Demystifying Medicine 2014 – Water, Water Everywhere and Not a Drop to Drink

Demystifying Medicine 2014 – Water, Water Everywhere and Not a Drop to Drink


>>GOOD AFTERNOON. NORMALLY THE TOPICS IN THIS COURSE ARE CLEARLY DEFINABLE MORALS THAT PEOPLE DON’T TALK ABOUT IN THE SENSE THAT IT COVERS PRETTY DISEASE. THE REASON WE’RE HAVING A SESSION ON WATER WILL BECOME ABUNDANTLY APPARENT WHEN YOU HEAR THE PRESENTATIONS. NORMALLY I WRITE A LITTLE SOMETHING ABOUT A WEEK AHEAD OF TIME AND PUT IT ON THE WEBSITE. INSTEAD OF KEPT GETTING E-MAILS SAYING WHAT’S THIS WATER BUSINESS, WHAT’S HAPPENING. SO WE MAY HAVE LOST ONLY OF OUR AUDIENCE BECAUSE THEY DIDN’T GET THE FULL INFORMATION UNTIL LATER. I ASSURE YOU EACH WEEK THERE ARE SEVERAL HUNDRED PEOPLE ON-LINE JUST HERE AT THE NIH SO WE HAVE A LARGE HOD YOUNG NO MATTER WHAT THE PRESENTATION. SO THE ANCIENT MARINER, WATER WATER EVERYWHERE NOT A DROP TO DRINK. HE HAD A REAL PROBLEM. WE HAVE A REAL PROBLEM. AND THOSE INTERESTED IN HUMAN HEALTH HAVE A REAL PROBLEM MANY TIMES OVER WHEN IT COMES TO CONSIDERATION OF WATER. I THINK THE LECTURE WAS GIVEN BY JOSHUA LETTERBERG WHO AT THE TIME WAS PRESIDENT OF ROCKEFELLER. AND JOSH TALKED ABOUT THE BOND ANGLES BETWEEN THE TWO HYDROGENS AND THE OXYGEN IN WATER. THE POINT OF IT WAS THESE BOND ANGLES POTENTIALLY GIVE THE EXTRAORDINARY PROPERTIES TO WATCH WHICH IS ESSENTIAL FOR LIFE IN ALL FORMS. CERTAINLY ON EARTH, AND JOSHUA WAS SAYING QUITE LODGELY ANYWHERE ELSE THERE IS LIFE. SO WE DON’T HAVE TO BELABOR THAT WATER IS IMPORTANT. MORE OF THE LARGE PART OF THE EARTH’S SURFACE, PARTICULARLY SEEN FROM SPACE, THE BLUE PLANET IS PART. FRESH WATER IS ONLY 2 OR 3%. BUT WATER IS THE ONLY SUB
SUBSTANCE THAT LIVE ON EARTH BY EITHER A VAPOR, SOLID OR LIQUID. THAT MAKES IT POSSIBLE FOR ANIMALS, PLANTS, PROTECTION FROM COSMIC ENERGIES AND SO FORTH AND INSULATION ASIDE FROM DRINKING AGRICULTURE, YOU NUMB IT. IT’S THE ESSENCE. SO WHEN WATER IS THREATENED, IT’S PRETTY SERIOUS BUSINESS BUT IT’S NOT SOMETHING THAT PEOPLE THINK ABOUT EVERY DAY IN THE WEEK BECAUSE YOU KNOW WATER IS WATER. HOW SAFE IS THE WATER THAT WE DRINK. AND HOW REALLY DOES ANYBODY KNOW. DOES ANYBODY MEASURE. WHAT DO THEY MEASURE WHEN THEY TALK ABOUT SAFETY OF WATER. WATER HASN’T ALWAYS BEEN SO SAFE AND SO TODAY’S PRESENTATIONS COVER TWO PARTS OF A GIANT SEESAW. THE FIRST IS WHEN THE PART IS THE MEDIUM, THE MEDIUM FOR THE TRANSMISSION OF INFECTIOUS DISEASES. NOW THESE ARE MANY INFECTIOUS DISEASES THAT SET THE HISTORY OF MANKIND BECAUSE THERE WERE GREAT DISEASES LIKE CHOLERA AND SO FORTH. NOT ONLY ARE THESE DISEASES IN EPIDEMIC PROPORTION STILL WITH US SPECIFICALLY IN THAT LARGE PART OF THE WORLD THAT’S REFERRED TO AS THE UNDER DEVELOPED THIRD WORLD OR FOURTH WORLD OR WHATNOT. AND THETZ THINGS ARE LETHAL AND THEY DEVELOPED WAYS OF GETTING AROUND SOME OF OUR EVEN PHARMACOLOGIC NEEDS. SO OUR FIRST SPEAKER KAREN FRANK IS GOING TO DISCUSS THIS ASPECT, WATER IN TODAY’S WORLD WITH TODAY’S METHODOLOGY, HOW DO WE HANDLE THESE SERIOUS OLD AND IN SOME CASES EMERGING ALMOST INFECTIONS. SOME OF THEM. THERE ARE A LARGE NUMBER OF THEM. 30 MINUTES CAN’T COVER EVERYTHING. NOW SHE’S A GRADUATE OF THE UNIVERSITY OF PENNSYLVANIA WHERE SHE GOT HER MD AND PH.D. TRAINED IN PATHOLOGY IN BOSTON AT THE BRIGHAM RESEARCH TRAINING AT CHILDREN’S AND THEN FOR 12 YEARS WAS IN MICRO BIOLOGY AT THE UNIVERSITY OF CHICAGO THEN CAME HERE IN 2012 AND SHE’S THE HEAD OF MICROBIOLOGY CLINICAL DIAGNOSTIC EXPERIMENTAL LABORATORY IN THE CLINICAL CENTER. AND SHE’S THERE ON THE FRONTLINE SEEING ALL OF THE INCREDIBLE PROBLEMS IN INFECTIOUS DISEASE THAT EVERY CLINICAL CENTER HAS CONFRONTED. SO THE SECOND PART OF THE PROGRAM CONCERNS AN ENTIRELY DIFFERENT DISCIPLINE AND IT’S A QUESTION THAT DEALS WITH WHY DO WE HAVE TWO-HEADED FISH IN THE POTOMAC RIVER. FIRST, IS THAT WATER. WHEN YOU’RE BUYING BOTTLED WATER, ARE YOU REALLY GET BEEN A BARGAIN. IS THE STUFF THAT’S IN THE WATER, WHAT IS IT AND HOW DO YOU MEASURE IT? SO WHAT YOU’LL SEE AND LEARN IS THAT THE NEW TECHNOLOGIES WHICH ONE MIGHT NEVER HAVE DREAMED TO BE A PRIORITY APPLICABLE TO WATER, IT TURNED OUT TO BE OPEN ENORMOUS OPPORTUNITIES FOR ANSWERING SOME OF THESE QUESTIONS. AND SO GORDON HAGER WHO IS THE DIRECTOR OF THE NIH CENTER OF EXCELLENCE IN PROGRAM CONTINUE BIOLOGY, GORDON GOT HIS PH.D. AT WASHINGTON UNIVERSITY, TRAINED AS A POST DOC IN GENEVA, AND IN SAN FRANCISCO, CAME TO THE NIH AND HAS BEEN HERE FOR QUITE A WHILE AND HAS AN ENORMOUS GLOBAL REPUTATION IN TERMS OF THE EXCITING DIMENSIONS OF CONTROLLABLE — CHROMATIN BIOLOGY. HOW IS CHROMATIN BIOLOGY HAVE TO DO WITH WATER. SO THE FIRST SPEAKER IS KAREN FRANK.>>THANK YOU.>>GOOD?l PLEASED TO BE IN THIS LECTURE SERIES. AS MENTIONED TODAY I’M GOING TO SPEAK ABOUT WATERBORNE DISEASE. SO INFECTIOUS DISEASES THAT ARE TRANSMITTED BY WATER USUALLY WITH CONTAMINATED WITH FECAL MATERIAL INVOLVE BACTERIA, VIRUSES, PROTOZOA AND PARASITIC WORMS. SO I’VE LISTED A NUMBER OF DIFFERENT ORGANISMS HERE. IT’S NOT A COMPLETE LIST BUT IT GIVES YOU A RANGE OF THE DIVERSITY OF ORGANISMS THAT ARE INVOLVED IN WATERBORNE DISEASES. THE ORGANISMS HIGHLIGHTED IN RED, POLIO, NOR VIRUS ARE THE FEW I’M GOING TO SPEAK ABOUT GIVING A LITTLE BIT OF THE HISTORY AND WHAT KIND OF DISEASES THEY CAUSE, A LITTLE BIT OF WHAT IS THE CURRENT STATE OF HOW WE TREAT THIS DISEASE OR WHAT IS THE CURRENT RESEARCH INVOLVED. SO FIRST THE BIG PICTURE. DIARRHEA DISEASES. WE DON’T UNDERSTAND THE NUMBER. TWO MILLION DEATHS PERYEAR. 90% OF THESE ARE CHILDREN UNDER THE AGE OF FIVE. IF YOU LOOK AT THE GLOBAL BURDEN OF DISEASE MARYBD BY THE HEALTH ORGANIZATION, 4% ARE DUE TO WATERBORNE INFECTIONS. VERY HIGH PERCENTAGE. OF THOSE WATERBORNE INFECTIONS, 88% ARE DUE TO UNSAFE WATER SUPPLY SANITATION AND HIGH GIME. THEORETICALLY FIXABLE PROBLEMS. IF YOU SEE A LITTLE GIRL DRINKING OUT OF A TIN CAN IN A PUDDLE, YOU CAN IMAGINE WHAT’S IN THAT WATER. OKAY. AGAIN WHAT WE NEED ARE CRITICAL SANITATION FACILITIES. IT’S A VERY STRIKING PICTURE OF MANY PEOPLE IN INDIA GATHERED AROUND A WELL GETTING THEIR WATER. VERY STRIKING PICTURE. A NUMBER OF THE WEBSITES THAT EITHER RAISE MONEY FOR THESE KIND OF THINGS MENTION THAT WOMEN SPEND 200 MILLION HOURS PER DAY COLLECTING WATER. SO A HUGE PART OF THE GLOBAL POPULATION SPENDS THEIR TIME JUST GETTING ENOUGH WATER TO SURVIVE. A LOT OF WHAT I’LL TALK ABOUT IS IN THE DEVELOPING WORLD. THAT’S WHERE THE BIGGEST BURDEN OF DISEASE IS, BUT WE ALSO HAVE WATERBORNE DISEASES IN THE DEVELOPED WORLD IN THE UNITED STATES. ONE EXAMPLE WOULD BE IN TRAVELERS. SO IN 2007, 30 MILLION AMERICANS TRAVELED TO DEVELOPING WORLDS. UP TO 50% OF THOSE PEOPLE HAD DIARRHEA. ABOUT 8% OF THE PEOPLE REQUIRED MEDICAL CARE AND OF THE PEOPLE WHO WENT FOR MEDICAL CARE, A QUARTER OF THAT WAS A GI SYMPTOM. THE SIGNIFICANT PATHOGENS, THE HIGHEST PERCENTAGE WAS PARASITES, THEN BACTERIAL THEN VIRAL. SO ALL THE DIFFERENT KINDS OF ORGANISMS PLAYING A ROLE FOR THOSE TRAVELERS AND THE DEVELOPING WORLD. SO THE FIRST OF THE FIVE THANKS I’M GOING TO TALK ABOUT IS POLIO. SO YOU SEE IN THE TOP RIGHT A PICTURE OF SOME CHILDREN WHO ARE VERY DISABLED BY POLIO. POLIO GENERALLY AFFECTS CHILDREN UNDER THE AGE OF FIVE. IN THE WILD TYPE INFECTION, ONE IN 200 INFECTIONS WOULD LEAD TO THIS IRREVERSIBLE PARALYSIS. OF THOSE PARALYZED, 5-10% WOULD DIE DUTY TO THE PRAL TUESDAY — PARALYSIS OF THEIR LIMBS. THE NUMBER HAS DECREASED 99% SINCE 1998. IT’S VERY STRIKING. THERE WERE 350 CASES IN 1998 BUT ONLY 223 IN 2012. AND THE THREE COUNTRIES THAT STILL HAVE POLIO ARE NIGERIA — THEY’LL HAVE TIREDNESS NAUSEA HEADACHE SORE THROAT BUT MOST PEOPLE WILL RECOVER COMPLETELY. SOME OF THEM WILL HAVE THIS PARALYSIS MORE OFTEN OF THE LEGS OR THEY MAY DIE FROM IT. IT IS SPREAD BY A PERSON TO PERSON CONTACT OR BY EATING AND DRINKING THINGS THAT ARE CONTAMINATED SUCH AS WATER. WATERBORNE DISEASE. THERE’S A VERY STRIKING PICTURE THAT I WOULD SAY MANY PEOPLE IN THE AUDIENCE HAVE NEVER SEEN IN PERSON. THIS IS SOMETHING YOU’VE SEEN IN THE HISTORY BOOKS. THESE ARE IRON LUNGS THAT ARE USED TO TREAT PEOPLE WITH POLIO. IT’S A VERY STRIKING PICTURE AND IN 1955, THERE ARE ABOUT 29,000 CASES OF POLIO’c IN THE UNITED STATES. HOWEVER, THEN WE HAVE SOME VACCINES. SO SALK DEVELOPED THE VACCINE THAT WAS VERY GOOD. THE VACCINE WAS MADE BY A VIRUS IN FORMLIN WHICH KILLED THEM WITH AN INJECTION. THERE’S ANOTHER VACCINE THE SABIN VACCINE DEVELOPED IN 1961 WHICH WAS AN ATTEND WITH US VIRUS. THERE’S THREE TYPES OF POLIO. ONE DOES NOT GIVE YOU RESISTANCE TO THE OTHER. YOU CAN SEE BY THE PICTURE WHAT THEY DID IS THEY GREW THE VIRUS IN SUBOPTIMAL CONDITIONS IN DIFFERENT KINDS OF CELL LINES TO MAKE IT LESS VARYNT. THEY WOULD TEST IT IN PRIMATES TO TEST FOR VIRULENCE. THIS IS A VACCINE THAT’S PREDOMINANTLY IN THE WORLD. AS I WAS PREPARING FOR THIS LECTURE, IT WAS VERY INTERESTING BECAUSE I LEARN A BUNCH OF THINGS I DIDN’T KNOW. I CAME ACROSS THIS NEWS ARTICLE. THIS WAS A WOMAN WHO WAS FIVE YEARS OLD IN 1953 AND THAT IS A PICTURE OF HER IN AN IRON LUNG. THE WOMAN IS NOW 65 YEARS OLD AND THAT’S A PICTURE OF HER IN HER IRON LUNG IN HER HOME. I DID NOT KNOW PEOPLE WERE STILL IN IRON LUNGS. THERE ARE ABOUT SIX TO EIGHT SURVIVORS IN THE U.S. WHO USE IRON LUNGS. SO SHE KEPT THIS GOING WITH PARTS. IT’S AN OLD MACHINE. SHE CAN GET UP AND WALK AROUND BUT SHE FOUND THE MORE SOPHISTICATED SYSTEMS THEY HAVE FOR FORCING AIR IN HER LUNGS WAS NOT COMPATIBLE WITH THE INFLAMMATION AND SHE WOULD RATHER BREATHE WITH THIS THAN THE OTHER THINGS. I JUST WAS STRUCK BY THAT. SOME OF HER CONDITIONER IN MAKING A NEWS ARGUMENT WAS NO ONE REMEMBERS POLIO. SHE IS A SPOKESPERSON FORGETTING HER VACCINATION. ANOTHER THING IN THE NEWS WHICH WAS VERY STRIKING IS POLIO IN SYRIA. SO DUE TO THE WAR IN SYRIA, WE HAVE AN OUTBREAK AND IT’S THE FIRST ONE IN 15 YEARS. SYRIA HAD BEEN A COUNTRY WITHOUT POLIO. IN DECEMBER THERE WERE 24 CASES REPORTED AND NOW WE HAVE SEVEN COUNTRIES HAVING A MASSIVE CAMPAIGN TO TRY AND HIT 22 MILLION CHILDREN. THE CDC IS CURRENTLY RECOMMENDING IF YOU WERE AN ADULT TRAVELING TO A REFUGEE CAMP IN EGYPT IRAQ LEBANON OR TURKEY YOU SHOULD GET A BOOSTER SHOT TO STOP THE SPREAD. POLIO’S NOT GONE. NOW ANOTHER THING THAT IS STRIKING ABOUT POLIO, WE HAVE THIS MASSIVE CAMPAIGN, GREATLY SUCCESSFUL, REDUCE THE POLIO CASES BUT NOW WE HAVE AN
ISSUE W OF BALANCING THE PROS AND CONS OF THE VACCINE VERSUS THE WILD-TYPE DISEASE. SO ORAL POLIO IS GIVEN A MIXTURE OF THREE ATTENUATED VIRUS AND THE VACCINE WITH CAUSE POLIO MYELITIS. THE CASES IS 1 IN 750,000 CASES OF PARALYSIS DUE TO THE VACCINE. AND THAT CAUSES 250 TO 500 ANNUALLY. THAT’S A LARGE NUMBER COMPARED TO ZERO BUT NOT THE NUMBER WHEN WE HAD POLIO EVERY. THE WILD TYPE IS ONE IN 100 OR 2,000. THE NUMBERS ARE DIFFERENT IN COMPARISON BUT WHEN YOU’RE GIVING A HEALTHY CHILD A VACCINE AND THEN GET PARALYSIS THAT’S STRIKING, VERY HARD. THE OTHER THING YOU CAN HAVE BESIDES GETTING THE PARALYSIS DIRECTLY FROM THE VACCINE IS YOU CAN HAVE A CIRCULATING STRAIN TO RISE FROM THE VACCINE. SO IT’S NOT A VACCINATED CHILD IT’S SOMEONE WHO GOT THE VIRUS AND CIRCULATING. WE’VE HAD 650 CASES WITH THE CIRCULATING STRAIN. SO IF WE’RE ABLE TO ERADICATE POLIO FROM THE WORLD, WE BELIEVE WITH SMALLPOX, WE MAY HAVE REEMERGED BECAUSE THE WILD TYPE HOON REALLY GONE OR BECAUSE WE’RE CONTINUING TO GIVE VACCINE STRAINS AND THEY’RE CIRCULATING. SO WHAT ARE, WHAT’S THE CURRENT STATE. WHAT IS THE RESEARCH THAT’S GOING ON AND THESE STRATEGIES FOR POLIO. I WILL ADD THAT THESE STRATEGIES HAVE A FACTOR, THEY’RE MORE COMPLICATED AND THEY COST MORE. SO UP IN THE OFFER LEFT YOU SEE A PICTURE OF THE POLIO VIRUS ONE, TWO AND THREE AND YOU SEE AN X THROUGH THE TWO. SO TWO HASN’T BEEN SEEN SO IT SEEMS TO BE PERHAPS ELIMINATED AND THREE HASN’T BEEN SEEN AS IS IT REALLY ELIMINATED OR NOT REQUESTING WE HAVEN’T SEEN IT IN TERMS OF THE WILD TYPE VIRUS. ONE IS THE ONE WE’VE SEEN THE MOST FOR WILD TYPE. SOME OF THE RECOMMENDATIONS ARE GOING FROM THIS VACCINE TO A MONO — THEY’RE SHORTENING THE INTERVAL. SO MY POINT OF THIS SLIDE IS THAT FOR US, WE’VE BEEN DOING THIS FOR YEARS. IT’S OLD HAT. PEOPLE ARE STILL WORKING WHAT’S THE BEST STRATEGY FOR VACCINATION. THE OTHER THING IS PHASING OUT THE CURRENT VACCINE BY 2016 AND THEN UNDERSTANDING WHY IN THE DEVELOPING WORLD THE VACCINE IS NOT AS EXPECTED. IT’S NOT AS IMMUNOGENIC. IS THAT RELATED TO THE OVERALL HEALTH OF THE CHILDREN, SOMETHING MORE COMPLICATED WITH THE IMMUNE SYSTEM TO UNDERSTAND BETTER THE E MARIJUANAANCE OF THESE VACCINE STRAINS. CAN WE DO ANYTHING ABOUT THAT, CAN WE MAKE IT ATTENUATED IN DIFFERENT WAYS. WORKING ON A BETTER VACCINE AND THEY’RE EXPANDING THE AGE WHO THEY ARE VASCULAR NOTING BECAUSE SOME OF THE OUTBREAKS THEY’RE SEEING OLDER CHILDREN SETTING THE DISEASE. AND THE LAST THING IS THEY’RE ADDING AN INTERDERMAL ADMINISTRATION IN ADDITION TO THE ORAL VACCINE TO BOOST THE GIVE KINDS OF IMMUNITY YOU GET AND THAT HASN’T BEEN SOMETHING THAT’S TYPICALLY SEEN BUT YOU CAN SEE WHERE COST CAN BE ADDED IF YOU’RE ADDING NUMBER OF TIME, A DIFFERENT KIND OF INJECTION. CAN YOU NOW DO IT OUT IN THE HOUSE OR DO YOU HAVE TO BRING IT INTO THE CLINIC. THERE ARE LOGISTICAL ISSUES CHANGING YOUR VACCINE STRATEGY TREATING 22 MILLION CHILDREN IN ELF DOING WORLD. ONE LAST THING YOU MIGHT HAVE HEARD IN THE NEWS THERE WAS A REPORT OF SOME CASES OF POLIO-LIKE DISEASE IN CALIFORNIA, ABOUT 25 CASES. AND IT WASN’T POLIO. THEY WERE ABLE TO SHOW THERE’S NO EVIDENCE OF THE POLIO AND THERE WAS SPECULATION IS THIS 68, 71. THERE ARE OTHER INTERVIRUSES IN THIS FAMILY THAT CAN ALSO CAUSE PARALYSIS AND THAT’S THE PICTURE OF THE GIRL INFECTED BY HER FATHER CARRYING HER IN THE NEWS. A PUBLIC HEALTH OFFICIAL SAYS THE NUMBER OF PRACTICING SUSCASES IN CALIFORNIA IS NOT MORE THAN WE SEE TYPICALLY IN NON- ENDEMIC, NON-POLIO ENDEMIC AREAS. THE NEWS IS SAYING IT’S NOT REALLY OUT OF LINE BUT IT SHOWS US PROGRAM — PARALYSIS AND INTERVIRUSES ARE STILL. THERE’S MORE TO UNDERSTAND ABOUT THE VIRUS. WE’LL MOVE TO THE SECOND CASE. WE’LL TALK ABOUT CHOLERA. IT’S A GRAM NEGATIVE BACTERIA IN THE SCENE IN THE UPPER LEFT. WE ARE CURRENTLY IN A GLOBAL PANDEMIC OF CHOLERA SINCE 1960. IT HASN’T STOPPED. THIS IS THE 7TH PANDEMIC SINCE THE 180 0’S, A SPEAK TYPE. AND CHOLERA CAUSES PROEXCUSE DIARRHEA LEADING TO DEHYDRATION AND DEATH. IN 2011, THERE WERE 58 COUNTRIES TO SIX CONTINENTS. THE CARTOON IS A PICTURE OF A WATERxD PUMP PUMPING OUT CHOLERA IN LONDON WHEN THEY IDENTIFIED CASES SURROUNDING PARTICULARLY STREETS WHERE THEY HAD COME FROM AND WERE ABLE TO IDENTIFY PARTICULAR PUMPS THAT WERE CONTAMINATED COMPARED TO THE MORE WEALTHY AREAS THAT WERE NOT HAVING CHOLERA CASES AND THEY REMOVED THE HANDLE IN THE PUMP IN ONE CASE TO STOP THE PEOPLE FROM USING THAT PUMP. WHAT YOU HEARD MOST IN THE NEWS WOULD HAVE BEEN IN THE CASE OF HAITI AFTER THE EARTHQUAKE. 2010-2012, GREATER THAN 700,000 CASES GREATER THAN 8400 DULTS. A HUGE NUMBER OF DEATHS IN THESE PEOPLEg?pu HAITI. AND THE CAUSE WAS ASSOCIATED WITH PEOPLE WHO CALL FROM KNOW PAL TO HELP AND WORK WITH THE EARTHQUAKE AND THEY WERE ON A TRIBUTARY NEXT TO THIS RIVER AND IT WAS SHOWN AVENUES A ASIAN STRAIN THAT WENT INTO THE WATER AND THIS WAS COMBINED WITH TENS OF THOUSANDS OF PEOPLE BATHING, SWIMMING DRINKING IN THAT WATER. CONFLUENCE OF MULTIPLE FACTORS. THE POPULATION LACKED IMMUNITY BECAUSE THEY HADN’T HAD CHOLERA. PEOPLE FLED THESE AREAS AND THEN DISBURSED THE DISEASE ACROSS THE COUNTRY AS WELL AS THE CHOLERA HAVING A HIGHER BELOW PRODUCTION. IT WAS HAVING A DEVASTATING EFFECT IN HAITI. HOW DO YOU TREAT CHOLERA. YOU MUST GIVE ORAL REHYDRATION. EVEN COUNTRIES THAT DON’T HAVE A SOPHISTICATED METHOD CAN ADD A CERTAIN AMOUNT OF SUGAR, CERTAIN AMOUNT OF SALT TO THE WATER AND FEED IT ORALLY TO THE PEOPLE. SO 80-90% OF THE PEOPLE IN AN EPIDEMIC CAN WE STREET WITH THIS ORAL HYDRATION IF YOU HAVE SOMEONE THERE TO GIVE IT TO THEM. IF YOU HAVE SOMEONE WITH A SARI CLOTH, IT GETS RID OF 99% OF THE CALL RON BECAUSE OF THE PHYTOPLANKTON AND THE PARTICULATES. WHAT ARE CURRENT RECOMMENDATIONS FOR TREATMENT. THE DEBATE ARE ANTIBIOTICS WORTH GIVING. DO WE WANT TO GIVE ANTIBIOTICS THAT DON’T MAKE A DIFFERENCE, ARE WE JUST CAUSING RESISTANCE UNNECESSARILY. CURRENT RECOMMENDATION IS YES YOU ARE GOING TO GIVE ANTIBIOTICS IF YOU GOT SOMEONE WHO IS MODERATELY OR SEVERELY DEHYDRATED IN ADDITION TO THE AGGRESSIVE HYDRATION AND NOW ZINC IS RECOMMENDED. NOT JUST SUGAR YOU’RE GOING TO ADD ZINC INTO THERE AND IT’S GOING TO HELP WITH THE THERAPY. THERE IS EVIDENCE TO SUGGEST THE CHOLERA IS INCREASING AND THERE ARE SPECULATIONS IT MADE BE ASSOCIATED WITH GLOBAL WARMING. AT THE TOP WHERE WE HAVE DATA. I’LL SHOW YOU THE SPECULATION. THEY ARE SHOWING YOU THE NORTH ATLANTIC OCEAN AND HOW MUCH PLANKTON THERE IS IN THERE. THE GREEN IS SHOWING AN INCREASE IN THE WARMTH AND THE BLUE IS SHOWING YOU DECREASE IN THE COLD VERSUS. VIBRIO IS IN FISH, SHRIMP, MOLLUSK. THE HYPOTHESES IS HOW MUCH CHOLERA IN THE WATER THAT’S NATURALLY OCCURRING. HATN’T PROVEN BUT PEOPLE ARE WORKING. THIS IS ONE AREA OF RESEARCH. HOW DOES CHOLERA CAUSE THIS PROFUSEPP9Y DIARRHEA. YOU SEE A CARTOON WHERE YOU HAVE THE BACTERIA REDUCES THE TOXIN, AN AB TOXIN MULTI MULTISUBUNIT
— THE CYCLIC A AND P IS INCREASED AND CAUSES THE RELEASE OF SALT IONS. THERE’S SUPPOSED TO BE SALT UP AT THE TOP. AND THEN YOU SEE THERE ARE PLACES IN THE PICTURE WHERE THEY’RE SHOWING WHERE THEY MIGHT TARGET AREAS FOR THERAPY AND I HAVE ANOTHER PICTURE THAT HOPEFULLY CAME OUT BETTER. SO WHAT ARE THE CURRENT RECOMMENDATIONS FOR VACCINES FOR CHOLERA. SO SHOULDN’T WE BE GIVING VACCINES OR NOT. THERE IS AN INJECTABLE VACCINE THAT’S BEEN USED WIDELY IN THE WORLD. HOWEVER WHEN THERE WAS A VERY GOOD STUDY IT SHOWED THE PROTECTION WAS KNOW THAT GREAT. ONLY 50% PROTECTION OVER SIX MONTHS AND IT LED TO A DECREASE LEADING PEOPLE TO THINK IT WAS WORSE AND CHANGING THE STRATEGY WORLDWIDE. THERE ARE NO ORAL VACCINES DEVELOPED FOR BETTER IMMUNITY AND THERE’S A CHANGE IN THE RECOMMENDATION BY THE WORLD HEALTH ORGANIZATION. THE RECOMMENDATION BEING IF YOU HAVE A HIGHLY ENDEMIC AREA OF HIGH RISK OF ENDEMIC CHOLERA, YOU SHOULD BE VACCINATING. IF THE OUTBREAK STARTS, IT’S WORTH JUMPING IN THERE AFTER THE REACTIVE DEEMPLOYMENT. THE EPIDEMIC’S ALREADY HERE, GO IN THERE AND GIVE VACCINES AND YOU’RE GOING TO CHANGE THE DYNAMIC OF THE EPIDEMIC. IT’S NOT TOO LATE. THE NEXT FOUR SLIDES ARE A SERIES OF PICTURES FROM A RECENT PAPER, 2013 SHOWING YOU A WHOLE SERIES OF CHEMICAL COMPOUNDS THAT ARE PROPOSED TO BE USED FOR CHOLERA. SO MIGHT ONE OF THESE BECOME A BETTER DRUG FOR TREATING CHOLERA. AND THEN IN EACH ONE IT HAS WHAT IS THE TARGET IN THOSE SERIES OF STEPS IS HOW THE CHOLERA TOXIN WORKS. SO THE FIRST IS ON MOTILITY AND VIRULENCE, THE BACTERIUM. ON THE RIGHT IS INHIBITORS OF THE GRADUATE LAW RECEPTOR AND THE TOXIN BINDING STEP. THEN YOU HAVE IN THE CENTER HERE INHIBITORS OF THE PROTEIN THAT REFOLDS IN THE CYTOPLASM. IN YOU CAN INHIBIT THAT STEP THEN YOU HAVE INHIBITORS OF THE CYCLIC A AND P METABOLISM. SO FOUR DIFFERENT TARGETS YOU’RE GETTING. THEN THE LAST ONE IS A WHOLE SERIES OF MOLECULES THAT INHIBIT THE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR. I DON’T KNOW WHETHER IT WAS LABELED WELL WHERE THE SALT IN THE WATER WAS GOING TO. THESE ARE A SERIES OF POTENTIAL DRUGS THAT ARE MAYBE DEVELOPED TO FIGHT CHOLERA. LET’S MOVE TO A NEW DISEASE, NUMBER 3. THIS IS A DIFFERENT KINDS OF DISEASE. IT’S A BLOOD FLECK OR WORMS. THIS CAN BE A CHRONIC OR ACUTE INFECTION. YOU CAN HAVE A CHRONIC DISEASE WHERE THEY LIVE WITNESS, ANEMIA, MALNUTRITION OR YOU CAN HAVE AN ACUTE CASE WHERE THEY HAVE ABDOMINAL PAIN, DIARRHEA, IN SOME CASES CYSTITIS, DEPENDS ON THE SPECIES. AND IN SOME CASES CEREBRAL DISEASE. THIS IS PRIMARILY A TROPICAL AND SUBTROPICAL DISEASE AND IT’S DUE TO INFECTED WATER. AGRICULTURE, DOMESTIC, RECREATIONAL ACTIVITIES, DIFFERENT WAYS PEOPLE USE THE WATER AND AGAIN A HUGE BURDEN WORLDWIDE. 200 MILLION PEOPLE AFFECTED IN 2012 AND 42 MILLION BEING TREATED ANNUALLY. A HUGE NUMBER. THE LIFE CYCLE IS DIFFERENT THAN A BACTERIA THAT I WAS THINKING ABOUT OR A VIRUS. THIS IS A COMPLICATED CYCLE. WE STARTED DOWN AT THE BOTTOM. YOU HAVE THREE DIFFERENT TYPES. YOU HAVE THE EGG THAT ARE HATCHED. IT GOES INTO A SNAIL, AN INTERMEDIATE HOST. IT DEVELOPS IN THE — IT DEVELOPS IN THE HUMAN BODY AND MATURES AND THE WORM LAYS THE EGGS AND START THE CYCLE AGAIN. SO THERE ARE SOME ATTEMPTS TO CONTROL SCHISTOSOMA — HAVING COMPLETE SANITATION AND DISCUSSION OF POSSIBLE SNAILS. I DON’T KNOW EXACTLY THE MESSAGE THEY WOULD FOCUS ON BUT THE SNAIL BE AN INTERMEDIATE CAN BE A POTENTIAL TARGET TO ADDRESS. WHAT IS CURRENT RESEARCH IN, IT’S ON THE DIAGNOSTIC ASSAY URES USING TO DETECT IT. WHY DO WE NEED THIS. SOMEONE GETS VERY SICK, I CAN SEE THE SYMPTOMS, EGGS IN THEIR STOOL AND THE ANSWER IS THERE ARE PLACES THEY ARE TRYING TO CLEAR AND THE ASSAYS ARE NOT SENSITIVE ENOUGH. LOOKING AT THE EGGS UNDER A MICROSCOPE IS NOT SENSITIVE ENOUGH HAVING A HAVE A NEUROLOGIC SYMPTOMS SO AGAIN YOU’RE NOT MAYBE DETECTING IT IN THE STOOL. SO THERE’S INVESTIGATORS WORKING ON DIFFERENT ASSAYS. THESE ARE IMMUNOASSAY WHICH WOULD BE VERY RELEVANT IN A THIRD WORLD WHERE THEY NEED POINT OF CARE TESTING AND A PCR AS SAY. IT MIGHT BE GREAT, SENSITIVE AND SPECIFIC AND YOU MAY OR MAY NOT BE ABLE TO USE IT IN THE REGION OF THE WORLD THAT YOU NEED IT IN AT THE MOMENT. ASSAY WAS CHANGING THE ANTIGEN THAT WAS BEING DETECTED. IT WAS CIRCULATING CAUSE THEODIC ANTIGEN, AND I DON’T KNOW IF YOU CAN SEE IT BUT A LITTLE PICTURE WAS SHOWING YOU RED FLORESCENCE WHO WAS BEING USED IN THAT ASSAY. PEOPLE WORKING IN DEVELOP BETTER ASSAYS FOR SCHISTOSOMA. THIS IS A GROUP TAKING A DIFFERENT APPROACH FOR DETECTION. THEY STARTED LOOKING AT THE MICRO RNA. THESE HAVE A NUMBER OF FUNCTIONS BOTH IN HUMANS AS WELL IN MICRO ORGANISMS AND THEIR FIRST ATTEMPT WAS TO LOOK AT THE SPECTRUM OF MICRO RNA IN THE HUMANS WHO SCHISTOSOMA — WHICH RNA WAS UP OR DOWN WASSABLE RELIABLE ENOUGH. THE THREE SHOWN HERE WERE FROM THE WORM AND THEY FOUND THAT THESE FOR DIAGNOSIS WE CAN DETECT THESE MICRO DNA IN THE WORM AND GIVE US BETTER SENSITIVITY. THIS IS A 2014 PAPER SO VERY RECENT WE HAVE TO SEE IF THIS PANS OUT. ORGANISM NUMBER FOUR. WE’RE GOING TO LOOK AT NOR OWE VIRUS. THIS IS WHAT YOU WOULD SEE IN THE NEWSPAPERS WHEN YOU READ IT. YOU CAN SEE IN A VERY SHORT PERIOD OF TIME OVER A MONTH YOU SEE FOUR DIFFERENT CRUISE LINERS REPORTING AN OUTBREAK OF NORO VIRUS. MAKES YOU WONDER WHY PEOPLE GO ON CRUISES. WHAT DOES IT CAUSE. IT CAUSES NAUSEA, VOMITING, DIARRHEA AND ABDOMINAL PAIN. IF YOU LOOK AT THE NUMBERS AGAIN 200,000 DEATHS IN THE
DEVELOPING WORLD IN CHILDREN UNDER AGE 5. IN THE UNITED STATES WE DO SEE 21 MILLION CASES. A LOT OF CASES NOT AS MANY DEATHS. WHEN YOU HAVE A CHILD IN THE UNITED STATES THAT GOES INTO THE EMERGENCY ROOM WITH GI SYMPTOMS. 21ERS% MAY HAVE NORA VIRUS ACTIVITY. 4% OF THE HEEL KIDS ARE GOING TO HAVE NORO VIRUS POSITIVE. THERE’S A CHANCE THAT CHILD HAS NORO POSITIVE. SO THE CLINICIAN HAS TO BE CAREFUL WHEN THEY’RE DIAGNOSING A CHILD WITH GI SYMPTOMS. IN THE UNITED STATES WE DO HAVE 800 DEATHS. MOSTLY IN YOUNG CHILDREN AND OLDER ADULTS THAT’S NOT INSIGNIFICANT AND A HUGE COST TO OUR HEALTH BURDEN IN TERMS OF COST. $2 BILLION IN TERMS OF PRODUCTIVITY LOST, HOSPITALIZATION, ETCETERA. WHY IS THIS THE CASE. WHY IS NORO VIRUS SO BAD. THE ANSWER IS BECAUSE IT’S VERY STABLE IN THE ENVIRONMENT. IT HAS A VERY LOW INFECTIOUS DOSE. IT DOESN’T TAKE MUCH TO CAUSE SOMEONE TO IT’S ONLY MODERATE VIRULENT BUT HAS A HIGH LOAD IN THE SPECIES. ONE EXAMPLE OF THAT IS A REPORT IN THE LITERATURE WHERE ONE BAKER CONTAMINATED SOME ICING HE WAS USING IN HIS BAKE SHOP AND THERE WERE 3,000 CASES FOUR DAYS AFTER THAT FROM THE CUPCAKE. OKAY. THIS IS A MODEL THAT HAS BEEN DEVELOPED AT THE HEALTH AND SAFETY LABORATORY IN THE UK TO EXPLAIN WHAT’S GOING ON WITH NORO VIRUS. THIS IS A MANNEQUIN THAT HAS FORCEFUL VOMITING, A FLUORESCENT VOMIT. WHAT THEY DO THE THEY PUT THIS INTO AN AREA, USE THE INSTRUMENT AND THEY SHOW WITH UV LIGHT HOW FAR THE PARTICLES HAVE SPREAD. AND THERE ARE CASES WHERE SOMEONE VOMITS IN A RESTAURANT AND SOMEONE ACROSS THE RESTAURANT GETS NORO VIRUS AND WERE ABLE TO GET SICK FROM THAT. IT’S NOT JUST DRINKING WATER THAT HAD FECES IN IT. I’VE BEEN MENTIONING CRUISE LINERS, ETCETERA BUT IN THE UNITED STATES THE BURDEN OF DISEASE IS IN A LONG TERM CARE FACILITY. SO 60% OF THE NORO VIRUS IS AFFECTING PEOPLE WHO ARE DEBILITATED OR COMPROMISES IN SOME WAY IN THESE LONG TERM FAIR FACILITIES AND LESS ABLE TO FIGHT IT OFF. WHAT ARE WE DOING CURRENTLY WITH NORO VIRUS IN TERMS OF DIAGNOSTICS, RESEARCH ETCETERA. THIS IS A PANEL SHOWING YOU A MOLECULAR ASSAY WHICH IS ONE OF A SERIES OF MOLECULAR ASSAYS THAT ARE BEING DEVELOPED AND BEING SUBMITTED FOR FDA APPROVAL, ETCETERA. THEY TEST A WIDE RANGE OF GI PATHOGENS. AND YOU CAN SEE IT INCLUDES BACTERIA, VIRUSES AND PARASITES ALL IN ONE MULTIFLEX PANEL. NORO VIRUS BEING ONE SPECIFIC EXAMPLE OF THAT. ONE THING THAT HAS TO BE CONSIDERED IN THE CLINICAL LABORATORY WHEN YOU’RE LOOKING AT THESE THINGS IS THE COST WORTH IT, AM I GETTING THE SENSITIVITY AND SPECIFICITY IN EACH OF THESE INDIVIDUALS MICRO ORGANISMS COMPARED TO WHATEVER MY OTHER TEST WAS THAT I WAS USING INDIVIDUALLY. AND WOULD I RATHER DO 15 TESTS OR THE TWO I WANT TO DO. THERE’S DECISIONS MADE COST IS ONE OF THE BIGGEST FACTORS. THE OTHER THING IS THESE ASSAYS ARE VERY HARD TO VALIDATE BECAUSE IF YOU HAVE ONE ASSAY YOU KNOW ONE EXAMPLE. IF YOU HAVE 15 TARGETS, 15 TARGETS TIMES THAT MANY CAUSES IT’S MUCH HARDER TO GET YOUR VALIDATIONS DONE. WHY DON’T WE HAVE A VACCINE FOR NORO VIRUS. WE CAN’T GROW IT IN CULTURE WE DON’T HAVE A ROBOT MODEL AND IT MAKES A TARGET VERY DIFFICULT. THIS IS ANALOGOUS TO INFLUENZA VIRUS OR VACCINE. YOU NEED A SHORT LIST. IF SOMEONE HAS THE INFECTION WITH THE NORO VIRUS TWO YEARS LATER THEY CAN GET THE SAME STRAIN AND THEY CAN GET SICK AGAIN. THEY DON’T HAVE LIFE LONG IMMUNITIES. ONE APPROACH THAT RESEARCH HAS TAKEN TO TAKAL NORO VIRUS THE IS TO USE VIRUS-LIKE PARTICLES. YOU HAVE THE P DIMER THE S PART PULL AND YOU MAKE A VIRUS LIKE PARTICLE AND THEY HAVE HAD SOME SUCCESS IN SOME MODELS FOR IMMUNIZING WITH THESE PARTICLES. THIS IS THE LAST SLIDE. WHAT THIS IS SHOWING YOU IS THE ANTIGENIC DRIP. SO THIS IS HIGH LIGHTING PARTICULAR EPITOPES IN THE NEUROVIRUS AND THESE IN THE NERVOUS STRAIN ARE NATURALLY OCCURRING STRAINS AND THEY’RE SEEING A CHANGE AND A CHANGE IN AN EPITOPE. SO IF YOU TAKE YOUR PARTICLE AND YOU DESIGN IT FOR THE PARTICULAR EPITOPE TO HAVE A VACCINE BUT THEN THE VIRUS SHIFT YOU NO LONGER HAD THE RIGHT EPITOPE OR VACCINE YOU NEED A MULTIPLE ANTIGEN IF THIS WERE TO WORK. THIS IS THE LAST ORGANISM I’M GOING TO TALK ABOUT. WATERBORNE INFECTIONS. THIS IS BACK TO THE UNITED STATES NOW. WHAT YOU CAN SEE FROM THE GRAPH, THE CDC GRAPH AND YOU’RE LOOKING FOR THE HASH MARK AND WHAT YOU SEE THERE’S MORE HASH MARKS IN THE CURRENT YEAR THAN THE YEAR BEFORE. THE HASH MARKS ARE LEGION ELLA. IN 20 09, 2010, WE HAD 45 OUTBREAKS IN THE UNITED STATES FROM DRINKING WATER AND RECREATIONAL WATER. 1200 CASES AND OF THE DEATHS DUE TO WATERBORNE DISEASE, 14 OR 15 OF THEM WERE LEGIONELLA. PROPORTIONATELY. WHAT IS IT. IT’S A BACTERIUM, CAUSES PNEUMONIA. WE HAVE PARTICULAR MEDIA THAT CAN BE USED AND PICKED UP IN CULTURE. IT CAUSES LEGIONNAIRESSITIES OR PONTIAC FEVER. WITH 8-18,000 PEOPLE HOSPITALLED IT COULD BE MILD OR FATAL. 12% FATALITY FR6iT LEGIONNAIRES PNEUMONIA. HOW DO WE GET THE NAME LEGIONNAIRESC;4 DISEASE. IN 1976 THE AMERICAN REGION HAD A CONFERENCE IN PHILADELPHIA AND PEOPLE GET SICK WITH AN ILLNESS NOBODY KNEW WHY AT THE TIME. 34 OF THOSE PEOPLE DIED THEY DISCOVERED IT WAS DUE TO THE LEGIONELLA ORGANISM. LEGIONELLA IS NOT TRANSMADE PERSON TO PERSON LIKE SOME OF THE THING I’VE BEEN TALKING ABOUT, IT’S TRANSMITTED FROM WATER THAT CONTAINS LEGIONELLA. IT’S THE SHOWER, THE HOT TUB, THE DECORATIVE FOUNTAIN THOSE ARE THE PLACES PEOPLE CAN GET LEGIONELLA. IT COULD BE A WHOLE LECTURE IN AND OF SIT IN TERMS OF THE BIOLOGY OF IT. LEGION GEL ELLA COMES INTO A
CELL INTO VACUUM — IT FUSES WITH THE MITOCHONDRIA AND THEN IT USES RIBOSOMAL PROTEINS TO FORM A VAC VACUOLE. THIS SHOWS YOU WAYS THAT LEGIONELLA IS HIJAKING THE HOST CELL. IT’S NOT ONE THING IT’S A WHOLE BUNCH OF DIFFERENT THINGS. YOU GOT UBIQUITIN — EACH ONE OF THOSE I’M SURE THERE ARE THREE TO FIVE LABS OR TEN LABS WORKING ON THAT ONE PATHWAY. THERE’S A HUGE AMOUNT OF RESEARCH GOING INTO UNDERSTAND HOW THIS INTRACELLULAR PATHOGEN IS WORKING AND CAN WE TARGET SOME OF THOSE AND GET A BETTER TREATMENT FOR LEGIONELLA IF WE INVESTIGATE THESE. SO I END WITH SOME PICTURES, STRIKING PICTURES SO THIS IS FROM A CATASTROPHE, EARTHQUAKE, FLOOD. THIS WHOLE ISSUE IS A SOCIETAL POLITICAL ENGINEERING ISSUE AS IT IS A MEDICAL ISSUE. WE UNDERSTAND ENOUGH AND WE DON’T TREAT IT IN THE UNITED STATES BUT NOT IMPLEMENTED ACROSS THE WORLD. IN THE PAST 20 YEARS THE NUMBER OF PEOPLE WITH SAFE DRINKING WAR HAS DROPPED TWO-FOLD. WE HAVE A LONG WAY TO GO BUT THAT IS PROGRESS HEADED IN THE RIGHT DIRECTION. THANK YOU VERY MUCH. [APPLAUSE] ANY QUESTIONS.>>I DIDN’T QUITE FOLLOW THE ARGUMENT HOW POLIO WAS TRANSMITTING AND NEEDED A VACCINE.>>THESE ARE LIVE VACCINES.>>THEY ARE SUPPOSED TO BE DISABLED.>>IT’S VERY INTERESTING. IT AMAZES ME IT ACTUALLY WORKS. IN VACCINE THEY TAKE A VIRUS AND THEY PACKAGE IT MANY TIMES THROUGH THESE CELL CULTURE SYSTEMS THROUGH A MONKEY AND YOU GETá SO SOMETHING HAPPENED TO THE VARIOUS TO MAKE IT LESS VIRULENT SO THEY CAN REVERT THE MUTATION. THAT’S PART OF THE RESEARCH. WE KNOW IT’S HAPPENING WE KNOW PEOPLE GET DISEASE AND THEY ARE CIRCULATING VIRUS. IT’S NOT DEAD. THAT IS SOME OF THE DISCUSSION IS SHOULD WE GO BACK TO A FAULT TYPE VACCINE — SALK TYPE VACCINE. WE HAVE TOO MANY CASES COMPARED TO THE WILD TYPE AND NO LONGER WANT TO USE A LIVE VACCINE. WHAT IS THE REVERTING AND I DIDN’T SEE AN ANSWER WHICH PROTEINS OR MUTATIONS ARE CHANGING.>>I REMEMBER WHEN THEY BUILT THE — DAM AND THE FISH FLOURISHED UP STREAM. VERY LITTLE ATTENTION WAS PAID TO THAT AS A LIKELY POSSIBILITY. BUT THEN I BELIEVE THAT THAT CAME UNDER CONTROL, RIGHT, BY SOME, I DON’T KNOW WHAT THEY PUT IN THE WATER. HOW DID THEY HANDLE THAT.>>I DON’T KNOW THAT ONE, SORRY. THANK YOU.>>THANK YOU VERY VERY MUCH AND WE WILL CONTINUE WITH GORDON. >>OKAY. SO WE’RE GOING TO SWITCH GEARS QUITE A BIT HERE TO SOMETHING THAT’S MUCH MORE UNKNOWN. THAT IS, IS IT A PROBLEM OR IS IT NOT A PROBLEM. IN THE PAST TWO OR THREE DECADES THERE’S BEEN INCREASING CONCERNS THAT BECAUSE OF AGRICULTURAL RUN OFF, EFFLUENT FROM LARGE INDUSTRIAL FIRM [INDISCERNIBLE] PROBABLY COMPOUNDS — THAT ARE NOT FOR HUMAN HEALTH. THIS WAS MENTIONED IN THE INTRODUCTION [INDISCERNIBLE] APPROACHES FOR ESSENTIALLY — THE WATER THAT THEY’RE SWIMMING IN. CERTAINLY FOR FISH LIVING IN CERTAIN PLACES THIS IS THE PROBLEM. THE QUESTION REALLY IS, IS IT FOR HUMANS. THIS GENERAL PHENOMENON IS REFERRED TO AS [INDISCERNIBLE] WHO REFERS TO ENDOCRINE DISRUPTOR AS A COMPOUND OR MIXTURE OF COMPOUND THAT AFFECTS THE ENDOCRINE SYSTEM AND CAUSES ADVERSE EFFECTS IN THE IMPACT ORGANISMS OR IN POPULATIONS. AND THE CHARACTERISTICS ARE THESE GROUP OF POTENTIAL DISRUPTORS. YOU CAN HAVE LOW DOSE EFFECTS OR HIGH DOSE EFFECTS. PARTICULARLY THE LOW DOSE EFFECTS VERY LONG TERM EXPOSURE MIGHT BE A PROBLEM. THERE’S A WIDE RANGE OF EFFECTS IN POTENTIAL FOR HUMAN ORGANISMS, THERE ARE LOTS OF CENTRALLING PATHWAYS THAT ARE SUBJECTED TO THESE STRUCTURES. NUCLEAR RECEPTORS, MEMBRANE RECEPTORS ARE TARGETS FOR THIS AND YOU ALL KNOW THE ENDOCRINE SYSTEM IS ENORMOUSLY IMPORTANT IN ENSURING HOMEOSTASIS IN THE HUMAN DEVELOPMENT OR THE HUMAN ANIMAL. THERE CAN BE A [INDISCERNIBLE] EFFECT PARTICULARLY IN DEVELOPMENTAL SYSTEMS — POTENTIALLY FOR THESE KIND OF COMPOUNDS — WITH THAT. SO BIG QUESTION IS THE IN SOME VERY SPECIFIC CASES YOU KNOW THAT SUCH CHEMICALS COULD BE PRESENT IN CERTAIN AREAS OF THE ENVIRONMENT HOW BIG A PROBLEM IS IT. PARTICULARLY WHAT WE’RE INTERESTED IN IS NUCLEAR RECEPTORS. THESE ARE ENORMOUSLY IMPORTANT GROUP OF MOLECULES IN MAMMALIAN CELLS. IN HUMANS THEY ARE 48 OF THESE RECEPTORS. I’VE LISTED A SIMPLE DIAGRAM OF THE VARIOUS FAMILIES HERE AND OF COURSE MANY OF THESE RECEPTORS HAVE VERY HIGH AFFINITY FOR TRADITIONAL STEROID, TRADITIONAL HORMONES YOU’RE ALL FAMILIAR WITH, PROGESTERONE, ESTROGEN, IT’S. THERE’S SUCH HIGH AFFINITY FOR THESE MOLECULES IT BECOMES AN IMPORTANT QUESTION WHETHER ACTIVITIES LIKE THIS WOULD BE PRESENT IN THE ENVIRONMENT. IF THEY WERE, THEY WOULD HAVE VERY SERIOUS EFFECTS. THE REASON WE GOT INTERESTED IN IT NOT BECAUSE WE’RE WATER PEOPLE BUT BECAUSE WE USE THESE RECEPTORS TO STUDY THE WATER REGULATION. WE HAVE SUCH INTERESTING REAGENTS WE SORT OF DECIDED TO TAKE A PEAK AT THESE ACTIVITIES IN THE ENVIRONMENT. HOW MIGHT YOU GO ABOUT, WHAT KIND OF AN ASSAY CAN YOU USE. ASSAY IS A BIG PROBLEM IN THIS FIELD. THERE’S SOMETHING YOU CAN DO THAT’S INTERESTING — THE RECEPTORS HERE ARE ONLY EXAMPLE. THEY MOVE AROUND THE CELL IN A VERY DRAMATIC WAY. THIS IS LOCATED IN THE PROTOPLASM IN THE CELL THAT YOU SEE IN THE PANEL OF THE GROUP OF EXPOSURES HERE. AS YOU INCREASE THE CONCENTRATION OF LIGANDS SHOWN ON THE LEFT HERE, THE RECEPTOR INCREASINGLY MOVES TO THE NUCLEUS SO YOU ESSENTIALLY HAVE A TOTAL MOVEMENT IN THE CYTOPLASMA — THESE MOLECULES WITH LABELS SUCH AS PROTEIN, YOU CAN VERY EASILY MONITOR THE MOVEMENT OF THESE RECEPTORS. AND THEREBY DETECT THE PRESENCE OF AN ACTIVITY THAT ACTS ON THAT MOLECULE. AND THIS APPROACH IS VERY FAST AND VERY SIMPLE. YOU FIRST HAVE TO DROP SOMETHING ON THE CELL. IF THERE’S CONCENTRATION YOU HAVE AN ACTIVITY THAT ACTS ON AT THAT TIME MOLECULE YOU’LL SEE IT MOVE TO THE NUCLEUS. AND OTHER RECEPTORS WILL ALSO BEHAVE IN A SIMILAR WAY. THIS IS AN EXAMPLE OF AN HYDRO CARBON RECEPTOR FOR EXAMPLE. BACK IN 76 OR 77 IT WAS DISCOVERED — THE LOCAL ENVIRONMENT IN THAT COMMUNITY BY A TERRIBLE — A BY-PRODUCT. AGAIN IN THIS PARTICULAR CASE WE CAN SEE THIS IS LABELED — ALMOST COMPLETELY AND YOU GET A VERY DRAMATIC MOVEMENT IN THE NUCLEUS. SO THIS IS AGAIN AN EXAMPLE WHERE YOU CAN ACTUALLY SEE THE PRESENCE OR ABSENCE OF THIS ACTIVITY IN THE ENVIRONMENT. HERE’S ANOTHER EXAMPLE. THIS IS AN ENERGY RECEPTOR. ENERGY RECEPTOR IS NOT QUITE SO DRAMATICALLY LOCALIZED IN THE ABSENCE OF THE LIGAND AND JUST SOME IN THE NUCLEUS BUT A LOT IN THE CYTOPLASM. YOU GET A COMPLETE E QUEST — SEQUESTRATION WITH THIS OTHER LIGAND. THIS IS AN EXAMPLE HOW THIS IS USED TO SEE THE ACTIVITY — SO WHAT ABOUT THE RECEPTORS THAT DON’T TRANSLOCATE. THEY’RE CALL NUCLEAR RECEPTORS BECAUSE THEY WORK IN THE NUCLEUS MOSTLY. THEY ARE A MODULATING GENE EXPRESSION BUT MOST IT HAPPENS IN THE NUCLEUS. MOST ARE RECEPTORS YOU SEE IN THE — HOW CAN YOU POSSIBLY USE THIS. TRANSLOCATE IS HOW TO DO THAT AND SOMETHING WE DEVELOPED A FEW YEARS AGO. THE RECEPTORS HAVE A FINE DEMONEY STRUCTURE AMONG THE FAMILY. THEY HAVE A TERMINUS — PART OF THE PROTEIN IS HORMONE BALANCE. SO THE LARGE ENZYMES. IN THE MIDDLE OF THE MOLECULE YOU HAVE A DNA BINDING WHERE THE MOLECULE BINDS AND REGULATES THEIR EXPRESSION. YOU HAVE THIS VARIABLE IMPERMANENCE AND SOME ACTIVITIES THAT ARE RESPONSIBLE FOR THE GENE REGULATORY PROPERTIES. IN SOME CASES THE A TERMINAL IS ALMOST COMPLETELY — AND THERE’S A SENSORY MODE. WHAT HAPPENS THE PROTEIN BINDS AS A STEROID, YOU HAVE THIS WHICH IS A 12 HELIX BUNDLE. THE HORMONE BINDS AND THE BINDING PROCESS IS THIS BUNDLE. IT’S PROTEIN, PART OF THE PROTEIN WHERE YOU GO TO THE CONFIRMATIONAL SHIFT CALLED HELIX 12 AND NOW IT CALMS ON AN ACTIVATED RECEPTOR. THIS IS A DOMAIN WHERE YOU CAN THINK ABOUT POSSIBLY USE THIS AS A WAY TO CREATE RECEPTORS THAT CAN TRANSLOCATE. WE DID THIS A COUPLE YEARS AGO. LIGAND REMAINS LIKE A RENT NOID RECEPTOR BUT DOES NOT TRANS LOCATE. Kú4B REPLACED THE LBD OVER THIS RECEPTOR. THIS IS RER, NOW YOU CAN CREATE A MOLECULE ESSENTIALLY THAT BEHAIDZ LIKE A RECEPTOR EVEN THOUGH IT BINDS — HERE’S AN EXAMPLE OF ONE OF THESE CHIMERA. YOU HAVE A HORMONE THAT ACTIVATES THAT RECEPTOR, THE NUCLEUS IS THE VERY DRAMATIC TRANSLOCATION. AND RETINOIC ACID DOES NOTHING TO THE MOVEMENT OF THAT MOLECULE. BUT IF YOU TAKE THIS RER AGAIN DOESN’T RESPOND TO THE LIGAND. YOU LOOK AT THIS CHIMERA THAT DOES NOT BIND BUT DOES MOVER TO THE NUCLEUS ALMOST COMPLETELY. WE COULD TAKE THE BEHAVIOR — TRANSLATE THE OTHER MEMBERS OF THE RECEPTOR FAMILY. THAT GIVES US NOW THE OPTIONS THAT NOT ONLY LOOKING FOR ACTIVITY THAT ARE BY USING THE NATURAL OCCURRING RECEPTORS BUT USE IT IN THEORY TO SUSPEND THIS ACTIVITY THROUGHOUT THE LARGE NUMBER WHICH WOULD BE VERY USEFUL. SO THIS IS THEN THE GENERAL IDEA OF WHAT WE’D LIKE TO DO. WE COULD USE THIS AS A GENERAL HOST FOR NOT JUST GENERAL OR FOR ANTIGEN BUT ANY ACTIVITIES THAT ACTS ON THE ENDOCRINE SYSTEM. IF WE COULD DO THAT WE WOULD BE A POWERFUL FIELD. IN FACT WE THINK WE COULD MAKE THIS WORK FOR A HORMONE REKOMPT WHICH IS ANOTHER IMPORTANT MEMBER IN THE HUMAN SYSTEM. SO WE’VE NOW, WE DECIDED TO TAKE A LEAP INTO THE UNKNOWN HERE AND SEE IF WE COULD USE THESE TOOLS TO STUDY, DETECT THE PRESENCE OF THESE ACTIVITIES IN U.S. WATER SUPPLY OR U.S. RIVERS. THIS WAS INITIATED IN OUR LAB BY — WHO IS HERE AND GOT A LOT OF HELP FROM — AND BASICALLY THE IDEA IS THESE ROBOTIC LARGE SCALE SCREENING SYSTEMS THAT ALLOW US TO SEE WHERE FLUORESCENTLY TAGGED PROTEINS ARE INSIDE CELLS IN AN AUTOMATIC FORMAT, IT IS NOW INTENTIONALLY SCREENED VERY LARGE NUMBERS OF SAMPLe
)hALLY. WHEN WE HAVE THIS APPROACH TO A SET OF WATER SAMPLES WE GOT FROM OUR COLLABORATORS AND HIS COLLEAGUES AT THE UNITED STATES GEOLOGIC SURVEY IN MARYLAND, HERE, THIS IS JUST A COMPLICATED SLIDE THAT SHOWS YOU A LOT OF INFOMATICS USED TO DO THE SCREENING PROCESS. WHAT YOU IMMEDIATELY RECOGNIZE IS THAT THERE ARE ACTIVITIES POPPING UP INz6;y HAVE A TREMENDOUS DIFFICULTY. ANOTHER COMPLEXITY WAS ILLUSTRATED RECENTLY BY THIS PAPER FROM A COUPLE GUYS WHO ARE LOOKING AT THIS — SYNTHETIC ANTI-BODY STEROID — ARE TREATED WITH THIS COMPOUND. WHAT THESE GUYS DISCOVERED WAS YOU TAKE THE ACTIVE FORM OF THIS ANTIBIOTIC STEROID AND IT’S A MULTIPLE — IN THE LABORATORY, YOU WOULD, AS THE COMPOUND WOULD SEE IT WAS IN THE WATER WAY SOMEWHERE AND DURING THE DAY IT’S DEGRADED OR DURING THE DARK CYCLE IT RECONSTITUTES IT SELL. IT APPEARS AGAIN. SO IF A COMPOUND IS BEING DEGRADED IN ONE CONDITION IS ACTUALLY RECONSTITUTED AND REAPPEARING IN A DARK CYCLE. THAT’S ANOTHER PROBLEM. IF YOU’RE TRYING TO FIGURE OUT WHAT’S IN THE WATER SUPPLY IT’S OBVIOUSLY BEING CONVERTED FROM ONE FORM TO ANOTHER. SO THAT PARTICULAR PAPER WAS REVIEWED IN THE NEWS RECENTLY AND THEY CAME UP WITH THE IMPORTANT OBSERVATIONS THEY MADE WERE FIRST OF ALL THERE ARE CHEMICALS MAYBE FAR MORE PREVALENT IN LAKES AND RIVERS THAN PREVIOUSLY THOUGHT. AND MORE IMPORTANTLY, THESE ENDOCRINE RECEPTORS ARE KNOWN OBVIOUSLY — FISH OR LIVE IN WATER THEY HAVE A MUCH GREATER POTENTIAL AND MUCH GREATER EXPOSURE. THERE’S GROWING EVIDENCE THAT HEALTH PROBLEMS MIGHT ACTUALLY BE LINKED TO THESE ACTIVITIES IN WATER SYSTEMS. AND AGAIN THEY POINT OUT PINPOINTING THESE CULPRITS IN A VAST ARRAY OF CHEMICALS PRESENT WITH A LOW CONCENTRATION IT’S GOING TO BE VERY DIFFICULT. ONE OF THE CENTRAL ARGUMENTS WE’RE MAKING IF THE SCHOOL PARENTS TRY TO GO INTO SPECIFIC SITES AND IDENTIFY A — CANNOT BE DONE. THAT’S THE APPROACH THE WATER MONITORING AGENCY THINK. THEY HAVE LOCAL PLACES THEY KNOW ARE BAD. IF THEY SUSPECT THERE’S A BAD CHEMICAL AT ONE PARTICULAR SITE THEY CAN LOOK FOR THAT CHEMICAL — IN GENERAL VERY EXPENSIVE. THAT’S NOT JUST GOING TO BE PROBABLE ON ANY LARGE SCALE AT ALL. IN FACT AS I SAID IT WOULD BE A WASTE OF TIME BECAUSE YOU DON’T KNOW WHAT TO LOOK FOR. THERE’S PROBABLY AN OUTLIER — YOU CAN EASILY PICK IT UP AND FOUND IT. THE — FOR EXAMPLE ARE MUCH LESS GENERAL AND DON’T HAVE A HIGH AFFINITY FOR RECEPTORS AND TURNS INTO A EXUNLD YOU TONIGHT EVEN KNOW. HOW ARE YOU GOING TO DO ANY KIND OF SCREENING IF YOU DON’T EXACTLY KNOW WHAT TO LOOK FOR. IT HAS ACTIVITY ASSAY RATHER THAN — CHEMICAL ONE. THIS IS THE REASON WE KNOW SO LITTLE ABOUT THE PRESENCE OF THESE COMPOUNDS IN THE U.S. WATER SYSTEMS. BECAUSE NOBODY KNOWS WHERE TO LOOK FOR THEM. THERE’S POTENTIAL EXAMINATION OF WATER WAYS WITH THESE, THIS GROUP OF ENDOCRINE — HORMONE LIKE MOLECULES THAT ACT ON THE NUCLEAR RECEPTORS HAVE LARGELY BEEN STUDIED AND THE REASON THEY’VE BEEN STUDIED IS AS I’VE SAID. PRIOR SUBSTITUTE APPEARANCE OF THESE KIND OF ACTIVITY ASSAYS THERE’S REALLY BEEN NO WAY TO DO IT. IT’S KIND OF A BIG BLACK BOX. IF YOU LOOK IN SPECIFIC PLACES, SPECIFIC ASSAYS, YOU CAN FIND STUFF AND THE QUESTION BECOMES HOW WIDE SPREAD IS THIS, IS THIS A PROBLEM GENERALLY IN THE U.S. WATER WAYS OR WORLDWIDE WATER WAYS. IT’S LIKE WE CAN DETECT LEVELS OF ANDROGEN ACTIVITY, THESE ARE THE ONLY TWO WE SCREENED FOR SO FAR BUT NOW WE WILL BE ABLE TO SCREEN FOR OTHERS. WE LOOK CAREFULLY, WE FIND THESE COMPOUNDS WITH FREQUENCY UNLESS OF COURSE — THE KEY QUESTION IS ARE THESE LEVELS OF SIGNIFICANCE IN RELATION TO ONE’S HEALTH. DO THEY PERSIST IN THE WATER SUPPLY, WATER PURIFICATION FACILITIES AND ACTUALLY SHOW UP IN YOUR PART AND AGAIN WE DON’T KNOW THE ANSWER TO THAT. ARE THERE LOW LEVELS. EVEN IF THE CONCENTRATION’S HIGH ENOUGH THAT WOULD REALLY ACTIVATE A RECEPTOR IN A GIVEN BIOLOGICAL EXPOSURE, IF YOU’RE EXPOSED TO THESE LOWER LEVELS YOU WOULD NOT THINK WOULD ACTIVATE THE RECEPTORS OVER A VERY LONG PERIOD OF TIME ARE THERE LOW LILY — LOW LEVEL
EFFECTS. IT STAYS OUT IN THE WATER IN THE ENVIRONMENT. AND FINALLY, AS I SHOWED YOU, THE RAPID CONVERSION OF COMPLEX MOLECULES IN MANY FORMS IN THE ENVIRONMENT ACTIVITIES HAVE TO BE DEVELOPED IN ORDER TO HAVE A SIGNIFICANT SCREENING PROGRAM THROUGHOUT THE ENVIRONMENT OF OUR COUNTRY AND OTHER COUNTRIES. THIS RAISES ANOTHER REGULATORY ISSUE. YOU CAN’T WRITE A REGULATION ABOUT SOMETHING THAT’S UNKNOWN. YOU SAY THERE’S BAD, YOU CAN WRITE A REGULATION IT’S EXTREMELY LOW LEVEL — OR ELSE IT’S NOT LEGAL. AS SOON AS YOU TALK ABOUT AN UNKNOWN ACTIVITY THAT YOU DON’T LOOK AT CHEMICAL FORMING ACTIVITY IS THERE’S GOING TO BE REGULATORY PROBLEMS TRYING TO WRITE REGULATION. BUT IT DOESN’T MEAN IT’S NOT IMPORTANT. WE’RE STRUGGLING WITH THE U.S. WATER SYSTEM. THAT IS NOT AN ARGUMENT. IF WE DON’T KNOW, THE ARGUMENT IS WE KNOW SO LITTLE ABOUT THIS, WE NEED TO HAVE LARGE SCALE SCREENS THAT TELL US WHERE, ON A COUNTRY-WIDE BASIS NOT JUST THESE LOOKED AT. THIS IS A SIGNIFICANT PROBLEM. THERE’S A LOT OF THIS STUFF FLOATING AROUND IN GENERAL IN THE U.S. WATER SYSTEMS. AND IMPORTANTLY AS YOU RUN THE WATER THROUGH THE TREATMENT PLANT THESE ACTIVITIES DISAPPEAR. OUR ARGUMENT IS YOU NOW HAVE TOOLS. THERE IS POTENTIALLY YOU HAVE EVIDENCE THAT THESE COMPOUNDS EXIST WITH FREQUENCIES WE
DIDN’T KNOW EXIST AND WHERE THEY COME FROM, INDUSTRIAL RUN OFF OR VERY LITTLE EVIDENCE OF EXACTLY WHERE THEY’RE COMING FROM. SO OUR ARGUMENT IS WE NEED TO HAVE LARGE SCALE SCREENS THAT WE CAN APPLY IN AN INEXPENSIVE ROBUST WAY THROUGHOUT THE WATER SYSTEM AND FIND OUT ONCE AND FOR ALL HOW MUCH IS THIS. THAT’S OUR STORY. I WILL BE HAPPY TO TAKE ANY QUESTIONS. [APPLAUSE]>>THANK YOU.>>SO YOU SHOWED US THE ORIGINAL DATA WITH PARTICULAR SITES AND YOU GOT THE WATER FROM SOMEONE AND YOU MENTIONED LATER YOU DON’T KNOW IF IT’S THE WAR THAT’S GONE THROUGH IT. HAVE YOU TAKEN ANY SAMPLES OUT OF A TAP. ARE YOU PLANNING TO.>>WELL WE’RE TRYING TO DEVELOP, WE’VE GOT, OUR FOCUS IN THE PAST, THIS IS NOT, THERE ARE BASIC STUDIES HOW RECEPTORS REGULATE GENE EXPRESSION AND CANCER AND ETCETERA ETCETERA. WE STUMBLED INTO THIS MORE OR LESS. AND WE HAVE OUR BASIC ARGUMENT IS REAGENTS THAT SHOULD BE USED ON A LARGE SCALE. ONCE YOU START USING FROM A FEW SITES, FEW HOT SPOTS ON SOME KIND OF LARGE SCALE SCREEN AND DOING THE FOLLOW UP STUDY AS YOU MENTIONED, IT BECOMES A SIGNIFICANT SUPPORT ISSUE. AND.>>[INDISCERNIBLE]>>NOT REALLY. I MEAN THESE WERE SAMPLES THAT HAVE BEEN COLLECTED BY THE U.S. GEOLOGICAL SURVEY FOR OVER 30 YEARS. THIS SAMPLE IS QUITE OLD.>>ARE THERE ANY HUMAN STUDIES THAT SHOW THE CERTAIN BASES, WATER BASES FOR CERTAIN DISEASES THAT MIGHT BE RELATED TO SOME OF THE FINDINGS YOU HAVE.>>THERE ARE OBVIOUS EXAMPLE. IN THE WESTERN CANAL FOR EXAMPLE. TREMENDOUS OWE IS CURVES, CANCER. BUT ON A LARGE, THERE’S A QUESTION WHETHER HORMONES IN PARTICULAR HAVE BEEN ASSOCIATED WITH DECREASE LEVELS OF CANCER. I DON’T KNOW THAT ANYBODY’S EVER LOOKED AT THAT BECAUSE THEY DON’T REALLY KNOW WHAT HORMONES ARE THERE.>>ANOTHER QUESTION. ALL THIS BUSINESS OF BUYING BOTTLED WATER AND NOT DRINKING FROM YOUR SINK AND ALL THAT KIND OF STUFF ARE THOSE ISSUES.>>[INDISCERNIBLE] THAT’S FOR SURE. BUT ONE OF THE ISSUES WE’RE TRYING TO DEVELOP IS TO GET THE COMMERCIAL INTEREST IN SCREENING SYSTEM THAT WILL ALLOW PEOPLE TO SCREEN THEIR OWN WATER AND SAY OKAY WE CAN TELL YOU YOUR WATER’S OKAY. THE PROBLEMS WE’VE RUN INTO IMMEDIATELY IS THE COMMERCIAL PEOPLE WILL SAY THE AMERICAN PUBLIC DON’T KNOW THERE’S ANY HORMONES IN THE WATER SO WE CAN’T TELL THEM ANYTHING THAT THEY’RE GOING TO BUY BECAUSE THEY DON’T EVEN KNOW IT’S THERE. CATCH 22.>>THE PEOPLE I’M TALKING TO, THEY CAN’T DRINK THE REGULAR WATER THEY HAVE TO BUY BOTTLED WATER AND I DON’T UNDERSTAND WHAT THE RATIONALE IS FOR THAT.>>THERE’S A LOT OF SUPERSTITION INVOLVED.>>ANY MORE QUESTIONS. GORDON, A FEW YEARS AGO BACK I GUESS PROBABLY ALMOST 5 NOW, THERE WAS SEVERAL GROUPS THAT WERE LOOKING AT THE DECLINE IN MALE SPERM COUNTS. AND THEY TRIED EPIDEMIOLOGICALLY TO RELATE THAT TO THESE PLASTICIZERS THAT HAVE ESTROGEN-LIKE ACTIVITY. I DON’T KNOW, THEY PROBABLY DIDN’T HAVE WATER SAMPLES IN THOSE STUDIES BUT WHAT’S YOUR TAKE ON THAT KIND OF STUDY.>>WELL, I THINK, I DON’T HAVE ANY, I DON’T HAVE AN OPINION. MOST OF THESE STUDIES WOULD BE PUT IN THE CATEGORY OF PROVOCATIVE. THERE ARE SOME SOLID SIGNS THAT SAY THIS IS BAD THIS IS GOOD. THE MEAN REASON WE HAVE SO LITTLE INFORMATION, JUST IGNORE THAT THEY’RE — OBVIOUSLY YOU DON’T HAVE TO WORRY ABOUT IT. I THINK THERE’S ENOUGH PRELIMINARY EVIDENCE THAT THERE SHOULD BE SOME EVIDENT TO
FIGUREjO, OUT WHAT THE LEVEL OF, THESE A CONCENTRATION PROBLEM, IS THERE ENOUGH CONCENTRATION OF COMPOUNDS AT CERTAIN PLACES THAT WE NEED TO WORRY ABOUT. MY ARGUMENT IS HERE. WE NEED TO REASSURE OURSELVES THAT THERE IS NO PROBLEM, RATHER THAN TO START TRY TO SHOW THERE IS A PROBLEM. WE’RE NOT TRYING TO SHOW THERE’S A PROBLEM. WE’RE TRYING TO REASSURE THE COMMUNITY THAT THERE IS NO PROBLEM. BUT NOBODY KNOWS. THERE’S SO LITTLE INVOLVED.>>FOR THE FISH THERE’S A PROBLEM.>>FOR THE FISH, YES. BUT WE’RE NOT FISH. WE DON’T SWIM IN THE WATER. AT LEAST NOT FOR VERY LONG.>>ANY OTHER QUESTIONS? OKAY. WELL LISTEN, THANK YOU BOTH. THIS WAS VERY INFORMATIVE.

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