I WANT TO TELL YOU ABOUT YOUR

PROGRAM, A CANCER VIRUS PROGRAM,

TO START WITH A VERY BRIEF

OVERVIEW, I'LL TRY TO GO THROUGH

THAT QUICKLY SINCE A COUPLE OF

POINTS HAVE BEEN COVERED BY

PREVIOUS SPEAKERS.

I WANT TO FOCUS ON A COUPLE OF

PROJECTS IN MY MIND (INAUDIBLE)

WHICH WE DO OUR WORK WHICH

INVOLVE A COMBINATION OF

INVESTIGATOR INITIATED RESEARCH

AND EXTENSIVE COLLABORATIVE

SUPPORT FROM OUR RESEARCH AND

PIs, AND AT THE END HIGHLIGHT

SPECIFIC NATURE OF SUPPORT FROM

SOME OF OUR CORES AND LEAF TIME

FOR QUESTIONS AND DISCUSSION.

IN TERMS OF THE ORIGINS OF OUR

PROGRAM, AS MANY ARE AWARE AT

NCI, I HOPE THIS ISN'T AN

AUDIENCE WHERE I HAVE TO JUSTIFY

WHY ARE YOU WORKING ON HIV AIDS

AT IF NATIONAL CANCER INSTITUTE.

THERE'S A LONG STANDING HISTORY

GOING BACK TO ANIMAL

RETROVIRUSES IN THE '70s AND

THAT'S THE ORIGIN OF OUR PROGRAM

AS WELL.

IN PARTICULAR, AT THE TIME

DIFFERENT CONTRACTORS SAIC, THE

INFRASTRUCTURE FOR LARGE SCALE

PROPAGATION AN PURIFICATION WITH

RETROVIRUSES ASSOCIATED WITH

CANCERS AND THAT WAS A VERY

PRODUCTIVE EXERCISE THAT

INFRASTRUCTURE WAS APPLIED TO

THE LARGE SCALE PROPAGATION OF

NEW HUMAN RETROVIRUSES FOR A

VARIETY OF DIFFERENT KINDS OF

STUDIES AND WHEN THE (INAUDIBLE)

FOR AGE WAS IDENTIFIED IN 384

MATERIAL WAS TRANSFERRED UP HERE

BECAUSE THAT'S WHERE THE

RESIDENT EXPERTISE WAS AND THE

OPPORTUNITY TO RESPOND AS YOU

HAVE HEARD RAPIDLY AND

DYNAMICALLY AND OVER THE COURSE

OF THE FIRST YEAR AFTER

RECEIVING THAT MATERIAL GREW UP

IN EXCESS OF 10,000-LITERS OF

PURIFIED VIRUS FROM THE LOW

INFECTED CELL, LYSATE AND

PROVIDED TO THE FIVE COMMERCIAL

LICENSEEES TO THE GOVERNMENT

PATENT WHICH GREATLY FACILITATED

THE DEVELOPMENT OF THE FIRST

GENERATION DIAGNOSTIC TEST FOR

BLOOD SCREENING WHERE THE FIRST

TEST WAS APPROVED.

AND LESS THAN A YEAR FROM TIME

WE RECEIVED THE MATERIAL.

IN TERMS OF EXPERTISE AROUND

THAT EXERCISE OR ANALYZING

RETROVIRUSES, NCI DECIDED IN

1987 TO FORM AN ENTERPRISE

CALLED THE AIDS VACCINE PROGRAM

UNDER LARRY ARTER WHICH

CONSISTED OF A RESEARCH

COMPONENT AND ONGOING FUNCTION

INCLUDING THE BASIC OPPORTUNITY

OF GROWING AND PURIFYING AND

CHARACTERIZING RETROVIRUSES.

THAT PROGRAM GREW AND FLOURISHED

OVER SEVERAL YEARS FOLLOWING A

RESEARCH AGENDA BEING

PERIODICALLY REVIEWED FOR OTHER

NCI PROGRAMS AND 2008 WE

ACTUALLY CHANGED OUR NAME

BECAUSE -- TO MORE ACCURATELY

REFLECT WHAT WE WERE DOING

THOUGH WE CONTINUE TO DO WORK ON

AIDS VACCINES, NOT TO BE

EXCLUSIVE FOCUS OF OUR WORK, WE

DO OTHER AIDS RELATED WORK WITH

THE INCORPORATION OF THAT WOULD

BE DOESN'T WORK ON HIF AT ALL

BUT WORKS ON HIV ASSOCIATED

MALIGNANCIES THOSE WITH SARCOMA

HERPES VIRUS, WE FELT IT A MORE

APPROPRIATE NAME N. 1995 THE

PROGRAM TOOK OVER AS DIRECTOR T

OF THE PROGRAM IN 2002, IN

CONJUNCTION WITH LARRY ARTHUR

ASSUMING RESPONSIBILITY FOR THE

OVERALL TECHNICAL SUPPORT

CONTRACT.

THE INVESTIGATOR INITIATED BASIC

AND APPLIED RESEARCH TO IMPROVE

DIAGNOSIS TREATMENT AND

INFECTION OF HIV AIDS WITH

CANCER ASSOCIATED VIRUSES.

A THING THAT'S DISTINGUISHES OUR

PROGRAM AND PROACTIVELY MAKING

IT AVAILABLE TO THE BROADER

RESEARCH IMMUNITY.

THIS IS IN A SENSE (INAUDIBLE)

FROM THE TIME IT WAS INITIATED

AND ONE I TRIED TO MAINTAIN AND

EXTEND.

TRY TO GIVE YOU EXAMPLES OF THAT

AS WE GO THROUGH.

IN TERMS OF WHAT WE DO,

INTEGRATED MULTI-DISCIPLINARY

PROGRAM OF BASIC AND APPLIED

VIROLOGY AND IN TERMS OF SCOPE,

THAT CAN EXTEND FROM VERY

FUNDAMENTAL STUDIES OF ANALYZING

THE EFFECTS OF A SINGLE POINT

MUTATION RETROVIRAL REPLICATION

FIND IN IN VITRO SYSTEMS THROUGH

TO ANALYSIS AND EVALUATION OF IN

VIVO PATHOGENESIS AN TESTING OF

VARIOUS (INAUDIBLE) AND

THERAPEUTIC MODALITIES IN

NON-HUMAN PRIMATE MODELS.

WEAPON A GROUP OF APPROXIMATELY

55 PEOPLE IN ANY GIVEN TIME

DIVIDED INTO FIVE RELATIVELY

SMALL PRINCIPLE INVESTIGATOR

RESEARCH SECTIONS, 8 RESEARCH

SUPPORT COURSE, COMPARED TO

OTHER ENTITIES HERE AND

ELSEWHERE.

ONE POINT IS THAT WE ARE 100%

SAIC STAFF.

WE CONDUCTED INVESTIGATOR

INITIATED RESEARCH BUT THE

COLLABORATIVE INTERACTION WITH

OTHER NCI INVESTIGATORS IN

PARTICULAR THE HIV DRUG

RESISTANCE PROGRAM.

YOU HEARD YOUR LAST NON-MITING

(INAUDIBLE) FROM THE ACTIVITIES

VACCINE BRANCH AND HIV AND AIDS

MALIGNANCY BRANCH.

ELSEWHERE IN NIH WE WORK CLOSELY

WITH A NUMBER OF NIAID LABS

INCLUDING VEHICLES AT THE BRC

AND MOLECULAR BIOLOGY AND THE

LABORATORY OF IMMUNOREGULATION.

YOU HER FROM CLIFF LANE WITH HIS

VISION WE'RE HELPING EXPERTISE

ON NON-HUMAN PRIMATE STUDIES AND

OTHER WORK.

AS CRAIG ALLUDED TO OUR FUNDING

AND DAY TO DAY ADMINISTRATIVE

OVERSIGHT IS THROUGH HIS OFFICE.

AND ALSO DESCRIBED OUR PIs AND

OUR CORES ARE SUBJECTED TO

(INAUDIBLE) UNDER AUSPICES OF

BRC OFFICE TESTIFY INVESTIGATOR.

RELATIVE TO MY EXPERIENCE AND

ACADEMIA AND WHERE I WORKED WE

HAVE SMALL RESEARCH GROUPS

TYPICALLY TWO OR THREE PEOPLE.

EXPERTISE BUT WE GET A LOT DONE

BECAUSE WE'RE AGAIN IN MY

EXPERIENCE THE MOST

EXTRAORDINARILY AND INTERACTIVE

AND SYNERGISTIC (INAUDIBLE)

ASSOCIATED WITH.

IN TERMS OF CORES WHERE THOSE

COME FROM IS BASICALLY ARISING

FROM AN INTERNAL NEED FROM PI

DRIVEN RESEARCH TO DEVELOP

CAPABILITIES FOR THAT RESEARCH

AND IF THERE IS SUFFICIENT

DEMAND FROM THAT PARTICULARLY

FROM SOURCES OUTSIDE THE

PROGRAM, WE THEN APPROACH NCI TO

SEE THAT'S SOMETHING NCI WOULD

BE INTERESTED AND ESTABLISHING

AS A CAPABILITY TO OFFER OTHER

INVESTIGATORS.

MANY CAPABILITIES ARE ONES THAT

AGAIN THAT ROSE FROM INTERNAL

NEEDS BUT ROSE FROM EXTERNAL

NEEDS AS WELL AND SOME UNIQUE

ENOUGH FOR EXTENSIVE DEMAND.

SO WE HAVE A LOT OF EXTENSIVE

INTERACTIONS WITH PEOPLE BOTH

WITHIN NIH AND IN PARTICULAR IN

THE EXTRAMURAL COMMUNITY.

WE REALLY TACKEN TO HEART THE

CONCEPT OF THIS BEING AN FFRDC

AND NATIONAL RESOURCE AND WE SEE

OURSELVES THAT WAY AND PROACTIVE

ABOUT SHARING OUR CAPABILITIES.

ONE OF THE THINGS THAT MAKES US

A LITTLE BIT UNIQUE IS THAT

WITHIN OUR PROGRAM WE HAVE A

BROAD RANGE OF COMMENTARY

EXPERTISE THAT ADDS TOGETHER AS

A WHOLE THAT IS MORE THAN THE

SUM OF ITS PARTS.

IN PARTICULAR NON-HUMAN PRIMATE

WORK WHICH I'M GOING TO TOUCH ON

NOW WE HAVE NCI HUMAN PRIMATE

FACILITY ON THE BETHESDA CAMPUS.

WE HAVE WHAT IS PROBABLY THE

MOST KINDLY REGARDED FACILITY

FOR DOING NON-HUMAN PRIMATE

VIRAL LOAD MONITORING,

SPECIALIZED ASSAY, GREAT

EXPERTISE FOR TISSUE BASED

ANALYSES USING

IMMUNOHISTOCHEMISTRY AND IN SITU

HYBRIDIZATION AND SEQUENCE BASED

ANALYSIS AB FLOW CYTOMETRY AND

COMBINING THESE THINGS TOGETHER.

TO ILLUSTRATE THIS I WANT TO

TALK TWO PROJECTS.

FIRST IS INTERNALLY, BY YOUNGER

INVESTIGATORS AND (INAUDIBLE)

EXAMINING SOME OF THE BASIC

ASPECTS OF MUCOSE OOL

TRANSMISSION OF RETROVIRUSES.

THEN TALK ABOUT HOW THAT WORK

HAS LED AND BEING APPLIED BY

OTHERS NM EXTRAMURAL COMMUNITY

AND OTHER VERY INTERESTING

VACCINE APPROACH.

MOST HIV TRANSMISSIONS ARE MIEW

CESSAL BUT HOW THAT HAPPENS IS

FAIRLY OBSCURE AND SOMETHING

THAT IS NOT AMENABLE TO ANALYSIS

IN THE CLINICAL SETTING.

YOU HAVE THE OPPORTUNITY TO

CHALLENGE MODELS, AT A KNOWN

DOSE WITH DEFINED TIMING AND

KNOWN ROUTE BECOMES INCREDIBLY

VALUABLE IF YOU CAN DO TIME

SAMPLING OF BLOOD AN TISSUE

INCLUDING US TO SCHEDULE

EUTHANASIA AND TISSUE ANALYSIS.

SO WE HAVE BEEN INTERESTED TO

TRY TO TAKE ADVANTAGE OF THIS TO

TRY TO COMPREHENSIVELY ADDRESS

KEY QUESTIONS, WHETHER THE CELLS

ARE INFECTED, KIN I

>> MS. KINSEY: TICKS OF

INFECTION, ROUTE OF INFECTION.

AND SO ON -- KINETICS OF

INFECTION AND SO ON.

SO THE APPROACH WE HAVE TAKEN TO

ADDRESS THIS IS TO DO RIGOROUS

SACRIFICE STUDIES WITH

COMPREHENSIVE TISSUE ANALYSIS

WITH MULTI-MODAL ANALYSES AND IN

PARTICULAR TO TAKE ADVANTAGE OF

A CLEVER IDEA THAT BRANDON CAME

UP WITH.

WHEN YOU DO A QUASI SPECIES OF

VIRUS BRANDON WHEN WORKING WITH

BEATRICE HAHN DEMONSTRATED IN

MOST CLINICAL TRANSMISSIONS

INFECTION OCCURS FROM USUALLY

ONLY ONE OR A FEW (INAUDIBLE).

AND SINCE HE CAME HERE TO JOIN

US HE EXTENDED THAT WORK AND

SAID YOU CAN SET UP CONDITIONS

LIKE THAT BUT YOU SEE ONE OR

ANOTHER VIRUS GOING ACROSS, YOU

CAN NEVER BE SURE, DUE TO THE

BIOLOGICAL PROPERTIES AN

DIFFERENCES BETWEEN ONE VIRUS OR

ANOTHER OR IS IT JUST A

STOCHASTIC PHENOMENON AND THE

IMPLICATIONS OF THAT ANSWER ARE

IMPORTANT FOR VACCINE DESIGN AND

ANOTHER PROPHYLACTIC MODALITY.

WHAT BRANDON CAME UP WITH WAS AN

APPROACH TO GENERATE IDENTICAL

INFECTIOUS CLONES, THE BEST

CHARACTERIZE (INAUDIBLE)

EXTENSIVELY CHARACTERIZED.

HE DID THAT BY INTRODUCING A

SERIES OF POINT MUTATIONS TO THE

(INAUDIBLE) REGION.

ALL OTHER MUTATIONS HE

INTRODUCED TO GENERATE VARIANTS

ARE VARIATIONS THAT OCCUR

NATURALLY, ALL REPLICATION

CONFIDENT, THEY ALL HAVE

COMPARABLE FITNESS IN VITRO BUT

THEY'RE DISCRIM NABL IN VITRO

AND IN VIVO, THE CONCEPT IS

STRAIGHT FORWARD.

YOU TAKE THESE VIRUSES, MIX THEM

TOGETHER, EQUAL INFECTIVITY

RATIOS AND DO A VAGINAL

CHALLENGE AND SERIALLY EUTHANIZE

AND NECROPSY MACAQUES AND

SUBJECT THEM TO TISSUE ANALYSIS.

THAT INCLUDES LIMITING DELUSION

SINGLE GENOME AMPLIFICATION AND

ANALYSIS OF THE TYPE SO THE

BASIC IDEA IS YOU CAN

COMPREHENSIVELY SAMPLE POST

CHALLENGE THE ENTIRE FEMALE

GENITAL TRACT AND YOU CAN THEN

COMPREHENSIVELY SAMPLE ALL THE

DIFFERENT REGIONS OF THAT.

AND SUBJECT THAT TO A VARIETY OF

DIFFERENCE ANALYSES.

WE CAN TAKE A SECTION AND

ANALYZE BY IN SITU HYBRIDIZATION

IMMUNOHISTOCHEMISTRY.

WE CAN TAKE ANOTHER SECTION FROM

THE SAME OR DIFFERENCE LOCATION

AND ANALYZE BY REAL TIME PCR.

AND LASER CAPTURE

MICRODISSECTION OF IN SITU

HYBRIDIZATION OR

IMMUNOHISTOCHEMISTRY STAIN

SECTIONS TO FOCUS THE WHOLE

ANALYSIS VIRAL LOAD IN SECTIONS

LIKE THAT.

WHEN WE DO THAT, WITH THE TAG

VIRUSES WE CAN DEFINE GENETIC

COMPOSITION OF THE VIRUS THAT WE

SEE BY IMMUNOHISTOCHEMISTRY AND

I WANT TO SHOW YOU IN THE

INTEREST O TIME A SINGLE EXAMPLE

A LARGE ONGOING STUDY THAT WE

HAVE IN PROCESS, THIS IS AN

ANIMAL EUTHANIZED IN STUDIES

FIVE DAYS AFTER INNOCULATION.

THIS IS A TIME WHEN THERE IS NO

EVIDENCE IN THE BLOOD STANDARD

ASSAY IS LESS THAN 35 RNA

INTELLECTUALLY LESS THAN THREE

COPIES.

IN A SUBSEQUENT ESSAY AND NO

EVIDENCE OF INFECTED PBMCs.

THE ANSWER IS ABSOLUTELY YES.

IN VAGINAL TISSUES AND IN THE

CERVIX.

IF WE LOOK AT THE REPRESENTATION

OF VARIANTS WE SEE AT LEAST

THREE VARIANTS THAT GOT ACROTS,

WHEN WE DO MORE EXTENSIVE

ANALYSIS WE SEE THERE ARE UP TO

FIVE VARIANTS THAT GOT ACROSS IN

THIS PARTICULAR INFECTION EVENT.

BEING ABLE TO TRACK THIS LEVEL

OF RESOLUTION IS SOMETHING THE

FIELD HAS NOT HAD ACCESS TO

BEFORE AND IS REALLY SOMETHING

THAT'S ENABLED BY THE

CONSTELLATION OF EXPERTISE AND

INFRASTRUCTURE THAT WE HAVE BEEN

ABLE TO ASSEMBLE BASED ON NCI'S

INVESTMENT.

WE KNOW WHAT IS HAPPENING AT THE

LOCAL SITES OF A CRITICAL

QUESTION FOR VACCINE

INTRODUCTION IS WHAT IS THE

MECHANISM AND ROUTE OF SPREAD.

SO WE ARE VERY ANXIOUS TO SEE

WHAT IS THE STATUS OF VIRUS AND

DRAINING LYMPH NODES, DISTAL

LYMPH NODES AND SO ON.

WE WERE ABLE TO DEMONSTRATE AT

THIS DAY FIVE DAYS AFTER

INNOCULATION AT A TIME WHEN

THERE'S NO VIRUS EVIDENT IN

BLOOD WE'RE ABLE TO READILY

DETECT VIRUS BY

IMMUNOHISTOCHEMISTRY IN DRAINING

LYMPH NODES BUT ALSO OCCASIONAL

DISTAL LYMPH NODES SUGGESTING

THE INITIAL SPREAD IS LYMPHATIC

REATHER THAN HEMOTOJ NOWS.

WHEN WE DO EXTENSIVE COLLECTING

50, 60 TISSUES INCLUDING TISSUES

THAT WE KNOW ARE PROMINENTLY

INVOLVED IN INFECTION EARLY

STAGE INFECTION IN THE GI TRACT

BY ONE WEEK WE SEE THE MAJORITY

ARE NEGATIVE.

SO WE'RE BEGINNING NOW TO DEFINE

THE STEP WISE PROFESSION OF

INFECTION FROM DEPOSITION OF

INOCULUM ON MUCOSAL SURFACE TO

THE RAISING SYSTEMIC INFECTION

YOU HAVE TWO WEEKS LATER.

SO THIS IS AN ON GOING STUDY, WE

STILL HAVE LOTS OF SPECIMENS TO

ANALYZE BUT WE HAVE DEMONSTRATED

THE FEASIBILITY OF THE APPROACH

AND GENERATED INITIAL FINDINGS.

I THINK AN ATTEMPT INITIAL STUDY

WITH VAGINAL CHALLENGE IS

PROBABLY A WORSE CASE ANALYSIS

BECAUSE FOR ANATOMICAL AND

HORMONAL VAGINAL IS THE P MOVE

VARIOUSABLE OF THE ROUTES WE

DEAL W. WE'RE GETTING READY TO

DO REPTILE AND PENILE CHALLENGES

AS WELL.

>> INTRIGUING, SORT OF ROUNDED

POINT HAND OF THE EGG WHICH ONE

IS BETTER ARGUMENT WITH THEM,

FIELD REALIZE BASEBALL PEOPLE

ARGUE WHETHER INFECTION IS

PREFERENTIALLY IN CERVICAL OR

VAGINAL AND THE ANSWER WHAT I

LEARNED AFTER 25 YEARS OF

WORKING ON HIV IF YOU HAVE A

QUESTION THE ANSWER IS USUALLY

YES.

SO THE VIRUS DOES WHAT IT CAN DO

AND IT DOES SEEM TO PRERVE AN

ENDOCERVICAL INFECTION BECAUSE

OF THE LESSER ANATOMICAL BARRIER

BUT IN PARTICULAR IF THERE ARE

SITES OF PRE-EXISTING

INFLAMMATION THE VIRUS WILL GET

ACROSS THERE JUST FINE AND

THAT'S WHAT WE SEE IN OUR STUDY.

IMPORTANTLY, SUGGESTING THAT

LYMPHATIC (INAUDIBLE) INITIAL

DISSEMINAILINGS.

WE SEE IT IN SOME SITES BEFORE

OTHER SITES.

AND INTRIGUE ILY THE MUCOSAL

VARIANTS THAT WE SEE ARE NOT

REPRESENTED AT DISSAL TIME

POINTS WHERE WE HAVE LOOKED AND

IT'S NOT CLEAR AT THIS POINT, WE

HAVE ANALYSIS TO SAY WHETHER

THOSE REPRESENT A BOARD OF

INFECTION POTENTIAL FOR LATER

TIME POINT THAT'S AN INTERESTING

POINT TO FOLLOW-UP.

IN TERMS OF THIS IS A VERY BASIC

RESEARCH PROJECT, ASKING BASIC

QUESTIONS ABOUT FUNDAMENTAL

PROCESSES, HAVING BEEN POSSIBLE

FOR THE FEEL TO ADDRESS BECAUSE

OF LACK OF CONSTELLATION OF

RESOURCES IN ONE PLACE WE'RE

TRYING TO MAKE THAT AVAILABLE TO

THE FIELD.

AND BRANDON AND OTHERS IN OUR

PROGRAM HAVE GENERATED LARGE

CHALLENGE (INAUDIBLE) VIRUSES OR

SUBMIT WE USED IN THE STUDY I

SHOWED YOU BUT OTHER INFECTIONS

DERIVED WITH (INAUDIBLE) AN

THOSE ARE BEING MADE AVAILABLE

FOR USE BY OTHER INVESTIGATORS.

IN PARTICULAR, IN A CONSORTIUM

WHERE WE'RE PROVIDING VIROLOGIC

SUPPORT TO A LARGE CONSORTIUM

OUT AT NIH THAT IS FOCUSING ON

EARLY EVENTS OF MUCOSAL

TRANSMISSION AN VACCINE

INTERDICTION DOING A COMPARISON

OF VAGINAL AND RECTAL

TRANSMISSION.

VACCINATED ANIMALS TO UNDERSTAND

SITES AN MEKTISMS AN

INTERDICTIONS THAT ARE AFFORDED

BY DIFFERENT VACCINES AND THAT

INCLUDES STUDIES WITH

RECOMBINANT ADINOVIRUS

(INAUDIBLE) INSTITUTE GENE

THERAPY DELIVERED APT BODY WITH

(INAUDIBLE) LIVE ATTENUATED

VACCINES WITH PAUL JOHNSON AT

HARVARD.

USING RECOMBINANT RHESUS CMV

VECTOR IN STUDYING WITH LUIS

TICKER.

THIS IS A LONG STANDING

COLLABORATION WE HAVE HAD THE

LAST SEVERAL YEARS, AND THE

INTEREST STEMS FROM THE FACT

MOST OF THE VACCINE APPROACHES

THAT HAVE BEEN TRIED FOR HIV

HAVE BEEN VARIATIONS ON A CRIME

BOOST TYPE APPROACH.

THE TYPE OF RESPONSE THIS GIVES

YOU TYPICALLY A COINCIDENCE WITH

THE TRANSIENT BURST OF ANTIGEN

YOU GET A NICE STRONG RESPONSE

INDICATES OVER TIME CENTRAL

MEMORY TYPE IMMUNE RESPONSE.

IN ORDER TO BE EFFECTIVE A

CENTRAL MEMORY RESPONSE MIEWS TO

C ANTIGEN, UNDERGO

PROLIFERATION, DIFFERENTIATION

TO EFFECTOR STATUS, SITES OF

VIRAL REPLICATIONS, ALL THAT

TAKES TIME.

THE PROBLEM IS THAT TIME WE

BELIEVE IS TOO LONG RELATIVE TO

THE KINETICS IN OUR REPLICATION

PARTICULARLY FOR SOMETHING THAT

GENERAL RATES AWZ MUCH VARIATION

AS HIV DOES IN THE IMMUNE

SYSTEM.

THE BASIC QUESTION WE WANTED TO

ASK, HOW ABOUT INSTEAD OF

GENERATING A CENTRAL MEMORY TYPE

RESPONSE WE GENERATED A RESPONSE

THAT HAS PRE-DEPLOYED EFFECTOR

MEMORY CELLS.

SO WOULD THAT GIVE YOU SOMETHING

DIFFERENT?

BASED ON EXPERIENCE WITH THE

IMMUNOVIROLOGY OF HUMAN CMB

GIVES VERY BROAD BUT PERSISTENT

CD4 AND CD8 RESPONSES.

AND BASEDDEN THAT, HE GENERATE

AD SERIES OF RHESUS RECOMBINANT

C AND B VECTORS WITH SIV INSERTS

TO SEE FIRST COULD YOU GENERATE

THOSE RESPONSES AND IF YOU COULD

WOULD YOU GET ANY DIFFERENCE IN

TERMS OF THE EXTENT AND

MECHANISM OF PROTECTIVE

EFFICACY.

SO WE SUMMARIZED SCHEMATICALLY

HERE WHERE YOU CAN SEE THE VIRUS

TAKING OFF AND WE BELIEVE THE

WINDOW OF OPPORTUNITY IS

PROBABLY A WEEK OR LESS IN TERMS

OF THERE'S SO MUCH VIRUS IT'S

STARTING TO GENERATE AN IMMUNE

INSULT IN CELLS GENERATING

ENOUGH VARIATION THAT IMMUNE

ESCAPE AT SOME LEVEL IS GOING TO

BE INEVITABLE.

AND THE PROBLEM IS THAT IF YOU

LOOK AT THE ONSET OF A PEEK

EFFECTOR T-CELL RESPONSE IN A

NAIVE ANIMAL THAT DOESN'T COME

FOR THREE WEEKS F. YOU DO A

TYPICAL CRIME BOOST VACCINE YOU

CAN SHIFT IT BAY WEEK OR SO BUT

THAT'S PROBABLY TOO LATE OUTSIDE

THE WINDOW.

SO WHAT WE WANTED TO SEE, WHAT

WOULD HAPPEN IF YOU HAD YOUR

RESPONSE PRESENT AT THE TIME OF

CHALLENGE BEFORE YOU GOT UP TO

HERE.

WHAT WE FOUND IS WE SAW FIRST

THAT WE COULD GET THE

APPROPRIATE INTENDED IMMUNE

RESPONSES AND THEY HAD VERY

INTERESTING EFFECTS.

CONTROL ANIMALS THE RANGE OF

(INAUDIBLE) PLASMA SIV RNA HERE

AND A RANGE WITHIN DIFFERENT

ANIMALS (INAUDIBLE) THAT GIVES

YOU A FEEL FOR THE BACKGROUND.

THIS SHOWS A DMA PRIME

ADINOVIRUS VACCINE BOOST, YOU

CAN SEE A TYPICAL EFFECT WITH A

MODEST ONE AND A HALF DECREASING

VIREMIA AND DECREASE IN CHRONIC

VIREMIA LOST OVER THE SUBSEQUENT

MONTH.

WHAT WE SAW WITH THE CMB VECTOR,

YOU CAN SEE A BOOST SIX MONTHS

LATER WITH A VERY DIFFERENT

PATTERN.

FIRST HAPPY ANIMALS WEREN'T

PROTECTED AND OF THE ONES THAT

WEREN'T PROTECTED WE SAW NO

DIFFERENCE FROM UNVACCINATED

ANIMALS.

THE ANIMALS THAT WERE PROTECTED

SHOWED A VERY DIFFERENT PROFILE.

I WANT TO EMPHASIZE USING THE

WORD PROTECTIVE IN AN

UNCONVENTIONAL SENSE HERE

BECAUSE WHEN YOU SAY PROTECTION

I AND MANY OTHER PEOPLE PROBABLY

THINK ABOUT A STERILIZING TYPE

IMMUNITY WITH COMPLETE

PROTECTION FROM INFECTION.

THAT WAS NOT A THEORETICAL

OUTCOME IN THE DESIGN WHICH WE

CHALLENGE THE ANIMALS

INTRARECTALLY UNTIL WE SAW

VIROLOGIC AND IMMUNOLOGIC

EVIDENCE OF INFECTION HOW DOES

THE T-CELL VACCINE CONTROL

INFECTION NOT TRY TO

PREINVENTORY IT.

AND BY IMMUNOLOGIC EVIDENCE,

EVIDENCE OF DE NOVO T-CELL

RESPONSES AGAINST VIRAL ANTIGENS

PRESENT IN THE VIRUS BUT WEREN'T

PRESENT IN THE VACCINE.

IF WE LOOK AT SOME OTHER GROUPS

THAT GOT CMB, (INAUDIBLE)

COMBINED EFFECT WHERE WE SEE

HAVE THE ANIMALS SHOWING UNUSUAL

CONTROL WHERE THERE'S AN INITIAL

PEAK, IT'S BROUGHT UNDER

SUCCESSFUL CONTROL.

HERE ARE THE ANIMALS THAT

WEREN'T COMPLETELY PROTECTED,

SHOWS SOMETHING SIMILAR TO

ADINOVIRUS BY ITSELF.

THESE VACCINES GIVE BROAD CD4

AND CD8 T-CELL RESPONSES WITH

LITTLE SPECIFICITY.

SO FROM A CONCEPTUAL PERSPECTIVE

IS A CLEAN TEST OF A T-CELL

VACCINE CONCEPT.

THERE'S NOT ONLY NO NEUTRALIZING

ANTIBODY, THERE'S BARELY

MEASURABLE BINDING ANTIBODIES TO

MEDIATE THE AFFECTS ON THE

ANALYSIS.

THESE PROTECTED ANIMALS ARE

CLEARLY INFECTED.

WE HAVE VIROLOGIC AND

IMMUNOLOGIC EVIDENCE OF

INFECTION BUT THE VIE REAMNA IS

-- VIREMIA IS TRANSIENT.

WE SEE CONTROL BLIPS AND WE SEE

SPECIFIC CD4 T-CELLS NOT LOST,

PROTECTION CORRELATES WITH THE

VACCINE BOOST AND LONG TERM

PROTECTED ANIMALS ARE MADE

VIREMIC WITH (INAUDIBLE) LEVEL

OF PROTECTION.

SO THESE ANIMALS HAVE LOW LEVELS

OF VIRUS DEMONSTRATED BY DIRECT

MEASUREMENT.

THIS IS REFLECTED BY THE

FREQUENCY OF OCCASIONAL BLIPS OF

VIREMIA DECAYING OVER TIME ALONG

WITH IMMUNE RESPONSES TO

NON-VACCINE ANTIGENS.

THIS SHOWS VIRAL LOAD

MEASUREMENTS, IN NON-HUMAN

PRIMATE SYSTEM DEVELOPED ULTRA

SENSITIVE TECHNIQUES USING PCR

METHOD AND HYBRID PCR AND

DIGITAL PCR COMPARISON LOOKING

AT DNA AND RNA IN SOME 50, 60

TISSUES FROM THE GI ASSOCIATED

LYMPH NODES, OTHERS LYMPHOID

TISSUES WHAT YOU CAN SEE IN AN

ANIMAL THAT IS CONTROLLING

INFECTION BASED, THIS IS

CONVENTIONALLY A GOOD

CONTROLLER, BASED ON LIVE

ATTENUATED VACCINATION.

THIS IS AN ANIMAL WITH 100

COPIES PER ML OF SLIERS, 100

VERSUS TEN TO THE 6 OR TO THE 7,

MEASURABLE LEVELS OF VIRUS.

WHERE THE DENOMINATOR THIS IS

ACTUALLY 10 TO THE 8 AFTER WE

BOOST THE SENSITIVITY BY

COMBINATION OF DIGITAL PCR,

APPROACHES N. CONTRAST, THIS IS

REPRESENTATIVE OF THE ANIMALS WE

LOOKED AT SO FAR, THE MAJORITY

OF TISSUES THAT WE LOOK AT A

YEAR OUT FROM THE INITIAL

CHALLENGE ARE NEGATIVE AT A

LEVEL OF LESS THAN TEN COPIES

PER -- SO THIS IS AN

EXTRAORDINARY RESULT THAT I HAVE

NOT SEEN BEFORE AND WE'RE

EXCITED ABOUT IT IN A

PROPHYLACTIC SETTING WE'RE

FINISHING A COMPARATIVE STUDY

WITH VAGINAL CHALLENGE, VERY

SIMILAR RESULTS SO FAR.

WE'RE ALSO COMPARING THIS TO

LIVE ATTENUATED VACCINES AND IN

THE INTEREST OF TIME I WON'T GO

INTO THAT.

EXCEPT TO SAY THE COMMON

DENOMINATOR OF PROTECTION

MEDIATED BY TWO VACCINES SEEMS

TO BE INDUCTION OF THE T

EFFECTOR TYPE RESPONSES.

ONE PREDICTION YOU MIGHT EXPECT

SINCE I SHOW YOU WE SAW VIRUS

EARLY THERE SEEM TO BE LITTLE

VIRUS IF WE WERE TO LOOK EARLIER

IN ANIMAL JUST STARTING TO

CONTROL VIRUS WE SEE MORE AND IN

FACT SO FAR WE DO.

THIS MAKES IT VERY EXCITING FOR

THERAPEUTIC IMMUNIZATION, ONE

PROBLEM WITH APPROACHES TOWARD

THERAPEUTIC IMMUNIZATION PEOPLE

TRIED SO FAR IS THE VACCINE THEY

HAVE USED ARE ONES THAT DEPEND

ON ANTIGEN FROM VIRUS STIMULATED

A DECAYED MEMORY RESPONSE IN

ORDER TO CONTROL THINGS INSTEAD.

HERE THE IMMUNE RESPONSES ARE

MAINTAINED INDEPENDENT OF VIRUS

AN THOSE RESPONSES ARE OUT THERE

WHENEVER VIRUS POPS OUT AND

PLAYS WACK A MOLE WE'RE IN THE

PROCESS TRYING TO ALIGN

RESOURCES TO TEST THAT AND AGAIN

THIS STARTED OUT AS PROOF OF

CONCEPT, IMMUNE RESPONSE,

DIFFERENT PROTECTION,

(INAUDIBLE) SOMETHING THAT IS

DEVELOPABLE FOR POTENTIAL

CLINICAL USE.

I HOPE THAT'S GIVEN YOU A SENSE

OF HOW WE DO THINGS AND SAMPLE

PROJECTS WHERE WE DEVELOP

TECHNOLOGY FOR ONE REASON

INTERNALLY AND IN A PROACTIVE

WAY PUSH TO COLLABORATIVE

STUDIES WITH FOLKS IN THE EXTRA

MURAL COMMUNITY AN END BY

HIGHLIGHTING SOME OF THE

MEASURES OF THAT, (INAUDIBLE)

WORKED WITH ME BACK IN THE EARLY

'90s HELPING TO DEVELOP VERY

FIRST ASSAYS FOR RIGOROUS

QUANTITATION OF HIV VIRAL LOAD

AND SINCE HE'S BEEN WITH US HAS

FOCUSED ON STATE-OF-THE-ART

MONITORING AND NON-HUMAN PRIMATE

MODELS.

WE'RE DOING 14, 15,000 SAMPLES A

YEAR.

THE MAJORITY OF THEM WERE

EXTRAMURAL INVESTIGATORS

SUPPORTING PROBABLY 40 PLUS

DIFFERENT INVESTIGATORS AT THIS

POINT.

DOING EVERYTHING FROM STANDARD

PLAZ VA MA VIREMIA, TISSUE BASED

CELL BASED DISCRIMINANT ASSAYS

CO-INFECTED ANIMALS AND SO ON.

BRANDON KEEL GEORGEED FROM

(INAUDIBLE) HAS EXTENNED THE

WORK HE PIONEERED ANALYSIS OF

VIRAL TRANSMISSION IN HUMAN

SETTINGS TO NON-HUMAN PRIMATE

SETTINGS.

BRING A WHOLE NEW LEVEL OF RIGOR

TO THE FIELD BY CHARACTERIZING

VIRAL DIVERSITY, GENETIC

DIVERSITY, HELPING PEOPLE WITH

ANALYSIS OF TRANSMISSION VACCINE

EFFECTS AND SOA&Ö ON.

AGAIN HALF OF WHAT HE DOES IS IN

SUPPORT OF EXTRAMURAL

INVESTIGATORS, ROUGHLY 20 OR SO

IN TERMS OF CURRENT STABLE OF

COLLABORATORS.

(INAUDIBLE) WHO TRAINED WITH

ASHLEY HUFF DOES ALL OF OUR

TISSUE ANALYSIS AND IN A

COLLABORATIVE WAY, STATE OF

STATE-OF-THE-ART EXPERT TEERS

FOR IN SITU

IMMUNOHISTOCHEMISTRY, CON FOCAL.

AUTOMATED IMAGE ANALYSIS AN

QUANTITATION.

HE SUPPORTS 20 PLUS DIFFERENT

INVESTIGATORS MOSTLY EXTRAMURAL

COMMUNITY.

I'M GOING TO END WHERE I

STARTED.

JULIAN BETH WAS THERE IN 1984

WHEN WE FIRST STARTED PURIFYING

HIV.

HE'S STILL HERE AN LUCKY TO HAVE

HIM.

ONE THING JULIAN NOTED ASSAY.

THEY WERE PROHIBITIVELY

(INAUDIBLE) THE READ OUTS YOU

SAY WAIT A MINUTE, WE

(INAUDIBLE) MAKE HIS OWN IN

HOUSE HITS AND WE STARTED

SHARING THEM AROUND.

WE CONTINUE TO DO THAT AND NOW

HAS GOT TON THE POINT WHERE WE

DO SOMETHING LIKE A THOUSAND PER

YEAR OVER THE LAST REVIEW PERIOD

WHEN WE SUMMARIZE THINGS FOR OUR

LAST (INAUDIBLE) LAST YEAR,

PRODUCED OVER 17,000 TIPS

DISTRIBUTED THEM TO 80%

INVESTIGATORS OUTSIDE THE

PROGRAM, SUPPORTING OVER 200

DIFFERENCE INVESTIGATORS.

ANOTHER THING THAT JULIAN AND

THE GROUP DOES IS GENERATE

PURIFIED INFECTIONS IN AN

ACTIVATED VIRUS USED FOR A

VARIETY OF DIFFERENT TECHNIQUES.

BASED ON SOME BASIC WORK ON

MOLECULAR VIROOLOGY OF

RETROVIRUSES, WE ACTUALLY

IDENTIFIED THE TECHNIQUE FOR THE

INFECTIVITY OF VIRUSES BY

COVALENTLY MODIFYING THE CAPSID

PROTEIN THAT DOESN'T AFFECT THE

GLYCO PROTEIN ON THE SURFACE

WHICH MAKES THEM INTERESTING

IMMUNOLOGICALLY, WE HAVE BEEN

PROVIDING THESE AS REAGENTS

SINCE WE MADE THE DISCOVERY.

IN EXCESS OF THREE LITERS OF

MATERIAL.

PURIFIED ACTIVATED UNTIL I

PROVIDED TO NEARLY 100

INVESTIGATORS ALMOST ALL

OUTSIDE.

SO I THINK THE REASON I WAS

ASKED TO SPEAK WITH YOU TODAY IS

BECAUSE OUR PROGRAM EVEN IN THE

ABSENCE OF MECHANISMS WE'RE

TALKING ABOUT IS AN EXAMPLE OF

THE KIND OF THING WE CAN TRY TO

DO FROM THE FFRDCH TO SUPPORT

BROADER RESEARCH COMMUNITY,

SOMETHING THAT FRANKLY IS ONE OF

THE REASONS I LIKE BEING HERE

BECAUSE IT'S EXTRAORDINARILY

GRATIFYING THING TO SHARE

CAPABILITIES WITH OTHER

INVESTIGATORS AND HELP

FACILITATE OVERALL RESEARCH

PROGRESS, THAT'S ONE REASON I

STAY HERE BECAUSE I DON'T KNOW

OF ANOTHER OPPORTUNITY THAT WILL

ALLOW ME TO DO SOMETHING LIKE

THAT.

THAT SAID, I THINK WE CAN DO

BETTER AND IN THE INTEREST OF

TIME I WON'T BELABOR THIS

DISCUSSION, BECAUSE DAVE HAS

ALREADY TOUCH ON KEY POINTS, WE

DISCUSS SOME OF THEM, SUFFICE TO

SAY IMPLEMENTATION OF THE

MECHANISM THE M CRADA MECHANISM

TO ALLOW US TO GET COST RECOVERY

TO EXPAND THE NUMBER OF

INVESTIGATORS THAT WE CAN

PROVIDE THESE KIND OF SERVICES

TO WOULD BE VERY HELPFUL AND

MORE GENERAL CONTRACTOR CREATE A

MECHANISM FROM OUR

PHARMACEUTICAL PARTNERS ON HUMAN

CARDIAC STUDIES WITHOUT

CUMBERSOME CRADA PROCESSES.

SO STOP THERE AND BE HAPPY TO

TRY TO ANSWER QUESTIONS YOU MAY

HAVE, I DON'T KNOW IF YOU WANT

TO GO TO THE GENERAL DISCUSSION.

>> NO.

IF THERE ARE QUESTIONS, THANK

YOU FOR A VERY INTERESTING

PRESENTATION.

VERY INTERESTING WHAT YOU'RE

DOING.

>> IT'S CLEAR BEING ABLE TO USE

PRIMATE MODELS I WONDER WITH ALL

THE PRESSURE NOW AGAINST THE USE

OF PRIMATES, STUDIES IF YOU FEEL

THAT'S GOING TO AFFECT FUTURE

WORK.

>> IT HASN'T BEEN AN ISSUE, IT'S

AN ISSUE WITH CHIMPS WHICH WE

DON'T WORK WITH.

THAT'S AT LEAST ONE SIGNIFICANT

REASON WE DON'T WORK WITH

CHIMPS, NOT A PARTICULARLY GOOD

MODEL FOR HIV.

AND I THINK THERE'S INCREASING

PRESSURE, I COLLABORATE WITH

PEOPLE AT ALL THE NATIONAL

PRIMATE CENTERS.

THEY'RE MORE UNDER MORE PRESSURE

THAN WE ARE HERE.

I THINK THERE ARE WILL BE

CHALLENGES, I DON'T SEE IT GOING

AWAY.

FRANKLY IF I THOUGHT THERE WERE

OTHER WAYS TO ADDRESS IMPORTANT

QUESTIONS WITHOUT USING

NON-HUMAN PRIMATES I WOULDN'T DO

NON-HUMAN PRIMATE RESEARCH.

>> NO,v

>> THE BEAUTIFUL WORK OF CARL

JUNE AND COLLEAGUES AT PENN THAT

ARE SHOWN THE FIRST SUCCESSFUL

T-CELL VACCINE AND CLL CAUSING

CLONAL DISAPPEARANCE WHICH IS

FANTASTIC.

ALL THOSE STUDIES WORKED IN

RETROSPECT IN A BEAUTIFUL

SEMINAR I JUST SAW HIM GIVE

BECAUSE THEY SHOWED THEY WERE

ABLE TO AFFECT THE C MEMORY

CELL, CENTRAL MEMORY CELL, THEY

DID A LATER DEPLOYED EFFECTOR

CELL THEY DIDN'T GET A SUSTAINED

RESPONSE AND THEY DIDN'T SUS

HAVE SUSTAINED REMISSION.

IS THERE DIFFERENT BIOLOGY WHEN

YOU DEVELOP AN ANTI-CANCER

VACCINE AND TRYING TO TARGET A

T-CELL POPULATION SOMEHOW THE

SYSTEM IS DIFFERENT?

WHERE YOU HAVE TO GO AFTER

CENTRAL MEMORY CELL?

I'M SURPRISED DEPLOYED EFFECTOR

MEMORY CELL WORKS HERE IN THAT

MUCH OF A SUSTAINED TIME FRAME.

>> I LOVE THE QUESTION BECAUSE

THERE'S A T-CELL IMMUNOLOGIST

DOING GREAT WORK AND

COLLABORATING WITH CARL ON

ANTI-ENGINEERED T CELLS.

HE'S DEVELOPING CLONES AND DOING

EXCITING STUFF WITH T-CELL --

DEFINE SPECIFICITIES AN

TRANSFERRING PROPERTIES INTO

DIFFERENCE T-CELL POPULATIONS.

THERE HE IS EXPLORING CENTRAL

MEMORY VERSUS EFFECTOR MEMORY IN

THAT SETTING.

THOSE GET COMPLICATED BECAUSE IN

ADDITION TO DIFFERENTIATION

THERE ARE OTHER FACTORS

INCLUDING IN VIVO TRAFFICKING IN

VIVO SURVIVAL, I THINK THAT --

THOUGH DATA ARE DEFINITIVE THEY

HAVE AS MUCH TO DO IN THAT

SETTING AS ANYTHING ELSE.

WHERE YOU'RE INFUSING A FINITE

NUMBER OF CELLS THAT HAVE FINITE

SURVIVAL IN CONTRAST TO A

SITUATION WHERE YOU'RE CONLEY

RESTIMULATING ONGOING BASIS

MAINTAINING THEM.

THERE'S MUCH MORE WORK TO BE

DONE THERE.

>> I SAW THIS IN YOUR REVIEW

(INAUDIBLE) ET CETERA IS SERVICE

HAVE BEEN --

>> WE JUST HAD A REVIEW LAST

YEAR, ALL OF OUR (INAUDIBLE) IN

ADDITION HAD REVIEWERS BASED ON

THE INNOVATION AND QUALITY OF

WORK PROVIDED TO THE EXTRAMURAL

COMMUNITY AND SO ON.

SO IT'S ALL REVIEWED SEPARATELY

BUT TOGETHER.

>> ARE THE NON-HUMAN PRIMATES

HERE?

>> SO THE FIRST STUDY THAT I

SHOWED YOU IS WORK THAT WAS DONE

AT NCI, NON-HUMAN PRIMATE

FACILITY ON THE BETHESDA CAMPUS

WHICH IS CURRENTLY IN THE MIDST

OF SO MUCH NEEDED RENOVATIONS.

THE SECOND STUDY WAS ACTUALLY A

COLLABORATIVE STUDY, THE IN VIVO

WORK, THE ANIMALS FOR THAT, THE

ORGAN PRIMATE SENOR WE WORK A

LOT WITH FULL -- AND ACTUALLY

THE NIAID HAS ANOTHER PRIMATE

FACILITY AND THEN A NUMBER OF

ABOVE LOCAL AN NATIONAL

COLLABORATORS ALSO UTILIZED

PRIVATE CONTRACTOR NON-HUMAN

PRIMATE FACILITIES IN THE AREA.

ONE NICE THING ABOUT THAT IT'S

CENTRALLY LOCATED WHERE WE ARE,

THE COORDINATING ASSESSMENT

SHIPMENT LOGISTICS IS STRAIGHT

FORWARD.

WE HAVE THE SYSTEMS WELL WORKED

OUT.

>> I'M CURIOUS, THIS IS

(INAUDIBLE) I'M CURIOUS HOW

WOULD YOUR CAREER HAVE DEVELOPED

DIFFERENTLY WHERE YOU'RE WITHIN

THE INTRAMURAL PROGRAM OF NCI AS

OPPOSED TO WITHIN THE FFRDC?

IS THAT A FAIR QUESTION?

>> I THINK IT'S A FAIR QUESTION.

I THINK WERE I TO HAVE -- I

GUESS THE FIRST POINT IS THAT I

DON'T KNOW THAT I WOULD HAVE

COME HERE TO BE AN INTRAMURAL

GOVERNMENT INVESTIGATOR IN TERMS

OF SEEING THAT AS DISTINCT

ENOUGH FROM AN ACADEMIC POSITION

OR SO ON THAT MIGHT HAVE DONE

OTHERWISE, WHAT (INAUDIBLE) TO

ME WAS INFRASTRUCTURE THAT THE

CHANCE TO BILL SOMETHING,

FRANKLY LARRY ARTHUR WAS A CHARS

MATTIC PERSON -- CHARSMATIC

PERSON.

BUT TO PROACTIVELY SPORE THINGS

SEEMED LIKE A UNIQUE OPPORTUNITY

TO ME.

IN FAIRNESS IN ACADEMIA OR AS AN

INDIVIDUAL PI, IN THE INTRAMURAL

PROGRAM, I DIDN'T WANT TO GIVE

THE IMPRESSION THAT INDIVIDUAL

PIs DON'T SHARE REAGENTS,

DON'T COLLABORATE OR ANYTHING

ELSE.

THEY JUST DONE HAVE THE

OPPORTUNITY TO DO IT IN THE

SCALE OR IN THE PROACTIVE MANNER

THAT WE HAVE THE PRIVILEGE AN

SUPPORT TO DO.

>> THAT'S A HELPFUL ANSWER.

>> I WANTED TO SAY THAT BEING AN

INTRAMURAL LABORATORY THAT

DEVELOPED REAGENTS IN THIS

SITUATION FOR PAPILLOMA VIRUSES

THAT MANY PEOPLE IN THE

COMMUNITY ARE INTERESTED IN FOR

DOING ASSAYS, WHAT WE HAVE HAD

TO DO IS GIVEN AWAY THE REAGENTS

TO PEOPLE THAT WANT TO USE THOSE

ASSAYS.

(INAUDIBLE).

>> I THINK THE CURRENT SITUATION

FOR JEFF'S LAB IS MUCH BETTER

BECAUSE BASICALLY IT'S A SINGLE

LABORATORY THEN THAT DOES THE

SAME ASSAY FOR MANY, MANY

DIFFERENT LABS SORKS IT'S NOT

LIKE YOUR LAB YOU GET ONE RESULT

AND IN ANOTHER LAB YOU GET

ANOTHER RESULT.

BUT IT'S ONE LABORATORY.

I THINK IT WILL BE EVEN BETTER

IF IT IS POSSIBLE FOR THERE TO

BE SOME KIND OF FEE FOR SERVICE

THROUGH THE CRADA PROCESS

BECAUSE IT'S EASIER TO DO THAT.

WE COULDN'T BEGIN TO THINK ABOUT

THAT JUST WITHIN THE INTRAMURAL

PROGRAM.

>> SO THE DEVELOPMENT OF KITS IS

SOMETHING THAT WOULD HAVE BEEN

UNLIKELY TO HAPPEN AND CERTAINLY

NOT THE SAME WAY IN THIS

INTRAMURAL PROGRAM.

I THINK IT'S HELPFUL TO SEE

BECAUSE IT'S -- ILLUSTRATE IT IS

BROADENED CAPABLES OF HAVING

INTRAMURAL RESEARCHERS AND FFRDC

RESEARCHERS IN THE SAME

COMMUNITY SERVING DIFFERENT

PURPOSES.

>> ANYTHING ELSE?

>> HE MIGHT HAVE SAID THIS AND I

MISSED IT BUT GENERALLY THIS

VACCINE, THIS IS CLINICAL TRIALS

AN WHO IS MAKING THAT, IS THAT A

COMPANY OUTSIDE?

>> AT THIS POINT THERE IS A

STARTUP WITH THE ACADEMIC

INVENTORS THAT ARE EARLY STAGE

TALKING ABOUT.

AT THIS POINT GOING TO CLINICAL

DEVELOPMENT IS A COUPLE OF

GENERATIONS DOWN THE ROAD.

WHAT I SHOWED YOU SO FAR IS WILD

TYPE VECTORS AND CMV, PROBABLY

NOT SOMETHING THAT'S GOING TO --

NOT REGULATORY VECTORS.

>> T-CELLS AND PUT IT IN.

SO THERE'S A WHOLE BUNCH AT THE

BEGINNING --

>> THE INITIAL INTEREST IS NOT

COMING UP WITH A THEME PER SE

BUT THEY ASK A BASIC QUESTION,

ALL THE OTHER VACCINES THAT A

LITTLE BIT CENTRAL MEMORY BIASED

RESPONSES AND THERE'S A CONCERN

BASED ON THAT KINETIC MISMATCH

BETWEEN THE VIRUS AND BOOST IN

IMMUNE RESPONSE.

IF YOU HAVE A DIFFERENT IMMUNE

RESPONSE HOW WOULD YOU DO THAT?

AND CMB WAS VEEN TO DO, DEVELOP

NEXT GENERATION.

Q. (INAUDIBLE) (INAUDIBLE).

>> IN INTEREST OF TIME WE

APPRECIATE YOU COMING AND YOUR

TALK.

IT'S HELPFUL FOR US.

TOM WANTS TO MAKE AN

ANNOUNCEMENT.

TWO BRIEF THINGS BEFORE YOU GET

ON WITH THE LAST ITEM ON THE

AGENCY.

ONE, PURPLE FOLDER, REMEMBER

THEY HAVE INFORMATION IN IT AND

A FORM TO SIGN.

IF YOU'RE NOT TAKING THE

INFORMATION WITH YOU AND YOU

NEED US TO DISPOSE OF IT PLEASE

LET US KNOW AND YOU CAN GIVE IT

TO US SO IT CAN BE DISPOSED

CONFIDENTIALLY.

FOR YOUR BOARD BOOK, LEAVE IT ON

THE SPACE FROM THE NAME TAG.

SEVERAL TALKS HAD UPDATES ON

THEIR SLIDES, WE'LL SEE THAT THE

UPDATES GET PLACED IN THERE AND

THE BOOK IS RETURNED TO YOU IN

YOUR OWN LOCATION.

>> LET ME START DISCUSSION WITH

TWO PRACT CAT MATTERS.

ONE A SITUATION I PARTIALLY TAKE

RESPONSIBILITY FOR, SCHEDULING

TODAY.

WE HAVE HAD A VERY FULL DAY AND

SOME WAYS LEF US WITHOUT ENOUGH

TIME FOR DISCUSSION.

SO I WILL CERTAINLY TRY TO WORK

WITH THOSE WHO SET THE PROGRAM

TO -- A PROGRAM THAT'S MORE

TIMELY SCHEDULED OF LIMITED

TIMES ON TALKS WITH TIMES

SEPARATELY FROM QUESTIONS SO WE

CAN GET TO IT IN AN ORDERLY WAY

AND STILL HAVE TIME AT THE END.

DISCUSSIONS HAVE BEEN VALUABLE,

THAT'S NOT A PROBLEM, WE JUST

NEED TO REALIZE GOOD TALKS

GENERATE DISCUSSION AND THAT

NEEDS TO BE PROGRAMMED IN.

NUMBER TWO, SLIGHTLY RELATED

ITEM, DAVID HEIMBROOK SUGGESTED

PARTICULARLY FOR THOSE WHO HAVE

TO TRAVEL SOME DISTANCE, WE

MIGHT PREFER TO HAVE MEETINGS A

DAY AND A HALF IN LENGTH AND

HAVE FEWER OF THEM.

ONE SUGGESTION SHOULD BE IT'S

SCHEDULED FOR THREE MEETINGS A

YEAR, IS THAT CORRECT?

I PRESUME THE POSSIBILITY OF

HAVING TWO MEETINGS A YEAR, WE

CAN MEET ALL ONE DAY, AND THEN

UNTIL NOON THE NEXT DAY.

THEN PEOPLE COULD GET OUT EARLY.

SO IF YOU WOULD LIKE US TO

EXPLORE THAT, WE CAN DO THAT.

I DON'T KNOW -- SO IF I COULD

GET EXPRESSION OF INTEREST OR

NOT ON THE PART OF THE COMMITTEE

--

>> AS LONG AS IT FITS THE NEEDS

OF THE NCI.

>> I'M SURE THERE WILL BE EIGHT

APPROVAL LEVELS.

>> IF I CAN ADD TO THAT PROCESS.

PART OF THE RATIONALE BEHIND

SUGGESTING IT WAS CERTAINLY

LOGISTICS FOR PEOPLE THAT

TRAVEL, I USED TO TRAVEL A LOT.

BUT THE SECOND ONE WAS IT TAKE

AS WHILE FOR A COMMITTEE TO GET

ITS RHYTHM SO TO BRING YOU IN

FIVE, SIX HOURS SEEMED LIKE IT

MIGHT BE BETTER FOR US TO SPEND

MORE TIME TOGETHER, INTERACTIONS

DEVELOP AN BECOME MORE

PRODUCTIVE AND GIVES MORE TIME.

WE VERY MUCH LOOK FORWARD TO

HAVING DINNER TONIGHT.

WE'LL HAVE A LONG DISCUSSION.

>> COME BACK IN THE MORNING.

>> INFORMAL DISCUSSIONS OVER

DINNER MIGHT BE VALUABLE.

>> WE SIMPLY NEED TO MAKE A

DECISION WHETHER YOU WANT THE

MEET TWICE OR THREE TIMES A

YEAR.

>> LET'S HAVE A RESOLUTION.

ASKING THE CONVENERS OF THE

COMMITTEE IF THEY WILL CONSIDER

THE FORMAT WHICH WE MEET TWICE A

YEAR OR DAY AND A HALF.

>> SO YOU, I THINK SOMEBODY ELSE

NEEDS A MOTION.

>> MOTION.

>> SECOND.

>> YOU YOU HAVE A SCHEDULE FOR MAY

AND SEPTEMBER.

(INAUDIBLE).

INDICATE WHETHER YOU WANT TO

HAVE NEXT MEETING IN MAY OR

SEPTEMBER.

>> GOT TO DO IT IN MAY BECAUSE

OF THE STRATEGIC REPORT THAT'S

GOING TO BE READY.

[LAUGHTER]

>> I WANT TO POINT OUT THAT IT

MOVED TO A DAY AND A HALF, THAT

THERE ARE SOME CONFLICTS THAT

MAY ARISE AND THE FACT THAT

NHGRI COUNCIL NEEDS THE DAYS

JUST --

>> NEGOTIATE WITH THEM WHEN YOU

CAME, THAT WE WOULD NOT IMPACT

--

>> I WOULD LIKE TO PROPOSE A

COMPROMISE.

BECAUSE I KNOW THAT IF YOU

CHANGE THE DAY I PROBABLY WON'T

BE ABLE TO COME.

>> I HAVE A PROPOSITION TO THE

MAY AND SEPTEMBER MEETING.

SCHEDULE MEETINGS EVERY SIX

MONTHS.

>> THAT WILL GIVE MEETINGS TO

COME UP.

>> A FRIENDLY AMENDMENT TO THE

MOTION.

DO WE HAVE A FREKDLY SECOND.

>> ALL IN FAVOR.

>> LOGISTICS.

I THINK IT'S A UNANIMOUS

DECISION.

I SUGGEST YOU BE ALLOWED TO COME

IN LAIG THE NIGHT BEFORE WEST

COASTERS BECAUSE GETTING HERE

FOR DINNER MEANS I LOSE A DAY ON

THE FRONT END.

HAVING THE DINNER AFTER THE

FIRST DAY WOULD BE ADVISABLE.

>> THAT'S WHAT WE'RE THINKING.

>> THAT'S WHEN WE MOVE TO A DAY

AND A HALF.

WHILE WE'RE AT A DAY COMING IN

THE NIGHT BEFORE HAVING THE DAY,

VERY HELPFUL.

>> I THINK WE CAN ALSO FOR THOSE

OF US WHO ARE AROUND GET HERE IN

TIME, WE COULD HAVE A DINNER BUT

-- IT WILL BE A DIFFERENCE KIND

OF DINNER.

>> HAVE A HOTEL THAT'S CLOSER TO

HERE.

>> I HAVE ALREADY SPOKEN TO

KATE.

THERE IS ANOTHER HAMPTON INN

WHICH IS CLOSER AN NEWER.

(OVERLAPPING SPEAKERS)

>> THAT BRINGS UP ANOTHER

QUESTION.

>> DO WE HAVE TO MEET IN FRONT

--

>> ONCE A YEAR, IS THAT RIGHT?

>> FREDERICK AND REST OF -- ONCE

A YEAR FREDERICK, REST OF THE

YEAR (INAUDIBLE).

>> SO THE NEXT TWO MEETINGS ARE

BETHESDA.

>> RIGHT.

>> JUST NEED TO SKIP

(INAUDIBLE).

>> THAT HAMPTON INN.

>> SO WE HAVE ABOUT 10 OR 12

MINUTES ACCORDING THE OUR

SCHEDULE TO DISCUSS ANY GENERAL

ISSUES OR GENERAL QUESTIONS THAT

YOU MAY HAVE.

DO YOU WANT TO CONSIDER

RECOMMENDING FOR OUR NEXT

MEETING.

>> SO THERE ARE A COUPLE OF

REALLY INTERESTING EXAMPLES OF

EMPOWERING GOVERNMENT MECHANISMS

OR SETTING EXTERNAL

COLLABORATIONS SO WHEN THE CRADA

SUBMITTED GOES -- DOESN'T HIT A

SNAG AND IS APPROVED, TOGETHER

WITH THE RECONFIGURING THE NEW

NAMES, NEW WEBSITES, THERE'S

GOING TO BE SOME PUB PUBLICITY TO

MAKE SURE THE WORLD KNOWS NEW

IDENTITIES TO NCI FREDERICK.

THERE IS SOME POSSIBILITY THAT

YOU WOULD RECEIVE LOTS OF

INTEREST.

AND THE QUESTION IS, ARE YOU

PREPARED TO HANDLE THAT.

>> THE CURRENT PLAN AND CURRENT

OBJECTIVE WAS TO TO MAKE SURE WE

HAVE A CERTAIN AMOUNT OF

PARTNERING SPACE AVAILABLE

WITHIN THE ATRF.

AND WE REALLY WANT TO BRING IN

PARTNERS TO DO THIS.

BUT IT IS (INAUDIBLE) IN TERMS

OF SPACE AVAILABLE SO IT'S PART

OF THE PLAN FOR SUPPORTING THE

CRADA WE WILL VERSUS HAVE A PLAN

FOR PRIORITIZING OPPORTUNITIES

THAT ARE REQUESTING SPACE, I

SHOULD EMPHASIZE FOR THE PEOPLE

GOING INTO THAT PARTNERING SPACE

IT'S NOT TO TAKE UP RESIDENCE,

IT'S A TEMPORARY THING FOR THEM

TO COME IN, WE HAVE A LIMITED

AMOUNT OF WORK THAT WE NEED TO

ACCOMPLISH SHOULDER TO SHOULDER

AND IF THEY WANT TO STAY CLOSE

BY, THAT'S FRANKLY WHAT THE REST

OF THE SPACE OF THAT TECHNOLOGY

PARK IS FOR.

SO THE IDEA IS TO BRING THEM IN,

GET DONE WHAT WE NEED TO GET

DONE AND ROLL THEM OUT AND BRING

OTHERS IN.

WE WILL AS PART OF THE OVERALL

PROCESS HAVE A PRIORITIZATION

DISCUSSION.

>> THAT'S ONE KIND OF

PARTNERSHIP.

I THINK THAT WE'RE IN PRETTY

GOOD SHAPE MOVING IN TO THE

ATRF.

THE OTHER KIND OF WORK FOR

OTHERS THAT JEFF JUST TALKED

ABOUT DOING ASSAYS AN THOSE

SORTS OF THINGS I THINK IS A BIT

MORE PROBLEMATIC.

BUT I DONE THINK IT WILL BE

IMPOSSIBLE TO OVERCOME, PART OF

THE PROCESS IS AS PEOPLE MOVE

FROM HERE TO THE ATRF, AS I

MENTIONED TO YOU EARLIER WE WILL

VACATE 100,000 SQUARE FEET OF

SPACE HERE.

PART OF THE DISCUSSION IS WHAT

WILL WE DO WITH THAT SQUARE FEET

OF SPACE.

ONE THING WE'RE LIKELY TO DO IS

EXPAND CORE RESOURCES THAT MIGHT

BE AVAILABLE TO OTHERS.

AS SAIC IS ABLE TO BRING IN AND

PAY FOR THE DIRECT INCREMENTAL

COSTS FOR THE LABOR MATERIALS

AND (INAUDIBLE).

WE HAVE SPACES AVAILABLE I THINK

WE CAN MEET IT, THAT'S MORE A

PROBLEMATIC SITUATION.

>> THERE IS A NEED TO TITRATE

CAPACITY DEMAND AND INCOMING

MONEY TO SUPPORT IT AND IN SPITE

OF BEST EFFORTS I'M CONFIDENT IT

WON'T GO AS SMOOTH AS WE WOULD

LIKE AT FIRST.

THE ONE THING I DON'T WANT IS

CREATE HUGE DEMAND AND THEN NOT

BE ABLE TO SATISFY 95% OF IT,

THAT WOULD GET US OFF TO A BAD

START.

>> CHARLES YOU HAVE A QUESTION?

>> I HAVE A PHILOSOPHICAL

COMMENT AS WE STRUGGLE TO GET

OUR HANDS AGAINST FREDERICK AN

UNDERSTAND PARTICULARLY THE

RELATIONSHIP OF FREDERICK

PROGRAMS TO MAIN CAMPUS

INTRAMURAL AND EXTRA MURAL

PROGRAMS.

AS WE CONTINUE TO GET PROGRAMS

PRESENTED IT WOULD BE NICE FOR

THE FIRST COUPLE OF SLIDES OF

ANY SPECIFIC LIKE WE HEARD NCL

LAB OUT OF CONTEXT OF THE ENTIRE

NANOALLIANCE PROGRAM.

SO THOSE THAT HAPPEN TO KNOW

ABOUT THAT, I WAS FINE, U KNOW

ABOUT ALL THE REST BUT I DON'T

KNOW THAT EVERYBODY ELSE DID.

HEAR JIM'S LITTLE BIT OF NEXT

PROGRAM BUT NOT IN THE CONTEXT

OF THE ENTIRE BRANCH SO WHAT

WOULD BE REALLY HELPFUL TO HAVE

A FEW CONTEXT SLIDES EVERY TIME

WE HAVE ONE OF THE PROGRAMS

PRESENTED.

HERE IS THE DIVISION OF CANCER

THERAPY DIAGNOSIS AN TREATMENT.

WE HAVE THESE FIVE MAJOR TRUSTS,

TOTAL BUDGETS HERE.

HERE IS THE 20% WE'RE PUTTING AT

FREDERICK AND WHY WE HAVE CHOSEN

TO DO THAT.

AND WHY IT MAKES SENSE TO US.

IT PARTICULARLY GETS TO THE

ISSUE, WE REVIEW CTR LAB OF

PATHOLOGY, WHY ARE WE

DUPLICATING SEQUENCING CENTERS.

DOES THAT MAKE SENSE?

ARE WE CONSOLIDATING DATA

ANALYSIS?

I THINK IT WOULD BE GOOD FOR US

TO CHALLENGE THOSE PRESENTERS TO

GIVE US SORT OF THAT OVERVIEW

AND CONTEXT SO WE CAN PUT THINGS

IN PERSPECTIVE.

>> THAT'S A GOOD SUGGESTION.

I HAVE ANOTHER THOUGHT WHICH I

WANT TO JUST MENTION.

I GUESS THERE'S BEEN SOME EFFORT

IN THIS DIRECTION BUT SEEMS TO

ME THERE COULD BE MORE.

AND THAT IS TO HAVE A PROGRAM

THAT WOULD ALLOW OR ENCOURAGE

EXTRAMURAL INVESTIGATORS TO COME

HERE FOR SABBATICAL.

I DON'T THINK THAT'S DONE

ENOUGH.

CERTAINLY IN THE NEUROLOGY

INSTITUTE IT WAS A RARE OCCASION

AND I THINK THERE'S A LOT FOR

PEOPLE TO PROFIT FROM AND AN

OPPORTUNITY.

I THINK ANY EXCHANGE BETWEEN THE

INTRAMURAL AND EXTRAMURAL

COMMUNITY IS VERY HEALTHY.

SO IF SOMEBODY COULD GIVE

THOUGHT AND MAKE SUGGESTIONS

BACK, THAT WOULD BE A REALLY --

>> IF I CAN MAKE A COMMENT.

CCR DOES THAT BUT THAT DOESN'T

DO VERY MUCH GOOD FOR THE SAIC

ACTIVITIES THAT ARE HERE.

THIS YEAR BEGINNING IN OKAY I

ASKED DAVE TO PUT TOGETHER A

DISTINGUISHED SCIENTIST VISITING

PROGRAM TO BRING IN PEOPLE ON

SABBATICAL TO LEARN TECHNOLOGIES

AN ADVANCED TECHNOLOGIES PROGRAM

TO WORK IN THE BIOPHARMACEUTICAL

DEVELOPMENT PROGRAM OR

NANOTECHNOLOGY CHARACTERIZATION

TERRITORY AND JUNIOR FACULTY,

WHO WOULD SOME EXTENT BE HELPFUL

TO US, WHO HAVE A TECHNOLOGY

WE'RE INTERESTED IN SO RATHER

THAN INVESTING IN HUGE

TECHNOLOGY AND DEVELOPMENT, WE

MAY PAY THEIR SAL IRYS WHILE

THEY -- SALARIES WHILE THEY'RE

HERE AN MAY PROFIT FROM --

>> (INAUDIBLE) LOS ALAMOS HAVE A

GREAT PROGRAM, THE CENTER FOR

INTEGRATED NANOTECHNOLOGY THAT'S

OUTSIDE THE WALL AND ANY

ACADEMIC USER CAN DROP IN, GET

PARTIAL SALARY SUPPORT, BRING A

PROJECT, EVEN BRING SOME MONEY

TO FUND THAT PROJECT.

THOSE MODELS ARE NICE.

>> AS PART OF THE DOB MODEL

YOU'RE TALKING AB, WE FELT WE

COULDN'T DO THAT NOW THAT WE CAN

DO THAT TRAINING AND THIS

INTERACTION WITH THE EXTRAMURAL

COMMUNITY (INAUDIBLE).

>> GIVE YOU A SUMMARY OF WHAT

THE PROGRAM IS NEXT TIME AND

HOPEFULLY BY THEN ACTUALLY WE

WILL BE IN A POSITION WHERE WE

EITHER ADVERTISE OR WILL BE

ADVERTISING LOOKING FOR PEOPLE

TO COME IN ON THAT.

>> I WOULD SAY MIGHT OR MIGHT

NOT BE USEFUL TO INCLUDE IN THAT

SOME PROVISION THAT WOULD ALLOW

TECHNICAL PEOPLE TO COME.

SOMEBODY WHO RUNS A CORE.

SOMEPLACE TO COME HERE, SPEND

MAYBE NOT A YEAR THREE MONTHS OR

SIX MONTHS OR SOMETHING LIKE

THAT.

NOT JUST DISTINGUISHED

SCIENTISTS.

>> THE TECHNOLOGY HERE IS VERY

IMPORTANT.

>> 

>> THAT'S WHAT I WAS TRYING TO

SAY.

ALL RIGHT.

THANKS TO EVERYBODY AND I THINK

THIS IS A TERRIFIC FIRST

MEETING.

AND I LOOK FORWARD TO SEEING YOU

ALL IN MAY.

>> THANK YOU.