Articles, Blog

Imagining the Next Flu Pandemic – and Preventing it!

October 21, 2019


>>THANK YOU, ANDY. THAT WAS REALLY NICE. AND THANK YOU, ALL, FOR BEING HERE. I REALLY WANT TO COMMEND THIS MORNING’S PRESENTATIONS. I THOUGHT YOU ALL DID A REALLY EXCELLENT JOB. I’M NOW GOING TO INTRODUCE THE FINAL SPEAKER, RALPH BARIC WHO IS A PERSON I REALLY ADMIRE AT THE SCHOOL. HE’S ONE OF THE MOST ACCOMPLISHED AND PROLIFIC SCIENTISTS. AND BROUGHT CREATIVITY, PERSISTENCE AND INNOVATION TO THE STUDY OF VIRUSES. I’VE HAD THE OPPORTUNITY TO TOUR HIS LAB AND ON A COUPLE OCCASIONS. IT’S JUST REALLY IMPRESSIVE TO SEE THE WAY HE AND HIS TEAMWORK TOGETHER. I’LL JUST HIGHLIGHT A FEW OF THE THINGS THAT ARE ON THE SLIDE SO WE CAN GET ON TO RALPH. HE’S THE PROFESSOR OF E PID EMIOLOGY AND MICROBIOLOGY IN THE SCHOOL OF MEDICINE. LIKE A NUMBER OF PEOPLE HAVE SPOKEN, YOU HAVE CROSSED SCHOOLS. HIS LAB SPECIALIZES IN VIRUSES AND EMERGING INFECTIONS LIKE ZIKA VIRUSES. I’LL JUST MENTION THAT THE FIRST TIME I WAS INTRODUCED TO RALPH WAS AT MY FIRST FACULTY MEETING WHEN I CAME TO THE SCHOOL PUBLIC HEALTH AFTER BEING AT THE NIH AND BILL ROBER WAS DEAN AT THE TIME AND TALKED ABOUT THE FACT THAT NIH JUST CALLED RALPH AND OFFERED HIM A BIG GRANT TO STUDY ZARS. AND HAVING BEEN AT THE NIH, I KNEW HOW UNUSUAL THAT WAS AND GOT CALLED AND OFFERED A LARGE GRANT. THAT TOLD ME A LOT ABOUT RALPH. AND I DECIDED I WANTED TO MEET HIM. AND EVERYTHING I’VE LEARNED ABOUT HIM SUBSEQUENTLY HAS SHOWN HOW IMPRESSIVE HE IS. WHAT A QUICK STUDY AND THE IMPORTANCE OF THE WORK THAT HE DOES. SO RALPH IS GOING TO TALK ABOUT HOW BAD IT COULD BE AND WHAT WE COULD DO ABOUT IT. SO RALPH, THANK YOU SO MUCH.>>HOW DO I ADVANCE? GREAT. THANK YOU. WELL, I HAVE TO ADMIT I’M WORRIED ABOUT GIVING THIS TALK. PARTIALLY BECAUSE IT’S TOUGH TO MAKE PREDICTIONS, ESPECIALLY ABOUT THE FUTURE. SO THERE’S A GOOD CHANCE I COULD BE WRONG. I STUDY CORONA VIRUSES, NORO VIRUSES AND SOME FLU VIRUS RESEARCH. THE OTHER REASON I’M A LITTLE BIT WORRIED IS BEING LABELED AS AN HARBENGER OF DOOM. THIS IS NOT ME. I’M NOT ONE OF THE FOUR HORSEMAN OF THE APOCALYPSE. I’M REALLY KIND OF A NICE GUY. [ LAUGHING ]>>SO PLEASE COME TALK TO ME AFTER THIS TALK. I WILL MENTION THAT VIRUSES ARE CERTAINLY IN THE POCKETS OF ALL OF THE FOUR HORSEMAN. THEY CAN BE USED IN ALL OF THESE SCENARIOS. SO I’D LIKE TO START OFF BY TAKING A STEP BACK AND TALK ABOUT HOW INFECTIOUS DISEASES RANKS OR STACKS UP AGAINST OTHER NATURAL DISASTERS IN TERMS OF FREQUENCY AND RELATIVE RISK. SO IF YOU STEP BACK EVERY 3 TO 400 MILLION YEARS OR SO, THERE’S A DANGER OF A GAMMA IRRADIATIN BURST. SHOOTS OUT THIS BURST OF GAMMA RADIATION. CAN CAUSE ACID RAIN, HIGH RADIATION LEVELS TO PLANT AN ANIMAL LIFE ON THE PLANET. AND THIS CAN OCCUR AS FAR AS 6500 LIGHT YEARS AWAY. FORTUNATELY, DOESN’T HAPPEN SO OFTEN. SO DON’T REALLY LOSE SLEEP ABOUT THIS AT NIGHT. LITTLE BIT MORE LIKELY TO CAUSE AN ISSUE IS AN ASTEROID STRIKE. THE EARTH RUNS INTO ABOUT 3700 TO ABOUT 7800 TONS OF DEBRIS AS IT FLOATS THROUGH SPACE. OCCASIONALLY SOME OF THESE ARE BIG ROCKS. WHEN A REALLY BIG ROCK HITS THE PLANET, CAN RESULT IN EXTINCTION LEVEL EVENT LIKE WHAT HAPPENED TO THE DINOSAURS. THE GOOD NEWS IS MAMMALS BECAME DOMINANT AND SO WE ARE HERE TODAY. OTHERWISE, WE’D PROBABLY BE LUNCH. THE U.S. TAKES THIS THREAT FAIRLY SERIOUSLY SO NASA HAS A NEAR EARTH OBJECT PROGRAM THAT TRACKS SATELLITES THAT ARE LARGE ENOUGH TO CAUSE DAMAGE TO THE PLANET. ONE PROBLEM THAT THEY FACE IS THEY CAN ONLY TRACK THEM FOR ABOUT 100 YEARS AND THE ACCURACY FALLS OFF. BUT FORTUNATELY, BRUCE WILLIS IS HERE. HE IS ALSO A PENSBROKE BOY. IT’S A LITTLE TOWN IN NEW JERSEY. 3500 OF US. A CLEAR EPICENTER OF PLANETARY DEFENSE. REMEMBER THAT, PLEASE. ANYWAY, MOVING UP ON THE LIST, SUPER VOLCANOES. THESE BECOME MORE FREQUENT. THEY ARE ABOUT EVERY MILLION YEARS. LARGE ENOUGH TO COAT CONTINENT WITH ABOUT HALF AN INCH OF ASH OR MORE. THE LAST BIG ONE WAS TABU IN INDONESIA AND KNOCKED THE HUMAN POPULATION DOWN TO ABOUT 10,000 INDIVIDUALS. THERE ARE ABOUT 20 OF THESE OF CONCERN ON THE PLANET. THIS IS OURS. IT’S YELLOWSTONE, OBVIOUSLY. GO TO THE CALDERA AND SPEND TIME AT THAT HOTEL. IT’S QUITE A TREAT. FINALLY, WE HAVE KERRINGTON LEVEL OF EVENTS. THESE ARE GEOMATIC STORMS. THROW OFF A LOT OF MASS, THEY CAN HIT OUR ELECTROMAGNETIC WAVES AROUND THE EARTH AND CAN RESULT IN MAGNETIC STORMS. THE BIGGEST ONE OCCURRED IN 1859. WASN’T MUCH ELECTRONICS AT THE TIME. BUT IT CAUSED FIRES AND TELEGRAPH WORKERS. MUCH SMALLER ONES OCCURRED IN THE 60s AND 70s AND KNOCKED OUT POWER GRIDS IN THE U.S. AND CANADA. THEY CAN CAUSE ABOUT $23 TRILLION IN DAMAGE AND POTENTIALLY KNOCKOUT THE POWER GRID FOR ONE TO FIVE YEARS. SO THIS IS NOT INSIGNIFICANT. AND WHAT’S A LITTLE BIT SCARY IS MUCH LARGER FLARES ARE POSSIBLE. SO NASA HAS TAKEN THIS PRETTY SERIOUSLY AND THEY ARE THE FIRST SOLAR PROBE THAT’S GOING TO GO AROUND THE SUN IS GOING TO BE LAUNCHED THIS SUMMER. AND THEY ARE GOING TO TAKE A LOOK AT THIS. THIS CAN CERTAINLY KNOCKOUT GPS, CELL PHONE, INTERNET AND POWER GRID FOR SEVERAL YEARS. OKAY. NOW BACK INTO INFECTIOUS DISEASES. HERE WE ARE. IT’S THE NUMBER ONE THREAT, FROM MY PERSPECTIVE. SINCE I’VE BEEN ON THE PLANET, THERE’S BEEN EPIDEMIC VIRUS EVERY DECADE STARTING WITH ASIAN FLU 1957. HONG KONG 1967. H1N1 FOLLOWED BY HIV, WEST NILE AND THEN TO THE 21ST CENTURY. AND THINGS SPED UP. SARS WAS THE FIRST. ABOUT 8,000 CASES IN 33 COUNTRIES WITH 10% MORTALITY. CHIKUNGUNYA SPREAD ACROSS ASIAN TO POLYNESIAN ISLANDS. AND MEXICAN FLU IN 2009 CAUSED 220,000 DEATHS WORLDWIDE. CORONA VIRUS EMERGED IN 2012. 2200 CASES. ABOUT THE SAME TIME H7N9 EMERGED IN SOUTHEAST ASIA WITH 1600 CASES AND 39% MORTALITY. STILL AROUND TODAY FOLLOWED BY EBOLA WITH 30,000 CASES AND 39% MORTALITY AND ZIKA VIRUS SORT OF DRIFTED ACROSS ASIA AND ENDED UP IN POLYNESIA. SO IF YOU LOOK AT VIRUS FAMILIES, CLEARLY INFLUENZA AND CORONA AND FLATY ARE THE THREE CAUSING PROBLEMS IN THE 21ST CENTURY. HATE BEING BEHIND FLU. I INCLUDE SWINE. FOUR MORE BIG PANDEMICS OF SWINE. CLEARLY, THE MOST DANGEROUS VIRUSES ARE CORONA VIRUSES. I HAD TO SAY THAT.>>[INAUDIBLE].>>YEAH, I KNOW. I’M A CORONAOLOGIST. SO I’M NOT TALKING ABOUT FLU. I HAVE HIGH INSECURITY LEVELS ABOUT FLUVIALITY. SO BASED ON THAT DATA, IT’S CLEARLY NUMBER ONE, IF YOU DON’T BELIEVE ME, YOU CAN BELIEVE BILL GATES. HE CLEARLY THINKS 10 MILLION PEOPLE CAN BE KILLED IN THE NEXT DECADE FROM INFECTIOUS DISEASES. THINGS LIKE SARS DISAPPEARED. EBOLA DISAPPEARED. ZIKA HAS ALMOST DISAPPEARED. THESE VIRUSES ACTUALLY EXTINCT OR JUST HIDING? WE’VE ASKED THAT QUESTION WITH SARS. THESE ARE, AGAIN, BETWEEN 2002 AND 2004, THESE ARE THE VIRUSES ASSOCIATED WITH THE EXPANDING SARS EPIDEMIC. MOST OF THEM ARE GONE. ALL OF THEM ARE GONE. WE CAN’T FIND THESE ANY MORE. WHEN YOU SEQUENCE BACK, THESE ARE HORSE SHOE BATS AND THIS IS A BAT WHO WANTS TO BITE WHOEVER SHORTHANDLING IT, YOU FIND SARS-LIKE VIRUSES. THESE ARE UP TO 97% IDENTICAL. SO DO THEY HAVE PRE-PANDEMIC POTENTIAL? THAT’S A QUESTION WE WERE INTERESTED IN. AND SO WHAT WE DID, THIS SPIKE LIKE A PROTEIN GENE MEDIATES SPECIFICITY. YOU CAN REMOVE THAT FROM THE EPIDEMIC STRAINS IN PLACE OF THEM. THIS WAS DONE BY PEOPLE IN THE LAB. AND OF THE FIVE THAT WE DROPPED IN BEING ALMOST IDENTICAL TO VERY DIFFERENT, THREE OF THESE COULD REPLICATE JUST FINE AND USE HUMAN RECEPTORS FOR ENTRY. IF YOU TOOK EPITHELIAL CELLS, REMOVED FROM TRANSPLANT RECIPIENTS. THE LUNG THEY GAVE UP NOT THE LUNG THEY RECEIVED. THEY TAKE ON THE ARCHITECTURE OF THE HUMAN LUNG. SARS LOVES TO REPLICATE IN THESE CELLS AND THESE VIRUSES GROW IN THOSE CELLS AS WELL AS THE EPIDEMIC STRAINS. AND YOU CAN DO A VARIETY OF EXPERIMENTS TO GET AN IDEA OF THEIR PRE-PANDEMIC POTENTIAL. THEY REPLICATE EXCEPTIONALLY WELL. IF THE PARENTAL STRAIN IS VALIENT — IF YOU TAKE A MOUSE THAT HAS THE HUMAN RECEPTOR IN IT, THESE VIRUSES ARE LETHAL. SO THEY CLEARLY HAVE THE POTENTIAL TO CAUSE LETHAL DISEASE. IF YOU TAKE VACCINES AGAINST SARS THAT WORK AGAINST SARS, THEY DON’T WORK AGAINST THE VARIANCE SITTING IN THE ANIMAL POOLS. AND THERAPEUTIC ANTIBODIES THAT WORK AGAINST SARS DON’T WORK AS WELL AGAINST THE MORE DISTANT STRAINS. SO THE ANSWER IS THERE’S STILL LOTS OF PRE-EPIDEMIC VIRUSES AROUND. THIS IS THE SARS STORY BUT YOU CAN GO TO FLU OR ANY OTHER VIRUS THAT HAS EMERGING POTENTIAL, POPS UP CAUSES AN OUT BREAK AND DISAPPEARS. THEY ARE WAITING TO RETURN. IN FACT, PEOPLE THAT LIVE AROUND THE CAVES WHERE THESE BATS HANG OUT WITH THESE VIRUSES ARE POSITIVE. AND MANY OF THEM HAVE NEUTRALIZING ANTIBODIES. THE VIRUS IS SPILLING OVER. IT WILL HAPPEN AGAIN. SO WE CAN GO TO OUR PANIC-O-METER. WHAT KIND OF PERSON WILL YOU SEE ON THE NEWS THAT WILL RAISE YOUR TENSION LEVEL AND CAUSE PANIC? THIS IS BY FIELDS. CLEARLY, THESE GUYS DON’T CAUSE MUCH PANIC. DOWN AT THIS END, ASTRONOMERS AND THE VIROLOGISTS CAN DO BETTER. THERE IS A REAL THREAT. CAN WE LEARN ANYTHING ABOUT PAST AND CURRENT PANDEMICS TO GIVE US AN IDEA HOW BAD THE NEXT ONE CAN BE? LET’S LOOK HISTORICALLY. WELL, WE HAVE BLACK DEATH. 75 MILLION PEOPLE IN EUROPE. THE SPANISH FLU THAT WE’RE TALKING ABOUT TODAY WITH 50 TO 100 MILLION DEATHS. HIV HAS KILLED A MILLION PEOPLE PLUS A YEAR. 35 MILLION ARE INFECTED. DEVASTATING DISEASE. SMALL POX DURING THE PLAGUE. 20 TO 30% MORTALITY IN ADULTS. 80% OF THE CHILDREN DIED. IN FACT, ALTHOUGH IT’S RARELY MENTIONED SMALL POX KILLED MORE PEOPLE IN THE 20TH CENTURY THAN ANY OTHER PASSAGE. 300 TO 500 MILLION WAS ERADICATED. ONE OF THE GREATEST PUBLIC HEALTH SUCCESS STORIES. TB, 1.3 TO 1.7 MILLION DEATHS PER YEAR. ASIAN FLU, 2 MILLION DEATHS. TYPHOUS. THIS IS JUST ONE EXAMPLE. THERE ARE MORE. YOU CAN GO TO MALARIA WHICH KILLS HALF A MILLION PEOPLE PER YEAR. AND GASTROINTESTINAL VIRUSES. I USUALLY TRY TO SHOW A VIDEO OF VICTORIA FALLS. IMAGINE THE WATER FLOWING OVER THAT AND YOU HAVE AN IDEA HOW MUCH DIARRHEA IS ON THE PLANET. IT’S A LITTLE SQUEAMISH BEFORE LUNCH. 1 OUT OF 9 CHILDREN DIE FROM THIS DISEASE. THIS IS TRAGEDY. WHEN NAÏVE POPULATIONS COME INTO CONTACT WITH NEW PATHOGENS, THE RESULTS CAN BE DEVASTATING. IN THE NEW WORLD WHEN COLUMBUS AND CORTEZ CAME, THEY BROUGHT SMALL POX, FLU AND MEASLES. THERE WERE ABOUT 250,000 NATIVES WHEN COLUMBUS FIRST ARRIVED. WITHIN 50 YEARS, 95% OF THEM WERE DEAD. 90%, SOME ARGUE, AS MUCH AS 90% OF THE NATIVE INDIAN POPULATIONS IN CENTRAL AMERICA DIED FROM THE 30 PLUS PATHOGENS THAT CAME OVER WITH THE COLONISTS. THAT’S PRETTY TRAGIC. LET’S NOT JUST THINK ABOUT HUMANS WHEN YOU THINK ABOUT THE POTENTIAL FOR CATASTROPHIC EVENTS. FOOD PRODUCTION IS CRITICAL. FUNGAL PATHOGENS LARGELY IGNORED HAVE CAUSED 70% OF THE GLOBAL AND REGIONAL EXTINCTIONS. THE BEST ONE IN MY MIND IS THE CHESTNUT TREE BLIGHT WHICH KILLED 2 BILLION TREES. FOOD CROPS. LOTS OF FOOD CROP PATHOGENS THAT ATTACK POTATO, RICE, SOY BEAN. THE BLIGHT RESULTED IN ABOUT A MILLION DEATHS FROM STARVATION. IT’S A LITTLE BIT OF A CONCERN THIS WHEAT STEM SUPER STRAIN CALLED EUGENE 99 HAS BEEN SLOWLY MAKING ITS WAY INTO THE MIDDLE EAST APPROACHING THE BIG WHEAT GROWING AREAS. THIS STRAIN WILL KILL 80 TO 100% OF THE 90% TYPES OF WHEAT THAT ARE GROWN ON THE PLANET. OF THE 700 MILLION TONS OF PRODUCT THAT ARE FUSED TO FEED 4.5 BILLION MAKING UP 20 TO 30% OF THEIR DIET, WE COULD LOSE 90% OF THAT. GMO’S MOST LIKELY THE SOLUTION AND THAT IRRITATES PEOPLE. SORRY. AND THEN SWINE PATHOGEN. I WANTED TO DOCUMENT CORONA VIRUSES LIKE TO KILL PIGS. IT’S JUST NOT FAIR. [ LAUGHING ]>>DIARRHEA VIRUS IN ABOUT 20 YEARS HAS KILLED OVER A BILLION PIGS ON THE PLANET. PATHOGENS CAN CAUSE A TREMENDOUS AMOUNT OF DISEASE DESPITE THE BEST FARMING PRACTICES. THIS SWEPT ACROSS THE U.S. AND KILLED TENS OF MILLIONS OF PIGS. AND SO RATHER THAN HAVING TRUCKS OR TRAIN LOADS OF HUMAN BODIES, YOU GET THE IDEA. THIS CAN HAPPEN. WHAT ARE THE PANDEMIC DRIVERS? ECO HEATH HAS MAPPED THE HOT SPOTS FOR VIRUS EMERGENTS. THESE ARE SHOWN HERE AS IT GETS MORE ENFLAMED. MORE EVIDENCE OF VIRUS SPREAD INTO HUMAN POPULATIONS. THIS IS SUPPORTED BY HUMAN GROWTH IN TERMS OF THE POPULATION GROWTH. BUT REALLY, PROBABLY, THE MOST IMPORTANT THING IS POPULATION DENSITY WHICH IS SHOWN HERE. AND YOU CAN OVERLAY THESE POPULATION DENSITY MAPS ON TOP OF THE GRIDS ASSOCIATED WITH PANDEMIC OUT BREAKS. NOT ONLY THE INTERFACE BETWEEN HUMANS AND WILDLIFE. ALLOWS FOR INCREASED AND MORE EFFICIENT TRANSMISSION. AND THEN THE AGING POPULATION. WE’RE GETTING A LOT OLDER. I’M HAPPY ABOUT THAT. HOWEVER, SEVERAL PATHOGENS CAUSE MUCH MORE INCREASE PATHOGENESIS AND MUCH MORE VARLIENT. I DON’T WANT TO STIGMATIZE A GROUP. ESPECIALLY A GROUP I’M IN. I WANT TO SHOW YOU AN EXAMPLE OF THIS USING MICE AS MODELS. IMAGINE EACH TRANSMISSION WAVE GOING FROM ONE PERSON TO THE NEXT. YOU CAN MIMIC THAT IN THE LABORATORY BY HAVING YOUNG MICE AND OLD MICE AND COMPARING THE AFFECT OF VIRUS TRANSMISSION ON NONPATHOGENIC VIRUS. AFTER ABOUT 15 TO 20 PASSAGES, THESE MICE WILL BE DEATH. THE VIRUS WILL BECOME LETHAL IN A YOUNG ANIMAL. IN AN OLD ANIMAL, FIVE TO SIX PASSAGES. WHEN YOU SEQUENCE THESE VIRUSES, 6 TO 10 MUTATIONS ARE CRITICAL FOR DISEASE EMERGENTS IN THE YOUNG ANIMALS. 1 TO 2 MUTATIONS IN THE OLD ANIMALS. THERE ARE PATTERNS OF CHANGE THAT YOU CAN SEE IN THE YOUNG ANIMALS THAT HAVE TO OCCUR. IN THE OLDER ANIMALS AND THESE ARE SIX DIFFERENT REPLICATES HERE, THERE’S NO PATTERN. THERE ARE MANY PATHWAYS TO INCREASE VARIANCE IN A COMPROMISED POPULATION. IF YOU ATENUATE THIS VIRUS EVEN FURTHER, THE VIRUS FIGURES OUT THE STRATEGY, IT BECOMES MORE VARLIANT. VIRUSES HAVE MANY TRICKS UP THEIR SLEEVE. THE GOOD NEWS IS THESE VIRUSES THAT ARE KILLING THE OLDER ANIMALS, IF YOU PUT THEM BACK IN THE YOUNG ANIMALS, THEY DON’T KILL THEM. IT’S POPULATION CONTROL, I GUESS. AT ITS WORST. AND SO THESE FACTORS ALL MERGE TOGETHER TO PRODUCE MAPS LIKE THIS. WE’VE ALL SEEN IT. EMERGING VIRUSES THAT ARE OCCURRING ALL OVER THE PLANET. IN ADDITION TO FLU AND THIS SCENARIO IS LIKELY NOT TO CHANGE ANY TIME SOON IN THE 21ST CENTURY. OKAY. SO I WANTED TO GIVE ONE OTHER EXAMPLE ABOUT THE EFFECT OF TRAVEL. IMAGINE AN OUT BREAK OCCURRING IN HONG KONG OR SOUTHEAST ASIA. TAKES ABOUT TWO MONTHS TO ARRIVE IN RURAL NORTH CAROLINA. DAVID WEBER, I ACTUALLY GOT THESE SLIDES FROM DAVID. AND I SAW THAT HE SHOWED THEM. THIS WAS SARS IN JUNE WHERE WE WERE SETTING UP A TRIAGE UNIT TO LOOK AT INDIVIDUALS WHO HAD BEEN EXPOSED TO THE SARS CASE. THIS IS NOT AN ISOLATED STORY. WHEN MERS EMERGED, THIS OCCURRED AT UNIVERSITY. THERE ARE REALLY NO PLACES TO HIDE. THEY ARE BASICALLY ABOUT 24 HOURS AWAY. SO WE HAVE TO THINK GLOBALLY RATHER THAN LOCALLY. HOW MUCH WORSE COULD IT BE? WELL, I LIKE THIS QUOTE. THIS IS FROM A U.S. ARMY PHYSICIAN. ONE OF THE MOST POWERFUL LETTERS I’VE EVER READ. IT’S IN THE NATIONAL ACADEMY OF REPORT ABOUT PANDEMIC FLU. HE’S WRITING HIS FATHER ABOUT TREATING CASES DURING THE FLU PANDEMIC. I WILL SAY THIS: THE DATA SUGGESTS IT CAN BE A LOT WORSE. SO IF YOU WERE GOING TO PRESSURE ME TO SAY WHICH FLU STRAIN WAS THE WORST AND I WASN’T ALLOWED TO SAY CORONA VIRUSES, MY BEST GUESS WOULD BE AN H2 VIRUS OR H7 VIRUS. I’LL TALK ABOUT H2 FIRST. H2 HAS BEEN IN THE HUMAN POPULATION IN 1959 AND — 1859 AND AGAIN IN 1957. IT HAS CAUSED HIGH MORTALITY RATES. THIS IS A GENE THAT CAN FUNCTION WELL IN HUMANS. ANYONE UNDER THE AGE OF 51 HAS NEVER SEEN IT. IN ESSENCE, THE SAME SCENARIO NOW EXISTS THAT EXISTS IN 1981 WITH H2 INSTEAD OF H1 VIRUS. IF YOU ARE OLD, YOU ARE GOING TO DO WELL. IF YOU ARE YOUNG, YOU ARE IN TROUBLE. YAY FOR THE AGED PEOPLE. FINALLY. HOWEVER, MUCH DIFFERENT STORY. NONE OF US HAVE ANY PRE-EXISTING IMMUNITIY. WE ARE ALL AT RISK. WHAT DOES THE DATA SUGGEST? THE NUMBERS CAN BE HORRIFYING. SO IF YOU LOOK AT ATTACK RATE DURING A FLU PANDEMIC, SOME PEOPLE SAY 10%, OTHERS SAY 50%. THAT’S THE RANGE THAT CAN OCCUR. IF YOU LOOK AT THE MORTALITY RATE, 0.1 TO 60%. THIS IS GENEROUS IN MY OPINION. THAT’S WHAT HAS BEEN REPORTED. YOU CAN USE IT AS THE TOP RATE. AND THE REASON I MENTION IT IS GENEROUS IS INFECTIONS PROBABLY DON’T GET CALCULATED IN THIS MORTALITY RATE. AND THERE’S THIS OTHER FACTOR WHICH THERE IS AN INVERSE RELATIONSHIP BETWEEN TRANSMISSION EFFICIENCY AND VARIANCE. IF YOU HAVE SOMEONE THAT DIES QUICKLY, THEY DON’T TRANSMIT. HAVING SAID THAT, HIV FIGURED OUT A WAY AROUND THAT. IT KILLS SLOWLY ALLOWING FOR A LONGER TRANSMISSION WINDOW. IT’S NOT NECESSARILY TRUE THIS WOULD OCCUR. AND ALSO INFLUENCED BY POPULATION DENSITY. SO WHEN YOU START DOING THE MATTHEWSING THE LOWER NUMBERS, MILLION DEATHS OUT OF 7 BILLION INDIVIDUALS. IF YOU USE THE HIGHER NUMBERS, IT’S 1.6 BILLION. THAT’S THE RANGE YOU ARE LOOKING AT. LET’S TAKE 1918 FLU-LIKE VIRUS, 106 MILLION DEATHS. IN THE U.S. THAT WOULD EQUATE TO 12 MILLION DEATHS. A FLU STRAIN THAT HAD A 10% MORTALITY RATE, THAT’S ABOUT WHAT SARS HAD. IT WAS EFFICIENTLY TRANSMITTED. SO IT’S LIKELY. YOU’D BE LOOKING AT ABOUT 266 MILLION DEATHS IN THE U.S. WOULD BE 30 MILLION DEATHS. H7N9 IS A BILLION INDIVIDUALS. AGAIN, UNLIKELY BUT COULD BE 10 TO 20% OR LESS. H5N1 WOULD BE 1.6 BILLION. THOSE ARE PRETTY HORRIBLE NUMBERS. YOU CAN MODIFY THAT A LITTLE BIT IF YOU THINK ABOUT TREATMENT WITH DRUGS. THAT WOULD REDUCE BOTH THE ATTACK RATE AND THE MORTALITY RATE. I’M GUESSING AT THESE NUMBERS. I GAVE IT A REDUCTION IN THE DISEASE MORTALITY RATE BY HALF EACH. THAT WOULD REDUCE THESE NUMBERS BY A QUARTER. SURPRISINGLY, AND I MIGHT BE WRONG ABOUT THIS. BUT EVERYTHING I READ SAID TREATMENT OF SECONDARY BACTERIAL INFECTIONS REALLY SHOW VERY LITTLE IMPROVEMENT OF FLU INFECTED INDIVIDUALS. AND SO IT REALLY HAS VERY LITTLE IMPACT ON THE OVERALL MORTALITY RATES. I’LL SHOW YOU A REASON WHY. THAT’S NOT REALLY GOING TO HELP. I DIDN’T TALK ABOUT OTHER BARRIERS TO INFECTION. THAT’S CERTAINLY GOING TO HELP. THOSE ARE THE NUMBERS YOU ARE LOOKING AT. IN TERMS OF OUR STOCKPILE, I THINK WE HAVE SOMEWHERE BETWEEN 50 AND 100 MILLION DOSES OF TAMIFLU. THAT WILL HELP QUITE A BIT IN THE FIRST WAVE. OKAY. WHAT ABOUT THE EFFICACY OF ANTI-VIRAL DRUGS? THESE EMERGING CORONA VIRUSES AND FLU VIRUSES CAUSE THIS DISEASE CALLED ACUTE RESPIRATORY DISTRESS SYNDROME. YOU ARE TRANSMITTING RECEIPT BLOOD CELLS. THEY LOVE THIS CELL RIGHT HERE. THEY KILL IT. THIS CELL SUPPORTS THESE TWO CELLS. SOME OF THE VIRUSES ALSO INFECTS THESE CELLS. THESE ARE CALLED TYPE 1 CELLS. AND THIS BARRIER THAT PREVENTS FLUID FROM COMING ACROSS THIS CAPALARY BED IS BROKEN DOWN. IN ADDITION, CELLS COME IN AND DUMP CYTOKINES. SO WHEN YOU THINK ABOUT THE DESCRIPTION OF THE STORY OF BEN AND THOMAS WOLVES’ NOVEL, YOU ARE NOW LOOKING INSIDE TO SEE WHAT HAPPENED TO HIS LUNG. HE WAS DROWNING IN HIS OWN FLUID. NOW, IF THIS IS BAD ENOUGH, YOU HAVE HEMORRHAGE, LOTS OF RED BLOOD CELLS. WHAT HAPPENS WHEN YOU HEMORRHAGE? YOU TRY TO CLOT AND WALL OFF THAT BLEEDING. AND THAT’S EXACTLY WHAT YOU DO IN YOUR LUNG. AND YOU LAY DOWN THE BIG CLOTS WHICH LOOK LIKE HIGHLAND MEMBRANES. LOTS OF CLOTTING FACTORS IN THEM. SO YOU ARE BUILDING A WALL TO PREVENT THIS FLUID COMING OUT. AND YOU HAVE E-FLUX PUMPS OPENING UP THE AIRWAY. THE PROBLEM IS THAT IS A THICK BARRIER. OXYGEN CAN’T TRANSFER ACROSS AND NOW YOU ARE SUFFOCATING. THIS IS DEVASTATING DISEASE. IT’S BEEN DIFFICULT TO CLINICALLY MANAGE FOR MANY, MANY YEARS. AND THERE ARE NO REAL TREATMENTS BESIDES SPENDING MILLIONS OF DOLLARS. SO WHAT HAPPENS — I WANTED TO MENTION THIS IS BOTH A VIRUS AND PATHOLOGIC DISEASE. SO YOU HAVE TO TREAT BOTH. OF ALL OF OUR ANTIVIRALS ONLY ATTACK THE VIRUS, NOT THE HOST RESPONSE. SO YOU ARE ONLY GETTING HALF OF THE DISEASE. SO THIS IS WHAT HAPPENS IN FLU, ALSO IN CORONA VIRUSES. IF YOU HAVE MOCK TREATED ANIMALS WITH NO DRUG, THEY ALL DIE, GET SICK OR DIE. IF YOU TREAT WITH A DRUG THAT WORKS AGAINST A VIRUS AND GIVE IT BEFORE INFECTION OR ONE DAY AFTER INFECTION, THESE GUYS GET MILD DISEASE AND DO WELL. AT DAY TWO OR BEYOND, THEY DIE. THAT MEANS THE VIRUS ALREADY HIT ITS PEAK TIGHTER. THE PROGRAM LEADING TO IMMUNE PATHOLOGIC MEDIATED DEATH HAS BEEN SET AND YOU CAN’T STOP IT EVEN IF YOU KNOCK DOWN VIRUS. HIGHLY PATHOGEN I CAN FLU VIRUS IS GOING TO RESULT IN MORE DEATH, LESS PATHOGEN I CAN ONE WILL MAKE DRUGS MORE EFFECTIVE. HARD TO PREDICT WHAT WILL HAPPEN. VACCINE AVAILABILITY. IF BARNY DOESN’T MAKE THE UNIVERSAL FLU WHICH HIS DATA LOOKS GREAT, WE’RE LIMITED TO TRADITIONAL METHODS. THAT’S 4 TO 8 MONTHS. SEED STOCKS WILL BE READY IN A FEW DAYS. IF WE USE REVERSE GENETICS OR REASSORTMENT DEVELOPED IN THE 50s AND 60s, IT TAKES LONGER. WE CAN DEVELOP THE SEED STOCKS QUICKLY. THE BOTTLENECKS ARE EGG PRODUCTION. AND THEN YOU HAVE TO PUT THE SURFACE PROTEINS INTO A BACKBONE THAT GROWS WELL IN EGGS. AND SOMETIMES THAT MATCH DOESN’T WORK. LIKE DURING THE 2009 PANDEMIC. DOESN’T GROW AS WELL. YOU MAKE LESS VACCINE. NOW THE VACCINE IS IN LIMITED QUANTITIES. SO YOU MISS THE EPIDEMIC WAVE FOR MOST PEOPLE OF THE THE OTHER PROBLEM IS EGG ADAPTATION. THE VIRUS COULD ADAPT TO THE EGG. AND THE MUTATION FROM GROWING IN THE EGG COULD BE THE JUICY EPITOPE YOUR IMMUNE SYSTEM RESPONDS TO. SO THAT’S THE OTHER PROBLEM. THEN YOU HAVE THE ANTI-VACCINE ADVOCATES. WE DON’T NEED TO GO INTO THEM. SOMETHING TRULY NOVEL CAN BE DIFFICULT LIKE HIV. I HAD NO IDEA HIV VIRUSES COULD EXIST IN 1980. SARS CORONA VIRUS. POTENTIAL HIGH-PATH VIRUSES. THESE CAN TAKE MONTHS TO YEARS TO DEVELOP USING CURRENT TECHNOLOGIES. THE NEWEST TECHNOLOGIES WILL DROP THAT QUITE A BIT. BUT THIS IS ALSO THEN COMPLICATED BY VACCINE INDUCED PATHOLOGY. THEY ARE TOUGH NUTS TO CRACK. LET’S MOVE ON TO SOCIAL ISSUES. AND TALK ABOUT HOW SOCIETY RESPONDS. SO IN 1918, THIS IS INFANT MORTALITY RATE. YOU CAN SUPER IMPOSE ON THIS GRAPH FOR ADULT, MEN AND WOMEN. OR PREGNANT WOMEN IN THAT THERE WAS HIGHMORE AT THAT TIME IN 1918, 1915. AND IT’S NOW VERY LOW. IN OTHER WORDS, PEOPLE IN THIS TIME PERIOD WERE QUITE FAMILIAR WITH DEATH. IT WAS A PART OF LIFE. WE NOW LIVE IN TO SOME EXTENT A STERILE ENVIRONMENT. THE PEOPLE WHO ARE ALIVE TODAY HAVE NO APPRECIATION FOR THE DISEASE SEVERITY THAT CAN EXIST IN POPULATIONS. GO TO ANY FARM HOME STEAD AND LOOK AT THE CEMETERY AND LOOK AT THE NUMBER OF 5 YEAR OLD KIDS UNDER THE AGE OF 5245 DIED. AND THE NUMBER OF WIVES THE FARMER HAD PROBABLY BECAUSE OF DEATH DURING PREGNANCY. SO WE HAVE NO FRAME OF REFERENCE FOR THIS. THE SCALE IS BEYOND OUR COMPREHENSION. MANY PEOPLE ARE LIKELY NOT GOING TO RESPOND AND BE AT THEIR BEST IN THIS ENVIRONMENT. THAT’S MORE POSITIVE WAY TO SAY THINGS COULD BE HORRIBLE. THE VAST MAJORITY OF NATIONS ARE NOT PREPARED. IN REALITY, SIX ARE PREPARED. INCLUDING THE U.S. THE REST ARE IN VARIOUS STAGES OF CONCEPTUAL DEVELOPMENT TO NO DEVELOPMENT TO PARTIAL DEVELOPMENT. THE U.S. IS WELL PLACED TO RESPOND. BUT THE REST OF THE WORLD ISN’T. THAT MEANS THE GLOBAL ECONOMY IS GOING TO SUFFER BECAUSE IT’S GOING TO COLLAPSE IN OTHER COUNTRIES. THIS IS GOING TO COLLAPSE OR BE IN SHAMBLES. SHORTAGES WITH VERY LITTLE INFRASTRUCTURES IN EQUITIES IN TERMS OF HEALTHCARE. PHYSICIANS WILL HAVE TO MAKE DIFFICULT DECISIONS ABOUT WHO GETS CARE, WHO LIVES AND WHO DIES. THAT’S BAD NEWS. WHAT ABOUT THE MARKET? I WANT TO GIVE YOU GOOD NEWS, EVENTUALLY. IN 1918, THAT OUT BREAK HAD VERY LITTLE EFFECT ON THE DOW AND THE S&P 500. IT DROPPED ABOUT 24% IN 1918 BUT REBOUNDED IN 1919. THE UK EQUITY MARKET WAS IN A BULL MARKET BOTH YEARS. TO SOME EXTENT, THAT WAS DUE TO WORLD WAR I. SUCH HIGH DEATH ESPECIALLY FOR THE BRITISH IN THAT WAR, THEY WERE SO GLAD THE WAR WAS OVER. THEY WERE VERY HAPPY. DURING THE SARS EPIDEMIC, VERY DIFFERENT THING. COMMERCIAL AIRLINES LOST BILLIONS OF DOLLARS. THERE WAS A $54 BILLION ECONOMIC LOSS DURING THE OUT BREAK. OH, YES, THERE IT IS. DURING THE EBOLA OUT BREAK, THERE WAS 8 TO 10% DROP IN THE MARKET. IT THEN QUICKLY RECOVERED. I WANTED TO GIVE YOU GOOD NEWS. THERE ARE WINNERS OUT THERE. IF YOU ARE LOOKING AT — IF YOU EVER WANT TO BE PREPARED AND MAKE MONEY IN THE PANDEMIC, IF THAT’S WHAT YOU WANT TO DO. BUY STOCK IN HAZMAT SUIT MAKERS AND PROTECTIVE CLOTHING OR COMPANIES THAT MAKE ANTI-VIRAL DRUGS. YOU’LL PROBABLY DO PRETTY WELL THERE. MUTUAL FUNDS FOR PANDEMIC PREPAREDNESS. YOU CAN BET ON ANYTHING IN THIS COUNTRY. [ LAUGHING ]>>SOME PRODUCTS DO WELL. 1918 INCLUDING MASKS. SAME THING TODAY. PANDEMICS REALLY ARE TIMES OF OPPORTUNITY AND I LIKE GEORGE MARTIN’S QUOTE OF CHAOS IS THE LATTER. THERE’S AN OPPORTUNITY FOR PEOPLE WHO HAVE POLITICAL GAIN, FINANCIAL GAIN AND PERSONAL GAIN DURING TIMES OF SOCIAL UPHEAVAL. THAT WILL PROBABLY OCCUR. MISLEADING STORIES ON SOCIAL MEDIA. MIRACLE CURES THAT WILL BE TOUTED. CONSPIRACY THEORIES. ONE THING THAT IS KIND OF NEW. YOU CAN PROBABLY BUY AND ORDER YOUR OWN VACCINE ON THE INTERNET FOR ABOUT $200 NOW. YOU CAN BUY YOUR OWN VACCINE AND VACCINATE YOURSELF. IF YOU HAVE A LITTLE BIT OF KNOWLEDGE AND MOST LIKELY SOMEBODY WILL COME UP WITH A SCHEME TO SELL THAT IN A LEGAL WAY, NOT A SAFE WAY. THE SCIENTIFIC COMMUNITY MAY RUN INTO ETHICAL DILEMMAS. AT UNC, THERE’S AT LEAST A DOZEN FACULTY WHO HAVE EXPERIMENTAL EXPERIMENTS READY WITHIN TWO WEEKS. THERE’S OTHER GROUPS THAT WILL BE ABLE TO TEST DRUGS FOR ABILITY TO INHIBIT VIRUS REPLICATION THAT WILL BE DONE WITHIN A MONTH. AND THOSE WILL GET PUBLISHED AND LOTS OF HYPE. NONE OF IT IS FDA APPROVED. BUT IF YOU ARE DEALING WITH A 10 TO 20% MORTALITY RATE, PEOPLE ARE GOING TO WANT TO TAKE IT. AND THAT LEAVES ALL KINDS OF ETHICAL DILEMMAS AROUND THE CONCEPT OF WHAT WOULD YOU DO TO PROTECT THOSE WHO YOU LOVE? AND ALSO UNIVERSITIES MAY GET HOUNDED WITH RIOTS IN TERMS OF HOARDING DRUGS AND VACCINES THAT COULD PROTECT THE PUBLIC. WHAT CAN WE DO? THESE HAVE BEEN COVERED. LEADERS AND HEALTH PROFESSIONALS HAVE TO RETAIN CREDIBILITY, SPEAK IN AN UNIDENTIFIED VOICE AND TELL THE TRUTH. THIS IS ABSOLUTELY ESSENTIAL. CERTAINLY, IT WILL LEAD THE PUBLIC TO LOOK FOR AN ANSWER AND THERE WILL BE PLENTY OF PEOPLE OUT THERE WILLING TO PROVIDE ANSWERS THAT WILL BE FOR THEIR OWN GAIN. WE LIVE IN AN INNER-CONNECTED WORLD. THIS IS NOT A LOCAL PROBLEM. IT’S A GLOBAL PROBLEM. WE CAN’T IGNORE THE REST OF THE WORLD. WE HAVE TO THINK ABOUT POVERTY, PUBLIC HEALTH, INFRASTRUCTURE AND TRYING TO HELP THOSE WHO ARE NOT AS WELL OFF AS WE ARE. AND WE HAVE TO RECOGNIZE THE PANDEMICS ARE INEVITABLE. I KNOW I RAN OVER. I THINK WE HAVE TO THINK ABOUT SCALE ABILITY PLANS AND SURGE CAPACITY. DAVE GAVE A GREAT TALK ABOUT UNC’S PREPAREDNESS. THE BIGGER QUESTION IN THE OTHER 5,260 PLUS HOSPITALS OR SO IN THE UNITED STATES ARE THEY EQUALLY AS READY? I DON’T KNOW THE ANSWER TO THAT QUESTION. I HOPE THE ANSWER IS YES. MOST LIKELY IT’S NOT. WE HAVE STOCKPILED DRUGS, MEDICAL SUPPLIES AND MEDICAL FACILITIES AND BEDS. I’M NOT SURE HOW WELL THE LOGISTICS WORK TO MOVE THAT AROUND IN THE FACE OF A LARGE PANDEMIC. AND I THINK IT’S CRITICAL TO CONTINUE TO SUPPORT BASIC AND APPLIED RESEARCH AND TO EMBRACE NEW TECH KNOWLEDGE GEEZ. I THINK BARNY AND BOTH ADOLFO AND YOSHI ALL GAVE STATE-OF-THE-ART TALKS TALKING ABOUT THE LATEST DEVELOPMENTS THAT ARE AVAILABLE THAT CAN BE APPLIED TO RAPID VACCINE DESIGN. THESE ARE LISTED HERE. I DON’T WANT TO REALLY RUN THROUGH THEM. IN TERMS OF DIAGNOSTICS, THERAPEUTICS AND VACCINES, WE REALLY ARE AT A PEAK IN TERMS OF THE REVOLUTIONARY CAPACITY TO RESPOND MORE QUICKLY THAN WE’VE EVER HAD BEFORE. THIS IS NOT 1918. WE HAVE MUCH MORE POWERFUL THINGS TECHNIQUES AVAILABLE IN OUR DISPOSAL WHICH WOULD SAVE LIVES. WITH THAT, I THANK YOU FOR YOUR ATTENTION. [ APPLAUSE ]

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