TO ME, THESE VIRUSES THAT WE'RE TALKING ABOUT, THE ONINGS BEING CHANGED TO MAMMALIAN TRANSMISSIBLE ARE CURRENTLY SENSITIVE TO OUR ANTIVIRALS. THAT ARE CURRENTLY OF STRAINS THAT WE SHOULD HAVE VACCINES AND COMMUNITY AGAINST. THE RESRCH IS NOT TO GO AND MODIFY THAT, NOT THAT IT COULDN'T HAPPEN THAT ACCIDENTLY SOMETHING CHANGES. SO TO ME THE WEIGHING OF THE RISK AND BENEFIT PUTTING TYPE 3 PLUS MAKES SEN P TO ME. THE OTHER ISSUE IS WE PUT ALL OF THESE INTO CLASS -- BSL-4 CLASSIFICATION, PROBLEM IS WHAT ABOUT THE LABORATORY THAT COMES AND ISOLATES A NATURAL STRAIN THAT IS RESISTANT, A NATURAL STRAIN THAT WE ACTUALLY HAVE NO COMMUNITY AGAINST -- IMMUNITY AGAINST, IS THAT A BSL-4 RESEARCH SITUATION AND THE TESTING DONE ON PATIENT SAMPLES, WITH THAT BE BSL-4. I THINK THAT WOULD BE A LITTLE TOO ONEROUS. BUT I AGREE, IF SOME MUTATION HAPPENS A NEW STRAIN CREATED FOUND TO BE RESISTANT THAT SHOULD CALL INTO ALL REGULATIONS THAT ALLOW US TO PUT IN APPROPRIATE CONTAINMENT FOR RESERGE OF THAT TYPE. SO THAT'S -- RESEARCH OF THAT TYPE. THAT'S MY PERSONAL VIEW AND I THINK WE SHALL DISCUSS IT SOME MORE. THE OTHER THINGS THAT WE SHOULD TALK ABOUT ARE THE SPECIFIC RECOMMENDATIONS THAT HAVE BEEN PUT ON THOSE SLIDES BY THE BIOSAFETY WORKING GROUP AND MAKE SURE THERE'S NO ADDITIONS AND DELETIONS. IN PARTICULAR I THANK ADMIRAL REDD FOR RECOMMENDING THAT WE ACTIVELY GO AND SURVEY INVESTIGATORS ABOUT THE FLU SYMPTOMS AND THAT THIS SHOULD AT LEAST BE A RECOMMENDATION TO PEOPLE WORNING IN THE FIELD. THE OTHER THINGS TO TALK ABOUT. SPECIFICALLY MAKE SURE THAT WE AGREE ON THIS, THAT THE SHOE WHETHER ANTIVIRALS SHOULD BE AVAILABLE FOR THE INVESTIGATORS. SHOULD THE INVESTIGATORS WORKING IN THIS AREA ALL BE VACCINATED AGAINST THE STRAINS BEING USED. THESE ARE OTHER ISSUES THAT WE SHOULD BRING UP AND DISCUSS AND COME TO A CONSENSUS. ANY COMMENTS OR ANYBODY WANT TO TAKE IT FROM THERE? DON. YOUR COMMENT HOW NATURE DOES THIS ON HER OWN, WE HAVE TO REMEMBER WE ARE CREATING MUTANTS THAT MAY NEVER BE SEEN IN NATURE AN CONDUCTING THE EXPERIMENTS IN A WAY THAT FORCES IT TO HAPPEN PERHAPS MORE READILY THAN IT COULD EVER IN NATURE. >> ZOLOTH. >> I DON'T WANT THE SPEAK TO THE SCIENTIFIC THINGS I WANT TO SPEAK TO THE ARGUMENT THEY'VE MAKING. THE FIRST IS THE DRIVERS AND JUSTIFICATIONS FOR THIS WORK. I WANT TO LIST THEM UP THE ONES I HAVE HEARD SO FAR. FIRST IS H5N1 IS A SERIOUS PUBLIC HEALTH PROBLEM THAT NEEDS AN URGENT RESPONSE. THAT'S SURFACE, LET ME SAY IT'S QUITE SERIOUS. MORE THAN OTHER THINGS WE'RE DEVOTING ATTENTION TO AND THE NEED -- THERE'S URGENCY AND RESPONSE BECAUSE YOU THINK THERE MIGHT BE A NATURALLY OCCURRING PANDEMIC. WE NEED TO DEDICATE SHARED RESOURCES ALL AROUND THE WORLD TO THESE PROBLEMS. SO I WANT TO PREFACE THAT. THE SECOND THIN IS IT'S SCIENTIFICALLY IMPORTANT TO DO THIS IMPORTANT RESEARCH. GET IT ON THE TABLE, WE HAVEN'T SAID IT, I WANT -- THAT THERE'S SOMETHING INDEPENDENTLY INTRINSICALLY IMPORTANT SCIENTIFICALLY INTERESTING IN DOING THIS SPECIFIC RESEARCH USING TECHNIQUES ABOUT PROTEINS, TRANSMISOMES, THAT INSEND ARGUMENT, PUBLIC HEALTH URGENCY IT'S A SCIENTIFIC IMPERATIVE. THE THIRD IS, IT'S JUSTIFIED BECAUSE WE CAN GO FORWARD BECAUSE WE HAVE AT LEAST ONE VACCINE TO ONE VARIANT OF IT, ONE PLATE OF IT. AND WE HAVE A GENERAL -- I HAVE ALSO HEARD GENERAL LEVEL OF PROTECTION BECAUSE OF OF THE 2009 VACCINE AND ALSO HEARD BECAUSE WE HAVE ANTIVIRALS. THOSE THREE THINGS MAKE THIS RESEARCH NECESSARY AND PERMISSIBLE NOW IN A WAY IT MIGHT NOT BE IN SOME OTHER TIME. THE FINAL ARGUMENT WE HAVE HEARD, TOO EXPENSIVE ESSENTIALLY TO DO IT IN A LEVEL 4 CONTAINMENT FACILITY. I KNOW THAT COVERS A LOT, IT'S TOO HARD, TOO THIS. BUT IF IT'S COST NEUTRAL NO ONE WILL MAKE THE ARGUMENT LEVEL 3 IS THE BETTER WAY TO DO IT. BECAUSE -- IF FUNDS WERE UNLIMITED YOU COULD BUILD UP THESE THINGS SO IT'S A MATTER OF HOW MUCH MUCH YOU'RE WILLING TO SPEND. SO IT EVOLVES TO AN ECONOMIC ARGUMENT. NOT THAT THAT'S A BAD ARGUMENT BECAUSE AN ECONOMIC IS ALSO A PUBLIC HEALTH ARGUMENT. BUT JUST WANT TO SURFACE IT. THAT'S WHAT I THINK WE HAVE CLARITY ON, WHAT WE HEARD TODAY SO FAR. I'M NOT JUDGING THOSE ARGUMENTS, JUST SAY THESE ARE 2001S I THINK WE HAVE HEARD. IF PEOPLE HAVE OTHERS I WOULD LOVE TO ADD THEM TO MY ARGUMENT LIST. SECOND POINT. WE TALK ABOUT THE DEDICATION OF DIFFERENT LEVELS OF LABORATORY SAFETY REQUIREMENTS. BASED ON THE KIND OF AGENT IT IS. AND I'M GOING TO MAKE A CASE THAT'S NOT ONLY THE KIND OF AGENT THAT YOU'RE WORKING WITH, IT TEASE KIND OF COMMUNITY UNTO WHICH THE I GENT IS GOING. IT'S IN GOOD -- NOT JUST PRODUCTION, IT'S RECEPTION. THIS IS A RECEPTION THEORY ARGUMENT. THE -- AND I THINK THAT'S WHERE WE HAVE TROUBLE. I DON'T KNOW HOW TO -- WHAT ADVICE TO GIVE BUT I WANT TO FLAG THE TROUBLE THAT OUR COMMUNITIES ARE IN. FIRST WE KNOW VACCINES AROUND 100% EFFECTIVE. IT -- IN THE A SURGICAL INTERVENTION. WE DON'T KNOW WHAT LEVEL OF SERO CONVERSION IS IMPORTANT. WE DONE KNOW THE TITERS FOR SEASONAL FLU. DON'T KNOW HOW IT WORKS IN DIFFERENT PEOPLE, IT -- NOT LIKE WHEN YOU GET A VACCINE YOU DONE GET THE FLU. TWO IS THE RECORDS THE ARGUMENT THAT RECORDS BACK TO 2009 VACCINE HAS THAT PROBLEM BUT ALSO WE LIVE IN AN AMERICA WHERE EVEN IT'S WIDELY AVAILABLE PEOPLE DON'T AVAIL THEMSELVES OF VACCINATION. AND THAT'S A PROBLEM. MUCH LESS THE REST OF THE WORLD. THREE IS SO THE 2009 VACCINE ARGUMENT SEEMS TO ME IS NOT MUCH HELP. 3 IS PEOPLE DON'T GET VACCINATED AS IS BECAUSE THEY DON'T TRUST -- THERE IS A LEVEL OF MISTRUST ABOUT VACCINES THAT IT'S UPHILL BATTLE. AS ANYONE KNOWS AND THAT'S A PROBLEM USING SAYING SOMETHING LIKE WE CAN WORK ON AGENTS WHICH THERE'S A VACCINE ASSUMES THERE IS A ZONE AN PEOPLE WILL GET VACCINATE AND THUS, A LOT OF ASSUMPTIONS UNDER THAT ONE SENTENCE. PEOPLE DON'T LIKE GENETICALLY MODIFIED POTATO CHIPS OR ANYTHING SO THESE HAVE A HIGHER LEVEL OF SUSPICION BECAUSE IT'S A GENETICALLY MODIFIED VIRUS TREATED BY A GENETICALLY MODIFIED VACCINE AND I THINK THE UPTAKE MIGHT BE LESS THAN SEASONAL VACCINE. IT WILL NOT HAVE BEEN TESTED IN HUMANS AND IT WILL TAKE SIX MONTHS TO WORK WHICH IS IMPRESSIVELY LONG TIME GIVEN WHAT YOU HAVE SAID -- WHAT DAWN AN ARMOND SAID ABOUT CAPACITY FOR VACCINE EVEN IN THE BEST OF CIRCUMSTANCES WITH 100% AMERICANS CHANGE TARGET MINE AND BECOMING VACCINATED AND KNOWING THE TITERS WOULD WORK EVEN THEN IT'S A PROBLEMATIC SOLUTION TO THE PROBLEM. THIRD CATEGORY OF THINGS TO SAY. A FEW NOTES ABOUT ARGUMENTS THAT MIGHT BE GOOD ONES AND BAD ONES. THE NATURALISTIC ARGUMENT, IT'S A VERY BAD ARGUMENT FOR PHILOSOPHERS. WHENEVER WE'RE HEAR IT WE REJECT IT. SO DR. PEIRIS RAISED THE ARGUMENT SAYING THEY'RE RUNNING AROUND THE POOR HAVE SUCH APPALLING HEALTH CONDITIONS OUR LABS ARE SO MUCH BETTER THAN WHAT HAPPENS TO THE POOR. IF WE FOLLOW THAT OUT WE WOULDN'T USE CAR SEATS. WE HOLD OURSELVES TO A DIFFERENT STANDARD BECAUSE WE ARE IN FACT WE DON'T LIKE THE IMPRESSION UNDER WHICH PEOPLE -- OPPRESSION WHICH PEOPLE RAISE CHICKENS. WE THINK IT'S A DREADFUL RACE AND DON'T WANT IT REPLICATED IN OUR LAB. THAT'S WHY IT'S CALLED THE IS TO THE OUGHT ARGUMENT BECAUSE IT OCCURS IN NATURE. IT'S NOT A GOOD ARGUMENT HOW WE BEHAVE AS MORAL AGENTS. WHEN YOU SAY NATURE IS A TERRORIST, WHEN NATURE -- THIS VERSION OF NATURE AS A BEING WITH AGENCY THAT IS DOING SOMETHING MORE DREADLY OR TERRIFYING, IT'S CONFUSING LESS THAN HELPFUL WAY TO THINK ABOUT IT SO I WOULD LIKE US TO AVOID THE NATURE OF TERRORIST IDEA OR VACCINE IS HAVING AGENCY OR VIRUS HAVING AGENCY OR VIRUS NOT NEEDING TO CHANGE BECAUSE IT HAS NAIVE HOST AS IF IT HAD AGENCY. THESE ARE ARGUMENTS THAT MAKE IT HARDER TO HELP US THINK CHEERILY ABOUT THE VIRUS SO THOSE ARE TWO ARGUMENTS TO THINK ABOUT AVOIDING ADS WE TRY TO WORK OUR WAY THROUGH THIS. THAT WAS A NOTE FROM THE MY (INAUDIBLE). SO THERE'S PROBLEMS, THERE'S GOOD STRONG REASONS TO DO THIS AND I LIKE EVERYONE ELSE AT THIS TABLE IT'S RESPONSE TO PUBLIC HEALTH. (INDISCERNIBLE) I TAKE IT SERIOUSLY PEOPLE KNOW THE WORLD SUP AS YOURSELF DOING IT ALL YOUR LIVES ARE WORRIED THIS IS A THREAT TO HUMANITY AND I WANT -- AND I DO HAVE TRUST THAT SCIENCE, IF SCIENTIFIC INVESTIGATIVE METHODS COULD BE USED TO ADDRESS AND THEY SHOULD BE, BUT I'M WORRIED ABOUT SAFEGUARDS. I'S TAKING A SIGNIFICANT LIST TO DO THIS WORK. IT WORRIES (INDISCERNIBLE) WORRYSOME SO WE OUGHT TO DO IT IF YOU DO IT WITH EXTRAORDINARY CARE AND HIGH LEVEL SUSPICION. >> YOU ARE ARGUING ABOUT THE COST. THE WAY I INTERPRET THIS IS IT'S TOO EXPENSIVE THEREFORE WE'LL BE LESS SAFE AND -- THAT'S WRONG. OKAY? SO BECAUSE IT IS DONE IN PAIRS OF THREE, IT IS NOT (INDISCERNIBLE) LEFT SAFE THAN DOING BSL-4. IF YOU DO 4 TYPE WORK YOU'LL RESTRICT THE NUMBER OF LABS THAT CAN DO IT, I WOULD SAY YOU'RE GOING TO DECREASE FIVE FOLD CHANCES OF A RELEASE BECAUSE COMPARING THE NUMBER OF BSL-3 LABS IN U.S. TO THE NUMBER OF 4 LABS, MAYBE THERE ARE FIVE TIMES MORE BSL-3 LABS THAN 4. THAT INCREASES BY FIVE FOLD. BUT THEN YOU HAVE THE OBLIGATION THE IF YOU WANT TO -- BECAUSE OF THE SITUATION TO RAMP UP THAT TYPE OF RESEARCH YOU'RE GOING TO HAVE THAT FACILE BEING OVERUSED TO TRY TO DO EVERYTHING THAT YOU NEED. WHICH THEN I THINK EVANS OUT RISK OF INCREASE. SO IT'S NOT THAT IT IS COSTLY THE REASON WHY WE SHOULDN'T BE MOVED TO 4. BSL-3 IS A VERY SAFE WAY DOING IT AND THERE ARE COUNTER MEASURES TO THAT. >> LET ME JUST ADD THAT'S ANOTHER ARGUMENT THAT I DIDN'T HAVE ON MY LIST, BUT BEING POWERFULLY MADE HERE. THE ARGUMENT LOOKS LIKE THIS. THE MORE PEOPLE YOU HAVE DOING IT, THE FASTER YOU GET TO THE ANSWER. NUMBERS OF PEOPLE, QUANTITY MATTERS NOT ONLY QUALITY AND THAT'S -- SO THANK YOU FOR CLARIFYING THAT. WE CAN DEBATE THAT PROPOSITION AS A PROPOSITION BUT SURFACE THAT'S ONE ARGUMENT BEING MADE. >> AND ALSO MORE PEOPLE DOING IT THE HIGHER THE RISK. THE MORE STATISTICALLY THE CHANCE SOMETHING WILL HAPPEN. WE'RE SAYING IT'S BEEN DONE ALREADY AND NOTHING HAPPENED. WE HAVE ONLY DONE A HANDLE -- THAT'S TWO LABS THAT HAVE DONE IT, ONLY A HANDFUL OF EXPERIMENTS SO STATISTICALLY THAT'S A SMALL END IT'S INSIS CAN'T RIGHT NOW. (OFF MIC) >> WHY ISN'T IT TRUE? (OFF MIC) >> BUT A LOT OF LABS HAVE BEEN TRYING TO SEE WHAT MAKES AN H5N1 TRANSMISSIBLE. I LOVE MORE PEOPLE HAVE BEEN DOING THIS TYPE OF WORK SINCE 1997. >> I WANTED TO SAY ONE PIECE HERE. THERE IS AN IMPORTANT MORAL DIFFERENCE BETWEEN OBSERVATIONAL INVESTIGATION. SINCE 1997 UNTIL LAST YEAR. WHICH IS LOOKING AT STUDYING WHAT MIGHT POSSIBLY BE THE CASE AND NOW DOING SOMETHING YOU'RE DOING GAIN OF FUNCTION RESEARCH, THAT YOU'RE GIVING THE VIRUS GAIN OF FUNCTION AND THAT GAIN OF FUNCTION RESEARCH IS A DIFFERENCE MORAL ACTIVITY THAN ANY OTHER OBSERVATIONAL RESEARCH. AGAIN, NOT SAYING IMPERMISSIBLE, JUST IT'S MORALLY DIFFERENT AND WE HAVE A HIGHER STANDARD, WE DELIBERATELY IN THE LANGUAGE OF THE LITERATURE PUSH THE VIRUS TO MUTATE IN SPECIFIC PATHWAYS. >> THE PAST WORK IS NOT OBSERVATIONAL. SIMILAR TYPE OF WORK HAS BEEN DONE IN THE PAST. TO SHOW TRANSMISSIBLE OF H5N1s, THERE ARE PAPERS PUBLISHED AND THE END RESULT IS THOSE VIRUSES WERE NOT TRANSMISSIBLE BUT BASICALLY ESSENTIALLY THE SAME WORK THAT WAS DONE AS IT WAS DONE NOW. THE ONLY DIFFERENCE IS THESE TWO LABS SUCCEEDED IN MAKING THEM TRANSMISSIBLE. IN THE PAST THEY WERE NOT TRANSMISSIBLE VIRUSES THAT I MEAN TO ATTEND -- THE INTENT TECHNOLOGY AND APPROACH WAS ESSENTIALLY THE SAME. >> SOUNDS LIKE THIS RESEARCH WAS WIDESPREAD. I DID NOT GET THAT IMPRESSION. I MEAN TWO LAB WERE SUCCESSFUL OUT OF HOW MANY LABS TRYING THIS? TO WE EVEN HAVE HANDLE ON THAT? AND WERE THE EMPERIMENTS THE SAME MUTATIONS THE SAME WAY, THE VIROPRODUCED IN THE SAME WAY? >> DR. WEBSTER. >> THERE WAS REQUEST FROM WHO AND ANOTHER REQUEST FROM NIAID TO DO THIS RESEARCH. MULTIPLE LABS, I WOULDN'T GIVE A NUMBER WILL TRY THE DO THIS RESEARCH. I DON'T THINK PEOPLE REALIZE THAT COCA AND POUCIER SPENT TENURE TRYING TO GET TRANSMISSIBLE VIRUSES, IT IS NOT EASY. PASSING AMONG FERRETS NOT DO IT UNTIL THEY PUT THOSE SPECIFIC MUTATIONS INTO THE RECEPTOR BINDING DOMAIN. THEN THEY WORKED OUT -- THEY PUT OTHER, IT'S JUST NOT EASY TO DO. SO THE NUMBER OF LABS TRYING TO DO WERE RESPONDING TO THE REQUEST OF THE WORLD. SO THEY WERE NOT DOING ANYTHING THAT THEY -- AGAINST WHAT WE SHOULD BE DOING. >> I WANT TO CLARIFY THE ARGUMENTS HERE. AS A BASIC SCIENTIST WORKING AT A SCHOOL OF PUBLIC HEALTH WHAT WE'RE DOING HERE IN MANY OCCASIONS IS MIXING UP TWO COMPLETELY DIFFERENCE SCENARIOS TALKING ABOUT THE RISK ASSESSMENT OF TRANSMISSIBLE H5N1s. WE'RE TALKING ABOUT RESPONDING TO A GLOBAL PANDEMIC WITH NO ANTIVIRALS, NO VACCINES, LONG TIME LINE, AND THAT IS A COMPLETELY SEPARATE ISSUE FROM LABORATORY WORKER SAFETY. IT IS INCREDIBLY DIFFICULT TO DEAL WITH THE SCENARIO HERE, NOVEL ANTIGEN CONTAINING INFLUENZA VIRUS WITH NO ANTIVIRAL SUSCEPTIBILITY AND HUMAN POPULATION BEING THE SPREAD AND TRYING TO COMBAT THAT FROM POINT ZERO UP TO PREVENTING SIGNIFICANT DAMAGE OR DISEASE. IT IS A DIFFERENT SCENARIO TO PROTECT LABORATORY WORKER TO SOMETHING GENERATING IN LABORATORY. UNDER THAT SCENARIO ANTIVIRALS AN VACCINES CAN BE AND HAVE SHOWN TO BE INCREDIBLY EFFECTIVE IN THAT BOTTLENECK OF PREINVENTORYING THE VIRUS FROM LEAVING THE VILE, THE CELL CULTURE, INPECKED ANIMAL AND ENTER -- INFECTED ANIMAL ENTERING THE HUMAN POPULATION. REALITY IS IT IS THAT INDIVIDUAL LABORATORY WORKER THAT IS THE PERSON WE WANT TO PROTECT THE MOST BECAUSE INFECTION OF THAT PERSON BECOMES THE ISSUE. IF WE FOCUS OUR ARGUMENT ON THAT, ALL THESE QUESTIONS ABOUT VACCINES AND ANTIVIRALS CAN BE MUCH MORE EFFECTIVELY UTILIZED. AND TO GUARANTEE MULTIPLE LEVELS OF HIGH CERTAINTY PROTECTION FROM INFECTION. SO WE HAVE TO KEEP THOSE ARGUMENTS SAFETY. WHEN WE TALK BIOSAFETY WE'RE TALKING INDIVIDUAL LABORATORY WORKERS AN EXPOSURES AND DO WE HAVE THINGS IN PLACE TO BE ABLE TO MITIGATE THE RISK OF THAT PERSON BEING INFECTED. >> I HAVE A COMMENT ON THAT, ALONG THE SAME LINES. I SEE THE PROBLEM IF YOU HAVE WORKERS AND AVAILABLE VACCINE AND YOU HAVE A VACCINE THAT'S HIGH SENTENCED TO PROTECT AGAINST SOME OF THESE STRAINS AND SOMETHING THAT'S SAID IMMINENT BUT WE DON'T HAVE IT YET, WE CAN WRITE GUIDELINES ON THAT. IF YOU LIMIT YOURSELF TO WORKING WITH THOSE STRAINS WHERE WE DON'T HAVE A VACCINE AND MAKE THE ARGUMENT STILL BE THE SAME GUIDELINE FOR WORKING WITH THOSE STRAINS BECAUSE THERE ARE ANTIVIRALS. I DON'T THINK THAT'S A COMPELLING ARGUMENT BECAUSE WE KNOW EVEN IF WE DON'T CREATE RESISTANCE SOMEHOW, YOU WOULD SHOW THAT WITH H5N1 PATIENTS THAT THEY HAVE TO BE TREATED WITHIN THE FIRST TWO DAYS TO BE 80% EFFICIENT. SO I CAN SEE A SCENARIO YOU HAVE WORKING WITH A STRAIN VIRUS, NO HOMOLOGOUS VACCINE AVAILABLE BUT SAY OKAY THIS VIRUS IS NOT RESISTANT TO THE ANTIVIRUS -- ANTIVIRAL. AND SO THAT'S FINE. I THINK THAT THAT'S VERY DIFFERENT RISK. YOU MIGHT NOT BE ABLE TO GET THAT INDIVIDUAL IN TIME ENOUGH TO TREAT IT AND IF YOU HAVE THE JENNIE OUT OF BOTTLE I DON'T THINK THAT IF YOU DONE HAVE AN AVAILABLE VACCINE YOU WILL NOT BE ABLE TO MAKE IT FAST ENOUGH. SO THAT -- AND YOU WILL NOT BE ABLE TO CONTAIN POTENTIAL PANDEMIC WITH ANTIVIRAL, EVEN IF YOU DON'T GET RESISTANCE WHICH YOU'LL PROBABLY GET IF F YOU TRIED. THAT'S MY DILEMA. >> I WANT TO ADDRESS THAT QUESTION OF AVAILABLE VACCINE. (INDISCERNIBLE) PUT IN PLACE AT THE VERY BEGINNING OF H5N1. AND FIRST THING WHEN THE INFORMATION BECAME AVAILABLE ON VACCINE IT REQUIRED 19 MICROGRAMS, THE WHOLE LABORATORY WAS VACCINATED INCLUDING MYSELF.—Qu; EVEN IN THE LABORATORY HEAD OF VACCINE SINCE GETS A BOOST THE H5. SO I GO BACK TO ANDREW'S STATEMENT, LET'S MAKE SURE WORKERS IN ALL LABORATORIES ARE VACCINATED AT LEAST WITH H-5 BECAUSE YOU PRIME TO H-5, ONCE YOU PRIME YOU CROSS REACT TO THE OTHER CLADES. SO THIS IS SOMETHING THAT WE HAVE HEARD THIS MORNING, NEW ADJUVANT VACCINES COMING ON BOARD TO VACCINATE ALL LAB WORKERS. THIS IS WHERE WE FOCUS THE (INDISCERNIBLE) >> ONE MORE COMMENT. WE HAVE TO CONSIDER EACH OF THESE AS ONE COMPONENT OF A MULTI-COMPONENT RESPONSE TO PREVENTIVE -- INVESTIGATOR FROM BEING INFECTED SO YES. ANTIVIRAL RESISTANCE, ANTIVIRAL TREATMENT HAS SOME ISSUES. ON A POPULATION LEVEL TO GET THOUSANDS OF PEOPLE ON THE RIGHT RIGOROUS DOSING SCHEDULE TO MAINTAIN PROTECTION AND RIGHT TIMING IS A VERY DIFFICULT THING TO DO. ON AN INDIVIDUAL PERSONS LEVEL IT'S MUCH EASIER TO DO THAT AND GET THAT COMPLIANCE. BUT EVEN THAT IS ONLY ONE COMPONENT OF A MULTI-COMPONENT PROTECTING THE INDIVIDUAL. SO THE LIKELIHOOD THEN OF ALL THEE DIFFERENT THINGS GOING DON FROM TWO BIOCONTAINMENT HOODS BREAKING DOWN, THE RESPIRATOR BREAKING DOWN, THE VACCINE NOT WORKING, THE ANTIVIRALS NOT WORKING, ALL THESE THINGS HAVE TO BE CONSIDERED AS A LINEAR SORT OF ARRAY OF THINGS THAT PROTECT US. NONE WHICH ARE 100% BUTTING TO WHICH GIVE US -- >> LET ME REFOCUS US FOR A SECOND. PURPOSEFULLY SEPARATED THIS AFTERNOON'S DISCUSSION INTO TWO PARTS. THE FIRST PART IS FOR THE PROPOSED RESEARCH WE'RE TALKING ABOUT IS THE BSL-3 PLUS WHAT WE'RE TALKING ABOUT IN TERMS OF ADEQUATE CONTAINMENT. THEN THE SECOND PART IS TO TALK ABOUT OTHER FUTURE RESEARCH IN SUCH VIRAL WORK WHICH IS MUCH MORE CONTROVERSIAL ISSUE AND DISCUSSION. AND SO LET ME JUST AGAIN, TRY TO SEPARATE THEM BACK INTO THOSE TWO PARTS. BECAUSE AGAIN THE FIRST PART THERE IS NO DOUBT WITH THE PUBLIC HEALTH ISSUES AND THE VIRAL ISSUES, THERE ARE MANY, MANY PEOPLE WHO FEEL THIS IS VERY, VERY WORTHWHILE WORK. THAT'S WHY THEY SPEND THEIR LIVES DOING IT. I THINK AS A FIRST JOB WE HAVE HERE TO TRY TO MAKE SURE THAT IF THAT WORK IS BEING DONE IN THE UNITED STATES THAT WE'RE DOING THE RIGHT CONTAINMENT AND SO THOSE ARE THE RECOMMENDATIONS THAT THE BIOSAFETY GROUP PUT TOGETHER FROM OUR COMMITTEE. THEN WE WILL COME TO MORE CONTROVERSIAL ISSUES WHERE IT HAPPENS IN TERMS OF CONTAINMENT. SO SURE. >> DOES TAKING -- I KNOW TAKING THE ANTIVIRAL WITHIN TWO DAYS REDUCES YOUR RISK OF DYING. BUT DOES IT MAKE YOU LESS CONTAGIOUS? >> DR. WEBSTER. >> TAKING THE ANTIVIRAL WITHIN THE FIRST TWO DAYS WE KNOW IT DECREASES CHANCE OF DEATH. BUT DOES IT DECREASE CHANCE OF TRACE MISSIBILITY? >> THE ANSWER IS YES. THE LEVEL OF VIRUS IS REDUCED. THE (INDISCERNIBLE). >> >> DR. CHATTERJEE. >> I HAVE A QUICK QUESTION. >> YOU MENTIONED GENERATING VARIANTS THAT ARE REFERENCES TO. SO WILL PEOPLE ROUTINELY TEST FOR DRUG RESISTANCE? SHOULD THAT BE PART OF THE SOP? >> >> THAT'S PART OF THEM NOW, IF YOU WORK WITH VIRUSES YOU SHOULD RECONFIRM F YOU START WITH IT YOU SHOULD HAVE ANTIVIRUS -- >> IT FALLS UNDER ALL THOSE OTHER RULES, FOR JUDGING AND ONLY QUESTION THAT DAWN HAD WAS IS THAT TOO LATE. AS LONG AS CONTAINMENT CONDITIONS ARE GOOD ENOUGH, IT PROBABLY NOT TOO LATE. THE IDEA OF BSL-3 PLUS, WE BELIEVE IT ACTUALLY KEEPS SIGNIFICANT PATHOGENS OUT OF THE THE POPULATION. DO WE BELIEVE THAT OR NOT. SO AGAIN, IN ORDER TO GET OUR TASK COMPLETED TODAY AND COME TO CONSENSUS, I THINK WE SHOULD GO BACK TO THE FIRST SET OF THINGS WE'RE TRYING TO IMPRESS WHICH IS BSL-3 PLUS FOR THIS TYPE OF WORK, YES, NO, SHOULD'c– GUIDE GUIDELINES AND MODIFICATIONS BE ONES MADE. SHOULD WE ACCEPT, CHANGE THEM. AGAIN ALL THE WORK THE BIOSAFETY WORKING GROUP HAD DONE BASICALLY I THOUGHT THEY HAD COME UP WITH A VERY, VERY GOOD SET OF RECOMMENDATIONS THAT SORT OF BALANCES STRINGENCY WITH NOT BEING ONEROUS. THEY PUT SOME MEAT ON IT AND MADE IT SPECIFIC ENOUGH SO HA WE CAN ACTUALLY GO IMPLEMENT AND AUDIT IT AND SPELL OUT FOR THE WORKERS, HAZARDS THAT MAY NOT HAVE BEEN SPELLED OUT EXPLICITLY. BUT AT THE SAME TIME FLEXIBLE ENOUGH THAT DIFFERENT INSTITUTIONS COULD ADAPT TO THEIR BSL-3. I THOUGHT IT WAS FAIRLY REASONABLE. BUT AGAIN WANT TO MAKE SURE EVERYBODY'S IDEAS GET INTO THE RECOMMENDATION THEN HEAD OFF TO THE MORE CONTROVERSIAL EVER AFTER TO WHERE WE'RE GOING SO THAT'S WHY WE'LL LEAVE TO IT DR. HAMMARSKJOLD AND CHATTERJEE LATER. >> WHEN WE SAY VACCINE AVAILABILITY OR THERE IS A VACCINE FOR, WHAT WE REALLY MEAN IS THERE'S A NOT NEVER BEEN TESTED IN HUMANS VACCINE THAT SEEMS EFFECTIVE IN FERRETS OR DO WE MEAN HUMAN VACCINE? >> TESTED IN HUMANS. BUT PROTECTION BY SURROGATE EFFICACY. >> WE ARE TALKING ABOUT -- >> HUMANS. >> EFFICACY IN POPULATIONS -- >> MEASUREMENT OF ANTIBODIES IN THE SERUM THAT NEUTRALIZE OR OTHERWISE INTERACT WITH VIRO. >> MORE THAN EFFECTIVE IN ANIMAL MODELS. >> THERE'S THAT TOO. THERE IS THAT AS WELL. >> IN ADDITION. OKAY. >> I WANT TO BRING BACK MAYBE BIOSAFETY WORKING GROUP MEMBER WHOSE WENT THROUGH THE TELECONFERENCE. WE HAD A TELECONFERENCE WHICH WE TALKED ABOUT VACCINE VERSUS ANTIVIRALS THAT BSL-3 AGENTS MAYBE, MAYBE YOU HAVE AN ANTIVIRAL, MAYBE VACCINE WHEN LOOKING AT 1918 SEVERAL YEARS AGO YOU DID NOT HAVE A VACCINE, WE DIDN'T KNOW 2009 H 1N 1. SO TRYING TO GET AT THE QUESTION WHICH MAY NOT BE COMPLETELY CLEAR. THERE ARE QUESTIONS SURROUNDING SHOULD YOU DO RESEARCH, SHOULD YOU NOT, WITH THE PUBLIC HEALTH BENEFIT. THAT'S NOT OUR ROLE. THERE'S OTHER COMMITTEES AN PEOPLE THAT HAVE TO DETERMINE WHETHER THE RESEARCH GETS DONE. THE QUESTION IS, LET'S ASSUME THE RESEARCH IS DONE BECAUSE SMART YOU ARE THE PEOPLE SAY THERE'S A VALUE TO IT. AND WE HAD TALKED ABOUT YES IT MIGHT BE IDEAL THAT A VACCINE ALONE, IT'S NOT DETERMINANT OF THE BIOSAFETY LEVEL HERE THAT'S HOW BUOY SAFETY WORKING GROUP CAME UP. A THAT'S WHAT THE RECOMMENDATIONS THAT I PUT OUT REFLECTED AND WHY WE DID FOCUS ON ANTIVIRAL. FOR ONE EVEN IF YOU HAVE A VACCINE TRY AND MEASURE WHETHER IT'S ANGIOGENETICLY WORK, WE CANNOT REQUIRE UNLICENSE VACCINE. WE APPLAUD RESEARCHERS WHO TAKE THE VACCINE UNDER WHATEVER CIRCUMSTANCES. SO I THINK THERE ARE FOLKS IN THE BIOSAFETY WORKING GROUP, MAYBE WEIGH IN ON THAT RATIONALE. THAT'S WHY THE VACCINE WAS IN A CRITICAL ONE IN OUR DISCUSSION TO DATE THAT'S WHAT THE RECOMMENDATIONS IN DETERMINING THE BIOSAFETY LEVEL. >> JOE, ARE YOU STILL ON THE LINE? >> I AM. >> WOULD YOU LIKE TO COMMENT ON THAT? Q. I AGREE. AS WE HAD OUR DISCUSSION IT IS SENSITIVITY TO ANTIVIRUS WAS KEY TO DISCUSSION. I GET MUCH LESS COMFORTABLE AS WE MOVE TOWARD VIRUSES THAT ARE RESISTANT TO TREATMENT THERAPIES BUT AGAIN THERE ARE MULTIPLE THERAPIES AVAILABLE SO THERE ARE WAYS OF APPROACHING THIS THERAPEUTICALLY WITH USING AGAIN MAYBE COCKTAILS OF ANTIVIRALS THAT COULD BE HELPFUL HERE. THIS IS OUT OF MY LEAGUE, THIS IS REALLY A MEDICAL QUESTION. I AGREE. JACKIE IS RIGHT. I THINK THE GREATER CONCERN BUT EXPRESSED WHERE WE HAVE VIRUSES THAT ARE RECESSTANT TO ANTIVIRALS. FROM Z Q. ANYBODY ELSE WEIGH IN ON THAT? ANY OTHER DISCUSSION AT THE TABLE ON THAT POINT? >> I GUESS ONE QUESTION WE HAVE BEEN TALKING ABOUT HINGES ON SENSITIVITY OF VIRUS ICE LETS TO DRUGS. AND IT'S BEEN SAID THAT'S TESTED BUT I ASSUME IT'S LIKE VECTOR TITERRING THAT'S VARIABLE LAB TO LAB. IS THAT STANDARDIZED HOW PEOPLE WOULD VERIFY, ARE THERE STANDARD SOPs HOW YOU SHOULD TEST YOUR ISOLATES TO SHOW IT'S SENSITIVE TO AGENTS BEFORE AND AFTER YOU MANIPULATE IT? >> DR. PEREZ. >> I DON'T THINK IN THE LAB WE HAVE A SET OF SOPs HOW TO DO IT. THAT'S SOMETHING ONE OF THE BREAKS WE WERE DISCUSSING WITH DR. WEBSTER ONE OF THE THINGS TO BRING SENSE OF PIECE OF MIND TO THE TYPE OF WORK WE DO WITH H5N1 IS THAT AS A COMMUNITY WE COULD DEVELOP A SET OF STANDARD SOPs AND ALLOW FACILITIES TO USE IT. SO WE ALL KNOW WHAT WE ARE DOING. I THINK THAT WOULD BE VERY HELPFUL. >> AND CERTAINLY ANTIVIRAL SENSE ACTIVETIVE IS LOOKED AT IN TWO WAYS. ONE, THERE IS A LOT KNOWN ABOUT GENETIC DETERMINANTS THAT MEDIATE IT. SO GENE SEQUENCES AND THERE'S A SET NUMBER OF MUTATIONS THAT YOU FOCUS ON. THERE ARE ALSO BIOLOGICAL ASSAYS UTILIZED FAIRLY REGULARLY TO TEST PHENOTIP HEALTHCARELY FOR RESISTANCE WHICH SHOULD THEORETICALLY CATCH THE NOVEL MUTATION THAT WE HAVE IDENTIFIED YET FOR THAT. BUT DIFFERENTIATING THOSE TWO THINGS ARE IMPORTANT. THERE WAS PHENOTYPIC TESTS AS WELL AS GENETYPIC TESTS FOR ANTIVIRAL SUSCEPTIBILITY. THE ISSUE CAME UP IN THE WORKING GROUP WHETHER THE LAB IS DOING THIS RESEARCH OR COMPETENT DOING THOSE ASSAYS, NOT CLEAR THEY ALL ARE. SHOULD IT BE COMPETENT WITH THOSE SCREENING ASSAYS GENERATING VARIANTS AND NEED TO SHOW SUSCEPTIBILITY DOING THE WORK. >> DR. WEBSTER. >> DURING THE DEVELOPMENT OSEL TAMIVIR, THERE WAS A GROUP SET UP TO REPORT ON RESISTANCE TO THE INTERNATIONAL COMMUNITY. AND THAT GROUP IS STILL IN EXISTENCE. IT WAS FUNDED BY DRUG COMPANIES TO GET THIS INFORMATION, I BELIEVE IT'S NOW TAKEN OVER BY WHO. SO THERE IS A GROUP THAT HAVE STANDARDS, RESISTANT VIRUSES AND DEFINITELY HAVE STANDARDS AND THEY MEET AT LEAST ONCE OR TWICE A YEAR TO DISCUSS THE EMERGENCE RESISTANCE, STANDARD WAYS OF DOING AND THERE ARE SOPs IN PLACE DOING IT. AND THE ORGANIZATION RESPONSIBLE FOR THOSE ASSAYS. >> THE DISCUSSION AT THE BIOSAFETY WORKING GROUP TO PUT THE RECORD STRAIGHT WAS NOT SUSCEPTIBILITY OF ANTIVIRALS, IT WAS WHETHER YOU CAN IF YOU HAD VACCINE AGAINST AGENT YOU CHANGE THE AGENT WOULD YOU KNOW WHETHER THAT VACCINE WORKS AGAINST THE RESULTING AND THOSE ASSAYS ARE MUCH MORE COMPLEX. WHAT THE GUIDELINE SAYS, THIS IS BASED ON CONSULTATIONS BACK IN 2009, WAS THAT SUSCEPTIBILITY SHOULD BE ESTABLISHED BY EITHER SEQUENCE ANALYSIS BASED ON THE MUTATIONS WE KNOW OR SUITABLE BIOLOGICAL ASSAY. SO WE GAVE FLEXIBILITY TO TRY FIGURE OUT HOW YOU ESTABLISH YOU'RE WORKING WITH A VIRUS. (OFF MIC) >> AND ABILITY TO PASS THAT WHETHER YOU DO HAVE A STRAIN IS CROSS REACTIVE WITH MR. WHETHER YOU GOT VACCINATED. SO THAT WAS THE QUESTION, I GUESS WE SAID AT THE END THAT WAS TOO CUMBERSOME SO I WANT TO ASK IF THAT'S TRUE OR IF YOU COULD DO THOSE TESTS. BECAUSE IF IT'S LIKE DR. WEBSTER SAID CROSS REACTIVE IT SEEMS TO ME LICENSE H5N1 AGAINST THAT SPECIFIC CLADE THAT IT WOULD STILL HAVE VALUE HAVING EVERYBODY WORK IF IT COMES OUT PEOPLE SHOULD (INAUDIBLE) THAT'S THE NEXT DISCUSSION BUT THAT EVERYBODY SHOULD BE VACCINATED AND THEN TESTED AGAINST THE STRAIN BY HEMOGLUTE NATION INHIBITION ASSAY. >> WE DO THAT IN LAB SO WE HAVE AMERICAN SURVEILLANCE PLAN EVERY YEAR EVERYONE GETS BLOOD TAKEN OUT. WE RUN HI ASSAYS WITH OTHER PEOPLE IN THE LAB AGAINST OTHER STRAINS WE HAVE BEEN USING THAT YEAR. SO WE KNOW WHAT IS GOING ON IN TERMS OF EXPOSURE. IT'S NOT DIFFICULT TO DO. >> STANDARDZATION WHICH I THINK IS A GOOD ONE I THINK IS VERY COMPLICATED TO STANDARDIZE AROUND THE WORLD AND I THINK WHO IS IN BETTER POSITION TO ESTABLISH GUIDELINES FOR THESE KINDS OF THINGS BUT QUESTION IS IF WE HAD WHO COMPLETE STANDARD AND STANDARD GUIDELINES WILL THAT BE ENOUGH FOR THIS COMMITTEE TO BE ACCEPTED OR UNACCEPTABLE? CAN WE JUST FOLLOW THOSE STANDARDS AND WOULD THAT BE ACCEPTABLE TO U.S. ORGANIZATIONS? >> MAKING THE ARGUMENT WHO WOULD LIKELY BE LESS STRINGENT OR IS THAT -- >> I'M JUST ASKING, IF WE -- LET'S SAY WE COME UP WITH A STANDARDIZED ASSAY FOR HUMAN GLUTE NATION THAT IS STANDARDIZED BY WHO AND WE HAVE INCLINATION OF STANDARDS FOR IMMUNOGENICITY TESTING OTHER VACCINE WHICH IS WHAT WE WERE RAISING EARLIER AND IN TERMS OF STANDARDIZING ALL THE LABS WOULD THAT BE ACCEPTABLE TO EVERYBODY, WOULD THAT BE ACCEPTABLE TO U.S. AUTHORITIES? >> I THINK THE QUESTION IS WE WANT THE HEMOGLUTENIN ASSAYS BECAUSE WE WANT TO KNOW THIS INFORMATION OR WE WOULD DO SOMETHING DIFFERENTLY IN TERMS OF CONTAINMENT? TWO DIFFERENT QUESTIONS GOING AROUND. SUSCEPTIBILITY TO ANTIVIRALS, IT WAS OUR UNDERSTANDING THAT THIS WAS SOMETHING THAT COULD BE DONE OR LOOKED AT AGAIN THERE WAS THIS QUESTION THEY MAY SOME LABS MAY DO IT DIFFERENT WAYS, IT MAYBE INFORMATION THAT YOU MIGHT WANT TO KNOW BUT IF NOT DONE ACROSS ALL LABS THE SAME, AND IT DOESN'T CHANGE WHAT WE'RE GOING TO THE IMMEDIATELY WITH THE CONTAINMENT ARE WE OPPOSING THIS FOR A REASON THAT'S NOT GOING TO CHANGE THE ULTIMATE THING -- ULTIMATE ISSUES. SO THAT WAS -- IT MAYBE VALUABLE INFORMATION THAT MAY WANT TO BE DONE BUT WHETHER WE MANDATE IT TO BE DONE IN CONJUNCTION OR A WAY IN ANOTHER INTERNATIONAL AGENCY WHICH CHANGES OVER TIME, NOT SURE THAT'S WHAT YOU WANT TO DO. WE WANT TO DECIDE WHAT WE WANT TO DO WITH VACCINE. SO >> DR. PER REWHAT DO YOUETH D&O WITH DATA FROM YOUR LAB WHEN YOU TEST EVERY YEAR IN >> LIKE I MENTIONED IN MY PRESENTATION WE GO EVERY YEAR, WE TRY TO SEE HOW WE CAN IMPROVE WHATEVER PROCEDURE, I HAVE TO POINT OUT WE DO A LOT OF WORK. THERE IS NOT -- ALL THE WORK WITH H-9. NOT A SELECT AGENT, NOT HIGHLY PATHOGENIC BASICALLY. BUT WE GO OVER THE SERO CONVERSION, SO FAR WE HAVE BEEN FORTUNATE. NOBODY HAS BEEN EXPOSED. WE HAVE BEEN WORKING WITH H-9 FOR THE PAST TEN YEARS AND WE DON'T HAVE A SERO CONVERSION. BUT IF SOMEONE SHOWS UP BEING SERO POSITIVE WE HAVE TO GO BACK AND SEE WHAT ARE WE DOING WRONG THAT IS FAILING. IT TAKES ONLY ONE PERSON TO FAIL THE TEST BASICALLY OR SHOW UP POSITIVE IN THE TEST. AND WE HAVE TO -- FORTUNATELY WE HAVEN'T HAD TO DO THAT. BUT BASICALLY WE HAVE TO RE-EVALUATE ALL THE PROCEDURES THAT WE HAVE IN THE LAB TO SEE WHAT WE NEED TO CHANGE. WE HAVE HAD INSTANCES OF -- IN WHICH WE REPORTED POTENTIAL EXPOSURE TO H5N1, THIS WAS WORK DONE WITH (INAUDIBLE) RATS. AND WE REPORTED MODALLY THE PERSON REPORTED THAT INCIDENT TO ME TO THE HEALTH CENTER AND WE FOLLOW EVERYTHING THAT WE NODE TO FOLLOW, REPORTING TO USDA AND TURN OUT TO BE NOT AN EXPOSURE. BUT THAT PERSON BUT SENT BECOME HOME, THIS IS NOT TRANSMISSIBLE H5N1 BUT SENT BACK HOME, WITH OSEL TAMIVIR. KEEPING DIARY OF SYMPTOMS. SO I THINK WE TRAIN PEOPLE TO DO THEIR HOME WORK. EVERYTHING ELSE THAT WE DO IS TO SEE HOW WHAT WE'RE DOING. >> MAYBE YOU HAVE ALL KNOW THIS, I'M NEW TO IT O SO MAYBE I DONE. WHAT'S THE MECHANISM WHICH THIS IS ENFORCED INTERNATIONALLY? I'M SENSITIVE TO WHAT I THINK IS A GOOD ARGUMENT THAT YOU MAKE SAYING WE NEED TO KEEP LAB WORKERS SAFE. THE HIGHEST LEVEL SCRUTINY TO THE LAB WORKERS AS INDIVIDUALS. BUT WHAT HAPPENS IF THEY DON'T WANT TO TAKE THE ANTIVIRALS OR DON'T WANT TO GET IMMUNIZED T ASSUMPTION I ASSUME HERE TODAY IS YOU DON'T HAVE A JOB, YOU AREN'T GOING TO BE HERE. BUT WHAT IF THEY DO THOSE THINGS BUT NOT EFFECTIVE IN INDIVIDUAL CASES? HOW DO WE KNOW THAT, WHAT TEASE PLAN B FOR THOSE PEOPLE? LINE OF DEFENSE BECAUSE WE CAN'T HANG HEADPHONES IN THE BACKSEAT, BUT LARGELY ON THE ANTIVIRALS. >> WE ARE A COMMITTEE THAT MAKES RECOMMENDATIONS AS TO WHAT SHOULD BE DONE. THERE ARE AGENCIES THAT MAKE RULES THAT HAVE TO BE FOLLOWED LIKE THE USDA. THAT'S WHY WE DEFAULT TO THEM WHENEVER IT IS THAT -- WHO OVERRIDES THE OTHER PEOPLE'S RECOMMENDATIONS, IT'S THE PEOPLE WHO HAVE ENFORCEMENT ARM. AND DOLLARS BEHIND IT AND JAIL TERMS MIND IT. WE ARE JUST A GROUP THAT MAKES THE RECOMMENDATIONS AND THEY ARE THEN SENT O THE NIH FOR FINAL EVALUATION INCORPORATED INTO THEIR FUNDING AND DECISION POLICIES. SO THAT'S WHY AGAIN WE SHOULD COME BACK TO CONTAINMENT ISSUES. MANY BIOSATISFITY COMMITTEES AND INSTITUTIONS PAY ATTENTION -- BIOSAFETY COMMITTEES PAY ATTENTION TO WHAT CONFINEMENTMENT SHOULD BE AND THEREFORE, I THINK THAT WE HAVE MORE SAY OVERALL OF PROGRAMS AN SATISFITY PROGRAMS ON THAT STANDPOINT. OTHER DISCUSSION. >> OTHER THAN LAB DO YOU ROUTINELY VACCINATE? >> NOBODY IN MY LAB VACCINATES H-5. UNTIL RECENTLY EVEN THOUGH WE COULD GET IT WE DO HAVE VACCINATION. I TRIED TO ADVISE PEOPLE TO GET THE FLU SO EVERYBODY THAT CAN GET THE FLU MIST EVERY YEAR GETS THE FLU MIST. IF THEY CANNOT THEY WILL GET THE REGULAR FLU SHOT BUT EVERYONE GETS VACCINATED. EVERY YEAR EVERYONE GOES TO (INAUDIBLE) AND RESPIRATORY TEST. BACK TO YOUR QUESTION, WHAT IF SOMEONE REFUSES WHAT IF SOMEONE HAS CONCERNS. THAT'S SOMETHING I DISCUSSION WITH THE STUDENTS IN MY LAB. EVEN DO YOU FEEL COMFORTABLE WORKING WITHEN MALLS. THERE ARE PEOPLE THAT DON'T WANT TO WORK WITH ANIMALS, DOESN'T MEAN THEY CAN'T THE A Ph.D.. THEY HAVE TO DO A Ph.D. ON SOMETHING ELSE WORKING IN VITRO. SO WE GO THROUGH THIS PROCESS OF INTERVIEWING PEOPLE AND SEEING WHAT THEY ARE CAPABLE OF DOING, AND WHAT THEY'RE FEELING COMFORTABLE DOING. THOSE THAT END UP IN BSL-3 THOSE PEOPLE HAVE BEEN TRAINED AND FEEL COMFORTABLE DOING THAT WORK. >> DR. WEBSTER. >> ADD VERY LITTLE TO THAT, VACCINE POLICY IN OUR LAB IS EVERYONE HAS TO BE VACCINATED AGAINST INFLUENZA IF THEY WISH TO WORK IN THE GROUP. WITH THE H-5 VACCINE ROBIN ROBINSON PRAISING BECAUSE I MAINTAIN THAT EVERYONE IN THAT WORKS ON H5N1 SHOULD BE KEPT VACCINATED. LIKE MYSELF. BUT WITH YOUNGER PEOPLE COMING IN THEY'RE NOT. SO I'M DELIGHTED TO HEAR THAT ROBIN IS TAKING NOTICE AND THAT PROGRAM IS ABOUT TO TAKE PLACE WHERE EVERYONE CAN GET VACCINATED. NOT ONLY GET VACCINATED, WE HAVE TO KEEP UP THE DATE WITH PEOPLE TURNING OVER THEIR -- THIS IS THE REQUIREMENT. >> OKAY. I'M GOING TO TAKE US THROUGH ALL THE RECOMMENDATIONS PIECE BY PIECE AND MAKE SURE THERE'S NOTHING PEOPLE AROUND THE TABLE ARE UNCOMFORTABLE W. CLEARLY THERE ARE AREAS THAT THERE ARE DISAGREEMENTS TO PRACTICE BUT WANT TO I CAN SURE WHAT WE'RE RECOMMENDING IS NOT UP FEASIBLE NOR WRONG. SO DOWN TO FACILITIES AND AIR HANDLING. WE ARE RECOMMENDING IN THE BLUE. MANDATORY HEPA FILTRATION OF EXHAUST AIR AND SEALED DUCK WORK SYSTEM FROM CONTAINMENT BARRIER TO FILTER. I'M GOING TO KEEP READING UNTIL SOMEBODY INTERRUPTS ME. AIR HANDLING IS DESIGNED SUCH THAT UNDER FAILURE CONDITIONS THE AIR FLOW SNOT REVERSED PERIODIC VALIDATION SHALL BE PERFORMED. BACK UP POWER SHALL BE AVAILABLE FOR CRITICAL CONTROLS AND INSTRUMENTATION NECESSARY TO MAINTAIN CONTAINMENT. (OFF MIC) >> WE PURPOSEFULLY LEFT THAT WAY BECAUSE THERE WAS GREAT DEBATE. (OFF MIC) >> SO WE CAN CERTAINLY DO THAT. >> AT LEAST ANNUAL. I THINK ANNUAL IS FEASIBLE. OKAY. >> PERFECT. NEXT SLIDE. >> BACK UP. SHOULD BE REQUIRED >> NOT ALL BSL-3 FACILITIES CORPLY HAVE BACK UP. -- CURRENTLY HAVE BACK UP. >> THAT'S A WEAKNESS WE HAVE THE TAKE CARE OF. >> SO YOU THINK IT SHOULD SAY FOR THIS WORK BACK UP IS REQUIRED. (OFF MIC) >> SHALL AND MUST WE USE INTERCHANGEABLY IN THE GUIDELINES. >> QUESTION ON CLIMATE CONTROL CLIMATE CHANGE QUESTION. GALVESTON OR OTHER -- IN OUR VULNERABLE LABS WHICH LOOKS LIKE THERE'S A LOT OF THEM COASTAL, IS THERE SOME -- SHOULD THERE BE SOMETHING ABOUT WHAT HAPPENS IF THAT'S DISASTER AND THERE'S FLOODS AND THAT -- A CLIMATE CATASTROPHE, IS THERE A PLAN FOR THAT? DO YOU WANT IT HIGHER LEVEL FOR THIS PARTICULAR THING? >> THIS IS JOE KANABROCKI. INCIDENT RESPOND PLANS INCLUDING FOR NATURAL DISASTERS IS ABSOLUTELY PART OF THE REQUIREMENT FOR THE SELECT AGENT PROGRAM. AGAIN REMEMBERING THESE ARE SELECT AGENTS SO ONE HAS TO HAVE A SPECIFIC PLAN TO ADDRESS ANY NATURAL DISASTER AND OBVIOUSLY FOR THOSE LABORATORIES OBJECT COASTAL REGION THAT WOULD INCLUDE FLOODING AN HURRICANES AND THOSE SORTS OF THINGS. I WOULD ALSO ADD THE SELECT AGENT PROGRAM IS IMMENSELY HELPFUL REACHING OUT TO LABORATORIES WHO WORK WITH SELECT AGENTS WHEN THERE ARE WEATHER SITUATIONS IN THE REGION SO COMMUNICATION BACK AND FORTH BETWEEN THE SELECT AGENT PROGRAM AND INDIVIDUAL ENTITY TO ENSURE THERE ISN'T ASSISTANCE NEEDED AT THAT TIME LOCATION. >> THANK YOU VERY MUCH, JOE. NEXT SLIDE. >> THIS IS DAVID, ONE ADDITIONAL COMMENT. >> SURE. >> I THINK THAT WHAT JOE IS TALKING ABOUT, THE INCIDENT RESPONSE PLAN IS PART OF THE BIOSAFETY PLAN. THAT WAS ON YOUR LIST OF ITEMS THAT ARE REQUIRED SO REALLY THE INCIDENT RESPONSE FOR NATURAL DISASTER SHOULD BE PART OF PHYSICAL SECURITY OF THE FACILITY WHETHER IT'S TORNADOES, ON SOUSE HURRICANES. OR MAYBE THE ICE STORMS IN THE NORTHEAST, THOSE ARE ALL PART OF THE INCIDENT RESPONSE, PART OF BIOSAFETY PLAN. >> THANK YOU VERY MUCH. WASTE DISPOSAL, LIQUID EFFLUENCE SHOULD BE DISINFECT OR EAT TREATED AND CHECKED AND PROCESSED PROCESSED IN CENTRAL EFFLUENT DECONTAMINATION SYSTEM. DECONTAMINATION OF SHOWER AND TOILET EFFLUENT IS NOT REQUIREMENT PROVIDED APPROPRIATE PRACTICES AND PROCEDURES ARE IN PLACE FOR PRIMARY -- SHOULD BE CONTAINMENT. THE NEXT ITEM, ANIMAL TISSUES, CARCASSES AND BEDDING ORIGINATING FROM THE ANIMAL ROOMS MUST BE DECONTAMINATED BY EFFECTIVE AND VALIDATED METH, USE OF AUTOCLAVE PREFERABLY BEFORE LEAVING CONTAINMENT BARRIER. IF WASTE IS TRANSPORTED SPECIAL PRACTICES SHOULD BE DEVELOPED FOR TRANSPORT OF INFECTIOUS MATERIALS TO DESIGNATED ALTERNATE LOCATIONS WITHIN THE FACILITY. ANY DISCUSSION HERE? >> DOES THAT ASSUME MEANS TO BE WITHIN THE FACILITY, CANNOT BE TRANSPORTED TO A -- DECONTAMINATED BEFORE TRANSPORT. >> BUT IF YOU CAN NOT -- >> BEFORE LEAVE FACILITY. WITHIN THE FACILITY. >> IS THAT DOABLE? OKAY. NEXT POINT, NEXT PAGE. IF IT IS DISCOVERED AS A RESULT OF GENETIC MODIFICATION OF SERIAL PASSAGING OF MAMMALIAN TRANSMISSIBLE HPAI, H5N1 SUSCEPTIBILITY UNDER AMINUTE DAYS OR OTHER APT VIRAL AGENTS IS LOST, ANY RESISTANCE TO THIS SHOULD BE STOP AND RESEARCH SHOULD BE -- SHOULD ONLY PROCEED AFTER REVIEW BY NIH OR APPROPRIATE FEDERAL REGULATION REGULATORY AGENCIES UNDER THE CONDITIONS SPECIFIED BY THAT REVIEW. NEXT. PROTECTIVE SLEEVES OVER GOWN WORKING BISAFETY CABINET, SPRAY OR WIPE DOWN P WITH A DISINFECTANT WITH ACTIVITY AGAINST INFLUENZA VIRUS PRIOR TO LEAVING CONTAINMENT, REQUIRED. IN ORDER TO PROMOTE ADHERENCE TO PROPER PRACTICE INCLUDING PROPER REMOVAL OF PPE REPORTING OF LOSS OF CONTAINMENT OR EXPOSURE AT LEAST TWO INDIVIDUALS SHOULD BE IN THE LAB AT ALL TIMES WHEN RESEARCH IS ONGOING AND DURING REMOVAL OF PPE. (OFF MIC) >> THE PRO PROCEDURES WAS GETSING THE GLOVES OFF AND TYVEK AND CAN CONSIDER SHOWERS SEPARATELY FROM THAT. (OFF MIC) >> THIS IS DAVID -- >> WE PUT SHOWER REQUIRED AT BOTTOM AFTER ALL THE PPE STIPULATIONS ARE DONE THE. THAT WILL MAKE IT MORE CLEAR. OKAY. >> ONE OTHER THING TO ADD IN WE'RE TAKING SPRAYING OR WIPING DOWN PPE. SOME IS DISPOSABLE FOR EXAMPLE GLOVES AN GOWNS AN SHOE COVERS YOU WOULDN'T WANT TO REUSE THOSE. THE ONLY THING DISCUSSING ABOUT DOING SPRAY DOWN DECONTAMINATION WOULD BE THE ACTUAL PPR THE POLICY RESPIRATOR AND EITHER THE SHOULDER LENGTH WHATEVER TYPE OF CONTAINMENT ENVELOPE IS AROUND IT, THAT YOU WOULD REUSE BUT PROBABLY NOT REUSE THE DISPOSE ABLE MATERIALS. >> WE WILL CHANGE THAT. BY SIGNING THE DOCUMENT -- I'M SORRY. BY SIGNING THIS DOCUMENT THE LABORATORY WORKER ACKNOWLEDGES THEIR UNDERSTANDING OF AND INTENT TO ADHERE TO BIOSAFETY THE, BIOSECURITY AND OCCUPATIONAL HEALTH REQUIREMENTS. THIS DOCUMENT SHALL INCLUDE A STATEMENT THE LABORATORY WORKER AGREES TO REPORT ANY EXPOSURES OR ACCIDENTS INCLUDING THOSE OBSERVED BY THE LABORATORY WORKER. FROM OCCUPATIONAL HEALTH STANDPOINT BASELINE SERUM SAMPLES SHOULD BE STORED FOR ALL LABORATORY WORKERS. FOR RESEARCH WITH HAPI H5N1 MAMMALIAN TRANSMISSIBLE BY RESPIRATORY DROPLET, IF A LICENSE VIRUS SPECIFIC VACCINE IS AVAILABLE AND THERE IS NO MEDICAL CONTRA INDICATIONS, IT SHOULD BE TAKEN BY ALL LABORATORY WORKERS. IF GIVEN A POST VACCINATION SERUM SAMPLE SHALL BE COLLECTED, ASSESSED FOR IMMUNE RESPONSE AND STORED. RESEARCHERS SHALL NOT -- >> CAN I ASK A QUESTION, WHO IS RESPONSIBLE FOR LONG TERM STORAGE OF THOSE SAMPLES? >> WE WERE THINKING LABORATORY OR THE INSTITUTION. >> THE INSTITUTION SURELY. WE THANK THEM FOREVER. >> SHOULD THAT BE ADDED? >> WHAT DR. SARZOTTI KELSOE WAS ASKING SHOULD THERE BE A TIME TO GET RID OF IT. IT'S NOT 50 YEARS LATER IT'S STILL IN THE FREEZER. >> THERE MIGHT BE INTERNAL CODES HOW THEY'RE BUILT ENGINEERING SPECIFICATIONS AND STORAGE FOR THEM IN SOME OTHER PLACES WE DON'T KNOW ABOUT. (INAUDIBLE). FOR ALL THEIR (INAUDIBLE) YOU HAVE TO DO THIS -- WHAT DO THEY DO WITH EBOLA AND MARBURG, THERE MUST BE -- LEVEL 3 MUST DO THE SAME FOR THEIR THINGS. >> THE QUESTION IS WHEN -- >> I HAVE SEEN IT, SHOULDN'T BE STANDARD ACROSS ALL THE OTHER THINGS, THERE MUST BE SOME STANDARDS THESE HAVE,ING RIGHT? Q. NO ROOM FOR HIV EITHER SO IT'S FOGGY. AND LONG RUN YOU WONDER IF ONE, PLASMA LOST OVER TIME AND TWO, SHOULD THERE BE GUIDELINE WHERE AND HOW AN HOW LONG THEY NEED TO BE STORED. >> CAN I TELL YOU -- SO WE KEEP THE SERUM INDIVIDUALLY SO EVERY SERA IS -- DOESN'T HAVE NAME ASSOCIATED ASSOCIATE TO IT. NOBODY KNOWS THE IDENTITY, SO WE COMMUNICATE TO THEM AND THEY TELL WHAT IS GOING ON. WHO WOULD BE THE RIGHT PERSON. SO WE KEEP THOSE FOR THREE YEARS. WE HAVE A SET OF SERA THAT IS NEGATIVE, SOMETIMES WHAT I DO IS PULL THOSE SERA AND USE IT AS ASSAYS FOR SUBSEQUENTs;Ö YEARS. THERE IS NO RULE IN TERMS OF HOW LONG WE SHOULD KEEP THEM. THE UNIVERSITY WILL TELL US HOW LONG WE HAVE TO KEEP THAT SERE SORE SIERRA. >> BUT THERE SHOULD BE SOME GUIDELINE. WHO SHOULD REGULATE THAT? (OFF MIC) >> I DON'T KNOW BUT IT'S VAGUE. >> THE FOLKS THAT WORK IN HIV -- >> NO. >> DR. HINKHE ARE YOU ONLINE? >> YES. >> I KNOW IT REQUIRES SERUM SAMPLES BASELINE TO BE STORED? >> CERTAIN INSTANCES WHEN THEY DO. BASICALLY THERE ARE PROS AND CONS KEEPING THE SERA FOR DIFFERENT LENGTHS OF TIME. IF YOU COLLECTED ANNUALLY WHAT IS THE PURPOSE NECESSARILY KEEPING THE ONE FROM THE YEAR BEFORE. THESE SAMPLES WILL ACCUMULATE AND YOU HAVE INVENTORY QUESTIONS THAT YOU HAVE TO TAKE CARE OF. SO YOU HAVE TO DEFINE THE PURPOSE KEEPING A SAMPLE. WHAT'S THE PURPOSE TO BE ABLE TO DETECT A CHANGE IN SEROLOGY OR SOME OTHER MEASUREMENT. IF YOUR POLICY IS DEVELOPED IN ORDER TO ALLOW YOU TO TEST, THIS WILL BE BASELINE ESSENTIALLY. AND BASELINE FROM FOUR YEARS AGO MAYBE A VALUE IN YOUR POLICY OR MAYBE NOT BUT IF YOU COLLECT THEM ANNUALLY, WE DON'T REQUIRE PEOPLE FOR EVERY SAMPLE COLLECTED BECAUSE IT'S CUMBERSOME AND SOME ISSUES OF MAINTAINING THE SAMPLES OVER PERIODS OF TIME MATTER. SO WE DON'T HAVE A STRICT GUIDELINE. BUT YOU NEED TO HAVE A POLICY BASED ON WHAT YOU'RE GOING TO DO WITH IT. >> BASELINE SERUM SAMPLES ARE COLLECT AND STORED (INAUDIBLE) BUT PERSONNEL BUT DOESN'T SAY FOR HOW LONG. >> SHOULD WE ADD FOLLOWING INSTITUTIONAL POLICIES? >> THAT'S WHAT THE BMBL SAYS. SOMETHING TO THAT EFFECT. >> SO THAT THROWS BACK TO THE INSTITUTION >> THERE WOULD BE A POLICY. >> I THINK THAT WOULD BE REASONABLE. YEAH. >> THE ONLY REASON WE KEEP IT SEPARATED SO WE TRIED TO DEVELOP MORE SENSITIVE ASSAYS TO CHECK FOR SERE ROW CONVERSION AGAINST VIRUSES IN THE LAB. SO WE HAVE COMPETITIVE ANALYSIS NOW FOR H-9 AND TESTING PEOPLE FOR THAT. (INAUDIBLE) MAY NOT PICK UP SERUM RESPONSE BUT PICKED UP BY SOME OTHER MEASURE SO THAT'S WHY WE TRY TO KEEP IT BUT WE DON'T HAVE POLICY OR OBLIGATION TO KEEP THIS HERE. >> FOLLOWING INSTITUTION POLICY MAKES SENSE BUT SHOULDN'T YOU KEEP KEEP THEM AS LONG AS THAT HAS BEENTORY IS WORKING IN THAT LAB? >> YEAH. I'LL BRING BACK TO THE POINT, THE POINT IS NOT JUST FORESTEROLOGY BASED ON EXPOSURE, PART OF THIS WOULD ALSO BE SAMPLES WOULD BE IMPORTANT TO VERIFY VACCINE, TAKE. IF THAT'S PART OF THE DEFINITION I WOULD SAY NUMBER ONE, BASELINE SAMPLES WOULD HAVE TO BE HELD BECAUSE THAT'S STANDARD YOU LOOK FOR IN TERMS OF BOOST AFTER VACCINATION. CERTAINLY SERUM SAMPLES NODE TO BE TAKEN SOME POINT IN TIME AFTER EACH VACCINATION AN VERIFY. SO THERE'S A KNEAD TO STORE SAMPLES FOR A LONG PERIOD OF TIME, IS THERE A NEED TO STORE THEM OF EMPLOYEE IS TERMINATED? NOT BASED THAN DEFINITION. BUT OTHER REASONS A LABORATORY WOULD WANT TO KEEP THEM. >> SHOULD THERE BE A NATIONAL REGISTRY FOR PEOPLE THAT WORK WITH SELECT AGENTS? >> WE HAVE NO SAY OVER SUCH REGISTRY AND THEREFORE IT WOULD BE HARD FOR US TO BE THE ONES MAKING THOSE RECOMMENDATIONS. I WOULD THROW ET BACK TO THE INSTITUTION. I WOULD ENCOURAGE INVESTIGATORS WORK IN HIGH RISK AGENTS TO GO AND PUSH YOUR SOCIETIES TO SET STANDARDS. THEN THE GOVERNMENT DOESN'T MAKE ET T FOR YOU. >> RESEARCHERS SHALL NOT HAVE CONTACT WITH AVIAN SPECIES FOR MINIMUM FIVE DAYS AFTER ENGAGENING WORK WITH THE VIRUS. >> A QUESTION ABOUT THE BUT WE DIDN'T SAY ANYTHING ABOUT THE BOOST. YOU HAVE ANY RECOMMENDATIONS FOR BOOST FOR H5N1 BECAUSE (INAUDIBLE) OFFERED TO THAT ONE TIME. SO YEARLY DO YOU HAVE ANY RECOMMENDATIONS BASED ON WHAT YOU WOULD EXPECT? >> I DON'T THINK WE WANT TO MAKE RECOMMENDATIONS ON VACCINES WE DONE KNOW WHAT THE LICENSE CRITERIA WOULD BE. I THINK THE -- THERE IS ONE BUT THERE MAYBE A DIFFERENT ONE NEXT TIME. SO WE CAN MAKE RECOMMENDATION FOR WHAT'S MEDICALLY CONTRAINDICATED BUT NOT SURE WE WANT TO TALK ABOUT HOW MANY IN ACCORDANCE WITH WHAT IS LICENSING IS. THAT'S WHY I WANT TO RELY ON LICENSING BECAUSE THEN WE HAVE AN FDA PACKAGE INSERT. SO I WANT TO GIVE FLEXIBILITY. >> HIGH RISK EXPOSURES TO MAMMALIAN TRANSMISSIBLE HIGHWAY PATROL AH5N1 REQUIRE ISOLATION OUTSIDE OF THE COMMUNITY AS IS DONE FOR 1918 H 1N 1. ANTIVIRALS FOR EXPOSURES SHALL BE ONLY BE PROVIDED AFTER MEDICAL EVALUATION. HOME SUPPLIES SHALL NOT BE GIVEN. EVERYBODY OKAY THOSE ARE THE RECOMMENDATIONS WE'RE VOWING ON. ANY OTHER ADDITIONS >> I WILL LIKE TO ASK EXPERTS HERE IF YOU'RE GOING TO ASK FOR ACTIVE MONITORING. Q. WHAT DR. REDD WAS SAYING IS HE WANTED A ROUTINE QUESTIONNAIRE. HE SAID HE WANTEDDED TO ROUTINELY QUESTION THE PEOPLE ABOUT FLU LIKE SYMPTOMS. IS THERE A DIFFERENT SUGGESTION FROM PEOPLE AT THE TABLE? HE THOUGHT NOT GOOD ENOUGH THE WAIT UNTIL PEOPLE REPORTED AND THERE SHOULD BE A PERIODIC QUESTIONNAIRE LIKE HEALTH QUESTIONNAIRES I ASK SPECIFIC FLU RELATED KIND OF SYMPTOMS SO THAT WE HAVE IT DOCUMENTED. WHAT DO PEOPLE THINK ABOUT THE TABLE? >> IT'S USEFUL TO REMIND WORKER IT'S IMPORTANT TO REPORT RESPIRATORY INFECTIONS. PEOPLEING IF, THEY THINK IT'S RIFFIAL AND COULD BE USEFUL TO PUT IT IN. >> PERIODIC RETRAINING? TR >> I WOULD LIKE TO SEE SOME RETRAINING ANNUAL REFRESHER TRAININGS ON WORK WITH H5N1 VIRUSES OR SOMETHING LIKE THAT. >> WE HAVE THIS IN GUIDANCE. RIGHT HERE THE PROPER TRAINING ESSENTIAL TALL COMPONENT PERIODIC ASSESSMENTS ANNUALLY IN B >> WE SAID WE DID THAT FOR 1918, I WOULD LIKE TO KNOW PEOPLE DO TRAVEL. PEOPLE DO THINGS. SHOULD THERE BE -- SHOULD THERE BE ANY FLEXIBILITY SAYING WE RECOGNIZE IF YOU'RE AWAY FOR 24 HOURS YOU'RE ON A PLANE TO AUSTRALIA, NOT GOING TO BE ABLE TO GET, DO WE WANT A VERY -- THE OPTION OF LIMITED HOME SUPPLY TO BE DONE ON CASE-BY-CASE BASIS AND I WOULD ASK DR. TUMPEY YOU WORK WITH 1918, WHAT'S DONE WITH THAT BECAUSE THAT'S ONE WE DIDN'T RECOMMEND HOME SUPPLIES WITH OR ANYONE ELSE WITH H5N1. >> WE DIDN'T HAVE A SPECIFIC POLICY FOR TRAVEL OUTSIDE CERTAIN AREA. DURING RECONSTRUCTION OF 1918 VIRUS I DID PROVIDE WEEKLY REPORTS TO THE OFFICE OF THE DIRECTOR ABOUT THINGS LIKE MY DAILY BODY TEMPERATURE AND WHETHER OR NOT I HAD ANY FLU LIKE ILLNESS. THAT WAS PRETTY MUCH THE EXTENT OF THAT. >> THE QUESTION JACKIE WAS ASKING IS AGAIN, WE PUT ON THE SLIDE THAT NO HOME SUPPLIES WOULD BE GIVEN. IF ONE YOUR INVESTIGATORS WERE HEADING TO A LONG TRIP WHERE HE OR SHE MAY COME DOWN WITH SYMPTOMS IN THE MIDDLE OF THE TRIP, SHOULD WE ARM THEM WITH A ANTIVIRAL? BECAUSE HE OR SHE MAY NOT BE ABLE TO GET IT IN NORTHERN THAILAND OR WHEREVER THEY ARE GOING TO. SO THAT'S THE QUESTION SHOULD WE ALLOWkWz FLEXIBILITY. >> THOUGHT ABOUT THIS 48 HOUR THIS CAN FOR H5N1 FAST WE WENT BACK AND FORTH WITH THE GROUP WHETHER 48 HOUR -- IN INVENTORY WE DIDN'T WANT PEOPLE HAVE 48 HOURS OF ANTIVIRUS AT HOME IF THEY STARTED USING THEM OR MINUTEMIZE THE RISK. SHALL ROUTINE HI BE PROVIDED BUT FLEXIBILITY IN TERMS OF TRAVELING THE A CONFERENCE OR SOME REASON MIGHT NOT BE ABLE TO REACH HEALTHCARE WITHIN 24 HOURS, WE MAY NOT WANT TO BUT DELAY 24 HOURS. >> I BELIEVE WE HAVE FLEXIBILITY WITH MY COLLEAGUE WORKING FOR MANY MANY YEARS IN AUSTRALIA TRIED FOR MANY YEARS TO HAVE IT AVAILABLE IN THE HOUSEHOLD EVERY HOUSEHOLD HE WAS VOTED DOWN. I THINK WE SHOULD HAVE FLEXIBILITY. >> WOULD YOU BE ABLE TO SAY ANN VIRUS FOR EXPOSURE SHALL ONLY BE PROVIDED FROM MEDICAL EVALUATION AND LEAVE OUT THE LAST PART? >> I GUESS I THINK HOME SUPPLIES MIGHT NOT BE ADVISABLEs SPECIALLY A WEEK LONG SUPPLY OF TAMIFLU. THERE'S OTHER THINGS PEOPLE MIGHT DO. I THINK WE HAVE TO BE SPECIFIC ABOUT THIS. IF WE MEAN IT FOR SOMEONE WHO WILL BE OUT OUT OF MEDICAL CARE, THEY DON'T TREAT AT HOME, DON'T GO TO LOCAL EMERGENCY ROOM, THEY HAVE SPECIAL PLACE TO TAKE THIS SERIOUSLY. WE'RE PUTTING BETS ON LAB WORKER PROTECTION IDEA. IF THAT'S THE CASE, IT SHOULD BE LONG TRIPS OUT OF CONTACT WITH THIS POLICY, SHOULD BE UNDERTAKEN ONLY AFTER APPEALS PROCESS I. IT HAS TO BE A BIG DEAL IF YOU'RE PLEATLY OUT OF COMMISSION FOR -- COMPLETELY OUT OF COMMISSION FOR SEVERAL DAYS. IN THOSE CASES, THERE COULD BE AN OVERRIDE. IF ANY LESS THAN VERY SPECIFIC THING REFERRING TO EXACT CASES, YOU'LL HAVE SOME LAB SAYING I FEEL MORE COMFORTABLE HAVING IT OR WHATEVER. THAT'S -- THEN YOU DON'T HAVE A POLICY. >> IN MY LAB I HAVE BASICALLY TWO COURSES IN THE OFFICE. SO WHAT IS THAT DIFFERENT FROM HAVING IN HOUSE? IF SOMEONE (INAUDIBLE) WORKING WITH FLU, CAN I TAKE WHAT'S THE DIFFERENCE IN HAVING THAT IN HOUSE? >> YOU DON'T HAVE THAT EVALUATED? >> I WILL ASK A LOT OF QUESTIONS. WHY DO YOU KNOW -- FIRST WHY ARE YOU ASKING ME THAT. THAT WOULD BE FIRST THING. WE HAVE USE IT ONLY ONCE I MENTION WITH THE (INAUDIBLE) EXPERIMENT. >> YOU WOULD REPORT THAT. I GUESS THE THOUGHT WAS THERE COULD BE FOLKS THINK THEY'RE GETTING SICK, THEY START TO TAKE IT, THEY FEEL BETTER, THEY DIDN'T KNOW IF IT WAS EXPOSURE OR -- I DON'T THINK PEOPLE DO THIS MUCH BUT THERE ARE THERE WAS BORDERLINE EXPOSURE. THEY TAKE THE TA MIFLU BECAUSE THEN YOU HAVE SOMEONE IN THE COMMUNITY ON ANTIVIRALS BE WHO IS NOT SICK BUT SHEDDING. THEREFORE, THAT PERSON IS A POTENTIAL VECTOR. YOU COULD GET UNDERREPORTING IF THEY ARE EXPOSED AND DON'T TAKE THE RIGHT DOSE IT COULD BE HARMFUL TO THEM TO UNDERDOSE THEMSELVES. I THINK DR. HAYDEN MENTIONED GETTING RESISTANCE. >> WHAT WOULD THAT BE DIFFERENT FROM RESPONSIBLE INDIVIDUAL, GOING TO GO ON A TRIP. I WILL GO TO CHINA. I CALL MY DOCTOR AND ASK FOR SLEEPING PILL. , SAME THING FOR TAMIFLU. >> LET ME TROY THE WALK THROW THIS. THE INTERNATIONAL RESEARCHERS ARE TRYING TO CONVINCE, MAKE THE CASE FOR AND JUSTIFY NOT ONLY DOING THIS IN LEVEL 4 CONTAINMENT BUT ALLOWING LEVEL 3 BECAUSE YOU WANT LOTS MORE PEOPLE TO DO IT. THE ARGUMENT MOST PERSUASIVE IS ARGUMENT TO HIGH LEVEL INDIVIDUAL BIOSAFETY PRECAUTION FOR INDIVIDUAL WORKER AS WORKER. IF THAT'S THE CASE THEN THE BURDEN OF SUSPICION FALLS NOT POLYON EQUIPMENT AND -- THE INDIVIDUAL MORAL AGENCY ON THE INDIVIDUAL LAB. THAT'S WHY SEEMS A HIGH LEVEL REQUIREMENT FOR THAT PARTICULAR PERSON DOING THIS PARTICULAR WORK BECAUSE YOU'RE DOING GAIN OF FUNCTION, DIFFERENT KIND OF ACTIVITY. AND YOU'RE TRYING TO MAKE CASE HERE BUT EVERY TIME WE GET TO HARD CASES IT GETS UNDONE I KIND OF FEEL LIKE WE'RE TREATING BACK TO LEVEL 4 SAFETY ZONE. I CAN SEE IT ERODED. I WANT SOMEONE WHO WILLING TO BE VACCINATED WITH AN HI VACCINE, SOMEONE WHO TAKES IT SERIOUSLY, STAYS AWAY FROM BIRDS. THIS IS THE MOST SERIOUS THING HUMANITY IS FACING NOW. I'M DEVOTED TO THIS WORK. AND I'M NOT -- I GUESS I CAN'T GO TO THAT TRIP TO CHINA UNLESS IT'S ABSOLUTELY NECESSARY WHILE I'M DOING THIS. SO THAT'S HOW WE SHOULD WRITE IT. >> SO IT BECOMES A QUARANTINE PERIOD. >> IN A SENSE IF YOU DON'T, YOU'RE MAKING THE CASE THAT YOU DON'T NEED A LEVEL 4, YOU DO IT IN LEVEL 3. BECAUSE YOU WANT TO INVOLVE MORE PEOPLE. TO THIS IMPORTANT HUMAN TASK. YOU'RE MAKING THE STRONG ARGUMENT. BUT AT THE SAME TIME IF THE KYE WANTS TAMI FLU THEN HE SHOULD HAVE IT. YOU'RE MAKING IT A PERSON RATHER THAN A CERTAIN KIND OF PLACE. THAT'S THE, ARGUMENT, MAKING THE WORKER IN THE LAB BEAR THE WIG OF HUMANITY'S CARE. THAT'S FINE BUT YOU HAVE TO TAKE IT SERIOUSLY EACH INDIVIDUAL PERSON. IT IS A GRAVE TEST THAT'S WHY I DON'T WANT THEM SMILING IN THE PICTURE, THE PUBLIC WON'T TRUST IT IF THEY FEEL THEY CAN HAVE A SPECIAL DEAL, IT HAS TO BE VERY CAREFULLY APPLIED. >> I THINK THE SPIRIT OF THIS SENTENCE WAS EXACTLY THAT, WE DON'T WANT ANY SAFETY BLANKET FOR SOMEBODY TO SAY WELL, ALL RIGHT, I HAVE SOMETHING AT HOME ANDK TAKE IT, I'M IN THE FEELING THAT BAD. WE WANT TO MIC SURE THE MESSAGE OF SEEKING MEDICAL ATTENTION IS FIRST AND FOREMOST THING THAT PERSON DOES. AND NOT THAT THERE'S SOMETHING ELSE THEY FEEL TAKING TAMI FLU SO I SHOULD BE OKAY WHEN I GO OUT TO DO SOMETHING ELSE. I THINK THERE SHOULD BE -- I AGREE THERE SHOULD BE A STRENGTH MAINTAINED IN THIS STATEMENT BUT EMPHASIZE THAT SPIRIT OF THE LAW IF U YOU'RE FEELING SICK FIRST THING YOU DO GO TO MEDICAL DOCTOR, NOT TAMI FLU IN CASE SOMETHING HAPPENS OR SOMETHING LIKE THAT. THERE NEEDS TO BE CONSIDERATION. PEOPLE NEED TO BE AWARE THAT THEY NEED TO HAVE THAT ACCESS TO MEDICAL CARE WITHIN PERIOD OF TIME OF LEAVING THE LABORATORY. I DON'T KNOW HOW TO CAPTURE THE WORDS BUT THAT'S THE SPIRIT OF THE LAW. >> I THINK THE SPIRIT IS THAT EVERYBODY DOSED WITH TAMIFLU SHOULD SEE A DOCTOR, BE EVALUATED. I DONE CARE IF THEY CARRY IN BRIEFCASE OR HAVE IT AT HOME, WE PROBABLY CAN'T STOP PEOPLE FROM GETTING DOSE THAT'S SITTING AROUND BUT IF THEY TAKE A DOSE, THEY HAVE TO SIGN SOMETHING THAT SAID IF THEY GOT A DEES, THEY GOT TO -- A DOSE THEY HAVE TO SEE SOMEONE AND BE EVALUATED FOR EXPOSURE. I THINK WE ARE ALL OUT FOR THE SAME THING, HOW TO SAY THAT IS HARD >> 48 HOURS SEEMED CRITICAL TO GET THE MEDICINE IN. AND IN SOME CIRCUMSTANCES 48 HOUR TREATMENT COURSE OF TAMIFLU SHOULD BE GIVEN TO BRIDGE THAT IMMEDIATE NEED TO GET TO A DOCTOR THE THOUGHT WAS AFTER TWO DAYS YOU SHOULD BE ABLE TO GET TO SOME MEDICAL FACILITY. DO WE WANT TO BE THAT SPECIFIC? AS LONG AS YOU GIVE A FULL 7 OR 10 DAYS, 7 DAY OR TEN DAY DEPENDING YOU TALK TO, YOU'RE ALLOWING SELF-TREATMENT AND WE WANT TO AVOID ENABLING SELF-TREATMENT THOUGH WE TRUST OUR LAB WORKERS, THERE COULD BE MECHANISMS TO AVOID TOTAL SELF-TREATMENT AND NOT COMING TO A DOCTOR. >> I WANT TO SAY A LITTLE BIT ABOUT THE RAC HISTORY. THE RAC HISTORY HAVE THIS DISCUSSION ABOUT (INAUDIBLE). THEY HAVE THE SAME PROBLEM. THEY HAD A SAFETY ISSUE THEN A MORAL ISSUE. THEY DECIDED TO DEAL WITH THE HANDLING OF THIS IN THE MORAL ISSUE HAVING A HIGH STANDARD FOR SAFETY. AND ORIGINALLY ALL THE COMMON DAN WORK WAS DONE IN ALL, ALL OF IT IN THE LABORATORIES. BECAUSE OF THE SUSPICION. WE'RE GOING TO MOVE BACK FROM THAT KIND OF HISTORY, YOU HAVE TO HAVE A HIGH BURDEN ON THE SAFETY. MAYBE IN -- MAYBE IN A TWO YEARS WHEN PEOPLE HAVE MORE SENSE OF KNOWING WHAT THEY'RE DOING, MORE THAN SIX MONTHS AFTER FIRST PAPER MAYBE THE SUSPICION COULD BE RELAXED IN SOME WAY. LOOK AT I AGAIN, PUT A SENSE O CLAUSE ON SOME STUDIES, IF THAT'S WHAT YOU WANT. I'M FOR THE HIGHEST STRICTEST BURDEN WE CAN DO GIVEN -- MAKING THE NON-IMPEDING IN WAYS COMPLETELY ADVANTAGEOUS TO THE GOAL OF ANSWERING AN ANSWER TO THIS -- ESTABLISHING AN ANSWER TO THIS PROBLEM. >> FOR THIS PARTICULAR POINT I WOULD PUSH TO JUST KEEP IT AS IS. THE REASON I PUSH TO KEEP IT AS IS IF I WERE DOING PIPETTING, I WOULDN'T LEAVE THE COUNTRY FOR 48 HOURS AFTER I PIPETTEED. SO AGAIN, IT'S HYPOTHETICALLY YOU REALLY HAVE TO GET ON A PLAN, NO MEDICAL CARE, YOU SHOULD CARRY IT BUT I WEIGH RISK AROUND WHERE I COULD GET MEDICAL CARE UNTIL I GET ANOTHER FIVE DAYS. KEEPING IT ALLOWS US TO SAY IT LIKE WE MEAN IT AND EVERYBODY UNDERSTANDS IT. THAT'S MY RECOMMENDATION. ANY PUBLIC COMMENTS? YES, DR. WILSON. >> YES, DR. WILSON. >> JUST A THOUGHT. I KNOW OUR PHYSICIAN WHO WHEN SOMEONE -- OUR MEDICAL DIRECT FOR WHEN SOMEONE BREAKS WITH A FEVER AND ISOLATES HIM AT HOME, AND HE'S MONITORING THAT INDIVIDUAL AND THE FEVER CONTINUES TO RISE HE WILL SAY TAKE TAMI FLU, THE TWO DOSES, TAKE IT, REPORT TO MY OFFICE, AND WE'LL DEAL WITH IT. IT'S UNDER A DOCTOR'S EVALUATION AND CARE. BUT THAT DRUG IS AT HOME.so! IT'S TO COVER TRANSPORT. IT'S TO COVER FAMILY WHO IS AROUND. THAT'S WHY I RAISE AND I THINK SHALL NOT BE GIVEN, I UNDERSTAND TOTALLY AND AGREE WITH THE REASON BUT THERE ARE OTHER CIRCUMSTANCES, I REMEMBER HAVING A DISCUSSION WITH JACKIE KATZ AT CDC ABOUT PEOPLE TRAVELING OUT OF THE INFLUENZA LAB AND BREAKING WITH FEVERS ABROAD OR WHILE EN ROUTE. I DO BELIEVE THE OCCUPATIONAL MEDICAL UNIT THERE AT THE TIME WAS GIVING THEM TAMIFLU TO TRAVEL WITH THEM. IS THAT CORRECT? >> YES. >> RIGHT. SO THERE ARE CIRCUMSTANCES THAT I THINK FEED INTO, I'M SORRY, I DON'T KNOW YOUR NAME. FEED TO YOUR NEED FOR THAT HIGHEST LEVEL. AND IN ONE HAND THE SHALL NOT GIVE IT TO BUT IN A NARROW PERSPECTIVE. SO THAT'S WHY I WOULD ARGUE FOR LALE RELIEF THERE BECAUSE YOU MIGHT ACTUALLY PROVIDE THAT HIGHER -- >> RYE THE FOLLOWING FOR WORDAGE. APT VIRALS FOR EXPOSURE SHALL ONLY IF PROVIDED AFTER MEDICAL EVALUATION. HOME SUPPLIES SHALL NOT BE GIVEN EXCEPT UNDER MEDICAL SUPERVISION. SO SOMEBODY ELSE HAS TO BE RESPONSIBLE FOR YOU. SOMEBODY HAS TO WRITE THE SO YOU HAVE TO TAKE IT AND SAY CAN I TAKE MY DOSES. HOW DOES THIS SOUND. (OFF MIC) >> I THINK THIS RESEARCH IS DONE BY PHYSICIANS. I KNOW PEOPLE TROY TO SAY THEY'RE GOOD. I THINK IT'S CASUAL. I THINK YOU SHOULD SAY NO AND IF SOMEONE WANTS THEY SHOULD SAY PROCEDURES OVERRIDE APPEALS PROCESS SHOULD BE ESTABLISHED OR SOMETHING. BUT I THINK IF YOU JUST TRUST ME I'M A DOCTOR, IT -- I DON'T, JUST DON'T. IF YOU MEAN IT WE MEAN IT. AND I WANT THIS TO BE DIFFERENT THAN THE PAST. BECAUSE THIS IS GAIN OF FUNCTION RESEARCH, THIS IS DIFFERENT AND IT'S USING SOPHISTICATED TOOLS OF SCIENCE THE MAKE SOMETHING NEW IN THE WORLD. THAT CREATES A HIGHER MORAL BURDEN. EVEN IN 1918 BECAUSE IN 1918 THIS WAS CLEARLY STRONGER ANTIVIRALS, MUCH MORE CONTAINMENT AND UNDERSTANDING OF IT. AND THAT'S -- I THINK THIS IS -- THIS KIND OF THING WILL BE LOOKED AT ALL ALONG THE LINE. THIS IS THERE WAS A REASON WHY THERE WAS A BIG DEBATE, THE REASON IT WAS ON THE FRONT PAGE NEWSPAPER OF EVERY REGION IN THE WORLD. THIS IS THE REASON, AND WE RESPOND BY CHANGING HOW THINGS ARE DONE TO ASSURE THE PUBLIC WE TAKE IT SERIOUSLY. >> THIS IS JOE KANABROKI, A QUICK COMMENT. I THINK IT'S REALLY IMPORTANT THAT THE PUBLIC UNDERSTAND THE VERY LOW RATE OF LABORATORY ACQUIREDDED INFECTIONS IN CONTAINMENT LABORATORIES. THERE ARE SOME RESEN STUDIES PUBLISHED ON THIS MATTER AND I THINK IF ANYTHING WE REALLY NEED TO DO A BETTER JOB COMMUNICATING TO THE PUBLIC HOW RESPONSIBLE SCIENTISTS WORK MANY THIS ARENA INDEED ARE. ALONG WITH HOW IMPORTANT THIS RESEARCH IS. I THINK A PR CAMPAIGN IF YOU WILL ABOUT THE SAFETY OF THE LABORATORY ONCE EMPERIMENTS ARE DONE NEEDS TO BE UNDERTAKEN. I DON'T THINK THE ANSWER IS RAISING CONTAINMENT TO A CERTAIN LEVEL. IT'S P CONVEYING TO THE PUBLIC THE SUCCESS OF WHAT WE CURRENTLY DO AND HOW IT DOES WORK. >> NOT TALKING ABOUT RAISING IT, TALKING ABOUT NOT SENDING PEOPLE HOME WITH TAMI FLI, IT'S A SMALL POINT, AND IF IT'S SUCH A LOW RISK THEN THIS SHOULDN'T BE A BIG DEAL. >> HOW ABOUT IF WE ADD ROUTINELY AT THE END, GIVE IT ROUTINELY IS THAT STILL TOO OPEN ENDED? >> YOU CAN HAVE BOTH. I DO THINK THIS KIND OF THING THESE DETAILS, THIS WORDING ALL ALONG THE LINES SHOWS THE SERIOUSNESS AND I BELIEVE THE REIS IS EXTREMELY LOW. VERY UNLIKELY. BUT I BELIEVE THIS THE THE TROUBLE IS IF THERE'S A MISTAKE, NOT ONLY IS THIS PERSON IN%> LET'S LEAVE AS IS. I WOULD RECOMMEND TOLAN TORES DOING THE WORK THEY HAVE SOME MECHANISM IN PLACE THAT ALLOWS QUICK AND GOOD ACCESS MEDICAL CARE FOR THOSE PATIENTS OR WORKERS THAT EXAMINE DOWN ILL SO THEY'RE TREATED AS QUICKLY AS POSSIBLE. HAVING THAT DOCUMENTED IS SO, SO IMPORTANT SO THAT THERE IS NO CHANCE ANYTHING IN THE LABORATORY CAN GET OUT TO THE PUBLIC ARENA. AGREE WITH DR. ZOLOTH ON THAT. DR. WEBSTER. Q. I WAS GOING TO FESS UP. -- Q. I WAS GOING TO SEARCH YOUR BRIEFCASE. >> YOU PROBABLY ALL KNOW I HAVE GONE TO PROBABLY EVERY SITE H5N1 HAS BEEN ISOLATED IN THE WORLD AND AFTER OSEL T,MIVIR BECAME AVAILABLE IT WAS ALWAYS MY TRAVELING COMPANION, IN CASE. IN THE LAST 15 YEARS I HAVE NEVER USED IT. >> I THINK IT'S IMPORTANT FOR PEOPLE WHO GO THROUGH THE FEEL TO BE CARRYING IT. >> I TOTALLY AGREE. WHEN I WENT THE THAILAND I TOLD MY DOCTOR THAT'S WHAT I WANTED AND I TOOK IT TOO. THIS IS A VERY SPECIFIC RAC PROTOCOL. AND THAT'S WHY WE MAKE THE ASSUMPTION. FIELD WORKERS ABSOLUTELY SHOULD HAVE IT. NO QUESTION. >> SO I DON'T THINK WE'RE SETTING REGULATIONS FOR FIELD WORKERS IN THE FIELD OF (INDISCERNIBLE). >> WE'RE NOT EVEN SETTING RECOMMENDATIONS FOR NON-MAMMALIAN TRANS MISSABLE H5N1 OR OTHER INFLUENZA RESEARCH. WE'RE ONLY SAYING FOR THIS SPECIFIC TYPE OF EXPERIMENT UNTIL YOU'RE (INAUDIBLE). >> JUST WANT TO MAKE SURE THAT'S ABSOLUTELY CLEAR. ANY PUBLIC COMMENTS? I WOULD MOVE WE HAVE A VOTE FROM THE RAC MEMBERS. DO I HAVE A SECOND? >> SECOND. >> GOOD. ALL RIGHT. LET'S START. DR. WOOLEY. >> RESPECTFULLY I VOTE NO BECAUSE I BELIEVE AT THE CURRENT TIME THESE INITIAL EMPERIMENTS SHOULD BE DONE BL-4. >> OKAY. THANK YOU. >> YES. >> FONG. >> YES. >> IF YOU COULD SPEAK INTO THE MICROPHONE SO WE HAVE IT ON RECORD. ZOLOTH. >> A GUARDED GRUMPY YES. >> ROSS, YES. >> HAMMARSKJOLD, YES. >> CHATTERJEE, YES. >> ON THE PHONE. >> MOLINO, YES. >> (INDISCERNIBLE) YES. >> COTE, YES. >> ANYBODY ELSE ON THE PHONE? >> DID DR. KOHN STEP OUT? >> YES. HE STEPPED OUT. WE'RE GOING TO MOVE TO THE FINAL PART OF OUR AGENDA AND TURN TO CHAIR OF THIS SESSION OVER TO DR. CHATTERJEE AND HAMMARSKJOLD. >> SO DR. FONG SAID -- >> HANG ON ONE SECOND. KOHN. >> YES. >> GOOD. >> DR. FONG SAID A WHILE AGO THIS WAS GOING TON TO BE A CONTROVERSIAL SECTION. THAT WAS NOT CONTROVERSIAL OR NOT WE'RE GETTING TO IT NOW. SO WE'RE GOING TO HAVE WHAT I HOPE IS NOT TOO LONG A PANEL DISCUSSION ABOUT RISK ASSESSMENT FOR FUTURE RESEARCH WITH PATHOGENIC INFLUENZA TRANSMISSIBLE VIRUS. WE HAVE THREE MAIN QUESTIONS WHAT SHOULD BE CRITERIA DETERMINING THE VIRUS REQUIRE MODIFY CONTAINMENT OF RISK MANAGEMENT AND SECOND ARE THE TYPES OF EXPERIMENTS WITH THE HIGHLY PATHOGENIC H5N1 NOT SPECIFICALLY INTENDED TO GENERATE MAMMALIAN TRANS MISSABLE STRAINS P BECAUSE OF THE SPECIFIC RISK WOULD STILL MAYBE INCREASE CONTAINMENT LIKE BS-3 AND ALSO SHOULD MAYBE ENHANCE CONTAINMENT MEASURES BE CONSIDERED WHEN PERFORMING RESEARCH TO INCREASE TRANSMISSIBILITY PATHOGENESIS OR RANGE OF OTHER POTENTIAL DUE TO LOW PRE-EXISTING IMMUNITY IN THE COMMUNITY. SO WE HAVE A NUMBER OF PANELISTS AND I GUESS WE SUGGEST -- SHOULD JUST GET RIGHT INTO HEARING OPINIONS ON THE HEAR. SO DR. WEBSTER. >> THANK YOU. LET ME GET RIGHT TO IT. I'LL BEGIN -- I WON'T READ ALL THE QUESTIONS. YOU HAVE THEM IN FRONT OF YOU. WHAT MAMMALIAN ASSAYS ARE COMPARABLE TO THE USDA ASSAY FOR (INAUDIBLE). THE AGRICULTURE AUTHORITIES MOLECULAR SEQUENCE MARKER IN THE HEMOGLUE TIN OF H-5 AND 7 VIRUSES. THAT ARE INDICATIVE PATHOGENICITY. IT'S NOT AN ABSOLUTE MARKER IN THIS HIGH PATHOGENICITY IS A POLYGENIC MARKER. BUT IT IS AN EXCELLENT MARKER. TO WE HAVE THE SAME KINDS OF MOLECULAR MARKERS IN MAMMALIAN TRANSMISSIBILITY? THE ANSWER IS BOTTOM LINE IS UNFORTUNATELY NO WE DONE. ON THE OTHER HAND, WE DO -- THERE ARE SOME INITIAL MARKERS THAT ARE ALL OVER THE PLACE LIKE RECEPTOR BINDING POCKET, 627 PB-1F-2, SO ON AND SO ON. SO THE AGRICULTURAL AUTHORITIES HAVE CONSIDERABLE ADVANTAGE OVER MAMMALIAN PEOPLE CONNECTING PEPTIDE OF HEMOGLUTENIN OF H-5 AND 7, IS AN EXCELLENT INDICATOR THAT WE DON'T HAVE. TURN TO THE (INDISCERNIBLE) VIRUSES, THEY DEFINE PARTICULAR RESIDUES IN THE HEMOGLUTANIN. BUT VIRUSES, TAKE ANOTHER BACKBONE, PROBABLY WON'T MEAN DIDLY SQUAT. SO FOR MAMMALIAN PREDICTABILITY WE DON'T HAVE A SET OF MARKERS. OTHER ASSAYS MAMMALIAN TRANSMISSIBILITY, OTHER MAMMALS INCLUDE OTHER MODELS INCLUDE GUINEA PIG, GUINEA PIG IS USED IN A COUPLE OF LABS, ADVANTAGES ARE CHEAPER READILY OBTAINABLE, FERRETS COST NOW $500 EACH, GUINEA PIGS PROBABLY $30 STILL. SO THAT'S A BIG ADVANTAGE. ON THE OTHER HAND THE GUINEA PIG DOESN'T SHOW ANY DISEASE SIGNS AND SO THAT'S A DISADVANTAGE THE OTHER MAMMALS OF COURSE THE PIG OR THE PRIMATE. WE TRY TO PHASE AWAY FROM. OTHER SYSTEMS INCLUDE EXVIVO LUNG CULTURES FROM HUMAN TO SWINE AND HUMAN BRONCO EPITHELIAL CELL CULTURE. BOTH CELL CULTURES YOU HAVE TO TWO BACK TO A MAMMALIAN SYSTEM TO EVALUATE. WHAT ASSAYS ARE AVAILABLE FOR MAMMALIAN TRANSMISSIBILITY. I THINK WE'RE DOWN TO THE FERRET. AS DANIEL RAISED A SHORT TIME AGO, WE NEED A SET OF SOPs FOR RESPIRATORY DROPLETS IN FERRETS. SO TURNING TO THE SECOND QUESTION I WON'T READ IT, HERE MY OPINION IS QUICKLY WITH COLLEAGUES IS THAT -- I THINK THAT MAN MADE HIGHLY PATHOGENIC H5N1 VIRUSES THAT DON'T EXIST IN NATURE DO REQUIRE SPECIAL ATTENTION. I'M NOT SUGGESTING BL-4 BUT I SUSPECT THAT WE HAVE TO GIVE IT THE TOP LEVEL BL-3 PLUS PERHAPS TIER 1. >> DR. WEBSTER. I THINK WE'RE DEALING WITH A DIFFERENT SET OF QUESTIONS. >> I APOLOGIZE. THE AGENDA CHANGED AFTER THE LAST TELECONFERENCE AND ALSO IN YOUR FOLDER. >> YOU'RE DOING WITH WHICH CRITERIA MODIFIED CONTAINMENT RISK MANAGEMENT WHETHER THE FERRET MODEL SUFFICES. I THINK LAST TELECONFERENCE THE QUESTION CAME UP WHETHER IF A VIRUS IS TRANSMISSIBLE BETWEEN FERRETS, IS IT TRANSMITTIBLE BETWEEN HUMANS. IS THERE ANY PROOF TO THAT EFFECT. I THINK THE ANSWER WAS NOT REALLY. >> NO. IT'S THE BEST WE HAVE GOT. THE FERRET IS NOT A CURE BUT IT IS THE BEST THAT WE HAVE AT THE MOMENT. BETTER THAN THE PIG, BETTER THAN THE FERRET. BETTER THAN THE GUINEA PIG, SO ON. AS DANIEL SAID IT'S NOT HUMAN. THAT'S THE BEST WE HAVE GOTTEN. >> THIS WAS THE CERTAIN VIRUS CERTAIN MUTATION THAT MAKES IT BIND TO HUMAN RECEPTORS. SHOULD THAT BE TREATED MAMMALIAN TRANSMISSIBLE VIRUS JUSTIFIED BY THAT FINDING ALONE? >> NO, THAT IS NOT ENOUGH. ON IT OWN THAT IS JUST ONE OF THE REQUIREMENTS. ON ITS OWN IT'S NOT ENOUGH. MANY OF THE VIRUSES WILL GO INTO HUMANS AND NOT SHOW THAT MARKER INITIALLY AND P ACQUIRE LATER AS THE H-2s DID. H 2N 2 FIRST WENT THE HUMANS WITH ALPHA 2, 3 BINDING AND THEN ACQUIRE THE ALPHA 26 LATER. SO ALPHA 26 ON ITS OWN IS NOT ENOUGH. IT'S POLYGENIC REQUIREMENT. SO NONE OF THESE CRITERIA THAT WE -- THERE ARE MULTIPLE MOLECULAR MARKERS IN MAMMALIAN VIRUSES BUT NONE ARE GOOD INDICATORS. LIKE THE AVIAN HEMOGLUTENIN MARKERS. >> DR. PEKOSZ WOULD YOU LIKE TO COMMENT ON THESE QUESTIONS? (OFF MIC) >> MICROPHONE, PLEASE. >> SO IN TERMS OF CRITERIA, FOR MODIFYING CONTAINMENT OF RISK MANAGEMENT, I'LL GO BACK TO THE BIOSAFETY ISSUES. I THINK THAT ANY KIND OF MUTATIONS THAT ARE ACTIVELY ENGINEERED THAT ARE GOING TO DRASTICALLY CHANGE ANTI-GENICITY OR VACCINE AND VIRAL SUSCEPTIBILITY NEED TO BE SERIOUSLY ADDRESSED. IF SOMETHING OCCURS NATURALLY, CERTAINLY A DIFFERENT REASON FOR UNDERTAKING THAT LINE OF RESEARCH. BUT IF INVESTIGATOR IS PROPOSING TO DRASTICALLY ANGIOGENETICLY CHANGE PROTEIN TO SEE HOW THE VIRUS MAY HAVES I THINK THAT NEEDS TO UNDERGO GREATER SCRUTINY BECAUSE THAT WEAKENS ONE OF THE LINKS THE VACCINE. IS IT FERRET THE BEST MODEL? I THINK IT IS. THERE ARE OTHER MODEL SYSTEMS FOR TRANSMISSION THAT COULD BE UTILIZED AND CONSIDERED. SHOULD A VIRUS CERTAIN MUTATIONS IN -- I AS DR. WEBSTER SAID, THIS IS ONE PIECE, THERE IS NOTHING CRITICAL, THERE'S NOTHING THAT WE KNOW SO FAR ABOUT HA THAT IS ALL OR NOTHING IN TERMS OF MOLECULAR SIGNATURE THAT WOULD CERTAINLY INDICATE IT DEFINITELY IS GOING TO BECOME PANDEMIC. SO I THINK FOCUSING TOO MUCH ON HA IS NOT THE RIGHT APPROACH. QUESTION TWO. IS TYPES OF EXPERIMENTS WHICH ARE NOT INTENDED, NOT INTENDED TO GENERATE STRAINS. HERE THIS BECOMES AN ISSUE OF EVOLUTION NATURAL SELECTION IN MY MIND. WE CAN PASSAGE VIRUSES ON HUMAN AND MAYBE DEGREE THEM TO GROW BETTER, BUT THAT DOESN'T MEAN THERE'S TRANSMISSION. I THINK DR. SWAYNE MENTIONED WE CAN PASSAGE VERSE IN ANIMALS AND RESULTS IN VIRUSES LESS VIRULENT SO IT COMES DOWN TO THE TYPE OF EXPERIMENT YOU'RE DOING. IF U YOU'RE THING THE EXPERIMENT THAT WILL REQUIRE A BOTTLENECK OF TRANSMITTING FROM ONE ANIMAL TO ANOTHER, THAT IS THE CRITICAL EXPERIMENT. THERE ARE OTHER TISSUE SYSTEMS WHERE YOU GRIND UP A LUNG AND EXPOSE TO ANOTHER ANIMAL DOESN'T RESULT IN INCREASED TRANSMISSION, IT RESULTS IN ATTENUATION OR LOSS OF TRANSMISSION BECAUSE YOU'RE NOT SELECTING FOR THAT. SO THE CRITICAL ASPECT, IS THIS RESEARCH SOMETHING THAT WILL SELECT FOR, THAT BRINGS TRANSMISSION INTO THE EQUATION. SO THE THIRD QUESTION I BELIEVE REFERS TO NON-H-5 VIRUSES. WHETHER OR NOT THINGS HIKE TRYING TO GET MAMMALIAN TRANSMISSIBILITY WITH OTHER SUBTYPES OF INFLUENCE SAY IS A PARTICULAR RISK. AND HERE -- INFLUENZA IS A PARTICULAR RISK. THE IMPORTANT PARAMETER BECOMES DISEASE. WHAT WE'RE CONCERNED ABOUT IS HIGHLY TRANSMISSIBLE VIRUS CAN CAUSE DISEASE. SO THAT NEEDS TO BE CONSIDERED WHEN EXPERIMENTS ARE BEGUN. ARE YOU STARTING WITH SOMETHING THAT HAS HIGH POTENTIAL TO CAUSE DISEASE IN MAMMALS, ARE YOU ASKING H A VIRUS BECOME, IS IT EASIER TO TRANSMIT. IF THERE'S NOT COMPARATIVE INCREASE IN DISEASE, YOU'RE PROBABLY NOT IN A RANGE OF EMPERIMENTS THAT REQUIRE HUGE AMOUNT OF SURVEILLANCE. BUT I THINK AS SOON AS YOU HAVE TO BRING IN DISEASE INTO THAT FACTOR BECAUSE TRANSMISSION ALONE NOT CRITICAL, IT -- SOMETHING THAT CAN CAUSE DISEASE THAT STARTS TO RING BELLS IN MY MINE. >> TO DO THE EXPERIMENTS FIRST BEFORE YOU CAN -- >> PART OF THE PROBLEM IS THAT PHENOTYPES LIKE TRANSMISSION CAN RESULT FROM A WHOLE RANGE OF DIFFERENCE GENOTYPES. AND EMPERIMENTS THAT STIMULATED THIS DISCUSSION PROBABLY REPRESENT ONE COMBINATION OF GENES AND SIGNATURES AND CHARACTERISTICS THAT LOAD TO TRANSMISSION WHETHER THOSE CHARACTERISTICS CAN BE ACHIEVEED WITH OTHER GENE TYPES IS UNKNOWN BUT PROBABLY IS LIKELY. IT'S DIFFICULT TO HAVE MOLECULAR GENETIC SIGNATURES, TISSUE CULTURE SIGNATURES THAT PREDICT WHAT WE'RE WORRIED ABOUT WHICH IS TRANSMISSIBLE HIGHLY LETHAL INFLUENZA VIRUSES. >> DO YOU THINK THOSE RESULTS WOULD -- WOULD THEY BE SPECULATIVE AS TO THE BREAKABILITY TO HUMANS? IT STILL MAY BE THE BEST MODEL. >> I THINK SO IN THE CASE OF THIS QUESTION, FOR INSTANCE, IF YOU HAD AVIAN VIRUS WHICH YOU ADAPTED IN FERRET AND BECAME TRANSMISSIBLE AND CAUSE DISEASE, THAT'S JUSTIFICATION THAT THERE'S A HIGH PROBABILITY THAT COULD CAUSE DISEASE AND TRANSMIT IN HUMANS. THAT WOULD BE A WARNING SIGN. >> WOULD CONVERSE BE TRUE? >> FERRETS AREN'T THE PERFECT MODEL SYSTEM SO THERE PROBABLY COULD BE VIRUSES THAT DIDN'T TRANSMIT IN FERRETS BUT COULD IN HUMANS. THAT'S THE LIMITATION OF ALL EXPERIMENTS USING MODEL SYSTEMS. >> DR. TUMPEY. >> SO I AGREE WITH MANY OF THE COMMENTS OF MY PREVIOUS COLLEAGUES >> IT'S IMPORTANT TO KNOW THE BIOSAFETY GUIDANCE THAT WE'RE TALKING ABOUT IS NOT TALKING ABOUT HERE TODAY IS NOT JUST ABOUT TRYING TO STUDY THE TRANSMISSIBLE H5N1 VIRUS IN MAMMALS. THE GUIDANCE SET FORTH IS GOING TO HAVE IMPACT ON ALL TYPES OF RESEARCH THAT'S RELATED TO RECEPTOR SPECIFICITY. AND OTHER THINGS THAT INVOLVE THE HA OF H5N1, WE HAVE HAD RESEARCH HALTED OVER A YEAR AGO IN TRYING TO DEVELOP CHANGE AND MAKE MUTATIONS IN H5N1 THAT WOULD ALLOW IT TO BE MORE ANGIOGENIC. VIRUSES THAT WORK WAS STOPPED AND WE'RE WAITING FOR SOME GUIDANCE ON WHEN TO START THE WORK UP. WITH REGARDS TO THE FERRET MODEL BEING THE BEST MODEL, IT'S NOT A PERFECT MODEL AS DR. PEREZ IS ALLUDED TO, BUT I BELIEVE IN GENERAL IT'S THE BEST MODEL DETERMINING WHETHER H5N1 VIRUSES ARE TRANSMISSIBLE BETWEEN MAMMALS IT'S THE BEST MODEL BECAUSE IN SINGLE EXPERIMENT YOU CAN OBTAIN TWO DATA SETS, ONE FOR TRANSMISSION AND ONE FOR PATHOGENESIS WHICH IS ALSO A COMPONENT OF WORKING WITH H5N1 VIRUSES. GUINEA PIG ALSO NOT SHOW WHETHER H5N1 IS PATHOGENIC AND WE SHOULD STAY CONSISTENT WITH THE MODEL THAT WE DECIDE ON MAKING A DIFFERENCE ON TRANSMISSION EFFICIENCIES. DOWN TO 1B, BASED ON THE AVAILABLE DATA AS DR. WEBSTER HAS ALREADY OUTLINED, IT APPEARS THAT CHANGES IN RECEPTOR BINDING REGION IS NOT SUFFICIENT FOR EFFICIENT RESPIRATORY DROPLETS SO THERE NEEDS TO BE OTHER CHANGES IN THE VOICE AND THAT WAS OUTLINED IN TWO MAJOR PAPERS DISCUSSED IS THERE HAS TO BE SOME OTHER CHANGES TO THE INTERNAL PROTEINS. THERE'S A NUMBER OF OTHER PAPERS THAT JUST DIDN'T GET THE PRESS FOR H5N1 THAT HAVEN'T BEEN DISCUSSED TODAY. THERE WAS A CDC PAPER WHERE THEY MADE A TRANSMISSIBLE H5N1 VIRUS THAT WAS PUBLISHED IN VIROLOGY THAT GOT LITTLE IMPACT AN WE HAVE BEEN WORKING ON THIS FOR A NUMBER OF YEARS, WE JUST WEREN'T SUCCESSFUL AT GENERATING A TRANSMISSIBLE H5N1 VIRUS AND WE PUBLISHED SOME OF THAT NEGATIVE DATA THAT I'M SURE MOST OF YOU READ. AS FAR AS NUMBER 2, THERE ARE TYPES OF EMPERIMENTS THAT MAY RESULT IN A TRANSMISSIBLE H5N1 VIRUS THOUGH THE ORIGINAL INTENTION IS NOT GENERATE TRANSMISSIBLE H5N1 VIRUS AS I JUST ALLUDED TO. YOU MAY BE INTERESTED IN MODIFYING THE GLYCOSYLATION SIDE OF H5N1 THAT MAY AFFECT TRANSMISSION, SO THESE ARE TYPES OF EMPERIMENTS THAT WOULD BE CONSIDERED TRANSMISSIBLE STRAINS. AS FAR AS 2A OR 2B I BELIEVE THAT AS I HAVE INDICATED BEFORE, BSL-3 ENHANCED WOULD BE THE ACCEPTABLE LEVEL FOR LOOKING AT H 5 TRANSMISSION CASES TRANSMISSIBLE VIRUSES AND HOPEFULLY WILL JUST AFFECT THE TRANSMISSION OF H5N1 AND NOT STUDY PATHOGENICITY OR HOST RANGE OF H5N1. >> I WAS INTERESTED TO SEE -- MAYBE YOU SHOULD GET -- >> SO I TRIED TO I AGREED WITH WHAT'S BEING SAID BASICALLY. BUT IN TERM OF BIOSAFETY PERSPECTIVE I THINK WE HAVE WITH TRANSMISSIBLE H5N1 PAPERS BEFORE AND AFTER IN TERMS OF HOW RESEARCH SHOULD BE LOOKED AT WITH H5N1. SO FROM BIOSAFETY PERSPECTIVE ANY STUDY THAT YOU DO THAT GENERATE AEROSOLS WHETHER ANIMAL STUDY OR IN VITRO THAT GENERATES AEROSOL WE SHOULD WORK WITH H5N1 UNDER ENHANCED CONDITIONS. THAT'S MAKES IT EASY FOR ANYONE TO TRY TO COME UP WITH RECOMMENDATIONS, WE KNOW AEROSOLZATION MAY LEAD TO H5N1. SO FROM THAT PERSPECTIVE I WOULD SAY IF IT IS A PATHOGENESIS STUDY YOU GO TO GENERIC AEROSOL YOU DON'T KNOW IF IT WILL RESULT IN TRANSMISSIBLE VIRUS OR VIRUS THAT WAS -- IMPOSES SOW ROW RISK BUT YOU'RE GENERATING IT SO YOU TREAT THAT EMPERIMENT AS IT WAS (INAUDIBLE). THAT'S WHAT I WOULD DO. THIS WOULD BE TRUE FOR FERRET STUDY, GUINEA PIG STUDY, OR EVEN STUDIES WITH CHICKENS OR ANY OTHER. MAYBE THE EXCEPTION WITH MICE BECAUSE THEY DON'T GENERATE AEROSOLS MEANING YOU HAVE BETTER WAYS TO CONTAIN IT. GOING BACK TO WHETHER THE FERRET MODEL IS THE BEST MODEL BUT IT'S NOT A PERFECT MODEL, 26 RECEPTORS SPECIFICITY OR MORE HUMAN LIKE, IS IT A WAY TO MAKE IT TO TREAT IT AS IF IT WAS MAMMALIAN TRANSMISSIBLE I AGREE WITH DR. WEST AND TERRY, NO IT DOESN'T MAKE IT MORE MAMMALIAN TRANSMISSIBLE. THAT'S A FEATURE WE RECOGNIZE IMPORTANT BUT WE ALSO RECOGNIZE THERE'S OTHER FEATURES THAT HAVE NOT BEEN REALLY IDENTIFIED YET. AND I THINK THAT'S WHAT GOES BACK TO THIS SLIDE I PUT TRANSMISON, WE WOULD LIKE TO HAVE ONE RELATED TO TRANSMISSIBLE AND SAY THESE ARE A SET OF CHANGES THAT IN THESE SUBTYPES CAN LEAD TO A TRANSMISSIBLE VIRUS. WE DON'T HAVE THAT AND WHAT WE'RE DOING IS ACTUALLY TO DEVELOP THAT KNOWLEDGE AND TO DEVELOP THE TOOLS TO EVALUATE. WITH RESPECT TO QUESTION 2, I THINK I IN AWAY ADDRESS IT. EVEN IF IT'S NOT TO DO TRANSMISSION EXPERIMENT YEN RATE AEROSOLS SHOULD BE TREAT AS IF YOU ARE GENERATING TRANSMISSIBLE VIRUS. HAVE WE ANSWERED QUESTION 3? I AGREE WE SHOULD INCREASE THE CONTAINMENT MEASURES. AND LIKE I SAID, NOW THAT WE KNOW H5N1 HAVE THE POSSIBLY TO BECOME TRANSMISSIBLE IN MAMMALS, ON THE DIAGNOSTIC SIDE I WOULD NOT CHANGE ANYTHING DONE SO FAR. ON THE RESEARCH SIDE THE EXPERIENCE HAS TO BE DISTINGUISHED BETWEEN THINGS THAT CAN GENERATE AEROSOLS AND THINGS THAT CANNOT GENERATE AEROSOLS IN GENERAL. THAT'S -- I THINK THAT WOULD MAKE IT EASIER FOR ANYONE TO DISCRIMINATE WHAT TYPE OF CONTAINMENT WE COULD USE. >> SO WE JUST VOTED THAT ALL H5N1 RESEARCH SHOULD BE ENHANCED BSL-3. DO YOU THINK THESE PARTICULAR EMPERIMENTS NEED FURTHER LEVEL? >> I WOULD GO WITH IF IN THE PROCESS WE IDENTIFY, -- IDENTIFIED BECOMES RESISTANT TO ANTIVIRUS, THAT HAS TO BE STOPPED. THAT NEEDS TO BE REVIEWED. PUT IT AGAIN IN THE CONTEXT OF WHAT IS OUT THERE. THIS VIRUS ACTUALLY HAPPENING OUT THERE THEN SEE HOW FAST WE CAN MOVE WITH THIS. IF NOT WE HAVE TO EVALUATE HOW MUCH EVALUATION WE CAN GAIN. >> SO DOES EVERYBODY AGREE ON THE PANEL THAT AEROSOLZATION WOULD BE THE BEST PREDICTOR RIGHT NOW FOR (INAUDIBLE)? >> DEFINITIONAL QUESTION. I THOUGHT WE HAD VOTED TO DO THE RESEARCH BUT IF ANY AGENTS WHEN DISCOVERED BECAME DESCRIPTIVE OF RISK GROUP 4 THEY HAVE TO BE DONE AT RISK GROUP 4 AND NOT DONE. WANT TO MAKE THAT CLEAR. >> FIRST QUESTION WAS RIGHT, EVERYTHING WAS GOING TO BE DONE IN THE WAY WE WERE TALKING ABOUT BUT WERE THERE CRITERIA THAT CAUSE THAT TO BE READDRESSED, IN OTHER WORDS MORE STRINGENT CRITERIA. >> THOSE HIGH INDIVIDUAL RISK AND COMMUNITY RISK SEEN ANY MODULATION OF THOSE TWO THINGS WOULD NEED (INAUDIBLE). >> WHAT WE'RE TRYING TO GET AT, WE HAVE BEEN TALKING ABOUT MAMMALIAN TRANSMISSIBLE H5N1. HOW DO WE DEFINE MAMMALIAN TRANSMISSIBLE. WE'RE GETTING THE FERRET IS THE ONLY MODEL WE CAN RELY ON AT THIS POINT, TRANSP MISSABLE OR NOT. LIKE >> I WOULDN'T RESTRICT OURSELVES TO JUST THE FACT THAT YOU NEED TO KNOW THAT MAMMALIAN TRANSMISSIBLE TO THINK ABOUT IT. SOMEBODY HAS ALREADY SHOWN IT HAS MAMMALIAN POTENTIAL. SO IF YOU'RE GOING TO GENERATE AEROSOLS, ASSUME THAT IT IS A MAMMALIAN TRANSMISSIBLE VIRUS. YOU DON'T NEED TO DEFINE CRITERIA BASED ON VIRUS, YOU DEFINE IT BASED ON THE EXPENNSYLVANIA YOU DO BECAUSE YOU DON'T NEED TO HAVE ANY MORE UNDERSTANDING OR MARKERS IN THE VIRUS TO FIND THE TYPE OF WAY YOU'RE GOING TO ADDRESS THE DEVICE. THAT'S WHAT I WAS TRYING TO -- >> WE WERE TRYING TO GET AT THE SECOND QUESTION, ARE THERE CERTAIN EMPERIMENTS YOU'RE STARTING WITH HPI, H5N1 AND GOING TO DO SOMETHING WITH THEM. AND THINK IN ATIVAN YOU MIGHT COME UP WITH BECAUSE OF EMPERIMENTAL DESIGN AND WHAT LEADS YOU TO SAY I SHOULD ENHANCE CONTAINMENT TO THESE OTHER ENHANCEMENTS THAT WE SPOKE ABOUT TODAY. >> WHEN YOU THINK ABOUT WHAT THE STUDIES HAVE DONE AND WHAT WE HAVE DONE AND OTHERS HAVE DONE, WITH THIS TRANSMISSIBLE VIRUSES, YOU GO THROUGH PROCESS ADAPTATION, THERE IS REALLY TO IS COUNTER INTUITIVE IN TERMS OF GENERATING VIRUS THAT TRANSMIT BY AEROSOL. BECAUSE YOU'RE DOING (INDISCERNIBLE) PUT INTO THE NEXT FABRIC AND YOU'RE ASKING THAT VIRUS TO MUTATE IN CERTAIN WAY TO BE ABLE TO TRANSMIT BY RESPIRATORY DROPLETS. IT'S COMPLETELY COUNTER SPEWTIVE. YOU THINK BY DOING THIS YOU WOULD END UP WITH A VIRUS THAT REPLICATES BETTER IN THE LOWER RESPIRATORY TRACK AS OPPOSED TO UPPER RESPIRATORY TRACK. TO IF ME THAT'S REMARKABLE ABOUT THESE STUDIES THAT YOU CAN GET RESPIRATORY DROPLET TRANSMISSIBLE VOICE BY DOING THIS. IF YOU'RE GOING TO DO SOMETHING LIKE THIS YOU HAVE TO ASSUME YES, YOU'RE GOING TO GET TRANSMISSIBLE VIRUS EVEN IF YOU'RE STUDYING PATHOGENESIS, DOESN'T MATTER. YOU'RE GOING TO GET -- YOU HAVE TO ASSUME CHANCES ARE YOU'RE GOING TO GET ONE. YOU MAY FAIL BUT -- -- >> I THINK AS EMPERIMENTS MOVE FORWARD BACK TO WHAT DR. WEBSTER SAID HOW – HARD TO GET THIS TO HAPPEN, THEY SPENT YEARS DOING THIS, BUT NOW THAT WE LEARNED THIS WE HAVE A NEW STARTING POINT. WE'RE GOING TO START WITH THESE MUTATIONS AN PUSH FURTHER AND THAT IS LIKELY HAPPEN IN THE FUTURE. JUST WANTED TO MAKE THAT POINT. >> SO I HAVE A QUESTION THEN. WOULD ENHANCED BSL-3 SUFFICE FOR STARTING POINT FOR THESE EXPERIMENTS AN BASED UPON THE FINDINGS, SPECIFIC EXPORTS MAY REQUIRE MORE. >> THAT'S WHAT I WOULD BE COMFORTABLE WITH. YES. >> IF YOU GENERATE VIRUSES WITH ANTIVIRAL RESISTANCE THEN (INDISCERNIBLE) BECAUSE SEQUENCING IS MORE COMMON IN HAS BEENTORY TO CONSTANT LYSE WITNESS YOUR STOCKS AND WE'RE ROUTINELY SEQUENCING WHAT COMES OUT OF FERRETS TO SEE IF THERE'S CHANGES BECAUSE YOU RECOGNIZE CHANGES AMONG THOSE VIRUSES THAT YOU INITIALLY PUT INTO THE FERRET. THAT MAY HAVE RESISTANT MARKERS, FOR EXAMPLE. >> THAT'S A VERY IMPORTANT POINT. JUST TO CLARIFY BEFORE, WHILE THERE AREN'T PARTICULAR MARKERS ASSOCIATED WITH THIS, CERTAINLY CHANGE IS SOMETHING THAT SHOULD SET OFF WARNING BELLS. JUST BECAUSE YOU HAVE GOT NOVEL MUTATIONS IN INNATE ADULT CORRESPOND NEW EXISTING ANTIVIRALS DOESN'T NECESSARILY MEAN IF I SHOULDN'T BE CONCERNED NOVEL MUTATIONS APPROXIMATE SEGMENTS SO I AGREE WITH TEARILY COMPLETELY. INVESTIGATORS SHOULD BE MR. CXFC AWARE OF VIRUSES THERE ARE. TRACKING VIRUSES FOR GENETIC CHANGES WHILE GENETIC CHANGES COULDN'T PREDICT SOMETHING IT COULD TELL YOU I NEED THE LOOK AT THIS VIRUS CAREFULLY BECAUSE IT CHANGES IN A WAY I DIDN'T PREDICT. >> CAN I ASK A QUESTION? IS THAT THE ONLY THING -- THE GENETIC LEVEL OR EVEN GENETIC CHANGES OR SOME OTHER WAYS THAT VIRUSES CHANGE THAT WAS SOMETHING ELSE ENTIRELY. IS THERE ANYTHING BESIDES THE GENES LOCK DIFFERENCE, ANY CRITERIA? >> THERE ARE OTHER BIOLOGICAL PROPERTIES THAT COULD AFFECT IT BUT THE PRIMARY DRIVING ONE WITH INFLUENZA IS GENE SEQUENCES. AND GENE MUTATIONS, PARTICULARLY ONES THAT AMINO ACID CHANGES ARE ONES WELL CORRELATED WITH PHENOTYPIC CHANGES. >> I WANT TO GET IT CLEAR. YOU'RE SUGGESTING THAT IN FACT -- ANYTHING WE DID USING RECOMBINANT DAN TECHNOLOGY -- DNA TECHNOLOGY, SUSPICION AND USING LEVEL 3 ENHANCED BECAUSE YOU COULDN'T KNOW UNTIL YOU HAD DONE THE EXPERIMENT HOW TRANSMISSIBLE YOU'RE MAKING IT. YOU CAN GUESS. THOSE HUNCHES, BUT THOSE ARE HYPOTHESES. SO YOU DO EXPERIMENT OR ENHANCED CRITERIA, IF IT TURNS OUT TO BE EITHER HIGH INDIVIDUAL RISK OR HIGH COMMUNITY RISK THAT YOU KNEW YOU GO TO LEVEL 4. ARE YOU SUGGESTING SOME MAN MAID INTERVENTIONS, HUMAN INTERVENTIONS THAT WOULDN'T BE CAPTURED IN THESE LEVELS 3 ENHANCED LABS; IS THAT WHAT I'M HEAR OR IS THAT WRONG? >> I THINK EVERYONE AGREES WITH -- >> LET ME GIVE YOU A SPECIFIC EXAMPLE. IF TOMORROW YOU WANTD THE TO TAKE ONE MAMMALIAN TRANSMISSIBLE H5N1s AND A NATURALLY OCCURRING RESISTANT STRAIN AND DO CO-INFECTION EXPERIMENTS IN A FERRET. DO YOU HAVE TO GO THROUGH THE FDA? >> RIGHT. THAT YOU WOULD NOT EVEN GO HEARD TO. >> SO THAT -- THAT WOULD HAVE TO GO SOMEWHERE. >> SOMEPLACE ELSE FOR APPROVAL. >> NOW, BUT IF I DID AN EXPERIMENT WITH TRANSMISSIBLE H5N1 FOR WHATEVER REASON, AND THEN FINDING ADDITIONAL MUTATIONS IN THE NA PROTEIN, THEN I WOULD SAY OKAY, I NEED TO STEP BACK HERE AND NOW SEE WHAT IS HAPPENING IN THE THIS EXPERIMENT WITH RESPECT TO ANTIVIRAL RESISTANCE. SO THE VIRUS IS TELLING YOU IT'S CHANGING IN SOME WAY BASED ON GENOTYPE SIGNALS THAT TO ME IS A STEP NOT COMPLETELY HALT BUT STAR TO ASSESS ALL RIGHT. WE OTHER SEEING CHANGES, PUTTING SELECTIVE PRESSURES WE MAY OR MAY NOTOMy KNOW AMONG VIRUS, IT'S RESPONDING. WE LOOK AT PHENOTYPES AND SEE HOW IT'S RESPONDING. >> I HAVE A SPECIFIC QUESTION WHAT WAS SAID BEFORE THE STUDIES NOW, THE TWO SCIENCE STUDIES THAT'S LED TO ALL THIS, WE NOW KNOW THAT THERE ARE MAMMALIAN TRANSMISSIBLE VIRUSES SO THAT IN ITSELF OKAY COURSE IS FOR HERE TODAY. THAT DIFFERS FROM THE POSSIBILITY THAT IT'S NOW -- BECAUSE OF THOSE STUDIES WE NOW HAVE ENOUGH INFORMATION SO THAT WE CAN USE THE SPECIFIC MUTATION FROM THAT AND PRETTY MUCH PREDICT HOW WE CAN MAKE OTHER TRANSMISSIBLE VIRUSES. WHAT DO YOU THINK -- ANY AS FAR AS TO MAKE VIRUS TRANSMISSIBLE EXCEPT AEROSOLS. SO I WOULD BE INTERESTED IN YOUR -- >> THOSE MUTATIONS TELL YOU THOSE ARE TRANS MISSEN BUT DOESN'T TELL YOU'RE TRANS-- >> IT GOES BACK TO WHAT DR. WEBSTER WAS SAYING. THESE TWO PAPERS SHOW IN THESE TWO PARTICULAR VIRUSES WE NEED TWO PARTICULAR CONSTELLATIONS OF GENES YOU CAN GET MAMMALIAN TRANSMISSIBLE VIRUS. IN ONE CASE I WOULD SAY NOT VERY GOOD TRANSMISSIBLE VIRUS BUT IT DOES TRANSMIT. DOES IT MEAN YOU COMBINE THOSE MUTATIONS WITH VIRUS AN YOU HAVE A SUPER BACK? THERE'S NO WAY TO PREDICT THAT. MAYBE YOU ENUP WITH A LOUSY VIRUS THAT DOESN'T WANT TO REPLICATE IN VITRO. THAT COULD BE -- IT IS ANOTHER POSSIBILITY. SO THE POTENTIAL IS THERE. BUT IT DOESN'T MEAN IT WILL BE THE SAME FOR EVERY STRAIN. THERE COULD BE MUTATIONS THAT LOAD TO PHENOTYPE. >> SO THEY DON'T PROVIDE A BLUE PREP FOR OTHER VIRUSES BECAUSE THEY EVOLVE SO MUCH SINCE 2004, 2005. THESE ARE STRAINS THAT WE'RE TALKING ABOUT. PEOPLE THAT ARE DOING MOLECULAR HA STRUCTURES ARE TRYING TO APPLY THE SAME FRAMEWORK MUTATIONS IN SOME MORE RECENT H 5 VIRUSES THAT ARE NOT FITTING SO YOU HAVE TO TRY TO LOCK FOR OTHER MUTATIONS IN ORDER TO SWITCH RECEPTOR FINDING SITE FOR H5N1. SO FAR SOME PEOPLE HAVEN'T BEEN ABLE TO DO IT BASED ON MOLECULAR STRUCTURE. SO IT'S NOT EXACTLY THE SMOKING GUN AS DR. WEBSTER ALLUDED TO THAT WE FOUND MUTATIONS THAT CAN BE APPLIED TO ALL H-5 VIRUSES. Q. I WOULD LIKE TO MOVE TO THE BROADER FIELD OF THE H-9N 2 VIRUSES BECAUSE DANIEL AND I BOTH KNOW IN MANY WAYS THEY ARE A GREATER THREAT TO HUMANITY THAN H5N1 OR H-7. AND MAYBE THE H-7 VIRUSES OR ANY EXPERIMENTS WHERE YOU DELIBERATELY SITTING OUT TO INCREASE PATHOGENICITY OR TRANSMISSIBILITY, THEY TOO HAVE GOT TO BE DONE BL-3 ADVANCED. THAT NEEDS TO BE UP THERE. IF YOU'RE DELIBERATELY TRYING TO INCREASE PATHOGENICITY OF ANY OF THE 17 HEMOGLUTENIN, THEY NEED TO BE DONE AT HIGHER LEVEL. >> NO MATTER WHAT FUNCTION IS GAINED OR WHAT -- >> I WOULDN'T PUT ANY GAIN OF FUNCTION BECAUSE INCREASING THE VIRULENCE COULD BE SEEN AS GAIN OF FUNCTION. BUT THEN BECOMES A MOUSE STRAIN THAT DOESN'T GO ANYWHERE. BUT GAIN FUNCTION -- NOT NECESSARILY A HUMAN PATHOGEN ANY MORE. I WOULD SAY ANYTHING -- ANY GAIN OF FUNCTION STUDY THAT INCREASES TRANSMISSIBILITY IN MAMMALS SHOULD BE SOMETHING ENHANCE BSL-3 CONDITION. FLU IS NOT DANGEROUS BECAUSE IT'S JUST BECAUSE DISEASE, IT'S DANGEROUS BECAUSE IT CAN TRANSMIT. FROM HUMAN TO HUMAN IT IS NOT BECAUSE FLU WILL CAUSE PANDEMIC. IT WILL CAUSE PANDEMIC BECAUSE IT TRANSMITSFROM PERSON TO PERSON. ANYTHING THAT INCREASES TRANSMISSIBILITY OF FLU VIRUS NOT FOUND IN HUMAN POPULATION AND EXHIBITING MAMMALIAN MODEL, THEN THAT SHOULD BE DONE UNDER BSL-3 ENHANCED CONDITIONS. >> I'M TRYING TO THOEF HIV NOT THAT EASILY TRANSMITTED BUT MAKES YOU SICK AND IS PROBLEM AND SAY YOU FOUND SOME VERSION OF IT AND THEN INCREASED PATHOGENICITY, I WOULD STILL BE THINKING THAT IS A DANGEROUS GAIN OF FUNCTION TO BE DONE THIS WAY. >> BUT TWO DIFFERENT PIECES HERE. THE MODE OF TRANSMISSION IS COMPLETELY DIFFERENT. WITH FLU YOU CAN END ONE A GAIN OF FUNCTION EFFECT OF TRANSMISSION THAT INCREASES VIRULENCE OR MAY DECREASE VIRULENCE. >> LOSS OF FUNCTION DECREASED -- >> NOT IF YOU GAIN TRANSMISSIBILITY. SO DEPENDS ON WHAT YOU WANT -- SO I WOULDN'T PUT GAIN OF FUNCTION AS SOMETHING THAT HAS TO BE DONE BSL-3 ENHANCE. I WOULD PUT GAIN OF FUNCTION INCREASING TRANSMISSIBILITY ENHANCED. THERE COULD BE STUDIES IN WHICH YOU -- IN CASE OF VIRULENCE BUT VIRUS NOT TRANSMITTED SO IT'S SOMETHING YOU CAN STUDY IN THE LAB SAFELY. THAT'S BEING DONE SINCE FLU WAS DISCOVERED. >> CAN YOU CLARIFY, YOU WERE SAYING LIMITING TO INFLUENZA VIRUSES WITH WE DON'T HAVE. COMMUNITY OR IMMUNITY, SO H-1 VIRUS HAVE A LOT OF THE IMMUNITY, WOULD THE SAME CRITERIA APPLY? >> WITH THE H-1, SO H-1 AND 3 I THINK WE HAVE TO BE 2009 HAVE TO PROVE US WRONG IN TERMS OF DOGMA. WE DON'T NEED SUBTYPE BECAUSE OF PANDEMIC, WE NEED A DISTINCT VIRUS TO CAUSE PANDEMIC. SO IF WE'RE GOING TO DO WORK WITH H-1 OR 3 AND WE FIND OUT THEY'RE ANGIOGENIC AND VERY DIFFERENT FROM -- WE TRY TO DO EMPERIMENTS LIKE GAIN OF FUNCTION INCREASE TRANSMISSION, WE ALSO HAVE TO DO THEM BSL-3 ENHANCE CONDITION. >> SO I THOUGHT THOSE WERE FAIRLY TRANSMISSIBLE. I THINK WE TRY TO MAKE IT MORE TRANSMISSIBLE THAN IT IS? >> AVIAN INFLUENZA VIRUSES OF THE H-3 SUBTYPE OR THE H-1 SUBTYPE NOT FOUND IN HUMANS AND NOT TRANSMISSIBLE IN FERRETS OR PROBABLY NOT IN HUMANS BECAUSE THEY HAVE NEVER BEEN BUT CAN BE DIFFERENCE FROM WHAT HUMANS SEE TODAY. SO YOU COULD HAVE PANDEMIC OF H-1 COMING FROM H-1 FROM A DUCK. PROBABLY WOULDN'T BE AS LETHAL BECAUSE WE HAVE IMMUNITY. BUT I DONE KNOW. >> ONE THAT DOESN'T CURRENTLY CIRCULATE IN HUMANSER ONE WE DONE -- HOW WOULD YOU SAY, THAT'S WHAT I'M TRYING TO -- >> I WOULD SAY GOING BACK TO WORK WITH H-9 AND H-7 AND 5, ANY OF THE H-17 SUBTYPES, IF YOU'RE DOING SOMETHING TO WHICH HUMANS HAVE NOT EXPERIENCED PANDEMICS IN THE PAST NOR RESEASONLY AND YOU'RE TRYING TO STUDY TRANSMISSION IN A MAMMALIAN MODEL YOU SHOULD ASSUME ENHANCED CONDITION THAT'S WHEN WE TRIED TO ADOPT THE TITER VIRUS TO FERRETS OR IF YOU CAN A REASSORTMENT WITH THE PANDEMIC VIRUS OR HUMAN VIRUS, I DON'T THINK RIGHT NOW, CORRECT ME, TERRY IF I'M WRONG BUT I DON'T THINK RIGHT NOW WE CAN PUT WEIGHT ON WHAT IS GOING TO BE MORE DANGEROUS IN TERMS OF TRANSMISSIBILITY AND VIRULENCE. I THINK THOSE ARE THE TYPE OF STUDIES, AGAIN, THE TYPE OF STUDY WHICH YOU WANT TOE CREATE AN AEROSOL AND YOU WANT TO CHANGE THE PHENOTYPE FOR A MAMMALIAN -- FROM MAMMALIAN TO MAMMALIAN VIRUS, THAT IS BETTER TO BE SAFE THAN SORRY. WE SHOULD DO BSL-3EN HANSED. >> ANY AVIAN VIRUS THAT HASN'T BEEN IN HUMAN, HUMAN TRANSMISSION YOU'RE TRYING TO MAKE IT MAMMAL TO MAMMAL TRANSMISSIBILITY BUT ANY OTHER MEASURES (OFF MIC) >> -- (INAUDIBLE) IN SWINE? >> >> I LIKE THE FORMULATION OF ALL 17. >> WHY WOULDN'T BE THE BROADEST POSSIBLE DEFINITION? YOU KNOW SO LITTLE ABOUT WHICH ARE GOING TO -- WHAT TO BE CHANGED OR MIXED, WHY NOT HAVE THE BROADEST POSSIBLE FORMULATION. WHY LIMIT TO H5N1 5? (OFF MIC) SNAP OPT LAST SENTENCE SECOND PARAGRAPH, THAT'S >> ONE PROBLEM YOU MAY NOT BE P TRYING TO CHANGE TRANSMISSIBILITY U YOU MAY BE CHANGING SOMETHING THAT RESULTS IN CHANGE IN TRANSMISSIBILITY AS WELL. (OFF MIC) >> I HAVE SEEN ANIMAL MODELS WHICH WE USE THEM AND P WE KNOW WE GENERATE AEROSOLS LIKE FERRETS HIKE PIGS, LIKE BIRDS. LIKE GUINEA PIGS. BUT THERE ARE OTHER ANIMAL MODELS THAT CAN BE AFFECTED BY AEROSOLS LIKE MICE BUT THEY DO NOT GENERATE AEROSOLS, NOT AT LEAST IN AMOUNTS THAT WOULD BE PROBABLY DANGEROUS TO HUMANS. WITH FLU VIRUSES, NOT ANY OTHER VIRUS. I'M NOT TALKING ABOUT ANTIVIRUSES, NOT TALKING ANY OF THAT. I'M TALKING FLU VIRUS. PERHAPS THOSE VIRUSES ONCE THEY BECOME MOUSE ADAPTED, THEY CAN BE SAFELY HANDLED AND UNDER BSL-2 CONDITIONS. IT HAS TO GO CASE BY CASE I GUESS. Q. OTHER COMMENTS? THESE ARE SORT OF JUST -- PEOPLE CAN JUST COMMENT ON WHAT WE'VE GOTTEN RIGHT OR NOT GOTTEN RIGHT OR FOR WHICH THERE IS LITTLE OR NO KNOWN COMMUNITY IMMUNITY, IS THAT WHAT WE'RE TALKING ABOUT? >> TO SUMMARIZE, JACKIE SUMMARIZED I GUESS OUR COG ANYZATION THE LAST FEW MINUTES, TO ESTABLISH TRANSMISSIBILITY IN PATHOGENICITY OF H5N1, IT IS DIFFICULT TO SAY EXPERIMENTS WITH SERO PASSAGING WILL LEAD TO TRANSMISSIBLE VIRUS. ANY EXPERIMENT WITH HPAI H5N1 THAT IS TO GENERATE AEROSOLS SHOULD BE DONE WITH ALL ENHANCEMENTS FOR H5N1 MAMMALIAN TRANSMISSIBLE VIRUS. IF YOU'RE INCREASING TRANSMISSIBILITY IN NOVEL VIRUS WITH HIGH POTENTIAL TO CAUSE DISEASE IN HUMANS AS DEMONSTRATED IN A FERRET MODEL, ENHANCED BSL-3 SHOULD BE CONSIDERED BUT IT IS IMPOSSIBLE TO PREDICT THE RISK. ANY EXPERIMENTS THAT ATTEMPT TO INCREASE TRANSMISSIBILITY IN MAMMALS BY RESPIRATORY ROUTE OF INFLUENZA VIRUS WHICH THERE IS NO COMMUNITY COMMUNITY. -- IMMUNITY. I THINK THAT -- (OFF MIC) >> SO LAST TWO BULLETS HIT ON THIS ISSUE YOU CAN HAVE A PANDEMIC WITH A VIRUS THAT DOESN'T CAUSE LOTS OF SERIOUS DISEASE. BUT YOU CERTAINLY CAN HAVE A PANDEMIC WITH A VIRUS THAT CAUSES SERIOUS DISEASE. I THINK AT LEAST FROM MY CONVERSATIONS WITH OUR PANDEMIC PREPAREDNESS PEOPLE THAT'S AN IMPORTANT DISTINCTION TO MAKE BECAUSE IT DICTATES PUBLIC PERCEPTION OF RISK. 2009 PANDEMIC WAS PERFECT EXAMPLE, EVERYBODY BUT UM IN ARMS UNTIL WE HAD SIGNIFICANT CASES AND NOBODY WANTED TO DO ANYTHING ABOUT IT BECAUSE THEY CONSIDERED IT THE FLU. AS OPPOSED TO PANDEMIC VIRUS WHICH WILL CARRY WITH IT A SIGNIFICANT AMOUNT OF.Jb„ MORBIDITY OR MORTALITY. THOSE TWO POINTS CAPTURE THOSE TWO ISSUES. IT'S VIRULENCE AND LACK OF IMMUNITY IN THE POPULATION WHICH LEADS TO PANDEMICS BUT THE VIRUSES RESULTING FROM THOSE TWO THING IT IS PERCEIVE PUBLICLY DIFFERENTLY. >> I THINK THE 2009 EXPERIENCE IS CONSTRUCTIVE AND PROVIDES INTERESTING HISTORY BUT IT'S AGAIN MORALLY DIFFERENT IF THAT HIGH TRANSMISSIBLE BUT LOW VIRULENCE EMERGES FROM AN NIH LAB. I THINK IT DOES. AND I THINK IF IT'S ESPECIALLY -- WE HAVE SEEN THIS WITH THE RODA VIRUS VACCINE. PEOPLE HAVE HIGH EXPECTATIONS THAT IT WON'T MAKE YOU EVEN A LITTLE SICK. SO IT IS A NON-(INAUDIBLE) SITUATION. WOULDN'T HAVE TO BE VERY VIRULENT T ALL. JUST HAVE TO COME FROM AN NIH LAB. I THINK THIS IS THE RISK OF THE RISK OF DESTROYING PUBLIC CONFIDENCE CAN BE OBVIOUSLY IF THERE'S A DEVASTATING 1918 TYPE PANDEMIC ENORMOUS HUMAN TRAGEDY, IN ADDITION IT WOULD CHANGE SCIENCE FUNDAMENTALLY HOW THE PUB HICK SEE SCIENCE, PUB HICK HEALTH GOVERNMENT FUNDAMENTALLY, EVEN IN A SITUATION WITH MILLIONS OF PEOPLE SICK FOR A WEEK AND DIP DIE IT WOULD CHANGE PUBLIC PERCEPTION SCIENCE CAN THEY TRUST THEIR GOVERNMENT AND NIH. THOSE ARE HIGH RISK SITUATIONS. THAT'S WHY YOU HAVE TO PAY ATTENTION >> ANYTHING IT USES, COMMENTING ON TECHNOLOGY, I THINK THAT'S OUR RESPONSIBILITY. >> I AGREE WHICH IS WHY I WANT TO KEEP THE LET POINTS OF TRANSMISSION IN ABSENCE OF SEVERITY IMPORTANT POINT TO CAPTURE SO WITH DAN ON THIS ONE. >> BUT O DO WE ALL AGREE ENHANCED BSL 3 TAKES CARE OF THE REST? >> UNTIL IT'S KICKED OVER TO LEVEL 4 DEFINITION. >> WHICH CASE IT WILL BE REVIEWED AND THERE WILL BE NEW GUIDANCE >> LET ME ASK YOU THE TEACH ME ONE MORE THING. YOU FIES ARE BOTH MANY IN MARYLAND. YOU GUYS BOTH WORK MAMMALIAN TRANSMISSIBLE VIRUS AND YOU WANT TO SEND ONE P TO HIM. HOW DOES THAT HAPPEN? WHO REGULATES THAT NOW? AND HOW DOES THAT PROCESS GO ON, WHO APPROVES IT AND HOW DO WE MAKE SURE THAT IT DOESN'T GET OUT TO THE PUBLIC. AS MORE PEOPLE DO THIS FOR VERIFICATION, FOR SHARING OF INFORMATION, FOR SHARING AGENTS YOU HAVE TO DO THIS. SO WHAT HAPPENS? >> PAPERWORK, PAPERWORK, PAPERWORK. AND LOTS OF REGULATIONS. YOU WILL PAY WILL COURT YOUR $1,500 IF YOU ARRANGE THE PAPERWORK I WILL GET YOU THE VIRUS. MCMIC >> JUST TRYING TO FIGURE OUT HERE IF WE'RE TALKING BSL-3 PLUS OR BSL-4, IS IT DIFFERENT THAN BSL-3, BSL-THE VIRUS AND HOW DIFFERENT? JUST EDUCATE ME. SO THAT I KNOW. >> THE CRITICAL ASPECT, FIRST QUESTION WHETHER IT'S A SELECT AGENT OR NOT. AND IF IT'S A SELECT AGENT THEN THERE'S ALL SORTS OF HOW YOU REGULATE IT, LOTS OF RULES AN THOSE THINGS THAT HAVE TO FALL INTO PLACE TO TRANSFER SELECT AGENT FROM ONE LAB TO ANOTHER INVOLVING CERTIFYING THAT LAB IS A SELECT AGENT, NOTIFYING APPROPRIATE AUTHORITIES ABOUT THAT AND THOSE KINDS OF THINGS TOO. THAT WOULD APPLY TO A PATHOGENIC TRANSMISSIBLE H5N1 VIRUS. IF YOU'RE ASKING IF I HAD A PARTICULARLY AVERSE I THOUGHT WAS PARTICULARLY INTERESTING AND I WANTED DAN TO LOOK AT IT, THAT VOICE FALLS UNDER REGULAR BSL-2 CONDITIONS AND THAT'S A SET OF REGULATIONS INVOLVING HOW TO PACKAGE, HOW NEED TO SHIP, WHO CAN SHIP IT, BECAUSE PEOPLE SHIPPING THOSE REAGENTS GO THROUGHt PACKAGE VIRUSES IN THE APPROPRIATE WAY WITH MULTIPLE LEVELS CONTAINMENT, ABSORBENTS, CERTAIN AMOUNTS OF ICE BUT NOT TOO MUCH, THOSE KINDS ISSUES. ALL THAT STUFF GOES THROUGH A CERTIFIED COURIER SYSTEM. AS AN EXAMPLE, WHEN I WAS BACK IN ST. LOUIS AT WASHINGTON UNIVERSITY I HAD A COLLABORATOR IN ST. LOUIS UNIVERSITY WORKING WITH US ON SARS VIRUS. AND LITERALLY WE FEDEX SAMPLES BACK AND FURTHER ACROSS THE CITY OF ST. LOUIS BECAUSE INITIALLY THAT WAS THE BEST WAY TO ENSURE SAMPLES BEING TRANSPORTED BECAUSE YOU HAD TO PACKAGE IT THE RIGHT WAY, GIVE O THE A COURT YOUR WHO NOT ONLY ACCEPTED THE PACKAGE BUT HAD A SPECIAL SET OF TRANSPORTATION VEHICLES TO MOVE IT OVER AND DELIVER IT IN A SAFE WAY ACCORDING TO REGULATIONS. >> IS THERE A NAME FOR THAT CLASSIC TRANSPORTATION THAT WE -- IF WE'RE TALKING BREECH OF CONFINEMENTMENT ABOUT AGENTS, NOVEL AGENTS OUT IN THE PUBLIC, HERE IS ANOTHER ROUTE THAT IS NOT THE SHOWERS, IT'S NOT THE HEPA FILTERS, IT'S IN A BOX IN A CAR. SO SHOULD WE SAY SOMETHING? IS THERE A STANDARD LANGUAGE THAT WE CAN SAY? I WILL ALSO ASK ISAAC WHO IS STILL ON THE PHONE, BECAUSE THIS IS PART OF CONTAINMENT AND CONTROL OF THESE AGENTS. ISAAC. >> SO I AGREE WITH PREVIOUS COMMENT ABOUT IN TERMS OF THE PROCESS IS THAT IT IS STILL REGULATED UNTIL WE KNOW IF IT'S MAMMALIAN TRANSFER H5N1 UNTIL WE KNOW WHETHER IT'S NOT PATHOGENIC TO AVIAN SPECIES OR ANY OTHER AGRICULTURAL SPECIES IT REMAINS REGULATED BY USDA SO YOU GO THROUGH THE PERMITS PROCESS. IF THE SPECIFIC QUESTION ON IS THERE SPECIFIC LANGUAGE NOT COLOR WHAT THE SPECIFIC QUESTION IS. >> WHAT I'M ASKING IS THAT DEPENDING ON LEVEL OF THREAT OF A AGENT IN TRANSFER, THIS MUST BE REGULATION TO WHAT LEVEL SECURITY FOR TRANSFER IT MUST BE. JUST TRYING TO FIGURE OUT WHAT THAT IS. >> THIS IS JOE KANABROKIC, I CAN HELP. IF WE TALK ABOUT STRAIN YOU HEARD WHAT HAPPENS WHERE SELECT AGENT IS STRANDED. HIGHLY REGULATED HIGHLY CONTROLLED TRANSFER THAT INVOLVES THREE ENTITIES, THE CENTER THE SHIPPER AND REGULATORY AGENCY WHETHER CDC OR USDA. I THINK YOU WHAT YOU'RE LOOKING FOR IS THAT THEY'RE SHIPPED ACCORDING TO INTERNATIONAL REGULATIONS, DEPARTMENT OF TRANSPORTATION IN THE US. AND IATA, INTERNATIONAL AIR TRAFFIC ASSOCIATION I BELIEVE IS WHAT THAT STANDS FOR. THERE ARE REGULATIONS THAT TICK AT A TIME HOW SHIP M.S SHOULD BE TRANSFERRED. SO THERE ARE REGULATIONS ALONG THAT ROUTE FOR PATHOGENS, THIS WOULD INCLUDE THE VIRUSES. >> CAN I PREFACE BY SAYING WHICH CLASS AND P LETTER IN 2 CA 43B >> YEAH. >> ISAAC, I WANTED TO ADD THAT IN TERMS OF TRANSPORT IN COMMERCE WHAT OUR POLICY HAS BEEN IS WE WANT TO PRESERVE THE LOST IN THE CLOUD CONCEPT WITH THESE PACKAGES. SO THEY NEED TO BE APPROPRIATELY PACKAGED TO DEPARTMENT OF TRANSPORTATION GUIDELINES, AND PACKAGED IN A SAFE MANNER SO YOU DOPE GET LEAK, ET CETERA. BUT WE DOPE WANT PEOPLE ODE FEWING THE PACKAGE, THIS IS A A HIGHLY VIRULENT AGENT. SO WE TRY TO KEEP LOST IN THE CROWD CONCEPT SO THEY ARE PACKAGED ACCORDING TO ACCEPTED STANDARDS LIKE IATA AND DEPARTMENT OF TRANSPORTATION GUIDELINES. BUT YOU KEEP THAT LOST IN THE CROWD CONCEPT, THE SECURITY COMES IN IN HAVING COURIERS WHO ARE COMMERCIAL CARRIERS WHERE YOU CAN TRACK THE PACKAGING. AND WE DO HAVE TRANSFER REQUIREMENTS SO PRIOR TO TRANSFERRING A SHIPMENT YOU DO HAVE TO GET PERMISSION FROM USDA OR CDC ONCE THEY RECEIVE THEY CONTACT THE CDC TO LET THEM KNOW VERIFYING THE SHIPMENT, LEFT THE PREMISES AND VERIFYING THE SHIPMENT WAS RECEIVED AT THE OTHER END FOR SELECT AGENTS SO THAT'S THE -- IF YOU WANT TO CALL IT ADDITIONAL SECURITY MEASURES, BUT THE PACKAGE ITSELF IS KEPT AS A LOST IN THE CROWD TYPE CONCEPT BECAUSE THERE'S THOUSANDS OF PACKAGES OUT THERE. WE THINK FROM THAT CONCEPT WE HAVEN'T HAD IN TEN YEARS WITH SELECT AGENT, WE HAVEN'T HAD ANY SERIOUS ISSUES. THIS MIGHT HAVE BEEN ONER TWO LOST PACKAGES BUT NOTHING THAT WAS DELIBERATE MISUSE OR DELIBERATE THEFT BASED ON THAT. SO I HOPE THAT'S A LITTLE BIT CLEARER. >> THANK YOU VERY MUCH. >> ANY OTHER PUBLIC COMMENTS? ZOLOTH? >> WHY ARE FERRETS COSTING THE FEDERAL GOVERNMENT $500 A FERRET? >> GENETICALLY ENGINEERED MICE ARE COSTING THE GOVERNMENT $300 AND $400. >> BUT THESE ARE JUST COMMON VARIETY -- THESE AREN'T GENETICALLY ENGINEERED FERRETS, RIGHT? THEY'RE JUST FERRETS. >> IT'S A SUPPLY DEMAND. >> THE OTHER DIFFICULTY IS SUSCEPTIBLE TO YOU HAVE TO READ SPECIAL CONDITIONS SO YOU DON'T -- YOUR ANIMAL CARETAKERS DON'T COUGH ON THEM AND SO YOU HAVE ANTI-POTTIES TO CURRENT CIRCULATING HUMAN STRAINS AND DANIEL WON'T BUY THEM, NEITHER WILL I. SO THEY BECOME -- THE CASE OF SUPPLY AND DEMAND. >> THAT CAN RAISE THEM -- >> I SEE A PUBLIC PRIVATE PARTNERSHIP OPPORTUNITY. >> I UNDERSTAND THE THINGS YOU NEED TO DO WITH THEM, SPECIAL HOUSING QUARANTINE AND TESTING. I DIDN'T UNDERSTAND THE BASELINE PRICE. (OFF MIC) >> ANY OTHER COMMENTS OR PUBLIC COMMENTS? THOSE RECOMMENDATIONS ON THE LIST ON SLIDE UP THERE WE ODE LIKE TO ADD TO THE RECORD AND SO WE'RE GOING TO TAKE ABOUT FROM THE RAC MEMBERS TO ADD IT TO THE RECORD SO STARTING WITH DON. >> KOHN. YES. >> WOOLEY NO FOR THE SAME REASON. >> (INAUDIBLE) YES. >> FONG, YES. >> DR. ZOLOTH. >> (INDISCERNIBLE) ACCOMPLISH, YES. >> ROSS, YES. >> HAMMARSKJOLD, YES. >> CHATTERJEE, YES. >> THOSE ON THE PHONE. >> >> MOLINO, YES. >> (INDISCERNIBLE), YES. >> ANYBODY ELSE? WITH THAT IF THERE ARE NO MORE COMMENTS, I THANK EVERYONE FOR THEIR PARTICIPATION TODAY. THOSE RAC MEMBERS, THOSE CONSULTANTS WHO HAVE SPENT ALL THIS TIME BOTH ON THE PHONE AND WITH US AND THE STAFF OF THE RAC THAT HAVE ARRANGED FOR THIS MEETING AND MOST OF ALL JACKIE, FOR ALL THE HARD WORK. SO I CALL THE 132ND MEETING OF THE RAC -- >> BEFORE WE GO I WOULD LIKE TO THANK EVERYONE MYSELF AND SPECIAL THANKS TO MAUREEN O'REILLY WHO IS THE BRAINS BEHIND THESE SLIDES AND BOMB HAMBU FOR ALL THE TECHNICAL EXPERTISE PULLING OFF THIS MEETING FOR SEVERAL COUNTRIES. THANK YOU, EVERYONE FOR COMING.