WE'RE GAVELING THIS SECOND MEETING ON THE ADVISORY COUNCIL FOR THE NATIONAL CENTER FOR ADVISING TRANSLATIONAL SCIENCES AND THE CURES ACCELERATION NETWORK REVIEW BOARD TO ORDER. I'M CHRIS AUSTIN, DIRECTOR OF NCATS AND I'M JUST SAY A FEW THINGS THEN HAND THIS OVER TO FREDA. THE FIRST THING, I WANT TO THANK EVERYBODY FOR COMING. I THINK YOU'LL HEAR THROUGH THE COURSE OF TODAY NCATS IS STILL AT A FAIRLY MOLTEN STAGE IF YOU WILL. THOSE OF YOU HERE FOR THE LAST MEETLING KNOW THE FIRST ORDER OF BUSINESS AT THAT MEETING WAS TO ANNOUNCE MY DIRECTORSHIP, MY APPOINTMENT AS DIRECTOR. SO I SPENT THE LAST THREE MONTHS OR SO SINCE THE LAST MEETING DOING A LOT OF CONSULTATION INSIDE AND OUT OF NCATS FOR WHAT NCATS SHOULD DO. AND THERE ARE MANY, MANY, MANY THINGS WHICH I WOULD LIKE NCATS TO DO AND YOU WOULD ALL TO DO, WE FIND OURSELVES IN AN UNPRECEDENTEDLY RESTRICTED BUDGET ENVIRONMENT. WHAT WE'RE GOING TO BE DOING OVER TODAY AND WITH OTHER GET TOGETHERS THAT YOU'VE GOTTEN EMAILS ABOUT IS TO COME UP WITH AN AMBITIOUS BUT DOABLE LONG TERM, SHORT TERM AND LONG TERM STRATEGIC PLAN FOR WHAT NCATS SHOULD DO. TODAY YOU'LLuhz NOTICE FROM THE AGENDA, THAT WE HAVE A RELATIVELY SMALL CLOSED SESSION. WE HAVE RELATIVELY SMALL GROUP OF GRANTS THAT WE NEED TO GO THROUGH. THOSE ON COUNCILS BEFORE KNOW THAT THAT IS FREQUENTLY THE MAIN BUSINESS OF THE COUNCIL. BUT BECAUSE OF THE WAY NCATS FUNDING CYCLE HAVE WORKED AND PROGRAM NCATS WE HAVE RELATIVELY FEW TODAY. THAT'S GOOD BECAUSE IT ALLOWS US TO FURTHER INTRODUCE Y'ALL TO SOME OF THE THINGS THAT NCATS IS DOING AS A WAY TO GET YOUR BRAINS GOING FOR WHAT WE SHOULD DO GOING FORWARD. I WANT TO MAKE A FEW LOGISTICAL OR HOUSEKEEPING POINTS. THE FIRST IS THIS SESSION IS BEING VIDEOCAST. SO WHEN YOU SPEAK PLEASE TURN ON YOUR MICROPHONE, OTHERWISE THE PEOPLE ON THE VIDEO WON'T HEAR WHAT YOU'RE SAYING. WHEN YOU'RE DONE SPEAKING, PLEASE TURN IT OFF BECAUSE THIS IS A FUNNY SYSTEM, A LOT OF YOU MAY KNOW ABOUT ALREADY THAT IF MORE THAN ONE IS OFF IT CAUSES INTERFERENCE AND SO PLEASE TURN IT OFF ONCE YOU'RE DONE TALKING BUT ALSO PREEVENTUAL, THINGS WERE BEING BROADCAST THAT YOU MIGHT THINK ARE PRIVATE SO YOU MIGHT TURN THEM OFF FOR THAT REASON TOO. WE HAD SOME UNCERTAINTY LAST TIME ABOUT THE VARIOUS ROLES THAT PEOPLE PLAYED. SO YOU WILL NOTICE IN YOUR FOLDER THERE IS A CHEAT SHEET HERE SO YOU CAN TELL FROM -- I'LL TELL YOU WHAT THE CHEAT SHEET IS, BUT PEOPLE WHO HAVE ON THEIR NAME TAG IF YOU'RE A RED PERSON YOU'RE A COUNCIL PERSON AND A CAN PERSON. IF YOU'RE BLUE PERSON YOU'RE JUST ON CAN. SO WE HAVE A SYSTEM WHERE WE CAN TELL WHO IS WHO. SO WHEN DIFFERENT PEOPLE ARE TALKING WE CAN TELL WHO IS ON THE CAN BOARD AND WHO IS ON THE COUNCIL. JUST TO REMIND YOU, THERE ARE 24 MEMBERS OF THE CAN BOARD BUT 18 MEMBERS OF THE COUNCIL. SO THERE'S ONE IS A SUBSET OF THE OTHER. PROBABLY THE FIRST THING I NEED TO DO IS JUST OFFICIALLY APPROVE THE MINUTES FROM LAST TIME. I THINK YOU HAVE ALL SEEN THE MINUTES, I HOPE YOU HAVE SEEN THE MINUTES. I NEED TO OFFICIALLY GET THEM APPROVED, I NEED A MOTION TO APPROVE THE MINUTES. >> SO MOVED. >> SECOND. ALL APPROVEDDED. ALL THIS FAVOR, AYE. OPPOSED. THANK YOU. SO THE MINUTES ARE APPROVED. THE LAST THING I WILL SAY BEFORE I LET FREDA GO IS I WANT TO EXPRESS A VERY DEEP MESSAGE OF GRATITUDE TO THE GENTLEMAN TO MY RIGHT. WHO IS RESPONSIBLE FOR EVERYTHING GOOD THAT HAPPENS OUT OF THIS MEETING. WHEN OUR PREVIOUS DIRECT TO OF OGMSR, OFFICE OF GRANTS MANAGEMENT AND SCIENTIFIC REVIEW GOT A PROMOTION TO SALLY ROCKEY'S SHOP A FEW MONTHS AGO IN A PANIC I WENT DOWN THE HALL TO DAN WHO HAD LIKE MOST PEOPLE AT NCATS ALREADY HAD A JOB AT NCATS DOING SOMETHING ELSE. AND APPEAL TO HIM TO TAKE THIS JOB OVER IN TYPICAL FASHION BOTH FOR DAN AND I LIKE TO SAY TO SAY FOR EVERYBODY AT NCATS, WHATEVER I CAN DO TO HELP, SURE. I DON'T KNOW IF YOU REALLY KNEW WHAT HE WAS GETTING HIMSELF INTO WHEN HE AGREED TO DO THAT BUT HE'S DONE A SPECTACULAR JOB WITH THIS. AND SO GOING TO BE LEANING ON HIM HEAVILY AND JUST WANT TO THANK HIM VERY PUBLICLY BEFORE WE GET GOING. THANK YOU, DAN. FREDA. >> GOOD MORNING TO ALL, THANK YOU. WELCOME TO THE SECOND JOINT MEETING. REALLY EXCITED THAT YOU ARE ALL HERE. WE PUT TOGETHER WHAT I THINK IS AN AMAZING QUITE ROBUST AGENDA. OUR TRUST IS THAT YOU ALL WILL BE AS FORTHCOMING WITH YOUR COMMENTS AND IDEAS AS YOU WERE AT THE LAST MEETING. THIS IS INDEED GOING TO BE AN INTERESTING AND CHALLENGING TIMEr FOR THE EVOLUTION OF THE WORK OF THIS GROUP AND NCATS AND ALL ALL OF THE ATTENDANT WORK. CHRIS AND I WERE TALKING THIS MORNING ABOUT THE NOTION THAT WE WERE TODDLERS BUT WE BETTER ACT LIKE SUPER HUMAN TODDLERS WITH SPECIAL POWERS TO FREE THINGS TO FLY, TO DO ALL KINDS OF AMAZING THINGS IF WE'RE GOING TO GET OUR WORK ADVANCED IN TIGHT ECONOMIC TIMES. AND UNDER QUITE ENORMOUS PRESSURE. WE'RE EXCITED TO HAVE Y'ALL HERE AND TO BE PREPARED TO LAUNCH THIS FURTHER. IT'S BEEN EXCITING TO WORK WITH DAN, AS WELL AS MANY OTHERS WHO HAVE CONTRIBUTED. CHRIS HAS BEEN AMAZING AS WE ALL EXPECTED. WITHOUT FURTHER ADIEU I THINK WE CAN LAUNCH INTO THE DIRECTOR'S REPORT. >> DAN REMINDS ME BRING YOUR ATTENTION TO THE FUTURE AND CAN BOARDS, THE FIRST PAGE PURPLE BOX. THE NEXT COUNCIL MEETING IS MAY 17th. THEN THERE'S ANOTHER VERY IMPORTANT MEETING IN SEPTEMBER. SO PLEASE KEEP THOSE ON YOUR CALENDARS. SO I'M GOING TO GET GOING WITH THE BREAKTOR'S REPORT NOW AND DO THAT VIA POWERPOINT. BUT I WANT TO PREFACE WHAT I SAY WITH THE FACT THAT LARRY TABAK IS COMING AT 9:15 AND WE ASKED HIM TO TALK ABOUT A SUBJECT OF CONCERN TO ALL OF US WHICH IS THE BUDGET SO I WILL SAY A FEW THINGS ABOUT THE BUDGET BUT LARRY HAS HAD THE IGNOMINIIOUS DUTY OF BEING AT THE TIP OF THE SPEAR WITH NIH SO WE'LL TALK TO US ABOUT THAT. >> SO I'M GOING TO GO THROUGH A FAIR AMOUNT OF MATERIAL QUICKLY BUT I REALLY WANT TO GIVE YOU A OVERVIEW OF ALL THAT'S HAPPENED THE LAST THREE MONTHS AND ALSO SAY A FEW THINGS ABOUT SOME SPECIAL PEOPLE WHO HAVE HELPED US ALONG THE WAY. TO REMIND YOU OF THE NCATS MISSION THAT ALL OF US HAVE BEEN REQUIRED TO MEMORIZE THIS, LIKE THE DEGREE TEASEBURG ADDRESS FOR LOT OF YOU. WE HAD TO MEMORIZE THESE THINGS BUT I WANT TO SHOW IT TO YOU AGAIN TO EMPHASIZE A FEW WORDS. AND THE FIRST WORD IS CATALYZE. THAT REALLY IS WHAT NCATS IS ALL ABOUT. YOU'LL HEAR US TELLING THIS OVER AND OVER AGAIN, IT'S A CATALYST IN MANY WAYS AS WE CONTINUE TO POINT OUT IT HAS TO BE A CATALYST FOR BOTH MISSION REASONS AN FUNDING REASONS. SO NCATS IS 2% OF THE NIH BUDGET SO IT HAS TO BE A CATALYST IN THE TRUEST SENSE, IT'S PRESENT IN VERY SMALL AMOUNTS BUT VERY PRODUCTIVE. IT DOES THAT BY BRINGING TOGETHER ORGANIZATIONS OR REAGENTS THAT ARE NOT REACTIVE BY THEMSELVES BUT WE MAKE GREAT THINGS HAPPEN BY BRINGING THE ORGANIZATION TOGETHER TO MAKE IT MORE EFFICIENT THAN ON THEIR OWN. THAT'S REALLY WHAT N CATS IS SUPPOSED TO DO. WE DO THAT IN A NUMBER OF WAYS, SOME THE FACT THAT WE ARE A COLLABORATIVE INSTRUMENT BY DESIGN. EEL COME BACK TO THAT. BUT IT'S ALSO BECAUSE OUR PURPOSE IS TO DEVELOP INNOVATIVE METHODS AND TECHNOLOGY THAT ENHANCE THE TRANSLATIONAL PROCESS. IN A DISEASE AGNOSTIC WAY. SO WHAT YOU'LL SEE THROUGHOUT THE COURSE OF TODAY IS ILLUSTRATION OF METHODS AND TECHNOLOGIES THAT DON INK BELL WILL TUCK ABOUT BUT ALSO YOU'LL SEE NOVEL PARADIGMS, COLLABORATIVE MECHANISM WHICH IS WORK ON SPECIFIC DISEASES BUT WE WORK ON THOSE DISEASES AS USE CASES TO ILLUSTRATE THE UTILITY OF NOVEL TECHNOLOGIES AND PARADIGMS SO NOVEL HOW CATEGORICAL WOULD APPROACH A PROBLEM. TOM INSEL WOULD APPROACH A PROBLEM BECAUSE HIS INSTITUTE HAS TO COME UP WITH TREATMENT FOR SCHIZOPHRENIA FOR EXAMPLE. WE MIGHT PICK IT BECAUSE WE THINK IT'S AN IMPORTANT WAY TO DEMONSTRATE A NOVEL APPROACH TO THE PROBLEM AT LARGE. SO WHAT'S CHANGED FROM LAST YEAR TO THIS YEAR, TO BEGINNING OF THIS YEAR, FROM THE DAY I TOOK OVER NCATS TO THE FIRST OF THE YEAR YOU REMEMBER LAST TIME YOU WERE HERE THERE WERE THESE TWO FOLKS WHO WERE HERE. TOM AND CATHY. AND AS OF THE 23RD, TOM RETIRED BACK TO NIMH, I ASKED HIM THE COME, SO THAT I COULD IN THE MOST PUBLIC FORUM WAY RECOGNIZE ALL THAT HE DID IN GETTING NCATS STARTED. YOU -- PROBABLY MANY HAVE STARTED NEW ORGANIZATIONS AND YOU KNOW HOW DIFFICULT THAT IS. PARTICULARLY WHEN TOM WAS CALLED SHORTLY AFTER CHRISTMAS ACTUALLY IN 2011 BY FRANCIS TO SAY WOULD YOU PLEASE TAKE THE HELM OF THIS CRAZY NEW ORGANIZATION THAT IS ACTUALLY A MERGER OF FOUR DIFFERENT ORGANIZATIONS, WE ACTUALLY DON'T HAVE ANYBODY TO RUN IT AN EVERYBODY IS TEMPORARY BUT IT ONLY WOULD BE A COUPLE OF MONTHS BECAUSE WE'RE GOING TO HAVE A DIRECTOR HERE PROBABLY BY MARCH, THAT WAS THE ORIGINAL THING. TOM TO BE THIS ON WITH A GENERAL JAN, BOTH CULTURALLY AND SCIENTIFICALLY SET A PATH FOR THE CENTER WHICH WHEN I TOOK OVER AS DIRECTOR MADE MY LIFE INFINITELY EASIER. SO I WANT TO THANK TOM, TOM IS HERE, COULD YOU STAND UP AND WE CAN -- GIVE EVERYBODY A ROUND OF APPLAUSE.$mm TOM AS YOU KNOW HAS -- IS RETURNED TO HIS DAY JOB RUNNING NIMH AND ONE OF THE THINGS THAT'S GREAT ABOUT THAT FOR US IS THAT MY OWN TRAINING IS IN PSYCHIATRY SO THE FIELD TOM WORKS IN IS NEAR AND DEAR TO MY HEART. BUT THERE ARE MANY ISSUES WHICH ARE PARTICULARLY ACUTE IN THE FIELD OF MENTAL ILLNESS IN DEVELOPMENT OF NOVEL INTERVENTIONS FOR MENTAL ILLNESS WHICH I LOOK FORWARD TO WORKING TOM AND NIMH ONGOING FORWARD. SO THAT CATHY ALSO ASKED TO BE HERE BUT CATHY IS ACTUALLY WITH HER FAMILY. HER FATHER HAS -- IS SICK SO SHE'S DOWN IN TEXAS SO SHE COULDN'T BE HERE TODAY. AND -- BUT SO WHO IS TAKEN THESE PEOPLE'S PLACE? IT'S THIS GUY. SO I TOOK OVER THE DEPUTY DIRECTOR JOB RIGHT BEFORE THANKSGIVING AFTER THE ELECTION. CATHY WHOSE DAY JOB AS YOU PROBABLY REMEMBER WAS AND IS FRANCIS COLLINS DEPUTY DIRECTOR, GOT RECALLED TO BUILDING 1 TO HELP FRANCIS. SO SHE HAD ALSO HAD TWO OR THREE MONTH ASSIGNMENT AND A YEAR LATER WAS STILL IN NCATS. SO SHE REALLY NEEDED TO GET BACK TO BUILDING 1 AND HELP THE NEXT BIG THING IN BUILDING ONE AS WELL AS DEAL WITH THE BUDGET AND OTHER THINGS. SO I BECAME DIRECTOR AND DEPUTY DIRECTOR AS OF RIGHT BEFORE THANKSGIVING. YOU PROBABLY REMEMBER JANE STEINBERG WHO RAN THE COUNCIL MEETING LAST TIME WAS ACTING HEAD OF OGMSR. I MENTIONED BEFORE DAN TAGLY IS ACT HEAD OF OGMSR AND I'LL TALK RECRUITMENTS IN A SECOND. CATHY WAS ALSO, CATHY HUDSON WAS ALSO ACTING DRIPTOR OF POLICY COMMUNICATIONS AND STRATEGIC ALLIANCES, TA PERSON IS NOW LILY TORTILLA. SO LILY HAS WEALTH OF EXPERIENCE IN NUMBER OF INSTITUTES TECHNOLOGY TRANSFER PARTICULARLY WITH PLUM AND EFFICIENCY AS WELL. I WAS RUNNING PRIOR TO SEPTEMBER 23RD AND I HAVE BEEN ABLE TO GIVE UP ONE JOB, THAT JOB IS MORE RUN BY JOHN MCKEW WHO YOU'LL HEAR FROM LATER TODAY. FINALLY THE DIVISION OF CLINICAL INNOVATION WAS RUN BY JOSIE BRIGGS AND I ASKED HIM TO BE HERE AS WELL SO THAT I COULD RECOGNIZE HER AND I EVEN HAVE A PLAQUE FOR YOSHI. WE HAD -- SO THIS PLAQUE THE DIRECTORS DISTINGUISHED SERVICE AWARD TO JOCIE BRIGGS AND SAYS IN RECOGNITION OF YOUR EXCEPTIONAL ACCOMPLISHMENTS WHILE SERVING INAUGURAL ACTING DIRECTOR OF NCATS DIVISION OF CLINICAL INNOVATION. THANK YOU, JOCIE. [APPLAUSE] >> THANK YOU. SO JOCIE ALSO HAS A DAY JOB AS YOU PROBABLY KNOW, DIRECTOR OF THE NATIONAL CENTER FOR ADVANCING COMPLIMENTARY AND ALTERNATIVE MEDICINE. JOCIE HAD OF ALL THESE JOBS ARE ALL HARD JOBS, THIS WAS PERHAPS HARDEST JOB. IT IS THE DIVISION THAT CONSTITUTES 80, 85% OF THE BUDGET. SO IT'S A VERY CHALLENGING JOB RUNNING THE CTSA PROGRAM. WE'LL TALK ABOUT THAT A LOT. JOCIE BROUGHT ENORMOUS WISDOM TO THIS TASK AND HAS SET THAT PROGRAM ON A TRAJECTORY WHICH I'M VERY ENTHUSIASTIC ABOUT AND WE'RE CONTINUING THE EVOLUTION OF. SO ANY SUCCESS THAT BCI HAS WILL BE A LEGACY OF WHAT JOCIE HAS DONE. SO THANK YOU. THAT JOB IS CURRENTLY BEING RUN BY THIS GENTLEMAN WHO ALSO IS NOW ACTING HEAD OF TCI AS THE FIRST OF JANUARY FOR THE SIMPLE REASON JOCIE CRIED UNCLE END OF LAST YEAR AND SAID MY INSTITUTE HAS BEEN WITHOUT A DIRECTOR FOR A YEAR. I NEED TO GO BACK AND RUN MY INSTITUTE. AND ALSO SHE FELT AND I AGREE, AS I GET -- LEARN ABOUT THIS ORGANIZATION THERE IS NOTHING LIKEph UNDERSTAND ITS GUTS AND HOW IT WORKS, HOW IT DOESN'T, STRENGTHS AND WHAT ITS WEAKNESSES ARE. THOUGH I AM AS YOU'LL SEE HERE SOMETIMES CALL MYSELF PRESIDENT, VICE PRESIDENT AND SPEAKER OF THE HOUSE AT THE MOMENT SO IN TRUE TOM INSEL FASHION I SPENT TIME TALKING TO MYSELF AND I'M TALKING TO TOM ABOUT THERAPIES FOR THAT T. REAL THERAPY IS TO GET PEOPLE TO TAKE THESE PLACES. I WANT TO SAY THE ADVANTAGE OF THIS TO BE SERIOUS FOR A MOMENT, IS THAT THOUGH IT HAS GIVEN EVERYBODY MORE THAN ONE JOB, WHAT WE HAVE NOW IS A GROUP OF PEOPLE WHO ARE VERY COMMITTED TO THE MISSION AND DON'T HAVE ANOTHER JOB AT ANOTHER INSTITUTE TO WORRY ABOUT. SO THEIR FULL TIME INTEREST IS IN THE CARE AND FEEDING AND DEVELOPMENT AND EVOLUTION OF N CATS. IT HAS A BIT OF A FEELING OF A STARTUP WHICH I LIKE AN ENORMOUS AMOUNT, THAT'S REALLY HOW THIS ORGANIZATION OUGHT TO FEEL. THOUGH IT IS A MERGER OF FOUR ORGANIZATIONS THAT PREVIOUSLY EXISTED AT NIH, IT FEELS LIKE A START UP WITH MULTIPLE PEOPLE DOING MULTIPLE JOBS AND THINKING ABOUT THE DIRECTION THE ORGANIZATION IS GOING TO GO IN. THAT IS THE GOOD SIDE. WE ARE REALLY RECRUITING A LOT. WHERE ARE WE NOW? WE'RE QUITE FAR ADVANCED SO THE DIVISION OF CLINICAL INNOVATION DIRECTOR, JOCIE AND STEVE CATS ARE THE SEARCH COMMITTEE HEADS FOR THAT COMMITTEE AND THEY'RE CURRENTLY INTERVIEWING CANDIDATES. WE HAVE A NUMBER OF GOOD CANDIDATES FOR THAT JOB SO I'M HOPEFUL OF FILLING THAT POSITION SOON. OFF AFTER FUSS OF GRANTS MANAGEMENT SCIENTIFIC REVUE DIRECTOR IS IN A SIMILAR STAGE, HAVE INTERVIEWED CANDIDATES. THE DEPUTY DIRECTOR SEARCH IS APPROVED, THAT'S UNDERWAY, (INDISCERNIBLE) SOME OF YOU KNOW IS GOING TO CHAIR THAT COMMITTEE FROM NINDS, THE EXECUTIVE OFFICER POSITION THAT SEARCH BEEN APPROVE AND IS UNDERWAY AS WELL. THE TWO THAT WE HAVE ARE JUST GETTING -- THINKING OF GETTING STARTING IN PRE-CLINICAL INNOVATION, MAINLY BECAUSE THEY'RE DOING QUITE WELL. AS IT IS. AND SO FELT THESE WERE ONES THAT WE CAN DEPRIORITIZE, THE FIRST FOUR ARE ONES I FELT WE NEEDED TO GET FILLED SOONER RATHER THAN LATER BUT WE'RE MAKING HEADWAY ON ALL OF THEM. SO JUST A COUPLE OF THINGS ABOUT THE BUDGET. AGAIN, LARRY WILL TALK MORE ABOUT THIS. WE'RE OPERATING YOU CAN CAN TEAR A CR CONTINUING RESOLUTION UNTIL MARCH 27th. THERE WAS AN ACT AS YOU KNOW PASSED ON P THE FIRST OF THE YEAR THAT WAS MAINLY ABOUT CHANGES IN THE TAX CODE. BUT WHAT IT ALSO DID WAS MOVE THE THREAT OF SEQUESTER DOWN FROM HAVING IMMEDIATELY OR ON JANUARY 2ND TEMPORARILY AVERTED, NOT -- THERE WAS SOME FEELING PEOPLE THOUGHT THE SEQUESTER HAS GONE AWAY, IT HASN'T GONE AWAY, A NEW SEQUESTER WILL HAPPEN UNLESS CONGRESS DOES SOMETHING TO AVERT IT. BUT THAT ESTIMATE FROM OMB NOW IS POTENTIAL REDUCTION WOULD NOT BE 8.2% BUT 6.4% FOR VARIOUS ARCANE BUDGET REASONS WE CAN GO INTO. THE IMPORTANT THING IS IT'S A LITTLE BETTER STORY THAN BEFORE. BUT I DON'T WANT TO UNDERESTIMATE THE DIFFICULTY OR PARTICULARLY BECAUSE THIS WOULD HAPPEN NOW HALFWAY THROUGH THE FISCAL YEAR. SO THERE'S ALL SORTS OF PLANNING THAT WE'RE TRYING TO DO SCENARIO BUILDING TO PLAN FOR WHAT WILL EVENTUALLY HAPPEN. YOU ALSO KNOW THERE'S BEEN A FEDERAL DEBT LIMIT REACHED THE END OF LAST YEAR. THE DEBT SEALING IS GOING TO BE -- CEILING IS GOING IT CAN ARGUED OVER THE NEXT MONTH. THIS WOULD HAVE INFLUENCE ON NIH'S SPENDING OF COURSE, BUT NOTHING SPECIAL FOR NIH, WOULD BE SOMETHING THAT WOULD APPLY TO ALL PARTS OF THE FEDERAL GOVERNMENT. SO WHAT WE'RE HOPING AND AS YOU KNOW ONE SAYS THE ADMINISTRATION WE'RE PART OF THE EXECUTIVE BRANCH SO WE'RE PART OF THE ADMINISTRATION, WE'RE HOPEFUL THAT THIS WILL BE AVERTED. I THINK THERE HAVE BEEN GOOD SIGNS THAT MAY HAPPEN. SO WE CERTAINLY HOPE THAT WILL HAPPEN. THE ONLY THING WE HAVE BEEN TOLD TO DO SO FAR IS WHAT WE ARE DOING, WE ARE PURSUING POLICY WHICH IS OPERATE UNDER A CR. AND THE MAIN ONE OF THOSE IS THAT WE'RE CONTINUING TO FUND NON-COMPETING GRANTS TYPE 5s FOR THOSE WHO KNOW THE VERNACULAR, 90% APPROVED LEVEL. THAT'S THE WAY THINGS ARE DONE UNDER A CR. SO THAT WILL GIVE FLEXIBILITY GOING FORWARD IN THE PRESENCE OF THE PRESENT SEQUESTER. SO RATHER THAN TALK ABOUT THIS NOW, THERE MAYBE QUESTIONS, LET'S PUT IT OFF UNTIL LARRY GETS HERE BECAUSE HE MAY HAVE MORE INFORMATION. SO I WANT TO GIVE A SENSE OF WHAT NCATS BUDGET LOOKS LIKE. THERE'S FOUR PIE CHARTS HERE THAT ARE CONFUSING BUT YOU HAVE THEM IN FRONT OF YOU. SO AT LEAST I HOPE YOU HAVE THEM IN FRONT OF YOU. SO YOU CAN PEER AT THEM. WE'RE LOOKING AT MULTIPLE WAYS TO SKIN THE NCATS CAT. AND WHAT WE'RE LOOKING AT FIRST HERE IS THE NCATS APPROPRIATION. WHAT IS THE NUMBER THAT YOU SEE IN IN THE ORIGINAL PRESIDENT'S BUDGET LAST YEAR. THIS WAS TOTAL BUDGET QUITE HIGHER THAN IT IS. THE MAJORITY OF THIS 639 MILLION, ABOUT 80% GOES TO THE CTSA PROGRAM. THERE ARE'S MULTIPLE OTHER P PROGRAMS THAT ARE IN THE OTHER DIVISIONS OVER HERE AND THESE GO BY NAMES HERE SOME WHICH YOU'LL RECOGNIZE. POINT I WANT TO MAKE IS THAT THIS IS -- THIS OTHER CATEGORY IS MADE UP OF ALL THE OTHER PROGRAMS THAT CATS DOES. TH IMPORTANT THING FOSI SO THAT Y'ALL RECOGNIZE THE ISSUE THAT WE'RE UNDER FARCE BUDGET FLEXIBILITY, THIS NUMBER OR NUMBER LIKE IT IS ACTUALLY WRITTEN INTO OUR APPROPRIATION. SO THERE IS A NUMBER CONGRESS HAS GIVEN THAT WE HAVE TO SPEND ON THIS PROGRAM. AND IT MAKES UP 80, 85% OF THE BUDGET. SO WE HAVE LIMITED FLEXIBILITY WITH REGARD TO THE REST OF THE BUDGET SO KEEP IT IN MIND WHEN WE TALK NEW PROGRAMS AND THINGS LIKE THAT. IT'S JUST WHAT WE HAVE -- THE CONDITIONS UNDER WHICH WE HAVE TO OPERATE. SO THIS WAS THE PRESIDENT'S BUDGET. IT NEVER WENT ANYWHERE SO THIS TURNED OUT TO BE FICTION. BUT THERE WAS THIS APPROPRIATION AND THEN THERE'S A NUMBER WHICH IS A LITTLE BIT HIGHER, THAT'S WHAT WILL BE REFERRED TO AS THE TOTAL PROGRAM. SO NCATS IN CLASSIC COLLABORATIVE FASHION HAS OTHER PROGRAMS NOT T IN OUR APPROPRIATION BUT THEY GET FUNDED BY OTHER INSTITUTES AND AGENTS. YOU NOTICE THE DIFFERENCE IN THIS NUMBER AN THIS NUMBER IS 15, $20 MILLION. THAT MONEY COMES FROM A BUNCH OF INSTITUTES THAT FUND NCATS TO DO COLLABORATIVE PROGRAMS. YOU'LL SEE TOTAL PROGRAMMING AND ROPEIATION AN THOSE THINGS ARE DIFFERENT. IN NIH VERNACULAR, REIMMERSABLES THAT'S WHAT THEY'RE TALKING ABOUT, MONEY FROM OTHER SOURCES, GOVERNMENT AGENCIES, OTHER ICs. SO YOU'LL NOTICE IMMEDIATELY THESE PIES ARE SMALLER. NOTICE THE CONTINUING RESOLUTION FOR FY 13, THIS IS WHAT WE'RE OPERATING UNDER. SO THIS IS THE APPROPRIATION THAT NCATS ACTUALLY GOT. NOTICE THE BUDGET IS 575 MILLION, PROBABLY THE NUMBER YOU'RE USED THE HEARING. AGAIN, THE VAST MAJORITY HERE MORE PERCENTAGE WISE IS IN THE CTSA BUDGET. IT'S THE OTHER CATEGORY THAT GOES DOWN DRAMATICALLY HERE. IN THE APPROPRIATION. HOWEVER, IT'S NOT QUITE THAT BAD BECAUSE IF YOU ADD THE TOTAL PROGRAM A LOT OF THE OTHER MONEY THAT NCATS HAS COMES FROM OTHER INSTITUTES AND CENTERS. WHILE THIS IS A GREAT THING BECAUSE IT ALLOWS NCATS TO -- INDICATES TWO THINGS, ONE, PEOPLE LOVE THE NCATS PROGRAM ENOUGH TO THROW MONEY AT US WHICH IS ALWAYS A GOOD THING. INDICATES CONFIDENCE IN THE PROGRAMS THAT WE DO. IT ALSO IN A UNCERTAIN BUDGET ENVIRONMENT DOES CAUSE HEART BURN. IT IS POSSIBLE THE PEOPLE WHO SUPPLY US MONEY TO DO THESE PROGRAMS WILL DECIDE WE'RE LIMITING BUDGET ENVIRONMENT, WE'RE GOING TO KEEP OUR MONEY AT HOME AND NOT FUND THESE EXTRA PROGRAMS. BUT WE'RE BUSY TALKING TO OUR COLLEAGUES ALL THE TIME TO MAKE SURE THIS PROGRAM -- THESE PROGRAMS CAN CONTINUE. ALL THESE PROGRAMS, I WANT TO STRESS ALL ARE EXTRAMURAL PROGRAMS WITH PEOPLE DEPENDENT UPON OR INTRAMURAL PROGRAMS WITH PEOPLE DEPENDENT ON THEM. THIS IS A REAL PROGRAMS WHERE PEOPLE ARE EMPLOYED. WE'RE THINKING ABOUT THIS A LOT. I REALIZE IT MIGHT BE CONFUSING AND TAKE YOU A WHILE TO GET USE TO THE SPORTS PORTION THAT MAKES UP NCATS. SOME COMES FROM THE FACT THIS WAS A PROGRAM FROM A MERGER OF FOUR DIFFERENT ORGANIZATIONS BUT SO I WANT TO INTRODUCE YOU TO ALL THESE TERMS THAT YOU'LL GET USED TO AS THE DAY GOES ON. THROUGHOUT THE DAY YOU'LL HEAR PRESENTATIONS ABOUT THE CTSA, TREND IN BRIDGES, ORDO, SOME OF THIS SBIR STTR PROGRAM, AND SOME CAN. SO YOU'LL HEAR MORE ABOUT EACH AND PUT THEM IN CONTEXT. SO COUPLE OF THINGS THAT HAPPENED SINCE -- THAT WILL AFFECT US, THERE'S APPROXIMATE AD CALLED FADASIA THAT SOME OF YOU WILL KNOW ABOUT, THERE'S A LOT OF TERMS, VERBIAGE THAT YOU CAN READ BUT THE IMPORTANT THING IS IT'S QUITE A POTENTIALLY ENABLING ACT WHICH APPLIES TO A LOT OF NCATS PROGRAMS BUT PARTICULARLY TREND WHICH WORKS IN THIS SPACE. THE IDEA IS THAT IT ESTABLISHES AN AUTHORITY THAT ALLOW FDA TO APPROVE TREATMENTS BASED ON DATA THAT MIGHT NOT HAVE BEEN PREVIOUSLY SUFFICIENT IN THE NORMAL APPROVAL PROCESS. A LOT HAS TO DO WITH DESIGNATING SOMETHING CALLED A BREAK THROUGH THERAPY WHICH WOULD ESSENTIALLY ALLOW FDA TO APPROVE A DRUG ON THE BASIS OF IN THE PAST MIGHT HAVE CALLED PHASE 2 DATA AND REQUIRE POST MARKETING DATA FOR DEFINITIVE EFFICACY AND SAFETY DATA. SO THIS IS SOMETHING THAT'S BEEN -- FLOATED MANY TIMES BUT IT'S ACTUALLY SOMETHING IS FDA HAS THE AUTHORITY TO DO NOW. THAT'S A GREAT THING, PARTICULARLY FOR PATIENTS WITH RARE DISEASES AS AN EXAMPLE WHERE IT CAN BE VERY HARD TO GET ENOUGH PATIENTS TO DO A CONVENTIONAL PHASE 3 TRIAL. THERE'S ALSO SOME FIXES TO ENABLE FDA TO ENGAGE MEDICAL AND SCIENTIFIC EXPERTS. IT'S BEEN A REAL PROBLEM WITH FDA GIVEN THE CONFLICT OF INTEREST RULES HARD TO ENGAGE PEOPLE WHO REALLY KNOW ABOUT THESE AREAS SO THEY'RE GIVEN MORE FLEXIBILITY THERE. ALSO SOMETHING WHICH IS NEAR AND DEAR TO MANY HEARTS IS ENHANCE DIRECT PATIENT ENGAGEMENT WITH FDA. SOMETHING NCATS DOES ACTIVELY AND SOMETHING WHICH WILL BENEFIT THE FDA AS WELL. SO WE HAD A POLICY WORKSHOP IN DECEMBER. ONE OF THE LAST THINGS CATHY HUDSON AND LARRY (INDISCERNIBLE) AND STEPHANIE DID. THIS IS PART OF THE ONGOING EFFORT NCATS HAS TO DO STRATEGIC PLANNING. AND ONE THING YOU HEARD ME SAY OVER AN OVER AGAIN, IN THE TRANSLATIONAL SPACE THERE ARE ENORMOUS SCIENTIFIC PROBLEMS. SOME OF THE MOST INTERESTING SCIENTIFIC PROBLEMS THESE DAYS I THINK IN THE TRANSLATIONAL SPACE. IF YOU ASK YOURSELF TRANSLATIONAL PROJECTS THAT FAIL, WHY DO THEY FAIL? THEY FAIL ABOUT HALF THE TIME PERHAPS STRICTLY SCIENTIFIC REASONS BUT THE OTHER HALF ARE NOT STRICTLY SCIENTIFIC REASONS, THEY'RE INCENTIVE OR POLICY OR IP REASONS OR COLLABORATIVE REASONS, SOMETHING WHICH IS NOT HOW WE HAVE TO THINK ABOUT THE STRICT BIOLOGY OR CHEMISTRY OR PHYSIOLOGY OF THE PROBLEM. BECAUSE NCATS' PURPOSE IS TO ACCELERATE TRANSLATION, AND IF THE PREMISE IS TRUE WHICH I THINK IT IS, THESE POLICY AND NON-SCIENTIFIC ISSUES ARE THINGS WHICH HOLD BACK TRANSLATION AS MUCH AS THE SCIENCE, THOSE NON-SCIENTIFIC ISSUES IF YOU WILL HAVE TO BE OR SOCIAL SCIENTIFIC ISSUES HAVE TO BE PROPER SUBJECTS OF STUDY FOR NCATS AS WELL. SO THAT WAS ONE OF THE THINGS THAT WE TALKED ABOUT AT THE POLICY WORKSHOP INCLUDING THINGS LIKE REGULATORY SCIENCE, INTELLECTUAL PROPERTY, BIOETHICS, THOSE KINDS OF THINGS. I SHOULD SAY, THERE'S A MEETING SUMMARY AND THAT'S ON THE WEBSITE NOW. SINCE BECOMING DIRECTOR, I HAVE BEEN DOING EXACTLY WHAT YOU WOULD EXPECT, NEW CHIEF EXECUTIVE OF A LARGE ORGANIZATION DOES THE SAME THING, I HAVE BEEN TALKING TO EVERYONE WITHIN THE ORGANIZATION, TALKING TO ALL OF MY 26 COLLEAGUES WHO WERE IC INSTITUTE AND CENTER DIRECTORS. I TALK TO VIRTUALLY ALL NOW ABOUT WHAT NCATS SHOULD DO AND HOW TO WORK WITH THEM AND OUTSIDE OF NIH PARTICULARLY VISITING THE CTSA LEADERSHIP AND VISIT TEN CTSAs TOGETHER WITH LANE COLLIER AS ACTING CO-DIRECTOR OF MY DIVISION. THOSE HAVE BEEN UNBELIEVELY USEFUL PHOTO LEARN ABOUT THE PROGRAM AND FANTASTIC THE POTENTIAL IS FOR THAT PROGRAM. I HAVE ABOUT FIVE MORE TO GO, I WILL HAVE VISITED 15 BY THE TIME I'M DONE. I MET WITH REPRESENTATIVES OF ALL KINDS OF ORGANIZATIONS. BIOTECH, PHARMA, FDA, OTHER GOVERNMENT AGENCIES. I WAS AT J.P. MORGAN LAST WEEK, THE FOLKS AT ELY LILLY LAST WEEK AS WELL AND PARTNERING FOR CURES, A LOT OF YOU WERE AT AND MARGARET IS OVER HERE WHO RAN THE MEETING. AND WE JUST WANTED TO SHOW YOU ONE CLIP HERE OF SOMETHING HOPEFULLY THE CLIP WILL WORK. THIS IS A PANEL THAT MARGARET MEDIATED IN THE LAST DAY HERE. BUT I GUESS WHAT I WOULD SAY IS THE BASIC RESEARCH ENTERPRISE IS DELIVERED ON P ITS COVENANT TO TELL US HOW TO MAKE NEW THERAPEUTICS, INTERVENTIONS DIAGNOSTICS, DEVICES. AND WHAT WE'RE NOW STRUCK WITH WITH IS A SYSTEM WHICH NEEDS TO BE CHANGED IN ORDER TO MAKE THAT HAPPEN. THE SYSTEM WE HAVE HAS DELIVERED ON WHAT IT WAS SUPPOSED TO DO. BUT THE SYSTEM WE HAVE WAS DESIGNED TO DO SOMETHING ELSE. IT WAS NOT DESIGNED TO DO THIS. THAT'S ONE OF THE REASONS NCATS WAS FORMED. Q. I THINK ONE OF THE THINGS THAT STRIKES US, THIS WAS THE RESPONSE THAT DALE EDGAR WAS SITTING NEXT TO ME AT THIS MEETING. I THOUGHT HE WAS GOING TO GIVE ME A HUG OR SOMETHING. SO DALE WAS HEAD OF EXTERNAL ALLIANCES AT LILY. ONE THING THAT IS SO EXCITING TO ME IS THAT -- AS ALL OF YOU REPRESENT, THERE REALLY IS A MEETING OF THE MINDS HERE WHERE PEOPLE IN ACADEMIA AND PHARMA AND BIOTECH AND BC AND REGULATORY ORGANIZATIONS REALIZE THAT THEY CAN'T DO THIS ALONE. AND WE NEED TO CREATE A NEW WAY OF DOING TRANSLATION IN A WAY THAT IS MORE COLLABORATIVE AND MORE EFFICIENT. THAT IS SOMETHING WHEN YOU THINK ABOUT IT, THERE ARE FEW ORGANIZATIONS IN THE WORLD THAT HAVE THAT AS THEIR MISSION OF THE POTENTIAL EXCEPT THE IMI IN EUROPE. IT'S A PROGRAM, NOT REALLY AN ORGANIZATION. SO WE HAVE A SPECIAL MISSION BUT A VERY SPECIAL OBLIGATION THAT I TAKE VERY SERIOUSLY AND I KNOW Y'ALL DO TOO. SOT IN THE SBIR WORLD, THE MANAGEMENT OF THESE PROGRAMS WAS REASSIGNED TO STRATEGIC ALLIANCES, UNDER THE DIRECTION OF LILY WHO KNOWS A HUGE AMOUNT ABOUT THIS AREA. LILY TORTILLA, NOT LILY THE COMPANY NOW. WE WOULD LIKE TO HAVE MANY STAFF NAMED AFTER PHARMACEUTICAL COMPANIES SO WE'RE LOOK FOR PEOPLE FROM MERCK AND PFIZER NOW. AND WE'LL REFOCUS THE PROGRAM IN A WAY THAT I THINK WILL BE PARTICULARLY USEFUL FOR NCATS BECAUSE NCATS DOES LIVE IN THIS DEMILITARIZED ZONE BETWEEN STRICTLY BASIC AND STRICTLY MECHANISTIC AND STRICTLY COMMERCIAL OR INTERVENTIONAL RESEARCH. SO IT'S PERFECT FOR THE SBIR PROGRAM. WE'RE LOOKING INTO AS TYPICAL WITH ALL OF NCATS PROGRAMS WE LOOK TO SEE HOW OTHER PEOPLE DO IT. WE'RE LOOKING HOW NCI AND NHLBI, THEY HAVE DONE INNOVATIVE THINGS IN THIS SPACE. SO THAT THE DIVISION OF CLINICAL INNOVATION, HEARSAY THE DIVISION RUN BY THE CTSA PROGRAM, THIS PROGRAM WE'RE DOING A LOT OF DIM NATION ON TO FIGURE HOW TO EVOLVE THIS PROGRAM TO HAVE IT MEET ENORMOUS POTENTIAL THAT IT HAS. THE MISSION OF NCRR WHICH THE CTSA PROGRAM CAME WAS FUNDAMENTALLY AN INFRASTRUCTURE MISSION. IT WAS NOT REALLY A SCIENCE MISSION THE WAY WE THINK ABOUT SCIENTIFIC DELIVERABLE. SO IT'S IMPORTANT AS THE MISSION OF THE INSTITUTE WHICH THIS PROGRAM LIVES HAS CHANGED. THE MISSION OF THE PROGRAM NEEDS TO EVOLVE AS WELL. THE EXCITING THING FOR ME AS I VISITED THE CTSA CENTERS IS THAT THE PIs ARE TOTALLY ON BOARD WITH THIS MISSION, THESE ARE FOLKS WHO GOT IN THE SCIENCE AND MEDICINE TO DO REALLY IMPORTANT SYSTEM-WIDE THINGS. AND THEY ARE EXCITED ABOUT POTENTIAL OF THE DIRECTION THAT WE'RE TAKING THE PROGRAM IN WHICH I'LL -- WHICH IS STILL AN EVOLUTION BUT LET ME GIVE YOU A FEW THOUGHTS. FIRST, THE PROGRAM HAS TO STAY TRUE TO ITS ROOTS TO PROVIDING NATIONAL LEADERSHIP AND QUALITY SAFETY EFFICIENCY, PARTICULARLY THE HUMAN SUBJECTS OF TRANSLATIONAL RESEARCH. BUT MORE EMPHASIS ON TRANSLATIONAL RESEARCH METHODS, WAYS TO DO THINGS BETTER INSTEAD OF SIMPLY PROVIDING RESOURCE WHICH IS ARE THE CURRENT STATE-OF-THE-ART. TRAINING CAREER DEVELOPMENT IS A HUGE PART OF WHAT THE CTSAs DO AND WILL CONTINUE TO BE. ONE THING THE NEW FUNDING ANNOUNCEMENT ALLOWS ORGANIZATIONS TO DO IS TO ENCOURAGE INSTITUTIONS THAT BUILD ON INSTITUTIONAL STRENGTHS. ALL PEOPLE TO BE ABLE TO BUILD ON PARTICULAR STRENGTHS. AND WORK THE PRINCIPLE WE'RE WORKING ON IS TO HAVE THE PROGRAM WORK MORE AS NETWORK, FOR THE SIMPLE REASON IN THIS SPACE THE BIGGEST PROBLEMS ARE SYSTEM WIDE WHICH NEED TO BE SOLVED AT A SYSTEM LEVEL. SO JUST A COUPLE OF THINGS TO WRAP UP HERE. A COUPLE OF REALLY GREAT STUDIES THAT CAME OUT TESTIFY THIS PROGRAM AND THE RTCRN THAT YOU'LL ALSO HEAR ABOUT. THIS IS A GREAT EXAM OF WHAT A NETWORK CAN DO, LOOKING AT AN OLD DRUG MANY OF YOU PROBABLY USED IN RARE DISEASE WHICH IS HARD TO STUDY BECAUSE IT'S IS RARE. THIS IS COLLABORATION BETWEEN TWO NCATS PROGRAMS THE RARE DISEASE CLINICAL RESEARCH NETWORK AND THE CTSA PROGRAM, SEVEN INSTITUTIONS AND FOUR COUNTRIES SO COULDN'T HAVE BEEN DONE BY AN INDIVIDUAL GROUP. THIS IS A SIMILAR STORY ON THE -- IN THE AREA OF DEVICES THAT WAS JUST PUBLISHED IN LANSETT LAST DECEMBER LOOKING AT -- YOU PROBABLY SAW THIS IN THE NEWSPAPER, PERHAPS 60 MINUTES, THIS WAS THIS WONDERFUL STORY OF PATIENTS WHO ARE DISABLED FROM A VARIETY OF NEUROLOGICAL ILLNESSES, ABLE TO USE ROBOTIC ARMS SIMPLY BY BRAIN ACTIVITY. SO AGAIN, SOMETHING THAT REQUIRED MANY COLLABORATORS ACROSS DIFFERENT ORGANIZATIONS AND INSTITUTIONS TO MAKE HAPPEN. PRE-CLINICAL INNOVATION, WE'RE GOING TO TALK ABOUT LATER SO I'LL SKIP THROUGH THESE. JUST WANT TO GIVE YOU A COUPLE OF HIGHLIGHTS SINCE LAST TIME WE MET. THIS ORGANIZATION CONTINUES TO BE TREMENDOUSLY PRODUCTIVE. THIS ORGANIZATION CO-AUTHORED OVER 100 PAPERS AND BOOK CHAPTERS LAST YEAR, A NUMBER AS AN EXAMPLE ARE GENERALLY USEFUL METHODS FOR ASSAY DEVELOPMENT HIGH THROUGH PUT SCREENING AND RNAi SCREENING. AND THIS IS A GREAT EXAMPLE OF DERISKING A NOVEL TARGET. THIS IS A HISTONE DEMETHYLASE WHICH REALLY SURPRISINGLY USING SMALL MOLECULE PROBES THAT THIS ORGANIZATION DEVELOPED TOGETHER WITH A NUMBER OF COLLABORATORS. APPEARS THE TO CONTROL THE HERPES VIRUS INFECTION AND REACTIVATION FROM LATENCY. THE TREND PROGRAM LAUNCHED A NUMBER OF -- TWO MORE TRIALS DURING THIS PERIOD. IT'S RATHER REMARKABLE RECORD THAT IN 15 MONTHS THIS PROGRAM HAS PUT FOUR DRUGS INTO PEOPLE. WHICH SHOWS THE POWER OF THIS COLLABORATIVE MODEL. ONE FOR HER RED TEAR INCLUSION BIOMYOOPATHY AND ANOTHER ONE JUST HAPPENED THIS WEEK ACTUALLY THIS IS A PRESS RELEASE WHICH IS DATED TODAY WHICH WE DID NOT WAIT UNTIL COUNCIL TO POINT THIS OUT BUT IT HAPPENS TO BE A REALLY WONDERFUL COINCIDENCE, THIS IS IN MY MIND AN EXON PAR OF WHAT NCATS OUGHT TO DO. THIS IS A CLINICAL TRIAL FOR A RARE FATAL NEUROLOGICAL DISORDER CALLED KNEEMAN PICK C DISEASE, A PROGRAM THAT STARTED IN ONE OF THE EARLIER PARTS P OF DPI AND ENDED UP IN TREND. BUT THE IMPORTANT THING IS THAT THIS IS THE PROJECT TEAM. AND THE PROJECT TEAM IS MADE UP OF 20 DIFFERENT PEOPLE FROM NINE ORGANIZATIONS BOTH INTRAMURAL, EXTRAMURAL AND COMPANIES. IF YOU LOOK AT THE EXPERTISE HERE, IT ILLUSTRATES BETTER THAN ANY I KNOW THAT TRANSLATION IS A TEAM SPORT. IT REQUIRES PEOPLE WHO ARE EXPERT AT EACH OF THESE AREAS, LOOK AT THESE ANIMAL MODELS, PHARMACOLOGY, NEUROLOGY, NEUROSURGERY, THERE'S NOBODY WHO HAS THIS EXPERTISE ON THEIR OWN. BUT TOGETHER THIS TEAM HAS MADE SOMETHING HAPPEN WHICH WAS IMPOSSIBLE BEFORE. THE FACT THAT THIS HAPPENED TOGETHER WITH NOT ONLY THE TEAM BUT WITH THE ACTIVE INVOLVEMENT OF THE FDA IS QUITE REMARKABLE. AND B THE COMPANIES INVOLVED HERE, PARTICULARLY J AND J WERE ABSOLUTELY CRITICAL IN PARTNERING WITH US GENERATING DATA WITH THE TEAM. AS A RESULT THIS TEAM WON ALSO LAST FALL WON AN EXCELLENCE IN TECH TRANSFER AWARD FOR THIS PROGRAM AS WELL. THIS IS DANNY PORTER WHO IS THE LEAD INVESTIGATOR, KNEEMAN PICK INVESTIGATOR AT NICHD, THESE WERE THE FOLKS FROM J AND J AND THIS IS LILY TORTILLA, HEAD OF OPICSA. HEAD OF OFFICE REQUIRE DISEASE RESEARCH STEVE GROFT RECEIVED A SOCIAL SECURITY ADMINISTRATION COMMISSIONERS APPRECIATION AWARD FOR HIS WORK TO ASSIST RARE DISEASE PATIENTS. DISABILITY BENEFITS ON -- AS A RESULT OF THE DIAGNOSIS THAT THEY HAVE. HE IS VERY INVOLVED IN THE SIXTH ANNUAL RARE DISEASE DAY THAT'S COMING UP AT THE I DID END OF FEBRUARY. SO TUNE IN FOR THAT. STEVE ALSO AND HIS TEAM GOT AN AWARD AT TREND AT THE BEGINNING OF THIS MONTH WHEN THE FDA CELEBRATED THE 30th ANNIVERSARY OF THE ORPHAN DRUG ACT THEY RECOGNIZE 30 RARE DISEASE HEROES OVER THE LAST 30 YEARS AN OFFICE OF RARE DISEASES RESEARCH WAS ONE OF THEM AND THE TREND GROUP WAS THE OTHER. HERE IS STEVE GROFT IN THE MIDDLE HERE, THAT'S JOHN MCKEW WHO RUNS TREND. IN THE NEW THERAPEUTICS FOR USES FOR EXISTING MOLECULES PROGRAM THAT YOU HEARD ABOUT, A BRIEF UPDATE HERE ON THAT. THIS IS A PROGRAM THAT MATCHES NIH RESEARCHERS WITH COMPOUNDS PRIORITIES BY VARIOUS FARM SUECAL COMPANIES AND ETHICAL AND BUSINESS REASONS. THERE ARE 58 COMPOUNDS FROM 8 COMPANIES CONTRIBUTED TO THIS. THIS WAS A PROGRAM THAT'S BEING RUN BY CHRISTINE COLVIS WITH NCATS. WHERE WE ARE IS THAT WE GOT LAST FALL ABOUT 160 APPLICATIONS FOR 58 COMPOUNDS, ALL IF I REMEMBER NUMBERS CORRECTLY ALL BUT ONE GOT AT LEAST ONE APPLICATION AND THERE WAS SOME COMPOUNDS WHICH GOT UP THE FOUR FOUR DIFFERENT INDICATIONS APPLIED FOR. SO THAT INITIAL METRIC THAT IS WOULD PEOPLE BE INTERESTED AND WOULD THEY COME UP WITH NOVEL IDEAS. THE ANSWER IS YES. THOSE WENT THROUGH INITIAL PEER REVIEW, THE XO-2 PROCESS AND FULL IMPLICATIONS WERE RECEIVED IN DECEMBER AN THESE ARE BEING REVIEWED, THESE ARE CO-APPLICATIONS BETWEEN THE ACADEMIC INVESTIGATOR AND THE COMPANY. AND WE WILL BE BRINGING THOSE TO YOU INr MAY FOR COUNCIL CONCURRENCE AND HOPE TO REWARD -- ISSUE THE AWARDS IN JUNE. YOU'LL HEAR MORE ABOUT THIS TISSUE CHIP PROGRAM LATER BUT I WANT TO REMIND YOU THAT THIS IS THIS JOINT PROGRAM THAT DAN TAGLY IS RUNNING. A JOINT PROGRAM BETWEEN NIH AND DRPA. EACH CONTRIBUTING ABOUT 70 MILLION, $75 MILLION OVER FIVE YEARS AND FDA INVOLVED IN REGULATORY AND TOX EXPERTISE. DAN AND TALKING ABOUT THIS THIS LATER IN THE APPROXIMATE. BUT THE -- AFTERNOON. BUT THE IDEA IS TO DEVELOP IN VITRO TISSUES IN HUMAN TISSUES TO EVALUATE INITIALLY TOXICITY BUT ALSO EFFICACY IN THAT PROGRAM IS EVOLVING AND YOU'LL HEAR THAT AS WELL. WHAT YOU'LL HEAR THROUGHOUT THE DAY THESE CHARACTERISTICS OF NCATS INITIATIVES AND WE SHOULD THINK ABOUT THESE GOING FORWARD WHAT THE NEW NCATS INITIATIVE SHOULD BE. THEY NEED TO ADDRESS SIGNIFICANT MODELS. ALL OF US WORK, SPEND OUR DAYS WORKING WITH BOTTLENECKS. WE'RE TRYING TO GET OVER HURDLES. THAT'S WHAT WE DO FOR A LIVING. SO WHAT I HAVE ASKED ALL THE PEOPLE WITHIN NCATS AND EVERYBODY I TALK TO AND ASK YOU TO DO TOO IS THINK ABOUT THE MOST PREVALENT BOTTLENECKS OR HURDLES THAT YOU HAVE TO JUMP THROUGH IN ORDER TO GET AN INTERVENTION TO PATIENTS WHICH YOU THINK WILL MAKE A BIG DIFFERENCE. WHAT ARE THOSE THINGS? AND WRITE THEM DOWN. THOSE ARE THE THINGS THAT NCATS OUGHT TO WORK ON. THEY NEED TO ADDRESS SIGNIFICANT BOTTLENECKS IN TRANSLATION. THEY WILL BE AS WE WILL KEEP COMING BACK TO GIVEN THE NATURE OF THESE PROBLEMS, HIGHLY COLLABORATIVE. ACROSS AGENCIES AND SPECIALTIES WITH THE PUBLIC AND PRIVATE SECTOR: AND WE HOPE THIS IS NOT A CONTRADICTION IN TERMS FOR A GOVERNMENT PROGRAM, QUICK WILL RESPOND TO NEEDS OF BIOMEDICAL RESEARCHERS, I WILL COME BACK TO THE RECORD OF THE -- SOME OF THE TREND PROGRAMS THAT IN TWO OF THOSE PROGRAMS WE HAVE GONE FROM SIGNING AGREEMENTS TO START THE PROGRAM TO BEING IN PEOPLE IN A YEAR. SO THIS CAN BE DONE, IT REQUIRES A MIND SET AND ATTITUDE TO MAKE IT HAPPEN. SO I WILL STOP THERE. I KNOW LARRY JUST WALKED IN SO WE WON'T TAKE ANY QUESTIONS NOW, I DON'T THINK BECAUSE I WANT TO BE RESPECTFUL OF LAYER IT'S TIME AND YOU CAN ASK ME QUESTIONS THROUGHOUT THE DAY. SO LARRY. (OFF MIC) (INAUDIBLE) WHAT HE COULD TALK ABOUT I MIGHT IMAGINE THE FIRST THING (INAUDIBLE) WHAT'S GOING ON WITH THE BUDGET (INAUDIBLE). >> THANKS, CHRIS. GOOD MORNING, EVERYBODY. IF ALL I WERE TO TALK ABOUT WAS THE BUDGET, IT WOULD BE A VERY, VERY SHORT DISCUSSION. BECAUSE I DON'T KNOW ANY MORE THAN YOU DO. BUT I WILL IN FACT GO THROUGH A NUMBER OF UPDATES, FRANCIS SENDS HIS REGRETS. HE'S CURRENTLY IN EUROPE, WHICH IS WHY I GET TO PINCH HIT HIM THIS MORNING. THE CURRENT STATUS OF THE BUDGET. AS I THINK Y'ALL KNOW WE'RE OPERATING UNDER A CONTINUING RESOLUTION THAT GOES THROUGH MARCH 27th. THE AMERICAN TAXPAYER RELIEF ACT IN JANUARY AVERTD THE IMMEDIATE THREAT OF THE 8.2% CUT THAT WAS TARGETED FOR THE NIH SPENDING. NEVERTHELESS, IF NO RESOLUTION IS ACHIEVEED, A NEW SEQUESTER WILL BE ORDERED BY THE PRESIDENT ON MARCH 1st. THE ACTUAL IMPLEMENTATION DOESN'T OCCUR UNTIL MARCH 27th FOR REASONS THAT I WON'T GO INTO. BECAUSE OF THE VARIOUS IMAGINATIONS, THE CUT AT THIS POINT IN TIME WOULD BE APPROXIMATELY 6.4%, THAT IS AN APPROXIMATION, THESE ARE STILL BEING REVIEWEDz„5„ BUDGET OFFICE. OUR FEDERAL DEBT LIMIT WAS REACHED DECEMBER 31st. WE HAVE UNTIL THE 28th DUE TO VARIOUS MANEUVERS THAT THE TREASURY DEPARTMENT USES. CONGRESS IS AMENABLE TO EXTENDING THIS BY THROW TO FOUR MONTHS. STAY TUNED. WE'LL SEE HOW THIS ALL PLAYS OUT. WITH REGARD TO THE ADMINISTRATION VIEWPOINT, THE ADMINISTRATION IS CONFIDENT THAT CONGRESS H AGREE TO REPLACE THE SEQUESTER WITH A BALANCED APPROACH ADDRESSING SPENDING AND BUDGET ISSUES. AT THE MOMENT WE'RE NOT RAMPING DOWN IN ANTICIPATION OF A SEQUESTER, WE CONTINUE TO OPERATE CAUTIOUSLY. GOVERNED BY A CONTINUING RESOLUTION. THIS IS BUSINESS AS USUAL, WE HAVE BEEN UNDER A CONTINUING RESOLUTION EVERY YEAR FOR AS LONG AS I CAN RECALL AND I HAVE BEEN HERE 13 YEARS. SO WE CONTINUE TO FUND NON-COMPETING AT 90% WHICH IS CONSISTENT WITH WHAT WE NORMALLY DO. SO I CAN STOP HERE IF THAT'S ALL YOU WANTED TO HEAR ABOUT AND ANSWER NONE OF YOUR QUESTIONS BECAUSE I HAVE NO ANSWERS. SO I'LL KEEP GOING AND SHARE WITH YOU VARIOUS UPDATES RELATED TO PLANS FOR IMPLEMENTATION OF RECOMMENDATIONS THAT DR. COLLINS RECEIVED BY WORKING GROUPS TO HIS ADVISORY COMMITTEE TO THE DIRECTOR, THE SO-CALLED ACD. I WILL ONLY HAVE TIME TO HIT SOME OF THE HIGHLIGHTS BUT ALL OF THE DETAILS ARE LOCATED AT THIS LINK. IF YOU ARE INTERESTED, I CERTAINLY ENCOURAGE YOU TO INTERROGATE THAT SITE. SO WE'LL BEGIN WITH A FEW COMMENTS ABOUT THE WORK RELATED TO THE ANALYSIS OF THE BIOMEDICAL RESEARCH WORK FORCE. AND YOU'VE ALL SEEN THESE ARTICLES. REFORM THE Ph.D. SYSTEM OR CLOSE IT DOWN, DOES THE U.S. PRODUCE TOO MANY SCIENTISTS. THE ANSWER IS SIMPLE. IF YOU HAVE A POST-DOC THAT GRADUATED FROM YOUR LAB AND IS LOOKING FOR A JOB, YES. IF YOU'RE LOOKING FOR THE REPLACEMENT TO THE POST-DOC, NO. IT DEPENDS ON YOUR PERSPECTIVE. SO FOR THE FIRST TIME IN A LONG TIME, A WORKING GROUP OF THE ADVISORY COMMITTEE TO THE DIRECTOR TOOK THIS ON, CO-CHAIRED BY SHIRLEY TILLMAN FROM PRINCETON AND SALLY ROCKEY WHO DIRECTS THE OFFICE OF EXTRAMURAL RESEARCH. THEY PRODUCED A STAG MODEL, A SNAP SHOT OF THE Ph.D. BIOMEDICAL RESEARCH WORK FORCE. THIS DOES NOT INCLUDE CLINICIAN SCIENTISTS OF ANY TYPE, THAT WILL BE TAKEN ON NEXT. BUT THIS IS A SNAP SHOT OF WHAT THE Ph.D. WORK FORCE LOOKS LIKE. AND THERE'S COLOR CODING TO THIS WITH NUMBERS IN RED BEING THE LEAST CONFIDENT IN TERMS OF THEIR RELIABILITY. AS YOU MIGHT IMAGINE MOST OF THAT IS DERIVED FROM THE SUBSET OF INDIVIDUALS WHO COME FROM THE INTERNATIONAL POOL OF TRAINEES AND FELLOWS. NEVERTHELESS, IT DOES GIVE YOU A SENSE ONLY 2% REPORT BEING UNEMPLOYED. THIS IS PARTICULARLY HEARTENING TO ME AS I HAVE A SON WHO IS A P DOCK NOW. SO I HOLD OUT HOPE. 13% ARE IN JOBS, THEY ARE EMPLOYED BUT THEY'RE NON-SCIENCE RELATED SO ONE COULD ARGUE OUT OF SCIENCE. BUT THE REMAINING GROUPS ARE ALL IN SCIENCE-RELATED JOBS. THERE'S A COHORT OF ABOUT 80% IN SO-CALLED SCIENCE NON-RELATED JOBS SO THESE ARE NON-RESEARCH JOBS. SO THESE ARE POLICY PHYSICIANS FOR EXAMPLE. BUT THEN THERE ARE A SERIES OF INDIVIDUALS WHO ARE IN RESEARCH AND/OR TEACHING POSITIONS REPRESENTING THE MAJORITY OF THE POOL. BE THEY INDUSTRY, ACADEMIA OR GOVERNMENT SITUATIONS. SO THE PROFILE SNOT AS DIRE AS SOME PREDICTED. BUT IS NEVERTHELESS POINTING OUT NOT EVERYBODY GOES INTO POSITIONS WHERE YOU TRAIN THE INDIVIDUAL IN YOUR OWN IMAGE. YES, SIR. >> DID THEY LOOK AT THE QUALITY OF THE JOB? BECAUSE OF THE SIX SPEAR OF A POST-DOC? >> EXCELLENT POINT THAT I'LL SPEAK TO IN A MOMENT. ALL THESE ACADEMIC POSITIONS, ONLY 23% ARE TENURED. THE REST PRESUMABLY ARE SO-CALLED RESEARCH ASSISTANT PROFESSOR JOBS WHICH AS YOU KNOW ARE SOFT MONEY. THE ISSUE OF THE QUALITY OF THE POSITION IS VERY, VERY IMPORTANT. I WILL GET TO THE THAT IN A SECOND. THE POINT IS FOR YEARS WE EQUATED RESEARCH CAREER TO BEING A TENURED PROFESSOR. AT THE TIME I WAS TRAINING FROM MY Ph.D. PEOPLE WHO WENT INTO INDUSTRY WERE SORT OF LOOKED AT WITH HALF A GLANCE, JUST BEGINNING TO CHANGE WITH THE EMERGENCE OF PLACES LIKE AMGEN. BUT CLEARLY THIS IS NO LONGER THE CASE. SO THE POINT IS WE NEED TO ADAPT TO WHAT IS A NEW REALITY. IN THE WORK FORCE POOL WE'RE CREATING. THIS IS NO SURPRISE TO YOU. IT'S INCREASINGLY IMPORTANT FOR THE FOLKS TO LAUNCH TRADITIONAL ACADEMIC CAREER. PARTLY BECAUSE MORE Ph.D.ES BUT MORE IMPORTANTLY THE NUMBER OF INVESTIGATOR CONTINUE THE RISE OR STAY IN THE FIELD. THIS SPEAKS TO THE POINT RAISED BY DR. SHEERER. AND OUR TRAINEES DO THE CALCULUS, ABOUT THE OPPORTUNITIES THAT PRESENT THEMSELVES PARTICULARLY AT ENTRY LEVEL PORTIONS OF BIOMEDICAL RESEARCH CAREER, THEY REALIZE THE LOW SALARIES AFFORDD BY POST DOCS OR RESEARCH ASSISTANT PROFESSORS, OR ADJUNCTS OR ANY OTHER TERMS THAT YOU USE IS ABYSMALLY LOW RELATIVE TO OPPORTUNITIES IN OTHER CAREER PATHS. OTHER PROFESSIONAL PATHS. SO WE CONTINUE TO LOSE A NUMBER OF BRIGHT YOUNG PEOPLE TO OTHER CAREER OPTIONS. YOU CAN ARGUE WHETHER THAT'S GOOD OR BAD THING BUT THIS IS THE REALITY WE NEED TO DEAL WITH. FINALLY TO RE-EMPHASIZE THE POINT NOT TRAINING PEOPLE IN OUR OWN IMAGE, OUR CURRENT TRAINING PROGRAMS OFFER LITTLE PREPARATION FOR CAREERS OUTSIDE ACADEMIA. DESPITE REALITY OF DECREASING LIKELIHOOD OF FINDING AN ACADEMIC POSITION. SO THIS INITIATIVE PROPOSES INNOVATIVE TRAINING APPROACHES THAT IT ASKS TO EXPAND THE OPPORTUNITIES OF TRAINING GRADUATE STUDENTS OR POST-DOCS IN THINGS THAT ARE NOT TRADITIONALLY ACADEMIC DRIVEN. IT WILL ASK US TO INCREASE THE AWARDS THAT WILL ENCOURAGE FIRST INDEPENDENCE, IT ASKS TO INCREASE THE SUPPORT WITH THE POST-DOC MAKING THAT ONRAMP A LITTLE MORE PALATABLE IN TERMS OF REMUNERATION. IT ALSO ASKS FOR US TO LOOK AT THE LEVEL OF FACULTY SUPPORT DERIVED FROM NIH GRANTS AS A WAY OF PERHAPS REBALANCING THE USE OF FUNDS, THAT IS TO BE CONDUCTED OVER A VERY LONG PERIOD OF TIME TO REPORT RECOMMENDS A 20 YEAR PERIOD. ONE OF THE PROBLEMS THAT WE HAD IN BOTH THIS INITIATIVE AND THE ONE RELATED TO DIVERSITY, IS THAT WE LACK A COMPREHENSIVE TRACKING SYSTEM FOR TRAINEES. WE DO A PRETTY GOOD JOB KNOWING WHERE THEY ARE WHEN THEY'RE IN OUR SYSTEM. BUT IF THEY LEAVE OUR SYSTEM, TEMPORARILY OR LONGER TERM TO PURSUE DIFFERENT CAREER OPPORTUNITIES AND COME BACK INTO OUR SYSTEM, IT IS VERY DIFFICULT TO RECONNECT WITH THEM. SO WE NEED TO PUT IN A MUCH MORE ROBUST TRACKING SYSTEM FOR ALL OUR TRAINEES. CONTINUE TO DO BETTER COORDINATION OF ACTIVITIES, AGAIN DETAIL OF THE PLAP IS FOUND AT THIS SITE. THIS FISCAL YEAR WE'LL LAUNCH A NEW WORKING GROUP TO LOOK AT THE ISSUES RELATED TO CLINICIAN SCIENTISTS. FINALIZE PLANS RELATED TO THE RECOMMENDATIONS ON THE TABLE INCLUDING THE ISSUANCE OF SOME RFAs. THE NEXT SET OF INITIATIVES COMES FROM THE WORK OF A WORKING GROUP LOOKING AT THE DIVERSITY OF THE BIOMEDICAL ARE SEARCH WORK FORCE. I WAS PRIVILEGED TO CO-CHAIR THIS WITH DR.'S JOHN RUFFIN, DIRECTOR OF NIMHD WHERE HE TALKS UNITED HEALTH. THE GENESIS OF THIS IS FAIRLY STRAIGHT FORWARD. ON YOUR LEFT IS A PIE GRAPH DEPICTING THE CENSUS OF THE NATION. ON YOUR RIGHT SAYING DISPLAY OF NIH PRINCIPLE INVESTIGATORS AND RPGs, DOESN'T TAKE HIGHER MATH TO OBSERVE WE ARE WOEFULLY UNDER-REPRESENTED AMONGST AFRICAN AMERICAN SCIENTISTS AND SIMILARLY AMONGST LATINOS AND HISPANICS OF ANY RACE. AND NUMBERS OF AMERICAN INDIANS ALASKA NATIVES, NATIVE HAWAIIANS AND OTHER PACIFIC ISLANDERS IS VERY, VERY SMALL. THEN OF COURSE BACK IN AUGUST OF 2011, THIS NIH SPONSORED PUBLICATION RACEETH MISTY NIH RESEARCH AWARDS POINTED OUT RACIAL DISPARITIES AMONG AFRICAN AMERICAN AND PLAQUE APPLICANTS RO-1 BUT IN ADDITION TO UNCOVERING THAT DISPARITY, IT POINTED OUT VANISHINGLY TINY NUMBERS OF BLACK AFRICAN AMERICAN APPLICANTS TO BEGIN WITH SO OF THE 83,000 RO-1 APPLICATIONS EXAMINED DURING THIS STUDY, ONLY 1149 CAME FROM BLACK OR AFRICAN AMERICANS. UNDERSCORING THE PIPELINE ISSUES IN GENERAL. SO THE CHALLENGES WE FACE WHILE DIVERSIFYING OUR WORK FORCE, FIRST NO ONE SET OF INITIATIVES IS GOING TO ACCOMPLISH THIS OVER NIGHT. THIS TAKES TIME. WE NEED TO ALL APPRECIATE THAT THERE'S A TREMENDOUS MISTRUST IN VARIOUS COMMUNITIES TO ENGAGE WITH WE HAVE TO WORK VERY HEAR TO TRUST THE GAINS IN THESE IMMUNITIES, WITHOUT THE HELP OF OUR EXTRAMURAL STAKEHOLDERS AND PARTNERS WE CAN'T ACCOMPLISH WHAT WE ARE SEEKING TO DO. AND THEN FINALLY AND MOVE IMPORTANTLY, DIVERSIFYING THE NIH FUNDED WORK FORCE AND ENSURING THE FAIRNESS OF THE PEER REVIEW SYSTEM, OUR COLLECTIVE RESPONSIBILITIES FOR EVERYBODY AT NIH. THE REASON FOR THAT IS PIMPLE. BECAUSE -- SIMPLE, BECAUSE EVERYBODY BENEFITS. SO TWO INITIATIVES WERE RECOMMENDED AND WILL BE IMPLEMENTED BY NIH IN RESPONSE TO THE RECOMMENDATIONS OF THE CCD WORKING GROUP. THE DIVERSITY BECAUSE WE HAVE COMPELLING EVIDENCE THIS WILL HELP ACCOMPLISH OUR MISSION. AND ARE ENHOUR ALL APPLICANTS ARE TREATED FAIRLY IN THE PEER REVIEW SYSTEM. THE OVERARCHING STRATEGY IS DEVELOPED THROUGH FOUR INTERRELATED APPROACHES THAT WILL BE IMPLEMENTED. AND INFRASTRUCTURE PROGRAM LEADING THE TO DIVERSITY THE SO CALLED BILL PROGRAM. THE NATIONAL RESEARCH MENTOR NETWORK DESIGNED TO AUGMENT BUT NOT REPLACE LOCAL MENTORING THAT NEEDS THE GO ON AT STUDENTS INDIVIDUAL INSTITUTION. A SERIES OF EFFORTS TO ENSURE FAIRNESS OF PEER REVIEW AND INCREASED ENGAGEMENT BY ALL OF NIH LEADERSHIP. AGAIN, THE FULL DETAILS ARE LOCATED AT THIS WEBSITE. THE BILL PROGRAM TARGETS STUDENTS OF 80,000 Ps PRODUCED EVERY YEAR IN BIOLOGY, HEM INDUSTRY AND PHYSICS, THOSE ARE SURROGATES FOR BIOMEDICAL RESEARCH. IT'S NOT PERFECT BUT IT'S A GOOD SURROGATE. OF THE 80,000,Ž ONLY 500 ARE AWARDED TO UNDER-REPRESENTED MINORITIES. THAT'S THE MAGNITUDE OF THE PROBLEM. SO WHAT THE BILL PROGRAM SEEKS TO DO IS ENHANCE NUMBER OF YOUNG PEOPLE WHO WILL CONVERT FROM THE BACCALAUREATE STAGE TO GO TO HIGHER TRAINING IN Ph.D.s RELEVANT TO BIOMEDICAL RESEARCH. THIS FISCAL YEAR, WE WILL BE RECRUITING A PERMANENT CHIEF OFFICER FOR SCIENTIFIC WORK FORCE DIVERSITY. ROBERT PEDIGREE IS SERVING IN ACTIVE COMPASSTISM HE'S DIRECTOR OF NIBIB. WE THOUGHT LONG AND HARD ABOUT THIS WHETHER THIS WAS A GOOD OR BAD IDEA. WE HAVE SEEN ORGANIZATIONS WHERE SUCH AN INDIVIDUAL IS APPOINTED AND THEN DIVERITY BECOMES THAT PERSON'S SOLE AND EXCLUSIVE PROBLEM. EVERYBODY ELSE WASHES THEIR HANDS. THIS IS EXACTLY WHAT WE DONE WANT TO HAVE HAPPEN SO THIS INDIVIDUAL WILL BE PROVIDED BY A FAIRLY BROAD MANDATE AND RESOURCES TO MAKE THINGS HAPPEN. PLANNING GRANTS FOR VARIOUS ACTIVITIES THAT I ARTICULATED IN THE PREVIOUS SLIDE WILL BE ISSUED THIS FISCAL YEAR ALONG WITH TECHNICAL WORKSHOPS WITH FUNDING OPPORTUNITIES ANNOUNCEMENTS FOR THE ACTUAL INITIATIVES LAUNCHED IN 2014. LAST THING THAT I WOULD LIKE TO DESCRIBE BRIEFLY ARE RELATED TO DATA AND INFORMATICS WORKING GROUP TO SET THE STAGE FOR THIS FINAL KEY STRATEGY IS TO ENSURE THAT THE NIH CULTURAL CHANGES ARE COMMENSURATE WITH RECOGNITION OF THE KEY ROLE OF INFORMATICS AND COMPUTATION FOR EVERY IC'S MISSION. IN OTHER WORDS, WE JUST CAN'T ASSUME NOT ONLY ONE OR TWO INSTITUTES OR CENTERS OR ONE OFFICE IS GOING TO TAKE CARE OF THIS ENTIRE COMPLEX SET OF ISSUES FOR THE ENTIRETY OF NIH. THIS IS EVERYBODY'S PROBLEM, EVERYBODY'S RESPONSIBILITY. SO PROBLEMS THAT NEED TO BE SOLVED WE NEED TO CREATE ADAPTIVE HOLY COLLABORATIVE ENVIRONMENT WITHIN NIH AS WELL AS IN THE EXTRAMURAL IMMUNITY TO ENABLE THE OPTIMAL USE OF MASSIVE AMOUNT OF DATA WE SUPPORT THE PRODUCTION OF EACH AND EVERY DAY. IF YOU THINK ABOUT IT YOURSELF, SEATED AROUND THIS TABLE, YOU OR YOUR COLLEAGUES PRODUCING MASSIVE DATA SETS, YOU KNOW ABOUT THEM, MAYBE YOUR NEXT DOOR NEIGHBOR KNOWS ABOUT THEM BUT UNTIL YOU PUBLISH THE GUY OR GAL ACROSS FROM YOU AT THIS TABLE DOESN'T KNOW ANYTHING ABOUT THAT DATA AND THEN WHEN YOU PUBLISH YOU ONLY PUBLISH A TINY SUBFRACTION OF THE DATA YOU ACTUALLY PRODUCED. WHAT THIS WILL SEEK TO DO IS COME UP WITH WAYS OF CATALOGING SO BETTER ACCESS OF ALL DATA AND COME UP WITH THE TOOLS NEEDED TO EXTRACT THE DATA FROM WHEREVER IT LIES, AND INTEGRATED REAL TIME COALESCE WITH DISPARATE DATA SETS SO YOU CAN DEBIN TO DO THE TYPES OF ANALYSES WITHOUT HAVING TO REDO THINGS ALREADY DONE. WE HAVE TO CREATE A GOVERNANCE STRUCTURE WITH RESOURCE MANAGEMENT AND YEAR SIGHT. AND PEER REVIEW AND SUPPORT FOR THE CENTER FOR SCIENTIFIC REVIEW, NIH HAS TO COMMIT TO A SHARED GOVERNANCE AND RESOURCE PLAN IS THAT THE USE AND OWNERSHIP OF BIG DATA IS ALL INSTITUTE AND CENTERS RESPONSIBILITY. THE INITIATIVES BEING PROPOSED, DD 2K TO ENABLE BIOMEDICAL RESEARCH ENTERPRISE TO MAXIMIZE THE VALUE OF BIOMEDICAL DATA AND INTERNAL EFFORT INFRASTRUCTURE PLUS TO MAKE OUR OWN ENVIRONMENT HERE AT NIH ADAPTIVE ENOUGH TO SUSTAIN WORLD CLASS BIOMEDICAL RESEARCH. TWO TRANS-NIH DATA COUNCILS WILL BE FORMED. ONE TO BE CHAIRED BY ANDREA NORRIS, THE NIH CIO, AND THE SECOND SCIENTIFIC DATA COUNCIL DATA SCIENCE WHO WILL BE RECRUITED. DR. ERIC GREEN HEAD OF THE GENOME INSTITUTE HAS AGREED TO SERVE IN THIS ROAM TEMPORARILY AS WE RECRUIT PERMANENT ASSOCIATE DIRECTORS. THE INITIATIVES AND SPECIFICS ARE LOCATED AT THIS WEBSITE. I URGE YOU THE TAKE A LOOK AT THAT. AS ARE DETAILS RELATED TO INTERNAL APPROACHES AS WELL. SO NEXT STEPS WE'RE CONSTITUTING VARIOUS ADVISORY BOARDS. WE'RE STARTING RECRUITMENT, WE'LL ISSUE RFAs THIS FISCAL YEAR WITH SOME WORKSHOPS. WITH MORE TO FOLLOW IN FISCAL YEARS 14 AND 15. WITH THAT I WILL STOP AND ANSWER ANY ADDITIONAL QUESTIONS YOU MAY HAVE. >> FROM THE POINT OF VIEW OFHv." VA WE HAVE CAREER SCIENTISTS AND ALL THAT AND HIGHER PROPORTION THIS DAY IN ACADEMICS. WE'RE TRYING TO FIGURE IT OUT AND WE ALSO LOSE TRACK OF A LOT OF PEOPLE. I WONDER IF YOU HAVE LOOKED AT CAREER TRAJECTORIES. THE MID CAREER PROBLEM IS A HUGE PROBLEM I THINK. AND HOW DO YOU -- HAVE YOU EXAMINED THAT AT ALL? >> THE PIECE OF THE PUZZLE RELATED TO IRRETENTION, IT IS TRUE WE BLEED A LOT OF PEOPLE OUT OF THE SYSTEM. WITHIN THE NIH WORLD OF COURSE, SECURING THE FIRST COMPETITIVE RENEWAL OF YOUR RO-1 GRANT BECOME ASCII POINT, FACILITATE YOUR RETENTION, TENURE OR WHATEVER THE EQUIVALENT IS AT THE INSTITUTION THAT YOU WORK, OR A DECISION TO MOVE ON TO SOMETHING ELSE. SHOESHINE BEGINNING TO LOOK AT BETTER WAYS OF ENSURING BETTER STABILITY FOR SCIENTISTS ENTERING THAT CRITICAL PHASE. A SUBPLOT TO THIS, WHILE WOMEN FAIR EQUALLY WELL TO MEN ON THE FIRST SUBMISSION, THE FIRST GRANT, THAT TRANSITION TO THE FIRST COMPETITIVE RENEWAL IS WHERE WE SEE A DISPARITY OF -- BETWEEN MEN AND WOMEN AND THERE'S A GROUP THAT IS LOOKING SPECIFICALLY AT THOSE ISSUES. LOTS OF ANECDOTES TO WHY THAT MAY BE HAPPENING. BUT WE NEED HARD DATA. BOTH KNOW PLURAL IS NOT ANECDOTE DATA. >> LAST POINT WE HAVEN'T LOOKED AT THAT AND I THINK WE WILL. >> YES, PLEASE. >> TWO QUESTIONS. ONE OF THEM RELATED TO THE ARTICLES THAT HIT THE NEWSPAPER THIS WEEKEND ON BIG DATA THAT DETERMINE DATA MINER CAN ACTUALLY IDENTIFY INDIVIDUALS WHOSE GENOME POSTED FOR SCIENTIFIC USE. HOW WILL THE NIH RESPOND TO THE IMPERATIVE TO PROTECT TO THE GREATEST EXTENT POSSIBLE THE PRIVACY ACCORDANCES OF OUR RESEARCH PARTICIPANTS? I WILL SAY AS SOMEONE WHO HAS THREE LARGE, FOUR LARGE AFFILIATED HOSPITAL SYSTEMS, THE DEGREE OF PARANOIA ABOUT THIS VARIES WIDELY AMONG THE HOSPITAL SYSTEMS IN TERMS OF HOW CONCERNED THEY ARE ABOUT BREECHING THE PRIVACY ISSUES. >> OBVIOUSLY CONFIDENTIALITY AND PRIVACY ARE PAIRMENT TO KEEP THE CONFIDENCE OF OUR PATIENT AND THOSE WHO VOLUNTEER TO ENROLL IN TRIALS. AS THE TECHNOLOGY GETS BETTER, IT OFFERS UP NEW CHALLENGES THAT WE NOW HAVE TO OVERCOME. SO NIH IS OBVIOUSLY AWARE OF THE MOST RECENT EVENTS AND IS WORKING HARD TOWARDS FEW FURRING OUT HOW ONE CAN OFFER BETTER PROTECTION. WHETHER OR NOT A DETERMINED INDIVIDUAL IS GOING TO BEhKo ABLE TO DO SOME IDENTIFICATION REGARDLESS OF THE EFFORTS THAT ONE TAKES, IT REMAINS TO BE SEEN. BUT CERTAINLY WE HAVE TO RESPOND. WE CERTAINLY WELCOME THE BENEFITS OF ENHANCED TECHNOLOGIES BUT WE ARE OBLIGATED TO DEAL WITH INCREASED ISSUES THOSE THINGS RAISE. >> THERE ARE SHORT TERM AND LONG TERM EVOLUTIONS. SHORT TERM PULL THE Y CHROMOSOME OUT OF DATA AND TAKE A FEW MONTHS TO FIGURE HOW TO DO IT. HOW TO DO SOMETHING MORE PERMANENT AND COMFORTABLE. BUT I THINK IT'S SOMETHING A NICE AD HOC GROUP OR STATEMENT FROM THE NIH OR STRATEGY WOULD REALLY HELP US IN THE IRBs THAT ARE OUT THERE THAT HAVE VARYING DEGREES OF UNDERSTANDING HOW DETERMINED YOU HAVE TO BE. AND ALSO REALLY HAVE GREAT PRIVACY CONCERNS. I HAVE ANOTHER QUESTION OR SUGGESTION. WONDER WHETHER NCATS IS UNIQUELY POSITIONED TO HELP WITH SOME OF THE DIVERSITY AND TRAINING ISSUES IN TERMS OF MAKING AVAILABLE THE KNOWLEDGE OF THE SPECTRUM OF CAREER OPPORTUNITIES FOR Ph.D.s. AND INDUSTRY AND REGULATORY AND OTHER KINDS OF NEEDS THE SCIENTIFIC COMMUNITY HAS THAT MAYBE FOR US AT NCATS ARE MORE PRESSING THAN MAYBE FOR SOME OF THE MORE CATEGORICAL INSTITUTES. THESE THINGS OFFER WORLDS -- OFFER OPPORTUNITIES FOR DIVERSITY IN WAYS THIS TRADITIONAL ACADEMIC UPWARD HIERARCHICAL PATHWAY MAY NOT. I'LL DEFER TO -- >> YOU STOLE MY THUNDER BECAUSE I WAS GOING THE THANK LARRY FOR TALKING ABOUT THESE BECAUSE I THINK ALL THREE OF THEM ARE THINGS THAT ARE PARTICULARLY RELEVANT FOR NCATS. THE FIRST ONE, I TALKED ABOUT THIS WITH HER WHEN WE WERE OUT VISITING HER IN CLEVELAND IS THE ISSUE, WHAT IS THE CAREER PATH FOR TRANSLATIONAL RESEARCHERS WHICH IS FREQUENTLY NON-TRADITIONAL IF YOU WANT TO THINK OF IT THAT WAY. WE TALKED IN THE EXCITING THINGS THAT I VIEW THIS AS AN OPPORTUNITY LIKE MANY THINGS, WHAT KIND OF A NEW CAREER PATH CAN WE HAVE FOR ACADEMIC DISCIPLINE OF TRANSLATIONAL SCIENCE. THAT'S ONE THING WE NEED TO DO AS AN ORGANIZATION. I HAVE GOTTEN THE DIVERSITY ISSUE THAT'S RIGHT. IT FITS PERFECTLY INTO THIS CATEGORY. I HAVE ACTUALLY GOTTEN INTERESTED THROUGH SOME WORK T AT LOCAL INSTITUTIONS IN THE ISSUE OF PARTNERING WITH WITH COMMUNITY COLLEGES AN JUNIOR COLLEGES THAT TRANSITION INTO FOUR YEAR INSTITUTIONS I WASD ON BOARD AND I GOT THIS JOB AND HAD TO BE OFF THE BOARD. 50% OF THE STUDENTS DOES FIRST TIME GOING TO COLLEGE MINORITY APPLICANTS. SO THEY'RE DOING THIS, THEY FIGURED HOW TO DO IT. SO HAVING NCATS INVOLVED IN THOSE WOULD BE VERY EXCITING. ON THE INFORMATICS SIDE, THOSE WHO TALK ABOUT THIS, I'M A ZEALOT ON ISSUE, WHEN YOU TALK ABOUT COLLABORATION AND TALK ABOUT THE NEED TO HAVE MULTIPLE DATA SETS GO INTO A PROJECT, GIVEN THAT TRANSLATION IS A TEAM SPORT, INFORMATICS IS THE ULTIMATE COLLABORATIVE ENTITY. SO THIS IS SOMETHING THAT IS A HUGE ISSUE FOR ALL THE DIVISIONS. ENYOU HEAR DPI TALK YOU'LL HEAR ABOUT THIS AND RARE DISEASE FOLKS, THE CTSI AND CTSA P DEVELOPING INTEROPERABLE NETWORKS ACROSS ALL THE CTSAs AND A COMMON IRBs, THESE ARE THINGS WHICH ARE REALLY IMPORTANT TO US PARTICULARLY. SO THERE ARE OPPORTUNITIES FOR US THAT LOOK FORWARD TO DISCUSSING ALL OF YOU. >> I HAVE A QUESTION BROAD USE OF BIG DATA, CAN YOU FURTHER DEFINE WHAT YOU MEAN BY BIG DATA HOW BROADLY DEFINING BIG DATA AND WHAT THE SOURCES MIGHT BE? >> WE ARE DEFINING THIS IN THE BROADEST POSSIBLE WAY. ELECTRONIC HEALTH RECORD, MANY IMAGING PIECES OF DATA ACCUMULATING. MARRYING THOSE UP EVEN WITH– RECORD IS A CHALLENGE. ALL THE OMICS, GENOMICS WHICH PEOPLE BEGINNING TO DO A REASONABLE JOB WITH, NOW TRYING FOR PROTEOMICS. GOOD LUCK WITH THAT. AND AS YOU DEVELOP DATA SETS, THE PROBLEM IS THEY SIT IN DIFFERENT PLACES AND THEY NEVER MEET ONE ANOTHER. AND THE CHALLENGE IS TO BE ABLE TO INTEGRATE AND INTERROGATE SIGH MULL TAPEIOUSLY ELECTRONIC HEALTH RECORD, THE IMAGING DATA. THE OMICS DATA. SIMULTANEOUSLY FROM DIFFERENT SYSTEMS. DIFFERENT LABORATORIES, FROM DIFFERENT HOPS. THAT'S THE ULTIMATE GOAL. WE HAVE TO START WORK AT THIS INCREMENTALLY. SO LET'S BEGIN FIGURING OUT THE BEST WAY OF INTEGRATING GENOMICS DATA WITH ELECTRONIC HEALTH RECORD. SOME OF YOU MAY KNOW HOW TO DO THIS, IF YOU DO, LET ME KNOW BECAUSELY SAFE TIME. >> ONE THING WE'RE CONCERNED ABOUT IS WHEN THERE ARE THESE DIFFERENT EFFORTS GOING ON LIKE CPAS, ARE YOU WORKING WITH THEM, AWARE OF THEM, COORDINATING WITH THEM AND NOT CREATING ANOTHER INITIATIVE? >> SO PART OF WHAT THIS INITIATIVE DOES IS THE OUTREACH TO THE STAKEHOLDERS. NOT SO MUCH TO GUIDE OR LEAD ANYTHING BECAUSE THESE ARE EFFORTS THAT ARE ONGOING BUT MERELY TO UNDERSTAND WHAT IS OCCURING IN THIS VERY VAST SPACE AND WHERE NIH CAN MAKE A CATALYTIC MARRIAGE OR A CATALYTIC APPROACH TO ACCELERATE SOMETHING OR ENHANCE WHAT'S GOING ON OVER HERE WITH WHAT'S GOING ON HERE, THAT'S WHERE WE HAVE TO MIC OUR INVESTMENT. SO DR. GREEN IS UP TO THE TASK INITIALLY AND WITH HELP AND HOPEFULLY COLLECTIVE HELP WE'LL BE ABLE TO FIND THE RIGHT PERSON TO LEAD THIS VERY, VERY IMPORTANT EFFORT FOR NIH. SFROM >> SO I WANT TO THANK LARRY FOR COMING, THIS IS A REALLY INTERESTING DISCUSSION BUT IN ORDER TO STAY ON TIME I'M GOING TO MOVE US ON. THANK YOU, LARRY, APPRECIATE IT. I WILL HAND THE OFFICIAL GAVEL TO FREE THE. >> I'M REALLY EXCITED ABOUT WHAT WE'RE ABOUT TO DO. WE'LL SPEND A FEW MINUTES DISCUSSING WHAT I THINK MIGHT BE A LEVERAGE POINT FOR US TO THINK ABOUT THE KINDS OF THINGS THAT CAN CAN DO. THERE WAS A MEETING, EACH OF YOU SHOULD HAVE RECEIVED THE SUMMARY FROM A MEETING HELD IN JUNE AT THE IOM LOOKING INTO OPTIONS IF YOU WOULD, AND IDEAS FOR CAN MOVING ITS WORK FORWARD. IT WAS A ROBUST TWO DAYS. MANY OF YOU WERE THERE. AND WE ASKED LOU DEGENNARO TO HELP FRAME, SHARE WITH YOU SOME OF THE WORK AND OUTPUT AND FRAME A DISCUSSION FOR US KNOWING WE WON'T WALK OUT TODAY HAVING DECIDED WHAT OF THIS WE WOULD APPLY. BUT BEGINNING TO GET THE DISCUSSION GOING AND THINKING HOW WE CAN LIST SOME OF THESE IDEAS, PRIORITIZE THEM AND MOVE THEM FORWARD. I THINK YOU KNOW LOU. I LOVE HIS JOB TITLE SO I SAY IT EVERY TIME I CAN. HE'S EXECUTIVE VICE PRESIDENT AND CHIEF MISSION OFFICER OF THE LEUKEMIA LYMPHOMA SOCIETY. SO WITHOUT FURTHER ADIEU, THANKS, LOU. >> THANK YOU, FREDA. GOOD MORNING, EVERYONE. THANKS FOR THE INTROWWW., FREDA. WHAT I WANT TO DO IS VERY BRIEFLY SUMMARIZE TWO DAYS OF DISCUSSION AT THE IOM. THE TITLE OF THE WORKSHOP WAS ACCELERATING THE DEVELOPMENT OF NEW DRUGS AND DIAGNOSTICS, MAXIMIZING THE IMPACT OF THE CURE ACCELERATION NETWORK. THANKS GO TO CAROLYN COME TON, MY CO-CHAIR AND IOM STAFF AND TWO DOZEN PARTICIPANTS IN THE WORKSHOP, MANY OF WHOM ARE IN THE ROOM. SO FEEL FREE TO SPEAK UP A Z WE GO THROUGH IT. WE'RE TRYING TO EXPLORE OPTIONS AND OPPORTUNITIES IN THE IMPLEMENTATION OF THE CURES ACCELERATION NETWORK. AGAIN, I WILL TRY TO SUMMARIZE THEM TO SPUR A CONVERSATION. I THOUGHT IT WOULD BE INSTRUCTIVE TO BRIEFLY REVIEW THE LEGISLATION THAT ACTUALLY CREATED THE CURES ACCELERATION NETWORK. BECAUSE I THINK THAT IN THE WORDING OF THE LEGISLATION THERE ARE SIGNALS SOMETHING ABOUT THE INTENT FOR WHAT CAN IS MEANT TO BE. THERE'S NO WAY I CAN PARAPHRASE THIS LEGALESE. CONDUCT AND SUPPORT REVOLUTIONARY ADVANCES IN BY BASIC RESEARCH, TRANSLATING SCIENTIFIC DISCOVERIES FROM BENCH TO BEDSIDE. AWAR GRANTS AND CONTRACTS TO ELIGIBLE ENTITIES TO ACCELERATE DEVELOPMENT OF HIGH NEED CURES. PROVIDE RESOURCES NECESSARY FOR GOVERNMENT AGENCIES INDEPENDENT INVESTIGATORS RESEARCH ORGANIZATIONS. BIOTECHNOLOGY COMPANIES, ACADEMIC RESEARCH INSTITUTIONS AND OTHER ENTITIES TO DEVELOP HIGH NEED CURES. REDUCE BARRIERS BETWEEN LABORATORY DISCOVERIES AN CLINICAL TRIALS FOR NEW THERAPIES. FACILITATE REVIEW FDA FOR HIGH NEED CURES BY CAN. THAT'S THE LEGISLATION, THE WORDING THAT CREATED THE CURES ACCELERATION NETWORK. IT WOULD BE INSTRUCTIVE TO UNDERSTAND WHAT THE DEFINITION OF HIGH NEED CURE WAS IN THE LEGISLATION. SO I'LL READ IT TO YOU AGAIN. HIGH NEED CURE A. DRUG, BIOLOGIC PRODUCT OR DEVICE THAT IS PRIORITY TO DIAGNOSE, MITIGATE, PREVENT OR TREAT HARM FROM ANY DISEASE OR CONDITION FOR WHICH INCENTIVES OF THE COMMERCIAL L MARKET ARE UNLIKELY TO RESULT IN ADEQUATE OR TIMELY DEVELOPMENT. THAT'S LEGISLATION THAT CREATED THE CURES ACCELERATION NETWORK. THE WORDING HERE SIGNALS TO SOME EXTENT WHAT THE CRAFTERS OF THIS LEGISLATION HAD IN MIND. THE WORKSHOP ASSEMBLED ACADEMIC SCIENCE AND MEDICINE, PEOPLE REPPING ACT SEMIE SCIENCE AND MEDICINE, INDUSTRY PROPERTY CAPITAL AND FOCUSED ON HIGH LEVEL DISCUSSION AREAS SUCH AS THE ONES THAT ARE HERE. HOW CAN CAN HAVE IMPACT. WHAT TOOLS AN METHODS AN APPROACHES SHOULD IT EMPLOY. WHAT'S THE BEST USE OF TWO UNIQUE FUNDING AUTHORITIES THAT CAN HAS, THE MATCHING AND FLEXIBLE AUTHORITIES. HOW CAN ASSIST IN PUBLIC PRIVATE PARTNERSHIPS. AND WHAT'S THE CAN FDA INTERACTION GOING TO LOOK LIKE. SO I'LL TRY TO DRILL DOWN QUICKLY SOME OF THE ANSWERS, INPUT AND OUTPUT FROM THE DISCUSSION. AROUND THESE QUESTIONS. WITH RESPECT TO ACCELERATING TRANSLATIONAL SCIENCE, I THINK FOR ME TWO THINGS POPPED. ONE WAS PARTNERSHIP AND POWER OF PARTNERSHIPS. THE CAN SHOULD BE ABOUT INCENTIVIZEING DERISKING AND FACILITATING RESEARCH PARTNERSHIPS BETWEEN MULTIPLE ORGANIZATIONS. ONE SUGGESTION, ONE PRACTICAL SUGGESTION FROM THIS DISCUSSION, CAN CAN IS CURE RATE THE FEATURES OF EXISTING PROMISING AND SUCCESSFUL ALLIANCES, FOR. BILL, ACADEMIC, PHILANTHROPIC ORGANIZES OR INDUSTRY GROUPS AND MAKE AVAILABLE A COMPILATION OF PROMISING FEATURES OF THOSE PARTNERSHIPS THAT COULD ACT AS GUIDELINES OR BEST PRACTICES FOR PEOPLE WANTING THE FORM PARTNERSHIPS IN THE FUTURE. A SECOND THING THAT CAME OUT IS IMPORTANCE OF PLANNING AND PROGRAMMATIC RATHER THAN EPISODIC BASIS. TO 'ALLY -- CHRIS LIKES TO SAY TRANSLATION IS A TEAM SPORT. AND I THINK PLANNING ON THE PROGRAMMATIC BASIS REALLY IS PART AND PARCEL OF EXECUTING AGAINST THE TEAM SPORT. A COUPLE OF THEMES FROM THE DISCUSSION WAS THAT THE -- THAT EFFECTIVE COMMUNICATION BETWEEN PROJECT MANAGEMENT TEAMS WERE AND ARE A KEY TO SUCCESS. FOR THESE PROGRAMS. INTERESTINGLY, MANY PEOPLE ECHO THE THOUGHT THAT A CONSENSUS BASED TRADITIONAL FUNDING REVIEW PROCESS COULD UNDERMINE SUPPORT FOR BREAK THROUGH PROJECTS AND THAT WAS SOMETHING WE NEED TO BE WARY OF. THE CAP LEGISLATION AS MENTIONED EARLIER CREATED TWO UNIQUE OR ENABLE TWO -- ENABLES TWO UNIQUE FUNDING AUTHORITIES, SO CALLED MATCHING AUTHORITY, AND THE OTHER TRANSLATION AUTHORITY BOTH WHICH OFFER OPPORTUNITIES TO ACT AS TOOLS FOR CHANGE FOR CURES ACCELERATION NETWORK. THE WAY WE THOUGHT ABOUT MATCHING AUTHORITY WHERE CAN OFFER DOLLARS TO MATCH FUNDING THAT EXISTS IN OTHER ORGANIZATIONS OR PROGRAMS IS THAT IT CAN PROVIDE A UNIQUE INCENTIVE. THE MATCHING REQUIREMENTS BUILT INTO CAN PROGRAMS CAN PROVIDE CAN WITH OPPORTUNITIES TO LEVERAGE ITS OWN RESOURCES. AND RECEIVE INPUT FROM THIRD PARTIES. AGAIN, A COUPLE OF SUGGESTIONS THAT BUBBLED UP FROM THE DISCUSSIONS MATCHING REQUIREMENTS, PROPERLY CRAFTED MATCHING REQUIREMENTS COULD BE USEDDED TO INCENTIVIZE AND ENGAGE COMPANIES IN EARLY IN THE DEVELOPMENT PROCESS TO ENSURE THAT THOSE COMPANY VERSUS A COMMITMENT THROUGHOUT MULTIPLE STAGES OF PRODUCT DEVELOPMENT. A KEEN FOCUS WAS UPON THE FACT THAT TIME LINES MILESTONES AND DELIVERABLES. BUILT INTO THE MATCHING AUTHORITY PROGRAMS CAN PROVIDE A STRUCTURE TO PARTNERSHIPS AND MAINTAIN FOCUS ON PROGRESS IN THOSE PARTNERSHIPS. FINALLY USING THE MATCHING AUTHORITY TO PROACTIVELY EBB COURAGE -- ENCOURAGE COLLABORATION BETWEEN MULTIPLE PARTIES COULD BE A POWERFUL TOOL HERE. AND A UNIQUE INCENTIVE. THE RESEARCH AUTHORITY OR OTHER TRANSACTION AUTHORITY AGAIN PROVIDES A UNIQUE OPPORTUNITY, I SIMPLIFIED IT BY SAYING THIS IS A AUTHORITY THAT ALLOWS CAN TO ASK SPECIFIC PROBLEM, DEFINE A SPECIFIC PROBLEM AND ASK FOR ANSWERS. DARPA FREQUENTLY USES THIS TYPE OF FUNDING AUTHORITY TO SURFACE NOVEL OPPORTUNITIES TO SOLVE PROBLEMS THEY'RE INTERESTED IN SOLVING. WHAT THE OTHER TRANSACTION AUTHORITY ALLOWS CAN TO DO IS IN CONTRACTING, BE SOMEWHAT FREED FROM SOME OF THE GOVERNMENT CONTRACTING REGULATIONS WHICH ALLOWS PARTNERSHIPS TO OCCUR THAT MIGHT NOT OTHERWISE HAPPEN. A COUPLE OF THEMES THAT ROSE OUT OF THE DISCUSSION, TO MAKE THIS KIND OF AUTHORITY WORK, A CLOSE AN EFFECTIVE RELATIONSHIP BETWEEN THE PROGRAM MANAGER AND CONTRACT OFFICER IS CRITICALLY IMPORTANT TO SHAPE THE CONTRACTING PROCESS. AND GIVEN THE EXPERTISE OF THE INDUSTRY, WITH WHICH YOU'RE PARTNERING THE EXPERTISE TO THE NEGOTIATING TABLE IS CRITICALLY IMPORTANT THAT CAN HAS EQUAL EXPERTISE AT THE TABLE AND ITS REPRESENTATIVES. WE TRIED THE TACKLE THE CURES ACCELERATION NETWORKS PLACE WITH THE DRUG DEVELOPMENT ECOSYSTEM. FREE DARKS I DON'T KNOW HOW YOU FEEL ABOUT THIS, BUT I THOUGHT THIS WAS THE PLACE WHERE WE WERE LEAST EFFECTIVE. IT IS A BIG QUESTION. THERE'S LOTS OF APPROACHES AND LOTS OF THOUGHTS. REALLY NOT GOING TO SPEND MUCH TIME HERE. BECAUSE THIS IS A WORK IN PROGRESS. HOWEVER IT'S CLEAR PEOPLE THOUGHT CAN INTERACTION WITH FDA IS CRITICALLY IMPORTANT TO SUCCESS. THAT CAN IN SOME WAY CONTRIBUTE TO THE EVOLUTION OF MASTER PLAN IN DRUG DISCOVERY AND DEVELOPMENT. -LY A NOTE OF CAUTION BECAUSE CAN HAS PROJECTS IN THE COMPETITIVE PRODUCT DEVELOPMENT SPACE, ISSUES SUCH AS CONFLICT OF INTEREST, ANTITRUST, CONFIDENTIALITY, DATA ACCESS AND DATA PROTECTION PUBLICATION AND INTELLECTUAL PROPERTY, ALL NEED TO BE ADDRESSED UP FRONT IN THE POLICIES THAT ARE PUT IN PLACE FOR CAN. SO LAST SLIDE, LET ME SUMMARIZE THE OUTPUT FROM WORKSHOP OF MAXIMIZING GOALS OF CAN. IT WAS FELT CAN HAS A UNIQUE OPPORTUNITY TO BREAK THE STATUS CO-BY SUPPORTING INDIVIDUALS AN COMPANIES OUTSIDE THE MAINSTREAM. THAT THE PORTFOLIO CAN ACCOMPLISHES FOCUSES NOT ONLY ON CURES BUT TRANSFORMING THE PROCESS THAT LEADS TO CURES. I HEARD THIS NEXT BULLET SPOKEN ABOUT BY MANY PEOPLE, ONE PERSON IN PARTICULAR JOSH BOGER COMES TO MIND, THAT PERSONAL PASSION AND TOLERANCE OF RISK AND I WOULD SAY FAILURE AS WELL, WILL BE IMPORTANT COMPONENTS IN CAN SUCCESS. HAVE TO BE WILLING TO STEP OUT OF THE BOX AND TAKE A CHANCE. FINALLY WITH REASON TO NEXT STEPS, THERE ARE MANY MORE THAT CAME OUT, JUST HIGHLIGHTED A FEW HERE. POPULATE THE NCATS STAFF WITH DEVELOPMENT EXPERTISE, IMPLEMENT MILESTONE BASED CONTRACTS WITH INCREASED ACCOUNTABILITY FOR DELIVERING ON THE PROJECTS. AND ESTABLISH GREATER COLLABORATIONS AND ROBUST PUBLIC PRIVATE PARTNERSHIPS. IN THE END PEOPLE FELT WE SHOULD FOCUS -- CAN FOCUSES ON REGULA IRTO SCIENCE AND DRUG DEVELOPMENT TOOLS AND DEVELOPMENT OF CURES, NEW THERAPIES AND DIAGNOSTICS. SO I'M GOING TO STOP THERE AND FREDA, THROW IT CK TO YOU TO SPUR THE CONVERSATION. >> HOPEFULLY THE CONVERSATION DOESN'T NEED MUCH SPURRING. I HAVE A QUICK QUESTION. YOU SAY ADVANCING REGULATORY SCIENCE. WHAT WERE SOME OF THE COMMENTS PEOPLE BROUGHT UP OR STRATEGIES PEOPLE WERE THINKING ABOUT TO DO THAT? >> THERE ARE A NUMBER OF PEOPLE IN THE ROOM PRESENT WHO CONTRIBUTEED THAT DISCUSSION. MARGARET SCOTT, WONDER IF YOU WOULD LIKE TO CHIME NAP ON THIS FREDA AS WELL. I DON'T WANT TO BE THE SOLE SPAR HERE. SCOTT. >> I KNOW AS AN EXAMPLE CERTAINLY SOMETHING WE HAVE LOOKED AT IN COLLABORATION BETWEEN NCATS, LEUKEMIA LYMPHOMA SOCIETY IN OUR PROGRAM, AND OUR PROGRAM IS REGULATORY SCIENCE STRATEGIES AND INITIATIVES THAT WE FEEL REALLY OUGHT TO BE ADDRESSED AND INCORPORATED AROUND EXPLORING NEW USES FOR APPROVED DRUGS AN EVEN ABANDONED DRUGS. STRATEGIES AROUND CLINICAL PROOF OF CONCEPT, BEING ABLE TO ACCELERATE DRUGS WHERE YOU HAVE A GREAT DEAL OF KNOWLEDGE IN PLACE LOOKING AT A HUGE UNMET MEDICAL NEED. THAT IS SOMETHING WE HAD DISCUSSIONS WITHŽ >> I THINK THE PIECE THAT'S PROBABLY TROUBLING TO ME IS THE BUDGE FOR CAN WHICH IS 10 MILLION, AND THE GRAN GRAND SCOPE OF WHAT CAN COULD BE. THEN IF YOU TAKE THE TOPIC OF REGULATORY SCIENCE THE FDA ADVOCACY SIDE OFFENSE, WHAT I HER MORE ABOUT THE LAST YEAR OR TWO YEARS IS LACK OF COLLABORATION BETWEEN THE NIH AND FDA. IF YOU TAKE IT FROM THE FDA STANCE AND COMMISSIONER HAMBERG IS NOT HERE TO SPEAK ABOUT IT FROM THEIR STANCE, BUT THEIR BUDGET IS QUITE SMALL COMPARED TO THE ENTIRE NIH BUDGET. SO I THINK THIS IS APPROXIMATE OPPORTUNITY FOR NCATS CAN TO REALLY HIT IT OUT OF THE PARK, SO TO SPEAK, AND I THINK FOR BOTH AGENCIES THERE'S GOING TO BE THIS INCREDIBLE HALO EFFECT IF WE CAN CONTINUE TO DESCRIBE OPPORTUNITIES AND EXECUTE ON THEM. >> ONE OF THE QUESTIONS I HAVE, CHRIS AND YOUR THINKING ABOUT YOUR ORGANIZATIONAL STRUCTURE OF NCATS AND -- I LOOK AT WHAT THE CHARGE, I LOOKED AT THE BOOK AND I'M THINKING ABOUT -- I LOOKED AT SOME OF YOUR OPENINGS AND SO FORTH, WHO IS GOING TO BE THE MOTHER OF THIS PARTICULAR PROJECT HERE. WE'RE TALKING ABOUT INTERFACING WITH OTHER AGENCIES, WE OTHER TALKING ABOUT THINGS, WE HAVE LOOKED AT THIS AND WE HAVE TO ESTABLISH PRIORITIES HERE. WE DO THIS WITH 10 MILLION BUCKS BUT WE NEED SUCCESS AND WE NEED IT SOON. ARE YOU LOOKING AT SOMEBODY WHO HEAD THE CAN EFFORT BE THE MOTHER OF THE PROJECT, HAVE THEIR OWN FREE-STANDING STAFF TO BE ABLE TO PROVIDE THE INPUT THAT THIS COMMITTEE NEEDS TO HELP IN ITS DELIBERATIONS? >> THE NCATS STAFF KNOW IN THE CAN BOARD AND COUNCIL KNOW, I THINK WE'RE NOT ONLY ENGAGED IN A STRATEGIC PLANNING PROCESS BUT ALSO RETREAT THAT WE'RE GOING TO BE HAVING INTERNALLY IN TWO WEEKS, WE'LL BE TALKING THE THE STRUCTURE OF THE ORGANIZATION BECAUSE THE STRUCTURE I SHOULD HAVE SAID THIS WHEN I SHOWED THE ORG CHART. A HISTORICAL CRITICAL APT SEE DENTS. AND IT'S NOT CLEAR THAT IS THE BEST WAY TO -- WHAT I ASKED THOUGH OUT THE CURRENT STRUCTURE, IMAGINE THERE IS NO STRUCTURE AND WE HAVE THE PROGRAMS AND MISSION NCATS HAS, DISTINCT FROM ANY OF ITS PREDECESSORS AND SAY WHAT SHOULD THE STRUCTURE BE. SHOULD WE HAVE ONE OR TEN DIVISIONS AND HOW SHOULD WE DO THIS. THE ISSUE OF A HEAD OF CAN AND WHAT YOU'LL FORGIVE ME CALLING A CAN PLAN. I THOUGHT TALKING TO DAN BECAUSE DAN IS RUNNING CAN SO THIS WOULD BE A CAN PLAN BY DAN. WHICH WOULD MAKE DR. SEUSS HAPPY. PART OF OUR PROBLEM HAS BEEN WE WERE UNDERGOING WHIPLASH WHEN IT COMES TO HOW BIG CAN IS SUPPOSED TO BE IN THE PRESIDENT'S BUDGET IT WAS $50 MILLION. THEN IT WAS SUPPOSED TO GO $100 MILLION AND NOW STUCK AT $10 MILLION. HOW YOU WOULD ENVISION A PROGRAM LIKE THIS IF IT WAS 10 MILLION-DOLLAR VERSUS 50 OR $100 MILLION IS FUNDAMENTALLY DIFFERENCE. I THINK REGARDLESS HOW WE DO THAT WE'RE GOING TO HAVE TO HAVE A CAN OFFICE. ESSENTIALLY THAT'S WHAT DAN'S DAY JOB HAS BEEN. THAT ALL THE CAN MONEY GOES TO THE PROGRAM DAN RUNS. NOTICE NEITHER THE TISSUE CHIP PROGRAM NOR REPURPOSING THE NEW THERAPEUTIC USES WERE ON THAT ORG CHART. WE REFER TO THEM AS ASTEROIDS THAT ARE ORBITING AROUND THE MOTHER SHIP. AND SO ONE THING WEAL TALK ABOUT T IN THE RETREAT IS HOW TO INCORPORATE THE ASTEROIDS INTHE A BETTER IN STRUCTURE. SO WE'RE GOING TO HAVE TO DO THAT. >> HELLO. JUST ADDRESSING MARGARET'S POINT BY WAY OF BRIEF INTRODUCTION I'M LEON (INDISCERNIBLE) FROM THE DP ASSOCIATE COMMISSIONER OF MEDICAL PRODUCTS AND TOBACCO. AND COMMISSIONER HAMBERG REPRESENT TO THE CAN BOARD SO I WANT TO COMMENT ON THE POINT THAT MARGARET MADE, IT'S INCREDIBLY IMPORTANT FOR COLLABORATIONS BETWEEN FDA AND NIH AND N CATS, IN FACT WE'RE CURRENTLY IN DISCUSSIONS WITH CHRIS AND OUR KEY CENTER LEADERS ET CETERA ABOUT IDENTIFICATION OF PROJECTS THAT CAN DO SO. OF COURSE THE IMPORTANT STRATEGIC OBJECTIVE OF FDA AROUND REGULATORY SCIENCE I THINK EVERYONE HAS HEARD COMMISSIONER HAMBERG SPEAK TOWARDS THAT BEFORE. SO I THINK THAT IS DEFINITELY IS AN OPPORTUNE TIME FOR US TO GET MORE SPECIFIC ABOUT THE TYPE OF PROGRAMS THAT WE CAN ENGAGE IN FDA WITH NCATS AND HOW THE CAN NETWORK AND FUNDING AGENCIES CAN HELP WITH THAT CERTAINLY SOMETHING THAT I THINK WE NEED TO THINK MORE ABOUT. ALSO CAREER PATH FOR TRANSLATIONAL SCIENTISTS, FDA INDEED IS VERY INTERESTED IN THE TRAINING OF SCIENTISTS IN REGULATORY SCIENCE TO FDA AS WELL. SO THIS IS AN OPPORTUNE TIME WITH INITIATIVES COMING TOGETHER WHICH ARE OPTIMISTIC. SO ONE OF THE OTHER AREAS OF DISCUSSION AT THE MEETING WAS REALLY AROUND SPECIFICALLY HOW WE MIGHT LOOK AT BARRIERS IN THE REGULATORY REVIEW SYSTEM PRIMARILY AND SEE IF THERE WERE SOME WINS, NO JUST POLICY FRONT BUT ACCEPTANCE OF SCIENCE FRONT. MORE AGGRESSIVE USE OF BUOY MARKERS FOR EXAMPLE AND A DIFFERENT ROAD TO VALIDATION. AND ON AND ON. IF U THINK THE TISSUE CHIP IS A GREAT EXAMPLE HOW WOULD THAT FIT IN THE REGULATORY VIEW PROCESS AGGRESSIVE INNOVATIVE SCIENCE TESTING EARLY AND HOW IT NEEDS TO FIT THE REGULATORY PROCESS AS A WAY TO ACCELERATE. AND THE REPRESENTATIVES THERE FROM THE FDA IN JUNE WERE REALLY ENTHUSIASTIC ABOUT THIS SO I'M GLAD TO HEAR THAT YOU'RE HERE APPROXIMATE ENTHUSIASTIC AS WELL. >> MY QUESTION IS MONEY WHICH HAS COME UP MORE THAN ANY OTHER TOPIC TODAY. I WOULD LIKE TO ASK PERHAPS TOPIC FOR RETREAT BUT HOW WE GET ABOUT 50 TO $100 MILLION BEING NOW AT 10 MILLION? IS THAT BY BRINGING PRODUCTS TO MARKET, DO WE NEED TO GO ALL THE WAY TO THAT POINT? I DOUBT IT'S PUBLICATIONS, IT'S NOT EVEN GRANT MONEY TO INSTITUTIONS BUT WHERE IN THE SPECTRUM OF WHAT LIES IN BETWEEN, WHAT COUNTS AS SUCCESS? AND WHO IS DETERMINING SUCCESS? CONGRESS? NIH DIRECTOR, PUBLIC? PERHAPS THIS IS TOO BIG FOR TODAY. >> IT IS. 'S A MORE GENERAL QUESTION, WHAT ARE THE METRIC FOR NCATS SUCCESS. I LOVE THEM AS MUCH AS EVERYBODY ELSE, PATIENTS CAN'T TAKE PUBLICATIONS WHEN SICK. SO WE NEED -- THIS FEEDS INTO THE DISCUSSION BEFORE ABOUT TRAINING AND CAREER ADVANCEMENT, PROMOTION AND TEN YOUR SYSTEMS. THE QUESTION ABOUT CAN IS A SPECIFIC ONE, IT IS A HIGH PRIORITY AT NIH GENERALLY BECAUSE IT IS A HIGH PRIORITY ALSO OF A NUMBER OF PEOPLE IN CONGRESS. SO CAN UNFORTUNATELY JUST HAPPENS TO BE -- HAVE BEEN BORN LIKE NCATS, IN LITERALLY THE WORST SITUATION OF THE NIH BUDGET SINCE FORMATION. SO THOUGH MANY PEOPLE ARE ENTHUSIASTIC ABOUT IT, IT'S -- MY SENSE IS THAT NO MATTER HOW SUCCESSFUL WE ARE IN THE CURRENT BUDGET ENVIRONMENT, IT WILL BE DIFFICULT TO GET MORE MONEY, THAT'S JUST THE WAY CONGRESS IS. HOWEVER, IF WE FOCUS ON TWO THINGS, I THINK THEY WILL STAND UP AND TAKE NOTICE. ONE IS THE KIND OF REVOLUTIONARY TECHNOLOGY THAT YOU'LL HEAR FROM DAN AND DON ABOUT SITTING OVER THERE, PERHAPS LATER THIS AFTERNOON, WHICH REALLY ARE POTENTIAL GAME CHANGERS THAT FOLKS UNDERSTAND. THE OTHER IS SOMETHING I HER FRANCIS SAY A NUMBER OF YEARS AGO WHEN THERE WAS FRUSTRATION ABOUT FOLKS ABOUT WHY CAN'T WE GET CONGRESS'S ATTENTION, WHY CAN'T THEY REALIZE THESE WONDERFUL THINGS, WHAT CAN WE DO TO GET THAT ARE ATTENTION? HE WAS FRUSTRATED. HE SAID YOU PEOPLE NEED TO GO OUT AND CURE SOMETHING. AND PEOPLE LOOKED AROUND AND SAY BUT THAT'S NOT REALLY WHAT WE DO. BUT THAT IS WHAT NCATS SHOULD DO AT LEAST IN PART. SO YEAH, SO IF YOU LOOK AT BOB'S STORY, NOTHING SUCCEEDS LIKE SUCCESS. YOU WILL HEAR A NUMBER OF THOSE FROM NUMBER OF PROGRAMS THIS AFTERNOON AND TRUMPETING THESE H FRONT OF CONGRESS IS REALLY IMPORTANT. ONE THING THAT HOW TO COMMUNICATE THAT MESSAGE. CURRENT DYNAMIC IS NOT ONLY I AS MEMBER OF THE PECKTIVE BRANCH CANNOT LOBBY CONGRESS, CANNOT TALK TO CONGRESS, THEY HAD TO CALL ME, I CAN'T CALL THEM. IT CAN'T BE MOTIVE ON P MY PART. HOWEVER IT CAN BE PROACTIVE ON YOUR PARTS BECAUSE YOU ARE REPRESENTATIVES OF THE ORGANIZATIONS THAT YOU ARE PART OF FIGURING HOW TO DO THAT EFFECTIVELY IS SOMETHING A THUMB OF YOU KNOW HOW TO DO FARBER THAN I DO. GOING TO LOOK SPECIFICALLY AT MARGARET HERE, WHO IS PARTICULARLY GOOD AT THIS. I THINK ONE OF THE REASONS IT'S SO IMPORTANT FOR US TO MAKE -- HAVE THE MESSAGE OVER AND OVER AN OVER AGAIN, WE ARE NOT YOUR FATHER'S NIH, WE ARE DIFFERENT, WE ARE VENTURE SPACE, WE ARE -- WE DO THINGS DIFFERENTLY, WE'RE FOCUSED ON DELIVERABLES THAT HAVE TAPINGABLE IMPACTS ON HUMAN HEALTH. THOSE ARE VERY POWERFUL MESSAGES THAT I THINK WE NEED TO BE ABLE TO DELIVER. ND IT WILL BE UP TO A LOT OF YOU TO DO THAT. >> SO YOU REFERENCED NEEDING SUCK SETS, NEEDING TO TELL THE STORY AND POINTED AT BEEN AND CYSTIC FIBROSIS STORY MOST RECENTLY THE PAST YEAR. HERE HEARING THE STORY, WHAT I WOULD SAY IS PASSIONATE, PATIENCE, FAMILIES, DRIVEN FOCUS, SORT OF NEVER SAY NEVER PEOPLE, FAMILIES HAVING ONLY REFRIGERATOR OF MANAGE NET WHAT THE GAME PLAN IS AND RECITING IT BACK AND VOILA, AFTER UM TEEN YEARS OF DOGGED DETERMINATION WE HAVE A THERAPY. THAT WILL SAVE CHILDREN'S LIVES AND THEN THE PROMISE FOR MORE. WHAT I WAS CRAVING AS YOU WERE GIVING YOUR INTRODUCTORY REMARKS, I SEE A SERIES OF ACTIVITIES THAT WE HAVEN'T THREADED TOGETHER. SO WE NEED SUCCESS THE TALK ABOUT BUT WE ALSO NEED TO EXPLAIN HOW THESE THINGS MAKE A DIFFERENCE, HOW TISSUE ON A CHIP CHANGE THE PARADIGM AT THE FDA? I'M CERTAINLY HAPPY TO HELP, I'M SURE MANY OTHERS WOULD BE. IT'S MANY JUST CURING SOMETHING TAKES FROM SURE OFF OF YOU, PERHAPS. >> THAT'S EXACTLY WHAT THE STRATEGIC PLANNING PROCESS IS. I MUST SAY A LOT OF THE LAST THREE MONTHS HAS BEEN -- WHEN THERE'S A NEW ORGANIZATION, PEOPLE GET WIGGED OUT WHEN THERE'S CHANGE. SO A LOT OF WHAT I HAVE BEEN DOING IS PSYCHOLOGICAL VALIUM FOR PEOPLE TO SAY EVERYTHING WILL BE OKAY, THEY'RE ALL IMPORTANT, I LOVE Y'ALL. AND SO IT'S BEEN IMPORTANT FOR ME NOT TO -- A LOT OF GIVEN HISTORY OF NCATS THERE WAS A LOT OF HEELING THAT HAD TO GO ON AS IT WERE. BUT WE ARE AT THIS POINT EXACTLY ONE OF THE BIGGEST CHALLENGES IS HOW DO WE, I THINK IT'S NOT THAT COMPLICATED ACTUALLY, WHO HOW DO WE WEAVE THESE TOGETHER. BECAUSE TOUCH POINTS ARE OBVIOUS FRANKLY. >> BEFORE WE GET OFF MONEY I WANT TO ADD ONE OTHER THING. WE HAVE SPECIAL FUNDING AUTHORITIES. I BELIEVE THAT A PART OF THIS SUCCESS WILL BE SHOWING WE KNOW HOW TO LEVERAGE THEM. SO PART OF IT, OF THE SUCCESS IS NOT JUST THINGS WE WERE TALKING ABOUT IN TERMS OF HEARING SOMETHING, THOUGH NOT SIGNED ONE THAT TEAM, WE ALSO HAVE TWO UNIQUE FUNDING AUTHORITIES AN PART OF OUR TEST WILL BE WHETHER OR NOT WE CAN FIGURE OUT HOW TO USE THEM IN WAY THAT GALVANIZES THE IMMUNITY AROUND -- COMMUNITY AROUND ALL TYPES OF RESOURCES INCLUDING MONEY. >> IF I COULD QUICKLY COME BACK TO SOMETHING BOB SAID EARLIER ABOUT CRAFTING PRIORITIES. SO WE SPENT TWO DAYS IN A WORKSHOP, A LOT OF OPTIONS THAT GOT PUT ON THE TABLE. THIS BODY CERTAINLY THERE ARE PEOPLE IN THIS BODY THAT WOULD APPROXIMATELY HELP YOU CRAFT PRIORITIES BUT IT'S INCREDIBLY IMPORTANT TO BEGIN TO FOCUS AND COME BACK TO THE CAN BOARD AND THE N CATS BOARD WITH THOUGHTS ABOUT WHERE THE NEAR TERM SUCCESSES ARE GOING TO BE, TO COME BACK TO BOB'S POINT. HOW WE MIGHT ACTUALLY GET THERE. KIND OF A FUNDAMENTAL QUESTION THAT FOLLOWS UP ON SOME OF THE DISCUSSION. I'M UNTIL TRYING TO WRAP IN MY MIND THE BALANCE BETWEEN DISEASE AGNOSTIC AND CURE SOMETHING AN LEVERAGING OTHER FUNDING. SO A LOT OF OTHER FUNDING WILL COME WITH A DISEASE SPECIFIC INTEREST. I STILL DON'T UNDERSTAND HOW THE VISION OF THAT WORKS. ANY THOUGHTS ON THAT? >> SURE. THE WAY I SEE THIS WORKING AND HOW WE HAVE DONE IT SO FAR IS IT MAKES IN SOME WAYS OUR LIVES EASIER THAN OTHER INSTITUTES. WHAT I MEAN BY THAT IS WHEN I SAY CURE SOMETHING THERE'S TWO PIECES OF THAT. ONE IS THAT IS SOMETHING -- ONE OF THE -- PROBABLY ONLY THING CONGRESS UNDERSTANDS, YOU CAN TALK TO ABOUT ALL KINDS OF THINGS BUT WHAT THEY WANT IS SOMETHING THAT IS HAD A TAPINGABLE EFFECT ON A PERSON YOU CAN TROT IN FRONT OF THEM. SO I THINK ONE OF THE THINGS WE HAVE DONE A NUMBER OF PROGRAMS IS TO HAVE A DESIGN DESIGN THE PORTFOLIO FROM THE BEGINNING TO HAVE EARLY WINS. WHAT LOU AND SCOTT WERE TALKING ABOUT, ABOUT THIS COLLABORATION WITH LLS IS A PERFECT EXAMPLE. AND IN THIS PROJECT I TALK ABOUT BRIEFLY WITH NPC IS ANOTHER EXAMPLE WHERE THERE WAS A PARTICULAR SCIENTIFIC OPPORTUNITY, PARTICULAR COLLABORATIVE OPPORTUNITY, PARTICULAR TEAM IN A PARTICULAR WAY THE TEAM WAS PUT TOGETHER WITH SOME CHARACTERISTICS OF WHAT A SUCCESSFUL TEAM LOOKS LIKE. KIND OF LIKE HOW DO YOU RUN THE NEW ZONE DEFENSE AND ZONE OFFENSE IN THE NFL. WHAT DOES THAT PLAN LOOK LIKE? THEN WE CHOOSE PROJECTS ACTUALLY NOT BECAUSE WE HAVE TO CURE NPC BECAUSE WE'RE A NEUROLOGICAL INSTITUTE BUT BECAUSE HERE IS AN OPPORTUNITY, DOESN'T MATTER WHETHER IT'S BLOOD DISEASE OR NEUROLOGIC DISEASE OR ANY OTHER DISEASE, IT NOT ONLY PROVIDES A TREATMENT FOR UNTREATABLE DISEASE BUT SHOWS HOW TO DO THIS WHOLE PROCESS BETTER. IN MY PREVIOUS LIVES FREQUENTLY BEEN CONFRONTED, DOESN'T HEAR HOW HARD THE PROBLEM, THIS IS UP AN IMPORTANT PROBLEM WE'RE GOING TO BANG AWAY. BOB'S EXAMPLE, 20 YEARS AGO CF WAS ATTRACTABLE. THAT IS ONE OF THE -- I THINK MANY WAYS BLAZED THE TRAIL HOW TO SOLVE THIS PROBLEM. IF YOU LOOK AT THE FACT IN MULTIPLE CASES WITHIN I'LL TAKE TREND AS AN EXAMPLE, WE HAVE DEVELOPED NOVEL MECHANISMS AND TREATMENTS IN THE COURSE OF A COUPLE OF YEARS. AN THOSE GIVE TWO THINGS, IT GIVES US SOMETHING CONGRESS UNDERSTANDS BECAUSE WE CAN SAY HERE IS A PATIENT PREVIOUSLY NOT TREATABLE. HERE IS HOW WE GOT THERE. HERE IS THE PLACE WE PLAYED ON THE FIELD. THAT OTHER PEOPLE CAN USE TOO. (OFF MIC) THE LAST WORD. >> BIG SHOES TO FILL. SO I WANT TO BUILD ON TODD'S COMMENTS. SEEMS LIKE THE THEME OF WHAT WE'RE TRYING TO ACCOMPLISH IS HOW DO WE GET SOME EARLY WINS ON A FINITE BUDGET AS WE START TO SET THIS UP. I WANT TO BUILD ON TODD'S COMMENTS. YOU MENTION CHRIS, BUILD THIS IN OUR DISCUSSION, THE VALUE THAT THE RARE DISEASE INITIATIVES WITHIN NCATS HAVE IN TERMS OF ESTABLISHING EARLY (INAUDIBLE) HERE, I ENCOURAGE ORTHOGONAL, NOT JUST FUNCTION THAT HELPS A BROADER T ARC PERSPECTIVE BUT ADDITIONAL BEACHHEADS COMING THE MIND, AN EXAMPLE IN THE CURRENT LEXICON, CAN WE FIND ADDITIONAL BEACHHEADS WHERE MULTIPLE PROJECTS, ONE TO TWO PROJECTS REALLY GET EARLY WINS TO HELP US GET ON OUR WAY. >> BOB SINCE WE CALLED HIS NAME TEN TIMES. MAKE A COMMENT? >> I THINK WE HAVE GOT THE TAKE INTO ACCOUNT AND TALKING ABOUT THE INTERFACE WITH ACADEMICS, WE HAVE A UNIQUE OPPORTUNITY AT THIS POINT TO MAKE SURE INDUSTRY IS AT THE TABLE. INDUSTRY HAS MOVED AWAY FROM THE (INAUDIBLE) MENTALITY. WE'RE LOOKING FOR RARE DISEASES, UNMET NEEDS, WE JUST SIGNED A $56 MILLION DEAL WITH PFIZER. TEN YEARS AGO THEY WOULD NEVER HAVE SPOKEN TO US ABOUT CYSTIC FIBROSIS. THESE ARE OTHER MOLECULES BESIDES THE VERTEX MOLECULE. SO I REALLY THINK -- AND THEY'RE LOOKING FOR OPPORTUNITIES ACADEMICS TO IDENTIFY PLATFORM TECHNOLOGIES AND THINGS LIKE THAT. SO HOPE THAT WE MAKE SURE THAT AS WE GO THANK YOU THIS PROCESS, WE CAN MAKE SURE, I KNOW FREDA WILL REMIND US, THAT WE WILL ABSOLUTELY HAVE THEM AT THE TABLE. THERE'S INTERFACE AND OPPORTUNITY FOR US TO CONTINUE TO LEVERAGE SOME TREMENDOUS RESOURCES ABOUT A NEED FOR THEM, THEY NEED US AS WE NEED THEM. >> LET ME SAY ONE THING IN CLOSING, THE -- I THINK WOULD BE ALREADY HELPFUL FOR US TO FOLLOW ON THIS IS TO HAVE IF FREDA WAS WILLING TO HAVE A SUBCOMITTEE OF THE CAN BOARD. CONTINUED WORK OF THE TWO DAY COMMITTEE TO HELP ESTABLISH WHAT ARE THE PRIORITIES, WHAT ARE THE PERFORMANCE METRICS FOR THIS ORGANIZATION. IF YOU COULD TO REPORT BACK TO COUNCIL AND REST OF THE CAN BOAR BY MAY, IF YOU CAN, THAT WOULD BE REALLY HELPFUL. >> WE HAVE VOLUNTEERS. SO SOUNDS LIKE BREAK TIME. I THINK WE HAVE 15 MINUTES SO IF EVERYONE CAN BE BACK AT 10:45 THAT WOULD BE FABULOUS. WE'LL BE OFF AND RUNNING AGAIN. >> CAME ABOUT WITH THE RECOGNITION IN THE GENERAL FIELD OF THE LACK OF EFFICACY AND TOXICITY IN THE PRE-CLINICAL MODELS BEING USED FOR DRUG DEVELOPMENT. PART OF THAT IS THE LACK OF CLINICAL SAFETY, AS WELL AS TOXICOLOGY WHICH ACCOUNTS FOR 33% OF FAILURES, CONFOUND THAT WITH 30 OR SO FAILURE EFFICACY THEN YOU'RE APPROACHING 60, 75% OF FAILURES ACCOUNTING FOR EFFICACY AND TOXICITY BECAUSE OF FOUR PREDICTIVE VALUES OF OUR PRE-CLINICAL MODELS. SO WE NEED ESSENTIALLY BETTER EVALUATIVE TOOLS TO GIVE US ALLOW US TO BE ABLE TO PREDICT ADVERSE EVENTS EARLIER FOR MITIGATION AN PREVENTION AND EFFICACY MODELS THAT IDENTIFY POPULATION WHO RESPOND TO NEW DRUG EARLIER TO SPEED DEVELOPMENT. THE PHYSIOLOGICAL SYSTEMS ORGANS AN CHIPS FOR DRUG SCREENING CAME INTO BEING IN SOME WAYS THE TO HELP ACHIEVE THIS PURPOSE SO THIS ORGAN ON A CHIP ESSENTIALLY USES HUMAN TISSUES TO MIMIC HUMAN PHYSIOLOGY AND THIS CAME ABOUT ACTUALLY THE PRECEDENT FOR THIS WAS AN EARLIER PROGRAM THAT WAS RUN AS A COMMON FUND, ADVANCING REGULATORY SCIENCE AND AT THAT TIME IT WAS JOINT FUNDING WITHIN NIH COMMON FUND AND FDA AND ONE OF THE FOUR COOPERATIVE AGREEMENT AWARDS THAT WE HAD FUNDED, DR. DON ENBAR, IT WAS A THEE YEAR AWARD, AND ACTIVE AND ON ITS LAST YEAR AND THE WORK WAS TO DEVELOP AND INTEGRATE LUNG IN CHIP APPROXIMATE HEART IN CHIP. BECAUSE OF TREMENDOUS PROGRESS AND STRIDES MADE IN THIS FIELD THAT'S A GENERAL RECOGNITION WITH THE FDA AND PARTNERS THAT INCLUDED DARPA, TO INVEST MORE TO THIS TECHNOLOGY AND REALLY DEVELOP REALLY USEFUL TOOLS FOR DRUG SCREENING. NIH INVESTMENT AS CHRIS MENTIONED EARLIER IN THIS TALK IS ABOUT $70 MILLION OVER FIVE YEARS, OF IS FROM THE CURES ACCELERATION NETWORK FUNDING AND $10 MILLION AND ABOUT 4 MILLION-DOLLAR FROM THE NIH COMMON FUND DARPA INVESTMENT IN THIS PROGRAM, $75 MILLION INVESTMENT IN FIVE YEARS AN FDA IS -- IT'S VERY MUCH PARTNER IS THIS THIS WORLD AND THEY ARE PROVIDING REGULATORY TEXAS DOG EXPERTISE. SO WE HAVE FDA STAFF PART OF PROJECT TEAM ADVISING OUR INVESTIGATORS ON A REGULAR BASIS. WE HAVE MONTHLY CALLS AS WELL AS FACE TO FACE MEETINGS EVERY SIX MONTHS. THOUGH WE WERE PROVIDING FUNDS NCATS AND DRPA ARE MANAGING THE PROGRAMS INDEPENDENTLY. DR. ENBAR IS ONE OF THE TWO FUNDED DPA INVESTIGATORS AND NCATS, ABOUT 19 INVESTIGATORS THAT WE'RE FUNDING. THIS IS THE OVERALL GOAL, PROGRAM IS ESSENTIALLY TO DEVELOP AND IN VITRO PLATFORM USING HUMAN CELLS AND TISSUES, EFFICACY, PHARMACOKINETICS, SAFETY AND TOXICITY. AND REPRESENTATION OF THE TEN MAJOR SYSTEM THAT INCLUDES CIRCULATORY, ENDOCRINE GASTROG, MUSCULOSKELETAL TALL SYSTEM, REST RESPIRATORY AND URINARY SYSTEM. WHAT WE HOPE TO ACCOMPLISH OVER THE NEXT FIVE YEARS IS IN VITRO SYSTEMS FIZZ QUO LOGICALLY RELEVANT, GENETICALLY DIVERSE AND AS WELL AS PATHOLOGICALLY MEANINGFUL. IN ORDER TO BE USEFUL WE NEED TO DEMONSTRATE TISSUE VIABILITY FOR AT LEAST FOUR WEEKS FOR REPEATED DOSE TESTING. AND OF COURSE TO MAKE THE RESOURCES AVAILABLE IN A RELATIVELY SHORT PERIOD OF TIME TO INDUSTRY AND ACADEMIC INVESTIGATORS. WITH THAT I WOULD LIKE TO INTRODUCE DR. DON INGBER TO TALK ABOUT WORK AT THE WYSS INSTITUTE. >> THANKS VERY MUCH FOR THE OPPORTUNITY. I AM HERE AS DIRECTOR OF NEW INSTITUTE AT HARVARD CALLED THE WYSS INSTITUTE FOR BIOLOGICALLY INSPIRED ENGINEERING. WE'RE JUST FOUR YEARS OLD. GIVEN WHAT YOU CAN TALKING ABOUT IT'S INTERESTING BECAUSE WE'RE A NEW MODEL FOR INNOVATION COLLABORATION AND TECHNOLOGY TRANSLATION, WE OTHER A TECHNOLOGY TRANSLATION INSTITUTE. THIS IS OUR LOGO, WE HAVE SELF-ASSEMBLING OVER THE LAST FOUR YEARS, ZERO TO 325 FULL TIME STAFF, FILLED OUT 100,000 SQUARE FOOT OF SPACE AND INVOLVE ABOUT 800 PEOPLE ACROSS HARVARD AND OTHER HOSPITALS AND OTHER UNIVERSITIES IN BOSTON. LET ME SAY THAT IN CONTEXT OF YOUR CHALLENGES OUR MEASURES OF SUCCESS INCLUDE ACADEMIC AND IP WE GENERATE, CORPORATE ALLIANCES, LICENSING AGREEMENTS AND NEW START UPS AND HAVING PRODUCTS IN THE PIPELINE IN FIVE YEARS. IN FOUR WE HAVE TWO CLINICAL TRIALS STARTING, PRODUCTS AND NON-MEDICAL ALSO, ABOUT 30 DIFFERENT CORPORATE PRODUCT FOCUS COLLABORATIONS AS WELL AS 30 -- OVER 30 IRBs APPROVED AT THIS POINT. SO I'M GOING TO TALK TODAY ABOUT SOMETHING THAT IS AS YOU HEARD WE CALL HUMAN ORGANS ON CHIPS REPLACEMENTS FOR ANIMAL TESTING, I HAD ONE OF THE MAJOR PLATFORMS THAT FOCUSES ON ON THE INSTITUTE. CALLED BIOMINIC MICROSYSTEM. OUR GOAL IS TO MICROCHIPS THAT CONTAIN HUMAN LIVING CELLS THAT RECONSTITUTE ORGAN LIVING CELLS. I DISAGREE WITH THE FUNCTION WE WILL NOT DO CELL OR TISSUE. WE DO ORGAN LEVEL FUNCTIONS FOR DRUG SCREENING TOXICOLOGY AN THERAPEUTIC APPLICATION FOR ACCELERATING DEVELOPMENT AND REPLACING ANIMAL TESTING. EARLY ON WE STARTED INTERNAL FUNDING BEFORE INITIATIVES. WE IDENTIFIED ONE OF THE BIGGEST CHALLENGES IN MEDICINE IS THE CURRENT DRUG DEVELOPMENT MODEL IS BROKEN, EVERY PHARMACEUTICAL COMPANY TELLS US THIS. FDA TELLS US THIS. IT TAKES OVER $2 MILLION A SINGLE COMPOUND, TAKES YEARS TO COMPLETE AND NUMEROUS ANIMAL LIVES ARE LOST. MORE OFTEN THAN NOT THE RESULTS DO IN THE PREDICT CLINICAL RESPONSES, AND RESULTS IN LOWER DRUGS REACHING PATIENTS. SO WE SET OUT TO DO THIS AND OUR FIRST TARGET WAS AND FIRST PROOF OF PRINCIPLE IS WHAT WE CALL A HUMAN BREATHING -- PUBLISHED TWO AND A HALF YEARS AGO AND THE BASIC IDEA WAS THAT THE LUNG MAJOR FUNCTIONAL UNIT OF LUNG IS THE ALVEOLAR CAPILLAIRE INTERFACE, THE AIR SACK WHERE WE HAVE GAS EXCHANGE, AEROSOL THEREFORE I ME THE TASTASIS, PNEUMONIA, INFLAMMATION, ET CETERA. AND IT'S BASICALLY A SIMPLE STRUCTURE, IT HAS A SEN TRAM COMPARTMENT FILLED WITH AIR. A SINGLE LAYER OF EPITHELIUM ALVEOLAR EPITHELIUM, A FLEXIBLE POUROUS MEMBRANE SINGLE CAPILLAIRE EPITHELIUM AND BLOOD. WE ALSO KNOW FROM RESPIRATORY -- THIS IS A MECHANICICALLY ACTIVE STRUCTURE, THERE'S FLOW OF AIR IN AND OUT, BLOOD IS FLOWING BY. SO -- ALL THESE ARE ABSOLUTELY CRITICAL FOR PULMONARY FUNCTION. SO WHAT WE WANTED TO DO NOT TO MIMIC CELLS OR TISSUE BUT ORGAN. AND AN OR GONE IS -- ORGAN IS MULTIPLE TISSUES COMING TOGETHER AT INTERFACE AND NEW FUNCTIONS EMERGING AND ORGAN PHYSIOLOGY IN TERMS OF MICROENVIRONMENT, MECHANICAL MICROENVIRONMENT. THIS IS HOW WE DID IT. IT'S A MOVIE BUT IT DOES IT QUICKLY SO I WILL PLAY IT FOR YOU. >> THE LUNG ON CHIP IS CRYSTAL CLEAR. FLEXIBLE AND ABOUT THE SIZE OF A SMALL COMPUTER MEMORY STICK. BUT CONTAINS TINY CHANNELS USING FABRICATION TECHNIQUES. A PORE OUTSIDE MEMBRANE SPRAY IT IS TWO CHANNELS AT T THE CENTER OF THE DEVICE. THE ON SIT SIDES OF THE MEMBRANE ARE ALIGNED BY HUMAN LUNG AND CAPILLARY BLOOD VESSEL CELLS. THIS MIMICS ARRANGEMENT OF LUNG AND BLOOD VESSEL CELLS L IN THE AIR SACK OF THE LUNG. APPLICATION OF CYCLIC SECTION AND SIDE CHANNELS MAKE IT IS ENTIRE FLEXIBLE SHEET AND CELLS STRETCH AND RELAX RHYTHMICALLY LIKE LUNG CELLS DO WHEN WE BREATHE. THE LUNG CHIP DEVICE AIR FLOWS OVER THE TOP OF THE HUMAN LUNG CELLS AN LIQUID MEDIUM CONTAINING HUMAN WHITE BLOOD CELLS FLOW BELOW THE CAPILLARY CELL LAYER. SO TEST HOW WELL THE LUNG AN CHIP DEVICE REPLICATE IT IS NATURAL RESPONSES OF LIVING LUNGS, WE INTRODUCED BACTERIA IN TO THE AIR CHANNEL TO MIMIC INFECTION. SFROM AND WE INTRODUCED WHITE BLOOD CELLS FOR THE BLOOD CHANNEL. WE THEN SAW THE WHY BLOOD CELLS MYIATE ACROSS THE CAPILLARY CELL LAYER THROW THE POROUS TESTIFY CENTRAL MEMBRANE AN TO THE AIR SPACE WHERE THEY ENGULF THE BECOME TIERIA. -- BACTERIA. HERE IS A VIDEO WITH THIS RESPONSE IN REAL TIME VIEWED THROUGH THE DEVICE. ATTORNEY CELLS ARE NOT VISIBLE BUT WE SEE THE WHITE BLOOD CELLS FLOWING IN THE CAPILLARY DEVICE OF CHANNEL JUST AS IN THE BLOOD VESSELS OF A HEALTHY PERSON. WHETHER WE INFECT THE AIR CHANNEL BY ADDING BACTERIA IMMUNE CELLS STICK TO SURFACE OF THE CAPILLARY CELLS L ON OPPOSITE SIDE OF THE MEMBRANE LOCATE BED LOW THE INFECTION SITES. HERE IS A MAGNIFIED VIEW SHOWING WHITE BLOOD CELL THROUGH THE FIRST CAPILLARY CELL LAYER, THROUGH THE HOLE AND FLEXIBLE MEMBRANE AND MOVING OUT OF FOCUS TO THE OTHER SIDE. WHEN VIEWED FROM THE AIR CHANNEL WITH ALL CELLS VISIBLE YOU CAN SEE A ROUND WHITE BLOOD CELL P POPPING UP FROM BELOW. JUST LIKE IN A REAL LUNG INFECTION, THE WHITE BLOOD CELL WHICH NOW COLORED RED ENGULF AND KILL THE BACTERIAL INVADERS. Q. THIS IS A LITTLE RUBBERY DEVICE AND IT HAS ONE CHANNEL MADE WITH MICROCHIP MANUFACTURING. THAT'S WHICH THEY CALL IT A CHIP. YOU PUT MANY TOGETHER AS WITH INTEGRATED CIRCUMSTANCES BUT IN THE BEGINNING WE HAVE IT TO HELD WITH OUR HAND. SO THIS MIMICKED THE SPIRE HUMAN INFLAMMATORY RESPONSE. JUST IN THISSIMPLE SYSTEM BUT WE HAVE COME FURTHER THAN THAT. THIS ACTUALLY IS SORT OF NIH FUNDING THOUGHT NIEHS AND WORKING ON NANOTOXICOLOGY, GIVE YOU AN EXAMPLE OF WHAT YOU SEE. SO HERE BECAUSE WE CAN DO HIRES LUG IMAGING WHICH IS REALLY A GREAT VALUE FOR THE PHARMACEUTICAL INDUSTRY AND FOR TOXICOLOGY, WE MEASURED REACTIVE OXYGEN SPECIES AS MEASURE OF INJURY AND WHEN WE GAVE STIMULANTS OF ENVIRONMENTAL PARTICULATES OF ANIMAL PARTICLE WHAT WE FOUND WAS INTERESTING. BASICALLY WE HAD NO INJURY MEASURED BY ROS PRODUCTION UNLESS WE HAD PHYSIOLOGICAL BREATHING MOTIONS. IF YOU DID THIS ON A -- A (INAUDIBLE) YOU WOULD HAVE NEVER SEEN THIS. WE ALSO CAN SEE BREATHING WAS CRITICAL FOR SEEING ACTIVATION OF INFLAMMATORY RESPONSE MEASURED BY ENDOTHELIAL EXPRESSION OF NEUTRAPHIL STICKING. WHAT'S MORE INTERESTING IS ABSORPTION OF NANOPARTICLES ACROSS CELL LAYERS IN THE EXTRA CELLULAR MATRIX WAS SIMILARLY AFFECTED BY BREATHE MOTION THAT NO ONE HAD EVER SEEN BEFORE. WE SAW 8 TO 10 FEEL INCREASE OF THESE PARTICLES PASSING THROUGH SO BASICALLY BIOAVAILABILITY ASSAY GIVING AEROSOL BASED DRUG FOR EXAMPLE. THIS IS NOT MIMICKING BIOLOGY, THIS IS PREDICTION. NO ONE HAS SOON THIS BEFORE SO WE DEVELOPED ANIMAL MODEL EXVIVO TO CONTROL FOR PERFUSION AN VENTILATION AN 8 TO 10 FEEL INCREASE IN ABSORPTION OF NANOPARTICLES 'CROSS THOSE LAYERS SO AGAIN, THIS CHIP NOT ONLY MIMIC BUT PREDICTED. THAT WAS 2010, IN TWO YEARS INTERVENING WE PUBLISHED IN TRANSLATION SCIENCE MEDICINE THE FIRST HUMAN DISEASE MODEL. THIS IS VERY IMPORTANT. THIS CAME BECAUSE WE TALKED TO PHARMACEUTICAL COMPANIES. BECAUSE OF EFFICACY PROBLEM BEING THE BIGGEST -- MANY WAN HUMAN DISEASE MODELS NOT TOXICOLOGY. SO WE BUILT A MODEL OF HUMAN PULMONARY EDEMA WITH CHEMOTHERAPY INDUCED MODEL. INTERLEUKIN 2 FDA APPROVED CANCER DRUG MAJOR DOSE LIMIT TOXICITY, PULMONARY VASCULAR LEAKAGE NUDE ON THE LUNGS. ON HISTOLOGICAL SECTION OR AUTOPSY YOU GET CLOT FORMATION IN THE ALVEOLAR SPACE. SO WE TOOK THE DEVICE, GAVE INTERLEUKIN 2 ON THE CAPILLARY SIDE. THIS IS WHAT YOU SEE IN THE DEVICE FROM ABOVE WHEN THAT'S AIR, IT'S NOT CLEAR. AS WE GET INTERLEUKIN 2 MOVING TO FILL THE SPACE, NOW EVERYTHING IS CRYSTAL CLEAR, WE CAN QUANTITATE -- IM, WE CAN LOOK AT BLOOD CLOT FORMATION PUTTING FLUORESCENT FIBRINOGEN UNDER CONTROL CONDITIONS YOU CAN BARELY SEE IT HERE. BUT IF YOU HAVE INTERLEUKIN 2 AT THE SAME DOSE AND SAME TIME COURSE AS IN HUMAN TOXICITY, YOU CAN SEE CLOT FORMATION IN REAL TOO MANY AND YOU CAN SEE BY CON FOE CALL THE CLOUD IN THE AIR SPACE LIKE IN HUMANS. WE CAN TAUNT AT A TIME THIS BY USING FLUORESCENT -- WHAT WE SAW WHEN I WAS T A MEETING IN EUROPE MY POST-DOC ACCEPT A SLIDE THAT WENT 0 TO 5. WE CAN SEISH L-2 EFFECTS IN THE DEVICE BUT THERE WAS NO BREATHINGS MOTION. IF YOU GIVE A BREATHING MOTION THIS IS WHAT YOU SEE. AGAIN, THIS IS NEVER SEEN BEFORE. WE CAN DO HIGH RESOLUTION IMAGING, GAPS FORMENING THE ENDOTHELIUM AN P EPITHELIUM, WE CAN QUANTITATE THIS, VERY POWERFUL FOR THE PHARMACEUTICAL INDUSTRY. WE WENT BACK TO IN VIVO ANIMAL MODEL AND BREATHING MOTIONS ARE CRITICAL FOR IL-2 TOXICITY WHICH IS IMPORTANT THERAPEUTICALLY AND YOU HAVE PATIENTS ON EVENTUALLYTORS. THIS IS SOMETHING YOU CAN PLAY WITH. BUT AS EXTREMELY IMPORTANT IN TERMS OF THINKING ABOUT THERAPIES, I WORKED ON MECHANIC KNOW BIOLOGY FOR 30 YEARS AN SHOWN ONE OF THE FIRST RESPONSES CELLS SENDS MECHANICAL STRETCH IS ACTIVATING ION CHANNEL CALLED TRIP V-4. WE WERE AWARE GLAXOSMITHKLINE WAS DEVELOPED INHIBITORS SO THEY GAVE U AN INHIBITOR AND WE INHIBITED THE IL-2 TOXICITY RESPONSE IN TERMS TERMS OF PULMONARY EDEMA ON A CHIP. IN PARALLEL THEY DID IT IN RATS AN DOGS AN CONFIRMED THE SAME THING. THESE WERE PUBLISHED IN BACK TO BACK PAPERS IN SCIENCE TRANSLATION MEDICINE. THIS MODEL IS USED FOR TOXICITY AS WELL AS EFFICACY AS WELL AS DRUG DISCOVERY. WE IN THE BEGINNING I HAD A POST-DOC AND GRAD STUDENT MAKE THESE INDIVIDUALLY, WE HAD TO START TO OUTSOURCE THESE, WE GET 50 TO 100 A TIME. THIS IS THE BEGINNINGS OF COMMERCIALIZATION AND DARPA IS PUSHING THAT FURTHER. YOU HER ABOUT THE HEART WE CALL A BEATING HEART CHIP KIT PARKER. FACULTY MEMBER DEVELOPED A COUPLE OF YEARS AGO A SIMPLE METHOD WHERE HE CAN MICROPATTERN EXTRA CELLULAR MATRIX ON A SUBSTRATE TO ALIGN CELLS. HE TAKES CARDIOMYOCITES FROM RAT AND ORIENT THEM AND THEY CONTRACT. THEY ROLL UP BUT IF U YOU MAKE CANDLE LEVERS YOU CAN QUANTITATE CONTRACTTILE STRESS GENERATION BY HOW MUCH THEY BEND. YOU CAN DO IT WITH OPTICAL MARKERS FLUORESCENT DYES OR ‡T(U)ON ARRAYS YOU CAN MEASURE ACTION POTENTIALS AND POTENTIALS AS PROPAGATION, YOU CAN DEVELOP ARRHYTHMIAS ON THESE CHIPS. WITH FUNDING FROM ADVANCING REGULATORY SCIENCES INITIATIVE WITH THE FDA AND NIH, AS DAN MENTIONED WE WERE FUNDED ONE FIRST GRANTS TO LINK THE BREATHING LUNG ON A CHIP TO THE BEATING HEART TO MEASURE ABSORPTION AND CARDIOTOXICITY OF AEROSOLIZED DRUGS AND THERAPEUTICS. IN OUR SCIENCE PAPER WE DELIVERED NANOPARTICLES TO THE AIR SPACE IN LIQUID AND THEN COMBINED AND PASSED AIR THROUGH BUT PHARMACEUTICAL COMPANIES WANTED TO SEE -- YOU TO BE ABLE TO DELIVER AEROSOL ON THIS LITTLE CHIP. WITH THIS GRANT WE DEVELOPED MANY IMPACTERS THAT WE CAN NOW BASICALLY HERE THESE ARE SHOCK AND AWE, LITTLE EGG EDGE MOTIONS -- EXPLOSIONS, DELIVERED FROM A COMMERCIAL NEBULIZER THROUGH THIS DEVICE RIGHT TO THE EPITHELIUM. THIS IS A VERY IMPORTANT BECAUSE YOU CAN BEGIN TO SEE WHAT HAPPENS DURING AEROSOL BASED DELIVERY WHICH SIMILAR POSSIBLE. NO PHARMACEUTICAL COMPANY KNOWS THAT. AN EXAMPLE, REACCEPTLY, -- RECENTLY THIS IS SHOWING INFLAMMATION WITH TNF ALPHA AND DELIVER DECK SILL METH ZONE TO THE AIR SPACE AN REPRESS THE RESPONSE. I DON'T HAVE THE DATA BECAUSE IT'S FAIRLY NEW BUT OUR GRANT ENDS IN JUNE BUT WE HAVE LINKED DOXORUBICIN TO THE LUNG AND TOXICITY TO THE HEART AND HAVE EXCITING RESULTS. SO WE THINK WE WILL MEET THE GOALS OF THE GRANT. WE HAVE GONE AND WITH THE HEART WE NOW PART OF THAT GRANT IS INTEGRATING KID MODEL INTO MICROFLUID iS. THAT'S WHAT THE ET BOOING CANDLE LEVERS WERE. WE HAVE DELIVERED TEN ORGANS ON CHIPS, BONE MARROW, KIDNEY, LIVER, SKIN, MUSCLE L, BLOOD BRAIN BARRIER, WE HAVE A BEAUTIFUL AAIRWAY, FUNDED BY PHARMACEUTICAL COMPANIES FOR COPD AND AS ASTHMA AND OTHER AREAS WORKING EXTREMELY WELL. THAT'S MORE IN THE DRPA GRANT THAT AREN'T ON HERE. THIS MODEL SCALES AN CAN BE ADAPTED TO DIFFERENT SYSTEMS. HUMAN GUT ON A CHIP THESE FINGER LIKE PROJECTIONS BUT HIGH POWER, EPITHELIUM POROUS EXTRA CELLULAR MATRIX AN ENDOTHELIAL. WE CHANGED THE HAGUE AND WIDTH AND DEGREE OF EXTENSION AND DID TRICKLING LIKE FLOW MORE LIKE INTESTIN THAN THE BLOOD. AND WE STARTED WITH KAKO-2 EVERY PHARMACEUTICAL COMPANY USES AND HATES. THEY BASICALLY SAY THEY'RE DEACCEPT BUT NOT DIFFERENTIATED. WE TOOK THESE CELLS, THE COMMERCIAL PRODUCT SOLD TO PHARMA TO GROW FOR THREE WEEKS STATIC, THEY'RE SQUAMOUS EPITHELIAL CELLS. PARASTALL TICK LIKE MOTIONS THAT ARE COLUMNAR, YOU GET INCREASED BARRIER INTEGRITY, THIS IS A TRANSWALL YOU GET WITH MECHANICICALLY ACTIVE ENVIRONMENT, PARACELLULAR PERMN 'T AND CELL DIFFERENTIATION INCREASE DRAMATICALLY. YOU GET VILLI FORMATION. THESE THINGS SPONTANEOUSLY FORM VILLI IN A PERIOD OF DAYS. THESE RKACO-2. WHAT WE HAVE DONE SINCE IS WE CAN SEE WE GET CRIP FORMATION. THIS IS A TWO HOUR LABELING WITH WITH EDU, WHICH IS LABELING DNA SYNTHESIS. I I HOPE YOU CAN SEE IN PINK. THE TIP IS HERE, YOU SEE PINK AT THE BOTTOM. IF YOU GO 24 HOURS YOU CAN SEE THEY MOVED UP AND GROWING UP. YOU ALSO SEE MUCOUS PRODUCTION, THESE ARE DIFFERENTIATING TO INTESTIN WITH WITH MICROVILLI. I WANT TO MAKE A BIG POINT WHICH IS PEOPLE WANT TO KNOW EVERYBODY WANTS THE IDEA CELLS, PRIMARY HUMAN CELLS APPROXIMATE WE'RE DOING BOTH. BUT THIS IS WHAT HAPPENS IF YOU TAKE CACO-2 CELL, THIS IS DONE IN QUADRUPLICATE AND DUPLICATE. THE GENE ARRAYS ACROSS 22 THOUSANDS HUMAN GENES IF THEY'RE STATIC, WHETHER OR NOT DIFFERENT MATRICES, THEY'RE BASICALLY THE SAME. IF YOU GIVE TRICKING FLOW LIKE INTESTINE THEY'RE TOTALLY DIFFERENCE. I CAN TELL YOU WE HAVE DONE MICROBIOME AND IT'S TOTALLY DIFFERENCE ABOUT LOOKS MORE LIKE HUMAN WITH MICROBIOME. SO THESE CELLS I SAY NOW THERE ARE NO BAD CELLS JUST NO BAD KIDS, JUST GET INTO BAD GROUPS, BAD ENVIRONMENTS, YOU GIVE THEM THE RIGHT ENVIRONMENT, WE HAVE SEEN IT ÖITH LUNG AND TISSUES. SO HAVING THIS WE CAN BASICALLY EXPLORE THE MICROBIOME BECAUSE OF THE IMPORTANCE FOR DISEASE AND DRUG DEVELOPMENT SO WE STARTED WITH (INDISCERNIBLE) THE HUMAN DERIVED PROBIOTIC THAT LIVES IN OUR GUT. WHAT WE SEE WITH TRANSEPITHELIAL ELECTRICAL RESISTANCE WHICH IS BARRIER FUNCTION F YOU GIVE IN A TRANSWELL THESE BUGS THEY DIE AS YOU EXPECT. IT'S CONTAMINATION APPROXIMATE YOU LOOSE FUNCTION. YOU PUT THEM IN OUR SYSTEM WITH PARASTALLSIS AND TRICKLING KNOW YOU GET BETTER BARRIER FUNCTION WHICH CONFERS RESULTS IN HUMAN CLINICAL STUDIES. PROBIOTICS INCREASE BIERIER FUNCTION. NOW -- BARRIER FUNCTION. USING COMPLEX PICTURE, WE FIND THEY LIVE IN THE CRIPS IF YOU LOOK CAREFULLY THEY'RE MOVING, THESE ARE THE VILLI THAT FORM. WE HAVE ENDOTHELIUM, WE HAVE DONE INFLAMMATORY RESPONSES AND WE WORK WITH DRUG COMPANIES MICROBIOME BASED THERAPEUTIC. SO THIS IS A HUGE BREAK TRUE BECAUSE YOU CAN'T IT ANY OTHER WAY RIGHT NOW. FEW YEARS AGO AT REVIEW WHERE WE SUGGESTED TO BEGIN TO LINK TOGETHER ORGANS MICROFLUIDICLY, WE HAD A COMMON ENDOTHELIAL LIKE CHANNEL, HAVING AEROSOL BASED DRUG WATCH IT BE METABOLIZED BY THE LIVER AND PEEED OUT BY THE KIDNEY AND LOOK AT THE CARDIO TOX. ORAL DRUG THROUGH THE GUT CAN DO SIMILAR THINGS. WE ALSO HAVE A BONE MARROW WHERE WE CAN MAKE MARROW AN RECONSTITUTE MARROW IN A LETHALLY IRRADIATED MOUSE, FULLY FUNCTION NOW ON A CHIP. SO THIS I GET GOT DRPA INSPIRED TO PUT OUT THE FIRST INITIATIVE THAT WE WERE ONE OF THE TWO WINNERS FDA FOLLOWED JUST A COUPLE OF MONTHS THEREAFTER, FUNDING A SEPARATE SUBPROJECT IN OUR GROUP, THIS IS A COLLABORATION WITH MY GROUP AND JOHN WIXSELL HAS NIH FUNDED AND (INDISCERNIBLE) WHO DOES PKPD MODELING, INCREDIBLE GROUP OF MODELERS, TO DEVELOP WE CALL IT INTERROGATOR INSTRUMENT THAT AUTOMATES TEN ORGANS, KEEPS THEM ALIVE FOR FOUR WEEKS. WE HAVE DESIGNED ONE THAT A'S A PLUG AND PLAY CARTRIDGE TO TAKE THE CHIPS AND PUT ANY -- TEN OF THE SAME, TENDER, PUT THEM IN DIFFERENT ORDERS. AND GENERATE DATA TO PREDICT HUMAN RESPONSE, WE'RE DEVELOPING PKPD MODELS. THIS IS JUST OUR PROGRESS IN SIX MONTHS, TO GIVE A FEEL HOW WE WORK. OUR INSTITUTE, WE HAVE OF THE 325 PEOPLE, 38 PEOPLE ARE HIRED FROM INDUSTRY WITH 10, 20 YEARS IN THE CHRONIC TEAM MANAGEMENT BOARD AT THE BENCH, THEY OTHER NOT MANAGERS, THEY'RE MEETING PRODUCT DEVELOPMENT TEAMS. I HAVE BUSINESS DEVELOPMENT PEOPLE. WE DO PARTNERSHIPS WITH INDUSTRY TO UNDERSTAND WHAT THE REAL PROBLEMS ARE BUT WHEN WE DO PRODUCT DEVELOPMENT WE REALLY DO IT. SO SIX MONTHS WE DEVELOPED AN INSTRUMENT TO EXTEND CULTURE AND PRE-CONDITIONING OF MULTIPLE ORGANS ON CHIPS AND PAIR LEGAL. SO THIS IS THE -- ONE CHIP AT A TIME, TUBES GOING OUT, THEY HAVE BIG SUCTION AND MACHINES OUTSIDE IT AND WE HAVE TO HAVE LIKE ONE INCUBATOR PER CHIP. SO THE FIRST SYSTEM WAS TO AUTOMATE EVERYTHING INSIDE INCUBATOR, AND PRE-CONDITION THEM A COUPLE OF WEEKS. EF GONE FIVE WEEKS. THERE'S NO LIMIT LIKE NASA MICROFLUIDIC CONTROL SYSTEM. WE DEVELOPED DIFFER CARTRIDGES MODELS TO PLUG ONE OF THESE CHIPS TO BE IN HERE AND WE DO ITERATIONS WEEKLY OR BIWEEKLY. WE DEVELOPED APPROXIMATE AUTOMATED MICROSCOPE AND FLOW SYSTEM, AND JUST FRIDAY I TOOK THIS PICTURE, THEY JUST SHOWED IT TO ME, THAT WAS A FATE OF A CAMERA THAT MOVES, WE HAVE FOUR CARTRIDGES AN CHIPS THAT PLUG IN, CLOSED SYSTEM, SO THIS N IS THE BEGINNING OF PRE-CONDITIONING. THIS IS THE HEART OF A SYSTEM THAT HAS ANALYTICAL CAPABILITY, HOOKS UP TO MASS SPEC, ET CETERA. SO THEYED ASKED ME TO BE REALLY FAST. THAT'S MY LAST SLIDE. I INVITE YOU, HE WAS WORRIED THAT I WOULD BE LONGER. THIS IS OUR WEBSITE, I INVITE YOU THERE, YOU CAN LEARN MORE ABOUT THIS AND OUR APPROACH TO INNOVATION AN HAPPY TO ANSWER QUESTIONS. THANK YOU. PAUSE PLUS HAS [APPLAUSE] >> VERY IMPRESSIVE SCIENCE FICTION. I GUESS TRUE. I HAD A GENERAL QUESTION -- >> THAT'S WHERE YOU START. MAYBE WHAT NIH NEEDS TO LEARN THAT'S HOW DRPA WORKS. >> IN TERMS OF THE TOXICOLOGY, IS THERE A WAY TO DO GENETIC MANIPULATION SO THAT SEPARATE FROM LOOKING FOR TOXICOLOGY ACROSS INDIVIDUAL THERAPIES YOU COULD LOOK AT TARGET ABILITY. >> GREAT QUESTION. I USUALLY HAVE A SLIDE WHICH IS WHEN I FIRST STARTED THIS WE TALKED PERSONALIZED MEDICINE SO YOU CAN MAKE YOUR LUNG ON A CHIP AND HIS LIVER ON A CHIP. WE REALIZED MORE VALUABLE TO BASICALLY EFFECTIVELY DEVELOP CLINICAL TRIALS ON CHIPS SO GEORGE CHURCH IS AT OUR INSTITUTE, HEADS THE PERMIZED GENOME PROJECT. HE'S GOT -- HE'S COLLECTING 16,000 SKIN BIOPSIES, MAYBE IPS CELLS AND HAS FULL GENOMES ON ALL. SO THE IDEA IS TO IDENTIFY GENETIC SUBPOPULATIONS AN DEVELOP ORGANS FOR THOSE POPULATIONS AN DEVELOP DRUGS FOR THAT SMALL GROUP WHICH I THINK WOULD BE A GAME CHANGER FOR PHARMACEUTICALS. YOUYOU HAVE A CLINICAL TRIAL, YOU FAIL AND DO STATISTICS TO FIGURE OUT WHAT'S THE RIGHT GROUP AND THREE YEARS LATE TORE DO THE RIGHT STUDY. WE CAN GENETICALLY MANIPULATE THESE SYSTEMS AS A DIFFERENT THERAPEUTIC THAT CAN BE DONE WITHOUT A DOUBT. >> IN OUR ROLE AS ACCELERATORS OF RESEARCH, CAN YOU TALK ABOUT THE FDA VIEW OF THIS? SOUND LIKE YOU HAVE BEEN WORKING WITH THEM. DO YOU HAVE DIFFERENT PERSPECTIVES FROM FDA ON TIMELINESS WHICH THESE PROJECTS ARE REALIZED? >> NOT SAYING THIS WAS FDA, FDA IS UNBELIEVABLY SUPPORTIVE. WE SPEAK EVERY MONTH. I HAVE BEEN DOWN TWICE, THEY COME UP TO OUR PLACE A FEW TIMES. I'M GOING BACK DOWN AGAIN. I PREPPED THIS TO A GROUP TO EXPLORE BIOMARKER APPROVAL. HOW THIS IS VIEW AS BIOMARKER. THEY OFFERED A SAFE HAVEN TO OUR PHARMACEUTICAL PARTNERS TO GET THEM OUT OF THEIR CAVES TALK. AMAZING. SO I THINK THEY REVIEW BIOMARKERS AN ESSENTIALLY IF WE CAN SHOW WE ARE AS GOOD OR BETTER AN ANIMAL MODEL, THEY WOULD SUPPORT HA AS BIOMARKER, DO WHATEVER YOU DO FOR BUOY MARKER AND WRITE A LETTER SAYING TO PHARMACEUTICAL COMPANIES THEY CAN PUT IT AS PART OF THE DRUG APPROVAL PACKAGES. I SAY WE'RE GOING -- I THINK THIS IS IS GOING TO WORK BY REPLACING ONE ANIMAL MODEL AT A TIME. I THINK THE PULMONARY EDEMA IS GOOD START. I THINK WHAT I LEARNED FROM TALKING TO THEM WE NEED TO DO THIS WITH THE PHARMACEUTICAL PARTNER WHO IS DRIVEN AROUND A PARTICULAR COMPOUND OR AREA, NOT SOMETHING ACADEME HEALTHCARE THAT WILL DO ON THEIR OWN. BUT IT'S ALL VERY GOOD INPUT AND VERY TIMELY WAY. OFTEN THINKER EAR PUSHING ME TO GET BACK TO ME FASTER THAN I HAVE TIME TO DO IT. SO THAT'S BEEN GREAT. THEY'RE VERY INVOLVED ON ANOTHER DRPA PROGRAM I'M ON, VERY SUPPORTIVE. SO THE PROBLEM IS NOT THE FDA, I THINK THE PHARMACEUTICAL COMPANIES COME TO US, THEY'RE ALL INTERESTED AND PEOPLE THAT ARE THINKING FORWARD AT THE COMPANY ARE ENORMOUSLY EXCITED. THE PEOPLE IN THE TRENCHES ARE VERY SKEPTICAL OR IT WILL CHANGE THE WAY THEY DO THINGS AND THEY DON'T WANT IT DONE SO IT'S FINDING THE RIGHT PEOPLE. WE HAD MEETINGS WHERE THERE WAS A SUBGROUP OF PEOPLE WHO POO POOED IT ABOUT WALKED AWAY. BUT THERE'S A NEW GROUP OF PEOPLE THERE THAT'S EXCITING AND SUPPORTIVE FROM THE TOP DOWN. >> IT SOUNDS LIKE WE'RE ON A CUSP OF TRANSFORMATION FROM ANIMAL MODELS TO THE TECHNOLOGY YOU DESCRIBE. AND WHEN WE'RE AT A HISTORICAL MOMENT, IT BEHOOVES US TO LOOK BACK A BIT AND SEE ARE THERE COMPONENT, I DO MEDICAL ETHIC, A HUGE AM OF ADVANTAGE TO THIS TRANSITION. WHAT ARE COMPONENTS IF ANY OF ANIMAL MODEL TESTING THAT WE MAY LEAVE BEHIND? >> I THEE ANIMAL MODELS WE'RE MIMICKING THE ALVEOLUS BUT NOT SMALL AIRWAYS P TUBERCULOSIS OCCURS IN PARTICULAR PARTS OF THE LUNG AND NOT OTHERS. IT COULD HAVE RELEVANT, MA NOT. THE MILLION SYSTEMS INTEGRATION GOES TO FAT DEPOSITS. THAT SAID MAYBE SOMEDAY 30, 40 YEARS FROM NOW POSSIBLE TO DO IT OR ANIMAL MODELING. THERE ARE MANY TIMES WHERE IT DOES NOT MAKE SENSE AND IT'S ETHICALLY WRONG TO DO THINGS TO THEM. WE, INTEREST IN RADIATION COUNTER MEASURES. YOU CAN'T DO STUDIES IN HUMANS, CERTAIN TIMES THERE'S CERTAIN TRANSPORTERS OR GENETIC MEDIATORS THAT ARE HUMAN SPECIFIC SO IT DOESN'T MAKE SENSE, YET PEOPLE DO IT BECAUSE THEY HAVE TO DO IT. SO I THINK THE FDA KNOWS THAT AND PHARMACEUTICAL COMPANIES KNOW THAT BUT NOBODY WANTS TO STOP DOING IT FIRST. SO THE FACT THEY'RE TALKING, I THINK THE DIALOGUE WHAT I SEE A LOT OF IS CONSORTIUMS WITH PHARMA WHICH IS POSITIVE IN SOME WAYS. ON THE OTHER HAND YOU WANT A CHAMPION. LIKE YOU GUYS WERE SAYING, I DON'T WANT A CONSORTIUM OF -- I WANT A PHARMACEUTICAL COMPANY TO GO WITH ME TO FDA TO SAY WE WANT TO PUSH THIS. SO I THINK ONE HAS TO BE CAREFUL ABOUT DOING EVERYTHING BY COMMITTEE. YOU NEED CHAMPIONS. >> REALLY BEAUTIFUL STUFF. I WAS WONDERING HOW YOU ADDRESS THE ISSUE OF HETEROGENEITY IN THE SENSE THAT ONE OF THE CONFOUNDERS OF CLINICAL STUDIES IS OUR HETEROGENEITY LEAD TO UNSUSPECTED AFFECTS. AND WASN'T CLEAR WHETHER THE CELLS USING ARE CLONEAL -- >> THIS IS A REALLY GOOD POINT. ENORMOUS PRESSURE TO USE IPS CELLS. IPS CELLS, THESE EMS VERSUS THAT ARE ARE TOTALLY DIFFER. WE'RE USING ESTABLISHED CELL LINES THAT ARE BEEN AROUND FOR YEARS, VERY ROBUST, EVERY. TIME WE COIT. I CAN SEE THE ADVANTAGES OF IPS CELLS BUT IF YOU DO THAT YOU NODE TO HAVE POPULATIONS. THAT'S LIKE HAVING GENETICALLY DEFINED STUDY HAVING GENOMES AND THOUSANDS OF DIFFERENT IPS CELLS, EVEN IF THEY'RE THE SAME THEY REPRESENT ETHNIC GROUPS, YOU CAN DO IT FASTER THAN CLINICAL TRIALS. RARE DISEASE, I THINK ABOUT DOING THIS FOR A RARE DISEASE, WHERE YOU DON'T HAVE MANY PATIENTS THAT GET SAMPLES FROM. THAT I THINK COULD BE REALLY VALUABLE. IF YOU HAVE A RARE DISEASE WE GET SAMPLES NOW YOU CAN KEEP THEM IN CULTURE HAHN MAKE THOUSANDS OF CHIPS, THAT COULD BE AT THAT PARTICULAR TIME FOR FAR MANY AND FOR THE NATION. YOU MENTIONED INTELLECTUAL PROPERTY. CAN YOU TELL US ABOUT HOW -- WHAT YOUR POLICIES ARE, THESE ARE GREAT TERRIFIC TECHNOLOGIES THAT SEEM IMMINENTLY PATENTABLE. BUT WHAT'S THE GOING FORWARD STRATEGY AS FAR AS PATENTING, WILL THESE WILL ESSENTIALLY LICENSED TO SINGLE COMPANY, MADE BROADLY VAIL SOMEBODY >> THIS IS UNDOUBTEDLY A STARTUP. SO BASICALLY TALK ABOUT IPS CELLS BUT JUST TO THINK ABOUT IT WE WORK WITH PHARMACEUTICAL COMPANIES AS PARTNERS NOW SO THAT THEY WILL BELIEVE IN THE SYSTEM. WE ARE WORKING ON THINGS THAT E CARE ABOUT. THEY UNDERSTAND THE PROBLEM. SO WE'RE DEVELOPING MANY COLLABORATIONS PHARMACEUTICAL COMPANY AND EFFECTIVELY THAT VALIDATES THE SYSTEM FOR THEM. WE HAVE -- WE WOULD HAVE DONE A COMPANY THAT GETS FUNDING TO BUILD AUTOMATED INSTRUM"cj BUT D RPA IS FUNDING THAT RIGHT NOW. ONCE WE HIT PROOF OF PRINCIPLE TIPPING POINT, THIS WOULD BE A STARTUP THAT WOULD EFFECTIVELY START AS SERVICE AND START HAVING INSTRUMENTS AND DISPOSABLES. THAT'S ONE SIDE. IP, WE STARTED WITH IP AROUND DEVICE DESIGNS BUT WE KNOW IP AND NEW MATERIALS I DIP SAY SMART PEOPLE KNOW THAT, WE USE PDMS AND SMALL ORGANIC SKIN ABSORBED TO IT, THAT CAN BE A PROBLEM FOR PHARMA. WE HAVE REPLACEMENTS NOW SO WE HAVE IP AROUND -- THERE'S AN UMBRELLA OF PATENTS AROUND IT BUT PHARMACEUTICAL COMPANIES WILL NEVER MAKE THESE. THEY DOPE WANT ANY IP. THERE'S NO IP RIGHTS ISSUES WHEN WE HAVE COLLABORATIONS WITH THEM. THEY'RE GETTING UPONSORRED RESEARCH FUNNING BUZZ THEY WANT FIRST IN, THEY WAN TO BE INVOLVED, THEY WANT TO KNOW WHAT'S GOING ON, IMPACT ON WHAT WE DO. ALL IP SITS WITHIN A COMPANY AND COULD BE THESE COMPANIES ARE INVESTORS IN THAT COMPANY LATER ON. >> I CAN CERTAINLY SEE ANY PARTICULAR PHARMACEUTICAL COMPANY HAVING AN INTEREST IN BEING THE ONLY COMPANY TO HAVE ACCESS TO HEART ON A CHIP FOR FIVE YEARS OR SOMETHING. >> WE WOULDN'T DO THAT BECAUSE THE VALUE IS BEING ABLE TO INTEGRATE THEM. EVERY COMPANY WE TALKED ABOUT SAYS I DONE CARE WHO YOU WORK WITH AS LONG AS YOU HELP US, WE'RE SO DESPERATE. AND I THIS THAT HAS NEVER BEEN AN ISSUE WITH ANY COMPANY. FANTASTIC AS ALL. GOOD THE HEAR THE UPDATE. LOOK FORE TO HAVING YOU BECOME AGAIN AFTER YOU HAD ANOTHER SIX MONTHS TO GET WORK DONE. GOING TO HAVE TO HAVE YOU BACK WITH INCREASING REGULARITY. SO THE NEXT SESSION WE'RE GOING TO MOVE TO CLINICAL AND TO ELAINE COLLIER. >> ALL RIGHT. THANK YOU. THIS WILL BE A PRESENTATION ABOUT THE TRAINING PROGRAM IN THE CTSA AWARD PROGRAM. AND I JUST WANTED TO INTRODUCE A LITTLE BIT ABOUT THE PROGRAM AND THEN ELLIOT ANTMAN FROM HARVARD WILL TALK ABOUT THEIR PROGRAM THERE AND ACTIVITIES THERE. SO FIRST THING IN THE CTSA PROGRAM, TRAINING IS A REQUIREMENT. SO ALL THE CTSA AWARDEES DO TRAINING. THEY HAVE MENTORED CAREER DEVELOPMENT AWARDS. KL-2 AWARDS, SO THEY HAVE APPROXIMATE TRAIN SCHOLARS. THEY DO CURRICULUM DEVELOPMENT, COURSE DEVELOPMENT BEYOND THE KL-2 PROGRAM. SOME OF THEM, AN P OPTIONAL PART OF THE PROGRAM IS TO HAVE A KEY PROGRAM, ESSENTIALLY EQUIVALENT OF A T-32 PROGRAM. BUT IT HAS SOME NUANCES RELATED TO CLINICAL. SO PRE-DOC AND POST-DOCTORAL IN THAT PROGRAM. MOSTLY POST-DOCTORAL ARE SUMMER PROGRAMS FOR MEDICAL STUDENTS. YEAR OUT PROGRAMS. I DON'T WANT TO GO INTO THE GO INTO DETAILS OF PROGRAM BUT THAT'S VERY INTERESTING THIS IS A LARGE PART OF THIS PROGRAM AND CERTAINLY SCHOLAR DEVELOPMENT P DOCTORAL CANDIDATES IS PART OF THE PROGRAM. THIS IS JUST STATISTICS ON LAST YEAR, ACTUALLY THE YEAR BEFORE BECAUSE WE DONE HAVE STATISTICS ON FY 12 YET. BUT IN THE PROGRAM IT'S HALF WOMEN AND HALF MEN. SLIGHTLY MORE WOMEN. THEY ARE SEEKING PROFESSIONAL DEGREES CERTAINLY TL-1 PROGRAM IN THE PRE-DOCTORAL PROGRAM. BUT MANY SCHOLARS WHO HAVE DEGREES IN THE KL-2 PROGRAM GET DEGREES IN CLINICAL TRANSLATIONAL SCIENCE SO MS DEGREES AND Ph.D. DEGREES. AND MOST OF THOSE PEOPLE HAVE MT DEGREES OR M.D. Ph.D. DEGREES. SO THIS IS A SLIDE FROM -- AND I APOLOGIZE, FOR THE SIZE BUT THIS IS A SLIDE FROM NIH CENTRAL; OER THAT SHOWS THIS SHOWS SUCCESS IN ARCH TIME FOR K AWARD TO GET A RESEARCH CAREER AWARD. SO THE AVERAGE YEARS TO THAT FUNNED KL-1 FOR KO-8 AND K-23 ARE BETWEEN FOUR AND SIX YEARS. FOR THE PEOPLE IN THE CTSA PROGRAM, IT'S TWO YEARS. SO THEY SIGNIFICANTLY INCREASE THE TIME TO GETTING THEIR FIRST RO-1. THERE ARE MANY ASPECTS WE CAN GO INTO, SOME YOU'LL HEAR FROM ELLIOT BUT THIS IS ONE OF THE AREAS WHERE THIS PROGRAM HAS BEEN SUCCESSFUL IN TRYING TO GET PEOPLE OUT OF TRAINING AND INTO THEIR CAREERS. SO FROM THE TIME THEY'RE IN THE PROGRAM. CAROL MERCHANT LEADS THE TRAINING PROGRAM FOR THE CTSA SO FROM TEAM THEY'RE IN THE PROGRAM. (OFF MIC) >> JUST TRYING TO UNDERSTAND WHEN WE SAY TIME FROM WHAT IT MEANS AND EQUIVALENT IN THE TWO KO-2 AND KO -- >> EQUIVALENT TO ALL PROGRAMS SO WHEN THIS PROGRAM -- WHEN THEY STARTED IN THEIR PROGRAM. USUALLY THE KL-2 PROGRAM IS A TWO YEAR PROGRAM, NOT A FOUR YEAR PROGRAM. SO JEFF SHE'S ALSO CARDIOLOGIST, HAS BEEN AT THE BRIGHAM AND WOMEN'S OVER 30 YEARS. AND CONTINUES TO DO HIS RESEARCH IN CARDIOLOGY AS WELL AS HAVING A SIGNIFICANT COMMITMENT TO TRAINING CLINICAL TRANSLATIONAL SCIENTISTS. DR. COOPER SMITH TOOK ME THANK YOU -- >> HE'S BEEN THERE 30 YEARS, I DIDN'T WANT YOU THE SAY THAT. >> DO THE MATH, YOU HAVE IT ALL RIGHT IN FRONT OF YOU. SO I THOUGHT I WOULD BEGIN THE DISCUSSION BY TAKING THE IMAGE FROM THE NCATS WEBSITE. THE WORDS THAT SURROUND THIS. IMAGINE, THE GOAL IS TO TRANSLATE NEW TREATMENTS AND PREVENTION STRATEGIES MORE EFFICIENTLY AS WE THINK ABOUT MOVING FROM LABORATORY DISCOVERIES AN PATIENT CENTERED RESEARCH AND IMPORTANTLY DELIVERY TO PATIENTS APPROXIMATE COMMUNITIES. WE THINK ABOUT THIS, THIS IS OBVIOUSLY A CRITICAL TASK, EVERYONE IN THIS ROOM, EVERYONE IN CONGRESS, EVERYONE IN UNITED STATES, VERY INTERESTED IN THIS. IT IS ALSO QUITE A COMPLEX TASK, A LOT OF CROSS TALK AND IMPORTANTLY THERE'S A BIDIRECTIONAL NATURE TO THIS. HAVING PUT THIS IMAGE UP IS A TERRIFIC STARTING POINT, IT FRAMES WHERE WE WANT TO GO. AS YOU MIGHT HAVE SEENv: ON THE HEADLINES FROM YESTERDAY'S USA TODAY, THERE WAS THE QUOTE FROM THE INAUGURAL ADDRESS SAYING OUR JOURNEY IS NOT COMPLETE. OBVIOUSLY NOT COMPLETE. AND OUR MISSION IS TO MAKE SURE WE ARE IN A POSITION TO TRAIN THE NEXT GENERATION, WORK FORCE OF THE FUTURE WHO WILL HELP MAKE THIS HAPPEN EVEN MORE EFFICIENTLY. SO IF WE THINK ABOUT THE ISSUES HERE, WE CONTINUE TO SPEND TIME THINKING ABOUT THIS AND REFLECTING ON THE WORDS FROM DR. COLLINS WHEN HE WROTE IN JULY 2011 IN SCIENCE TRANSLATIONAL MEDICINE ABOUT RE-ENGINEERING TRANSLATIONAL SCIENCE AND POINTED OUT CTSAs ARE THE NATURAL HOME FOR TRAINING THE CT WORK FORCE OF THE FUTURE. AND THIS SLIDE OUTLINES ON THE LEFT THE INDIVIDUALS THAT WE WOULD BE INTERESTED IN TRAINING AND REPRESENTING HERE Ph.D. SCIENTISTS, SOME WILL HAVE A BASIC BIOMEDICAL ORIENTATION, SOME ARE M.D. SCIENTIST, COLLABORATIVE CT RESEARCH PERSONNEL. I AM GOING TO ILLUSTRATE HOW I THINK THE CTSA TRAINING PROGRAM CAN ACCOMPLISH WHAT WE WANT TO GET TO WHICH IS ON THE RIGHT HAND SIDE AND I'LL USE EXAMPLES HOW WE HAVE BEEN WORKING THIS IN OUR CTSA WHICH IS CO-NAMED HARVARD CATALYST. WE CERTAINLY WANT THE INDIVIDUALS ON THE LEFT TO END UP TO BE INDEPENDENT INVESTIGATORS BUT THAT'S NOT ENOUGH BECAUSE WE HAVE HEARD, AS YOU WELL KNOW, THE IMPORTANCE OF COLLABORATION AND EVEN MORE SO TODAY, THE CONCEPT OF TEAM SCIENCE SO ONE THING THAT PREVENTS US FROM GETTING THE TRAINEES ON THE LEFT SO THAT POINT -- TO THE POINT ON THE RIGHT, WE HAVE GOT THEM IN THREE CATEGORIES. THE FIST IS A PROBLEM WHICH WE ENUNCIATED WHEN WE STARTED THINKING ABOUT HOW TO STRUCTURE OUR EDUCATION PROGRAM. THIS IS CONSIDERABLE VARIATION IN THE INTEREST, EXPERIENCE, THE SKILL SETS, AWARENESS OF AVAILABLE RESOURCES AND MENTORING RELATIONSHIPS WHICH SEEM RANDOM WHEN YOU TALK TO TRAINEE WHOSE THEY GOT CONNECTED UP TO. SO THIS NEEDS TO BE SOLVED. THERE ARE BARRIER, I PUT TWO IN THE CENTER OF THE SLIDE. ONE IS THE RANDOM INTERFACE WITH THE TRAINING RESOURCES. WE HAVE ENORMOUS NUMBER OF FELLOWS AND JUNIOR FACULTY WE NEED TO TRAIN AND AS WE BEGAN TO SPEAK WITH THEM THEY WERE NOT AWARE OF THE VARIOUS TRAIN REGULAR SOURCES THAT THEY COULD PARTAKE OF. SOME OF THOSE TRAINING OPPORTUNITIES EXIST AT INSTITUTIONS THAT ARE AFFILIATED WITH OUR CTSA, WE HAVE 27 AFFILIATES WHICH IS A COMPLEX TASK IN AND OF ITSELF. EACH OF THOSE HAS THEIR OWN INSTITUTIONAL PRIORITIES, A WORK IN WHERE WE SIT DOWN AND ASK THAT WE DO THIS AS A TEAM. THE MOST OBVIOUS IS GAPS IN THE CURRICULUM WE CERTAINLY MAKE A LIST OF ALL THE THINGS WE NEED TO DO THE TRAIN PEOPLE TO GET THE EXPERIENCE RESEARCH OR STATE. SO ONE OF THE FIRST THINGS WE DID WAS TO TRY TO PUT EVERYBODY ON SAME PAGE, THIS IS A DIAGRAM THAT WOULD BE DISCUSSED EQUALLY WELL BY ANY OF YOU, THIS IS THE LANDING PAGE FOR OUR WEBSITE FOR OUR C TS,A. WE DEPICT HERE THE BASIC BIODISCOVERY AND T DOMAINS, WHERE WE HAVE THE IMPROVEMENT IN HEALTH AND P 0 BASIC BIOMEDICAL DISCOVERY, T-1 TRANSLATION TO HUMAN, FIRST IN HUMAN EMPERIMENTS HERE. I LIVE IN THIS AREA, TRANSMATION TO -- TRANSLATION TO PATIENTS WHERE CLINICAL TRIALS CAN BE DONE HOPEFULLY MORE EFFICIENTLY THROW THE WORK DR. INGBER TOLD US ABOUT. WE HAVE TO TRANS LIT TO PRACTICE AND GET OUR CLINICAL COMMUNITY TO ACT IN ACCORDANCE WITH WHAT IS FOUND TO BE EFFECTIVE AND SAFE AND TRANSLATION ON THE POPULATION LEVEL. OUR WEBSITE ACTUALLY, THIS IS THE OPEN INTERNET PORTION OF OUR WEBSITE APPROXIMATE YOU CAN CLICK ON ANY ONE OF THESE BUTTONS AND BE TAKEN TO A SUBPAGE WHICH GIVES YOU A FURTHER DESCRIPTION, EXAMPLES OF THE ACTIVITIES THAT OCCUR IN EACH T DOMAIN, ILLUSTRATES SOME OF THE SPANNING ACTIVITIES IN THE WHITE BOXES HERE. WE POINT OUT IN THE TEXT THAT DESCRIBE THIS IS DIAGRAM, ON THE LEFT-HAND DEGREE OF CONTROL EMPERIMENTAL CONDITIONS AN TYPICALLY WORKING WITH A SMALL SAMPLE SIZE. MY COLLEAGUE PAUL FARMER IS WORKING WITH A LARGE SAMPLE SIZE AND POPULATION HEALTH AND HE'S LOST CONSIDERABLE DEGREE OF CONTROL OF THE EXPERIMENTAL CONDITIONS. THE THINKING THAT'S INVOLVED IN RESEARCH ON BOTH ENDS OF THE SPECTRUM AND EVERYTHING IN BETWEEN IS DIFFER. THE BIOSTATISTICAL ANALYSES THAT ARE FOR THE ENDS OF THE SPECTRUM ARE DIFFERENT. SO AN IMPORTANT FRAMING POINT FOR INDIVIDUALS EMBARKING ON A TRAINING CAREER IN CT SCIENCE. ENGRAFTING ON THAT DIAGRAM, WE TRY TO GIVE EXAMPLES FOR Ph.D. SCIENTISTS AND M.D. SCIENTISTS WHERE THEY MIGHT SEE THEMSELVES IN THIS PICTURE BECAUSE VERY OFTEN THEY JUST CAN'T FIND WHERE THEY FIT. SO WE DESCRIBE THE FACT THEY MAYBE INVOLVED IN BASIC BIOMEDICAL DISCOVERY, MAYBE INVOLVED IN BIOMARKS IN FIRST IN HUMAN STUDY, MAYBE INVOLVED IN BIOSTATISTICS HERE FOR DATA SAFETY MONITORING BOARD TYPE ANALYSIS, THEY MAY ACTUALLY BE INTERESTED IN ULTIMATELY DEVELOPING A CAREER THAT LEADS THEM TO WORK WITH THE FDA. OUR M.D. SCIENTISTS ARE STUDYING HUMAN HEALTH, THEY ARE ONES WHO ARE SEEN FIRST AS INDIVIDUALS DOING THE HUMAN INVESTIGATION, THEY MAYBE INVOLVED IN MULTI-CENTER TRIALS. MANY INDIVIDUALS WILL BE INVOLVED IN HEALTH ECONOMIC ANALYSES OF ALL THE PRODUCTS THAT ARE DISCOVERED. EVERYBODY HAS THE SAME GOAL WHICH IS TO IMPROVE HUMAN HEALTH. WE DEPICT HERE THE BIDIRECTIONAL NATURE OF THIS BUT THERE IS A KEY ISSUE THAT IS IMPORTANT TO ADDRESS WHEN WE PUT THESE DIAGRAM LIKE THIS TOGETHER. Ph.D.s ON WITHIN LINE AND M.D.s ON THE OTHER LINE. HERE WE HAVE TO HAVE Ph.D. SCIENTISTS BECOME AWARE OF THE FACT THIS THEY SHOULD AND CAN BE INVOLVED IN HUMAN INVESTIGATION. TO GET THAT STARTED WE HAVE EMBARKED ON A MENTORED CLINICAL RESEARCH EXPERIENCE FOR OUR Ph.D. TRAINEES. IN FACT, IT WAS THEIR SUGGESTION THAT WE ESTABLISH THAT EXPERIENCE.Ž SO Ph.D. TRAINEES ARE BEING LINKED TO MENTORS IN OUR CLINICAL RESEARCH CENTERS AND THEY WILL HAVE A DIDACTIC EXPERIENCE AS WELL AS A CLINICAL EXPERIENCE. THE GOAL IS TO GET THEM TO BE WRITING THAT ARE OWN HUMAN RESEARCH PROTOCOLS. MOVING ON TO WHAT -- HOW WE'RE GOING TO ORGANIZE OUR THINKING, LET ME TELL YOU, ONE OF THE SMART THINGS I DID AS I BECAME THE DIRECTOR OF THE EDUCATIONAL PROGRAM THERE WAS TO HIRE THAT LADY THERE WHO IS A PROFESSIONAL EDUCATOR. HE SHE'S A SHE HAS A DOCTOR RATE IN EDUCATION FROM HARVARD GRADUATE SCHOOL OF EDUCATION. THROUGH WORK WITH -- WE HAVE LEARN AD LOT ABOUT THE PEDAGOGICAL PRINCIPLES SO IMPORTANT, THIS IS NOT CME EDUCATION. THIS IS A VERY DIFFERENT TYPE OF EDUCATION. SO SHOWN ON THE LEFT IS BLOOM'S TAXONOMY OF THE COGNITIVE DOMAIN AND MUCH TO HAVE WHAT WE HAVE DONE IN OUR TRAINING TO TODAY HAS BEEN TO MEMORIZE FACTS AND STAY AT THE BOTTOM LEVEL AND REPORT BACK THE KNOWLEDGE WE HAVE GAINED. WHAT WE WANT TO HAVE OUR TRAINEES DO IS ASCEND THE PYRAMID AND REACH A POINT OF CRITICAL THINKING O TO USE THE FACTS. WE ARE IN A POSITION TO DO THAT TODAY, THAT WAS NOT POSSIBLE IN THE PAST. ON RIGHT IS A PYRAMID. HOW DO WE PROVIDE THE LEARNING EXPERIENCE FOR TRAINEES? THEY CAN READ SOMETHING, THEY CAN HEAR US TALK ABOUT IT. THEY CAN DESIGN AN PERFORM PRESENTATION, THEY CAN DO THE REAL THING. SO THE TOP PORTION IS PASSIVE LEARNING. MUCH OF WHAT WE HAVE DEALT WITH IS PASSIVE AND EVERYTHING WE HAVE BEEN WORKING ON IN OUR EDUCATION PROGRAM VERY IMPORTANT PICK FOR CTSA EDUCATION ACROSS THE COUNTRY IS TO UNDERGO A SHIFT, MUCH MORE ACTIVE LEARNING. WE USE THE KEY FUNCTION COMMITTEE FOR THE CT INVESTIGATOR AS THE BASIS FOR OUR OWN THINKING WHAT THE CORE COMPETENCIES SHOULD LOCK LIKE. SO ONE CAN FIND THE LISTING FROM THE KEY FUNCTION COMMITTEE. WE ORGANIZED THOSE AREAS INTO RESEARCH METHODS, IMPLEMENTATION, IMPLEMENTATION AND COMMUNICATION AND ADDED OUR OWN ON TOP OF THE BASIC LIST FROM THE KEY FUNCTION COMMITTEE. SO AS YOU GLANCE AT THIS LIST YOU CAN SEE WORKEDDED HARD ON IN THE CTSA EDUCATION PROGRAM SIMPLY STATING TO TRAINEES, COMMUNICATING WHAT YOU HAVEN DONE. IT'S AS IF THEY DIDN'T EXIST. YOU HAVE TO COMMUNICATE TO PATIENTS, SCIENTIFIC COLLEAGUES, SCIENTIFIC PAPER AND IN THIS WORLD I DON'T HAVE TO TELL YOU I DON'T HAVE TO WRITE A SCIENTIFIC GRANT. THE RANGE OF EDUCATION IS QUITE CONSIDERABLE HERE AS WELL. PROBABLY MOST FAMILIAR WITH THAT ON THE LEFT, QUANTITATIVE TERMS WHERE WE DEAL WITH NUMBERS AND TEST HYPOTHESIS AN POTENTIAL BIASES, PHONE KNOWN TO US BUT WE HOP THE MINIMIZE BY LARGE SAMPLE SIZE AND APPROPRIATE DESIGN OF CLINICAL TRIALS. WE CONTROL THE ENVIRONMENT. BUT IT IS A COMPLIMENTARY AN EQUALLY IMPORTANT. COPOINT OF CT SCIENCE TO THINK IN TERMS OF QUALITATIVE TERMS. E STUDY SOCIAL INTERACTIONS AN PURPOSEFULLY ANTICIPATE THERE WILL BE A BIAS AND MAKE USE OF THAT, INSTEAD OF CONTROLLING THE ENVIRONMENT, WE'RE STUDYING MANAGE IN THE NATURAL ENVIRONMENT. THIS IS EQUALLY IMPORTANT AND WE ACTUALLY HAVE A LOT OF EDUCATIONAL PROGRAM DEMONSTRATING BOTH ASPECTS OF THIS RANGE OF REASONING. THIS IS A VERY INTERESTING PAPER, A FASCINATING EXPERIMENT BY BETSY SPARROW AN COLLEAGUES IN THE PSYCHOLOGY DEPARTMENT AT CLAM BEEIA. THEY REPORTED ESSENTIALLY THAT APPARENTLY WE ARE REWIRING OUR BRAINS. THERE ARE SO MANY FACTS WE NEED TO BECOME AWARE OF. IT'S VERY DIFFICULT TO INTEGRATE ALL THE FACTS BUT NOW THAT WE HAVE THE ABILITY TO ACQUIRE INFORMATION AS FAST AS WE CAN TYPE IT AND RETRIEVE THE INFORMATION BACK WE ARE FOCUSING LESS ON THE WHAT AND MORE ON THE WHERE. AS LONG AS WE CAN RETRIEVE THE INFORMATION THAT'S KEY BECAUSE WE CAN HAVE PEOPLE NOT OR E ABOUT MEMORIZING FACTS BUT7B!Q DOING THE CRITICAL THINKING SO IMPORTANT TO MAKE THESE ADVANCES IN CLINICAL TRANSLATIONAL RESEARCH. SO THIS IS HOW WE HAVE BEGUN TO THE ATTACK THE PROBLEM AT THE CTSA PROGRAM. WE ORGANIZED OURSELVES TO LAYERS AND YOU CAN SEE THAT I'M BUILDING ON THIS DIAGRAM. WE HAVE ARRAY OF INTRODUCTORY COURSES, ADVANCED COURSES, WE HAVE SEVERAL MASTERS PROGRAMS, AND WE DO HAVE THE KO-2 PROGRAM. WE DO HAVE A TL-1 PROGRAM ELAINE DESCRIBEED TO YOU WHICH IS LINKED TO THE CTSA THROUGH THE U-54 COOPERATIVE AGREEMENT. WHEN WEAPON FIRST STARTED BUILDING OUR EDUCATION PROGRAM WE SURVEYED THE IMMUNITY AN FOUND THE GAPS IN THE CURRICULUM. AND BETWEEN 2008 AND 2012 WE BILL 13 NEW COURSES, SOME INTRODUCTORY, SOME ADVANCED OVER THAT PERIOD OF TIME WE PUT 1,646 TRAINEES THROUGH THOSE 13 COURSES. I'M JUST GOING TO GIVE YOU HIGHLIGHTS OF A COUPLE OF THESE. OUR TL-1 PROGRAM IS REFERRED TO LOCALLY AS THE LEADER HUMAN BIOLOGY TRANSLATIONAL MEDICINE. THIS IS OUR TRAINING PROGRAM FOR OUR Ph.D. SCIENTISTS, SHOWN AT THE TOP HOW INTEGRATED WITH HARVARD UNIVERSITY RIDING THE BACKBONE OF THIS, HARVARD INTEGRATED LIFE SCIENCES. WHICH IS A FEDERATION OF ALL UNIVERSITY LIFE SCIENCES Ph.D. PROGRAMS, DEPARTMENTS AND SUBJECT AREAS. THERE ARE 12 Ph.D. PROGRAMS THAT HARVARD HAS, NINE ARE ACTUALLY IN LIFE SCIENCES THAT IS. NINE ARE ON THE MEDICAL SCHOOL CAMPUS AND THREE ARE ON THE CAMBRIDGE CAMPUS. ANYBODY FROM ANY ONE OF THOSE 12 Ph.D. LIFE SCIENCES CAN APPLY FOR THE 18 MONTH ENRICHMENT EXPERIENCE WHICH IS WHAT HUMAN BIOLOGY IS, WE HAD INDIVIDUALS FROM 7 OF 12 Ph.D. PROGRAMS APPLY. THERE ARE A RANGE OF EXPERIENCES THAT THEY HAVE INCLUDING PAIRING WITH Ph.D. RESEARCHERS, THEY ATTEND GRAND ROUNDS, THEY HAVE CLINICAL PARACURRICULAR ACTIVITIES AS WELL. WE HAVE THEM INTERFACENING OUR EDUCATIONAL PROGRAM AT THE CTSA WITH OUR INTRODUCTORY COURSE, THERE ARE NANOCOURSES THAT THEY ARE TAKING ALONGSIDE INDIVIDUALS WHO MAYBE M.D. SCIENTIST IN THE ADVANCE COURSE AREA AND THEY TAKE PART OF THIS WHICH IS THE TRANSLATIONAL PHARMACOLOGY PROGRAM ALONGSIDE THOSE INDIVIDUALS IN OUR MASTERS PROGRAM. IN CLINICAL TRANSLATIONAL SCIENCE. LET ME TELL YOU ABOUT A PROGRAM WE PUT TOGETHER AND WE PUT IT ON NINE TIMES, IT'S A FIVE DAY COURSE OF CLINICAL INVESTIGATIONS SO FOR THOSE INDIVIDUALS HEARING ABOUT THE WORLD BUT HAVEN'T GOT INVOLVED IN IT SUFFICIENTLY AND WANT TO KNOW MORE ABOUT IT, MAY NOT KNOW EXACTLY WHERE THEY FIT, WE PUT THEM THROUGH THIS SURVEY COURSE OVER FIVE DAYS AND FOLLOW A WHITE POWDER THROW ITS PRE-CLINICAL AND CLINICAL DEVELOPMENT, THE CLINICAL TRIALS THAT SUPPORT IT UNDERSTAND HEALTH ECONOMIC IMPLICATIONS OF DEVELOPING A DRUG HERE AND POTENTIAL GLOBAL IMPACT WOULD BE. THERE ARE DIDACTIC EXPERIENCES HERE AND THERE ARE INTEGRATED WORKSHOPS. WE HAVE ABOUT 100 PEOPLE IN EACH OF THESE FIVE DAY COURSES. INDIVIDUALS GROUP THEM NEVER MET THEM BEFORE IN DISTRIBUTED CAMPUS WORKING TOGETHER IN A TEAM SCIENCE FASHION THEY HAVE NOT HAD THE EXPERIENCE WITH BEFORE. THIS IS AS BEST WE CAN TELL AN EXTREMELY SUCCESSFUL PROGRAM BECAUSE -- WE HAD A GOOD OPPORTUNITY TO DEVELOP DATA HERE. WHEN WE FIRST PUT THE COURSE TOGETHER THERE WAS OBVIOUSLY PENT UP NEED IN THE COMMUNITY, 435 APPLICANTS FOR THE HUNDRED SEATS WE HAD. WE COULD NOT TAKE ALL 435 INDIVIDUALS SO THEY FORM OUR CONTROLS. THEY ARE SHOWN HERE IN RED. THOSE VICTIMS WHO WERE ABLE TO TAKE THE COURSE SHOWN IN BLUE. WE SURVEYED BOTH GROUPS AND ASKED THEM TO INDICATE ON A SELF-RATING SCALE FROM 0 TO 100 HOW WELL THEY THOUGHT ONE MONTH PRIOR TO CURSE AN SIX MONTHS AFTER COURSE, INDIVIDUAL WHOSE TOOK THE COURSE FELL BETTER PREPARED TO PUT TOGETHER A GRANT, DESIGN RESEARCH PROJECT OR MEET IRB REQUIREMENTS. THE INDIVIDUAL WHOSE LIVE AND WORK IN VIBRANT UNIVERSITY ARE ALSO IMPROVING SO THE INDIVIDUALS IN THE RED BEFORES GOT BETTER AS WELL. WE RECOGNIZE THIS IS NOT A RANDOMIZED EXPERIENCE BUT ONE OF OUR MOST INTERESTING SETS OF DATA THAT SUGGEST WE ARE MAKING HEADWAY. WE BUILT ON THAT AND FOCUSED ON THE T-1 DOMAIN AND PUT TOGETHER A TWO WEEK COURSE WHERE INDIVIDUALS WILL GO THROUGH DEVELOPMENT OF DRUGS DEVICES BIOLOGIC AND BIOMARK KEY AREAS AT THE BOTTOM AND THESE INDIVIDUALS FORMED SOCIAL NETWORKS AN P GO THROUGH THE EXPERIENCE SAYING WHAT WOULD I DO TO DEVELOP THAT PARTICULAR DEVICE. ONE WAY TO HANDLE THE PROBLEM OF NOT BEING AWARE OF COURSES TO TAKE WAS TO ACTUALLY GET ALL THE SPONSORING INSTITUTIONS THAT HAD COURSES AS WELL AS ONES WE CREATED CENTRALLY AND BUILT A COURSE CATALOG WHICH IS SEARCHABLE ON THE CORE COMPETENCY AREAS SHOWN ON THE LEFT, THE T DOMAIN SHOWN HERE IS ONE OF THE FILTERS, THE ACTUAL LOCATIONS ARE ANOTHER FILTER. SEARCH ON KEY WORDS. WE HAVE 230 OR SO COURSES THAT ARE LISTED IN THAT SEARCHABLE CATALOG. THIS IS ARRAY OF PORTFOLIO OF MASTERS PROGRAMS IN CT SCIENCE THAT WE HAVE. THERE ARE TWO THAT HAVE BEEN AROUND FOR BETTER PART OF ALMOST TWO DECADES, CLINICAL INVESTIGATORTOR TRAINING PROGRAM AND SCHOLARS. THEY EACH TRAIN APPROXIMATELY 20 TRAINEES, ROUGHLY ALIGNED ON THE CT SPECTRUM AS YOU SEE. WHAT REWITH DOING THIS SPRING IS MERGING THESE TWO INTO ONE VERY ROBUST MASTERS PROGRAM IN CT SCIENCE TO COVER THE SPECTRUM ALONGSIDE THAT MASTERS IN CT SCIENCE SINCE OUR EXISTING BIOMEDICAL INFORMATICS GLOBAL HEALTH DELIVERY AND MPH MASTERS PROGRAMS. ONE THING THAT WE BELIEVE IS IMPORTANT IS TO ACTUALLY STRUCTURE THE CAREER PATH A LITTLE BIT MORE. IN FACT, MUCH MORE THAN IT HAS BEEN IN THE PAST. AND THIS IS OUR PROJECTED PATH. SO READING UP FROM THE BOMB WE ANTICIPATE HAVE -- BOTTOM, WE ANTICIPATE 20 TRAINEES A YEAR WHO WILL GO IN TO THE THE MASTERS PROGRAMS THAT I SHOWED YOU THERE IS A BIPASS LOOP FOR INDIVIDUALS WHO WANT THE APPLY FOR MORE ADVANCED TRAINING WHO DON'T NEED A MASTERS OR DON'T -- ALREADY MIGHT HAVE A MASTERS BUT THE MAIN FLOW WOULD LOOK AS FOLLOWS. INDIVIDUALS GO THROUGH MASTERS PROGRAM FOR TWO YEARS THEN THEY GO THROUGH A HIGHER TRAINING PROGRAM WHICH WE CALL CATALYST MEDICAL RESEARCH INVESTIGATOR TRAINING PROGRAM WHICH WILL BE FUNDED THROUGH THE KL-2 MECHANISM FOR HALF OF THESE 20 TRAINEES AND THROUGH THE GENEROUS CONTRIBUTIONS OF OUR AFFILIATED HOSPITAL CENTERS, THE INSTITUTIONAL MONEY ESSENTIALLY FOR THE OTHER HALF. WE BELIEVE THE INDIVIDUALS WHO TAKE THIS MASTERS PROGRAM WILL BE AMONG THE BEST EQUIPPED TO BE SUCCESSFUL AWARDEES IN THE C MERIT KL-2 LIKE PROGRAM. WE ALSO THINK THOSE INDIVIDUALS ARE GOING TO BE ESPECIALLY WELL-POSITIONED FOR THE HIGHER K AWARD. THIS PROVIDES A COMMUNITY OF INDIVIDUALS WHO FOR THE FOUR YEARS SHOWN HERE IN PINK WILL BE LIVING AND WORKING TOGETHER IN A VIBRANT COMMUNITY EXPERIENCE WHICH HAS BEEN LACKING TO DATE. OUR DREAM IS TO HAVE INDIVIDUALS WHO ARE TAKING ADVANCE COURSES, MASTERS PROGRAMS OR KL-2 COURSES SITTING IN THE SAME CLASSROOM AND YOU WOULD NOT BE ABLE TO TELL BY LOOKING AT THEM, WHICH PARTICULAR PROGRAM THEY'RE IN. BECAUSE THEY'RE TAKING THAT COURSE BECAUSE OF WHAT THEY NEEDTOR CT RESEARCH EXPERIENCE. WE'RE GOING TO BUILD OUT MORE COURSES AND LOAD THEM TO THE SEARCHABLE CATALOG. ONE THING I WANT TO EMPHASIZE HERE IS I BELIEVE UNIQUE OUR CTSA, THE GRANT REVIEW AND SUPPORT PROGRAM TO CREATE SYNERGY WITH OTHER NIH FUNDED PROGRAMS, THE EASE TO K TO R TRANSITION. WE HAD CONVERSATION ABOUT THIS A MOMENT AGO WHEN ELAINE WAS SPEAKING. THIS IS OPEN TO INDIVIDUALS WHO ARE IN THEIR FIRST YEAR K-23, KO-8 AND K-25 GRANTS AND AS WELL AS THE KL-2 APPLICANTS, AWARDEES APPLYING FOR THE FIRST HIRE K AWARD. IT CONSISTS OF DIDACTIC COMPONENTS OF SHORT ELEMENTS OF GRANT WRIGHT. ON LIPOEXPERIENCE AND -- ONLINE EXPERIENCE AND ONE TO ONE MENTORING EXPERIENCE. OUR WEBSITE ONE CAN FIND THE ONLINE MATERIAL WHICH CONSISTS OF GRANT WRITING TIPS, PEOPLE WHO GENEROUSLY DONATED COPIES OF GRANTS WERE FUNDED. AND THOSE NOT FUNDED SO THEY COULD BE CRITIQUED BY INDIVIDUALS WITHIN THIS TRAINING PROGRAM. SIP DIHAS BEEN INSTRUMENTAL HELPING TO PREPARE THIS PROJECT MANAGEMENT SCHEME SO THAT INDIVIDUALS STARTING THEIR K-23 WILL KNOW WHAT THEY OUGHT TO BE DOING IN YEARS ONE, TWO, THREE, FOUR AND FIVE Z THEY POSITION THEMSELVES FOR THEIR RO-1 GRANTS. WORK MANAGEMENT SCHEME. WE HAVE TAKEN THE OPPORTUNITY TO VIDEOTAPE AS MANY OF THE LECTURES IN THE COURSES THAT WE CAN. HERE IS AN EXAMPLE OF WHAT IT LOOKS LIKE WHEN ONE COMES TO EDUCATION VIDEO LIBRARY. SEARCHABLE BY TOPIC AND COURSE. I WANT TO POINT OUT THIS RIGHT HERE. WHICH IS THE CITATION HERE. IN THIS CASE TO THE ANNULS OF INTERNAL MEDICINE. BUT THAT'S THE KEY. WE CANNOT PUT THIS ON OPEN INTERNET ACCORDING TO OUR GENERAL COUNCIL. BECAUSE WE'LL BE PUBLISHING SOMETHING THAT WAS ALREADY PUBLISHED FROM ANNULS OF INTERNAL MEDICINE. WHAT WE HAVE DONE IS PUT IT BEHIND OUR FIREWALL WHICH IS OUR LOG IN COMMENTS TO LOG IN AVAILABLE TO ANYBODY AFFILIATED WITH OUR CTSA. WE HAVE MET WITH ALL THE CTSAs IN MASSACHUSETTS AND HAVE AGREED THAT WE SHARE OUR EDUCATIONAL PORTFOLIOS AND WE HAVE GIVEN ACCESS TO OUR EDUCATION VIDEO LIBRARY AS LONG AS THEY ARE WILLING TO PUT ET BEHIND THEIR FIREWALL AS WELL. WE CAN CERTAINLY USE IT UNDER THE FAIR USE POLICY WHEN WE'RE BEHIND THE FIREWALL FOR LOG IN. LET'S THINK HOW WE ACTUALLY CONNECT PEOPLE WITH THE RESEARCHs HOW WE FIND SOMEBODY NAMED DON INGBER IF THEY HAVE NEVER MET HIM. SO I'LL USE MYSELF AND WE CAN GO TO A PORTION OF OUR WEBSITE CALLED PROFILES, AND YOU SEE FOUR REPRESENTATIONS OF MY PUBMED ANALYSES OF MY WORK. SO I'M IN PINK HERE. IN THIS TOP ONE. YOU SEE A FORCE DIRECTED CO-AUTHOR GRAPH. SO I'M THE AUTHOR HERE. MY CO-AUTHORS ARE IN BLUE. CO-AUTHORS OF MY CO-AUTHORS ARE SHOWN -- I'M SORRY, MY ARE IN GREEN, THEIRS ARE IN BLUE. YOU CAN SEE THE RADIAL SPREAD LOOKING AT THE INDIVIDUALS. HERE YOU CAN SEE WHO I HAVE BEEN WORKING WITH OVER TEAM PLOTTED HERE FROM 1983 TO 2011. THIS IS RESEARCH PUBLISHED BY INFORMATICS GROUP, MORE LIKELY TO HAVE A PUBLICATION IF YOU'RE LOCATED MENTION TO A PERSON WHO YOU'RE RESEARCH COLLABORATOR. FRANKLY ONLY AT HARVARD WOULD SOMEBODY NAME THIS THE EGO CENTRIC CO-AUTHOR RADIO GRAPH WHICH SHOWS IN THIS CASE ME AT THE CENTER, MY CO-AUTHORS AN CO-AUTHORS OF MY CO-AUTHORS AROUND THAT. APPARENTLY THERE IS A WAY TO MEASURE SOMETHING CALLED REACH. BY TRACKING A PERSON'S REACH OVER TIME YOU CAN TRACK THEIR PROGRESS. AT STEADY STATE THIS IS WHERE WE WOULD LIKE TO BE. WE WILL HAVE OUR EDUCATION PORTFOLIO HERE AND WE WILL HAVE INPUT ON THE LEFT HARVARD UNDERGARAGE WAITS, HARVARD MEDICAL STUDENTS. YESTERDAY WE WERE SPEAKING TO 40 HARVARD UNDERGRADUATES, FRESHMEN THROUGH SENIORS AND A COUPLE OF ALUMNI. GIVING A COURSE ON INTRODUCTION TO CLINICAL TRANSLATIONAL RESEARCH. OUR HOPE IS THAT BY THIS EFFORT WE H EXPAND THE CT WORK FORCE. WE ARE GOING TO PUSH MATERIAL OUT TO CT CONSORTIUM, OTHER INSTITUTES ARE CERTAINLY GETTING INPUT FROM INDUSTRY AND ACADEMIC RELATIONSHIPS ARE KEY. I WANT TO CLOSE WITH THIS SLIDE WHICH IS TO ME ONE OF THE MOST EXCITING THINGS THAT OUR TEAM HAS BEEN ABLE TO ASSEMBLE. UP IN THAT CLOUD IS SOMETHING CALLED INTEGRATED CURRICULUM COMPENDIUM SHOWN ON THE LEFT ARE THE HIVE COURSES, OUR EDUCATION VIDEO LIBRARY IN THE MIDDLE AND THE ONLINE EXPERIENCE, I HAVEN SPENT MUCH TIME TELLING YOU HOW WE'RE BUILDING OUT ONLINE COURSES PAR IN COLLABORATION WITH HARVARD ETTEX, AN ONLINE LEARNING PLATFORM THE UNIVERSITY DEVELOPED AS WELL AS ONLINE PROGRAMS THAT WE'RE DEVELOPING SPECIFICALLY IN OUR CTSA. WE HAVE ON OUR BOTTOM FAMILIAR GROUPING OF INDIVIDUALS WHO ARE TRAINEE TARGET POOL. IT'S A STANDARD THING ON THE LEFT. FOR THEM TO BE ABLE TO REACH OUT TO THIS CLOUD NOW AND QUERY THE DATABASE. THE REAL ADVANCE THAT I THINK WE NEED TO GET TO IS TO ACTUALLY PUSH THE MATERIAL HERE IN A DIRECTED FASHION. TO THE SPECIFIC TRAINEE. PERSONALIZED INFORMATION TO THE TRAINEE ON DINE MECHANICALLY UPDATED FROM FILE MUCH LIKE WHEN YOU BUY A BOOK AT AMAZON.COM AND YOU GO THERE TO LOOK FOR YOUR NEXT BOOK AND THEY SAY WE HAVE LEARNED ABOUT YOU AND YOU MAYBE INTERESTED IN THESE FIVE OTHER BOOKS. IF WE CAN LEARN MORE PROGRESSIVELY ABOUT A TRAINEE, THEY'RE INTERESTED IN BIOENGINEERING, WE WANT THEM TO GET CONNECTED WITH TIME BAR. IF THEY'RE INTERESTED IN INTERNATIONAL MULTI-SENT TRIALS AN CARDIOVASCULAR DISEASE, THEY SHOULD BE CONNECTED WITH ME. SO WE HAVE NAMED THIS PERSONAL PATH OUR CTSA IS QUITE ENAMORED OF THIS AND ASKED US TO WORK HARD TO GET IT UP WITHIN JUST THE NEXT FOUR TO SIX MONTHS. SEE HOW WELL WE CAN ACCOMPLISH THAT. WE WILL WRITE THIS AS OPEN SOURCE. WE WILL CERTAINLY SHARE THIS WITH OTHER MEMBERS OF THE CONSORTIUM AND TAKE ANY INFORMATION ANYBODY ELSE THINKS VALUABLE TO LOAD IN THIS COME PEN YUM INTEGRATED WITH PERSONAL PATH. THANK YOU VERY MUCH FOR THE ATTENTION. I'LL BE HAPPY TO ANSWER ANY QUESTIONS. >> I NOTICE ON YOUR GEOSPATIAL MAP THAT A SIGNIFICANT AM OF TRANSLATIONAL WORK IN THE BOSTON AREA DOESN'T APPEAR, THAT'S IN A LOT OF BIOTECH COMPANY AND FARM SUECAL COMPANIES THAT ARE DENSE IN THAT AREA. CAN YOU TALK A LITTLE BIT ABOUT MENTORS, ARE THEY ACADEMIC, DO I THEY COME FROM INDUSTRY? >> THE REASON IT DIDN'T APPEAR ON THAT GEOSPATIAL MAP IS BECAUSE ITWAS MY PUBMED. I HAVE NOT DONE THAT MUCH T-1 WORK WHERE COLLABORATIONS WOULD BE THERE. I THINK IF YOU HAD A MAP FOR JOSH (INDISCERNIBLE), YOU MIGHT SEE THAT EXPERIENCE. WE DO HAVE MENTORS ACROSS THE RANGE THE UNIVERSITY, HOSPITALS AND WE HAVE THE UNIVERSITY HAS MADE AVAILABLE TO US SOMETHING CALLED EVENVATION LAB, iLAB WHICH IS PHYSICALLY LOCATED AT HARVARD BUSINESS SCHOOL. IT'S A THINK TANK AREA. YOU CAN REQUEST SPACE THERE FOR YOUR RESEARCH TEAM. YOU JUST SCHEDULE IT AS LONG AS YOU NEED IT. WHAT'S INTERESTING IS THE HARVARD iLAB HAS ON THEIR FACULTY SOME VENTURE CAPITAL EXPERTS, BIOTECHNOLOGY EXPERTS WHO WILL OFFER THEIR TIME THE SIT IN WITH THE RESEARCH TEAMS AND INDICATE WHAT MIGHT BE A PROPER DIRECTION TO TURN IN FOR A PARTICULAR RESEARCH PROJECT. IT'S A SKILLS DEVELOPMENT RESOURCE CENTER AND WE OTHER ACTUALLY STARTING TO MAKE USE OF IT EXAMPLE OF INDIVIDUAL INTERESTED IN NETWORK MEDICINE, WHO WANT TO UNDERSTAND BIOCONDUCTOR AND HOW THEY CAN USE THAT KIND OF PROGRAMMING METHODOLOGY FOR THEIR GENOMICS WORK. SO WE ANTICIPATE PULLING MANY INDIVIDUALS AS MENTORS FROM THE BIOTECHNOLOGY COMMUNITY. THAT YOU'RE ALLUDING TO. >> THAT WAS TERRIFIC ANDUP INVESTIGATIVE. A COUPLE OF COMMENT YOU MADE AND IN THE CONTEXT OF WHAT WE TALK ABOUT THIS MORNING WITH RESPECT TO BIG DATA AND HUH YOU THINK ABOUT ADAPTING AND INTEGRATING TO YOUR TRAINING PROGRAM THE KINDS OF SKILL SETS THAT ARE GOING TO BE ANTICIPATED AT LEAST WE AN IT IS PATE WILL BE NEEDED TO HANDLE COMPLEX DATA SETS PARTICULARLY AMONG THE CLINICAL TRAINEES THAT WE HEARD ABOUT GENOMIC INFORMATION AND ELECTRONIC MEDICAL RECORDS AND RESEARCH AND CLINICAL TOOL. HOW DO YOU THINK ABOUT TRAINING THAT POSITION OF CLINICIAN SCIENTISTS FOR THE FUTURE WITH BIG DATA? >> CRITICAL POINT. WE HAVE AT THE LIBRARY OF MEDICINE SEPTEMBERER FOR BIOMEDICAL INFORMATICS WOULD ACTUALLY HAS A WHOLE SERIES OF COURSES, I DON'T HAVE THE TIME TO ENUMERATE FOR YOU BUT THEY DO GIVE COURSES ON RNA SOAK FOR EXAMPLE AND NEXT GEN SEQUENCING AS WELL AS THE KINDS OF THICKS THAT ARE SO IMPORTANT FOR GENOMICS AND GENETICS ANALYSES. THOSE INDIVIDUALS WITH OUR GENETICS EDUCATION COMPONENT COLLABORATING WITH THE INFORMATICS GROUP MORE ADVANCED AND NANOCOURSES ON THE RADAR SCREEN TO BE BUILT OUT WILL INCLUDE THIS INFORMATICS TRAINING AND HANDLING OF BIG DATA. I MENTIONED BIOCONDUCTOR IS ANOTHER EXAMPLE. AND THAT IS LOADED IN THE SEARCHABLE CATALOG. IF WE CAN GET THIS RIGHT WE CAN PUSH OUT ON A PERSONAL PATH THE INFORMATION A TRAINEE NEEDS. THAT MAY NOT BE AWARE OF THE FACT THEY NEED THAT TRAINING IN HOW TO HANDLE BIG DATA BUT IF WE CAN SAY IT LOOKS LIKE YOU'RE HEADING DOWN A PATH OF GENOMICS RESEARCH, IN ORDER TO AM PIFULLY I YOUR SKILL SET AMPLIFY YOUR SKILL SET CONSIDER THE FOLLOWING COURSES THAT ARE AVAILABLE. THIS IS THE LOCATION WHERE THEY'RE FOUND. >> ELLIOT WITH THE EXPANSION OF THE ON LIPOCOURSES YOU MENTIONED ETTEX BUT IS THERE ANYTHING HAPPENING WITHIN CTSA TO TRY TO COORDINATE INDETECTION WHAT OTHER PROGRAMS ARE DOING? >> DR. COLLINS HAD THE SAME QUESTION WHEN HEAVY SITED US. IT WAS REALLY IN RESPONSE TO THIS CHALLENGE THAT HE PUT FORWARD AS WELL THAT WE SHORTLY THEREAFTER HIS MEETING WITH US MET WITH ALL THE MEMBERS OF THE MASSACHUSETTS CTSA AND WE HAVE FORMED WHAT I SHOWED YOU WHICH WAS APPROXIMATE AGREEMENT THAT WE WILL SHARE OUR COLLECTIVE EDUCATION VIDEO LIBRARY EXPERIENCE. WE WILL LIST RESPECTIVE COURSES IN EACH OTHER'S PROGRAMS. AND I THINK WHAT WE NEED TO DO, AND WE HAVEN'T SPENT TIME TALKING ABOUT THIS TODAY BUT WE NEED TO SEE COLLABORATION AMONG THE VARIOUS CTSAs SO EVERYBODY CAN LOAD THIS A COMMON DATA SET, SURE CHRIS WOULD LOVE TO SEE THIS, SO THAT WE'RE NOT REDUPLICATING THE COURSE THAT YOU MIGHT HAVE AT STANFORD SO VALUABLE TO OUR TRAINEES. IF IT'S ONLINE WE OWING TO MAKE USE OF IT. >> THANK YOU FOR A GREAT PRESENTATION. MY QUESTION IS ENTREPRENEURSHIP. DO YOU TEACH ENTREPRENEURSHIP IN? I DIDN'T HEAR, WOULD LIKE TO HEAR FROM WHERE THAT FALLS. >> WE DO, NOT ENOUGH. WE ARE PLANNING TO DO MORE. AND WE'LL USE THAT INNOVATION LAB AT THE HARVARD BUSINESS SCHOOL AS THE PLACE WHERE WE CAN DO A BETTER JOB OF SKILLS DEVELOPMENT AND ENTREPRENEURSHIP. VERY IMPORTANT POINT YOU'RE RAISING. >> IT WOULDN'T NEED TO COME FROM CTSA, IT ALREADY EXISTS ON CAMPUS. Q. TRUE. RIGHT. IN FACT THERE ARE COURSES AT THE BUSINESS SCHOOLS IN MANY OF THE CTSAs IN THEIR AFAILIATION WITH THE UNIVERSITY HAVE A BUSINESS SKOL PLACE SO YES, WE ACTUALLY HAVE -- SOME TRAINEES TWO TO THE HARVARD BUSINESS SCHOOL FOR SOME OF THE COURSES THERE. >> JUST HAD A COUPLE OF QUESTIONS. I WAS GOING TO SAY EXACTLY WHAT YOU SAID ELLIOT, ONE OF THE DIRECTIONS THAT I WOULD LIKE THE CTSA PROGRAM THE GO IN IS EXACTLY WHAT ELLIOT IS TALKING ABOUT IN EDUCATION BUT IN GENERAL WAYS, SO IF YOU THINK ABOUT IT, ORGANIZATIONS THOUGHT ABOUT THIS WHILE YOU WERE TALKING, UNIVERSITIES ARE GENERALLY COMPETED OVER THEIR ABILITY TO THEIR EDUCATIONAL MATERIALS WHICH IS A LITTLE SILLY REALLY. AND THE FACT THAT WITH THE POSSIBLE EXCEPTION THAT THERE ARE THINGS WHICH OCCUR IN BOSTON THAT OCCUR NOWHERE ELSE IN THE WORLD, THE PHYSICAL LAWS IN BOSTON ARE DIFFERENT THAN ELSEWHERE, HAVING TRAINED THERE THAT'S A PROMINENT FEELING BUT ASSUMING PHYSICAL LAWS ARE THE SAME IN CALIFORNIA AS THEY ARE IN BOSTON, THE THINGS THAT ARE IMPORTANT TO TRAIN PEOPLE IN BOSTON ARE THE SAME AS THEY ARE IN CALIFORNIA, ANYWHERE ELSE. AND WHAT WE NEED TO GO TO I THINK IS A SYSTEM WHEREBY PEOPLE HAVE THIS KIND OF SYSTEM AS A METRIC, A SUCCESS METRIC FOR THEIR CAREERS. AND THEN Z YOU SAY, GET PUBLISHED, OPEN SOURCE, AND LOOK THEY WOULD IN ANY OTHER AREA OF SCIENCE SAY WELL, GOSH, THESE HARVARD PEOPLE DID THIS EXPERIMENT AND STANFORD SAYS I'M GOING TO BUILD ON THAT AND THEN TAKE THAT AND BUILD ON THAT AND THAT'S HOW SIGN WORKS. BUT EDUCATION REALLY HASN'T WORKED THAT WAY. AND IT REALLY HAS TO. AND YOU CAN UNDERSTAND FOR MOST OF HISTORY WHERE WE DIDN'T HAVE THE ABILITY TO DISSEMINATE THIS KIND OF INFORMATION OR TRANSFER, I CAN SEE THAT THAT WOULD BE THE CASE, IT CERTAINLY ISN'T ANY MORE. THE SECOND THING IS, I WONDERED WITH NORTH EASTERN DOWN THE STREET WITH SO MUCH SUCCESS WITH P CORP RATING INTERN IP -- INCORPORATING INTERNSHIPS TO TRAINING PROGRAMS, I COME FROM -- THINKING B WHEN BOB MENTIONED THIS, WE TALKED TO THE FDA ABOUT THIS AS WELL. FANTASTICICALLY USEFUL, HAVE YOU THOUGHT ABOUT THAT AS PART OF YOUR PROGRAM AS WELL? >> YES. WE HAVE ACTUALLY. AND IT'S JUST -- IT'SEN OUR LIST AND WE JUST HAVE TO GET THE TIME THE GET OVER THERE AND START WORKING WITH THEM. WE HAVE WORKED WITH THE BOSTON COLLEGE OF NURSING FOR EXAMPLE, SO ANOTHER GROUP IN TOWN. I THINK YOU'RE REFERRING TO SOME OF THE PHARMACY EXPERIENCES AT NORTH EASTERN OR INTERNSHIP EXPERIENCED THERE. THAT'S EXTREMELY VALUABLE. I THINK ONCE WE GET THE PLATFORM BUILT, WE HAVE IT WILL CLOUD MECHANISM, IT'S JUST A MATTER OF LOADING IT IN. I TALKED TO HIGH ABOUT THE FACT THAT THERE IS A PROGRAM CAUGHTED EAGLE EYE, A LISTING OF RESOURCES SO THAT INDIVIDUALS IN ONE PART OF THE COUNTRY, THERE'S NO REASON WHY WE SHOULDN'T BE ABLE TO LIST AS RESOURCE THE EDUCATIONAL RESOURCES AS WELL. I WOULD LOVE TO SEE US TRY THE LOAD THE KIND OF EDUCATIONAL RESOURCES IN A COLLABORATIVE FASHION IN OPEN EYE. >> MY LAST QUESTION IS SOMETHING I ASKED WHEN I WAS T YOUR PLACE BUT BE INTERESTED IN ANSWERING FOR THE BENEFIT OF THE COMMITTEE, THE BOARD, COUNCIL, BECAUSE IT'S SOMETHING I THINK ABOUT A LOT. BUT WE'RE TALKING ABOUT BEFORE, THE WORK LARRY TALKED ABOUT BEFORE, THE WORK ON WORK FORCE DEVELOPMENT AND CAREER PATHS. AND WE TALK ISSUE OF TEAM SCIENCE, ET CETERA. TAME, WE'RE A WARE THE PREDOCUMENT INNOCENT MODEL OF PROMOTION APPROXIMATE TEN YEAR WITHIN ACADEMIC ORGANIZATIONS HAS NOT CHANGED MUCH IN THE LAST DECADES, CENTURY, ET CETERA. MILLENNIA. SO Q1 THING THOUGH I LOVE THESE PROGRAMS AND HAD THE SAME DISCUSSION AT MICHIGAN, MULTIPLE OTHER PLACES, I DO WORRY A LITTLE BIT ABOUT WHETHER WE'RE CODOING AS MUCH PLANNING ON WHERE THESE PEOPLE ARE GOING TO GO WHEN THEY'RE DONE TRAINING. ARE WE TRAINING FOR A CAREER THAT DOESN'T REALLY EXIST? TRAINING PEOPLE TO MARCH OFF A LIVE? THAT'S NOT THE JOB OF A TRAINING PERSON T TRAINING PERSON IS TO TRAIN. ON THE OTHER HAND, SOMETHING Z9dAT ABOUT THE CT SEASONA PROGRAM IS THERE'S PEOPLE WHO ARE HIGH UP IN THE ORGANIZATION, DEANS, VICE DEANS, WHO COULD BE PARTNERS HERE FIGURING OUT WHEN THESE PEOPLE HAVE THIS FANTASTIC TRAINING WHAT IS THEIR AT THAT PARTICULAR TIME UNCONVENTIONAL CAREER PATH. -- FANTASTIC CAREER PATH OR GET SQUELCHED BY THE SYSTEM. >> TWO THINGS I HEARD YOU DISCUSS. ONE WAS CRITERIA FOR PROMOTION AN TRYING TO GET OUR MEDICAL SCHOOLS TO WRITE INTO THE PROMOTION CRITERIA, A MUCH MORE RECOGNITION OF COLLABORATION AND SEEM SCIENCE. WHICH MOST PROMOTION COMMITTEES DOPE GET PUT ON THE SCALE TO THE SAME DEGREE AS THE INDEPENDENT RESEARCH EFFORT. WE HAVE HAD THOSE -- IT'S AN ONGOING CONVERSATION WITH OUR ADMINISTRATION AT HARVARD MEDICAL SCHOOL AND THEY ADJUSTED A LITTLE BIT MORE IN THIS DIRECTION. THERE'S MORE WORK THAT NEEDS TO BE DONE. YOU'RE ASKING A BROADER QUESTION IN THE SECOND POINT WHICH IS WHAT IS THE TARGET HERE FOR THE INDIVIDUAL WHO GO THROUGH THE TRAINING PROGRAM, WHERE WILL THEY END UP. THAT'S WHY THIS DIAGRAM WAS HELPFUL TO ME BECAUSE I CAN SEE THEM ACTUALLY HAVING POSITIONS, CT-RELATED RESEARCH POSITIONS THE FDA AND INDUSTRY AND ACADEMIA. I THINK IF THEY'RE ONLY SEEING THIS AS A JOB IN ACADEMIA, IT REALLY -- THEY'RE LOOKING WITH BLINDERS ON AND WE HAVE TO TAKE THOSE OFF TO GET THEM TO UNDERSTAND THE FULL SPECTRUM HERE. I CERTAINLY HOPE WE DON'T HAVE A 64% SEQUESTER HERE. SO THAT WE DON'T HAVE TO WORRY ABOUT THAT AS MUCH. >> WE DID TALK ABOUT THIS WHEN YOU WERE AT CASE AND I THINK THERE ARE A COUPLE OF THINGS RELEVANT TO THIS DISCUSSION. ONE IS I AGREE WITH YOU ONE OF THE CAREER PATHS IS OUTSIDE OF ACADEMIA. I THIS ISLYTHY THE MODELS HOW WE DO SCIENCE INSIDE ACADEMIA ARE CHANGING. THEY'RE LESS DEPARTMENTALLY BASED, LESS EVEN SCHOOL BASED. I THINK THEY'RE STARTING TO BE INSTITUTES AND CENTERS THAT BROADLY INTEGRATE ACROSS DISCIPLINES. AS YOU KNOW, WE HAVE CHANGEDDED OUR CRITERIA FOR APPOINTMENTS PROMOTIONS AND TEN YOUR, THEY CHANGED IN 2006. IT'S ONE STEP TO DO IT OFFICIALLY. IT'S ANOTHER STEP TO HAVE YOUR COMMITTEES BELIEVE IN IT. SO EVERY YEAR THE DEAN HERE GOES TO THE COMMITTEES AND CHARGES THEM AN EVERY YEAR WE HAVE ANOTHER DISCUSSION ABOUT WHOEVER'S PORTFOLIO IS UP. SO I DO THINK THAT'S A PROCESS BUT IF YOU DONE GET THE TECHNICAL PIECE OF IT STARTED, YOU'RE NOT GOING ANYWHERE. THE OTHER PIECE THAT SURPRISED ME, PHYSICIST DOES THIS A LONG TIME, ARTS AND SCIENCES ENGINEERING WOULD HAVE TEAM SCIENCE CRITERIA. AT LEAST AT OUR INSTITUTION. THEY DON'T. WE NEED THAT TO HAVE THE BROAD-BASED INTEGRATION. SO I DON'T KNOW WHETHER THERE ARE THINGS THAT COULD BE DONE FROM THE NIH LEVEL OR OTHER THINGS, AS THEY SAY MONEY TALKS ABOUT EVEN WITH THE 6.4% SEQUESTER, THERE'S UPWARDS OF $25 BILLION FLOWING OUT OF NIH THAT WILL TALK. MAYBE YOU COULD THINK ABOUT THE VALUE SYSTEM THAT YOU WOULD LIKE TO PROMULGATE AND/OR SUGGEST O THE INSTITUTIONS. >> PROMOTION AND TENURE IS ECONOMICALLY DRIVEN ON AN INDIVIDUAL BASIS. FIRST QUESTION IS THIS GOING TO BE FUNDED THE REST OF HIS OR HER LIFE, AS THERE IS MORE MONEY FOR THESE AREAS, IT WILL CHANGE ON ITS OWN WITHOUT THE MONEY FOR THE INDIVIDUALS OUT OF FUNDING IT'S NOT GOING TO CHANGE. I THINK THE CONSENSUS OF THE COUNCIL ENTITY IS PART OF CHANGE. THE OTHER THING, WE HAVE THIS ISSUE A LOT. RECOGNITION FOR TEAM SCIENCE AND HOW YOU RECOGNIZE THAT AND HOW YOU RECOGNIZE THE IMPORTANCE IN FUNDING OF A GIVEN MEMBER OF THE TEAM WHO MAY BE INDIRECTLY FUNDED. THAT BECOMES AN ISSUE ON PROMOTION AND TEN YOUR COMMITTEE SOMETIMES, NOT RECOGNIZED AT ALL. THE ONLY THING THAT'S RECOGNIZED IS NIH GRANTS, YOU DON'T GET TENURE. SO THAT'S ANOTHER THING WE HAVE TO BE MORE SUBTLE ABOUT. >> IT HAS BEEN POINTED OUT WHEN WE HAD THIS DISCUSSION WITH FOLKS, IT HAS BEEN POINTED OUT, WE HAVE SEEN THE ENEMY AND HE ISRCV US, BECAUSE A LOT IS DRIVEN BY NIH GRANT POLICY. AND CERTAINLY NCATS IS 2% OF THE BUDGET CAN HELP SOLVE 2% OF THE PROBLEM BUT WE NEED TO BE ICE BREAKERS AN THIS IS EVERYTHING ELSE SO HOPEFULLY WE CAN SHOW OUR FELLOW INSTITUTES HOW TO DO THIS, I THINK DOING THIS KIND OF THING COMING UP WITH CRY TIER FOR WHAT -- HOW DO YOU EVALUATE TEAM SCIENCE AN THIS WAS WHEN I WAS IN INDUSTRY THIS IS A SOLVED PROBLEM IN PHARMA, THEY HAD THIS PROBLEM ALL THE TIME BUT (INDISCERNIBLE) YOU MUST HAVE BIG TEAMS TOO. (OFF MIC) >> IN MY WORLD IT'S PASSIONATE PEOPLE, NOT WHAT THEY KNOW BUT WHAT THINK DO WITH IT. THIS IS FANTASTIC BUT I DON'T SEE -- LIKE HARVARD BUSINESS SCHOOL TENDS TO TEACH YOU HOW TO DO THINGS BUT NOT A LOT OF PEOPLE ARE DOING THINGS THERE. SO -- [LAUGHTER] >> THEY KNOW IT THAT'S WHY THEY'RE TRYING TO COME UP WITH NEW MODELS. >> GREAT PLACE TO WORK. >> YOU HAVE TO COMBINE THE TWO. WE FACE THE SAME PROBLEMS. OTHER THING IS PUBLICATIONS IN MATH THEY PUT IT ON THE WEB THEN PUBLISH LATER ON. THAT WOULD CHANGE OUR SYSTEM. USING OUTREACH JUST BY PUBLICATIONS DOESN'T MAKE SENSE IF YOU'RE TRYING TO DO TECHNOLOGY INNOVATION, IT SHOULD BE CLINICAL TRIALS OR PATENTS. >> YEAH, YEAH. >> I THINK THEY HAVE A CLINICAL ROUTE NOW AND VISITOR ROUTE, STARTING TO TAKE PATENTS TO CONVERSATIONS THERE USED TO BE A JOKE IN THE '80s OR '90s IF YOU DIP FORM A COMPANY YOU WOULD NEVER BECOME A TENURED PROFESSOR. THE ENEMY IS US WHEN IT COMES DOWN THE PEOPLE. WE HAVEN'T ANSWERED THAT QUESTION YET. >> ANY OTHER QUESTIONS, COMMENTS? OKAY. WE'RE A LITTLE BIT OVER TIME. WE NOW HAVE 55 MINUTE OR SO OR 50 MINUTE FOR LUNCH. PLEASE COME BACK AT 1:15. SO THANKS FOR COMING BACK AFTER LUNCH. WE'RE GOING TO SWITCH GEARS FOR THE NEXT TWO SESSIONS TO THE RARE DISEASE RESEVERAL AND THERAPEUTICS. THAT'S TWO PIECES OF THIS. THE FIRST IS A PRESENTATION FROM OFFICE OF RARE DISEASES, A PROGRAM THAT THEY HAVE ON THE SLIDE THERE, THE RARE DISEASES CLINICAL RESEARCH NETWORK. WE HAVE ALAN PERCY AND MICHAEL KNOWLES HERE TO TALK ABOUT THAT AS WELL. AND JOHN MCKEW IS GOING TO HOOD THREE A DISCUSSION OF A TREND PROGRAM AND„ HE MAY HAVE SOMETHING SAY ABOUT BRIDGES AS WELL. THE THEME NOTICING THROUGH THE DAY WE HAVE A NCATS PERSON THEN A PERSON WHO HAS BEEN -- A COLLABORATOR ON ONE OF THE PROJECTS. FOR THIS ONE STEVE SEILER IS GOING TO TALK. SO STEVE TAKE IT AWAY. >> THANK YOU, CHRIS. TRY TO GET START AND MOVE THROUGH BECAUSE I KNOW A LOT HAVE EARLY FLIGHTS OUT OF HERE SO E WE'LL KEEP THINGS MOVING. FIRST BACKGROUND INFORMATION, BOB -- WE COMMANDED UNDER THE UMBRELLA OF NCATS. WE WERE ESTABLISHED LEGISLATIVELY IN 2002 BY THE RARE DISEASES ACT AND TO SHOW YOU WHAT WE'RE DEALING WITH HERE AT HIPPOAS FAR AS EXTENT OF RESEARCH AND RARE DISEASE, THERE'S APPROXIMATELY 9400 RESEARCH PROJECTS RELATED TO RARE DISEASE AND THAT INCLUDES 1650 PROJECTS FOR ORPHAN DRUG RESEARCH. SO QUITE AN EXTENSIVE PORTFOLIO. THIS IS 2011 DATA, WE'RE HOPING 2012 DATA WILL SOON BE COMING ONLINE, USUALLY THE END OF JANUARY, BEGINNING OF FEBRUARY WE GET THAT INFORMATION SO WE'LL UPDATE THIS. IT IS A SEARCHABLE DATABASE YOU CAN FIND WHAT YOU WOULD LIKE. SO CONSIDERABLE AMOUNT OF RESEARCH. THE NEXT IS A WEB-BASED HERE WE'RE OFFING MANY INSTITUTES, LIBRARY OF MEDICINE PATIENT GENETIC ALLIANCE AND OTHER ORGANIZATIONS WHO ARE DEVELOPING DATA ELEMENT AND SHARING AMONG EACH OTHER WITH EACH OTHER. STILL TREMENDOUS AMOUNT OF WORK, AS WE GET INTO IT MORE AN MORE WE FINE HOW COMPLICATED IT IS TO BUILD ONE PATIENT REGISTRY, ONE THING BUT TO TRY TO GET A GLOBAL TYPE REGISTRY FOR ALL RARE DISEASES IS A WHOLE OTHER SET OF -- ANOTHER SET OF PROBLEMS THAT WE HAVE TO DEAL WITH INCLUDING SOME FEDERAL REQUIREMENTS FOR DATA STORAGE AND MANAGEMENT. SO SOME COMPLICATIONS WE'RE RUNNING INTO. WE HAVE ALSO DEVELOPED A REGISTRY OF BIOSPECIMEN REPOSITORIES, MANAGE WE WANT TO LOOK AT AND WE'RE LOOKING TO POPULATE THIS WITH MANY, MANY MORE SAMPLES FROM DIFFERENT REPOSITORIES THAT ARE ALREADY IN EXISTENCE. WE HAVE BEEN MAJOR PARTICIPANTS IN THE BEDSIDE TO BENCH RESEARCH PROGRAM AT THE CLINICAL CENTER. YOU HEARD LAST COUNCIL MEETING, YOU'LL SEE OTHER EXAMPLES TODAY OF SCIENTIFIC CONFERENCES THAT WE HAVE BEEN CO-FUNDING OVER THE YEARS. ANOTHER SUCCESSFUL PROGRAM TO IDENTIFY RESEARCH OPPORTUNITIES AND DEVELOP RESEARCH RESEARCH AGENDA WITH MULTIPLE INSTITUTES AND PARTIES INVOLVED. WE'RE INVOLVED WITH INITIATING UNDIAGNOSED DISEASES PROGRAM AND THERE'S BEEN AN ANNOUNCEMENT ABOUT THE EXPANSION OF THAT BETWEEN 5 AND 7 ADDITIONAL CENTERS THROUGHOUT THE UNITED STATES. AGAIN, GREAT DEAL OF INTEREST. WE SUPPORT THE GENETIC RARE DISEASES OF THE GENETIC CENTER. THIS IS VERY IMPORTANT. IF ANY HAVE ANY QUESTIONS AFTERWARDS OR AS WE FINISH THE MEETING WE'LL BE HAPPY TO TALK WITH YOU AFTERWARDS OR TODAY OR SOME OTHER POINT IN TIME. SO TODAY WE'RE GOING TO FEATURE PRIMARILY THE ALREADY OFFICE OF RARE DISEASE NETWORK. WE STARTED THIS IN 2003. AT THAT TIME NCRR WAS THE MANAGING ORGANIZATION. (INAUDIBLE) COLLIER WAS OUR MAJOR LEADER THROUGH THIS WITH NCRR. THIS HAS EXPANDED IN 2009 WHEN WE WEPT TO 19 -- WENT TO 19 CONSORTIA IN ONE DATA MANAGEMENT COORDINATING CENTER AND SENSE THEN IT'S REDUCED TO 17, AR AREA FUND WERE PROVIDED AND WE WENT THROUGH THE RECOMPETITION. ONE WAS SUCCESSFUL IN OBTAINING ADDITIONAL FUNDS. EACH OF THE CONSORTIA REQUIRES INVESTIGATORS TO INVOLVE SEVERAL DISEASES, HOPEFULLY RELATED OR SOME PATHWAY, MULTIPLE INVESTIGATORS, MULTIPLE SITES. AND A STRONG COLLABORATIVE PROGRAM INVOLVING THE PATIENT ADVOCACY GROUPS. A FIVE YEAR AWARD TO $1.25 MILLION PER YEAR TOTAL COST. NOT EXTENSIVE AMOUNT OF MONEY BUT IT IS WHAT WE FELT ENOUGH MONEY TO GET THINGS INITIATED AND PERHAPS TO LOOK FOR OTHER SOURCES OF MONEY. VARIOUS PARTNERS AT THE INSTITUTES WE'RE INVOLVED WITH IN THE FIRST ROW AND SO I BELIEVE THERE ARE EIGHT THERE. AND HAVE BEEN VERY GOOD RELATIONSHIPS. YOU CAN SEE THE VARIOUS DISEASES AN GROUPS OF DISEASES THAT ARE INCLUDED WITHIN THE RD CRN L. AND TODAY WE'RE HEAR FROM TWO INDIVIDUAL CONSORTIA PI. THE 17 CONSORTIA THAT CURRENTLY ARE -- EXISTS, 170 INSTITUTIONS WORLDWIDE. THE LAST FIVE YEARS, LAST THREE YEARS WE HAVE SEEN TREMENDOUS EXPANSION TO THE GLOBAL RESEARCH ARENA WITH MANY, MANY MORE INTERNATIONAL INVESTIGATIONS UNDERWAY AND INVOLVEMENT OF MANY DIFFERENT RESEARCHERS AND COUNTRIES THROUGHOUT THE WORLD. WE HAVE 84 ACTIVE PROTOCOLS, 37 IN DEVELOPMENT AT THE PRESENT TIME. AS WE COME UPON RECOMPETITION, WE HAVE TO BE CAREFUL WHICH TO INITIATE, WHICH WE WILL NOT PERMIT TO GO FORWARD AT THIS TIME DEPENDING IF THERE'S SUFFICIENT RESOURCES TO PLEAT THE STUDIES WE DON'T LET THE STUDIES GO FORWARD. WE HAD PATIENT CONTACT REGISTRY, THROUGH ALL THE WORK OF THE PATIENT ADVOCACY GROUPS AND THE PUBLIC GOING THROUGH THE WEBSITE. WE IDENTIFIED APPROXIMATELY 16,000 PATIENTS ELIGIBLE AND ABOUT 15,400 ENROLLED IN DIFFERENT STUDIES. WHEN PATIENTS COME ON WE TRY TO GET THEM ENROLLED IN THE VERY STUDIES EVEN IF LONGITUDINAL OR NATURAL HISTORY TYPE STUDIES. A GREAT DEAL OF SUCCESS FOR GAINING ACCESS TO PATIENTS BUT A MAJOR PART IS THE ACTIVE ROLE OF THE PATIENT ADVOCACY GROUP STIMULATING PATIENTS TO JOIN US. GOALS BASICALLY THE RESEARCH GOALS WE TRY TO DO IS IDENTIFY BIOMARKERS FOR DISEASE RISK SEVER I AND ACTIVITY. AND I THINK ALAN AND MIKE WILL TALK ABOUT SEVERAL GOALS SO I OWN GO INTO THESE TOO MUCH. WE'RE LOOKING TO HELP DEFINE BETTER CLINICAL OUTCOMES AND DEVELOP NEW APPROACH IT IS TO DIAGNOSIS, PREVENTION AND TREATMENT OF RARE DISEASES. THE REQUIRED ACTIVITIES FOR EACH CONSORTIA, THERE HAS TO BE TWO CLINICAL RESEARCH PROJECT, ONE IS LONGITUDINAL STUDY, VERY EARLY ON. WE RECOGNIZE THE VALUE AND NEED FOR NATURAL HISTORY STUDIES TO BEGIN TO UNDERSTAND THE DISEASES BETTER THAN WHAT WE -- WHAT CURRENTLY EXISTED. WE REQUIRE A PILE OR DEMONSTRATION PROJECT. A CLINICAL STUDY, A PHASE 1 STUDY, WE HAVE A TRAINING COMPONENT INVOLVING NEW INVESTIGATORS. EVERYONE HAS AN ACTIVE WEBSITE FOR EDUCATIONAL RESEARCH RESOURCES IN THOSE PARTICULAR RARE DISEASES. AND AS WEDNESDAYED WE DO HAVE A REQUIREMENT TO HAVE ACTIVE INVOLVEMENT WITH PATIENT ADVOCACY GROUP. THERE IS THE CONTACT INFORMATION FOR THE OFFICE. AND I WILL JUST END IT WITH THAT. I THINK CHRIS SHOWED A PICTURE EARLIER THIS MORNING OF THE STAFF THAT WERE THERE AT THE DAY. WHEN THE PICTURE WAS TAKEN. VERY ACTIVE GROUP. I'LL END WITH THAT AND TURN TO IT ALAN PERCY. ANY QUESTIONS WHILE WE GET AL LISTEN'S SLIDES PUT UP? WE CAN HOLD UNTIL THE END CHRIS, WHATEVER YOU WOULD LIKE TO DO. THANK YOU VERY MUCH. >> THANK YOU VERY MUCH. PLEASURE TO REPRESENT VARIOUS RARE DISEASE NETWORK ORGANIZATIONS. WHERE WE HAVE MANY DISORDERS. BUT ONE GOAL. WHY ARE RARE DISEASES IMPORTANT? THERE ARE MANY REASONS. THE TRUE BURDEN IS DIFFICULT TO ESTIMATE. THERE ARE ABOUT 7,000 RARE DISEASES IN THE COUNTRY, PERHAPS AS MANY AS 30 MILLION PEOPLE AFFECTED. TO BE INCLUDED AS A RARE DISEASE YOU HAVE TO BE -- HAVE TO HAVE LESS THAN 200,000 INDIVIDUALS AFFECTED. SO WE HAVE LITTLE GENERAL INFORMATION, THE TRUE BURDEN IS DIFFICULT TO ESTIMATE. BOTH FROM A PERSONAL LEVEL AND PUBLIC HEALTH LEVEL. DIFFICULTY WITH RESEARCH FUNDING IN GENERAL HEALTH SERVICES ARE POOR IN SOME AREAS. THE TREATMENTS ARE INEFFECTIVE OR LIMITED. THE BIOCHEMICAL MOLECULAR PLACES WERE DIAGNOSIS CAN BE MADE. SOMETIMES ARE SCARCE. PARTICULARLY IN OTHER COUNTRIES. THE GOALS OF THE RDC ARE IN THREEFOLD. FACILITATE CLINICAL RESEARCH BY DEVELOPING A SONSOR SHAH INTERACT DIRECTLY WITH PATIENTS AN PATIENT ADVOCACY GROUPS, AND ENHANCE TRAINING OF NEW INVESTIGATORS. THIS IS AN ARRAY, DIFFERENCE PICTURE OF THE 17 DIFFERENT RESEARCH NETWORKS ALONG WITH ADVOCACY GROUP AND UNIVERSITY OF SOUTH FLORIDA. YOU CAN SEE THE NIH PARTNERS AND ORDR IS OBVIOUSLY CENTER PIECE OF THIS PICTURE. RARE DISEASE DATA MANAGEMENT COORDINATING CENTER ALSO HAS IMPORTANT FUNCTIONS, IT CREATES, HELPS GUIDE DEVELOPMENT OF PROTOCOLS, ALLOWS FOR ONLINE ENTRY AND MAINTAINS THOSE IN A VERY, VERY GOOD FASHION. IT TRAINS NEW INVESTIGATORS OR STAFF. WE HAVE A MEMBERS WEBSITE AS WELL AS PUBLIC WEBSITE WHICH HAS 2 MILLION HITS PER YEAR AND OVERSEES A CONTACT REGISTRY WHICH I WILL TALK IN A MOMENT. THERE'S 17 CONSORTIA. THERE'S 84 ACCRUING PROTOCOLS, THREE PLEATED ACCRUAL. ADDITIONAL 3, 170 CLINICAL SITES. THIS IS A DISTRIBUTION OF THE UNITED STATE>„ OF CLINICAL SITES, THERE ARE ALSO SITES IN CANADA, EUROPE, AND IN JAPAN. WITH ONE OR ANOTHER DISORDERS. THIS IS THE ACCRUAL BY 17 CONSORTIA. AGAIN, THE NUMBER IS OVER 15,000 TOTAL. AND FOR THE PASCAL DOOR YEAR, A LITTLE BIT OVER 6,000. THIS REPRESENTS PARTNERSHIPS DEVELOPED WITH OTHER INSTITUTES AT NIH. THE DISEASE CONSORTIA, THE ACTIVE PROTOCOLS PROTOCOLS UNDER DEVELOPMENT. STEP BACK A MOMENT AND TALK ABOUT THREE ADVANCES THAT HAVE RESULTED FROM WORK OF THESE CONSORTIUM. THE FIRST IS FROM THE RARE LUNG DISEASE CONSORTIA, WHETHER WHERE THEY STUDIED THE DRUG (INDISCERNIBLE) MYOMATOSIS. IT WAS A 12 MONTH PLACEBO DOUBLE BLIND CONTROL 12 MONTH FOLLOW OBSERVATION PERIOD. THIS IS A DISORDER OF CYSTIC LUNG DISEASE IN WOMEN. STABILIZE LUNG FUNCTION, REDUCE SYMPTOMS APPROXIMATE IMPROVE THE QUALITY OF -- AND IMPROVE THE QUALITY OF LIFE, THIS WAS PUBLISHED IN THE NEW ENGLAND JURY ROOM. THE TOP REPORT HERE, CHRIS MENTIONED EARLIER THIS MORNING THE OHIO I WON'T DISCUSS IT ANY FURTHER. THE CYCLE DISORDER CONSORTIUM HAS LOOKED AT THE AGENT BICHEMICAL, TO REDUCE GLUTAMINE AND DECREASE UREA GENESIS AND APPROPRIATE PRIONIC ACIDEMIA. A DEVASTATING METABOLIC DISORDER. THIS COMPOUND CAN BE USED ACUTELY FOR HYPERANONEMIA THAT OCCURS IN THIS DISORDER. SO THESE ARE JUST THREE OF THE MANY GREAT ADVANCES THAT HAVE COME THROUGH THE RARE DISEASE NETWORK. THE CONTACT REGISTRY IS QUITE DIFFERENT. IN THE SENSE IT'S OPEN INTERNATIONALLYK ONLINE REGISTRY SYSTEM OPEN TO PATIENTS THE DISEASE UNDER STUDY OF VERYIUS CONSORTIA SO THERE'S 179 DISEASES REPRESENTED AND HAVE MORE THAN 10,000 REGISTRANTS. THIS IS A TWO WAY STREET. NOT ONLY CAN PEOPLE COME ON AND REGISTER CONTEXT THEY CAN ALSO GIVE CONSENT TO BE RECONTACTED FOR DRUG STUDIES OR FOR SPECIFIC RESEARCH THAT HAS BEEN CONDUCTED IN ONE OR ANOTHER DISORDER. IN TALKING WITH JEFF CRISHER HEAD OF THE DMCC, IT'S REMARKABLE HOW FAST DATA CAN BE COLLECTEDS IN WAY. OVER A MATTER OF WEEKS. THIS IS A REGISTRATION OF THE REGISTRANTS IN THE US. THERE'S A SIMILAR PICTURE OF THE WORLD SHOWING REGISTRANTS ACROSS THE WORLD. THE PATIENT ADVOCACY GROUP IS A VERY, VERY IMPORTANT PARTNERSHIPNIST PROCESS. IT'S COALITION OF MANY DIFFERENT PATIENT ADVOCACY GROUPS THAT COLLABORATE IN ORGANIZING PATIENTS TO GET INVOLVED IN THE STUDY. IT APPROACH IT IS COMPLEXITY OF THE DISORDERS BY WORKING WITH STAKEHOLDERS AND IT HELPS TO PROVIDE ADDITIONAL FUNDS FOR TRAINING OR PILOT PROJECTS THAT MAYBE DEVELOPED PART OF THE INDIVIDUAL CONSORTIA. I LIKE TO HIGHLIGHT POINTS OF PATIENT ADVOCACY GROUP WITH MY OWN SPECIFIC DISORDER WHICH IS LET'S SYNDROME. THIS IS A DISORDER WHICH WAS BASICALLY UNKNOWN IN THIS COUNTRY IN 1983 WHEN THIS PAPER APPEARED IN THE ANNULS OF NEUROLOGY. FIRST WIDELY READ ENGLISH LANGUAGE PUBLICATION. THEY HAD BEEN KNOWN IN EUROPE AND PERHAPS THE FAR EAST FOR AS LONG AS 20, 25 YEARS BEFOREHAND. SO ONCE WE BEGAN TO EVALUATE THIS PROBLEM WE REALIZED IT WAS AN ENDURING PROBLEM. 16 YEARS LATER, 1999 A MUTATION IN THE METHYL CBG BINDING PROTEIN 2 WAS IDENTIFIED. PRESENTLY 95% OF THOSE CLASSIC LET WILL HAVE A MUTATION. THERE ARE ABOUT 250 DIFFERENT MUTATIONS. EIGHT SPECIFIC POINT MUTATIOojO ACCOUNT FOR 60%. DELETIONS, INSERTIONS IN THE GENE REPRESENT ANOTHER 15 TO CLOSER TO 20%. FROM Z Z IS A DISORDER LARGELY IN FEMALES, INCIDENCE 1 IN 10,000 FLEABITES. IT'S MAINLY SPORADIC DUE THE TO DE NOVO MUTATIONS IN THE PATERNAL GERM LINE CELLS. I CAN EXPLAIN THAT IF ANYONE HAS QUESTIONS. FAMILIAL ROTE SYNDROME IS VERY, VERY UNUSUAL. IT DOES OCCUR BUT UNUSUAL. BARION FORMS MAKE UP 15% OF TOTAL AND AMONG THE VARIANTS, ABOUT 75% HAVE A MUTATION IN THIS GENE. FROM NATURAL HISTORY STUDY NOW GOING ON ENROLLMENT SEVEN YEARS WE HAVE 1100 PARTICIPANTS. 40% OF THESE ARE ENGAGED FROM TRAVEL, I'LL COME BACK TO THIS IN A MOMENT. SEE THE DISTRIBUTION OF RHETT SYNDROME IN VARIOUS FORMS. APPROXIMATELY 90 INDIVIDUALS EQUALLY REPRESENTATIVE OF MALES AND FEMALES. I HAVE MUTATIONS BUT DO NOT HAVE RHETT SYNDROME. THE TRAVEL CLINIC WAS SUPPORTED COMPLETELY BY PATIENT ADVOCACY GROUP. INTERNATIONAL RHETT SYNDROME FOUNDATION, ASSOCIATION BEGINNING WITH, NOW IT'S THE FOUNDATION. THIS IS BECAUSE ENROLLING SITES WERE IN BOSTON AND IN THE SOUTH. SO WE DIDN'T COVER THE COUNTRY VERY WELL. SO WE GO TWICE A YEAR EACH TO OAKLAND, CHICAGO, BRUNSWICK NEW JERSEY AND FLORIDA TO ENGAGE FAMILIES AND PROVIDE GENERAL INFORMATION THAT WE CAN TO PARTICIPANTS THERE SO IT REPRESENTS A SIGNIFICANT PORTION OF THIS CONSORTIUM. WITHOUT THE PATIENTED HAVE CHASSI GROUP WE COULDN'T HAVE DONE THIS. THIS IS THE FIRST GIRL I SAW IN 1983. SHE'S NOW NEARLY 33, STILL QUITE ACTIVE. LIKE MOST OTHER GIRLS WITH RHETT SYNDROME, SHE DOESN'T TALK, SHE DOESN'T USE HAND VERY WELL FOR FINE MOTOR USE BUT SHE GETS AROUND PRETTY WELL. THANK YOU VERY MUCH. [APPLAUSE] >> I'M MICHAEL KNOWLES, PEDIATRIC -- UNIVERSITY OF NORTH CAROLINA. I'LL SHOW YOU RARE DISORDERS OF MUCOCILIARY CLEARANCE CONSORTIUM FUNNED BY ORKR, ADMINISTERED BY NHLBI. THIS WORK IS SUPPORTD BY THE RARE DISEASE CLINICAL RESEARCH NETWORK AND DATA COORDINATING MANAGEMENT CENTER. IT FUNCTIONS AT A COMPLIMENTARY FASHION TO CTSA SITES BUT IS UNIQUE TO THE EXTENT WE CAN ASSEMBLE A NUMBER OF INVESTIGATORS AT MULTIPLE SITES AROUND THE U.S. DEVELOP PROTOCOLS STANDARD OPERATING PROCEDURES AND RAPIDLY ENROLL PATIENTS FOR GOOD QUALITY DATA. SO WHAT I HOPE AS I GO THROUGH THESE FEW SLIDES TODAY YOU'LL SEE A POSITIVE RIPPLE EFFECT WHEREBY THE DATA COLLECTED HERE ACTUALLY GENERATES OTHER PROJECTS AND OTHER QUESTIONS. OF COURSE WE WORK IN CONJUNCTION WITH PATIENT ADVOCACY GROUPS TO HERE SHOWN THE CF FOUNDATION AND THE PRIMARY SILL LAYER DISKY KNEE SHAH AND PCG FOUNDATION. I HAVE ONLY TEN MINUTES SO WE'LL HIGHLIGHT QUICKLY SLIDES TO COME BACK TO DETAIL IF WE HAVE TIME. MUCOCILIARY COUGH CLEARANCE IS THE PRIMARY INATE MECHANISM IN CONDUCTING BRONCHI OF THE LUNGS WHETHER CILIATE BE MUCOUS, CLEAR ENTRAPPED PARTICLES FROM THE LUNG AND PROTECT THE LUNG. AS DEPICTED HERE ON A NORMAL AIRWAY CELL WHERE YOU HAVE MODE FORCE. ENHAILED RADIO ACTIVE PARTICLES THERE'S CLEARANCE OF THOSE PARTICLES FROM THE NORMAL AIRWAY AT A RATE OVER AN HOUR 20 MINUTES. CF RESULTS IN MUTATIONS IN THE CFTR CHLORIDEICALLY CLICK AMP CHLORIDE CONDUCTANCE CHANNEL. IT ADVERSELY AFFECTS THE MUCOUS AND PERICILIARY LIQUID LAYER SO THERE'S DEFECTIVE MUCOCILIARY CLEARANCE. IT'S COMPLICATED BECAUSE THERE'S ENDOGENOUS COMPENSATORY MECHANISMS THAT AD BORROW GATE THIS DEFECT. PRIMARY CILIARY DISKY KNEE SHAH IS GENETIC ABNORMALITY OF THE CILIA WHERE THE CILIA DON'T WORK AT ALL. AS YOU CAN SEE HERE IF YOU DO STUDIES OF CLEARANCE THERE'S NO CLEARANCE IN PCD UNLESS YOU COUGH AND THAT IS HOW YOU CLEAR YOUR AIRWAYS. THIS IS A CROSS SECTION OF NORMAL BRONCHI, CONDUCTING AIRWAY AND IT IS CLEAR IN PATIENTS WHERE YOU HAVE ABNORMALITIES IN MUCOCILIARY CLEARANCE YOU GET IMPACTION OF SECRETIONS AND BACTERIA REPLICATE YOU GET INFECTION INFLAMMATION AND AIRWAY OBSTRUCTION, THIS VICIOUS CYCLE CAUSES STRUCTURAL DAMAGE TO THE AIRWAY CALLED BRONCHI (INDISCERNIBLE) PRIMARY CILIARY DISKY KNEE SHAH IS THE PRIMARY FOCUS TODAY. THIS IS IMMOTILE CILIA SYNDROME IN 1976 AND IT REFLECTS DYSFUNCTION OF MOTILE CILIA IN RESIDENT LOCATIONS SUCH AS THE AIRWAYS OF THE SINUSES. IN THE EMBRYO LOGICAL NODE THAT DRIVE IT IS ORGAN ASYMMETRY. ESTIMATES SUGGEST THERE ARE 15,000 INDIVIDUALS IN THE U.S. PCD BUT FEWER DIAGNOSED BECAUSE OF CHALLENGING DIAGNOSTIC PROBLEMS I'LL SPEAK TO LATER. WHEN WE GOT INCH TO THE BUSINESS IN NEARLY 2000s, THERE WERE HUGE CHALLENGES. NO GOOD LAB TESTS, YOU CAN'T CHARGE RISE THE DISEASE, YOU DON'T UNDERSTAND THE LONGITUDINAL COURSE. DIDN'T KNOW EXTENT OF PHENOTYPES AND WE DIDN'T HAVE ANY STANDARD TREATMENTS. THIS IS A SUMMARY SLIDE SHOWING PATIENTS ENROLLED IN TWO PROTOCOLS USING STANDARDIZED EVALUATIONS AT MULTIPLE SITES AROUND THE U.S. COLLECTING DATA. WHEN YOU COLLECT DATA YOU LEARN STUFF SO I'LL TRY TO SHOW YOU IN SIX OVERSEEN SLIDES, HIGHLIGHT IMPORTANT THINGS WE LEARNED. WE CONFIRM THAT USING CILIA LEADS TO INACCURACY OF DIAGNOSIS. THESE ARE DATA COLLECTED FROM ONE OUR POST DOC MD TRAINEES, AND FOR PEOPLE WHO CAME INTO THE CONSOR YUM PRESUMED BASIS OF CILIARY STRUCTURAL ABNORMALITY, 153, 18% OF PATIENTS AFTER EXTENSIVE EVALUATION WAS SHOWN NOT TO HAVE PCD. SO THIS TEST IS NOT PERFORMED VERY WELL CURRENTLY AND THERE'S TECHNICAL ENTERPRETIVE CHALLENGES. IN ORDER TO AMEND THIS WE WORKED HARD TO DEVELOP A SCREENING TEST IN PCD. IT'S THE EQUIVALENT OF THE SWEAT TEST 60 YEARS AGO BECAUSE WE DON'T UNDERSTAND TRUELY WHY THIS IS BUT IT'S CLEAR BASED ON THE STUDY INITIAL HI PERFORMED AT UNC WITH WITH HELL CONTROLS THAT PCD PATIENTS OVER AGE OF 5 YEARS THERE'S CLEAR CUT OFF IN PATIENTS WITH PRIMARY DISKINETIA HAVE LOW NASAL NITRIC OXIDE. WE ALSO STATED DISEASE CONTROLS AND THESE FINDINGS WERE REPLICATED AT THE OTHER CONSORTIUM SITES AND SPECIFICITY AND POSITIVE AND NEGATIVE PREDICTIVE VALUE IS HIGH HERE IF THE PATIENTS ARE RULED OUT FOR CF. CF IS THE ONLY DISEASE WE SEE LOW NASAL NITRIC OXIDES SO THIS MAYBE A USEFUL DIAGNOSTIC TEST. THE DID THING IS -- THIRD THING IS WE FOUND THE LATERALLY DEFECTS ARE ASSOCIATED WITH,4S CONGENITAL HEART DISEASE. CILIA CONGENITAL HEART DISEASE. THE HEART IS AN ASYMMETRIC ORGAN IN THE BODY. YOU HAVE TWO THAT FOLD BACK ON ITSELF AND CILIA ARE IMPORTANT IN THAT. MOST PATIENT VERSUS NORMAL SINUS OR THEIR ORGANS ARE ON THE WRONG SIDE OF THE BODY BUT AT LEAST #% HAVE HETEROTAXY WHICH MEAN IT IS HEART MAYBE IN THE CORRECT POSITION BUT THE LIVER MAYBE OPT OTHER SIDE. OF THOSE OVER A THIRD HAVE CONGENITAL HEART DISEASE, IT IS NOW RECOGNIZED THAT PATIENTS WITH CONGENITAL HEART DISEASE HAVE WORSE OUTCOMES PROBABLY BECAUSE SOME OF THEM HAVE PCD IN ONE COMPLICATIONS AND THAT'S A RECENT REPORT SUGGESTING A LINK BETWEEN CILIARY DYSFUNCTION HETEROTAXY AND CONGENITAL HEART DISEASE REPORTED IN CIRCULATION AND WITH EDITORIAL BY MARTINA BRUKNER. FIFTH THING IS RESPIRATORY DISTRESS AND HIGH POXEMIA ARE COMMON IN I PAS WITH GENETIC ABNORMALITIES OF CILIA. THIS OCCURS IN 80 TO 90% OF PATIENTS, REQUIRE SUPPLEMENTAL OXYGEN AND A RANGE OF SEVERITY WITH DIFFERENT STAYS IN THE HOSPITAL. SO THAT MAKES IT VERY CLEAR THAT FUNCTIONAL CILIA ARE VERY IMPORTANT FOR CLEARING THE LUNG OF LIQUID AT THE TIME OF BIRTH WHEN THE LUNG TRAN SIGNATURES FROM FLUID-FILLED TO GAS FILLED. SO WE'RE TRYING TO BRING THIS TO THE ATTENTION OF CARDIOLOGIST, PEDIATRIC CARDIOLOGISTS AN NEONAY TOLL GISTS. TURNS OUT THERE'S ACTUALLY SOME NOTION THEY MAY START DOING OXYGEN SATURATION STUDIES AT BIRTH TO SCREEN FOR HEAR DISEASE AND PCD COULD BE A SECONDARY TARGET FOR THAT SCREENING PROJECT. CONTRARY TO CONVENTIONAL WISDOM PCD KIDS HAVE LUNG DISEASE EARLY IN LIFE. THEY HAVE IMAGING ABNORMALITIES, RESPIRATORY PATHOGENS, AIR FLOW OBSTRUCTION LUNG DYSFUNCTION AS SHOWN HERE, THEY HAVE BRONCHIEXTASIS OR DILATION IN THE STRUCTURE OF THE AIRWAYS, THIS IS NOT RECOGNIZED, WE HAVE TWO LONGITUDINAL STUDIES ONGOING FIVE YEARS LONG AND 170 PATIENTS SO WE LEARN MUCH MORE ABOUT SPECIFICS THERE. THE FINAL THING WE LEARNED A BUNCH ABOUT IS THE GENETICS. SO CF IS A MONOGENIC DISORDER. YOU HAVE MUTATIONS IN ONE GENE, CFTR THAT CAUSES THE DISEASE. CF YOU CAN HAVE MUTATIONS IN MANY GENES WHICH CAUSE IT IS CILIA TO BE DYSFUNCTIONAL SO IT'S GENETICALLY HETEROGENEOUS BETWEEN 1999 AND 2010 WE IDENTIFIED NINE GENES WHICH WOULD MUTATED CAUSE PCD AND THEN CAME EXOME SEQUENCING UNDER THE PROJECT, OTHER COLLABORATORS USE THIS TO IDENTIFY OTHER DISEASE CAUSING GENES, RIGHT NOW THERE ARE 18 PCD CAUSING GENES WHICH WILL IDENTIFY 65% OF WHAT WE CURRENTLY RECOGNIZE AS PCD. WE HAVE ADDITIONAL HITS BEING WRITTEN UP NOW. GENETIC TESTING IS A WAY FORWARD AND PROBABLY BE IN 80 TO 85% RANGE IN NOT TOO DISTANT FUTURE. TRAINING AND EDUCATION IS VERY SUCCESSFUL AT OUR CONSORTIUM. WE HAVE TRAINED 20 M.D. POST DOCS AND 14 BECAME FACULTY AND DOING TRANSLATIONAL RESEARCH. WE HAVE SUCCESSFUL PUBLICATIONS AND PRESENTATIONS IN THE NATIONAL AND INTERNATIONAL CIRCUIT. WE STARTED OUT WITH FOUR SITES IN RED. IN OUR CONSORTIUM. WE INCREASE THE NUMBER BY ADDING ADDITIONAL SITES. LATER AND MOST RECENT IN WORKING WITH OUR PATIENT ADVOCACY GROUP THE PCD FOUNDATION THERE HAVE BEEN FOUR SITES IDENTIFIED AS PRIMARY CLINICAL SITES WITH ADDITIONAL SITES AROUND THE COUNTRY SO WE HAVE THE OPPORTUNITY TO PERFORM CLINICAL TRIALS IN THIS NETWORK. SO ANSWERS TO CHALLENGES WE HAD IN 2004, WE HAVE BETTER DIAGNOSTIC CAPABILITIES AND GENETICS IS GOING TO PAVE THE WAY. WE RECOGNIZE NEONATAL RESPIRATORY SYNDROME AND HAVE THE POSSIBILITY OF DOING NEONATAL SCREENING AS PART OF SCREENING FOR CONGENITAL HEART DISEASE, LONGITUDINAL STUDIES ARE GOING ON. WE NOW KNOW CILIARY ABNORMALITIES CAN BE LINKED TO CONGENITAL HEART DISEASE. WE NOW ARE LINKING IT TO IDIOPATHIC BRONCHI (INDISCERNIBLE) DISINSTRUCTION OF THE AIRWAYS AND IT'S NOT CURRENTLY RECOGNIZED TO BE GENETICALLY BASED. WE ARE SEEING VARIANTS IN CILIA GENES THAT MAYBE LINKED TO MORE SEVERE CHRONIC OBSTRUCTIVE PULMONARY DISEASE.2Öw3 WE'RE FINISHING THE QUALITY OF LIFE OUTCOME MEASURES AND HAVE TREATMENT REGIMEN, TREATMENT TRIALS UNDERWAY. SO THIS IS NOT A COMPLETE LIST BUT IT GIVES YOU AN IDEA OF HOW SUPPORT FROM RDCRN RIPPLES OUT TO DO OTHER GOOD THINGS. PCD FOUNDATION NEW SITES DELIVER CLINICAL CARE AND DO TESTS. A NUMBER OF GRANTING BENEFITS CTSA PILOT PROJECT, RO-1s AND WE ARE ACTIVE PARTICIPANTS IN A EUROPEAN UNION GRANT BEST CILIA. THERE ARE A NUMBER OF OTHER PROGRAMMATIC ACTIVITIES THAT EVOLVE THAT RELATE TO OUTCOME MEASURE, THE INTERFACE BETWEEN PCD AND IDIOPATHIC BRONCHI ECTASIS, BIOMARKERS PROGRAM, ET CETERA. SO I WANTED TO WE CAN'T GO THROUGH ACKNOWLEDGEMENTS FOR ALL BUT I WANT TO CALL YOUR ATTENTION TO THE TOP, THE PEOPLE WE WERE ABLE TO IDENTIFY TO BE PIs OF THE SITES WERE YOUNG PEOPLE. NOTICE MOST OF THESE PEOPLE ARE QUITE YOUNG. FIVE STARTED AS ASSISTANT PROFESSORS PROMOTED TO ASSOCIATE PROFESSORS. WE TRY TO IDENTIFY NICHES IN THE RESEARCH ACTIVITY THAT EACH PI COULD DEVELOP. HERE ARE PICTURES OF OUR RECENT AND CURRENT TRAINEES. THANK YOU VERY MUCH. [APPLAUSE] SO YOU ARE FOCUSED ON SCIENTIFIC QUESTION BELIEVE IT OR NOT. PRIMARY CILIARY DYSFUNCTION, OBVIOUSLY THE MOST COMMON CAUSE OF ACQUIRED CILIARY DYSFUNCTION IS ANOTHER THING THAT'S POPULAR DOWN YOUR WAY. WHICH IS TOBACCO SMOKE. WHAT HAVE YOU LEARNED ABOUT THOSE CONNECTIONS BETWEEN THOSE? >> OBVIOUSLY TOBACCO SMOKE IS A TOXIN FOR CILIA ACTIVITY. MOST INTERESTING LINK I MENTION BRIEFLY, WE'RE LOOKING BECAUSE WE HAVE EXOME SEQUENCING CILIA THAT CONTRIBUTES TO MORE SEVERE COPD SO MAY PLAY A ROLE THERE. IN TERMS OF TOBACCO SMOKE OTHERWISE I CAN'T SAY ANYTHING SPECIFIC. >> THERE'S AN AMAZING COLLECTION OF PHENOTYPES, I WONDER IF THERE'S SEQUENCING ACROSS AS MANY PHENOTYPES AS POSSIBLE. >> CAN I SHOW YOU ONE SLIDE? IT TURNS OUT, I DIDN'T MENTION ANOTHER CILIA. A NON-MOTILE PRIMARY SENSORY CILIA. THESE SENSORY CILIA DON'T MOVE IMMOTILE BUT THAT EAR COATED WITH RECEPTOR SENSOR MOLECULES, ET CETERA. AND ARE IMPORTANT FOR PLAINER CELL POLARITY, ET CETERA, ET CETERA. THERE'S ACTUALLY SOME POSSIBILITY THERE COULD BE SOME INTERFACE BETWEEN SENT SRI CILIA. THEY'RE ON STEM CELLS. WE HAVE AN INTERNATIONAL SYMPOSIUM IN ST. LOUIS 18 MONTHS AGO WHICH IS PUBLISHED AND THERE'S BEGINNING TO MERGE SOME POSSIBILITY THAT THERE MAYBE INVOLVEMENT OF GENES THAT AFFECT BOTH SENSORY CILIA AND MOTILE CILIA. WE'RE GOING TO FIND THE PHENOTYPIC SPECTRUM THAT IS GREATER THAN CURRENTLY RECOGNIZED. THE SENSORY CILIA CAUSE A VARIETY OF SYNDROMES OR MULTIPLE TYPE SYNDROMES, ET CETERA, ET CETERA. SO I THINK THE FIELD IS IN ITS INFANCY IN TERMS OF WHAT WE UNDERSTAND IN TERMS OF PHENOTYPIC EXPRESSION. >> SUPPORTS A BIOBANK WE HAVE A LARGE REPOSITORY THERE. INDIVIDUAL PROJECTS ARE BEGINNING TO DO WHOLE EXOME SEQUENCING THOUGH I DON'T KNOW ANY CONCERTED EFFORT TO LOOK AT ALL OF THEM. THE TREND PROGRAM HAS BEEN INVOLVED IN QUITE WIDE RANGE OF RESEARCH ON RARE DISEASES OVER THE LAST TEN YEARS OR SO. HOW FREAKILY HAS THIS RESEARCH BEEN ABLE TO INFORM UNDERSTANDING OF MORE COMMON DISEASES? >> YOU'RE ASKING ABOUT DO STUDY OF RARE DISEASE INFORM US ABOUT COMMUNIQUES? THE ANSWER IS UNEQUIVOCALLY ASTONISHINGLY FREQUENTLY. COPD, ACTUAL HI CFTR PROBABLY PLAYS A ROLE IN COPD BECAUSE SMOKING KNOCKS DOWN COTR AND YOU LOSE NORMAL COTR FUNCTION. THERE'S THE CONCEPT OF USING MEDICATIONS BEING DEVELOPED FOR CF AND COPD THAT'S ONE EXAMPLE, THE FEW WE HAVE HERE FOR CONCH GENITAL HEART DISEASE ARE QUITE STRIKING. THERE ARE MANY, MANY OTHER EXAMPLES. I THINK AS SOON AS YOU START STUDYING RARE DISEASES YOU'RE GOING TO GAIN INSIGHT INTO THE PHENOTYPES OF OTHER DISEASES. I CAN CAN OFFER ANOTHER EXAMPLE IN CF, TURNS OUT IF YOU LOOK FOR THE GENES THAT CONTRIBUTE RISK TO CF RELATED DIABETES, YOU SEE MANY OF THE SAME GENES INVOLVED IN TYPE 2 DIABETES IN THE GENERAL POPULATION THOUGH CF PATIENTS ARE NOT OBESE AS COMMON THE TYPE # DIABETES IN GENERAL POPULATION. BOB DOESN'T KNOW THIS BUT WE HAVE GOTTEN DATA BACK AND COLLABORATORS AT HOPKINS ARE GETTING READY TO SUBMIT A PAPER WHERE WE HAVE IDENTIFIED A NOVEL GENE. THAT CONTRIBUTES TO THE RISK FOR DIABETES AND CF. IT'S GOING TO BE VERY INTERESTING TO SEE THE REACTION OF THE TYPE 2 DIABETES COMMUNITY. >> IT'S INTERESTING BECAUSE AT LEAST IN THE GENERAL PUBLIC I GET THE IMPRESSION THE CONNECTION BETWEEN RARE DISEASES AND P MORE COMMON DISEASES ARE UNDERAPPRECIATED. OFTENTIMES YOU READ MISSION FORM OPINIONS ABOUT WHY WE'RE SPENDING THIS MONEY ON RARE DISEASE WHEN SO FEW PEOPLE BENEFIT. I THINK THERE MIGHT BE SOMMER RATE IN HAVING THAT RELATIONSHIP MAYBE BETTER KNOWN AND POSSIBLY ALSO LEVERAGE IN ORDER TO GET MORE FUNDING FOR RARE DISEASES. >> I WOULD AGREE WITH THAT COMPLETELY. >> I HAD THAT OPINION STATED ME BY DISCONCERTING NUMBER OF NIH PROGRAM STAFF. AT INSTITUTES WITH COMMON DISEASE WHICH PEOPLE FROM NHLBI WILL SAY WHAT IS RARE DISEASE EVER CONTRIBUTED TO WHAT WE KNOW ABOUT COMMON DISEASE? THINGS THAT BLOW YOUR MIND. THE OTHER THING STEPHEN AND I HAVE BEEN TALKING ABOUT IS TO THINK ABOUT GOING FORWARD F. YOU FLIP ON ITS HEAD THE PROBLEM WE ALL HAVE 7,000 DISEASES TO SOLVE BEFORE WE RETIRE WHICH IS THE UNOFFICIAL MOTTO OF NCATS MISSION STATEMENT, WE HAVE THE ABILITY TO LOOK ON GOD HELP ME FOR SAYING ANOTHER OME, THE DISEASE OME AS ENTIRETY. ONE THING I LIKE ABOUT WHAT STEVE HAS DONE WITH CRN, NOT LOOKING AT DISEASE AS SINGLE ENTITIES BUT DISEASE GROUPED BY THE GENE AFFECTED, SO ALLELIC DISORDERS OR DISEASES THAT AFFECT THE SAME CELL TYPE OR STRUCTURE OR ORGAN OR -- THAT HELPED BIOLOGY ORGANIZE. BUT HOW WE FUND SCIENCE TENDS NOT TO BE THAT WAY. WE FUND SCIENCE IN A LOGICAL WAY THAT IGNORE IT IS FACT THAT ALL THE CELLS HAVE THE SAME GENES AND SAME PATHWAYS. SO ONE OF THE THING GOING FORWARD, ONE WAY TO GET BETTER AT GETTING DESIGNING INTERVENTIONS IS WE BEGIN TO LOOK AT THIS PROBLEM, SO WHAT OVER TIME WE NEED TO DO AS AN ORGANIZATION IS THINK ABOUT THIS AS A GIANT JIG SAW PUZZLE. IT'S BACK TO WHAT JEFF WAS SAYING, BECAUSE GENETICS BEING ONE WAY TO PULL THESE TOGETHER, AND WE PURPOSEFULLY HAVE PROGRAMS WHICH SAY AS WE PUT EACH PIECE OF THE PUZZLE TOGETHER IT SHOULD GET EASIER TO PUT THE NEW PIECES IN PLACE. YOU HAVE FREEDOM OF THE NEW PIECES. THAT IS AN APPROACH WE WILL BE TAKING. WE DO HAVE THAT MISSION. IT'S A FANTASTIC BASIC SCIENCE QUESTIONS TOO. THAT IS SYSTEMS BIOLOGY AT ITS MOST EXTREME. >> THIS IS SOMETHING THAT PERHAPS NCATS SHOULD FUND. >> WE'RE BACK TO THAT F WORD AGAIN. >> I THINK YOU'RE RIGHT. YOU TALK ABOUT SOMETHING THAT ACCELERATE UNDERSTANDING OF NEW DISEASES. THAT'S ONE OF THEM. >> IF I CAN MAKE ONE ADDITIONAL COMMENT. CTSA LOCATIONS, WE HAVE BEEN HOLDING DISCUSSIONS INTERNALLY, HOW TO INTEGRATE THE ACTIVITY, HOW TO UTILIZE THE SERVICES AND RESOURCES. OF BOTH ORGANIZATIONS AND COME TOGETHER NOW. SO IT'S SOMETHING WE CONTINUE. RFA WILL BEGIN TO REISSUE WE ARE LOOKING TO BE ABLE TO UTILIZE THOSE RESOURCES TO GET GREATER INVOLVEMENT OF THE CTSA LOCATION WITHIN THE RDCRN. WHAT EXTENT ARE THEY COLLABORATING WITH OUTSIDE INSTITUTIONS THAT MIGHT HAVE THERAPEUTIC IDEAS? BIOTECH COMPANIES OR -- NON-PROFITS? >> AS I MENTION THE FUND PROGRESS SIDED WAS NOT A LARGE -- IS NOT LARGE AMOUNT OF MONEY SO A NUMBER OF INDIVIDUAL LOCATIONS HAVE BEEN WORKING WITH INDIVIDUAL COMPANIES TO DO STUDIES. WE HAVE ENCOURAGED THEM TO CONTINUE TO DEVELOP COLLABORATIONS WITH INDUSTRY WHEN POSSIBLE. I THINK AS SCIENCE MOVES FORWARD, Z WITH E GET TO KNOW MORE ABOUT THE DISEASE AND IDENTIFY POTENTIAL COMPOUNDS, THAT'S WHEN WE TRY TO BRING THEM, EVEN AT THE EARLIEST MOMENT WE ENCOURAGE INVESTIGATORS TO TAKE AN ACTIVE ROLE WITHIN THE INDUSTRY. MANY HAVE SCIENTIFIC CONFERENCES AND AT THAT TIME BRING THE PARTIES TOGETHER INCLUDING PATIENT GROUPS, FDA AND EXTRAMURAL PROGRAM PEOPLE. AND TREND. SEVERAL PROJECTS WE TALKED ABOUT EARLY ON HAVE GONE ON TOP RECEIVE TREND AND BRIDGES FUNDING FOR SEVERAL PROJECTS. IT'S BEEN PRETTY GOOD. >> FOR RHETT SYNDROME WE HAVE TWO PROGRAMS GOING ON IN CLINICAL RESEARCH ONE AT HARVARD, BOTH WITH IGF 1. ONE IS FULL LENGTH PROTEIN. AND THEN BAILOR IS A PEPTIDE OF IGF-1, A PILOT SPONSORED OR AT LEAST IN PART BY NURIN A COMPANY THAT HAS A CONTRACT WITH THE DEPARTMENT OF DEFENSE. ONGOING TRIAL HERE AT WALTER REED. >> WE HAVE ONGOING DISCUSSIONS WITH THREE DIFFERENT COMPANIES IN THE PRIVATE SECTOR RELATED TO THERAPEUTICS AND DIAGNOSTICS. ONE QUICK COMMENT. POTENTIAL OPPORTUNITY FOR THIS AREA WITH NCATS, CLINICAL CENTERS ARE DOING GENOME OR EXOME SEQUENCING FOR UNDIAGNOSED DISEASE. TO MY KNOWLEDGE MOST INFORMATION REMAINS SEQUESTERED AT THE LOCAL SITES AND IDEA OF HARNESSING, WHAT OTHER GROUPS ARE FUNDING AND BRINGING AND ATTACHING IT TO THIS MIGHT BE A SIGNIFICANT ADVANTAGE FOR US. >> TWO SITES RELATED TO RHETT SYNDROME RELATED THE PLACES DOING WHOLE JOEL SEQUENCE SO WHEN YOU -- GENOME SEQUENCING SO ARE TALKING TO THEM ACTIVELY. >> THANKS, EVERYBODY. WE'RE GOING TO CONTINUE ON THE RARE DISEASE THEME HERE. WE'RE ALMOST ON TIME. WITH DISCUSSION FROM JOHN McCAIN AND STEVE SEILER. NOT SURE WHY I'M DOING INTRODUCTION, JUST GOING TO INTRODUCE JOHN AND THAT'S MY INTRODUCTION. IN CASE YOU HAVE MISSED IT YOU MAY HAVE MISSD THE NEW NIH LOGO AT THE BOTTOM. I DON'T KNOW IF YOU ARE AWARE OF THIS BUT THE COAT HANGER IS NO MORE. THAT HAPPENED A FEW MONTHS AGO. SO YOU WILL BE SEEING THAT INCREASINGLY ON NIH COMMUNICATIONS AND ALL INSTITUTES HAVE BEEN ENCOURAGED TO BEGIN USING THAT LOGO. SO THE IDEA IS EACH -- INSTEAD OF EACH 27 INSTITUTES HAVING ITS OWN LOGO, TO HAVE ONE COMMON NIH LOGO AND THEN THE NAME OF THE INSTITUTE TO THE RIGHT IN TEXT AS YOU SEE THERE. THE REASON THIS WAS DONE IS A LOT OF POLLING HAS BEEN DONE TO ASK THE AMERICAN PUBLIC WHAT IS THE -- WHO IS THE PRIMARY FUNDER OF MEDICAL RESEARCH IN THIS COUNTRY. BY FAR THE BIGGEST NUMBER IS I DON'T KNOW. FDA AND CDC ARE ABOVE NIH. AND NIH COMES ABOUT 9%. WHILE THAT WAS NEVER A GREAT SITUATION IN AN ENVIRONMENT WHERE WE TRY TO ARGUE TO PUBLIC AND CONGRESS THAT NIH FUNDING IS IMPORTANT IF CONSTITUENTS HAVE NO IDEA WHAT NIH IS WHICH MOST DON'T, IT'S VERY HARD TO GET THEM EXCITED ABOUT CUTS AT NIH FUNDING FOR AN ORGANIZATION THEY HAVE NO IDEA EVEN EXISTS MUCH LESS WHAT IT DOES. SO THE GOAL WAS TO HAVE SOMETHING VERY CLEAR, NOT NECESSARILY THAT PEOPLE WILL UNDERSTAND EVEN WHAT NIH STANDS FOR, THE ANALOGY USED BY COMMUNICATIONS PEEP JOHN BURK LOW AND OTHERS IN -- PEOPLE LIKE JOHN BURKLOW AND PEOPLE IN BUILDING 1, THEY TONE KNOW WHAT NASA STANDS FOR BUT THEY KNOW IT'S THE PRIMARY FUNDER OF SPACE RESEARCH. SO THAT'S O THE GOAL WITH THE NIH LOGO. YOU MIGHT ASK WHY IT LOOKS LIKE SOMETHING A FOUR-YEAR-OLD COULD HAVE MADE. HOW MUCH THEY PAY TO CONSULT TO COME UP WITH THAT. I WOULD BE INTERESTED TO KNOW. RATHER NOT KNOW. THE REASON IS, IT'S DESIGNED TO BE VERY UNDERSTANDABLE. NOT SOME ARCANE THING. I NEVER UNDERSTOOD THE COAT HANGER. YOU KNOW DAVE, THE PREVIOUS THE THING THAT'S ON THE PODIUM. WHERE THAT CAME FROM IS ALWAYS >> IT'S A FLASK. LOOKS LIKE A COAT HANGER TO ME. THERE WAS A GOAL TO HAVE SOME MOVEMENT ASSOCIATED WITH THE LOGO THAT LOGO GOES AROUND IN CIRCLES WHICH IS NOT WHAT WE WANT TO CONOTE. WHEREAS THIS ONE HAS MOVEMENT ASSOCIATED WITH IT. >> (OFF MIC) >> THIS WAS HOW IT WAS EXPLAINED TO ME. IN CASE YOU'RE WONDERING THAT'S WHAT EVERYBODY IS SUPPOSED TO USE IN THEIR PRESENTATIONS. THE INSTITUTE DIRECTORS BELIEVE IT OR NOT HAVE AGREED TO NOT -- TO STOP USE THEIR OWN LOGOS. SO WE'LL SEE. JOHN. SO JOHN MCKEW. TAKE IT AWAY. JOHN AS YOU REMEMBER IS ACTING HEAD OF DIVISION OF PRE-CLINICAL INNOVATION. (OFF MIC) >> THAT DOES NOT LOOK LIE ANY FLASK. >> IT'S A GREAT PLEASURE TO BE HERE TODAY TO TALK ABOUT THE PRE-CLINICAL INNOVATION SO WE'LL FOCUS ON THE TREND PROGRAM, THE RARE NEGLECTED DISEASE PROGRAM. WHAT I WOULD LIKE TO DO TODAY IS THREE THINGS. INTRODUCE YOU TO THE MISSION OF THE TREND PROGRAM, TALK ABOUT WHAT WE'RE DOING, HOW WE DO IT. TALK ABOUT IN DEPTH SOLICITATIONS HOW TO BRING IN NEW PROJECTS BECAUSE THIS IS THE COUNCIL WE BRING PROPOSED PORTFOLIO TO. THIRDLY, HIGHLIGHT ONE OF THE PROGRAMS THAT WE HAVE BEEN WORKING ON TWO PLUS YEARS, THAT'S WHY I ASKED OUR COLLABORATOR STEVE SEILER TO COME GIVE HIS PERSPECTIVE HOW WHAT IT'S LIKE TO WORK WITH US IN A EARLY CLINICAL DEVELOPMENT DRUG DISCOVERY PROJECT. THE MODEL OF THE TREND PROGRAM IS UNIQUE. IT IS A COMPREHENSIVE DRUG DEVELOPMENT COLLABORATION. A COLLABORATION WHERE INTRAMURAL LABS AT THE NIH THAT WE BUILT UP OVER TWO AND A HALF YEARS WILL SOLICIT PEOPLE FROM THE OUTSIDE TO COLLABORATE WITH US. THOSE PEOPLE ON THE OUTSIDE BRING DEEP EXPERTISE AND THERAPEUTIC DEVELOPMENT PROGRAM EITHER EARLY OR LATE. AND IT'S TEST COMBINATION OF THOSE TWO THINGS, FUNCTIONAL SCIENTIFIC DISCIPLINE EXPERTISE WE BROUGHTwp IN TO THE NIH AND CLAY RAYTORS WITH DISEASE AREA TARGET EXPERTISE THAT MAKES THIS WORK. PROJECTS COME AT VARIOUS STAGES OF PRE-CLINICAL DEVELOPMENTMENT THE CRITERIA TO COME IN ARE THAT THE DISEASE MUST BE ABLE TO GET AN FDA ORPHAN DESIGNATION OR BE ON THE WORLD HEALTH ORGANIZATION NEGLECTED TROPICAL DISEASE LIST. OUR GOAL IS TO TAKE THESE THERAPEUTICS AND DERISK THEM. MANY OF OUR COLLABORATORS HAVE INTERESTING SCIENCE IN THE PRE-CLINICAL REALM. THEY DON'T HAVE ENOUGH DATA TO GO OUT IN THIS ENVIRONMENT AND GENERATE FUNDING TO TEST WHETHER THESE IDEAS WORK IN A CLINICAL SETTING. SO OUR GOAL IS TO WORK WITH THEM AND GENERATE DATA PACKAGES TO ENABLE THEM TO MOVE THE PROJECT TO A POINT WHERE OUTSIDE INVESTMENT IS FEASIBLE. SO THE -- ALL THE PROJECTS WE PUT TOGETHER ARE MILESTONE DRIVEN. SO THAT MEANS WHEN WE START A PROJECT WE SET UP OUR GOALS AND GO, NO GO DECISIONS AN DRIVE THE PROJECTS TOWARDS THEM AND THE ONES THAT DON'T MAKE IT AFTER SIGNIFICANT EFFORT IS EXPANDED TO ENSURE THAT WE CLOSE IT OUT AND REF THE MONEY ELSEWHERE. WE LIKE TO ALSO USE WE LIKE TO HELP DEVELOP PLATFORM TECHNOLOGIES THAT MAYBE BROADLY APPLICABLE TO A RANGE OF DIFFERENT RARE DISEASES IS A COUPLE OF PROJECTS WE HAVE INVESTED IN THAT ARE REALLY PLATFORM TECHNOLOGIES THAT APPLY TO SPECIFIC RARE OR NEGLECTED TROPICAL DISEASES. AND OUR ELIGIBLE (INAUDIBLE) RANGE ACROSS THE BOARD FROM ACADEMIC TO NON-PROFIT, GOVERNMENT LAB, BIOTECH AND LARGE PHARMA, INSIDE THE U.S. AND OUTSIDE U.S. APPLICANTS ARE ACCEPTED. WE HAVE APPLICATION FROM EVERY PART OF THE SPREAD. THE WAY WE DEFINE RARE NEGLECTED DISEASE IS COMMON. THE NEGLECTED DISEASES ARE WELL DEFINED BY THE FDA THESE DAYS, ANYTHING LESS THAN # HUNDRED THOUSAND PATIENTS IN THE UNITED STATES AND USING THESE CRITERIA AS CHRIS MENTIONED, WE HAVE 7,000 RARE DISEASES THAT WE HAVE TO INPUT IN ON OUR CAREERS WHICH HOPEFULLY WILL BE VERY LONG. BUT THE IMPORTANT THING IS THAT FROM A DRUG DISCOVERY PERSPECTIVE, THERE ARE MANY DISEASES THAT ACTUALLY ARE SINGLE GENE DISEASES THAT HAVE THE ABILITY TO REALLY APPLY SOME MODERN DRUG DISCOVERY TECHNIQUES THAT COULD PRODUCE THERAPEUTICS. SO WE HAVE A LONG WAY TO BE AND THERE ARE LESS THAN 250 OF THESE PHARMACO THERAPY AVAILABLE PATIENTS SO THAT GIVES A LARGE RANGE OF DISEASES TO WORK ON. THE OTHER SIDE OF THE COIN ARE NEGLECTED TROPICAL DISEASES WHICH ARE NEGLECTED NOT BECAUSE THERE AREN'T ENOUGH PATIENTS BUT BECAUSE THOSE PATIENTS DON'T HAVE NEGLECTED TERM COMES FROM. SO WE HAVE TAKEN PROJECTS FROM BOTH GROUPS TO SOLICITATION. CHEVRON DRUG DISCOVERY DEVELOPMENT APPROACH TO HIGHLIGHT WHERE WE TAKE IN PROJECTS. WE CAN TAKE IN PROJECTS AS EARLY AS WHAT I WOULD CALL EARLY LEAD OPTIMIZATION OF SMALL MOLECULE TO PRE-IND FILING. WE DON'T TAKE ON PROJECTS THAT HAVE OPEN INDs IN THE DISEASE AREAS THEY'RE WORKING IN. WE WILL TAKE THEM INTO EARLY CLINICAL DEVELOPMENT BUT NOT TAKING THEM ON IF THEY HAVE AN OPEN IND. WE HAVE RIGHT NOW WE RESTRICTED OURSELVES TO NOT TAKE ON GENE THERAPY VACCINE DEVICES OR DIAGNOSTICS OR PROCEDURES. AND FOCUSING ON SMALL MOLECULE AND BIOLOGIC MODALITIES. SO WHAT WE WANT IN THE BARE MINIMUM IS A PROJECT WITH A DEFINED TUMOR TYPE OR LEAD SERIES IDENTIFIED PREVIOUSLY THROUGH A HIT FINDING EXERCISE. AND HAS VALIDATION ORTHOGONAL ASSAYS TO FIND YOU'RE HITTING YOUR TARGET. SO THE PROJECT SELECTION PROCESS, I WANT TO HIGHLIGHT QUICKLY, THEN WE'LL GO THROUGH THE SOLICITATION PROCESS AND EXPLAIN HOW WE GO THROUGH AND DEFINE COLLABORATORS. IT'S DIFFERENT AND UNIQUE TO THE TREND PROCESS SO WE'LL SPEND TIME ON THAT. WE LAUNCH A SOLICITATION TO LOOK FOR PAROLES FROM THE OUTSIDE AND WE DEVELOP AN -- PROPOSALS FROM THE OUTSIDE AN DEVELOP A REVIEW PROCESS THAT WE PUT TOGETHER WHERE WE CREATED OUR OWN ADVISORY GROUP, REVIEW PANEL DRAWN FROM A VARIETY OF DIFFERENT SECTOR, PRIMARILY SMALL TO MEDIUM BIOTECH COMPANIES, VENTURE CAPITALISTS, ACADEMICS SUCCESSFULLY DEVELOP DRUGS, AND SOME INPUT FROM LARGE PHARMA AS WELL. SO THIS GROUP IS OUR CORE GROUP THAT THESE APPLICATIONS GO THROUGH. THEY DO A COMPLETE REVIEW AND HIGHLIGHT STRENGTHS AND WEAKNESSESES, THAT'S THE KEY FIRST STEP. THERE ARE A COUPLE MORE STEPS I LONG THE WAY TO HIGHLIGHT AFTER WE HAVE DONE A LARGE AMOUNT OF DUE DILIGENCE WITH THE REVIEW COMMITTEE AS WELL AS THROUGH OUR OWN WORK WE PUT TOGETHER PROPOSED PORTFOLIO AND THEN WE BRING THAT PORTFOLIO TO NCATS ADVISORY COUNCIL FOR CONCURRENCE. SO THAT'S THE PROCESS I WOULD LIKE TO OUTLINE WITH YOU TODAY. THE OVERALL PROCESS, WE HAVE TO SET IT UP IN A WAY THAT WE USE GUIDELINES FOR REVIEWERS BUT THE OVERALL MISSION IS REALLY TO IDENTIFY THE BEST SCIENTIFIC OPPORTUNITIES IN THE SPACE. AND WE USE AN ONLINE SYSTEM CALLED PROPOSAL CENTRAL AS WAY TO ACCEPT AND THE OUR INITIAL ONLINE REVIEW. THE GOAL OF ONLINE REVIEW TO IDENTIFY THE TOP TIER APPLICATIONS FROM OUR FULL POOL AND THEN WHEN WE GET TO THAT LEVEL WE BRING ALL OUR REVIEWERS IN TO DO A IN PERSON REVIEW. SO THIS -- IN THIS CASE WE'RE GOING TO TALK TOP TIER APPLICATIONS BUT NOT JUST PRE-REVIEWERS BUT WITH ALL 20 SOME ODD REVIEWERS WEIGHING IN. TO GIVE THEIR INSIGHTS. SO IN THE eCOUNCIL BOOK THERE'S A ROSTER OF TREND REVIEW PANEL FOR YOU FOLKS TO LOOK AT. AND REALLY THE REVIEW PROCESS IS SIMILAR TO TRADITIONAL NIH STUDY SECTION. EACH PRIMARY REVIEW, EACH PERSON HAS PRIMARY ASSIGNMENTS AND SECONDARY ASSIGNMENTS. PRIMARY ASSIGNMENTS IS AVERAGE FOR WHAT WE ASK THE REVIEWERS TO DO, THEY PROVIDE TEXTURAL STRENGTHS AN WEAKNESSES AS WELL AS SECONDARY SCORES. THE SECONDARY ASSIGNMENTS, IN THE TEXT COLUMN. THIS IS THE ANONYMOUS FEEDBACK APPLICANTS GET. SO VERY TRADITIONAL FIRST STEP HERE IN THE PROCESS. THIS IS OUR SCORING MATRIX THAT WE GAVE TO EACH REVIEWER TO LOOK AT THIS IS OUR GRID WE ASK THEM TO WORK TOWARDS. WE'RE LOOKING AT APPLICATIONS THAT SPAN A LARGE SPACE IN THE DRUG DEVELOPMENT PIPELINE. THERE'S EARLY PROJECT AND LATE PROJECTS AS WELL. SO WE WANT THE OVERRIDING MECHANISM TO BE GOOD SIGN ACTIVE UK OPPORTUNITIES ARE THE ONES WE LOOK FOR. BUT WE DIDN'T WANT TO TRY TO PUT INTO SOME KIND OF SCORE OR FASHION WHAT WE WERE LOOKING FOR SO THERE ARE FIVE BUCKETS THAT GET SCORED, TARGETED THERAPEUTIC VALIDATION IS A WEIGHTED SCORE OF 30%, THE STRENGTH OF THE CURRENT DATA PACKAGE HAS A WEIGHTED SCORE OF 30%. FEASIBILITY TO REACH FIRST IN HUMAN WEIGHTED SCORE OF 20%. MEDICAL IMPACT RELATIVE TO CURRENT STANDARD OF CARE 10% AND LIKELIHOOD OF EXTERNAL ADOPTION IS 10% PART OF THE SCORE. THEN WE EITHER A HIGH SCORE 1 TO 3, ARCH SCORE 4 TO 6 OR POOR SCORE 7 TO 9 FOR EACH ONE OF THESE CRITERIA. AND WEIGHED AVERAGE IS PRODUCED SO NOT LIKE NIH SCORING WHERE THE NUMBERS ADD UP AND YOU'RE GETTING 20 OR 15, ALL THE NUMBERS YOU'RE GOING TO SEE FROM OUR SCORES ARE GOING TO BE IN THE ONE TO NINE RANGE. AFTER WE HAVE ONLINE REVIEW AND WE GET A SET OF SCORES FOR EACH PROPOSAL, WE LOOK IN THE TOP TIER OF THOSE PROPOSALS AND WE TAKE EACH OF THE TOP 20 TO 25% TO FACE TO FACE MEETING TO BRING THE ENTIRE PANEL IN TO WEIGH IN. WE DO AND IN DEPTH, EACH PRIMARY REVIEWER INTRODUCES THE APPLICATIONS. AND GIVES COMMENTS. THE SECOND REVIEWER ADDED ADDITIONAL COMMENTS AND THE WHOLE PANEL CAN PRIORITIZE THINGS. AS THEY LEAVE EACH IS ASKED TO RANK THE PROJECT BY THE END OF THE DAY LOOKING AT HIGH, MEDIUM OR LOW. THEN THE TRANSFAT TAKE OVER AND WE CONSIDER THE PRIORITY RANKING AND DAYS DISCUSSIONS WHICH TURN UP SOME OF THE DEFICIENCIES, SOME OF THE THINGS THAT ARE MISSING OR PARTS OF THE DEVELOPMENT PLAN THAT NEED FINE TUNING. THEN PROPOSALS TO FOCUS ON FOR FURTHER DUE DILIGENCE. THE NEXT STEP IS THE TREND DUE DILL GENS BY THE STAFF. WE TAKE THAT SMALLER GROUP OF APPLICANTS AND WE SIGN CONFIDENTIAL DISCLOSURE AGREEMENTS WITH THEM AND WE CREATE A DUE DILIGENCE PACKAGE WITH A BROAD LIST OF QUESTIONS BASED ON DISCUSSIONS WE HAD IN THE FACE TO FACE MEETING AND ALL OF THE THINKING WE HAVE DONE ABOUT WHAT IT WOULD TAKE FOR US TO MAKE THIS PROJECT MOVE FORWARD. WE ALSO REACH OUT TO A TAG GROUP A TRANSRESEARCH ADVISORY GROUP. A FUNCTIONAL INSTITUTE FOCUSED ON TRANSLATIONAL SCIENCE AND NOT SPECIFIC DISEASE AREAS WE TRY TO BRING THESE REPRESENTATIVES OF OTHER INSTITUTES AND CENTERS TO BRING DISEASE INPUT. THEN THE LAST PART OF THIS APPLICANTS BACK FOR A FACE TO FACE MEETING, WE HAVE THEM PRESENT WE GO THROUGH IN REAL DEPTH ANY REMAINING QUESTIONS THAT WE HAVE. WE ALSO TRY TO ASSESS ABILITY TO COLLABORATE AND GO THROUGH THE SCOPE AND HOW WE CAN WORK IN COLLABORATION. ONE THING TO REMIND THEM, THESE ARE NOT GRANTS, THESE ARE COLLABORATIONS. SO THIS IS ESSENTIALLY ALLOWING ACCESS TO RESOURCES AND GOVERNMENT CONTRACTS, SO WE GENERATE DATA OR WE USE OUR GOVERNMENT CONTRACT TO GENERATE DATA AT A CONTRACT RESEARCH ORGANIZATION SO THE CONTRACT DOES NOT GET MONEY BACK TO THE LABS BUT ENORMOUSLY BENEFICIAL DATA TO HELP ADVANCE THE DRUG DISCOVERY PROJECT. SO TODAY WE'RE AT THE POINT WHERE WE'RE COMING TO THE COUNCIL P TO EXPLAIN THIS WHOLE PROCESS AND LATER IN THE CLOSED SESSION I WILL CHAT ABOUT THE PORTFOLIO. SO JUST TO GIVE A SNAP SHOT OF THE HIGHLIGHTS. WE HAVE TAKEN 14 PROJECTS WE PUT TOGETHER A MIXTURE OF SMALL MOLECULES AND BIOLOGICS AND PLATFORM TECHNOLOGIES. ONE THING OF BEING ABLE TO DO IN THOSE TWO PLUS YEARS IS BRING FOUR INVESTIGATIONAL DRUGS INTO HUMANS. WITH CLL WE WORKED WITH LLS AND KANSAS UNIVERSITY TO MOVE THE REPURPOSED MOLECULE QUICKLY INTO PATIENTS. FOR SICKLE CELL DISEASE THAT'S WHAT WE'RE HERE ABOUT TODAY. FOR INCLUSION BIOMYOPATHY WE'RE ABLE TO START A NATURAL HISTORY STUDY TO EVALUATE OR HELP UNDERSTAND BETTER WHAT THE CLINICAL END POINT FOR THAT SHOULD BE AND THE THERAPEUTIC TRIAL STARTED IN SEPTEMBER OF THIS YEAR. THE LAST PIECE OF THE PUZZLE THAT HAS COME TOGETHER FOR THE PIECE OF PROJECT, THE KNEEMAN PICK TYPE C PROJECT. BRIEFLY ON CLINICAL HOLD WHILE WAITING TO FILE ADDITIONAL DATA. BUT ON JANUARY 11 WE RECEIVE APPROVAL TO GO FORWARD AND THE FIRST PATIENT IN THAT TRIAL GETS TODAY SO EXCITING DAY. HOPEFULLY BY EARLY FEBRUARY WE'LL DO THE FIRST DOSING WHICH IS PRETTY EXCITING. THEN WE INITIATED THE NATURAL HISTORY STUDY. ONE OF THE MORE IMPORTANT THINGS TO REMEMBER IS EVERYONE OF THESE PROJECTS IS UNIQUE PUBLIC PRIVATE PARTNERSHIP. MANY FOUNDATION ADVOCACY INPUT BUT MANY ARE MULTI-PARTY PARTNERSHIPS AND I THINK WE CAN SERVE AS A REAL CATALYST TO BRING PIECES TOGETHER TO GIVE US THE TOOLS THAT WE NEED TO DEVELOP PROJECTS. THE NPC IS A GREAT EXAMPLE OF IT. JUST TO GO THROUGH THE EXISTING PORTFOLIO, A COUPLE OF THINGS OF NOTE. WE HAVE THE FOUR COMPOUND THAT ARE CLINICAL, THE OTHER PROJECTS ARE ALL VARIOUS STAGES OF EARLY TO LATE PRE-CLINICAL DEVELOPMENT. BUT IN LOOKING AT THE AGENT, WE HAVE A REALLY NICE RANGE OF NEW MOLECULAR ENTITIES, REPURPOSED MOLECULES, AS WELL AS BUY LODGE INC.S INCLUDING REPURPOSED BIOLOGICS. AND THE OTHER PIECE IS REALLY WHO ARE OUR COLLABORATORS. THEY'RE A RANGE OF SMALL BIOTECH COMPANIES FOUNDATIONS ACADEMICS, KNEEMAN PICK TYPE C IS CLASSIC, EVERYTHING FROM THREE OR FOUR UNIVERSITIES, A COUPLE OF INSTITUTES, THREE INSTITUTES AT THE NIH AS WELL AS LARGE FARM PSEUDOCAL COMPANY. WORKING ON AN INTERESTING MOLECULE THAT I THINK WOULD NOT HAVE MOVED AS FAR AS IT HAS TODAY WITHOUT THAT KIND OF EFFORT. THE LAST THING TO THINK ABOUT IS AGAIN THE BREADTH OF THE THERAPY OF THE DISEASE WE'RE WORKING ON, FROM SICKLE CELL DISEASE TO MULTIPLE MUSCLE WEIGHT AND DISEASE, DUE SHAN MUSCULAR DYSTROPHY PROJECT AND CAR OWE MYOOPATHY PROJECT. STREPTOCOCCAL MENINGITIS FOR COMPROMISED PATIENTS. SO IT'S A REAL SPREAD OF BOTH MODALITY AND THERAPY. SO THIS IS WHY WE REACH OUT STRONGLY TO FIND COLLABORATORS WITH DEEP DISEASE OR EXPERTISE BECAUSE WE CAN WORK CLOSELY WITH THEM AND IT'S A COMBINATION OF TWO PARTS WE BRING TO THE PUZZLE THAT I THINK ENABLE US TO SUCCEED IN THESE PROJECTS. SO JUST TO HIGHLIGHT SICKLE CELL DISEASE IS A PROJECT THAT WE STARRED PROBABLY TWO AND A HALF YEARS AGO. AS A MOLECULE THAT DEFINED FUNCTION, IT AL CO-LATES HEMOGLOBIN AND IT'S THE OXYGEN SATURATION CURVE IN THE DIRECTION YOU WOULD LIKE AND DATA EXVIVO TO SAY INTERESTING MECHANISM OF ACTION AND PEOPLE GO THROUGH THIS IN A LITTLE MORE DETAIL. BUT WE GOT INVOLVED BECAUSE THERE WAS EARLY WORK THAT NEEDED TO BE DONE A DECENT AMOUNT OF PRE-CLINICAL TOXICOLOGY, A LOT OF REGULATORY INTERACTIONS WITH THE FDA INCLUDING AN IND IN FILING. AND THINKING ABOUT THE PROOF OF COMPLEX CLINICAL TRIALS. WE BUILT AN ENTIRE TEAM AGAIN WHERE WE WORKED WITH NHLB ISH, THE NIH CLINICAL CENTER PHARMACY, AS WELL AS ONE OF THE OTHER PROGRAMS, THE NIH RAID PROGRAM WHICH HAD ALREADY SCALED UP ATI FOR TOXICOLOGY STUDIES FOR US. SO IT GIVES A SNAP SHOT TO SERVE AS CATALYST TO BRING THE TEAM TOGETHER TO BRING THE TEAM FORWARD. AS A QUICK SNAP SHOT, WE HAVE DECENT DATA TO SAY THIS IS NOVEL POTENT ANTI-SICKLING AGENT AND IT WAS AVAILABLE AND READILY ACCUMULATED IN RED BLOOD CELL MEMBRANES. BUT PUTTING TOGETHER SOME OF THESE EXPENSIVE STUDIES LIKE PRE-CLINICAL ACUTE OR CHRONIC GOP TOXICOLOGY STUDIES, BASIC PACKAGE, SCALEUP GENE MANUFACTURING AN FORMULATION. AND THEN THE COMPLETE IND PACKAGE. WE ACHIEVEED MOST OF THESE VERY, VERY QUICKLY IN THE COURSE OF 18 MONTHS AS STEVE WILL HIGHLIGHT. SO WITH THAT, I WILL INTRODUCE STEVE SEILER, HE'LL GO THROUGH THE SPECIFICS OF SICKLE CELL DISEASE FROM US HIS SIDE AND THEN WE'LL COME UP AT THE END AND ANSWER QUESTIONS ABOUT TREND OR THE SPECIFIC PROJECT SO MY PLEASURE TO WELCOME STEVE SEILER, CEO OF SMALL COMPANY CALLED AESRX, A SMALL COMPANY FOUNDD ON ORPHAN DRUG DEVELOPMENT, SICKLE CELL DISEASE PREVIOUS TO THAT I GUESS STEVE STARTED HIS CAREER AT DUKE IN INVESTMENT BANKING WORKING IN LON TON AND NEW YORK AND MOVED FROM THAT REALM TO WORK FORMING A COMPANY AND DOING THAT. HE DID AT ELON, EXECUTIVE VP AT ELON AND THEN CEO FOR A NUMBER OF COMPANIES INCLUDING ADARE PHARMACEUTICALS. HE BRINGS EXPERIENCE AND DEVELOPMENT OF THERAPEUTICS HE STARTED HIS OWN COMPANY. I THINK HE CAN GIVE A GOOD PERSPECTIVE ON THE PROJECT AS WELL AS HOW TRENDS HAVE BEEN ABLE TO COLLABORATE SO WELL TOGETHER. SO STEVE. >> THANKS FOR THE INTRODUCTION, JOHN. I'M GOING TO TALK ABOUT THE TREND PROGRAM FROM PERSPECTIVE AS A COLLABORATOR. FIRST LET ME GIVE YOU A LITTLE BACKGROUND ON THE DISEASE AND THE CHALLENGES WE FACED. SICKLE CELL DISEASE IS A GENETIC DISEASE, AUTOSOMAL DISORDER OF THE CHROMOSOME. WHEN THESE RED BLOOD CELLS, HEMOGLOBIN ARE IN THE T STATE, THEY POLYMER RISE WHICH INCLUDES THE ARTERIES TO A WIDE VARIETY OF MORBIDITIES AND EVEN EARLY DEATH THE. THERE WAS DATA PRESENTED AT THE CDC, BY THE CDC LAST MONTH THAT SUGGESTED THE AVERAGE AGE OF DEATH OF SICKLE CELL PATIENT IN THE U.S. IS 39 YEARS. TO GIVE YOU SOME PERSPECTIVE7r— ON THE IT WAS DISCOVERED A HUNDRED YEARS AGO WAS THE FIRST DISEASE THAT WAS DETERMINED TO BE OF GENETIC ORIGIN, 1949, AND STILL NEVER A DRUG EVER DEVELOPED SPECIFICALLY TO TREAT SICKLE CELL DISEASE. IT'S A GLOBAL DISEASE. AS YOU CAN SEE, THE PEOPLE IN THE -- IN AFRICA, IN THE DEVELOPED WORLD, ARABIAN PENINSULA. IN FACT UNFORTUNATELY THE ABILITY TO PAY HERE IS INVERSELY PROPORTIONAL TO NUMBER OF PEOPLE WHO HAVE THE DISEASE. YOU CAN SEE OVER HERE. THIS PROBABLY SHOULD BE A NEGLECTED TROPICAL DISEASE, IT'S A BENEFIT FROM THE PRIOR VOUCHERS BUT NOT, THAT'S ANOTHER DISCUSSION ENTIRELY. SO WHY DO WE THINK OUR COMPOUND WAS AN ATTRACTIVE ENCOUNTER WHEN WE STARRED DOWN THIS PATHWAY? MY EXPERIENCE DRUGS TEND TO FAIL FOR ONE OF THREE REASONS, NUMBER ONE, IT TURNS OUT IN RETRO SPECK YOUR PROPOSED MECHANISM OF ACTION ISN'T CLINICALLY RELEVANT. NUMBER 2, MECHANISM IS RELEVANT BUT YOU CAN'T HIT YOUR TARGET. 3, YOUR MECHANISM IS RELEVANT, YOU HIT YOUR TARGET BUT YOU'RE TOXIC. WE KNEW ABOUT EACH OF THOSE THREE RISKS FOR S 103. THE MECHANISM OF ACTION TO STABILIZE HEMOGLOBIN WHERE IT CANNOT POLYMER RISE WAS UNDERSTOOD IN THE LITERATURE FOR SOMETIME. IN FACT WITH THAT THE SAME MECHANISM OF ACTION WENT INTO THE CLINIC, SHOWED BENEFIT IN CIRCLE CELL PATIENTS BUT THEY FELL AT THE THIRD POST THEY WERE TOXIC. ALREADY DONE X-RAY CRYSTALOGRAPHY. WE KNEW WE COULD HIT YOU ARE TARGET, IT WAS WELL UNDERSTOOD. FOR A VARIETY OF REASONS THERE HAVE A PRE-EXISTING BODY OF SAFETY AN TOX DATA. THE NATIONAL TOXICOLOGY PROGRAM FUNDED IN EARLIER TWO YEAR STUDY AND PREVIOUS HUMAN STUDY PUBLICKED ON JOINT HUMAN ACUTE EXPOSURE AND GIVING IMPORTANT SAFETY DATA. EVEN WITH ALL GOING FOR US, IT WAS DIFFICULT, MAYBE IMPOSSIBLE TO FIND PRIVATE FUNDING FOR THIS PROGRAM WHICH HAD ALREADY HIT THREE HOT BUT TOPS. THE NEED FOR TREND IS DREICH BY CHANGES IN BIOTECH STARTUP ECOSYSTEM. AS MANY IN THE PRIVATE SECTOR PARTICULARLY VENTURE CAPITALISTS KNOW, VENTURE FUNDING FOR EARLY STAGE TRANSLATIONAL BIOTECH DROPPED DRAMATICALLY. WHY IS THAT? BECAUSE DEMAND FROM BUYERS OF PROGRAMS FROM THE BCs, PARTICULARLY THE IPO MARKET ARE INCREASINGLY REQUIRING MORE MATURE PROGRAMS WHICH PUT TRANSLATIONAL RESEARCH BEYOND THE INVESTMENT TIME FRAME OF MOST FIRMS. AN EXAMPLE, WHEN I WAS YOUNGER I WAS AN REMIT BANKER. IN THE HAY DAY YOU COULD TAKE A COMPANY PUBLIC, IT WAS PRE-CLINICAL, AS LONG AS YOU HAD A COOL BUSINESS PLAN, LEAD MOLECULE, ON YOUR BOARD OF ADVISERS AND PARTNER. YOU COULD GO PUBLIC. THESE PEOPLE COULD EXIT. THEY CANNOT DO THAT ANY MORE. DEMAND IS DISAPPEARING, AND THERE'S INCREASED PERCEPTION OF REGULATORY RISK. MOVING AWAY FROM DRUG DEVELOPMENT BECAUSE THEY CONSIDER THE REGULATORY RISK TOO HIGH. FINALLY EVERYBODY IS CHASING THE NEXT FACEBOOK. IT WAS A FAST TURNAROUND, IT WAS A BIG HIT, IT SURE BEATS WORKING FOR A LIVING. SO THE COMBINATION OF THIS MEANS THAT THERE'S LESS CAPITAL AVAILABLE FOR TRANSLATIONAL RESEARCH PROGRAMS. THIS CREATED THE BIOTECH VALLEY OF DEATH. HOW DO WE PROPOSE TO GET ACROSS THE VALUE LIFE DEATH? A MULTI-STAGE MULTI-INSTITUTE PUBLIC PRIVATEAL RESEARCH COLLABORATION. HARD TO SAY RIGHT LET ALONE RUN RIGHT. IT WAS ALL CATALYZED BY TREND FUNDING. NONE WOULD HAVE HAPPENED WITHOUT THEM. THE PARTICIPANTS ARE AESRX OUR COMPANY. THE NATIONAL HEART LUNG AND BLOOD INSTITUTE IS PARTICIPATING AND DOING A TRIAL IN SICKLE CELL PATIENTS AT THE NIH CLINICAL CENTER. AND THE DRUG IS BEING DISPENSED BY THE NIH CLINICAL PHARMACY. I DIDN'T EVEN THE RAID GROUP WHICH MANUFACTURED DRUG PRIOR TO INVOLVEMENT. ALSO THE TREND FUNDING CATALYZED ADDITIONAL LEVERAGE FOR AESRX. NONE OF THE MONEY COMES FROM THE COMPANY. WE HAVE TOQUET THE LIGHTS ON SOMEHOW. SO ONCE TREND WAS INVOLVED WE WERE ABLE TO LEVERAGE AND GET MASS LIFE SCIENCES, A QUASI GOVERNMENTAL ENTITY IN THE STATE OF MASSACHUSETTS THAT PROVIDES FUNDING, ABLE TO RAISE ANGEL FUNDING. IMPORTANT CATALYTIC PARTICIPATION HERE. SO WHAT WAS OUR COLLABORATION OF OBJECTIVES WHEN WE STARTED? NUMBER ONE, COMPLETE A COMPREHENSIVE INDUSTRIAL STRENGTH IND PACKAGE. INDUSTRIAL STRENGTH WE NEW EVENTUALLY PHARMA COMPANY, WE WANT TO DO PHARMA COMPANY DONE TO BECOME A PARTNER. COW WANT TO FILE AN IND TAKE EARLY CLINICAL TRIALS TO THE ASSET. ESSENTIALLY ACHIEVE PROF OF CONCEPT. WE NEEDED TO MEET WITH THE FDA TO CLARIFY THE END POINTS AND REGULATORY PATHWAY FOR SICKLE CELL DISEASE. AS I TALK EARLY TON SOME INDUSTRIAL PARTNER, IT BECAME CLEAR ONE REASON THEY WERE NOT WILLING TO PARTICIPATE IN SICKLE CELL CLINICAL DEVELOPMENT IS THE END POINTS ARE CHALLENGING TO ACHIEVE. PEOPLE SAID STEVE, I KNOW YOUR DRUG WORKS, I DON'T THINK YOU CAN PROVE TO IT THE BENEFIT OF THE FDA. THIS HAS TURNED OUT NOT TRUE AT ALL. WE HAD A VERY, VERY POSITIVE INTERACTION WITH THE FDA. WE CLARIFIED END POINTS WE NEED TO ACHIEVE. AS A RESULT WE SOLVED A PROBLEM NOT ONLY FOR US AS A COMPANY BUT POTENTIALLY FOR SICKLE CELL RESEARCH GENERALLY. YOU CANNOT GET PEOPLE INVOLVED IF THEY DONE KNOW WHERE THE GOAL LINE IS. NEW WE HAVE A REASONABLE GOAL LINE, SO EVEN IF WE GET OUR DRUG INVOLVED PEOPLE WILL FOLLOW BEHIND AND BENEFIT FROM WHAT WE HAVE DONE SO FAR. TALK ABOUT SPILL OFF BENEFITS FROM A SINGLE PROGRAM. SO WHERE ARE WE? FILED A COMPREHENSIVE IND PROPORTIONAL PK, HIGH UPTAKE IN READABLE CELLS AND A WIDE SAFETY WINDOW, VERY SAFE AS WE THOUGHT IT WOULD BE. WE COMPLETED A HEALTHY PHASE 1 TRIAL. WE PLEATED THE TRIAL LAST MONTH. OVER THE DOSE RANGE TESTED 300-MILLIGRAMS TO 4,000-MILLIGRAMS, VERY SAFE. IN FACT, ONE OF OUR DEVELOPMENT PARTNERS VP OFFER DRUG DEVELOPMENT IN THE BUSINESS 30 YEARS, THIS IS THE CLEANEST DRUG HE'S SEEN. WE ALSO SHOWED BIOLOGICAL ACTIVITY CONSISTENT WITH PROPOSED MECHANISM OF ACTION,SICKLE CELL. THE NIH IN THE CLINICAL CENTER, RECAPITULATING THIS TRIAL HEALTHY VOLUNTEERS, DOING THE SAME THING NOW IN SICKLE CELL PATIENTS. SAFETY PROFILE SIMILAR TO RESULTS WE HAVE SEEN IN THE HEALTHY VOLUNTEERS. THE PK IS VERY SIMILAR AGAIN TO NORMAL SUBJECTS THE PK IS STILL BLINDED. THE NEXT STEP IN THE FIRST HALF OF THIS YEAR, IS A TWO-DAY TRIAL 28 DAY, THE CLINICAL END POINTS DISCUSSED WITH THE FDA. AND PROVIDE CLINICAL PROOF OF CONCEPT WHICH POINT WE'LL BE ON OTHER SIDE OF THE BIOTECH VALLEY OF DEATH. THE PROGRAM WILL BE EMINENTLY PARTNERRABLE WITH THE PRIVATE SECTOR. SO I SHOWED THE PREVIOUS SLIDE WE HAVE SEEN BIOLOGICAL ACTIVITY CONSISTENT WITH OUR PROPOSED MECHANISM OF ACTION. THIS IS A CHALLENGING SLIDE TO EXPLAIN IN ONE GO ROUND BUT I'LL TRY TO DO IT. IN HEALTHY VOLUNTEERS, THEY DON'T OBVIOUSLY HAVE ANY BLOOD THAT'S SICKLE BLOOD. PROPOSED MECHANISM OF ACTION WAS TO STABILIZE SICKLE HEMOGLOBIN IN THE R STATE TESTIMONY R STATE IS HIGH OXYGEN AFFINITY STATE. SO WE RECKON IF WE STABILIZE THE HEMOGLOBIN HEALTHY VOLUNTEERS IN THE R STATE WE'D SEE MORE OXYGEN ON THE CELLS. HOW WOULD YOU TELL? MOST OF THE TIME WHEN BLOOD LEAVES THE LUNG, IT'S 100% OXYGENATED. SO WE SUBJECTED HEALTHY VOLUNTEERS TO A FIVE MINUTE HYPOXIC CHALLENGE. OXYGEN MASK GOES ON, THEY BREATHE 12% OXYGEN FOR FIVE MINUTE, PUT A FINGER CLIP ON AND WATCH P WHAT HAPPENS TO THE SPO-2. THIS FALLS, FALLS, FALLS. AT THE END OF FIVE MINUTES WE KNOW WHERE IT IS. WE GET DRUG OR PLACEBO, REPEAT THE EXPERIMENT. AND SEE IF THERE'S MORE OXYGEN ATTACHED THEN WITHOUT DRUG AND IF THERE IS THAT SHOWS WE STABILIZE THE HEMOGLOBIN IN R STATE THAT'S WHAT HAPPENEDDED. THESE ARE THE MEANS, THESE ARE INDIVIDUAL PATIENTS, LOW DOSE NOT MUCH HAPPENING BUT TOP THREE DOSES WE OTHER STARTING TO SEE A MOVEMENT OCCUR, THE ERROR BARS ARE OBVIOUSLY VERY WIDE BUT WE'RE PUSHING THE NEEDLE IN THE RIGHT DIRECTION. SO WE CAN DEFINITIVELY SAY WE'RE STABILIZING THE HEMOGLOBIN IN THE R STATE. THE OTHER POINT IN THE PREVIOUS SECTIONS SPILL OFF FROM ORPHAN DISEASES INTO OTHER DISEASES WHICH ARE IMPORTANT. IF YOU CAN INCREASE OXYGEN AFFINITY HEMOGLOBIN, A COUPLE OF PERCENTAGE POINTS, THAT WOULD BE CLINICALLY RELEVANT TO PEOPLE WITH COPD. IT WOULD BE ENTIRELY NEW MECHANISM OF ACTION. EVERY OTHER APPROACH DEALS WITH INCREASING LUNG FUNCTION GOING AT IT FROM THE OTHER SIDE NO ONE THOUGHT ABOUT WHICH IS INCREASED AVAILABILITY OF THE BLOOD. SO SICKLE CELL DISEASE, THAT'S THE MODEL DISEASE BUT POTENTIAL SPILL LOSS TO MUCH LARGER DISEASE. AS JOHN ALLUDED TO, MILESTONES ACHIEVEED WITH INCREDIBLE RAPIDITY. BIG COMPANIES, SMALL COMPANIES COULDN'T GET IT DONE FASTER OR ANY OTHER WAY. WE FILED AN IND IN LESS THAN A YEAR, COMPLETED HEALTHY VOLUNTEER STUDY IN LESS THAN 15 MONTHS. WE WERE IN SICKLE CELL PATIENTS IN 18 MONTHS FROM STANDING START TO BEING IN PATIENT, 18 MONTHS. WE HAD A SUCCESSFUL MEETING WITH THE FDA, TO CLARIFY THE REGULATORY END POINTS AND I THINK THAT'S IMPORTANT FOR OTHER DRUGS THAT WILL FOLLOW IN OUR PATH. SO WHY TO WE THINK AS A COLLABORATOR THIS COLLABORATION IS SO SUCCESSFUL? WHAT CAN WE LEARN YOU MIGHT APLOY TO ADDITIONAL MULTI-STAGE MULTI-INSTITUTE PUBLIC PRIVATE TRANSLATIONAL RESEARCH COLLABORATIONS? ONE, PLAN WAS PROGRAMMATIC, NOT EPISODIC. WE AT THE BEGINNING SAID WE NEED TO DO A BUNCH OF THINGS TO GET TO THE OTHER SIDE OF BIOTECH VALLEY OF DEATH. UNWELLS PLAN AND BUDGET ALL, WE'LL GET HALFWAY ACROSS THE VALLEY AND SCRATCH OUR HEADS WHAT WILL HAPPEN NEXT. POTENTIALLY ALL THE MONEY COULD BE WASTED. THERE WAS VERY QUICK TRANSPARENT DECISION MAKING. WE CAN MAKE DECISIONS AS A TEAM WITHIN WEEKS. -- CAN'T IMAGINE A COMPANY COULD DO IT ANY QUICKER, I'M SURE BIG PHARMA WOULD FIND THAT VIRTUALLY IMPOSSIBLE. THERE WAS A GENUINE COLLABORATIVE FOCUS. JOHN TOUCHED ON THAT EARLIER. GOOD SCIENCE IS A NECESSARY BUT NOT SUFFICIENT CONDITION FOR SUCCESS. AND WE WERE FLEXIBLE AS THE PROGRAM MOVES FORWARD, GET DATA, WE ADJUST THE PROGRAM IN LIGHT OF THE DATA. WE WEREN'T BLOCKED IN TO A SPECIFIC PATH TO ACHIEVE OUR END POINTS. THIS IS SIGNIFICANT ADVANTAGE TO WORKING WITH A VIRTUAL MODEL T AESRX IS A VIRTUAL CAPITAL, CAPITAL EFFICIENT AND LOW OVERHEAD SO GETTING MORE BANG FOR THE BUCK IN TERMS OF TREND FUNDING. FINALLY, AS AN INDUSTRY BASED PARTNER, WE WERE ABLE TO BRING BIG PHARMA DEVELOPMENT EXPERTISE TO THE PROGRAM. WE KNEW WHAT NEEDED TO GET DONE. WE KNEW WHY IT NEEDED TO GET DONE AND KNEW WHAT BIG PHARMA WOULD WANT ON THE OTHER SIDE OF THE BIOTECH VALLEY OF DEATH IF THIS PROGRAM IS GOING TO BE PARTNERRABLE. SO WE INFORMED THE DEVELOPMENT OF THE PROGRAM IN TERMS OF SPECIFICITY AND BREADTH BY THAT KNOWLEDGE. I THINK BASED ON EARLY DISCUSSIONS WITH POTENTIAL PARTNERS, AS WE MOVE TOWARDS GETTING CLINICAL PROOF OF CONCEPT OUR HYPOTHESIS PROVED CORRECT. SO THE NEXT STEPS FOR THE PROGRAM TO COMPLETE THE CURRENT PHASE 1/2A TRIAL AT NHLBI AND UNDERTAKE PHASE 2A PROOF OF CONCEPT TRIAL WHICH WE EXPECT TO BEGIN SECOND QUARTER. HAVING CROSSED THE BIOTECH VALLEY OF DEATH GENERATE FURTHER DEVELOPMENT SUPPORT FROM THE PRIVATE SECTOR, BE THAT BIG PHARMA, OR BCs. SO THAT IS THE EXPERIENCE OF ONE TREND COLLABORATOR. I THINK WE HAVE SOME Q&A SCHEDULED? >> PATIENT GROUP FUNDING, GOVERNMENT FUNDING, ALSO MAYBE THE DIFFERENCES BETWEEN THE TYPES OF GOVERNMENT FUNDING, INCLUDING SBER AND OTHER -- SBIR AND OTHER TYPES. FROM FUNNY YOU SHOULD ASK THE QUESTION. IN ANOTHER PRESENTATION I HAD SLIDES THAT SAID WHERE DO WE NEED TO IMPROVE. BUT THE PRESENTATION WAS LIMITED TO 12 SLIDES. THAT WOULD HAVE BEEN SLIDE 13. PART OF THE PROBLEM IS GOVERNMENT PROCUREMENT PROCESS. WORKING CONTRACTS THROUGH THED BY BIDS AND HOW YOU MANAGE THEM. I BELIEVE WE COULD HAVE GOT THE PROGRAM DONE WITH 25% LESS MONEY. IT'S COMPLICATED AND LOCK. NOT THE DECISION MAKING. THE DECISION MAKING IS IMPLEMENTED VERY QUICKLY. THERE WAS ONE PROJECT WHICH IS ACTUALLY TOOK LONGER TO PUT THE CONTRACT IN PLACE THAN TO GET IT DONE. WHAT WAS WRONG WITH THAT PICTURE? SO I THINK THAT'S THE BIGGEST NEGATIVE. IN TERMS OF PATIENT ADVOCACY GROUPS IN OUR PARTICULAR RARE DISEASE, SICKLE CELL ADVOCACY GROUPS ARE UNORGANIZED. THEY KNOW THEY NEED TO DO BETTER BUT THEY'RE NOT MUCH HELP TO ANY PRIVATE COMPANY OR ANY INSTITUTION. (OFF MIC) >> I CAN'T THINK OF WHAT THEY HAVE DONE DIFFERENTLY THAT WOULD MAKE THEM PREFERRED. THEY MIGHT HAVE DONE AS WELL BUT I DON'T SUSPECT THEY WOULD HAVE DONE ANYTHING DIFFERENTLY. OTHER THAN FUNDING PROCESS, COULDN'T GET BETTER SO IT'S A HIGH BAR. >> THE ONLY THING TO ADD TO THAT IS NOT JUST FUNDING, IT'S HAVING SCIENTIFIC EXPERTISE. ZOISITE HAS ACCESS TO TOXICOLOGIST IN MY GROUP, AN EXPERIENCED PKPD PERSON, HIS PROJECT DIDN'T NEED ACCESS TO EVERYTHING. IN HOUSE IS EFFECTIVE SO GET BOTH FUNDING BUT ALSO GET SCIENTIFIC DISCIPLINE EXPERTISE YOU WOULDN'T GET AT A FOUNDATION. THE FOUNDATION SBIR GRANT ARE NON-DILUTIVE INVESTMENTS IN A COMPANY. SO THAT'S PART ALL ON A RELATIVE PLAYING FIELD. >> FROM A SCIENTIFIC PERSPECTIVE THESE GUYS GOT IT FROM ESSENTIALLY THE FIRST MEETING. I DON'T KNOW IF THAT WOULD BE TRUE BECAUSE OF -- SOME FOUNDATIONS HAVE BETTER SCIENTIFIC EXPERTISE THAN OTHERS. >> TWO QUESTIONS. ONE IS A FOLLOW-UP AND IT RELATES TO THE PROCESS OF REVIEW AND CRITERIA. GIVEN THAT YOU AT THE NIH NCATS GROUP IS BRINGING EXPERTISE HOW DO YOU TAKE THAT INTO ACCOUNT PERHAPS THE APPLICANT AND APPLICATION MAYBE WEAK IN THAT AREA BECAUSE IT LOOKED LIKE THAT WAS 30% OF THE SCORE. DO THEY HAVE THE EXPERTISE AND THE PLAN AROUND SOME OF THE DRUG ABILITY ASPECTS. SO WHEN I THINK ABOUT HOW THIS WAS PRESENTED, IT WOULD BE WORTH CONSIDERING ACTUALLY WEIGHING THAT LESS IN THE REVIEW BECAUSE YOU CAN FIX THAT IN YOUR FURTHER INTERACTIONS IF POTENTIAL AND IDEA IS BETTER. I DON'T KNOW HOW YOU INTEGRATE THAT. >> 30% ISN'T THEIR EXPERTISE, EYE TESTATE OF DATA PACKAGE AND TARGET RATIONALE. EACH ONE OF THOSE IS WORTH 30%. >> IF THE STATE IS DIRECTLY RELATED TO EXPERTISE? HOW IT'S PRESENTED? IF THEY DON'T KNOW TO DO THIS ONE PARTICULAR EXPERIMENT? >> THEY HAVE TO HAVE DATA THAT SUPPORTS WHAT THEY'RE TRYING TO DO. DEPENDING WHERE THEY ARE IS THERE IN VIVO PHARMACOLOGY DATA THAT RELATES TO WHAT THEY WANT TO THE LATER ON. WE ASK THEM TO PUT A FULL DEVELOPMENT TIME LINE AN STRATEGY TOGETHER AS PART OF THE APPLICATION AND IT'S NOT RATED. MOST IS IMAGINENATIVE WHEN THEY GET IT SO WE DON'T DING THEM FOR COMING IN WITHOUT A BROAD KNOWLEDGE. THEY HAVE TO HAVE DATA TO PRESENT THEIR MOLECULE MEETS THE CRITERIA. A LOT OF TIMES WE REDESIGN THE ENTIRE PROGRAM WITH THEM WHEN THEY COME IN AS A NEW APPLICANT. SO IT'S REALLY HAVE THE DATA TO SUPPORT WHERE THEY ARE IN THE DEVELOPMENT STRATEGY. IF THEY DON'T THEY'LL GET THAT FEEDBACK FROM THE APPLICANT AND HOPEFULLY THEY CAN GO AND GENERATE SOME OF THAT DATA AND REAPPLY LATER >> THE OTHER QUESTION WAS MINOR. I WAS WANDING TO UNDERSTAND THE RATIONALE FOR EXCLUDING GENE THERAPYP@!Ö PARTICULARLY GIVEN YOUR STATEMENT A NUMBER OF INDICATIONS WE KNOW THE GENE. >> THERE ARE PROBABLY 2500 WHERE THE GENE IS IDENTIFIED AS A SINGLE GENE. THIS WAS BASED PRIMARILY ON WHAT EXPERTISE WAS WHEN WE PUT UP THE PROGRAM. ONLY TWO YEARS OLD, WE WANTED SUCCESS WITH SMALL MOLECULES AND BIOLOGICS, ADDITIONAL FUNDING TO EXPAND EXPERTISE ON STAFF TO TAKE ON SOMETHING LIKE THAT. THE BIGGEST PART OF THE BRIDGES PROGRAM DOES HAVE ACCESS TO PROGRAMS WITH GENE THERAPY AND TAKEN ON 3 GENE THERAPY PROJECTS. NOT RESTRICTED TO RARE DISEASES. THERE ARE RESOURCES FOR GENE THERAPY. WE DIDN'T FEEL LIKE WE HAVE THE EXPERTISE IN HOUSE THE TIME WE STARTED. >> YEAH, I WAS WONDERING TO WHAT EXTENT ARE YOU TAKING SYSTEM PHARMACOLOGY APPROACH IN YOUR PHASE 1, 2 STUDIES WHERE YOU MIGHT HAVE THE ABILITY TO LOOK AT PROTEOMIC OR TRANSCRIPTOMIC EFFECT TO UNDERSTAND THE ON TARGET OFF TARGET EFFECTS OF THE DRUG. I'M THINKING SHOULD ONE OF YOUR PROGRAMS FAIL, HOW ARE YOU THINKING ABOUT LESSONS LEARNED FROM THAT AND WHY THEY FAILED FROM A MECHANISTIC AND BIOLOGICAL POINT OF VIEW? >> WE WOULD LOVE TO DO MUCH MORE OF THAT ON EACH TRIAL. WHAT WE'RE FOCUSING ON INITIALLY IS HAVING SOME BIOCHEMICAL MARKERS OF EFFICACY FIRST. WHAT WE LIKE TO SEE IS THAT. AS PART OF THAT WE'RE TRYING TO CAST A WIDE NET INITIALLY TO UNDERSTAND WHAT ELSE TO MONITOR AS WE GO FORWARD. FOR EACH ONE OF THESE WE HAVE SOME BIOMARKER PD MARKER MEAN SICKLE CELL DISEASE YOU CAN -- YOU HAVE NICE PHARMACODYNAMIC MARKERS THAT AREN'T BIOMARKER, YOU CAN LOOK AT OX GENERAL SATURATION CURVES, AND SICKLING OF CELLS AND HYPOXIC CONDITIONS. BUT FOR MANY OTHER WE HAVE AT LEAST ONE OR TWO BIOMARKERS WE'RE TRYING TO FOLLOW SO WE'LL CAST AS WIDE A NET AS WE CAN TO TROY TO UNDERSTAND IF AND WHEN SOMETHING GOES WRONG, IT IS ANT MERIT OF THIS, WE CAN START TO THINK ABOUT HOW CAN WE GO BACK. THAT'S OUR GOAL IS TO GENERATE A BODY OF DATA AROUND THAT DISEASE WHETHER PUBLISHING NATURAL HISTORY DATA, PUBLISHING AS MUCH Z WE CAN FOR MOLECULES THAT DON'T MAKE IT THROUGH THIS EARLY CLINICAL EVALUATION SO THAT THAT KNOWLEDGE GETS OUT THERE INTO THE FIELD. WE HAVEN'T SET UP AN ENTIRE COMMON ARRAY TO TAKE INTO EVERY PHASE 1 OR EARLY CLINICAL TRIAL. WE'D LIKE TO DO THAT. IT'S A LITTLE BIT DEPENDENT ON FUNDING TO STEP UP INTERNALLY SO BENCH TO BEDSIDE TO FILL IN THAT GAP. WE DO A LOT OF PROFILING OF APPROVED DRUGS AND LATE CLINICAL DRUGS IN VITRO. LOTS OF REPURPOSING STUDIES, SCREENING STUFF YOU'LL HEAR ABOUT IN COUNSEL PRESENTATIONS. CLINICALLY WE'RE STILL DOING -- WE HAVE A GRAND VISION BUT WE HAVEN'T ENACTED IT FULLY YET. >> JOHN OR CHRIS, WANTING TO ASK ONE GREAT CONCERN HA SEEMS TO BE EVOLVING AND WE'RE LIVING WITH EVERY DAY IS THAT IN SPITE OF YOUR INPUT THE GOVERNMENT INPUT IN YOUR CASE, IN OUR CASE, IT WAS THE FOUNDATION INPUT, THE PRICE OF SYSTEM OF THESE RARE DISEASE DRUGS IS PROHIBITIVE. WAS GOING TO BECOME EVEN MORE PROHIBITIVE AS WE SEE THE RESTRAINTS THIS ARE GOING TO BE OCCURRING IN THE HEALTH REIMBURSEMENT MARKETPLACE. CL IT CANECO IS ALMOST # HUP -- $300,000 A YEAR FOR SMALL MOLECULE. AND THERE'S OTHERS OUT THERE THAT YOU'RE DOENING THAT SPACE AND I DON'T WANT TO BACK TO THE OLD COLLABORATIVE AGREEMENTS THAT CREATED PROBLEMS 25 YEARS AGO BUT IS THIS SOMEBODY THAT IS IN YOUR DISCUSSIONS OR SCENARIO FOR DISCUSSION? IF WE OOH EAR GOING TO GET INVOLVEDDED -- IF WE'RE GOING TO GET INVOLVED WE HAVE TO DEAL WITH THAT SPHERE OR AT LEAST CATALYZING SOME DISCUSSIONS IN THAT SPEAR BECAUSE I THINK YOU WOULD GET A LOT OF PUSH BACK IF YOU WERE SUPPORT THESE THINGS AT EARLY STAGE AND GROUPS CAN'T AFFORD IT. >> ONE THING I WOULD SAY TO THAT, THERE ARE DISEASES THAT WE HAVE ENTERTAINED APPLICATION FOR THAT HAVE BIOLOGICS ON THE MARKET THAT ARE IN THAT PRICE RANGE. THE REASON WE'RE ENTERTAINING THEM IS BECAUSE THEY'RE SMALL MOLECULE APPROACH THAT HAS TO BE SIGNIFICANTLY LESS MONEY THAN THE BIOLOGIC APPROACH. >> JOHN WE THOUGHT OF THAT ALSO. >> YOU HAVE A SMALL MOLECULE THERE THAT IS QUITE EXPENSIVE BUT THE DIFFERENT IS THERE'S NOTHING ELSE ON THE MARKET TO CONTRAST THAT. IF YOU THINK HIGOT CASES, TWO YEARS AGO DIDN'T CAR THEY JUST WANTED A MEDICATION THAT WAS DISEASE MODIFYING. ONLY AFTER YOU HAVE SOME THERAPEUTIC TO CHOOSE FROM THAT YOU REALLY START TO THINK ABOUT NOW PATIENTS HAVE TO HAVE ACCESS TO IT. THERE ARE MANY DISEASES WHERE THERE'S NO THERAPY AVAILABLE AND YOU'RE TRYING TO DEVELOP THE FIRST THERAPY AND STIMULATE ADDITIONAL RESEARCH, NOVEL MECHANISMS OR NEW MOLECULE THAT MIGHT BE CHEAPER. I THINK IT'S GOING TO BE HARD TO GO BACK TO SOME OF THE OLDER APPROACHES THAT FIXED PRICES >> I WOULD LIKE TO THE ADD ANOTHER PERSPECTIVE PARTICULARLY IN THE CASE OF SMALL MOLECULES. TYPICALLY THE FIRST DRUG IS NEVER THE BEST ONE. IT'S JUST THE FIRST. THE CHALLENGE IN ORPHAN DISEASES IS PEOPLE HAVE THE PERCEPTION THAT IT CAN'T BE DONE AND YOU CAN'T MAKE ANY MONEY. AS SOON AS YOU SHOW IT CAN BE DONE AND YOU CAN MAKE MONEY EVERYBODY AND HIS BROTHER WANTS TO PILE N. LOOK AT THE HIV DRUGS. FIRST ONE THAT KIM OUT WAS $25,000 A YEAR. NOW YOU CAN GET THREE FOR TEN. TOGETHER. SO THE PRICE WILL FALL PARTICULARLY SMALL MOLECULES IF THERE'S A COMPOUND OUT THERE THAT SHOWS IT CAN BE DONE. I THINK THAT MAY NOT QUITE BE THE CASE IN GENE THERAPY BECAUSE OF THE NATURE OF DEVELOPMENT, MAYBE NOT BIOTECH BUT IN SMALL MOLECULES I PERFECTLY EXPECT OUR MOLECULES CAN BE SUPER SEEDD BY A BETTER VERSION. MAYBE OURS, MAYBE SOMEBODY ELSE'S. BUT WE GOT TO GET ONE THING DONE. EVERYBODY ELSE WILL FOLLOW AFTER THAT. >> I GUESS BOB DO YOU THINK THAT'S THE CASE WITH YOU? >> I THINK BOB AND I -- I THINK IT IS PROBLEMATIC WHEN DRUG AFTER DRUG AFTER DRUG IS COMING IN AT 250 AND ABOVE. AND WE'RE ALSO IN A HEALTHCARE ENVIRONMENT WHERE WE'RE LOOKING AT HOW DO WE CUT, NOT EXPAND HOW DO WE GAIN MORE EFFICIENCY. I THINK THAT -- I KNOW YOU AGREE WE'RE WORRIED ABOUT WHAT IS GOING TO HAPPEN TO INNOVATION IF SUDDENLY EVERY DRUG IS PRICED AT THIS RANGE. DO YOU THINK CF PRICE ALSO START TO -- >> THAT'S WHY WE HAVE A COLLABORATION WITH PFIZER TO MY RIGHT. HOPEFULLY GET BETTER MOLECULES. AND DRIVE DOWN THE PRICE AND WE'RE WORKING TO EXPAND THE INDICATION. SO HOPEFULLY ALL THOSE THINGS WILL HAPPEN. MEANTIME WE'RE SEEING BARRIERS PUT -- PUT UP THAT HAVE TO BE INFECTED TODAY. NOT WAITING A YEAR FROM NOW. WE HAVE STATES THAT ARE PUTTING UP -- NOT SAYING NO BUT THEY'RE PUTTING UP SUCH BARRIERS THAT IT MAKES IT VIRTUALLY IMPOSSIBLE. I JUST THINK IT'S -- I BELIEVE -- HOPE YOU'RE RIGHT. WE HOPE COLIDECO WORKS WITH COPD AND WE HOPE WE HAVE A PFIZER PROJECT TOO. BUT MEANTIME IT'S CREATING A SITUATION THAT I THINK WE AS YOU THINK ABOUT, AND WE THINK ABOUT IT HAS GOT TO BE PART OF THE DIALOGUE THAT -- AND BELIEVE ME, I BELIEVE IN INNOVATION. WE ALL -- ANYBODY AROUND THIS ROOM BELIEVES IN THE CONCEPT OF INNOVATION. THINK WE HAVE GOT TO HAVE SOME SORT OF DISCUSSION OF THE CONCEPT OF CONTINUING TO AWARD INNOVATION BUT AT THE SAME TIME RECOGNIZING THAT THERE'S STILL SOME PATIENTS WILL BE DENIED TO SYSTEM OF THESE DRUGS. >> I HAVE HEARD STATISTICS IN THE NEXT THREE YEARS WE CAN SEE TEN STATES BASICALLY GO BANKRUPT AND NOT PROVIDE ANY ASSISTANCE. SO I THINK YOUR POPULATION WOULD BE IMPACTED BY THAT, I KNOW YOU HAVE A POLICY PROGRAM THAT LOOKS AT STATE MEDICAID POLICIES. NOT THAT I THINK NCATS CAN BECOME ALL OF A SUDDEN HEALTHCARE REIMBURSEMENT GURU BUT IT'S HOW DO YOU THREAD THE NEEDLE SO THAT IF WE DERISK THE SYSTEM, AND SAVE THE SYSTEM MONEY WE CAN SEE SOMETHING ON THE OTHER SIDE TOO. IT'S A GREAT IDEA AND WE HAVE THE DRUGS ALREADY. THEY OR SITTING IN OUR LAB. BUT WE JUST SUCH AN OBVIOUS THING TO DO. BUT YEAH WE HAVE THE MONEY TO DO IT. IT'S OBVIOUS THAT BOTH FROM A PATIENT ADVOCACY -- PATIENT ACCESS STANDPOINT, IF WE MAKE A DRUG THAT NOBODY CAN GET WE HAVEN'T REALLY MADE HEADWAY. SECONDLY, IT'S A HUGE POTENTIAL POLITICAL PROBLEM FOR US. SAYING WHY DID WE PUT THIS -- SO MUCH MONEY INTO THIS AN PATIENTS CAN AFFORD IT. BUT PROBABLY LIKE YOU, WITH VERTEX AND OTHERS, THESE REASONABLE PRICING CLAUSES JUST ARE -- THEY ARE -- STAKES THROUGH THE HEART OF BUSINESS PROGRAMS. I THINK WE ALL UNDERSTAND WHY. A POLY ANNA ANSWER AND A SLIGHTLY MORE REAL ANSWER. THE POLY ANNA ANSWER IS TO DECREASE DRUG DEVELOPMENT. THE REASON PEOPLE CHARGE SO MUCH IS THEY HAVE TO GET A RETURN ON INVESTMENT IF THE INVESTMENT IS STILL $2 BILLION WITH COST OF CAPITAL, ET CETERA. THEN PEOPLE WILL CHARGE LARGE AMOUNTS OF MONEY ON ONES THAT WIN. SO THE OVER THE LONG TERM ONE PURPOSE OF N CATS IS TO MAKE IT CHEAPER LONG TERM. THAT WON'T HELP US WITH THIS PROJECT OR OTHER ONES. THE LESS POLY ANNA MORE IMMEDIATE ANSWER IS AS I GUESS, TWO THINGS. ONE IS FOR PROJECTS LIKE -- NOT THIS PROJECT BUT OTHERS THAT WE HAVE WHERE WE ACTUALLY GENERATE IP SO THERE'S A NUMBER OF PROJECTS WHERE WE'RE DOING MED CHEM SO THERE'S ACTUALLY STEPS THERE, AND GOVERNMENT IS A CO-INVENTOR AND WE HAVE HIGH SENSE TERMS THAT GO TO THE COMPANY. THOSE ARE NOT REASONABLE PRICING TERMS ARE NOT IN THERE EITHER BUT IT AT LEAST GUARANTEES SOME RETURN TO THE GOVERNMENT IN CASE OF APPROVAL. NOT ANSWERING YOUR QUESTION. BUT IT'S PART OF THE ANSWER. BEYOND THAT I MUST SAY WHAT WE'RE HOPING TO DO IS GOING TO SOUND FUNNY PERHAPS BUT TO DO THIS BY PUBLIC PROGRAM SO STEVE KNOWS THAT THIS IS A REAL PROBLEM AND THAT LIKE OTHER THINGS WHICH HAPPEN IN PUBLIC LIKE WHY DO PEOPLE NOT SPIT IN PUBLIC ANY MORE, EVERYBODY KNOWS YOU DON'T SPIT IN PUBLIC. SO WE NEED TO ESTABLISH THIS KIND OF EFOS -- ETHOS THAT IF YOU WORK WITH THIS ORGANIZATION THAT THERE -- THIS IS TAKEN INTO CONSIDERATION IN SOME WAY. I REALIZE THE THING THAT GIVES ME PAUSE ABOUT THIS IS I'M SURE THAT'S EXACTLY WHAT YOU THOUGHT, YOU GUYS -- THE GUYS WITH WHITE HATS IF THERE WAS ONE. AND THIS IS NOT TURNED OUT TO BE GREAT PRICING STRATEGY. SO THIS IS NOT AN EASILY SOLVED PROBLEM. I THINK IT'S SOMETHING THAT WE'VE GOT TO ADDRESS AS AN ORGANIZATION. I WOULD BE VERY INTERESTED IN EVERYBODY'S OPINION, YOUR OPINION, STEVE'S OPINION, OTHER PEOPLE ON THE DEVELOPMENT SIDE PEOPLE LIKE BOB AND OTHERS WHO DO BC, WHAT IS THE RIGHT ANSWER HERE. IS THERE SOME VOLUNTARY GUIDELINE OR SOMETHING THAT WHICH ALSO SOUNDS LIKE A BAD IDEA. BECAUSE THE OTHER PROBLEM THAT WE'RE DEALING WITH WHAT HE'S GOING TO DO IS LICENSE TO SOMEBODY ELSE. IF THERE IS -- IF HE HAS A ANVIL ATTACHED TO HIMSELF, HE'S GOT TO DRAG ALONG, WE'RE GOING TO HAVE TO KEEP DEVELOPING IT LONGER UNTIL HE CAN LICENSE IT. THAT'S THE PROBLEM. I DON'T KNOW WHAT THE RIGHT ANSWER IS. YOUR INPUT IS GREATLY DESIRED. >> JUST AS A TACTICAL POINT, AND NOT MY FIELD, I WOULD GUESS THE COST EFFECTIVENESS ARGUMENT IN CF IS STILL GOOD, RIGHT? EVEN THOUGH IT'S EXPENSIVE DRUG? >> TOO EARLY TO TELL. LONGEST ANY PATIENT HAS BEEN ON THE COLITECO IS TWO YEARS. SO WE DONE KNOW WHAT IT'S GOING TO DO TO REDUCING ANTIBIOTIC USE OR OTHER USE OR -- WE KNOW IT REDUCES HOSPITALIZATION RATES, PATIENTS ARE GAINING WEIGHT WHICH IS GOOD. WE DON'T KNOW ABOUT WHETHER THEY CAN WITHDRAW ANTIBIOTIC YET. SO IT'S STILL TOO EARLY TO TELL SO THE PRICING, THOSE THINGS IN THE PHARMACO ECONOMIC AREA CANNOT BE PUT INTO THE EQUATION AT THIS POINT. >> YOU PROBABLY HEARD ME SAY THIS NUMBER BEFORE, WHICH I ALWAYS FIND FRIGHTENING, IF YOU DO A CALCULATION, IF WE HAD A DRUG FOR EVERY PATIENT WITH A RARE DISEASE TOMORROW, AND YOU PRICED IT AT LEVELS $200,000 A YEAR, DRUGS FOR RARE DISEASE PATIENTS ALONE JUST THAT, WOULD EAT ONE-HALF THE U.S. GDP. THE ANSWER IS DON'T BOTHER. JUST DON'T DO IT. NEVER ABLE TO AFFORD IT. SO IT IS -- AND I PERMLY WHAT EVERYBODY ELSE THINKS, PEOPLE WHO THINK THAT THIS PRICING FLEXIBILITY IS GOING TO GO ON MUCH LONGER, I THINK THEY'RE SMOKING SOMETHING. I THINK THE LIKELIHOOD THAT ORGANIZATIONS PAYERS ARE GOING TO PUT UP WITH $200,000, $300,000 A YEAR MUCH -- I JUST CAN'T -- I DON'T SEE IT. SO I THINK SOMETHING THAT WE HAVE TO -- >> AND I WOULD REMIND YOU IN THE MID 20th CENTURY THERE WERE LAWS AGAINST SPITTING IN THE STREETS. >> >> AT THE SEPTEMBER MEETING DR. COLLINS TALKED ABOUT DISCUSSIONS THAT HE WAS HAVING WITH CMS. AND P TALKED ABOUT PAYERS AREN'T GOING TO TOLERATE, CMS IS OBVIOUSLY THE LEAD ON THAT. AS WE GO FORWARD MAYBE COUNCIL WOULD LIKE A REPORT BACK ON HOW THESE DISCUSSIONS WITH CMS ARE GOING. THIS IS ONE OF THESE AREAS WHERE THOSE TWO PARTS OF THE EXECUTIVE BRANCH WORKING TOGETHER MIGHT HELP. >> SOMETHING ON MY TO DO LIST, WE'RE DOING WELL WITH FDA BUT CMS NOT SO MUCH. AND -- BUT MY -- WHAT INTERACTIONS I HAVE BEEN -- I HAVE HAD WITH THEM, ANSWER IS MAKE IT CHEAPER. (OFF MIC) >> -- THEY DO COVERAGE. EVEN THOUGH EVERYBODY ON THE OUTSIDE WOULD SAY THAT'S NOT THE CASE. >> SEEMS TO ME THE ONLY REAL ANSWER IS TO HAVE THE R&D COST LESS, THAT'S WHAT A LOT OF THIS EFFORT IS ABOUT. AND A LOT OF MANY OTHER EFFORTS. SO WITH THE NEW TECHNOLOGY, WITH NEW WAYS FDA IS ALLOWING THE RESEARCH TO BE DONE WITH A LOT FEWER L, TO -- PEOPLE, WE NEED TO FORGE AHEAD AND FIND NEW WAYS TO DO RESEARCH, DO IT FASTER AND CHEAPER SO THEY CAN LEGITIMATELY BRING DOWN THE PRICE OF THE PRODUCTS WITHOUT JEOPARDIZING THEIR BUSINESS INTERESTS. >> I WOULD DISAGREE WITH THAT. I KNOW HOW MUCH WE PUT INTO THE EFFORT TO DERISK IT. IT'S SORT OF -- I BELIEVE THE PRICING MODEL IS PIN THE TAIL ON THE DONKEY AND YOU LOOK AT AN ORPHAN -- LOOK AT THE ORPHAN ULTRA ORPHAN DRUGS U YOU SEE THE PRICE RANGE AND SAY THIS IS ORPHAN AND WE PIN OUR TAIL RIGHT THIS. I WISH -- THERE. I WISH YOU WERE RIGHT BUT I'M NOT SURE THAT THAT'S ALWAYS THE CASE. I THINK IT'S RIGHT NOW FOR A WHILE I THINK IT'S WHAT THE MARKET IS GOING TO BEAR AND WHAT THE MARKET HAS BEEN ABLE TO BEAR WITH THE OTHER ORPHAN DISEASES. THAT'S WHY I WORRY ABOUT THE THINGS YOU THROW OUT HERE WITH THE ONES IN THE PIPELINE, ONES WONDERFULLY WE'RE CREATING. WHAT THE ULTIMATE IMPACT THAT THAT'S GOING TO BE ON ISSUE OF ACCESS. P AND REPUTATIONS. WE HAVE A REPUTATION, WE HAVE A REPUTATION. YOU HAVE A REPUTATION. I THINK THAT'S ONE OF THE THINGS THAT WE HAVE TO MAINTAIN. >> THE -- UNFORTUNATELY WE HAVE TO GET ON TO CONCEPT CLEARANCE BUT I STARTED WITH A CONVERSATION WITH THIS -- ABOUT THIS TO THE CANCER PEOPLE. FOLKS AT THE NCI THROUGH COOPERATIVE GROUPS ARE INVOLVED IN DEVELOPING ACTUALLY THE MAJORITY OF CANCER DRUGS NOW. SO NCI IS IN THIS SITUATION AND I DON'T KNOW HOW THEY SOLVE THIS OR ADDRESS THIS PROBLEM BUT THEY HAVE BEEN DEALING WITH IT FOR A LONG TIME. MAYBE IT'S BECAUSE MOST CANCER DRUGS ARE IN THE 10,000 RANGE, NOT 100,000 OR 200,000. >> AND LIFETIME. >> AND LIFETIME. RIGHT. YES. THAT'S TRUE. YEP. GLEVAK IS A LIFETIME DRUG, WHAT IS THAT A YEAR DO YOU KNOW? >> GLEV AK IS 40 TO $50,000 A YEAR. >> I HAVE A FEELING WE'LL REVISIT THIS. >> I'M SORRY I WANT TO ADD ONE THING. IT IS AN IMPERFECT SCIENCE. I'LL GO WITH YOU ON THAT ONE. IT ISN'T JUST THE COST OF DEVELOPING, IT'S THE COST OF THE LENGTH OF TIME THAT YOU HAVE EXCLUSIVITY IN THE MARKETPLACE, IT IS HOW DIFFICULT IT IS TO IDENTIFY PATIENTS AND LITERALLY PROVIDE THEM ACCESS IF YOU ADD UP ALL THESE FACTORS THERE IS PROBABLY A SWEET SPOT TO SMOOTH THE SYSTEM OUT. SO THAT THE TIME THAT YOU HAD, INCENTIVES THAT ARE DEVELOPED, THE OPPORTUNITIES TO HAVE PATIENTS READILY IDENTIFIED AND AVAILABLE TO TREATMENT, ALL THOSE TOGETHER WE CAN'T SOLVE ALL OF THEM BUT THE QUESTION WOULD BE MAYBE THIS IS ONE THING WE THINK ABOUT IN TERMS OF OUR PRIORITIZATION, THERE ARE A COUPLE OF THINGS THAT SHOULD BE RIGHT IN THE MIDDLE OF THIS TABLE >> SQUARELY IN OUR SWEET SPOT. AND I THINK THAT THOSE SHOULD FLOAT UP QUICKLY BECAUSE YOU'RE RIGHT, IF WE DON'T SOLVE THIS ONE IT WILL BE HARD TO KEEP IT FRONT AND CENTER FOR OTHER INTERESTED PARTIES AND STAKEHOLDERS. >> FANTASTIC SCIENCE AND MEDICINE AND GREAT DISCUSSION, EXACTLY WHAT WE WANTED TO HAVE. THANK YOU. WE JUST HAVE ONE OTHER THING WHICH IS THE CONCEPT CLEARANCE, CLEARANCES, WHICH AREN'T GOING TO TAKE LONG AND THEN WE'RE -- WE'LL BE DONE WITH OPEN SESSION. ELAINE COLLIER WILL COME BACK AND TALK TO US ABOUT TWO CONCEPT CLEARANCES. >> JUST TO REMIND YOU, SINCE COUNCIL IS NEW, I KNOW YOU HAVE DONE ONE OF THESE, CONCEPT CLEARANCES ARE POTENTIAL INITIATIVES, NOT INITIATIVES, THEY ARE POTENTIAL INITIATIVES. SO -- AND WE'RE BRINGING THEM TO YOU FOR YOUR INPUT AND ALSO FOR NOT THAT IT WILL STOP, YO„R INPUT STOPS HERE AND FOR YOUR APPROVAL FOR US TO PROCEED TO DEVELOP THESE CONCEPTS. JUST AS CLARIFICATION. SO THE FIRST ONE I WILL PRESENT IS RELATED TO ETHICAL CHALLENGES AND TRANSLATIONAL RESEARCH AND THE PROBABLY TO DEVELOP EVIDENCE BASED RESEARCH IN THIS AREA. PART OF THE ISSUE CAME UP EARLIER TODAY, MANY ETHICAL CHALLENGES IN THIS SPACE. THE RECENT ARTICLES ABOUT DISCOVERY OF PATIENTS IN THE OMES PROJECTS, OTHER PRIVACY ISSUES RELATED TO DATA INTEGRATION AND HOW MUCH DATA SETS WE NEED TO INTEGRATE IN ORDER TO DO AND DISCOVER POTENTIAL NEW TREATMENT. SO DISEASE PHENOTYPING AS WE DO DISEASE PHENOTYPE WIG WE NEED TO DO TO FIGURE OUT WHICH GROUPS BENEFIT FROM THE DISEASES AN WHICH ONE WE SHOULD GIVE THEM TO SO WE CAN BE MORE EFFECTIVE. WE GET MORE INTO RARE DISEASE ISSUES RELATED TO ETHICS OF HOW WE DO THAT IN THOSE POPULATIONS. DISEASES CURRENT EFFECTIVE TREATMENTS, RARE DISEASES RECENTLY THE ISSUE OF VERY EFFECTIVE TREATMENT OF MICE FOR ALZHEIMER'S DISEASE CAME UP, HOW QUICKLY DO YOU MOVE IT TO PEOPLE. AND THE DIFFERENCE NOW. SOME FAST TRACK BUT WHAT ARE ETHICS HOW YOU DO THAT AND HOW YOU DECIDE WHAT PIECES YOU CAN HOW YOU CAN FAST TRACK THINGS. BIOSPECIMENS CONTINUES TO BE AN ISSUE WITH CONSENT AND HOW YOU ACTUALLY MANAGE SPECIMENS FROM CLINICAL CARE FROM RESEARCH. THE LEARNING HEALTHCARE SYSTEM, THE WHOLE COP SEPTEMBER OF INTEGRATING HEALTHCARE AND RESEARCH AND THAT WE NEED THE LEARN ON ONGOING BASIS FROM TREATING PEOPLE HOW TO TREAT THEM BETTER AND HOW TO -- THERE'S A RESEN HASTINGS REPORT THAT CAME OUT IN THIS AREA AND THE FRAMEWORK FOR HOW WE ACTUALLY DEAL WITH THIS ISSUE. IT'S ALSO COMPLICATED. BUT IT'S DOWN THE PRACTICAL ISSUES BECAUSE WE'RE DOING STUDIES NOW AND MANY MORE AREAS. SO ETHICAL CHALLENGES AFFECT ALL AREAS AND STAGES, ALL DOMAINS OF SCIENCE AND ALL STAGES OF TRANSLATION. IT REQUIRES VILLAGE RESEARCHERS PATIENTS COLLABORATIONS WITH INSTITUTIONS, PUBLIC NON-PRIVATE, PRIVATE TO GET THIS DONE. WE NEED IMPLEMENTATION AND EVIDENCE BASE TO GO BACK TO THE THREE THINGS THAT CHRIS MENTIONED THIS MORNING ABOUT NCATS. RESEARCH AND OUR FOCUS AND TRYING TO ACTUALLY WE'RE GOING TO COLLABORATE, WE'RE GOING TO CHRIS. COLLABORATE AND WE HAVE TO WORK TOGETHER AND WE HAVE TO IMPLEMENT GENERALIZABLE PROJECTS GENERALIZABLE NEW TECHNOLOGIES. THIS WILL NEED TO COLLABORATE WITH OTHER ICs. SO THIS CONCEPT IS A COLLABORATION WITH THE OFFICE OF DIRECTOR, THE ARRA FUNDS WILL BE PROVIDED FOR THIS PROJECT. NO NCATS FUNDS WOULD BE USED. IT WILL BE A COLLABORATIVE TRANSPROJECT. LEVERAGING CTSA COMMUNITY AND OTHER NIH NETWORKS AND PROJECTS. WE PARTICULARLY LOOK FOR INNOVATIVE WAYS TO PARTNER IN THIS, INTEGRATION OF ETHICS PROJECTS TO CURRENT ACTIVITY SO THE PROBLEMS THAT ARE CURRENT RESEARCH GENERATING WILL BE ADDRESSED. EMPHASIS WILL BE ON HIGH CALL MEANINGFUL QUESTIONS, INNOVATIVE METHODOLOGY AND DEFINED RESULTS. AND N CATS WOULD CONVENE A MANAGEMENT GROUP FOR THE PROJECTS WOULD BE DISTRIBUTED. ARE THERE QUESTIONS OR DISCUSSION? >> GO AHEAD. >> GO AHEAD. >> SO THANKS FOR THIS. THIS LOOKS INTERESTING AND PROMISING. I GUESS I'M THINKING BACK TO THE DECEMBER POLICY WORKSHOP THAT WE HAD. JUST THINKING THATETHICS IS JUST ONE COMPONENT OF WHAT'S MORE BROADLY CALLED ELSI RESEARCH, RIGHT? SEE PEOPLE SHAKING THEIR HEADS. BUT IT IS -- AT GENOME CHANGED MOVED AWAY FROM LC BUT IF YOU THINK ABOUT TRADITIONAL AREAS, SOCIAL SCIENCE, LAW ANDETHICS, THEY'RE GENERALLY DISCUSSED IN THE SAME BREATH. WHY DID YOU CHOOSEETHICS AS THE ONE AREA TO FOCUS ON? WHY NOT HAVE A BROODER SCOPE, WHY NOT COVER SOME OF THESE OTHER AREAS AS WELL, WHICH I THINK WE SAW AT THIS WORKSHOP IN DECEMBER WERE PRETTY PRESSING AND IMPORTANT AS WELL. >> SO THIS IS A PRACTICAL ISSUE BUT I THINK THAT MUCH FOR OFFICE OF OD IS EARMARKED FOR BIOETHICS. IT'S BEEN EARMARKED SEVERAL YEARS, THEY HAVE BEEN MANAGED IT IN VARIOUS WAYS AND THEY DECIDED IT WOULD BE MORE APPROPRIATE TO ASK NCATS TO MANAGE THAT TO ADDRESS ETHICAL ISSUES AND SO THAT'S WHY THE FOCUS IS ONETHICS VERSUS -- I'M NOT ANSWERING A QUESTION THE WAY YOU WISH. >> IT'S NOT A SCIENCE BASED ANSWER. >> NOT A SCIENCE BASED ANSWER. >> IT'S WHAT THE MONEY WAS -- WE WERE TOLD TO SPEND THE MONEY ONETHICS. THAT'S THE REASON. >> SO PEOPLE ASKED ME WHY I WENT INTO MEDICALETHICS AND I OFTEN SAY FOR THE MONEY. [LAUGHTER] >> CAN YOU JUST PUT THE LAST SLIDE UP, PLEASE. >> SURE. >> THE THIRD BULLET POINT I JUST WANTED TO POINT OUT THAT WHILE IT'S GREAT TO LEVERAGE CTSA AND NIH FUNDED NETWORK I WOULD HOPE THAT IT'S NOT A REQUIREMENT GOING FORWARD. BECAUSE I THINK THE LAST ITERATION THE REQUIREMENT IF THE GOAL WAS TO GET THE BEST IDEAS WE CAN FOR PEOPLE TO APPLY, I THINK WE DON'T WANT TO LIMIT IT TO THAT BUT LEVERAGE. >> I THINK THERE IS THE EMPHASIS IS CERTAINLY ON ENGAGING THOSE COMMUNITIES AND EFFORTS THAT WOULD GO ON BUT CERTAINLY OTHER COLLABORATORS AND OTHER PARTNERS AND IT WOULD BE A CLEAR -- SO SOME DIFFERENCES FROM THE LAST ITERATION. I CAN'T SAY -- BUT I THINK THAT THE INTENT WOULD BE THAT WE WOULD WANT TO HAVE ALL THE PARTNERS ENGAGED IN WHATEVER PROJECT THAT NEEDED TO BE THERE. AND OPPORTUNITY TO DO IT BUT EMPHASIS ON UTILIZING THE IMMUNITIES AND GETTING ANSWERS AN ADDRESSING QUESTIONS FOR NIH FUNDED RESEARCHERS. >> PAM. JOE. >> SO I THINK IT'S A GREAT IDEA. I THINK THERE ARE A LOT OF PRESSING ETHICAL QUESTIONS. I THINK THERE ARE GETTING TO BE MORE OF THEM AND THEY BLEND WITH PRIVACY ISSUES AND OTHER KINDS OF THINGS THAT ARE CRITICAL. THINK ABOUT PUTTING IT IN AS POTENTIALLY A TRAINING COMPONENT. TRAINING IN BIOETHICS IS NOT AS PREVALENT AS WE NEED FOR THE FUTURE AND MAKING THE AS -- CONSIDERING A COMPONENT OF YOUR INITIATIVE BEING A TRAINING COMPONENT AT THE FELLOW LEVEL OR GRADUATE LEVEL, I THINK WOULD GO A LONG WAY TOWARD STIMULATING THE FIELD. >> I THINK TRAINING IS VERY IMPORTANT ISSUE. I THINK THE QUESTION IS CAN ONE INITIATIVE DO ALL THINGS. SO THAT WOULD BE WHY WE LIMIT IT. YEAH. >> WE HAVE SPENT TIME ON ALL THESE ISSUES PARTICULARLY WITH THE GENOMIC DATABASE AND ELECTRONIC HEALTH RECORD AND ALL LARGE DATABASES. I THINK IT'S IMPORTANT ALTHOUGH LABELEDETHICS AND I UNDERSTAND -- OBVIOUS REASON FOR IT, THERE COULD BE A SCIENTIFIC BASIS FOR ETHICS. AND I THINK THAT'S SPECIALLY WITH PRIVACY, WE HAVE A LOT TO LEARN ABOUT PRIVACY. EVERY NOW AND THEN SOMEBODY WRITES AN ARTICLE AND SAYS WE IDENTIFY THIS. BUT WE NEED TO LOOK AT THIS. THE OTHER THING IS THAT SOME OF THIS SHOULD LEAD TO LEGISLATION. PRIVACY PARTICULARLY. OUR VIEW HAS BEEN THAT PROBABLY WE CAN'T STOP PEOPLE FROM FINDING OUT THINGS ABOUT OTHER PEOPLE IN THE MODERNER RA. THE SANCTIONS ARE AN AREA OF FOCUS THAT IS GOING TO BE IMPORTANT BECAUSE MISUSE OF THAT INFORMATION IS GOING TO BE WHERE FOCUS HAS TO BE. BECAUSE PEOPLE WILL FIND OUT THINGS AND ACT IN WHATEVER THEY DO TO DISRUPT PRIVACY. I DO THINK THAT THE SCIENCE OF PRIVACY IS A BIG AREA THAT NEEDS WORK. >> INTERESTING GIVEN YOUR QUESTION THE LARRY THIS MORNING ABOUT THESE IDENTIFIED PEOPLE. TO ME IT'S AN ISSUE THAT N CATS CAN'Ts CAPITAL FROM. SOME INSTITUTES CAN BECAUSE THEY CAN STUDY ENZYME SUBUNITS. WHICH HAVE NO ETHICS THAT I'M AWARE OF. BUT WE CAN'T. IT'S LIKE THE PRICING ISSUE. WE'VE GOT THE DEAL WITH THAT. >> SAME POSITION HAVING A HEALTHCARE SYSTEM AND HAVING DATABASES IS THE SAME THING. >> SO I AGREE THIS IS AN IMPORTANT TOPIC AND THAT'S POTENTIALLY A PLACE FOR IT IN NCATS. I WANT TO TAKE A CONTRARIAN STANCE FOR A MOMENT. IT'S TEMPTING BECAUSE THAT'S MONEY FROM SOMEWHERE ELSE BUT I'M A LITTLE BIT FEARFUL THAT N CATS TRIES TO BECOME ALL THINGS TO ALL PEOPLE. SO WHAT I ASK STAFF TO DO IS ASK THEMSELVES IF THEY'LL ADOPT SOMETHING LIKE THIS AS NEW INITIATIVEK ARE THEY GOING TO STOP DOING? SO THERE'S GOT TO BE A BALANCE THERE.a SPREAD OTHERWISE THINGS DON'T GET DONE PARTICULARLY WELL. >> THE GOOD THING, WE SHOULD MAKE THIS CLEAR. THIS IS UNLIKE EVERY OTHER NCATS PROGRAM, THIS IS A PROGRAM THAT COMES NOT ONLY WITH RESPONSIBILITY BUT ACTUALLY COMES WITH MONEY. SO THIS IS $5 MILLION ADDITIONAL MONEY. FROM THE OFFICE OF DIRECTOR. TO DO THIS. SO IT IS -- ELAINE AND I HOWEVER DID TALK ABOUT THIS QUITE A BIT. AND I CAME THIS CLOSE, I WAS TELLING ERIC AT LUNCH THIS CLOSE FROM SAYING WE GOT -- WE GOT TO SOLVE EVERY OTHER PROBLEM IN THE KNOWN UNIVERSE, CAN'T SOMEBODY ELSE SOLVEETHICS? BUT I WAS CONVINCED THAT WAS A BAD IDEA. SO WE'RE GOING TO TAKE -- BUT IT DOES COME WITH MONEY. WHICH IS ADDITIONAL MONEY. >> IF I CAN TAKE A CONTRARIAN VIEW TO THE CONTRARIAN VIEW, IT IS BEGINNING TO SOUND LIKE AN ETHICAL DISCUSSION, I DO THINK -- I AGREE WHAT YOU SAID, THIS IS SOMETHING, MANY PROBABLY NOT ALL BUT A NUMBER OF TOPICS ARE ESSENTIAL TO THE FUNCTION AS I WOULD AN OUTSIDER OF NCATS. IT WILL BE IMPORTANT. SOMEBODY HAS GOT TO DEAL WITH THIS IN A SORT OF BALANCED WAY. IT IS VERY IMPORTANT. WE DID A GENOMIC SURVEY, 98, 99% IS THE MOST IMPORTANT ISSUE. THEY WERE STRONGLY IN FAVOR OF IT, PRIVACY AND SECURITY ARE HUGE ISSUES. VETERANS MAYBE MORE CONSCIOUS OF THOSE THINGS BUT NOT MUCH. IT COMES OUT MANY OTHER AREAS AS WELL. >> ON THIS SAME TOPIC AND AT THE RISK OF ADDING MORE TO THE LIST, TAKE IT FOR WHAT IT IS. I THINK THERE'S ALSO AN ETHICAL ISSUE TALKING PRIVACY AND NOT LETTING OTHER PEOPLE SEE YOUR GENETIC DATA BUT YOU'RE NOT ALLOWED TO SEE YOUR OWN GENETIC DATA. THAT IS SOMETHING THAT SHOULD BE PARTS OF THAT DISCUSSION. IT IS HAPPENING. PEOPLE CAN SEND IN AND GET THEIR DNA RIGHT NOW. THERE ISN'T GOOD GUIDELINES OR HOW IS THE WORLD GOING TO HANDLE THAT. IT'S ONLY GOING TO GET EASIER FOR PEOPLE TO DO THAT OVER TIME. IT DOES RELATE TO THE PRIVACY BECAUSE SOMEONE CAN PUT IT RIGHT ON THEIR FACEBOOK PAGE IF THEY WANTED TO. >> I HAD A LITTLE BIT OF A DIFFERENT QUESTION. I WENT BACK AND LOOKED AND TRIED TO REMEMBER EVERYTHING YOU SAID. SO PARDON ME IF I'M NOT UNDERSTOOD THIS. EXACTLY WHAT IS IT THAT WILL BE PRODUCED OUT OF THIS? WILL IT BE A SET OF GUIDANCES, POLICIES, LEGISLATIVE AGENDA, TRAINING, AT THE END OF $5 MILLION, WORK OF THE PEOPLE AND THE END OF THE DAY, WHAT EXACTLY IS IT WE EXPECT TO HAVE IN HAND TO -- AS A RESULT OF THIS? >> I THINK THAT'S A VERY IMPORTANT QUESTION. THIS ISN'T P -- THIS IS A PROPOSAL FOR AN INITIATIVE THAT WOULD BE LIKELY A SOLICITATION FOR GRANTS. I THINK YOUR POINT IS WHAT DO WE DO AND HOW DO WE ACTUALLY DEAL WITH THE RESULTS AND THE DATA WE GET OUT OF THIS. I THINK IN THINKING THIS THROUGH, WE CERTAINLY FELT THAT IT WAS VERY IMPORTANT WE ENDED UP WITH DATA AT THE END OF THIS OF SOME KIND. SO THAT WOULD BE A HUGE EMPHASIS IN THESE GRANTS TRYING TO HAVE METHODOLOGIES MEANINGFUL QUESTIONS DEFINED RESULTS AND THEN A -- CERTAINLY A GROUP ACROSS NIH TO DISCUSS WHAT COMES OUT OF THESE. AND WE'LL SEE WHETHER THERE WOULD BE A REPORT. BUT CERTAINLY THERE WOULD BE FINAL REPORTS AND PUBLICATIONS FROM (INAUDIBLE). SO I CAN'T PROMISE BUT YOUR THOUGHTS WOULD BE HELPFUL. >> YEAH. I MEAN, WE MAY AS OUR WORK CONTINUES ON PROVIDE INPUT AND IDEAS ON THIS. BUT I'M NERVOUS WE'LL HAVE DATA IN HAND WITH WHICH WE WON'T BE ABLE TO DO ANYTHING, WON'T BE ABLE TO ACTION ANYTHING. MINIMALLY I WOULD HOPE WHATEVER IT IS WHATEVER DATA WE COLLECT WE HOPE WILL INFORM DECISIONS THAT WE'RE GOING TO MAKE DOWN THE ROAD SOMEWHERE, THAT I THINK WOULD BE REALLY HELPFUL THING. TO LOU'S POINT IF IT HELPS MOVE THIS AGENDA FORWARD AS WELL AS COLLECTIVE AROUND RESEARCH THEN HALLELUIAH TO THAT. >> MAYBE FOCUSING ON ISSUES THAT COME UP TODAY, THE WHOLE ISSUE GOVERNMENT INPUT INTO DEVELOPMENT OF AGENTS AND PRICING AND OTHER ISSUES. THERE -- MAYBE THERE'S ISSUES THAT ARE OF IMPORTANCE TO THE COUNCIL THAT YOU CAN SEND ONv œ TOES >> WE WANT TO APPROACH THIS IN A NCATSIAN WAY WHICH IS AN ADJECTIVE YOU'LL PROBABLY START USING, START HEARING. WHICH IS THAT EVERY OTHER PROGRAM WE DO WE GENERATE DATA FINDINGS THAT HAVE TANGIBLE EFFECT ON HUMAN HEALTH OR HEALTHCARE. THAT'S NOT ALL PROGRAMS. LOTS OF OTHER INSTITUTES HAVE THINGS WHICH HAVE PROGRAMS WHICH ARE NOT SO THEY'RE DONE FOR PURE RESEARCH PURPOSES. HAVING BEEN IN GENOME MANY YEARS ONE HIT OPT LC PROGRAM IS THAT -- ON THE LC PROGRAM, AT LEAST IN SOME PEOPLE'S OPINIONS DIDN'T HAVE ENOUGH REAL WORLD IMPACT APPLICATION. SO ONE THING WE'RE STRUGGLING IS NOT ONLY WHAT THE SUBJECT AREAS OUGHT TO BE IN THE RFA, WHY THIS DISCUSSION IS USEFUL TO FOCUS IT ON THINGS WHICH AS WE GO THROUGH OUR STRATEGIC PLANNING WHAT ARE THE BIG QUESTIONS WE IMMEDIATE DATA ON. BUT ALSO TO HAVE WHATEVER THE HOW IS. HOWEVER WE DO THIS, THAT'S THE WHAT QUESTION. HOW QUESTION IS WHAT IS THE MECHANISM. SHOULD THEY BE R 1, COOPERATIVE AGREEMENTS, WHAT SHOULD THEY BE BECAUSE I AGREE WITH JOEL, SOMEBODY WHO SAID THAT ULTIMATELY WE WOULD LOVE THESE THINGS TO IMPACT POLICY OR LEGISLATION OR SOMETHING. THE PROBLEM FOR NIH IS THAT PATH -- THERE'S NOT A DIRECT PATH TO DO THAT. AS YOU PROBABLY KNOW. BUT YOUR HELP DESIGNINGETHICS PROGRAM WHICH IS DELIVERABLE FOCUSED AS THE REST OF OUR PROGRAMS I THINK WOULD BE REALLY HELPFUL. >> I WOULD SAY IF YOU PICK THE RIGHT INVESTIGATORS AND I THINK RO-1 K KIND OF APPROACH IS THE WAY TO DO IT GET THE RIGHT PEOPLE, THEN THE BALL IS IN THEIR COURT FOR THE DELIVERABLES. >> RIGHT. >> YOU HAVE TO TRUST YOU PICK THE INVESTIGATORS WITH GOOD IDEAS AND YOU CAN SEE THE NEXT STEP THEY WOULD TAKE. >> RIGHT. OKAY. MOVING ON. >> SO WE DO NEED TO TAKE A VOTE ON THIS AND THEN WE MOVE ON TO THE NEXT ONE. THIS -- REMEMBER THIS IS A CONCEPT, THIS IS WE HAVE BEEN TALKING ABOUT A CONCEPT, THIS IS A WHETHER, NOT SO MUCH THE WHAT, THEN THERE'S THE HOW QUESTION. THIS IS THE WHETHER QUESTION. WHETHER, WHETHER WE SHOULD DO THIS. WHY IT'S A CONCEPT CLEARANCE. IF YOU LIKE TO IT THE POINT LOU WAS MAKING, THEN THIS FITS OR DOESN'T WITHIN THE NCATS PORTFOLIO, THEN WE'LL DO IT. THEN IT'S UP TO US TO DO THE NEXT STEP. FIGURE OUT WHAT MECHANISM RFA IS BLAH BLAH BLAH. ALL IN FAVOR IF YOU COULD SAY AYE. ALL OPPOSED. VERY GOOD. THANK YOU. THAT ONE PASSED THEN WE HAVE ONE OTHER CONCEPT CLEARANCE FOR INCREASE NATIONAL CAPACITY FOR CLINICAL AND TRANSLATIONAL RESEARCH. >> SO THIS CONCEPT RELATED TO THE CTSA PROGRAM. THE CTSA PROGRAM HAS BEEN FOCUSED INSTITUTIONAL CLINICAL TRANSLATIONAL SCIENCE AWARDS. WE HAVE THOSE APPLICATIONS IN, THEY'RE BEING REVIEWED. WE SIGNALED IN THAT FOA THAT WE WOULD DO OTHER THINGS IN THE CLINICAL TRANS-- OTHER FOA IN CLINICAL TRANSLATIONAL SCIENCE ARENA. THIS IS A CONCEPT TO FOCUS THAT AREA OF INCREASING NATIONAL CAPACITY ACROSS THE CTSA AND WITH OTHER PARTNERS REGULATORY AND SO NOW SEEMS LIKE REASONABLE TIME TO DO THIS. WE HAVE STARTED AND WE NEED A NATIONAL ENVIRONMENT THAT HAS OPERATIONAL EFFICIENCY. WE NEED PRINCIPLES IN THAT OPERATIONAL EFFICIENCY THAT ENCOURAGED TRANSPARENCY AND ACCOUNTABILITY. AGAIN, WE TALKED ABOUT THIS HERE BEFORE. WHY THE NCATS CTSA PROGRAM? IT'S POISED AT THIS POINT TO PROVIDE LEADERSHIP IN THIS AREA. MAJOR ACADEMIC INSTITUTIONS HAVE FORMED LOCAL PARTNERSHIPS INCLUDING WITH A RANGE OF STAKEHOLDERS INCLUDING INDUSTRY. REGIONAL PARTNERSHIPS ACROSS CTSA, STATE PARTNERSHIP WITH CTSA AND OTHER PARTNERS AND CROSS COUNTRY PARTNERSHIPS EXIST, THEY HAVE LEARNED LESSONS ABOUT ENGAGING STAKEHOLDERS, LISTENING PILOTING AND FORMING DECISIVE ACTION IN AREAS. IT'S A BALANCE BETWEEN TOP DOWN AND BOTTOM UP AND THEY HAVE TOM EXPERIENCE IN THAT AREA. OFFERS OPPORTUNITY FOR ADOPTION OF NETWORK FROM COMMON PRACTICES AN STANDARDS THAT ARE DEVELOPED IN THIS WAY. THE INITIATIVE CONCEPT IS FOR PARTNERSHIP OF CTSA IN THE CONSORTIUM, IT WAS FOCUSED IN THE AREA OF BUILDING CAPACITY FOR CLINICAL TRANSLATIONAL RESEARCH. IT WOULD BE A COLLABORATION AGAIN WITH OTHER NIH FUNDED INVESTIGATORS. AND OUTSIDE PARTNERS. NOT JUST HIPPOINVESTIGATORS. AND CTSA INSTITUTIONS. PROJECTS WOULD BE ACROSS THE SPECTRUM OF TRANSLATIONAL RESEARCH BECAUSE WE DO INTEND TO KEEP THE WHOLE SPECTRUM OF TRANS HAGUE RESEARCH. THE -- NOT JUST T-1 OR T-4. THE CONCEPT IS TO PILOT SUSTAINABLE PRACTICES METHODOLOGIES, TECHNOLOGIES ACROSS MULTIPLE SITES AND REAL TIME CIRCUMSCRIBED PROJECTS ON PROJECT AND SCALABILITY, DEFINED TARGETS AND MILESTONES FOR EACH PROJECT A MILESTONE DRIVEN APPROACH THAT'S BEEN DONE IN MOST GRANTS. SO COMMENTS, DISCUSSION. >> HOW IS THIS DIFFERENT FROM THE HOW IS IT DIFFERENT FROM THIS? >> SO GORDON IS THE PI OF THIS -- THE CONSORTIUM CTSA COORDINATING CENTER. AND THAT COORDINATEN -- COORDINATING CENTER WAS FUNDED TO SUPPORT THE DISCUSSIONS ACROSS THE CTSA, IT WAS TO DISCUSS AND COLLABORATION, COLLABORATIVE SPACE, A WEBSITE, AND COMMUNICATION ACROSS THAT. TO GATHER GEAT FROM THOSE BUT IT WAS NOT TO FUND INDIVIDUAL PROJECTS OR ACTUALLY PILOT PARTICULAR AT THIS TIMES. -- ACTIVITIES. >> MY UNDERSTANDING IS THEY'RE ENGAGED IN STUDIES TO BASICALLY DEVELOP BETTER METHODS, WAYS, PROCESSES. >> THERE'S A LOT OF DISCUSSION ACROSS THE STRATEGIC GOAL COMMITTEES AND P I THINK MANY OF THE CONSORTIUM COMMITTEES FOR PROJECTS, MANY DOING THIS ON UNFUNDED KIND OF OUT OF THEIR CTSA APPROACH. AND THERE WAS SOME SUPPLEMENT FUNDED IN THE PAST IN PRIOR ITERATIONS FOR DOING THAT KIND OF ACTIVITY. RATHER THAN DOING THAT IN THAT WAY, THIS WAS AN APPROACH TO DRIVE THAT ACTIVITY FROM NCATS WITH MILESTONES AND -- >> THE WAY I WOULD PUT IT, THERE'S COORDINATING CENTER MAINLY DOING PHONE CALLS, MEETINGS, MINUTES SOME INFORMATICS PLATFORMS THAT WILL ALLOW PEOPLE TO WORK TOGETHER. BUT THE ISSUE WE HEAR OVER AN OVER AGAIN IS WE REALLY WANT TO WORK TOGETHER. BUT WE CAN'T DO THAT WITH NO MONEY. SO WHAT YOU NEED TO HAVE IS A PROGRAM THAT HAS CONSOR SHALL GOALS, AND IS BUILT THAT WAY. AND THAT'S AND THE CURRENT WAY IT'S FUNDED, THERE ARE PEOPLE DOING THIS, AS ELAINE SAID ON THEIR OWN. BUT IT'S ALMOST DESPITE THE WAY THE PROGRAM IS FUNDED INSTEAD OF BECAUSE OF IT. >> YOU MAY WANT TO CHECK FUNDING BECAUSE I THINK THE GRANTS WAS FOR $20 MILLION. (OFF MIC) >> I DON'T THINK IT'S BEING COMPLETELY DONE ON THEIR OWN. OTHER ICs HAVE SPECIFICALLY HAD RFAs ENCOURAGED THE CTSA SPECIFICALLY TO DEVELOP CONSORTIA TO ACCOMPLISH PROJECTS. WHAT'S -- AGAIN, RELATED TO BERNARD'S QUESTION, WHAT IS DIFFERENT ABOUT THIS COMPARED TO WHAT'S ALREADY DONE THROUGH OTHER ICs. >> I THINK THIS IS NOT TO DO SPECIFIC SCIENTIFIC PROJECTS IN DIABETES OR HEART DISEASE. BUT COULD DO THAT BUT TO SHOW A PRINCIPLE OF HOW YOU INCREASE EFFICIENCY TO DO IRBs OR TO DO INFORMATICS SHARING OF DATA OTHER ASPECTS. SO I'M A CTSA PI SO I HAVE AN IMMEDIATE COP FLICK OF INTEREST HERE. AND I'M ALSO SOMEONE WHO HAS SPEARHEADED A STATEWIDE CONSORTIUM OF THREE CTSAs IN THE STATE OF OHIO. LET ME GIVE YOU A COUPLE OF EXAMPLES AND WHAT WE'RE HOPING ARE STATE GOVERNMENT IS GOING TO HELP US DO. SO WE PUT TOGETHER IRB AGREEMENTS THAT ALLOW THE CTSAs ACROSS THE STATE OF OHIO TO USE ONE ANOTHER'S IRBs, FOR EITHER RELIANCE OR FACILITATED REVIEW. THIS ONLY WORKS WE HAVE DONE THE PILOT IN CLEVELAND WITH FOUR INSTITUTIONS. THIS ONLY WORKS IF YOU HAVE AN ELECTRONIC HUB. THE HUB WE HAVE NOW, DOESN'T HAVE ENOUGH SEATS TO I COME DATE THE OTHER CTS'S. SO WHAT WE NEED TO DO IS HELP GET THE SEATS AND EXPAND THAT HUB SO THAT WE CAN ACCOMMODATE THE ADDITIONAL TRAFFIC. WE ALSO PUT TOGETHER AN IT SYSTEM, IN CLEVELAND AN IT SYSTEM THAT ALLOWS US TO QUERY THE INSTITUTIONS IN CLEVELAND AND FIND OUT WHETHER WE HAVE ENOUGH SUBJECTS OR POTENTIAL SUBJECTS FOR A GIVEN CLINICAL TRIAL. BY PULLING INFORMATION FROM THE ELECTRONIC HEALTH RECORD. THIS CAN BE EXPANDED ACROSS THE STATE OF OHIO BUT THERE ARE NO DOLLARS TO DO THAT. SO THAT IS ANOTHER EXAMPLE OF -- WE CAN START OUT WITH SOMETHING IN OUR OWN CTSAs, BUILD WITH OUR OWN MONEY BUT I DON'T HAVE THE MONEY IN THE CLEVELAND CTSA THE DO IT AT OHIO STATE OR CINCINNATI. SO THAT'S THE KIND OF THING. THIS IS A GREAT IDEA. I LOVE THE IDEA OF DEFINED TARGETS, I LOVE THE IDEA OF MILESTONES. BECAUSE THEY WILL REALLY DRIVE -- >> AGREE. >> THEY WILL DRIVE THE PROCESS. IN A DEFINED MANNER. THEY ALSO ALLOW YOU TO SAY IF I CAN'T MEET THIS MILESTONE THEN THE REST OF IT ISN'T GOING TO WORK. SO I LIKE THIS PIECE OF IT SOME THINGS ENVISIONED WITH THIS, AKYE KNOWN, IF YOU CAN'T DO THE BASIC STUFF YOU CAN'T MOVE FORWARD. SO I THINK THAT THAT HAS TO HANG IN. >> HAVING LESS BANG GROUND IT FEELS LIKE THIS INITIATIVE AND OPERATIONAL EFFICIENCY, COLLABORATION SHOULD BE PART OF THE DNA OF WHAT CTSAs ARE DOING. SO MAYBE -- INCLUDING A SPECIAL INITIATIVE LIKE WE DISCUSS ARE SOMETHING THAT SHOULD BECOME MORE GENERAL PRACTICE IN A COMMON POINT OF VIEW. MAYBE TO BORROW YOUR PHRASE, CHRIS, IN AN NCATSIAN POINT OF VIEW, ARE THERE WAYS THAT WE CAN -- IF WE'RE GOING TO DO THIS REALLY THINK ABOUT ADDING ELEMENTS TO IT LIKE COLLABORATION WITH OTHER ENTITIES, PARTICULARLY NCATS UMBRELLA BUT ALSO THE OTHER TRANSLATION ARM MEN TEAR YUM, THIS GOES A LONG WAY TO LOU'S POINT OF ADVANCING THE MISSION. >> YOU HAVE READ OUR MINDS. YES. I THINK YOU'RE RIGHT. REALLY PART OF THIS IS THIS EVOLUTION I WAS TALKING ABOUT EARLY THIS MORNING FROM THE PREVIOUS CONCEPT OF WHAT THE CTSAs WERE WHICH IS FINE, DIFFERENT FROM WHAT THE CURRENT MISSION, I THINK ALSO IT'S APPROPRIATE FOR THE TIME. A LOT OF TIMES A LOT OF ISSUES HERE ARE SYSTEM INC. ISSUES. AND IT REALLY NEEDS TO BE AS YOU SAID PART OF THE DNA OF THE PROGRAM NOW. >> I DON'T REALLY KNOW A LOT ABOUT THE CTSAs SO I GUESS A GENERAL COMMENT SINCE THAT IS SUCH A LARGE PERCENTAGE OF THE ALLOCATIONS OF THE INSTITUTE. IT WOULD BE HELPFUL TO SPEND MORE TIME ON THAT AT A FUTURE MEETING. MY RECOLLECTION OF THE PRESENTATION LAST TIME IS THAT ON HIS LIST OF MILESTONES WAS CENTRAL IRB. IT'S HARD TO PIECE TOGETHER WHETHER THAT SHOULD BE INCLUDED NOW. AND JUST ISN'T HAPPENING. A SPECIFIC QUESTION IS SORT OF WHAT BUDGET ARE YOU PROPOSING FOR THIS. AND ASKING SORT OF A QUESTION IN THE CURRENT BUDGET, IS IT NOT POSSIBLE TO FIND THAT WITHIN THE 400 SOMETHING MILLION IN THE PIE CHART. >> IT WOULD BE IN THAT SET OF MONEY. >> SO IT'S MONEY THAT'S -- HOW IS THAT -- IT'S ALREADY ALLOCATED TO CENTERS OR IT'S -- >> SO I THINK THE ISSUE IS WE HAVE A TARGET FOR THE CTSA PROGRAM FOR NCATS. IT'S HOW WE ALLOCATE THE MONEY WITHIN THAT PROGRAM. IN THAT PIECE OF THE PIE. I THINK THE QUESTION IS PREVIOUSLY IT'S BEEN 61 GRANTS SO THE QUESTION IS THIS MIGHT BE A CONCEPT THAT HAS 60 GRANTS BUT ALSO HAVE OTHER GRANTS THAT DO THINGS IN THAT PROGRAM TO ADVANCE THE PROGRAM. AGAIN, THE PIE IS THE SAME. >> CONCEPTUALLY MIGHT BE LESS SENORS. >> OBVIOUSLY AS CHRIS SAYS WE HOPE THAT THE PROGRAM GROWS. AS WE HOPE ALL PROGRAMS AT NCATS GROW. BUT I THINK THAT TO RATHER THAN HAVING A LOT OF THINGS GOING ON LOCALLY, ACTUALLY FOCUS SOME OF OUR FUNDS ON P MAKING THINGS HAPPEN ACROSS THE NATIONAL SCENE, ACROSS CTSA, AND ENGAGING OTHER PARTNERS IN TRYING TO MAKE THINGS MORE EFFICIENT IN MULTI-SITE EFFORTS IS WHAT WE THOUGHT. >> ONE LAST QUESTION, I REMEMBER ALSO THE LAST BOARD MEETING, THERE WAS DISCUSSION OF ON GOING INDEPENDENT REVIEW OF THE PROGRAM. DID THIS COME OUT OF THE REVIEW, THE REVIEW IS STILL GOING ON BUT YOU'RE ALREADY MAKING THIS CHANGE >> POTENTIAL INITIATIVE. >> ALL PROGRAMS, ALL NIH PROGRAMS EVOLVE, GOOD PROGRAMS EVOLVE. >> THIS IS NO DIFFERENCE FROM ANY OTHER PROGRAM AT NIH. BUT THE POINT OF IOM THAT'S WHAT YOU'RE REFERRING TO, THE IOM IS ACTUALLY DOWN THERE WITH ELAINE TOMORROW, PROBABLY OTHER PEOPLE TALKING TO THE IOM GROUP AGAIN, THEY'RE MEETING THE THIRD TIME TOMORROW, THE REPORTS IS SUPPOSED TO BE OUT IN JUNE. (OFF MIC) >> AT LEAST PART OF IT. A LOT OF THIS CONCEPT IS ACTUALLY COME FROM DISCUSSIONS WITH PEOPLE IN THIS ROOM OR PEOPLE LIKE YOU. ABOUT NEEDS IN THE COMMUNITY ARE. IN DISCUSSIONS WITH >> ANY OTHER COMMENTS? SO WHAT WE'RE ASKING FOR HERE IS A CLEARANCE OF A CONCEPT