>> GOOD AFTERNOON, EVERYONE AND WELCOME TO THE 2018 LAMONTAGNE MEMORIAL LECTURE. TODAY WE HONOR THE MEMORY OF AND CONTRIBUTION OF MY DEAR FRIEND AND COLLEAGUE, DR. JOHN LAMONTAGNE WHO JOINED NIAID IN 1976 AS THE INSTITUTE'S FIRST INFLUENZA PROGRAM OFFICER. JOHN'S SUCCESS AT DRAWING ATTENTION TO INFLUENZA AND UNDER STUDIED INFECTIOUS DISEASE AT THAT TIME, EXEMPLIFIED HIS SKILL AT MARSHALING INTERNATIONAL RESEARCH EFFORTS TO ARRANGE A CRITICAL, GLOBAL HEALTH ISSUES, INCLUDING MALARIA, TUBERCULOSIS AND HIV/AIDS. JOHN HELD VARIOUS POSITIONS IN NIAID'S DIVISIONS OF MICROBIOLOGY AND INFECTIOUS DISEASES AND ROSE TO BECOME DIVISION DIRECTOR FOR 11 YEARS IN 1998. I APPOINTED HIM AS MY PRINCIPLE DEPUTY DIRECTOR, A POSITION HE HELD UNTIL HIS UNTIMELY DEATH IN 2004. JOHN IS REMEMBERED FONDLY BY ALL OF US WHO KNEW HIM FOR HIS WARMTH, SCIENTIFIC VISION, AND HIS DEDICATION TO GLOBAL HEALTH RESEARCH AS WELL AS HIS BREATHS OF RESEARCH INTERESTS. WE ARE PARTICULARLY PLEASED THIS AFTERNOON TO HAVE WITH US IN THE AUDIENCE, JOHN'S WIFE, ELAINE LAMONTAGNE, THANK YOU FOR BEING HERE, ELAINE. [ APPLAUSE ] SO, OUR SPEAKER TODAY, DR. DAVID MORENS HAS SIMILARLY WIDE-RANGING INTERESTS. A DETROIT NATIVE, HE RECEIVED HIS UNDERGRADUATE AND MEDICAL DEGREES FROM THE UNIVERSITY OF MICHIGAN AND COMPLETED HIS RESIDENCY IN PEDIATRICS AT THE UNIVERSITY OF HAWAII AND HONOLULU AND THE UNIVERSITY OF MICHIGAN MEDICAL CENTER IN AN HARBOR. IN 1976, DAVID JOINED CDC'S EPIDEMIC INTELLIGENCE SERVICE, REMARKABLY IN THAT YEAR ALONE HE BECAME DIRECTLY INVOLVED IN INVESTIGATING THREE EMERGING DISEASES, LEGIONNAIRES DISEASE, EBOLA VIRUS DISEASE, AND SWINE FLU. A FEW YEARS LATER, DAVID HELPED INVESTIGATE THE FIRST CASES OF A MYSTERIOUS NEW DISEASE THAT CAME TO BE KNOWN AS AIDS. HE ALSO SPENT TWO YEARS AS A MEDICAL OFFICER WITH THE CDC RESEARCH PROJECT IN SIERRA LEONE AND BETWEEN 1982 AND 1998, DAVID WAS ON THE FACULTY OF THE UNIVERSITY OF HAWAII. HE JOINED US HERE AT NIAID IN 1998 AS A MEDICAL OFFICER AND IS CURRENTLY ONE OF MY SENIOR ADVISORS. DAVID HAS A LONGSTANDING INTEREST IN THE HISTORY OF PUBLIC HEALTH AND MEDICINE AS EVIDENCE BY HIS WORD NARY LIST OF PUBLICATIONS WHICH SPANS GREAT BREATH GEOGRAPHICALLY AND CHRONOLOGICALLY. HE WRITTEN ABOUT THE PLAGUE OF ATHENS OF 430BC, THE BIRTH OF EPIDEMIOLOGY DURING THE 1832 PARIS CHOLERA EPIDEMIC AND THE 1875 MEASLES EPIDEMIC THAT KILLED 40,000 FIJI ISLANDERS AND SPARKED A REBELLION AMONG BRITISH COLONIALISTS. HIS CONTRIBUTIONS HAVE NOT HOWEVER BEEN LIMITED TO IMPROVING OUR UNDERSTANDING OF HISTORICAL OUTBREAKS. RECENTLY FOR EXAMPLE, HE'S PLAYED A ROLE IN SHAPING OUR INSTITUTE'S RESPONSE TO THE ARRIVAL IN THE WESTERN HEMIS FAIR OF CHIKUNGUNYA AND ZIKA VIRUSES. INFLUENZA, THE TOPIC OF TODAY'S LECTURE, HAS LONG CAPTURED DAVID'S INTEREST. HE HAS AUTHORED OR COAUTHORED DOZENS AND DOZENS OF PAPERS IN THE FIELD, INCLUDING A 2010 PUBLICATION THAT TRACED THE FIRST RECOGNITION OF PANDEMIC FLU BACK TO 1510. WRITING WITH JEFF ANDIO HON, DAVID PLACED A 2005 RECONSTRUCTION OF THE 1918 PANDEMIC VIRUS INTO ITS HISTORICAL CONTEXT WHILE A 2006 PAPER ALSO CO-WRITTEN WITH SHOWED HOW THE 1918 VIRUS COULD BE SAID TO BE THE MOTHER OF ALL PANDEMICS. THIS YEAR MARKS THE CENTENNIAL OF THE PANDEMIC CAUSED BY THAT NOTORIOUS MOTHER VIRUS AND HER UNRULY LINEAGE PERSISTS TO THIS DAY AND PERHAPS NO ONE IN THE WORLD IS MORE QUALIFIED THAN DAVID TO HELP US EXPLORE HOW WE CAN PREPARE FOR THE SECOND CENTURY OF DESCENDANTS ON THIS 1918 PANDEMIC VIRUS. SO PLEASE JOIN ME IN WELCOMING DR. DAVID MORENS. [ APPLAUSE ] >> DR. MORENS: THANK YOU, TONY AND THANK YOU ALL OF YOU FOR COMING HERE TODAY. IT'S A GREAT HONOR TO BE ABLE TO SPEAK ABOUT A SUBJECT THAT JOHN LOVED, AND TALK IN JOHN'S HONOR. SO, I'M GOING TO SAY A LITTLE BIT ABOUT JOHN. BUT FOR THOSE OF YOU WHO NAY NOT HAVE KNOWN JOHN, GO TO OUR WEBSITE AND YOU CAN READ A MUCH LONGER STORY OF JOHN'S LIFE AND HIS CAREER HERE, AND ALSO AT UNIVERSITY OF TEXAS AUSTIN. THIS IS MY FAVORITE PHOTO OF JOHN. HE WAS A GREAT FRIEND, AND HE AS TONY SAID, HE IS STILL MISSED 14 YEARS AFTER HIS UNTIMELY DEATH. NOW IN SAYING A FEW WORDS ABOUT JOHN, I WANT TO TAKE US ALL THE WAY BACK TO THE YEAR 1976 AS TONY MENTIONED. THAT IS WHEN JOHN CAME TO NIH AS THE FIRST INFLUENZA PROGRAM OFFICER. IT'S ALSO THE YEAR THAT I WENT TO CDC AND IT WAS A PRETTY INTERESTING YEAR. THERE WERE ALL THESE BAD EPIDEMICS. IT WAS A REALLY BAD YEAR FOR BAD DISEASES. IT WAS ALSO THE BICENTENNIAL YEAR, THE YEAR OF WOMEN AND THE YEAR OF THE FIRST APPLE COMPUTER. HARD TO BELIEVE. THIS WAS BEFORE IT WAS WHITE. EVN THEN, ALTHOUGH I DIDN'T KNOW JOHN IN 1976, EVEN THEN, OUR PATHS WERE CONVERGING. WE BOTH WALKED INTO THE MIDDLE OF SOMETHING THAT IS CALLED THE SWINE FLU AFFAIR. AND AS I SAID, JOHN WAS THE FIRST PROGRAM OFFICER AT NIAID AND HE IMMEDIATELY HAD TO DEAL WITH THE SWINE FLU AFFAIR, WHICH FOR THOSE WHO DON'T KNOW WHAT IT IS, THERE WAS AN OUTBREAK OF INFLUENZA IN THAT BEGAN IN VORTEX NEW JERSEY, AND IT WAS TRACED TO A VIRUS THAT WAS IDENTIFIED AS A SWINE VIRUS, A PIG VIRUS. IT WAS VERY MUCH LIKE THE 1918 VIRUS IN SOME OF THE GENETIC AND PHENOTYPIC ASPECTS. AND IT WAS BELIEVED AT THE TIME BY ALMOST EVERYBODY IN PUBLIC HEALTH, THAT THIS COULD BE THE RETURN OF THE DEADLY 1918 PANDEMIC. IT TURBED OUT IT WASN'T. BUT IN THE MEANTIME, THE UNITED STATES GEARED UP IN A MASSIVE VACCINE CAMPAIGN, 45 MILLION DOSES OF VACCINE WERE GIVEN. BUT THE PANDEMIC NEVER CAME AND WORSE YET, 450 PEOPLE DEVELOPED A NEUROLOGIC COMPLICATION OF THE VACCINE, OR ALLEGEDLY RELATED TO THE VACCINE. NOBODY REALLY KNOWS FOR SURE WHAT HAPPENED CALLED GAM BARRET SYNDROME. AND THAT SHUT DOWN THE VACCINATION CAMPAIGN. THERE WAS A BIG GOVERNMENT INVESTIGATION. A REPORT THAT YOU SEE ON THE LEFT AUTHORED BY A YOUNG MAN WHO LATER WE ALL CAME TO KNOW WHEN HE WAS THE HEAD OF THE INSTITUTE OF MEDICINE, AND DR. CENSER, THE DIRECTOR OF CDC WAS FIRED BY THE SECRETARY OF WHAT IS NOW HHS, THEN HEALTH EDUCATION AND WELFARE. IT WASN'T UNTIL 19 -- ALTHOUGH I MET JOHN AND KNEW JOHN IN THE INTERIM, IT WASN'T UNTIL 1998 WHEN OUR PATHS FINALLY CROSSED WHEN HE RECRUITED ME TO COME HERE IN MULTIPLE TELEPHONE CALLS AND A FEW IN-PERSON VISITS OVER THE COURSE OF 6-12 MONTHS, TELLING ME HOW WONDERFUL NIAID WAS. OF COURSE I KNEW THAT. I HAVE BEEN WORKING WITH NIAID EVEN BACK WHEN I WAS AT CDC. BUT HE FINALLY GOT ME TO COME HERE AND I'M VERY GLAD I DID. IT WAS THE BEST DECISION I EVER MADE. AND WE WERE THROWN IMMEDIATELY INTO ALL SORTS OF NEW PROBLEMS LIKE HOTTA SHIELD. AND COWBOY BOOTS. WHAT DOES COWBOY BOOTS HAVE TO DO WITH THIS? ONE OF MY BEST MEMORIES OF JOHN IS WHEN HE AND I AND MAYBE OTHERS TRAVELED TO AUSTIN, TEXAS FOR SOME KIND OF MEETING. I DON'T BELIEVE WHAT. BUT I HAD NEVER OWNED A PAIR OF COWBOY BOOTS AND I HAD AN AFTERNOON OFF AND JOHN RECOMMENDED SOME PLACE TO GO TO BUY COWBOY BOOTS. I THINK IT WAS ALAN'S BOOT STORE. I REMEMBER I HAD TO CROSS A BRIDGE EITHER OVER A RIVER OR A VERY BIG ARROYO AND I BROUGHT THESE COWBOY BOOTS. THERE THEY ARE. I HAVE THEM WITH ME TODAY. I WOULD BE WEARING THEM EXCEPT I WOULD BE OUT OF UNIFORM AND THE SURGEON GENERAL WOULD PROBABLY FIRE ME. BUT I'M GOING TO PUT THEM ON AS SOON AS THIS TALK IS OVER. OKAY. NOW LET'S TALK ABOUT FLU. JOHN'S FAVORITE SUBJECT. OR AT LEAST ONE OF HIS FAVORITE SUBJECTS. I THINK WE ALL KNOW WHAT FLU IS. IT'S A REALLY BAD DISEASE. WHEN YOU GET IT YOU FEEL LIKE YOU HAVE BEEN RUN OVER BY A TRAIN. AND IT'S ONE OF THE MAJOR KILLERS OF HUMAN BEINGS. NOW THIS IS SUPPOSED TO BE THE MOVIE THAT HAS TO BE RUN FROM UPSTAIRS. CAN WE RUN IT? SO INFLUENZA IS A VIRAL DISEASE WHICH IS SPREAD IN THREE DIFFERENT WAYS, BY AEROSOL DROP LET, VERY, VERY SMALL PARTICLES, TOO SMALL TO SEE, BY BIGGER DROP LETS, WHICH IS WHAT YOU SEE HERE, AND ALSO BY FOE MITES AND BY HAND, THAT IS CONTACT SPREAD. INFLUENZA IS ACTUALLY BEEN AROUND AS DR. FAUCI MEANED, FOR AT LEAST 500 YEARS. AND IT'S BEEN COMING BACK AND REPEATED PANDEMICS AT UNPREDICTABLE INTERVALS AND THE SYMPTOMS ARE THE SAME TODAY AS THEY WERE 500 YEARS AGO. WE ALL KNOW THEM, FEVER, HEADACHE, MUSCLE ACHES, FEELING LIKE YOU WANT TO BE IN BED. THAT IS IN ALL PANDEMICS RECOGNIZED, DEATHS OCCUR PREDOMINANTLY IN THE VERY YOUNG, VERY OLD, AND IN PREGNANT WOMEN. 1918 PANDEMIC, THE SUBJECT OF WHAT I'M GOING TO TALK ABOUT THE REST OF MY TALK, WAS THE MOST FATAL EVENT IN HUMAN HISTORY EXCEEDING THE NUMBER OF DEATHS IN THE BLACK DEATH OF THE 14TH CENTURY. IN THE UNITED STATES IT KILLED AN ESTIMATED 675,000 PEOPLE, GLOBALLY 50 OR 100 MILLION IS THE ACCEPTED ESTIMATE AND MOST OF THIS IS WITHIN A PERIOD OF& JUST A FEW MONTHS. AND RECENT RESEARCH SUGGESTS THAT THE DEATH COUNT COULD BE EVEN HIGHER. THERE ARE NEW DATA COMING OUT FROM INVESTIGATORS SUCH AS DR. CHANDRA, THIS IS SRI LANKA, IN WHICH THEY MEASURE POPULATION GROWTH, TRENDS OVER TIME BEFORE AND AFTER THE YEAR OF 1918. AND THEY HAVE DONE THIS FOR 5 OR 6 DIFFERENT COUNTRIES IN THE DEVELOPING WORLD WHERE THERE WERE NEVER VERY GOOD VITAL STATISTICS DATA. AND THEY ARE COMING UP EVERYWHERE THEY GO WITH HIGHER ESTIMATES OF DEATHS IN 1918. SO IMAGINE THAT OVER TIME THE ESTIMATES OF THE NUMBER OF PEOPLE WHO DIED IN 1918 ARE LIKELY TO GO UP. IN THE UNITED STATES, UNBELIEVABLY, IN THAT ONE YEAR ALONE, LIFE EXPECTANCY DROPPED 12 YEARS. JUST FROM THE PANDEMIC. BEFORE I GET INTO THE SCIENCE, I THINK BECAUSE THIS WAS SUCH A TERRIBLE HUMAN TRAGEDY, I WANT TO JUST SPEND ABOUT A MINUTE THINKING ABOUT WHAT LIFE MUST HAVE BEEN LIKE IN 1918 WHEN EVERYBODY WAS DYING AROUND YOU. AND HERE ARE SOME IMAGES, A FEW IMAGES FROM 1918 AND 1919 THAT GIVE US SOME IDEA OF WHAT LIFE MUST HAVE BEEN LIKE DURING THAT DEADLY PANDEMIC. AND OF COURSE MOST TRAGIC OF ALL IS THE DEATHS OF MILLIONS OF CHILDREN AND MILLIONS MORE WHO BECAME ORPHANS DURING THAT TIME. THE 1918 PANDEMIC WAS MYSTERIOUS IN MANY DIFFERENT WAYS. I'LL TALK ABOUT THESE POINTS YOU SEE HERE. THE REOCCURRENCE IN WAVES, THE UNEXPECTEDLY HIGH MORTALITY OF ALL AGES, THE PARADOXICAL MORTALITY PATTERN REFERRED TO AS THE W-SHAPED CURVE. WE'LL SEE THAT IN A MINUTE. IT'S SOMETHING THAT WAS NEVER SEEN BEFORE AND NEVER BEEN SEEN SINCE. AND DEATHS FROM SEVERE BACTERIAL BRONCHOPNEUMONIA. THERE ARE ALSO SOME KENNARD I'LL TOUCH ON. NOW THOSE OF YOU WHO KNOW FRENCH KNOW THAT KENNARD IS A FRENCH WARD FOR DUCK. WHICH IS IMPORTANT. WE'LL SEE WHY IN A MINUTE. BUT IN ENGLISH, KIN ARD IS SOMETHING THAT IS SAID TO BE SO OR MAY NOT BE SO OR AT LEAST MAY NOT BE FULLY TRUE, SUCH AS WHAT YOU SEE HERE. THE HERALD WAVE IDEA, AND I'M USING HAROLD WAVE IN THE OLD SENSE, NOWADAYS PEOPLE MEAN IT TO BE SOMETHING DIFFERENT. THAT THE PANDEMIC SOME SAY WAS CAUSED BY THE DISRUPTIONS OF WORLD WAR I OR PEOPLE DIDN'T EVEN SUSPECT WHAT THE CAUSE WAS AND IN FACT, THEY ACTUALLY DID. SO WHERE DID THE VIRUS COME FROM? THANKS TO MY COLLEAGUE, JEFF, WHO IS SOMEWHERE HERE IN THE AUDIENCE, I HOPE, THERE HE IS. JEFF. JEFF IS THE GUY WHO FOUND THE HOLY GRAIL OF INFECTIOUS DISEASE -- AT LEAST VIRALLOLOGY IN DISCOVERING, QUOTE/UNQUOTE, DISCOVERING THE 1918 VIRUS, WHICH IS TO SAY BEING ABLE TO SEQUENCE AND STICH TOGETHER THE RNA FRAGMENTS OF THE VIRUS, NOT JUST ONE VIRUS BUT IN WHOLE OR IN PART SEVERAL DIFFERENT VIRUSES SPANNING AN INTERVAL OF 1918 AND 1919 AND THEREFORE IDENTIFIED GENETICALLY SO IT COULD BE RECONSTRUCTED AND STUDIED. THIS IS A HUGE ACCOMPLISHMENT DONE BY JEFF AND BY JEFF'S LABORATORY TEAM AND WITH THE HELP OFIO HAN, WHO ASSISTED IN EXHUMING A BODY BURIED IN ALASKA FROM WHICH VIRAL RNA WAS TAKEN AND SHOWED THE VIRUS IN A HUMAN BEING RATHER THAN IN -- THE OTHER SPECIMENS WERE FROM PATHOLOGY SLIDES. WHAT WE FOUND, WHAT JEFF FOUND AND WHAT SCIENCE LEARNED, WAS THAT THIS WAS A BIRD-LIKE VIRUS, A WILD WATERFOWL-LIKE VIRUS, AND THE GENETIC CHANGES THAT WERE IDENTIFIED LED TO THE CONCLUSION THAT THIS VIRUS HAD BEEN A BIRD VIRUS IN BIRDS, NOT VERY LONG BEFORE 1918. BUT WHAT KIND OF BIRD? THIS IS A TEST. WAS THE 1918 MOTHER OF ALL PANDEMICS A MOTHER HEN? NO. ACTUALLY NOT. IT'S NOT A POULTRY VIRUS. HAVING BEEN IN A CHICKEN OR A TURKEY. IT'S PERHAPS A MOTHER GOOSE, A VIRUS THAT HAD BEEN IN WILD WATERFOWL, GOOSE, GEESE, DUCKS AND SO ON. NOW WHY IS THAT IMPORTANT? BECAUSE ALL INFLUENZA A VIRUSES ARE DESCENDED FROM EITHER R OR -- OR ARE DESCENDED FROM VIRUSES THAT EXIST IN A RESERVOIR OF BILLIONS OF WILD BIRDS, ALL OVER THE WORLD. AND THESE ARE INFECTING BIRDS. THEY ARE SPREAD INTO THE WATER. THEY DON'T - AUTO INFLUENZA VIRUS DOESN'T EXIST AS STABLE VIRUSES FOR VERY LONG IN THE WILD IN BIRDS BECAUSE THE EIGHT GENES ARE ALSO REASSORTED. THEY ARE SHAKING AND BAKING AND MIXING AND MATCHING. IT'S ONLY WHEN ONE OF THESE BIRD VIRUS GETS OUT INTO AN UNNATURAL HOST, A HUMAN, MAMMAL, EVEN A CHICKEN, THAT IT CAN BE PASSED ON AS A STABLE VIRUS. LET'S LOOK FIRST AT THE PROGRESS OF THE PANDEMIC IN THE UNITED STATES. AND WE ARE GOING TO SEE THE SPREAD OF THE VIRUS OVER FIVE WEEKS BEGINNING IN SEPTEMBER 1918, AND THIS IS THE BLUEST BLUE STATES I EVER SEEN, I THINK. THEY ARE GOING TO TURN RED IN A MINUTE AS THE PANDEMIC APPEARS FIRST ON THE EAST COAST AND ALSO ON THE WEST COAST. THERE WE SEE THE WEEK ONE, WE SEE A NUMBER OF CITIES AND AREAS IN THE UNITED STATES NOTE THE EAST COAST BUT NOTE ALSO THE THREE MAJOR CALIFORNIA CITIES. AND OTHER CITIES AS WELL WHICH TEND TO BE EITHER LARGE CITIES LIKE CHICAGO, CLEVELAND, AND YOU CAN ALSO SEE SOME THAT ARE NEAR LARGE CITIES IN OTHER STATES AS WELL. NOW WE ARE GOING TO GO TO WEEK 2. STAY FOCUSED ON THE NORTHEAST BECAUSE THAT IS THE ONLY PLACE WHERE THINGS ARE HAPPENING. SPREADING A LITTLE MORE IN THE NORTHEAST. WEEK 3. NOW IT'S SPREADING IN THE INTERIOR AND IT'S UP ALL OVER THE GULF COAST. WEEK 4. IT'S STILL HASN'T GOTTEN TO KANSAS, THE REPUTED HOME OF THE PANDEMIC, ACCORDING TO SOME HISTORIANS. BUT IT'S CLEARLY IN ALL THE POPULOUS AREAS IN THE UNITED STATES. AND BY WEEK 5, THE WHOLE UNITED STATES. THIS IS HOW QUICKLY IT WENT THROUGH. NOW LET'S LOOK AT THE WORLD. WE ARE GOING TO GO BACK A LITTLE BIT AND WHAT I'M GOING TO SHOW YOU IS THE PROGRESS OVER A PERIOD OF A YEAR AND A HALF IN THE WORLD AND LET'S RECOGNIZE THAT THESE ARE -- LOOKING AT PLACES WITH SIGNIFICANT EXCESS MORTALITY BUT WE HAVE NO WAY OF KNOWING, EARLY ON AT LEAST, THIS WAS THE 1918 FLU AS O MODES TO THE PNEUMONIA AND THE FLU THAT HAPPENS EVERY YEAR IN THE WINTER NO MATTER WHAT THE VIRUS IS. BUT NEVERMIND THAT. I JUST PUT THIS TOGETHER AND LET'S JUST SEE. IN FEBRUARY 1918, WE SEE THERE IS SIGNIFICANT ACCESS MORTALITY IN TWO CHINESE CITIES. IN HONG KONG AND IN CHANG HIGH. JUMP FORWARD FOUR MONTHS TO JUNE, WE SEE IT IS IN TWO LARGE CITIES, JAKARTA AND MUMBAI, AND ALSO THERE ARE ACCESS MORTALITY IN NORTHERN GERMANY. GERMANY WAS AT WAR, AND LAB DORE. JULY, NOW IT'S APPEARED IN OTHER BIG CITIES NEAR THE EQUATOR BUT ALSO IN NORTHERN CITIES AND IF I HAD FILLED THEM ALL IN, ALL THE SCANDINAVIAN COUNTRIES, DENMARK AND LITHUANIA, LATVIA, ALL THE NORTHERN EUROPEAN COUNTRIES WERE INVOLVED IN JULY. IN AUGUST, WE HAVE JAPAN. IN SEPTEMBER THIS IS THE BIG WAVE. ALMOST EVERY PLACE IN THE WORLD HAD BECOME INVOLVED IN OR BISEPTEMBER. AND IF THEY DIDN'T, MOST OF THOSE PLACES BECAME INVOLVED BY OCTOBER OF 1918. AND THEN, IN NOVEMBER A FEW SMALL ISLANDS AND A FEW REMOTE PLACES WERE STRAGELLING AND THE LAST STRAGGLER WAS AUSTRALIA, WHICH THE FLU APPEARED IN SIDNEY IN MARCH 1919, AND ADD LAID IN APRIL 1919. IN QUEENS LAND MAY 1919 AND THEN IN AUGUST IN PERTH. NOW LET'S TALK ABOUT INFLUENZA WAVES, THE W I MENTIONED EARLIER, AND A LOT OF OTHER WIERD BEHAVIORAL ASPECTS OF THIS PANDEMIC. FIRST OF ALL, HOW MANY WAVES WERE THERE IN A GIVEN PLACE? THE ANSWER IS, THERE WAS ONE. THERE WAS TWO? OR THERE WAS 3? THIS IS LONDON. OR THERE WAS 6? THITHIS IS NOW POLE LAPPED. AND THEN WE HAD VERY WOOD WIERD THINGS LIKE IN HAWAII. THIS IS THE THEN TERRITORY OF HAWAII. IN 1918 IN THE SPRING -- I'M SORRY, IN THE SUMMER, LATE SUMMER AND FALL, THERE WAS A HUGE EPIDEMIC, THE MORBIDITY WAS ENORMOUS BUT THE MORTALITY WAS LOW. YOU CAN SEE A BUMP IN 1918. JUST A BUMP. NOT MUCH DEATH. LOTS OF CASES OF FLU. THIS IS WHEN THE WHOLE WORLD WAS EXPERIENCING HIGH DEATH RATES, HAWAII HAD A SMALL BUMP. AND THEN, THE FLU CAME BACK THE NEXT YEAR IN 1919 AND THERE WAS A LITTLE BIGGER BUMP. AND THEN A HUGE EPIDEMIC IN 1920, MORE THAN TWO YEARS LATER. NOBODY KNOWS WHY. JUST ANOTHER ASPECT OF THE VERY STRANGE BEHAVIOR OF THIS VIRUS. THIS IS A BUSY SET OF SLIDES ONLY FOR THE GEEKY SCIENTISTS. I'LL TRY TO WALK EVERYBODY THROUGH IT. WHAT WE ARE LOOKING AT NOW IS ALL OF THE MILITARY PUT TOGETHER, THE UNITED STATES MILITARY AND CAMPS IN THE UNITED STATES, THE ADMISSIONS FOR INFLUENZA OVER TIME ON THE BOTTOM OR X AXIS WE SEE TIME. AND WE CAN SEE OF COURSE WE JUST MENTIONED THE UNITED STATES AND ALL THE MILITARY CAMPS HAD THIS BIG PANDEMIC WAVE IN SEPTEMBER AND OCTOBER OF 1918. BUT THERE WAS SOMETHING GOING ON HERE. AND SOME PEOPLE SAY THERE WAS A SPRING WAVE. WHAT WAS THIS? WAS THIS AN EARLY APPEARANCE OF THE VIRUS? IF SO, WHY DIDN'T IT BECOME PANDEMIC THEN? WHY DID IT HARDLY KILL ANYBODY THEN? NOW, I WANT YOU TO IGNORE THIS Y AXIS HERE. WE ARE GOING TO BE LOOKING AT THIS DIFFERENT Y AXIS OVER HERE WHICH MAPS DEATHS. AND THIS IS ON A THREE CYCLE ALLOWING SCALE. THE WHAT THAT MEANS IS THAT IT MAKES -- LOG SCALE -- IT MAKES STUFF AT THE BOTTOM LOOK HUGE AND THESE ARE DEATHS FROM PEOPLE WHO WERE ADMITTED WITH INFLUENZA AND DIED OF EITHER A DIAGNOSIS OF INFLUENZA OR PNEUMONIA AND THAT IS GOING TO BE MOSTLY -- PNEUMONIA. NOW WE SEE ANOTHER CURVE OF PEOPLE ADMITTED WITH INFLUENZA WHO DIED OF BRONCHOPNEUMONIA, INFLUENZA AND BRONCHOPNEUMONIA. AND IF WE SUPER IMPOSE THEM, WE NOTICE SOMETHING KIND OF STRANGE. THAT WHATEVER THIS SPRING WAVE WAS, WHATEVER THIS SPRING EVENT WAS, IT WASN'T CAUSING BRONCHOPNEUMONIA, VERY MUCH AT LEAST. THE CLASSICAL WAY IN WHICH INFLUENZA KILLS YOU. AND IT WASN'T CAUSING MUCH MORTALITY AT ALL. THIS IS BLOWN UP A LOT. IT LOOKS HUGE. BUT IF WE WERE ON A LINEAR SCALE LIKE THIS, THIS WOULD BE A DOT DOWN HERE. IT WOULDN'T BE BLOWN UP LIKE IT WAS. SO, WHATEVER WAS HAPPENNG IN THE SPRING, AT LEAST IN THE ARMY CAMPS, HAD A LITTLE BIT OF FATALLY BUT IT DIDN'T HAVE ANY OF THE HALLMARKS OF THE 1918 FLU. AS WITH MOST INFECTIOUS DISEASES, THE POOR AND THE DISADVANTAGED WERE MORE LIKELY TO BECOME ILL AND MORE LIKELY TO DIE, NOT SURPRISING BUT NONETHELESS TRAGIC. IF WE LOOK AT THE EPIDEMIOLOGY, WE SEE THIS IS THREE DIFFERENT THINGS. THIS IS THE MORBIDITY. THAT IS THE GETTING SICK OF IT. AGE ON THE X AXIS AND INCIDENTS OR ATTACK RATE ON THE Y AXIS. AND WHAT WE SEE IS TWO BUMPS. YOU SEE THESE IN ALL INFLUENZA PANDEMICS. A BUMP OF INFLUENZA IN SCHOOL AGED CHILDREN AND A BUMP IN WORKING AGED ADULTS WHO IN THIS ERA WERE ALMOST ALL PARENTS AND HAVE LITTLE KIDS IN THEIR HOUSE. NEXT DOWN WE SEE THE FAMOUS W. MORTALITY CURVES STEPPED TO, FOR INFLUENZA, ALMOST ALWAYS, BEFORE AND SINCE, ALWAYS HAVE BEEN IN THE VERY YOUNG AND THE VERY OLD AND LOW MORTALITY IN BETWEEN. SAME THING FOR CASE FATALITY DOWN HERE. THIS WOULD BE A U SHAPED CURVE OF NORMAL CASE FATALLY AND I DIDN'T DRAW IT IN HERE TO MORTALITY TO MAKE IT LOOK LESS BUSY. BUT I THINK YOU CAN SEE THERE IS A W IN 1918 FOR BOTH MORTALITY AND FOR CASE MORTALITY AND THIS IS A COMPARISON FROM 10 YEARS LATER, 1928 AND 1929. SO, THIS W HAS NEVER BEEN EXPLAINED SATISFACT REALLY. THAT'S ONE OF THE GREAT MYSTERIES. BUT IT EVEN GETS MORE MYSTERIOUS. LET'S LOOK AT WHAT HAPPENS TO THE W-SHAPED MORTALITY CURVE OVER TIME IN POLAND. THIS IS THE BIG WAVE IN OCTOBER 1918, MOSTLY. IT COMES BACK A YEAR -- YOU SEE A BIG W. A BIG HUMP IN THE MIDDLE. WHEN IT COMES BACK THE NEXT YEAR, THE HUMP HAS GOTTEN SMALLER. WHEN IT COMES BACK THE YEAR AFTER THAT, IT'S GONE ENTIRELY. THE W, WHATEVER IT IS, WENT AWAY WITH REOCCURRENCE OF THE PANDEMIC PRESUMABLY THE SAME VIRUS. SO, DID SOMETHING HAPPEN TO THE VIRUS? WELL, REMEMBER HAWAII HAD THE FREE PANDEMIC OCCURRENCES IN 1918 AND 19 AND 20. THIS IS 1917 AS A BACKGROUND, NOT MUCH GOING ON. A VERY LOW NUMBER OF DEATHS FROM INFLUENZA AND THOSE DEATHS ARE ALMOST ALL IN THE VERY YOUNG INFANTS AND THE VERY OLD. NOW WE HAVE THE BIG 1918 EPIDEMIC IN HAWAII. AND AGAIN, VERY YOUNG, VERY OLD, THERE IS ALMOST NO MORTALITY IN YOUNG ADULTS THAT MAKE UP THE W. AND IF THERE IS A W THERE AT ALL, IT IS PRETTY UNNOTICEABLE. THEN IN 1919, OF COURSE IT CAME BACK AND NOW WE ARE BEGINNING TO SEE A FEW MORE DEATHS IN ADULTS, YOUNG ADULTS. AND IN 1920, THAT THIRD WAVE NOW THERE IS A BEGINNING TO BE THE APPEARANCE OF A W. SO THE W GIVEth AND THE W TAKEth AWAY. IT APPEARS AND GOES AWAY AND NOBODY CAN FIGURE OUT WHY. AND PEOPLE HAVE BEEN SCRATCHING THEIR HEADS ABOUT THIS FOR 100 YEARS. AND I SHOULD SAY, JUST TO GO BACK A LITTLE BIT, THIS IS 1921 TO SHOW WHATEVER W THERE MIGHT HAVE BEEN IN 1920 IT IS IT GONE FOREVER AFTER. ANOTHER STRANGE THING ABOUT 1918 WAS THE SUPPOSED DEATHS FROM UNUSUAL CLINICAL PICTURE, WHICH IS WHAT IS CALLED AT THE TIME, HELIOTROPE CYANOSIS. THIS THE IS A DRAWING BY A MEDICAL ILLUSTRATOR OF HOW PEOPLE DIED WITH THIS BLUISH COLORATION OF THE LIPS AND THE EARLOBES AND OTHER PARTS OF THE FACE, THAT PRESUMABLY REFLECTS SUFFOCATION, THE LUNGS ARE DROWNING IN FLUID, NO OXYGEN GETTING IN. AND IT MAY WELL HAVE BEEN SEEN IN PREVIOUS PANDEMICS BUT CERTAINLY IT WAS SAID TO BE CHARACTERISTIC OF THIS AND HERE WE SEE A DRAWING AND A PHOTOGRAPH OF THE HANDS IN THE 1918 INFLUENZA. ONE OF THE IMPORTANT THINGS WE HAVE LEARNED, AND DR. FAUCI AND I AND OTHERS WERE AMONG THE FIRST TO REALLY DRAW ATTENTION TO THIS ABOUT 10 YEARS AGO; WAS THAT IN 1918, HARDLY ANYBODY DIED OF INFLUENZA. THEY DIED OF SECONDARY BACTERIAL PNEUMONIA. YOU GOT INFLUENZA AND SOMEHOW THROUGH SOME MECHANISM, AND I'M NOT GOING TO GO INTO WHAT THAT IS, WE CAN TALK ABOUT IT IF ANYBODY IS INTERESTED. PEOPLE WHO GOT INFLUENZA WERE MUCH MORE LIKELY, HUNDREDS FOLD, TO GET BACTERIAL PNEUMONIA FROM STANDARD BACTERIA THAT ARE IN THE NOSE AND THROAT OF PEOPLE ALL THE TIME. PNEUMOCOCCUS, STREPTOCOCCUS AND STAPHYLOCOCAUS ORUOUS AND A NUMBER OF OTHERS. WHAT WE ARE LOOKING AT IS NOT A PAINTING BUT THESE ARE PATHOLOGY SPECIMENS STAINED WITH THE STANDARD STAIN, AND WE SEE BRONCHI FILLED WITH BLIGHT BLOOD CELLS. WE SEE AVELI, THE AIR SACKS IN THE LUNGS INFECTED AND DAMAGED AND IT'S EASY TO IMAGINE FOR A PATHOLOGIST, LOOKING AT THESE, THAT THE PERSON WHOSE THESE LUNGS CAME FROM WOULD -- THERE WAS A REASON THEY WERE DEAD AND THE REASON IS TO BE FOUND IN THE LUNGS. AS I MENTIONED, THIS IS A PAPER THAT I WORKED WITH DR. FAUCI AND OTHERS IN WHICH WE LOOKED AT 58 RE-CUT PATHOLOGY SPECIMENS FROM 1918, AND ALSO REVIEWED OVER 8000 AUTOPSIES THAT HAD BEEN PUBLISHED AROUND THE TIME OF 1918 AND AFTER IN WHICH BACTERIAL CULTURES WERE DONE. AND WHAT WE FOUND WAS THAT ANALYZING ALL THESE DATA TOGETHER, WERE THAT ABOUT 96% OF ALL THESE AUTOPSIES, THEY WERE ABLE TO CULTURE PNEUMOPATHOGENS, MAINLY STAFF, STREP AND PNEUMOCOCCUS FROM THE LYNX. IN 80%, PLEURAL FLUIDS CONTAINED THOSE SAME BUGS AND IN 70%, BLOOD CULTURES ARE POSITIVE. SO PEOPLE WERE DYING WITH MASSIVE PNEUMONIA, WITH BACTEREMIA OR SEPTICEMIA. BUT, IF THERE IS ANOTHER INTERESTING EPIDEMIOLOGIC ASPECT TO THESE DEATHS, THIS IS AGAIN A LITTLE BIT HARD TO THINK ABOUT. IT'S A BUSY SLIDE. BUT I WANT TO DRAW YOUR ATTENTION JUST TO THIS ONE BLUE LINE HERE. THE LIGHT BLUE LINE. AND I WANT TO MAKE THE POINT THAT THIS LINE WHICH IS PNEUMONIA CASE FATALLY, IS JUST ABOUT PARALLEL, JUST ABOUT EVEN BETWEEN THE AGES OF 25 AND 55, THE AGES OF WHICH EVERYBODY WAS DYING. WHEREAS I'M GOING TO DROP THAT LINE OUT NOW AND WE'LL SEE WHAT IS LEFT. WE HAVE INFLUENZA CASE FATALLY AND THE PERCENTAGE OF CASES COMPLICATED BY PNEUMONIA. WHAT THIS -- TO TURN THIS INTO ENGLISH, WHAT THIS SAYS IS THE MORTALITY OF INFLUENZA IN 1918 IS DETERMINED PRIMARILY BY THE INCIDENTS OF COMPLICATING BACTERIAL PNEUMONIA. IN OTHER WORDS, IT WAS NOT TRUE THAT THOSE PEOPLE WHO DIED HAD MORE SEVERE PNEUMONIA. IT'S JUST THEY WERE MORE LIKELY TO GET PNEUMONIA ONCE THEY HAD INFLUENZA. BUT BELIEVE IT OR NOT, THERE WERE SO-CALLED INFLUENZA VACCINES IN 1918, 15 YEARS BEFORE THE VIRUS WAS DISCOVERED. THEY WEREN'T REALLY INFLUENZA VACCINES, ALTHOUGH THEY WERE CALLED THAT. THEY WERE ACTUALLY VACCINES WHICH WERE MADE FROM CRUDE PREPARATIONS OF BACTERIA THAT HAD BEEN INACTIVATED, KILLED. AND THEY WERE GIVEN ALL OVER THE WORLD TO CIVILIANS AND TO MILITARY ALIKE. THERE WERE HUNDREDS, GOD KNOWS HOW MANY VACCINES THEY WERE. THEY WERE HOMEMADE CONCOCTIONS OF INNERACTIVATED STUFF. MOST HAD PNEUMOCOCCUS IN THEM. MANY HAD STREPTOCOCCUS AND BACILLUS INFLUENZA AND VARIOUS OTHER THINGS. AND YOU WOULD THINK THESE VACCINES WOULD NOT BE LIKELY TO WORK. BUT, WHAT WE FOUND WHEN WE DID -- THIS WAS DONE WITH KEITH AND HIS GRADUATE STUDENT. KEITH IS NOW AT THE GATES FOUNDATION AND HEADS THE PNEUMOCOCCUS INITIATIVE THERE AT GATES. WHAT WE FOUND BY DOING METANALYSIS IN PUBLISHED STUDIES IN CIVILIANS AND IN THE MILITARY, IN LOOKING AT THE RELATIVE RISKS OF GETTING PNEUMONIA OR DYING OF PNEUMONIA WHEN YOU HAD INFLUENZA, AFTER GETTING A VACCINE OR NOT GETTING A VACCINE, BUT THESE VACCINES ACTUALLY WORKED AND WILL SIGNIFICANTLY SO. NOW IT'S TIME TO TALK ABOUT THE MOTHER'S CHILDREN, THE CHILDREN BEING THE PANDEMIC VIRUSES THAT HAVE COME AFTER 1918 AND THERE RE A NUMBER OF THEM. THERE WAS 1957 WE HAD A PANDEMIC CALLED H2N2. WE'LL SEE IT MORE IN A MINUTE. 1968. IN 1977 THE OLD 1918 VIRUS CAME OUT OF A FREEZER OR A DESCENDANT OF IT CAME OUT OF A FREEZER, PERHAPS BY A ACCIDENT WITH A CLINICAL TRIAL, AND GOT LOOSE IN THE WORLD AGAIN. AND THEN IN 2009 OF COURSE WE HAD THE SO-CALLED SWINE FLU PANDEMIC. AND EACH OF THESE SUBSEQUENT PANDEMICS CAUSED SUBSTANTIAL DEATH ALTHOUGH DIMINISHING OVER TIME. FORTUNATELY AND MAYBE BY COINCIDENCE. IN THE UNITED STATES, WE HAD AS I MENTIONED, 675,000 DEATHS IN 1918. 70,000 IN 1957 WITH ASIAN FLU PANDEMIC. 30,000 IN 1968 WITH THE HONG KONG FLU. AND ABOUT 12,000 IN 2009. LET'S LOOK AT THE BOTTOM OF THIS BUSY SLIDE HERE AND WHAT WE ARE LOOKING AT IS INFLUENZA MORTALITY BEGINNING IN ABOUT 1955 GOING THROUGH TODAY. AND WE SEE THE FOUR PANDEMIC ERAS, THE H2N2 ERA THAT BEGAN IN 1957 AND ENDED IN 1967. THE H3N2 ERA WHICH BEGAN IN 1968 AND IS STILL GOING ON. THEN THE RETURN OF THE H1N1. THESE CATCH COLORS MEAN THAT WE HAVE THE TWO DIFFERENT VIRUSES, THE OLD H1N1 VIRUS AND THE H3N2 VIRUS TOGETHER AND THEN FINALLY OUT HERE, SINCE 2009, THE NEW PANDEMIC 2009 VIRUS PLUS H3N2. AND SUBSTANTIAL MORTALITY, PARTICULARLY BACK HERE, BUT STILL A LOT OF MORTALITY THROUGHOUT INTERVENING YEARS. YEAR TO YEAR IT VARIES. IF WE LOOK UP HERE, THE COLORS ARE THE SAME. AND WHAT WE ARE LOOKING AT HERE IS EVERY TIME YOU GO UP A STEP AND THINK OF IT AS GOING UP A STEP ON A LADDER, STAIR WAY. EVERY TIME YOU GO UP A STEP HERE, THE VACCINE IS CHANGING YEAR TO YEAR BECAUSE THERE IS ANTIGENIC CHANGE. THE VACCINE HAS TO CHANGE IN NEW FORMULAS. SO THIS IS A MARKER OF VIRAL EVOLUTION. AND I THINK YOU CAN SEE THAT THESE VIRUSES ARE EVOLVING BUT THE H3N2 HAS BEEN INVOLVING AT A DRAMATIC RATE WHEREAS THE OLD H1N1 AND THE NEW H1N1 AREN'T EVOLVING MUCH AT ALL, WHICH HAS A LOT OF IMPLICATIONS FOR VACCINE DEVELOPMENT. AND I SHOULD SAY ALSO THAT THERE IS MULTIPLE MECHANISMS OF VIRAL EVOLUTION. THERE IS DRIFT WHICH MEANS MUTATION, WHICH CAUSES EITHER NEW EPITOPES TO APPEAR, THE VIRUS GETTING AROUND THE POPULATION IMMUNITY EITHER NEW EPITOPES OR NEW GLYCOSYLATION SITES. THERETO IS INTRASUBTYPIC REAASSORTMENT IN WHICH A HEMAGLUTEN IS REPLACED BY A DIFFERENT FLAVOR OF A HEME GLUTEN OF THE SAME SUBTYPE AND WHEN THERE IS A PANDEMIC, THERE IS SHIFT. WHAT HAVE WE DONE WITH ALL THESE CHALLENGES WITH ALL THESE VIRUSES? WHAT HAVE WE BEEN DOING TO TRY TO PREVENT SOMETHING LIKE 1918 FROM COMING BACK AGAIN? WE NOW HAVE INFLUENZA VACCINES. THEY ARE NOT ALL THAT GOOD. BUT WE ARE GOING TO MAKE THEM BETTER, I THINK, AS I'LL SAY IN A MINUTE. WE HAVE ANTIVIRAL DRUGS AND MORE ON THE HORIZON, BETTER ONES ON THE HORIZON. THIRD-GENERATIONS ON THE HORIZON. WE HAVE ANTIBIOTICS THAT CAN TREAT VIRTUALLY ALL THE CAUSES OF BACTERIAL PNEUMONIA DEATHS. WE HAVE MUCH BETTER INFLUENZA DIAGNOSTICS, SOME CAN BE USED POINT OF CARE AT THE BEDSIDE. LITTLER CAN BE USED IN CLINICS. -- OTHERS CAN BE USED -- AND WE HAVE A REALLY REMARKABLE SURVEILLANCE SYSTEM FOR INFLUENZA. I MUST SAY THE UNITED STATES SURVEILLANCE SYSTEM IS THE BEST IN THE WORLD. CDC HAS ABOUT 5 MAJOR DIFFERENT MECHANISMS OF SURVEILLANCE AND IN ADDITION TO THE PEOPLE THEY COUNT WITH FLU AND WITH FLU DEATHS, THEY ACTUALLY ENCOUNTER AND DO LAB STUDIES ON ABOUT A MILLION PEOPLE A YEAR. THAT'S HOW WE GET THE INFORMATION. BACK HERE AT NIAID, WE'VE LONG HAD A VERY ROBUST PROGRAM OF INFLUENZA COUNTERMEASURES RESEARCH AND DEVELOPMENT THAT IS CONDUCTED BY LABORATORIES ALL AROUND THE WORLD AS WELL AS BY SOME OF OUR OWN SCIENTISTS HERE AT NIAID. AND WE ARE WORKING ON ALL OF THESE AREAS AND ALSO WORKING WITH INDUSTRY. I WANT TO GIVE A BIT OF A SHOUT OUT TO THE NIH LIBRARY. IN NIAID, WE BEGAN THIS PROJECT CALLED THE PANDEMIC DIGITAL ARCHIVE, WHICH IS ESSENTIALLY AN -- WHEN IT GOES LIVE IN A MATTER OF MONTHS, IT WILL HAVE THOUSANDS OF PUBLICATIONS FROM 1918 ABOUT THE 1918 PANDEMIC AND MANY OTHER RELATED THINGS AS WELL, WHICH WILL BE ACCESSIBLE THROUGH LOTS OF METADATA, INCLUDING GEOSPATIAL. THIS WILL BE USEFUL TO RESEARCHERS AND SCHOOLKIDS IN THE INTEREST OF PUBLIC AROUND THE WORLD. AND I WANT TO ALSO GIVE A SHOUT OUT TO ALL THE MANY SCIENTISTS THAT ARE WORKING ON SOME OF THESE BIG PROBLEMS. HERE YOU SEE SOME OF OUR SCARS AT NIAID. BUT IN ADDITION TO THEM, WE FUND THE BEST INFLUENZA RESEARCHERS AROUND THE WORLD. WE, MEANING DMID AND THE OTHER PARTS OF NIAID AND NIH. IF YOU'RE REALLY GREAT INFLUENZA RESEARCHER, YOU ARE PROBABLY BEING FUNDED BY US. AND I THINK THAT AS WE GO FORWARD WITH DEVELOPING NEW AND BETTER VACCINES, SO-CALLED UNIVERSAL VACCINES, I THINK WE ARE GOING TO ENTER A NEW ERA OF BEING ABLE TO CONTROL INFLUENZA. NOW THE TERM UNIVERSAL INFLUENZA VACCINE HAS BEEN VARIOUSLY USED FOR DIFFERENT PURPOSES BY DIFFERENT PEOPLE. AT THE VERY LEAST I THINK WE WANT A VACCINE TO PROTECT AGAINST ALL THE NEW INFLUENZA VIRUSES THAT MIGHT OCCUR IN A PANDEMIC AND THE SEASONAL VIRUSES AS WELL. BUT BEFORE A BRING THIS TO A CLOSE, I WANT TO THINK FOR A MINUTE ABOUT WHAT THE WORLD WAS LIKE DURING THE PANDEMIC AND IMAGINE WHAT IT MIGHT HAVE BEEN LIKE HAD THE PANDEMIC NOT OCCURRED. THE PANDEMIC WAS ONE OF THE REASONS THAT THE WORLD WAR I ENDED. THE GERMANS SURRENDERED IN PART, ONE OF THE GENERALS ADMITTED, BECAUSE OF ALL OF THE ILLNESS AND DEATHS FROM THE FLU. BUT ALSO THE ILLNESS THAT IT CAUSED AND OUR PRESIDENT WILSON AND OTHERS, PROGRAMS PREVENTED A SUCCESSFUL CONCLUSION IN THE TREATY AND IN THE ENSUING YEARS THAT MIGHT HAVE PREVENTED US FROM GOING INTO WORLD WAR II. AND MANY HISTORIANS SAY THAT WORLD WAR II WAS REALLY THE END OF WORLD WAR I. THERE WAS JUST A LULL IN THE ACTION FOR 20-SOMETHING YEARS IN BETWEEN. HERE WE SEE PRESIDENT WILSON AND LLOYD GEORGE AND THE KEISER AND GENERAL PERSHING. THERE IS A LOT OF FAMOUS ART THAT RELATES TO 1918. ON THE TOP WE SEE THE NOVELLA BY CATHERINE ANN PORTER, SOME OF US BOOKS DID READ IN HIGH SCHOOL OR COLLEGE. AND THIS IS A TRUE STORY. CATHERINE ANN PORTER, ONE OF THE GREAT LITERARY GIANTS OF THE LAST CENTURY ACTUALLY ALMOST DIED OF THE FLU AND HER STORY, IN THIS BOOK, WHICH IS A TRUE STORY, IS A TRAGIC ONE. SHE HAD A FIANCEE WHO WAS A SOLDIER AND HE WAS ON LEAVE AND THEY WERE TOGETHER. SHE GOT INFLUENZA JUST ABOUT THE TIME THAT HE LEFT TO GO BACK TO HIS MILITARY ASSIGNMENT. AND SHE WAS IN THE HOSPITAL FOR MANY MONTHS UNCONSCIOUS AND UNAWARE. AND WHEN SHE FINALLY CAME TOO TO MONTHS LATER, SHE LEARNED THAT HE HAD CAUGHT INFLUENZA A FEW DAYS LATER AFTER LEAVING HER, AND DIED. THAT'S WHAT THE BOOK IS ABOUT. AND THEN WILLIAM FAULKNER, ANOTHER GREAT WRITER, LIKE MANY PEOPLE ACTUALLY SURVIVED THE 1918 FLU BECAUSE HE WAS PLACED UNDER QUARANTINE IN AN AERONAUTICS SCHOOL IN TORONTO AND HE NEVER GOT IT. ON THE LEFT IS EDWARD MONK, THE PAINTER OF THE SCREEN. THIS IS WHEN HE HAD SOMETHING TO SCREAM ABOUT. A SELF PORTRAIT OF HIM SITTING IN A CHAIR RECOVERING FROM THE 1919 INFLUENZA OF THE THE FRENCH POET WHO SURVIVED A HEAD WOUND IN THE WAR AND CAME BACK ONLY TO DIE OF THE 1918 INFLUENZA. AND ONE OF THE MUTATE WRITERS, THOMAS WOLF, AN AMERICAN CLASSIC HE WROTE, WHICH IN MY DAY, EVERY KID HAD TO READ IT. I LOVED IT. IT'S ALSO A TRUE STORY. AND AS IN REAL LIFE, THOMAS WOLF WAS THE SON OF A GRAVESTONE CUTTER. IN THE BOOK HIS BROTHER DIES OF INFLUENZA IN 1918 AND THE GHOST OF HIS BROTHER COMES BACK AS A CENTRAL PART OF THIS STORY. AND IN FACT, HIS REAL BROTHER, BENJAMIN HARRISON WOLF, DID DIE IN 1918, DID DIE OF THE FLU, AND I KNOW THE EVENTS IN THE BOOK ARE ACCURATE BECAUSE I WAS ABLE TO OBTAIN FROM THE WOLFE PEOPLE THE DEATH CERTIFICATE OF BENJAMIN DEPICTING OR CONSISTENT WITH THE DEATH OF THAT WAS DESCRIBED IN THE BOOK. EVEN AMERICAN FILM STARS DIED. ANNETTE IS NOT REALLY REMEMBERED TODAY BUT SHE WAS A LEADING LADY OF CHARLIE CHAPLIN. AND PERHAPS THE MOST TRAGIC DEATH IN 1918 IS OF SHEILA, WHO IS NOT REMEMBERED TODAY UNLESS YOU'RE AN ART LOVER BUT HE WAS THE MOST NOTORIOUS AND PERHAPS ONE OF THE GREATEST PAINTERS OF HIS ERA. THE ERA OF PICASSO. AND I THINK IT IS FAIR TO SAY HE WAS MORE FAMOUS THAN EVEN PICASSO AND BROCK AT THE TIME AND OTHERS OF THIS ERA. BUT IN OCTOBER 1918, HE AND HIS WIFE, THEN SIX MONTHS PREGNANT, GOT INFLUENZA AT THE SAME TIME AND THEY WENT INTO THEIR APARTMENT AND LIVED FOR A FEW DAYS AND THEY ALL THREE DIED TOGETHER. ALMOST TOGETHER. HE DIED LAST. AND THE LAST THING HE DID AS HE DIED WAS TO SKETCH PORTRAITS OF HIS DYING WIFE. THIS PHOTOGRAPH IS HIS DEATHBED PHOTO WHICH IS TAKEN BY A PHOTOGRAPHER AND THE PHOTOGRAPHER WAS -- THE CIRCUMSTANCES OF THE PHOTO ARE NOT KNOWN. IT'S A PROFESSIONAL PHOTO. PROFESSIONALLY LIT. SHE DID NOT GET INFLUENZA BUT SHE DIED. AND SORT OF IRONIC THE 15 YEARS LATER, HER PAINTINGS WERE WORTH FORTUNES AND WHEN THE NAZIS CAME IN, THEY CONFISCATED ALL THE PAINTINGS THEY COULD FIND. SOME NEVER HAVE BEEN RETURNED AND ALSO CONFISCATED THE PHOTOGRAPHER AND THREW HER IN THE GHETTO IN POLAND AND SHE SOMEHOW SURVIVED THE WAR. BUT OF COURSE THESE ARE FAMOUS PEOPLE. THERE IS A LOT OF OTHER PEOPLE NOT SO FAMOUS WHO ARE NOT INDIVIDUALLY REMEMBERED A CENTURY LATER. BUT I THINK IT IS WORTH REMEMBERING THEM BECAUSE AS BIOMEDICAL SCIENTISTS, WE HAVE TO REMEMBER THE 1918 PANDEMIC. THE REASON IS THAT SOMETHING LIKE IT WILL HAPPEN AGAIN. ONE DAY, OUR POPULATION ANTIBODIES TO THESE H1N1 VIRUSES WILL WAYNE OR GO AWAY. BUT THE GENES AND THE VIRUSES THAT CAUSE THEM ARE STILL OUT THERE IN WILD BIRDS. THEY WILL BE THERE 100 YEARS FROM NOW. THEY ALWAYS WILL BE READY TO COME BACK UNLESS WE FIND A WAY TO STOP THEM. IT WILL HAPPEN AGAIN. THINKING ABOUT THIS PAST CENTURY OF PANDEMIC INFLUENZA CAUSED BY THE MOTHER OF ALL PANDEMIC VIRUSES, AND HER OFFSPRING, AND WORKING AS WE DO HERE AT NIAID TO BRING THIS PANDEMIC ERA TO AN END, WE REALIZE THAT THE PAST IS NEVER DEAD BECAUSE WILLIAM FAULKNER SAID, IT'S NOT EVEN PAST. AS WE LOOK AHEAD, WE HAVE TO ALWAYS KEEP LOOKING BACKWARD TO REMEMBER, THINK AND TRYING TO UNDERSTAND WHAT HAPPENED IN 1918 AND WHAT IT IS WE HAVE TO PREVENT. I WANT TO END THIS BY THANKING SO MANY FOLKS LISTED HERE, JEFF AND HIS TEAM, JULIE WHO DID THE ART WORK THAT YOU SAW IN THE POSTER AND MANY AND OTHER WORK AS WELL. AND JOHN AND ANN AND OF COURSE TONY FAUCIY WHO HAS BEEN A STIMULATING COLLEAGUE AND BOSS FOR MANY YEARS THAT HELPED ME THINK ABOUT SOME OF THESE THINGS. AND I THANK ALL OF YOU. [ APPLAUSE ] >> THAT WAS FANTASTIC. REALLY GOOD. ANY QUESTIONS, COMMENTS FOR DAVID? WHILE THEY ARE THINKING, LET ME ASK YOU A COUPLE. SO WE SPOKEN ABOUT THE PREPANDEMICS WE KEEP HAVING TO ADDRESS, THE H1N1, H7N9 AND WHEN THE 1918 PANDEMIC CAME, IT DIDN'T, TO OUR KNOWLEDGE, LINGER AROUND AND INFECT A FEW PEOPLE AND THEN ADAPT ITSELF A LITTLE BIT MORE AND MORE AND MORE. SO WHAT IS YOUR OPINION ABOUT THE DANGER OF SOMETHING THAT IS PRE-PANDEMIC, LIKE H7N9 HANGING AROUND FOR A LONG TIME. H5N1 SINCE 1997 STILL HASN'T ADAPTED TO HUMAN. THE CHANCES OF THAT HAPPEN HAVINGS SOMETHING COMING OUT OF NOWHERE THE WAY 1918 CAME. >> AN INTERESTING QUESTION. I TALK A LOT ABOUT THIS WITH JEFF AND WE DON'T NECESSARILY 100% AGREE. BUT I THINK THAT WILD BIRD VIRUSES ARE ALWAYS GOING TO BE A POTENTIAL SOURCE -- WHEN I SAY WILD BIRD, I MEAN DUCKS AND GEESE. I DON'T MEAN CHICKENS. I THINK THOSE ARE ALWAYS A POTENTIAL SOURCE AND THEY COULD COME IN ANY MOMENT. I THINK THE H2N2 VIRUS WHICH CAUSED THE PANDEMIC IN 1957 AND IS STILL IN FREEZERS AROUND THE WORLD, IF THAT GETS OUT IT WILL PROBABLY CAUSE A PANDEMIC. AS FAR AS BIRD VIRUSES GO, I NEVER WANT TO SAY I'M NOT -- I WOULD NEVER WANT TO SAY THEY ARE NOT LIKELY TO CAUSE A PANDEMIC. BUT I WOULD OBSERVE THAT THESE POULTRY VIRUSES LIKE H5N1 AND H7N9, WHETHER THEY ADAPT TO CHICKENS, THEY GO THROUGH COMPLICATED MUTATIONAL PATHWAYS THAT PERHAPS MAKE IT MORE DIFFICULT TO BACK ADAPT AND GET INTO A HUMAN BEING. ANYTHING IS POSSIBLE BUT I'M NOT AS WORRIED AS MOST ARE ABOUT THESE CHICKEN VIRUSES CAUSING A PANDEMIC. >> YOU TOOK A LONG TIME TO SAY THAT. I HAVE BEEN TRYING TO COAX YOU INTO SAYING THAT. ANY OTHER -- YES? >> HI, THANK YOU FOR A WONDERFUL TALK. I'M INTERESTED IN THE DIGITAL LIBRARY AND WHETHER THERE WILL BE RESOURCES FOR GENEALOGY AND SEE WHETHER YOU HAVE A LINEAGE THAT DIED FROM INFLUENZA IN THE PAST. >> THERE WON'T BE ANY -- NO PLANS AT THIS POINT FOR THERE TO BE ANY GENEALOGICAL CONNECTIONS. BUT A LOT OF THAT YOU CAN DO ON ANCESTRY.COM RIGHT NOW. THE PANDEMIC DIGITAL ARCHIVES IS REALLY RELATED MOSTLY TO SCIENTIFIC PUBLICATIONS. THE GEOSPATIAL STUFF IS BUILT IN BECAUSE PUBLICATIONS COME FROM A CERTAIN PLACE, DESCRIBE A CERTAIN CITY OR A CERTAIN NEIGHBORHOOD. BUT I DON'T THINK I CAN IMAGINE ANY DIRECT LINK WITH ANCESTRY-TYPE INFORMATION. >> THANK YOU FOR A GREAT TALK. GETTING BACK TO THE 1918 PANDEMIC, IT SEEMS IF YOU LOOK AT THE DATA, THE PHILADELPHIA AND SAN FRANCISCO HAD REALLY HIGH MORTALITY. I THINK PHILADELPHIA HAD SOMETHING LIKE 27 DEATHS BETWEEN SEPTEMBER AND NOVEMBER. WHAT DO YOU CHOCK THAT UP TO? JUST SOCIAL AND BEHAVIORAL FACTS? THE INFAMOUS BOND PARADE IN PHILADELPHIA? OR WAS THE VIRUS SOMEHOW DIFFERENT? >> WELL, I DON'T THINK THE VIRUS IS DIFFERENT. I SHOULD SAY I HAVEN'T SAID THIS BUT, THE TABENBURGER LABORATORY SEQUENCED A NUMBER OF DIFFERENT VIRUSES OR THEIR GENES, SPANNING 10 MONTHS AND THE VIRUS IS THE SAME. THERE IS NO EVIDENCE THAT IT IS CHANGING. SO VIRAL CHANGE IS NOT A VERY LIKELY THING. WITH RESPECT TO PHILADELPHIA AND OTHER CITIES THAT WERE HARD HIT, TWO SCIENTISTS, MARTY AT CDC AND HOWARD AT UNIVERSITY OF MICHIGAN, HAVE PROPOSED THAT THE HIGHER DEATH RATES WERE ASSOCIATED WITH LESS ROBUST PUBLIC HEALTH ACTIONS. AND THOSE CITIES THAT HAD LOWER DEATH RATES HAD BETTER PUBLIC HEALTH. AND IT'S AN INTERESTING IDEA. I'M NOT CONVINCED JUST BECAUSE I'M SKEPTICAL BY NATURE ABOUT THINGS LIKE THIS, THAT CITIES WHO HAVE BETTER PUBLIC HEALTH ACTIVITY PROBABLY HAVE BETTER OTHER STUFF AS WELL. AND THE BETTER PUBLIC HEALTH ACTIVITY MAYBE A MARKER FOR ALL SORTS OF THINGS THAT CAN'T EASILY BE MEASURED, CROWDING AND OTHER THINGS. SO, I WOULD SAY THE RETURNS ARE OUT. WE DON'T REALLY KNOW WHAT THE ANSWER TO THAT IS. BUT IT'S NOT VIRAL, I'M SURE OF IT. >> HELLO. SO, I HEARD THAT THERE IS LITTLE IF ANY AIRBORNE TRANSMISSION OF INFLUENZA IF HUMIDITY LEVELS ARE ABOVE A CERTAIN LEVEL BASED ON RESEARCH DONE WITH FERRETS. AND I WAS WONDERING IS THAT INDEED THE CASE? IF SO, WERE THERE FEWER DEATHS IN PARTS OF THE WORLD WHERE THE TEMPS WARMER AND THE HUMIDITY LEVELS ARE HIGHER IN 1918? >> SO YES IT IS TRUE THAT HUMIDITY -- TWO THINGS THERE ARE CLIMATIC. HUMIDITY AND HEAT INACTIVATE INFLUENZA VIRUSES. HUMIDITY BY THERMAL IN ACTIVATION. TEMP BY THERMAL INACTIVATION AND HUMIDITY BY WHEN THERE IS HUMIDITY, THERE ARE LARGE DROP LETS OF WATER IN THE AIR AND THEY FALL TO THE GROUND. YES, THAT IS TRUE. I DON'T KNOW THAT ANYBODY EVER DONE A COMPARISON TO DIFFERENT PARTS OF THE WORLD WITH DIFFERENT HUMIDITY AND TEMP THINGS. IT'S INTERESTING THAT IN EUROPE, THE FIRST REAL HIGH-LEVEL MORTALITY OCCURRED IN NORTHERN EUROPE WHERE IT IS COLDER THAN IN SOUTHERN EUROPE. SO FOR EXAMPLE, YOU HAD ALL OF SCANDINAVIA GETTING INVOLVED WELL BEFORE ITALY AND SOUTHERN FRANCE. BUT THEN ON THE OTHER HAND, MUMBAI AND OTHER INDIAN CITIES WHICH ARE NOT SO FAR FROM THE EQUATOR IN THE NORTHERN HEMISPHERE, INDIA HAD THE WORST FATALITY OF ALL. SO I DON'T THINK THE WAY TO LOOK AT IT IS THE VIRUS WILL GET YOU EVENTUALLY. AND YES, EVERY PANDEMIC THAT OCCURS, IT SHUTS DOWN IN THE SUMMER IN TEMPERATE ZONES. 1957 WHEN THE H2N2 CAME, IT GOT TO THE UNITED STATES IN THE SPRING AND STARTED TO GO GANGBUSTERS AND THEN THE SUMMER CAME AND IT LEVELED OFF AND WENT AWAY AND WHEN THE FALL CAME IT CAME BACK AGAIN. SO IN THE SHORT-TERM, THESE CLIMATIC THINGS CAN BLUNT A PANDEMIC BUT I THINK IT WILL FIND YOU EVENTUALLY IF IT DOESN'T GET YOU NOW, IT WILL GET YOU NEXT YEAR. >> THANK YOU. >> THANK YOU, DAVID. YOU WANT TO SAY A WORD ABOUT HOW THE SPANISH GOT TAGGED FOR THE BLAME? >> HOW DID THE SPANISH GET TAGGED FOR THE BLAME? IT WAS WORLD WAR I AND SPAIN WAS A NEUTRAL COUNTRY AND MOST OF THE OTHER COUNTRIES IN EUROPE WERE INVOLVED WITH THE WAR IF NOT COMBATANTS OR ALLIES. AND SO THEY HAD RESTRICTION OF THE PRESS. AND SO IN GERMANY, YOU WEREN'T LIKELY TO READ ABOUT THE PANDEMIC FLU KILLING YOU. THE ALLIES DIDN'T WANT THE OTHER GUYS TO KNOW THAT THEIR CITIZENS WERE DYING. SO SPAIN DIDN'T HAVE A NEWS BLACKOUT. IT WAS IN ALL THE SPANISH NEWSPAPERS THAT THERE WAS A FLU OUTBREAK IN THE SPRING OR IN MARCH, LATE MARCH AND APRIL. AND THIS WHOLE THING OF BLAMING IT ON ANOTHER COUNTRY GOES BACK TO THE 1889 PANDEMIC, EVERYBODY CALLED IT THE RUSSIAN FLU BECAUSE IT WAS FIRST NOTICED IN RUSSIA. YOU HAVE TO BLAME SOMEBODY. THE IT'S HUMAN NATURE. >> THANK YOU AGAIN FOR A WONDERFUL LECTURE. THE WHAT DO YOU THINK THE IMPACT OF VACCINES LIKE PNEUMOVAX, WHICH PREVENT SOME BACTERIAL PNEUMONIAS MIGHT HAVE ON A FUTURE PANDEMIC? >> I THINK THE WHOLE PNEUMOVAX STORY IS AN INTERESTING ONE AND THE USE OF THESE VACCINES ON A LARGE-SCALE IS BEING STUDIED NOW PARTICULARLY BY THE GATES FOUNDATION. A LOT OF STUFF HAS BEEN PUBLISHED ABOUT IT. I'M NOT REALLY UP ON IT BUT I THINK KEITH AT GATES AND THE LADY WHO HE WORKS WITH WHOSE NAME I'M BLANKING ON AT THE MOMENT. SHE IS AT GATES AND WORKS WITH KEITH ON THE PNEUMOCOCCAL VACCINES. THEY WILL BE LOOKING AT THESE THINGS. I THINK CLEARLY IT WILL BE THE CASE THAT PNEUMOCOCCAL VACCINES PREVENT DEATHS FROM PNEUMONIA IN PEOPLE WHO GET FLU. BUT I'M NOT SURE HOW THE DATA IS ALL HUNG TOGETHER YET. BUT YOU COULD BET, I WOULD BE SHOCKED AND YOU PROBABLY WOULD TOO IF PNEUMOCOCCAL VACCINES DID NOT HAVE AN EFFECT ON PEOPLE DYING FROM INFLUENZA. >> THANK YOU. >> THANK YOU, DAVID. COULD YOU COMMENT ON THE SO-CALLED FON CONMOWS NEUROLOGICAL DISEASE THAT PERHAPS THERE WAS A TEMPORAL ASSOCIATION WITH PANDEMIC OF 1918, 1919? IS THERE ANY EVIDENCE FOR CAUSAL RELATIONSHIP? >> SO ENCEPHALITIS LE THANK CA, OR SLEEPING SICKNESS WAS A PANDEMIC THAT OVERLAPPED WITH THE 1918 PANDEMIC AND THERE HAS LONG BEEN A BELIEF THAT SOMEHOW THE TWO WERE LINKED. DR. TAUBENBERGER LOOKED AT BRAINS OF PEOPLE WHO DIED OF ENCEPHALITIS LE THANK CATO LOOK FOR EVIDENCE OF A VIRUS, FLU VIRUS. FLU DOESN'T GET INTO THE BRAIN. OF COURSE HE DIDN'T FIND IT. I DON'T KNOW THE ANSWER TO THAT BUT I WOULD NOTE A COUPLE OF THINGS. ENCEPHALITIS LETHARGIC, THE PANDEMIC BEGAN IN 191622 YEARS BEFORE THE 1918 FLU AND IT LASTED UNTIL 1926, 10 YEARS, AT WHICH TIME THE 1918 FLU WAS QUIESCENT. AND SO THE RELATIONSHIP IS NOT CLEAR AND YOU WOULD SPECULATE BUT SINCE YOU BROUGHT IT UP, I'M GOING TO GIVE YOU MY THEORY WHAT IT IS. I THINK THAT IN SOME STUDIES OF PEOPLE -- MOST PEOPLE WHO GOT THIS DISEASE DID NOT HAVE A RECENT FLU INVENTION. THAT IS CLEAR. BUT OF THOSE WHO DID, THERE IS A LOT OF LITERATURE TO SUGGEST THAT IF YOU GOT FLU AND GOT THIS DISEASE, IT ATTENDED TO BE ABOUT 6 MONTHS LATER. SO I THINK THIS COULD BE A BACTERIAL COMPLICATION AND I WOULD PROPOSE THIS, THAT PEOPLE WHO GOT THIS DISEASE MAY HAVE HAD THEIR FLU MAY HAVE BEEN COMPLICATED BY STREPTOCOCCAL BACTERIAL INFECTION AND THIS DISEASE COULD BE A STREPTOCOCCAL COMPLICATION AS IS SID EN HAM'S PA RIA AND THE PAN DEATH SYNDROME WHICH IS WORKED ON HERE AT NIH. BUT IT'S JUST A THEORY. >> HI. I HAD TO STEP OUT FOR A MINUTE SO APOLOGIES IF YOU ALREADY MENTIONED THIS. I'M WONDERING IF YOU HEARD OF THE HYPOTHESIS THIS OVER TREATMENT WITH ASPIRIN WAS A CONTRIBUTORY FACTOR TO MORTALITY AND IF YOU COULD COMMENT ON THAT? >> YES, THAT IS A THEORY OF KARIN STARKO WHO IS THE LADY WHO -- SHE WAS AN EIS OFFICER WITH ME AT CDC WHO SHOWED ASPIRIN WAS RELATED TO RICIN DOME. WHEN SHERIFF'S OFFICE PUBLISHING THAT PAPER SHE WAS IN COMMUNICATION WITH ME AND I TOLD HER AGAIN AND AGAIN, NO, I DON'T THINK SO. -- WHEN SHE WAS PUBLISHING THAT PAPER. BUT I DON'T THINK THAT ASPIRIN IS RELATED. BUT IT IS AN INTERESTING THING TO THINK ABOUT BECAUSE THIS IS THE ERA IN WHICH ASPIRIN IS USED ALL OVER THE WORLD AND IT HAD COME FROM BAYER AND THEY HAD A MONOPOLY ON IT. EVEN IN INDIA THEY WERE USING ASPIRIN. SO IT'S NOT A CRAZY IDEA. I JUST THINK THE DATA DON'T SUPPORT IT. >> SO YOU SAID YOU THINK IT IS NOT -- THE NEXT PANDEMIC ISN'T GOING TO BE COMING FROM CHICKENS. WHAT KEEPS YOU UP AT NIGHT? >> WHAT KEEPS ME UP AT NIGHT IS IF YOU THINK ABOUT IS IT, THE NEXT BIG THING, THE NEXT BIG PANDEMIC, THE NEXT BIG DEADLY DISEASE IS ALWAYS, ALWAYS THE ONE YOU NEVER COULD HAVE POSSIBLY IMAGINED. THAT'S WHAT KEEPS ME UP. >> THANK YOU. THAT WAS JUST TERRIFIC. I WONDERED IF YOU COULD SAY A FEW WORDS ABOUT THE IMPACT ON SOME OF THE MORE REMOTE POPULATIONS LIKE NATIVE-AMERICANS AND THOSE WHO WERE IN THE URBAN AREAS, FOR EXAMPLE AND HOW THEY WERE IMPACTED OR SPARED. >> WELL, SO NATIVE PEOPLES AND PEOPLE IN REMOTE AREAS, THEY WERE A LOT OF REMOTE AREAS THAT ENTIRELY ESCAPED THE PANDEMIC AND NEVER GOT INFLUENZA FOR DECADES. BUT THERE WERE OTHER REMOTE AREAS SUCH AS VEHICLES IN ALASKA WHERE THE MORTALITY WAS ALMOST 100%. AND SO -- CHALLENGES -- SO IT IS VERY HARD TO MAKE A RULE OF THUMB FROM THAT. BUT I THINK I WOULD SAY THAT WE DON'T KNOW WHY, FOR EXAMPLE, ALASKAN VILLAGES HAD 80 OR HIGHER PERCENT MORTALITY BUT IT PROBABLY HAD TO DO WITH NUTRITION AND IT PROBABLY HAD TO DO WITH LACK OF GOOD MEDICAL CARE AND LACK OF MEDICINES AND BACTERIAL -- ALASKANS ARE HIGH CARRIERS OF STREP COX I AND OTHER BACTERIA. IT'S JUST -- WE REMEMBER THAT WITH MEASLES FOR EXAMPLE, A DIFFERENT DISEASE, MEASLES AND PNEUMONIA YOU ALSO DIED THE SAME WAY. YOU GET A VIRAL PNEUMONIA AND THEN THE BACKTERIA KICK IN. WITH MEASLES, EVEN LOW VITAMIN A CAN INCREASE YOUR RISK OF SEVERE DISEASE AND DEATH. I SPECULATE SOMETHING IS GOING ON WITH FLU IN VITAMIN A OR AREAS WITH VITAMIN A DEFICIENT. THAT IS MUCH OF THE TROPICAL AREA, NOT SO MUCH UP IN ALAS I DON'T THINK EVEN WITH DIETS IN 1918. AND THEN IN INNER CITIES, THE DEATH RATES IN THE INNER CITIES IN THE UNITED STATES WERE NOT THAT MUCH FURTHER ABOVE THE DEATH RATES OF WELL-TO-DO PEOPLE IN THE SAME CITIES. >> THANK YOU FOR A VERY NICE LECTURE AND THANK YOU FOR THOSE KIND WORDS ABOUT THE NIH LIBRARY LIBRARY. COULD YOU COMMENT ON PERHAPS ANY CONNECTIONS WITH THE 1918 FLU AND THE FORMATION OF THE IH ITSELF. >> WELL, OF COURSE KINNIAN, THE FOUNDER OF THE HYGIENIC LABORATORY WHICH BECAME NIAID, AND BECAME HYGIENIC LAB ALSO BECAME NIH. WE ARE NIH. WAS ALIVE AND WORKING IN THE HYGIENIC LAB IN 1889 AT THE TIME OF THE PREVIOUS PANDEMIC. AND THEY DID DO SOME WORK ON IT AS DID THE PUBLIC HEALTH SERVICE, BUD KINNIAN HIMSELF DIDN'T DO A LOT OF WORK ON INFLUENZA. HE WAS INVOLVED IN IT BUT NOT TO A GREAT EXTENT. BUT DURING THE 1918 PANDEMIC, OTHER PUBLIC HEALTH SERVICES, HE HAD RETIRED BY THEN AND ACTUALLY DIED IN 1919 DURING THE FLU PANDEMIC. BUT BY THAT TIME, OTHER PUBLIC HEALTH SERVICE OFFICERS WERE WORKING ON FLU AND THEY DID AN AWFUL LOT OF GOOD WORK. >> SO DAVID, JUST FOR ANOTHER CONGRATULATIONS. THIS IS A FANTASTIC LECTURE BUT THE AUDIENCE COULDN'T HELP BUT SEE WHEN DAVID PREPARES SOMETHING, HE REALLY PREPARES IT. THEY MADE ME NOTICE THAT MAYBE 250 ADDITIONAL SLIDES WERE SHOWN WHILE YOU WERE ANSWERING THE QUESTION. THEY DIDN'T FALL OUT OF THE SKY. HE MADE THEM. THANK YOU VERY MUCH. [ APPLAUSE ]