 --> 00:56:23,780
PLUS OR MINUS 20% AT ANY GIVEN

1727
00:56:23,847 --> 00:56:25,882
WEIGHT OF THE PIG THAT THE HEART

1728
00:56:25,949 --> 00:56:28,485
MASS IS 20% PLUS OR MINUS.

1729
00:56:28,551 --> 00:56:30,754
SO YOU KNOW, I THINK WE GOT

1730
00:56:30,820 --> 00:56:33,156
HEART MASS MINUS ON OUR LAST

1731
00:56:33,223 --> 00:56:37,827
PATIENT, AND THAT HURT US.

1732
00:56:37,894 --> 00:56:39,529
WE DO THESE ANIMAL STUDIES, OF

1733
00:56:39,596 --> 00:56:41,431
COURSE, SO THE PIG SIZE THAT WE

1734
00:56:41,498 --> 00:56:45,702
CHOOSE FOR THE NON-HUMAN

1735
00:56:45,769 --> 00:56:47,203
PRIMATES IS ABOUT 18 KILOGRAMS,

1736
00:56:47,270 --> 00:56:49,839
AND WE PUT IT INTO MAYBE A

1737
00:56:49,906 --> 00:56:51,141
20-KILOGRAM BABOON.

1738
00:56:51,207 --> 00:56:52,976
SO THAT WORKS OUT JUST FINE AT

1739
00:56:53,042 --> 00:56:53,643
THAT LEVEL.

1740
00:56:53,710 --> 00:56:55,145
BUT IT DOESN'T SCALE QUITE AS

1741
00:56:55,211 --> 00:56:56,146
WELL WHEN EVERYBODY IS GETTING

1742
00:56:56,212 --> 00:56:57,881
BIGGER.

1743
00:56:57,947 --> 00:57:01,785
WE HAVE DECIDED BECAUSE IT IS

1744
00:57:01,851 --> 00:57:05,955
DIFFICULT TO DO THE TYPE OF

1745
00:57:06,022 --> 00:57:08,458
ECHOCARDIOGRAPHY IN A PIG TO GET

1746
00:57:08,525 --> 00:57:09,726
HEART MASS THAT WE'RE GOING TO

1747
00:57:09,793 --> 00:57:12,695
USE STROKE VOLUME, OKAY, BASED

1748
00:57:12,762 --> 00:57:18,802
UPON THE PHILOSOPHY INDEX COMING

1749
00:57:18,868 --> 00:57:21,504
OUT OF THE OUTFLOW TRACK AND THE

1750
00:57:21,571 --> 00:57:23,139
SIZE OF THE OUTFLOW TRACK.

1751
00:57:23,206 --> 00:57:25,008
SO KNOWING PRESSURE

1752
00:57:25,074 --> 00:57:26,709
DIFFERENTIALS AND THE SIZE OF

1753
00:57:26,776 --> 00:57:28,478
THE OUTFLOW TRACT AND THE

1754
00:57:28,545 --> 00:57:29,212
VELOCITIES WHICH KIND OF COME

1755
00:57:29,279 --> 00:57:31,147
WITH THE ECHO, YOU CAN GET

1756
00:57:31,214 --> 00:57:33,249
STROKE VOLUME AND IT'S PRETTY

1757
00:57:33,316 --> 00:57:34,450
DARN ACCURATE, AND THAT'S A

1758
00:57:34,517 --> 00:57:35,819
WINDOW WE CAN GET IN THESE

1759
00:57:35,885 --> 00:57:36,486
ANIMALS WITHOUT HAVING TO PUT

1760
00:57:36,553 --> 00:57:39,989
THEM TO SLEEP TO PUT A SCOPE

1761
00:57:40,056 --> 00:57:40,523
DOWN.

1762
00:57:40,590 --> 00:57:42,458
ONCE THE ANIMALS HAVE ALL THAT

1763
00:57:42,525 --> 00:57:44,060
DONE, THEY GO INTO QUARANTINE,

1764
00:57:44,127 --> 00:57:46,262
AND SO IF YOU DON'T LIKE YOUR

1765
00:57:46,329 --> 00:57:47,130
PICTURES, TOO BAD, YOU'RE NOT

1766
00:57:47,197 --> 00:57:49,532
GOING TO GET THAT PIG OUT OF

1767
00:57:49,599 --> 00:57:50,500
QUARANTINE AGAIN, AGAIN, AND

1768
00:57:50,567 --> 00:57:52,802
THAT'S BECAUSE WE WORRY ABOUT

1769
00:57:52,869 --> 00:57:55,104
VIRUSES INFECTING THE ANIMALS.

1770
00:57:55,171 --> 00:57:58,675
SO IT'S NOT REALLY A PROBLEM.

1771
00:57:58,741 --> 00:58:02,178
THE RECEPTOR KNOCKOUT MAY NOT

1772
00:58:02,245 --> 00:58:04,113
SURVIVE IN THE HEART POPULATION

1773
00:58:04,180 --> 00:58:06,316
OF PIGS AFTER THE I ND.

1774
00:58:06,382 --> 00:58:08,952
WE WILL HAVE TO CHOOSE MEDIUM

1775
00:58:09,018 --> 00:58:11,187
WEIGHT HUMANOIDS FOR HEARTS THAT

1776
00:58:11,254 --> 00:58:15,158
ARE GOING TO BE NO BIGGER MAYBE

1777
00:58:15,225 --> 00:58:18,094
THAN FAIR FOR MAYBE AN 80 TO

1778
00:58:18,161 --> 00:58:19,863
90-KILOGRAM MALE MAX.

1779
00:58:19,929 --> 00:58:20,697
>> GREAT, THANK YOU.

1780
00:58:20,763 --> 00:58:25,001
>> YOU'RE WELCOME.

1781
00:58:25,068 --> 00:58:26,636
>> YOU MENTIONED THAT THE

1782
00:58:26,703 --> 00:58:28,004
ANTIBODY RESPONSES INCLUDED BOTH

1783
00:58:28,071 --> 00:58:28,872
IGG AND IGM.

1784
00:58:28,938 --> 00:58:30,206
>> YES, SIR.

1785
00:58:30,273 --> 00:58:33,576
>> IS THERE A NEW WAVE OF NEW

1786
00:58:33,643 --> 00:58:35,311
ANTIBODIES GENERATED WITH THE

1787
00:58:35,378 --> 00:58:36,512
IGM RESPONSE?

1788
00:58:36,579 --> 00:58:38,915
AND HAVE YOU BEEN ABLE TO FIND

1789
00:58:38,982 --> 00:58:40,750
CD4 CELLS THAT WOULD ACCOMPANY

1790
00:58:40,817 --> 00:58:45,054
THE CLASS SWITCHING TO IGG?

1791
00:58:45,121 --> 00:58:46,823
>> YES, THERE IS CLASS SWITCHING

1792
00:58:46,890 --> 00:58:48,725
OF COURSE, AND THE IGM IS

1793
00:58:48,791 --> 00:58:54,163
THOUGHT TO BE AN EARLY PHASE

1794
00:58:54,230 --> 00:58:54,931
REACTED AND PROBABLY MORE

1795
00:58:54,998 --> 00:58:57,100
RELATED TO THE ANTIBODY

1796
00:58:57,166 --> 00:58:58,201
DEPENDENT CYTOTOXICITY.

1797
00:58:58,268 --> 00:59:01,471
SO I THINK BOTH CLASSES ARE

1798
00:59:01,537 --> 00:59:02,572
IMPORTANT, AND THAT'S REALLY ALL

1799
00:59:02,639 --> 00:59:04,841
I KNOW ABOUT IT.

1800
00:59:04,908 --> 00:59:08,344
I DON'T THINK WE HAVE DUG AS

1801
00:59:08,411 --> 00:59:09,445
DEEPLY AS WE COULD, AND IF YOU

1802
00:59:09,512 --> 00:59:11,147
HAVE AN INTEREST IN ANTIBODIES

1803
00:59:11,214 --> 00:59:12,682
AND ANTIBODY SWITCHING, I'D LOVE

1804
00:59:12,749 --> 00:59:18,154
TO TALK TO YOU.

1805
00:59:18,221 --> 00:59:19,422
>> ANY QUESTIONS FROM THE

1806
00:59:19,489 --> 00:59:24,560
AUDIENCE?

1807
00:59:24,627 --> 00:59:26,229
WE GET QUESTIONS IN FROM --

1808
00:59:26,296 --> 00:59:27,864
>> B CELL SWITCHING, NOT

1809
00:59:27,931 --> 00:59:28,364
ANTIBODY SWITCHING.

1810
00:59:28,431 --> 00:59:31,000
>> FIRST OF ALL, THANK YOU FOR

1811
00:59:31,067 --> 00:59:31,634
YOUR PRESENTATION BUT VERY

1812
00:59:31,701 --> 00:59:32,835
IMPORTANTLY I WANT TO THANK YOUR

1813
00:59:32,902 --> 00:59:33,903
TWO PATIENTS WHO WERE PARTNERS

1814
00:59:33,970 --> 00:59:35,471
WITH YOU IN SCIENCE AND

1815
00:59:35,538 --> 00:59:40,510
ADVANCING THIS, SO WITHOUT THEIR

1816
00:59:40,576 --> 00:59:42,679
PARTICIPATION, I THINK ONE OF

1817
00:59:42,745 --> 00:59:43,947
THE STORIES YOU'VE SHARED WITH

1818
00:59:44,013 --> 00:59:45,648
THE STUDENTS THIS MORNING WAS

1819
00:59:45,715 --> 00:59:47,684
ONE OF YOUR PATIENTS SAID HOPE

1820
00:59:47,750 --> 00:59:48,985
YOU LEARN SOMETHING.

1821
00:59:49,052 --> 00:59:51,154
SO WITH THAT, A QUESTION COMES

1822
00:59:51,220 --> 00:59:52,588
IN FROM A VIDEO CAST VIEWER.

1823
00:59:52,655 --> 00:59:54,424
HOW IS THE ROLE OF THE BIOETHICS

1824
00:59:54,490 --> 00:59:55,525
PLAYED INTO YOUR WORK AND

1825
00:59:55,591 --> 00:59:57,360
CAREER?

1826
00:59:57,427 --> 01:00:02,532
>> TO THIS WORK OR OVERALL?

1827
01:00:02,598 --> 01:00:03,833
>> █PROBABLY THIS WORK.

1828
01:00:03,900 --> 01:00:05,501
>> SO IN OUR FIRST PATIENT,

1829
01:00:05,568 --> 01:00:06,769
BECAUSE HE WAS SO SICK, OUR DEAN

1830
01:00:06,836 --> 01:00:07,971
KEPT THINKING HE COULDN'T GIVE

1831
01:00:08,037 --> 01:00:09,839
TRUE CONSENT.

1832
01:00:09,906 --> 01:00:10,273
RIGHT?

1833
01:00:10,340 --> 01:00:11,207
DEAN CAME TO SEE HIM.

1834
01:00:11,274 --> 01:00:11,774
I DON'T KNOW.

1835
01:00:11,841 --> 01:00:12,976
IT WAS THE DEAN'S PROBLEM, I

1836
01:00:13,042 --> 01:00:13,509
THINK.

1837
01:00:13,576 --> 01:00:14,711
WE HAD FOUR PSYCHIATRISTS SEE

1838
01:00:14,777 --> 01:00:16,879
HIM AND ALL OF THEM AGREED HE

1839
01:00:16,946 --> 01:00:17,313
COULD CONSENT.

1840
01:00:17,380 --> 01:00:20,183
ON TOP OF THAT, WE HAVE AN

1841
01:00:20,249 --> 01:00:21,117
ETHICS COMMITTEE AT THE

1842
01:00:21,184 --> 01:00:24,387
UNIVERSITY OF MARYLAND, AND IT'S

1843
01:00:24,454 --> 01:00:25,154
AN OUTSTANDING COMMITTEE AND

1844
01:00:25,221 --> 01:00:28,424
NONE OF THEM HAVE CONFLICT OF

1845
01:00:28,491 --> 01:00:30,193
INTEREST IN THE PROCEDURE, AND

1846
01:00:30,259 --> 01:00:32,428
THE CHAIRMAN OF THE COMMITTEE

1847
01:00:32,495 --> 01:00:33,763
STAYED WITH US AND ROUNDED EVERY

1848
01:00:33,830 --> 01:00:34,931
MORNING WITH US AFTER SURGERY,

1849
01:00:34,998 --> 01:00:36,232
WHICH IS WONDERFUL AND HE'S

1850
01:00:36,299 --> 01:00:38,634
WRITTEN A PAPER ON IT.

1851
01:00:38,701 --> 01:00:42,705
AND YOU KNOW, THEY BASICALLY DO

1852
01:00:42,772 --> 01:00:44,340
WHAT ETHICISTS DO.

1853
01:00:44,407 --> 01:00:45,808
THERE'S ALWAYS TWO SIDES OF AN

1854
01:00:45,875 --> 01:00:47,944
ETHICAL ARGUMENT, AND I GUESS

1855
01:00:48,011 --> 01:00:49,312
YOU COULD BEGIN, IS IT ETHICAL

1856
01:00:49,379 --> 01:00:50,747
TO TAKE A PIG, YOU KNOW, AND

1857
01:00:50,813 --> 01:00:53,149
SACRIFICE A PIG FOR AN

1858
01:00:53,216 --> 01:00:54,050
EXPERIMENTAL HUMAN TRANSPLANT.

1859
01:00:54,117 --> 01:00:55,318
THERE'S SOME PEOPLE THAT THINK

1860
01:00:55,385 --> 01:00:57,620
WE SHOULDN'T.

1861
01:00:57,687 --> 01:00:59,589
I THINK THEY'RE IN THE MINORITY,

1862
01:00:59,655 --> 01:01:00,690
BUT, YOU KNOW, THAT'S PART OF

1863
01:01:00,757 --> 01:01:01,724
THE ISSUE.

1864
01:01:01,791 --> 01:01:03,826
AND THEN, OF COURSE, IS IT

1865
01:01:03,893 --> 01:01:05,361
ETHICAL TO SPEND THE MONEY,

1866
01:01:05,428 --> 01:01:08,297
RIGHT, ON THIS TYPE OF EXPENSIVE

1867
01:01:08,364 --> 01:01:09,032
RESEARCH, AND WE TALKED ABOUT

1868
01:01:09,098 --> 01:01:10,433
THAT A LITTLE BIT EARLIER WITH

1869
01:01:10,500 --> 01:01:15,471
THE NHLBI GROUP, AND YOU KNOW,

1870
01:01:15,538 --> 01:01:16,572
WHAT'S NOT ETHICAL ABOUT IT?

1871
01:01:16,639 --> 01:01:18,307
I DON'T UNDERSTAND IT.

1872
01:01:18,374 --> 01:01:21,544
IF YOU'RE NOT WORRIED ABOUT

1873
01:01:21,611 --> 01:01:23,079
ZOOINOSIS, INFECTING A WHOLE NEW

1874
01:01:23,146 --> 01:01:25,148
GROUP OF NURSES AND THIS AND

1875
01:01:25,214 --> 01:01:26,916
THAT, AND BY THE WAY, OUR NURSES

1876
01:01:26,983 --> 01:01:28,184
HAD AN OPT OUT, THEY DIDN'T HAVE

1877
01:01:28,251 --> 01:01:29,952
TO TAKE CARE OF THE PATIENT.

1878
01:01:30,019 --> 01:01:33,356
AND ONLY ABOUT 10 OUT OF 300

1879
01:01:33,423 --> 01:01:33,790
OPTED OUT.

1880
01:01:33,856 --> 01:01:35,925
IT WAS KIND OF NEAT.

1881
01:01:35,992 --> 01:01:37,026
SO THEY BLEW THROUGH THAT.

1882
01:01:37,093 --> 01:01:39,429
THEY DIDN'T WORRY ABOUT IT.

1883
01:01:39,495 --> 01:01:40,696
SO THAT WAS ABOUT ALL.

1884
01:01:40,763 --> 01:01:43,332
I MEAN, THE MOST IMPORTANT

1885
01:01:43,399 --> 01:01:46,736
ETHICAL QUESTION IS, AM I

1886
01:01:46,803 --> 01:01:50,006
PROMISING THE PATIENT, OKAY,

1887
01:01:50,073 --> 01:01:52,408
THAT THERE'S A GREATER

1888
01:01:52,475 --> 01:01:54,477
LIKELIHOOD OF THERAPY, OKAY,

1889
01:01:54,544 --> 01:01:55,912
OVER WHAT I'M GOING TO LEARN.

1890
01:01:55,978 --> 01:01:58,247
IN OTHER WORDS, THERAPEUTIC

1891
01:01:58,314 --> 01:01:59,048
MISCONCEPTION IS A VERY

1892
01:01:59,115 --> 01:02:00,550
IMPORTANT THING THAT ETHICISTS

1893
01:02:00,616 --> 01:02:01,317
TALK ABOUT.

1894
01:02:01,384 --> 01:02:03,619
AND THAT KIND OF MEANS, AGAIN,

1895
01:02:03,686 --> 01:02:05,455
THAT I'M PROMISING THE PATIENT

1896
01:02:05,521 --> 01:02:06,856
THAT HE HAS A LIKELIHOOD OF

1897
01:02:06,923 --> 01:02:09,492
LIVING LONGER WHEN, IN FACT, HE

1898
01:02:09,559 --> 01:02:11,094
DOESN'T HAVE A LIKELIHOOD OF

1899
01:02:11,160 --> 01:02:11,661
LIVING LONGER.

1900
01:02:11,727 --> 01:02:13,529
I HAVE NO -- THERE'S NO JUSTICE

1901
01:02:13,596 --> 01:02:15,832
IN THAT BECAUSE I DON'T KNOW,

1902
01:02:15,898 --> 01:02:16,365
RIGHT?

1903
01:02:16,432 --> 01:02:19,969
WHAT IS PRETTY SURE IS THAT IESM

1904
01:02:20,036 --> 01:02:20,903
GOING TO GAIN BY THE KNOWLEDGE

1905
01:02:20,970 --> 01:02:23,473
THAT WE LEARN FROM HIS

1906
01:02:23,539 --> 01:02:24,974
INVOLVEMENT IN THE PROCEDURE.

1907
01:02:25,041 --> 01:02:28,678
SO AT NO TIME CAN WE TELL THE

1908
01:02:28,744 --> 01:02:30,847
PATIENT, RIGHT, OR CONVINCE THE

1909
01:02:30,913 --> 01:02:32,148
PATIENT THAT YOU SHOULD SIGN ON

1910
01:02:32,215 --> 01:02:33,149
THIS PAPER BECAUSE YOU'RE GOING

1911
01:02:33,216 --> 01:02:36,119
TO DIE IF YOU DON'T.

1912
01:02:36,185 --> 01:02:37,520
YOU SIGN ON THIS PAPER BECAUSE

1913
01:02:37,587 --> 01:02:39,889
WE HAVE NOTHING ELSE TO TREAT

1914
01:02:39,956 --> 01:02:40,323
YOU WITH.

1915
01:02:40,389 --> 01:02:41,457
WE HAVE EXPERIMENTAL SCIENCE

1916
01:02:41,524 --> 01:02:44,961
THAT WE NEED TO LEARN MORE FROM

1917
01:02:45,027 --> 01:02:46,996
WE'RE GOING TO LEARN A LOT FROM

1918
01:02:47,063 --> 01:02:48,764
YOU, AND WE HOPE THAT YOU MAY

1919
01:02:48,831 --> 01:02:49,966
LIVE A LITTLE LONGER TO GET

1920
01:02:50,032 --> 01:02:52,268
HOME.

1921
01:02:52,335 --> 01:02:55,771
THAT'S IT.

1922
01:02:55,838 --> 01:02:58,374
[APPLAUSE]

1923
01:02:58,441 --> 01:03:01,878
>> THANK YOU ALL AGAIN VERY MU

1924
01:03:01,944 --> 01:03:02,078
MUCH.

1925
01:03:02,145 --> 01:03:04,046
AS YOU MAY KNOW, THERE'S SOME --

1926
01:03:04,113 --> 01:03:05,982
WE DO HAVE -- UNFORTUNATELY WE

1927
01:03:06,048 --> 01:03:07,517
WEREN'T ABLE TO OPEN UP TO EVERY

1928
01:03:07,583 --> 01:03:09,051
SINGLE HUMAN PERSON, WE WOULD

1929
01:03:09,118 --> 01:03:10,253
LOVE TO HAVE DONE THAT, BUT IF

1930
01:03:10,319 --> 01:03:11,554
YOU HAVE AN EMAIL, YOU KNOW WHO

1931
01:03:11,621 --> 01:03:13,589
YOU ARE, THERE'S AN INVITATION

1932
01:03:13,656 --> 01:03:16,359
LUNCH, WE HAD TO MOVE IT UP TO

1933
01:03:16,425 --> 01:03:18,961
THE FAES TERRACE, SO IN CASE

1934
01:03:19,028 --> 01:03:22,031
THAT EMAIL WAS CONFUSING, ADD TO

1935
01:03:22,098 --> 01:03:23,633
THE OTHER LIST OF CONFUSING

1936
01:03:23,699 --> 01:03:24,167
EMAILS I SEND.

1937
01:03:24,233 --> 01:03:25,501
>> I DIDN'T GET AN EMAIL.

1938
01:03:25,568 --> 01:03:28,404
>> YEAH, THAT'S WHY I'M HERE.

1939
01:03:28,471 --> 01:03:32,008
AGAIN, THANKS, ERCH, HAVE A GOOA

1940
01:03:32,074
GOOD DAY.