Welcome to the Clinical Center Grand Rounds, a weekly series of educational lectures for physicians and health care professionals broadcast from the Clinical Center at the National Institutes of Health in Bethesda, MD. The NIH Clinical Center is the world's largest hospital totally dedicated to investigational research and leads the global effort in training today's investigators and discovering tomorrow's cures. Learn more by visiting us online at http://clinicalcenter.nih.gov GOOD MORNING. THE LABORATORY CLINICIAN OF INFENCER CITIES AT MAINE. IT'S MY PLEASURE TO INTRODUCE THE SPEAKER. IF AN EPIDEMIC IS AN UNUSUAL OCCURRENCE IN A POPULATION, THERE ARE TWO KINDS OF EPIDEMIOLOGISTS. SHOE LEATHER, AND SWIVEL CHAIR. SHOE LEATHER EPOLOGISTS FOUND THE PAVEMENT TRACKING DOWN CASES. SEEKING LINKS, CONTROLS TO TRY TO FIGURE OUT WHAT CAUSES EPIDEMICS AND HOW TO STOP IT. A SHOE WITH A HOLE IN IT HERE IS A LOGO OF THE EPIDEMIC INTELLIGENCE SERVICE WHERE TODAY'S SPEAKER, DR. ROBERT HALEY CUT HIS TEETHES BACK HE BE THE 1970s AS AN EPIDEMIOLOGIST. SWIM CHAIROLOGISTS PREFER TO SIT IN FRONT OF A COMPUTER ANALYZING DATA THAT WAY. DR. HALEY HAS MASTERED BOTH THESE TECHNIQUES, MERGED THEM TO DO SOME VERY INTERESTING IMPORTANT EPIDEMIOLOGY, BOTH AT CDC AND LATER BACK IN DALLAS, TEXAS, HIS HOMETOWN AT THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL SCHOOL. WHERE HE'S NOW PROFESSOR OF INTERNAL MEDICINE AND THE CHAIR OF THE EPIDEMIOLOGY DEPARTMENT. AMONG THE NUMEROUS CONTRIBUTIONS, THE ESTABLISHMENT OF EFFICACY OF INFECTION CONTROL AT THE CDC. AND THIS WORK WAS ACTUALLY CITED AT THE 50th ANNIVERSARY OF THE CDC AS ONE OF THE 3 MOST IMPORTANT CONTRIBUTIONS OF THE ORGANIZATION OVER THAT TIME PERIOD. RUSHING TO DALLAS HE ESTABLISHED THE CONNECTION BETWEEN TATTOOING AND HEPATITIS C ACQUISITION. SET UP THE STRUCTURE OF A VERY PRODUCTIVE DALLAS HEART STUDY TO STUDY THE FACTORS THAT IMPINGE ON DEVELOPING HEART DISEASE. RECENTLY USED ANALYSIS TO CREATE ANALOGY ALSO TO PREVENT -- ALGORITHM TO PREVENT WELL NILE SYNDROME. I COULD KEEP GOING. HE'LL SAY IT'S A GREAT PLEASURE TO WELCOME BOB TO THE NIH TODAY. AND SAY HE'S GOING TO TELL US ABOUT HIS MOST CONSUMING REWARDING ACTIVITY OVER THE LAST 20 YEARS, THIS FASCINATING INVESTIGATION OF THE CAUSE OF THE GOLF WAR ILLNESS THAT OCCURRED IN THE UNITED STATES SOLDIERS DURING THE 1991 GULF WAR. SO JOIN ME IN WELCOMING DR. ROBERT HALEY. IT'S QUITE AN HONOR. I CALL IT SHOE LEATHER AND SEAT OF THE PANTS EPIDEMIOLOGY. I HAVE A SLIDE WITH A SEAT OF THE PANTS HOLE IN IT WHICH I ENJOY. SO LET'S SEE. WHAT I'M GOING TO TALK ABOUT WITH THE EPIDEMIOLOGIC NEURO IMAGING AND GENOMIC RESEARCH INTO CHRONIC NEURO IMAGING ENCEPHALOPATHY FROM THE 1991 GULF WAR. EVERY ONE KNOWS THIS IS A VERY CONTROVERSIAL SUBJECT, VERY POLITICAL. I'M GOING TO TRY TO AVOID THE POLITICS AND CONTROVERSY AND JUST TALK ABOUT WHAT WE'VE DONE. AND TRY TO CONVINCE YOU THAT THIS IS NOT ONLY OF INTEREST TO 150 GULF WAR VETERANS WHO ARE COMPLAINING OF ILLNESS AND NOT LARGELY TAKEN -- BEING CONSIDERED BY PHYSICIANS TO HAVE SOMETHING. THIS IS A MORE COMMON DISEASE IN THE CIVILIAN WORLD THAN WE MAY REALIZE, MAKE UP A COMPONENT OF WHAT WE CALL PSYCHIATRIC DISEASE. CHRONIC BEERSLOSIS IN THE 50s. THEY RECOVERED AND THEN HAD A LIFE LONG DEBILITATING COGNITIVE FATIGUING ILLNESS. THINK OF -- REMEMBER THE PULMONARY INHALATION ANTHRAX CASES. THE SURVIVORS ARE STILL LEFT WITH A CHRONIC FATIGUING COGNITIVE ILLNESS. THINK OF THE EBOLA SURVIVORS. THEY HAVE -- ARE LEFT WITH A COGNITIVE DEBILITATING PAINFUL LISTENS. I THINK THESE -- LISTENS. ILLNESS. CHRONIC FATIGUE SYNDROME AND FIBROMAALJAY ARE WHAT MANY OF THESE PEOPLE ARE CONNECTED IN THE VA FOR. 5% OF OUR POPULATION HAVE THOSE CONDITIONS. WHAT IS THIS? MY FATHER WAS A LONG TIME INTERNAL IN DALLAS. I REMEMBER ONCE WHEN I WAS A MEDICAL SCHOOL, I WAS IN THE CLINICS AND I HEARD ABOUT CROCK. CROCK IS A PERSON WITH ONE OF THESE ILLNESSES, YOU DON'T FIND ANYTHING WRONG WITH THEM. MY DAD SAID I'VE LEARNED A CROCK IS SOMEBODY YOU JUST HAVEN'T WORKED UP YET. SOMETHING IS GOING ON THERE WE JUST AREN'T SMART ENOUGH TO KNOW WHAT IT IS. LET ME SEE IF I CAN GO THROUGH WHAT WE'VE DONE, SEE IF THIS SHEDS LIGHT ON THESE PROBLEMS. NO POTENTIAL CONFLICTS TO DISCLOSE. WHAT I WANT TO TALK ABOUT IS FOUR ISSUES. FIRST, TO EXPLAIN THE -- HOW THE GULF WAR ILLNESS AND THREE VARIANTS. DEFINED SYMPTOMS, RESEARCH INDICATION DEFINITION. DESCRIBE OUR FALLOUT FROM BOMBING OF IRAQ AND CHEMICAL WEAPONS COULD HAVE TRANSITED LONG DISTANCE TO EXPOSE U.S. TROOPS. THE EXPOSURE REALLY DID HAPPEN. EXPLAIN HOW DIFFERENT NEURO IMAGING, EEG AND GENOMIC MORTALITYIES. AND FINALLY, HOW A TEN MINUTE RESTING EEG MIGHT BE ABLE TO DIAGNOSE GULF WAR ILLNESS AND DIFFERENTIATE VARIANTS. THAT'S WHERE WE'RE GOING. IN 191 DEGREES INVADED KUWAIT, TAKING OVER THE OIL WELLS VITAL TO THE WEST. AND THAT HAPPENED IN AUGUST, 199O WE IMMEDIATELY STARTED DEPLOY TROOPS. BY JANUARY OF 91, WE HAD 700,000 TROOPS, THE LAWMAKER MOVEMENT OF U.S. TROOPS IN HISTORY WITH THE POSSIBLE EXCEPTION OF THE BATTLE OF THE BUDGE IN WORLD WAR II. HALF AWAY AROUND THE WORLD. HIGH LAUNCH, THE WAR WAS OVER. LATELY FIRST OF -- ACTUALLY FIRST OF MARCH. THE WAR WAS OVER VERY QUICK. THERE WAS FIVE WEEK AIR WAR, A BOMBING CAMPAIGN. HERE IS KUWAIT. SAUDI ARABIA, IRAQ. AND WE BOMBED FOR FIVE WEEKS, BOMBED TO TRY TO NEUTRALIZE FORCES. THERE WAS A PUNCTUATED BY A FIVE DAY GROUND WAR A TANK BATTLE AT LONG DISTANCE. AND IT WAS A SMASHING VICTORY, 150 DEATHS. MOSTLY CRITICAL, FRIENDLY FIRE ON THE U.S. AND COALITION SIDE. ACHIEVED AIMS. THEN RESISTED GOING TO BAGHDAD BECAUSE IT MIGHT PRECIPITATE A LONG IDEOLOGICAL WARFARE WHICH WE DID LATER, AND THAT'S WHERE WE ARE. BUT -- AND THEN -- BUT WHAT HAPPENED IS DURING THIS PERIOD, A NUMBER OF TROOPS BEGAN GETTING ILL WITH DIARRHEA, FATIGUING ILLNESS, THUMP WITH COGNITIVE PROBLEMS. AND AS THEY WERE COMING HOME IN MARCH, APRIL AND MAY OVER 6 MONTHS OR MORE, PROBABLY 100,000 PEOPLE DEVELOPED THIS ILLNESS. AND I KNOW IN TALKING TO ONE OF THE INEFFICIENCY DISEASE FELLOWS AT WALTER REED, THEY WERE CONVINCED THIS WAS AN INFENCER DISEASE. IT WAS A VERY DRAMATIC THING. THESE PEOPLE COMING BACK WITH DRAMATIC SYMPTOMS AND ONE AFTER ANOTHER COMPLAINING OF THE SAME CONSTELLATION OF SYMPTOMS. THEY WERE CONVINCED IT WAS AN EPIDEMIC. THERE WAS A VIGOROUS EFFORT IN THE FIRST COUPLE YEARS AFTER THE WAR TO DECIDE THIS. TO FIGURE OUT WHAT IT WAS. AND THEY CAME UP WITH SEVERAL IDEAS. BUT NONE OF THEM PANNED OUT. SO BY 1994, IT LOOKED LIKE THIS WAS GOING TO BE DECLARED JUST A STRESS REACTION TO BEING DEPLOYED. BECAUSE MOST OF THEM WEREN'T EVEN INVOLVED IN COMBAT. SO STRESS OF A DEPLOYMENT. YET YOU SEE THESE PEOPLE, AND MANY OF THEM ARE REALLY UNABLE TO FUNCTION. SO WHY? SO THE TYPICAL SYMPTOMS ARE CHRONIC FATIGUE, AND INTERESTING HEY, HYPER AROUSAL. THE BRAIN IS RACING BUT THEY'RE SO TIRED THEY CAN'T FUNCTION. COGNITIVE PROBLEMS, ATTENTION, CONCENTRATION, CONFUSION. THEY MENTIONED MEMORY PROBLEMS BUT IT'S MAINLY ATTENTION CONCENTRATION PROBLEMS, I THINK. AND SOME ACTUALLY A GLOBAL CONFUSION. SPEECH DIFFICULTIES. PARTICULARLY CAN'T FIND THE WORDS ANYMORE. ADULT ON SET STUTTERING IN A SMALL NUMBER. CHANGE, WITHDRAWN, EASILY ANGERED FROM A PREVIOUSLY GREGARIOUS, REGULAR PERSON. CONSTANT BODY PAIN. HIPS, SHOULDERS, BACK. BUT WITHOUT ARTHRITIS. IT'S OFTEN CALLED ARTHRITIS BUT THERE IS NOTHING WRONG WITH THEIR JOINTS. PARINGSNESIAS, BALANCE, VERTIGO ATTACKS WITH THE ROOM SPINNING. UNREFRESHING SLEEP, INSOMNIA, HOT FLASHES, NIGHT SWEATS. WATT ARDIARRHEA, ALIENATING CONSTIPATION. ALL SUBJECTIVE -- WITH THE EXCEPTION OF DIARRHEA, ALL SUBJECTIVE SYMPTOMS AND THEY HAVE NO OBJECTIVE SIGNS. SO A CLINICIAN LOOKS AT THEM AND THERE IS NOTHING THEY CAN'T FIND ANYTHING. THEY DO THE USUAL LAB TESTS, MAIN A BRAIN MRI. EVERYTHING IS NORMAL. KNEES ARE CROCKS, THE PROBLEM IS THERE WERE 150,000 OF THEM IN AN ALL VOLUNTEER ARMY THAT ALL BECAME SICK ABOUT THE SAME TIME. AND -- SO IT'S HARD TO EXPLAIN AWAY AS A CROCK. AS MOST OF THEM WERE YOUNG. NOW, AFTER THE WAR THIS WAS SO DRAMATIC THAT THE DEFENSE SCIENCE BOARD, STANDING EXPERT COMMITTEE THAT ADVISES THE NIH DEPARTMENT, CAME UP WITH ABOUT THE SAME LIST OF ENVIRONMENTAL EXPOSURES THAT MIGHT PRODUCE CHRONIC LISTENS. THEY WERE CHEMICAL WARFARE AGENTS. SARIN AND CYCLOSARIN WERE IN THE THEATER AND WERE HEAVILY BOMBED. I'LL TALK ABOUT THIS. PESTICIDES. LIBERAL SPRAYING TO COMBAT ORTHOUGHT PODS BORN DISEASES. PESTICIDES ON UNIFORMS. HEAVY CONCENTRATED INCORRECT REPELLANTS. AN ANTINERVE GAS ANTIDOTE. SIPRO FLOXCIN. ANTHRAX. MULTIPLE IMMUNE NATIONS, SMOKE FROM OIL WELLS, GEUMS, PEROLIUM IN DRINKING WATER. DEPLETED URANIUM, AND SPECIAL PROTECTIVE PAINTS THAT MIGHT PRODUCE -- IN USING THESE, MIGHT PRODUCE PULMONARY SYNDROME. COMBAT STRESS AND POST TRAUMATIC STRESS DISORDER. AFTER VIETNAM, THE VA GEARED UP SEVERAL LARGE POST TRAUMATIC STRESS DISORDER CENTERS AND THEY WERE EXPECTLING SEVERE CASUALTIES FROM THIS WAR. SO THEY WERE GEARED UP TO FIND POST TRAUMATIC STRESS DISORDER. SO WHEN THESE PEOPLE CAME BACK THERE WERE A LOT OF POST TRAUMATIC STRESS DISORDER ORIENTED STUDIES. AND THIS ILLNESS LOOKED A LITTLE BIT LIKE POST TRAUMATIC STRESS DISORDER. SO AT FIRST, THAT WAS THE LEADING IDEA. AT FIRST. IN COMPETITION WITH THE INFENCER DISEASE THEORY. LATER ON THIS HAS BEEN GIVEN UP, THOUGH, BECAUSE THESE -- WHEN YOU REALLY TEST RIGOROUSLY, THEY DON'T HAVE POST TRAUMATIC STRESS DISORDER. IT DOESN'T FIT THE CASE DEFINITION OR THE DSM-IV DEFINITION. WELL, IMMEDIATELY AFTER THE WAR WAS OVER -- I'M SORRY, ABOUT 1993 AND 94, IT HAD BEEN DECIDED THIS WAS A STRESS REACTION. BUT THERE WAS A REPORT BY A SENATE COMMITTEE, DONE REGAL, THE HEAD OF THIS COMMITTEE. RETIRING DEMOCRATIC WHO COULD TAKE THIS. AND HE MOUNTED AN INVESTIGATION. HERE IS HIS REPORT. AND THEY COLLECTED A LARGE NUMBER OF ANECDOTES OF PEOPLE IN THESE LOCATIONS. YOU SEE THE NUMBERS. HERE IS KUWAIT, IRAQ, AND MOST OF OUR TROOPS WERE LOCATED HERE BEFORE THE ASSAULT. IT WENT THIS WAY. AND THESE WERE ALL EYES REPORTS OF -- ON A CERTAIN DAY, THE THIRD DAY OF THE AIR WAR, SUDDENLY ALL THE ALARMS, CHEMICAL ALARGES STARTED GOING OFF. THEY HAD DETECTORS ON THE CHAIRS OR DESKS, TABLES IN THEIR CAMPING AREA. EVERY UNIT DID. THESE THINGS STARTED GOING OFF. 10,000 OF THEM WERE GOING OFF ALL DAY. THEY CONTINUED FOR A WEEK AND PERIODICALLY THROUGH THE WAR THEY WOULD GO OFF AGAIN FOR A DAY OR SO. AND THEY WERE -- AFTER THEY WENT OFF AND NOBODY DIED, THEY WERE CONSIDERED FALSE ALARMS. BUT THEY WERE COLLECTED, SOME PEOPLE REPORTED ILLNESS AFTER THIS. BUT THIS SORT OF REMAINED AS AN UNEXPLAINED FINDING OF -- AND ACTUALLY, ON THE DAY THAT -- THE NIGHT BEFORE THIS STARTED, APPEARED NEAR BAGHDAD, U.S. TROOPS -- U.S. AND COALITION AIRCRAFT BOMBED TWO SITES THAT WERE MAJOR WAREHOUSES THAT CONTAINED CHEMICAL WEAPONS, PRIMARILY SARIN AND CYCLOSARIN. A REAGENT IN 50-GALLON DRUMS STACKED TO THE CEILING READY TO BE LOADED. WE BLEW THOSE THINGS UP. THE NEXT KAY ALL THESE ALARMS WENT OFF. THAT HAD BEEN DISREGARDED BECAUSE THERE WERE NO REPORTS OF PEOPLE DYING UP NEAR THAT SITE. IMAGINE IF THEY BLEW THOSE UP AND A CLOUD DRIFTED, IT WILL KILL MANY PEOPLE UP HERE BEFORE IT BECAME DILUTE AND EXPOSED OUR TROOPS TO LOW LEVEL EXPOSURE. SO THAT IT HAD BEEN -- IT HAD -- IT WAS DISCOUNTED AS A POSSIBILITY. OKAY. SO IN STARTING TO DO -- TO LOOK AT THIS, ACTUALLY, THE ROPE I LOOKED INTO IT IS THAT ABOUT EARLY 1994, ROSS PEROT WHO LIVES IN DALLAS CAME TO OUR UNIVERSITY AND SAID SINCE THE WAR I HAVE BEEN SEEING A LARGE NUMBER OF TROOPS, SOME OF WHOM I KNEW BEFORE THE WAR. COMING BY MY OFFICE, TELL ME THAT THEY'RE SICK AND THEY CAN'T FIND ANYBODY TO FIGURE OUT WHAT IT IS, AND THEY REALLY NEEDED HELP. AND HE WAS SO MOVED BY THIS HE CAME AND SAID IF YOU GUYS WOULD DO A STUDY, I'LL PAY FOR IT. AND I'LL RUN ANY POLITICAL INTERFERENCE THAT'S NECESSARY. AND WHAT HE WAS DESCRIBING, IF IT WAS TRUE, WAS AN EPIDEMIC. AND I SAID WELL, LOOK. I'VE BEEN TO CDC. I CAN INVESTIGATE EPIDEMICS,Ez TAKE ONE L OOK AT IT FOR YOU. IF IT'S TRUE WE'LL LET YOU KNOW. IF NOT, WE'LL TELL YOU THAT, TOO. SO WE UNDERTOOK AN INVESTIGATION. AND WE DID FIND SOMETHING. WHICH I'LL SHOW YOU IN A MINUTE. AND OVER TIME WE IDENTIFIED THESE QUESTIONS WHICH -- AND IN ORDER TO CONVINCE PEOPLE, IN THAT YOU HAVE TO ANSWER ALL OF THESE QUESTIONS TO GET BY. USED TO BE I THOUGHT YOU COULD PROVE ONE OR TWO OF THEM. I THINK YOU NEED TO ANSWER ALL OF THEM FOR A NEW DISEASE LIKE THIS. FIRST OF ALL, HOW DO YOU -- YOU HAVE TO HAVE A CASE DEFINITION. YOU HAVE TO DEVELOP A CASE DEFINITION FOR GULF WAR ILLNESS, A RESEARCH CASE DEFINITION. THEN WHAT CAUSED THE DISEASE? DEPLOYMENT STRESS, OR IS IT A NEUROTOXIC CHEMICAL PROBLEM? THIS IS A DICHOTOMY AND PEOPLE ARE VERY DIVIDED AND BELIEVE STRONGLY WAY WAY OR THE OTHER. YOU HAVE TO DECIDE THAT. WHAT IS THE DISEASE PROCESS? IS IT PSYCHOLOGICAL OR ORGANIC? WHAT'S THE PATHOPHYSIOLOGY. WHAT'S GOING ON IN THE BODY. HOW DO YOU DIAGNOSE IT? YOU HAVE TO HAVE A TEST OR THERE IS NO INTEREST IN BELIEVING THIS. THERE IS NOTHING YOU CAN DO ABOUT IT. HOW DO YOU CONTROL THE SYMPTOMS OR HOW DO YOU REVERSE THE PROCESS, IDEALLY REVERSE THE PROCESS? ED AND HOW DO YOU PREVENT IT THE NEXT TIME? I'M GOING TO TALK ABOUT EACH OF THESE. HOW DO YOU DEFINE GOLF WAR SYNDROME? IN OUR EIS TRAINING, THE FIRST -- THE EPIDEMICOLOGISTS RULE NUMBER ONE, THE FIRST STEP IN INVESTIGATING A NEW DISEASE IS ESTABLISH A CASE DEFINITION. THIS IS IN THE CDC FIELD EPIDEMIC EPIDEMIC BOOK NOW. TAUGHT TO US BACK THEN. AND THEN MORE RECENTLY, AT THE 50th ANNIVERSARY CELEBRATION CDC, CONRAD, ONE OF OUR OLD MENTORS DASHINGED THIS. -- ADDED THIS. IF YOU CAN'T, THEN ESTABLISH CASE DEFINITION. OKAY. BECAUSE IF YOU DON'T, YOU VICE-PRESIDENT STARTED. YOU'LL NEVER FIND ANYTHING. -- YOU HAVEN'T STARTED. YOU'LL NEVER FIND ANYTHING. ONE OF THE EARLY PROBLEMS IN THIS INVESTIGATION WAS THERE WAS A GREAT SKEPTICISM OF WHETHER THIS WAS A DISEASE SO THERE WAS A LOT OF PRESSURE NOT TO HAVE A CASE DEFINITION, BECAUSE THAT ADMITS THERE IS A DISEASED. THAT SEEMS TO PREJUDGE THERE IS A DISEASE. BUT I BELIEVE IF YOU DON'T HAVE A CASE DEFINITION, YOU HAVEN'T STARTED THE RESEARCH. I THINK THAT EXPLAINS A LOT OF THE NEGATIVE FINDINGS AND CONFUSING ASPECTS OF THIS LITERATURE. SO WE PICKED A UNIT, A NAVAL RESEARCH CONSTRUCTION. A RESERVE UNIT, BECAUSE THEY WERE NOT IN THE MILITARY AND WE COULD GET TO THEM WITHOUT GOING THROUGH CHANNELS. THEY WERE ALL EAGER TO PARTICIPATE. SO WE DEVELOPED A QUESTIONNAIRE ON EXPOSURES. RISK FACTORS. AND A QUESTIONNAIRE ON SYMPTOMS. OKAY? AND NEURO PSYCHOLOGICAL QUESTIONNAIRE. AND WE MET THESE GUYS IN GROUPS, IN KNOXVILLE, BIRMINGHAM, WINTSTAN, CHARLOTTE AND ATLANTIC. WENT OUT SHOE LEATHER STYLE AND COLLECTED DATA FROM THESE PEOPLE WHO WERE ORDERED IN THE SOUTHEASTERN STATES. WE PICKED THEM BECAUSE THEY GO ALL OVER THE THEATER. THESE GUYS ARE GOING EVERYWHERE, BUILDING THINGS, DELIVERINGAGES. SO IF THERE IS A GEOGRAPHICAL EXPOSURE, THAT WOULD HELP US PINPOINT THAT. ALSO, THEY WOULD HAVE MORE -- WIDER EXPOSURE. WE WOULDN'T MISS IT. HERE IS WHAT WE FOUND FROM OUR QUESTIONNAIRE. YOU COULD IMAGINE A SPREADSHEET WITH THE SOLDIERS AS ROWS, AND THE SYMPTOMS AS COLUMNS. WE DID MATH MATICAL TECHNIQUE CALLED FACTOR ANALYSIS TO LOOK FOR STRUCTURE IN THAT ARRAY. AND WE FOUND PRINCIPLE COMPONENTS ANALYSIS, WE FOUND THAT THERE WERE 3 VERY STRONG FACTORS WHICH ARE POTENTIAL SYNDROMES, IF YOU WILL. BUT AT THIS TIME THEY'RE ONLY MATHEMATICAL CURIOSITIES. AND 3 MODERATE ONES. AFTER THAT, IT'S ALL GARBAGE. SO IT LOOKED LIKE THERE MIGHT BE THREE SYNDROMES. LOOKING AT WHAT THE QUESTIONS LOADED ON EACH OF THOSE, ONE WAS JUST A MILD COGNITIVE IMPAIRMENT. DIFFICULTY THINKING, CONCENTRATING, REMEMBERING. OTHERWISE VERY FUNCTIONAL. SECOND WAS WHAT WE CALL CONFUSION ATAXIA. YOU'LL HEAR ALL THE WAY THROUGH THIS, SYNDROME 2 IS THE BAD ONE. THESE GUYS ARE COMPLETELY UNABLE TO FUNCTION. NOT COMPLETELY. BUT LARGELY UNABLE TO FUNCTION. BECAUSE THEY HAVE A CONFUSIONAL SYNDROME. THEY -- THEY'RE IN A FOG. THEY TEND TO SIT THERE ALL DAY, WIFE SAYS I CAN'T SEND JOHN INTO THE TOWN IN THE TRUCK ANYMORE. HE WON'T FIND HIS WAY BACK. IT'S LIKE EARLY ALZHEIMER'S IN A WAY. IT'S NOT. THEY ALSO HAVE ALMOST ALL HAVE VERTIGO ATTACKS. UNEXPECTED, DRIVING A CAR AND SUDDENLY, THEY'RE TURNING AROUND IN SPACE FOR TWO OR THREE SECONDS. THERE IS ACTUALLY A HIGH RATE OF AUTOMOBILE ACCIDENTS IN THESE GUYS. FROM A POPULATION POINT OF VIEW. FINALLY, THE THIRD GROUP HAS SOME ITEMS IN COMMON WITH THIS, ALSO, MUCH MORE DRAMATIC PAIN ISSUES. JUST CONSTANT ACHING PAIN IN THE SHOULDERS, LOWER BACK, BUTTOCKS. AND LITTLE BIT IN THE EXTREMITIES. MUSCLE PAIN. AND THEN THESE 4-6, THESE GUYS ARE REALLY SUBGROUPS OF THIS. ECHOING IN THE FACTOR ANALYSIS. THESE TAXPAYERED IN TO 63. THERE WERE 116 OTHERS IN THIS BATTALION THAT SAID YES, I HAVE GOLF WAR ILLNESS. I GOT ILL AFTER THE WAR AND IT'S DUE TIGHT. THESE PEOPLE HAD HEART ATTACKS, CUSTODINY PROBLEMS, AND HEPATITIS, AND THIS AND THAT. WHICH -- YOU KNOW, POST -- THEY ATTRIBUTED TO THEIR WAR EXPERIENCES BUT DIDN'T FIT ANY GROUPS. THEY HAD REGULAR DISEASES. THEY THOUGHT THEY HAD IT. IF YOU ASK A BURN OF VETERANS, COME TO MY STUDY IF YOU HAVE GOLF WAR LEGISLATION, YOU'LL GET ALL THESE. BUT WE THINK ONLY THESE ARE PROBABLY SOMETHING DIFFERENT. YOU SEE HOW COMPLICATED THIS IS. SO IF PEOPLE ARE DOING STUDIES AND DON'T REALIZE THAT, YOU SEE THE TRAPS THEY'LL FALL IN. SO BASICALLY, HERE IT IS. HERE IS EVERYBODY IN THE BATTALION. HERE ARE THE PEOPLE WHO THINK THEY HAVE GOLF WAR ILLNESS. HEAR ARE THESE SYNDROMES THAT SEEM TO GAL TOGETHER. SOME -- FALL TOGETHER. SOME REAL ILLNESS THAT IS COMMON AMONG A GROUP OF PEOPLE. NOW, LOOKING AT THESE, WE LOOKED AT THE PERCENT WHO ARE EMPLOYED. SYNDROME ONE, ALMOST NO SIGNIFICANT DIFFERENCE. BUT SYNDROME TWO WERE MUCH LESS LIKELY TO BE ABLE TO HOLD A JOB. MORE EVIDENCE THAT THERE IS SOMETHING UNUSUAL ABOUT THE SYNDROME 2 GROUP. OKAY. SO THAT'S A WORKING CASE DEFINITION. AND WE WERE ABLE TO RUN THAT IN THIS BATTALION AND ABLE THROUGH A NATIONAL SURVEY I'LL TALK ABOUT IN A BIT WHERE WE USE THE SAME QUESTIONNAIRE, BUT IN A NATIONAL SURVEY. AND FIND THE SAME SYNDROMES. SO NEXT, WHAT CAUSED THIS? THIS, OF COURSE, WE LOOKED AT THE RISK FACTORS FOR EACH SYNDROME AND SAID WHAT RISK FACTORS ARE ASSOCIATED WITH EACH OF THESE 3 CONDITIONS? THOSE WOULD WORE FLEE COLORS THAT PUT ON DOG AND CAT, A VERY IMPORTANT PEST CROWD WHICH HAS BEEN BANNED BECAUSE IT PRODUCES A LONG TERM COGNITIVE PROBLEM IN PEOPLE IF YOU'RE EXPOSED TO IT. THEY WERE WEARING THESE TO PREVENT INCORRECTS FROM GETTING INTO THEIR CLOTHING. AND THE ONCE WHO WORE THOSE BROUGHT THEM FROM HOME. THEY WERE UNAUTHORIZED. 8 FOLD INCREASE IN SYNDROME ONE COMPARED TO THOSE THAT DIDN'T. THE BAD ONE, SYNDROME TWO, THESE WERE PEOPLE IN THE AREAS WHERE THE NERVE GAS WENT OFF. MANY ADVANCED SIDE EFFECTS, THIS IS AN AGENT, GIVES YOU DIARRHEA, URGENT URINATION, AND SOME CLOUDY THINKING, SO FORTH T ONES THAT HAD THE WORST SIDE EFFECTS WERE HIGH HAY RELATED TO THAT. AND THEN A GROUP THAT WAS IN NORTHEASTERN SAUDI ARABIA ON THIS FOURTH DAY OF THE AIR WAR THAT I'VE ALREADY TALKED ABOUT. RELATIVE RISK OF 4. SYNDROME 4 WAS SIMILAR. WAS A I HAVE BEEN OUR FIRST OUTING, THIS WAS THE HYPOTHESIS RAISING SURVEY. THEY BOMBED THESE STU CHEMICAL FACTORIES WEST OF BAGHDAD. HEAR WERE THE TROOP CONCENTRATIONS AT THAT TIME, RESERVED FOR THE ATTACK, BUT WAITING FOR THE AIR WAR TO BE OVER. THAT NEXT DAY, 10,000 NERVE GAS ALARMS WENT OFF. WHERE YOU SEE THESE FLASKS, THESE WERE WHERE CHEMICAL WEAPON EXPERTS IN BIG VANS WITH LIQUID COM TOM GRAFY WERE LOOKING FOR NERVE GAS. AND THEY WERE DETECTING SERON IN THE ATMOSPHERE IN THESE LOCATIONS ON THIS DAY. SINCE ALARMS, NOBODY DIED, IT WAS DECLARED FALSE ALARMS. PEOPLE STOPPED REACTING AND STOPPED PUTTING ON PROTECTIVE GEAR. THIS WENT ON AND OFF FOR THE NEXT TWO OR 3 WEEKS. NOW, SO HOW IN THE WORLD COULD IT GET DOWN HERE AND EXPOSE THESE PEOPLE TO LOW LEVEL WITHOUT KILLING PEOPLE UP HERE? THEY'RE WERE NOT MASKED DEATHS UP HERE. THIS CAUSED THIS TO BE REJECTED FOR A LONG TIME. WE PUBLISHED A PAPER, NEURO EPIDEMIC EPIDEMIC A COUPLE YEARS AGO WORKING WITH JIM, AN INTELLIGENCE EXPERT I WORKED WITH FOR 20 YEARS ON THIS TRYING TO LOOK AT THE PROBLEM. THE IDEA IS IN METEOROLOGIST, THERE IS A WELL-KNOWN PHENOMENON CALLED THE KNOCK TERM BOUNDY LAYER. ON A COLD NIGHT, THE COLD AIR SINKS TO THE GROUND. AND FOR THE COUPLE HUNDRED METERS, YOU GET A COLD LAYERED MOVEMENT. SO IT'S STILL ON WINTER NIGHTS. BUT ABOVE THAT YOU GET THE RESIDUAL LAYER THAT MAY HAVE HIGH WINDS. THAT CAN MOVE THINGS. AND A 500 TO 1,000-POUND BOMB USING, BLOWS THINGS ABOVE THE LAYER INTO THE RESIDUAL LAYER. IF THERE ARE HIGH LEVEL WINDS THEY WILL MOVE THAT CLOUD THROUGH HIGH LEVEL AIR, NOT TOUCHING THE GROUND. UNTIL MORNING WHEN THE SUN WARMS BOTH LAYERS AND COMES BACK TO GROUND. AND SO THE THEORY IS, WELL -- SO HERE WEATHER CHART SHOWING THAT THERE WAS A HIGH -- A LOW FORM EIGHTS THAT WOULD PRODUCE FROM NORTH TO SOUTH, ON THAT NIGHT, HIGH LEVEL WINDS, AND HERE WE THOUGHT -- WE WERE ABLE TO UNEARTH WEATHER SATELLITE VIEWS. WHAT IS THAT, 7:00 IN THE EVENING BEFORE THE BOMBING, AND JUST REGULAR CLOUDS. THIS WAS WHERE THE CHEMICAL WEAPON STORES, THIS IS WHERE OUR TROOPS WERE. THIS IS A DEBRIS CLOUD. BY 7:00 A.M. THIS IS ALMOST EXTENDED TO OUR TROOPS. HEAR IS A DIFFERENT SATELLITE SHOWING THE SAME THING AT 9:00 P.M. IS THAT 9:00 P.M.? OH, YEAH. 9:00 P.M. AND NOW YOU CAN SEE A CLOUD FORMING BY MIDNIGHT. AND THEN IT GETS BIGGER, REMOVES SOUTH BY 3:00 A.M. BY 7:00 A.M. IT'S NEAR OUR TROOPS. AND BY 10:00 A.M. IT'S RIGHT NEXT TO OUR TROOPS THERE. AND HERE IS A HIGHER RESOLUTION PICTURE. HERE ARE THE TWO CHEMICAL WEAPON STORAGE GOES. YOU SEE A CLOUD RISING AND YOU SEE THIS DIRTY YELLOW FORMATION HERE. THAT'S A DEBRIS CLOUD. THE TROOP FORMATIONS ARE RIGHT HERE. IT'S ENVELOPING THE TROOP FORMATIONS BY 2:30 A.M. WHEN 10,000 NERVE GAS ALARMS GO OFF. WE THINK THIS IS FAIRLY CONVINCING EVIDENCE, AT LEAST THERE WAS SOMETHING COMING DOWN. THE QUESTION, IS IT NERVE GAS? HOW DO YOU PROVE THAT THIS WAS SOMETHING THAT INJURED PEOPLE? SO LET'S SEE. YEAH. OKAY. SO SEEING, THAT I DID A 15 MINUTE MED LINE SEARCH OF GENES AN SARIN. ALL THE ARTICLES WERE WRITTEN BY ONE GUY, BERT LADU AT THE UNIVERSITY OF MI. HE DIED SEVERAL YEARS AGO. HE WORKED A LOT OF THE BIOCHEMISTRY, PARAOX NASE, AN ENZYME THAT LIVES ON THE HDL PARTICLE IN YOUR BLOOD. PAIRED DOWN AS A PESTICIDE. IN THE LIVER. IT'S TRANSFORMED T450, CONVERTED TO PARO OX OPEN, THE POISON. YOU HAVE AN ENZYME, THAT HYDROLIESES IT. IT'S A PROTECTIVE ENZYME. THIS IS THE MOLECULE. WHAT'S INTERESTING IS THERE IS A POLY MOOREISM. >> AND IF I HAVE THE Q FORM, YOUR Q ICO ENZYME HYDRO LIES SARAN BUT NOT VERY GOOD PESTICIDES. THE R IS JUST THE OPPOSITE, HYDROLIESES PESTICIDES BUT NOT NERVE AGENT. IT'S A VERY CONVENIENT GIFT TO HELP UNTANGLE THIS GULF WAR PROBLEM. WE HEALTH DISPARITIESIZE THAT THE PEOPLE WHO GOT -- HE HYPOTHESIZE THAT PEOPLE WHO HEARD THE NERVE GAS GOES OFF IN THEIR AREA, HAD LOW LEVELS OF THE Q ICO ENZYME. SO BURT CONTRIBUTED HIS LAST POSTDOC, WE CREATED A BIO CHEMISTRY LAB FOR JOHN TABER, HIS LOST POSTDOC. WE TOOK OUGHT BURT'S CHEMISTRY ENZYME CHEMISTRY AND CONVERTED IT TO RAPID PRODUCTION, ROW BOTHS SO WE COULD TEST THOUSANDS OF PEOPLE. SO FIRST OF ALL, THOUGH, BACK IN OR ORIGINAL STUDY, BURT COLLABORATED WITH US INITIALLY. WE DID A CASE CONTROL STUDY OUT OF OUR UNIT, AND SENT HIM BLOODS FROM THE -- OTHER THAN OF THE REPRESENTATIVE MEMBERS OF EACH OF THE GROUPS. HERE IS THE Q ISO ENZYME ACTIVITY BLOOD LEVELS IN THE CONTROLS, IN THE SYNDROME ONES, TWOS, AND THREES. LOOKS LIKE THIS MIGHT FIT. BUT IT WAS A SMALL STUDY. WE DIDN'T HAVE ENOUGH TO DO A GENE ENVIRONMENT INTERACTION STUDY. LATER AS I'LL TALK ABOUT, WE DID A NATIONAL STUDY. WHERE WE TOOK A RANDOM SIMPLE OF ALL GULF WAR VETERANS, 8,000 IN ALL. AND DID OUR SURVEY QUESTIONNAIRE AND DEFINED THE CASE IN THE GROUPS. AND THEN SELECTED ALL THE CASES THAT MET THE CASE DEFINITION IN A RANDOM SIMPLE. A GROUP OF 2,000. AND WENT OUT AND GOT BLOOD, DNA AND RNA FROM THESE PEOPLE. AND BROUGHT IT BACK AND DID A STUDY. HERE IS THE SURVEY QUESTION, DID YOU HEAR THE NERVE GAS ALARMS GO OFF IN YOUR AREA WHICH IS NOT SOMETHING YOU FORGET BECAUSE IT'S A CHARACTERISTIC ALARM. YOU'RE TRAINED TO RECOGNIZE. YOU HAVE TO, THEN, GET IN YOUR RUBBER SUIT AND BE AFRAID THAT THERE IS NERVE GAS AROUND YOU. SO YOU DON'T FORGET THAT. DID YOU HAVE THIS EXPERIENCE, YES, NO. AND THIS IS THE RELATIVE RISK OF THE -- OUR CASE DEFINITION, IF YOU SAID YES. OKAY. AND THEN STRATIFIED BY THE LIST QUARTILE OF PO. >> , THE Q ICO ENZYME. THIS WOULD BE THE MOST AT RISK. NOW TO THE HIGHEST QUARTILE WHICH WOULD MAKE YOU THE MOST RESISTANT TO IT. AND IN THE MOST RESISTANT GROUP, HEARING THE ALARMS HAD ONLY A 2.7 FOLD INCREASE IN RISK. 3.9, 5.2, AND IF YOU'RE IN THE MOST SUSCEPTIBLE GROUP YOU HAD AN 8.7, ALMOST NINE FOLD INCREASE IN RISK FOR HEARING THE ALARMS. SO THIS IS A VERY STRONG HIGH LAY STATISTICALLY SIGNIFICANT GENE INTERACTION, VERY CONVICINITIESING EVIDENCE THAT HEARING THOSE ALARMS AND BEING SUSCEPTIBLE TO NERVE AGENT, WHICH IS WHAT THIS IS, IS WHAT CAUSED THE GOLF WAR ILLNESS. OKAY. IF WE CAN -- IN THE QUESTION PERIOD WE CAN TALK ABOUT THIS. AND HERE JUST SUMMARIZES, SHOWS YOU THE PATTERN OF THE RELATIVE RISK AND THE DIFFERENT LEVELS OF GENETICS SUSCEPTIBILITY. THAT'S OUR ANSWER TO WHAT CAUSED THIS. LOOKS LIKE IT REALLY MAY BE A CHEMICAL, LOW LEVEL SERON. NOW, THE NEXT -- WHAT IS THE DISEASE PROCESS? OKAY, IS IT PSYCHOLOGICAL OR ORGANIC? OKAY? AND TO ANSWER THAT, WE FIRST TOOK A SMALL SIMPLE FROM OUR TROUPE TO RAISE HYPOTHESIS. WE TOOK FIVE SYNDROME 1s, 1342 SAID, FIVE SYNDROME 3 AND 20 WELL CONTROLS. AGE SEX EDUCATION MATCHED TO THE SYNDROME 2 AND 3s. THESE WERE YOUNGER AND SEEMED TO BE DIFFERENT. FIRST, WE BROUGHT THEM INTO DALLAS. ROSS PEROT PAID TO FLY THEM TO DALLAS. PUT THEM THROUGH A BUNCH OF NEUROLOGICAL, NEURO PHYSIOLOGICAL, NEURO PSYCHOLOGICAL TESTS. HERE IS THE IMPAIRMENT INDEX, SEPARATES ORGANIC BRAIN DYSFUNCTION FROM PSYCHOLOGICAL THINGS. SYNDROME 2 AND 3 SEEMS TO BE HIGHER THAN CONTROLS. MUCH MORE ABNORMAL. VERTIGO ATTACKS, WHICH TEND TO BE ORGANIC IN NATURE. MOSTLY IN SYNDROME 2 SAID. THE ROTATING CHAIR TESTS, SYNDROME 2. A LITTLE BIT OF 1. ENG WITH CALORIC STIMULATION. IMPAIRED IN ALL 3 SYNDROMES. BRINE STEM EVOKED POTENTIAL SYNDROMES 1 AND 2. AND POTENTIALS OF SPINAL CORD SYNDROME 2 PRIMARILY INCREASED LATENCY IN SYNDROME 2. NOT IN THE OTHERS. SO THIS, THEN, SUGGESTED THAT JUST IN A RAISING SENSE THERE MAY BE SOMETHING REALLY ORGANIC ABOUT THIS. SO WE PUBLISHED THESE. WE SUBMITTED 3 PAPERS TO JAMA. THEY PUBLISHED ALL 3 OF THEM IN THE SAME URN. IS THIS A GOLF WAR SYNDROME, THE FACTOR ANALYSIS, DECIDING THE CASE DEFINITION. EVALUATION OF NEURALLOGICAL FUNCTION, WHAT I SHOWED YOU. THE NEURO PHYSIOLOGICAL TESTS OF THOSE SYNDROMES. AND FINALLY, THE RISK FACTOR DATA IMPLICATING SERON IN SYNDROMES 2 AND 3. SO THIS LED TO THE HYPOTHESIS THAT LOW LEVELS SERON EXPOSURE MAY HAVE DAMAGED, WE WERE THINKING DEEP BRAIN STRUCTURES. THE AMYGDALA, THE HIPPOCAMPUS, BECAUSE THESE ARE DEGENERATING IN HUNTINGTON'S, WILSON'S, AND FARR'S DISEASE. THIS LOOKS JUST LIKE GULF WAR ILLNESS BUT THESE ARE RELENTLESSLY PROGRESSIVE TO SEVERE FATAL RELATIONS. WHICH THE GULF WAR ISN'T. IT GOT WORSE, THEN REMAINED STABLE FOR 24 YEARS. TO ORIENT YOU OF WHAT WE'VE DONE IN 20 YEARS, THAT FIRST SURVEY -- THEN WE BROUGHT THE GUYS IN FOR THE TESTING I DESCRIBED HERE. AND THEN A YEAR LATER WE BROUGHT THEM ALL BACK FOR OUR MORE EXTENSIVE BATTERY OF TESTS. THIS, THEN, REALLY FOCUSED THE HYPOTHESIS, SO THEN WE SPENT ABOUT 7 YEARS DEVELOPING A NATIONAL SURVEY TO DEFINITIVELY SURVEY THE POPULATION TO SEE IF THE SYNDROMES ARE PRESENT MORE GENERALLY IN THE POPULATION. WE PULLED OFF THE SURVEY HERE. AND THEN WE GOT 2,000 BLOODS WHICH WAS ALL THESE PEOPLE, MET THE CASE DEFINITION AND RANDOM SAMPLE OF THE ONES THAT DIDN'T. AND THEN SIMULTANEOUSLY, MY POINTER IS RUNNING OUT. SIMULTANEOUSLY, WE BROUGHT -- WE GOT OUR OWN 3T MAGNET. BROUGHT IN A PHYSICIST, RICHARD BRIGGS FROM THERE WHO WAS A TERRIFIC GUY WHO -- WE INVITED ANYONE WHO WANTED TO PLAY IN OUR SAND BOX TO COME DEVELOP AN IMAGING TECHNIQUE TO LOOK AT GOLF WAR ILLNESS. WE DEVELOPED 6 REALLY GOOD FMRI STUDIES TO LOOK AT SYMPTOMS. THE MOST OUTSTANDING SYMPTOMS. ARTERIAL SPIN LABELING, LOOKING AT BRAIN BLOOD FLOW AND OTHER IDEAS. WE DID THE -- REDID THE GROUP HERE. LOOK AT LONG TERM. WE HAD A TEN YEAR INTERVAL TO SEE WHAT HAPPENED TO THESE GUYS. THEN A SIMPLE MIND FROM THE NATIONAL, WHAT WE CALLED THE NATIONAL SAMPLE. WE HAVE TWO SAMPLES, WE'VE DONE ALL OF THESE ON ALL THESE PEOPLE. AT THE SAME TIME WE DID PRECLINICAL STUDIES IN A MOUSE MODEL THAT WE DEVELOPED BACK HERE TO SEE IF WE COULD FIND OUT HOW SARIN COULD EFFECT THE BRAIN. SO IN THE 19 -- THIS IS THE 1998 STUDY. THIS IS THE 2008-2010 STUDY. SO WE BROUGHT THEM IN AND WOULD HAVE THEM ON A PROTOCOL LIKE THIS. WE PUT THEM IN THE GCRC, CLINICAL RESEARCH CENTER. THEY HAD ALL THESE TESTS EFFICIENTLY DONE IN A WEEK, HAD A RESEARCH NURSE THAT WOULD TAKE THEM AROUND. IT WAS VERY SUCCESSFULLY DONE. HERE THE SORT OF THINGS THAT WE WERE DOING. THAT WAS THE 1998 STUDY, AND THEN WE BROUGHT THEM BACK FOR THE TEN YEARS LATER. FOR THE 2008 TO 2009 AND 2010 STUDY. THIS WAS THE PROTOCOLINGS, MORE ELABORATE. REBROUGHT 3 AT A TIME. YOU CAN SEE HOW WE SCHEDULED THINGS. AND BASICALLY, WE KEPT THAT 3T MAGNET GOING ABOUT 12-13 HOURS A DAY 6 DAYS A WEEK. VERY EXCITING PERIOD OF TIME. SO WHAT IS THE DISEASE PROCESS? FIRST OF ALL, THE MR SPECTROSCOPY FROM THE 1998 STUDY, MR, THOSE THAT DON'T KNOW YOU DEFINE A VOLUME PIXEL OR VOXEL. LIKE A SUGAR CUBE VOLUME OF BRAIN TISSUE. YOU FOCUS THE MAGNET ON THAT. AND YOU DO A SCAN. THE SCAN GIVES YOU A SPECTRUM. THIS IS NMR. YOU GET A SPECTRUM. IN BRAIN YOU GET COLLEEN, AN [INDISCERNIBLE] -- CHOLINE SPIKES. THIS IS FOUND UNNEURONS, A MEASURE OF IN YOUR ONAL HEALTH. SOME MEMBRANES AND ENERGY METABOLISM. I RUSSIAO NAA TO CRETIN OR CHILL LIEN, AND THOSE ARE MEASURES OF BRAIN HEALTH. HERE IS SPECTRUM FROM A TYPICAL CONTROL. YOU SEE A BIG SPIKE IN NAA AND THESE OTHERS. HERE IS A SYNDROME, TYPICAL SYNDROME TWO. SO THE NAA TO CHEATEN LEVEL WOULD BE -- CRETIN LEVEL WOULD BE LOWER. THIS IS THE GROUP SECRETARIES. THE LEFT BASAL CANNINGGIA, THE CONTROLS HERE. THE SYNDROME ONE, NO DIFFERENT. SYNDROME TWO IS GREATLY DECREASED. SYNDROME 3 IS NOT DECREASED. TEEN WE DID A SURVEY IN THE DALLAS VA, RECREATED OTHER SYNDROME 2s, BROUGHT THEM IN AND THEY WERE LOW, TOO. SUGGESTED THAT THERE IS SOME CHEMICAL PROBLEM AFFECTING NEURONS POSSIBLY IN THE DEEP BRAIN STRUCTURES. THIS WAS REPLICATED BY A GROUP, MIKE WEINER AT UCFS, TOOK THE RIGHT BASIL GANG GEIA, OUR MAIN FINDING AND RECREATED VETERANS OUT OF THE GULF WAR CLINIC. WE WENT OUT AND HELPED THEM DO THIS, PICKED SUITABLE PEOPLE THAT SEEMED TO LOOK LIKE OUR SYNDROME TWO GROUP. HE FOUND SOMETHING SIMILAR. AND THEN DR. MENIN AT THE JACKSON MISSISSIPPI VA LOOKED AT THE HIPPOCAMPUS AND FOUND SOMETHING SIMILAR IN HIS GROUP. MIKE THEN DID A LARGER STUDY. HE ENDED UP ADVERTISING BECAUSE HE HAD TROUBLE RECRUITING. HE RAN INTO THIS PROBLEM, TWICE AS MANY PEOPLE THAT THINK THEY HAVE IT THAT DON'T HAVE IT, SO HE DIDN'T FIND ANY DIFFERENCE. BUT AGAIN, BACK IN 2008, WE'VE RECENT LIENALED THAT DATA OF THE HERE IS THE CONTROLS. THIS IS THE RATIO AGAIN. HERE ARE THE PROPOSALS ALL GROUPED TOGETHER. YOU CAN -- SYNDROMES AGAIN. LEFT BASAL AND RIGHT BASAL GANGGIA AS WELL. SO IT APPEARS TO HAVE PERSISTED IN THESIS A AND WE'RE NOW ANALYZING THE NATIONAL SAMPLE. WE LOOKED, THEN, FOR A CIRCADIAN VARIATION IN HEART RATE VARIABILITY. AS YOU BREATHE IN, YOUR HEART RATE SLOWS DOWN, BREATHING OUT IT SPEEDS OUT. IT'S A NORMAL -- IT'S CONTROLLED BY THE VEGAS NERVE. IT'S ONE OF THE ONLY PURE MEASURES OF SYMPATHETIC NERVE ACTIVITY. HERE IS THE 24 HOUR PERIOD. FROM 7:00 A.M. TO 67:00 A.M. THE NEXT MORNING. -- 6:00 A.M. THE NEXT MORNING. HEART RATE VARIABILITY GOES UP USUALLY, AT NIGHT, WHEN YOU SLEEP. AS YOU HAVE THIS BIG [INDISCERNIBLE] OUTPOURING. IN THE NORMALS. YOU SEE THE SICK GULF WAR VETERANS DIDN'T HAVE THAT. WE DON'T SEPARATE THE SYNDROMES. WE DIDN'T HAVE ENOUGH TO SEPARATE THE SYNDROMES HERE. IN 2008, WE DOPPLER RADAR IT AGAIN. THIS TIME WE DID A FULL WORKUP. SOME OF YOU MAY STEVE, THE DEPUTY CHAIRMAN OF NEUROLOGY, AND GILL WOLF, CHAIRMAN AT ABOVE LOFT, NOW. THEY DID A FULL BATTERY OF STUDIES, AUTO NOMIC SYMPTOM PROFILE, BREAKING DOWN THE VARIOUS SYMPTOMS INTO SUBSCALES LOOKING AT VARIOUS ASPECTS OF AUTO NOMIC FUNCTION. THE MAYO CLINIC BATTERY OF TESTS, AND THEN WE REPEATED THE HALTER MONITOR LOOKING AT -- TO REPEAT THAT. WHAT THEY FOUND IS THIS IS THE QUESTION, THE SYMPTOM QUESTIONNAIRE DOMAIN. AND THIS IS THE DEGREE OF ASSOCIATION OF THIS SYMPTOM DOMAIN WITH OUR SYNDROMES AND CONTROL CLASSIFICATION. SO THIS IS HIGHLY ASSOCIATED, THESE ARE NOT ASSOCIATED MOVE AS YOU SEE, THE SYMPTOMS THAT ARE MOST HIGHLY ASSOCIATED WITH OUR SYNDROME GROUPS ARE THE COLON EDGERIC SYMPTOMS. THE ADEN EDGERIC ARE NOT ASSOCIATED. IN THE OBJECTIVE TESTS, THE QSART WAS THE ONLY ONE THAT SHOWED A RELATIONSHIP TO THE SYMPTOMS. PSEUDO MOTOR REFLEX TEST. YOU STIMULATE A PART OF THE SKIN, SEE HOW MUCH SWEAT OCCURS. THIS WAS MOST ABNORMAL IN THE SYNDROME TWOS IN THE FEET. NEXT IN THE ANKLE, NEXT IN THE UPPER LEG AND LEAST IN THE ARMS. SO THIS IS A PATTERN OF A LENGTH RELATED PERIPHERAL NEAROPATHY. THE LONGEST THEY HAVE BEENS BEING MOST EFFECTED. THIS IS A COLIN EDGERIC, ADRENERGIC FUNCTION. IT'S THE CHOLINERGIC ASPECT OF THE PERIPHERAL NERVOUS SYSTEM. THIS IS WHAT WE FOUND. AND YOU SEE SAME THING, THE NORMALS INCREASE AT NIGHT PULMONARY THE SYNDROMES DON'T -- BUT THE SYNDROMES DON'T. WE HAD NOW ENOUGH TO SEPARATE THE THREE SYNDROMES. 1, 2, AND HERE IS -- I'M SORRY 3. AND HERE IS 2. HAS ABSOLUTELY NO EVIDENCE OF INCREASING A PARASYMPATHETIC CHOLINERGIC SYMPTOM AT NIGHT. ONE OF THE MAIN COMPLAINTS, UNREFRESHING SLEEP OR INSOMNIA. A LOT OF THEM DON'T HAVE INSOMNIA, BUT THEY WAKE UP THE NEXT MORNING AS IF THEY HADN'T SLEPT. AND THIS IS, YOU KNOW, THE PAR ASYMPATHETIC OUTPOURING IS THOUGHT TO BE RELATED TO THOSE RESTORATIVE ASPECTS OF SLEEP. NOW. THIS LED US TO ANOTHER SET OF EXPERIMENTS. IF SOLDIERS SURED DAMAGE TO COLON URGEN NEURONS OR RECEPTORS IN THE BRAIN FROM SARIN NERVE AGENTED -- REMEMBER, SARIN GETS IN YOUR BRAIN AND STAYS THERE. INACTIVATES SO YOU GET AN OUT POURING ON EXCESS OF CHOUGH LIEN. SO YOU GET A CHOLINERGIC STIMULATION THAT LASTS DAYS TO WEEK. SO A SUSTAINED STIMULATION. SO THE IDEA THAT THAT DAMAGE RECEPTORS, CHOLINERGIC RECEPTORS NEURONS IN THE BRAIN. TO TEST THAT, WE REPEATED AN OLD EXPERIMENT THAT WAS DONE IN EARLY ALZHEIMER'S THAT IMPLICATED COLON URGEN FUNCTION IN RECEPTORS IN THE BRAIN. WE DID A 60 MINUTE INFUSION WITH SALINE, INJECTED THE EXPECT MARKER. OF BLOOD FLOW. AND THEN WE DID A SPE CT SCAN TO GET AN IMAGE. THE BRIGHT IS A HIGHER BLOOD NO. WE CAME BACK 3 DAYS LATER AFTER THIS MARKER WAS GONE. THIS TIME WE SPIKED THE IV, A COLON URGIC STIMULANT. THE IDEA -- IF THESE CHOLINERGIC RECEPTORS ARE DAMAGED, THE CASES WOULD REACT DIFFERENTLY TO THIS STIMULATIONS THAN THE ALCOHOLS. THAT WOULD, THEN, IN PLIICATE CHOLINERGIC RECEPTORS OR NEURONS. WHAT YOU DO, HERE IS A PIXEL OR AREA OF PIXELS. YOU BASICALLY DO A LARGE SET OF T. TESTS. 200,000 VOXELS IN A SPECT BRAIN. YOU DO A T. TEST BETWEEN THE GROUPS. YOU HAVE 200,000 TEST AND VERY HARSH COMPARISONS CORRECTION. AND SO IT'S VERY HARD TO GET ANYTHING BUT A VERY LARGE LESION TO BE SIGNIFICANT SUCH THAT MANY PEOPLE JUST ABANDON THE CORRECTION BECAUSE THEY NEVER GET ANYTHINGSO WE DID THIS. WITH USING STATISTICAL PARAMETRIC MAPPING, THE COMMON PROGRAM THAT DOES THIS. WE DIDN'T FIND ANYTHING. DUE TO THE HARSH CORRECTION, NOTHING WAS SIGNIFICANT BETWEEN THE GROUPS. SO I WENT OUT TO SMU, HAS A VERY, VERY STATISTICS DEPARTMENT. SOME OF WHOM I KNOW. THIS IS WAYNE WOODWARD, BILL, DICK, MYSELF, AND TWO OTHERS GRADUATE STUDENTS WHO GOT TROOP FORMATIONS Ph.D.s -- WHO GOT THEIR Ph.D.s ON THIS. THEY APPLIED GEOSTATISTICS. THE STATISTICS OF ALL OIL PROSPECTING, MINERAL PROSPECTING. THERE IS A BODY OF STATISTICS SHOWING WHEN YOU HAVE A VOLUME DATASET, THREE DIMENSIONAL, PIXELS THAT ARE CLOSE TOGETHER TEND TO BE CORRELATED JUST DUE TO THE LIMITS OF RESOLUTION OF YOUR SCANNER. OR YOUR MEASUREMENT. SO PIXELS ARE RIGHT NEXT TO EACH OTHER CORRATED, SO PIXELS -- SO NO SPACE BETWEEN THEM. HIGHLY -- VERY LOW VARIANTS. AS YOU GET FURTHER AWAY FROM THAT PIXEL, THE VARIANTS GOES UP. THE CORRELATION GOES DOWN. AND UNTIL YOU FINALLY REACH A POINT AT WHICH THIS IS NO LONGER TRUE AND DOESN'T CHANGE AFTER, THAT AS YOU GET FURTHER AWAY. CLOSE TOGETHER PIXEL RAZZ HIGHLY CORRELATED. THAT MEANS THAT THEY'RE NOT 200,000 PIECES OF INFORMATION. THERE IS ONLY 1500, BECAUSE MOST OF THEM ARE TELLING YOU THE SAME THING. THEY'RE IN A NEIGHBORHOOD, ALL TELLING YOU THE SAME. SO THEY USED A TECHNIQUE CALLED [INDISCERNIBLE] WHICH MEANS YOU DEFINE THIS STRUCTURE IN EVERY BRAIN AREA. YOU FIND HOW FAR YOU HAVE TO GO BEFORE THIS GOES AWAY. THEN YOU PRODUCE LITTLE BLOCK, WE CALL THEM BLOCKS. THAT ARE HIGHLY CORRELATED WITHIN A BLOCK AND YOU TAKE A VARIANTS -- ADJUSTED MEAN OF THE SIGNAL IN THAT BLOCK AND USE THAT TO REPRESENT THE BLOCK, AND THEN INSTEAD OF A CORRECTION 200,000, YOU HAVE A CORRECTION OF 1500. OR ANOTHER KIND OF CORRECTION THAT'S MORE EFFICIENT. BUT -- SO YOU CAN SEE HERE, WE DEFINE BLOCKS. IN THE THALAMUS WHERE IT MATTERS, YOU MAKE THEM ANATOMICALLY CORRECT. YOU TRY TO DEFINE THEM ACCORDING TO THE NUCLEI OF THE THALAMUS. ELSE WHERE I DEFINE BLOCKS. THEN YOU DO IT AND HERE IS WHAT WE FOUND. HERE IS THE CONTROL GROUP SYNDROME ONE, SYNDROME TWO, SYNDROME THREE, AS YOU SEE DOWN HERE. THIS IS THE SALINE, THE GREEN IS SALINE. THE RED IS STIMULATED, CHOLINERGIC STIMULATED. IT'S NORMAL FERROCHOLINATE SLOW YOUR BRAIN DOWN. THE SYNDROMES TWOS HAVE A PARADOXAL OPPOSITE RESULT. IT INCREASES THEIR BLOOD BRAIN NO. THE METABOLISM OF THE NEURONS. THIS HAPPENS THROUGHOUT THE BRAIN. BUT IT'S MOST -- THERE IS ACTUALLY A STRONG GROUP STRUCTURE INTERACTION. SOME AREAS OF THE BRAIN STRONGLY THIS HAPPENS. OTHER AREAS FAIRLY WEEK, SOME AREAS DOESN'T OCCUR. IT'S WIDELY DISTRIBUTED. IN SOME AREAS, REALLYING DRAMATIC. AND THE ONES WHERE IT'S REALLY DRAMATIC SHOWN DOWN HERE WITH THE LOWER AND MEDIAL PART OF THE HEAD, THE RIGHT HIPPOCAMPUS, ACTUALLY THE AMYGDALA AND SOME IN THE PU TANEM, WERE THE MOST DRAMATIC AREAS. WE, THEN, DEVELOPED A DISCRIMINATE ANALYSIS WITH 17 OF THOSE BLOCKS IN THE BRAIN. AND THIS IS THE WAY -- THIS IS HOW WELL WE CAN CLASSIFY DECAYS AND CONTROLS HERE. SYNDROME ONES, AT THIS AND THREES AND THE CONTROLS. AS YOU CAN SEE THE SYNDROME THREES AND TWOS ARE ON THE SAME SIDE OF THE CONTROL GROUP, ALTHOUGH AT DIFFERENT PLACES. BUT THE SYNDROME ONES ARE ALL THE WAY ON THE OTHER SIDE OF THE CONTROL GROUP. I SHOWED YOU SOME INFORMATION A WHILE AGO THAT WOULD -- WE SHOULD HAVE ANTICIPATED THIS. AND NOTICE WHAT WOULD HAPPEN IF YOU DIDN'T DEVELOP THESE THREE GROUPS? YOU HAD ALL THREE OF THESE IN ONE GROUP. AND YOU DID THIS AT THE TIMES. WHAT WOULD HAPPEN. >> -- IT WOULD ALL BE OVER THE CONTROL GROUP. YOU WOULD SEE NOTHING. OKAY? AND -- SO THEN WE CAME ALONG TEN YEARS LATER AND REPEATED THE SAME THING. THIS TIME INSTEAD OF A SPECT WE USED ARTERIAL SPIN LABELING, MR, AND HERE YOU HAVE RADIATION EXPOSURE. AND YOU SEE TEN YEARS LATER THE SAME GROUP, THE CONTROL SYNDROME ONE, TWO, AND NOW THREE IS GOING THE OTHER WAY. SUGGESTING THAT THESE PEOPLE MAY HAVE THE SYNDROME 3 SAID, MAY HAVE BECOME MORE LIKE THE SYNDROME 2 SAID. HERE ARE THE DIFFERENT SCORES. YOU CAN SEE THESE ARE HIGHLY SIGNIFICANTLY DIFFERENT THAN THOSE. NOW, WHAT'S GOING ON? WE'RE NOT SURE WHAT'S GOING ON. BUT HERE IS WHAT WE THINK. THAT SARIN IN ANY CONCENTRATION SELECTIVELY DAMAGES INHIBITORY 2 RECEPTORS, THERE ARE 5, M1-5. 1, 3, 4, AND 5 TEND TO BE SOMETIMELY. M2s DENIED TO BE DOMINATE, INHIBITORY. IF YOU GIVE A CHO, THE BRAIN WILL SLOW DOWN. IF YOU FOOT YOUR FOOT ON THE GAS AND BRAKE, THE CAR WILL SLOW DOWN. THE BRAKE IS MORE POWERFUL THAN THE GAS. SO THE IDEA IS WHEN YOU STIMULATE THESE YOU GET A DECREASE EXCEPT WHERE YOU GOT M2 RECEPTORS DAMAGED, SO YOU DON'T HAVE AN INHIBITOR RESPONSES. YOU GET THE EXRITA RESPONSE OF THE M1, 3, 4, AND 5 RECEPTORS. THIS WOULD ACCOUNT, THEN, FOR THE AROUSAL, YOUR BRAIN IS CONSTANTLY BEING OVERSTIMULATED. OKAY? AND THE FATIGUE AND INSOMNIA, BECAUSE YOU'RE WORN OUT. THIS MAY BE OVERSIMPLISTIC. ALSO, IT WOULD ACCOUNT FOR THE PARRY SYMPATHETIC DYSFUNCTION. YOU'RE LOSING YOUR COLON EDGERIC STIMULATION. YOUR RESPONSE IS ABNORMAL, DAMAGED. AND WOULD EXPLAIN THIS PARADOXICAL INCREASING BLOOD FLOW PATTERN. WE THOUGHT THIS WAS A PRETTY CLEVER IDEA. THEN WE -- READ A PAPER IN 2011 FROM EDDIE BAUER AND HER GROUP, IN THE ISRAELI MEDICAL RESEARCH INSTITUTE WORKING WITH THEIR DEFENSE DEPARTMENT. THEY WERE DOING RAT STUDIES OF SARIN. AND WHEN YOU GIVE SARIN INHALATION TO RATS, STIMULATING THE GOLF WAR EXPOSURE, OVER TIME, THE SARIN -- THE SARIN EXPOSURE AT POINT 8LD50, OR LCT50, SAME THING, THEY FOUND IT ACTUALLY DAMAGES M2 RECEPTORS AND CAUSES THEM TO LOSE AFFINITY OR DECREASE AFFINITY TO CHOLINE. THE RECEPTORS DON'T BIND AS WELL. BUT, THE NUMBER OF RECEPTORS INDICATED BY THE B MAX HERE, THE BINDING MAXIMUM BINDING, THE NUMBER OF RECEPTORS GOES UP. BUT THE BINDING AFFINITY GOES DOWN. THIS IS THE ASSOCIATION CONSTANT SO THE BINDING IS GOING DOWN. SO WHAT WE THINK IS HAPPENING IS HERE IS THE M2 RECEPTOR, 7 UNIT TRANSMEMBRANE RECEPTOR. BINDS, DOES THE STIMULATION, AND THEN IT'S INTERNALIZED INTO ENDOSOMES. SOME ARE DESTROYED, REGENERATED, OTHERS ARE -- JUST REMOVED AND MOVED BACK UP AND PUT BACK IN THE MEMBRANE TO BE IMMEDIATELY RECYCLED. AND THIS IDEA IS THAT SARIN IS SOMEHOW EITHER DAMAGING THIS RECYCLING THING OR BEING INCORPORATED INTO THE RECYCLED PARTICLE. SO THAT THIS IS NO LONGER VERY FUNCTIONAL. SO SOME OF THE RECEPTORS ARE NO LONGER FUNCTIONAL. THE BRAIN RECOGNIZES THAT AND CREATES MORE RECEPTORS. BUT NEVER CAN CATCH UP. SO THAT'S WHAT WE THINK IS THE LEADING HYPOTHESIS. OKAY. FINALLY, HOW DO YOU DIAGNOSE IT? WE NEED A COST EFFECTIVE TEST. WELL, WE DID A BUNCH OF THINGS, EEG, ALL THE fMRI. THE ONE THING THAT STICKS OUT LIKE IT MIGHT WORK IS THIS EEG STUDY. WE DID IN THE 2008 AND WE'RE REPLICATING IT IN THE NATIONAL SAMPLE NOW. 64 CHANNELS NEURO SCAN EEG, 64 ELECTRODES. OKAY. CONTINUOUSLY RECORDING. TEN MINUTE RESTING SCAN. OKAY? AND OVER THAT TEN MINUTES, TEN, ONE MINUTE BLOCKS, ALTERNATING EYES OPENED, EYES CLOSED. TEN MINUTES YOU LIE THERE AND OPEN YOUR EYES FOR A MINUTE AND CLOSE YOUR EYES FOR A MINUTE. YOU DO THAT FOR TEN MINUTES. THAT'S IT. YOU GET UP AND LEAVE SO IT DOESN'T COST MUCH. IT WOULD BE VERY EASY TO DO. RECORDING IN DC MODE, 1KH SIMPLE RATES. HERE IS WHAT WE FIND. THIS IS COMPARED TO 15 CONTROLS. WHO UNDERWENT THIS. SO WHEN HE COMPARE THE SYNDROME ONES WITH THE CONTROLS, HERE IS WHAT'S DIFFERENT. IN THE POSTERIOR HEMISPHERE. HERE IS EYES OPEN AND EYES CLOSED. EYES OPEN, EYED CLOSED. HERE IS THE CONTROLS, SYNDROME ONE. WHEN YOU OPEN YOUR EYES, NORMALLY, YOU GET THIS BIG DROP AND THIS IS IN THE ALPHA RANGE. HERE IS DELTA, THEDA, ALPHA, BETA. THE REGIONS. IN THE ALPHA REGION, YOU NORMALLY GET A BIG DROP WHEN YOU OPEN YOUR EYES. THE DROP IS LESS IN THE SYNDROME ONES, WE DON'T KNOW WHAT THIS MEANS. WE'RE NOT LOOKING TO INTERRUPT THIS. WE WANT -- INTERPRET THIS. WE WANT SOMETHING THAT WOULD DIFFERENTIATE THE GROUPS. HERE IS SYNDROME TWOS, MOST SERIOUSLY ILL. A LITTLE BIT IN THE APTEARIER HEMISPHERE. NORMALLY, WHEN YOU HAVE YOUR EYES OPEN AND CLOSE THEM, YOU GET A GREAT INCREASE, OKAY? IN THE ALPHA RANGE. NOT IN THE SYNDROME TWOS. SO IT'S -- YOU GET SOMETHING SIMILAR IN THE SYNDROME THREES. REMEMBER, THOSE ARE RELATED. MAYBE THE SAME THING. AND YOU GET -- BUT IT'S NOT AS BAD AS HERE. IN THE SAME ALPHA RANGE. BUT IN ADDITION TO -- SO IT LOOKS LIKE THESE THREE ALL OF SOMETHING GOING ON IN THE POSTERIOR AREA. THAT LOOK -- ALL IN THE SAME ALPHA RANGE. SO KIND OF THINKS MAYBE THERE IS AN OVERALL GOLF WAR SYNDROME. THESE ARE MAYBE MORE PROFOUND OR SOMETHING. YOU LOOK FURTHER, IN THE SYNDROME TWOS AND THREES, YOU GET THIS BIG POSTERIOR REGION. THAT IS NOT AN INTERACTION, IT'S A MAIN EFFECT IN THAT YOU GET THIS BOTH EYES OPEN AND EYES CLOSED, THIS HUGE SLOWING, THIS HUGE INCREASE IN DELTA ACTIVITY. THIS IS SLOW WAIVE. YOU MIGHT HAVE HEARD IN METABOLIC ENCEPHALOPATHIES OR BRAIN LESIONS YOU GET SLOWING OF THE EEG. THIS IS MASSIVE SLOWING IN THIS AREA. IN THE SYNDROME '3, YOU GET THE FRONTAL AREA, PROMPT -- PRIMARILY LATERALIZED TO THE LEFT YOU GET SOMETHING SIMILAR. NOT SINK HOLE LAR. IT'S -- NOT SIMILAR. IT'S IN THE BETA RANGE SO WHEN YOU OPEN YOUR -- SORRY. WHEN YOU CLOSE YOUR EYES -- WHEN YOU OPEN YOUR EYES -- SORRY. WHEN YOU CLOSE YOUR EYES, NORMALLY YOU GET A DECREASE IN BETA. THIS IS ALERT HYPER AROUSAL. WHEN THE SYNDROME 3s CLOSE THEIR EYES THEY DON'T GET A MUTING OF THIS HYPER AROUSAL ANXIETY INSOMNIA THING. IT STAYS WHEN THE EYES ARE CLOSED. OKAY? SO -- YEAH, I'M ABOUT DONE. SO THAT'S BASICALLY IT. ONE FINAL WORD. HOW DO YOU TREAT IT. >> WE DON'T KNOW. AND SO WE STILL HAVE TWO QUESTIONS. UNTIL WE ANSWER THESE, I DON'T THINK WE'LL GET BY BECAUSE WHO WANTS TO DIAGNOSE A DISEASE WHERE YOU DON'T HAVE A TREATMENT AND YOU DON'T KNOW HOW TO PREVENT IT? FINAL WORD, CAN WE PREVENT IT? I PRESENTED ALL THESE THINGS BACK IN 1997 AFTER THOSE JAMA PAPERS. AND EVEN THOUGH THERE WAS A LOT OF POLITICAL ANXIETY OVER THIS, THEY CONTROL THE PILLS, CHANGED THE POLICY ON THAT. THEY CHANGED THE POLICY ON BOMBING SARIN AND CHEMICAL WEAPONS. REMEMBER IN SYRIA RECENTLY WHEN THEY WERE ACCUSED OF USING CHEMICAL WEAPONS AGAINST THE REBELS AND SO FORTH, THERE WAS INITIAL STIR, CONGRESSIONAL PEOPLE WERE STAYING WE GOT TO BOMB THOSE CHEMICAL WEAPONS. THAT LASTED ABOUT THREE DAYS. YOU NEVER HEARD ABOUT IT AGAIN. SO I THINK THEY INTERNALIZED THIS. I THINK THERE IS BUY IN, IN THE DEFENSE DEPARTMENT THAT THESE THINGS ARE REAL AND WE WANT TO AVOID THIS IN THE FUTURE. BUT THE QUESTION IS, WE NEED TO FINISH THE RESEARCH AND FIGURE OUT A TREATMENT BECAUSE WE MAY KNOW WHAT THIS IS. THAT'S IT. [APPLAUSE] TIME FOR QUESTIONS? SORRY I WENT OVER. >> [INAUDIBLE QUESTION] >> A GOOD QUESTION. I THINK OUR STUDIES RAISE A LOT OF IDEAS LIKE THAT. AND WE DON'T KNOW WHY THAT ALPHA DISTURBANCE IS THIS. WE CAN'T REALLY -- AT LEAST YET. I DON'T THINK WE CAN EVEN POSIT AN IDEA WHY. BUT YEAH, I THINK AT SOME POINT WE NEED TO TRY TREATMENTS THAT LOOK LIKE THEY WOULD BE REASONABLE REACTIONS TO THIS, SEE IF VETERANS WOULD BE BETTER. BUT YEAH. >> [INAUDIBLE QUESTION] IS THERE A BRAIN COLLECTION, THE ANSWER IS NO. WE PRODUCE ANIMAL MODELS OF PESTICIDE, SOME SIMILAR PROPERTIES TO SARIN, SOME DIFFERENT. WE'VE GOTTEN SOME PROMISING MIMRY DATA. THOSE EXPERIMENTS WERE NEVER FINISHED. WE DON'T KNOW THE ANSWER. YOUR ANSWER -- YOUR QUESTION IS EXACTLY THE RIGHT QUESTION. BUT SOME RESEARCH NEEDS TO BE DONE BUT THERE IS A LOT OF CONCERN ABOUT DOING RESEARCH ON THIS. IT HASN'T BEEN DONE. [INAUDIBLE QUESTION] >> ANY CASES IN KUWAITIS? YOU WOULD EXPECT -- KUWAIT IS NOT A DEMOCRACY. AND SAUDI ARABIA. AND SO YOU CAN IMAGINE THERE IS CONCERN HERE. THERE IS NO BAY THAT THAT WOULD -- STUDIES WOULD BE DONE THERE. IN THE WAY THAT THEY SHOULD BE DONE. HOWEVER, I GOT -- WHEN WE FIRST PUBLISHED OR JAMA PAPERS, WE HAD AN OUT POURING OF RESPONSE FROM VETERANS, AND OTHER RESEARCHERS. AND I MET A LOT OF PEOPLE, AND THEN ONE DAY I GOT AN E-MAIL FROM AN UNDESIRABLE ADDRESS THAT IDENTIFIED HIMSELF AS A CIA PERSON. SENT BE TWO ABSTRACTS. AND ONE OF THEM WAS AN ABSTRACT -- THESE WERE ABSTRACTS FROM A PROPHYLACTIC TYPE MEETING IN -- PROPAGANDA TYPE MEETING IN IRAQ. THEY WERE TRYING TO SHOW -- IT WAS A CONFERENCE ON THE HEALTH -- BAD HEALTH EFFECTS OF THE EMBARGO THAT WE HAD ON IRAQ. SO IT WAS TRYING TO -- BUT THERE WAS ONE ABSTRACT THAT THE GUY SENT ME, THE GUY OR GIRL, I DON'T KNOW WHO IT WAS, ENT DOCTOR. WHO DESCRIBED AN EMDEMIC OF EYE ABNORMALITIES. COMBINED WITH CLINICAL SYMPTOMS HE DIDN'T REALLY DESCRIBE. AND HE SAYS THIS HAS BEEN GOING ON FOR MONTHS. FROM SOUTHERN IRAQ. AND HE SAID IT'S BEEN GOING ON FOR MONTHS AND WE'RE NOW DOWN TO ONLY ABOUT 20 OR 30 CASES A WEEK. SO -- WHO KNOWS. >> THANK YOU VETERAN. GREAT. [APPLAUSE] GREAT HONOR TO BE HERE.