1 00:00:05,720 --> 00:00:10,080 >> WELCOME TO THE SECOND SESSION 2 00:00:10,080 --> 00:00:15,000 OF THE 20TH YEAR OF DEMYSTIFYING 3 00:00:15,000 --> 00:00:19,960 MEDICINE. 4 00:00:19,960 --> 00:00:22,360 FOR THOSE WHO ARE TUNING IN 5 00:00:22,360 --> 00:00:24,360 PERHAPS FOR THE FIRST TIME, 6 00:00:24,360 --> 00:00:26,880 PERHAPS A WORD OF EXPLANATION IS 7 00:00:26,880 --> 00:00:29,520 TO FIRST POWERPOINT HERE. 8 00:00:29,520 --> 00:00:31,320 THIS IS THE BROOKLYN BRIDGE 9 00:00:31,320 --> 00:00:35,520 WHICH IS THE LOGO FOR THIS 10 00:00:35,520 --> 00:00:38,480 COURSE, IT IS BASICALLY A COURSE 11 00:00:38,480 --> 00:00:41,200 IN BRIDGE BUILDING, CONNECTING 12 00:00:41,200 --> 00:00:42,120 DIFFERENT DISCIPLINES IN SCIENCE 13 00:00:42,120 --> 00:00:44,040 BIOLOGY ENGINEERING AND 14 00:00:44,040 --> 00:00:44,480 MEDICINE. 15 00:00:44,480 --> 00:00:46,320 WE ARE LIKE THE TWO INDIVIDUALS 16 00:00:46,320 --> 00:00:49,920 ON THE CAT WALK, WHO TODAY ARE 17 00:00:49,920 --> 00:00:51,920 DISCUSSING THE SPLIT PERSONALITY 18 00:00:51,920 --> 00:00:53,480 THAT TWO IMAGES OF HELICOBACTER 19 00:00:53,480 --> 00:00:54,640 PYLORI. 20 00:00:54,640 --> 00:01:02,960 PRIOR TO ABOUT 1990, GASTRITIS 21 00:01:02,960 --> 00:01:04,720 AND PEPTIC ULCER DISEASE WERE 22 00:01:04,720 --> 00:01:06,000 MOST COMMON MEDICAL ILLNESSES. 23 00:01:06,000 --> 00:01:09,520 IT WAS GENERALLY BELIEVED THEIR 24 00:01:09,520 --> 00:01:11,400 ETIOLOGY WAS RELATED TO 25 00:01:11,400 --> 00:01:13,120 SECRETION OF HYDRO COLORRIC ACID 26 00:01:13,120 --> 00:01:17,400 BY THE STOMACH PLUS ADDITIONAL 27 00:01:17,400 --> 00:01:20,280 FACTORS TERM STRESS. 28 00:01:20,280 --> 00:01:21,480 THE STRESS A DRUG, IT COULD 29 00:01:21,480 --> 00:01:25,360 BE ALCOHOL, DIET, OR SO CALLED 30 00:01:25,360 --> 00:01:28,280 TYPE A PERSONALITY. 31 00:01:28,280 --> 00:01:31,640 THE TREATMENT INVOLVED ANTACID 32 00:01:31,640 --> 00:01:33,800 AND FOR COMPLICATIONS SURGERY. 33 00:01:33,800 --> 00:01:35,120 TREATMENT ALSO SOMETIMES 34 00:01:35,120 --> 00:01:38,600 INVOLVED COUNSELING AND OTHER 35 00:01:38,600 --> 00:01:41,160 THERAPIES BASED ON THE PREMISE 36 00:01:41,160 --> 00:01:47,720 OF THIS BEING A COMBINATION OF 37 00:01:47,720 --> 00:01:49,280 PSYCHOLOGIC AND PHYSIOLOGIC 38 00:01:49,280 --> 00:01:50,800 DISEASE. 39 00:01:50,800 --> 00:01:53,280 THE COMPLICATIONS WERE SERIOUS. 40 00:01:53,280 --> 00:01:56,480 THERE WERE PERFORATION, 41 00:01:56,480 --> 00:02:01,800 HEMORRHAGE, AND RELATIONSHIP OF 42 00:02:01,800 --> 00:02:03,280 GASTRIC CANCER PARTICULARLY TO 43 00:02:03,280 --> 00:02:04,440 GASTRIC ULCERS. 44 00:02:04,440 --> 00:02:10,040 THE SURGERY WAS IDENTIFIED BY A 45 00:02:10,040 --> 00:02:11,360 WIDE VARIETY OF NAMES OF 46 00:02:11,360 --> 00:02:12,480 INDIVIDUAL SURGEONS WHO PUT 47 00:02:12,480 --> 00:02:13,720 THEIR OWN NAME ON THEIR 48 00:02:13,720 --> 00:02:15,960 PARTICULAR PROCEDURE. 49 00:02:15,960 --> 00:02:22,320 BUT ALMOST ALL INVOLVED SOME 50 00:02:22,320 --> 00:02:24,280 TOTAL GAS TREKTOMY WITH OR 51 00:02:24,280 --> 00:02:25,840 WITHOUT SEGREGATION OF THE VAGUS 52 00:02:25,840 --> 00:02:27,680 NERVE WHICH HOPED TO REGULATE 53 00:02:27,680 --> 00:02:32,120 HYDRO COLORRIC ACID SECRETION. 54 00:02:32,120 --> 00:02:33,760 UNTIL 1990 THINGS BEGAN TO 55 00:02:33,760 --> 00:02:35,640 CHANGE IN UNEXPECTED DRAMATIC 56 00:02:35,640 --> 00:02:36,440 IMPORTANT WAY. 57 00:02:36,440 --> 00:02:38,440 SUDDENLY THE CONCEPT THAT PEPTIC 58 00:02:38,440 --> 00:02:40,520 ULCER DISEASE AND GASTRITIS 59 00:02:40,520 --> 00:02:45,080 COULD BE A BACTERIAL DISEASE WAS 60 00:02:45,080 --> 00:02:45,840 EARTH SHAKING. 61 00:02:45,840 --> 00:02:48,160 THE TREATMENT BEGAN TO CHANGE, 62 00:02:48,160 --> 00:02:49,960 THE PROTON PUMP INHIBITORS TO 63 00:02:49,960 --> 00:02:55,600 BLOCK ACIDS SECRETION AND 64 00:02:55,600 --> 00:02:57,200 ANTIBIOTICS TO AFFECT BACTERIA 65 00:02:57,200 --> 00:02:57,400 FOUND. 66 00:02:57,400 --> 00:02:59,160 THE RATE OF COMPLICATIONS 67 00:02:59,160 --> 00:03:04,440 DECREASED TREMENDOUSLY AND SOME 68 00:03:04,440 --> 00:03:05,960 TOTAL GASTRECTOMY IS NOWHERE 69 00:03:05,960 --> 00:03:07,600 NEAR WHAT IT WAS LIKE IN 70 00:03:07,600 --> 00:03:11,720 PRE-1990 ERA. 71 00:03:11,720 --> 00:03:17,280 HOW DID ALL THIS COME ABOUT? 72 00:03:17,280 --> 00:03:18,880 HOW DID THIS AMAZING CHANGE 73 00:03:18,880 --> 00:03:19,680 OCCUR? 74 00:03:19,680 --> 00:03:28,800 IT BEGAN ABOUT 1981 WHEN IN 75 00:03:28,800 --> 00:03:30,440 PERT, AUSTRALIA, IF YOU WANTED 76 00:03:30,440 --> 00:03:32,960 TO FIND A CITY FURTHER FROM THE 77 00:03:32,960 --> 00:03:35,000 EAST COAST OF THE UNITED STATES, 78 00:03:35,000 --> 00:03:35,800 YOU GO TO PERT. 79 00:03:35,800 --> 00:03:36,560 A BEAUTIFUL CITY ON THE WEST 80 00:03:36,560 --> 00:03:38,160 COAST OF AUSTRALIA, SURROUNDED 81 00:03:38,160 --> 00:03:41,880 BY GORGEOUS BEACHES, WILD LIFE 82 00:03:41,880 --> 00:03:44,280 AND A GREAT UNIVERSITY, THE 83 00:03:44,280 --> 00:03:45,880 UNIVERSITY OF WESTERN AUSTRALIA, 84 00:03:45,880 --> 00:03:48,240 WHICH IS WHERE OUR FIRST SPEAKER 85 00:03:48,240 --> 00:03:49,880 BARRY MARSHALL RECEIVED HIS 86 00:03:49,880 --> 00:03:54,000 MEDICAL TRAINING. 87 00:03:54,000 --> 00:04:00,880 WHILE A REGISTRAR RESIDENT AT 88 00:04:00,880 --> 00:04:02,880 THE ROYAL SCHOOL BARE REMET AND 89 00:04:02,880 --> 00:04:05,520 COLLABORATED WITH A PATHOLOGIST, 90 00:04:05,520 --> 00:04:07,760 ROBIN WARREN WHO HAD BEEN 91 00:04:07,760 --> 00:04:13,560 OBSERVING SPIRAL BACTERIA IN 92 00:04:13,560 --> 00:04:19,600 SPECIMENS OF HUMANS WHO HAD 93 00:04:19,600 --> 00:04:20,720 PATIENT GASTRITIS. 94 00:04:20,720 --> 00:04:23,600 THIS WAS LATER IDENTIFIED AS 95 00:04:23,600 --> 00:04:24,440 HELICOBACTER PYLORI. 96 00:04:24,440 --> 00:04:27,560 A VARIETY OF STUDIES LED TO THE 97 00:04:27,560 --> 00:04:30,280 IDEA THAT MAYBE PEPTIC ULCER 98 00:04:30,280 --> 00:04:31,280 DISEASE WAS THE RESULT OF 99 00:04:31,280 --> 00:04:31,760 INFECTION. 100 00:04:31,760 --> 00:04:36,520 THIS WAS MET WITH GREAT 101 00:04:36,520 --> 00:04:37,880 SKEPTICISM FROM CLINICIANS, 102 00:04:37,880 --> 00:04:41,680 SOCIETIES PUBLICATIONS, FUNDING 103 00:04:41,680 --> 00:04:42,360 SOURCES. 104 00:04:42,360 --> 00:04:44,880 HOWEVER, MARSHALL AND WARREN DID 105 00:04:44,880 --> 00:04:47,560 SOMETHING THAT ALL GOOD 106 00:04:47,560 --> 00:04:49,480 INVESTIGATORS DO WHO BELIEVE 107 00:04:49,480 --> 00:04:50,920 THEY ARE FOLLOWING SOMETHING OF 108 00:04:50,920 --> 00:04:54,280 INTEREST AND CHALLENGE, THEY 109 00:04:54,280 --> 00:04:55,960 PERSEVERED IN A SERIES OF 110 00:04:55,960 --> 00:04:59,680 REMARKABLE STUDIES, THEY 111 00:04:59,680 --> 00:05:03,640 ESTABLISH A LINK BETWEEN 112 00:05:03,640 --> 00:05:05,800 HELICOBACTER INFECTION AND 113 00:05:05,800 --> 00:05:07,720 PEPTIC ULCER DISEASE. 114 00:05:07,720 --> 00:05:11,120 FOR THIS WORK IN 2005, HAY 115 00:05:11,120 --> 00:05:13,800 SHARED THE NOBEL PRIZE IN 116 00:05:13,800 --> 00:05:24,640 PHYSIOLOGY AND MEDICINE. 117 00:05:24,640 --> 00:05:27,560 DR. MARSHALL HAD RECEIVED AFTER 118 00:05:27,560 --> 00:05:31,400 RECEIVING THE NOBEL PRIZE AS 119 00:05:31,400 --> 00:05:34,440 RECEIVED A HUGE NUMBER OF 120 00:05:34,440 --> 00:05:37,440 SPECIAL PRIZES AND AWARDS, THE 121 00:05:37,440 --> 00:05:39,320 LASKER AWARD, THE GARDENER 122 00:05:39,320 --> 00:05:43,520 FOUNDATION AWARD, THE ERLICH 123 00:05:43,520 --> 00:05:45,440 AWARD, GOLDEN PRIZE OF THE 124 00:05:45,440 --> 00:05:50,000 AMERICAN ACADEMY OF ACHIEVEMENT, 125 00:05:50,000 --> 00:05:51,680 BUCHANAN MEDAL OF ELECTED 126 00:05:51,680 --> 00:05:54,680 SOCIETY, ELECTED O THE FELLOW OF 127 00:05:54,680 --> 00:05:57,520 ROYAL SOCIETY, ALL BASED UPON 128 00:05:57,520 --> 00:06:00,960 THESE EXTRAORDINARY STUDIES THAT 129 00:06:00,960 --> 00:06:02,880 WERE PERFORMED. 130 00:06:02,880 --> 00:06:06,560 IN ADDITION IS WORK WHICH 131 00:06:06,560 --> 00:06:09,080 PERSISTED AND HAS CONTINUED IS 132 00:06:09,080 --> 00:06:13,040 ALSO RAISED THE QUESTION 133 00:06:13,040 --> 00:06:15,920 HELICOBACTER INFECTION IS A 134 00:06:15,920 --> 00:06:17,920 DOUBLE BARREL EVENT HAVING SOME 135 00:06:17,920 --> 00:06:20,160 BENEFICIAL EFFECT PERHAPS AND 136 00:06:20,160 --> 00:06:22,520 CERTAINLY IN THE CASE OF THEIR 137 00:06:22,520 --> 00:06:26,880 STUDIES DELETERIOUS ONE. 138 00:06:26,880 --> 00:06:28,800 ONE OF THE INDIVIDUALS WHO 139 00:06:28,800 --> 00:06:30,800 PROFOUNDLY DISAGREED IN THE 140 00:06:30,800 --> 00:06:35,280 BEGINNING WITH HYPOTHESIS THAT 141 00:06:35,280 --> 00:06:38,040 ULCERS WERE INFECTIOUS DISEASE 142 00:06:38,040 --> 00:06:43,280 WERE OUR SECOND SPEAKER, MARTY 143 00:06:43,280 --> 00:06:43,680 GLASER. 144 00:06:43,680 --> 00:06:46,880 MARTIN IS A PHYSICIAN 145 00:06:46,880 --> 00:06:49,080 MICROBIOLOGIST, HE GRADUATED 146 00:06:49,080 --> 00:06:51,400 FROM NEW YORK UNIVERSITY, TOOK 147 00:06:51,400 --> 00:06:54,440 HIS RAINING IN COLORADO THEN WAS 148 00:06:54,440 --> 00:06:57,280 CHAIRMAN OF MEDICINE AT NEW YORK 149 00:06:57,280 --> 00:06:58,040 UNIVERSITY. 150 00:06:58,040 --> 00:07:01,240 ACTUALLY MOVED TO RUTGERS 151 00:07:01,240 --> 00:07:03,640 UNIVERSITY WHERE HE IS AT THE 152 00:07:03,640 --> 00:07:05,640 ROBERT WOOD JOHNSON MEDICAL 153 00:07:05,640 --> 00:07:08,920 SCHOOL PROFESSOR OF MEDICINE AND 154 00:07:08,920 --> 00:07:10,840 PATHOLOGY AND LABORATORY 155 00:07:10,840 --> 00:07:11,320 MEDICINE. 156 00:07:11,320 --> 00:07:15,280 HE HOLDS THE HENRY RUTGERS CHAIR 157 00:07:15,280 --> 00:07:18,920 OF THE HUMAN MICROBIOME AND IS 158 00:07:18,920 --> 00:07:20,680 DIRECTOR OF THE CENTER FOR 159 00:07:20,680 --> 00:07:25,080 ADVANCED BIOTECHNOLOGY AND 160 00:07:25,080 --> 00:07:26,440 MEDICINE. 161 00:07:26,440 --> 00:07:28,080 HIS WORK THE PAST 30 OR MORE 162 00:07:28,080 --> 00:07:32,000 YEARS HAS RELATED HUMAN 163 00:07:32,000 --> 00:07:33,760 MICROBIOME TO DISEASES, TO 164 00:07:33,760 --> 00:07:37,320 HEALTH AS WELL AS TO DISEASES. 165 00:07:37,320 --> 00:07:43,680 IN PARTICULAR HE FOCUSED ON 166 00:07:43,680 --> 00:07:46,040 CAMPILOBACTER AND HELICOBACTER 167 00:07:46,040 --> 00:07:46,640 PYLORI. 168 00:07:46,640 --> 00:07:47,880 IMPOSED THE QUESTION OF WHETHER 169 00:07:47,880 --> 00:07:51,040 IT HAS ACTUALLY A PROTECTIVE 170 00:07:51,040 --> 00:07:52,160 ROLE. 171 00:07:52,160 --> 00:07:54,160 DURING THIS WORK HE DEVELOPED 172 00:07:54,160 --> 00:07:59,080 THE HYPOTHESIS H PYLORI IS AN 173 00:07:59,080 --> 00:08:02,040 ANCIENT UNIVERSAL INHABITANT OF 174 00:08:02,040 --> 00:08:03,680 THE HUMAN STOMACH AND THAT IT'S 175 00:08:03,680 --> 00:08:06,920 BEEN DISAPPEARING AS A RESULT OF 176 00:08:06,920 --> 00:08:10,000 20TH CENTURY CHANGES IN 177 00:08:10,000 --> 00:08:11,520 SOCIOECONOMIC STATUS INCLUDING 178 00:08:11,520 --> 00:08:14,640 THE USE OF ANTIBIOTICS AND THIS 179 00:08:14,640 --> 00:08:17,480 LOSS OF HEALTH CONSEQUENCE IS 180 00:08:17,480 --> 00:08:19,120 NOT ONLY GOOD IN THE SENSE THAT 181 00:08:19,120 --> 00:08:21,840 IT IS REDUCING SOME DISEASES OF 182 00:08:21,840 --> 00:08:26,320 THE STOMACH INCLUDING GASTRIC 183 00:08:26,320 --> 00:08:29,880 CANCER BUT BAD AS WELL, HE'S 184 00:08:29,880 --> 00:08:31,680 DONE EXTENSIVE WORK ON THE 185 00:08:31,680 --> 00:08:35,600 RELATIONSHIP OF THE MICROBIOME 186 00:08:35,600 --> 00:08:37,800 THROUGH ASTHMA, DIABETES, 187 00:08:37,800 --> 00:08:41,040 OBESITY AND NEOPLASTIC DISEASE. 188 00:08:41,040 --> 00:08:45,840 HE IS HIGHLY RECOGNIZED BY ALL 189 00:08:45,840 --> 00:08:47,880 THE PROFESSIONAL SOCIETIES THAT 190 00:08:47,880 --> 00:08:51,480 HE HAS BEEN A MEMBER OF, 191 00:08:51,480 --> 00:08:56,000 PRESIDENT OF THE SOCIETY OF 192 00:08:56,000 --> 00:08:57,080 INFECTIOUS DISEASE, MEMBER OF 193 00:08:57,080 --> 00:08:59,880 THE NATIONAL ACADEMY OF MEDICINE 194 00:08:59,880 --> 00:09:05,280 ARTS AND SCIENCES, HE GAVE THE 195 00:09:05,280 --> 00:09:07,880 KUNYON LECTURE AT THE NIH 196 00:09:07,880 --> 00:09:09,600 SEVERAL YEARS AGO, HE RECEIVED 197 00:09:09,600 --> 00:09:14,160 AWARDS, THE FLEMING MEDAL AND IN 198 00:09:14,160 --> 00:09:16,680 2015 TIME MAGAZINE ANNOUNCED 199 00:09:16,680 --> 00:09:20,360 THAT HE WAS AMONG THE 100 MOST 200 00:09:20,360 --> 00:09:23,560 SIGNIFICANT INFLUENTIAL PEOPLE 201 00:09:23,560 --> 00:09:26,760 IN THE WORLD SO TODAY WE ARE 202 00:09:26,760 --> 00:09:29,160 EXTREMELY FORTUNATE THAT TWO 203 00:09:29,160 --> 00:09:32,520 HIGHLY ACCOMPLISHED EXPERIENCED 204 00:09:32,520 --> 00:09:35,480 INDIVIDUALS DISCUSSED THIS VERY 205 00:09:35,480 --> 00:09:37,320 IMPORTANT QUESTION AND A 206 00:09:37,320 --> 00:09:38,080 CHALLENGING ONE FROM THE 207 00:09:38,080 --> 00:09:40,960 CLINICAL AND THE BASIC SCIENCE 208 00:09:40,960 --> 00:09:43,840 PERSPECTIVE SUMMARIZED AS THE 209 00:09:43,840 --> 00:09:47,120 SPLIT PERSONALITY OF 210 00:09:47,120 --> 00:09:48,040 HELICOBACTER. 211 00:09:48,040 --> 00:09:49,840 OUR FIRST SPEAKER WILL BE BARRY 212 00:09:49,840 --> 00:09:51,760 MARSHALL. 213 00:09:51,760 --> 00:09:54,800 AND AS I MENTIONED PLEASE SUBMIT 214 00:09:54,800 --> 00:09:56,120 YOUR QUESTIONS DURING HIS TALK 215 00:09:56,120 --> 00:09:59,600 AND WE WILL HAVE A QUESTION AND 216 00:09:59,600 --> 00:10:01,560 ANSWER SESSION AT ITS 217 00:10:01,560 --> 00:10:02,280 CONCLUSION. 218 00:10:02,280 --> 00:10:07,280 BARRY YOU ARE ON. 219 00:10:07,280 --> 00:10:09,440 THANKS VERY MUCH FOR THAT IRWIN 220 00:10:09,440 --> 00:10:15,280 THIS IS A LOGO AND WE HAD THIS 221 00:10:15,280 --> 00:10:17,160 ON T SHIRTS AT A CONFERENCE IN 222 00:10:17,160 --> 00:10:19,400 PERTH IN 2002 BECAUSE THAT WAS 223 00:10:19,400 --> 00:10:21,800 20 YEARS AFTER THE ORIGINAL 224 00:10:21,800 --> 00:10:24,480 CULTURE HELICOBACTER PYLORI. 225 00:10:24,480 --> 00:10:29,120 IT IS AMAZING THAT THIS 226 00:10:29,120 --> 00:10:33,840 DISCUSSION AND PRESENCE IS STILL 227 00:10:33,840 --> 00:10:35,840 IN HELICOBACTER SO THANK YOU FOR 228 00:10:35,840 --> 00:10:39,600 SAVING ME FROM HAVING TO GET 229 00:10:39,600 --> 00:10:42,040 INVOLVED WITH THIS BECAUSE 230 00:10:42,040 --> 00:10:45,000 USUALLY WHEN -- IF I DISCUSSED 231 00:10:45,000 --> 00:10:46,400 THIS IN A LATE YEAR I'M 232 00:10:46,400 --> 00:10:47,880 PRESENTING A LOT OF IDEAS THAT 233 00:10:47,880 --> 00:10:50,360 COME FROM MARTIN BLAZER'S WORK 234 00:10:50,360 --> 00:10:52,240 OVER THE YEARS -- BLASERS WORK 235 00:10:52,240 --> 00:10:53,720 OVER THE YEAR SO IT IS GREAT TO 236 00:10:53,720 --> 00:10:56,800 HAVE HIM ON THE FACULTY THERE. 237 00:10:56,800 --> 00:10:59,920 SO THERE'S THE GOOD AND THE BAD 238 00:10:59,920 --> 00:11:00,280 HELICOBACTER. 239 00:11:00,280 --> 00:11:02,000 THE ONE ON THE RIGHT PRODUCES A 240 00:11:02,000 --> 00:11:04,600 TOXIN AND THE ONE ON THE LEFT 241 00:11:04,600 --> 00:11:05,400 PROBABLY DOESN'T. 242 00:11:05,400 --> 00:11:09,720 OF COURSE WE CAN THEN FIGURE OUT 243 00:11:09,720 --> 00:11:11,680 WHICH WE BELIEVE AND IN 244 00:11:11,680 --> 00:11:14,520 DIFFERENT AGE GROUPS PROBABLY 245 00:11:14,520 --> 00:11:17,120 GOING TO BE DIFFERENT. 246 00:11:17,120 --> 00:11:19,960 SO I WILL SHOW A FEW MORE OF 247 00:11:19,960 --> 00:11:22,960 THESE OVER THE SLIDE AS WE GO 248 00:11:22,960 --> 00:11:23,320 ALONG. 249 00:11:23,320 --> 00:11:25,880 SO NOW I'M GOING TO ADVANCE THE 250 00:11:25,880 --> 00:11:26,400 SLIDES THERE. 251 00:11:26,400 --> 00:11:29,480 SO MY FINANCIAL DISCLOSURE, I AM 252 00:11:29,480 --> 00:11:30,960 PARTNERING A COMPANY THAT 253 00:11:30,960 --> 00:11:33,400 EFFECTIVELY MAKES A BUSINESS OUT 254 00:11:33,400 --> 00:11:38,480 OF SELLING THINGS RELATED TO 255 00:11:38,480 --> 00:11:40,840 HELICOBACTER PYLORI TREATMENT 256 00:11:40,840 --> 00:11:41,440 DIAGNOSIS. 257 00:11:41,440 --> 00:11:42,800 NOT ALL THAT I TALK ABOUT NOT 258 00:11:42,800 --> 00:11:46,640 REALLY TREATMENT STUDY LECTURE 259 00:11:46,640 --> 00:11:48,200 BUT WE WILL TALK ABOUT THINGS 260 00:11:48,200 --> 00:11:50,280 PROBABLY NOT AVAILABLE IN THE 261 00:11:50,280 --> 00:11:51,400 UNITED STATES BUT NOT HAVE ANY 262 00:11:51,400 --> 00:11:54,800 BENEFIT FROM THAT. 263 00:11:54,800 --> 00:11:56,160 SO APPROVED OFF LABEL DRUGS. 264 00:11:56,160 --> 00:11:59,160 LEARNING OBJECTIVES, IN THE 265 00:11:59,160 --> 00:12:03,320 ENVIRONMENT AND HOW HELICOBACTER 266 00:12:03,320 --> 00:12:07,400 PYLORI WAS PEPTIC ULCER AND 267 00:12:07,400 --> 00:12:07,800 GASTRIC CANCER. 268 00:12:07,800 --> 00:12:09,080 THE RESEARCH PATHWAY IS GETTING 269 00:12:09,080 --> 00:12:10,200 HYPOTHESIS TO TESTING IT AND 270 00:12:10,200 --> 00:12:11,560 MOVING ON GETTING ANOTHER 271 00:12:11,560 --> 00:12:14,400 HYPOTHESIS AND TESTING IT SO 272 00:12:14,400 --> 00:12:18,960 THAT'S A GOING TO APPLY TO EVERY 273 00:12:18,960 --> 00:12:20,200 RESEARCH EFFORT. 274 00:12:20,200 --> 00:12:23,400 THE CLINICAL THING IS YOU MUST 275 00:12:23,400 --> 00:12:25,600 SEE THE IMPORTANCE OF THE 276 00:12:25,600 --> 00:12:29,360 PROSPECT OF RANDOMIZED DOUBLE 277 00:12:29,360 --> 00:12:31,840 BLIND STUDY WHICH IF IT WASN'T 278 00:12:31,840 --> 00:12:33,800 FOR THE FDA BEING SO DIFFICULT 279 00:12:33,800 --> 00:12:35,480 WITH THE PHARMACEUTICAL 280 00:12:35,480 --> 00:12:36,520 COMPANIES IN THE UNITED STATES 281 00:12:36,520 --> 00:12:37,760 IT WOULD HAVE BEEN MANY, MANY 282 00:12:37,760 --> 00:12:39,840 YEARS BEFORE THE WORLD STARTED 283 00:12:39,840 --> 00:12:40,800 DOING THAT. 284 00:12:40,800 --> 00:12:44,840 I ALWAYS HAVE RESPECT FOR -- 285 00:12:44,840 --> 00:12:47,600 THEY GET A BAD RAP SOMETIMES. 286 00:12:47,600 --> 00:12:49,960 WE CAN TALK ABOUT HOSE SEATS AND 287 00:12:49,960 --> 00:12:51,920 HOW WE CHANGE THINKING OVER 288 00:12:51,920 --> 00:12:52,320 TIME. 289 00:12:52,320 --> 00:12:54,520 THEN THINK HOW MANY YEARS IT 290 00:12:54,520 --> 00:12:56,200 TOOK FOR OUT ALL TO HAPPEN FOR 291 00:12:56,200 --> 00:13:00,200 IMPORTANT THINGS TO CHANGE IN 292 00:13:00,200 --> 00:13:01,200 MEDICINE. 293 00:13:01,200 --> 00:13:03,800 SO YES GO HERE TO WAR -- WE GO 294 00:13:03,800 --> 00:13:05,920 TO WAR REASON'S FIRST CASE, 1979 295 00:13:05,920 --> 00:13:09,400 ON HIS BIRTHDAY SO IT IS THE 296 00:13:09,400 --> 00:13:12,520 11TH OF JUNE 1949 AND HE WAS 40 297 00:13:12,520 --> 00:13:13,480 AT THIS POINT. 298 00:13:13,480 --> 00:13:15,200 THERE HE IS IN THAT OFFICE A 299 00:13:15,200 --> 00:13:16,440 COUPLE OF YEARS LATER. 300 00:13:16,440 --> 00:13:17,760 ON THE LEFT-HAND SIDE YOU CAN 301 00:13:17,760 --> 00:13:21,000 SEE THAT SMALL PRINTING, THAT'S 302 00:13:21,000 --> 00:13:23,160 THE REPORT, FIRST CASE OF 303 00:13:23,160 --> 00:13:26,360 HELICOBACTER PYLORI AND HE MAKES 304 00:13:26,360 --> 00:13:29,320 THE POINT THERE IS A 305 00:13:29,320 --> 00:13:32,400 SUPERFICIAL, JUST GOING TO SET 306 00:13:32,400 --> 00:13:34,800 MY POINTER OPTIONS, HOLD ON, I'M 307 00:13:34,800 --> 00:13:37,800 GOING TO CHANGE TO LASER 308 00:13:37,800 --> 00:13:38,040 POINTER. 309 00:13:38,040 --> 00:13:42,800 SO YOU CAN SEE DESCRIBE PLASMA 310 00:13:42,800 --> 00:13:46,200 CELLS AND THEN DIFFERENT THINGS, 311 00:13:46,200 --> 00:13:48,440 THESE BACTERIA SHOW MORPHOLOGY 312 00:13:48,440 --> 00:13:50,200 OF CAM LOWBACTER, THEY ARE 313 00:13:50,200 --> 00:13:52,400 GROWING AND NOT A CONTAMINANT. 314 00:13:52,400 --> 00:13:54,080 NOT SURE SIGNIFICANCE OF THESE 315 00:13:54,080 --> 00:13:56,520 FINDINGS BUT FURTHER 316 00:13:56,520 --> 00:14:01,600 INVESTIGATION OF EATING FUNCTION 317 00:14:01,600 --> 00:14:02,200 CASTRO FUNCTION AND MICROBIOLOGY 318 00:14:02,200 --> 00:14:02,640 MIGHT BE WORTHWHILE. 319 00:14:02,640 --> 00:14:05,760 I WENT TO WORK WITH HIM ON THIS. 320 00:14:05,760 --> 00:14:08,000 SO HE'S -- I HAPPEN TO BE IN THE 321 00:14:08,000 --> 00:14:09,320 RIGHT PLACE RIGHT TIME LOOKING 322 00:14:09,320 --> 00:14:13,080 FOR A RESEARCH PROJECT WHICH IN 323 00:14:13,080 --> 00:14:18,240 YOUR TRAINING IN TO BE PHYSICIAN 324 00:14:18,240 --> 00:14:20,320 IN WESTERN AUSTRALIA, YOU ARE 325 00:14:20,320 --> 00:14:21,400 SUPPOSED TO DO CLINICAL ANY KIND 326 00:14:21,400 --> 00:14:22,880 OF RESEARCH PROJECT EACH YEAR SO 327 00:14:22,880 --> 00:14:25,200 DO THAT AS NORMAL ACTIVITIES. 328 00:14:25,200 --> 00:14:27,960 VERY INTERESTED IN WARREN'S 329 00:14:27,960 --> 00:14:28,520 BACTERIA. 330 00:14:28,520 --> 00:14:30,200 JUST TRYING TO FIGURE OUT HOW 331 00:14:30,200 --> 00:14:32,440 COULD BACTERIA LIVE IN THE 332 00:14:32,440 --> 00:14:36,880 STOMACH, IT WAS EXCITING TO FIND 333 00:14:36,880 --> 00:14:38,600 OUT THAT THE ALL THE TEXTBOOKS 334 00:14:38,600 --> 00:14:39,560 WERE WRONG THERE WERE THINGS 335 00:14:39,560 --> 00:14:40,960 LIVING IN THE STOMACH NOT 336 00:14:40,960 --> 00:14:42,200 REPORTED THE THE TEXTBOOK. 337 00:14:42,200 --> 00:14:43,800 I THOUGHT GREAT I'LL GET A 338 00:14:43,800 --> 00:14:45,280 PUBLICATION OUT OF THIS AND THEN 339 00:14:45,280 --> 00:14:47,560 GO ON WITH MY CAREER. 340 00:14:47,560 --> 00:14:50,120 SO DIDN'T START OFF TRYING TO 341 00:14:50,120 --> 00:14:52,720 FIND THE ULCERS, IT IS A CASE OF 342 00:14:52,720 --> 00:14:55,000 CURIOSITY DRIVEN RESEARCH, HOW 343 00:14:55,000 --> 00:14:56,840 BACTERIA SURVIVE IN THE STOMACH 344 00:14:56,840 --> 00:14:58,520 WHEN THERE'S ACID THERE. 345 00:14:58,520 --> 00:15:06,840 SO MOVING ON THIS IS WARREN'S 346 00:15:06,840 --> 00:15:08,640 FIRST CASE. 347 00:15:08,640 --> 00:15:11,080 SO THIS IS -- ON THE LEFT-HAND 348 00:15:11,080 --> 00:15:13,000 SIDE IS ONE OF THESE COMMENTS 349 00:15:13,000 --> 00:15:14,640 FROM AN ARTICLE THAT HE DID 350 00:15:14,640 --> 00:15:18,040 SOMEWHERE A FEW YEARS LATER. 351 00:15:18,040 --> 00:15:20,280 HE SAYS THEY WERE CLOSELY 352 00:15:20,280 --> 00:15:24,440 RELATED TO THE ACTIVE GASTRITIS 353 00:15:24,440 --> 00:15:26,880 SO HISTOLOGY BUT NOT THE 354 00:15:26,880 --> 00:15:27,440 BACTERIA BEFORE. 355 00:15:27,440 --> 00:15:29,560 THE PRESENCE OF NEUTROPHILS IN 356 00:15:29,560 --> 00:15:32,080 THE STOMACH WAS ALMOST PA KNOW 357 00:15:32,080 --> 00:15:34,400 PNEUMONIC OF HELICOBACTER, YOU 358 00:15:34,400 --> 00:15:36,520 CAN SEE MANY CURVE SPIRAL 359 00:15:36,520 --> 00:15:39,040 BACTERIA PARTICULARLY AROUND THE 360 00:15:39,040 --> 00:15:40,600 TIGHT JUNCTIONS, THAT'S WHERE 361 00:15:40,600 --> 00:15:44,080 THEY LIKE TO LIVE, HAY ALSO ON 362 00:15:44,080 --> 00:15:45,080 THE 3-D STRUCTURE IF YOU CAN 363 00:15:45,080 --> 00:15:45,440 IMAGINE. 364 00:15:45,440 --> 00:15:49,320 THESE YELLOW PARTS HERE IS THE 365 00:15:49,320 --> 00:15:51,240 YELLOW STAIN AND SILVER STAIN 366 00:15:51,240 --> 00:15:53,320 AND EPITHELIAL CELLS SECRETING 367 00:15:53,320 --> 00:15:54,200 MUCOUS AND THERE WAS 368 00:15:54,200 --> 00:15:56,920 HELICOBACTER SO NORMAL CULTURES 369 00:15:56,920 --> 00:15:59,120 OF THE MOUTH IF YOU LIKE WOULD 370 00:15:59,120 --> 00:16:01,640 BE GRAHAM POSITIVE, GRAHAM 371 00:16:01,640 --> 00:16:04,240 NEGATIVE COCCI FUNGI NOT 372 00:16:04,240 --> 00:16:05,400 HOMOGENOUS CURVE BACTERIA LIKE 373 00:16:05,400 --> 00:16:07,840 THIS. 374 00:16:07,840 --> 00:16:10,560 AT THAT TIME CAMPYLOBACTER WAS 375 00:16:10,560 --> 00:16:13,720 CULTURED THE FIRST FEW YEARS, 376 00:16:13,720 --> 00:16:15,520 AND THAT WAS WHERE THE 377 00:16:15,520 --> 00:16:17,800 MICROBIOLOGY WAS VERY EXCITING 378 00:16:17,800 --> 00:16:22,320 AND ACTUALLY MARTY BLASER AT THE 379 00:16:22,320 --> 00:16:24,200 CAMPYLOBACTER MEETING IN BROS 380 00:16:24,200 --> 00:16:26,000 SELLS IN 1983 I GUESS. 381 00:16:26,000 --> 00:16:29,840 THAT WAS WARREN'S FIRST CASE. 382 00:16:29,840 --> 00:16:32,000 THE QUESTION WAS HOW DID BACK 383 00:16:32,000 --> 00:16:32,680 TIER WHERE SURVIVE IN THE 384 00:16:32,680 --> 00:16:33,920 STOMACH BECAUSE THEY ARE KILLED 385 00:16:33,920 --> 00:16:38,640 WITH PH LESS THAN THREE. 386 00:16:38,640 --> 00:16:40,640 GASTRIC SECRETION ACID IN THE 387 00:16:40,640 --> 00:16:43,320 STOMACH OR PH LESS THAN TWO 388 00:16:43,320 --> 00:16:46,160 OFTEN NEAR 1.5 SO DEFINITELY YOU 389 00:16:46,160 --> 00:16:47,960 CAN SHOW IT KILLS BACTERIA. 390 00:16:47,960 --> 00:16:49,320 ALMOST EVERYTHING SO NOBODY WAS 391 00:16:49,320 --> 00:16:52,280 LOOKING FOR BACTERIA IN THE 392 00:16:52,280 --> 00:16:54,320 STOMACH SO THAT WAS POSITIVE. 393 00:16:54,320 --> 00:16:58,480 WE STARTED THIS COLLABORATION IN 394 00:16:58,480 --> 00:16:59,560 1981. 395 00:16:59,560 --> 00:17:03,800 THERE'S ME AND ROBIN IN HIS LAB 396 00:17:03,800 --> 00:17:05,200 STUDYING PATHOLOGY BOOKS ET 397 00:17:05,200 --> 00:17:07,800 CETERA, THAT WAS ABOUT '84 I 398 00:17:07,800 --> 00:17:08,240 THINK. 399 00:17:08,240 --> 00:17:13,640 SOME YEARS LATER I -- I'M MOVING 400 00:17:13,640 --> 00:17:15,200 MY SCREEN, FIX THE SCREEN 401 00:17:15,200 --> 00:17:17,000 AROUND, I DID AN INTERVIEW WITH 402 00:17:17,000 --> 00:17:22,000 READERS DIGEST IN '88. 403 00:17:22,000 --> 00:17:23,040 SCIENTISTS FOUND IT HARD TO 404 00:17:23,040 --> 00:17:24,200 ACCEPT TEACHING TO AUSTRALIANS 405 00:17:24,200 --> 00:17:28,720 NOT ONLY WITH THE INVESTIGATORS, 406 00:17:28,720 --> 00:17:29,480 SEEM SUPREMELY CONFIDENT THEIR 407 00:17:29,480 --> 00:17:31,360 HYPOTHESIS WAS CORRECT. 408 00:17:31,360 --> 00:17:33,360 SO AFTER PRESENTING YOUR ONE 409 00:17:33,360 --> 00:17:34,920 INTERNATIONAL MEETING AND 410 00:17:34,920 --> 00:17:36,600 MEETING SOME PRETTY GOOD 411 00:17:36,600 --> 00:17:38,160 SCIENTIFIC THOUGHTFUL GASTRO 412 00:17:38,160 --> 00:17:39,200 ENTEROLOGISTS AND INFECTIOUS 413 00:17:39,200 --> 00:17:45,320 DISEASE PEOPLE IN EUROPE, NOTICE 414 00:17:45,320 --> 00:17:47,920 NOTICING THAT THESE BACTERIA 415 00:17:47,920 --> 00:17:50,240 WERE IN EVERY COUNTRY AND 416 00:17:50,240 --> 00:17:54,000 REPORTED BEFORE, SO WE BECAME 417 00:17:54,000 --> 00:17:56,200 CONFIDENT YOU SEE BY THE TIME IT 418 00:17:56,200 --> 00:17:59,600 WAS PUBLISHED WE HAD BEEN 419 00:17:59,600 --> 00:18:00,840 TESTING THIS FOR THREE YEARS SO 420 00:18:00,840 --> 00:18:02,760 MADE IT DIFFICULT FOR US BECAUSE 421 00:18:02,760 --> 00:18:05,840 PEOPLE SAID THEY ONLY GOT ONE 422 00:18:05,840 --> 00:18:08,600 PAPER AND THEY THINK -- THERE 423 00:18:08,600 --> 00:18:13,400 WAS REASON TO SKIP I SUPPOSE. 424 00:18:13,400 --> 00:18:15,120 SO THE PREVIOUS DISCOVERIES WERE 425 00:18:15,120 --> 00:18:18,400 THAT MANY PEOPLE HAD SEEN THESE 426 00:18:18,400 --> 00:18:19,760 BACTERIA AND LATER PUBLISHED A 427 00:18:19,760 --> 00:18:23,800 BOOK ON THIS OF COURSE. 428 00:18:23,800 --> 00:18:26,400 AND THE EARLY DISCOVERIES IS 429 00:18:26,400 --> 00:18:35,600 ALSO IN ITALY AND -- FREEBURG, 430 00:18:35,600 --> 00:18:36,760 FITZGERALD THESE PEOPLE WERE 431 00:18:36,760 --> 00:18:40,200 STILL ALIVE, I THINK WHEN WE 432 00:18:40,200 --> 00:18:44,400 MADE OUT A DISCOVERY, SONNENBURG 433 00:18:44,400 --> 00:18:45,720 CO-AUTHORED SOMETHING THERE. 434 00:18:45,720 --> 00:18:47,280 I THINK IT WAS -- SO A LOT OF 435 00:18:47,280 --> 00:18:49,080 PEOPLE SAW THE BACTERIA BUT 436 00:18:49,080 --> 00:18:50,960 COULDN'T GET ANY TRACTION 437 00:18:50,960 --> 00:18:53,280 TOWARDS RESEARCH PROJECT OR 438 00:18:53,280 --> 00:18:53,640 ANYTHING. 439 00:18:53,640 --> 00:18:54,800 AND MOVED ON. 440 00:18:54,800 --> 00:18:57,040 SO THEY PRODUCED ONE PAPER ON IT 441 00:18:57,040 --> 00:19:00,120 BUT REALLY DIDN'T THINK THAT WAS 442 00:19:00,120 --> 00:19:03,720 SOMETHING CONNECTED WITH ULCERS. 443 00:19:03,720 --> 00:19:08,200 SO FREEBURG WAS FAMOUS ONE FROM 444 00:19:08,200 --> 00:19:10,880 1939, '40 IN BOSTON HE PUBLISHED 445 00:19:10,880 --> 00:19:13,800 HIS PAPER SPY ROQUETTES IN 446 00:19:13,800 --> 00:19:17,360 GASTRIC MUCOSA. 447 00:19:17,360 --> 00:19:20,400 THAT IS HIM IN 1940 WHEN I MET 448 00:19:20,400 --> 00:19:23,040 HIM AND 2005 IN NEW YORK TIMES 449 00:19:23,040 --> 00:19:25,000 HE GOT A BIG TIME WRITE UP 450 00:19:25,000 --> 00:19:25,480 DISCOVERY. 451 00:19:25,480 --> 00:19:28,600 HE LATER CAME UP HEAD OF 452 00:19:28,600 --> 00:19:33,080 CARDIOLOGY ISRAEL IN BOSTON BUT 453 00:19:33,080 --> 00:19:37,320 ALWAYS HAD NOSTALGIC IDEAS ABOUT 454 00:19:37,320 --> 00:19:39,240 HIS FOR RAYS INTO MICROBIOLOGY 455 00:19:39,240 --> 00:19:40,960 OF THE STOMACH. 456 00:19:40,960 --> 00:19:42,200 AND HERE IS ILLUSTRATION FROM 457 00:19:42,200 --> 00:19:42,800 HIS PAPER. 458 00:19:42,800 --> 00:19:45,160 YOU CAN SEE THE SPATIAL 459 00:19:45,160 --> 00:19:47,920 BACTERIA, HE WAS DOING SILVER 460 00:19:47,920 --> 00:19:52,640 STAINS SAME STAIN Z AS ROBERT 461 00:19:52,640 --> 00:19:54,640 WARREN, HE WAS REMOVING STOMACHS 462 00:19:54,640 --> 00:19:59,880 AND FEW POSTMORTEM SPECIMENS SO 463 00:19:59,880 --> 00:20:04,560 HE IDENTIFIED THE BACTERIA AND 464 00:20:04,560 --> 00:20:06,440 NOBODY BELIEVED THAT BACTERIA 465 00:20:06,440 --> 00:20:14,560 COULD LIVE IN THE ACID STOMACH 466 00:20:14,560 --> 00:20:15,840 AND P CONTAMINATIONS. 467 00:20:15,840 --> 00:20:19,080 A FEW YEARS LATER THE TOP 468 00:20:19,080 --> 00:20:19,960 PATHOLOGIST IN THE UNITED STATES 469 00:20:19,960 --> 00:20:22,120 AT WALTER REED HOSPITAL IS EDDIE 470 00:20:22,120 --> 00:20:27,080 PALMER AND HE HAD ONE OF HIS 471 00:20:27,080 --> 00:20:29,800 FELLOWS LOOK AT THOUSAND 472 00:20:29,800 --> 00:20:32,480 SPECIMENS IN THE COLLECTION. 473 00:20:32,480 --> 00:20:35,800 HE SAYS NONE OF THE ELIMINATING 474 00:20:35,800 --> 00:20:39,040 SPECIMENS WAS FOUNDED TO CONTAIN 475 00:20:39,040 --> 00:20:44,440 SPY ROQUETTES, TO BE SPY ROW 476 00:20:44,440 --> 00:20:45,000 CHEAT NATURE. 477 00:20:45,000 --> 00:20:47,840 SO HE WAS UPSET WHEN THEY DIDN'T 478 00:20:47,840 --> 00:20:49,640 CONFIRM BECAUSE IT IMPLIED THE 479 00:20:49,640 --> 00:20:51,640 FINDINGS WERE WRONG SO THEY 480 00:20:51,640 --> 00:20:52,600 CARRIED A GRUDGE ON HIS SHOULDER 481 00:20:52,600 --> 00:20:55,960 AND MOVED TO CARDIOLOGY AND WAS 482 00:20:55,960 --> 00:20:57,800 SUCCESSFUL THERE. 483 00:20:57,800 --> 00:20:59,600 PEOPLE ASK ME, IF IT WASN'T FOR 484 00:20:59,600 --> 00:21:02,920 THIS PAPER BEING INCOMPETENTLY 485 00:21:02,920 --> 00:21:09,600 DONE, I DON'T KNOW WHY. 486 00:21:09,600 --> 00:21:11,280 THEN THIS MIGHT HAVE BEEN WORKED 487 00:21:11,280 --> 00:21:16,040 OUT IN THE '50s AND STUDIES 488 00:21:16,040 --> 00:21:20,080 OUT BEFORE. 489 00:21:20,080 --> 00:21:23,920 THE -- HE WAS AN ECZEMA VENEREAN 490 00:21:23,920 --> 00:21:26,560 IN THE JAPANESE REGIMENT IN 491 00:21:26,560 --> 00:21:32,880 WORLD WAR II AND THEY WOULD SEND 492 00:21:32,880 --> 00:21:34,560 JAPANESE REGIMENT, IT WAS IN 493 00:21:34,560 --> 00:21:36,520 ITALY AND GERMANY AND PLACES 494 00:21:36,520 --> 00:21:37,600 WHERE JAPANESE -- WITH HIS PALS 495 00:21:37,600 --> 00:21:39,640 AND MADE IT THROUGH AND WENT TO 496 00:21:39,640 --> 00:21:40,960 MEDICAL SCHOOL AT HARVARD AND 497 00:21:40,960 --> 00:21:42,760 BECAME ONE OF THE FIRST AGNAT 498 00:21:42,760 --> 00:21:44,520 MISTS WITH A GOOD ELECTRON 499 00:21:44,520 --> 00:21:46,720 MICROSCOPE AND HERE HE IS 500 00:21:46,720 --> 00:21:49,040 PUBLISHING A BIOPSY HE TOOK OF 501 00:21:49,040 --> 00:21:50,840 HIS OWN STOMACH BECAUSE HE HAD 502 00:21:50,840 --> 00:21:53,600 DONE ANATOMY OF CAT SO STOMACH 503 00:21:53,600 --> 00:21:55,240 AND WONDERED WHETHER PEOPLE HAD 504 00:21:55,240 --> 00:21:58,200 THESE BACTERIA SO HE SWALLOWED 505 00:21:58,200 --> 00:21:59,280 HIS OWN SUCTION BIOPSY CHEW, IT 506 00:21:59,280 --> 00:22:00,840 WAS A LITTLE BIT DANGEROUS AND 507 00:22:00,840 --> 00:22:03,840 TOOK A BIOPSY OF HIS OWN STOMACH 508 00:22:03,840 --> 00:22:06,480 AND GOT BEAUTIFUL FRESH 509 00:22:06,480 --> 00:22:08,720 MICROSCOPY AND HERE YOU SEE ONE 510 00:22:08,720 --> 00:22:10,480 OF THE MAJOR TEXTBOOKS OF 511 00:22:10,480 --> 00:22:11,400 PHYSIOLOGY HE PUBLISHED A 512 00:22:11,400 --> 00:22:12,960 BEAUTIFUL PICTURE OF 513 00:22:12,960 --> 00:22:14,520 HELICOBACTER PYLORI WITH 514 00:22:14,520 --> 00:22:17,120 MULTIPLE FLAGELLULA ON THE END 515 00:22:17,120 --> 00:22:18,440 STUCK TO EPITHELIAL CELLS BUT 516 00:22:18,440 --> 00:22:21,800 HIS TEACHING WAS LOTS OF ANIMALS 517 00:22:21,800 --> 00:22:23,040 HAVE THEM, EVERYBODY HAS THEM 518 00:22:23,040 --> 00:22:25,800 AND NOBODY IN BOSTON SHOWED ANY 519 00:22:25,800 --> 00:22:26,800 INTEREST IN HELICOBACTER UNTIL 520 00:22:26,800 --> 00:22:29,000 MANY, MANY YEARS LATER. 521 00:22:29,000 --> 00:22:30,600 PERHAPS BECAUSE THEY HAD SEEN A 522 00:22:30,600 --> 00:22:31,840 PICTURE IN MEDICAL SCHOOL AND 523 00:22:31,840 --> 00:22:34,400 MOVED ON. 524 00:22:34,400 --> 00:22:37,920 SO WARREN AND I GOT TOGETHER WE 525 00:22:37,920 --> 00:22:39,680 STUDIED A HUNDRED PATIENTS AND 526 00:22:39,680 --> 00:22:43,120 THIS IS A STUDY DONE IN 1982 SO 527 00:22:43,120 --> 00:22:44,280 I THINK ABOUT APRIL, FINISHED IN 528 00:22:44,280 --> 00:22:48,200 JUNE. 529 00:22:48,200 --> 00:22:50,040 TO SEE HOW MANY HAD BACTERIA, IT 530 00:22:50,040 --> 00:22:51,960 WAS PROSPECTIVE AND BLINDED IN 531 00:22:51,960 --> 00:22:54,920 THAT WE WERE JUST DOING A STUDY 532 00:22:54,920 --> 00:22:57,240 IF YOU LIKE AND WE WANT TO SEE 533 00:22:57,240 --> 00:22:58,240 WHO HAD IT. 534 00:22:58,240 --> 00:23:01,880 SO I WAS SENDING THE BIOPSIES 535 00:23:01,880 --> 00:23:02,560 WITHOUT MUCH CLINICAL 536 00:23:02,560 --> 00:23:05,600 INFORMATION TO WARREN AND ALSO 537 00:23:05,600 --> 00:23:09,200 THE ENDOSCOPY CULTURE THEM AND 538 00:23:09,200 --> 00:23:11,840 STATISTICIAN RECEIVED THE 539 00:23:11,840 --> 00:23:17,560 AMALGAMATED DATA EVENTUALLY SO 540 00:23:17,560 --> 00:23:19,840 HUNDRED PATIENTS FROM ENDOSCOPY, 541 00:23:19,840 --> 00:23:21,280 I HAD A NICE QUESTIONNAIRE ABOUT 542 00:23:21,280 --> 00:23:22,680 THE PEOPLE AND I MUST HAVE BEEN 543 00:23:22,680 --> 00:23:27,800 CONVINCING BECAUSE OUT OF 1 O 01 544 00:23:27,800 --> 00:23:29,200 PATIENTS INVITED TO PARTICIPATE 545 00:23:29,200 --> 00:23:31,200 I HAD A HUNDRED, SO ALMOST NO 546 00:23:31,200 --> 00:23:33,040 DROP OUTS OF REFUSALS. 547 00:23:33,040 --> 00:23:34,840 58% HAD THE BACTERIA. 548 00:23:34,840 --> 00:23:37,400 BUT WHEN WE LOOK AT THIS TABLE 549 00:23:37,400 --> 00:23:41,800 YOU SEE OF THE PATIENTS WITH 550 00:23:41,800 --> 00:23:44,440 ULCER, 13 OF 100% HAD THE 551 00:23:44,440 --> 00:23:48,800 BACTERIA SO P VALUE .3, NOW .4 552 00:23:48,800 --> 00:23:53,200 AND GASTRIC BYPASS IS 77% AND 553 00:23:53,200 --> 00:23:57,920 HELD UP IN OTHER STUDIES SO THAT 554 00:23:57,920 --> 00:24:00,400 WAS PRETTY INTERESTING AND OTHER 555 00:24:00,400 --> 00:24:03,000 THINGS ON VARIOUS PUNCH CARDS 556 00:24:03,000 --> 00:24:06,120 CALLED KALAMAZOO CARDS. 557 00:24:06,120 --> 00:24:08,200 WE PUBLISHED THIS EVENTUALLY, A 558 00:24:08,200 --> 00:24:11,560 YEAR LATER IN THE LANSETT. 559 00:24:11,560 --> 00:24:13,560 ONE THING ABOUT NO MATTER WHAT 560 00:24:13,560 --> 00:24:17,040 YOUR P VALUE IS, IF THE PEER 561 00:24:17,040 --> 00:24:20,360 REVIEWERS DON'T BELIEVE IT, JUST 562 00:24:20,360 --> 00:24:22,680 ASSUME THAT YOU SAVE THE DATA 563 00:24:22,680 --> 00:24:24,000 AND ALWAYS TELL OR WASN'T 564 00:24:24,000 --> 00:24:27,000 BLINDED IN THE PROPER WAY, 565 00:24:27,000 --> 00:24:28,920 PEOPLE JUST IN THEIR HEARTS 566 00:24:28,920 --> 00:24:33,440 COULDN'T BELIEVE IT. 567 00:24:33,440 --> 00:24:36,120 AND SO THERE WERE VARIOUS 568 00:24:36,120 --> 00:24:37,920 REASONS WHY WE MIGHT HAVE 569 00:24:37,920 --> 00:24:38,960 SELECTED GROUP, ET CETERA, ET 570 00:24:38,960 --> 00:24:39,280 CETERA. 571 00:24:39,280 --> 00:24:41,360 SO WE WENT OFF AND TRIED TO 572 00:24:41,360 --> 00:24:42,400 PROVE US WRONG AFTER WE 573 00:24:42,400 --> 00:24:47,160 ANNOUNCED IT. 574 00:24:47,160 --> 00:24:48,760 BY THE TIME THIS WAS PUBLISH WED 575 00:24:48,760 --> 00:24:50,080 FOUND ASSOCIATION WITH 576 00:24:50,080 --> 00:24:50,920 ALLOTTERS, STARTED TO TREAT A 577 00:24:50,920 --> 00:24:52,480 FEW PEOPLE, GETTING PRETTY 578 00:24:52,480 --> 00:24:54,280 EXCITED ABOUT IT. 579 00:24:54,280 --> 00:24:57,600 SO IT WAS HARD TO KEEP US UNDER 580 00:24:57,600 --> 00:25:00,400 WRAPS NOT SURE WHAT THE NEXT 581 00:25:00,400 --> 00:25:04,480 SLIDE IS. 582 00:25:04,480 --> 00:25:08,000 THE ACID BLOCKER TREATMENT WAS A 583 00:25:08,000 --> 00:25:10,560 BILLION DOLLAR BUSINESS, 3 584 00:25:10,560 --> 00:25:12,800 BILLION IN 1993, '84. 585 00:25:12,800 --> 00:25:14,400 WOULD THE WORLD ACCEPT A NEW 586 00:25:14,400 --> 00:25:16,640 COURSE OF ULCERS ON THE BATE OF 587 00:25:16,640 --> 00:25:17,680 DATA FROM 13 PATIENTS? 588 00:25:17,680 --> 00:25:20,120 THE ANSWER IS NO WAY. 589 00:25:20,120 --> 00:25:23,880 SO I JUST WARN THE YOUNG 590 00:25:23,880 --> 00:25:24,880 INVESTIGATORS NEVER PUBLISH A 591 00:25:24,880 --> 00:25:28,440 PAPER WITH 100% OF ANYTHING, IN 592 00:25:28,440 --> 00:25:29,040 BIG MEDICINE. 593 00:25:29,040 --> 00:25:34,080 NO ONE BELIEVES IT, NOTHING IS 594 00:25:34,080 --> 00:25:36,880 100%, FIND AN EXCEPTION AND PUT 595 00:25:36,880 --> 00:25:40,400 IT IN IF YOU CAN SO THIS IS 596 00:25:40,400 --> 00:25:43,280 WHERE I WAS TELLING MARTIN I 597 00:25:43,280 --> 00:25:45,400 ACTUALLY DISCOVERED THE GOOD AND 598 00:25:45,400 --> 00:25:47,200 BAD HELICOBACTER SITUATION 599 00:25:47,200 --> 00:25:48,840 BECAUSE THERE WAS I WASN'T GREAT 600 00:25:48,840 --> 00:25:50,440 STATISTICIAN BUT LOOK AT THIS 601 00:25:50,440 --> 00:25:53,400 TABLE AND THIS LINE HERE, 602 00:25:53,400 --> 00:25:57,240 ESOPHAGUS ABNORMAL. 603 00:25:57,240 --> 00:26:00,120 SO WHEREAS THE AVERAGE WAS 58% 604 00:26:00,120 --> 00:26:02,640 INFECTED, 41% ESOPHAGUS. 605 00:26:02,640 --> 00:26:04,680 SO PEOPLE WITH ACID REFLUX WOULD 606 00:26:04,680 --> 00:26:05,800 HAVE BEEN IN THAT GROUP. 607 00:26:05,800 --> 00:26:09,240 HAD LESS THAN NORMAL 608 00:26:09,240 --> 00:26:10,400 HELICOBACTER. 609 00:26:10,400 --> 00:26:12,960 SO IF YOU WOULD LOOK AT THIS P 610 00:26:12,960 --> 00:26:14,560 VALUE NON-SIGNIFICANT BUT OF 611 00:26:14,560 --> 00:26:17,560 COURSE IT IS THE OTHER TAIL OF 612 00:26:17,560 --> 00:26:19,120 THE NORMAL DISTRIBUTION AND IT 613 00:26:19,120 --> 00:26:21,320 SHOWS THERE'S SOME PROTECTION OF 614 00:26:21,320 --> 00:26:23,400 THE ESOPHAGUS BY HELICOBACTER 615 00:26:23,400 --> 00:26:23,800 PYLORI. 616 00:26:23,800 --> 00:26:28,240 I DIDN'T PICK UP THIS UNTIL THE 617 00:26:28,240 --> 00:26:30,280 '90s WHEN OTHER PEOPLE STARTED 618 00:26:30,280 --> 00:26:32,720 MAKING A CAREER OUT OF IT SAYING 619 00:26:32,720 --> 00:26:34,720 HELICOBACTER MAY BE SHOULDN'T BE 620 00:26:34,720 --> 00:26:36,720 TREATED IF YOU HAVE ESOPHAGITIS 621 00:26:36,720 --> 00:26:38,960 BECAUSE IT COULD BE ACID A BIT 622 00:26:38,960 --> 00:26:40,160 LOWER AND YOU WOULD BE HARMING 623 00:26:40,160 --> 00:26:41,400 PEOPLE IF YOU RETURN ACID TO 624 00:26:41,400 --> 00:26:43,000 NORMAL. 625 00:26:43,000 --> 00:26:44,880 SO THIS IS WHERE I DISCOVERED 626 00:26:44,880 --> 00:26:46,400 THE GOOD AND BAD HELICOBACTER, 627 00:26:46,400 --> 00:26:48,640 DIDN'T REALIZE I HAD DISCOVERED 628 00:26:48,640 --> 00:26:50,760 IT UNTIL FIVE OR SIX YEARS LATER 629 00:26:50,760 --> 00:26:53,560 IN MY DATA TABLE IN THE LANSETT. 630 00:26:53,560 --> 00:26:55,080 SO LET'S PRESS ON WE TRIED TO 631 00:26:55,080 --> 00:26:57,880 PRESENT THAT, THIS IS THE 632 00:26:57,880 --> 00:26:58,480 REJECTION LETTER I STILL HAVE 633 00:26:58,480 --> 00:27:01,480 THAT FRAMED IN MY OFFICE FROM 634 00:27:01,480 --> 00:27:03,360 THE GASTRO ENTEROLOGY SOCIETY 635 00:27:03,360 --> 00:27:03,720 AUSTRALIA. 636 00:27:03,720 --> 00:27:05,400 WE REGRET YOUR RESEARCH PAPER 637 00:27:05,400 --> 00:27:08,720 WAS NOT ACCEPTED, NUMBER OF 638 00:27:08,720 --> 00:27:12,880 ABSTRACTS FROM THIS MEETING, 67 639 00:27:12,880 --> 00:27:15,640 SUBMITTED, WE GO 56 SO IN THE 640 00:27:15,640 --> 00:27:17,200 BOTTOM 20%, THEY WOULDN'T GIVE 641 00:27:17,200 --> 00:27:19,480 ME A POSTER. 642 00:27:19,480 --> 00:27:21,600 NOT ONLY DIDN'T I GET AN ORAL 643 00:27:21,600 --> 00:27:23,720 BUT I DIDN'T GET A POSTER EITHER 644 00:27:23,720 --> 00:27:26,800 SO THAT POINT IT WAS SHAMEFUL TO 645 00:27:26,800 --> 00:27:30,880 BE INTERESTED IN CAMPYLOBACTER 646 00:27:30,880 --> 00:27:32,120 IN THE STOMACH BECAUSE IT 647 00:27:32,120 --> 00:27:34,600 COULDN'T BE TRUE, IT CAME FROM 648 00:27:34,600 --> 00:27:35,320 NOWHERE. 649 00:27:35,320 --> 00:27:37,400 SO FOUND IT INTERESTING, IT MADE 650 00:27:37,400 --> 00:27:38,720 MORE CHALLENGING AND MORE FUN 651 00:27:38,720 --> 00:27:42,040 FOR US I SUPPOSE. 652 00:27:42,040 --> 00:27:45,800 TO PROVE EVERYONE ELSE IS WRONG. 653 00:27:45,800 --> 00:27:47,320 HOW DO YOU PROVE GERMS ARE 654 00:27:47,320 --> 00:27:49,320 HARMFUL, A HARMFUL PATHOGEN, WE 655 00:27:49,320 --> 00:27:53,080 TRIED TO INFECT MICE RATS GINNY 656 00:27:53,080 --> 00:27:56,280 PIGS PIGS AND ULTIMATELY HAD 657 00:27:56,280 --> 00:27:58,400 SOME SUCCESS WITH HUMAN. 658 00:27:58,400 --> 00:28:00,800 THESE BEFORE INFORMAL 659 00:28:00,800 --> 00:28:02,120 ADMINISTRATION TO RARE VARIOUS 660 00:28:02,120 --> 00:28:03,960 ANIMALS ONE OR TWO USUALLY AND 661 00:28:03,960 --> 00:28:05,600 NOTHING -- EVERYTHING WAS 662 00:28:05,600 --> 00:28:07,920 RESISTANT AND I DID A FORMAL 663 00:28:07,920 --> 00:28:10,120 EXPERIMENT ON SOME PIG LETS 664 00:28:10,120 --> 00:28:12,560 WHICH GREW AND ULTIMATELY AFTER 665 00:28:12,560 --> 00:28:13,520 SIX MONTHS THEN DISCOVERED IT 666 00:28:13,520 --> 00:28:16,080 WAS NOT LONG ENOUGH TO PERFORM 667 00:28:16,080 --> 00:28:19,240 ENDOSCOPY ON THIS PIECE SO 668 00:28:19,240 --> 00:28:20,720 NEARLY FULL SIZE AND THE 669 00:28:20,720 --> 00:28:22,200 BACTERIA COULDN'T BE INFECTED SO 670 00:28:22,200 --> 00:28:25,480 THE EXPERIMENT FAIL SOD THE END 671 00:28:25,480 --> 00:28:26,960 EXASPERATED I SAID THE CRUCIAL 672 00:28:26,960 --> 00:28:28,280 QUESTION IS WHAT COMES FIRST 673 00:28:28,280 --> 00:28:31,080 BACTERIA OR THE ULCERS. 674 00:28:31,080 --> 00:28:34,000 SO THE HUMAN VOLUNTEER 675 00:28:34,000 --> 00:28:34,400 EXPERIMENT. 676 00:28:34,400 --> 00:28:36,000 THIS WAS PUBLISHED MANY YEARS 677 00:28:36,000 --> 00:28:39,000 LATER BY THE ABBOTT COMPANY YOU 678 00:28:39,000 --> 00:28:41,640 MAYBE ERYTHROMYOSIN, THAT WAS A 679 00:28:41,640 --> 00:28:44,320 FIRST GOOD ANTIBIOTICS FOR 680 00:28:44,320 --> 00:28:49,920 HELICOBACTER AND THEY PRODUCED A 681 00:28:49,920 --> 00:28:51,760 ULCER TALES AND GAVE IT TO EVERY 682 00:28:51,760 --> 00:28:52,600 DOCTOR IN AMERICA. 683 00:28:52,600 --> 00:28:55,080 HERE I AM DRINKING THE BACTERIA 684 00:28:55,080 --> 00:28:57,160 SO I DRANK TWO FRESH PETRI 685 00:28:57,160 --> 00:29:00,240 DISHES OF STRAIN OF HELICOBACTER 686 00:29:00,240 --> 00:29:01,760 WE ISOLATED FROM A PATIENT AND I 687 00:29:01,760 --> 00:29:04,800 WAS BEING CAREFUL, IT WAS 688 00:29:04,800 --> 00:29:07,200 SENSITIVE TO IN VITRO AND WE HAD 689 00:29:07,200 --> 00:29:12,200 CURED THE PATIENT BY GIVING HIM 690 00:29:12,200 --> 00:29:14,200 METRANITIS, THE WORST CASE 691 00:29:14,200 --> 00:29:15,000 SCENARIO ARE GOOD BLEEDING ULCER 692 00:29:15,000 --> 00:29:17,080 BUT I CAN TAKE THE TREATMENT AND 693 00:29:17,080 --> 00:29:19,200 GET RID OF THE GERM SO THAT'S 694 00:29:19,200 --> 00:29:21,360 HAPPENED. 695 00:29:21,360 --> 00:29:22,800 I DRANK IT, VARIOUS THINGS 696 00:29:22,800 --> 00:29:25,280 HAPPENED, I HAD ENDOSCOPY 697 00:29:25,280 --> 00:29:26,720 BASELINE, STOMACH WAS NORMAL, 698 00:29:26,720 --> 00:29:29,360 BIOPSIES NORMAL, I DRANK THAT 699 00:29:29,360 --> 00:29:32,960 BACTERIA AND THEN I DEVELOPED 700 00:29:32,960 --> 00:29:34,600 HISTOLOGICAL GASTRITIS WHICH WAS 701 00:29:34,600 --> 00:29:37,240 BIOPSIED ON DAY 10 SO SHOW AD 702 00:29:37,240 --> 00:29:38,760 HEALTHY PERSON CAN PICK UP AND 703 00:29:38,760 --> 00:29:40,400 CARRY THE BACTERIA, WE DIDN'T 704 00:29:40,400 --> 00:29:41,840 HAVE TO HAVE THE YOU WILLER 705 00:29:41,840 --> 00:29:43,080 FIRST WHICH WAS ALWAYS THE 706 00:29:43,080 --> 00:29:44,680 ARGUMENT PEOPLE HAD. 707 00:29:44,680 --> 00:29:47,080 THIS IS MY GASTRIC MUCOSA 708 00:29:47,080 --> 00:29:51,400 SIMILAR TO THE CASE THAT WARREN 709 00:29:51,400 --> 00:29:52,720 SOUGHT FIRST TIME AROUND AND 710 00:29:52,720 --> 00:29:53,200 MANY HELICOBACTERS. 711 00:29:53,200 --> 00:29:57,600 SO INTERESTING I HAD A 712 00:29:57,600 --> 00:29:58,680 HELATOSIS, VOMITING AND THERE 713 00:29:58,680 --> 00:30:01,040 WAS NO ACID IN THE VOMIT SO A 714 00:30:01,040 --> 00:30:06,400 LOT OF THINGS HAPPENED THAT 715 00:30:06,400 --> 00:30:07,840 SHOOK MY MEMORY ABOUT THE THINGS 716 00:30:07,840 --> 00:30:16,400 I READ IN THE MEDICAL BOOKS. 717 00:30:16,400 --> 00:30:19,640 IT REMIGHT BED ME OF TEXAS 718 00:30:19,640 --> 00:30:21,000 EPIDEMIC WHERE THEY STUDIED A 719 00:30:21,000 --> 00:30:23,640 ACID SECRETION AND BLOCKING IN 720 00:30:23,640 --> 00:30:26,400 1978 AND THE PERSON WAS PETE 721 00:30:26,400 --> 00:30:33,280 PETERSON AND JERRY RAMSEY, A FEW 722 00:30:33,280 --> 00:30:35,680 FAMOUS NAMES IN GASTRO 723 00:30:35,680 --> 00:30:36,040 ENTEROLOGY. 724 00:30:36,040 --> 00:30:42,200 HE HAD COME FROM BOSTON THEY HAD 725 00:30:42,200 --> 00:30:45,520 A EPIDEMIC OF SUDDEN GASTRITIS 726 00:30:45,520 --> 00:30:50,040 IN 30 VOLUNTEERS BECAUSE PASSING 727 00:30:50,040 --> 00:30:52,600 GASTRIC NIACIN TUBES AND CHAIN 728 00:30:52,600 --> 00:30:54,600 KNOW HOW TO STERILIZE THEE, THEY 729 00:30:54,600 --> 00:30:56,000 INCLUDED THEY WERE BE STERILE IN 730 00:30:56,000 --> 00:30:58,200 STOMACH ACID SO THEY MADE THAT 731 00:30:58,200 --> 00:30:58,680 MISTAKE. 732 00:30:58,680 --> 00:31:01,000 THEY INFECTED EVERYBODY AND THEY 733 00:31:01,000 --> 00:31:01,880 WERE SOME OF THE BIGGEST 734 00:31:01,880 --> 00:31:04,240 SKEPTICS OF THIS GROUP IN DALLAS 735 00:31:04,240 --> 00:31:06,400 PARTICULARLY CALLED THE ACID 736 00:31:06,400 --> 00:31:09,080 MAFIA FOR MANY YEARS BECAUSE 737 00:31:09,080 --> 00:31:14,520 THEY WERE U STILL ON THE ACID 738 00:31:14,520 --> 00:31:17,800 BOAT RATHER THAN MOVING TO THE 739 00:31:17,800 --> 00:31:26,360 HELICOBACTER TREATMENT. 740 00:31:26,360 --> 00:31:29,360 THEY WERE QUITE PROKOFIEV IN THE 741 00:31:29,360 --> 00:31:29,840 HELICOBACTER AREA. 742 00:31:29,840 --> 00:31:32,000 THE OTHER THING ABOUT BUSINESS 743 00:31:32,000 --> 00:31:33,200 MUT, THEY THOUGHT IT WAS SOME 744 00:31:33,200 --> 00:31:35,920 KIND OF A COATING PRODUCT AND 745 00:31:35,920 --> 00:31:38,800 HAD BEEN USED AS AN ANT ACID 746 00:31:38,800 --> 00:31:41,000 SUPPLEMENT FOR MANY YEARS IN 747 00:31:41,000 --> 00:31:43,000 GERMANY, 200 YEARS IN FACT, IT 748 00:31:43,000 --> 00:31:45,720 WAS AROUND OVER COUNTER MEDICINE 749 00:31:45,720 --> 00:31:47,960 AND I HEAR YOU SEE THIS IS 750 00:31:47,960 --> 00:31:51,200 ACTUALLY BISMUTH ON A DISC OF 751 00:31:51,200 --> 00:31:54,600 HELICOBACTER PYLORI PROVIDED IN 752 00:31:54,600 --> 00:31:54,800 1983. 753 00:31:54,800 --> 00:31:59,400 I PREDICTED THAT ANY DRUG WHICH 754 00:31:59,400 --> 00:32:04,360 HAD A LOW RELAPSE RATE OF PEPTIC 755 00:32:04,360 --> 00:32:06,240 ULCER YOU TREAT A PATIENT FOR 756 00:32:06,240 --> 00:32:09,600 THREE MONTHS AND STOP THE 757 00:32:09,600 --> 00:32:11,520 TREATMENT, THE ULCER WOULD COME 758 00:32:11,520 --> 00:32:12,800 BACK SO VERDICTLY EVERYONE WAS 759 00:32:12,800 --> 00:32:16,320 ON ACID BLOCKERS THE REST OF 760 00:32:16,320 --> 00:32:17,120 THEIR LIME BUT WHEN PATIENTS 761 00:32:17,120 --> 00:32:19,360 WERE TAKING BISMUTH TREATMENT IT 762 00:32:19,360 --> 00:32:24,600 WAS NOT AN ACID BLOCKER 30% 763 00:32:24,600 --> 00:32:26,040 PEOPLE NEVER HAD RECURRENCE OF 764 00:32:26,040 --> 00:32:28,720 ULCER SO THIS WAS NOTED IN 765 00:32:28,720 --> 00:32:29,600 ENGLAND AND EUROPE. 766 00:32:29,600 --> 00:32:30,960 SO PEOPLE WERE EXCITED ABOUT IT 767 00:32:30,960 --> 00:32:34,600 IN THE YEARS JUST BEFORE -- 768 00:32:34,600 --> 00:32:36,560 ARRIVED SO I PREDICTED MUST BE 769 00:32:36,560 --> 00:32:40,280 AN ANTIBIOTIC AND METALS LIKE 770 00:32:40,280 --> 00:32:43,680 ARSENIC WERE USED AS 771 00:32:43,680 --> 00:32:45,360 ANTIBACTERIALS BEFORE ADVENT OF 772 00:32:45,360 --> 00:32:46,720 PENT SILL LYNN. 773 00:32:46,720 --> 00:32:48,080 PEOPLE HAD FORGOTTEN ABOUT THAT, 774 00:32:48,080 --> 00:32:50,920 IT IS AN ANTI-BACK EARIAL AND 775 00:32:50,920 --> 00:32:53,320 U.S. PEOPLE WERE TAKING IT AS A 776 00:32:53,320 --> 00:32:54,880 WELL KNOWN DRUG. 777 00:32:54,880 --> 00:32:59,080 SO 30 MINUTES AFTER SWALLOWING 778 00:32:59,080 --> 00:33:01,600 THE MISDEMEANOR SIN, YOU SEE 779 00:33:01,600 --> 00:33:03,840 BACTERIA ARE DECOME POSING AND 780 00:33:03,840 --> 00:33:05,640 DETACHED, ET CETERA. 781 00:33:05,640 --> 00:33:07,200 SO IT IS STILL GOOD TREATMENT 782 00:33:07,200 --> 00:33:09,400 FOR HELICOBACTER, ONE OF THE 783 00:33:09,400 --> 00:33:10,880 HINGES THE BUG CANNOT WELCOME 784 00:33:10,880 --> 00:33:11,800 RESISTANT TOO. 785 00:33:11,800 --> 00:33:14,080 THAT POINT I CONNECTED UP WITH 786 00:33:14,080 --> 00:33:16,080 PROCTER & GAMBLE WHO MAKE PEPTO 787 00:33:16,080 --> 00:33:17,840 BUSINESS MALL AND THEY HAD THESE 788 00:33:17,840 --> 00:33:20,280 DREAMS OF GETTING BILLION DOLLAR 789 00:33:20,280 --> 00:33:23,040 SALES WITH PEPTO BISMAL, GAVE ME 790 00:33:23,040 --> 00:33:25,720 A FELLOWSHIP AND THERE'S MY BOSS 791 00:33:25,720 --> 00:33:28,640 RICHARD GRANT AT THE UVA 792 00:33:28,640 --> 00:33:31,480 GEOGRAPHIC MEDICINE, I WAS IN 793 00:33:31,480 --> 00:33:32,840 GASTROP ENTEROLOGY DOING 794 00:33:32,840 --> 00:33:34,680 CLINICAL TRIALS FUNDED BY 795 00:33:34,680 --> 00:33:36,360 PROCTER & GAMBLE. 796 00:33:36,360 --> 00:33:37,920 IT WAS A FANTASTIC TIME TO TURN 797 00:33:37,920 --> 00:33:39,000 UP IN THE UNITED STATES AND 798 00:33:39,000 --> 00:33:40,920 CARRY ON THE RESEARCH. 799 00:33:40,920 --> 00:33:43,400 I HAD A DOUBLE BLIND STUDY IN 800 00:33:43,400 --> 00:33:47,000 AUSTRALIA NEARLY FINISHED THAT 801 00:33:47,000 --> 00:33:47,760 POINT. 802 00:33:47,760 --> 00:33:49,160 THAT'S WHEN I STARTED MEETING 803 00:33:49,160 --> 00:33:50,000 EVERYBODY IN THE UNITED STATES 804 00:33:50,000 --> 00:33:55,760 AND MARTIN BLASER AND I HAD 805 00:33:55,760 --> 00:33:57,320 MEETINGS WITH PROCTER & GAMBLE 806 00:33:57,320 --> 00:33:58,760 AND TRYING TO GET RID OF 807 00:33:58,760 --> 00:33:59,800 HELICOBACTER IN THOSE DAYS. 808 00:33:59,800 --> 00:34:03,000 HERE YOU SEE THE HIS HISTORY OF 809 00:34:03,000 --> 00:34:05,320 PEPTO BISMAL AROUND A HUNDRED 810 00:34:05,320 --> 00:34:08,520 YEARS, IN THE LITERATURE, IN 811 00:34:08,520 --> 00:34:10,400 CONJUNCTION WITH REMEDIES IT IS 812 00:34:10,400 --> 00:34:12,080 SERVICE TREATING GASTRIC ULCERS 813 00:34:12,080 --> 00:34:16,360 AS WELL AS RELIEF OF ACUTE 814 00:34:16,360 --> 00:34:18,160 GASTRITIS U.S. LITERATURE FROM 815 00:34:18,160 --> 00:34:22,800 1900 WAS USING IT ANYTHING GUT 816 00:34:22,800 --> 00:34:28,160 RELATED THOUGH TRIED PEPTO 817 00:34:28,160 --> 00:34:29,080 BISMMAL AND TWEET A FEW TOOK IT 818 00:34:29,080 --> 00:34:29,680 FOR EXACERBATION. 819 00:34:29,680 --> 00:34:35,200 THAT WAS DISCOVERED ALREADY. 820 00:34:35,200 --> 00:34:37,360 SEW LATER ON THIS IS A PICTURE 821 00:34:37,360 --> 00:34:40,080 OF A MOUSE PAD I GOT FROM ASTRA 822 00:34:40,080 --> 00:34:43,520 ZENECA AND NOW THAT ASTRA ZENECA 823 00:34:43,520 --> 00:34:46,440 AND GLAXO WELCOME SO THAT WAS 824 00:34:46,440 --> 00:34:47,360 THE FIRST TREATMENT FOR 825 00:34:47,360 --> 00:34:48,600 HELICOBACTER AND THEY KIN LIKE 826 00:34:48,600 --> 00:34:51,240 THAT THEY WERE COMPETING AGAINST 827 00:34:51,240 --> 00:34:53,600 BISMUTH AT THAT STAGE SO THEY 828 00:34:53,600 --> 00:34:58,560 WERE ADVERTISING NO BISMUTH 829 00:34:58,560 --> 00:35:02,400 IMPLYING -- THEY HAD THE 830 00:35:02,400 --> 00:35:06,360 TREATMENT AMOXICILLIN. 831 00:35:06,360 --> 00:35:08,280 SO IT WAS FAKE NEWS THAT IT WAS 832 00:35:08,280 --> 00:35:09,960 DANGEROUS AND THEY WERE CLAIMING 833 00:35:09,960 --> 00:35:15,440 THEY DIDN'T USE BISMUTH AND PPI 834 00:35:15,440 --> 00:35:17,800 AMOXICILLIN AND BISMUTH IS STILL 835 00:35:17,800 --> 00:35:18,800 AROUND TODAY ONE OF THE GOOD 836 00:35:18,800 --> 00:35:19,200 TREATMENTS. 837 00:35:19,200 --> 00:35:22,680 SO HERE IS A I THINK I'M GOING 838 00:35:22,680 --> 00:35:23,320 ALL RIGHT. 839 00:35:23,320 --> 00:35:27,960 ANOTHER TEN MINUTES OR SO. 840 00:35:27,960 --> 00:35:31,160 THIS IS OUR UNDERSTANDING OF THE 841 00:35:31,160 --> 00:35:32,440 EPIDEMIOLOGY EARLY ON YOU SEE 842 00:35:32,440 --> 00:35:35,360 THE WHOLE POPULATION OF 843 00:35:35,360 --> 00:35:36,840 AUSTRALIA, UNITED STATES IS IN 844 00:35:36,840 --> 00:35:39,680 THE GREEN AND THEN ABOUT A THIRD 845 00:35:39,680 --> 00:35:41,640 TO 30 TO 50% OF THE POPULATION 846 00:35:41,640 --> 00:35:45,040 IS GOING SO HAVE HELICOBACTER 847 00:35:45,040 --> 00:35:47,000 PYLORI AND THEN IT IS VERY 848 00:35:47,000 --> 00:35:48,760 INTERESTING THAT NEARLY ALL 849 00:35:48,760 --> 00:35:50,400 PEPTIC ULCER DISEASES IN THE RED 850 00:35:50,400 --> 00:36:01,520 GROUP ARE THE DUE DENUMB ULCER 851 00:36:01,520 --> 00:36:03,040 SO IT LOOKS LIKE IT IS 852 00:36:03,040 --> 00:36:05,760 IMPOSSIBLE TO GET A ULCER IN THE 853 00:36:05,760 --> 00:36:07,200 GREEN BECAUSE SURELY PEOPLE 854 00:36:07,200 --> 00:36:09,000 WOULD LOSE THESE BACTERIA, 855 00:36:09,000 --> 00:36:12,840 ACCIDENTLY TAKING ANTIBIOTICS. 856 00:36:12,840 --> 00:36:14,600 SO THEY WOULD BE IN THE GREEN 857 00:36:14,600 --> 00:36:16,280 ROOM, YET THERE WAS HARDLY 858 00:36:16,280 --> 00:36:17,840 ANYBODY IN THE GREEN GROUP 859 00:36:17,840 --> 00:36:21,280 GETTING A DUODINAL ULCER SO THE 860 00:36:21,280 --> 00:36:22,960 PREDICTION WOULD BE IF YOU COULD 861 00:36:22,960 --> 00:36:25,040 GET RID OF THE HELICOBACTER AND 862 00:36:25,040 --> 00:36:27,280 MOVE THE PATIENT IN THE GREEN 863 00:36:27,280 --> 00:36:28,440 GROUP YOU WOULD CURE PEPTIC 864 00:36:28,440 --> 00:36:29,080 ULCERS. 865 00:36:29,080 --> 00:36:32,480 SO THAT IS WHAT WE WANTED TO DO, 866 00:36:32,480 --> 00:36:34,840 PROSPECTIVE STUDY WE ARE 867 00:36:34,840 --> 00:36:38,240 EVENTUAL -- I GOT FUNDED BY 868 00:36:38,240 --> 00:36:40,880 AUSTRALIA AND NIH STARTING IN 869 00:36:40,880 --> 00:36:44,800 '85 WE START AD THREE YEAR STUDY 870 00:36:44,800 --> 00:36:45,200 OF THAT. 871 00:36:45,200 --> 00:36:47,000 THIS IS THE OUTCOME PUBLISHED IN 872 00:36:47,000 --> 00:36:49,400 LANSETT IN 1988. 873 00:36:49,400 --> 00:36:55,480 SO WHAT WE GAVE WE GAVE PEOPLE 874 00:36:55,480 --> 00:36:56,720 BISMUTH UNTIL THE ULCER WAS 875 00:36:56,720 --> 00:36:57,960 HEALED SO EIGHT WEEKS OF 876 00:36:57,960 --> 00:36:58,600 TREATMENT. 877 00:36:58,600 --> 00:37:00,400 IF THEY DIDN'T HEAL THEY WOULD 878 00:37:00,400 --> 00:37:02,040 DISCARD AUTO OF THE STUDY AND 879 00:37:02,040 --> 00:37:03,400 SAY YOU HAVE TO BE HEALED OF 880 00:37:03,400 --> 00:37:04,760 ULCER TO GET STARTED ON THIS 881 00:37:04,760 --> 00:37:05,280 FOLLOW UP. 882 00:37:05,280 --> 00:37:06,960 WE STOPPED EVERYTHING. 883 00:37:06,960 --> 00:37:08,600 JUST KEPT OUR FINGERS CROSSED 884 00:37:08,600 --> 00:37:10,000 AND FOLLOWED PEOPLE UP. 885 00:37:10,000 --> 00:37:12,320 YOU SEE IF THE PATIENT HAD JUST 886 00:37:12,320 --> 00:37:15,280 RECEIVED SEMETADINE ACID CLOCKER 887 00:37:15,280 --> 00:37:18,040 AND PLACEBO ANTIBIOTICS, THE 888 00:37:18,040 --> 00:37:20,800 PATIENTS QUICKLY RELAPSED. 889 00:37:20,800 --> 00:37:23,120 THEY HAD THREE MONTHS FOLLOW-UP 890 00:37:23,120 --> 00:37:25,200 ENDOSCOPY AND WE REMOVED SOME OF 891 00:37:25,200 --> 00:37:27,080 THEM RELAPSED STRAIGHT AWAY, WE 892 00:37:27,080 --> 00:37:29,000 REMOVED LOTS AT THREE MONTHS, 893 00:37:29,000 --> 00:37:30,520 HAD RECURRENCE AT ENDOSCOPY AND 894 00:37:30,520 --> 00:37:33,720 CONTINUED TO RELAPSE THERE. 895 00:37:33,720 --> 00:37:35,680 AND AT SIX MONTHS WE DID ANOTHER 896 00:37:35,680 --> 00:37:37,800 ENDOSCOPY AND TOOK MORE OUT. 897 00:37:37,800 --> 00:37:40,760 AT 12 MONTHS WE DID A FINAL 898 00:37:40,760 --> 00:37:41,880 ENDOSCOPY AND TOOK MORE OUT SO 899 00:37:41,880 --> 00:37:44,600 IN THE PLACEBO GROUP A LOT 900 00:37:44,600 --> 00:37:45,320 RELAPSED. 901 00:37:45,320 --> 00:37:47,920 WHEREAS IN THE ANTIBIOTIC GROUP 902 00:37:47,920 --> 00:37:50,240 IF WE HAD ERADICATED THE 903 00:37:50,240 --> 00:37:51,280 HELICOBACTER VERY FEW RELAPSED. 904 00:37:51,280 --> 00:37:54,440 IN FACT THEY HAD REFLUX 905 00:37:54,440 --> 00:37:55,000 ESOPHAGITIS SYMPTOMS SO THEY 906 00:37:55,000 --> 00:37:57,000 WERE TAKEN OUT A STUDY AS 907 00:37:57,000 --> 00:38:00,680 RELAPSE BUT THEY DIDN'T HAVE A 908 00:38:00,680 --> 00:38:02,600 DUODENAL ULCER SO QUITE A 909 00:38:02,600 --> 00:38:03,280 REMARKABLE DIFFERENCE, I DON'T 910 00:38:03,280 --> 00:38:08,200 KNOW WHY I'M NOT SEEING ANY LOSS 911 00:38:08,200 --> 00:38:10,560 THE TRANSITION THERE BUT 80% 912 00:38:10,560 --> 00:38:12,640 CURE IN THE TOP GROUP VERSUS 20% 913 00:38:12,640 --> 00:38:14,000 BOTTOM GROUP. 914 00:38:14,000 --> 00:38:15,200 PEOPLE DIDN'T LIKE THE FACT YOU 915 00:38:15,200 --> 00:38:17,840 USE BISMUTH BECAUSE YOU CAN'T 916 00:38:17,840 --> 00:38:21,160 BLIND IT, NOT GOOD ENOUGH SO WE 917 00:38:21,160 --> 00:38:22,520 PUBLISHED IN THE LANSETT, NOT 918 00:38:22,520 --> 00:38:24,120 THE NEW ENGLAND JOURNAL BECAUSE 919 00:38:24,120 --> 00:38:26,200 MEDICATIONS ARE NOT AVAILABLE IN 920 00:38:26,200 --> 00:38:27,600 THE U.S. AND WOULD HAVE CAUSED 921 00:38:27,600 --> 00:38:30,240 CHAOS TO PUBLISH THIS IF THERE 922 00:38:30,240 --> 00:38:32,840 WAS NO TREATMENT AVAILABLE. 923 00:38:32,840 --> 00:38:35,760 THAT WAS ALL RIGHT AND 924 00:38:35,760 --> 00:38:37,000 EVENTUALLY IT WAS THE STATE 925 00:38:37,000 --> 00:38:40,280 STUDY WAS -- SAME STUDY WAS DONE 926 00:38:40,280 --> 00:38:45,040 IN AUSTRALIA AND THEY USE R 927 00:38:45,040 --> 00:38:46,640 AMOXICILLIN AND METRA ZYNOL, WE 928 00:38:46,640 --> 00:38:48,840 HAD A GOOD CURE RATE, YOU SEE 929 00:38:48,840 --> 00:38:52,840 THIS GROUP THE RELAPSE WAS 10% 930 00:38:52,840 --> 00:38:55,400 AND 90% THIS THIS GROUP SO SAME 931 00:38:55,400 --> 00:38:57,640 RESULT BUT REALLY NO ONE ARGUES 932 00:38:57,640 --> 00:39:00,720 WITH BLINDING OF THAT STUDY 933 00:39:00,720 --> 00:39:03,200 PUBLISHED IN NEW HE CAN LAND 934 00:39:03,200 --> 00:39:03,600 JOURNAL 1993. 935 00:39:03,600 --> 00:39:06,160 SO THERE WERE OTHER STUDIES THAT 936 00:39:06,160 --> 00:39:09,480 DID IT, THERE WAS DOUBLE BLIND 937 00:39:09,480 --> 00:39:12,240 STUDY, THIS CONFIRMATION BY ROSS 938 00:39:12,240 --> 00:39:16,920 IN AMSTERDAM USING A BISMUTH 939 00:39:16,920 --> 00:39:17,200 COMBINATION. 940 00:39:17,200 --> 00:39:22,040 DAVID GRAHAM USED PEPTO BISMAL 941 00:39:22,040 --> 00:39:24,040 AND TETRA ZYCLEAN, 90% 942 00:39:24,040 --> 00:39:25,200 HELICOBACTER GREAT STUDIES 943 00:39:25,200 --> 00:39:28,520 PUBLISHED THERE IN GASTRO 944 00:39:28,520 --> 00:39:31,480 ENTEROLOGY AND HENSHELL IN VIE 945 00:39:31,480 --> 00:39:34,360 YEAHNA SO THAT CHANGED THINKING 946 00:39:34,360 --> 00:39:35,800 SO NOW IT WAS RESPECTFUL TO TALK 947 00:39:35,800 --> 00:39:37,240 ABOUT HELICOBACTER, IT WAS 948 00:39:37,240 --> 00:39:39,480 PUBLISHED BY THE CONSENSUS 949 00:39:39,480 --> 00:39:41,480 MEETING AT THE NIH. 950 00:39:41,480 --> 00:39:44,360 TO END OF IT LIMITED TREATMENT 951 00:39:44,360 --> 00:39:46,920 INDICATION, PATIENTS WITH 952 00:39:46,920 --> 00:39:50,240 ULCERS, IF THE PATIENT HAD 953 00:39:50,240 --> 00:39:51,640 HELICOBACTER WHICH WAS WHICH WAS 954 00:39:51,640 --> 00:39:55,440 80% THAT DIDN'T HAVE ULCERS SO 955 00:39:55,440 --> 00:39:57,400 THEY WEREN'T SURE ABOUT THAT 956 00:39:57,400 --> 00:39:58,240 ONE. 957 00:39:58,240 --> 00:40:00,240 THERE IS NO PROVEN TREATMENT BUT 958 00:40:00,240 --> 00:40:01,600 AMOXICILLIN WAS TOUTED AT THAT 959 00:40:01,600 --> 00:40:03,880 POINT, NO LONGER EMBARRASSING TO 960 00:40:03,880 --> 00:40:05,440 TALK ABOUT HELICOBACTER SO 961 00:40:05,440 --> 00:40:09,200 PEOPLE WITH BAD ULCERS AT THAT 962 00:40:09,200 --> 00:40:09,560 POINT. 963 00:40:09,560 --> 00:40:12,040 BACK TO THE ORIGINAL QUESTION WE 964 00:40:12,040 --> 00:40:13,760 HAD ALPHA BACTERIA LIVE MANAGE 965 00:40:13,760 --> 00:40:14,800 THE STOMACH. 966 00:40:14,800 --> 00:40:18,800 HOLLAND NOTICED UREASE AND WE 967 00:40:18,800 --> 00:40:23,560 LOOKED AT THAT, ONE DAY ON A 968 00:40:23,560 --> 00:40:25,040 PLANE WE WERE DISCUSSING IT AND 969 00:40:25,040 --> 00:40:27,520 FIGURED OUT IT WAS THE UREASE OF 970 00:40:27,520 --> 00:40:31,000 H PYLORI WITH SPOONING UREA, 971 00:40:31,000 --> 00:40:33,200 CONSUMING A HYDROGEN AND 972 00:40:33,200 --> 00:40:36,520 GENERATING AMMONIA AND BY 973 00:40:36,520 --> 00:40:37,320 CARBONATE SO H PYLORI PROTECT 974 00:40:37,320 --> 00:40:38,840 ITSELF FROM ACID SO WE RAISED 975 00:40:38,840 --> 00:40:40,640 BACK TO LAB AND DID SOME NICE 976 00:40:40,640 --> 00:40:42,320 EXPERIMENTS. 977 00:40:42,320 --> 00:40:44,240 SO IN THIS STUDY IF YOU LOOK 978 00:40:44,240 --> 00:40:47,080 HERE WE HAVE GOT AN ACCESS OF PH 979 00:40:47,080 --> 00:40:49,400 SO THIS IS NEUTRAL IN THE LEFT 980 00:40:49,400 --> 00:40:52,800 GOING THROUGH ACID SOLUTION ON 981 00:40:52,800 --> 00:40:55,000 THE RIGHT AND THEN LOG OF 982 00:40:55,000 --> 00:40:58,600 SURVIVING BACTERIA AFTER 30 983 00:40:58,600 --> 00:41:04,400 MINUTES, THE DOTTED LINE IS C 984 00:41:04,400 --> 00:41:06,240 JUJUNI IS THE CROSSES AND IF YOU 985 00:41:06,240 --> 00:41:10,920 PUT C JUJUNI IN DIFFERENT PH, 986 00:41:10,920 --> 00:41:12,120 AFTER 3.5 IT IS GETTING KILLED 987 00:41:12,120 --> 00:41:17,040 AND IS NEARLY ALL KILLED AT PH 988 00:41:17,040 --> 00:41:17,200 3. 989 00:41:17,200 --> 00:41:21,640 THEN PROTEASE WHICH IS A 990 00:41:21,640 --> 00:41:25,200 MODERATE UREASE PRODUCER BUT NOT 991 00:41:25,200 --> 00:41:28,200 AS STRONG H PYLORI. 992 00:41:28,200 --> 00:41:31,760 YOU CAN SEE 19TH TO THE 9TH. 993 00:41:31,760 --> 00:41:34,720 AND 3.5 YOU HANDLE IT AND THIS 994 00:41:34,720 --> 00:41:39,240 IS ACTUALLY SOLUTIONS OF GASTRIC 995 00:41:39,240 --> 00:41:41,400 SOME UREA PRESENT IN THE ACID, 996 00:41:41,400 --> 00:41:44,720 YOU SEE IT IS KILLED AT BELOW 997 00:41:44,720 --> 00:41:46,600 2.5, NO PROTEASE SURVIVING BUT 998 00:41:46,600 --> 00:41:48,800 HELICOBACTER YOU PUT IT IN ANT 999 00:41:48,800 --> 00:41:53,080 ACID WITH UREA PRESENT SO UREA 1000 00:41:53,080 --> 00:41:55,800 IS GASTRIC JUICE GASTRICLY ONE 1001 00:41:55,800 --> 00:41:57,200 MILLIONLY MOLAR AND HELICOBACTER 1002 00:41:57,200 --> 00:41:58,560 IS SURVIVING. 1003 00:41:58,560 --> 00:42:01,760 NOTHING ELSE SURVIVES 1004 00:42:01,760 --> 00:42:02,320 HELICOBACTER DOESN'T NEED 1005 00:42:02,320 --> 00:42:03,560 SPECIAL TRICKS, IT IS THE ONLY 1006 00:42:03,560 --> 00:42:05,080 THING THAT'S GROWING THERE IN 1007 00:42:05,080 --> 00:42:08,160 ANY NUMBERS IN YOUR GASTRIC 1008 00:42:08,160 --> 00:42:09,320 MUCOSA. 1009 00:42:09,320 --> 00:42:12,840 I OFTEN ARGUE WHETHER THERE IS A 1010 00:42:12,840 --> 00:42:14,400 GASTRIC MICROBIOME, I WOULD SAY 1011 00:42:14,400 --> 00:42:16,400 IT IS NOT, IT IS WHAT YOU 1012 00:42:16,400 --> 00:42:17,720 SWALLOW IN YOUR SPIT AND SOON 1013 00:42:17,720 --> 00:42:18,920 KILLED BY THE ACID. 1014 00:42:18,920 --> 00:42:24,000 SO THIS IS THE IDEA, THE UREA IS 1015 00:42:24,000 --> 00:42:26,560 COMING THERE AND IT SPLITS AND 1016 00:42:26,560 --> 00:42:29,720 MAINTAINS INTERNAL PH OF 5 TO 6 1017 00:42:29,720 --> 00:42:31,800 UNDER FAIRLY UNDER CONDITION 1018 00:42:31,800 --> 00:42:35,320 WHERE IS IT CAN COLONIZE IN 1019 00:42:35,320 --> 00:42:37,800 GASTRIC MUCOSA. 1020 00:42:37,800 --> 00:42:40,800 IT IS SO STRONG IN FACT YOU TAKE 1021 00:42:40,800 --> 00:42:43,640 BIOPSY FROM THE STOMACH AND PUT 1022 00:42:43,640 --> 00:42:48,640 IN KRISTIN UREASE BACTERIA, WE 1023 00:42:48,640 --> 00:42:53,160 CAN SEE PINK AFTER FEW HOURS IN 1024 00:42:53,160 --> 00:42:54,680 SO WE MADE A STRONG ONE AND THAT 1025 00:42:54,680 --> 00:42:55,600 IS A COMMON HELICOBACTER AND 1026 00:42:55,600 --> 00:42:57,920 THAT IS A BIOPSY FROM THE 1027 00:42:57,920 --> 00:43:00,800 PATIENT WITH A DUODENAL ULCER SO 1028 00:43:00,800 --> 00:43:03,080 THAT WAS RAPID DIAGNOSTIC TEST 1029 00:43:03,080 --> 00:43:05,480 WITH FIRST RAPID TEST WHERE THE 1030 00:43:05,480 --> 00:43:08,000 FIRST TEST ON THE MARKET FOR 1031 00:43:08,000 --> 00:43:09,040 HELICOBACTER AND IT WAS CALLED 1032 00:43:09,040 --> 00:43:10,080 THE CLO TEST. 1033 00:43:10,080 --> 00:43:13,000 THAT IS THE TEST THAT MY COMPANY 1034 00:43:13,000 --> 00:43:15,760 STILL SELLS ALL OVER THE WORLD 1035 00:43:15,760 --> 00:43:18,160 KIMBERLY CLARK, SO PATENT IS 1036 00:43:18,160 --> 00:43:22,280 EXPIRED SO I CAN'T SHOW IT ON MY 1037 00:43:22,280 --> 00:43:25,920 -- WE RECOMMEND 30 MILLION AT 1038 00:43:25,920 --> 00:43:27,200 LEASTUREASE TESTS DONE AROUND 1039 00:43:27,200 --> 00:43:28,920 WORLD TO SHOW YOU I'M NOT BIASED 1040 00:43:28,920 --> 00:43:33,120 I SHOW YOU THE BILLIONS OF KNOCK 1041 00:43:33,120 --> 00:43:34,920 YOU HAVE A TESTS AROUND THE 1042 00:43:34,920 --> 00:43:36,080 WORLD IN EVERY COUNTRY YOU CAN 1043 00:43:36,080 --> 00:43:37,640 MAKE IT FOR ABOUT A CENT SO 1044 00:43:37,640 --> 00:43:39,600 THERE'S STILL VERY, VERY USEFUL 1045 00:43:39,600 --> 00:43:40,960 TESTS. 1046 00:43:40,960 --> 00:43:43,600 SO THEN THERE WAS ANOTHER BIT OF 1047 00:43:43,600 --> 00:43:46,480 INTERESTING RESEARCH WE HAD 1048 00:43:46,480 --> 00:43:47,400 DONE. 1049 00:43:47,400 --> 00:43:50,400 WE MEASURED UREA IN GASTRIC USE 1050 00:43:50,400 --> 00:43:52,760 OF PATIENTS WITH AND WITHOUT 1051 00:43:52,760 --> 00:43:54,120 HELICOBACTER PYLORI, THIS WAS A 1052 00:43:54,120 --> 00:43:59,280 STUDY I HAD DONE IN 1983 AT FREE 1053 00:43:59,280 --> 00:44:01,160 METAL HOSPITAL ABOUT UREA 1054 00:44:01,160 --> 00:44:01,520 HYDROLYSIS. 1055 00:44:01,520 --> 00:44:04,480 WE NOTICED IF YOU WERE NORMAL 1056 00:44:04,480 --> 00:44:09,680 PERSON YOU HAD UREA IN YOUR GAY 1057 00:44:09,680 --> 00:44:11,600 STRICT JUICE SIMILAR TO BLOOD 1058 00:44:11,600 --> 00:44:13,240 UREA. 1059 00:44:13,240 --> 00:44:16,760 IF YOU HAD H PYLORI ALL THE UREA 1060 00:44:16,760 --> 00:44:19,320 WAS GONE, LESS THAN ONE 1061 00:44:19,320 --> 00:44:22,360 MILLIONLY MOLAR PER -- 1062 00:44:22,360 --> 00:44:23,040 MILLIMOLAR. 1063 00:44:23,040 --> 00:44:24,880 INSTEAD OF BIOPSY WHAT ABOUT A 1064 00:44:24,880 --> 00:44:30,160 BETH TEST SO THE ONE I CHOSE WAS 1065 00:44:30,160 --> 00:44:33,320 CARBON 14 UREA, ALMOST 1066 00:44:33,320 --> 00:44:35,200 SIMULTANEOUSLY DAVID GRAHAM AND 1067 00:44:35,200 --> 00:44:38,760 COMPANY STARTED USING CARBON 13 1068 00:44:38,760 --> 00:44:40,200 UREA, THEY STABILIZED THE 1069 00:44:40,200 --> 00:44:43,600 TECHNOLOGY IN HOUSTON AND DOING 1070 00:44:43,600 --> 00:44:45,000 METABOLIC STATES. 1071 00:44:45,000 --> 00:44:49,960 IN C 14 WE PUT UREA IN A 1072 00:44:49,960 --> 00:44:51,840 CAPSULE, IF H PYLORI IS PRESENT 1073 00:44:51,840 --> 00:44:53,840 IT'S SPLIT TO AMMONIA AND CO 2 1074 00:44:53,840 --> 00:44:58,000 YOU CAN SEE THE SIGNAL OF THE CO 1075 00:44:58,000 --> 00:44:59,760 2 CARBON ISOTOPE COMING OUT IN 1076 00:44:59,760 --> 00:45:00,800 THREE OR FOUR MINUTES. 1077 00:45:00,800 --> 00:45:03,000 IF YOU DIDN'T HAVE H PYLORI IT 1078 00:45:03,000 --> 00:45:05,880 WAS EXTREAT CRETEED UNCHANGED IN 1079 00:45:05,880 --> 00:45:08,000 THE URINE, -- EXCRETED IN THE 1080 00:45:08,000 --> 00:45:12,200 URINE, TURNED IN TO BICARBONATE 1081 00:45:12,200 --> 00:45:14,080 WHICH YOU CHECKED IN A BREATH IN 1082 00:45:14,080 --> 00:45:15,480 A BALLOON SO ULTIMATELY THIS 1083 00:45:15,480 --> 00:45:20,400 TEST WAS APPROVED BY THE FDA IN 1084 00:45:20,400 --> 00:45:22,320 ABOUT 1896. 1085 00:45:22,320 --> 00:45:24,480 IT IS ALSO ABOUT 30 MILLION 1086 00:45:24,480 --> 00:45:26,200 TESTS A YEAR, I THINK MOSTLY IN 1087 00:45:26,200 --> 00:45:31,200 CHINA SO IT IS IN MANY 1088 00:45:31,200 --> 00:45:33,200 COUNTRIES: SOMEONE DOING THE 1089 00:45:33,200 --> 00:45:35,560 BREAST TEST THERE, SWALLOWING 1090 00:45:35,560 --> 00:45:37,800 THE CAPSULE BALLOON AND ONE 1091 00:45:37,800 --> 00:45:41,000 BREATH ISOTOPE TO MEASURE IN A 1092 00:45:41,000 --> 00:45:44,120 ISOLATION COUNTER OR SOMETHING. 1093 00:45:44,120 --> 00:45:45,240 MILLIONS -- THOUSANDS OF 1094 00:45:45,240 --> 00:45:49,360 VERSIONS OF THIS TEST AROUND THE 1095 00:45:49,360 --> 00:45:53,080 WORLD IN USE USE. 1096 00:45:53,080 --> 00:45:55,360 SO I'LL GET BACK TO FINAL 1097 00:45:55,360 --> 00:45:59,400 SLIDES, ORIGINS OF GOOD BUG BAD 1098 00:45:59,400 --> 00:46:02,200 BUG SAGA SO BECAME EXCITING 1099 00:46:02,200 --> 00:46:04,960 ABOUT 1999 AS I SAID IN EARLY 1100 00:46:04,960 --> 00:46:07,120 STUDY IF YOU HAD ESOPHAGEAL 1101 00:46:07,120 --> 00:46:10,000 DISEASE LIKE ESOPHAGITIS THERE 1102 00:46:10,000 --> 00:46:12,520 WAS A CASE AGAINST TREATING 1103 00:46:12,520 --> 00:46:14,040 HELICOBACTER PYLORI BECAUSE A 1104 00:46:14,040 --> 00:46:16,000 LOT OF PEOPLE LOWERS ACID 1105 00:46:16,000 --> 00:46:17,880 SECRETION MAYBE NOT IN SO MUCH 1106 00:46:17,880 --> 00:46:20,680 IN DUODENAL PATIENTS BUT OTHER 1107 00:46:20,680 --> 00:46:23,200 PEOPLE. 1108 00:46:23,200 --> 00:46:26,160 SO THIS ONE IS ESOPHAGEAL REFLUX 1109 00:46:26,160 --> 00:46:28,360 AS RISK FACTOR FOR CARCINOMA, 1110 00:46:28,360 --> 00:46:31,920 THIS IS A BIG STUDY DONE OUT OF 1111 00:46:31,920 --> 00:46:32,520 SWY DEAN WITH FANTASTIC LONG 1112 00:46:32,520 --> 00:46:35,040 TERM RECORDS OF ALL PEOPLE WITH 1113 00:46:35,040 --> 00:46:37,000 REFLUX DISEASE, ACID REFLUX AND 1114 00:46:37,000 --> 00:46:39,000 WHAT HAPPENED TONEME IN THE LONG 1115 00:46:39,000 --> 00:46:40,440 TERM. 1116 00:46:40,440 --> 00:46:50,000 SO HERE IS THE THIS 1117 00:46:50,000 --> 00:46:52,600 RETROSPECTIVE COHORT STUDIES. 1118 00:46:52,600 --> 00:46:54,600 820 CONTROLS AND THEY HAD PEOPLE 1119 00:46:54,600 --> 00:46:56,600 THAT DEVELOPED ESOPHAGEAL 1120 00:46:56,600 --> 00:46:57,800 CARCINOMA, AS KNOW CARCINOMA OF 1121 00:46:57,800 --> 00:47:00,000 THE STOMACH. 1122 00:47:00,000 --> 00:47:01,840 AND ESOPHAGEAL SQUAMOUS 1123 00:47:01,840 --> 00:47:04,000 CARCINOMA. 1124 00:47:04,000 --> 00:47:10,920 YOU SEE BOTH AT LEAST JUAN WEEK 1125 00:47:10,920 --> 00:47:12,160 TEN YEARS BEFORE THE CANCER, 1126 00:47:12,160 --> 00:47:14,680 THAT WAS -- LOOK BACK TEN YEARS 1127 00:47:14,680 --> 00:47:17,560 AND SELECTED OUT THESE PEOPLE, 1128 00:47:17,560 --> 00:47:19,360 SO HEART BURN REFLUX BOTH AT 1129 00:47:19,360 --> 00:47:21,040 NIGHT AT LEAST ONCE PER WEEK SO 1130 00:47:21,040 --> 00:47:25,720 THEY DIDN'T HAVE IT IN THEIR 1131 00:47:25,720 --> 00:47:29,160 CONTROLS, 8%, IF THEY HAD 1132 00:47:29,160 --> 00:47:30,520 ESOPHAGEAL ADENOCARCINOMA, TEN 1133 00:47:30,520 --> 00:47:32,680 TIMES MORE LIKELY TO HAVE HAVE 1134 00:47:32,680 --> 00:47:35,120 HAD REFLUX DISEASE TEN YEARS 1135 00:47:35,120 --> 00:47:35,680 BEFORE. 1136 00:47:35,680 --> 00:47:38,000 BUT THAT ASSOCIATION WASN'T 1137 00:47:38,000 --> 00:47:41,560 PRESENT FOR GASTRIC CARCINOMA OR 1138 00:47:41,560 --> 00:47:43,120 SQUAMOUS CARCINOMA OF THE 1139 00:47:43,120 --> 00:47:45,400 ESOPHAGUS SO THIS IS MAJOR AND 1140 00:47:45,400 --> 00:47:48,840 IT TOLD EVERYBODY OKAY ACID 1141 00:47:48,840 --> 00:47:50,320 CAUSES ADENOCARCINOMA OF THE 1142 00:47:50,320 --> 00:47:54,280 ESOPHAGUS, YOU DON'T JUST WALK 1143 00:47:54,280 --> 00:47:54,880 AROUND SIPPING ANTI-ACID FROM 1144 00:47:54,880 --> 00:47:56,400 TIME TO TIME, YOU NEED TO TREAT 1145 00:47:56,400 --> 00:47:59,600 PROPERLY WITH PPI AND MAYBE 1146 00:47:59,600 --> 00:48:01,200 THINGS WHICH MAKE ESOPHAGITIS 1147 00:48:01,200 --> 00:48:04,040 WORSE ARE GOING TO BE RISK 1148 00:48:04,040 --> 00:48:07,200 FACTORS FOR THE ESOPHAGUS 1149 00:48:07,200 --> 00:48:10,600 ADENOCARCINOMA, ONE OF THE FEW 1150 00:48:10,600 --> 00:48:13,120 CANCERS INCREASING IN THE UNITED 1151 00:48:13,120 --> 00:48:14,600 STATES, I THINK LEVELED OFF BUT 1152 00:48:14,600 --> 00:48:16,400 WAS INCREASENING THE UNITED 1153 00:48:16,400 --> 00:48:18,120 STATES WHEREAS MOST OTHERS WERE 1154 00:48:18,120 --> 00:48:18,800 DECREASING. 1155 00:48:18,800 --> 00:48:23,400 SO THAT LEADS INTO MARTY'S 1156 00:48:23,400 --> 00:48:24,160 DISCUSSION. 1157 00:48:24,160 --> 00:48:26,120 I WILL KEEP OUT OF OF HIS 1158 00:48:26,120 --> 00:48:26,680 TERRITORY. 1159 00:48:26,680 --> 00:48:29,520 LET'S SEE IF WE CAN GO FURTHER. 1160 00:48:29,520 --> 00:48:32,040 I WILL JUST ACKNOWLEDGE THAT 1161 00:48:32,040 --> 00:48:33,320 THIS -- ONE OF THE IMPORTANT 1162 00:48:33,320 --> 00:48:36,960 PEOPLE IN MY LIFE ADRIENNE, DR. 1163 00:48:36,960 --> 00:48:38,440 WARREN, HIS WIFE HAS PASSED AWAY 1164 00:48:38,440 --> 00:48:39,360 SADLY. 1165 00:48:39,360 --> 00:48:41,480 AT THE MOMENT I'M STILL 1166 00:48:41,480 --> 00:48:42,440 UNIVERSITY OF WEST AUSTRALIA AND 1167 00:48:42,440 --> 00:48:49,000 I HAVE A LAB MARSHALL LABNA NICE 1168 00:48:49,000 --> 00:48:50,840 GRANT AT MARSHALL LAB OF 1169 00:48:50,840 --> 00:48:52,320 BIOENGINEERING SO WE ARE DOING 1170 00:48:52,320 --> 00:48:54,840 POINT OF CARE GADGETS AS OUR 1171 00:48:54,840 --> 00:48:55,200 AIMS. 1172 00:48:55,200 --> 00:49:02,000 AND YOU WILL SEE MORE OF THAT IF 1173 00:49:02,000 --> 00:49:03,400 PEOPLE WANT TO PHOTOGRAPH THIS 1174 00:49:03,400 --> 00:49:05,840 AND GET A WE CHAT LINK. 1175 00:49:05,840 --> 00:49:08,800 ONE MORE SLIDE. 1176 00:49:08,800 --> 00:49:12,160 SO THE TWO DECADES OF HIGH 1177 00:49:12,160 --> 00:49:15,200 CO-BACTER PYLORI WITH THE NICE 1178 00:49:15,200 --> 00:49:17,040 AND NAUGHTY HELICOBACTER WE CAN 1179 00:49:17,040 --> 00:49:21,840 TALK ABOUT THAT ANOTHER 20 1180 00:49:21,840 --> 00:49:27,640 YEARS, WE MAY GET ANOTHER 1181 00:49:27,640 --> 00:49:31,840 CONFERENCE IN PERTH IN 2024. 1182 00:49:31,840 --> 00:49:32,840 WE CAN PUT A BID IN THAT I 1183 00:49:32,840 --> 00:49:33,440 THINK. 1184 00:49:33,440 --> 00:49:34,800 THAT'S THE END OF MY TALK. 1185 00:49:34,800 --> 00:49:35,200 THANK YOU. 1186 00:49:35,200 --> 00:49:38,400 >> THANK YOU VERY MUCH. 1187 00:49:38,400 --> 00:49:45,440 I THINK IT MIGHT BE USEFUL TO 1188 00:49:45,440 --> 00:49:48,560 NOW HAVE MARTY BLAZER GIVE 1189 00:49:48,560 --> 00:49:49,560 MISTALK AND AT THE END HAVE 1190 00:49:49,560 --> 00:49:51,040 QUESTIONS FOR BOTH. 1191 00:49:51,040 --> 00:49:52,800 MARTY BLASER. 1192 00:49:52,800 --> 00:49:55,000 BECAUSE MOST QUESTIONS ACTUALLY 1193 00:49:55,000 --> 00:49:57,880 FALL INTO EITHER/OR CATEGORY OR 1194 00:49:57,880 --> 00:49:58,360 BOTH. 1195 00:49:58,360 --> 00:50:03,880 SO MARTY WOULD YOU BEGIN PLEASE. 1196 00:50:03,880 --> 00:50:05,880 THANK YOU FOR THE INVITATION TO 1197 00:50:05,880 --> 00:50:07,640 GIVE THIS TALK, IT IS ALWAYS 1198 00:50:07,640 --> 00:50:09,680 VERY INTERESTING TO HEAR BARRY. 1199 00:50:09,680 --> 00:50:11,680 HE TELLS US ABOUT THE PAST. 1200 00:50:11,680 --> 00:50:13,880 GOING TO TRY TO MOVE INTO THE 1201 00:50:13,880 --> 00:50:14,240 FUTURE. 1202 00:50:14,240 --> 00:50:16,640 THIS IS CALLED THE SPLIT 1203 00:50:16,640 --> 00:50:21,560 PERSONALITY OF H PYLORI. 1204 00:50:21,560 --> 00:50:26,480 SO MY FINANCIAL DISCLOSURE, I 1205 00:50:26,480 --> 00:50:29,280 HAVE NOTHING TO DISCLOSE. 1206 00:50:29,280 --> 00:50:30,960 THE OBJECTIVES ARE TO UNDERSTAND 1207 00:50:30,960 --> 00:50:32,440 THE BIOLOGY OF HELICOBACTER 1208 00:50:32,440 --> 00:50:34,880 PYLORI TO UNDERSTAND THE BASE OF 1209 00:50:34,880 --> 00:50:37,080 INTERACTIONS WITH HOSTS, TO 1210 00:50:37,080 --> 00:50:38,320 BETTER UNDERSTAND THE 1211 00:50:38,320 --> 00:50:39,320 PATHOPHYSIOLOGY ASSOCIATE WITH 1212 00:50:39,320 --> 00:50:40,680 THE INTERACTIONS. 1213 00:50:40,680 --> 00:50:42,480 AND TO CONSIDER THE COST AND 1214 00:50:42,480 --> 00:50:48,720 BENEFITS OF CARRYING H PYLORI. 1215 00:50:48,720 --> 00:50:50,680 THIS SLIDE SHOWED THE GEOGRAPHIC 1216 00:50:50,680 --> 00:50:53,480 STRUCTURE THE WORLDWIDE H PYLORI 1217 00:50:53,480 --> 00:50:56,600 POPULATION FOR STUDY OF MORE 1218 00:50:56,600 --> 00:50:59,080 THAN 700 HELICOBACTER ISOLATES 1219 00:50:59,080 --> 00:51:01,320 FROM AROUND THE WORLD USING 1220 00:51:01,320 --> 00:51:02,320 MULTI-LOCUST TYPE SEQUENCING AND 1221 00:51:02,320 --> 00:51:03,680 THE ISOLATES WERE ORGANIZED 1222 00:51:03,680 --> 00:51:05,240 ACCORDING TO THEIR SEQUENCE 1223 00:51:05,240 --> 00:51:05,440 TYPE. 1224 00:51:05,440 --> 00:51:06,320 THEY ARE SHOWN IN COLORS. 1225 00:51:06,320 --> 00:51:08,080 AND YOU CAN SEE THAT THE COLORS 1226 00:51:08,080 --> 00:51:09,880 AREN'T RANDOM. 1227 00:51:09,880 --> 00:51:12,280 THEY ARE QUITE ORDER. 1228 00:51:12,280 --> 00:51:14,080 THIS ORDINATION IS CONSISTENT 1229 00:51:14,080 --> 00:51:15,680 WITH THE IDEA THAT HUMANS HAVE 1230 00:51:15,680 --> 00:51:19,200 BEEN CARRYING HELICOBACTER SINCE 1231 00:51:19,200 --> 00:51:22,320 BEFORE THE OUT OF AFRICA EVENT 1232 00:51:22,320 --> 00:51:24,120 WHICH WAS 58,000 YEARS AGO. 1233 00:51:24,120 --> 00:51:26,400 AS HUMANS DIVERGED AROUND THE 1234 00:51:26,400 --> 00:51:27,880 WORLD, SO DID THEIR 1235 00:51:27,880 --> 00:51:28,280 HELICOBACTERS. 1236 00:51:28,280 --> 00:51:29,480 THIS IS EVIDENCE FOR THE 1237 00:51:29,480 --> 00:51:32,080 VERTICAL TRANSMISSION OF 1238 00:51:32,080 --> 00:51:32,880 HELICOBACTER AND ONE OF THE 1239 00:51:32,880 --> 00:51:35,720 PIECES OF EVIDENCE THAT 1240 00:51:35,720 --> 00:51:37,040 HELICOBACTER IS QUITE ANCIENT, 1241 00:51:37,040 --> 00:51:39,120 THIS TOOK IT BACK ABOUT 58,000 1242 00:51:39,120 --> 00:51:41,680 YEARS AGO, THERE'S NOW STRONG 1243 00:51:41,680 --> 00:51:44,000 WORK TAKING IT BACK MORE THAN 1244 00:51:44,000 --> 00:51:46,320 100,000 YEARS IN HUMANS. 1245 00:51:46,320 --> 00:51:48,280 AND BY INFERENCE IT IS PROBABLY 1246 00:51:48,280 --> 00:51:50,880 IN HUMANS AND ANCESTORS SINCE 1247 00:51:50,880 --> 00:51:51,920 BEFORE WE WERE HUMANS. 1248 00:51:51,920 --> 00:51:54,160 SO THIS IS CLEARLY AN ANCIENT 1249 00:51:54,160 --> 00:51:56,440 ORGANISM. 1250 00:51:56,440 --> 00:51:58,480 SECOND SHOWN HERE IS A SCHEMATIC 1251 00:51:58,480 --> 00:52:01,920 OF THE INTERACTIONS BETWEEN A 1252 00:52:01,920 --> 00:52:03,640 CO-EVOLVED COLONIZING MICROBE OF 1253 00:52:03,640 --> 00:52:04,120 THE HOST. 1254 00:52:04,120 --> 00:52:07,920 THIS IS WORK WITH DENISE A MATT 1255 00:52:07,920 --> 00:52:08,200 PETITION. 1256 00:52:08,200 --> 00:52:11,200 HER IDEA OF CO-EVOLVED ORGANISMS 1257 00:52:11,200 --> 00:52:13,480 IS KNOWING HOW TO TALK TO THE 1258 00:52:13,480 --> 00:52:14,640 HOST THROUGH PHYSICAL AND 1259 00:52:14,640 --> 00:52:16,280 CHEMICAL SIGNALS AND THEY 1260 00:52:16,280 --> 00:52:18,200 RECEIVE SIGNALS AND NUTRIENTS 1261 00:52:18,200 --> 00:52:19,160 BACK. 1262 00:52:19,160 --> 00:52:23,160 DENISE MODELED THIS A DYNAMIC 1263 00:52:23,160 --> 00:52:24,600 EQUILIBRIUM, ROBUST, RESILIENCE, 1264 00:52:24,600 --> 00:52:26,600 INVOLVES NEGATIVE FEEDBACK LOOPS 1265 00:52:26,600 --> 00:52:28,880 AND THE REAL QUESTION IS WHAT 1266 00:52:28,880 --> 00:52:31,680 HAPPENS WHEN A CO-EVOLVED 1267 00:52:31,680 --> 00:52:34,000 PERSISTENT ORGANISM IS LOST? 1268 00:52:34,000 --> 00:52:35,120 WHAT HAPPENS TO THE PHYSIOLOGY 1269 00:52:35,120 --> 00:52:35,640 OF THE HOST? 1270 00:52:35,640 --> 00:52:39,200 THAT IS WHAT I WILL BE TALKING 1271 00:52:39,200 --> 00:52:39,680 ABOUT. 1272 00:52:39,680 --> 00:52:42,640 SO LET ME VERY -- BARRY SPOKE 1273 00:52:42,640 --> 00:52:44,880 ABOUT PEPTIC ULCER DISEASE, I'M 1274 00:52:44,880 --> 00:52:46,800 ONLY GOING TO MENTION IT 1275 00:52:46,800 --> 00:52:49,800 BRIEFLY, STARTING WITH GASTRIC 1276 00:52:49,800 --> 00:52:52,480 CANCER, 50 YEARS AGO A P 1277 00:52:52,480 --> 00:52:53,440 PATHOLOGIST FROM COLUMBIA 1278 00:52:53,440 --> 00:52:54,680 DEVELOPED A SEQUENCE BEGINNING 1279 00:52:54,680 --> 00:52:57,680 WITH THE NORMAL GASTRIC MUCOSA 1280 00:52:57,680 --> 00:53:00,880 GOING TO GASTRITIS TO ATROPHY 1281 00:53:00,880 --> 00:53:02,240 METAPLASIA TO DYSPLASIA TO 1282 00:53:02,240 --> 00:53:02,880 CANCER. 1283 00:53:02,880 --> 00:53:04,920 OVER THE YEARS EACH STEPS WERE 1284 00:53:04,920 --> 00:53:07,400 CONFIRM BUD NO ONE UNDERSTOOD 1285 00:53:07,400 --> 00:53:08,400 WHY THERE WAS TRANSITION FROM 1286 00:53:08,400 --> 00:53:09,880 WHAT WAS CALLED NORMAL TO WHAT 1287 00:53:09,880 --> 00:53:13,120 WAS CALLED GASTRITIS UNTIL H 1288 00:53:13,120 --> 00:53:14,640 PYLORI WAS IDENTIFY. 1289 00:53:14,640 --> 00:53:17,480 WITH THE IDENTIFICATION OF H 1290 00:53:17,480 --> 00:53:19,240 PYLORI AND ITS STRONG 1291 00:53:19,240 --> 00:53:20,960 ASSOCIATION WITH GASTRITIS AS 1292 00:53:20,960 --> 00:53:22,640 BARRY AND ROBIN SHOWED NOW WE 1293 00:53:22,640 --> 00:53:24,800 CAN SAY IS HELICOBACTER REALLY 1294 00:53:24,800 --> 00:53:28,520 RELATED TO GASTRIC CANCER SO WE 1295 00:53:28,520 --> 00:53:30,320 AND OTHERS DID PROSPECTIVE 1296 00:53:30,320 --> 00:53:32,880 STUDIES LOOKING AT ASSOCIATION 1297 00:53:32,880 --> 00:53:35,680 OF HELICOBACTER WITH DEVELOPMENT 1298 00:53:35,680 --> 00:53:36,920 OF CANCER. 1299 00:53:36,920 --> 00:53:38,760 THREE STUDIES, I WAS INVOLVED IN 1300 00:53:38,760 --> 00:53:43,240 THIS STUDY INVOLVING HAWAII, 1301 00:53:43,240 --> 00:53:44,560 STUDY JAPANESE AMERICAN MEN 1302 00:53:44,560 --> 00:53:46,800 ENROLLED IN A COHORT IN THE 1303 00:53:46,800 --> 00:53:48,320 1950s, THEY WERE FOLLOWED FOR 1304 00:53:48,320 --> 00:53:51,600 THE NEXT 21 YEARS, OVER THAT 1305 00:53:51,600 --> 00:53:53,080 TIME 109 MEN DEVELOPED STOMACH 1306 00:53:53,080 --> 00:53:55,760 CANCER, WE MATCHED THEM WITH 109 1307 00:53:55,760 --> 00:53:57,960 CONTROLS WHO DIDN'T HAVE STOMACH 1308 00:53:57,960 --> 00:53:59,240 CANCER, WE WENT BACK TO THE 1309 00:53:59,240 --> 00:54:01,520 FREEZER AND TOOK OUT THEIR SERUM 1310 00:54:01,520 --> 00:54:03,280 TO SEE IF THEY -- WE COULD 1311 00:54:03,280 --> 00:54:05,000 DETECT ANTIBODIES TO 1312 00:54:05,000 --> 00:54:06,640 HELICOBACTER MEANING THEY WERE 1313 00:54:06,640 --> 00:54:07,040 INFECTED. 1314 00:54:07,040 --> 00:54:08,480 WE FOUND THOSE MEN WHO CARRIED 1315 00:54:08,480 --> 00:54:10,440 HELICOBACTER WERE SIX TIMES MORE 1316 00:54:10,440 --> 00:54:12,880 LIKELY TO DEVELOP GASTRIC CANCER 1317 00:54:12,880 --> 00:54:15,680 IN ENSUING 21 YEARS THAN THE MEN 1318 00:54:15,680 --> 00:54:16,040 WHO DIDN'T. 1319 00:54:16,040 --> 00:54:18,240 ALL THE STUDIES WERE POSITIVE, 1320 00:54:18,240 --> 00:54:21,880 META ANALYSIS ODDS RATIO ABOUT 4 1321 00:54:21,880 --> 00:54:24,280 AND WE ADJUSTED FOR CONFOUNDERS 1322 00:54:24,280 --> 00:54:27,240 GIVES AN ODDS RATIO OF 9. 1323 00:54:27,240 --> 00:54:29,680 HELICOBACTER PYLORI BECAME CLEAR 1324 00:54:29,680 --> 00:54:31,200 THAT HELICOBACTER PYLORI ARE WAS 1325 00:54:31,200 --> 00:54:33,240 THE MAJOR CAUSE OF GASTRIC 1326 00:54:33,240 --> 00:54:35,960 CANCER AROUND THE WORLD, AS WARY 1327 00:54:35,960 --> 00:54:37,280 INDICATED THIS IS A VERY 1328 00:54:37,280 --> 00:54:38,120 IMPORTANT DISEASE. 1329 00:54:38,120 --> 00:54:39,280 ONE OF THE QUESTIONS THOUGH IS 1330 00:54:39,280 --> 00:54:41,680 THAT MOST PEOPLE WHO HAVE 1331 00:54:41,680 --> 00:54:42,280 HELICOBACTER DON'T DEVELOP 1332 00:54:42,280 --> 00:54:44,160 GASTRIC CANCER AND THEY DON'T 1333 00:54:44,160 --> 00:54:45,240 DEVELOP ULCERS EITHER. 1334 00:54:45,240 --> 00:54:47,320 SO THE QUESTION IS WHAT IS GOING 1335 00:54:47,320 --> 00:54:48,640 ON. 1336 00:54:48,640 --> 00:54:51,000 WE AND OTHERS HAVE FOR GASTRIC 1337 00:54:51,000 --> 00:54:51,800 CANCER HAVE BEEN FOLLOWING THE 1338 00:54:51,800 --> 00:54:53,880 PATHWAY OF ATROPIC GASTRITIS 1339 00:54:53,880 --> 00:54:56,080 EFFECTS ON EPITHELIAL CELLS 1340 00:54:56,080 --> 00:54:57,400 LEADING TO CANCER, WHAT CAN 1341 00:54:57,400 --> 00:54:59,720 CAUSE THE DIFFERENCES AMONG 1342 00:54:59,720 --> 00:55:01,080 PEOPLE MAYBE STRAIN DIFFERENCES 1343 00:55:01,080 --> 00:55:02,840 OF BACTERIA OR HOST DIFFERENCES 1344 00:55:02,840 --> 00:55:04,600 OR CO-FACTOR DIFFERENCES, WE 1345 00:55:04,600 --> 00:55:05,760 WORK IN THESE DIFFERENT AREAS 1346 00:55:05,760 --> 00:55:07,800 BUT I WILL SHOW YOU ONE AREA 1347 00:55:07,800 --> 00:55:11,440 THAT WE WORKED ON LIKE BARRY'S 1348 00:55:11,440 --> 00:55:13,160 EXPERIMENT, WE WERE FISHING FOR 1349 00:55:13,160 --> 00:55:16,200 GENES IN HELICOBACTER, AND WE 1350 00:55:16,200 --> 00:55:18,880 MADE IT A LIBRARY IN 1351 00:55:18,880 --> 00:55:21,080 HELICOBACTER GENES IN 1989 AND 1352 00:55:21,080 --> 00:55:22,600 WE PROBED IT WITH SERUM FROM 1353 00:55:22,600 --> 00:55:24,360 SOMEBODY WHO HAD ANTIBODIES 1354 00:55:24,360 --> 00:55:25,640 POSITIVE TO HELICOBACTER, I 1355 00:55:25,640 --> 00:55:27,000 REMEMBER THIS EXPERIMENT VERY 1356 00:55:27,000 --> 00:55:29,080 WELL BECAUSE IT WAS MY SERUM. 1357 00:55:29,080 --> 00:55:31,960 MY SERUM PICKED UP A PROTEIN IN 1358 00:55:31,960 --> 00:55:36,600 A LAMBDA GT 11 BANK THAT WASN'T 1359 00:55:36,600 --> 00:55:37,080 IN BACKGROUND. 1360 00:55:37,080 --> 00:55:39,240 THAT IS A PROTEIN THAT 1361 00:55:39,240 --> 00:55:41,880 EVENTUALLY WE CALLED CAGA. 1362 00:55:41,880 --> 00:55:44,600 WE DISCOVERED A YEAR BEFORE 1363 00:55:44,600 --> 00:55:47,560 RENAL BUT TOGETHER WE CALLED IT 1364 00:55:47,560 --> 00:55:48,600 THE SAME. 1365 00:55:48,600 --> 00:55:50,880 NOW WE KNOW A LOT ABOUT CAGA. 1366 00:55:50,880 --> 00:55:53,000 IT IS A PROTEIN THAT 1367 00:55:53,000 --> 00:55:55,560 HELICOBACTER PYLORI INJECTS INTO 1368 00:55:55,560 --> 00:55:57,280 EPITHELIAL CELLS, A HIGH 1369 00:55:57,280 --> 00:55:58,520 MOLECULAR WEIGH PROTEIN, 1370 00:55:58,520 --> 00:56:00,480 HELICOBACTER HAS A TYPE 4 1371 00:56:00,480 --> 00:56:03,880 SECRETION SYSTEM INJECTING IT, 1372 00:56:03,880 --> 00:56:05,280 PROTEIN UNDERGOES TYROSINE 1373 00:56:05,280 --> 00:56:05,960 PHOSPHORYLATION. 1374 00:56:05,960 --> 00:56:07,440 IT INTERACTS WITH MULTIPLE HOST 1375 00:56:07,440 --> 00:56:10,080 CELL PATHWAYS AND ALTERS MANY 1376 00:56:10,080 --> 00:56:11,440 PHENOTYPES IN EPITHELIAL CELLS, 1377 00:56:11,440 --> 00:56:13,200 THAT'S LINKED TO INCREASE RISK 1378 00:56:13,200 --> 00:56:15,800 FOR ULCER DISEASE AND IN MANY 1379 00:56:15,800 --> 00:56:17,680 STUDIES INCREASE RISK OF STOMACH 1380 00:56:17,680 --> 00:56:18,160 CANCER. 1381 00:56:18,160 --> 00:56:19,680 SO WE HAVE BEEN BEGINNING TO 1382 00:56:19,680 --> 00:56:21,120 UNDERSTAND WHAT MAKES THE 1383 00:56:21,120 --> 00:56:22,280 DIFFERENCE BETWEEN PEOPLE WHO 1384 00:56:22,280 --> 00:56:24,320 HAVE HELICOBACTER. 1385 00:56:24,320 --> 00:56:27,080 BUT WHILE ALL THIS WAS 1386 00:56:27,080 --> 00:56:29,200 HAPPENING, HELICOBACTER PYLORI 1387 00:56:29,200 --> 00:56:30,080 WAS DISAPPEARING. 1388 00:56:30,080 --> 00:56:31,480 HERE ARE DATA FROM STUDIES WE 1389 00:56:31,480 --> 00:56:33,360 DID LOOKING AT THE N HAYNES 1390 00:56:33,360 --> 00:56:36,320 SURVEYS IN THE UNITED STATES 1391 00:56:36,320 --> 00:56:37,560 LOOKING AT HELICOBACTER 1392 00:56:37,560 --> 00:56:39,480 PREVALENCE BY AGE AND YEAR OF 1393 00:56:39,480 --> 00:56:41,440 BIRTH IN BOTH MALES AND FEMALES 1394 00:56:41,440 --> 00:56:43,480 AND WHAT WE FOUND IS THAT PEOPLE 1395 00:56:43,480 --> 00:56:45,000 BORN EARLY IN THE 20TH CENTURY 1396 00:56:45,000 --> 00:56:47,840 HAD HIGH RATES OF THE ORGANISM 1397 00:56:47,840 --> 00:56:49,720 AND LATER IN THE 20TH CENTURY 1398 00:56:49,720 --> 00:56:51,080 HAD LOW RATES. 1399 00:56:51,080 --> 00:56:52,720 THIS WAS CONSISTENT WITH THE 1400 00:56:52,720 --> 00:56:54,560 IDEA THAT THIS ANCIENT ORGANISM 1401 00:56:54,560 --> 00:56:56,680 OF HUMANS WAS DISAPPEARS FROM 1402 00:56:56,680 --> 00:57:00,840 HUMANS OVER A FEW GENERATIONS. 1403 00:57:00,840 --> 00:57:02,440 THERE HAVE BEEN MANY STUDIES 1404 00:57:02,440 --> 00:57:03,760 THAT CONFIRMED THIS, I WANT TO 1405 00:57:03,760 --> 00:57:06,400 SHOW YOU THIS CLEARLY, THIS 1406 00:57:06,400 --> 00:57:07,880 DISAPPEARANCE OF HELICOBACTER IN 1407 00:57:07,880 --> 00:57:10,400 JAPANESE FAMILIES STUDIED BY 1408 00:57:10,400 --> 00:57:12,560 URUTA ET AL WHO LOOKED AT GRAND 1409 00:57:12,560 --> 00:57:14,120 MOTHERS MOTHERS AND CHILDREN AND 1410 00:57:14,120 --> 00:57:15,120 YOU CAN SEE THE STEP DOWN. 1411 00:57:15,120 --> 00:57:18,560 IN FACT THIS IS WHAT HELPED ME 1412 00:57:18,560 --> 00:57:19,560 UNDERSTAND THERE IS -- THAT 1413 00:57:19,560 --> 00:57:21,640 THERE ARE DISAPPEARING ORGANISMS 1414 00:57:21,640 --> 00:57:23,720 THAT SOME OF OUR ANCIENT 1415 00:57:23,720 --> 00:57:27,440 ORGANISMS WE CARRY MAY 1416 00:57:27,440 --> 00:57:28,080 DISAPPEAR. 1417 00:57:28,080 --> 00:57:30,240 SO THE GOOD NEWS IS THAT STOMACH 1418 00:57:30,240 --> 00:57:32,160 CANCER IS DISAPPEARING AS YOU 1419 00:57:32,160 --> 00:57:34,200 MIGHT EXPECT SINCE HELICOBACTER 1420 00:57:34,200 --> 00:57:35,200 IS THE MAJOR CAUSE. 1421 00:57:35,200 --> 00:57:37,880 NO MATTER HOW YOU COUNT IT, 1422 00:57:37,880 --> 00:57:39,760 STOMACH CANCER IS DISAPPEARING. 1423 00:57:39,760 --> 00:57:42,120 HERE IN 1982 HERE IS A DISCOVERY 1424 00:57:42,120 --> 00:57:43,560 OF HELICOBACTER, ACTUALLY 1425 00:57:43,560 --> 00:57:44,760 STOMACH CANCER LARGELY 1426 00:57:44,760 --> 00:57:49,040 DISAPPEARED BEFORE THE DISCOVERY 1427 00:57:49,040 --> 00:57:49,360 DISCOVERY. 1428 00:57:49,360 --> 00:57:51,320 BUT SO THIS HAS BEEN GOING ON 1429 00:57:51,320 --> 00:57:54,680 SINCE THE EARLY 20TH CENTURY. 1430 00:57:54,680 --> 00:57:59,640 SO ALL THIS IS VERY GOOD NEWS. 1431 00:57:59,640 --> 00:58:02,480 MANY GASTROENTEROLOGISTS THINK 1432 00:58:02,480 --> 00:58:04,040 THE ONLY GOOD HELICOBACTER IS A 1433 00:58:04,040 --> 00:58:06,040 DEAD HELICOBACTER, WHY NOT GET 1434 00:58:06,040 --> 00:58:07,920 RID OF IT FOR EVERYBODY, CAUSES 1435 00:58:07,920 --> 00:58:10,320 ULCERS CAUSES STOMACH CANCER, 1436 00:58:10,320 --> 00:58:12,240 AND IN FACT GASTRO ENTEROLOGISTS 1437 00:58:12,240 --> 00:58:14,240 ALL OVER THE WORLD ARE SEARCHING 1438 00:58:14,240 --> 00:58:16,120 AND DESTROYING. 1439 00:58:16,120 --> 00:58:18,680 GETTING RID OF HELICOBACTER FROM 1440 00:58:18,680 --> 00:58:19,040 EVERYBODY. 1441 00:58:19,040 --> 00:58:20,760 BUT UNFORTUNATELY THAT IS NOT 1442 00:58:20,760 --> 00:58:21,960 THE WHOLE STORY. 1443 00:58:21,960 --> 00:58:25,120 BECAUSE AS BARRY SAID THE OTHER 1444 00:58:25,120 --> 00:58:28,680 DISEASES ARE RISING AND ONE IS 1445 00:58:28,680 --> 00:58:30,560 ADENOCARCINOMA OF THE ESOPHAGUS, 1446 00:58:30,560 --> 00:58:33,120 THE FASTEST RIDING CANCER IN THE 1447 00:58:33,120 --> 00:58:34,640 UNITED STATES AND IN FACT ALL 1448 00:58:34,640 --> 00:58:35,720 DEVELOPED COUNTRIES THIS CANCER 1449 00:58:35,720 --> 00:58:38,400 IS GOING UP BETWEEN SIX AND 16% 1450 00:58:38,400 --> 00:58:42,240 A YEAR ACROSS THE DEVELOPED 1451 00:58:42,240 --> 00:58:42,720 WORLD. 1452 00:58:42,720 --> 00:58:44,960 AS BARRY MENTIONED, THIS CANCER 1453 00:58:44,960 --> 00:58:48,480 IS STRONGLY LINKED TO REFLUX 1454 00:58:48,480 --> 00:58:49,440 ESOPHAGITIS FIRST DESCRIBED IN 1455 00:58:49,440 --> 00:58:51,120 THE MEDICAL LITERATURE IN 1456 00:58:51,120 --> 00:58:55,200 1930s AND HAS BEEN INCREASING. 1457 00:58:55,200 --> 00:58:57,240 INTERMEDIATE STEP IS BARRETTES 1458 00:58:57,240 --> 00:58:59,680 ESOPHAGUS FIRST DESCRIBED IN 1459 00:58:59,680 --> 00:59:02,080 1950 AND THEN CANCER DESCRIBED 1460 00:59:02,080 --> 00:59:03,720 AROUND 1970 SO THESE ARE NESTED 1461 00:59:03,720 --> 00:59:06,320 CURVES ALL INCREASING AT A TIME 1462 00:59:06,320 --> 00:59:08,080 THAT HELICOBACTER IS GOING AWAY. 1463 00:59:08,080 --> 00:59:10,760 SO THE QUESTION IS ARE THEY 1464 00:59:10,760 --> 00:59:11,000 RELATED? 1465 00:59:11,000 --> 00:59:12,600 THERE HAVE BEEN MANY STUDIES 1466 00:59:12,600 --> 00:59:14,080 BARRY SHOWED UP AN INTERESTING 1467 00:59:14,080 --> 00:59:15,760 ILLUSTRATION OF THAT, WE DID A 1468 00:59:15,760 --> 00:59:17,720 MORE FORMAL STUDY, THIS WAS A 1469 00:59:17,720 --> 00:59:18,800 STUDY WITH COLLEAGUES AT THAT 1470 00:59:18,800 --> 00:59:22,680 TIME NATIONAL CANCER INSTITUTE, 1471 00:59:22,680 --> 00:59:25,440 LED BY FERRIN AND BILL BLOT. 1472 00:59:25,440 --> 00:59:29,080 HERE WE LOOK AT THE ATBC STUDY 1473 00:59:29,080 --> 00:59:34,600 IN FINLAND, COHORT OF 29,000 MEN 1474 00:59:34,600 --> 00:59:35,840 MIDDLE AGE FOLLOWED FOR SIX 1475 00:59:35,840 --> 00:59:40,600 YEARS, DURING THAT TIME 234 MEN 1476 00:59:40,600 --> 00:59:42,800 DEVELOPED CANCER, 173 WERE 1477 00:59:42,800 --> 00:59:46,280 TRADITIONAL STOMACH CANCER, THEN 1478 00:59:46,280 --> 00:59:48,080 61 WERE CANCERS -- THIS IS THE 1479 00:59:48,080 --> 00:59:52,000 JUNCTION CANCERS THAT ARE LIKE 1480 00:59:52,000 --> 00:59:55,000 ADENOCARCINOMA OF ESOPHAGUS SO 1481 00:59:55,000 --> 00:59:57,080 LOOK AT THE TRAY US THAL CANCER 1482 00:59:57,080 --> 00:59:58,920 THE ODDS RATIO ABOUT 8 AS WE 1483 00:59:58,920 --> 01:00:02,520 HAVE COME TO EXPECT BUT FOR THE 1484 01:00:02,520 --> 01:00:04,280 PROXIMAL CANCER, THE ODDS RATIO 1485 01:00:04,280 --> 01:00:07,000 IS LESS THAN ONE, IT IS INVERSE, 1486 01:00:07,000 --> 01:00:08,280 ASSOCIATED WITH PROTECTION. 1487 01:00:08,280 --> 01:00:10,680 SO THIS IS ONE OF MANY STUDIES 1488 01:00:10,680 --> 01:00:12,120 THAT HAVE SHOWN THE SAME EFFECT, 1489 01:00:12,120 --> 01:00:14,000 THEY SHOW THIS BECAUSE WE HAVE 1490 01:00:14,000 --> 01:00:16,440 BOTH DATA IN THE SAME STUDY, IT 1491 01:00:16,440 --> 01:00:19,880 WAS ALL LARGE STUDY BLINDED AND 1492 01:00:19,880 --> 01:00:21,800 THERE'S MANY INDEPENDENT STUDIES 1493 01:00:21,800 --> 01:00:24,200 SHOWING THE SAME THING. 1494 01:00:24,200 --> 01:00:26,440 SO ABOUT 20 YEARS AGO I PROPOSED 1495 01:00:26,440 --> 01:00:27,880 A RECIPROCAL RELATIONSHIP 1496 01:00:27,880 --> 01:00:30,000 BETWEEN THE ADENOCARCINOMA OF 1497 01:00:30,000 --> 01:00:31,600 THE LOWER STOMACH AND THOSE OF 1498 01:00:31,600 --> 01:00:33,880 THE ESOPHAGUS IN UPPER STOMACH. 1499 01:00:33,880 --> 01:00:35,520 THE IDEA WENT IF YOU HAD 1500 01:00:35,520 --> 01:00:37,720 HELICOBACTER ESPECIALLY CAG 1501 01:00:37,720 --> 01:00:38,840 POSITIVE STRAIN YOU WOULD HAVE A 1502 01:00:38,840 --> 01:00:42,560 LOT OF INFLAMMATION IN YOUR 1503 01:00:42,560 --> 01:00:45,800 STOMACH LEADING TO ATROPIC 1504 01:00:45,800 --> 01:00:46,920 GASTRITIS AND GAINS IN THE LOWER 1505 01:00:46,920 --> 01:00:48,840 STOMACH, A PROCESS THAT TAKES 1506 01:00:48,840 --> 01:00:50,800 DECADES N CONTRAST IF YOU DON'T 1507 01:00:50,800 --> 01:00:51,640 HAVE HELICOBACTER AND YOU DON'T 1508 01:00:51,640 --> 01:00:54,400 HAVE A CAGA POSITIVE THAT I CALL 1509 01:00:54,400 --> 01:00:57,080 A CAG WHICH UNFORTUNATELY STILL 1510 01:00:57,080 --> 01:00:58,440 HASN'T CAUGHT ON THEN YOU ARE 1511 01:00:58,440 --> 01:01:01,360 HIGH RISK FOR REFLUX BARRETT'S 1512 01:01:01,360 --> 01:01:03,600 AND CANCER ALL SHOWN, A PROCESS 1513 01:01:03,600 --> 01:01:06,280 THAT ALSO TAKES MULTIPLE DECADES 1514 01:01:06,280 --> 01:01:10,200 SO BOTTOM LINE IS YOU CAN'T WIN. 1515 01:01:10,200 --> 01:01:11,640 IT'S BAD TO HAVE HELICOBACTER 1516 01:01:11,640 --> 01:01:13,880 AND GOOD TO HAVE HELICOBACTER. 1517 01:01:13,880 --> 01:01:15,200 MOST DON'T DEVELOP EITHER CANCER 1518 01:01:15,200 --> 01:01:17,280 SO THE REAL QUESTION IS WHAT IS 1519 01:01:17,280 --> 01:01:19,000 GOING ON, CAN WE UNDERSTAND THE 1520 01:01:19,000 --> 01:01:23,800 PROCESS A LITTLE BETTER. 1521 01:01:23,800 --> 01:01:25,280 SO ABOUT TEN YEARS AGO A GROUP 1522 01:01:25,280 --> 01:01:27,840 FROM THE NATIONAL CANCER 1523 01:01:27,840 --> 01:01:29,800 INSTITUTE LED BY BILL ANDERSON 1524 01:01:29,800 --> 01:01:30,920 PUBLISHED SOME VERY INTERESTING 1525 01:01:30,920 --> 01:01:36,520 DATA LOOKING AT GASTRIC CANCER 1526 01:01:36,520 --> 01:01:39,600 RATES BY SUBSET OF CAUCASIANS IN 1527 01:01:39,600 --> 01:01:42,280 THE UNITED STATES IN ABOUT 30 1528 01:01:42,280 --> 01:01:42,960 YEARS. 1529 01:01:42,960 --> 01:01:44,480 MOST RATES ARE GOING DOWN 1530 01:01:44,480 --> 01:01:46,760 CARDIAC CANCERS WERE GOING UP AS 1531 01:01:46,760 --> 01:01:48,280 WE NOW KNOW. 1532 01:01:48,280 --> 01:01:50,680 THEY FOUND ANOTHER CANCER OF THE 1533 01:01:50,680 --> 01:01:53,080 CORPUS THAT WAS DEFINED -- 1534 01:01:53,080 --> 01:01:55,080 DEFYING THE TREND WHEREAS OTHERS 1535 01:01:55,080 --> 01:01:57,200 GOING DOWN IT WAS GOING UP 1536 01:01:57,200 --> 01:01:57,600 SLIGHTLY. 1537 01:01:57,600 --> 01:01:59,480 AND WHEN THEY LOOK AT THE DATA 1538 01:01:59,480 --> 01:02:01,760 BY AGE, THEY FOUND THAT CANCER 1539 01:02:01,760 --> 01:02:03,560 IN OLDER PEOPLE WERE GOING DOWN 1540 01:02:03,560 --> 01:02:05,880 AT A FAST RATE, NOT SO OLD 1541 01:02:05,880 --> 01:02:07,680 PEOPLE GOING DOWN AT SLOW RATE 1542 01:02:07,680 --> 01:02:09,960 BUT YOUNG PEOPLE THE GASTRIC 1543 01:02:09,960 --> 01:02:12,400 CANCER WERE GOING UP. 1544 01:02:12,400 --> 01:02:15,280 THIS WAS BIRTH COMORTALITY BORN 1545 01:02:15,280 --> 01:02:16,520 SINCE 1952 WHICH INTERESTINGLY 1546 01:02:16,520 --> 01:02:20,240 IS AROUND THE TIME ANTIBIOTICS 1547 01:02:20,240 --> 01:02:22,160 CAME INTO WIDE PRACTICE. 1548 01:02:22,160 --> 01:02:23,600 SINCE THEN THE GROUP HAS 1549 01:02:23,600 --> 01:02:24,840 CONTINUED THESE STUDIES HERE 1550 01:02:24,840 --> 01:02:29,440 THEY ARE LOOKING AT THE RATES OF 1551 01:02:29,440 --> 01:02:31,880 NON-CARDIAC CANCER IN MEN AND 1552 01:02:31,880 --> 01:02:34,360 WOMEN, BY AGE IN OLDER PEOPLE IT 1553 01:02:34,360 --> 01:02:37,360 IS GOING DOWN NOT SO OLD, IT IS 1554 01:02:37,360 --> 01:02:38,640 FLAT AND IN YOUNGER PEOPLE IT IS 1555 01:02:38,640 --> 01:02:41,480 GOING UP. 1556 01:02:41,480 --> 01:02:43,120 AND IN FACT WE WERE ASKED TO 1557 01:02:43,120 --> 01:02:46,480 WRITE AN EDITORIAL ABOUT THIS 1558 01:02:46,480 --> 01:02:47,480 AND WE BELIEVE THIS WAS -- THEIR 1559 01:02:47,480 --> 01:02:49,080 WORK HAS SHOWN US THAT THERE'S A 1560 01:02:49,080 --> 01:02:52,000 NEW CANCER AMONG US. 1561 01:02:52,000 --> 01:02:55,400 WE CALL THE SIF CANCERS, CORPUS 1562 01:02:55,400 --> 01:02:56,960 DOMINANT YOUNG FEMALE DOMINANT 1563 01:02:56,960 --> 01:02:58,640 BECAUSE THE RATES WERE HIGHER IN 1564 01:02:58,640 --> 01:03:00,080 FEMALES HAHN MALES AND IN FACT 1565 01:03:00,080 --> 01:03:03,280 THE ANNUAL INCREASE IN WOMEN IS 1566 01:03:03,280 --> 01:03:05,120 TWICE THE RATE IN MEN. 1567 01:03:05,120 --> 01:03:07,320 THESE ARE GOING RAPIDLY. 1568 01:03:07,320 --> 01:03:11,400 SO MUCH RAPIDLY THAT THE NCI HAS 1569 01:03:11,400 --> 01:03:14,400 ESTIMATED BY 2050 THE SEX 1570 01:03:14,400 --> 01:03:15,640 DISTRIBUTION OF GASTRIC CANCER 1571 01:03:15,640 --> 01:03:18,400 WILL FLIP, FROM MALE PREDOMINANT 1572 01:03:18,400 --> 01:03:20,240 TO FEMALE PREDOMINANT. 1573 01:03:20,240 --> 01:03:22,680 VERY RECENTLY LAST MONTH ANOTHER 1574 01:03:22,680 --> 01:03:25,040 GROUP FROM THE METASTASIS 1575 01:03:25,040 --> 01:03:28,000 INCLUDING SOFT SAME 1576 01:03:28,000 --> 01:03:31,720 INVESTIGATORS LED BY MINKO SUNG 1577 01:03:31,720 --> 01:03:35,040 LED ANTI-INFLAMMATION PARIETAL 1578 01:03:35,040 --> 01:03:37,040 CELLS AND GASTRIC CANCER RISK 1579 01:03:37,040 --> 01:03:39,200 THEY WEREN'T USING THE FINISHED 1580 01:03:39,200 --> 01:03:41,640 MATERNITY COHORT OF A MILLION 1581 01:03:41,640 --> 01:03:44,680 PREGNANT WOMEN BORN OVER 50 YEAR 1582 01:03:44,680 --> 01:03:46,680 PERIOD, 529 CASES OF GASTRIC 1583 01:03:46,680 --> 01:03:47,680 CANCER, THEY MATCH WITH THAT 1584 01:03:47,680 --> 01:03:49,760 SAME NUMBER OF CONTROLS. 1585 01:03:49,760 --> 01:03:52,280 THEY HAD SERUM FROM PREGNANCIES, 1586 01:03:52,280 --> 01:03:54,560 17 YEARS BEFORE THEY DEVELOPED 1587 01:03:54,560 --> 01:03:55,840 CANCER SO HERE THEY ARE LOOKING 1588 01:03:55,840 --> 01:03:59,240 AT A THE ASSOCIATION OF 1589 01:03:59,240 --> 01:04:03,080 AUTOANTIBODIES, WITH THE CANCER 1590 01:04:03,080 --> 01:04:04,680 DEVELOPMENT ALL TOLD ALL 1591 01:04:04,680 --> 01:04:06,120 PARTICIPANTS THEY HAD 1592 01:04:06,120 --> 01:04:06,680 HELICOBACTER, HAIRPIN CREASE 1593 01:04:06,680 --> 01:04:09,040 RISK FOR STOMACH CANCER AS 1594 01:04:09,040 --> 01:04:10,880 CONFIRMING WHAT WE ALREADY KNOW 1595 01:04:10,880 --> 01:04:13,000 BUT IF THEY HAD ANTI-PARIETAL 1596 01:04:13,000 --> 01:04:14,480 CELL ANTIBODIES THEY WERE ALSO 1597 01:04:14,480 --> 01:04:15,840 INCREASE RISK. 1598 01:04:15,840 --> 01:04:18,040 THE RISK WAS PARTICULARLY HIGH 1599 01:04:18,040 --> 01:04:20,680 IF H HIGH LORI NEGATIVE, ODDS 1600 01:04:20,680 --> 01:04:23,040 RATIO IS FIVE AND A HALF NOT 1601 01:04:23,040 --> 01:04:26,240 REALLY SIGNIFICANT H PYLORI 1602 01:04:26,240 --> 01:04:26,760 NEGATIVE. 1603 01:04:26,760 --> 01:04:27,480 WHAT IS INTERESTING WHEN THEY 1604 01:04:27,480 --> 01:04:29,160 LOOK AT THE CANCER OF THE CORPUS 1605 01:04:29,160 --> 01:04:32,800 AND THE FUNGUS IN THOSE THAT HAD 1606 01:04:32,800 --> 01:04:33,760 ANTI-PARIETAL CELLS ANTIBODIES 1607 01:04:33,760 --> 01:04:36,360 THE ODDS RATIO WAS 25. 1608 01:04:36,360 --> 01:04:38,360 IT IS A REALLY STRIKING 1609 01:04:38,360 --> 01:04:39,360 ASSOCIATION WITH THESE NEW 1610 01:04:39,360 --> 01:04:44,480 CANCERS OF THE CORPUS. 1611 01:04:44,480 --> 01:04:46,040 I WAS IMPRESSED BY THIS AND 1612 01:04:46,040 --> 01:04:47,920 WROTE HER AND ASKED HER IF SHE 1613 01:04:47,920 --> 01:04:49,800 WOULD EXAMINE THE RELATIONSHIP 1614 01:04:49,800 --> 01:04:52,760 BETWEEN THESE ANTIBODIES AND H 1615 01:04:52,760 --> 01:04:54,360 PYLORI SERO NEGATIVITY. 1616 01:04:54,360 --> 01:04:56,480 SHE SENT ME THE DATA AND I'M 1617 01:04:56,480 --> 01:04:57,600 APPRECIATIVE OF HER SENDING IT 1618 01:04:57,600 --> 01:04:59,600 AND LETTING ME SHARE THIS 1619 01:04:59,600 --> 01:05:01,840 BECAUSE SERO NEGATIVE PEOPLE IN 1620 01:05:01,840 --> 01:05:03,080 GENERAL WERE TWICE AS LIKELY TO 1621 01:05:03,080 --> 01:05:06,400 HAVE ANTIBODIES AS THE SERO 1622 01:05:06,400 --> 01:05:09,360 POSITIVE PEOPLE BUT PEOPLE THE 1623 01:05:09,360 --> 01:05:11,600 WOMEN WHO HAD GASTRIC CANCER IF 1624 01:05:11,600 --> 01:05:12,800 THEY WERE SERO NEGATIVE THEY 1625 01:05:12,800 --> 01:05:15,120 WERE SIX TIMES MORE LIKELY TO 1626 01:05:15,120 --> 01:05:16,680 DEVELOP GASTRIC CANCER THAN IF 1627 01:05:16,680 --> 01:05:18,880 THEY DID NOT HAVE THESE 1628 01:05:18,880 --> 01:05:19,440 ANTIBODIES. 1629 01:05:19,440 --> 01:05:21,480 SO THIS IS A VERY STRONG RISK 1630 01:05:21,480 --> 01:05:24,480 FACTOR IN PEOPLE WHO DON'T HAVE 1631 01:05:24,480 --> 01:05:26,400 H PYLORI. 1632 01:05:26,400 --> 01:05:28,520 IN FACT THEIR POPULATION 1633 01:05:28,520 --> 01:05:30,120 ATTRIBUTABLE RISK FOR GASTRIC 1634 01:05:30,120 --> 01:05:32,360 CANCER FROM THESE AUTOANTIBODIES 1635 01:05:32,360 --> 01:05:33,600 IS ABOUT A THIRD. 1636 01:05:33,600 --> 01:05:35,560 SO THEY IDENTIFIED WITH 1637 01:05:35,560 --> 01:05:36,880 POTENTIALLY A VERY IMPORTANT 1638 01:05:36,880 --> 01:05:37,360 CAUSE. 1639 01:05:37,360 --> 01:05:39,600 SO THE QUESTION IS WHY DO PEOPLE 1640 01:05:39,600 --> 01:05:41,520 WHO DON'T HAVE HELICOBACTER HAVE 1641 01:05:41,520 --> 01:05:45,400 ALL THESE AUTOANTIBODIES TO 1642 01:05:45,400 --> 01:05:46,320 THEIR STOMACH. 1643 01:05:46,320 --> 01:05:48,000 THIS IS A SUMMARY OF THE 1644 01:05:48,000 --> 01:05:50,600 CHANGING EPIDEMIOLOGY OF GASTRIC 1645 01:05:50,600 --> 01:05:53,280 AND ESOPHAGEAL ADENOCARCINOMA. 1646 01:05:53,280 --> 01:05:54,440 THE ANCIENT GASTRIC CANCER 1647 01:05:54,440 --> 01:05:56,680 THAT'S THE ONE ASSOCIATED WITH 1648 01:05:56,680 --> 01:05:59,040 HELICOBACTER PYLORI, ASSOCIATED 1649 01:05:59,040 --> 01:06:02,200 WITH ATROPIC GASTRITIS, OLDER 1650 01:06:02,200 --> 01:06:04,080 PEOPLE MALE PREDOMINANT, THE 1651 01:06:04,080 --> 01:06:06,840 MODERN IS GE JUNCTION CANCER, 1652 01:06:06,840 --> 01:06:08,840 RELATED TO BARRETT'S ESOPHAGUS 1653 01:06:08,840 --> 01:06:11,040 AND NOW THE POST MODERN ONE 1654 01:06:11,040 --> 01:06:13,520 CORPUS SEEMS TO BE RELATESSED TO 1655 01:06:13,520 --> 01:06:14,840 AUTOIMMUNE GASTRITIS, IT IS IN 1656 01:06:14,840 --> 01:06:17,440 THE YOUNGEST PEOPLE WITH THIS 1657 01:06:17,440 --> 01:06:18,200 STRIKING DIFFERENCE IN SEX 1658 01:06:18,200 --> 01:06:19,240 RATIO. 1659 01:06:19,240 --> 01:06:23,680 SO WHAT IS GOING ON? 1660 01:06:23,680 --> 01:06:26,280 LAUREN AND MICHAEL AWE DESCRIBED 1661 01:06:26,280 --> 01:06:27,640 HELICOBACTER IN CELLULAR 1662 01:06:27,640 --> 01:06:29,320 INFILTRATION IN THE STOMACH 1663 01:06:29,320 --> 01:06:32,840 WHICH WARREN CALLED GASTRITIS, 1664 01:06:32,840 --> 01:06:34,680 THEY ARE INFLAMMATORY CELLS IN 1665 01:06:34,680 --> 01:06:35,600 THE STOMACH. 1666 01:06:35,600 --> 01:06:39,240 I WONDER MAYBE THERE IS AN 1667 01:06:39,240 --> 01:06:41,520 ALTERNATIVE NAME, RATHER THAN 1668 01:06:41,520 --> 01:06:44,840 CALL IT GASTRITIS IT IS THE 1669 01:06:44,840 --> 01:06:46,880 RESPONSE TO THE ANCIENT 1670 01:06:46,880 --> 01:06:47,400 MICROBIOTA. 1671 01:06:47,400 --> 01:06:49,120 IN OTHER WORDS THIS IS NORMAL 1672 01:06:49,120 --> 01:06:51,080 AND THE STOMACHS THAT DON'T HAVE 1673 01:06:51,080 --> 01:06:54,880 CELLS ARE HISTORICALLY ABNORMAL. 1674 01:06:54,880 --> 01:06:57,360 SO WHAT COULD THOSE CELLS BE 1675 01:06:57,360 --> 01:06:58,280 DOING? 1676 01:06:58,280 --> 01:07:00,280 WHY MIGHT WE HAVE CO-EVOLVE WITH 1677 01:07:00,280 --> 01:07:01,200 HELICOBACTER? 1678 01:07:01,200 --> 01:07:03,280 ONE IDEA IS THESE IMMUNOSITES 1679 01:07:03,280 --> 01:07:05,160 ARE IMMUNE ADJUVANT AND HELPING 1680 01:07:05,160 --> 01:07:06,760 US DEAL WITH INFECTION. 1681 01:07:06,760 --> 01:07:10,320 I WILL SHOW YOU THREE EXAMPLES. 1682 01:07:10,320 --> 01:07:12,920 HERE IS A STUDY LOOKING AT THE 1683 01:07:12,920 --> 01:07:14,160 RELATIONSHIP BETWEEN 1684 01:07:14,160 --> 01:07:15,720 HELICOBACTER AND DIARRHEA, THOSE 1685 01:07:15,720 --> 01:07:17,480 KIDS WITH HELICOBACTER HAD LESS 1686 01:07:17,480 --> 01:07:19,160 DIARRHEA THAN THE KIDS WHO DID 1687 01:07:19,160 --> 01:07:19,480 NOT. 1688 01:07:19,480 --> 01:07:22,080 HERE WE ARE LOOKING AT IMMUNE 1689 01:07:22,080 --> 01:07:24,280 RESPONSES TO LIVE ORAL TYPHOID 1690 01:07:24,280 --> 01:07:26,080 VACCINES IN VOLUNTEERS PEOPLE 1691 01:07:26,080 --> 01:07:27,320 WHO HAD HELICOBACTER HAD 1692 01:07:27,320 --> 01:07:28,800 STRONGER RESPONSES, THAN PEOPLE 1693 01:07:28,800 --> 01:07:30,960 WHO DID NOT. 1694 01:07:30,960 --> 01:07:35,680 HERE IS A STUDY, IN WHICH 41 1695 01:07:35,680 --> 01:07:38,040 MACAQUES WERE GIVEN 1696 01:07:38,040 --> 01:07:40,240 MICROBACTERIUM TUBERCULOSIS AND 1697 01:07:40,240 --> 01:07:41,120 AS WHO WOULD DEVELOP ACTIVE 1698 01:07:41,120 --> 01:07:44,240 DISEASE OVER THE NEXT SIX TO 1699 01:07:44,240 --> 01:07:44,960 EIGHT MONTHS. 1700 01:07:44,960 --> 01:07:46,240 THE PEOPLE HELICOBACTER POSITIVE 1701 01:07:46,240 --> 01:07:49,280 WERE PROTECTED FROM ACTIVE TB 1702 01:07:49,280 --> 01:07:52,560 ODDS RATIO .31 SO THESE ARE SOME 1703 01:07:52,560 --> 01:07:55,560 EXAMPLES OF POTENTIAL BENEFIT 1704 01:07:55,560 --> 01:07:57,400 HISTORICALLY THAT MIGHT EXPLAIN 1705 01:07:57,400 --> 01:07:58,080 WHY SO MANY PEOPLE HAD 1706 01:07:58,080 --> 01:08:03,720 HELICOBACTER. 1707 01:08:03,720 --> 01:08:04,880 WHAT ARE THESE CELLS DOING? 1708 01:08:04,880 --> 01:08:06,840 IN ADDITION TO TH 1 CELLS 1709 01:08:06,840 --> 01:08:08,360 THERE'S T REGULATORY CELLS, 1710 01:08:08,360 --> 01:08:13,320 CELLS THAT MAKE IL 10, FOX P 3 1711 01:08:13,320 --> 01:08:14,440 TGF BETA. 1712 01:08:14,440 --> 01:08:16,120 SO THE QUESTION IS WHAT IS THE 1713 01:08:16,120 --> 01:08:17,680 BIOLOGICAL SIGNIFICANCE OF 1714 01:08:17,680 --> 01:08:19,280 GASTRIC IMMUNE POPULATIONS? 1715 01:08:19,280 --> 01:08:20,800 JUST FIGHTING INFECTION OR 1716 01:08:20,800 --> 01:08:24,080 PERHAPS HAS TO DO WITH 1717 01:08:24,080 --> 01:08:27,000 REGULATION OF ALLERGIC RESPONSE? 1718 01:08:27,000 --> 01:08:30,800 AS YOU ALL KNOW ASTHMA AS GONE 1719 01:08:30,800 --> 01:08:33,320 UP DRAMATICALLY IN THE POST WAR 1720 01:08:33,320 --> 01:08:34,080 PERIOD. 1721 01:08:34,080 --> 01:08:36,480 THERE'S RELATIONSHIP BETWEEN 1722 01:08:36,480 --> 01:08:39,880 ASTHMA AND GERD SO WE BEGAN TO 1723 01:08:39,880 --> 01:08:41,240 STUDY COULD HELICOBACTER 1724 01:08:41,240 --> 01:08:43,440 PROTECTING FROM GERD PROTECT 1725 01:08:43,440 --> 01:08:44,440 FROM ASTHMA? 1726 01:08:44,440 --> 01:08:46,560 THE FIRST STUDY WAS A STUDY IN 1727 01:08:46,560 --> 01:08:49,840 NEW YORK LOOKING AT 318 ASTHMA 1728 01:08:49,840 --> 01:08:52,120 PATIENTS AND 208 NON-ASTHMA 1729 01:08:52,120 --> 01:08:54,320 CONTROLS AND WE ORGANIZED THE 1730 01:08:54,320 --> 01:08:55,160 DATA, OUR REFERENCE GROUP FOR 1731 01:08:55,160 --> 01:08:56,520 PEOPLE WHO DON'T HAVE 1732 01:08:56,520 --> 01:08:58,800 HELICOBACTER AND DON'T HAVE A 1733 01:08:58,800 --> 01:09:01,080 CAGA POSITIVE STRAIN, THAT IS A 1734 01:09:01,080 --> 01:09:02,880 REFERENCE GROUP ODDS RATIO ONE. 1735 01:09:02,880 --> 01:09:07,720 PEOPLE INFECTED WITH IT CAG 1736 01:09:07,720 --> 01:09:10,440 NEGATIVE ODDS RATIO OF 3.4 BUT 1737 01:09:10,440 --> 01:09:13,360 C, AG POSITIVE ODDS RATIO .63 1738 01:09:13,360 --> 01:09:14,600 INVERSE ASSOCIATION CONSISTENT 1739 01:09:14,600 --> 01:09:17,480 WITH THE IDEA THAT HELICOBACTER 1740 01:09:17,480 --> 01:09:20,760 MIGHT PROTECT AGAINST ASTHMA. 1741 01:09:20,760 --> 01:09:23,480 IN THIS STUDY WE ALSO LOOK AT 1742 01:09:23,480 --> 01:09:25,320 ACID FREE SURVIVAL AMONG ADULTS 1743 01:09:25,320 --> 01:09:27,960 IN THIS STUDY SO EVERYBODY IN 1744 01:09:27,960 --> 01:09:30,080 THIS SURVIVAL CURVE, EVERYONE 1745 01:09:30,080 --> 01:09:32,480 BEGAN LIFE FREE OF ASTHMA AND 1746 01:09:32,480 --> 01:09:33,600 EVERYONE DEVELOPED ASTHMA 1747 01:09:33,600 --> 01:09:36,080 BECAUSE THAT IS WHO WE CHOSE. 1748 01:09:36,080 --> 01:09:40,600 IF WE LOOK AT THE AIDS THAT 1749 01:09:40,600 --> 01:09:42,360 DEVELOPED ASTHMA THEY DEVELOPED 1750 01:09:42,360 --> 01:09:44,160 ON AVERAGE IN THEIR 20s, THOSE 1751 01:09:44,160 --> 01:09:46,960 WHO DEVELOPED -- WHO HAVE -- WHO 1752 01:09:46,960 --> 01:09:48,360 DID NOT HAVE HELICOBACTER 1753 01:09:48,360 --> 01:09:50,880 DEVELOPED IT WHEN THEY WERE 1754 01:09:50,880 --> 01:09:51,480 ABOUT 11. 1755 01:09:51,480 --> 01:09:52,160 VERY STRONG DIFFERENCE. 1756 01:09:52,160 --> 01:09:54,280 SO WE THEN DID A STUDY, AGAIN 1757 01:09:54,280 --> 01:09:58,160 LOOKING AT THE N HAYNES, THIS IS 1758 01:09:58,160 --> 01:09:59,440 WORK THAT U CHEN AND I DID. 1759 01:09:59,440 --> 01:10:02,480 WE LOOKED PAT ODDS RATIO FOR 1760 01:10:02,480 --> 01:10:05,880 ASTHMA, THE REFERENCE GROUP WAS 1761 01:10:05,880 --> 01:10:06,440 NO HELICOBACTER. 1762 01:10:06,440 --> 01:10:08,400 IF WE LOOK AT ADULT ONSET ASTHMA 1763 01:10:08,400 --> 01:10:09,720 THERE'S NO RELATIONSHIP WITH 1764 01:10:09,720 --> 01:10:10,200 HELICOBACTER. 1765 01:10:10,200 --> 01:10:13,280 THE CHILDHOOD ONSET ASTHMA AGAIN 1766 01:10:13,280 --> 01:10:15,120 CAG POSITIVE STRAIN STRONG 1767 01:10:15,120 --> 01:10:16,200 INVERSE ASSOCIATION. 1768 01:10:16,200 --> 01:10:18,600 WE HAVE NOW DONE THREE LARGE 1769 01:10:18,600 --> 01:10:20,400 INDEPENDENT STUDIES ALL BLINDED 1770 01:10:20,400 --> 01:10:22,600 WITH THOUSANDS OF PEOPLE WE 1771 01:10:22,600 --> 01:10:25,880 CONTINUE TO FIND THIS 1772 01:10:25,880 --> 01:10:27,800 EPIDEMIOLOGIC ASSOCIATION. 1773 01:10:27,800 --> 01:10:29,600 WE KNOW THIS IS ASSOCIATION 1774 01:10:29,600 --> 01:10:31,040 CORRELATION IS NOT CAUSE. 1775 01:10:31,040 --> 01:10:32,680 SO IN FACT THERE HAVE BEEN 1776 01:10:32,680 --> 01:10:33,840 EXPERIMENTAL STUDIES AND I WANT 1777 01:10:33,840 --> 01:10:37,800 TO POINT TO THE WORK OF ANN 1778 01:10:37,800 --> 01:10:41,080 MUELLER'S LAB TO DEVELOP A MOUSE 1779 01:10:41,080 --> 01:10:42,280 MODEL IN WHICH MICE WERE 1780 01:10:42,280 --> 01:10:44,920 SENSITIZED WITH ALLERGEN, HOUSE 1781 01:10:44,920 --> 01:10:47,200 MICE DUST ANTIGEN AND CHALLENGE 1782 01:10:47,200 --> 01:10:49,240 THEY DEVELOP ASTHMA LIKE 1783 01:10:49,240 --> 01:10:49,760 FINDINGS. 1784 01:10:49,760 --> 01:10:54,160 THEIR STUDIES INCLUDING STUDY BY 1785 01:10:54,160 --> 01:10:55,280 ISABELLE ARNOLD HAD THREE GROUPS 1786 01:10:55,280 --> 01:10:56,840 OF MICE, MICE WITHOUT 1787 01:10:56,840 --> 01:10:59,800 HELICOBACTER OR MICE GIVEN 1788 01:10:59,800 --> 01:11:00,560 HELICOBACTER WHEN THEY WERE 1789 01:11:00,560 --> 01:11:02,600 INFANTS OR ADULTS. 1790 01:11:02,600 --> 01:11:04,080 SO THIS SLIDE SHOWS THE MAIN 1791 01:11:04,080 --> 01:11:07,480 RESULT OF THE STUDY, THEY DID A 1792 01:11:07,480 --> 01:11:09,000 METHYL CHOLINE CHALLENGE, USED 1793 01:11:09,000 --> 01:11:12,880 IN MICE AND HUMANS, IF YOU 1794 01:11:12,880 --> 01:11:16,440 INGEST METHYL CHOLINE YOU'LL 1795 01:11:16,440 --> 01:11:17,360 START TO WHEEZE SO HERE WE ARE 1796 01:11:17,360 --> 01:11:19,560 LOOKING AT MICE THAT DIDN'T GET 1797 01:11:19,560 --> 01:11:22,640 THE DUST MITE ANTIGEN WITH MORE 1798 01:11:22,640 --> 01:11:25,200 METHYL CHOLINE BUT NOT BY MUCH. 1799 01:11:25,200 --> 01:11:27,400 IF THEY GOT HOUSE DUST MITE 1800 01:11:27,400 --> 01:11:29,600 ANTIGEN AND DIDN'T GET ANY 1801 01:11:29,600 --> 01:11:31,360 INFECTION THEY ARE WISING A LOT. 1802 01:11:31,360 --> 01:11:32,960 WHEN THEY GOT HELICOBACTER IN 1803 01:11:32,960 --> 01:11:33,960 ADULTS, IT DIDN'T MAKE A 1804 01:11:33,960 --> 01:11:36,280 DIFFERENCE BUT IF THEY GOT IT AS 1805 01:11:36,280 --> 01:11:37,840 A CHILD IT MADE A BIG 1806 01:11:37,840 --> 01:11:38,360 DIFFERENCE. 1807 01:11:38,360 --> 01:11:39,760 WE CAN SEE BACK TO BASELINE. 1808 01:11:39,760 --> 01:11:42,720 WE CAN SEE INFLAMMATORY SCORE 1809 01:11:42,720 --> 01:11:44,280 PAS POSITIVE CELLS WE CAN SEE IT 1810 01:11:44,280 --> 01:11:45,520 IN HISTOLOGY. 1811 01:11:45,520 --> 01:11:46,880 IN FURTHER WORK I DON'T HAVE 1812 01:11:46,880 --> 01:11:50,760 TIME TO SHOW YOU, IN ANN 1813 01:11:50,760 --> 01:11:53,240 MUELLER'S LAB SHOWED 1814 01:11:53,240 --> 01:11:54,880 HELICOBACTER PROGRAMS DENDRITIC 1815 01:11:54,880 --> 01:11:57,200 CELLS TO MAKEICSL 18 WHICH 1816 01:11:57,200 --> 01:11:59,760 INCLUDES T REGULATORY CELLS, WE 1817 01:11:59,760 --> 01:12:01,800 HAVE DONE FURTHER WORK THAT 1818 01:12:01,800 --> 01:12:02,600 EXTENDED THIS WORK. 1819 01:12:02,600 --> 01:12:03,840 ONE OTHER FUNCTION OF THE 1820 01:12:03,840 --> 01:12:05,400 STOMACH IS THAT IT PRODUCES 1821 01:12:05,400 --> 01:12:05,760 HORMONES. 1822 01:12:05,760 --> 01:12:11,840 IT PRODUCES LEPTON AND PRODUCES 1823 01:12:11,840 --> 01:12:12,240 DCALIN. 1824 01:12:12,240 --> 01:12:13,400 IT IS IMPORTANT BECAUSE WHEN YOU 1825 01:12:13,400 --> 01:12:14,480 WAKE UP MANY THE MORNING AND YOU 1826 01:12:14,480 --> 01:12:17,680 ARE HUNGRY, GHREHLIN IS TELLING 1827 01:12:17,680 --> 01:12:21,440 YOU IT IS TIME TO EAT. 1828 01:12:21,440 --> 01:12:26,160 SO DID AN HELICOBACTER ON 1829 01:12:26,160 --> 01:12:30,680 FASTING POST MEAL SERUM 1830 01:12:30,680 --> 01:12:31,280 GHREHLIN. 1831 01:12:31,280 --> 01:12:34,600 HAIR FASTING IS HIGH, AFTER THEY 1832 01:12:34,600 --> 01:12:37,240 EAT IT GOES DOWN AS EXPECTED. 1833 01:12:37,240 --> 01:12:39,600 AFTER HELICOBACTER ERADICATION 1834 01:12:39,600 --> 01:12:42,680 PRE-MEAL IS HIGH, AND POST MEAL 1835 01:12:42,680 --> 01:12:43,240 DOESN'T GO DOWN. 1836 01:12:43,240 --> 01:12:45,560 THIS IS ONE OF MANY PIESES OF 1837 01:12:45,560 --> 01:12:48,080 EVIDENCE THAT HELICOBACTER IS 1838 01:12:48,080 --> 01:12:51,560 AFFECTING HORMONAL PHYSIOLOGY IN 1839 01:12:51,560 --> 01:12:55,080 THE STOMACH. 1840 01:12:55,080 --> 01:12:56,320 SO DEVELOPED A MOUSE MODEL WHICH 1841 01:12:56,320 --> 01:12:59,880 WE WERE LOOKING AT EFFECTS OF 1842 01:12:59,880 --> 01:13:02,400 HELICOBACTER IN THE STOMACH AND 1843 01:13:02,400 --> 01:13:02,760 SYSTEMICALLY. 1844 01:13:02,760 --> 01:13:04,880 WE SAW INFECTING MICE 1845 01:13:04,880 --> 01:13:06,000 HELICOBACTER AFFECTED 1846 01:13:06,000 --> 01:13:08,200 COLONIZATION AND ANTIBODIES AND 1847 01:13:08,200 --> 01:13:09,640 PRODUCED HISTOPATHOLOGY, 1848 01:13:09,640 --> 01:13:10,880 AFFECTED HORMONES, IT CHANGED 1849 01:13:10,880 --> 01:13:12,640 THE MICROBIOTA IN THE STOMACH 1850 01:13:12,640 --> 01:13:14,280 AND ELSEWHERE AND CHANGED TO 1851 01:13:14,280 --> 01:13:15,720 GENE EXPRESSION IN STOMACH AND 1852 01:13:15,720 --> 01:13:18,080 IN THE LUNG. 1853 01:13:18,080 --> 01:13:19,640 AND PULMONARY T-CELL RESPONSES 1854 01:13:19,640 --> 01:13:21,040 AS WELL. 1855 01:13:21,040 --> 01:13:23,160 HELICOBACTER IS NOT JUST LIMITED 1856 01:13:23,160 --> 01:13:25,560 TO AFFECT ON THE STOMACH. 1857 01:13:25,560 --> 01:13:27,880 SO JUST TO SUMMARIZE, AS THE 1858 01:13:27,880 --> 01:13:30,760 WORLD HAS CHANGED FROM 1859 01:13:30,760 --> 01:13:31,560 HELICOBACTER DOMINATED STOMACH 1860 01:13:31,560 --> 01:13:34,320 TO A STOMACH FREE OF 1861 01:13:34,320 --> 01:13:36,040 HELICOBACTER, THERE'S BIG 1862 01:13:36,040 --> 01:13:37,160 CHANGES IN CANCER THAT I TOLD 1863 01:13:37,160 --> 01:13:38,680 YOU ABOUT AND THERE ARE CHANGES 1864 01:13:38,680 --> 01:13:41,200 IN OTHER ASPECT OF PHYSIOLOGY 1865 01:13:41,200 --> 01:13:44,280 INVOLVING GASTRIC OF META 1866 01:13:44,280 --> 01:13:47,600 STATIN, ACIDITY LEPTON AND T 1867 01:13:47,600 --> 01:13:49,640 REGULATORY CELLS HAVE BEEN SHOWN 1868 01:13:49,640 --> 01:13:50,760 AND THERE ARE CONSEQUENCES 1869 01:13:50,760 --> 01:13:51,960 ASSOCIATED WITH THIS, THE 1870 01:13:51,960 --> 01:13:54,080 DECREASE IN ULCERS AND GASTRIC 1871 01:13:54,080 --> 01:13:56,080 CANCER THAT'S GOOD NEWS. 1872 01:13:56,080 --> 01:13:58,720 ALSO THE RISE IN GERD AND THE 1873 01:13:58,720 --> 01:14:01,000 CANCER THAT FOLLOW, ASTHMA, 1874 01:14:01,000 --> 01:14:02,400 INFECTION AND SILL YAK DISEASE 1875 01:14:02,400 --> 01:14:03,400 SO THE LAST QUESTION I'M GOING 1876 01:14:03,400 --> 01:14:06,360 TO ADDRESS IS HELICOBACTER GOOD 1877 01:14:06,360 --> 01:14:08,800 FOR US OR BAD FOR US. 1878 01:14:08,800 --> 01:14:10,320 SO U CHEN AND I DID ANOTHER 1879 01:14:10,320 --> 01:14:12,720 STUDY WE LOOKED AT N HAYNES HAD 1880 01:14:12,720 --> 01:14:14,360 DATA ON PEOPLE WE HAD 1881 01:14:14,360 --> 01:14:16,560 HELICOBACTER STATUS IN 1988 AND 1882 01:14:16,560 --> 01:14:20,520 WE FOLLOWED THEM TO DEATH IN 1883 01:14:20,520 --> 01:14:20,720 2006. 1884 01:14:20,720 --> 01:14:24,640 WE HAD 100,000 ADULT PERSON 1885 01:14:24,640 --> 01:14:26,240 YEARS, 2,000 PEOPLE DIED DURING 1886 01:14:26,240 --> 01:14:27,960 THOSE 18 YEARS IN THE N HAYNES 1887 01:14:27,960 --> 01:14:30,080 STUDIES, MOST FROM 1888 01:14:30,080 --> 01:14:31,160 CARDIOVASCULAR DISEASE OR CANCER 1889 01:14:31,160 --> 01:14:33,840 AND OUR QUESTION IS, WAS 1890 01:14:33,840 --> 01:14:34,680 HELICOBACTER GOOD FOR THEM OTHER 1891 01:14:34,680 --> 01:14:35,960 BAD FOR THEM. 1892 01:14:35,960 --> 01:14:39,640 SO FIRST WE JUST LOOK AT GI 1893 01:14:39,640 --> 01:14:39,880 CANCER. 1894 01:14:39,880 --> 01:14:41,920 WHEN WE LOOK AT GASTRIC CANCER 1895 01:14:41,920 --> 01:14:44,360 THE ODDS RATIO WAS 40. 1896 01:14:44,360 --> 01:14:46,680 IF YOU HAD HELICOBACTER YOU ARE 1897 01:14:46,680 --> 01:14:49,640 40 TIME MORRIS LIKELY TO DIE OF 1898 01:14:49,640 --> 01:14:50,720 GASTRIC CANCER THAN IF YOU 1899 01:14:50,720 --> 01:14:51,240 DIDN'T. 1900 01:14:51,240 --> 01:14:52,760 SO BASICALLY HELICOBACTER IS 1901 01:14:52,760 --> 01:14:55,200 RESPONSIBLE FOR ALL GASTRIC 1902 01:14:55,200 --> 01:14:56,840 CANCER IN THE UNITED STATES OF 1903 01:14:56,840 --> 01:14:59,680 THE CLASSIC KIND BUT THERE WERE 1904 01:14:59,680 --> 01:15:01,080 ONLY 16 EVENTS LESS THAN 1 1905 01:15:01,080 --> 01:15:02,520 PERCENT OF THE POPULATION DIED 1906 01:15:02,520 --> 01:15:03,800 FROM GASTRIC CANCER. 1907 01:15:03,800 --> 01:15:07,240 FOR THE OTHER CANCERS THERE 1908 01:15:07,240 --> 01:15:08,680 WASN'T SIGNIFICANCE THOUGH 1909 01:15:08,680 --> 01:15:11,000 INVERSE SIGNIFICANCE OF KAG 1910 01:15:11,000 --> 01:15:12,160 NEGATIVE STRAINS WITH PANCREATIC 1911 01:15:12,160 --> 01:15:12,480 CANCER. 1912 01:15:12,480 --> 01:15:15,120 THERE'S MORE CASES WITH CAG 1913 01:15:15,120 --> 01:15:17,280 NEGATIVE THAN ALL GASTRIC 1914 01:15:17,280 --> 01:15:17,520 CANCER. 1915 01:15:17,520 --> 01:15:18,880 BUT WE WANTED TO LOOK AT THE 1916 01:15:18,880 --> 01:15:20,800 BOTTOM LINE, ALL CAUSE 1917 01:15:20,800 --> 01:15:21,080 MORTALITY. 1918 01:15:21,080 --> 01:15:23,160 SO WHEN WE COMPARED THE PEOPLE 1919 01:15:23,160 --> 01:15:24,440 WHO WERE HELICOBACTER NEGATIVE 1920 01:15:24,440 --> 01:15:26,080 AS THE REFERENCE GROUP, THOSE 1921 01:15:26,080 --> 01:15:27,560 WERE HELICOBACTER POSITIVE THE 1922 01:15:27,560 --> 01:15:31,320 ODDS RATIO WAS 1.00. 1923 01:15:31,320 --> 01:15:32,440 IT COULDN'T HAVE BEEN CLOSER IF 1924 01:15:32,440 --> 01:15:34,520 WE TRIED. 1925 01:15:34,520 --> 01:15:35,760 THERE WAS NO NET EFFECT ON 1926 01:15:35,760 --> 01:15:38,200 MORTALITY. 1927 01:15:38,200 --> 01:15:40,680 IT DIDN'T MATTER WHETHER C AG 1928 01:15:40,680 --> 01:15:42,160 POSITIVE OR NEGATIVE STRAIN, 1929 01:15:42,160 --> 01:15:45,960 ESSENTIALLY THE SAME. 1930 01:15:45,960 --> 01:15:47,240 BUT SOMETHING MUST BE MAKING UP 1931 01:15:47,240 --> 01:15:48,320 FOR THOSE CASES OF GASTRIC 1932 01:15:48,320 --> 01:15:51,040 CANCER SO WHEN WE LOOK AT CARDIO 1933 01:15:51,040 --> 01:15:53,920 VASCULAR MORTALITY WE SEE 1934 01:15:53,920 --> 01:15:56,520 TENDING TOWARD NEGATIVE BUT IN 1935 01:15:56,520 --> 01:15:59,280 PARTICULAR WE LOOK AT STROKE 1936 01:15:59,280 --> 01:16:02,480 THERE WAS STRONG INVERSE 1937 01:16:02,480 --> 01:16:03,560 ASSOCIATION, WE DIDN'T SUSPECT 1938 01:16:03,560 --> 01:16:05,240 IT IN THE LEAST BUT THAT IS WHY 1939 01:16:05,240 --> 01:16:06,640 WE DO RESEARCH, TURNS OUT THIS 1940 01:16:06,640 --> 01:16:08,240 WAS THE SECOND STUDY SHOWING 1941 01:16:08,240 --> 01:16:10,680 INVERSE ASSOCIATION OF 1942 01:16:10,680 --> 01:16:11,800 HELICOBACTER WITH STROKE. 1943 01:16:11,800 --> 01:16:13,520 THERE'S SOME EVIDENCE THAT T 1944 01:16:13,520 --> 01:16:15,040 REGULATORY CELLS PROTECT AGAINST 1945 01:16:15,040 --> 01:16:16,080 STROKE AS WELL. 1946 01:16:16,080 --> 01:16:17,880 SO POTENTIALLY A MECHANISM. 1947 01:16:17,880 --> 01:16:22,080 SO IF I HAVE TO SUMMARIZE THERE 1948 01:16:22,080 --> 01:16:24,640 IS A BIPHASIC NATURE OF 1949 01:16:24,640 --> 01:16:25,880 HELICOBACTER PYLORI IN 1950 01:16:25,880 --> 01:16:27,000 INTERACTIONS WITH HUMANS. 1951 01:16:27,000 --> 01:16:29,080 THERE IS COST AND BENEFIT, THE 1952 01:16:29,080 --> 01:16:32,840 COST ARE MOSTLY LATER IN LIFE 1953 01:16:32,840 --> 01:16:34,640 ULCER DISEASE METABOLIC 1954 01:16:34,640 --> 01:16:35,960 SYNDROME, WHICH I HAVEN'T TALKED 1955 01:16:35,960 --> 01:16:37,440 ABOUT IN CLASSICAL GASTRIC 1956 01:16:37,440 --> 01:16:39,320 CANCER AND PERHAPS THERE'S 1957 01:16:39,320 --> 01:16:41,240 BENEFIT EARLY IN LIFE INFECTIONS 1958 01:16:41,240 --> 01:16:44,440 ASTHMA, THERE'S EVIDENCE ON SILL 1959 01:16:44,440 --> 01:16:46,200 YAK DISEASE STROKE AS I SHOWED 1960 01:16:46,200 --> 01:16:50,480 YOU REFLUX EOSINOPHILIC 1961 01:16:50,480 --> 01:16:51,680 ASPHAGITIS AND OTHER CANCERS I 1962 01:16:51,680 --> 01:16:52,080 TALKED ABOUT. 1963 01:16:52,080 --> 01:16:54,840 SO JUST TO FINISH THE ONLY GOOD 1964 01:16:54,840 --> 01:16:59,440 HELICOBACTER PYLORI A DEAD 1965 01:16:59,440 --> 01:16:59,760 HELICOBACTER? 1966 01:16:59,760 --> 01:17:00,400 I DON'T THINK. 1967 01:17:00,400 --> 01:17:04,440 WHAT I WOULD SAY IS HELICOBACTER 1968 01:17:04,440 --> 01:17:08,520 PYLORI IS A HUMAN MICROBIOTA, 1969 01:17:08,520 --> 01:17:10,040 ISOR ITS DISAPPEARANCE HAS 1970 01:17:10,040 --> 01:17:11,280 CONSEQUENCE GOOD AND BAD, THAT 1971 01:17:11,280 --> 01:17:12,280 IS FUTURE OF MEDICINE. 1972 01:17:12,280 --> 01:17:14,080 MANY PEOPLE HAVE HELPED ME, HAVE 1973 01:17:14,080 --> 01:17:15,720 TRIED TO ACKNOWLEDGE SOME OF 1974 01:17:15,720 --> 01:17:18,280 THEM BUT IS A GREAT TEAM EFFORT 1975 01:17:18,280 --> 01:17:18,880 OVER THE YEARS. 1976 01:17:18,880 --> 01:17:21,840 WITH THAT I WILL STOP. 1977 01:17:21,840 --> 01:17:28,560 >> THANK YOU, VERY MUCH, MARTY 1978 01:17:28,560 --> 01:17:32,200 AND AND DARRELL FOR THIS 1979 01:17:32,200 --> 01:17:32,720 STIMULATING CONVERSATION. 1980 01:17:32,720 --> 01:17:34,520 THERE'S SEVERAL QUESTIONS THAT 1981 01:17:34,520 --> 01:17:36,680 COME UP, PERHAPS EITHER ONE CAN 1982 01:17:36,680 --> 01:17:37,880 VOLUNTEER OR BOTH OF YOU TO 1983 01:17:37,880 --> 01:17:39,840 RESPOND TO IT. 1984 01:17:39,840 --> 01:17:43,800 WHAT DO YOU THINK IS THE ORIGIN 1985 01:17:43,800 --> 01:17:46,000 OF H PYLORI? 1986 01:17:46,000 --> 01:17:49,520 SEEMS TO ME I READ SOMEWHERE 1987 01:17:49,520 --> 01:17:53,600 EVEN IN THE ORGANISMS IN THE 1988 01:17:53,600 --> 01:17:57,040 DEEP SEA EVENTS, FAMILY MEMBERS 1989 01:17:57,040 --> 01:18:00,880 OF THE CAMPYLOBACTER 1990 01:18:00,880 --> 01:18:03,640 HELICOBACTER FAMILY ARE PRESENT. 1991 01:18:03,640 --> 01:18:08,160 >> LET ME TAKE THIS ONE IRWIN. 1992 01:18:08,160 --> 01:18:11,880 SO CAMPYLOBACTER HELICOBACTER, 1993 01:18:11,880 --> 01:18:14,000 THEY COLONIZE THE DIGESTIVE 1994 01:18:14,000 --> 01:18:16,040 TRACKS OF MANY ANIMALS, IT IS A 1995 01:18:16,040 --> 01:18:20,600 BIG FAMILY OF ORGANISMS AND IF 1996 01:18:20,600 --> 01:18:24,040 YOU LOOK AT MOUNTAINS THAT HAVE 1997 01:18:24,040 --> 01:18:28,000 (INAUDIBLE) WHICH IS IN THEIR 1998 01:18:28,000 --> 01:18:29,720 ACID SECRETION, THEY ALL HAVE 1999 01:18:29,720 --> 01:18:32,240 ORGANISMS THAT ARE HELICOBACTERS 2000 01:18:32,240 --> 01:18:34,080 OR ARE SIMILAR TO HELICOBACTERS. 2001 01:18:34,080 --> 01:18:37,080 THIS IS ANCESTRAL TO ACID 2002 01:18:37,080 --> 01:18:38,120 SECRETING STOMACHS. 2003 01:18:38,120 --> 01:18:39,880 OF COURSE IF YOU LOOK AT 2004 01:18:39,880 --> 01:18:41,760 NON-HUMAN PRIMATES THEY ALL HAVE 2005 01:18:41,760 --> 01:18:43,000 HELICOBACTER THAT LOOK VERY 2006 01:18:43,000 --> 01:18:45,120 SIMILAR TO H PYLORI. 2007 01:18:45,120 --> 01:18:47,680 SO THIS IS ANCESTRAL JUST LIKE 2008 01:18:47,680 --> 01:18:49,280 WE HAVE MANY OTHER ANCESTRAL 2009 01:18:49,280 --> 01:18:53,200 BACTERIA. 2010 01:18:53,200 --> 01:18:54,320 >> WHAT DO YOU THINK IS THERE 2011 01:18:54,320 --> 01:18:57,280 ANY SIGNIFICANCE TO THEIR 2012 01:18:57,280 --> 01:19:01,800 PRESENCE IN THE DEEP SEA VENTS 2013 01:19:01,800 --> 01:19:03,320 THOUGHT BY EVOLUTIONARY 2014 01:19:03,320 --> 01:19:04,280 BIOLOGISTS THAT HAVE SOMETHING 2015 01:19:04,280 --> 01:19:06,440 TO DO WITH THE ORIGIN OF LIFE? 2016 01:19:06,440 --> 01:19:08,080 >> WELL THESE ARE SOME OF THE 2017 01:19:08,080 --> 01:19:10,000 EARLIEST PLACES THAT BACTERIA 2018 01:19:10,000 --> 01:19:11,640 ROSE AND AS YOU KNOW BACTERIA 2019 01:19:11,640 --> 01:19:13,760 THE OLDER FORM OF LIFE ON EARTH 2020 01:19:13,760 --> 01:19:16,040 THEY PRECEDE ALL OTHER FORMS OF 2021 01:19:16,040 --> 01:19:17,320 LIFE ON EARTH BY 2 BILLION 2022 01:19:17,320 --> 01:19:17,880 YEARS. 2023 01:19:17,880 --> 01:19:19,680 I'M NOT AWARE THAT THERE ARE 2024 01:19:19,680 --> 01:19:23,440 TRULY CAMPYLOBACTERS IN THE DC 2025 01:19:23,440 --> 01:19:26,320 VENTS BUT WORK OF CARL LOUIS AND 2026 01:19:26,320 --> 01:19:28,200 NORMAN PACE HAVE SHOWN US A 2027 01:19:28,200 --> 01:19:32,720 GREAT PHYLOGENY OF BACTERIA IN 2028 01:19:32,720 --> 01:19:33,440 THE WORLD. 2029 01:19:33,440 --> 01:19:38,160 >> I'LL MAKE A FEW COMMENTS, WE 2030 01:19:38,160 --> 01:19:43,520 HAVE SEEN LOOK AT THE ECOLOGY IN 2031 01:19:43,520 --> 01:19:47,040 THE ROOM MICROFLUIDIC FLORA THAT 2032 01:19:47,040 --> 01:19:50,400 TAKES THE LAST VESTIGE OF OXYGEN 2033 01:19:50,400 --> 01:19:54,000 OUT OF THE ROOM AND ALLOWS THE 2034 01:19:54,000 --> 01:19:55,280 INTERNAL PART OF THE ROOM TO BE 2035 01:19:55,280 --> 01:19:59,640 AN AEROBIC, THERE ARE SOME 2036 01:19:59,640 --> 01:20:00,880 INTERESTING EMs SHOWING 2037 01:20:00,880 --> 01:20:03,520 SIMILAR LOOKING BACTERIA, 2038 01:20:03,520 --> 01:20:06,080 SOMETIMES COLONIZING THE ACID 2039 01:20:06,080 --> 01:20:12,480 SECRETING STOMACH OF REMNANTS SO 2040 01:20:12,480 --> 01:20:15,280 MY OPINION IS HUMANS PICKED THEM 2041 01:20:15,280 --> 01:20:16,280 UP FROM RHEUM FANTASTICS IN 2042 01:20:16,280 --> 01:20:22,040 AFRICA JUST EATING THE GUTS. 2043 01:20:22,040 --> 01:20:24,280 AND 30,000 YEARS AGO IT PICKED 2044 01:20:24,280 --> 01:20:25,520 UP THE HELICOBACTER PICKED UP 2045 01:20:25,520 --> 01:20:29,800 THE CAG TOXIN WHICH STARTED 2046 01:20:29,800 --> 01:20:31,920 PRODUCING THESE DISEASES LIKE 2047 01:20:31,920 --> 01:20:34,680 PEPTIC ULCERS AND MAYBE MAKING 2048 01:20:34,680 --> 01:20:35,800 GASTRIC CANCER MORE LIKELY. 2049 01:20:35,800 --> 01:20:38,120 THAT HAPPENED IN THE JOURNEY OF 2050 01:20:38,120 --> 01:20:42,280 HUMANS FROM AFRICA OVER TO ASIA. 2051 01:20:42,280 --> 01:20:44,920 SO IT IS A BIT OF A STORY. 2052 01:20:44,920 --> 01:20:48,920 WE FOUND SIMILAR HELICOBACTER IN 2053 01:20:48,920 --> 01:20:49,920 DOLPHINS. 2054 01:20:49,920 --> 01:20:54,000 ALSO IN MARSUPIAL MICE OF 2055 01:20:54,000 --> 01:20:57,520 DIFFERENT KINDS, IN AUSTRALIA. 2056 01:20:57,520 --> 01:20:59,600 SO AT THE MOMENT WE DON'T KNOW 2057 01:20:59,600 --> 01:21:01,320 BUT I WOULD SAY HUMANS ATE 2058 01:21:01,320 --> 01:21:04,840 SOMETHING AT SOME POINT. 2059 01:21:04,840 --> 01:21:07,080 >> THE ALTERNATIVE IS IF THESE 2060 01:21:07,080 --> 01:21:09,280 ARE ANCESTRAL IN ALL MAMMALS AND 2061 01:21:09,280 --> 01:21:11,320 THERE IS A LOT OF EVIDENCE FOR 2062 01:21:11,320 --> 01:21:11,680 THAT. 2063 01:21:11,680 --> 01:21:14,440 >> IN VIRGINIA WE LOOK AT A 2064 01:21:14,440 --> 01:21:15,880 COUPLE OF POSSUMS AND COULDN'T 2065 01:21:15,880 --> 01:21:16,680 FIND ANY HELICOBACTER IN THEIR 2066 01:21:16,680 --> 01:21:19,040 STOMACH. 2067 01:21:19,040 --> 01:21:19,240 SO -- 2068 01:21:19,240 --> 01:21:23,640 >> DEPENDS HOW YOU LOOK. 2069 01:21:23,640 --> 01:21:26,320 DEPENDS HOW YOU LOOK. 2070 01:21:26,320 --> 01:21:29,520 >> THERE'S QUESTIONS ABOUT HOW 2071 01:21:29,520 --> 01:21:33,840 REALLY DOES H PYLORI, LIVE IN 2072 01:21:33,840 --> 01:21:36,880 THE STOMACH, DOES IT FORM 2073 01:21:36,880 --> 01:21:37,280 BIOFILMS? 2074 01:21:37,280 --> 01:21:39,440 IS THAT ONE OF THE MECHANISMS 2075 01:21:39,440 --> 01:21:42,800 THAT MANY HOPE TO PROTECT IT? 2076 01:21:42,800 --> 01:21:45,680 DO WE KNOW ANYTHING ABOUT BARRY 2077 01:21:45,680 --> 01:21:49,720 YOU MENTIONED ABOUT ITS 2078 01:21:49,720 --> 01:21:50,960 ASSOCIATION AT LEAST IN EARLY 2079 01:21:50,960 --> 01:21:54,040 OBSERVATIONS AND LOCALIZATION 2080 01:21:54,040 --> 01:21:55,200 AIRTIGHT JUNCTIONS, ARE THERE 2081 01:21:55,200 --> 01:22:01,080 ANY CLUES AS TO WHAT IT IS AT 2082 01:22:01,080 --> 01:22:04,920 THE LEVEL OF CELLS PARTICULARLY 2083 01:22:04,920 --> 01:22:08,000 THE PARIETAL CELL HOW THE 2084 01:22:08,000 --> 01:22:09,120 ORGANISM EXISTS. 2085 01:22:09,120 --> 01:22:11,680 AREN'T BIOFILMS AN IMPORTANT 2086 01:22:11,680 --> 01:22:13,520 PART OF H PYLORI? 2087 01:22:13,520 --> 01:22:16,400 >> I'M NOT SURE -- IF YOU SAY 2088 01:22:16,400 --> 01:22:18,680 BIOFILMS THEN YOU -- I'M 2089 01:22:18,680 --> 01:22:22,480 THINKING QUORUM SENSING, IT CAN 2090 01:22:22,480 --> 01:22:24,920 REACH PRETTY ANY CONCENTRATIONS 2091 01:22:24,920 --> 01:22:27,680 AND ARE BEING SHAREED FROM THE 2092 01:22:27,680 --> 01:22:29,880 STOMACH IN REPLENISHED WITHIN 2093 01:22:29,880 --> 01:22:31,880 THE GLANDS AND ALTHOUGH ET 2094 01:22:31,880 --> 01:22:33,280 COLONIZES THE STOMACH IT IS 2095 01:22:33,280 --> 01:22:35,760 USUALLY IN RATHER LOW NUMBERS IN 2096 01:22:35,760 --> 01:22:37,080 ACID SECRETING TOP END OF THE 2097 01:22:37,080 --> 01:22:39,000 STOMACH IN THE CORPUS. 2098 01:22:39,000 --> 01:22:40,480 SO SUPERFICIAL. 2099 01:22:40,480 --> 01:22:43,840 IT IS PRETTY CONCENTRATED IN THE 2100 01:22:43,840 --> 01:22:46,440 DEEP PARTS, DEEP GLANDS IN THE 2101 01:22:46,440 --> 01:22:49,680 INTERIM IN DUODENA ULCER 2102 01:22:49,680 --> 01:22:50,840 PATIENTS AND THOSE PEOPLE HAVE 2103 01:22:50,840 --> 01:22:53,440 LITTLE ECTOPIC AREAS OF GASTRIC 2104 01:22:53,440 --> 01:22:56,240 MUCOSA IN THE DUODENUM, WHERE 2105 01:22:56,240 --> 01:22:59,000 THE INFLAMMATION IS REALLY 2106 01:22:59,000 --> 01:23:04,680 SEVERE, H PYLORI GROW IN DENSE 2107 01:23:04,680 --> 01:23:05,320 CONCENTRATIONS. 2108 01:23:05,320 --> 01:23:12,120 SO BIOFILM, IT IS A BIOFILM AND 2109 01:23:12,120 --> 01:23:15,200 JUST THE SHEER NUMBERS ACTUALLY 2110 01:23:15,200 --> 01:23:18,680 BECAUSE THE AMMONIA IN THE 2111 01:23:18,680 --> 01:23:21,040 INTERLEUKINS YOU DO FIND H 2112 01:23:21,040 --> 01:23:23,720 PYLORI IF THE ACID SECRETING 2113 01:23:23,720 --> 01:23:24,440 GLANDS AND INSIDE THE PARIETAL 2114 01:23:24,440 --> 01:23:26,080 CELLS WHICH ARE PROBABLY MY 2115 01:23:26,080 --> 01:23:28,280 OPINION TURNED OFF THAT STAGE. 2116 01:23:28,280 --> 01:23:31,280 THAT'S ONE REASON IT IS HARD TO 2117 01:23:31,280 --> 01:23:31,680 ERADICATE. 2118 01:23:31,680 --> 01:23:33,080 BUT NOT SURE WHERE THE RELEVANCE 2119 01:23:33,080 --> 01:23:35,800 OF BIOFILM IS, MAYBE YOU ARE 2120 01:23:35,800 --> 01:23:36,480 THINKING THAT MAYBE YOU COULD 2121 01:23:36,480 --> 01:23:38,360 STOP IT FROM STICKING. 2122 01:23:38,360 --> 01:23:43,040 GET RID OF IT THAT WAY CUT DOWN 2123 01:23:43,040 --> 01:23:43,600 THE NUMBERS. 2124 01:23:43,600 --> 01:23:49,920 >> H PYLORI IS SUPERBLY ADAPTED 2125 01:23:49,920 --> 01:23:51,600 FOR HUMAN STOMACH JUST AS 2126 01:23:51,600 --> 01:23:55,000 BACTERIA LIVE IN VOLCANOS THEY 2127 01:23:55,000 --> 01:23:57,880 CAN LIVE IN DEEP SEA VENTS, IN 2128 01:23:57,880 --> 01:23:58,440 GRANITE. 2129 01:23:58,440 --> 01:24:02,000 NEW F YOU GIVE BACTERIA 2130 01:24:02,000 --> 01:24:04,680 NUTRIENTS THEY WILL MULTIPLY, H 2131 01:24:04,680 --> 01:24:10,720 PYLORI IS WELL ADAPTED, 2132 01:24:10,720 --> 01:24:12,880 HELICOBACTER ARE ACTIVELY 2133 01:24:12,880 --> 01:24:14,840 MULTIPLYING MANY THE PRESENCE OF 2134 01:24:14,840 --> 01:24:15,840 80 YEARS OF LIFE SOMEBODY HAS 2135 01:24:15,840 --> 01:24:17,560 BECAUSE IF THEY DIDN'T THEY 2136 01:24:17,560 --> 01:24:20,520 WOULD BE ELIMINATED BY 2137 01:24:20,520 --> 01:24:22,120 PERISTALLSIS BUT THEY ARE 2138 01:24:22,120 --> 01:24:25,120 MULTIPLYING SO THERE IS AN 2139 01:24:25,120 --> 01:24:26,680 EQUILIBRIUM BETWEEN RATE OF LOSS 2140 01:24:26,680 --> 01:24:28,280 AND RATE OF GAIN AND THEY HAVE 2141 01:24:28,280 --> 01:24:31,080 DONE WELL BUT NOTHING PREPARED 2142 01:24:31,080 --> 01:24:33,440 THEM FOR 20TH CENTURY LIFE WITH 2143 01:24:33,440 --> 01:24:35,080 CHLORINATED WATER AND 2144 01:24:35,080 --> 01:24:40,840 ANTIBIOTICS. 2145 01:24:40,840 --> 01:24:44,640 >> INTERESTING IMMUNOLOGIC H 2146 01:24:44,640 --> 01:24:46,720 PYLORI WE STILL GOT TO TEST THIS 2147 01:24:46,720 --> 01:24:49,840 IN SOME HUMAN MODELS TO SEE IF 2148 01:24:49,840 --> 01:24:51,120 WE CAN GET CLINICAL EFFECT AND I 2149 01:24:51,120 --> 01:24:52,680 KNOW MARTY HAD DISCUSSIONS ON 2150 01:24:52,680 --> 01:24:53,120 IT. 2151 01:24:53,120 --> 01:24:54,800 ONE OF THE PROJECTS I HAVE ON 2152 01:24:54,800 --> 01:24:56,760 THE BACK BURNER AT THE MOMENT 2153 01:24:56,760 --> 01:25:01,440 LIMITED FUNDING, ET CETERA, 2154 01:25:01,440 --> 01:25:04,280 WOULD BE TO CREATE A PRODUCT 2155 01:25:04,280 --> 01:25:07,720 CONTAINING LIKE A ACTIVE PYLORI, 2156 01:25:07,720 --> 01:25:11,440 ORIGIN MALI WE RIDE TO FIND IT 2157 01:25:11,440 --> 01:25:12,480 HARMLESS LIVE HELICOBACTER 2158 01:25:12,480 --> 01:25:15,200 PERHAPS GENERATE SOME OF THESE 2159 01:25:15,200 --> 01:25:19,200 BENEFICIAL IMMUNOLOGIC FIX BUT 2160 01:25:19,200 --> 01:25:22,440 WE COULD NOT FIND A HARMLESS 2161 01:25:22,440 --> 01:25:26,120 HELICOBACTER PYLORI EVEN ONES 2162 01:25:26,120 --> 01:25:28,680 WITHOUT TOXIN SOMETIMES PRODUCE 2163 01:25:28,680 --> 01:25:31,960 ULCERS OR EROSIONS IN THE ACUTE 2164 01:25:31,960 --> 01:25:33,520 STATE SO NOT SUITABLE AT THE 2165 01:25:33,520 --> 01:25:39,000 MOMENT TO CREATE A VACCINE OR 2166 01:25:39,000 --> 01:25:41,080 PROBIOTIC TREATMENT BUT 2167 01:25:41,080 --> 01:25:42,880 INTERESTING IN THIS 2168 01:25:42,880 --> 01:25:46,280 INVESTIGATING KILLED H PYLORI, 2169 01:25:46,280 --> 01:25:47,840 HAVING THE ANGIOGENIC STRUCTURE 2170 01:25:47,840 --> 01:25:49,560 AND ALL THE COMPONENTS OF 2171 01:25:49,560 --> 01:25:52,280 HELICOBACTER PYLORI PRESENT IN 2172 01:25:52,280 --> 01:25:53,800 SOME KIND OF A PRODUCT WHICH YOU 2173 01:25:53,800 --> 01:25:58,720 COULD TAKE ORALLY, IF IT WERE -- 2174 01:25:58,720 --> 01:26:01,080 WE CAN SOLVE TECHNICAL ISSUES 2175 01:26:01,080 --> 01:26:04,400 WITH IT, THEN THREE YEARS FROM 2176 01:26:04,400 --> 01:26:06,320 NOW, WE MIGHT GET TO STAGE OF 2177 01:26:06,320 --> 01:26:07,240 DOING A CLINICAL TRIAL WHERE WE 2178 01:26:07,240 --> 01:26:10,720 LOOK AT THE IMMUNE EFFECT OF 2179 01:26:10,720 --> 01:26:13,400 TAKING HELICOBACTER AND THE 2180 01:26:13,400 --> 01:26:16,680 ULTIMATE WOULD BE AS A 2181 01:26:16,680 --> 01:26:18,680 SUPPLEMENT TO PROTECT OUR 2182 01:26:18,680 --> 01:26:21,960 CHILDREN FROM ASTHMA IN ALLERGIC 2183 01:26:21,960 --> 01:26:23,200 FAMILIES, IF EVERYONE IN 2184 01:26:23,200 --> 01:26:26,080 FAMILIES GOT ALLERGIES AND 2185 01:26:26,080 --> 01:26:28,120 ASTHMA IS PARTICULARLY COMMON, 2186 01:26:28,120 --> 01:26:31,440 IT MIGHT BE POSSIBLE TO SOMEHOW 2187 01:26:31,440 --> 01:26:33,880 MODULATE THIS EFFECT BY 2188 01:26:33,880 --> 01:26:37,560 INTRODUCING HELICOBACTER TYPE OF 2189 01:26:37,560 --> 01:26:39,680 ANTIGEN MANY THE DIET AT THE 2190 01:26:39,680 --> 01:26:42,440 VERY EARLY AGE. 2191 01:26:42,440 --> 01:26:43,720 SO WE DON'T KNOW. 2192 01:26:43,720 --> 01:26:47,600 >> ALONG THOSE LINES MARTY, 2193 01:26:47,600 --> 01:26:50,800 FRANCESCA ASKS BASED ON YOUR 2194 01:26:50,800 --> 01:26:52,920 PRESENTATION WOULD IT MAKE SENSE 2195 01:26:52,920 --> 01:26:56,520 TO ENCOURAGE H PYLORI IN YOUNGER 2196 01:26:56,520 --> 01:26:57,760 PEOPLE, AND TO TREAT THE 2197 01:26:57,760 --> 01:27:01,440 BACTERIA LATER IN LIFE? 2198 01:27:01,440 --> 01:27:03,880 >> YEAH SO IN 1998 I WROTE IN 2199 01:27:03,880 --> 01:27:05,800 THE BRITISH MEDICAL JOURNAL THAT 2200 01:27:05,800 --> 01:27:07,240 WE WILL BE GIVING HELICOBACTER 2201 01:27:07,240 --> 01:27:13,000 BACK TO PEOPLE IN THE FUTURE. 2202 01:27:13,000 --> 01:27:16,040 AND I THINK THAT'S WHERE THE 2203 01:27:16,040 --> 01:27:19,600 LOGIC LEADS, THAT MOTHERS PASS 2204 01:27:19,600 --> 01:27:23,280 HELICOBACTER TO THEIR KIDS SINCE 2205 01:27:23,280 --> 01:27:25,080 TIME IN MEMORIAL AND HAD EARLY 2206 01:27:25,080 --> 01:27:27,080 LIFE BENEFITS, NOW BECAUSE WE 2207 01:27:27,080 --> 01:27:28,880 ARE LIVING LONGER AND MAYBE 2208 01:27:28,880 --> 01:27:30,080 BECAUSE WE CHANGED THE ECOLOGY 2209 01:27:30,080 --> 01:27:33,080 OF THE STOMACH, WE ARE SEEING 2210 01:27:33,080 --> 01:27:35,960 SOME EFFECTS, GASTRIC CANCER IS 2211 01:27:35,960 --> 01:27:38,840 A DISEASE FROM ANTIQUITY, PEPTIC 2212 01:27:38,840 --> 01:27:41,280 ULCER DISEASE IS A DISEASE THAT 2213 01:27:41,280 --> 01:27:42,840 ERODES IN 19TH CENTURY. 2214 01:27:42,840 --> 01:27:44,600 IT IS A RELATIVELY NEW DISEASE, 2215 01:27:44,600 --> 01:27:47,200 SOMETHING CHANGED IN GASTRIC 2216 01:27:47,200 --> 01:27:49,640 ECOLOGY IN 19TH CENTURY WE DON'T 2217 01:27:49,640 --> 01:27:54,080 -- NOBODY KNOWS WHAT IT WAS. 2218 01:27:54,080 --> 01:27:58,440 I THINK FRANCESCA IS ON TO 2219 01:27:58,440 --> 01:28:00,560 SOMETHING THAT WE SHOULD 2220 01:28:00,560 --> 01:28:02,400 REPOPULATE PEOPLE WITH 2221 01:28:02,400 --> 01:28:03,320 HELICOBACTER WHEN THEY ARE 2222 01:28:03,320 --> 01:28:04,440 YOUNG, GET THE BENEFIT WHEN 2223 01:28:04,440 --> 01:28:07,920 YOUNG AND AT SOME AGE MAYBE 30 2224 01:28:07,920 --> 01:28:10,080 OR 40 AFTER GIVING BIRTH TO THE 2225 01:28:10,080 --> 01:28:11,400 NEXT GENERATION SO THEY CAN PASS 2226 01:28:11,400 --> 01:28:13,960 IT ON, AGAIN THIS ORGANISM HAS 2227 01:28:13,960 --> 01:28:16,120 BEEN IN HUMANS FOR COUNTLESS 2228 01:28:16,120 --> 01:28:17,920 HUMAN GENERATIONS. 2229 01:28:17,920 --> 01:28:19,360 THAT'S SOMETHING THAT SHOULD NOT 2230 01:28:19,360 --> 01:28:23,880 BE DISCOUNTED. 2231 01:28:23,880 --> 01:28:27,400 >> I WILL GET ALONG WITH THAT 2232 01:28:27,400 --> 01:28:28,840 POINT, THAT IS RADICAL BUT OF 2233 01:28:28,840 --> 01:28:30,160 COURSE THAT IS A GOOD IDEA -- 2234 01:28:30,160 --> 01:28:34,040 >> JUST AS RADICAL AS YOU WERE 2235 01:28:34,040 --> 01:28:34,560 IN 1980. 2236 01:28:34,560 --> 01:28:37,160 >> OBVIOUSLY I WAS THINKING OF 2237 01:28:37,160 --> 01:28:40,960 AN IMMUNE MODULATION IN TRYING 2238 01:28:40,960 --> 01:28:44,480 TO FIND A HARMLESS HELICOBACTER 2239 01:28:44,480 --> 01:28:47,720 AND AFTER WE DID ABOUT 30 2240 01:28:47,720 --> 01:28:48,240 VOLUNTEERS. 2241 01:28:48,240 --> 01:28:52,840 WE HAD THE MOST BENIGN 2242 01:28:52,840 --> 01:28:55,280 HELICOBACTER WE COULD FIND AND 2243 01:28:55,280 --> 01:28:57,200 IT -- WE STILL HAD A COUPLE OF 2244 01:28:57,200 --> 01:28:59,080 PATIENTS WHO HAD TO BE TAKEN OFF 2245 01:28:59,080 --> 01:29:01,920 TREATMENT BECAUSE THEY HAD 2246 01:29:01,920 --> 01:29:04,000 EROSION. 2247 01:29:04,000 --> 01:29:05,440 AS WE UNDERSTAND IT MORE THESE 2248 01:29:05,440 --> 01:29:06,280 THINGS PROBABLY GOING TO BE 2249 01:29:06,280 --> 01:29:07,280 POSSIBLE. 2250 01:29:07,280 --> 01:29:08,960 >> THE INTERESTING THING IS THAT 2251 01:29:08,960 --> 01:29:11,440 THE CAGA POSITIVE STRAINS ARE 2252 01:29:11,440 --> 01:29:14,680 THE MOST PATHOGENIC AND MOST 2253 01:29:14,680 --> 01:29:15,560 BENEFICIAL BECAUSE THEY ARE THE 2254 01:29:15,560 --> 01:29:17,120 ONES THAT ARE THE MOST 2255 01:29:17,120 --> 01:29:18,160 INTERACTIVE AS A HOST. 2256 01:29:18,160 --> 01:29:21,680 THEY ARE -- THERE'S LIKE THE LOW 2257 01:29:21,680 --> 01:29:23,400 INTERACTIVE STRAIN, THE CAG 2258 01:29:23,400 --> 01:29:25,120 NEGATIVE AND POSITIVES, PROBABLY 2259 01:29:25,120 --> 01:29:28,280 IN THE OLD DAYS, MOST PEOPLE 2260 01:29:28,280 --> 01:29:29,360 HAVE MULTIPLE STRAINS IN THEIR 2261 01:29:29,360 --> 01:29:32,520 STOMACH, THEY HAD A KIND OF 2262 01:29:32,520 --> 01:29:34,280 ECOLOGICAL COMMUNITY MET WITH 2263 01:29:34,280 --> 01:29:35,880 BUFFERING AND MAYBE RISE OF 2264 01:29:35,880 --> 01:29:37,640 ULCER DISEASE IS WHEN 2265 01:29:37,640 --> 01:29:38,440 MULTIPLICITY OF HELICOBACTER OF 2266 01:29:38,440 --> 01:29:40,240 THE STOMACH WHEN COUNT SO INNED 2267 01:29:40,240 --> 01:29:41,120 THE OF FIVE STRAINS YOU ONLY HAD 2268 01:29:41,120 --> 01:29:45,280 ONE AND IT WAS A CAG POSITIVE 2269 01:29:45,280 --> 01:29:45,480 STRAIN. 2270 01:29:45,480 --> 01:29:47,840 >> THE OTHER THING IS, THE 2271 01:29:47,840 --> 01:29:50,120 PARADOX WITH H PYLORI IS IT WAS 2272 01:29:50,120 --> 01:29:51,800 ALWAYS ULCERS ARE CAUSED BY 2273 01:29:51,800 --> 01:29:53,560 STRESS WHICH IS CAUSED BY THE 2274 01:29:53,560 --> 01:29:56,880 20TH CENTURY BUT IN THE 19TH AND 2275 01:29:56,880 --> 01:30:00,200 20TH CENTURY, HUMANS HAD NEVER 2276 01:30:00,200 --> 01:30:03,920 BEEN SO HEALTHY IN THAT THE 2277 01:30:03,920 --> 01:30:07,080 AMOUNT OF PROTEIN AND THE ACID 2278 01:30:07,080 --> 01:30:10,600 SECRETION IN 20TH CENTURY HUMANS 2279 01:30:10,600 --> 01:30:11,960 PARTICULARLY PEOPLE IN CHICAGO, 2280 01:30:11,960 --> 01:30:17,400 NEW YORK WHERE THE DUODENAL 2281 01:30:17,400 --> 01:30:19,120 ULCER EPIDEMIC STARTED TO BE 2282 01:30:19,120 --> 01:30:20,840 NOTED ESPECIALLY SO PEOPLE WHO 2283 01:30:20,840 --> 01:30:23,080 ATE PLENTY OF PROTEIN WERE 2284 01:30:23,080 --> 01:30:24,560 BIGGER IN THIS RECENT 2285 01:30:24,560 --> 01:30:26,080 GENERATIONS AND HAD HIGHER ACID 2286 01:30:26,080 --> 01:30:28,200 SECRETION SO THEY GOT INTO THIS 2287 01:30:28,200 --> 01:30:30,200 -- THEY EXCEEDED THIS THRESHOLD 2288 01:30:30,200 --> 01:30:33,480 WITH MUCOSAL DAMAGE AND ACIDITY 2289 01:30:33,480 --> 01:30:37,040 LED TO DUODENAL ULCER. 2290 01:30:37,040 --> 01:30:38,960 THE PARADOX WAS VISIBLE MANY THE 2291 01:30:38,960 --> 01:30:42,360 AIDS EPIDEMICK, I DON'T THINK I 2292 01:30:42,360 --> 01:30:44,360 EVER SAW HIV PATIENT WITH PEPTIC 2293 01:30:44,360 --> 01:30:46,120 ULCER AND NEVER A PROBLEM WITH 2294 01:30:46,120 --> 01:30:47,280 PATIENTS WITH CHEMOTHERAPY. 2295 01:30:47,280 --> 01:30:51,440 YOU KNOCK OUT MOST OF THE IMMUNE 2296 01:30:51,440 --> 01:30:52,880 SYSTEM YOU CANNOT GET PEPTIC 2297 01:30:52,880 --> 01:30:54,680 ULCER SO IT IS THE REACTION 2298 01:30:54,680 --> 01:30:55,520 AGAINST THE HELICOBACTER THAT 2299 01:30:55,520 --> 01:30:58,600 CAUSED THE DUODENAL ULCER AND IT 2300 01:30:58,600 --> 01:31:00,440 IS A SIGN OF ROBUST HEALTH. 2301 01:31:00,440 --> 01:31:03,320 IN A PERSON WITH HELICOBACTER. 2302 01:31:03,320 --> 01:31:05,680 >> WE HAVE AN INTERESTING 2303 01:31:05,680 --> 01:31:08,240 QUESTION ON THE SCORE MAYBE BOTH 2304 01:31:08,240 --> 01:31:10,200 WILL COMMENT ON, DOES 2305 01:31:10,200 --> 01:31:13,800 HELICOBACTER ACTUALLY INDUCE AN 2306 01:31:13,800 --> 01:31:16,800 IMMUNE TOLERANCE? 2307 01:31:16,800 --> 01:31:19,240 THAT IS INFLAMMATION THAT 2308 01:31:19,240 --> 01:31:22,080 PERSISTS DESPITE THE ACTIVATION 2309 01:31:22,080 --> 01:31:24,960 OF A WHOLE RANGE OF IMMUNE 2310 01:31:24,960 --> 01:31:27,800 MEDIATED MECHANISMS. 2311 01:31:27,800 --> 01:31:31,280 >> WHAT WE KNOW IS SUCCESSFUL 2312 01:31:31,280 --> 01:31:33,680 MICROBES ALL HAVE SECRETS, THEY 2313 01:31:33,680 --> 01:31:35,560 ALL HAVE THEIR TRICKS THAT 2314 01:31:35,560 --> 01:31:38,320 ENABLE THEM TO BE SUCCESSFUL, 2315 01:31:38,320 --> 01:31:39,760 HELICOBACTER HAS FOUND A NICHE 2316 01:31:39,760 --> 01:31:41,880 THAT OTHER ORGANISMS CAN'T 2317 01:31:41,880 --> 01:31:42,680 COLONIZE VERY WELL. 2318 01:31:42,680 --> 01:31:44,880 AND IT IS ACTUALLY TO 2319 01:31:44,880 --> 01:31:46,520 HELICOBACTER BENEFIT TO KEEP AN 2320 01:31:46,520 --> 01:31:47,720 ACID STOMACH BECAUSE NOW THEY 2321 01:31:47,720 --> 01:31:50,200 DON'T HAVE TO COMPETE WITH STREP 2322 01:31:50,200 --> 01:31:52,040 AND E. COLI. 2323 01:31:52,040 --> 01:31:55,440 WHEN ACIDITY GOES DOWN LATER IN 2324 01:31:55,440 --> 01:31:56,440 LIFE HELICOBACTER IS LOST AND 2325 01:31:56,440 --> 01:31:58,800 THE OTHER GUYS COME IN. 2326 01:31:58,800 --> 01:32:03,080 SO THEY ARE MANIPULATING ACID. 2327 01:32:03,080 --> 01:32:05,560 THEY INCREASE -- FOR EXAMPLE 2328 01:32:05,560 --> 01:32:07,200 HELICOBACTER RECRUITS T 2329 01:32:07,200 --> 01:32:08,320 REGULATORY CELLS TO SUPPRESS THE 2330 01:32:08,320 --> 01:32:09,000 IMMUNE RESPONSE. 2331 01:32:09,000 --> 01:32:10,680 THERE'S LOTS OF EVIDENCE THAT 2332 01:32:10,680 --> 01:32:12,000 HELICOBACTER IS UNDER IMMUNE 2333 01:32:12,000 --> 01:32:15,080 SELECTION. 2334 01:32:15,080 --> 01:32:17,960 THEREFORE IT IS BENEFICIAL. 2335 01:32:17,960 --> 01:32:20,680 THAT IS THE SYMBIOSIS, NOT ONLY 2336 01:32:20,680 --> 01:32:24,240 BENEFICIAL HELICOBACTER BUT TO 2337 01:32:24,240 --> 01:32:26,200 THE HOST BECAUSE IT CUTS DOWN 2338 01:32:26,200 --> 01:32:29,800 CERTAIN ALLERGIC RESPONSES. 2339 01:32:29,800 --> 01:32:31,640 >> DO YOU WANT TO COMMENT ABOUT 2340 01:32:31,640 --> 01:32:33,400 THAT BARRY? 2341 01:32:33,400 --> 01:32:37,520 >> I PRETTY GO ALONG WITH THAT. 2342 01:32:37,520 --> 01:32:39,520 IT IS FOUND -- WE DID A STUDY 2343 01:32:39,520 --> 01:32:41,480 WHERE WE INFECTED A COUPLE OF 2344 01:32:41,480 --> 01:32:45,640 PEOPLE WITH HELICOBACTER AND DID 2345 01:32:45,640 --> 01:32:47,440 FORGE SEQUENCING ON THE 2346 01:32:47,440 --> 01:32:51,320 ORGANISMS BEFORE THEY TOOK IT 2347 01:32:51,320 --> 01:32:53,000 AND THEN THINK COUPLE OF WEEKS 2348 01:32:53,000 --> 01:32:54,800 LATER, THREE MONTHS LATER. 2349 01:32:54,800 --> 01:32:58,120 WE JUST SEE AN AMAZING NUMBER OF 2350 01:32:58,120 --> 01:33:00,280 SNPS, LIKE 70 SNPS IN THE FIRST 2351 01:33:00,280 --> 01:33:03,800 ISOLATE WE GOT FROM THE PERSON. 2352 01:33:03,800 --> 01:33:07,560 THIS WAS THE MUTATION RATE MANY 2353 01:33:07,560 --> 01:33:11,080 THE HELICOBACTER WAS SIMILAR UP 2354 01:33:11,080 --> 01:33:12,520 THERE WITH SOME OF THE VIRUSES 2355 01:33:12,520 --> 01:33:15,960 SO WHEN YOU THINK ABOUT IT 2356 01:33:15,960 --> 01:33:17,280 HELICOBACTER ONE OF ITS TWIN 2357 01:33:17,280 --> 01:33:19,280 BROTHERS, IT DOESN'T CARE ABOUT, 2358 01:33:19,280 --> 01:33:21,680 CHECKING THE ACCURACY OF THE 2359 01:33:21,680 --> 01:33:22,720 SECOND GENOME COPYING, IF IT 2360 01:33:22,720 --> 01:33:24,400 MAKES AN ARROW, OKAY LET'S TRY 2361 01:33:24,400 --> 01:33:27,640 THAT, LET'S GO AHEAD WITH IT. 2362 01:33:27,640 --> 01:33:29,960 THE WORST CASE SCENARIOS ONE 2363 01:33:29,960 --> 01:33:32,920 TWIN BROTHERS DIES OFF AND THE 2364 01:33:32,920 --> 01:33:36,640 OTHER ONE POPULATES, AND 2365 01:33:36,640 --> 01:33:38,080 SUCCEEDS, THIS WAS CARBOHYDRATE 2366 01:33:38,080 --> 01:33:41,280 ANTIGENS AND ADHESINS THAT 2367 01:33:41,280 --> 01:33:42,960 HELICOBACTER HAD. 2368 01:33:42,960 --> 01:33:45,640 IF YOU TALK SAY SOMETHING -- 2369 01:33:45,640 --> 01:33:48,480 TOOK SAY SOMETHING CARBOHYDRATE 2370 01:33:48,480 --> 01:33:53,280 SOME KIND OF SUGAR, IT'S INTO H 2371 01:33:53,280 --> 01:33:54,960 PYLORI, FUCOSE. 2372 01:33:54,960 --> 01:33:55,840 IS THAT RIGHT? 2373 01:33:55,840 --> 01:33:57,080 >> FUCOSE. 2374 01:33:57,080 --> 01:33:57,880 >> YEAH. 2375 01:33:57,880 --> 01:33:59,880 T THERE'S LADY IN CANADA WHO HAD 2376 01:33:59,880 --> 01:34:05,880 DONE THOSE STUDIES, IN CALGARY. 2377 01:34:05,880 --> 01:34:07,880 BUT ALL THAT HAPPENED WAS H 2378 01:34:07,880 --> 01:34:09,480 PYLORI TURNED OFF THOSE GENES OR 2379 01:34:09,480 --> 01:34:10,960 TURNED THEM BACK ON, THEY HAD A 2380 01:34:10,960 --> 01:34:13,480 LOT OF POLYAs IN IT, RANDOMLY 2381 01:34:13,480 --> 01:34:17,440 TURNING ON AND OFF THESE SURFACE 2382 01:34:17,440 --> 01:34:21,680 ANTIGENS OR ADHESINS. 2383 01:34:21,680 --> 01:34:24,440 IT WOULD ADAPT TO YOUR STOMACH 2384 01:34:24,440 --> 01:34:26,040 OR MY STOMACH DIFFERENT WAYS 2385 01:34:26,040 --> 01:34:28,160 DEPENDING WHAT OUR BLOOD GROUP 2386 01:34:28,160 --> 01:34:29,400 WAS. 2387 01:34:29,400 --> 01:34:31,160 AND EVENTUALLY EXACTLY LIKE A 2388 01:34:31,160 --> 01:34:35,160 LOCK AND KEY ON TO YOUR PERSONAL 2389 01:34:35,160 --> 01:34:36,680 GASTRIC MUCOSA. 2390 01:34:36,680 --> 01:34:38,640 SO THAT IS ONE OF THE TRICKS. 2391 01:34:38,640 --> 01:34:43,800 >> BARRY REMINDS ME THAT STOMACH 2392 01:34:43,800 --> 01:34:47,000 HAD FOUR MAJOR BLOOD GROUP 2393 01:34:47,000 --> 01:34:50,600 ANTIGENS, LOUIS A, B, X AND Y 2394 01:34:50,600 --> 01:34:51,880 AND HELICOBACTER HAS ALL THE 2395 01:34:51,880 --> 01:34:55,720 GENES TO MAKE LOUIS A B X AND Y. 2396 01:34:55,720 --> 01:34:57,480 SO YOU CAN IMAGINE THAT IF THE 2397 01:34:57,480 --> 01:34:59,840 STOMACH IS GREEN AND YOU INGEST 2398 01:34:59,840 --> 01:35:01,280 HELICOBACTER THAT'S RED OVER 2399 01:35:01,280 --> 01:35:04,600 TIME DUE TO THIS MUTAGENESIS 2400 01:35:04,600 --> 01:35:06,360 THAT STRAIN WILL CONVERGE TO 2401 01:35:06,360 --> 01:35:12,280 LOOK LIKE STOMACH OF THE HOST. 2402 01:35:12,280 --> 01:35:15,160 WE -- HELICOBACTER IS A 2403 01:35:15,160 --> 01:35:16,120 CHAMELEON, TRYING TO MERGE WITH 2404 01:35:16,120 --> 01:35:17,720 THE HOST SO THAT IT WON'T BE 2405 01:35:17,720 --> 01:35:20,440 DETECTED. 2406 01:35:20,440 --> 01:35:23,800 >> IS HELICOBACTER FOUND IN 2407 01:35:23,800 --> 01:35:26,400 OTHER INTESTINAL ORGANS? 2408 01:35:26,400 --> 01:35:29,920 >> HELICOBACTER PYLORI ONLY 2409 01:35:29,920 --> 01:35:31,840 LIVES IN GASTRIC MUCOSA, PEOPLE 2410 01:35:31,840 --> 01:35:36,120 WITH ECTOPIC MUCOSA IN THEIR 2411 01:35:36,120 --> 01:35:39,880 DUODENUM OR METHYL DI VEER TICK 2412 01:35:39,880 --> 01:35:40,760 LAM, IT WON'T COMPETE WITH THE 2413 01:35:40,760 --> 01:35:42,600 ORGANISMS IN THE COLON. 2414 01:35:42,600 --> 01:35:44,800 >> WE PUBLISHED A CASE OF 2415 01:35:44,800 --> 01:35:47,680 ECTOPIC GASTRIC MUCOSA IN THE 2416 01:35:47,680 --> 01:35:49,600 RECTUM AND IN SPITE THE FACT IT 2417 01:35:49,600 --> 01:35:52,760 WAS COVERED IN FECES IS THE ONLY 2418 01:35:52,760 --> 01:35:53,840 THING GROWING ON THAT MUCOSA 2419 01:35:53,840 --> 01:35:56,880 WHICH WAS ACID SECRETING MUCOSA 2420 01:35:56,880 --> 01:35:58,880 THE SIZE OF ONE PIECE WAS 2421 01:35:58,880 --> 01:36:01,880 HELICOBACTER PYLORI, SO NO 2422 01:36:01,880 --> 01:36:04,840 PROBLEM COMPETING, PROVIDED THAT 2423 01:36:04,840 --> 01:36:06,840 IT HAS GASTRIC MUCOSA AND ACID 2424 01:36:06,840 --> 01:36:12,840 BEING SECRETED SO WHENEVER THAT 2425 01:36:12,840 --> 01:36:13,080 HAPPENS -- 2426 01:36:13,080 --> 01:36:15,320 >> AGAIN VERY GOOD EVIDENCE FOR 2427 01:36:15,320 --> 01:36:20,480 TERRIFIC ADAPTATION TO HUMAN 2428 01:36:20,480 --> 01:36:22,640 BIOLOGY. 2429 01:36:22,640 --> 01:36:24,440 ONE OTHER POINT THE INTEREST 2430 01:36:24,440 --> 01:36:26,120 THING ABOUT HELICOBACTER YOU DO 2431 01:36:26,120 --> 01:36:28,120 DEVELOP AN IMMUNE RESPONSE TO IT 2432 01:36:28,120 --> 01:36:31,800 WITH IGG IGA IGM ALL THE USUAL 2433 01:36:31,800 --> 01:36:35,400 THING, ABOUT 80% O PEOPLE WILL 2434 01:36:35,400 --> 01:36:36,560 PRODUCE SECRETE IGA. 2435 01:36:36,560 --> 01:36:38,680 THAT HAS ABSOLUTELY NO 2436 01:36:38,680 --> 01:36:40,040 CORRELATION WITH THE PERSISTENCE 2437 01:36:40,040 --> 01:36:43,440 OR ERADICATION OF THE ORGANISM. 2438 01:36:43,440 --> 01:36:46,360 SO PARADOXICAL IN A WAY. 2439 01:36:46,360 --> 01:36:48,200 >> WHAT YOU SAY IS GENERALLY 2440 01:36:48,200 --> 01:36:50,720 TRUE THOUGH WHEN YOU ERADICATE 2441 01:36:50,720 --> 01:36:51,880 HELICOBACTER OVER TIME THE 2442 01:36:51,880 --> 01:36:53,680 ANTIBODIES GO AWAY. 2443 01:36:53,680 --> 01:36:56,240 BUT IT TAKES A LONG TIME. 2444 01:36:56,240 --> 01:36:58,800 IT MAY TAKE UP TO A YEAR IN SOME 2445 01:36:58,800 --> 01:37:00,080 CASES TWO YEARS FOR THE 2446 01:37:00,080 --> 01:37:01,560 ANTIBODIES TO GO AWAY BUT THEY 2447 01:37:01,560 --> 01:37:02,160 GO AWAY. 2448 01:37:02,160 --> 01:37:04,280 >> SO WE GAVE -- HAD AN 2449 01:37:04,280 --> 01:37:06,280 EXPERIMENT WE REINFECTED PEOPLE 2450 01:37:06,280 --> 01:37:08,480 WITH THEIR OWN STRAIN AFTER 2451 01:37:08,480 --> 01:37:10,520 CURING THEM OF HELICOBACTER AND 2452 01:37:10,520 --> 01:37:12,080 ANTIBODIES WERE SKY HIGH, WE 2453 01:37:12,080 --> 01:37:13,440 GAVE THEIR OWN STRAIN OF 2454 01:37:13,440 --> 01:37:14,320 HELICOBACTER BACK AND EACH TIME 2455 01:37:14,320 --> 01:37:18,960 WE DID THAT ON TWO OCCASIONS, IT 2456 01:37:18,960 --> 01:37:22,320 COLONIZED AGAIN AND JAY IN 2457 01:37:22,320 --> 01:37:23,880 RHESUS MONKEYS DID THE SAME 2458 01:37:23,880 --> 01:37:24,280 THING. 2459 01:37:24,280 --> 01:37:28,080 >> IT MAKES YOU ANY IN SOME WAYS 2460 01:37:28,080 --> 01:37:29,600 HELICOBACTER HAS -- HAS 2461 01:37:29,600 --> 01:37:30,800 HITCHHIKED AND THE ANTIBODY 2462 01:37:30,800 --> 01:37:31,960 RESPONSES ARE IN SOME WAYS 2463 01:37:31,960 --> 01:37:33,200 ADAPTIVE. 2464 01:37:33,200 --> 01:37:35,040 FOR HELICOBACTER. 2465 01:37:35,040 --> 01:37:36,040 BUT WE DON'T KNOW. 2466 01:37:36,040 --> 01:37:38,600 JUST LIKE YOU CAN HAVE HIV WITH 2467 01:37:38,600 --> 01:37:40,440 PLENTY OF ANTIBODIES BUT IT IS 2468 01:37:40,440 --> 01:37:41,720 NOT SUFFICIENT TO ERADICATE THE 2469 01:37:41,720 --> 01:37:45,120 ORGANISM. 2470 01:37:45,120 --> 01:37:48,480 >> SO JORDAN ASKS WHETHER IS 2471 01:37:48,480 --> 01:37:52,560 GENE EDITING BEING EXPLORED AT 2472 01:37:52,560 --> 01:37:54,680 PRESENT WITH THE IDEA OF 2473 01:37:54,680 --> 01:37:59,240 MODIFYING H PYLORI SO THAT IT 2474 01:37:59,240 --> 01:38:00,680 WOULD BE BENEFICIAL? 2475 01:38:00,680 --> 01:38:02,960 >> I THINK THAT IS A GREAT IDEA 2476 01:38:02,960 --> 01:38:04,280 BUT FIRST WE HAVE TO GET OVER 2477 01:38:04,280 --> 01:38:06,400 THE DOGMA THAT THE ONLY GOOD 2478 01:38:06,400 --> 01:38:07,400 HELICOBACTER IS A DEAD ONE 2479 01:38:07,400 --> 01:38:09,240 BECAUSE IF YOU JUST WANT TO 2480 01:38:09,240 --> 01:38:10,480 ELIMINATE ALL HELICOBACTER 2481 01:38:10,480 --> 01:38:12,280 THERE'S NO POINT DOING GENETIC 2482 01:38:12,280 --> 01:38:13,040 ENGINEERING. 2483 01:38:13,040 --> 01:38:14,480 BUT IF YOU THINK THERE MAYBE 2484 01:38:14,480 --> 01:38:17,200 SOME BENEFITS TO HELICOBACTER 2485 01:38:17,200 --> 01:38:19,600 THEN WE CAN START APPLYING 2486 01:38:19,600 --> 01:38:21,880 SCIENCE TO IMPROVE THE STRAIN. 2487 01:38:21,880 --> 01:38:23,360 >> IT WILL HAPPEN. 2488 01:38:23,360 --> 01:38:26,920 QUITE SURE IT WILL HAPPEN AND WE 2489 01:38:26,920 --> 01:38:29,440 WILL HAVE DIFFERENT FLAVORS, 2490 01:38:29,440 --> 01:38:31,320 PEOPLE ACTUALLY OFTEN ASK ME 2491 01:38:31,320 --> 01:38:32,680 WHAT IT TASTES LIKE AND THE GOOD 2492 01:38:32,680 --> 01:38:36,640 NEWS IS THAT IT DOESN'T HAVE ANY 2493 01:38:36,640 --> 01:38:38,640 FLAVOR, IT IS TASTELESS SO BIG 2494 01:38:38,640 --> 01:38:40,880 OPPORTUNITY FOR PRODUCTS WITH 2495 01:38:40,880 --> 01:38:44,360 HELICOBACTER IN THE MIDDLE OF 2496 01:38:44,360 --> 01:38:44,560 THEM, 2497 01:38:44,560 --> 01:38:47,120 >> IT WILL TAKE A LOT OF 2498 01:38:47,120 --> 01:38:47,400 MARKETING. 2499 01:38:47,400 --> 01:38:48,880 >> THERE'S A LOT OF INTEREST THE 2500 01:38:48,880 --> 01:38:51,640 LAST FEW YEARS OF INFLAMMATION 2501 01:38:51,640 --> 01:38:55,520 AS A CAUSE OF CANCER AND IT HELD 2502 01:38:55,520 --> 01:39:01,600 UP IN HEPATITIS AND CERVICAL 2503 01:39:01,600 --> 01:39:03,600 CANCER, LIVER CANCER GASTRIC 2504 01:39:03,600 --> 01:39:06,080 CANCER I SUPPOSE SO THAT YOU 2505 01:39:06,080 --> 01:39:08,960 HAVE TO FIGURE OUT -- YOU HAVE 2506 01:39:08,960 --> 01:39:10,400 TO KNOW MORE ABOUT IMMUNE 2507 01:39:10,400 --> 01:39:13,680 RESPONSE CREATING INFLAMMATION 2508 01:39:13,680 --> 01:39:15,560 IN THE STOMACH YOU ARE GOING TO 2509 01:39:15,560 --> 01:39:18,560 HAVE TO HAVE A LOT OF DATA ON 2510 01:39:18,560 --> 01:39:22,400 THE OUTCOME OF THAT BEFORE THE 2511 01:39:22,400 --> 01:39:26,360 FDA WILL GIVE YOU A TICK. 2512 01:39:26,360 --> 01:39:29,000 >> BARRY MENTIONS AFTER CANCER, 2513 01:39:29,000 --> 01:39:30,760 I MENTION THIS ABOUT GASTRIC 2514 01:39:30,760 --> 01:39:32,320 CANCER RISING IN YOUNG PEOPLE, 2515 01:39:32,320 --> 01:39:34,040 THAT'S NOT THE ONLY CANCER THAT 2516 01:39:34,040 --> 01:39:37,120 IS RISING IN YOUNG PEOPLE, 2517 01:39:37,120 --> 01:39:38,440 THERE'S'S COLON CANCER RIDING, 2518 01:39:38,440 --> 01:39:41,240 KIDNEY CANCER RISING, SOMETHING 2519 01:39:41,240 --> 01:39:42,280 IS HAPPENING. 2520 01:39:42,280 --> 01:39:44,080 BEING A MICROBIOLOGIST I THINK 2521 01:39:44,080 --> 01:39:46,600 IS BECAUSE OF THE CHANGE IN THE 2522 01:39:46,600 --> 01:39:47,960 MICROBIOME AND THAT OBVIOUSLY 2523 01:39:47,960 --> 01:39:51,400 THAT LEADS TO NUMBER OF TESTABLE 2524 01:39:51,400 --> 01:39:52,480 HYPOTHESES. 2525 01:39:52,480 --> 01:39:54,400 BUT SOMETHING VERY STRIKING IS 2526 01:39:54,400 --> 01:39:55,880 HAPPENING WITH CANCER IN 2527 01:39:55,880 --> 01:40:00,360 DEVELOPING COUNTRIES. 2528 01:40:00,360 --> 01:40:05,440 >> KEEP AN EYE ON THAT. 2529 01:40:05,440 --> 01:40:07,440 >> HERE IS A MORE PERSONAL 2530 01:40:07,440 --> 01:40:08,680 QUESTION FOR YOU. 2531 01:40:08,680 --> 01:40:13,440 VAL ASKS HOW DIFFICULT WAS IT TO 2532 01:40:13,440 --> 01:40:16,200 TRUST YOURSELF AND YOUR RESULTS 2533 01:40:16,200 --> 01:40:18,560 DESPITE THE OBVIOUS PUSH BACK 2534 01:40:18,560 --> 01:40:20,160 FROM THE SCIENTIFIC COMMUNITY? 2535 01:40:20,160 --> 01:40:22,280 YOUR ONLY ALLOWED ONE HOUR TO 2536 01:40:22,280 --> 01:40:25,200 ANSWER THAT QUESTION. 2537 01:40:25,200 --> 01:40:28,680 >> SO I DIDN'T TRUST MYSELF. 2538 01:40:28,680 --> 01:40:33,160 IN FACT ALL THE TIME I WAS 2539 01:40:33,160 --> 01:40:37,440 SAYING COULD IT REALLY BE TRUE 2540 01:40:37,440 --> 01:40:41,160 HOW CAN I TEST THIS HYPOTHESIS, 2541 01:40:41,160 --> 01:40:43,360 IF YOU -- I'M NOT SAYING I WAS A 2542 01:40:43,360 --> 01:40:46,840 GOOD SCIENTIST NECESSARILY, 2543 01:40:46,840 --> 01:40:48,560 OBVIOUSLY AN EXPERIMENT WITH THE 2544 01:40:48,560 --> 01:40:51,160 N OF 1 IS NOT SCIENTIFICALLY 2545 01:40:51,160 --> 01:40:54,040 VALID PEOPLE HAVE MADE SOME BIG 2546 01:40:54,040 --> 01:40:55,600 MISTAKES OVER THE YEARS BY 2547 01:40:55,600 --> 01:40:59,680 TESTING THINGS ON THEMSELVES BUT 2548 01:40:59,680 --> 01:41:04,720 WHAT YOU CAN SAY IS THAT I LOST 2549 01:41:04,720 --> 01:41:06,680 MY TRAIN OF THOUGHT, IT IS FIVE 2550 01:41:06,680 --> 01:41:13,560 O'CLOCK IN THE MORNING HERE. 2551 01:41:13,560 --> 01:41:16,880 SO WHAT WAS -- YES SO WHAT YOU 2552 01:41:16,880 --> 01:41:22,920 HAVE TO DO IS BE OWN MAJOR 2553 01:41:22,920 --> 01:41:23,680 CRITIC. 2554 01:41:23,680 --> 01:41:25,600 SO INITIALLY IT WAS OKAY IF IT 2555 01:41:25,600 --> 01:41:29,040 IS TRUE THAT THESE BACTERIA ARE 2556 01:41:29,040 --> 01:41:29,880 CAUSING GASTRITIS IF WE TREAT 2557 01:41:29,880 --> 01:41:31,360 THEM ERADICATE THEM WE SHOULD BE 2558 01:41:31,360 --> 01:41:33,440 ABLE TO SEW A CHANGE IN THE 2559 01:41:33,440 --> 01:41:34,080 GASTRITIS SO THAT'S WHERE I 2560 01:41:34,080 --> 01:41:36,760 STARTED OFF WITH ANTIBIOTICS AND 2561 01:41:36,760 --> 01:41:38,520 ADDITIONAL TREATMENTS. 2562 01:41:38,520 --> 01:41:39,880 LET'S TEST IT ON OTHER PEOPLE 2563 01:41:39,880 --> 01:41:42,320 WITH SEVERE RECURRENT ULCERS AND 2564 01:41:42,320 --> 01:41:43,880 SEE WHAT HAPPENS WITH AN OPEN 2565 01:41:43,880 --> 01:41:45,480 MIND. 2566 01:41:45,480 --> 01:41:47,520 WE HAD ABOUT NINE OUT 11 2567 01:41:47,520 --> 01:41:51,080 PATIENTS IN 1985 AND PRESENTED 2568 01:41:51,080 --> 01:41:52,080 THAT IN OTTAWA AND THEN SO THEN 2569 01:41:52,080 --> 01:41:55,800 THE NEXT THING IS THERE MUST BE 2570 01:41:55,800 --> 01:41:59,240 SOME WAY, A WAY THAT SOMEHOW I'M 2571 01:41:59,240 --> 01:42:00,840 SELECTING THE PATIENTS, IT IS 2572 01:42:00,840 --> 01:42:02,480 NOT BLINDED OR WHATEVER SO LET'S 2573 01:42:02,480 --> 01:42:05,480 DO A PROSPECTIVE DOUBLE BLIND 2574 01:42:05,480 --> 01:42:06,080 STUDY. 2575 01:42:06,080 --> 01:42:08,160 AND SEE. 2576 01:42:08,160 --> 01:42:09,880 SO THAT WE WENT THROUGH ALL 2577 01:42:09,880 --> 01:42:14,320 KINDS OF HOOPS AND SO IN FACT IN 2578 01:42:14,320 --> 01:42:17,120 OUR STUDY, EVERYBODY ON PLACEBO 2579 01:42:17,120 --> 01:42:18,640 THOUGHT ABOUT GETTING THE REAL 2580 01:42:18,640 --> 01:42:22,280 DRUG SO THE PATIENTS WE BLINDED 2581 01:42:22,280 --> 01:42:24,880 THE PATIENTS AND THE CRITICS 2582 01:42:24,880 --> 01:42:27,000 WOULD SAY THAT IS THE STOOL WENT 2583 01:42:27,000 --> 01:42:28,880 BLACK BUT THE PATIENTS WERE NOT 2584 01:42:28,880 --> 01:42:29,320 TOLD THAT. 2585 01:42:29,320 --> 01:42:35,200 YOU MAY NOTICE DISCOLORATION, SO 2586 01:42:35,200 --> 01:42:37,440 IT WAS A PROSPECTIVE STUDY WHEN 2587 01:42:37,440 --> 01:42:38,680 WE HAD RESULT WE LOOK AT 2588 01:42:38,680 --> 01:42:41,880 GRADATION OF CURE RATE OF THE 2589 01:42:41,880 --> 01:42:43,880 PEPTIC ULCER WAS PROPORTIONAL NO 2590 01:42:43,880 --> 01:42:46,040 TO NUMBER OF PATIENTS IN EACH OF 2591 01:42:46,040 --> 01:42:48,120 FOUR GROUPS THAT HAD COMPLETE 2592 01:42:48,120 --> 01:42:49,880 ERADICATION OF HELICOBACTER. 2593 01:42:49,880 --> 01:42:52,520 HAVING SUPPRESSION AND THEN NOT 2594 01:42:52,520 --> 01:42:54,760 TOTAL ERADICATION DIDN'T MAKE 2595 01:42:54,760 --> 01:42:56,680 MUCH DIFFERENCE IN 12 MONTH 2596 01:42:56,680 --> 01:42:57,280 FOLLOW-UP. 2597 01:42:57,280 --> 01:43:00,160 IF YOU HAD ERADICATION LIKELY 2598 01:43:00,160 --> 01:43:02,280 DIDN'T CATCH IT BACK AGAIN, THEN 2599 01:43:02,280 --> 01:43:06,000 YOU HAVE THIS REMARKABLE 2600 01:43:06,000 --> 01:43:07,160 DIFFERENCE WHICH HELD UP. 2601 01:43:07,160 --> 01:43:08,320 BUT BY THE TIME I CAME TO THE 2602 01:43:08,320 --> 01:43:10,640 UNITED STATES WHICH ALREADY HAD 2603 01:43:10,640 --> 01:43:13,360 THAT STUDY HALF FINISHED. 2604 01:43:13,360 --> 01:43:15,200 AT THAT POINT I WAS CONFIDENT WE 2605 01:43:15,200 --> 01:43:16,360 TESTED IT SEVERAL DIFFERENT 2606 01:43:16,360 --> 01:43:17,200 WAYS. 2607 01:43:17,200 --> 01:43:19,080 THE ANSWER FOR SCIENTISTS, 2608 01:43:19,080 --> 01:43:21,600 ANYBODY DOING ANY 2609 01:43:21,600 --> 01:43:23,360 EXPERIMENTATION WHENEVER YOU GET 2610 01:43:23,360 --> 01:43:29,640 A GOOD RESULT, HOW CAN YOU 2611 01:43:29,640 --> 01:43:31,080 ACCIDENTLY FAKED IT, HOW CAN IT 2612 01:43:31,080 --> 01:43:32,440 BE JUST BIT OF LUCK? 2613 01:43:32,440 --> 01:43:35,960 HOW COULD YOU HAVE SELECTED THE 2614 01:43:35,960 --> 01:43:39,280 SAMPLES THAT YOU WERE TESTING. 2615 01:43:39,280 --> 01:43:44,280 MAYBE THAT ONE THAT YOU HAD 2616 01:43:44,280 --> 01:43:45,280 REMOVED THAT WAS OUTLIER, MAYBE 2617 01:43:45,280 --> 01:43:46,000 THAT SHOULD HAVE BEEN KEPT IN, 2618 01:43:46,000 --> 01:43:48,720 THAT'S THE SORT OF THING, I LOT 2619 01:43:48,720 --> 01:43:52,080 OF THESE FORENSIC ANALYSES THAT 2620 01:43:52,080 --> 01:43:54,280 ELIZABETH DOES ALL THE TIME 2621 01:43:54,280 --> 01:43:57,280 LOOKING AT PEOPLE WHO ERASED THE 2622 01:43:57,280 --> 01:43:59,600 OUTLIERS OUT OF THE EFFECTS 2623 01:43:59,600 --> 01:44:02,880 RESULT OR SOME KIND OF 2624 01:44:02,880 --> 01:44:04,680 ILLUSTRATIONS JUST COPIED A FEW 2625 01:44:04,680 --> 01:44:05,680 BANDS INTO THEIR GEL. 2626 01:44:05,680 --> 01:44:09,560 I'M GOING TO LOOK AT YOUR GEL 2627 01:44:09,560 --> 01:44:11,080 CAREFULLY, LOOKS LIKE IT IS TOO 2628 01:44:11,080 --> 01:44:12,720 GOOD TO BE TRUE. 2629 01:44:12,720 --> 01:44:17,440 >> WHEN WE FOUND CAGA WE FOUND 2630 01:44:17,440 --> 01:44:21,280 THAT CAG -- PEOPLE HAD ULCERS 2631 01:44:21,280 --> 01:44:23,040 WAS 100% OF PEOPLE WITH ULCERS 2632 01:44:23,040 --> 01:44:24,560 AND 63% OF PEOPLE WITH 2633 01:44:24,560 --> 01:44:24,960 GASTRITIS. 2634 01:44:24,960 --> 01:44:25,880 >> REMEMBER THOSE NUMBERS. 2635 01:44:25,880 --> 01:44:28,000 >> ONE YEAR LATER, ONE AND A 2636 01:44:28,000 --> 01:44:34,000 HALF YEARS LATER, GENE CRAB TREE 2637 01:44:34,000 --> 01:44:35,960 PUBLISHED RESULTS ACROSS THE 2638 01:44:35,960 --> 01:44:39,200 OCEAN, 100% ULCER, 62% 2639 01:44:39,200 --> 01:44:39,800 GASTRITIS. 2640 01:44:39,800 --> 01:44:41,040 AT THAT POINT WE KNEW IT WAS 2641 01:44:41,040 --> 01:44:41,960 TRUE. 2642 01:44:41,960 --> 01:44:44,080 INDEPENDENT CONFIRMATION SHOWING 2643 01:44:44,080 --> 01:44:45,680 EXACTLY THE SAME THING. 2644 01:44:45,680 --> 01:44:46,960 SO -- CONFIRMATION. 2645 01:44:46,960 --> 01:44:49,280 >> SO THE PEOPLE WHO REALLY 2646 01:44:49,280 --> 01:44:51,880 HATED HELICOBACTER WERE THE 2647 01:44:51,880 --> 01:44:55,960 GASTROENTEROLOGISTS IN MELBOURNE 2648 01:44:55,960 --> 01:44:57,600 AND JOHN LAMBERT REPEATED OUR 2649 01:44:57,600 --> 01:44:59,200 STUDY IN MELBOURNE THE FOLLOWING 2650 01:44:59,200 --> 01:45:03,120 YEAR, WE HAD 92% OF ULCERS WERE 2651 01:45:03,120 --> 01:45:04,720 POSITIVE WHEN WE DID A LARGE 2652 01:45:04,720 --> 01:45:08,400 STUDY OF 70 ULCERS. 2653 01:45:08,400 --> 01:45:11,680 HE GOT 92 OR 93% INDEPENDENTLY 2654 01:45:11,680 --> 01:45:17,360 IN MELBOURNE. 2655 01:45:17,360 --> 01:45:18,320 SO CONFIRMATION IS SO IMPORTANT. 2656 01:45:18,320 --> 01:45:21,680 >> SO THE OTHER QUESTION IS WHEN 2657 01:45:21,680 --> 01:45:24,440 YOU GOT SOMETHING EXCITING AND 2658 01:45:24,440 --> 01:45:25,720 HOW DO YOU GET SOMEBODY TO 2659 01:45:25,720 --> 01:45:27,280 SUPPORT YOUR RESEARCH, IT IS 2660 01:45:27,280 --> 01:45:28,840 MUCH -- SO BEAUTIFUL IF YOU CAN 2661 01:45:28,840 --> 01:45:31,480 GET A COMPANY LIKE PROCTER & 2662 01:45:31,480 --> 01:45:33,440 GAMBLE BANK ROLLING YOU FOR A 2663 01:45:33,440 --> 01:45:36,000 FEW YEARS, THINGS TO MOVE ALONG, 2664 01:45:36,000 --> 01:45:37,320 YOU MIGHT BE TO CUSSED ON THE 2665 01:45:37,320 --> 01:45:39,880 PRODUCTS A LITTLE BIT. 2666 01:45:39,880 --> 01:45:41,080 I ALWAYS SAY WELL THE FIRST 2667 01:45:41,080 --> 01:45:42,760 THING YOU DO IS FIND THE COMPANY 2668 01:45:42,760 --> 01:45:46,720 THAT'S THE BIGGEST IN THAT 2669 01:45:46,720 --> 01:45:48,200 INDUSTRY, AND TRY TO ASK THEM TO 2670 01:45:48,200 --> 01:45:49,880 SUPPORT YOU, BECAUSE THEN YOU 2671 01:45:49,880 --> 01:45:51,640 ARE ON EASY STREET. 2672 01:45:51,640 --> 01:45:53,680 IF THEY DON'T SUPPORT YOU THEN 2673 01:45:53,680 --> 01:45:57,280 YOU GO COMPETITION. 2674 01:45:57,280 --> 01:45:59,680 AND SAY YOU CAN BE THE KINGS IF 2675 01:45:59,680 --> 01:46:03,680 YOU CAN SUCCEED IN OUR -- SO 2676 01:46:03,680 --> 01:46:04,880 GLAXO WELCOME AND GOT NOWHERE 2677 01:46:04,880 --> 01:46:06,760 AND THEN SO THE NEXT THING I 2678 01:46:06,760 --> 01:46:12,240 WENT TO THE BISMUTH COMPANIES 2679 01:46:12,240 --> 01:46:14,120 AND THE BOSTON IT WAS QUITE 2680 01:46:14,120 --> 01:46:16,440 HOSTILE WITH THE RESEARCH 2681 01:46:16,440 --> 01:46:20,520 PEOPLE, YOU HAVE TESTED THESE IN 2682 01:46:20,520 --> 01:46:22,120 PRODUCTS IN EVERY POSSIBLE WAY, 2683 01:46:22,120 --> 01:46:24,440 YOU NEVER DID THE MIC OF COMMON 2684 01:46:24,440 --> 01:46:25,680 BACTERIA WITH THEM. 2685 01:46:25,680 --> 01:46:28,800 AND THEY HADN'T DONE THAT SO 2686 01:46:28,800 --> 01:46:31,560 THEY WERE IN TOTAL DISGRACE. 2687 01:46:31,560 --> 01:46:35,760 LUCKILY A FELLOW MIKE AT PROCTER 2688 01:46:35,760 --> 01:46:37,760 & GAMBLE HAD BEEN LOOKING AT 2689 01:46:37,760 --> 01:46:41,400 TRAVELERS DIARRHEA WITH PEPTO 2690 01:46:41,400 --> 01:46:43,040 BISMOL AND ALL OF A SUDDEN HAD 2691 01:46:43,040 --> 01:46:46,040 THE IDEA THAT BISMUTH COMES BACK 2692 01:46:46,040 --> 01:46:49,120 AS A ULCER TREATMENT, IT WAS 2693 01:46:49,120 --> 01:46:50,680 TESTED IN EARLY JOHNNY, NOT A 2694 01:46:50,680 --> 01:46:55,000 GOOD CURE BY ITSELF, ANTIBIOTIC 2695 01:46:55,000 --> 01:46:55,880 AS WELL. 2696 01:46:55,880 --> 01:46:59,080 SO IT WAS EXCITING THERE FOR A 2697 01:46:59,080 --> 01:46:59,480 WHILE. 2698 01:46:59,480 --> 01:47:02,120 SO YOU TRY TO PROVE IT I DON'T 2699 01:47:02,120 --> 01:47:04,280 THINK AND IF YOU CAN'T PROVE IT 2700 01:47:04,280 --> 01:47:05,440 WRONG MAYBE IT IS RIGHT. 2701 01:47:05,440 --> 01:47:09,880 THE THING TO DO IS TRY AND DO IN 2702 01:47:09,880 --> 01:47:12,280 YOUR OWN LAB WITH YOUR OWN 2703 01:47:12,280 --> 01:47:13,600 RESEARCH WHAT EVERYONE ELSE IS 2704 01:47:13,600 --> 01:47:15,400 GOING TO TRY TO DO AS PART OF 2705 01:47:15,400 --> 01:47:18,480 THE SCIENTIFIC PROCESS. 2706 01:47:18,480 --> 01:47:20,880 THAT'S WHAT I -- IN THE UNITED 2707 01:47:20,880 --> 01:47:23,720 STATES IS THAT ONCE IF THERE WAS 2708 01:47:23,720 --> 01:47:25,360 THE SLIGHTEST CHINK IN THE 2709 01:47:25,360 --> 01:47:26,880 ARMOR, EVERYONE WHO WOULD GO FOR 2710 01:47:26,880 --> 01:47:30,760 IT AND TRY TO PREVIEW A WRONG, 2711 01:47:30,760 --> 01:47:32,440 SO -- PROVE YOU WRONG SO IT IS 2712 01:47:32,440 --> 01:47:33,280 DIFFICULT FOR A YOUNG 2713 01:47:33,280 --> 01:47:35,640 INVESTIGATOR TO HANDLE THAT. 2714 01:47:35,640 --> 01:47:37,600 JUST SO VERY UNFAIR THAT YOU 2715 01:47:37,600 --> 01:47:38,880 LOSE ALL YOUR FRIENDS SOON AS 2716 01:47:38,880 --> 01:47:43,880 YOU HAVE A NEW IDEA. 2717 01:47:43,880 --> 01:47:45,920 THAT IS THE WAY SCIENCE GOES AND 2718 01:47:45,920 --> 01:47:47,080 MAYBE SOME PLACES IN THE WORLD 2719 01:47:47,080 --> 01:47:49,080 NOT HAVING SO MUCH SUCCESS AS 2720 01:47:49,080 --> 01:47:53,080 THE UNITED STATES IS BECAUSE 2721 01:47:53,080 --> 01:47:56,000 THEY AREN'T PUTTING ALL THEIR 2722 01:47:56,000 --> 01:47:58,880 CARDS OUT. 2723 01:47:58,880 --> 01:47:59,440 REALLY BITING THE BULLET AND 2724 01:47:59,440 --> 01:48:01,840 TAKING CRITICAL LOOK AT THEIR 2725 01:48:01,840 --> 01:48:03,280 OWN EXPERIENCE. 2726 01:48:03,280 --> 01:48:05,320 >> SURE YOU WOULD AGREE THAT 2727 01:48:05,320 --> 01:48:06,920 THERE IS A LOT OF FOLLOW THE 2728 01:48:06,920 --> 01:48:10,920 LEADER IN BOTH MEDICINE AND 2729 01:48:10,920 --> 01:48:11,160 SCIENCE. 2730 01:48:11,160 --> 01:48:14,600 THE PAIR OF DOGMA IS ASTOUNDING. 2731 01:48:14,600 --> 01:48:18,160 >> I LOOK AT MY EARLY -- LOOKING 2732 01:48:18,160 --> 01:48:20,280 AT LATEST FROM THE LANSETT, 2733 01:48:20,280 --> 01:48:21,720 THERE'S THOUSANDS OF PAPERS LIKE 2734 01:48:21,720 --> 01:48:25,040 THAT THAT ARE OUT THERE, 2735 01:48:25,040 --> 01:48:29,960 HELICOBACTER THAT ARE WELL CITED 2736 01:48:29,960 --> 01:48:32,040 PAPERS, SO IF YOU SEARCH FOR 2737 01:48:32,040 --> 01:48:34,280 HELICOBACTER YOU DON'T FIND 2738 01:48:34,280 --> 01:48:36,160 THOSE EARLY REFERENCES. 2739 01:48:36,160 --> 01:48:38,120 IT'S A LITTLE BIT SAD. 2740 01:48:38,120 --> 01:48:40,160 I WAS COMPLAINING LIKE ANYTHING 2741 01:48:40,160 --> 01:48:41,600 YES THAT I WENT I WAS FILLING 2742 01:48:41,600 --> 01:48:45,680 OUT THE JOHNS HOPKINS CONFLICT 2743 01:48:45,680 --> 01:48:48,640 OF INTEREST DOCUMENTS AND DOING 2744 01:48:48,640 --> 01:48:51,360 THOSE ONLINE FORMS. 2745 01:48:51,360 --> 01:48:56,200 THE DEFINITION OF -- THIS SORT 2746 01:48:56,200 --> 01:49:00,200 OF ETHICS OF PRESENTATIONS IN 2747 01:49:00,200 --> 01:49:05,240 THE JOHN HOPKINS CME PROGRAM ET 2748 01:49:05,240 --> 01:49:05,440 CETERA. 2749 01:49:05,440 --> 01:49:07,160 YOU WERE NOT PRESENT ANY 2750 01:49:07,160 --> 01:49:11,920 INFORMATION THAT'S ANECDOTAL OR 2751 01:49:11,920 --> 01:49:13,880 NOT PROVEN, YOU WANT TO PROMOTE 2752 01:49:13,880 --> 01:49:15,320 UNPROVEN PRODUCTS THAT HAVE NOT 2753 01:49:15,320 --> 01:49:16,880 BEEN TESTED IN A PROPER DOUBLE 2754 01:49:16,880 --> 01:49:19,440 BLIND WAY, ALL KINDS OF GOOD 2755 01:49:19,440 --> 01:49:20,640 SCIENTIFIC CLINICAL RESEARCH 2756 01:49:20,640 --> 01:49:23,280 RULES IN THERE ABOUT WHAT YOU 2757 01:49:23,280 --> 01:49:26,600 CAN PRESENT AT THE JOHNS HOPKINS 2758 01:49:26,600 --> 01:49:27,000 CME. 2759 01:49:27,000 --> 01:49:28,880 SO I PRINTED THAT OUT, I WILL 2760 01:49:28,880 --> 01:49:31,480 TALK ABOUT IT TO MY BLOOD PEOPLE 2761 01:49:31,480 --> 01:49:33,680 AND CLINICS BECAUSE THIS IS THE 2762 01:49:33,680 --> 01:49:36,000 PROBLEM AROUND THE WORLD. 2763 01:49:36,000 --> 01:49:38,600 PARTICULARLY IN CHINA THERE'S 2764 01:49:38,600 --> 01:49:40,840 PEOPLE WHO EASILY FUNDED ON 2765 01:49:40,840 --> 01:49:43,680 NATURAL MEDICINE AND TRADITIONAL 2766 01:49:43,680 --> 01:49:44,040 MEDICINE. 2767 01:49:44,040 --> 01:49:47,880 IT IS REALLY GOT NO SCIENTIFIC 2768 01:49:47,880 --> 01:49:48,280 BASIS. 2769 01:49:48,280 --> 01:49:50,000 IN CHINA I KNOW 2770 01:49:50,000 --> 01:49:51,000 >> THERE ARE GREAT SCIENTISTS IN 2771 01:49:51,000 --> 01:49:52,720 THE INSTITUTION, THE TOP 2772 01:49:52,720 --> 01:49:53,440 INSTITUTIONS JUST LIKE 2773 01:49:53,440 --> 01:49:54,440 EVERYWHERE ELSE IN THE WORLD 2774 01:49:54,440 --> 01:49:55,880 WHERE THERE IS EUROPE, UNITED 2775 01:49:55,880 --> 01:49:58,240 STATES OR AUSTRALIA, THEY ARE -- 2776 01:49:58,240 --> 01:49:59,960 THEY HAVE REALLY HARD CORE 2777 01:49:59,960 --> 01:50:03,600 SCIENCE GOING ON THERE AND THE 2778 01:50:03,600 --> 01:50:07,840 CHINESE FDA HAS GOT HARD CORE 2779 01:50:07,840 --> 01:50:10,920 RULES EMULATING THE U.S. FDA. 2780 01:50:10,920 --> 01:50:13,280 BUT A LOT OF PEOPLE STILL 2781 01:50:13,280 --> 01:50:20,800 BELIEVE THAT THERE IS MORE THAN 2782 01:50:20,800 --> 01:50:23,360 SCIENCE OR -- HARD TO EXPLAIN, 2783 01:50:23,360 --> 01:50:25,440 TRADITIONAL STUFF I GUESS, IN 2784 01:50:25,440 --> 01:50:27,800 EVERY COUNTRY AND A LITTLE BIT 2785 01:50:27,800 --> 01:50:34,880 HORRIFIED WHEN THE CHINESE 2786 01:50:34,880 --> 01:50:36,280 WHATEVER NATURAL MEDICINES AND 2787 01:50:36,280 --> 01:50:38,280 TCM WAS ACCEPTED OR ADDED ON TO 2788 01:50:38,280 --> 01:50:40,040 THE WORLD HEALTH ORGANIZATION 2789 01:50:40,040 --> 01:50:41,960 ACCEPTED MEDICINES LIST. 2790 01:50:41,960 --> 01:50:43,320 SO NOT SURE WHAT THE DEAL IS 2791 01:50:43,320 --> 01:50:46,200 WITH THAT. 2792 01:50:46,200 --> 01:50:52,120 IT REALLY BROUGHT WHO DOWN A FEW 2793 01:50:52,120 --> 01:50:55,680 WRUNGS IN MY VIEW AS WELL. 2794 01:50:55,680 --> 01:50:57,480 IT IS SOMETHING THAT IS A BIT OF 2795 01:50:57,480 --> 01:51:00,000 A DICHOTOMY IN MANY PLACES. 2796 01:51:00,000 --> 01:51:04,280 >> SO WE HAVE A SORT OF MOST 2797 01:51:04,280 --> 01:51:06,480 RECENT QUESTION, MAYBE YOU WANT 2798 01:51:06,480 --> 01:51:06,880 TO COMMENT ABOUT. 2799 01:51:06,880 --> 01:51:11,680 IS THERE A GENETIC 2800 01:51:11,680 --> 01:51:13,040 PRE-DISPOSITION TO CANCER 2801 01:51:13,040 --> 01:51:15,680 RELATIONSHIP TO H PYLORI? 2802 01:51:15,680 --> 01:51:23,520 >> YEAH, IT'S BEEN SHOWN LMR AND 2803 01:51:23,520 --> 01:51:25,960 RAPKIN AND COLLEAGUES SHOWED 20 2804 01:51:25,960 --> 01:51:28,440 YEARS AGO THAT PEOPLE WHO HAD 2805 01:51:28,440 --> 01:51:30,800 CERTAIN POLYMORPHISMS IN THEIR 2806 01:51:30,800 --> 01:51:33,880 CYTOKINE GENES WERE MORE LIKELY 2807 01:51:33,880 --> 01:51:38,880 TO GET GASTRIC CANCER, OBVIOUSLY 2808 01:51:38,880 --> 01:51:41,840 NOT A STRONG HELICOBACTER IS SO 2809 01:51:41,840 --> 01:51:42,600 IMPORTANT IN HELICOBACTER 2810 01:51:42,600 --> 01:51:43,920 GASTRIC CANCER YOU CAN HAVE ANY 2811 01:51:43,920 --> 01:51:45,240 GENOTYPE, IF YOU DON'T HAVE 2812 01:51:45,240 --> 01:51:46,120 HELICOBACTER YOU ARE NOT GOING 2813 01:51:46,120 --> 01:51:47,920 TO GET TRADITIONAL CANCER BUT IT 2814 01:51:47,920 --> 01:51:49,280 INCREASES RISK. 2815 01:51:49,280 --> 01:51:51,400 THERE'S IN QUESTION. 2816 01:51:51,400 --> 01:51:54,200 >> THAT SOMETHING THAT IS OFTEN 2817 01:51:54,200 --> 01:51:56,960 IGNORED BECAUSE PEOPLE WITHIN 2818 01:51:56,960 --> 01:51:59,840 EARLY GASTRIC CANCER MIGHT GO 2819 01:51:59,840 --> 01:52:03,000 THROUGH PARTIAL GASTRICTOMY AND 2820 01:52:03,000 --> 01:52:05,280 HAVE A CURE THAT IS A LEAD TO 2821 01:52:05,280 --> 01:52:06,040 FAMILY BECAUSE IMMEDIATE 2822 01:52:06,040 --> 01:52:09,000 RELATIVES IF THEY HAD 2823 01:52:09,000 --> 01:52:09,760 HELICOBACTER THEY HAVE SAME 2824 01:52:09,760 --> 01:52:12,440 STRAIN AND GENES AND RELATIVE 2825 01:52:12,440 --> 01:52:14,080 RISK IS FOUR TIMES NORMAL IF 2826 01:52:14,080 --> 01:52:15,920 YOUR BROTHER HAD GASTRIC CANCER 2827 01:52:15,920 --> 01:52:18,680 YOU NEED TO BE IMMEDIATELY 2828 01:52:18,680 --> 01:52:20,240 TESTED FOR HELICOBACTER AND GET 2829 01:52:20,240 --> 01:52:20,640 TREATED. 2830 01:52:20,640 --> 01:52:22,680 THAT WILL CUT THE RISK DOWN BY 2831 01:52:22,680 --> 01:52:25,920 ABOUT 50% BUT YOU ARE STILL -- 2832 01:52:25,920 --> 01:52:27,080 YOU COULD HAVE STEM CELLS 2833 01:52:27,080 --> 01:52:28,480 FLOATING AROUND IN GASTRIC 2834 01:52:28,480 --> 01:52:29,080 MUCOSA. 2835 01:52:29,080 --> 01:52:33,120 THIS IS WHY I THINK AS PEOPLE 2836 01:52:33,120 --> 01:52:35,400 HAVE LOOKED AT HELICOBACTER OVER 2837 01:52:35,400 --> 01:52:39,120 LONG TERM IF YOU NEVER HAD YOU 2838 01:52:39,120 --> 01:52:40,480 HARDLY GET GASTRIC CANCER. 2839 01:52:40,480 --> 01:52:42,400 IF YOU LOOK AT PEOPLE WITH 2840 01:52:42,400 --> 01:52:44,960 GASTRIC CANCER HALF OF THEM WITH 2841 01:52:44,960 --> 01:52:45,800 HELICOBACTER AND HALF DON'T SO 2842 01:52:45,800 --> 01:52:48,120 YOU MIGHT SAY THERE IS ANOTHER 2843 01:52:48,120 --> 01:52:50,280 50% WHO DIDN'T HAVE HELICOBACTER 2844 01:52:50,280 --> 01:52:53,080 SO MUST BE ANOTHER COURSE BUT 2845 01:52:53,080 --> 01:52:55,560 JANE CRABTREE I THINK IT WAS, 2846 01:52:55,560 --> 01:52:58,400 THEY CULTURED GASTRIC MUCOSA 2847 01:52:58,400 --> 01:52:59,520 FROM GASTRIC CANCER PATIENTS WHO 2848 01:52:59,520 --> 01:53:01,440 HAD NO HELICOBACTER AT THE TIME 2849 01:53:01,440 --> 01:53:04,960 OF THEIR SURGERY. 2850 01:53:04,960 --> 01:53:06,960 HEADACHE SHOW TISSUE FROM THE 2851 01:53:06,960 --> 01:53:08,720 STOMACH WAS GENERATING 2852 01:53:08,720 --> 01:53:10,840 ANTIBODIES AGAINST HELICOBACTER 2853 01:53:10,840 --> 01:53:12,040 THOUGH THERE IS NO MORE ORGANISM 2854 01:53:12,040 --> 01:53:12,800 THERE. 2855 01:53:12,800 --> 01:53:15,120 >> YOU SEE WHAT HAPPENS IS WITH 2856 01:53:15,120 --> 01:53:17,800 THE DEVELOPMENT OF ATROPIC 2857 01:53:17,800 --> 01:53:18,880 GASTRITIS THAT LEADS THE GASTRIC 2858 01:53:18,880 --> 01:53:20,320 CANCER, TAKES DECADES BUT DURING 2859 01:53:20,320 --> 01:53:23,200 THAT TIME THE HELICOBACTER WHICH 2860 01:53:23,200 --> 01:53:27,400 INITIATED THE PROO SYCES IS 2861 01:53:27,400 --> 01:53:29,040 GONE. IT CAN'T SHRIVER IN 2862 01:53:29,040 --> 01:53:29,680 ATROPIC GASTRITIS ENVIRONMENT SO 2863 01:53:29,680 --> 01:53:31,280 THAT'S WHY SO MANY PEOPLE ARE 2864 01:53:31,280 --> 01:53:33,280 NEGATIVE, THAT'S WHY THE 2865 01:53:33,280 --> 01:53:35,800 STRONGEST RESULTS WERE STUDIES 2866 01:53:35,800 --> 01:53:37,480 PROSPECTIVE WHEN AS CERTAINMENT 2867 01:53:37,480 --> 01:53:39,280 OF HELICOBACTER STATUS WAS A 2868 01:53:39,280 --> 01:53:41,680 DECADE OR MORE PRIOR TO THE 2869 01:53:41,680 --> 01:53:42,360 CANCER. 2870 01:53:42,360 --> 01:53:44,960 >> THE OTHER THING IS THOUGH 2871 01:53:44,960 --> 01:53:47,080 PEOPLE SAY HELICOBACTER IS A 2872 01:53:47,080 --> 01:53:49,440 CARCINOGEN, I THINK IT RUNS THE 2873 01:53:49,440 --> 01:53:53,880 LINING OF THE STOMACH, LOWERS 2874 01:53:53,880 --> 01:53:55,520 ACIDITY, YOU GET OTHER BACTERIA 2875 01:53:55,520 --> 01:53:57,320 THAT CONTINUE THE CANCER RISK. 2876 01:53:57,320 --> 01:53:59,440 HOE THE HELICOBACTER IS GONE. 2877 01:53:59,440 --> 01:54:01,880 THE EXAMPLE FOR THIS IS THAT 2878 01:54:01,880 --> 01:54:04,520 PEOPLE WITH DUODEN ABOUTL ULCER 2879 01:54:04,520 --> 01:54:05,440 NEVER GET CANCER. 2880 01:54:05,440 --> 01:54:07,440 NEVER GET GASTRIC CANCER UNTIL 2881 01:54:07,440 --> 01:54:10,280 MANY YEARS LATER WHEN THE ULCER 2882 01:54:10,280 --> 01:54:13,400 IS LONG GONE SO 2883 01:54:13,400 --> 01:54:15,120 GASTROENTEROLOGIST NEVER BIOPSY 2884 01:54:15,120 --> 01:54:17,280 PATIENTS WITH DUODENAL ULCER, 2885 01:54:17,280 --> 01:54:18,400 WHAT IS THE POINT? 2886 01:54:18,400 --> 01:54:19,880 WE NEVER FIND CANCER. 2887 01:54:19,880 --> 01:54:22,840 SO THEY ARE ONLY BIOPSY GASTRIC 2888 01:54:22,840 --> 01:54:27,320 ULCERS AS ONE OF THE REASONS IT 2889 01:54:27,320 --> 01:54:29,440 WAS FAMOUSLY MISTED HELICOBACTER 2890 01:54:29,440 --> 01:54:29,880 FOR SO LONG. 2891 01:54:29,880 --> 01:54:31,480 >> THERE'S PARADOXES WITH 2892 01:54:31,480 --> 01:54:32,800 HELICOBACTER THAT STILL EXIST 2893 01:54:32,800 --> 01:54:34,880 FOR EXAMPLE, HELICOBACTER 2894 01:54:34,880 --> 01:54:37,480 ASSOCIATED WITH BOTH GASTRIC AND 2895 01:54:37,480 --> 01:54:39,360 DUODENAL ULCER BUT ONE IS LOW 2896 01:54:39,360 --> 01:54:41,360 ACID STATE, OTHER IS HIGH ACID 2897 01:54:41,360 --> 01:54:44,360 STATE AND AS BARRY SAID DUODENAL 2898 01:54:44,360 --> 01:54:47,200 ULCERS PROTECT AGAINST GAY VIC 2899 01:54:47,200 --> 01:54:49,280 CANCER IN EPIDEMIOLOGIC STUDIES. 2900 01:54:49,280 --> 01:54:53,760 SO WHY SOMEONE GETS A GU, WHY 2901 01:54:53,760 --> 01:54:54,360 SOMEONE GETS DU, WE DON'T 2902 01:54:54,360 --> 01:54:55,520 UNDERSTAND. 2903 01:54:55,520 --> 01:54:59,080 >> YOU DO SEE PEOPLE WHO HAD 2904 01:54:59,080 --> 01:55:02,080 DUODENAL ULCER IN THE PAST NOW 2905 01:55:02,080 --> 01:55:02,880 GASTRIC YOU WILL CERTAIN MANY 2906 01:55:02,880 --> 01:55:06,040 YEARS LATER GOT NEITHER. 2907 01:55:06,040 --> 01:55:07,880 SO I THINK THAT GOES ON BUT HARD 2908 01:55:07,880 --> 01:55:08,080 TO -- 2909 01:55:08,080 --> 01:55:10,880 >> HAVE GU ON THE PATHWAY. 2910 01:55:10,880 --> 01:55:13,560 >> WELL, I WANT TO -- WE HAVE 2911 01:55:13,560 --> 01:55:15,520 COME TO THE END OF OUR TIME 2912 01:55:15,520 --> 01:55:18,480 ALTHOUGH I SUSPECT WE COULD HAVE 2913 01:55:18,480 --> 01:55:20,880 GONE ON CONSIDERABLY LONGER. 2914 01:55:20,880 --> 01:55:22,880 BUT ON BEHALF OF EVERYONE I 2915 01:55:22,880 --> 01:55:26,040 REALLY WANT TO THANK BOTH OF YOU 2916 01:55:26,040 --> 01:55:27,840 VERY MUCH PARTICULARLY BARRY FOR 2917 01:55:27,840 --> 01:55:29,800 BEING SO VIBRANT AT FIVE O'CLOCK 2918 01:55:29,800 --> 01:55:32,320 IN THE MORNING, THAT IS 2919 01:55:32,320 --> 01:55:34,440 ADMIRABLE AND MARTY, THANK YOU 2920 01:55:34,440 --> 01:55:35,680 AGAIN, YOU HAVE GIVEN EVERYONE 2921 01:55:35,680 --> 01:55:38,720 MUCH TO THINK ABOUT AND MY 2922 01:55:38,720 --> 01:55:40,400 SUSPICION IS THAT THE VAST 2923 01:55:40,400 --> 01:55:42,880 MAJORITY OF PEOPLE AROUND THE 2924 01:55:42,880 --> 01:55:45,560 WORLD WHO ARE LISTENING TO THIS 2925 01:55:45,560 --> 01:55:50,120 PROGRAM ARE NOT AWARE OF THE 2926 01:55:50,120 --> 01:55:54,560 BASIC PROPOSITION THAT YOUR 2927 01:55:54,560 --> 01:55:55,600 PRESENTATIONS OFFERED UNDER THE 2928 01:55:55,600 --> 01:55:58,160 IDEA OF THE SPLIT PERSONALITY. 2929 01:55:58,160 --> 01:56:00,080 IT IS MORE COMPLICATED. 2930 01:56:00,080 --> 01:56:03,360 MORE CHALLENGING AND MORE 2931 01:56:03,360 --> 01:56:05,880 OPPORTUNITIES FOR YOUNG PEOPLE 2932 01:56:05,880 --> 01:56:09,440 PARTICULARLY USING ADVANCE 2933 01:56:09,440 --> 01:56:12,480 TECHNOLOGY AND CONCEPTS TO LOOK 2934 01:56:12,480 --> 01:56:13,720 AT THESE PROBLEMS, THEY AREN'T 2935 01:56:13,720 --> 01:56:16,280 GOING AWAY BY THEMSELVES. 2936 01:56:16,280 --> 01:56:19,920 AND WITH ALL GOOD SCIENCE IT 2937 01:56:19,920 --> 01:56:20,800 RAISES GOOD QUESTIONS. 2938 01:56:20,800 --> 01:56:22,720 THANK YOU BOTH FOR RAISING THE 2939 01:56:22,720 --> 01:56:26,680 GOOD QUESTIONS, AS WELL AS 2940 01:56:26,680 --> 01:56:27,480 RELATING VERY GOOD SCIENCE. 2941 01:56:27,480 --> 01:56:29,480 THANK YOU VERY, VERY MUCH WE ALL 2942 01:56:29,480 --> 01:56:30,760 APPRECIATE IT. 2943 01:56:30,760 --> 01:56:31,760 WERE YOU WELL. 2944 01:56:31,760 --> 01:56:32,640 >> THANK YOU. 2945 01:56:32,640 --> 01:56:35,160 >> THANK YOU VERY MUCH. 2946 01:56:35,160 --> 01:56:36,080 >> GOOD TO SEE YOU. 2947 01:56:36,080 --> 01:56:45,680 >> THANK YOU.