>> I AM IRA PASTINI IN THE LABORATORY OF MOLECULAR BIOLOGY AT THE NATIONAL CANCER INSTITUTE. I WAS IN THE ENDOCHRONOLOGY BRANCH AND MET BOB THERE. I'M VERY THRILLED TO HAVE BOB HERE AS A SPEAKER AND TO HAVE A CHANCE TO INTRODUCE HIM AS PART OF THE OFFICE OF NIH HISTORY BIOMEDICAL SERIES. NOW THE SERIES IS DESIGNED TO PROVIDE THOUGHTFUL EXAMINATIONS OF PAST SUCCESSES AND FAILURES IN MEDICAL RESEARCH TO HELP GUIDE OUR FUTURE. A PREVIOUS SPEAKER WHO I WILL POINT OUT WAS ALSO TRAINED AS AN ENDO CHRONOLOGY AND TALKED ABOUT THE DARK HISTORY OF EUGENICS IN THE UNITED STATES AND ITS IMPLICATIONS THIS THESE DAYS OF GENE EDITING. IT'S AVAILABLE FOR YOU TO WATCH. THE MOST IMPORTANT THING TO KNOW ABOUT BOB IS HE WON THE NOBEL PRIZE FOR STUDIES OF GENE COUPLED PROTEIN RECEPTORS. I COULD TELL YOU A LOT ABOUT THAT BUT I'LL REFRAIN AND NOT SPOIL BOB'S TALK ABOUT HOW IT ALL BEGAN. MAYBE AT THE END I'LL HAVE A FEW THINGS TO SAY. DON'T FORGET, YOU CAN SUBMIT QUESTIONS DURING THE LECTURE. WE SHOULD BEGIN WITH THE SCIENCE. THE SCIENCE WAS CELL SURFACE RECEPTORS. AT THE TIME BOB CAME TO NIH, I WAS WORKING WITH JESSE ROTH ON RECEPTORS AND BOB WAS SELECTED TO WORK WITH JESSE ON RECEPTORS. BECAUSE WE WERE COLLABORATING, BOB WORKED PART TIME IN MY LAB AND PART TIME WITH JESSE. LOB, LIKE MOST YOUNG SCIENTISTS THEN, HAD VERY LITTLE EXPERIENCE IN RESEARCH. BUT LIKE MOST YOUNG SCIENTISTS THEN, HE QUICKLY CAUGHT ON. HE PROBABLY COULD DO ANYTHING, MAKE MONEY IN WALL STREET, DO SCIENCE, WHATEVER. WE WERE BLESSED WITH MANY BRILLIANT PEOPLE AT THAT TIME. ANOTHER POST DOC AT THE TIME WAS HAROLD. IT WAS AN EXCITING TIME IN THE LAB TO WORK WITH THEM BOTH. THIS WAS A TIME AT WHICH YOUNG PHYSICIANS WERE BEING DRAFTED AND ONE WAY ONE COULD SERVE THE COUNTRY AND NOT GO TO VIETNAM WAS TO ENLIST IN THE COMMISSION CORP. AND BE ASSIGNED TO NIH. BOB WAS AMONG A SELECT GROUP OF YOUNG PHYSICIANS WHO WERE SELECTED FOR THAT PROGRAM AND ALL OF THEM WERE REALLY PRETTY AMAZING. SOME WERE EVEN MORE AMAZING THAN OTHERS. BOB WAS CLEARLY AT THE TOP OF THAT LIST. BOB LIKE OTHER YOUNG PHYSICIANS HAD NOT PLANNED TO DO RESEARCH, BUT HE TOOK TO IT VERY QUICKLY AND I MUST SAY BECAME VERY RAPIDLY VERY SKILLFUL AND TOOK OVER MANAGING THE PROJECT WHILE HE WAS WORKING IN THE LAB. SO THAT IS THE BACKGROUND FOR THE TALK WE'RE GOING TO HEAR TODAY. BOB HAS A BOOK ON THIS WHICH IS NEWLY PUBLISHED CALLED "A FUNNY THING HAPPENED ON THE WAY TO STOCKHOLM." SO WITH APOLOGIES PLEASE WELCOME BOB. . >> Bob Leftkowitz: I GAVE A LOT OF THOUGHT WHAT TO TITLE THIS TALK. INITIALLY I CAME UP WITH THE IDEA OF CALLING IT THE LEGACY OF THE YESSIN YELLOW BERETS. ON THE OTHER HAND I JUST PUBLISHED A MEMOIR CALLED "A FUNNY THING HAPPENED ON THE WAY TO STOCKHOLM" WITHOUT COVERING INFORMATION ABOUT THE YELLOW BERETS TELLS A LOT OF FUNNY AND QUIRKY AND MUCH MORE SERIOUS ANECDOTES ABOUT MY CAREER. I THOUGHT ABOUT USING THAT "A FUNNY THING HAPPENED ON THE WAY TO STOCKHOLM." THAT DOESN'T REALL REALLY CAPTURE IT EITHER. I DECIDED TO CALL IT A TALE OF TWO CALLINGS. A PRACTICING PHYSICIAN AND AS A SCIENTIST AS A TRUE CALLING. I KIND OF THINK I'LL GO WITH THAT. THEY ARE REALLY ELEMENTS OF ALL THREE TITLES. IN TERMS OF MY PROFESSIONAL DOINGS. THERE WERE REALLY TWO KEY POINT SES. POINTS. THE GENESIS AND MY DESIRE TO BE A PHYSICIAN WAS THIS MAN. HE WAS MY FAMILY PHYSICIAN. HE MADE HOUSE CALLS. I WORSHIPED HIM. I WOULD SAY BY THE TIME I'M ABOUT THIS OLD, IN THIS PHOTOGRAPH, MAYBE SEVEN OR EIGHT YEARS OLD. I HAD HAD NO DOUBT I WAS GOING TO FOLLOW IN HIS FOOT STEPS. I WAS ABSOLUTELY CAPTIVATED BY THE MAN. HE MADE HOUSE CALLS AND CAME WITH THAT BLACK BAG OF HIS. HE PRODUCED ALL THESE MAGICAL THINGS, A VIBRATING FORK, REFLEX HAMMER, PRESCRIPTION PAD. HE LAID ON HANDS AND YOU FELT BETTER. BECAUSE I COULDN'T EXPERIENCE IT AT THAT YOUNG AGE, I FELT A CALLING TO BE A PHYSICIAN. I NEVER WADED FROM THAT AND I WENT RIGHT THROUGH MY EDUCATION ALWAYS KNOWING I WAS GOING TO BE A PRACTICING DOCTOR. I ATTENDED THE BRONX HIGH SCHOOL OF SCIENCE. IT'S A REMARKABLE PLACE AND STILL EIGHTH. I'M THE EIGHTH NOBEL LAUREATE TO GRADUATE FROM THIS HIGH SCHOOL F. IT WERE A COUNTRY RATHER THAN A HIGH SCHOOL, IT WOULD BE 20TH ON THE LIST. THERE'S ONLY 20 COUNTRIES IN THE WORLD THAT HAVE MORE NOBEL LAUREATES THAN THIS ONE HIGH SCHOOL. I WENT ONTO COLUMBIA. AT NO POINT IN MY HIGH SCHOOL, COLLEGE OR MEDICAL SCHOOL CAREER DID I EVER DO ANY INDEPENDENT RESEARCH OR DEPENDENT RESEARCH ESPECIALLY IN MEDICAL SCHOOL WITH WHICH WE HAD CLEAR ELECTIVE PERIOD IT DO RESEARCH, I ALWAYS DID CLINICAL. I WAS TOTALLY FOCUSED ON BEING THE BEST PHYSICIAN I COULD. HERE IS A PICTURE OF MY MOM AND DAD. MY FATHER WOULD DIE ONLY TWO YEARS LATER OF HIS FOURTH MIE CARDIAL INFARCTION. OUR FAMILY HAD A HISTORY OF HEART DISEASE. MY DAD TOLD ME ON THIS DAY, IT WAS THE PROUDEST DAY OF HIS LIFE TO SEE ME GRADUATE FROM MEDICAL SCHOOL. I HAVE THOUGHT MANY TIMES SINCE WHAT HE MIGHT HAVE THOUGHT IF HE LIVED TO SEE WHAT CAME LATER. I WENT ONTO DO AN INTERNSHIP AND RESIDENCY AT COLUMBIA. THIS IS SOME OF MY INTERN CLASS. FUTURE ACADEMICS AND MYSELF. I WOULD HAVE HAPPILY WENT ON MY WAY TO CLINICAL PRACTICE EXCEPT FOR THE VIETNAM WHICH WAS RAGING. THERE WERE DEMONSTRATIONS AND EVEN RIOTS. THERE WAS AS A RESULT SUBSCRIPTION. FOR A LOT OF MEN OVER 18 THERE WAS A LOTTERY DRAFT. FOR PHYSICIANS THERE WAS NO LOTTERY. YOU WERE REFERRED AT THE END OF MEDICAL SCHOOL AND DRAFTED. THIS DOCTOR DRAFT MEANT THAT FOLLOWING YOUR INTERNSHIP, YOU WERE INDUCTED FOR TWO YEARS OF SERVICE IN THE ARMED FORCES DESTRUCTING YOUR PLANS FOR TRAINING IN A RO RESEARCH CAREER. THE PLAN ALLOWED YOU TO HAVE A FURTHER DEFERMENT AFTER GRADUATION. THE CHARACTERISTICS OF THAT PLAN ARE SHOWN HERE. IT WAS DEVELOPED DURING THE KREEN AKOREAN WAR. IT ALLOWED THE MILITARY TO DRAW UPON THE WORK FORCE AND PHYSICIANS AND ALLOWED SERVICES AS A COMMISSIONED OFFICER IN THE ARMY, NAVY, PUBLIC HEALTH SERVICE. THE PUBLIC HEALTH SERVICE OPPORTUNITIES WERE THE NIH. THE PROGRAM AT THE NIH FOR PHYSICIANS WHO WERE FORTUNATE ENOUGH TO GET INTO IT WAS CALLED THE ASSOCIATE TRAINING PROGRAM OR ATP WHICH BECAME KNOWN AS THE YELLOW BERETS WHICH WE'LL DISCUSS IN A MOMENT. YOU CAN IMAGINE HOW POPULAR THIS WAS. IT WAS AN OPPORTUNITY TO AVOID BEING IN THE ACTIVE WAR THEATER AND AT THE SAME TIME BE ASSIGNED TO A LABORATORY AT THE NIH. OF THE SEVEN HUNDRED OR SO ANNUAL MEDICAL GRADUATES A THIRD WOULD APPLY FOR THIS PROGRAM. THERE WAS A SHARP FUNNEL SUCH THAT IN THE END, IT WENT FROM ONE HUNDRED TO TWO HUNDRED PEOPLE WERE FORTUNATE ENOUGH TO GET THE CALL THAT THEY WOULD BE ASSIGNED TO THE NIH. FORTUNATELY FOR ME I WAS ABLE TO MEET THE STANDARD AND BE ACCEPTED INTO THE PROGRAM. IT WAS EXTRAORDINARILY COMPETITIVE. I HAD HIGH GRADES AND CAME FROM A TOP SCHOOL. I WAS ABLE TO GET INTO THE PROGRAM. THE PROGRAM BECAME KNOWN ALMOST IMMEDIATELY AS THE YELLOW BERETS. YOU MAY WONDER ABOUT THAT. OF COURSE IT WAS OBVIOUSLY INITIALLY MEANT AS A MONIKER, FRANKLY IT CAME TO BE SEEN ESPECIALLY BY THOSE OF US IN THE PRODPRPL APROGRAM AS A BATH BADGE OF HONOR . THE GENESIS OF THE TERM CAME FROM A PAI PARODY SONG IN 1966. A TUNE ROSE TO THE TOP OF THE POP CHARTS CALLED THE GREEN BERETS SPEAKING OF OUR HEROIC COMMANDO SPECIAL FORCES. IN THE SAME YEAR, BOB SEGER RECORDED A PARODY, THIS A PROTEST AGAINST PROTESTERS. HE WAS REFERRING NOT TO PHYSICIANS BUT FOR PEOPLE AVOIDING THE LOTTERY DRAFT. IN ANY CASE THAT WAS THE GENESIS OF THE YELLOW BERETS. THOSE OF US WHO WERE DRAFTED INTO THAT PROGRAM WERE COMMISSIONED AS LIEUTENANT COMMANDERS IN THE UNITED STATES PUBLIC HEALTH SERVICE. THAT CORRESPONDS TO A MAJOR IN THE ARMY. UPLIKE THIS GENTLEMAN IN THE UNIFORM, WE DID NOT WEAR UNIFORMS WE WORE WHITE COATS. WE WORE WHITE COATS GENERALLY AT WORK WHETHER IN THE CLINICS OR THE LABORATORIES. THE FACT THAT WE DIDN'T WEAR UNIFORMS LIKE THIS GUY, OCCASIONALLY LED TO SOME EMBARRASSING BUT ALSO AMUSING SITUATIONS. FOR EXAMPLE, THERE WAS A REGULATION ENFORCED AT THE TIME THAT IF YOU WERE ACTIVE DUTY MILITARY AS WE WERE IN UNIFORM, YOU COULD FLY ANYWHERE IN THE UNITED STATES STAND BY, BUT YOU HAVE TO BE IN UNIFORM. THAT WAS A NICE PERK. WHAT WE WOULD DO IS JOIN GROUPS OF SIX OR EIGHT GUYS AND CHIP IN FOR ONE BATTERED OLD UNIFORM. WHOEVER WANTED TO TRAVEL BY AIR, WOULD WEAR THE UNIFORM. IN A GROUP OF SIX OR EIGHT, THE HEIGHT RANGE WAS FIVE 'FIVE TO SIX 'FIVE. I WAS FORTUNATELY RIGHT IN THE MIDDLE. WE ALSO DIDN'T HAVE MUCH OF AN IDEA OF HOW TO SALUTE OR ANYTHING LIKE THAT. AN EXAMPLE OF A SOMEWHAT EMBARRASSING SITUATION OCCURRED TO A COLLEAGUE OF MINE WHO RELATED THIS STORY TO ME. HE WENT TO WASHINGTON NATIONAL TO FLY WEARING THE UNIFORM. HE WAS SITTING AT THE GATE AWAITING THE FLIGHT. AT THAT POINT HE SAW WHAT HE TOOK TO BE A SENIOR OFFICER WALKING BY AND OF COURSE, WE DIDN'T KNOW MUCH ABOUT MILITARY PROTOCOL BUT WE DID KNOW THAT IN THE PRESENCE OFFICER A MORE JUNIOR OFFICER IS TO STAND AND INITIATE A SALUTE. I HAD PRACTICED HOW TO SALUTE THE TWO TIMES I WAS IN UNIFORM. MY FRIEND A COLLEAGUE IN THE PUBLIC HEALTH SERVICE JUMPED UP AND PUT HIMSELF IN FRONT OF WHAT HE TOOK TO BE THIS UNIFORM SENIOR OFFICER WHO SEEMED TO HAVE A NUMBER OF DECORATIONS ON HIS UNIFORM AND DID HIS BEST IMITATION OF A CRISP SALUTE WHICH WAS IMMEDIATELY RETURNED BY THE SENIOR MAN. AT THAT POINT THEY STARTED TO CHAT AND MY FRIEND WAS CHATTING WITH HIM AND THE SENIOR MAN ASKED WHAT BRANCH OF THE SERVICE HE WAS IN. HE SAID UNITED STATES PUBLIC HEALTH SERVICE. HE SAID WHICH BRANCH ARE YOU IN. HE SAID, I'M NOT IN THE SERVICE AT ALL. I'M THE PILOT WAITING FOR YOUR PLANE TO ARRIVE. IN TERMS OF THE DUTIES OF THE CLINICAL ASSOCIATES, WE CARED FOR THE PATIENTS AND CONDUCTED MENTORED RESEARCH. THE AMOUNT OF CLINICAL VERSUS RESEARCH TIME VARIED PROGRAM TO PROGRAM. I SPENT 20 PERCENT OF MY TIME SERVING ON THE CLINICAL END OF ENDO CHRONOLOGY BRANCH. ALL SORTS OF FASCINATING DISEASES. 80% OF MY TIME WORKING WITH JESSE AND LEARNING HOW TO DO RESEARCH. AS YOU MIGHT EXPECT GIVEN THE FACT THAT THE VIETNAM WAR WAS SUCH A DRIVER OF FOLKS WANTING TO WORK IN THIS YELLOW BERET PROGRAM. IT PEAKED ABOUT 1970. THERE WAS A DRAMATIC DECLINE AFTER THE VIETNAM WAR ENDED IN 1973. MY MEMBERS AT THE NIH ARE SHOWN IN THIS SERIES OF PHOTOGRAPHS. HERE IS JESSE ROTH. HERE IS FILL GOURDON. HE WAS THE CLINICAL CHIEF OF THE ENDOCRINE SERVICE. I LEARNED A LOT OF ENDO CHRONOLOGY FROM HIM. I WAS 25 YEARS OLD WHEN I WENT TO THE NIH. I SAW THESE GUYS AS REALLY SENIOR GUYS. REAL OLD TIMERS BUT IN FACT THEY WERE ALL IN THEIR MID THIRTIES. THAT CAN BE NO DOUBT THAT I OWE THEM A HUGE DEBT OF GRATITUDE BECAUSE THEY SET ME ON MY WAY AS A SCIENTIST AND INTRODUCED ME TO A FIELD OF STUDY THAT WOULD BECOME MY LIFE'S WORK. I'M NOT GOING TO TALK ABOUT MY SCIENCE TO ANY SIGNIFICANT EXTENT TODAY. I DO THAT ON MANY OTHER OCCASIONS AND IT'S KIND OF FUN TO GET INTO SOME OTHER DIRECTIONS. TO GIVE YOU A SENSE OF WHAT IT WAS ALL ABOUT AT THE TIME, EARL WAS A FEW YEARS AWAY FROM WINNING HIS NOBEL PRIZE. THIS SLIDE IS TAKEN FROM HIS 1971 NOBEL. IT CAME FROM A PAPER OUT OF 1968. A KEY POINT I WANT TO MAKE ABOUT THIS SLIDE, IT WAS KNOWN THAT HORMONES COULD STIMULATE LEVELS. IT WAS SOUTHER LAND THAT THIS WAS BECAUSE HORM MOAN HORMONES WERE ABLE TO BIND DIRECTLY TO THE ENZYME AND ACTIVATE IT. THERE WAS NO CREDENCE GIVEN TO THE IDEA OF SOME INDEPENDENT RECEPTOR AS PART OF THE SYSTEM. THE IDEA OF RECEPTORS HAD BEEN ABOUT FOR DECADES BUT WAS VERY CONTROVERSIAL. TWO WHO BELIEVED IN THE IDEA THAT THERE MUST BE SPECIFIC RECEPTOR BINDING SITES WERE IRA AND JESSE. USING A SYSTEM THEY HAD BEEN HAD WORKING ON IN THE LAB FOR A WHILE WHICH WAS A ACTH REACTOR CARCINOMA I BEGAN LOOKING AT RECEPTORS USING A TECHNOLOGY THAT WAS NON EXISTENT AT THE TIME. IT WAS A VERY CHALLENGING PROJECT BUT IGNITED MY INTEREST AND PASSION FOR THE AREA. AFTER ABOUT A YEAR OF STRUGGLING TO GET MY FEET UNDER, THE RESEARCH WAS TOTALLY NEW TO ME. I HAD NO EXPERIENCE WITH IT AT ALL. I FINALLY BEGAN TO MAKE SOME HEAD WAY AND PUBLISHED MY FIRST PAPER AND A COUPLE MORE TO FOLLOW. OUR SUCCESS IN LABELING BINDING SITES IN ADRENAL CORTICAL TUMORS. IT WAS THAT WHICH SET ME ON MY WAY. BEFORE I LEAVE THESE EXPERIENCES AT THE NIH, I WANT TO GIVE A SPECIAL SHOUT OUT TO WHAT I'M CALLING THE CLASS OF 1968, THOSE OF US WHO WENT TO NIH FOR A TWO YEAR STINT. IRA MENTIONED THE REMARKABLE CALIBER OF THESE INDIVIDUALS BUT TO JUST GIVE YOU A SENSE OF THAT, LET ME SHOW YOU A COUPLE OF PHOTOGRAPHS. I SHOWED YOU BEFORE, THIS WAS THE STAFF OF -- I THINK WE WERE CALLED NIAMD AT THE TIME. THIS IS CROPPED FROM A LARGER PHOTO. NOT SHOWN IN THE PHOTOGRAPH BECAUSE HE WAS A FELLOW IN THE HEART INSTITUTE WAS JOE GOLDSTEIN. HERE IS ANOTHER GUY IN THE SAME CLASS. YOU MIGHT RECOGNIZE HIM. THAT'S TONY FA UC HI. WE MET AT THE NIH. THIS IS FROM THE 1990S WHEN WE SERVED ON THE COUNCIL OF ASSOCIATION OF AMERICAN PHYSICIANS. ONE LAST PHOTO BY MEANS OF REMINISCENCE, FOUR OF US FROM THE CLASS OF '68 WHEN WE HAPPENED TO BE AT A MEETING TOGETHER IN NEW YORK CITY TWO YEARS AGO. THAT'S ALMOST EXACTLY 50 YEARS LATER. IT WAS NOT A BAD CLASS. WHEN I FINISHED AT THE NIH IN 1970, THE RESEARCH AFTER A VERY DIFFICULT FIRST YEAR REALLY WAS TAKING OFF. THEY ADVISED ME TO EXTEND MY TIME AND CONTINUE WORKING. BY THEN I HAD ALREADY MADE A COMMITMENT TO CONTINUE MY CLINICAL TRAINING AT HARVARD AND THE MASSACHUSETTS GENERAL HOSPITAL. I FELT OBLIGATED TO DO THAT. I CAUGHT THE RESEARCH BUG AT NIH. I WAS UNDECIDED, I FELT THIS CALLING TO CLINICAL MEDICINE FOR AS LONG AS I COULD REMEMBER. THE IDEA OF ANYTHING OTHER THAN BEING A FULL TIME PRACTICING PHYSICIAN WAS STILL SOMETHING I COULDN'T WRAP MY HEAD AROUND. I WENT FOR A SENIOR RESIDENCY IN MEDICINE TO BE FOLLOWED BY A TWO YEAR CARDIOLOGY FELLOWSHIP SINCE CARDIOLOGY WAS THE FIELD I ALWAYS DREAMED OF WORKING IN. PERHAPS SUBCONSCIOUSLY INFLUENCED BY MY FATHER'S DISEASE. THIS IS A PHOTO OF ME WITH A BEARD WORKING AS A MEDICAL RESIDENT. INTERESTINGLY, I SHOULD POINT OUT IT WAS HERE AT THE MASSACHUSETTS GENERAL HOSPITAL IT WAS SIX MONTHS OF INTENSE CLINICAL WORK THAT I REALLY ENJOYED THAT I REALLY HAD MY EFIEPIPEPIPHANY. I REALLY MISSED THE LABORATORY. I REALIZED THAT I WAS CLEARLY GOING TO HAVE TO ALTER MY CAREER PLANS SO THAT THERE HAD TO BE A SIGNIFICANT RESEARCH COMPONENT TO IT. I DIDN'T KNOW QUITE HOW I WOULD DO THAT BUT THAT WAS A DECISION THAT I MADE. I SOUGHT OUT THE CHIEF OF CARDIOLOGY HIMSELF, A YELLOW BERET WHO WAS THE YOUNG CHIEF OF CARDIOLOGY. HE AGREED TO TAKE ME ON AND LET ME WORK IN HIS LABORATORY PRETTY MUCH ON WHATEVER I WANTED TO DO. FOR THE REMAINING SEVERAL YEARS AT THE MASS GENERAL I COMPLETED MY CLINICAL RESPONSIBILITIES WHILE AT THE SAME TIME BEGINNING TO WORK IN THE LAB AGAIN. IN 1973 I RECEIVED A FINE RESEARCH OFFER. HE WAS MY CHIEF AT DUKE FOR ALMOST A DECADE BEFORE LEAVING FOR THE NIH TO BECOME THE DIRECTOR. WHEN I WENT TO DUKE IN 1973, FIRST YEAR OR TWO, I REALLY DID SPLIT MY TIME VERY MUCH BETWEEN BEING A CLINICIAN AND GOING TO CLINICS AND WORKING IN THE LABORATORY. BUT VERY QUICKLY THE RESEARCH PROGRAM TOOK OFF, I HAD SWITCHED MY ALLEGIANCE TO WORKING ON ACTH RECEPTORS AND MADE THE DELIBERATE CHOICE, I WANTED TO WORK ON A RECEPTOR CLEARLY RELEVANT TO CARDIOVASCULAR DISEASE. THE CLEAR CHOICE WAS TO WORK ON THE BETA A ADRENERGIC RECEPTOR. AS MY RESEARCH TOOK OFF OVER THE PAST COUPLE YEARS I WENT TO 60% IN THE LAB TO 40% IN THE CLINIC. IN THREE TO FIVE YEARS I WAS SPENDING 90% OF MY TIME IN MY LABORATORY PRODPRAM. PROGRAM. I'M NOT GOING TO REALLY TALK ABOUT MY RESEARCH AT ALL. I WANT TO POINT OUT WHAT I SPENT MY CAREER DOING WAS TRYING TO FILL OUT THAT DIAGRAM, THAT BLACK BOX OF SIGNALING THAT HAD HAD SERVED THE BASIS FOR THE NOBEL LECTURE IN 1971. WDISCOVERED THIS HUGE FAMILY OF RECEPTORS. WE WERE DISCOVERING GENE PROTEINS AND THOSE TWO BODIES OF WORK WERE VERY COMPLIMENTARY. I WAS FASCINATED BY THIS PROCESS OF RECEPTOR KE DECENTRALIZATION. KINASES LEADING TO THE BINDING OF BETA WHICH BLOCK FURTHER SIGNALING BY THE GENE PROTEIN BY BLOCKING GENE PROTEIN INTERACTION WITH THE RECEPTORS. IN THE YEARS AFTER THAT WE WERE ABLE TO LEAD TO A WIDE VARIETY OF OTHER THINGS. FROM MOLECULES WE DISCOVERED AS A SHUT OFF MECHANISM, THEY SERVE AS ALTERNATIVE IT THE GENE PROTEINS. MORE RECENTLY WE FOUND THERE ARE DRUGS THAT ARE ACTUALLY ABLE TO STIMULATE THE RECEPTORS AND ONLY STIMULATE SIGNALLY EITHER DOWN THE GENE PROTEIN PATH OR ONE AND NOT THE OTHER. THAT OPENED UP THE POSSIBILITY OF DEVELOPING A WHOLE NEW TYPE OF DRUG CALLED A BIASED AGONIST. THE FIRST OF THE OA OPIOID RECEPTOR WHICH THE FDA APPROVED JUST LAST YEAR. THIS FAMILY OF RECEPTORS THAT WE DISCOVERED WAS SO HUGE TO INCLUDE A THOUSAND DIFFERENT RECEPTORS IN HUMANS INCLUDING ONE THAT'S YOU'RE FAMILIAR WITH ALL THE HORMONES PARA THYROID AND ON AND ON. ALSO OF COURSE, SMELL RECEPTORS, TASTE RECEPTORS. IT'S A REMARKABLE FAMILY. RELATIVELY ACCESSIBLE TO DEVELOPMENT OF THERAPEUTICS AND DRUGS THAT FIT REALLY NICELY INTO THE SEVEN MEMBRANES SPANNING BARREL FORMED BY THE POLYPEPTIDE CHAIN OF RECEPTORS. TODAY THERE ARE 700FDA DRUGS THAT COUPLE GENE RECEPTORS ACCOUNT FOR ABOUT A THIRD OF THE FDA APPROVED DRUGS. I WANT TO SAY SOMETHING ABOUT THE REMARKABLE LEGACY OF THE LETTER AS. IN 1998 WHICH THIS DATA WAS COMPILED ALMOST A QUARTER OF ALL PROFESSORS AT HARVARD HAD BEEN YELLOW BERETS. 20 PERCENT OF ALL CLINICAL CHAIRS AT HARVARD HAD BEEN YELLOW BERETS. DUKE, 15. ALMOST 30% OF ALL DIVISION CHIEFS OF DEPARTMENT OF MEDICINE HAD BEEN YELLOW BERETS. UNFORTUNATELY THIS WAS THE ONLY DATA I COULD REALLY FIND. IT'S 15 YEARS OLD. THESE NUMBERS ARE MUCH MUCH HIGHER. AT THAT TIME 15 YEARS AGO 64 YELLOW BERETS HAD BEEN ELECTED TO THE NIH. FOUR NIH DIRECTORS. TEN INSTITUTE DIRECTORS. REALLY A REMARKABLE LEGACY. THIS STUDY SHOWED THAT YELLOW BERETS WERE THREE TIMES AS LIKELY TO BECOME DEANS, TWICE AS LIKELY TO BECOME DEPARTMENT CHAIRS, ONE AND A HALF TIMES AS LIKELY TO ACHIEVE FULL PROFESSOR RANKS. PERHAPS, YOU KNOW, JUST THE MOST REMARKABLE THING OF ALL IS THE WHOLE BUSINESS OF NOBEL LAUREATES. I LOOKED INTO THIS A COUPLE OF YEARS AGO BECAUSE I HAD FOUND THIS VERY INTERESTING. THIS IS A DIAGRAM I MADE UP SHOWING THE FACT THAT OF THE YELLOW BERETS THAT SERVED BETWEEN 1964 AND 172, THE EIGHT YEAR PERIOD CORRESPONDING TO THE PEAK OF THE VIETNAM WAR, TEN WENT ONTO WIN THE NOBEL PRIZE. I HAVE THOSE TEN INDIVIDUAL NAMES EACH INCLUDED IN A BLUE RECTANGLE IN THIS YELLOW BAR. OKAY? AND THEN ABOVE THEM I'VE CONSTRUCTED PARTIAL FAMILY TREES OF WHO MENTORED THEM AND WHO MENTORED THEIR MENTORS ET CETERA. IN THIS DIAGRAM EVERY RECTANGLE COLORED BLUE IS A NOBEL LAUREATE. WHAT YOU CAN SEE RIGHT OFF THE BAT FOR FOUR OF THE LAUREATES SHOWN HERE THEY ACTUALLY TRAINED IN THE LAB FOR A NOBEL LAUREATE. FOR THE OTHER SIX OF US IN NO CASE DO YOU HAVE TO GO FURTHER BACK THAN A SCIENTIFIC GRANDPARENT TO FIND A NOBEL LAUREATE. IF YOU LOOK GOING EVEN FURTHER BACK YOU CAN SEE THAT ABOUT HALF OF THE PEOPLE IN FAMILY TREE ARE NOBEL LAUREATES. SOME OF THE LINEAGES ARE PRETTY AMAZING. LOOK AT THIS ONE HERE. HERE OUT OF ABOUT SEVEN GENERATIONS DOWN TO STANLEY AND MICHAEL BROWN. THE ONLY ONE NOT A NOBEL LAUREATE IS EARL WHO BY THE WAY TRAINED TWO NOBEL LAUREATES. HE ALSO TRAINED IRA WHO IN TURN TRAINED MYSELF. ANOTHER THING THAT'S FASCINATED. IF YOU GO BACK ENOUGH GENERATION GENERATIONS YOU COME TO NOBEL PRIZE WINNING PHYSICISTS. IT'S REALLY REMARKABLE. IT SPEAKS VERY MUCH. EXCUSE ME THAT'S MY PHONE RINGING WHICH I FORGOT TO TURN OFF. WE'LL HAVE TO LET THAT RING BUT IT SHOULDN'T LAST TOO LONG. I THINK IT SPEAKS VERY MUCH TO THE ISSUE OF LINEAGE IN SCIENCE. CLEARLY THERE ARE THINGS WHICH ARE TRANSFERABLE FROM ONE SCIENTIST TO ANOTHER. I THINK MANY OF THESE ARE SUBTLE. THEY ARE NOT THINGS YOU CAN READ IN A BOOK. SUBTLE THING ABOUT HOW TO CHOOSE AN IMPORTANT SCIENTIFIC PROBLEM. WHETHER TO PERSIST IN PURSUING SOMETHING OR GIVE IT UP. NO WHEN TO HOLD THEM, KNOW WHEN TO FOLD THEM. KNOW WHEN TO PER SUE AN UNEXPECTED ANNOYING RESULT THAT COMES UP OR DISMISS IT AS AN UNNECESSARY DISTRACTION. ALL OF THESE KINDS OF SUBTLE THINGS ARE THINGS THAT ARE PASSED DOWN FROM ONE GENERATION TO ANOTHER FROM ONE SCIENTIST TO ANOTHER. IN MY MIND THIS HAS A LOT TO DO WITH THESE REMARKABLE LINEAGES IN SCIENCE. THE QUESTION THAT ALWAYS COMES UP IS WHY WAS THIS PROGRAM SO REMARKABLY SUCCESSFUL? ONE OF THE BEST DISCUSSIONS OR DISSECTIONS OF THIS WAS DONE BY MIKE BROWN AND JOE AND PUBLISHED IN A PIECE THEY PUBLISHED IN SCIENCE WHICH I HIGHLY RECOMMEND IN 2012. FIRST THING THEY ASKED IS WHAT WERE THE CONDITIONS THAT LED TO THIS REMARKABLE OUT POURING OF TOP SCIENTISTS AND NOBEL LAUREATE FROM THIS YELLOW BERET PROGRAM. THE VIETNAM WAR DROVE SUCH INTENSE COMPETITIONS. OUTSTANDING MENTORS BOTH PH.D. AND MD. EVENING COURSES IN MANY CUTTING EDGE AREAS. FOCUS ON FUNDAMENTAL RATHER THAN TRANSLATIONAL RESEARCH WITH DISCOVERIES STRONGLY INFLUENCING DRUG DEVELOPMENT, MEDICAL PRACTICE AND HUMAN HEALTH. BASIC SCIENCE WAS AT THE CORE OF MEDICAL EDUCATION. THE FACT THAT MEDICAL STUDENTS WERE TAUGHT THE JOY OF FINDING NEW FACTS AND OVERTURNING OLD ONES. TRYING TO ANALYZE WHAT HAD CHANGED OVER THE PAST 50 YEARS. THERE'S NO SERVICE O OBLIG OBLIGATION. IT'S RESTRICTED TO A DISEASE RELEVANT FACTS WITH LITTLE HISTORIC RESEARCH ON WHERE THE FACTS CAME FROM. SERVICE ROLE MODELS. PROGRESS IN MEDICINE RESTS ON A FUNDAMENTAL UNDERSTANDING OF PHYSIOLOGY HAS BEEN LARGELY LOST. A CURIOSITY IN DRIVEN SCIENCE HAS BEEN LOST IN THE HOPES OF ANSWERING FUNDAMENTAL QUESTIONS. WHICH OF ANY OF THESE CAN BE FIXED, IF THAT'S THE APPROPRIATE WORD, IS A SUBJECT AT WHICH WE CAN DISCUSS AT GREAT LENGTH. I TOLD YOU THAT ONE OF THE TITLES I CONSIDERED WAS THE SAME AS MY BOOK "A FUNNY THING HAPPENED ON THE WAY TO STOCKHOLM." I DID FEEL THE NEED TOWARD THE END OF THIS PRESENTATION TO NOTE A FEW SOMEWHAT AMUSING STORIES THAT HAVE HAPPENED. NOT ALL OF THEM WERE ALL THAT AMUSING AT THE TIME. I WAITED UNTIL I WAS ALMOST 70 YEARS OLD TO WIN THE NOBEL PRIZE. I WAS 69. THERE WERE SOME NEAR MISSES WHEN THE GENE PROTEINS WERE AWARDED AND PERHAPS TH OLFACTORY SYSTEM ET CETERA. I TOOK A LOT OF RIBBING ABOUT IT. PEOPLE WERE FOREVER ASKING ME, DO YOU THINK YOU'LL WITHIN. PARTICULARLY MORTIFYING WAS THIS STORY ON THE FRONT PAGE OF THE SUNDAY LOCAL PAPER HERE. FRONT PAGE, FIRST SECTION, SUNDAY PAPER ABOVE THE FOLD, LEFT COLUMN, YOU SEE THE STORY. THIS IS IN OCTOBER THE WEEK AFTER THEY JUST ANNOUNCED NOBEL PRIZES. NOBEL CALLING, ALAS, NOT THIS YEAR. HOW MANY PEOPLE DO YOU KNOW WHO GOT ON THE FRONT PAGE OF THE NEWSPAPER WITH A PHOTOGRAPH FOR NOT WINNING A NOBEL PRIZE? THAT WAS A GUT TO MY REACTION AFTER READING THIS STORY. NINE YEARS LATER, I DID WIN THE PRIZE. I EVENTUALLY WON IT. HOW DID THE LOCAL PRESS COVER THAT. HERE IS A LOCAL NEWSPAPER. WHY IS THIS MAN SMILING. HE FINALLY WON THE NOBEL PRIZE. THAT WAS AN INTERESTING THING. IT WAS EXCITING WHEN I DID FINALLY WIN. I'LL NEVER FORGET THIS. THEY BROUGHT OUT A CAKE FOR ME WHEN I GOT TO THE LAB. THEY MISSPELLED MY NAME THAVMENT WA.THAT WAS A COMMON THING IN MY LIFE. AS TO WHY I FINALLY WON THE MOBILE NOBEL PRIZE, I WILL CA CALL YOUR ATTENTION TO THIS ARTICLE. THIS IS A REAL ARTICLE THAT APPEARED IN THE OCTOBER 10TH, 2012 NEW ENGLAND JOURNAL OF MEDICINE WHICH IRONICALLY IS THE STAY I RECEIVED THE CALL FROM STOCKHOLM ABOUT THE PRIZE. I WAS NOT AWARE OF THIS ARTICLE UNTIL SIX MONTHS LATER. IT'S A PLOT ON THE X AXIS OF CHOCOLATE CONSUMPTION KILOGRAMS PER YEAR PER CAPITA VERSUS THE Y AXIS, NUMBER OF LAUREATES. YOU CAN SEE THAT THERE'S A HIGHLY SIGNIFICANT STRAIGHT LINE CORRELATION RELATIONSHIP SHOWN HERE. INTERESTINGLY THE ONLY ONE THAT'S OFF THE LINE IS SWEDEN WHICH HAS GOT MORE PRIZES THAN THEY DESERVE BASED ON THE AMOUNT OF CHOCOLATE. IT RAISES THE ISSUE OF WHETHER THEY'VE BEEN FAVORING THEIR OWN. WHY DO I SHOW THIS? THIS IS A TRUE STORY. I RELAYED IT IN MY MEMOIR. I HAVE LOVED DARK CHOCOLATE FOR MANY YEARS. I ALSO HAVE CORONARY DISEASE. TWO TIMES A WEEK I ALLOW MYSELF A SMALL SQUARE OF DARK CHOCOLATE WHICH I LOVE. I SAID TO MY WIFE. MY LIMB IMY LIPIDS ARE EXEMPLARY. WHY AM I LIMITING MYSELF TO DARK CHOCOLATE. I SAID, I'M GOING TO HAVE IT SEVEN NIGHTS A WEEK. THAT'S GOING TO BE MY SNACK. I BEGAN EATING DARK CHOCOLATE ON A NIGHTLY BASIS. TWO YEARS LATER, I WON THE NOBEL PRIZE. WHAT CAN ONE CONCLUDE FROM THAT. THERE'S OBVIOUSLY A THRESHOLD DOSAGE WHICH I HAD FINALLY AFTER ALL THESE YEARS EXCEEDED. I WANT TO CLOSE BY TELLING YOU A COUPLE QUICK STORIES ABOUT SOME OF THE INTERESTING PEOPLE I HAVE MET IN RELATION TO HAVING WON THE NOBEL LAUREATE. I MET THE PRESIDENT OF THE UNITED STATES OBAMA. HE HAD A TRADITION OF MEETING NOBEL LAUREATES IN THE OVAL OFFICE WHEN THEY WERE ON THEIR WAY TO STOCKHOLM TO RECEIVE THE PRIZES. HE WAS VERY ENGAGING, HE WAS PLEASANT TO TALK TO. I REMEMBER HIM SAYING, I REALLY RELATE TO YOU FOLKS. THERE WERE FIVE OF US IN MY GROUP. I RELATE TO YOU GUYS BECAUSE AS YOU KNOW, LIKE YOU I TOO AM A NOBEL LAUREATE. THERE'S ONE KEY DIFFERENCE, HE SAID. YOU EARNED YOURS. YOU MAY REMEMBER WHEN HE GOT THE PRIZE DURING HIS FIRST YEAR IN OFFICE BEFORE HE HAD A CHANCE TO DO ANYTHING. ANOTHER AMAZING EXPERIENCE I HAD WAS TO GET TO KNOW COACH K. THE WINNINGEST COACH IN N AA CP BASBASKETBALL. HE SAID, BOB, I REALLY RELATE TO WHAT YOU'VE ACCOMPLISHED. I BROUGHT DUKE OUR FIRST CHAMPIONSHIP. YOU BROUGHT US OUR FIRST NOBEL PRIZE. I WOULD LIKE YOU TO COME DOWN AND BE HONORED BY THE FANS. I DID THE VERY NEXT WEEK. THERE IS ME STANDING BY THE COURT BEING CHEERED BY THE FANS. IT'S THE STUDENTS WHO SIT CLOSEST TO THE FIELD. AS I STOOD THERE AND THEY HAD JUST PRESENTED ME, THE TEAM DID, WITH THIS DUKE JERSEY WITH MY NAME ON THE BACK AND THE NUMBER ONE. THE STUDENTS ARE CHEERING WILDLY. THERE'S A LONG TRADITION IN THE STADIUM FOR THE STUDENTS TO CHANT CUTE THINGS IN UNISON. USUALLY AT OPPOSING PLAYERS LIKE WHEN THEY ARE FOULING OUT OF A GAME OR SOMETHING LIKE THAT. I COULD HEAR THE STUDENTS SAYING SOMETHING. THEY WERE ALL POINTING AT ME. I COULDN'T MAKE OUT WHAT THEY WERE SAYING. IT CAME INTO FOCUS. THEY WERE CHANTING, HE'S SO SMART. I PUT UP MY HANDS. IT WAS REALLY QUITE A HIGH. THERE'S MY JERSEY AND MY WIFE NEXT TO ME. A FRIEND OF MINE. WE'VE GOTTEN TOGETHER ON MANY OCCASIONS SINCE AN DONE SOME FUNDRAISING TOGETHER. THAT'S NOT THE END OF THIS STORY. THREE YEARS LATER IN 2015 THE TEAM WINS THEIR FIFTH NATIONAL CHAMPIONSHIP WITH THE COACH. THEY ARE INVITED TO THE WHITE HOUSE TO BE HONORED BY OBAMA WHO WAS A HUGE BASKETBALL FAN. THIS PICTURE A COUPLE DAYS AFTER THAT APPEARS IN THE DUKE CHRONICLE, THE STUDENT NEWSPAPER. IT SHOWS THE PRESIDENT, AND COACH K, PRESIDENT BROAD HEAD AND ARE PRESENTING OBAMA WITH A JERSEY. AS YOU CAN SEE, IT'S GOT THE NUMBER ONE. THIS GAVE ME PAUSE. I DIDN'T LIKE IT. THAT'S MY NUMBER. I'M NUMBER ONE. THERE'S A LONG STANDING TRADITION AT DUKE THAT WHENEVER A STAR BASKETBALL PLAYER JERSEY NUMBER IS RETIRED, THEY HANG IT AND MAKE A SUPERSIZED VERSION OF IT. IT'S A LONG STANDING TRADITION. FOLLOWING THAT AFTER I RECEIVED MY JERSEY, I HANG IT FROM THE RAFTERS IN MY OFFICE. I'M FRAMED BETWEEN MY TWO MOST PRIZED PROFESSIONAL POSSESSIONS. MY NOBEL PRIZE SHOWN HERE AND MY JERSEY. THE IDEA THAT HAVING RETIRED MY JERSEY NUMBER, THEY WENT OUT GIVING IT TO SOMEONE ELSE, I WAS NOT AMUSED. BY THEN I KNEW THE COACH VERY WELL. I IMMEDIATELY TEXTED HIM THIS PHOTOGRAPH, I SAID COACH WHAT ARE YOU DOING. AS YOU CAN SEE THAT NUMBER IS RETIRED AND HANGING FROM THE RAFTERS IN MY OFFICE. I'M NOT VERY HAPPY ABOUT THIS. WITHIN MINUTES HE TEXTED BACK. HE SAID, BOB, WHAT WERE WE GOING TO DO, IT'S THE PRESIDENT OF THE UNITED STATES FOR GOODNESS SAKE. HE SAID PLEASE BEAR WITH ME. YOU KNOW AND I KNOW, YOU'RE THE REAL NUMBER ONE. WHAT COULD I SAY? I SAID, COACH, ALL IS FOR GIVING. FORGIVE FOR GIVEN. THE LAST STORY I WANT TO TELL YOU IS WHEN YOU WIN A NOBEL PRIZE, YOU GET INVITED TO THROW THE FIRST PITCH. I WAS INVITED TO YANKEE'S STADIUM. THEY SUBSTITUTED FOR ME. FORTUNATELY I WAS ALSO ASKED TO THROW OUT THE FIRST PITCH AT A BULLS GAME. I'M SHOWN HERE AT THE CEREMONY, THEY ARE A VERY WELL KNOWN TRIPLE A DIVISION MINOR LEAGUE TEAM. TO THE LEFT IN THIS PHOTOGRAPH IS WILLY BULL, THE TEAM MASCOT, MYSELF, PRESIDENT OF THE NATIONAL ACADEMY OF MEDICINE. MAYOR BILL BELL. IT WAS HONORING ME ET CETERA. YOU CAN SEE THE JUMBO TRON IN THE BACKGROUND. I PRACTICED LONG AND HARD FOR THIS OPPORTUNITY. I HAD TWO MONTH IT GET READY. I WAS REALLY PRACTICING VERY HARD FOR THE OPPORTUNITY TO THROW OUT THIS FIRST PITCH P. LET ME SHOW YOU WHAT HAPPENED. TWO MONTHS OF PRACTICE. PERFECT STRIKE. PERFECT STRIKE. I THINK YOU WANT TO SEE THAT AGAIN. I KNOW I DO. THIS HAS BEEN VIEWED 397 TIMES BY MYSELF. PERFECT STRIKE. ALAS I ACTUALLY SENT THAT TO MY GOOD FRIEND TONY FAUCI. THE MORNING AFTER HE THREW HIS DISASTROUS FIRST PITCH. AFTERWARDS I FELT KIND OF GUILTY GUILTY. THEY CAME OUT AND GAVE ME THE BALL. THEY PUT THAT BALL IN MY MITT. DOC THAT WAS ONE HELL OF A THROW. THAT WAS ABOUT AS GOOD AS IT GETS. THIS IS MY LAST SLIDE, IT SHOWS THREE OLD ROCKERS STANDING TOGETHER. I'M THE ONLY ONE STANDING. THE OTHER TWO ARE KNEELING IN FRONT OF ME IN A FAUX DEMONSTRATION OF RESPECT AND ADMIRATION. THAT'S PETER GABRIEL ON THE LEFT AND STING ON THE RIGHT. IF YOU WANT TO KNOW WHAT IN THE WORLD WAS THIS ALL ABOUT, I'M NOT GOING TO TELL YOU. YOU HAVE TO READ MY MEMOIR "A FUNNY THING HAPPENED ON THE WAY TO STOCKHOLM." YOU CAN GET IT IN THE BOOKSTORE. IF YOU'RE INTERESTED IN READING MORE ABOUT OR HEARING MORE ABOUT THE YELLOW BERET PROGRAM, I KNOW YOU HEARD FROM RAY GREEN BERG IN HIS BOOK, THAT'S ALSO ON DISPLAY IN THE BOOKSTORE. THERE'S A FOUR PART POD CAST CALLED SOLDIERS OF SCIENCE WHICH INTERVIEWS A NUMBER OF US, MANY FROM THE CLASS OF '68 TO TELL THE STORY. HERE ARE VERSIONS OF OURSELVES. THESE ARE THE PHOTOGRAPHS THAT WE SENT IN OUR APPLICATIONS TO THE PROGRAM TONY FA UC HI. I DON'T KNOW WHO THIS IS. THAT'S MYSELF. THANKS VERY MUCH FOR YOUR ATTENTION. I'VE ENJOYED SHARING SOME OF MY STORIES WITH YOU. I HOPE YOU HAVE ENJOYED LISTENING TO THEM. >> : I WANT TO THANK YOU -- CAN YOU HEAR ME, BOB. . >> Bob Leftkowitz: I CAN HEAR YOU LOUD AND CLEAR. >> : I WANT TO THANK YOU SO MUCH FOR A VERY INTERESTING AND WELL TOLD -- I HAVE A FEW COMMENTS AND THEN WE HAVE SOME QUESTIONS. THE OTHER THING THAT -- WHAT I LEARNED FROM EARL SOUTHER LAND -- BECAUSE I HAD BEEN DOING REA SEARCH FORESEARCH FOR IS HOW TO FORMULATE A QUESTION AND DESIGN AN EXPERIMENT THAT COULD BE DONE. IT WAS IN MY GRASP. THOSE ARE THE THINGS I THANK EARL FOR ALL THE TIME. MAYBE HE LEARNED THAT FROM THE LONG LIST BEFORE HIM. THE OTHER THING THAT STRUCK ME ALWAYS, BOB WAS THAT THE SERENDIPITY. HERE WE WERE ALL THINKING ABOUT RECEPTOR AND ONLY SERENDIPITY BROUGHT US ALL TOGETHER. OKAY. NOW I'M GOING TO SWITCH AND GO TO SOME OF THE QUESTIONS. THE FIRST ONE WAS WHO ARE THE TWO WOMEN IN THAT EARLY PICTURE WITH YOU AND ME AND FILL GOURDON. ONE IS LESLIE -- I'M NOT SURE WHO THE OTHER ONE WAS. SHE DIDN'T WORK WITH ME. I'LL CHECK WITH PHIL. IT MUST HAVE BEEN SOMEONE IN THE DIDIABETES GROUP. WHAT ADVICE DO YOU HAVE FOR YOUNG RESEARCHERS TODAY TO MAKE A DIFFERENCE IN THEIR WORK. OR HOW SHOULD ONE CHANGE TRAINING PHYSICIAN IT RECREATE THE SUCCESSES OF 50 YEARS AGO. LESSONS IN MEDICAL HISTORY THAT YOU ENCOURAGE. THEY ARE ALL THE SAME QUESTION. THEY WANT YOU TO SPEAK WISELY ON THIS POINT. . >> Bob Leftkowitz: AS WE TALKED ABOUT, THIS IS A VERY COMPLEX ISSUE. ONE OF THE THINGS THAT I HAVE FELT FOR A LONG TIME, IT'S A BROADER ISSUE THAN JUST PHYSICIAN SCIENTISTS IS THAT I REALLY THINK THERE SHOULD BE A DRAFT. BY WHICH, I MEAN I THINK THERE SHOULD BE MANDATORY SERVICE FOR TWO YEARS OF ALL CITIZENS. I FELT THAT WAY FOR A LONG TIME. MORE AND MORE KIDS, THOSE OF US INVOLVED IN EDUCATION KNOW THIS. MORE AND MORE KIDS EITHER TAKE A YEAR OUT DURING THEIR FOUR YEARS OF COLLEGE OR DO ONE, TWO, OR THREE GAP YEARS BEFORE GOING ONTO FURTHER EDUCATION. IF WE HAD FORMAL PROGRAMS TO INTEREST KIDS IN BIOMEDICAL RESEARCH, THAT WOULDN'T BE AS EFFECTIVE IN A DRAFT OR A WAR BUT IT WOULD BE USEFUL. SOME OF THE OTHER ISSUE THAT'S WERE RAISED IN THOSE SLIDES WOULD BE IN MEDICAL SCHOOL TO REORIENT WHAT'S GOING ON. THOSE OF US WHO WERE INVOLVED IN MEDICAL EDUCATION HAVE WATCHED THIS OVER THE LAST 50 YEARS. JUST AS MIKE AND JOE SAID, THERE'S BEEN A PROGRESSIVE ERODING OF THE IMPORTANCE OF BASIC SCIENCE IN MEDICAL EDUCATION. IN MANY PLACES IT'S DOWN TO ONE YEAR. ALAS DUKE HAS BEEN A PIONEER, IF I CAN USE THAT WORD IRONICALLY IN DOING THAT. WE'VE HAD ONE YEAR OF BASIC SCIENCE SINCE BEFORE I GT THERE. GOT THERE. I REALLY THINK AN ADMIRATION AND ENJOYMENT FOR BASIC SCIENCE IS SOMETHING THAT WOULD REALLY BE HELPFUL. THE QUESTION ABOUT YOUNG SCIENTISTS, TO ME, I'VE GOTTEN MORE AND MORE INTERESTED IN THE WHOLE IDEA OF MENTORING. THAT'S WHY I DREW UP THAT LINEAGE CHART. WHAT IRA SAID ABOUT SOME OF THE THINGS HE LEARNED FROM STATON IS EXACTLY THE KIND OF THING THAT I'M TALKING ABOUT. IT'S THE KIND OF THING THAT YOU CAN'T WRITE DOWN FOR SOMEBODY. YOU CAN ONLY SHOW SOMEBODY. THAT'S WHAT MENTORING IS. YOU HAVE TO ROLE MODEL IT. WHEN YOU ARE MENTORED BY SOMEBODY. YOU'RE IN THEIR LAB FOR A FEW YEARS. MAYBE NOT IN THE LAB, YOU MOVE FURTHER ALONG. YOU WATCH THEM. IT'S AN APPRENTICESHIP. THE THINGS I LEARNED FROM IRA, WERE NOT BECAUSE HE SPECIFICALLY TOLD ME. I WATCHED WHAT HE WAS DOING. I LOOKED AT WHAT HE WORKED ON. I CAN'T TELL YOU HOW MANY TIMES I TOLD PEOPLE THAT. THERE'S NO MORE IMPORTANT THING, DECISION THAT ANY SCIENTIST EVER MAKES THAN WHAT DO YOU WORK ON? WHAT'S YOUR PROBLEM? TO ME IT'S LIKE BEING AN ART CRITIC OR LI LITERARY CRITIC. WHEN I ATTEND SIM NARES OU NARES OUT SEMIN ARS OUT SIDE OF MY FIELD, WHEN I'M PRESENTING, IS THIS A GOOD PROBLEM. I CAN'T BELIEVE WHY SOMEBODY WOULD BE DOING WORK ON THIS. SOMETIMES I BELIEVE. OTHER TIMES I SAY, YEAH, THIS IS A REALLY GOOD PROBLEM. IS THIS A GOOD PROBLEM? IS IT TRACTABLE? IT MAY BE A FABULOUS PROBLEM? THERE'S A SPECTRUM AND IT DETERMINES HOW YOU FAIL OR HOW YOU SUCCEED. ON ONE END ARE PROBLEMS WHICH ARE ESSENTIALLY TRIVIAL. YOU WILL SOLVE THE PROBLEM, GET THE DATA, PUBLISH, ET CETERA. NOBODY WILL CARE AND NOBODY WILL CITE BECAUSE IT WAS A TRIVIAL PROBLEM WITH A TRIVIAL ANSWER.