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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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OUR SPEAKER TODAY IS Dr.

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MICHAEL M. GOTTESMAN THE

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NATIONAL INSTITUTE OF HEALTH OR

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NIH DEPUTY DIRECTOR FOR

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INTERMURAL RESEARCH SINCE 1993.

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Dr. GOTTESMAN IS A SENIOR

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INVESTIGATORS AND CHIEF OF THE

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LABORATORY OF CELL BIOLOGY AND

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HEAD OF THE MULTI-DRUG RESISTANT

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SECTION AT THE NATIONAL CANCER

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INSTITUTE OR NCI.

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Dr. GOTTESMAN EARNED HIS

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MEDICAL DEGREE FROM HARVARD

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UNIVERSITY MEDICAL SCHOOL AND

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COMPLETED HIS INTERNSHIP AND

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RESIDENCY IN MEDICINE AT THE

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PETER BENT BRIGHAM HOSPITAL IN

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BOSTON, MASSACHUSETTS.

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HE RECEIVED HIS POSTDOC TO BAL

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RESEARCH TRAIN NORTH MOLECULAR

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GENETICS AT THE NIH.

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HE RETURNED TO HARVARD MEDICAL

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SCHOOL AS AN ASSISTANT PROFESSOR

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IN THE DEPARTMENT OF AN  A MAT .

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HE WAS THE CHIEF OF LABORATORY

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OF CELL BIOLOGY AND NCI AND IN

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1990 AND FROM 1992, TO 1993, HE

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WAS THE ACTING DIRECTOR FOR THE

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NATIONAL CENTER FOR HUMAN GENOME

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RESEARCH OR NHGRI.

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HE SERVED AS THE ACTING

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SCIENTIFIC DIRECTOR FOR NHGRI IN

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1993 BEFORE HE BECAME THE NIH

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DEPUTY DIRECTOR FOR INTERMURAL

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RESEARCH.

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WITH OVER 550 PEER REVIEWED

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SCIENTIFIC PUBLICATIONS, Dr.

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GOTTESMAN RESEARCH INTEREST HAS

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RANGED FROM HOW DNA IS

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REPLICATED IN BACTERIA TO HOW

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CANCER CELLS ELUDE CHEMOTHERAPY.

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HIS LABORATORY IDENTIFIED THE

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HUMAN GENE THAT CAUSES CANCER

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CELLS TO RESIST ANTICANCER

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DRUGS, AND HAS USED THIS

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INFORMATION TO CREATE GENE

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TRANSFER VECTORS TO CIRCUMVENT

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DRUG RESISTANCE IN CAN SEPTEMBE.

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HIS WORK HAS DETERMINED THE

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CLINICAL RELEVANCE OF THESE

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MECHANISMS.

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IN HIS ROLL-OVER SEEING THE

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INTRAMURAL RESEARCH PROGRAM AT

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THE NIH, Dr. GOTTESMAN HAS

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INITIATED SEVERAL TRAINING AND

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MENTORING PROGRAMS FOR HIGH

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SCHOOL, COLLEGE, POSTBAC

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LAUREATE, MEDICAL AND GREAT WAD

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STUDENTS.

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THIS INCLUDES TRAINING PROGRAMS

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FOR STUDENTS FROM DISADVANTAGED

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POPULATIONS, PROGRAMS TO ADVANCE

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CAT REOF WOMEN SCIENTISTS AND

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LOAN REPAYMENT PROGRAMS AND THE

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TENURE TRACK FACULTY DEDICATED

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TO BUILDING A MORE DIVERSE AND

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INCLUSIVE SCIENTIFIC COMMUNITY

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AND FOR BOTH CLINICAL AND

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LABORATORY BASED INVESTIGATORS

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AND THE TRANS NIH TENURE TRACK

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RECRUIT MANY PROGRAM AND THE

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LASKERS PROGRAM.

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HE OVERSEES THE REVIEW PROCESS

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AND FOR 1100 PRINCIPLE

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INVESTIGATORS AND IS THE

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INSTITUTION OFFICIAL FOR HUMAN

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SUBJECTS RESEARCH AND ANIMAL

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CARE AND USE AND TECHNOLOGY

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TRANSFER AT THE NIH AND THE

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AMERICAN SEWIZATION OF

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PHYSICIANS AND THE AMERICAN

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SOCIETY FOR PHARMACOLOGY AND

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EXPERIMENTAL THERAPEUTICS AND

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BEEN A ELECTED MEMBER OF THE

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NATIONAL ACADEMY OF MEDICINE

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SINCE 2003 AND THE ACADEMY OF

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ARTS AND SCIENCES SINCE 2008,

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AND THE NATIONAL ACADEMY OF

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SCIENCES SINCE 2018.

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THE TITLE OF Dr. GOTTESMAN'S

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PRESENTATION TODAY IS

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"CONDUCTING AN OVERSEEING

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RESEARCH, LESSONS LEARNED"

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PLEASE JOINED ME IN EXTENDING A

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WARM WELCOME TO TODAY'S GREAT

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SPEAKER/TEACHER, Dr. MICHAEL

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GOTTESMAN.

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>>THANK YOU SO MUCH FOR
THAT

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VERY GENEROUS INTRODUCTION.

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IT'S NOT SURPRISING THAT I'M

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EXHAUSTED.

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 [LAUGHTER] 

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SO, TOM BERKLOW THE DIRECTOR OF

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THIS SERIES ASKED IF I WOULD

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GIVE A LECTURE ABOUT MY

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EXPERIENCE BOTH AS A SCIENTIST

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AT THE NIH AND AS THE

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ADMINISTRATOR WHO IS RESPONSIBLE

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FOR OVERSEEING THE INTRAMURAL

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RESEARCH PROGRAM.

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I THOUGHT QUITE A LOT ABOUT HOW

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TO DO THIS.

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I'VE GIVEN SIMILAR TALKS BEFORE.

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I THOUGHT IT WOULD BE NICE TO

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TELL YOU WHAT I'VE LEARNED

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DURING MY EXPERIENCE HERE,

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ALMOST 50 YEARS AT THE NIH, IN

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TERMS OF THE WAY SCIENCE CAN BE

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CONDUCTED AND THE BEST WAY TO

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OVERSEE SCIENCE AND I DISCOVERED

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SOME COMMONALITIES AND I'D LIKE

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TO FOCUS ON THOSE COMMONALITIES

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AS I TALK TODAY TO YOU.

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I HAVE NO FINANCIAL CONFLICTS OF

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INTEREST TO REPORT AND THERE

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WILL BE NO UNAPPROVED OR

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OFF-LABEL DRUGS IN MY

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PRESENTATION.

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SO, AGAIN, MY OBJECTIVES ARE TO

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SUMMARIZE THE CHALLENGES

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ASSOCIATED WITH PURSUING A MAJOR

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RESEARCH PROGRAM AS WELL AS

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OVERSEEING RESEARCH AT THE NIH.

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HOPEFULLY ACQUAINT YOU WITH BEST

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PRACTICES MOVING FORWARD.

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LET ME START WITH A MAJOR MENTOR

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AND ADD V ADVOCATES, RUTH

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KIRSCHSTTEIN.

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SHE HAS THE NRSA AWARDS ARE

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NAMED AFTER HER IN HER HONOR.

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SHE WAS FOR SEVEN YEARS, WHEN I

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FIRST BEGAN AS DEPUTY DIRECTOR

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FOR INTRAMURAL RESEARCH SHE WAS

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THE PRINCE PAP DEPUTY DIRECTOR

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AND ACTING NIH DIRECTOR AND RUTH

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USED TO SAY AND THE QUOTE IS

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HERE BUT NOT PRECISE, SHE SAID

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IN MY EXPERIENCE, PROBLEMS

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ACCOUNTED IN MANAGING SCIENCE

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MAY BE MORE DIFFICULT THAN THOSE

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ENCOUNTERED IN THE RESEARCH

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LABORATORY AND I THINK I SHARE

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THAT BELIEF THE LAB IS GREAT

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FUND AND A GREAT CHALLENGE BUT

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MANAGING MANY PEOPLE WHO ARE

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DOING SCIENCE CAN BE EVEN MORE

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CHALLENGING AND THERE ARE MANY

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OPPORTUNITIES, BOTH TO DO GOOD

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AND ALSO TO MAKE MISTAKES.

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SO, I'M GOING TO CARRY THROUGH A

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CERTAIN NUMBER OF LESSONS THAT

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I'VE LEARNED AND LESSON NUMBER

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ONE IS YOU HAVE TO FOCUS ON AN

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IMPORTANT PROBLEM AND THAT'S IN

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ADMINISTRATIVE AND SCIENTIFIC

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WORK.

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MY SCIENTIFIC WORK, AS DAN

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MENTIONED, HAS BEEN FOCUSED ON

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WHAT IS THE MOLECULAR BASIS FOR

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MULTI-DRUG RESISTANCE IN CANCER.

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THE PROBLEM OF COURSE IS THAT

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WE'RE VERY SUCCESSFUL IN

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TREATING CANCER THAT IS SPREAD

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WITH CHEMOTHERAPY.

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MANY PATIENTS REALLY HAVE

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PROFOUND LOSS OF SYMPTOMS OF

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CANCER.

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VERY FREQUENTLY AND FOR SOLID

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TUMORS THE CANCER RECURES AND

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THE TUMORS ARE RESISTANT TO

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THERAPY AND THE PATIENTS DIE

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UNFORTUNATELY.

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WE WERE INTERESTED IN FIGURING

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OUT WHAT WE COULD LEARN ABOUT

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MULTI DRUG RESISTANCE THAT WOULD

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IMPROVE THE TREATMENT OF CANCER.

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WITH RESPECT TO THE SCIENCE

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MANAGEMENT ISSUE, WHAT IS THE

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MISSION OF THE INTRAMURAL

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RESEARCH PROGRAM?

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WELL, IT'S RELAT REALLY AN IMPOT

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MISSION FOR HIGH-IMPACT

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LABORATORY CLINICAL AND

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POPULATION-BASED RESEARCH TO

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FACILITATE NEW APPROACHES TO

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IMPROVE HEALTH THROUGH

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PREVENTION, DIAGNOSIS, TREATMENT

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AND RESPOND TO PUBLIC-HEALTH

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EMERGENCIES AND TO TRAIN THE

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NEXT GENERATION OF BIOMEDICAL

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RESEARCHERS.

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CLEARLY ALL IMPORTANT PROBLEMS.

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SO, TO GO BACK TO MY RESEARCH,

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YOU NEED TO SET ACHIEVABLE GOALS

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AND I ACTUALLY RECENTLY CAME

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UPON A STRATEGIC PLAN I WROTE

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WHEN WE FIRST STARTED WORKING ON

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MULTI-DRUG RESISTANCE AND I SHOW

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HERE SOME PICTURES OF THE PEOPLE

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WHO MADE THIS POSSIBLE AND

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ANOTHER THEME THAT'S GOING TO BE

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RECURRENT IS THAT THE PEOPLE YOU

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WORK WITH ARE REALLY CRITICAL IN

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HELPING YOU SOLVE PROBLEMS.

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OUR FIRST GOAL WAS TO SELECT

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CELLS AND WE WANTED HUMAN LINES

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BECAUSE WE WANTED REAGENTS, GENE

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PROBES AND ANTIBODIES AND SO ON,

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THAT COULD BE USED FOR HUMAN

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STUDIES.

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AND SO THAT WORK BEGAN WITH

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SHIN-ICHI AKIYAMA AND WE NEEDED

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TO CLONES THE GENES RESPONSIBLE

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FOR RESISTANCE AND I WAS AT A

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GORDON CONFERENCE PRESENTING OUR

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WORK ON THESE HIGHLY DRUG

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RESISTANT CELL LINES AND I HAD A

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POSTER NEXT TO IGOR ROBINSON A

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POSTDOC TO BAL FELLOW AT MIT AND

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IGOR, A BRILLIANT MOLECULAR

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BIOLOGIST FIGURED OUT HOW TO

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CLONE GENES THAT WERE MANY NOT .

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WE DIDN'T HAVE EASY WAY TO CLONE

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GENES, IT WAS THE 197 '50‘S.

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HE CLONED AMPLIFIED GENES AND WE

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GOT TOGETHER AND WE CLONED THE

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GENES AMPLIFIED IN OUR DRUG

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RESIST APARTMENT CELLS AND IT

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TURNED OUT THAT WHEN OE A DA

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CAME TO A LAB AND THAT WE COULD

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CON FUR A PHENOTYPE OF MULTI

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DRUG RESISTANCE, CROSS

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RESISTANCE TO MULTIPLE DIFFERENT

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DRUGS, JUST BY PUTTING IN ONE

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PARTICULAR GENE.

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AND THAT GENE TURNED OUT TO BE

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GENE THAT VICTOR LING CALLED P

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LACK PROTEIN WE CALLED IT MDR

259
00:10:30,720 --> 00:10:33,640
ONE AND THE OFFICIAL NAME IS

260
00:10:33,640 --> 00:10:35,320
ABCB1 AND IT'S A MEMBER OF A

261
00:10:35,320 --> 00:10:37,400
FAMILY OF ATP DID HE PENDANT

262
00:10:37,400 --> 00:10:39,760
TRANSPORTERS AND I'LL SAY MORE

263
00:10:39,760 --> 00:10:41,200
ABOUT THAT.

264
00:10:41,200 --> 00:10:44,400
SO, AS WE BEGAN TO STUDY DRUG

265
00:10:44,400 --> 00:10:46,120
RESISTANCE, WE REALIZED THAT IT

266
00:10:46,120 --> 00:10:49,280
WAS REALLY A MULTI FACTORIAL

267
00:10:49,280 --> 00:10:49,640
PROCESS.

268
00:10:49,640 --> 00:10:52,680
THERE WERE MANY WAYS, AT LEAST

269
00:10:52,680 --> 00:10:54,360
AT THE CELLULAR LEVELS THAT

270
00:10:54,360 --> 00:10:57,760
CELLS CAN BE RESISTANT AND AT

271
00:10:57,760 --> 00:11:00,080
THE LEVEL THEY'RE EVEN MORE

272
00:11:00,080 --> 00:11:02,080
MECHANISMS AND IN GENERAL,

273
00:11:02,080 --> 00:11:03,400
THEY'RE CHARACTERIZED AS SHOWN

274
00:11:03,400 --> 00:11:05,640
IN THIS SCHEMATIC.

275
00:11:05,640 --> 00:11:08,840
DRUGS CAN FAIL TO BE TAKEN UP.

276
00:11:08,840 --> 00:11:12,400
THERE ARE 386 UPTAKE

277
00:11:12,400 --> 00:11:14,440
TRANSPORTERS IN THE CELLS AND

278
00:11:14,440 --> 00:11:16,600
THOSE CAN BE ALTERED OR MISSING.

279
00:11:16,600 --> 00:11:18,800
AND SO DRUGS THAT REQUIRE UPTAKE

280
00:11:18,800 --> 00:11:19,800
TRANSPORTERS DON'T GET INTO

281
00:11:19,800 --> 00:11:23,880
CELLS WHEN THOSE ARE ALTERED.

282
00:11:23,880 --> 00:11:27,080
THERE ARE ALSO WHAT ARE CALLED

283
00:11:27,080 --> 00:11:28,520
EFFLUX TRANSPORTERS AND WE

284
00:11:28,520 --> 00:11:31,240
DISCOVERED THESE WHEN WE FIRST

285
00:11:31,240 --> 00:11:32,880
BEGAN TO STUDY MULTI DRUG

286
00:11:32,880 --> 00:11:34,880
RESISTANCE IN OUR CULTURE CELLS.

287
00:11:34,880 --> 00:11:37,480
THESE ARE ENERGY DEPENDENT AND

288
00:11:37,480 --> 00:11:38,880
THERE ARE 48 KNOWN SYSTEMS OF

289
00:11:38,880 --> 00:11:40,520
WHICH THREE ARE INVOLVED IN

290
00:11:40,520 --> 00:11:42,040
MULTI-DRUG RESISTANCE AND CANCER

291
00:11:42,040 --> 00:11:45,520
AND I'LL SAY MORE ABOUT THOSE IN

292
00:11:45,520 --> 00:11:46,320
A MOMENT.

293
00:11:46,320 --> 00:11:48,120
OF COURSE NOT ALL CELLS

294
00:11:48,120 --> 00:11:51,800
DEMONSTRATE DECREASED UPTAKE OR

295
00:11:51,800 --> 00:11:54,360
INCREASED EFFLUX BUT THEY CAN BE

296
00:11:54,360 --> 00:11:55,520
RESISTANT IN THE WAY SHOWN IN

297
00:11:55,520 --> 00:11:57,440
THIS SLIDE WITH ALTERATIONS AT

298
00:11:57,440 --> 00:12:00,560
PEE TOE SIS AND CHECKPOINTS AND

299
00:12:00,560 --> 00:12:04,600
GROWTH PATHWAYS AND METABOLISM

300
00:12:04,600 --> 00:12:09,120
AND MANY WAYS THROUGH RESISTANCE

301
00:12:09,120 --> 00:12:10,200
TO OCCUR.

302
00:12:10,200 --> 00:12:13,760
SO TO GET BACK TO THESE' FLUX

303
00:12:13,760 --> 00:12:17,960
PUMPS, THROW CONFIRM MULTI DRUG

304
00:12:17,960 --> 00:12:23,680
RESISTANCE AND WE HAVE

305
00:12:23,680 --> 00:12:25,360
STRUCTURES FOR THESE THREE ABC

306
00:12:25,360 --> 00:12:30,960
DEPEND ANT TRANSPORTERS AND

307
00:12:30,960 --> 00:12:32,600
THEY LOOK THE SAME BUT THEY'RE

308
00:12:32,600 --> 00:12:33,280
DIFFERENT.

309
00:12:33,280 --> 00:12:38,240
IN THE S THE SITE OWE PLAS MICKD

310
00:12:38,240 --> 00:12:40,800
THE TRANS MEMBRANE PARTS THERE

311
00:12:40,800 --> 00:12:42,320
ARE DOMAINS WHICH AS YOU WILL

312
00:12:42,320 --> 00:12:43,920
HEAR, SEEM TO BE THE REGIONS IN

313
00:12:43,920 --> 00:12:54,440
WHICH THE DRUGS ARE TRANSPORTER.

314
00:13:02,000 --> 00:13:04,240
THEY EACH PROGRESS DOZENS OR

315
00:13:04,240 --> 00:13:05,640
HUNDREDS OF DIFFERENT DRUGS.

316
00:13:05,640 --> 00:13:07,320
SOME SUBSTRATES ARE IN COMMON IN

317
00:13:07,320 --> 00:13:09,200
THOSE TEND TO BE THE ONES

318
00:13:09,200 --> 00:13:10,960
INVOLVED IN DRUG RESISTANCE IN

319
00:13:10,960 --> 00:13:12,960
CANCER AND THEY'RE SHOWN HERE

320
00:13:12,960 --> 00:13:14,640
AND OTHERS MAY HAVE MORE

321
00:13:14,640 --> 00:13:17,600
SPECIFIC METABOLICS FUNCTIONS IN

322
00:13:17,600 --> 00:13:17,800
CELLS.

323
00:13:17,800 --> 00:13:20,000
IT'S IMPORTANT TO REALIZE IF YOU

324
00:13:20,000 --> 00:13:21,320
STUDY ANY PARTICULAR CANCER,

325
00:13:21,320 --> 00:13:22,840
THAT THE EXPRESSION OF ONE OR

326
00:13:22,840 --> 00:13:25,000
MORE OF THESE TRANSPORTERS CAN

327
00:13:25,000 --> 00:13:27,920
CONTRIBUTE TO DRUG RESISTANCE.

328
00:13:27,920 --> 00:13:32,760
THEY PLAY IMPORTANT ROLES,

329
00:13:32,760 --> 00:13:35,520
PHYSIOLOGICAL ROLES IN THE HUMAN

330
00:13:35,520 --> 00:13:38,640
BODY AND IN ALL ORGANISMS

331
00:13:38,640 --> 00:13:40,280
BASICALLY AND MY VERSION OF THE

332
00:13:40,280 --> 00:13:42,280
HUMAN BODY SHOWN ON THE LEFT AND

333
00:13:42,280 --> 00:13:44,680
IT'S TOTALLY ROUND WHICH IS

334
00:13:44,680 --> 00:13:46,280
PROBABLY A SIGN OF THE WAY

335
00:13:46,280 --> 00:13:50,560
EVOLUTION IS GOING AND THESE

336
00:13:50,560 --> 00:13:53,440
TRANSPORTERS, PARTICULARLY PLA

337
00:13:53,440 --> 00:13:56,160
PROTEIN OR MDR1 ARE AT BARRIER

338
00:13:56,160 --> 00:13:59,200
SITES IN THE BODY AND THEY'RE AT

339
00:13:59,200 --> 00:14:04,160
BLOOD PLACENTAL BARRIER AND THE

340
00:14:04,160 --> 00:14:05,560
BRAIN BLOOD BARRIER AND THEY

341
00:14:05,560 --> 00:14:07,600
HAVE FUNCTION IN THE KIDNEY,

342
00:14:07,600 --> 00:14:09,000
LUNG, LIVER AND INTESTINE.

343
00:14:09,000 --> 00:14:12,440
AND SO, THE PHARMA CO DYNAMICS

344
00:14:12,440 --> 00:14:14,440
OF MANY, MANY DRUGS ARE AFFECTED

345
00:14:14,440 --> 00:14:16,360
NORMALLY BY EXPRESSION OF THESE

346
00:14:16,360 --> 00:14:17,680
TRANSPORTERS AND SOME OF THOSE

347
00:14:17,680 --> 00:14:18,840
DRUGS ARE SHOWN TO THE RIGHT.

348
00:14:18,840 --> 00:14:22,360
EACH ONE OF THEM IS KIND OF AN

349
00:14:22,360 --> 00:14:23,280
INTERESTING STORY.

350
00:14:23,280 --> 00:14:33,960
SINCE YOU'VE HEARD ABO IVORMECT,

351
00:14:35,320 --> 00:14:37,960
IT IS NOT TOXIC TO HUMANS TO THE

352
00:14:37,960 --> 00:14:39,800
CENTRAL NERVOUS SYSTEM AND IT

353
00:14:39,800 --> 00:14:41,280
CAN'T GET INTO THE BRAIN IT'S A

354
00:14:41,280 --> 00:14:45,240
SUBSTRATE FOR THIS TRANSPORT

355
00:14:45,240 --> 00:14:48,040
SYSTEM.

356
00:14:48,040 --> 00:14:50,640
VETERINARIAN KNOW WHEN THEY

357
00:14:50,640 --> 00:14:58,320
DEWORM ANIMALS, THEY CAN'T GIVE

358
00:14:58,320 --> 00:14:59,920
IVORMECTINS BECAUSE COLLIES DO

359
00:14:59,920 --> 00:15:03,720
NOT HAVE AN ACTIVE PROTEIN AT

360
00:15:03,720 --> 00:15:05,120
THEIR DRUG BRAIN BARRIER AND THE

361
00:15:05,120 --> 00:15:07,360
DRUG GETS IN AND THEY DEVELOP

362
00:15:07,360 --> 00:15:10,280
NEUROLOGICAL SYMPTOMS AND THEY

363
00:15:10,280 --> 00:15:10,800
DIE.

364
00:15:10,800 --> 00:15:13,240
A ARTICLE ABOUT A FRENCH PATIENT

365
00:15:13,240 --> 00:15:17,240
WHO WAS GIVEN IT TO TREAT

366
00:15:17,240 --> 00:15:18,440
SCABIES INDICATED THE PATIENT

367
00:15:18,440 --> 00:15:20,640
DEVELOPED SEIZURES AND THE DRUG

368
00:15:20,640 --> 00:15:22,240
WAS STOPPED, THE PATIENT

369
00:15:22,240 --> 00:15:24,680
SURVIVED AND THEY THOUGHT TO

370
00:15:24,680 --> 00:15:26,320
SEQUENCE PROTEIN IN THIS PATIENT

371
00:15:26,320 --> 00:15:32,640
AND THE PATIENT WAS A COMPOUND

372
00:15:32,640 --> 00:15:34,280
HETERO SYGAT AND THEY WERE

373
00:15:34,280 --> 00:15:42,280
EFFETIVE.THERE'S NOT A LOT OF HN

374
00:15:42,280 --> 00:15:45,200
BEINGS WALKING AROUND WITH A LOT

375
00:15:45,200 --> 00:15:48,160
OF P OF PROTEIN AND THERE'S

376
00:15:48,160 --> 00:15:49,080
TREATING RIVER BLINDNESS IN

377
00:15:49,080 --> 00:15:52,200
AFRICA DONE WITH IVERMECTIN BUT

378
00:15:52,200 --> 00:15:53,680
NO ONE HAS PERSUADE THAT.

379
00:15:53,680 --> 00:15:57,480
I WOULD EXPECT WITH THE CURRENT

380
00:15:57,480 --> 00:15:58,920
INTEREST IN THE DRUG AS A

381
00:15:58,920 --> 00:16:00,080
TREATMENT POTENTIAL TREATMENT

382
00:16:00,080 --> 00:16:05,360
FOR COVID-19, AND A LOT OF

383
00:16:05,360 --> 00:16:08,720
PEOPLE TAKING IT WITHOUT ANY

384
00:16:08,720 --> 00:16:12,760
GOOD INDICATION, BUT WE'RE

385
00:16:12,760 --> 00:16:15,320
TALKING ABOUT FEWER THAN

386
00:16:15,320 --> 00:16:16,360
1/100,000 PEOPLE WOULD BE SO

387
00:16:16,360 --> 00:16:18,480
EFFECTIVE AND THERE ARE OTHER

388
00:16:18,480 --> 00:16:24,320
STORIES AMONGST THIS LIST.

389
00:16:24,320 --> 00:16:29,280
ANTIHISTAMINES AND DRUGS SUCH AS

390
00:16:29,280 --> 00:16:31,760
LOPERMIDE, USED TO TREAT

391
00:16:31,760 --> 00:16:34,240
DIARREAH, ARE POTENT BUT THEY'RE

392
00:16:34,240 --> 00:16:35,400
NOT INTOXICATING BECAUSE THEY

393
00:16:35,400 --> 00:16:36,920
CAN'T CROSS THE DRUG-BRAIN

394
00:16:36,920 --> 00:16:37,360
BARRIER.

395
00:16:37,360 --> 00:16:38,320
AND ON AND ON AND ON.

396
00:16:38,320 --> 00:16:40,520
A LOT OF WAYS THE FUNCTION OF

397
00:16:40,520 --> 00:16:42,640
PGP AFFECTED IMPORTANT

398
00:16:42,640 --> 00:16:45,360
PHARMACOLOGICAL RESPONSES.

399
00:16:45,360 --> 00:16:47,560
NOW, FOR THE INTRAMURAL RESEARCH

400
00:16:47,560 --> 00:16:49,960
PROGRAM, ACHIEVABLE GOALS ARE

401
00:16:49,960 --> 00:16:52,680
EVEN HARDER TO ACHIEVE.

402
00:16:52,680 --> 00:16:55,400
AND THE WAY THAT WE GO ABOUT

403
00:16:55,400 --> 00:16:56,520
MAKING SIGNIFICANT CHANGE, AND

404
00:16:56,520 --> 00:16:57,320
YOU HEARD ABOUT A LOT OF

405
00:16:57,320 --> 00:16:58,400
DIFFERENT THINGS THAT HAPPENED

406
00:16:58,400 --> 00:17:02,120
DURING MY TIME AS DDIR, IS WE

407
00:17:02,120 --> 00:17:04,120
TEND TO USE OUTSIDE EXTERNAL

408
00:17:04,120 --> 00:17:05,800
REVIEW AND WE ASK EXPERTS TO

409
00:17:05,800 --> 00:17:07,840
COME IN AND WE DO THIS TO REVIEW

410
00:17:07,840 --> 00:17:09,600
OUR SCIENCE BUT WE DO IT ALSO TO

411
00:17:09,600 --> 00:17:13,320
REVIEW OUR INTRAMURAL RESEARCH

412
00:17:13,320 --> 00:17:14,520
PROGRAMS IN GENERAL.

413
00:17:14,520 --> 00:17:16,640
AND THOSE REVIEWS ARE SHOWN HERE

414
00:17:16,640 --> 00:17:20,000
SOME OF THOSE REVIEWS AND THEY

415
00:17:20,000 --> 00:17:22,640
AVERAGE ABOUT ONE EVERY 10

416
00:17:22,640 --> 00:17:22,840
YEARS.

417
00:17:22,840 --> 00:17:24,200
THEY'RE MAJOR ACTIVITIES, HALF

418
00:17:24,200 --> 00:17:26,960
OF THE NIH BY OUTSIDE VERY

419
00:17:26,960 --> 00:17:28,880
SENIOR ADVISERS.

420
00:17:28,880 --> 00:17:30,240
AND EACH ONE OF THEM HAVE LED TO

421
00:17:30,240 --> 00:17:32,640
SOME OF THESE CHANGES THAT

422
00:17:32,640 --> 00:17:33,440
YOU'VE HEARD ABOUT.

423
00:17:33,440 --> 00:17:36,680
FOR EXAMPLE, THE IOM REPORT IN

424
00:17:36,680 --> 00:17:37,720
1988 RECOMMENDED THAT WE HAVE A

425
00:17:37,720 --> 00:17:40,240
FOUNDATION FOR THE NIH, WHICH

426
00:17:40,240 --> 00:17:40,680
OCCURRED.

427
00:17:40,680 --> 00:17:41,680
RECOMMENDED THAT THE DIRECTOR

428
00:17:41,680 --> 00:17:44,320
HAVE A DISCRETIONARY FUND, WHICH

429
00:17:44,320 --> 00:17:45,440
OCCURRED AND RECOMMENDED THAT WE

430
00:17:45,440 --> 00:17:47,840
DEVELOP A TENURE PROGRAM AT THE

431
00:17:47,840 --> 00:17:49,560
NIH, WHICH OCCURRED.

432
00:17:49,560 --> 00:17:52,200
AND THE MAJOR REVIEW THAT HAS

433
00:17:52,200 --> 00:17:55,240
AFFECTED MY ACTIVITIES AS DDIR,

434
00:17:55,240 --> 00:17:58,200
WAS THE SO-CALLED MARKS CASTLE

435
00:17:58,200 --> 00:18:00,520
REVIEW IN 1994 WHICH WAS

436
00:18:00,520 --> 00:18:01,680
CONGRESSIONAL LEHMAN DATED TO

437
00:18:01,680 --> 00:18:03,240
LOOK AT THE INTRAMURAL PROGRAM

438
00:18:03,240 --> 00:18:05,480
AND LED TO WHAT WE CONSIDER A

439
00:18:05,480 --> 00:18:07,640
RIGOROUS PROCESS OF A REVIEWS

440
00:18:07,640 --> 00:18:18,160
AND CENTRAL TENURE COMMITTEE AND

441
00:18:23,520 --> 00:18:25,480
AND THIS IS BEEN A BLUE PRINT TO

442
00:18:25,480 --> 00:18:27,480
ENABLE US TO MAKE IMPORTANT

443
00:18:27,480 --> 00:18:29,760
CHANGES IN THE INTRAMURAL

444
00:18:29,760 --> 00:18:30,000
PROGRAM.

445
00:18:30,000 --> 00:18:32,600
THERE WAS ANOTHER REPORT IN

446
00:18:32,600 --> 00:18:32,920
2003.

447
00:18:32,920 --> 00:18:34,720
AND THEN THERE WAS A BLUE RIBBON

448
00:18:34,720 --> 00:18:39,080
REPORT ON CLINICAL RESEARCH IN

449
00:18:39,080 --> 00:18:40,720
2004 WHICH CREATED WHAT WAS THEN

450
00:18:40,720 --> 00:18:46,240
THE AD ADVISORY BOARD ON CLINICL

451
00:18:46,240 --> 00:18:48,360
RESEARCH AND CLINICALLY ORIENTED

452
00:18:48,360 --> 00:18:49,720
ENHANCEMENT THIS IS OUR PROGRAM.

453
00:18:49,720 --> 00:18:52,880
THE ASSISTANT CLINICAL

454
00:18:52,880 --> 00:18:54,320
INVESTIGATORS, THE CLINICAL

455
00:18:54,320 --> 00:18:55,560
SCHOLARS PROGRAM AND THE MOST

456
00:18:55,560 --> 00:18:58,800
RECENT REVIEW WAS IN 2014 AND

457
00:18:58,800 --> 00:19:00,120
MADE SOME IMPORTANT

458
00:19:00,120 --> 00:19:01,160
RECOMMENDATIONS TO IMPROVE

459
00:19:01,160 --> 00:19:04,560
DIVERSITY AT THE NIH INCLUDING

460
00:19:04,560 --> 00:19:05,880
THE DISTINGUISH SCHOLARS

461
00:19:05,880 --> 00:19:08,560
PROGRAMS AND THE RESEARCH

462
00:19:08,560 --> 00:19:10,080
SCHOLARS PROGRAM AND GENERAL

463
00:19:10,080 --> 00:19:12,360
IMPROVED REVIEW OF OUR CLINICAL

464
00:19:12,360 --> 00:19:13,440
RESEARCH THROUGH THE DEVELOPMENT

465
00:19:13,440 --> 00:19:15,920
OF A CENTRALIZED IRB SO, THESE

466
00:19:15,920 --> 00:19:18,680
GIVE YOU SOME EXAMPLES AND THE

467
00:19:18,680 --> 00:19:19,720
CHANGES THAT YOU ARE HAVE TO

468
00:19:19,720 --> 00:19:21,400
DEAL WITH ON A REGULAR BASIS

469
00:19:21,400 --> 00:19:24,360
DON'T COME OUT OF THE BLUE.

470
00:19:24,360 --> 00:19:26,000
THEY USUALLY ARE HIGHLY

471
00:19:26,000 --> 00:19:28,360
CONSIDERED AND RECOMMENDED BY

472
00:19:28,360 --> 00:19:29,880
OUTSIDE EXPERTS.

473
00:19:29,880 --> 00:19:30,960
SO, THE THIRD THING AND I

474
00:19:30,960 --> 00:19:32,960
REFERRED TO THIS AS THE

475
00:19:32,960 --> 00:19:34,120
IMPORTANCE OF BUILDING DIVERSE

476
00:19:34,120 --> 00:19:35,280
TEAMS TO ACCOMPLISH THESE GOALS

477
00:19:35,280 --> 00:19:38,000
AND THIS IS MY LAB AT NIH.

478
00:19:38,000 --> 00:19:40,240
PICTURE TAKEN, NO MASKS, SO

479
00:19:40,240 --> 00:19:42,800
TAKEN RIGHT BEFORE THE PANDEMIC.

480
00:19:42,800 --> 00:19:44,200
AND WE'VE REALLY MADE AN EFFORT

481
00:19:44,200 --> 00:19:45,960
TO BRING IN PEOPLE WITH MANY

482
00:19:45,960 --> 00:19:49,280
TALENTS, MANY SKILLS, MANY

483
00:19:49,280 --> 00:19:50,480
DIFFERENT BECOME GROUNDS TO MAKE

484
00:19:50,480 --> 00:19:52,320
SURE THAT WE GET THE BEST

485
00:19:52,320 --> 00:19:53,880
POSSIBLE SCIENTISTS TO WORK ON

486
00:19:53,880 --> 00:19:56,000
OUR PROJECTS.

487
00:19:56,000 --> 00:19:57,680
AND IN MY OFFICE OF ININTEREST

488
00:19:57,680 --> 00:20:00,600
MURAL RESEARCH, I HAVE EIGHT

489
00:20:00,600 --> 00:20:01,840
SORT OF PERMANENT MEMBERS OF THE

490
00:20:01,840 --> 00:20:04,520
OFFICE WHO ARE ON THE PAYROLL

491
00:20:04,520 --> 00:20:07,560
AND THEY'RE SHOWN HERE AS WELL

492
00:20:07,560 --> 00:20:09,960
AS SEVEN OR EIGHT VOLUNTEERS WHO

493
00:20:09,960 --> 00:20:12,400
COME AND MEET WITH US RUGLY WHO

494
00:20:12,400 --> 00:20:13,400
BRINGER PECK TEASE FROM THE

495
00:20:13,400 --> 00:20:17,720
INSTITUTES AND GIVES US A GOOD

496
00:20:17,720 --> 00:20:26,720
FEEDBACK AND OFFERS HELP FREE OF

497
00:20:26,720 --> 00:20:28,080
CHARGE TO THE ACTIVITIES YOU

498
00:20:28,080 --> 00:20:29,920
GROW TO KNOW AND LOVE THAT WE

499
00:20:29,920 --> 00:20:33,480
TAKE CARE OF.

500
00:20:33,480 --> 00:20:37,200
NOW THE LESSON FLOOR HAS TO DO

501
00:20:37,200 --> 00:20:38,600
WITH COLLABORATION AND I WANT TO

502
00:20:38,600 --> 00:20:41,000
SAY SOMETHING HERE ABOUT AND IRA

503
00:20:41,000 --> 00:20:42,760
WHO I HAVE COLLABORATED FOR

504
00:20:42,760 --> 00:20:47,120
MANY, MANY YEARS AND IRA HAS

505
00:20:47,120 --> 00:20:50,520
MADE CONTRIBUTIONS IN MANY

506
00:20:50,520 --> 00:20:51,560
DIFFERENT FIELDS AND HE

507
00:20:51,560 --> 00:20:54,360
RECRUITED ME AND MY WIFE, ZOOS

508
00:20:54,360 --> 00:21:01,280
ARRSUSAN,IN 1985 TO COME BACK AE

509
00:21:01,280 --> 00:21:01,520
POSITIONS.

510
00:21:01,520 --> 00:21:03,040
WE HAD DISCUSSIONS ABOUT

511
00:21:03,040 --> 00:21:04,920
IMPORTANT PROJECTS THE LAB AS A

512
00:21:04,920 --> 00:21:05,520
WHOLE COULD UNDER TAKE.

513
00:21:05,520 --> 00:21:07,640
AND WE DECIDED TO GO AHEAD WITH

514
00:21:07,640 --> 00:21:09,320
THIS PROJECT TO UNDERSTAND THE

515
00:21:09,320 --> 00:21:13,480
BASIS OF MULTI-DRUG RESISTANCE

516
00:21:13,480 --> 00:21:15,960
AND IT'S REALLY BEEN A WONDERFUL

517
00:21:15,960 --> 00:21:17,320
EXPERIENCE AND IT'S BEEN MANY

518
00:21:17,320 --> 00:21:18,840
YEARS SINCE WE COLLABORATED

519
00:21:18,840 --> 00:21:19,920
DIRECTLY BUT WE STILL ARE IN

520
00:21:19,920 --> 00:21:21,320
CONTACT WITH EACH OTHER AND

521
00:21:21,320 --> 00:21:25,280
STILL SHARE IDEAS ABOUT

522
00:21:25,280 --> 00:21:25,840
EXPERIMENTS.

523
00:21:25,840 --> 00:21:27,040
I MENTIONED ALREADY THAT WE

524
00:21:27,040 --> 00:21:29,520
WOULD NOT HAVE BEEN ABLE TO

525
00:21:29,520 --> 00:21:30,760
CLONE THIS PROTEIN GONE THE

526
00:21:30,760 --> 00:21:33,480
FIRST MEMBER OF THE ABC FAMILY

527
00:21:33,480 --> 00:21:34,440
OF TRANSPORTERS WITHOUT THE HELP

528
00:21:34,440 --> 00:21:40,520
OF EGGIGOR ROBINSON.

529
00:21:40,520 --> 00:21:43,040
THIS IS ONE REASON WHY IT'S

530
00:21:43,040 --> 00:21:44,520
IMPORTANT TO GET BACK TO

531
00:21:44,520 --> 00:21:45,280
IN-PERSON MEETINGS.

532
00:21:45,280 --> 00:21:50,920
THESE CONVERSATIONS ARE HARD TO

533
00:21:50,920 --> 00:21:56,240
HAVE OVER REMOTE MECHANISMS.

534
00:21:56,240 --> 00:21:57,120
WE'VE WORKED PEOPLE TO

535
00:21:57,120 --> 00:22:02,120
UNDERSTAND THE BIOLOGY,

536
00:22:02,120 --> 00:22:04,040
BIOCHEMISTRY OF PLAC PROTEIN AND

537
00:22:04,040 --> 00:22:06,680
HOW IT WORKS AND I WANT TO SAY

538
00:22:06,680 --> 00:22:08,360
MORE ABOUT MECHANISM OF ACTION.

539
00:22:08,360 --> 00:22:10,160
ONE IDEA THAT CAME OUT OF A

540
00:22:10,160 --> 00:22:15,520
COLLABORATION WITH BOB

541
00:22:15,520 --> 00:22:16,440
BLOOMENTHAL WHO WAS INTERESTED

542
00:22:16,440 --> 00:22:18,120
IN FLIP AND FLOP ACES AND

543
00:22:18,120 --> 00:22:19,920
MEMBRANE PRE TEENS AND HOW TO

544
00:22:19,920 --> 00:22:22,160
MEASURE THE EXISTENCE AND THE

545
00:22:22,160 --> 00:22:24,120
ACTIVITIES OF MEMBRANE PROTEINS,

546
00:22:24,120 --> 00:22:26,400
HE HAD A PROBE WHICH WAS VERY

547
00:22:26,400 --> 00:22:29,680
HYDRO PHOBIC, ONLY EXISTED IN

548
00:22:29,680 --> 00:22:32,720
MEMBRANES AND WE SHOWED THAT YOU

549
00:22:32,720 --> 00:22:40,280
COULD TRANSFER ENERGY AND IODINE

550
00:22:40,280 --> 00:22:45,520
TO DOXORUBICIN TO THIS P-GP IN

551
00:22:45,520 --> 00:22:47,200
THE MEMBRANES AND THE

552
00:22:47,200 --> 00:22:48,760
TRANSPORTERS WAS RECOGNIZING

553
00:22:48,760 --> 00:22:50,160
THESE CANCER DRUGS WITHIN THE

554
00:22:50,160 --> 00:22:51,120
BUY LAYER.

555
00:22:51,120 --> 00:22:52,800
AND WE CAME UP WITH THIS IDEA

556
00:22:52,800 --> 00:22:56,800
THAT WAS THE PUMP WAS A HIGHDRO

557
00:22:56,800 --> 00:22:58,480
PHOBIC VACUUM CLEANER SHOWN ON

558
00:22:58,480 --> 00:22:59,200
THE LEFT.

559
00:22:59,200 --> 00:23:01,960
DRUGS ENTERED THE CELL, THEY GET

560
00:23:01,960 --> 00:23:05,600
TRAPPED IN THE INTER MEMBRANE.

561
00:23:05,600 --> 00:23:06,240
THEY'RE RECOGNIZED BY A DOMAIN

562
00:23:06,240 --> 00:23:07,760
IN THE TRANCE MEMBRANE REGION OF

563
00:23:07,760 --> 00:23:09,880
THE TRANSPORTER AND UNDER THE

564
00:23:09,880 --> 00:23:12,320
INFLUENCE OF ATP, WHICH IS HYDRO

565
00:23:12,320 --> 00:23:12,680
LIESED.

566
00:23:12,680 --> 00:23:14,880
THEY'RE EXCLUDED FROM THE CELL.

567
00:23:14,880 --> 00:23:16,960
ON THE RIGHT IS AN ALTERNATIVE

568
00:23:16,960 --> 00:23:17,520
MODEL.

569
00:23:17,520 --> 00:23:22,200
WHICH IS THAT PGP IS LIKE A

570
00:23:22,200 --> 00:23:24,320
LIPID FLIPASE AND THEY'RE

571
00:23:24,320 --> 00:23:26,720
FLIPPED WHERE THEY CAN

572
00:23:26,720 --> 00:23:30,760
DIFFUSE OUT OF THE CELL AND

573
00:23:30,760 --> 00:23:33,120
BOUND TO PROTEIN AND THERE'S END

574
00:23:33,120 --> 00:23:35,840
IT'S AN IMPORTANT PART OF THE

575
00:23:35,840 --> 00:23:38,640
TRANSPORT PROCESS OUT OF CELLS.

576
00:23:38,640 --> 00:23:41,560
THIS MODEL, WHICH WE REALLY, I

577
00:23:41,560 --> 00:23:45,080
THINK, CAME UP WITH 25 YEARS

578
00:23:45,080 --> 00:23:46,720
AGO, IS ACTUALLY WITHSTOOD THE

579
00:23:46,720 --> 00:23:48,600
TEST OF TIME AND A GOING MODEL

580
00:23:48,600 --> 00:23:51,120
FOR HOW THESE MULTI-DRUG

581
00:23:51,120 --> 00:23:52,160
TRANSPORTERS CAN RECOGNIZE SO

582
00:23:52,160 --> 00:23:52,480
MANY DRUGS.

583
00:23:52,480 --> 00:23:54,680
THESE ARE HYDRO PHOBIC

584
00:23:54,680 --> 00:23:57,320
INTERACTIONS MOSTLY AND THEIR

585
00:23:57,320 --> 00:24:02,680
RULES ARE DIFFERENT FROM NORMAL

586
00:24:02,680 --> 00:24:04,040
SUBSTRATES SPECIFICITY.

587
00:24:04,040 --> 00:24:05,480
HOW DOES THIS WORK?

588
00:24:05,480 --> 00:24:08,800
AND AGAIN, WE HAVE PRETTY HIGH

589
00:24:08,800 --> 00:24:10,240
RESOLUTION CRYSTAL GRAPHIC

590
00:24:10,240 --> 00:24:12,960
STUDIES FROM DEE SHAW A MEMBER

591
00:24:12,960 --> 00:24:16,400
OF MY LABORATORY OF CELL BIOLOGY

592
00:24:16,400 --> 00:24:18,480
SHOWING THAT THE CRYSTAL GRAPHIC

593
00:24:18,480 --> 00:24:22,160
FORM MOST COMMON FORM OF P-GP IS

594
00:24:22,160 --> 00:24:24,640
SHOWN ON THE LEFT IN WHAT IS

595
00:24:24,640 --> 00:24:25,520
CALLED INWARD OPEN CONFIRMATION

596
00:24:25,520 --> 00:24:30,000
AND THE ATP SITES ARE FAR APART.

597
00:24:30,000 --> 00:24:35,040
IT BRINGS THE TWO SITES TOGETHER

598
00:24:35,040 --> 00:24:38,200
WHEN IT BOUNDS AND JU CHEN AT

599
00:24:38,200 --> 00:24:39,600
ROCKEFELLER HAS BEAUTIFUL CRYO

600
00:24:39,600 --> 00:24:41,280
EM AND HE GAVE A WALLS TALK LAST

601
00:24:41,280 --> 00:24:42,560
YEAR ABOUT THIS.

602
00:24:42,560 --> 00:24:44,240
SHE HAS BEAUTIFUL CRYO EM

603
00:24:44,240 --> 00:24:45,160
STUDIES SHOWING THE STRUCTURES

604
00:24:45,160 --> 00:24:50,760
THAT ARE SHOWN ON THE RIGHT.

605
00:24:50,760 --> 00:24:54,600
WHEN THE TWO SITES COME TOGETHER

606
00:24:54,600 --> 00:24:55,440
THEY CHANGE THEIR AFFINITY AND

607
00:24:55,440 --> 00:24:57,440
THE DRUGS CAN BE EXCRETED.

608
00:24:57,440 --> 00:24:59,040
THIS IS THE OVER ALL MECHANISM.

609
00:24:59,040 --> 00:25:00,200
BECAUSE THE STRUCTURES ARE

610
00:25:00,200 --> 00:25:01,280
SOMEWHAT DIFFERENT, THE

611
00:25:01,280 --> 00:25:02,560
MECHANISMS MAY BE SOMEWHAT

612
00:25:02,560 --> 00:25:05,080
DIFFERENT FROM ABC TRANSPORTER

613
00:25:05,080 --> 00:25:07,400
TO ABC TRANSPORTERS.

614
00:25:07,400 --> 00:25:08,360
AND ANOTHER THING WE'VE BEEN

615
00:25:08,360 --> 00:25:12,400
INTERESTED IN IS HOW ARE THE

616
00:25:12,400 --> 00:25:12,960
VARIOUS SUBSTRATES BOUND AND

617
00:25:12,960 --> 00:25:14,600
OTHER SENIOR MEMBER OF MY LAB

618
00:25:14,600 --> 00:25:16,760
HAS BEEN STUDYING THIS FOR MANY

619
00:25:16,760 --> 00:25:17,000
YEARS.

620
00:25:17,000 --> 00:25:18,320
AMONG OTHER THINGS, HE HAS MADE

621
00:25:18,320 --> 00:25:20,120
A MUTATIONS IN THE SITES THAT

622
00:25:20,120 --> 00:25:21,560
APPEAR TO BE THE SUBSTRATE

623
00:25:21,560 --> 00:25:22,120
BINDING SITES.

624
00:25:22,120 --> 00:25:25,000
AND THE STRIKING FINDING IS YOU

625
00:25:25,000 --> 00:25:32,440
CAN CHANGE 13 OR 14 OF OF WHAT

626
00:25:32,440 --> 00:25:35,400
APPEAR.

627
00:25:35,400 --> 00:25:37,080
IF YOU CHANGE ENOUGH OF THESE,

628
00:25:37,080 --> 00:25:40,280
THE TRANSPORTER, WHICH NORMALLY

629
00:25:40,280 --> 00:25:41,800
WOULD EXCRETE DRUGS FROM THE

630
00:25:41,800 --> 00:25:43,360
CELL PUMPS DRUGS INTO THE CELL.

631
00:25:43,360 --> 00:25:49,120
SO THE MISSION TER MYSTERY LIESE

632
00:25:49,120 --> 00:25:52,040
AFFINITY OF THE DRUGS FOR THE

633
00:25:52,040 --> 00:25:53,840
TRANCE MEMBRANE REGIONS AND MORE

634
00:25:53,840 --> 00:25:54,680
STRUCTURE AND MORE WORK NEEDS TO

635
00:25:54,680 --> 00:25:57,720
BE DONE TO SUPPORT AND EXPAND

636
00:25:57,720 --> 00:26:01,400
THIS HIGH POTH SIS.

637
00:26:01,400 --> 00:26:03,800
AND FINALLY, THIS IS ANOTHER

638
00:26:03,800 --> 00:26:09,400
OBSERVATION MADE SEVERAL YEARS

639
00:26:09,400 --> 00:26:09,600
AGO.

640
00:26:09,600 --> 00:26:12,480
BY A SENIOR SCIENTIST AT THE

641
00:26:12,480 --> 00:26:13,000
FDA.

642
00:26:13,000 --> 00:26:16,600
SO, WE HAD NOTICED THAT THE

643
00:26:16,600 --> 00:26:19,000
TRANSPORTER WE HAD WHICH WAS

644
00:26:19,000 --> 00:26:20,840
ORIGINALLY CLONED FROM HEILO

645
00:26:20,840 --> 00:26:25,560
CELLS FROM HENRIETTA LAX, AN

646
00:26:25,560 --> 00:26:26,640
AFRICAN AMERICAN INDIVIDUAL, HAD

647
00:26:26,640 --> 00:26:28,160
A CERTAIN SEQUENCE BUT THAT

648
00:26:28,160 --> 00:26:29,960
OTHER SEQUENCES OBTAINED FROM

649
00:26:29,960 --> 00:26:32,800
NORTHERN EUROPEANS AND ASIAN

650
00:26:32,800 --> 00:26:35,880
POPULATIONS HAD DIFFERENT POLY

651
00:26:35,880 --> 00:26:39,040
MORPHIC FORMS OF P-GP AND THEY

652
00:26:39,040 --> 00:26:40,280
WERE SUBTLE BUT REAL DIFFERENCES

653
00:26:40,280 --> 00:26:43,400
THAT APPEARED TO BE DOING THESE

654
00:26:43,400 --> 00:26:49,760
POLY MORPHISMS AND THE C3435T

655
00:26:49,760 --> 00:26:53,400
WAS SILENT AND IT DID NOT ENCODE

656
00:26:53,400 --> 00:26:55,320
A CHANGE IN AMINO ACIDS SO WE

657
00:26:55,320 --> 00:26:56,840
GOT VERY INTERESTING IN THIS

658
00:26:56,840 --> 00:26:57,240
OBVIOUSLY.

659
00:26:57,240 --> 00:27:00,440
HOW DOES A SILENT POLY MORPHISM

660
00:27:00,440 --> 00:27:01,840
CHANGE SUBSTRATE SPECIFICITY AND

661
00:27:01,840 --> 00:27:03,480
ONE OF THE THINGS WE DISCOVERED

662
00:27:03,480 --> 00:27:09,240
USIRNA FOOTPRINTING THERE WAS A

663
00:27:09,240 --> 00:27:10,280
DELAY CAUSED BY A CHANGE IN THE

664
00:27:10,280 --> 00:27:12,440
STRUCTURE OF THE RNA AND THAT IS

665
00:27:12,440 --> 00:27:15,040
SHOWN IN THE SLIDE HERE AS A

666
00:27:15,040 --> 00:27:17,480
PAUSE SIGNAL SO THE PROTEIN

667
00:27:17,480 --> 00:27:18,920
WOULD BEGIN TO BE TRANSLATED AND

668
00:27:18,920 --> 00:27:21,280
THEN IT WOULD STOP AND THEN

669
00:27:21,280 --> 00:27:22,840
AFTER A LONG PAUSE, IT WOULD

670
00:27:22,840 --> 00:27:24,600
START AGAIN AND THE STOP WAS DUE

671
00:27:24,600 --> 00:27:27,320
TO THIS CHANGE AND MRNA

672
00:27:27,320 --> 00:27:32,280
STRUCTURE AND THAT APPARENTLY

673
00:27:32,280 --> 00:27:33,960
CHANGED RATHER SUBJECTLY THE

674
00:27:33,960 --> 00:27:35,280
SUBSTRATE BINDING SITE AND

675
00:27:35,280 --> 00:27:38,360
ENOUGH SO THAT SOME SUBSTRATES

676
00:27:38,360 --> 00:27:39,680
WOULD BIND MORE READILY THAN

677
00:27:39,680 --> 00:27:41,240
OTHER SUBSTRATES AND WOULD BE

678
00:27:41,240 --> 00:27:41,680
TRANSPORTED.

679
00:27:41,680 --> 00:27:44,320
SO THIS WAS ONE OF THE FIRST

680
00:27:44,320 --> 00:27:48,520
EXAMPLES OF SILENT POLY

681
00:27:48,520 --> 00:27:49,320
MORPHISMS SINCE THEN THERE ARE

682
00:27:49,320 --> 00:27:51,280
MANY MORE AND IT'S PRETTY MUCH

683
00:27:51,280 --> 00:27:52,800
UNDERSTOOD THAT MANY PROTEINS

684
00:27:52,800 --> 00:27:55,200
HAVE MULTIPLEEL FOLDS AND THEY

685
00:27:55,200 --> 00:27:58,800
CAN EXIST IN FOLD A OR FOLD B

686
00:27:58,800 --> 00:28:03,480
DEPENDING ON SHAPER OWNS SO IT'S

687
00:28:03,480 --> 00:28:10,680
A REDUNDANCY WHICH HAS HAD ADAPO

688
00:28:10,680 --> 00:28:12,560
MANY DIFFERENT PROTEINS.

689
00:28:12,560 --> 00:28:13,640
I THINK THIS ILLUSTRATES THE

690
00:28:13,640 --> 00:28:15,600
POINT IF YOU STUDY ANYTHING IN

691
00:28:15,600 --> 00:28:16,760
GREAT ENOUGH DETAIL YOU LEARN

692
00:28:16,760 --> 00:28:18,120
SOMETHING EVEN THOUGH YOU ARE

693
00:28:18,120 --> 00:28:21,000
STUDYING SOMETHING SPECIFIC, YOU

694
00:28:21,000 --> 00:28:26,320
LEARN AGAKNOWLEDGE.

695
00:28:26,320 --> 00:28:29,440
THE INTERACTIONS WITH MY

696
00:28:29,440 --> 00:28:31,120
ADMINISTRATIVE JOB ARE EVEN MORE

697
00:28:31,120 --> 00:28:33,360
COMPLICATED THAN THE ONES IN MY

698
00:28:33,360 --> 00:28:33,920
SCIENTIFIC JOB.

699
00:28:33,920 --> 00:28:35,840
I HAVE A SERIES OF SLIDES HERE

700
00:28:35,840 --> 00:28:38,640
THAT SHOW THE VARIOUS GROUPS

701
00:28:38,640 --> 00:28:41,040
WHICH I INTERACT ON I REGULAR

702
00:28:41,040 --> 00:28:41,240
BASIS.

703
00:28:41,240 --> 00:28:42,600
I REPORT TO THE NIH DIRECTOR,

704
00:28:42,600 --> 00:28:45,440
I'M A DEPUTY DIRECTOR FOR IN TRA

705
00:28:45,440 --> 00:28:46,720
MURAL RESEARCH AND REPORTING TO

706
00:28:46,720 --> 00:28:49,280
ME IS THE DEPUTY DIRECTOR FOR IN

707
00:28:49,280 --> 00:28:53,320
TRA MURAL CLINICAL RESEARCH AND

708
00:28:53,320 --> 00:28:56,000
JANICE LEE.

709
00:28:56,000 --> 00:28:59,320
WE'VE HAD DIFFERENT DDICRs

710
00:28:59,320 --> 00:29:00,480
OVER THE LAST SEVERAL YEARS.

711
00:29:00,480 --> 00:29:01,680
THERE'S NOT A REPORTER

712
00:29:01,680 --> 00:29:03,160
REQUIREMENT BUT WE OVERSEE THE

713
00:29:03,160 --> 00:29:04,600
BOARD OF SCIENTIFIC DIRECTOR

714
00:29:04,600 --> 00:29:07,680
WHICH IS A GROUP WHO GETS

715
00:29:07,680 --> 00:29:09,160
TOGETHER TO MAKE DECISIONS ABOUT

716
00:29:09,160 --> 00:29:11,320
POLICIES AND THE INTRAMURAL

717
00:29:11,320 --> 00:29:11,640
PROGRAM.

718
00:29:11,640 --> 00:29:16,240
I ALSO GET INPUT FROM MANY

719
00:29:16,240 --> 00:29:17,520
ADVISORY GROUPS CONSISTING OF

720
00:29:17,520 --> 00:29:19,760
SCIENTISTS AT THE NIH, THE NIH

721
00:29:19,760 --> 00:29:20,480
EQUITY COMMITTEE, WOMEN

722
00:29:20,480 --> 00:29:22,120
SCIENTISTS, THE ASSEMBLY OF

723
00:29:22,120 --> 00:29:23,440
SCIENTISTS, THE CENTRAL TEN YOUR

724
00:29:23,440 --> 00:29:24,880
COMMITTEE AND OTHERS.

725
00:29:24,880 --> 00:29:26,400
AND THEY ARE FREE IN THEIR

726
00:29:26,400 --> 00:29:28,640
ADVICE TO ME AND I FREQUENTLY GO

727
00:29:28,640 --> 00:29:30,320
TO THEM FOR ADVICE.

728
00:29:30,320 --> 00:29:31,600
THEN THERE ARE MANY OFFICES IN

729
00:29:31,600 --> 00:29:33,880
THE OFFICE OF THE DIRECTOR.

730
00:29:33,880 --> 00:29:36,000
OFFICE OF RESEARCH SERVICES,

731
00:29:36,000 --> 00:29:38,760
OFFICE RESEARCH FACILITIES,

732
00:29:38,760 --> 00:29:41,880
MANY OTHERS WHICH I INTERACT

733
00:29:41,880 --> 00:29:43,880
ABOUT ISSUES RELATED TO POLICY,

734
00:29:43,880 --> 00:29:46,440
COMPLIANCE AND SO ON.

735
00:29:46,440 --> 00:29:48,880
AND THEN THE BOARD OF SCIENTIFIC

736
00:29:48,880 --> 00:29:50,280
DIRECTORS IN ADDITION THROUGH

737
00:29:50,280 --> 00:29:52,600
THE IC DIRECTORS, INTERACTS WITH

738
00:29:52,600 --> 00:29:54,680
THE CLINICAL DIRECTORS AND ALL

739
00:29:54,680 --> 00:29:56,080
OF THIS CREATES A COMPLEX

740
00:29:56,080 --> 00:29:58,120
NETWORK OF INTERACTIONS THAT

741
00:29:58,120 --> 00:30:00,600
NEED TO BE MANAGED BUT ALSO ARE

742
00:30:00,600 --> 00:30:04,560
HE A REAL ASSET TO ME AS I MEET

743
00:30:04,560 --> 00:30:05,760
WITH MANY MANY GROUPS AS I CAN

744
00:30:05,760 --> 00:30:07,480
AND DEVELOP POLICIES THAT ARE

745
00:30:07,480 --> 00:30:09,760
BROADLY SUPPORTED AND THAT CAN

746
00:30:09,760 --> 00:30:13,280
MOVE THE NIH FORWARD.

747
00:30:13,280 --> 00:30:15,000
NOW, I HAVE ANOTHER DIAGRAM OF

748
00:30:15,000 --> 00:30:17,720
WHAT GOES ON IN MY OFFICE WHICH

749
00:30:17,720 --> 00:30:20,840
IS NOT A STRUCTURAL I DO A GRAM

750
00:30:20,840 --> 00:30:22,440
BUT A FUNCTIONAL DIAGRAM AND

751
00:30:22,440 --> 00:30:24,280
THIS IS KNOWN IN THE KINDEST WAY

752
00:30:24,280 --> 00:30:27,160
IN MY OFFICE AS THE MEATBALL

753
00:30:27,160 --> 00:30:27,560
SANDWICH.

754
00:30:27,560 --> 00:30:28,960
SO WE GET MONEY FROM VARIOUS

755
00:30:28,960 --> 00:30:30,720
SOURCES FROM THE OFFICE OF THE

756
00:30:30,720 --> 00:30:34,720
DIRECTOR AND INDIRECTLY FROM THE

757
00:30:34,720 --> 00:30:36,760
ICs AND OUR RESPONSIBILITIES

758
00:30:36,760 --> 00:30:37,320
ARE THREEFOLD.

759
00:30:37,320 --> 00:30:39,160
RESEARCH OVER SITE THAT YOU HAVE

760
00:30:39,160 --> 00:30:40,200
HEARD A FAIR AMOUNT ABOUT AND

761
00:30:40,200 --> 00:30:41,440
YOU WILL HEAR MORE ABOUT.

762
00:30:41,440 --> 00:30:42,880
TRAINING AND CAREER DEVELOPMENT.

763
00:30:42,880 --> 00:30:44,080
THE OFFICE OF INTRAMURAL

764
00:30:44,080 --> 00:30:49,160
TRAINING AND EDUCATION IS IN MY

765
00:30:49,160 --> 00:30:49,400
OFFICE.

766
00:30:49,400 --> 00:30:51,400
THEY HAVE THE VISITING

767
00:30:51,400 --> 00:30:53,280
SCIENTISTS AND THE REGULATORY

768
00:30:53,280 --> 00:30:55,640
DEPARTMENT AND YOU HEARD THAT

769
00:30:55,640 --> 00:30:57,080
I'M INSTITUTIONAL OFFICIAL FOR

770
00:30:57,080 --> 00:30:58,560
HUMAN SUBJECTS RESEARCH ANIMAL

771
00:30:58,560 --> 00:31:00,800
CARE AND USE TECH TRANSFER AND

772
00:31:00,800 --> 00:31:02,000
THOSE ARE IMPORTANT ACTIVITIES

773
00:31:02,000 --> 00:31:05,800
THAT KEEP THE NIH OUT OF TROUBLE

774
00:31:05,800 --> 00:31:06,560
AND MABEL SURE OUR SCIENTISTS

775
00:31:06,560 --> 00:31:08,200
ARE DOING THE RIGHT THING ON A

776
00:31:08,200 --> 00:31:09,240
REGULAR BASIS.

777
00:31:09,240 --> 00:31:10,480
WE MAKE POLICY WITH THE HELP OF

778
00:31:10,480 --> 00:31:11,760
ALL THE GROUPS I MENTIONED AND

779
00:31:11,760 --> 00:31:14,120
WE TRY TO COMMUNICATE CLEARLY

780
00:31:14,120 --> 00:31:17,640
THAT POLICY, CHRIS WANCHECK IS

781
00:31:17,640 --> 00:31:19,320
THE HEAD OF THE COMMUNICATIONS

782
00:31:19,320 --> 00:31:21,080
OFFICE AND THAT IS SUPPORTING

783
00:31:21,080 --> 00:31:22,400
THE INTRAMURAL PROGRAM.

784
00:31:22,400 --> 00:31:25,800
THERE ARE ALL THESE COMPLEXITIES

785
00:31:25,800 --> 00:31:28,840
THAT ARE GOING ON AT THE SAME

786
00:31:28,840 --> 00:31:32,000
TIME THAT I'M TRYING TO RUN MY

787
00:31:32,000 --> 00:31:33,440
RESEARCH PROGRAM.

788
00:31:33,440 --> 00:31:35,360
SO, THE NEXT THING I WANTED TO

789
00:31:35,360 --> 00:31:37,080
SAY, LESSON NUMBER FIVE, WE

790
00:31:37,080 --> 00:31:41,600
SHOULD BE FOCUSING ON INTRA

791
00:31:41,600 --> 00:31:42,200
PERSONAL SKILLS.

792
00:31:42,200 --> 00:31:44,000
THERE'S EMPHASIS ON CIVIL LATELY

793
00:31:44,000 --> 00:31:45,360
AND PEOPLE TREATING EACH OTHER

794
00:31:45,360 --> 00:31:48,200
WELL AND ON MUTUAL RESPECT AND

795
00:31:48,200 --> 00:31:50,840
ON LISTENING AND ON LEARNING AND

796
00:31:50,840 --> 00:31:54,880
I GOT THIS ADD VOICE FROM AL

797
00:31:54,880 --> 00:31:56,280
RABSON THE SCIENTIFIC DIRECTOR

798
00:31:56,280 --> 00:31:58,320
AND DIVISION DIRECTOR IN NCI

799
00:31:58,320 --> 00:32:00,240
WHEN I WAS RECRUITED WHO WAS AN

800
00:32:00,240 --> 00:32:01,880
ADVISER TO MANY, MANY PEOPLE AT

801
00:32:01,880 --> 00:32:03,560
NIH, UNFORTUNATELY DIED SEVERAL

802
00:32:03,560 --> 00:32:04,200
YEARS AGO.

803
00:32:04,200 --> 00:32:05,800
BUT HE USED TO SAY, TREAT

804
00:32:05,800 --> 00:32:07,480
EVERYONE WHO WORKS FOR YOU WITH

805
00:32:07,480 --> 00:32:09,920
KINDNESS AND RESPECT BECAUSE ONE

806
00:32:09,920 --> 00:32:11,120
DAY YOU WILL BE WORKING FOR

807
00:32:11,120 --> 00:32:11,320
THEM.

808
00:32:11,320 --> 00:32:13,000
I THINK THAT WAS HIS SENSE OF

809
00:32:13,000 --> 00:32:15,520
HUMOR, HE OBVIOUSLY KNEW THE

810
00:32:15,520 --> 00:32:16,760
INTRINSIC RIGHTNESS OF BEING

811
00:32:16,760 --> 00:32:23,320
CIVIL TO EVERYBODY.

812
00:32:23,320 --> 00:32:26,600
HERE HE IS WITH KATIE COURIC WHO

813
00:32:26,600 --> 00:32:27,920
REALLY LIKED AL, KATIE IS A

814
00:32:27,920 --> 00:32:30,160
SPOKESPERSON FOR COLON CANCER

815
00:32:30,160 --> 00:32:31,440
BECAUSE OF HER FAMILY

816
00:32:31,440 --> 00:32:32,240
CIRCUMSTANCES WITH HER HUSBAND

817
00:32:32,240 --> 00:32:33,680
DYING OF COLON CANCER.

818
00:32:33,680 --> 00:32:35,480
SO THIS IS A GREAT PICTURE I

819
00:32:35,480 --> 00:32:39,680
THOUGHT I WOULD SHARE.

820
00:32:39,680 --> 00:32:41,080
LESSON NUMBER SIX, REALLY

821
00:32:41,080 --> 00:32:42,640
IMPORTANT IF YOU ARE GOING TO BE

822
00:32:42,640 --> 00:32:43,880
A GOOD SCIENCE MANAGER AND A

823
00:32:43,880 --> 00:32:46,080
GOOD SCIENTIST, YOU HAVE TO KNOW

824
00:32:46,080 --> 00:32:49,520
A LOT ABOUT SCIENCE AND I'VE HAD

825
00:32:49,520 --> 00:32:51,920
THE GOOD FORTUNE TO INTEGRATE MY

826
00:32:51,920 --> 00:32:55,000
INTEREST IN SCIENCE AND GENERAL

827
00:32:55,000 --> 00:32:57,280
BIOLOGY IN PARTICULAR WITH BOTH

828
00:32:57,280 --> 00:32:59,200
THE LAB AND WHAT I DO AT THE NIH

829
00:32:59,200 --> 00:33:00,720
TO MAKE SURE YOU ARE ALL

830
00:33:00,720 --> 00:33:02,280
EDUCATED ABOUT SCIENCE.

831
00:33:02,280 --> 00:33:04,040
SO,  OUR SCIENTIFIC PROJECT

832
00:33:04,040 --> 00:33:08,320
INVOLVED MOLECULAR BIOLOGY,

833
00:33:08,320 --> 00:33:09,840
BIOCHEMISTRY AND X-RAY CRYSTAL

834
00:33:09,840 --> 00:33:11,600
OLE RA FEE AND BY OWE PHYSICS

835
00:33:11,600 --> 00:33:12,880
AND IN EACH CASE WE LEARNED WHAT

836
00:33:12,880 --> 00:33:14,680
WE NEEDED TO KNOW OR MOST LIKELY

837
00:33:14,680 --> 00:33:18,520
WE WENT TO A COLLABORATOR AND

838
00:33:18,520 --> 00:33:22,200
FOUND SOMEONE AT THE NIH.

839
00:33:22,200 --> 00:33:24,200
WITH 1100PI THERE'S SOMEONE WITH

840
00:33:24,200 --> 00:33:26,520
EQUIPMENT AND KNOWLEDGE YOU NEED

841
00:33:26,520 --> 00:33:28,720
AND PEOPLE WILLING TO HELP.

842
00:33:28,720 --> 00:33:30,800
SO WHAT DO WE DO IN MY OFFICE TO

843
00:33:30,800 --> 00:33:32,560
MAKE SURE YOU ARE ALL EDUCATED?

844
00:33:32,560 --> 00:33:34,600
WE SUPPORT A COUPLE OF LECTURE

845
00:33:34,600 --> 00:33:36,840
SERIES, THE WEDNESDAY AFTERNOON

846
00:33:36,840 --> 00:33:37,840
LECTURES AND FRIDAY MONTHLY

847
00:33:37,840 --> 00:33:41,640
SPEAKERS AND OF COURSE MEDICAL

848
00:33:41,640 --> 00:33:43,520
GRAND ROUNDS AT THE CLINICAL V

849
00:33:43,520 --> 00:33:49,720
CLIN WE HAVETHE CATALYST WHICH U

850
00:33:49,720 --> 00:33:50,000
KNOW.

851
00:33:50,000 --> 00:33:52,640
THE DDIR WEB BOARD WHICH YOU MAY

852
00:33:52,640 --> 00:33:54,280
NOT KNOW IS SUB DESCRIPTION ONLY

853
00:33:54,280 --> 00:33:56,200
AND WE REMIND PEOPLE EVERY THREE

854
00:33:56,200 --> 00:33:57,520
MONTHS THEY CAN SUB DESCRIBE

855
00:33:57,520 --> 00:34:01,640
IT'S FULL OF INTEREST TIDBITS OF

856
00:34:01,640 --> 00:34:02,760
INFORMATION SO SUB DESCRIBE TO

857
00:34:02,760 --> 00:34:07,000
THAT AND THEN WE HAVE A ACTIVE

858
00:34:07,000 --> 00:34:08,160
WEBSITE AND THEY HAVE MADE THAT

859
00:34:08,160 --> 00:34:10,440
INTO A VERY ATTRACTIVE WAY OF

860
00:34:10,440 --> 00:34:11,960
FINDING OUT WHO IS AT THE NIH

861
00:34:11,960 --> 00:34:12,920
AND WHAT THEY'RE DOING AND WHAT

862
00:34:12,920 --> 00:34:14,560
IS HOT AND WHAT IS NOT SO I URGE

863
00:34:14,560 --> 00:34:17,440
YOU WHEN YOU GET THOSE REMINDERS

864
00:34:17,440 --> 00:34:18,360
EVERY WEEK ABOUT ABOUT WHAT TO

865
00:34:18,360 --> 00:34:20,040
LOOK UP, CLICK ON THEM AND SEE

866
00:34:20,040 --> 00:34:22,400
WHAT IS HAPPENING IN THE IRP.

867
00:34:22,400 --> 00:34:24,360
WE DEVELOPED A SCIENTIFIC

868
00:34:24,360 --> 00:34:26,920
INTEREST GROUPS AND CLOSE TO 100

869
00:34:26,920 --> 00:34:28,120
OF THOSE COVERING ALL KINDS OF

870
00:34:28,120 --> 00:34:30,480
FIELDS FROM VERY BROAD AREAS TO

871
00:34:30,480 --> 00:34:34,000
VERY FOCUSED ONES AND THE INTENT

872
00:34:34,000 --> 00:34:38,040
THERE IS TO ENCOURAGE TRANS NIH

873
00:34:38,040 --> 00:34:39,800
INTERACTIONS, KNOWLEDGE,

874
00:34:39,800 --> 00:34:40,200
COLLABORATIONS.

875
00:34:40,200 --> 00:34:41,160
AND THEN THERE'S SOMETHING ELSE

876
00:34:41,160 --> 00:34:42,680
THAT MANY PEOPLE DO KNOW ABOUT,

877
00:34:42,680 --> 00:34:45,040
THERE'S A DATABASE, ALL THOSE

878
00:34:45,040 --> 00:34:45,800
ANNUAL REPORTS THAT YOU ARE

879
00:34:45,800 --> 00:34:47,240
WRITE GO INTO A DATABASE WHICH

880
00:34:47,240 --> 00:34:50,000
IS FULLY SEARCHABLE AND YOU CAN

881
00:34:50,000 --> 00:34:51,480
FIND ANYTHING YOU NEED AT THE

882
00:34:51,480 --> 00:34:53,160
NIH THROUGH THAT DATABASE.

883
00:34:53,160 --> 00:34:55,480
WHO HAS A DIFFERENT CELL LINE, A

884
00:34:55,480 --> 00:34:57,280
PIECE OF EQUIPMENT, WHO IS WORK

885
00:34:57,280 --> 00:34:58,840
ON A SUBJECT YOU MIGHT BE

886
00:34:58,840 --> 00:35:00,360
INTERESTED IN SO I URGE TO YOU

887
00:35:00,360 --> 00:35:02,520
GO TO THAT DATABASE AND MAKE USE

888
00:35:02,520 --> 00:35:06,360
OF IT AS WELL.

889
00:35:06,360 --> 00:35:08,240
SO, LESSON NUMBER SEVEN, DON'T

890
00:35:08,240 --> 00:35:09,640
BE TECHNIQUE LIMITED.

891
00:35:09,640 --> 00:35:11,200
I LEARNED THIS FROM IRA.

892
00:35:11,200 --> 00:35:12,520
YOU KNOW, WE WOULD COME UP

893
00:35:12,520 --> 00:35:13,960
AGAINST A PROBLEM THAT WE NEEDED

894
00:35:13,960 --> 00:35:16,440
TO SOLVE AND DIDN'T KNOW HOW.

895
00:35:16,440 --> 00:35:18,520
WE KNEW CELL CULTURE, WE KNOW

896
00:35:18,520 --> 00:35:20,640
CLONING, WE KNEW MOLECULAR

897
00:35:20,640 --> 00:35:22,040
BIOLOGY BUT WE NEEDED BIO

898
00:35:22,040 --> 00:35:23,360
PHYSICS OR SOMETHING ELSE AND

899
00:35:23,360 --> 00:35:25,480
SO, WE ALWAYS TOOK ADVANTAGE OF

900
00:35:25,480 --> 00:35:29,560
DECK KNOWLEDGES AS THEY WERE

901
00:35:29,560 --> 00:35:31,520
EMERGING.

902
00:35:31,520 --> 00:35:33,800
AND THERE HAVE BEEN MANY

903
00:35:33,800 --> 00:35:35,960
ADVANCES AND STRUCTURAL AND CELL

904
00:35:35,960 --> 00:35:38,240
BIOLOGY AND I'VE TRIED IN MY

905
00:35:38,240 --> 00:35:41,440
SUPPORT OF ACTIVITIES, USING THE

906
00:35:41,440 --> 00:35:43,160
LITTLE FUNDS THAT WE HAVE IN MY

907
00:35:43,160 --> 00:35:46,080
OFFICE BUT ALSO STIMULATING

908
00:35:46,080 --> 00:35:49,480
IDEAS AND DISCUSSIONS TO SUPPORT

909
00:35:49,480 --> 00:35:50,800
THESE ACTIVITIES A CROSS THE NIH

910
00:35:50,800 --> 00:35:54,440
AND I'VE JUST A FEW EXAMPLES

911
00:35:54,440 --> 00:35:56,920
HERE, IN STRUCTURAL BIOLOGY AND

912
00:35:56,920 --> 00:36:00,200
BIO ENGINEERING WE HAVE SUPPORT

913
00:36:00,200 --> 00:36:05,040
CRYO EM AND THEY HAVE NICE, NIH,

914
00:36:05,040 --> 00:36:14,600
INTRAMURAL CRYO EIM AND NMR, BOB

915
00:36:14,600 --> 00:36:17,800
TIE CO AND IN NIDDK THERE'S A

916
00:36:17,800 --> 00:36:23,840
LOT OF WORK ON SUPER RESOLUTION

917
00:36:23,840 --> 00:36:26,040
INCLUDING NIBIB, A FACILITY

918
00:36:26,040 --> 00:36:27,560
WE'RE ALL ABLE TO USE AND OF

919
00:36:27,560 --> 00:36:29,440
COURSE, ENORMOUS ADVANCES IN

920
00:36:29,440 --> 00:36:34,800
CLINICAL IMAGING, MRI, CT PET.

921
00:36:34,800 --> 00:36:36,840
THE USE OF RADIOLOGICAL

922
00:36:36,840 --> 00:36:38,840
APPROACHES TO BOTH IMAGE AND

923
00:36:38,840 --> 00:36:41,920
TREAT DISEASES PO TONIC AND ON

924
00:36:41,920 --> 00:36:52,160
AND ON AND ON.

925
00:37:00,000 --> 00:37:03,480
>> THIS IS A HUB FOR A
MORE

926
00:37:03,480 --> 00:37:05,400
BROADLY-BASED BIO ENGINEERING

927
00:37:05,400 --> 00:37:08,600
ACTIVITY AT THE NIH WITH MANY

928
00:37:08,600 --> 00:37:09,280
IC-SPECIFIC INVESTMENTS.

929
00:37:09,280 --> 00:37:13,720
THE PICTURE IS FROM NIEHS, CRYO

930
00:37:13,720 --> 00:37:17,320
EM STUDY OF SARS-CoV-2, SPIKE

931
00:37:17,320 --> 00:37:19,400
PROTEIN WITH THE BOUND TO THE

932
00:37:19,400 --> 00:37:21,320
ARB RECEPTORS AND THIS IS

933
00:37:21,320 --> 00:37:22,240
IMPORTANT, PARTICULARLY SOME OF

934
00:37:22,240 --> 00:37:23,400
THESE VARIANTS COME UP THAT HAVE

935
00:37:23,400 --> 00:37:25,200
A LOT TERRATIONS AND THESE

936
00:37:25,200 --> 00:37:28,160
INTERACTIONS AND THIS PHOTO IS

937
00:37:28,160 --> 00:37:29,920
FROM MARIO BORNIA WHO RUNS THE

938
00:37:29,920 --> 00:37:34,360
CRYO EM FACILITY AT THE EHS.

939
00:37:34,360 --> 00:37:36,160
HUGE ADVANCES IN CELL BOYOLOGY

940
00:37:36,160 --> 00:37:37,280
OVER THE YEARS AND A LOT OF

941
00:37:37,280 --> 00:37:42,480
BASED ON SINGLE CELL GENOMICS,

942
00:37:42,480 --> 00:37:44,760
CHRIS PER AND TISSUE ON A SHIP

943
00:37:44,760 --> 00:37:47,120
ADVANCES IN A CLINICAL CENTER

944
00:37:47,120 --> 00:37:49,720
AND NCATS AND THE USE OF

945
00:37:49,720 --> 00:37:52,200
ORGANOIDS TO STUDY BEHAVIOR OF

946
00:37:52,200 --> 00:37:57,400
CELL COMPLEXES AND RNA, DNA,

947
00:37:57,400 --> 00:38:00,040
PROTEIN LOCALIZATION EFFORTS.

948
00:38:00,040 --> 00:38:03,560
OTHER OMIC APPROACHES, GLYCOLIC,

949
00:38:03,560 --> 00:38:05,600
LIPID OMICS, AND ON AND ON AND

950
00:38:05,600 --> 00:38:07,840
ON SOME OF HAVE LED TO CENTERS

951
00:38:07,840 --> 00:38:09,280
THAT CAN HELP YOU SOLVE PROBLEMS

952
00:38:09,280 --> 00:38:11,480
THAW MAY HAVE IN THE LAB.

953
00:38:11,480 --> 00:38:14,720
AND OF COURSE, SUB CELLULAR

954
00:38:14,720 --> 00:38:15,720
VISUALIZATION TECHNIQUES WHICH

955
00:38:15,720 --> 00:38:18,920
WE'VE MENTIONED SOME.

956
00:38:18,920 --> 00:38:20,320
AND I WANT TO SAY SOMETHING

957
00:38:20,320 --> 00:38:22,000
ABOUT PHARMACOLOGY BECAUSE IT'S

958
00:38:22,000 --> 00:38:23,920
THE FIELD IN WHICH WE'VE DONE

959
00:38:23,920 --> 00:38:25,960
MOST OF OUR WORK.

960
00:38:25,960 --> 00:38:32,040
WE HAVE, THANKS TO SOME OF THE

961
00:38:32,040 --> 00:38:35,680
FACILITIES IN NCI IT'S EASY TO

962
00:38:35,680 --> 00:38:38,520
DO HIGH THROUGH PUT SCREENS AND

963
00:38:38,520 --> 00:38:41,040
THERE'S A LOT OF IN VITRO

964
00:38:41,040 --> 00:38:43,160
MODELING AND MOLECULAR DYNAMIC

965
00:38:43,160 --> 00:38:44,480
STIMULATION AND MODELING THAT

966
00:38:44,480 --> 00:38:45,960
LAWS YOU TO MAKE PREDICTIONS

967
00:38:45,960 --> 00:38:48,160
ABOUT WHAT KIND OF MOLECULES

968
00:38:48,160 --> 00:38:49,840
WILL INTERACT WITH YOUR TARGETS.

969
00:38:49,840 --> 00:38:51,680
COMMON CHEMISTRY AND WE MENTION

970
00:38:51,680 --> 00:38:54,720
THE CRYO EM.

971
00:38:54,720 --> 00:38:56,840
SO, LET ME, BEFORE I COME TO A

972
00:38:56,840 --> 00:38:59,680
CLOSE HERE, SAY SOMETHING ABOUT

973
00:38:59,680 --> 00:39:02,760
MY COLLEAGUE AND HELP ME OFFER

974
00:39:02,760 --> 00:39:04,800
THE YEARS RICHARD WYATT.

975
00:39:04,800 --> 00:39:07,040
RICHARD IS TAUGHT ME QUITE A

976
00:39:07,040 --> 00:39:07,400
LOT.

977
00:39:07,400 --> 00:39:08,920
ONE OF THE MOST IMPORTANT THINGS

978
00:39:08,920 --> 00:39:10,200
THAT HE KEEPS REMINDING ME ABOUT

979
00:39:10,200 --> 00:39:12,440
IS THAT THE SAFETY OF OUR

980
00:39:12,440 --> 00:39:13,840
WORKFORCE AND OUR PATIENTS

981
00:39:13,840 --> 00:39:15,600
ALWAYS COMES FIRST.

982
00:39:15,600 --> 00:39:17,160
AND SO, WE'VE HAD OVER THE

983
00:39:17,160 --> 00:39:18,600
YEARS, MANY POLICIES AND

984
00:39:18,600 --> 00:39:22,520
PRACTICES TO ASSURE SAFETY OF

985
00:39:22,520 --> 00:39:25,120
OUR STAFF AND JUST A REMINDER IF

986
00:39:25,120 --> 00:39:26,440
YOU SEE PRACTICES THAT ARE

987
00:39:26,440 --> 00:39:29,040
UNSAFE WE NEED TO KNOW ABOUT

988
00:39:29,040 --> 00:39:30,440
THEM AND STOP THEM AND EDUCATE

989
00:39:30,440 --> 00:39:31,600
PEOPLE ABOUT THE PROPER WAY TO

990
00:39:31,600 --> 00:39:33,240
TAKE CARE OF THEIR EXPERIMENT

991
00:39:33,240 --> 00:39:35,400
AND THEIR PATIENTS.

992
00:39:35,400 --> 00:39:37,400
YOU ALL REMEMBER THE RED TEAM

993
00:39:37,400 --> 00:39:37,640
REPORT.

994
00:39:37,640 --> 00:39:39,200
THIS WAS A FORMATIVE EXPERIENCE

995
00:39:39,200 --> 00:39:40,440
FOR AWFUL US.

996
00:39:40,440 --> 00:39:42,480
AND LED TO MANY, MANY CHANGES IN

997
00:39:42,480 --> 00:39:44,040
THE WAY THAT WE TAKE CARE OF

998
00:39:44,040 --> 00:39:45,440
PATIENTS THAT ARE IMPROVED THE

999
00:39:45,440 --> 00:39:48,920
SAFETY OF OUR PATIENTS AND THE

1000
00:39:48,920 --> 00:39:50,240
SAFETY OF THE INDIVIDUALS WHO

1001
00:39:50,240 --> 00:39:51,400
WORK WITH OUR PATIENTS.

1002
00:39:51,400 --> 00:39:53,080
THE NURSING STAFF, THE SUPPORT

1003
00:39:53,080 --> 00:39:54,720
STAFF AND SO ON.

1004
00:39:54,720 --> 00:39:58,040
AND WE WANT TO LIMIT THE

1005
00:39:58,040 --> 00:39:59,920
LABORATORY SAFETY PROBLEMS.

1006
00:39:59,920 --> 00:40:01,720
WE ARE ALL RESPONSIBLE FOR THE

1007
00:40:01,720 --> 00:40:03,680
PEOPLE WHO SUPERVISE IN OUR LABS

1008
00:40:03,680 --> 00:40:06,000
AND WE WANT TO MAKE SURE THAT WE

1009
00:40:06,000 --> 00:40:08,480
TAKE GOOD CARE THAT THEY ARE

1010
00:40:08,480 --> 00:40:10,240
HEALTHY AND WELL AND DON'T GET

1011
00:40:10,240 --> 00:40:10,760
INTO TROUBLE.

1012
00:40:10,760 --> 00:40:12,400
I CAN TELL THAW OVER THE YEARS,

1013
00:40:12,400 --> 00:40:15,760
THERE'S BEEN ISOLATED EXAMPLES,

1014
00:40:15,760 --> 00:40:17,400
USUALLY INVOLVING TRAINEES OF

1015
00:40:17,400 --> 00:40:18,880
PEOPLE WHO HAVE GONE INJURED AS

1016
00:40:18,880 --> 00:40:21,080
A RESULT OF SAFETY CONCERNS AND

1017
00:40:21,080 --> 00:40:24,880
WE TAKE THESE VERY, VERY

1018
00:40:24,880 --> 00:40:28,120
SERIOUSLY.

1019
00:40:28,120 --> 00:40:30,040
SO, GETTING BACK TO MY RESEARCH,

1020
00:40:30,040 --> 00:40:31,720
I'M AT A STAGE IN THE RESEARCH

1021
00:40:31,720 --> 00:40:33,320
NOW HOPING TO GO BACK TO THE LAB

1022
00:40:33,320 --> 00:40:36,400
FULL TIME SOON AND WE HAVE SOME

1023
00:40:36,400 --> 00:40:37,720
CHALLENGES TO SOLVE.

1024
00:40:37,720 --> 00:40:39,720
AS I MENTIONED, WE THINK MOST

1025
00:40:39,720 --> 00:40:41,720
DRUG RESISTANCE AND CANCER IS

1026
00:40:41,720 --> 00:40:44,200
MULTI FACTORIAL AND A BIG

1027
00:40:44,200 --> 00:40:45,720
QUESTION IS, IS THAT MEAN WHEN

1028
00:40:45,720 --> 00:40:53,400
YOU SEE   A TUMOR DOES THE

1029
00:40:53,400 --> 00:40:55,240
RESISTANCE EXIST OR DOES IT LEAD

1030
00:40:55,240 --> 00:40:58,080
TO THE EVOLUTION OF DRUG

1031
00:40:58,080 --> 00:40:58,480
RESISTANCE.

1032
00:40:58,480 --> 00:41:00,080
THIS IS IMPORTANT ISSUE FOR

1033
00:41:00,080 --> 00:41:02,440
DEALING WITH DRUG RESISTANCE.

1034
00:41:02,440 --> 00:41:04,480
WE'VE START TODAY ASSEMBLE A

1035
00:41:04,480 --> 00:41:08,320
CATALOG OF DRUG RESISTANCE

1036
00:41:08,320 --> 00:41:08,520
GREENS.

1037
00:41:08,520 --> 00:41:11,320
WE'RE NOT JUST A ONE-INSTRUMENT

1038
00:41:11,320 --> 00:41:11,560
BAND.

1039
00:41:11,560 --> 00:41:13,200
ONE OF THE WAYS WE'VE DONE THAT

1040
00:41:13,200 --> 00:41:17,200
IS SELECTIONS BUT ALSO USING

1041
00:41:17,200 --> 00:41:19,680
CHRIS PER, A TOWERFUL TOOL TO

1042
00:41:19,680 --> 00:41:22,520
PULL OUT GOWNS THAT HAVE THE

1043
00:41:22,520 --> 00:41:24,800
SENSITIVITY CELLS, ANTI CANCER

1044
00:41:24,800 --> 00:41:25,040
DRUGS.

1045
00:41:25,040 --> 00:41:27,080
AND FINALLY IT'S IMPORTANT TO

1046
00:41:27,080 --> 00:41:29,160
KNOW WHETHER THEIR MECHANISMS

1047
00:41:29,160 --> 00:41:31,600
WERE DERIVING IN THE LAB ARE

1048
00:41:31,600 --> 00:41:33,120
RELEVANT AND WE NEED BETTER WAYS

1049
00:41:33,120 --> 00:41:38,400
OF ANALYZING THE EVOLUTION OF

1050
00:41:38,400 --> 00:41:48,160
TUMORS AND WHAT MECHANISMS ARE

1051
00:41:48,160 --> 00:41:59,320
PRE 'EM INANT TO'IMMINENT.

1052
00:42:00,880 --> 00:42:03,400
I WANT TO THANK THOSE IN MY LABS

1053
00:42:03,400 --> 00:42:07,280
FOR THE LAST 45 YEARS AND THOSE

1054
00:42:07,280 --> 00:42:09,480
ARE THE MINIMAL NUMBER OF PEOPLE

1055
00:42:09,480 --> 00:42:10,680
I HAVE WORKED OVER THE YEARS.

1056
00:42:10,680 --> 00:42:12,560
MANY HAVE BEEN POSITIVELY

1057
00:42:12,560 --> 00:42:13,720
INFLUENCED BY WHAT I HAD DO SAY

1058
00:42:13,720 --> 00:42:15,960
TO THEM AND I'VE HAD MANY, MANY

1059
00:42:15,960 --> 00:42:17,760
SENIORS COLLEAGUES, SOME OF WHOM

1060
00:42:17,760 --> 00:42:23,760
I'VE MENTIONED IN MY REPORT.

1061
00:42:23,760 --> 00:42:24,760
BEFORE I TAKE QUESTIONS IF YOU

1062
00:42:24,760 --> 00:42:26,640
HAVE ANY, I WANT TO REMIND

1063
00:42:26,640 --> 00:42:33,480
EVERYBODY HERE TO REMEMBER YOUR

1064
00:42:33,480 --> 00:42:38,920
FAMILY THIS IS MY FAMILY TAKEN

1065
00:42:38,920 --> 00:42:40,040
AT THE ACADEMY.

1066
00:42:40,040 --> 00:42:43,640
I'M THERE WITH SUSAN, IN THE

1067
00:42:43,640 --> 00:42:45,040
MIDDLE, TO MY LEFT IS MY

1068
00:42:45,040 --> 00:42:46,720
DAUGHTER REBECA AND HER HUSBAND

1069
00:42:46,720 --> 00:42:49,800
ED, AND TO MY RIGHT AT THE END

1070
00:42:49,800 --> 00:42:52,440
IS MY SON DANIEL AND JUST TO MY

1071
00:42:52,440 --> 00:42:57,560
RIGHT IS HIS WIFE, LUCY AND MY

1072
00:42:57,560 --> 00:43:02,160
THREE GRANDCHILDREN,LY A, NAOMI

1073
00:43:02,160 --> 00:43:03,200
AND PIPPEN AND THEY MAKE THIS

1074
00:43:03,200 --> 00:43:03,920
WORTH WHILE.

1075
00:43:03,920 --> 00:43:05,920
THEY'RE UNDERSTANDING,

1076
00:43:05,920 --> 00:43:07,360
SUPPORTIVE AND MANY OF THEM HAVE

1077
00:43:07,360 --> 00:43:08,640
TURNED OUT TO BE INTERESTED IN

1078
00:43:08,640 --> 00:43:10,320
SCIENCE AS WELL WHICH IS A

1079
00:43:10,320 --> 00:43:16,640
DOUBLE BLESSING.

1080
00:43:16,640 --> 00:43:19,440
WON'T BE PRESUMPTION TO LIST 10

1081
00:43:19,440 --> 00:43:20,560
LESSONS AND I THOUGHT NINE WOULD

1082
00:43:20,560 --> 00:43:21,320
BE TODAY.

1083
00:43:21,320 --> 00:43:22,720
I WILL END AND BE HAPPY TO TAKE

1084
00:43:22,720 --> 00:43:29,280
ANY QUESTIONS THAT YOU MAY HAVE.

1085
00:43:29,280 --> 00:43:32,240
>>THANK YOU FOR A WONDERFUL AND

1086
00:43:32,240 --> 00:43:34,880
ENGAGING LECTURE THAT REALLY

1087
00:43:34,880 --> 00:43:36,640
WELL-BALANCED SIMILAR TO YOUR

1088
00:43:36,640 --> 00:43:38,760
CAREER, YOUR ENDEAVORS IN THE

1089
00:43:38,760 --> 00:43:40,320
LABORATORY AND THE OVERSIGHT

1090
00:43:40,320 --> 00:43:42,080
LEADERSHIP AND ADMINISTRATIVE

1091
00:43:42,080 --> 00:43:45,360
SPACE FOR SUCH A LONG JOURNEY

1092
00:43:45,360 --> 00:43:48,040
THAT YOU'VE HAD.

1093
00:43:48,040 --> 00:43:49,680
I THINK THE WAY THAW APPROACHED

1094
00:43:49,680 --> 00:43:53,520
YOUR LECTURE WAS REALLY ENGAGING

1095
00:43:53,520 --> 00:43:56,000
AND A GREAT FORMAT SO WE DO HAVE

1096
00:43:56,000 --> 00:43:59,560
A QUESTION OR TWO BUT AS THE

1097
00:43:59,560 --> 00:44:06,720
MODERATOR, I'M GOING TO TAKE THE

1098
00:44:06,720 --> 00:44:08,560
LIBERTY TO START OFF WITH MY OWN

1099
00:44:08,560 --> 00:44:08,840
QUESTION.

1100
00:44:08,840 --> 00:44:10,000
I HAVE A COUPLE FOR YOU.

1101
00:44:10,000 --> 00:44:12,600
BUT I'LL START WITH ONE.

1102
00:44:12,600 --> 00:44:14,000
AND THIS QUESTION IS MEANT TO

1103
00:44:14,000 --> 00:44:16,320
TRY TO TAKE ADVANTAGE OF THE

1104
00:44:16,320 --> 00:44:18,680
WISDOM THAT YOU HAVE GLEANED

1105
00:44:18,680 --> 00:44:20,360
OVER THE YEARS THAT YOU'VE

1106
00:44:20,360 --> 00:44:23,080
SERVED AT NIH AND TO USE THAT

1107
00:44:23,080 --> 00:44:25,880
WISDOM TO SORT OF PROJECT INTO

1108
00:44:25,880 --> 00:44:28,760
THE FUTURE, AND THE QUESTION IS,

1109
00:44:28,760 --> 00:44:32,120
YOU KNOW, WHAT DO YOU SEE ARE

1110
00:44:32,120 --> 00:44:35,800
THE GREATEST CHALLENGES THAT ARE

1111
00:44:35,800 --> 00:44:39,040
BASIC TRANSLATIONAL AND CLINICAL

1112
00:44:39,040 --> 00:44:42,360
SCIENTIFIC WORKFORCE ARE FACING

1113
00:44:42,360 --> 00:44:46,800
NOW AND WILL FACE IN THE FUTURE

1114
00:44:46,800 --> 00:44:49,040
AND ARE THERE NOT INDIVIDUAL

1115
00:44:49,040 --> 00:44:53,640
LEVEL BUT STRUCTURAL LEVEL

1116
00:44:53,640 --> 00:44:56,240
CHANGES OR MODIFICATIONS THAT

1117
00:44:56,240 --> 00:44:58,840
YOU SEE THAT MIGHT HELP MITIGATE

1118
00:44:58,840 --> 00:45:01,600
OR OVERCOME SOME OF THOSE

1119
00:45:01,600 --> 00:45:01,880
CHALLENGES?

1120
00:45:01,880 --> 00:45:03,640
>> THANK YOU, DAN.

1121
00:45:03,640 --> 00:45:05,120
THAT IS A SOFTBALL QUESTION

1122
00:45:05,120 --> 00:45:06,720
BECAUSE I JUST WROTE AN ESSAY

1123
00:45:06,720 --> 00:45:08,520
FOR THE CATALYST ABOUT THE

1124
00:45:08,520 --> 00:45:10,640
CHALLENGES FACING THE NEW DDIR

1125
00:45:10,640 --> 00:45:13,640
WHEN I STEPPED DOWN.

1126
00:45:13,640 --> 00:45:15,760
AND THESE HAVE BEEN A MATTER OF

1127
00:45:15,760 --> 00:45:16,960
SOME DISCUSSION CONSIDERING ABLE

1128
00:45:16,960 --> 00:45:18,360
DISCUSSION WITH THE SCIENTIFIC

1129
00:45:18,360 --> 00:45:19,520
DIRECTOR AND THE CLINICAL

1130
00:45:19,520 --> 00:45:20,480
DIRECTOR BECAUSE WE'RE TRYING TO

1131
00:45:20,480 --> 00:45:22,200
PUT TOGETHER A SERIES OF

1132
00:45:22,200 --> 00:45:24,000
DESCRIPTIONS OF WHAT THE

1133
00:45:24,000 --> 00:45:26,080
CHALLENGES ARE AND PRESCRIPTIONS

1134
00:45:26,080 --> 00:45:27,920
FOR SOLUTIONS THAT MAY BE WOULD

1135
00:45:27,920 --> 00:45:31,400
BE POSSIBLE FOR THE NEW NIH

1136
00:45:31,400 --> 00:45:33,440
DIRECTOR AND THE NEW DDIR TO PUT

1137
00:45:33,440 --> 00:45:35,120
 PLACE.

1138
00:45:35,120 --> 00:45:37,360
SO, NUMBER ONE AND THIS IS AN

1139
00:45:37,360 --> 00:45:38,920
APPROPRIATE SETTING TO BRING

1140
00:45:38,920 --> 00:45:45,760
THTHISSUPPOSE THE CHALLENGES FAG

1141
00:45:45,760 --> 00:45:46,960
THE CLINICAL V IT'S UNIVERSAL

1142
00:45:46,960 --> 00:45:48,440
WITH THE NIH AND ALL THE

1143
00:45:48,440 --> 00:45:49,640
DIRECTORS AND LEADERSHIP FIELDS

1144
00:45:49,640 --> 00:45:50,800
AT THE CLINICAL CENTER IS THE

1145
00:45:50,800 --> 00:45:52,000
HEART OF THE NIH AND IT'S AN

1146
00:45:52,000 --> 00:45:54,000
ESSENTIAL PART OF THE NIH AND

1147
00:45:54,000 --> 00:45:57,000
YET IT HAS BEEN UNDERFUNDED FOR

1148
00:45:57,000 --> 00:45:59,240
MANY YEARS AND THE MECHANISM FOR

1149
00:45:59,240 --> 00:46:01,840
FUND PARTICULAR IS COMPLICATED

1150
00:46:01,840 --> 00:46:03,040
AND IT'S SCHOOL TAX AND OTHER

1151
00:46:03,040 --> 00:46:05,480
KINDS OF CONTRIBUTIONS AND IT

1152
00:46:05,480 --> 00:46:08,200
NEEDS A STABLE INFLATION-PROVE

1153
00:46:08,200 --> 00:46:09,440
MECHANISM OF FUNDING.

1154
00:46:09,440 --> 00:46:10,920
SO, THAT'S A BIG CHALLENGE.

1155
00:46:10,920 --> 00:46:12,720
WE'VE HAD GROUPS IN THE PAST

1156
00:46:12,720 --> 00:46:14,160
COME TO THINK ABOUT THIS ISSUE

1157
00:46:14,160 --> 00:46:15,880
AND MANY PEOPLE HAVE DIFFERENT

1158
00:46:15,880 --> 00:46:17,480
IDEAS AND ALL OF THEM HAVE THEIR

1159
00:46:17,480 --> 00:46:20,120
PLUSES AND MINUSES AND IT'S COME

1160
00:46:20,120 --> 00:46:22,360
TO THE POINT AS MANY OF YOU WHO

1161
00:46:22,360 --> 00:46:23,880
WORK IN THE CLINICAL CENTER,

1162
00:46:23,880 --> 00:46:30,840
RESOURCES ARE LIMIT AND THAT

1163
00:46:30,840 --> 00:46:34,960
LIMITATION SO I THINK IT'S A

1164
00:46:34,960 --> 00:46:38,480
NUMBER ONE CHALLENGE AND A

1165
00:46:38,480 --> 00:46:42,520
SECOND CHALLENGE IS IS ABOUT

1166
00:46:42,520 --> 00:46:44,760
INFRASTRUCTURE AT THE NIH.

1167
00:46:44,760 --> 00:46:46,400
IN THE 30 YEARS I'VE BEEN IN

1168
00:46:46,400 --> 00:46:47,840
CHARGE OF THE INTRAMURAL PROGRAM

1169
00:46:47,840 --> 00:46:49,600
WE'VE REPLACED HALF OF OUR

1170
00:46:49,600 --> 00:46:52,880
RESEARCH FACILITIES WITH NEW

1171
00:46:52,880 --> 00:46:53,200
FACILITIES.

1172
00:46:53,200 --> 00:46:55,520
HALF OF THEM ARE STILL ANTIQUE

1173
00:46:55,520 --> 00:46:59,280
AT GREAT RISK OF BAIL YOU'RE AND

1174
00:46:59,280 --> 00:47:01,120
ANYONE WHO WORK IN THE CLINICAL

1175
00:47:01,120 --> 00:47:03,560
CENTER COMPLEX IN BUILDING 10,

1176
00:47:03,560 --> 00:47:05,640
THE OLD PART OF THE BUILDING,

1177
00:47:05,640 --> 00:47:08,880
KNOWS HARDLY A DAY GOES BY WHEN

1178
00:47:08,880 --> 00:47:10,520
THERE'S NOT A FLOOD.

1179
00:47:10,520 --> 00:47:12,760
SO THEY'RE MAJOR DESTRUCTIVE

1180
00:47:12,760 --> 00:47:13,880
ACTIVITIES AND MAINTAINING THE

1181
00:47:13,880 --> 00:47:17,360
BUILDING IS BECOMING

1182
00:47:17,360 --> 00:47:18,320
INCREASINGLY DIFFICULT AND DAN

1183
00:47:18,320 --> 00:47:21,520
USED TO BRING AROUND PIPES AND

1184
00:47:21,520 --> 00:47:22,720
THAT DAY AND WE ARE FINDING IN

1185
00:47:22,720 --> 00:47:24,040
THE WALLS OF THE OLD BUILDING

1186
00:47:24,040 --> 00:47:28,920
AND PLUMBING AND VENT LAKE THAT

1187
00:47:28,920 --> 00:47:30,960
LOOKED LIKE ADVANCE FOUR-VESSEL

1188
00:47:30,960 --> 00:47:33,320
CORN ARY ARTERY DISEASE AND THE

1189
00:47:33,320 --> 00:47:35,000
PIN HOLE IN THE MIDDLE, THROUGH

1190
00:47:35,000 --> 00:47:36,640
WHICH THE WATER WAS SUPPOSED TO

1191
00:47:36,640 --> 00:47:38,080
COME AND COR ORGANIZATION AND SO

1192
00:47:38,080 --> 00:47:41,720
ON AND SO FOURTH SO THE

1193
00:47:41,720 --> 00:47:42,720
INFRASTRUCTURE IS A PROBLEM AT

1194
00:47:42,720 --> 00:47:45,000
THE NIH AND SOME OF THAT CAN BE

1195
00:47:45,000 --> 00:47:45,640
FIXED.

1196
00:47:45,640 --> 00:47:47,400
THE RENOVATIONS HAVE BEEN MADE

1197
00:47:47,400 --> 00:47:52,000
IN BUILDING 10 AND WE'RE ADDING

1198
00:47:52,000 --> 00:47:54,280
SOME SURGICAL RADIOLOGY AND

1199
00:47:54,280 --> 00:47:55,200
LABORATORY MEDICINE PIECE TO THE

1200
00:47:55,200 --> 00:47:57,920
BUILDING TO REPLACE THE OLDER

1201
00:47:57,920 --> 00:47:59,080
FACILITIES IN BUILDING 10.

1202
00:47:59,080 --> 00:48:01,360
BUT THOSE ARE REALLY CRITICAL

1203
00:48:01,360 --> 00:48:02,600
INFRASTRUCTURE AND IT'S TRUE FOR

1204
00:48:02,600 --> 00:48:04,480
ALL OF OUR BUILDINGS, NOT JUST

1205
00:48:04,480 --> 00:48:06,200
THE CLINICAL CENTER.

1206
00:48:06,200 --> 00:48:08,000
ANY OF THE OLD BUILDINGS REALLY

1207
00:48:08,000 --> 00:48:12,280
NEED MASSIVE MAINTENANCE OR

1208
00:48:12,280 --> 00:48:12,720
REPLACEMENT.

1209
00:48:12,720 --> 00:48:13,840
YOU MAY KNOW THAT THE NATIONAL

1210
00:48:13,840 --> 00:48:15,720
ACADEMY OF SCIENCE IS

1211
00:48:15,720 --> 00:48:18,680
ENGINEERING MEDICINE CAME AND

1212
00:48:18,680 --> 00:48:19,760
WROTE A REPORT CLEARLY

1213
00:48:19,760 --> 00:48:21,640
INDICATING WE NEED A MUCH BIGGER

1214
00:48:21,640 --> 00:48:23,280
INVESTMENT IN INFRASTRUCTURE.

1215
00:48:23,280 --> 00:48:25,960
THE THIRD AREA FOR CONSIDERATION

1216
00:48:25,960 --> 00:48:27,720
HAS TO DO WITH NOT MAKING FULL

1217
00:48:27,720 --> 00:48:30,360
USE OF WHAT I DESCRIBED AS THE

1218
00:48:30,360 --> 00:48:33,080
COLLABORATIVE ENVIRONMENT AT THE

1219
00:48:33,080 --> 00:48:33,480
NIH.

1220
00:48:33,480 --> 00:48:35,880
THE OPPORTUNITY TO SOLVE

1221
00:48:35,880 --> 00:48:38,480
VIRTUALLY ANY PROBLEM AT THE NIH

1222
00:48:38,480 --> 00:48:40,160
EXISTS AND SOMETIMES THERE ARE

1223
00:48:40,160 --> 00:48:41,640
UNNECESSARY BARRIERS OR

1224
00:48:41,640 --> 00:48:42,640
SOMETIMES IT JUST LACK OF

1225
00:48:42,640 --> 00:48:43,920
KNOWLEDGE OF OF WHAT IS POSSIBLE

1226
00:48:43,920 --> 00:48:46,000
AND WHAT IS AVAILABLE AND

1227
00:48:46,000 --> 00:48:47,240
SOMETIMES THERE ARE

1228
00:48:47,240 --> 00:48:48,440
ADMINISTRATIVE REASONS WHY

1229
00:48:48,440 --> 00:48:51,520
PEOPLE ARE NOT WILLING TO WORK

1230
00:48:51,520 --> 00:48:51,800
TOGETHER.

1231
00:48:51,800 --> 00:49:02,840
JOWE HAVE AWARDS THAT WEGIVE NIT

1232
00:49:04,280 --> 00:49:05,880
WE GIVE EVERY YEAR FOR AN

1233
00:49:05,880 --> 00:49:09,280
INNOVATION AWARDS TO TRY TO

1234
00:49:09,280 --> 00:49:10,480
ENCOURAGE TRANS NIH

1235
00:49:10,480 --> 00:49:11,400
COLLABORATIONS BUT IT COULD BE

1236
00:49:11,400 --> 00:49:21,800
DONE ON A WIDER SCALE.

1237
00:49:22,520 --> 00:49:23,120
MARSHAL HAD TWO OR THROW PEOPLE

1238
00:49:23,120 --> 00:49:24,760
IN HIS LAB AND THEY COULD NOT

1239
00:49:24,760 --> 00:49:27,360
HAVE SOLVED ALL THE PROBLEMS

1240
00:49:27,360 --> 00:49:30,880
GIVEN WHAT HE HAD IN THE WAY OF

1241
00:49:30,880 --> 00:49:31,520
RESOURCES.

1242
00:49:31,520 --> 00:49:33,280
NIHERS FLOCKED TO HIS HELP AND A

1243
00:49:33,280 --> 00:49:35,120
DOZEN PEOPLE, VERY SENIOR PEOPLE

1244
00:49:35,120 --> 00:49:36,760
SAID, THE RESOURCE IN MY LAB ARE

1245
00:49:36,760 --> 00:49:37,960
AT YOUR COMMAND.

1246
00:49:37,960 --> 00:49:40,960
LET'S DO THIS, LET'S GET THIS

1247
00:49:40,960 --> 00:49:41,520
DONE.

1248
00:49:41,520 --> 00:49:43,360
AND SO WE NOW HAVE GENETIC CODE

1249
00:49:43,360 --> 00:49:45,080
AND HE DID IT IN SHORT ORDER.

1250
00:49:45,080 --> 00:49:46,640
THAT WAS A GREAT EXAMPLE OF

1251
00:49:46,640 --> 00:49:48,040
PEOPLE AT NIH COMING TOGETHER TO

1252
00:49:48,040 --> 00:49:50,840
SOLVE A REALLY IMPORTANT

1253
00:49:50,840 --> 00:49:51,240
PROBLEM.

1254
00:49:51,240 --> 00:49:52,400
I WARRANT THERE ARE OTHER SUCH

1255
00:49:52,400 --> 00:49:53,560
PROBLEMS THAT WE CAN DO A BETTER

1256
00:49:53,560 --> 00:49:55,720
JOB OF COMING TOGETHER ON AND

1257
00:49:55,720 --> 00:49:56,360
SOLVING.

1258
00:49:56,360 --> 00:49:57,280
SO, WE'VE BEEN THINKING ABOUT

1259
00:49:57,280 --> 00:49:59,320
WAYS TO ENCOURAGE COLLABORATIONS

1260
00:49:59,320 --> 00:50:01,320
AND I MENTIONED SOME OF THE

1261
00:50:01,320 --> 00:50:02,800
THINGS IN MY TALK.

1262
00:50:02,800 --> 00:50:05,520
AND THEN FINALLY, BY NO MEANS

1263
00:50:05,520 --> 00:50:07,160
LEAST, WE REALLY HAVE TO DO A

1264
00:50:07,160 --> 00:50:10,120
MUCH BETTER JOB AT IMPROVING THE

1265
00:50:10,120 --> 00:50:11,400
DIVERSITY, EQUITY INCLUSION AND

1266
00:50:11,400 --> 00:50:13,560
ACCESSIBILITY AT THE NIH.

1267
00:50:13,560 --> 00:50:17,800
WE ARE TRYING VERY HARD TO

1268
00:50:17,800 --> 00:50:19,000
RECRUIT PEOPLE WITH A DEDICATION

1269
00:50:19,000 --> 00:50:20,880
TO THIS ISSUE AND THE

1270
00:50:20,880 --> 00:50:22,440
DISTINGUISHED SCHOLARS PROBLEM

1271
00:50:22,440 --> 00:50:24,080
IS AN EXAMPLE AND WE'VE EXTENDED

1272
00:50:24,080 --> 00:50:26,440
IT NOW TO SENIOR FOLKS.

1273
00:50:26,440 --> 00:50:29,120
IT'S A REALLY BIG PROBLEM.

1274
00:50:29,120 --> 00:50:30,840
THERE ARE MANY, MANY TALENTED

1275
00:50:30,840 --> 00:50:32,160
PEOPLE OUT THERE WHO WOULD COME

1276
00:50:32,160 --> 00:50:33,360
TO WORK AT THE NIH.

1277
00:50:33,360 --> 00:50:34,800
WE NEED TO FIND THEM AND

1278
00:50:34,800 --> 00:50:37,880
INTEGRATE THEM FULLY IN OUR

1279
00:50:37,880 --> 00:50:40,000
ACTIVITIES AND IN SOME WAYS, WE

1280
00:50:40,000 --> 00:50:41,160
MAY NEED TO CHANGE THE CULTURE

1281
00:50:41,160 --> 00:50:42,240
OF NIH.

1282
00:50:42,240 --> 00:50:44,240
UNITE HAS BEEN DOING A GREAT JOB

1283
00:50:44,240 --> 00:50:45,680
OF IDENTIFYING BARRIERS THAT WE

1284
00:50:45,680 --> 00:50:48,560
ARE OURSELVES HAVE CREATED, TO

1285
00:50:48,560 --> 00:50:50,440
THAT DIVERSITY THAT WE WANT TO

1286
00:50:50,440 --> 00:50:50,640
HAVE.

1287
00:50:50,640 --> 00:50:52,800
ALL OF THOSE ARE GOING TO

1288
00:50:52,800 --> 00:50:54,600
ACQUIRE A LOT OF ATTENTION AND

1289
00:50:54,600 --> 00:50:55,800
INTEREST AND EVERYBODY SORT OF

1290
00:50:55,800 --> 00:50:57,160
PULLING TOGETHER TO GET THIS

1291
00:50:57,160 --> 00:50:57,520
DONE.

1292
00:50:57,520 --> 00:50:59,080
SO THOSE ARE THE FOUR KIND OF

1293
00:50:59,080 --> 00:51:03,640
MAJOR AREAS, MAYBE MORE THAN YOU

1294
00:51:03,640 --> 00:51:04,440
WANTED TO HEAR.

1295
00:51:04,440 --> 00:51:06,120
THEY'RE RIGHT AT THE TIP OF MY

1296
00:51:06,120 --> 00:51:06,360
TONGUE.

1297
00:51:06,360 --> 00:51:08,040
READ IT IN THE CATALYST YOU WILL

1298
00:51:08,040 --> 00:51:09,600
HEAR MORE ABOUT IT.

1299
00:51:09,600 --> 00:51:11,280
>> I FEEL FORTUNATE LIKE I
ASKED

1300
00:51:11,280 --> 00:51:14,600
THE RIGHT QUESTION AND ARE

1301
00:51:14,600 --> 00:51:16,080
SPENCE IS EACH AND EVERY ONE OF

1302
00:51:16,080 --> 00:51:22,160
THE TOPICS THAT YOU RAISED IN

1303
00:51:22,160 --> 00:51:25,240
YOUR ITEMS RESINATES WITH ME SO

1304
00:51:25,240 --> 00:51:26,880
I THINK THOSE ARE ABSOLUTELY

1305
00:51:26,880 --> 00:51:27,480
SPOT ON.

1306
00:51:27,480 --> 00:51:28,880
WE HAVE SOME QUESTIONS FROM THE

1307
00:51:28,880 --> 00:51:31,000
AUDIENCE SO I WANT TO GIVE

1308
00:51:31,000 --> 00:51:32,760
INDIVIDUALS THEIR OPPORTUNITY TO

1309
00:51:32,760 --> 00:51:34,280
ASK YOU THEIR TARGETED

1310
00:51:34,280 --> 00:51:34,560
QUESTIONS.

1311
00:51:34,560 --> 00:51:38,000
WE HAVE A QUESTION FROM AN

1312
00:51:38,000 --> 00:51:39,120
AUDIENCE MEMBER AND PLEASE

1313
00:51:39,120 --> 00:51:41,720
FORGIVE ME IF I MISPRONOUNCED

1314
00:51:41,720 --> 00:51:46,640
YOUR NAME.

1315
00:51:46,640 --> 00:51:51,520
IT'S SIDAR HANAHLIE, CAN YOU PUT

1316
00:51:51,520 --> 00:51:54,280
A NUMBER ON THE FRACTION OF ALL

1317
00:51:54,280 --> 00:51:58,080
DRUG RESISTANT CASES IN THE

1318
00:51:58,080 --> 00:52:00,600
CLINIC, MEANING FOR CANCER

1319
00:52:00,600 --> 00:52:03,360
RESISTANCE, THAT CAN BE

1320
00:52:03,360 --> 00:52:05,240
EXPLAINED BY THE RESISTANCE

1321
00:52:05,240 --> 00:52:07,120
MECHANISMS THAT ARE DISCUSSED IN

1322
00:52:07,120 --> 00:52:08,080
YOUR TALK?

1323
00:52:08,080 --> 00:52:10,400
>> SO, FOR INDIVIDUAL
TUMORS WE

1324
00:52:10,400 --> 00:52:11,240
HAVE SOME IDEA.

1325
00:52:11,240 --> 00:52:14,480
I'LL GIVE YOU SOME EXAMPLES.

1326
00:52:14,480 --> 00:52:16,920
SO, FOR OVARIAN CANCER, WHAT

1327
00:52:16,920 --> 00:52:18,120
HAPPENED, IT'S AN INTERESTING

1328
00:52:18,120 --> 00:52:20,320
TUMOR MOST PATIENTS PRESENT WITH

1329
00:52:20,320 --> 00:52:22,960
STAGE THREE OR FOUR DISEASE IT'S

1330
00:52:22,960 --> 00:52:25,200
SPREAD AND IT IS RESPONSIVE TO

1331
00:52:25,200 --> 00:52:28,000
CHEMOTHERAPY AND CHEMOTHERAPY

1332
00:52:28,000 --> 00:52:30,240
INCLUDES FIRST-LINE CHEMOTHERAPY

1333
00:52:30,240 --> 00:52:40,800
TWO DRUGS AND ONE OF PLAXOL AND

1334
00:52:41,400 --> 00:52:44,640
RESISTANCE DEVELOPS IN FIRST OF

1335
00:52:44,640 --> 00:52:46,160
ALL, HALF THE PATIENTS DO

1336
00:52:46,160 --> 00:52:47,000
RESPOND THAT WELL.

1337
00:52:47,000 --> 00:52:49,240
OF THOSE THAT RESPOND RESISTANCE

1338
00:52:49,240 --> 00:52:50,320
WILL DEVELOP IN HALF OF THOSE

1339
00:52:50,320 --> 00:52:52,080
AGAIN SO ONLY ABOUT 25% OF THE

1340
00:52:52,080 --> 00:52:54,120
PEOPLE WILL SURVIVE WITH STAGE 4

1341
00:52:54,120 --> 00:52:57,320
OVARIAN CANCER SO IT'S A LETHAL

1342
00:52:57,320 --> 00:52:57,920
DISEASE.

1343
00:52:57,920 --> 00:52:59,360
RESISTANCE SEEMS TO BE THE KEY

1344
00:52:59,360 --> 00:53:02,320
TO UNDERSTANDING WHAT GOES ON

1345
00:53:02,320 --> 00:53:02,680
THERE.

1346
00:53:02,680 --> 00:53:04,080
AMONG PATIENTS WHO HAVE

1347
00:53:04,080 --> 00:53:06,200
RESPONDED INITIALLY, AND THEN

1348
00:53:06,200 --> 00:53:07,200
RELAPSED, WHICH IS ABOUT HALF OF

1349
00:53:07,200 --> 00:53:10,880
THE PEOPLE WHO RESPOND, THERE

1350
00:53:10,880 --> 00:53:13,800
ARE REARRANGEMENTS INVOLVING

1351
00:53:13,800 --> 00:53:18,600
P-LACK PRE TEEN IN 10% OF THOSE

1352
00:53:18,600 --> 00:53:19,080
CASES.

1353
00:53:19,080 --> 00:53:21,080
SO, IN REARRANGEMENTS WHICH A

1354
00:53:21,080 --> 00:53:22,640
PROMOTER FROM UPSTREAM HAS

1355
00:53:22,640 --> 00:53:24,160
BROUGHT DOWNSTREAM TURNING ON

1356
00:53:24,160 --> 00:53:25,720
EXPRESSION OF THE GONE IT'S

1357
00:53:25,720 --> 00:53:27,280
PRETTY GOOD EVIDENCE IT'S BEING

1358
00:53:27,280 --> 00:53:28,680
SELECTED FOR AND THAT IS ONE OF

1359
00:53:28,680 --> 00:53:32,080
THE MAIN REASONS FOR THE

1360
00:53:32,080 --> 00:53:32,520
RESISTANCE.

1361
00:53:32,520 --> 00:53:33,960
IT'S MORE COMPLICATED BECAUSE

1362
00:53:33,960 --> 00:53:35,000
THERE ARE TWO DRUGS AND THEY

1363
00:53:35,000 --> 00:53:36,720
HAVE TO BE RESISTANT TO PLATINUM

1364
00:53:36,720 --> 00:53:38,680
AS WELL AND IT'S A MORE

1365
00:53:38,680 --> 00:53:39,640
COMPLICATED STORY.

1366
00:53:39,640 --> 00:53:45,280
SO I THINK THE ANSWER IS 10% OF

1367
00:53:45,280 --> 00:53:47,040
THE 50% RESPONDING PROBABLY ARE

1368
00:53:47,040 --> 00:53:50,840
REIS THE ANT ON THE BASES OF P

1369
00:53:50,840 --> 00:53:52,280
LACK OF PROTEIN.

1370
00:53:52,280 --> 00:53:58,280
AML IS ANOTHER DISEASE WE'VE

1371
00:53:58,280 --> 00:53:58,880
STUDIED IN DETAIL.

1372
00:53:58,880 --> 00:54:02,040
THE PATIENTS THAT DON'T RESPOND

1373
00:54:02,040 --> 00:54:06,640
TO TREATMENT THERE AND A PTP

1374
00:54:06,640 --> 00:54:06,960
SUBSTRATE.

1375
00:54:06,960 --> 00:54:09,000
A SUBSET OF THOSE PATIENTS ABOUT

1376
00:54:09,000 --> 00:54:11,360
30% OF INRESISTANT AND ABOUT A

1377
00:54:11,360 --> 00:54:19,840
THIRD OF THOSE ARE OR EXPRESS

1378
00:54:19,840 --> 00:54:20,120
ABDG2.

1379
00:54:20,120 --> 00:54:21,640
IT LOOKS AS IF WE'RE TALKING

1380
00:54:21,640 --> 00:54:27,040
ABOUT A SUBSET OF A SUBSET THAT

1381
00:54:27,040 --> 00:54:29,160
ARE CLEARLY DUE IN MANY CANCERS

1382
00:54:29,160 --> 00:54:30,520
TO PGP EXPRESSION.

1383
00:54:30,520 --> 00:54:32,360
IT'S PRESSED IN OVER 50% OF

1384
00:54:32,360 --> 00:54:34,160
TUMORS AND CONTRIBUTES TO

1385
00:54:34,160 --> 00:54:36,320
RESISTANCE, IT MAY NOT BE THE

1386
00:54:36,320 --> 00:54:37,720
ULTIMATE CAUSE OF RESISTANCE AT

1387
00:54:37,720 --> 00:54:38,920
THE END OF THE TREATMENT

1388
00:54:38,920 --> 00:54:39,400
SCHEDULE.

1389
00:54:39,400 --> 00:54:41,920
SO, IT PLAYS A ROLE AND WE NEED

1390
00:54:41,920 --> 00:54:43,680
TO GO BACK AND DO MORE DETAILS

1391
00:54:43,680 --> 00:54:45,200
TO STUDY TO FIGURE OUT WHETHER

1392
00:54:45,200 --> 00:54:47,480
IT'S WORTH ENTERSER SEENING BY

1393
00:54:47,480 --> 00:54:55,000
INTERVENING BUT EACH TUMORIS DI.

1394
00:54:55,000 --> 00:54:56,840
>> THANK YOU FOR THAT
RESPONSE.

1395
00:54:56,840 --> 00:54:59,480
WE HAVE ANOTHER QUESTION FROM AN

1396
00:54:59,480 --> 00:55:00,920
AUDIENCE MEMBER HOWARD YOUNG.

1397
00:55:00,920 --> 00:55:04,280
WHO WANTS TO KNOW A LITTLE BIT

1398
00:55:04,280 --> 00:55:07,000
ABOUT YOUR GREATEST

1399
00:55:07,000 --> 00:55:09,560
UNACCOMPLISHED GOAL AT NIH?

1400
00:55:09,560 --> 00:55:13,800
>> IN THE LAB OR AT THE
NIH?

1401
00:55:13,800 --> 00:55:14,200
 [LAUGHTER] 

1402
00:55:14,200 --> 00:55:16,440
>> THE LAB IS EASY, RIGHT.

1403
00:55:16,440 --> 00:55:17,960
THE NIH --

1404
00:55:17,960 --> 00:55:20,320
>> AT YOUR DISCRETION.

1405
00:55:20,320 --> 00:55:22,920
IT DOESN'T SAY THE LAB, IT SAYS

1406
00:55:22,920 --> 00:55:23,400
AT NIH.

1407
00:55:23,400 --> 00:55:29,760
>> I THINK I'M 80% OF MY
EFFORT

1408
00:55:29,760 --> 00:55:32,000
IS GOING TO CHANGING CULTURE IN

1409
00:55:32,000 --> 00:55:33,280
A WAY THAT ACCEPTS DIVERSITY AS

1410
00:55:33,280 --> 00:55:35,600
BEING AN ESSENTIAL ELEMENT OF

1411
00:55:35,600 --> 00:55:36,680
OUTSTANDING SCIENCE.

1412
00:55:36,680 --> 00:55:37,840
AND THAT REQUIRES A CHANGE IN

1413
00:55:37,840 --> 00:55:39,480
THE WAY SOME PEOPLE THINK ABOUT

1414
00:55:39,480 --> 00:55:41,120
WHAT THEY DO, CHANGE IN THE WAY

1415
00:55:41,120 --> 00:55:44,720
WE DO BUSINESS, AND A CHANGE IN

1416
00:55:44,720 --> 00:55:46,040
THE PEOPLE WHO ARE WORKING AT

1417
00:55:46,040 --> 00:55:47,960
THE NIH AND AWFUL WHICH WILL

1418
00:55:47,960 --> 00:55:49,800
HAPPEN IN TIME AND I WILL BE

1419
00:55:49,800 --> 00:55:51,000
PATIENT AND I HOPE THAT OTHERS

1420
00:55:51,000 --> 00:55:52,600
WHO ARE REALLY INVOLVED DEEPLY

1421
00:55:52,600 --> 00:55:54,600
IN THIS WILL BE BUT WE NEED HELP

1422
00:55:54,600 --> 00:55:56,960
WITH EVERYBODY AT NIH TO DO

1423
00:55:56,960 --> 00:55:57,160
THIS.

1424
00:55:57,160 --> 00:55:57,920
>> PERFECT.

1425
00:55:57,920 --> 00:56:00,160
WE HAVE A QUESTION, I WANT TO

1426
00:56:00,160 --> 00:56:03,560
GET A COUPLE HERE.

1427
00:56:03,560 --> 00:56:05,680
WE HAVE A QUESTION FROM KEN

1428
00:56:05,680 --> 00:56:07,720
KRAMER WHO WANTS TO KNOW -- HOW

1429
00:56:07,720 --> 00:56:09,960
YOU ARE ABLE TO KEEP YOUR

1430
00:56:09,960 --> 00:56:12,320
RESEARCH EFFORTS SEPARATE FROM

1431
00:56:12,320 --> 00:56:14,480
POLITICAL INTERFERENCE SO, YOU

1432
00:56:14,480 --> 00:56:18,120
SHOWED A DIAGRAM WITH A LOT OF

1433
00:56:18,120 --> 00:56:21,480
INTERSECTING PIECES AND YOU HAVE

1434
00:56:21,480 --> 00:56:22,560
A LOT OF TOUCH POINTS.

1435
00:56:22,560 --> 00:56:24,040
DOES THAT INTER VEER YOU WITH

1436
00:56:24,040 --> 00:56:25,160
YOUR RESEARCH EFFORTS?

1437
00:56:25,160 --> 00:56:26,680
>> SO,  I'M GOING TO KIND
OF

1438
00:56:26,680 --> 00:56:28,440
CHANGE THE QUESTION, I MEAN, THE

1439
00:56:28,440 --> 00:56:30,400
HARD PART IS AVOIDING CONFLICT

1440
00:56:30,400 --> 00:56:32,320
OF INTEREST FOR ME.

1441
00:56:32,320 --> 00:56:34,000
SO, BECAUSE I'M CAPABLE OF

1442
00:56:34,000 --> 00:56:36,080
CHANGING POLICY AT NIH, I HAVE

1443
00:56:36,080 --> 00:56:36,680
TO BE CAREFUL NOT TO DO THINGS

1444
00:56:36,680 --> 00:56:41,200
THAT ARE IN MY SELF-INTEREST.

1445
00:56:41,200 --> 00:56:43,880
AND SO N.

1446
00:56:43,880 --> 00:56:46,880
>> Catherine: WILL
FREQUENTLY

1447
00:56:46,880 --> 00:56:47,120
COMPLAIN.

1448
00:56:47,120 --> 00:56:48,280
RICK CLAUSENER USED TO EXPLAIN

1449
00:56:48,280 --> 00:56:50,800
TO ME ABOUT VARIOUS THINGS SAID

1450
00:56:50,800 --> 00:56:53,920
THE PROBLEM WITH YOU BE DDIR YOU

1451
00:56:53,920 --> 00:56:55,320
FEEL LIKE YOU HAVE TO BE EVEN

1452
00:56:55,320 --> 00:56:58,560
HANDED IN WHAT YOU DO.

1453
00:56:58,560 --> 00:57:00,480
SO THAT IS CERTAINLY BEEN AN

1454
00:57:00,480 --> 00:57:02,720
ISSUE AND I REALLY THINK ABOUT

1455
00:57:02,720 --> 00:57:04,000
THIS ALL THE TIME THAT WE NEED

1456
00:57:04,000 --> 00:57:06,280
TO BE FAIR TO THE SMALLER

1457
00:57:06,280 --> 00:57:10,440
INSTITUTES, TO THE BIGGER ONES

1458
00:57:10,440 --> 00:57:11,760
AND THAT REQUIRES A LOT OF

1459
00:57:11,760 --> 00:57:14,480
EFFORT AND A LOT OF THOUGHT.

1460
00:57:14,480 --> 00:57:15,960
AND I NEVER WOULD DO ANYTHING IN

1461
00:57:15,960 --> 00:57:18,520
THE WAY OF POLICY THAT WOULD

1462
00:57:18,520 --> 00:57:20,520
EFFECT MY ABILITY TO DO RESEARCH

1463
00:57:20,520 --> 00:57:22,600
EXCEPT TO PROVIDE AN ENVIRONMENT

1464
00:57:22,600 --> 00:57:23,760
IN WHICH EVERYBODY CAN DO

1465
00:57:23,760 --> 00:57:26,080
RESEARCH SO THAT WOULD BE MY

1466
00:57:26,080 --> 00:57:26,280
GOAL.

1467
00:57:26,280 --> 00:57:31,080
THANK YOU FOR THAT TRICKY

1468
00:57:31,080 --> 00:57:31,360
QUESTION.

1469
00:57:31,360 --> 00:57:33,280
 [LAUGHTER] 

1470
00:57:33,280 --> 00:57:34,200
WHILE WE'RE WAITING FOR

1471
00:57:34,200 --> 00:57:35,280
QUESTIONS, I'M GOING TO SPEAK

1472
00:57:35,280 --> 00:57:40,360
ANOTHER ONE OF MY QUESTIONS.

1473
00:57:40,360 --> 00:57:45,840
MY QUESTION RELATES TO BALANCING

1474
00:57:45,840 --> 00:57:49,720
A NEED FOR POLICY AND OVERSIGHT

1475
00:57:49,720 --> 00:57:53,520
WITH A NEED FOR NIMBLENESS TO

1476
00:57:53,520 --> 00:57:56,520
ADAPT AND INNOVATE.

1477
00:57:56,520 --> 00:58:01,520
AND DO YOU HAVE THOUGHTS ABOUT

1478
00:58:01,520 --> 00:58:04,560
THAT BALANCE AND HOW WELL WE'RE

1479
00:58:04,560 --> 00:58:06,360
ACHIEVING THAT BALANCE IN THE

1480
00:58:06,360 --> 00:58:08,000
INTRAMURAL AND EXTRAMURAL SPACES

1481
00:58:08,000 --> 00:58:10,480
AND ANOTHER WAY OF FRAMING THAT

1482
00:58:10,480 --> 00:58:17,880
IS ARE WE OVER INCUMBERED WITH D

1483
00:58:17,880 --> 00:58:20,160
BUREAUCRATIC REQUIREMENTS THAT

1484
00:58:20,160 --> 00:58:22,600
ARE EFFECTING OUR NIMBLENESS AND

1485
00:58:22,600 --> 00:58:23,040
OWE HAVE A TIVENESS.

1486
00:58:23,040 --> 00:58:25,000
>> THAT'S A VERY GOOD
QUESTION.

1487
00:58:25,000 --> 00:58:28,240
THE BOTTOM-LINE ANSWER IS YES.

1488
00:58:28,240 --> 00:58:31,000
WE ARE OVER INCUMBERED.

1489
00:58:31,000 --> 00:58:33,680
I LIVE AT THE INNER FACE BETWEEN

1490
00:58:33,680 --> 00:58:37,040
THE LEGAL REQUIREMENTS, THE

1491
00:58:37,040 --> 00:58:37,840
COMPLIANCE REQUIREMENT AND

1492
00:58:37,840 --> 00:58:39,160
TRYING TO ADAPT THOSE AND

1493
00:58:39,160 --> 00:58:40,400
EXPLAIN THOSE TO THE SCIENTIFIC

1494
00:58:40,400 --> 00:58:40,600
STAFF.

1495
00:58:40,600 --> 00:58:41,800
WE CAN'T IGNORE THEM.

1496
00:58:41,800 --> 00:58:43,880
THEY'RE LEGAL REQUIREMENTS.

1497
00:58:43,880 --> 00:58:46,120
SOME OF THEM MAKE REALLY GOOD

1498
00:58:46,120 --> 00:58:46,520
SENSE.

1499
00:58:46,520 --> 00:58:48,720
SOME OF THEM RELATE TO SINGLE

1500
00:58:48,720 --> 00:58:50,040
INCIDENTS THAT HAPPEN 20 YEARS

1501
00:58:50,040 --> 00:58:51,640
AGO THAT HAVEN'T HAPPENED SINCE

1502
00:58:51,640 --> 00:58:55,720
BUT HAVE INCUMBERED OF US DOING

1503
00:58:55,720 --> 00:58:58,440
A WAY OF BUSINESS.

1504
00:58:58,440 --> 00:59:02,960
THE ANSWER IS THAT BUREAUCRACY

1505
00:59:02,960 --> 00:59:03,360
SAY PROBLEM.

1506
00:59:03,360 --> 00:59:05,040
IT'S A PROBLEM FOR AWFUL NIH.

1507
00:59:05,040 --> 00:59:10,200
YOU'VE HEARD ABOUT ARPA-H, AND

1508
00:59:10,200 --> 00:59:12,120
IT'S INTENT WAS TO CUT THROUGH

1509
00:59:12,120 --> 00:59:15,000
SOME OF THE BUREAUCRACY AND GET

1510
00:59:15,000 --> 00:59:16,200
FUNDING TO IMPORTANT PROJECTS

1511
00:59:16,200 --> 00:59:18,520
THAT NEED TO MOVE FORWARD

1512
00:59:18,520 --> 00:59:18,760
QUICKLY.

1513
00:59:18,760 --> 00:59:20,440
IT REMAINS TO BE SEEN WHETHER IT

1514
00:59:20,440 --> 00:59:22,920
WILL MAKE ANY DIFFERENCE.

1515
00:59:22,920 --> 00:59:25,880
ONE OF THE PROBLEMS IS IT'S

1516
00:59:25,880 --> 00:59:27,240
BEING SEPARATED FROM THE NIH SO

1517
00:59:27,240 --> 00:59:29,440
ALL THE EXPERIENCE, ALL THE

1518
00:59:29,440 --> 00:59:32,760
WONDERFUL TALENT OF NIH IS NOT

1519
00:59:32,760 --> 00:59:36,120
BEING BROUGHT NECESSARILY THE

1520
00:59:36,120 --> 00:59:39,760
BEAR ON ARPH-H.

1521
00:59:39,760 --> 00:59:42,320
IT SHOULD BE A RAPID RESPONSE

1522
00:59:42,320 --> 00:59:44,760
MECHANISM FOR DEALING WITH

1523
00:59:44,760 --> 00:59:46,520
PUBLIC-HEALTH ISSUES AND OUR

1524
00:59:46,520 --> 00:59:50,800
RESPONSE TO COVID-19 WAS

1525
00:59:50,800 --> 00:59:52,440
INSTANTANEOUS.

1526
00:59:52,440 --> 00:59:53,320
LITERALLY WITHIN WEEKS THERE WAS

1527
00:59:53,320 --> 00:59:57,040
A VACCINE DEVELOPED AT THE NIH

1528
00:59:57,040 --> 01:00:02,160
AND THIS IS MAZING AND 250P Is

1529
01:00:02,160 --> 01:00:04,680
ARE WORKING ON COVID AND MAKING

1530
01:00:04,680 --> 01:00:06,760
SUBSTANTIAL ADVANCE AND WE CAN

1531
01:00:06,760 --> 01:00:07,720
TURN ON TIME.

1532
01:00:07,720 --> 01:00:09,160
IT DIDN'T REQUIRE GETTING GRANT

1533
01:00:09,160 --> 01:00:16,760
MONEY OR ANYTHING ELSE.

1534
01:00:16,760 --> 01:00:19,480
IT'S I HOPE WHOEVER REPLACES ME

1535
01:00:19,480 --> 01:00:23,480
AND TO MAKE SURE THAT WHOEVER

1536
01:00:23,480 --> 01:00:25,720
COMES IN IS AWARE OF THOSE NEEDS

1537
01:00:25,720 --> 01:00:27,840
AND DAN, YOU COULDN'T BE MORE ON

1538
01:00:27,840 --> 01:00:29,040
TARGET IN SAYING WE HAVE TO

1539
01:00:29,040 --> 01:00:30,920
CLEAR AWAY UNNECESSARY

1540
01:00:30,920 --> 01:00:34,960
BUREAUCRACY AND EXPLAIN THE

1541
01:00:34,960 --> 01:00:41,680
BUREAUCRACY WE HAVE.

1542
01:00:41,680 --> 01:00:43,400
>> I WANT TO THANK YOU FOR
YOUR

1543
01:00:43,400 --> 01:00:44,320
THOUGHTFUL RESPONSE TO THAT

1544
01:00:44,320 --> 01:00:45,320
QUESTION AND ALL THE QUESTIONS

1545
01:00:45,320 --> 01:00:47,560
AND FOR YOUR EXCELLENT

1546
01:00:47,560 --> 01:00:53,000
PRESENTATION TODAY AND FOR YOUR

1547
01:00:53,000 --> 01:00:55,800
DECADES OF TRUE SERVICE.

1548
01:00:55,800 --> 01:00:58,080
WE'RE OUT OF TIME BUT THANK YOU

1549
01:00:58,080 --> 01:00:59,280
SO MUCH FOR EVERYTHING THAT YOU

1550
01:00:59,280 --> 00:00:00,000
DO FOR US.