1 00:00:06,669 --> 00:00:09,305 >> GOOD MORNING, EVERYBODY. 2 00:00:09,305 --> 00:00:11,073 I HOPE YOU ALL ENJOYED THE DAY 3 00:00:11,073 --> 00:00:13,376 YESTERDAY AND ARE READY TO 4 00:00:13,376 --> 00:00:14,844 FINISH UP WITH A LITTLE BIT OF A 5 00:00:14,844 --> 00:00:16,579 LIGHTER DAY TODAY, SO WE HAVE 6 00:00:16,579 --> 00:00:20,383 TWO MORE SESSIONS, BOTH OF WHICH 7 00:00:20,383 --> 00:00:22,451 WE'LL HAVE A DISCUSSION PANEL, 8 00:00:22,451 --> 00:00:24,353 AN EXTRA DISCUSSION PANEL IN THE 9 00:00:24,353 --> 00:00:33,195 AFTERNOON TO TALK ABOUT 10 00:00:33,195 --> 00:00:34,263 REAGENT AND THOSE KIND OF 11 00:00:34,263 --> 00:00:34,597 THINGS. 12 00:00:34,597 --> 00:00:35,931 FOR THOSE WHO WANT TO ORDER 13 00:00:35,931 --> 00:00:37,233 LUNCH, WE HAVE THE SAME SYSTEM 14 00:00:37,233 --> 00:00:39,101 TODAY AS WE DID YESTERDAY. 15 00:00:39,101 --> 00:00:41,704 SO LUNCH CAN BE ORDERED USING 16 00:00:41,704 --> 00:00:43,439 THE QR CODE ON THE AGENDA OR ON 17 00:00:43,439 --> 00:00:45,641 THE FLYERS ON YOUR TABLES. 18 00:00:45,641 --> 00:00:47,276 THAT'S FROM CHOPT. 19 00:00:47,276 --> 00:00:49,045 PLEASE DO THAT BY 9:30, IF 20 00:00:49,045 --> 00:00:50,112 THAT'S WHERE YOU WANT TO GET 21 00:00:50,112 --> 00:00:53,749 YOUR LUNCH FROM. 22 00:00:53,749 --> 00:00:55,084 TODAY IS A LITTLE BIT SHORTER OF 23 00:00:55,084 --> 00:00:55,584 A DAY TOO. 24 00:00:55,584 --> 00:00:57,653 WE WILL ADJOURN IN EARLY 25 00:00:57,653 --> 00:01:00,756 AFTERNOON, SO BY 3:15 HOPEFULLY, 26 00:01:00,756 --> 00:01:03,025 UNLESS THE DISCUSSION IS VERY 27 00:01:03,025 --> 00:01:07,430 RIVETTING, WE'LL KEEP GOING, B 28 00:01:07,430 --> 00:01:10,900 BUT -- I DON'T THINK THERE'S ANY 29 00:01:10,900 --> 00:01:12,201 ADDITIONAL HOUSEKEEPING ITEMS. 30 00:01:12,201 --> 00:01:13,569 SO TODAY WE'RE GOING TO START 31 00:01:13,569 --> 00:01:16,205 WITH SESSION 3, WHICH IS THE 32 00:01:16,205 --> 00:01:19,008 UTILITY OF ANIMAL MODELS IN 33 00:01:19,008 --> 00:01:20,242 RESPIRATORY VIRUS TRANSMISSION. 34 00:01:20,242 --> 00:01:22,712 WE HAVE OUR MODERATOR IS SABRA 35 00:01:22,712 --> 00:01:24,146 KLEIN, AND OUR FIRST SPEAKER 36 00:01:24,146 --> 00:01:27,283 WILL BE DELIVERING HIS TALK 37 00:01:27,283 --> 00:01:28,417 VIRTUALLY. 38 00:01:28,417 --> 00:01:38,961 AND THE REST WILL BE IN PERSON. 39 00:01:40,763 --> 00:01:47,103 >> GOOD MORNING, EVERYONE. 40 00:01:47,103 --> 00:01:48,337 HOW IS EVERYBODY DOING? 41 00:01:48,337 --> 00:01:49,305 CAN EVERYBODY HEAR ME? 42 00:01:49,305 --> 00:01:51,707 >> WE CAN HEAR YOU WELL. 43 00:01:51,707 --> 00:01:53,876 >> THANK YOU, SABRA. 44 00:01:53,876 --> 00:01:55,311 I APOLOGIZE FOR NOT ATTENDING IN 45 00:01:55,311 --> 00:01:56,946 PERSON. 46 00:01:56,946 --> 00:01:58,247 I SUFFERED FROM A BIT OF A HEAD 47 00:01:58,247 --> 00:01:59,381 COLD AND I DIDN'T WANT TO SHARE 48 00:01:59,381 --> 00:02:05,054 THAT WITH THE ENTIRE CONFERENCE. 49 00:02:05,054 --> 00:02:06,689 BEFORE I START, I WANT TO THANK 50 00:02:06,689 --> 00:02:08,324 MICHELLE AND STEVEN FOR ACTUALLY 51 00:02:08,324 --> 00:02:09,759 PUTTING TOGETHER A FANTASTIC 52 00:02:09,759 --> 00:02:10,092 WORKSHOP. 53 00:02:10,092 --> 00:02:11,927 I LEARNED A LOT YESTERDAY, AND 54 00:02:11,927 --> 00:02:13,195 I'M LOOKING FORWARD TO LEARNING 55 00:02:13,195 --> 00:02:14,196 A LOT MORE TODAY. 56 00:02:14,196 --> 00:02:16,198 FOR THOSE OF YOU WHO DON'T KNOW 57 00:02:16,198 --> 00:02:18,501 ME, MY NAME IS JACCO BOON, AND I 58 00:02:18,501 --> 00:02:20,269 AM IN THE DEPARTMENT OF MEDICINE 59 00:02:20,269 --> 00:02:21,704 AT WASHINGTON UNIVERSITY IN 60 00:02:21,704 --> 00:02:22,505 ST. LOUIS, MISSOURI, IN THE 61 00:02:22,505 --> 00:02:24,106 MIDDLE OF THE COUNTRY. 62 00:02:24,106 --> 00:02:25,741 AND I'M GOING TO TALK A LITTLE 63 00:02:25,741 --> 00:02:27,710 BIT ABOUT THE HAMSTER MODEL AND 64 00:02:27,710 --> 00:02:31,514 HOW IT'S USED IN SARS-COV-2 AND 65 00:02:31,514 --> 00:02:34,183 INFLUENZA. 66 00:02:34,183 --> 00:02:35,951 THIS IS THE LAYOUT OF THE TALK. 67 00:02:35,951 --> 00:02:37,419 A LITTLE BIT OF HISTORY, THEN, 68 00:02:37,419 --> 00:02:39,188 OF COURSE, THE EXPLOSION OF 69 00:02:39,188 --> 00:02:41,490 HAMSTER RESEARCH FOLLOWING THE 70 00:02:41,490 --> 00:02:43,359 EMERGENCE OF SARS-COV-2, SOME OF 71 00:02:43,359 --> 00:02:44,693 THE ADVANTAGES AND CURRENT 72 00:02:44,693 --> 00:02:46,061 NEEDS. 73 00:02:46,061 --> 00:02:48,764 SO WHEN I LOOKED AT INFLUENZA 74 00:02:48,764 --> 00:02:52,301 VIRUS IN PUBMED AND SYRIAN 75 00:02:52,301 --> 00:02:53,836 HAMSTERS, I RAO HELY FOUND ONE 76 00:02:53,836 --> 00:02:54,170 PAPERS. 77 00:02:54,170 --> 00:03:01,177 ONE FROM 1965 WHO USED PRA VIRUS 78 00:03:01,177 --> 00:03:03,345 SHOWING PULMONARY LESIONS IN 79 00:03:03,345 --> 00:03:05,014 SYRIAN GOLDEN HAMSTERS FOLLOWING 80 00:03:05,014 --> 00:03:05,481 INFECTION. 81 00:03:05,481 --> 00:03:07,850 THIS IS REALLY WHAT I WOULD CALL 82 00:03:07,850 --> 00:03:10,586 A SEMINAL STUDY IN 2018, ALMOST 83 00:03:10,586 --> 00:03:13,522 50 YEARS LATER, SHOWING THAT THE 84 00:03:13,522 --> 00:03:14,757 SYRIAN HAMSTER MODEL COULD BE 85 00:03:14,757 --> 00:03:17,059 USED TO STUDY HUMAN INFLUENZA 86 00:03:17,059 --> 00:03:18,360 VIRUS INFECTION. 87 00:03:18,360 --> 00:03:23,833 AND WHAT THEY SHOWED IS THAT 88 00:03:23,833 --> 00:03:27,736 SOME HUMAN INFLUENZA VIRUSES, 89 00:03:27,736 --> 00:03:34,877 H1N1 AND TYPE B VIRUSES -- HIGH 90 00:03:34,877 --> 00:03:38,781 TITERS -- WHAT WAS EVEN MORE 91 00:03:38,781 --> 00:03:39,682 SURPRISING IS THEY FOUND IN THE 92 00:03:39,682 --> 00:03:42,284 CASE OF SOME VIRUSES SUCH AS 93 00:03:42,284 --> 00:03:44,019 THIS H1N1 CALIFORNIA VIRUS THAT 94 00:03:44,019 --> 00:03:47,089 YOU ACTUALLY SAW AIRBORNE 95 00:03:47,089 --> 00:03:48,324 TRANSMISSION FROM THE INFECTED 96 00:03:48,324 --> 00:03:52,261 DONOR ANIMALS TO THE EXPOSED 97 00:03:52,261 --> 00:03:52,595 CONTACTS. 98 00:03:52,595 --> 00:03:54,463 BUT THIS WAS THE EXTENT OF 99 00:03:54,463 --> 00:03:56,632 INFLUENZA VIRUS FIELD IN SYRIAN 100 00:03:56,632 --> 00:03:59,268 HAMSTERS UNTIL THE PANDEMIC, 101 00:03:59,268 --> 00:04:03,906 WHEN GROUPS STARTED LOOKING AT 102 00:04:03,906 --> 00:04:07,109 SIMILARITIES AND DIFFERENCES 103 00:04:07,109 --> 00:04:09,545 BETWEEN THE MODELS AND I'LL TALK 104 00:04:09,545 --> 00:04:11,146 A LITTLE ABOUT THAT LATER. 105 00:04:11,146 --> 00:04:13,148 SO ANOTHER REALLY IMPORTANT 106 00:04:13,148 --> 00:04:18,954 PAPER I THINK THAT STARTED THE 107 00:04:18,954 --> 00:04:19,822 SARS-COV-2 FIELD AS WELL AS THE 108 00:04:19,822 --> 00:04:25,127 HAMSTER FIELD WAS THIS PAPER AND 109 00:04:25,127 --> 00:04:27,229 THIS WAS FOLLOWING THE EMERGENCE 110 00:04:27,229 --> 00:04:31,433 OF THE ORIGINAL SARS COV IN 111 00:04:31,433 --> 00:04:35,871 2003, AND THEY SHOWED UPON 112 00:04:35,871 --> 00:04:37,640 INTRANASAL INOCULATION YOU GOT 113 00:04:37,640 --> 00:04:41,810 VERY TIE TIT. 114 00:04:41,810 --> 00:04:42,912 TERS BOTH IN THE 115 00:04:42,912 --> 00:04:44,346 UPPER AIRWAY SHOWN IN BLACK AS 116 00:04:44,346 --> 00:04:46,615 WELL AS IN THE LUNGS FOLLOWING 117 00:04:46,615 --> 00:04:48,584 INTRANASAL INFECTION. 118 00:04:48,584 --> 00:04:53,155 THEY CONFIRMED THIS USING VERY 119 00:04:53,155 --> 00:04:55,391 NICE CHEMISTRY DETECTING VIRAL 120 00:04:55,391 --> 00:04:57,326 PROTEIN IN THE UPPER AIRWAYS AS 121 00:04:57,326 --> 00:04:58,727 WELL AS IN THE LOWER AIRWAYS. 122 00:04:58,727 --> 00:04:59,561 BUT IMPORTANTLY THERE WAS NO 123 00:04:59,561 --> 00:05:00,930 EVIDENCE FOR CLINICAL SYMPTOMS 124 00:05:00,930 --> 00:05:02,898 CONSISTENT WITH SARS-COV-2. 125 00:05:02,898 --> 00:05:04,466 THIS IS STILL SOMETHING UNTIL 126 00:05:04,466 --> 00:05:06,201 THIS DAY THAT A LOT OF 127 00:05:06,201 --> 00:05:08,637 SCIENTISTS WOULD LIKE TO SEE 128 00:05:08,637 --> 00:05:10,572 WEIGHT LOSS, PERHAPS EVEN DEATH 129 00:05:10,572 --> 00:05:14,944 FOLLOWING VIRUS INFECTION. 130 00:05:14,944 --> 00:05:16,145 HOWEVER, I THINK THESE TWO 131 00:05:16,145 --> 00:05:18,547 PAPERS LED TO THIS TEAM AND 132 00:05:18,547 --> 00:05:21,283 ANOTHER TEAM TO HONE IN ON THE 133 00:05:21,283 --> 00:05:23,819 SYRIAN HAMSTER EARLY DURING THE 134 00:05:23,819 --> 00:05:25,020 SARS-COV-2 PANDEMIC, AND THIS IS 135 00:05:25,020 --> 00:05:26,555 WORK THAT WAS LED BY OUR 136 00:05:26,555 --> 00:05:33,228 COLLEAGUES WITHIN THE NETWORK, 137 00:05:33,228 --> 00:05:35,597 TOGETHER WITH ANOTHER GROUP ALSO 138 00:05:35,597 --> 00:05:38,100 AT HONG KONG UNIVERSITY SHOWING 139 00:05:38,100 --> 00:05:42,071 HOW GOOD THE SYRIAN GOLDEN 140 00:05:42,071 --> 00:05:44,673 HAMSTER WAS FOR SARS-COV-2 141 00:05:44,673 --> 00:05:44,940 STUDIES. 142 00:05:44,940 --> 00:05:46,141 JUST TO SUMMARIZE THEIR WORK AS 143 00:05:46,141 --> 00:05:47,509 WELL AS MANY, MANY OTHER 144 00:05:47,509 --> 00:05:49,178 PEOPLE'S WORK AND I APOLOGIZE IF 145 00:05:49,178 --> 00:05:50,512 YOUR PAPER IS NOT SOMEWHERE IN 146 00:05:50,512 --> 00:05:53,882 MY PRESENTATION, BUT THE OVERALL 147 00:05:53,882 --> 00:05:56,719 CONCLUSION WAS THAT THE SYRIAN 148 00:05:56,719 --> 00:05:58,821 HAMSTER RECAPITULATES MANY 149 00:05:58,821 --> 00:05:59,888 ASPECTS OF HUMAN CLINICAL 150 00:05:59,888 --> 00:06:00,322 DISEASE. 151 00:06:00,322 --> 00:06:04,259 WE GOT SEVERE PATHOLOGY AFTER 152 00:06:04,259 --> 00:06:07,363 INFECTION, THE VIRUS HAS SIMILAR 153 00:06:07,363 --> 00:06:09,131 TROPISM, SO SEVERE PATHOLOGY 154 00:06:09,131 --> 00:06:10,966 SPECIFICALLY BEFORE THE 155 00:06:10,966 --> 00:06:12,234 EMERGENCE OF THE OMICRON 156 00:06:12,234 --> 00:06:14,003 VARIANT, MORE ON THAT LATER. 157 00:06:14,003 --> 00:06:16,739 WE SAW SOMEWHAT SIMILAR TROPISM 158 00:06:16,739 --> 00:06:19,241 COMPARED TO HUMAN INFECTION WITH 159 00:06:19,241 --> 00:06:21,010 PREDOMINANTLY UPPER AIRWAYS, THE 160 00:06:21,010 --> 00:06:22,745 NASAL TURBINATES AND THE LUNGS 161 00:06:22,745 --> 00:06:25,147 WITH SOME DISSEMINATION TO EXTRA 162 00:06:25,147 --> 00:06:27,249 PULMONARY TISSUE SUCH AS THE 163 00:06:27,249 --> 00:06:28,250 OLFACTORY BULB AS PRESENTED 164 00:06:28,250 --> 00:06:30,085 YESTERDAY IN A BEAUTIFUL TALK, 165 00:06:30,085 --> 00:06:31,720 AS WELL AS THE HEART AND THE THE 166 00:06:31,720 --> 00:06:33,088 INTESTINE. 167 00:06:33,088 --> 00:06:35,457 THIS IS A LITTLE BIT MORE 168 00:06:35,457 --> 00:06:38,060 CONTENTIOUS A STATEMENT BUT 169 00:06:38,060 --> 00:06:39,928 LIMITED TO -- APPLICATION IN THE 170 00:06:39,928 --> 00:06:42,765 BRAIN, AT LEAST NOT IN OUR HANDS 171 00:06:42,765 --> 00:06:45,367 AS WELL AS MANY OTHER LABS. 172 00:06:45,367 --> 00:06:47,836 THIS IS NOT TO SAY THERE ARE NO 173 00:06:47,836 --> 00:06:49,438 NEUROLOGICAL PHENOTYPES 174 00:06:49,438 --> 00:06:50,973 FOLLOWING SARS-COV-2 INFECTION, 175 00:06:50,973 --> 00:06:55,878 WHICH IS SHOWN -- AS WELL, 176 00:06:55,878 --> 00:06:58,547 FOLLOWING THE EXCESSIVE 177 00:06:58,547 --> 00:06:59,615 INFLAMMATION CAUSING THE 178 00:06:59,615 --> 00:07:01,250 NEUROLOGICAL SYMPTOMS. 179 00:07:01,250 --> 00:07:03,752 AND SHORT-TERM MEMORY LOSS. 180 00:07:03,752 --> 00:07:06,388 THERE WAS MORE SEVERE DISEASE IN 181 00:07:06,388 --> 00:07:08,157 ELDERLY ANIMALS AND 182 00:07:08,157 --> 00:07:09,591 IMMUNOCOMPROMISED ANIMALS. 183 00:07:09,591 --> 00:07:11,326 VERY IMPORTANT TO ME AND MANY 184 00:07:11,326 --> 00:07:12,394 OTHERS IS THAT AIRBORNE 185 00:07:12,394 --> 00:07:13,629 TRANSMISSION WAS READILY 186 00:07:13,629 --> 00:07:15,264 DETECTED, WHICH REALLY KIND OF 187 00:07:15,264 --> 00:07:17,466 OPENED UP THE FIELD, I THINK 188 00:07:17,466 --> 00:07:18,834 REALLY HELPED ALSO THE HAMSTER 189 00:07:18,834 --> 00:07:20,602 MODEL BEING SO PROMINENT FOR 190 00:07:20,602 --> 00:07:23,138 SARS-COV-2 RESEARCHERS. 191 00:07:23,138 --> 00:07:26,075 AND THEN ANOTHER PAPER FROM 192 00:07:26,075 --> 00:07:27,609 BEN'S LAB SHOWING THAT IMMUNE 193 00:07:27,609 --> 00:07:30,145 MEMORY FROM PREVIOUS INFECTIONS 194 00:07:30,145 --> 00:07:31,880 OR VACCINATIONS PREVENTED 195 00:07:31,880 --> 00:07:32,414 DISEASE. 196 00:07:32,414 --> 00:07:36,485 AND THIS WORK -- AND MORE ON 197 00:07:36,485 --> 00:07:37,019 THAT LATER. 198 00:07:37,019 --> 00:07:38,654 SO IN TERMS OF AIRBORNE 199 00:07:38,654 --> 00:07:39,321 TRANSMISSION, WHAT HAVE WE 200 00:07:39,321 --> 00:07:40,722 LEARNED SO FAR? 201 00:07:40,722 --> 00:07:43,125 ME, MY LAB AND MANY OTHER LABS 202 00:07:43,125 --> 00:07:45,761 HAVE DONE A LOT OF WORK ON THIS. 203 00:07:45,761 --> 00:07:47,529 THE THINGS WE'VE LEARNED IS THAT 204 00:07:47,529 --> 00:07:48,831 CONTACT TRANSMISSION IS MORE 205 00:07:48,831 --> 00:07:49,932 EFFICIENT IN AIRBORNE 206 00:07:49,932 --> 00:07:51,133 TRANSMISSION. 207 00:07:51,133 --> 00:07:53,435 PROLONGED EXPOSURES ALSO 208 00:07:53,435 --> 00:07:53,936 INCREASED TRANSMISSION 209 00:07:53,936 --> 00:07:55,938 EFFICIENCY. 210 00:07:55,938 --> 00:07:58,474 IN OUR SYSTEM, AIRBORNE 211 00:07:58,474 --> 00:08:00,209 TRANSMISSION WAS OPTIMAL AT 24 212 00:08:00,209 --> 00:08:01,977 HOURS POST INOCULATION OF THE 213 00:08:01,977 --> 00:08:04,179 DONOR ANIMAL BUT IT CAN LAST AS 214 00:08:04,179 --> 00:08:05,547 LONG AS THREE TO FOUR DAYS WITH 215 00:08:05,547 --> 00:08:06,782 SOME OF THE OTHER VARIANTS. 216 00:08:06,782 --> 00:08:08,183 TRANSMISSION CAN BE DETECTED 217 00:08:08,183 --> 00:08:09,952 REALLY EARLY, ALMOST 30 MINUTES 218 00:08:09,952 --> 00:08:11,286 AFTER EXPOSURE. 219 00:08:11,286 --> 00:08:14,756 AND IN OUR VERY SIMPLE SYSTEM 220 00:08:14,756 --> 00:08:17,326 WHERE THE TWO ANIMALS ARE 221 00:08:17,326 --> 00:08:20,662 SEPARATED BY A SMALL SPACE AND 222 00:08:20,662 --> 00:08:22,731 DIRECTIONAL AIR FLOW, WE CAN SEE 223 00:08:22,731 --> 00:08:23,899 100% TRANSMISSION AT EIGHT 224 00:08:23,899 --> 00:08:25,167 HOURS. 225 00:08:25,167 --> 00:08:26,668 TRANSMISSION IS MORE EFFICIENT 226 00:08:26,668 --> 00:08:28,770 WITH HIGHER TITERS AND IS 227 00:08:28,770 --> 00:08:29,638 INFLUENCED BY PARTICLE SIZE. 228 00:08:29,638 --> 00:08:31,707 SO LARGER PARTICLES TEND TO BE 229 00:08:31,707 --> 00:08:33,342 THE ONES THAT ACTUALLY CARRY THE 230 00:08:33,342 --> 00:08:35,410 VIRUS AND TRANSMIT. 231 00:08:35,410 --> 00:08:39,481 THERE'S DIFFERENCES IN ARRAY OF 232 00:08:39,481 --> 00:08:42,084 AIRBORNE TRANSMISSION BETWEEN 233 00:08:42,084 --> 00:08:44,553 STRAINS OF COV2. 234 00:08:44,553 --> 00:08:45,254 OMICRON, 100% TRANSMISSION OF 235 00:08:45,254 --> 00:08:51,627 THE ORIGINAL VIRUS, AS WELL AS 236 00:08:51,627 --> 00:08:53,195 D614G, BETA, DELTA, YOU NAME IT, 237 00:08:53,195 --> 00:08:55,330 AND THIS REALLY FELL OFF A CLIFF 238 00:08:55,330 --> 00:08:58,300 WITH THE EMERGES OF THE 239 00:08:58,300 --> 00:08:59,034 BA1 OMICRON VARIANT. 240 00:08:59,034 --> 00:09:03,972 THIS HAS PICKED UP A LITTLE WITH 241 00:09:03,972 --> 00:09:06,508 THTHESE. 242 00:09:06,508 --> 00:09:08,677 SO YESTERDAY -- THERE'S NO 243 00:09:08,677 --> 00:09:09,344 AIRBORNE TRANSMISSION WITH 244 00:09:09,344 --> 00:09:11,313 THE -- SO THIS SEEMS TO VARY A 245 00:09:11,313 --> 00:09:12,281 LITTLE BIT DEPENDENT ON THE 246 00:09:12,281 --> 00:09:15,017 STRAIN AND I HOPE OTHERS WILL 247 00:09:15,017 --> 00:09:16,752 ACTUALLY -- WHAT IT IS ABOUT 248 00:09:16,752 --> 00:09:18,520 THESE VIRUSES AND WHAT FEATURES 249 00:09:18,520 --> 00:09:21,056 ARE ASSOCIATED WITH EFFICIENT 250 00:09:21,056 --> 00:09:22,558 AIRBORNE TRANSMISSION IN SYRIAN 251 00:09:22,558 --> 00:09:24,960 HAMSTERS. 252 00:09:24,960 --> 00:09:28,130 AND BECAUSE IT'S SO EFFICIENT, 253 00:09:28,130 --> 00:09:29,131 ONWARDS OR SECONDARY 254 00:09:29,131 --> 00:09:30,332 TRANSMISSION FROM THE DONOR TO 255 00:09:30,332 --> 00:09:31,333 THE PRIMARY AND THEN THE PRIMARY 256 00:09:31,333 --> 00:09:34,269 TO THE SECONDARY AND EVEN 257 00:09:34,269 --> 00:09:36,371 TERTIARY ANIMAL CAN BE READILY 258 00:09:36,371 --> 00:09:37,239 DETECTED, WHICH IS SOMETHING 259 00:09:37,239 --> 00:09:39,007 THAT I'LL TOUCH UPON LATER AS 260 00:09:39,007 --> 00:09:40,309 WELL, WHICH IS REALLY HELPFUL 261 00:09:40,309 --> 00:09:45,647 FOR STUDYING COMMUNITY 262 00:09:45,647 --> 00:09:47,849 TRANSMISSION OR -- DAYCARE TYPE 263 00:09:47,849 --> 00:09:49,918 OF TRANSMISSION MODEL. 264 00:09:49,918 --> 00:09:52,921 SO PROBABLY THE MOST EFFICIENT 265 00:09:52,921 --> 00:09:54,323 USE OF THE HAMSTER SO FAR HAS 266 00:09:54,323 --> 00:09:56,058 BEEN TO DEMONSTRATE THE MANY 267 00:09:56,058 --> 00:09:59,328 DIFFERENT VACCINES, PRE-CLINICAL 268 00:09:59,328 --> 00:10:00,662 VACCINES OR EVEN CLINICAL 269 00:10:00,662 --> 00:10:02,264 VACCINES IN THE HAMSTER MODEL. 270 00:10:02,264 --> 00:10:03,966 I LOOKED THIS UP, I THINK THE 271 00:10:03,966 --> 00:10:05,801 FIRST PAPER IN HAMSTER MODEL MAY 272 00:10:05,801 --> 00:10:08,537 HAVE BEEN THIS ONE SHOWING THAT 273 00:10:08,537 --> 00:10:10,272 THE AD26 VACCINE PROTECTED 274 00:10:10,272 --> 00:10:11,473 AGAINST SEVERE DISEASE, BUT 275 00:10:11,473 --> 00:10:14,109 THERE HAVE BEEN MANY, MANY 276 00:10:14,109 --> 00:10:15,210 OTHERS. 277 00:10:15,210 --> 00:10:16,545 -- MOST OF THE PEOPLE IN THE 278 00:10:16,545 --> 00:10:17,045 ROOM HERE. 279 00:10:17,045 --> 00:10:18,480 I WOULD LIKE TO NOTE THAT SOME 280 00:10:18,480 --> 00:10:21,383 OF THESE PAPERS WERE ACTUALLY 281 00:10:21,383 --> 00:10:22,517 STUDYING MUCOSAL VACCINES. 282 00:10:22,517 --> 00:10:25,354 FOR EXAMPLE HERE, YOU'RE LOOKING 283 00:10:25,354 --> 00:10:29,424 AT THE CHADOX VIRUS AND VINCENT 284 00:10:29,424 --> 00:10:31,893 MUNSTER AS WELL AS OUR 285 00:10:31,893 --> 00:10:33,862 CONTRIBUTION AND HERE A 286 00:10:33,862 --> 00:10:34,529 LENTIVIRAL VECTOR WHERE PEOPLE 287 00:10:34,529 --> 00:10:36,198 WERE LOOKING AT INTRANASAL 288 00:10:36,198 --> 00:10:37,599 VACCINES AND SOMETIMES COMPARE 289 00:10:37,599 --> 00:10:40,035 THEM TO INTRAMUSCULAR DELIVERY 290 00:10:40,035 --> 00:10:41,470 SHOWING THAT INTRANASAL VACCINES 291 00:10:41,470 --> 00:10:44,273 WERE ACTUALLY MORE EFFECTIVE IN 292 00:10:44,273 --> 00:10:46,475 PREVENTING UPPER -- LOWERING 293 00:10:46,475 --> 00:10:50,412 UPPER AIRWAY TITERS THAN 294 00:10:50,412 --> 00:10:50,846 INTRAMUSCULAR. 295 00:10:50,846 --> 00:10:52,914 TO COME BACK TO THIS ONWARDS 296 00:10:52,914 --> 00:10:53,782 TRANSMISSION OR COMMUNITY 297 00:10:53,782 --> 00:10:55,550 TRANSMISSION MODEL, AGAIN, 298 00:10:55,550 --> 00:10:56,752 VINCENT'S LAB AS WELL AS MY LAB 299 00:10:56,752 --> 00:11:00,489 HAVE USED THIS TO SHOW HOW 300 00:11:00,489 --> 00:11:02,324 MUCOSAL VACCINES CAN IMPACT THIS 301 00:11:02,324 --> 00:11:05,027 COMMUNITY SPREAD, AND HOW IT MAY 302 00:11:05,027 --> 00:11:06,795 NOT ONLY PROTECT AGAINST THE 303 00:11:06,795 --> 00:11:07,796 INITIAL INFECTION BUT MAY ALSO 304 00:11:07,796 --> 00:11:09,765 LOWER THE RISK OF ONWARDS 305 00:11:09,765 --> 00:11:10,132 TRANSMISSION. 306 00:11:10,132 --> 00:11:15,771 SO THIS IS JUST ONE PANEL IN A 307 00:11:15,771 --> 00:11:19,241 FIGURE IN 2003 SHOWING IN BLACK 308 00:11:19,241 --> 00:11:23,545 THERE'S AN INFECTED ANIMAL, IN 309 00:11:23,545 --> 00:11:26,281 WHITE IS AN UNINFECTED OR AN 310 00:11:26,281 --> 00:11:27,249 ANIMAL THAT NEVER GOT IT. 311 00:11:27,249 --> 00:11:29,117 SO WHAT HE SHOWED IS THAT IF YOU 312 00:11:29,117 --> 00:11:31,420 WERE PREVIOUSLY INFECTED, P.I., 313 00:11:31,420 --> 00:11:33,755 YOU ACTUALLY HAD A VERY LOW RISK 314 00:11:33,755 --> 00:11:35,691 OF ONWARDS TRANSMISSION, EITHER 315 00:11:35,691 --> 00:11:36,758 GETTING INFECTED OR ACTUALLY 316 00:11:36,758 --> 00:11:40,162 SHEDDING THE VIRUS TO A SECOND 317 00:11:40,162 --> 00:11:42,831 OR THIRD ANIMAL. 318 00:11:42,831 --> 00:11:45,667 THE NEXT BEST THING WAS 319 00:11:45,667 --> 00:11:46,902 INTRANASAL IMMUNIZATION FOLLOWED 320 00:11:46,902 --> 00:11:49,137 BY INTRAMUSCULAR IMMUNIZATION 321 00:11:49,137 --> 00:11:50,872 AND THEN -- AND WE RECENTLY GOT 322 00:11:50,872 --> 00:11:52,441 OUR PAPER ACCEPTED IN SCIENCE 323 00:11:52,441 --> 00:11:55,811 ADVANCES SHOWING VERY SIMILAR. 324 00:11:55,811 --> 00:11:57,512 SO THIS IS LOOKING AT SECONDARY 325 00:11:57,512 --> 00:11:59,614 TRANSMISSION, SO FROM THE 326 00:11:59,614 --> 00:12:00,716 PRIMARY CONTACT TO THE SECONDARY 327 00:12:00,716 --> 00:12:02,617 ANIMAL. 328 00:12:02,617 --> 00:12:04,119 LOOKING AT -- SHOWN HERE ON Y 329 00:12:04,119 --> 00:12:07,622 AXIS IS THE PERCENT SARS-COV-2 330 00:12:07,622 --> 00:12:08,290 POSITIVE CONTACTS. 331 00:12:08,290 --> 00:12:09,691 SO IN THE NAIVE ANIMALS, YOU 332 00:12:09,691 --> 00:12:11,660 HAVE ALMOST AN 80% TRANSMISSION 333 00:12:11,660 --> 00:12:13,128 RATE FROM THE PRIMARY TO THE 334 00:12:13,128 --> 00:12:15,597 SECONDARY ANIMAL. 335 00:12:15,597 --> 00:12:16,932 THIS DEPENDS A LITTLE BIT ON HOW 336 00:12:16,932 --> 00:12:18,333 LONG YOU EXPOSE AND WHAT TIME 337 00:12:18,333 --> 00:12:21,336 YOU EXPOSE. 338 00:12:21,336 --> 00:12:22,504 TO INTRAMUSCULAR IMMUNIZATION 339 00:12:22,504 --> 00:12:24,172 WITH MRNA, YOU ACTUALLY STILL 340 00:12:24,172 --> 00:12:25,874 GET A LOT OF ONWARDS OR 341 00:12:25,874 --> 00:12:26,641 SECONDARY TRANSMISSION. 342 00:12:26,641 --> 00:12:29,277 HOWEVER, IF YOU USE A MUCOSAL 343 00:12:29,277 --> 00:12:32,447 VACCINE, REFERENCED HERE AS 344 00:12:32,447 --> 00:12:34,416 CHAD-S, VECTOR CHIMPANZEE ADD 345 00:12:34,416 --> 00:12:37,552 FLOW VIRUS VECTOR VACCINE, YOU 346 00:12:37,552 --> 00:12:38,720 ACTUALLY BLOCK SECONDARY 347 00:12:38,720 --> 00:12:40,522 TRANSMISSION NOT ONLY TO OTHER 348 00:12:40,522 --> 00:12:41,957 VACCINATED ANIMALS BUT ALSO TO 349 00:12:41,957 --> 00:12:42,424 NAIVE ANIMALS. 350 00:12:42,424 --> 00:12:44,025 SO I THINK THIS KIND OF 351 00:12:44,025 --> 00:12:46,161 HIGHLIGHTS ONE OF THE UNIQUE 352 00:12:46,161 --> 00:12:48,630 FEATURES OF THE SYRIAN HAMSTER 353 00:12:48,630 --> 00:12:50,198 MODELS IN TERMS OF THE ABILITY 354 00:12:50,198 --> 00:12:52,467 TO TRANSMIT THE VIRUS AND TO USE 355 00:12:52,467 --> 00:12:55,637 LARGE ENOUGH ANIMALS AND GROUP 356 00:12:55,637 --> 00:13:01,443 SIZES TO REALLY ASSESS THE 357 00:13:01,443 --> 00:13:04,045 IMPACT OF VACCINE TRANSMISSION 358 00:13:04,045 --> 00:13:04,713 AND -- TRANSMISSION OF THE 359 00:13:04,713 --> 00:13:05,147 VIRUS. 360 00:13:05,147 --> 00:13:07,149 SO FOUR YEARS INTO THE PANDEMIC, 361 00:13:07,149 --> 00:13:09,317 SO WHAT ARE HAMSTERS CURRENTLY 362 00:13:09,317 --> 00:13:09,851 USED FOR? 363 00:13:09,851 --> 00:13:12,053 I'M SURE I'M MISSING SEVERAL 364 00:13:12,053 --> 00:13:13,889 REALLY IMPORTANT SEMINAL STUDIES 365 00:13:13,889 --> 00:13:15,657 HERE, BUT I THINK THE FIELD HAS 366 00:13:15,657 --> 00:13:19,828 SETTLED ON A LOT OF THESE. 367 00:13:19,828 --> 00:13:21,329 AND THEY FALL IN ONE OR MORE OF 368 00:13:21,329 --> 00:13:21,963 THESE CATEGORIES. 369 00:13:21,963 --> 00:13:23,532 SO THERE ARE GOING TO BE MORE 370 00:13:23,532 --> 00:13:24,733 AND MORE VACCINE STUDIES COMING 371 00:13:24,733 --> 00:13:26,601 DOWN, BEING DONE RIGHT NOW IN 372 00:13:26,601 --> 00:13:27,602 MANY DIFFERENT LABS. 373 00:13:27,602 --> 00:13:29,638 PEOPLE WILL IMPROVE MUCOSAL 374 00:13:29,638 --> 00:13:30,972 VACCINES, THEY WILL IMPROVE 375 00:13:30,972 --> 00:13:34,910 VECTOR VACCINES, MRNA VACCINES, 376 00:13:34,910 --> 00:13:35,677 RECOMBINATION VACCINES. 377 00:13:35,677 --> 00:13:38,647 PEOPLE WILL START TO STUDY 378 00:13:38,647 --> 00:13:39,514 VACCINE EFFICACY AGAINST 379 00:13:39,514 --> 00:13:40,816 PRE-EXISTING IMMUNITY AS WE AND 380 00:13:40,816 --> 00:13:42,150 OTHERS HAVE DONE ALREADY. 381 00:13:42,150 --> 00:13:44,419 PEOPLE ARE LOOKING AT VARYING 382 00:13:44,419 --> 00:13:45,620 VACCINES AND THE EFFICACY 383 00:13:45,620 --> 00:13:47,155 AGAINST NEWLY EMERGING 384 00:13:47,155 --> 00:13:49,157 SARS-COV-2 VIRUSES, WHICH IS 385 00:13:49,157 --> 00:13:50,358 SOMETHING MY LAB DOES QUITE A 386 00:13:50,358 --> 00:13:52,093 BIT OF, AND THEN UNDERSTANDING 387 00:13:52,093 --> 00:13:53,395 CORRELATES OF IMMUNE PROTECTION. 388 00:13:53,395 --> 00:13:54,629 I THINK THE HAMSTER WILL START 389 00:13:54,629 --> 00:13:59,701 TO BE USED MORE FOR ANTIVIRAL -- 390 00:13:59,701 --> 00:14:01,036 MEASURE STUDIES SUCH AS SMALL 391 00:14:01,036 --> 00:14:01,636 MOLECULES. 392 00:14:01,636 --> 00:14:03,138 THIS WILL REQUIRE -- THIS IS NOT 393 00:14:03,138 --> 00:14:05,674 MY AREA OF EXPERTISE, I THINK IT 394 00:14:05,674 --> 00:14:06,608 WILL REQUIRE A SIGNIFICANT 395 00:14:06,608 --> 00:14:10,779 INVESTMENT IN UNDERSTANDING THE 396 00:14:10,779 --> 00:14:12,881 PHARMACOKINETICS AND DYNAMICS 397 00:14:12,881 --> 00:14:14,549 AND SMALL MOLECULE CLEARANCE IN 398 00:14:14,549 --> 00:14:15,851 THE HAMSTER COMPARED TO SOME OF 399 00:14:15,851 --> 00:14:19,187 THE OTHER MORE ESTABLISHED SMALL 400 00:14:19,187 --> 00:14:21,156 ANIMAL MODELS. 401 00:14:21,156 --> 00:14:22,591 SO I THINK MORE AND MORE PEOPLE 402 00:14:22,591 --> 00:14:24,693 WILL DO FUNDAMENTAL BIOLOGY OF 403 00:14:24,693 --> 00:14:25,660 SARS-COV-2 INFECTION, 404 00:14:25,660 --> 00:14:26,995 PATHOGENESIS AND TRANSMISSION. 405 00:14:26,995 --> 00:14:29,598 THIS IS A PAPER FROM MY LAB 406 00:14:29,598 --> 00:14:32,534 LOOKING AT THE SIGNIFICANCE OF A 407 00:14:32,534 --> 00:14:36,104 RNA MOTIF CALLED S2M IN THE 408 00:14:36,104 --> 00:14:38,473 3 PRIME REGION OF SARS-COV-2, 409 00:14:38,473 --> 00:14:40,242 AND WE SHOWED IT ACTUALLY WAS 410 00:14:40,242 --> 00:14:41,743 DISPENSABLE FOR SARS-COV-2, AND 411 00:14:41,743 --> 00:14:44,179 THEN WHILE WE WERE WRITING THIS 412 00:14:44,179 --> 00:14:48,517 PAPER, THE VIRUS ITSELF ACTUALLY 413 00:14:48,517 --> 00:14:51,520 EVOLVED AND DELETED A SLIGHTLY 414 00:14:51,520 --> 00:14:53,655 DIFFERENT S2M REGION, A 415 00:14:53,655 --> 00:14:55,490 DIFFERENT SEQUENCE BUT STILL IT 416 00:14:55,490 --> 00:14:57,826 DELETED THE S2M IN ITS GENOME. 417 00:14:57,826 --> 00:15:00,228 SO THE CURRENT VARIANTS OF SARS 418 00:15:00,228 --> 00:15:06,034 CHSARS-COV-2 NO LONGER CARRY IT. 419 00:15:06,034 --> 00:15:07,235 SEVERAL PAPERS, AND MORE WILL 420 00:15:07,235 --> 00:15:08,737 COME, ARE LOOKING AT MUTATIONS, 421 00:15:08,737 --> 00:15:11,473 THE ROLE OF ORF AND DELETION 422 00:15:11,473 --> 00:15:14,309 MUTANT VIRUSES ON PATHOGENESIS 423 00:15:14,309 --> 00:15:15,310 REPLICATION AND HOPEFULLY 424 00:15:15,310 --> 00:15:19,147 TRANSMISSION. 425 00:15:19,147 --> 00:15:26,087 HE SEVERAL GSEVERAL GROUPS ARE T 426 00:15:26,087 --> 00:15:28,890 THE ROLE OF CO-INFECTION ON 427 00:15:28,890 --> 00:15:30,959 SARS-COV-2 DISEASE, REPLICATION 428 00:15:30,959 --> 00:15:31,393 AND TRANSMISSION. 429 00:15:31,393 --> 00:15:33,361 AND THIS IS NOT JUST INFLUENZA 430 00:15:33,361 --> 00:15:35,764 VIRUS BUT ALSO OTHER 431 00:15:35,764 --> 00:15:36,064 CORONAVIRUS. 432 00:15:36,064 --> 00:15:37,198 I HOPE THE FIELD WILL EVOLVE 433 00:15:37,198 --> 00:15:38,533 FURTHER TO INCLUDE MANY, MANY 434 00:15:38,533 --> 00:15:42,003 MORE PATHOGENS SUCH AS RSV, 435 00:15:42,003 --> 00:15:44,306 OTHER CORONAVIRUS, ET CETERA. 436 00:15:44,306 --> 00:15:46,174 AND THEN BARCODED SARS-COV-2, 437 00:15:46,174 --> 00:15:47,142 SOMETHING THAT MY LAB HAS BEEN 438 00:15:47,142 --> 00:15:48,610 WORKING ON EXTENSIVELY IN THE 439 00:15:48,610 --> 00:15:51,313 LAST COUPLE OF YEARS. 440 00:15:51,313 --> 00:15:53,315 SO WE RECENTLY POSTED A 441 00:15:53,315 --> 00:15:54,482 PRE-PRINT ON BIOARCHIVES. 442 00:15:54,482 --> 00:15:57,752 THIS IS WORK DONE BY A VERY 443 00:15:57,752 --> 00:15:59,187 TALENTED GRADUATE STUDENT, 444 00:15:59,187 --> 00:16:02,924 POSTDOC IN MY LAB, TRENDE. 445 00:16:02,924 --> 00:16:05,193 WHAT WE DID IS ESSENT ESSENTIALK 446 00:16:05,193 --> 00:16:07,495 AT SOME OF THE LITERATURE ON 447 00:16:07,495 --> 00:16:09,164 BARCODED VIRUSES. 448 00:16:09,164 --> 00:16:10,432 WE DECIDED TO INTRODUCE, 449 00:16:10,432 --> 00:16:12,300 TOGETHER WITH ANOTHER LAB, DAVE 450 00:16:12,300 --> 00:16:13,535 WANG AT WASHINGTON UNIVERSITY, 451 00:16:13,535 --> 00:16:16,871 WE DECIDED TO INTRODUCE A NINE 452 00:16:16,871 --> 00:16:20,508 NUCLEOTIDE BARCODE IN ORF10 IN 453 00:16:20,508 --> 00:16:22,777 SARS-COV-2. 454 00:16:22,777 --> 00:16:23,244 GNNGNNGNN. 455 00:16:23,244 --> 00:16:24,946 WE INDIVIDUALLY GENERATED OVER 456 00:16:24,946 --> 00:16:26,848 200 UNIQUE VIRUSES THROUGH THIS 457 00:16:26,848 --> 00:16:28,717 METHOD. 458 00:16:28,717 --> 00:16:32,187 WE PULLED THESE AT EQUAL AMOUNTS 459 00:16:32,187 --> 00:16:39,194 OF INFECTIOUS TITER AND THEN 460 00:16:39,194 --> 00:16:41,062 MEASURED THE RELATIVE BARCODE 461 00:16:41,062 --> 00:16:43,064 FREQUENCY IN THIS POOL OF OURS. 462 00:16:43,064 --> 00:16:47,168 IT'S SHOWN HERE IN THE TOP BAR 463 00:16:47,168 --> 00:16:52,307 IN THIS KIND OF RAINBOW. 464 00:16:52,307 --> 00:16:53,541 ONE PICTURE ACTUALLY MATCHES THE 465 00:16:53,541 --> 00:16:54,376 COLORS THROUGHOUT THE 466 00:16:54,376 --> 00:16:54,709 PRESENTATION. 467 00:16:54,709 --> 00:16:57,712 WE HAD TO DO A LOT OF UP-FRONT 468 00:16:57,712 --> 00:16:58,546 INVESTIGATIVE STUDIES TO MAKE 469 00:16:58,546 --> 00:17:00,315 SURE THAT THE VIRUSES WERE GOOD, 470 00:17:00,315 --> 00:17:04,152 AND WE DIDN'T HAVE EITHER GROSS 471 00:17:04,152 --> 00:17:05,987 ATTENUATION OR INCREASED 472 00:17:05,987 --> 00:17:06,655 REPLICATION. 473 00:17:06,655 --> 00:17:09,491 SO IN VITRO, ALL THE VIRUSES 474 00:17:09,491 --> 00:17:11,860 REPLICATED TO THE SAME TITER AND 475 00:17:11,860 --> 00:17:13,762 IN VIVO, COMPARING THE BARCODE 476 00:17:13,762 --> 00:17:18,700 FREQUENCY BETWEEN THE INNOCULUM 477 00:17:18,700 --> 00:17:20,969 AND 32 AND 72 HOURS POST 478 00:17:20,969 --> 00:17:21,970 INOCULATION IN HAMSTERS IN 479 00:17:21,970 --> 00:17:23,605 VARIOUS TISSUES BUT WE DIDN'T 480 00:17:23,605 --> 00:17:24,606 REALLY SEE A SIGNIFICANT 481 00:17:24,606 --> 00:17:26,675 INCREASE IN ONE BARCODE OVER 482 00:17:26,675 --> 00:17:28,309 ANOTHER OVER MANY, MANY 483 00:17:28,309 --> 00:17:28,843 DIFFERENT EXPERIMENTS. 484 00:17:28,843 --> 00:17:31,279 SO I'M NOT GOING TO TALK ABOUT 485 00:17:31,279 --> 00:17:32,914 THE ENTIRE PAPER BUT I KIND OF 486 00:17:32,914 --> 00:17:34,449 WANT TO SHOW A VIGNETTE OF SOME 487 00:17:34,449 --> 00:17:35,750 THINGS YOU CAN DO WITH THIS 488 00:17:35,750 --> 00:17:36,851 REALLY UNIQUE RESOURCE. 489 00:17:36,851 --> 00:17:38,153 SO THE FIRST THING THAT WE DID 490 00:17:38,153 --> 00:17:40,655 IS TO SHOW THAT THESE BARCODED 491 00:17:40,655 --> 00:17:43,191 VIRUSES ACTUALLY TRANSMIT AND 492 00:17:43,191 --> 00:17:45,060 HOW EFFICIENT IS SARS-COV-2 493 00:17:45,060 --> 00:17:45,393 TRANSMISSION. 494 00:17:45,393 --> 00:17:47,028 SO IN OUR MODEL SYSTEM, AGAIN 495 00:17:47,028 --> 00:17:48,296 IT'S RELATIVELY STRAIGHTFORWARD, 496 00:17:48,296 --> 00:17:50,532 SO WE TAKE A DONOR ANIMAL, WE 497 00:17:50,532 --> 00:17:52,867 INOCULATE IT WITH 100,000 498 00:17:52,867 --> 00:17:54,002 INFECTIOUS UNITS, BARCODED 499 00:17:54,002 --> 00:17:54,669 VIRUSES. 500 00:17:54,669 --> 00:17:56,871 WE WAIT 24 HOUR, THEN EXPOSE OUR 501 00:17:56,871 --> 00:17:58,506 CONTACT ANIMAL FOR A BRIEF 502 00:17:58,506 --> 00:17:59,941 AMOUNT OF TIME, EIGHT HOURS, AND 503 00:17:59,941 --> 00:18:01,810 WE CAN DO EITHER DIRECT CONTACT 504 00:18:01,810 --> 00:18:03,178 OR AIRBORNE. 505 00:18:03,178 --> 00:18:04,946 THIS IS DATA FROM AIRBORNE 506 00:18:04,946 --> 00:18:05,213 EXPOSURES. 507 00:18:05,213 --> 00:18:08,149 AND THEN WE WAIT A TOTAL OF 508 00:18:08,149 --> 00:18:09,784 72 HOURS BEFORE WE SACRIFICE THE 509 00:18:09,784 --> 00:18:10,752 CONTACT ANIMAL. 510 00:18:10,752 --> 00:18:13,788 WE COLLECT THE TISSUES, HERE I 511 00:18:13,788 --> 00:18:15,457 JUST AM SHOWING YOU THE NASAL 512 00:18:15,457 --> 00:18:16,458 TURBINATES AND SEE THE TRACHEA 513 00:18:16,458 --> 00:18:18,293 AND THE LUNGS, AND WE JUST 514 00:18:18,293 --> 00:18:19,627 MEASURE HOW MANY BARCODES CAN WE 515 00:18:19,627 --> 00:18:20,595 DETECT. 516 00:18:20,595 --> 00:18:21,730 AND THERE'S A COUPLE THINGS THAT 517 00:18:21,730 --> 00:18:23,098 I WANT YOU TO TAKE AWAY FROM 518 00:18:23,098 --> 00:18:23,865 THIS SLIDE. 519 00:18:23,865 --> 00:18:25,767 SO FIRST OF ALL, YOU DETECT A 520 00:18:25,767 --> 00:18:27,602 LOT OF DIFFERENT BARCODES. 521 00:18:27,602 --> 00:18:30,138 IN THIS PARTICULAR ANIMAL, WE 522 00:18:30,138 --> 00:18:31,406 HAD 13 DIFFERENT BARCODES. 523 00:18:31,406 --> 00:18:32,974 THIS ONE WE HAVE 20 UNIQUE 524 00:18:32,974 --> 00:18:33,475 BARCODES. 525 00:18:33,475 --> 00:18:36,711 SO AS I INDICATED EARLIER, SARS 526 00:18:36,711 --> 00:18:41,382 TRSARS-COV-2 AIRBORNE TRANSMISSN 527 00:18:41,382 --> 00:18:43,885 IN HAMSTERS IT REALLY VERY 528 00:18:43,885 --> 00:18:44,152 EFFICIENT. 529 00:18:44,152 --> 00:18:46,955 THERE ARE MULTIPLE BARCODES 530 00:18:46,955 --> 00:18:48,156 THROUGHOUT THE VARIOUS TISSUES 531 00:18:48,156 --> 00:18:49,257 AND MANY ARE SHOWN HERE. 532 00:18:49,257 --> 00:18:50,558 SO EACH CIRCLE IN THE VENN 533 00:18:50,558 --> 00:18:52,427 DIAGRAM IS A DIFFERENT TISSUE. 534 00:18:52,427 --> 00:18:55,930 WE'VE ACTUALLY ALSO DONE THIS AT 535 00:18:55,930 --> 00:18:58,700 DAY 1 AND DAY 2 POST EXPOSURE 536 00:18:58,700 --> 00:19:01,202 AND WE ACTUALLY SEE MORE 537 00:19:01,202 --> 00:19:01,936 TISSUE-SPECIFIC BARCODES. 538 00:19:01,936 --> 00:19:03,071 FOR EXAMPLE, THIS BLUE ONE HERE 539 00:19:03,071 --> 00:19:04,239 IS REALLY SPECIFIC TO THE LUNGS 540 00:19:04,239 --> 00:19:06,875 BUT NOT THE NASAL TURBINATES, 541 00:19:06,875 --> 00:19:08,810 SUGGESTING THAT THE VIRUS CAN 542 00:19:08,810 --> 00:19:10,979 TEUMLY BYPASS THE UPPER AIRWAYS 543 00:19:10,979 --> 00:19:13,548 AND DIRECTLY INFECT THE LOWER 544 00:19:13,548 --> 00:19:13,882 AIRWAYS. 545 00:19:13,882 --> 00:19:15,383 SO THIS IS ONE THING THAT WE 546 00:19:15,383 --> 00:19:16,651 DID, WE LOOKED AT EXPOSURE 547 00:19:16,651 --> 00:19:17,352 TIMES. 548 00:19:17,352 --> 00:19:19,354 WE CAN SEE THAT THERE IS A 549 00:19:19,354 --> 00:19:19,954 SIGNIFICANT DIFFERENCE IN THE 550 00:19:19,954 --> 00:19:21,589 AMOUNT OF BARCODES DETECTED IF 551 00:19:21,589 --> 00:19:24,325 YOU EXPOSE FOR ONE HOUR, FOUR 552 00:19:24,325 --> 00:19:26,327 HOURS OR EIGHT HOURS. 553 00:19:26,327 --> 00:19:29,597 AND I INCLUDED THIS SLIDE FOR 554 00:19:29,597 --> 00:19:32,567 SABRA, WE COMPARED THE NUMBER OF 555 00:19:32,567 --> 00:19:34,302 BARCODES OR AIRBORNE 556 00:19:34,302 --> 00:19:35,403 TRANSMISSION BETWEEN MALE AND 557 00:19:35,403 --> 00:19:39,307 FEMALE HAMSTERS AND THERE ARE NO 558 00:19:39,307 --> 00:19:40,108 CLEAR DIFFERENCES IN THE AMOUNT 559 00:19:40,108 --> 00:19:42,544 OF BARCODES DETECTED, SUGGESTING 560 00:19:42,544 --> 00:19:44,646 THAT THERE'S NO LARGE DIFFERENCE 561 00:19:44,646 --> 00:19:47,415 IN TRANSMISSION OR 562 00:19:47,415 --> 00:19:48,216 SUSCEPTIBILITY BETWEEN BOTH 563 00:19:48,216 --> 00:19:52,687 SEXES. 564 00:19:52,687 --> 00:19:54,489 SO WHAT ARE THE ADVANTAGES OF 565 00:19:54,489 --> 00:19:55,423 THE HAMSTER? 566 00:19:55,423 --> 00:19:57,292 THEY'RE CLEAR LEHIGHLY 567 00:19:57,292 --> 00:19:58,893 SUSCEPTIBLE TO SARS-COV-2 AND 568 00:19:58,893 --> 00:20:01,429 THEY'RE PERMISSIVE TO OTHER -- 569 00:20:01,429 --> 00:20:02,530 AND INFLAWN IS A VIRUS. 570 00:20:02,530 --> 00:20:05,433 I THINK THIS OPENS UP A WHOLE 571 00:20:05,433 --> 00:20:08,670 NEW FIELD THAT -- TO STUDY THE 572 00:20:08,670 --> 00:20:11,272 ROLE OF COINFECTIONS, PRIOR 573 00:20:11,272 --> 00:20:13,007 INFECTIONS ON TRANSMISSION, 574 00:20:13,007 --> 00:20:13,708 SUSCEPTIBILITY OF THE VIRUS, ET 575 00:20:13,708 --> 00:20:17,745 CETERA. 576 00:20:17,745 --> 00:20:24,185 HAMSTER ARE RELATIVELY CHEAP, 577 00:20:24,185 --> 00:20:25,820 EASY TO HOUSE AND HANDLE. 578 00:20:25,820 --> 00:20:27,922 I SEE TOO MANY PAPERS LOOKING AT 579 00:20:27,922 --> 00:20:29,123 REALLY SMALL NUMBERS, AND I 580 00:20:29,123 --> 00:20:30,258 DON'T THINK THAT IS JUSTIFIED IN 581 00:20:30,258 --> 00:20:31,960 THE CONTEXT OF SYRIAN HAMSTERS. 582 00:20:31,960 --> 00:20:33,528 WE REALLY SHOULD USE LARGER 583 00:20:33,528 --> 00:20:35,630 GROUP SIZES AND REPEATING 584 00:20:35,630 --> 00:20:35,930 EXPERIMENTS. 585 00:20:35,930 --> 00:20:37,432 AND WE SHOULD INCLUDE MALE AND 586 00:20:37,432 --> 00:20:42,470 FEMALE HAMSTERS WHEN REQUIRED. 587 00:20:42,470 --> 00:20:44,639 THE HAMSTERS, THE GENOME IS 588 00:20:44,639 --> 00:20:46,741 AVAILABLE, THE ANIMALS ARE 589 00:20:46,741 --> 00:20:48,943 INBRED, AND THIS WAS ALLUDED TO 590 00:20:48,943 --> 00:20:50,178 YESTERDAY BUT WE HAVE EVIDENCE 591 00:20:50,178 --> 00:20:55,016 TO STRONGLY SUGGEST THAT, REALLY 592 00:20:55,016 --> 00:20:56,351 SIMPLIFYING SOME OF THE 593 00:20:56,351 --> 00:20:58,386 TRANSCRIPTIONAL STUDIES 594 00:20:58,386 --> 00:21:02,590 INCLUDING SINGLE CELL RNA SEQ 595 00:21:02,590 --> 00:21:03,358 THAT ARE AVAILABLE. 596 00:21:03,358 --> 00:21:06,127 THERE ARE A HUGE GAP IN 597 00:21:06,127 --> 00:21:06,861 IMMUNOLOGICAL REAGENTS AND 598 00:21:06,861 --> 00:21:07,595 ASSAYS THAT ARE AVAILABLE. 599 00:21:07,595 --> 00:21:08,730 I THINK MY LAB AS WELL AS OTHERS 600 00:21:08,730 --> 00:21:10,331 HAVE REALLY PUSHED THIS ENVELOPE 601 00:21:10,331 --> 00:21:12,233 AND THE ASSAYS THAT ARE NOW 602 00:21:12,233 --> 00:21:14,269 ONLINE REALLY IMPROVE THE MODEL 603 00:21:14,269 --> 00:21:18,339 AS A WHOLE. 604 00:21:18,339 --> 00:21:19,674 JUST TO SHOW YOU TWO EXAMPLES OF 605 00:21:19,674 --> 00:21:21,509 THIS, THIS IS A PAPER CURRENTLY 606 00:21:21,509 --> 00:21:23,711 UNDER REVISION FROM MY LAB 607 00:21:23,711 --> 00:21:27,749 SHOWING OR DEVELOPING A B CELL 608 00:21:27,749 --> 00:21:29,083 ELISPOT ASSAY FOR SYRIAN 609 00:21:29,083 --> 00:21:30,451 HAMSTERS MEASURING BOTH THE IGG 610 00:21:30,451 --> 00:21:35,890 AS WELL AS THE IGA ANTIBODY 611 00:21:35,890 --> 00:21:36,925 RESPONSE AT THE CELLULAR LEVEL 612 00:21:36,925 --> 00:21:37,792 IN THESE ANIMALS. 613 00:21:37,792 --> 00:21:40,962 SO THIS IS JUST HOW THIS LACKS. 614 00:21:40,962 --> 00:21:44,365 AND WE CAN MEASURE, AND BEEF 615 00:21:44,365 --> 00:21:48,436 DONE THIWE'VEDONE THIS NOW IN DT 616 00:21:48,436 --> 00:21:49,637 VACCINE CONTEXTS. 617 00:21:49,637 --> 00:21:52,674 THIS IS AN EXAMPLE OF A PROTEIN 618 00:21:52,674 --> 00:21:56,945 VACCINE, NOVAVAX, IGG AND IGA 619 00:21:56,945 --> 00:22:01,816 LEVEL IN BOTH THE SPLEEN AND D 620 00:22:01,816 --> 00:22:02,183 DLN. 621 00:22:02,183 --> 00:22:04,919 AND WE CAN DETECT EITHER 622 00:22:04,919 --> 00:22:06,821 INTRANASAL VECTOR OR MRNA, WE 623 00:22:06,821 --> 00:22:09,190 CAN DETECT IT IN MULTIPLE 624 00:22:09,190 --> 00:22:09,924 DIFFERENT TISSUES. 625 00:22:09,924 --> 00:22:12,694 WE ALSO IMPLEMENTED THE T-CELL 626 00:22:12,694 --> 00:22:13,261 ELISPOT. 627 00:22:13,261 --> 00:22:15,964 THIS IS A COMMERCIAL ASSAY, 628 00:22:15,964 --> 00:22:17,298 AVAILABLE FROM MED TECH, AND WE 629 00:22:17,298 --> 00:22:18,599 MADE SURE THAT IT WORKED AND IT 630 00:22:18,599 --> 00:22:20,835 WAS ROBUST, CONFIRMING SOME OF 631 00:22:20,835 --> 00:22:22,437 THE STUFF THAT PEOPLE HAVE DONE 632 00:22:22,437 --> 00:22:24,706 IN MICE SHOWING THE OPTIMAL TIME 633 00:22:24,706 --> 00:22:29,010 POINT FOR TISSUE COLLECTION, 634 00:22:29,010 --> 00:22:30,311 OPTIMIZING THE ASSAYS FOR 635 00:22:30,311 --> 00:22:31,746 MEASURING T-CELL RESPONSES IN 636 00:22:31,746 --> 00:22:36,017 BOTH THE SPREEN, DRAINING LYMPH 637 00:22:36,017 --> 00:22:36,851 NODE AS WELL AS IN HERE. 638 00:22:36,851 --> 00:22:43,124 I'M SHOW SHOWING YOU T-CELL RES 639 00:22:43,124 --> 00:22:45,159 THROUGH -- USING EX VIVO 640 00:22:45,159 --> 00:22:49,263 DEPREETDEPLETION ASSAYS, FOLLOWG 641 00:22:49,263 --> 00:22:51,532 IMMUNIZATION, TAKE THE TISSUES, 642 00:22:51,532 --> 00:22:53,601 THE SPLEEN, DRAINING LYMPH NODE 643 00:22:53,601 --> 00:22:56,671 OR EVEN THE LUNGS, SHOWING THAT 644 00:22:56,671 --> 00:22:59,841 IN THIS PARTICULAR SITUATION 645 00:22:59,841 --> 00:23:01,576 FOLLOWING PROTEIN-BASED 646 00:23:01,576 --> 00:23:03,111 NANOPARTICLE VACCINE THAT THE 647 00:23:03,111 --> 00:23:05,446 T-CELL RESPONSE IS PREDOMINANTLY 648 00:23:05,446 --> 00:23:06,080 CD4 MEDIATED. 649 00:23:06,080 --> 00:23:08,282 SO IF YOU DEPLETE THE CD4s, 650 00:23:08,282 --> 00:23:09,817 YOU HAVE A TENFOLD REDUCTION IN 651 00:23:09,817 --> 00:23:12,086 THE AMOUNT OF SPOTS DETECTED 652 00:23:12,086 --> 00:23:14,589 WHEREAS IF YOU DEPLETE THE 653 00:23:14,589 --> 00:23:16,324 CD8s, YOU DON'T REALLY GET ANY 654 00:23:16,324 --> 00:23:16,624 DIFFERENCE. 655 00:23:16,624 --> 00:23:19,627 SO BEFORE I OPEN THE FLOOR TO 656 00:23:19,627 --> 00:23:21,262 QUESTIONS, BUT THERE'S STILL 657 00:23:21,262 --> 00:23:22,397 MANY NEEDS FOR THE HAMSTER 658 00:23:22,397 --> 00:23:22,830 MODELS. 659 00:23:22,830 --> 00:23:24,532 SO WE NEED MORE VALIDATED 660 00:23:24,532 --> 00:23:24,866 REAGENTS. 661 00:23:24,866 --> 00:23:26,634 I WANT TO EMPHASIZE THE 662 00:23:26,634 --> 00:23:27,402 VALIDATED PART. 663 00:23:27,402 --> 00:23:29,504 AND THIS NEEDS TO BE VALIDATED 664 00:23:29,504 --> 00:23:33,508 IN MANY WAYS, PREFERABLY USING 665 00:23:33,508 --> 00:23:34,509 MASS SPECTROMETRY SHOWING 666 00:23:34,509 --> 00:23:35,810 WHATEVER YOU PULL DOWN OR WHAT 667 00:23:35,810 --> 00:23:37,211 THE ANTIBODY DETECTS IS REALLY 668 00:23:37,211 --> 00:23:41,082 WHAT YOU WANT IT TO BE, AND NOT 669 00:23:41,082 --> 00:23:41,649 CROSS-REACTIVE TO SOMETHING 670 00:23:41,649 --> 00:23:42,450 ELSE. 671 00:23:42,450 --> 00:23:44,585 AND THIS IS IN MY CASE REALLY 672 00:23:44,585 --> 00:23:51,225 IMPORTANT FOR FLOW CYTOMETRY, 673 00:23:51,225 --> 00:23:56,297 B220, CD19, IFN GAMMA, CD103, ET 674 00:23:56,297 --> 00:23:57,732 CETERA. 675 00:23:57,732 --> 00:24:02,170 IN MY LAB, IDENTIFYING MHC CLASS 676 00:24:02,170 --> 00:24:04,472 I AND II ALLELES AND DISCOVER 677 00:24:04,472 --> 00:24:07,275 ROW OF T-CELL EPITOPES, ALLOWING 678 00:24:07,275 --> 00:24:14,682 US TO DEVELOP TRE MA TETRAMERS. 679 00:24:14,682 --> 00:24:18,019 WE WANT TO KNOW MORE ABOUT B 680 00:24:18,019 --> 00:24:20,021 CELL AND T-CELL UTILIZATION. 681 00:24:20,021 --> 00:24:22,857 I THINK THIS IS ANOTHER EXCITING 682 00:24:22,857 --> 00:24:29,997 AREA OF RESEARCH, THE DWARF 683 00:24:29,997 --> 00:24:32,467 HAMSTER, WHICH CONTINUES TO BE 684 00:24:32,467 --> 00:24:34,001 MORE SUSCEPTIBLE TO EVEN THE 685 00:24:34,001 --> 00:24:36,304 CURRENT VARIANCE OF SARS-COV-2, 686 00:24:36,304 --> 00:24:38,606 I THINK WE NEED TO NOT LOSE 687 00:24:38,606 --> 00:24:40,141 SIGHT OF THE DEVELOPMENT OF 688 00:24:40,141 --> 00:24:42,009 TOOLS AND AGENTS FOR THIS. 689 00:24:42,009 --> 00:24:43,744 SO WITH THAT I'D LIKE TO THANK A 690 00:24:43,744 --> 00:24:44,946 LOT OF DIFFERENT PEOPLE AND 691 00:24:44,946 --> 00:24:45,513 FUNDING SOURCES. 692 00:24:45,513 --> 00:24:48,015 SO IN MY LAB, A LOT OF PEOPLE, 693 00:24:48,015 --> 00:24:56,090 SPECIFICALLY TRACI, TAMARAND AND 694 00:24:56,090 --> 00:25:00,828 REED, THE WANG LAB, KLEIN LAB, 695 00:25:00,828 --> 00:25:03,564 ELLEBEDY LAB, DIAMOND LAB. 696 00:25:03,564 --> 00:25:08,636 I WANT TO MAKE A PLUG FOR THE 697 00:25:08,636 --> 00:25:10,438 SAVE COMMUNITY THAT WAS STARTED 698 00:25:10,438 --> 00:25:11,672 VERY EARLY AFTER THE PANDEMIC 699 00:25:11,672 --> 00:25:13,207 AND IT'S BEEN A FANTASTIC 700 00:25:13,207 --> 00:25:14,142 COMMUNITY THAT WAS STARTED VERY 701 00:25:14,142 --> 00:25:16,577 EARLY AFTER THE PANDEMIC, 702 00:25:16,577 --> 00:25:18,246 SHARING DATA, RESOURCES AND 703 00:25:18,246 --> 00:25:19,380 WHATNOT. 704 00:25:19,380 --> 00:25:23,584 SINCE THE START, THIS COMMUNITY 705 00:25:23,584 --> 00:25:24,519 ACTUALLY CONTINUES TO EXIST AND 706 00:25:24,519 --> 00:25:25,853 IF YOU WANT TO KNOW MORE ABOUT 707 00:25:25,853 --> 00:25:28,689 IT, PLEASE REACH OUT TO ME. 708 00:25:28,689 --> 00:25:29,790 WITH THAT, I'LL TAKE ANY 709 00:25:29,790 --> 00:25:33,961 QUESTIONS. 710 00:25:33,961 --> 00:25:37,331 >> YES, LET'S START WITH SOME 711 00:25:37,331 --> 00:25:37,798 QUESTIONS. 712 00:25:37,798 --> 00:25:42,703 >> HI, I REALLY LIKED YOUR TALK. 713 00:25:42,703 --> 00:25:45,439 I ALSO REALLY LIKE YOUR PUSH 714 00:25:45,439 --> 00:25:46,741 FOR -- SPECIFIC REAGENTS. 715 00:25:46,741 --> 00:25:50,611 I THINK WE ALL REALLY PEN FIT BT 716 00:25:50,611 --> 00:25:51,245 FROM THAT. 717 00:25:51,245 --> 00:25:52,213 MY QUESTION IS ABOUT THE 718 00:25:52,213 --> 00:25:53,347 TRANSMISSION OF OMICRON IN THE 719 00:25:53,347 --> 00:25:55,650 HAMSTER MODEL, BECAUSE IT JUST 720 00:25:55,650 --> 00:25:56,851 DOESN'T TRANSMIT THAT WELL IN 721 00:25:56,851 --> 00:25:59,453 HAMSTERS AND IT'S 722 00:25:59,453 --> 00:26:00,054 COUNTERINTUITIVE WHAT WE'RE 723 00:26:00,054 --> 00:26:01,889 SEEING IN A HUMAN POPULATION. 724 00:26:01,889 --> 00:26:03,524 SO WHAT DO YOU THINK THAT MEANS, 725 00:26:03,524 --> 00:26:04,725 HOW MUCH DO YOU THINK THE 726 00:26:04,725 --> 00:26:08,062 HAMSTER MODEL REALLY RE REPRESES 727 00:26:08,062 --> 00:26:12,266 TRANSMISSION IN HUMANS? 728 00:26:12,266 --> 00:26:14,135 >> THAT'S A VERY FAIR POINT. 729 00:26:14,135 --> 00:26:16,037 WE AND OTHERS AS WELL AS YOUR 730 00:26:16,037 --> 00:26:18,406 LAB IS STILL SEEING DIRECT 731 00:26:18,406 --> 00:26:23,077 CONTACT TRANSMISSION SO I THINK 732 00:26:23,077 --> 00:26:24,946 IT IS DOWN TO EFFICIENCY OF 733 00:26:24,946 --> 00:26:26,614 INFECTION. 734 00:26:26,614 --> 00:26:31,419 IF I HAD INFINITE AMOUNT OF 735 00:26:31,419 --> 00:26:33,721 RESOURCES IN THE LAB I WOULD 736 00:26:33,721 --> 00:26:37,992 LOVE TO DO -- TITER DOWN HOW 737 00:26:37,992 --> 00:26:41,262 MUCH VIRUS IS NEEDED TO ZERO 738 00:26:41,262 --> 00:26:42,697 CONVERT AN ANIMAL. 739 00:26:42,697 --> 00:26:44,532 MY PREDICTION IS THAT SOME OF 740 00:26:44,532 --> 00:26:46,300 THE MORE RECENT OMICRON 741 00:26:46,300 --> 00:26:48,402 VARIANTS, THIS NUMBER GOES UP BY 742 00:26:48,402 --> 00:26:49,604 LET'S SAY TENFOLD COMPARED TO 743 00:26:49,604 --> 00:26:51,405 SOME OF THE ORIGINAL SARS-COV-2 744 00:26:51,405 --> 00:26:51,906 VIRUSES. 745 00:26:51,906 --> 00:26:53,207 THIS IS ENOUGH, GIVEN NOW WE 746 00:26:53,207 --> 00:26:54,942 KNOW WHAT THE BOTTLENECK IS, 747 00:26:54,942 --> 00:26:56,844 IT'S SOMEWHERE AROUND 10 TO 20 748 00:26:56,844 --> 00:26:59,013 DIFFERENT PARTICLES IN A 749 00:26:59,013 --> 00:27:00,848 TRANSMISSION SETUP THAT EVEN 750 00:27:00,848 --> 00:27:03,684 THAT TENFOLD INCREASE IN 751 00:27:03,684 --> 00:27:05,019 INFECTIOUSNESS OR INFECTABILITY 752 00:27:05,019 --> 00:27:10,258 FOR LACK OF A BET TERM BETTER TN 753 00:27:10,258 --> 00:27:12,426 THESE OMICRON VARIANTS IN A 754 00:27:12,426 --> 00:27:14,095 HAMSTER MODEL WILL REDUCE 755 00:27:14,095 --> 00:27:14,829 TRANSMISSION EFFICIENCY. 756 00:27:14,829 --> 00:27:18,432 SO I WOULD LOVE FOR SOMEONE TO 757 00:27:18,432 --> 00:27:19,300 DO THAT. 758 00:27:19,300 --> 00:27:20,835 IT COULD ALSO BE THAT THE DONOR 759 00:27:20,835 --> 00:27:22,069 ANIMAL, THERE'S NOT AS MUCH 760 00:27:22,069 --> 00:27:23,437 VIRUS IN THE UPPER AIRWAYS OF 761 00:27:23,437 --> 00:27:26,107 THE DONOR ANIMAL. 762 00:27:26,107 --> 00:27:29,310 MAYBE THERE'S A CHANGE IN HOST 763 00:27:29,310 --> 00:27:30,211 RESPONSE, CREATING DIFFERENT 764 00:27:30,211 --> 00:27:30,945 PARTICLE SIZES. 765 00:27:30,945 --> 00:27:32,813 SO IT COULD BE A MULTITUDE OF 766 00:27:32,813 --> 00:27:34,515 THINGS BUT I THINK IT'S AN 767 00:27:34,515 --> 00:27:35,082 IMPORTANT QUESTION. 768 00:27:35,082 --> 00:27:36,517 NOT TO LOSE SIGHT OF THE FACT 769 00:27:36,517 --> 00:27:38,386 THAT THE HAMSTER IS STILL NOT AN 770 00:27:38,386 --> 00:27:39,987 EXACT REPLICA OF THE HUMAN FOR 771 00:27:39,987 --> 00:27:44,058 SURE. 772 00:27:44,058 --> 00:27:45,393 STEPHANIE. 773 00:27:45,393 --> 00:27:46,594 >> HI. 774 00:27:46,594 --> 00:27:47,228 YES, GOOD MORNING. 775 00:27:47,228 --> 00:27:48,195 REALLY GREAT TALK. 776 00:27:48,195 --> 00:27:50,064 I LOVE THE ELISPOT DEVELOPMENT. 777 00:27:50,064 --> 00:27:51,299 THAT'S GOING TO BE REALLY 778 00:27:51,299 --> 00:27:52,300 HELPFUL FOR THE FIELD. 779 00:27:52,300 --> 00:27:54,802 I'M CURIOUS, YOUR FEMALE HAMSTER 780 00:27:54,802 --> 00:27:56,637 STUDIES, WERE THOSE ONLY SINGLY 781 00:27:56,637 --> 00:27:57,204 HOUSED? 782 00:27:57,204 --> 00:27:59,040 HAVE YOU GROUP-HOUSED FEMALES 783 00:27:59,040 --> 00:28:00,441 AND DO YOU HAVE ANY TIPS AND 784 00:28:00,441 --> 00:28:02,543 TRICKS BECAUSE THEY DO GET QUITE 785 00:28:02,543 --> 00:28:05,079 TERRITORIAL. 786 00:28:05,079 --> 00:28:06,580 >> SO NO. 787 00:28:06,580 --> 00:28:10,117 SO ALL -- SO WE WERE VERY 788 00:28:10,117 --> 00:28:11,719 FORTUNATE WITH OUR ANIMAL 789 00:28:11,719 --> 00:28:13,154 STUDIES COMMITTEE IN THAT WE 790 00:28:13,154 --> 00:28:16,791 COULD USE OUR MOUSE CAGING, OUR 791 00:28:16,791 --> 00:28:18,426 MOUSE BIOCONTAINMENT CAGING FOR 792 00:28:18,426 --> 00:28:20,061 ALL OUR HAMSTER STUDIES WITH 793 00:28:20,061 --> 00:28:21,462 SARS-COV-2. 794 00:28:21,462 --> 00:28:22,997 FOR THOSE OF YOU WHO'VE WORKED 795 00:28:22,997 --> 00:28:24,298 WITH THESE CAGED SYSTEMS, 796 00:28:24,298 --> 00:28:25,533 THEY'RE NOT VERY LARGE. 797 00:28:25,533 --> 00:28:29,337 SO WE'VE NEVER DONE GROUP 798 00:28:29,337 --> 00:28:30,438 COMMUNITY TRANSMISSION. 799 00:28:30,438 --> 00:28:32,506 WE ONLY LOOK FROM ONE DONOR 800 00:28:32,506 --> 00:28:35,176 ANIMAL TO ONE CONTACT ANIMAL IN 801 00:28:35,176 --> 00:28:35,876 EVERY SINGLE SITUATION. 802 00:28:35,876 --> 00:28:37,445 SO ALL THE DATA AND ALL THE DATA 803 00:28:37,445 --> 00:28:40,915 POINTS THAT I SHOWED YOU ARE ONE 804 00:28:40,915 --> 00:28:41,782 TO ONE PAIRINGS. 805 00:28:41,782 --> 00:28:43,884 AND THEN FOR THE ONWARDS 806 00:28:43,884 --> 00:28:45,519 TRANSMISSION, FOLLOWING OUR 807 00:28:45,519 --> 00:28:48,723 EIGHT-HOUR EXPO SEU W EXPOSURE,S 808 00:28:48,723 --> 00:28:52,326 SOMEWHERE BETWEEN LET'S SAY THE 809 00:28:52,326 --> 00:28:52,993 SLEEPOVER THAT STACEY WAS 810 00:28:52,993 --> 00:28:54,595 TALKING ABOUT AND MAYBE THE 811 00:28:54,595 --> 00:28:56,797 SHOPPING, THE KROGER EVENT, MORE 812 00:28:56,797 --> 00:28:59,934 OF A NIGHT OUT, I WOULD SAY, IS 813 00:28:59,934 --> 00:29:03,571 THEN USING THAT CONTACT ANIMAL, 814 00:29:03,571 --> 00:29:06,006 PUT IT SEPARATE FOR TWO TO THREE 815 00:29:06,006 --> 00:29:07,608 DAYS, AND THEN USE THAT AGAIN IN 816 00:29:07,608 --> 00:29:16,484 A ONE TO ONE TRANSMISSION SETUP. 817 00:29:16,484 --> 00:29:17,551 >> GREAT, THANK YOU. 818 00:29:17,551 --> 00:29:22,390 >> HI, IT'S SEEMA. 819 00:29:22,390 --> 00:29:23,824 I FIRST HAD A COMMENT AND THEN I 820 00:29:23,824 --> 00:29:24,692 HAD A QUESTION. 821 00:29:24,692 --> 00:29:26,127 MY COMMENT WAS THAT I THINK YOU 822 00:29:26,127 --> 00:29:27,294 MAYBE MISSPOKE A LITTLE BIT AND 823 00:29:27,294 --> 00:29:29,397 I'M JUST GOING TO CORRECT YOU A 824 00:29:29,397 --> 00:29:31,365 SMIDGE IN THAT YOU SAID THAT IT 825 00:29:31,365 --> 00:29:33,467 WAS A NUMBER OF PARTICLES THAT 826 00:29:33,467 --> 00:29:35,202 INITIATED AN INFECTIOUS BASED ON 827 00:29:35,202 --> 00:29:37,238 YOUR BARCODE DATA, AND THAT'S 828 00:29:37,238 --> 00:29:39,039 ACTUALLY NOT RIGHT. 829 00:29:39,039 --> 00:29:40,541 THE WAY TO INTERPRET THAT IS 830 00:29:40,541 --> 00:29:42,376 IT'S THE NUMBER OF UNIQUE 831 00:29:42,376 --> 00:29:44,412 GENOTYPES THAT INITIATED AN 832 00:29:44,412 --> 00:29:45,813 INFECTION, NOT CORRELATE TO THE 833 00:29:45,813 --> 00:29:46,714 NUMBER OF PARTICLES THAT 834 00:29:46,714 --> 00:29:48,315 ACTUALLY WENT ACROSS. 835 00:29:48,315 --> 00:29:51,285 I THINK THAT'S SOMETHING THAT'S 836 00:29:51,285 --> 00:29:52,386 MISINTERPRETED A LOT, AND I 837 00:29:52,386 --> 00:29:53,587 WANTED TO SORT OF LIKE CALL THAT 838 00:29:53,587 --> 00:29:55,222 OUT BECAUSE I THINK WE SORT OF 839 00:29:55,222 --> 00:29:57,892 AS WE DO THESE SORT OF 840 00:29:57,892 --> 00:29:58,726 BOTTLENECK EXPERIMENTS, IT'S 841 00:29:58,726 --> 00:30:00,461 REALLY IMPORTANT TO MAKE THAT 842 00:30:00,461 --> 00:30:02,329 CLEAR. 843 00:30:02,329 --> 00:30:04,732 AND MY -- SO MY QUESTION WAS 844 00:30:04,732 --> 00:30:06,700 THEN ABOUT EXPULSION IN YOUR 845 00:30:06,700 --> 00:30:07,034 SYSTEM. 846 00:30:07,034 --> 00:30:09,770 SO OBVIOUSLY CLOSE CONTACT 847 00:30:09,770 --> 00:30:10,938 TRANSMISSION, ALL MODES OF 848 00:30:10,938 --> 00:30:12,173 TRANSMISSION ARE FEASIBLE, AND 849 00:30:12,173 --> 00:30:14,708 WHAT DO WE KNOW ABOUT THE 850 00:30:14,708 --> 00:30:15,576 AEROSOL DISTRIBUTION THAT'S 851 00:30:15,576 --> 00:30:17,344 EXPELLED FROM HAMSTERS AND WHAT 852 00:30:17,344 --> 00:30:20,981 DO YOU KNOW ABOUT THE DIFFERENT 853 00:30:20,981 --> 00:30:23,217 PERHAPS EXPULSION AMOUNTS FROM 854 00:30:23,217 --> 00:30:24,418 HAMSTERS INFECTED WITH 855 00:30:24,418 --> 00:30:26,854 SARS-COV-2 VARIANTS? 856 00:30:26,854 --> 00:30:28,155 >> THOSE ARE -- THANK YOU, 857 00:30:28,155 --> 00:30:28,689 SEEMA. 858 00:30:28,689 --> 00:30:30,257 THOSE ARE EXCELLENT QUESTIONS 859 00:30:30,257 --> 00:30:31,592 AND YEAH, THANKS FOR CORRECTING 860 00:30:31,592 --> 00:30:32,860 ME ON THAT. 861 00:30:32,860 --> 00:30:36,497 SO IT'S TRUE, THIS IS GENOTYPES 862 00:30:36,497 --> 00:30:37,598 DETECTED. 863 00:30:37,598 --> 00:30:42,036 I MUST SAY THAT I THINK THERE 864 00:30:42,036 --> 00:30:43,571 WILL BE DIFFERENCES BETWEEN THE 865 00:30:43,571 --> 00:30:44,772 INFLUENZA SYSTEM AND THE 866 00:30:44,772 --> 00:30:46,974 SARS-COV-2 SYSTEM. 867 00:30:46,974 --> 00:30:49,076 THAT I THINK THE VARIOUS LABS 868 00:30:49,076 --> 00:30:51,679 WILL HAVE TO FIGURE OUT. 869 00:30:51,679 --> 00:30:52,880 GIVEN THE SENSITIVITY OF THE 870 00:30:52,880 --> 00:30:54,815 HAMSTER TO SARS-COV-2 AND THE 871 00:30:54,815 --> 00:30:56,717 FACT THAT IT'S NOT A SEGMENTED 872 00:30:56,717 --> 00:31:00,254 VIRUS, I DO THINK THE RATIO OF 873 00:31:00,254 --> 00:31:04,391 TRANSMITTED AND INFECTION IS 874 00:31:04,391 --> 00:31:06,393 CLOSER TO WHATEVER ONE TO ONE IT 875 00:31:06,393 --> 00:31:09,063 IS THAN FOR INFLUENZA VIRUS, BUT 876 00:31:09,063 --> 00:31:10,865 YOU'RE RIGHT, I SHOULD REFER TO 877 00:31:10,865 --> 00:31:13,334 IT AS GENOTYPES. 878 00:31:13,334 --> 00:31:15,069 IN TERMS OF THE PARTICLE SIZE, 879 00:31:15,069 --> 00:31:16,504 THIS IS SOMETHING THAT I'M 880 00:31:16,504 --> 00:31:18,906 INTERESTED IN BUT I WILL REFER 881 00:31:18,906 --> 00:31:26,580 YOU TO WORK FROM WAYLAND YEN 882 00:31:26,580 --> 00:31:32,386 WHO'S DONE REALLY INTERESTING 883 00:31:32,386 --> 00:31:36,423 WORK, SHE MEASURED FROM HER LAB 884 00:31:36,423 --> 00:31:38,926 INFECTED -- DIFFERENT SIZES HOW 885 00:31:38,926 --> 00:31:40,427 IT IS ASSOCIATED WITH RNA VIRAL 886 00:31:40,427 --> 00:31:40,794 LOAD. 887 00:31:40,794 --> 00:31:45,733 THEN SHE USED HER IMPACTER THAT 888 00:31:45,733 --> 00:31:47,368 ALLOWS PARTICLES OF DIFFERENT 889 00:31:47,368 --> 00:31:50,271 SIZES TO PASS THROUGH FROM THE 890 00:31:50,271 --> 00:31:52,139 DONOR TO THE RECIPIENT ANIMAL, 891 00:31:52,139 --> 00:31:55,676 AND SHE SHOWED THAT FOR SARS 892 00:31:55,676 --> 00:31:58,812 KROSARS-COV-2, YOU NEED LARGER 893 00:31:58,812 --> 00:32:02,850 PARTICLE SIZES, WHEREAS YOU GET 894 00:32:02,850 --> 00:32:04,118 SMALLER BOTTLENECK WITH SMALLER 895 00:32:04,118 --> 00:32:06,387 PARTICLES AND IF YOU LOWER THE 896 00:32:06,387 --> 00:32:08,589 PARTICLE SIZE BEYOND THE CERTAIN 897 00:32:08,589 --> 00:32:10,257 SET POINT, THERE'S ACTUALLY NO 898 00:32:10,257 --> 00:32:17,765 TRANSMISSION DETECTED. 899 00:32:17,765 --> 00:32:18,299 >> GREAT TALK. 900 00:32:18,299 --> 00:32:19,099 THANK YOU SO MUCH. 901 00:32:19,099 --> 00:32:21,001 I HAVE A COMMENT AND A QUESTION 902 00:32:21,001 --> 00:32:23,404 AS WELL. 903 00:32:23,404 --> 00:32:25,406 THE FIRST ONE IS SHARING 904 00:32:25,406 --> 00:32:26,273 INFORMATION ABOUT THE HOUSING 905 00:32:26,273 --> 00:32:27,308 WHICH WAS A QUESTION THAT CAME 906 00:32:27,308 --> 00:32:30,010 UP YESTERDAY. 907 00:32:30,010 --> 00:32:32,212 OUR EXPERIENCE HANDLING HAMSTERS 908 00:32:32,212 --> 00:32:35,382 AND HOUSING THEM SOCIALLY, 909 00:32:35,382 --> 00:32:36,917 MALE/FEMALE, DID NOT HAVE ANY 910 00:32:36,917 --> 00:32:37,384 ISSUE. 911 00:32:37,384 --> 00:32:39,853 I WOULD SAY IT'S ALSO SOMETIMES 912 00:32:39,853 --> 00:32:42,156 DEPENDENT ON THE VENDOR. 913 00:32:42,156 --> 00:32:43,958 THE ONLY ONE ISSUE WE HAD WAS 914 00:32:43,958 --> 00:32:45,125 WITH MALES. 915 00:32:45,125 --> 00:32:48,329 WE JUST SWITCHED THE VENDOR AND 916 00:32:48,329 --> 00:32:49,296 IT WAS NEVER AN ISSUE FOR THE 917 00:32:49,296 --> 00:32:50,698 PAST FOUR YEARS. 918 00:32:50,698 --> 00:32:53,534 AND THE OTHER QUESTION IS BASED 919 00:32:53,534 --> 00:32:55,536 ON ANTIVIRALS AND HAMSTERS, AND 920 00:32:55,536 --> 00:32:57,938 YOU BRIEFLY MENTIONED ABOUT IT. 921 00:32:57,938 --> 00:32:59,673 WITH ALL THE STUDIES WE HAVE 922 00:32:59,673 --> 00:33:01,976 DONE, IT SEEMS TO BE 923 00:33:01,976 --> 00:33:02,977 CHALLENGING, SO I KNOW YOU 924 00:33:02,977 --> 00:33:04,478 MENTIONED THAT MORE WORK IS 925 00:33:04,478 --> 00:33:05,779 IMPORTANT SO WHAT ARE YOUR 926 00:33:05,779 --> 00:33:06,814 THOUGHTS ON THAT? 927 00:33:06,814 --> 00:33:10,284 IS IT THE TYPICAL CLASS OF THE 928 00:33:10,284 --> 00:33:11,852 SMALL MOLECULES ANTIVIRALS OR 929 00:33:11,852 --> 00:33:15,956 IT'S JUST THE SYSTEM METABOLISM 930 00:33:15,956 --> 00:33:16,757 IN HAMSTERS? 931 00:33:16,757 --> 00:33:19,126 THANK YOU SO MUCH. 932 00:33:19,126 --> 00:33:20,327 >> YEAH, I DON'T HAVE ANY 933 00:33:20,327 --> 00:33:22,029 FURTHER COMMENTS ON THE FIRST 934 00:33:22,029 --> 00:33:25,633 ONE ABOUT SOCIAL BEHAVIOR. 935 00:33:25,633 --> 00:33:28,569 WE TRI TRY TO SINGLE-HOUSE THEM 936 00:33:28,569 --> 00:33:29,637 WHENEVER POSSIBLE. 937 00:33:29,637 --> 00:33:31,138 SIZE AND AGE MAKES A HUGE 938 00:33:31,138 --> 00:33:33,907 DIFFERENCE, SO IF YOU PUT A 939 00:33:33,907 --> 00:33:36,210 6 MONTH OLD MALE WITH A 6 WEEK 940 00:33:36,210 --> 00:33:38,178 OLD MALE, ONE WILL LOSE AND YOU 941 00:33:38,178 --> 00:33:39,546 CAN GUESS WHICH ONE. 942 00:33:39,546 --> 00:33:42,449 AND IT WILL KILL IT, IN FACT. 943 00:33:42,449 --> 00:33:44,084 SO THERE ARE -- YOU'VE GOT TO BE 944 00:33:44,084 --> 00:33:48,022 CAREFUL AND I THINK SAME WITH 945 00:33:48,022 --> 00:33:49,023 FERRETS, I'VE NEVER WORKED WITH 946 00:33:49,023 --> 00:33:50,991 THEM BUT I'VE HEARD THAT IF YOU 947 00:33:50,991 --> 00:33:52,626 WORK WITH THEM A LOT, YOU HANDLE 948 00:33:52,626 --> 00:33:54,495 THEM A LOT, THEY ARE ACTUALLY 949 00:33:54,495 --> 00:33:56,897 MUCH MORE -- MUCH KINDER THAN IF 950 00:33:56,897 --> 00:33:57,998 YOU JUST GET THEM STRAIGHT FROM 951 00:33:57,998 --> 00:34:01,035 THE VENDOR AND THEY'RE NOT -- 952 00:34:01,035 --> 00:34:03,270 THEY'RE NEVER HANDLE PERSONALLY. 953 00:34:03,270 --> 00:34:04,872 SO I SUSPECT THAT HAMSTERS MAY 954 00:34:04,872 --> 00:34:07,808 HAVE A SIMILAR BEHAVIOR THERE. 955 00:34:07,808 --> 00:34:10,010 IN TERMS OF ANTIVIRAL MOLECULES 956 00:34:10,010 --> 00:34:11,645 AND SMALL MOLECULES, THIS IS NOT 957 00:34:11,645 --> 00:34:13,847 MY AREA OF EXPERTISE AT ALL. 958 00:34:13,847 --> 00:34:15,382 IT COULD BE METABOLISM, THERE 959 00:34:15,382 --> 00:34:17,618 COULD BE SOMETHING ELSE GOING 960 00:34:17,618 --> 00:34:20,821 ON, BUT I HOPE SOMEONE WILL 961 00:34:20,821 --> 00:34:25,759 INVESTIGATE THIS MORE, PERHAPS 962 00:34:25,759 --> 00:34:31,765 VODEVELOP AKNOCKOUT MOUSE, KNOCR 963 00:34:31,765 --> 00:34:32,966 TO DEVELOP ONE OF THE PUMPS FOR 964 00:34:32,966 --> 00:34:35,035 EXAMPLE OR BREAKDOWN MOLECULES 965 00:34:35,035 --> 00:34:40,641 THI WWHICH WAS DONE FOR MICE AS, 966 00:34:40,641 --> 00:34:43,510 BUT CERTAINLY IT'S IMPORTANT. 967 00:34:43,510 --> 00:34:47,414 >> JUST A COMMENT ON THE 968 00:34:47,414 --> 00:34:48,348 BEHAVIOR OF HAMSTERS. 969 00:34:48,348 --> 00:34:53,153 IN THE PAST 10 YEARS, WE USUALLY 970 00:34:53,153 --> 00:34:54,421 PRODUCED MORE THAN SEVERAL 971 00:34:54,421 --> 00:34:59,460 THOUSAND OF HAMSTERS AND THIS -- 972 00:34:59,460 --> 00:35:01,161 BEHAVIOR, WE OBSERVED THEM. 973 00:35:01,161 --> 00:35:05,399 THEY ARE VERY FRIENDLIMENT I FR. 974 00:35:05,399 --> 00:35:07,434 I HAVE BEEN WORKING WITH A 975 00:35:07,434 --> 00:35:09,002 SOCIAL BEHAVIORAL SCIENTIST. 976 00:35:09,002 --> 00:35:10,204 IN ORDER TO ENCOURAGE THE FEMALE 977 00:35:10,204 --> 00:35:12,506 TO BE MORE AGGRESSIVE, THEY HAVE 978 00:35:12,506 --> 00:35:15,209 TO TEMPORARILY SEPARATE THEM FOR 979 00:35:15,209 --> 00:35:16,210 A WHILE. 980 00:35:16,210 --> 00:35:19,713 IF THEY ARE TOGETHER, YOU KEEP 981 00:35:19,713 --> 00:35:20,881 THEM, I KEEP THEM FOR MONTHS, 982 00:35:20,881 --> 00:35:22,316 THEY ARE VERY FRIENDLY, THEY 983 00:35:22,316 --> 00:35:23,550 HUDDLE WITH EACH OTHER. 984 00:35:23,550 --> 00:35:25,819 SO I DON'T THINK THAT THE 985 00:35:25,819 --> 00:35:29,656 FIGHTING IS A BIG ISSUE. 986 00:35:29,656 --> 00:35:30,090 >> OKAY. 987 00:35:30,090 --> 00:35:34,261 THANK YOU. 988 00:35:34,261 --> 00:35:34,928 , JACCO, THANK YOU SO 989 00:35:34,928 --> 00:35:36,330 MUCH FOR JOINING US EVEN 990 00:35:36,330 --> 00:35:36,697 REMOTELY. 991 00:35:36,697 --> 00:35:41,201 [APPLAUSE] 992 00:35:41,201 --> 00:35:43,871 I'D LIKE TO INVITE DIEGO DIEL 993 00:35:43,871 --> 00:35:44,705 FROM CORNELL UNIVERSITY TO THE 994 00:35:44,705 --> 00:35:46,340 PODIUM. 995 00:35:46,340 --> 00:35:48,642 TO GIVE HIS TALK ENTITLED "THE 996 00:35:48,642 --> 00:35:54,648 FERRET AND FELINE MODELS OF SARS 997 00:35:54,648 --> 00:35:57,384 SARS-COV-2 INFECTION AND 998 00:35:57,384 --> 00:35:57,718 PATHOGENESIS. 999 00:35:57,718 --> 00:35:58,018 THANK YOU. 1000 00:35:58,018 --> 00:35:59,820 >> THANK YOU, SABRA, FOR THE 1001 00:35:59,820 --> 00:36:01,321 INTRODUCTION AND THANKS, 1002 00:36:01,321 --> 00:36:01,889 MICHELLE AND STEVEN FOR THE 1003 00:36:01,889 --> 00:36:05,425 OPPORTUNITY TO BE HERE TO TALK A 1004 00:36:05,425 --> 00:36:06,927 LITTLE BIT ABOUT THE WORK WE 1005 00:36:06,927 --> 00:36:09,663 HAVE BEEN DOING ON MODELS THAT 1006 00:36:09,663 --> 00:36:13,167 ARE NOT AS TRADITIONAL MODELS OF 1007 00:36:13,167 --> 00:36:13,967 SARS-COV-2 INFECTION AND 1008 00:36:13,967 --> 00:36:16,436 PATHOGENIC. 1009 00:36:16,436 --> 00:36:17,738 SO JUST A BRIEF OUTLINE OF THE 1010 00:36:17,738 --> 00:36:18,739 TALK. 1011 00:36:18,739 --> 00:36:20,707 I'M GOING TO GIVE A BRIEF 1012 00:36:20,707 --> 00:36:21,942 BACKGROUND AND THEN WE'LL TALK A 1013 00:36:21,942 --> 00:36:23,110 LITTLE BIT ABOUT THE WORK THAT 1014 00:36:23,110 --> 00:36:26,947 WE HAVE DONE ON FERRET MODEL 1015 00:36:26,947 --> 00:36:29,449 INCLUDING STUDIES ON AGE-RELATED 1016 00:36:29,449 --> 00:36:32,853 SUSCEPTIBILITY TO SARS-COV-2 AND 1017 00:36:32,853 --> 00:36:36,256 THEN COMPARATIVE PATHOGENESIS OF 1018 00:36:36,256 --> 00:36:38,559 A FEW SARS-COV-2 COV-2 VARIANTS 1019 00:36:38,559 --> 00:36:40,194 ON THAT MODEL, AND THEN WE'LL 1020 00:36:40,194 --> 00:36:42,763 TALK MORE ON THE FELINE MODEL ON 1021 00:36:42,763 --> 00:36:45,032 COMPARATIVE PATHOGENESIS OF VAIR 1022 00:36:45,032 --> 00:36:46,800 YENTS, CHARACTERIZATION OF 1023 00:36:46,800 --> 00:36:48,335 VIRULENCE AND VIRUS-HOST 1024 00:36:48,335 --> 00:36:49,870 INTERACTIONS WITH FOCUS ON THE 1025 00:36:49,870 --> 00:36:55,609 ROLE OF SPIKE ON PATHOGENESIS 1026 00:36:55,609 --> 00:36:56,410 AND R3A. 1027 00:36:56,410 --> 00:37:01,148 SO MY LAB ESTABLISHED A PIPELINE 1028 00:37:01,148 --> 00:37:05,085 FOR STUDYING THE EVOLUTION OR 1029 00:37:05,085 --> 00:37:10,824 THE PHENOTYPES, GENOTYPE TO 1030 00:37:10,824 --> 00:37:11,792 PHENOTYPE ON SARS-COV-2. 1031 00:37:11,792 --> 00:37:17,130 I LED THE CORNELL TESTING LAB, 1032 00:37:17,130 --> 00:37:18,365 ESTABLISHMENT OF THAT COVID 1033 00:37:18,365 --> 00:37:20,868 TESTING LAB THE A CORNELL AND 1034 00:37:20,868 --> 00:37:22,302 OVER THE PANDEMIC, WE WERE ABLE 1035 00:37:22,302 --> 00:37:25,305 TO TEST OVER 2.1 MILLION 1036 00:37:25,305 --> 00:37:27,007 SAMPLES, SO THAT PROVIDED A 1037 00:37:27,007 --> 00:37:31,078 PERFECT PIPELINE OF SAMPLES AND 1038 00:37:31,078 --> 00:37:32,279 ISOLATES THAT WE LEMPLED TO 1039 00:37:32,279 --> 00:37:35,449 ACTUALLY STUDY SOME OF THE 1040 00:37:35,449 --> 00:37:36,683 DIFFERENCES BETWEEN THE VIRUSES. 1041 00:37:36,683 --> 00:37:38,185 SO OVER THE COURSE OF THE 1042 00:37:38,185 --> 00:37:40,587 PANDEMIC, WE SEQUENCED OVER 3500 1043 00:37:40,587 --> 00:37:44,625 SAMPLES AND OBTAINED CLOSE TO A 1044 00:37:44,625 --> 00:37:49,396 THOUSAND ISOLATES OF THE VIRUS. 1045 00:37:49,396 --> 00:37:53,267 THE GOAL OF THAT PIPELINE WAS 1046 00:37:53,267 --> 00:37:56,336 REALLY TO LOOK AT THOSE VIRUSES, 1047 00:37:56,336 --> 00:37:57,404 CHARACTERIZE THEM IN VITRO AND 1048 00:37:57,404 --> 00:38:00,040 THEN ASSESS THEIR PATHOGENESIS 1049 00:38:00,040 --> 00:38:05,078 IN ANIMAL MODELS. 1050 00:38:05,078 --> 00:38:06,847 WE REALLY TRIED TO FOCUS OUR 1051 00:38:06,847 --> 00:38:09,149 ANIMAL MODEL WORK ON SPECIES 1052 00:38:09,149 --> 00:38:11,151 THAT WERE NATURALLY SUSCEPTIBLE 1053 00:38:11,151 --> 00:38:13,453 TO THE VIRUS AND WE ALL KNOW 1054 00:38:13,453 --> 00:38:15,756 THAT THE INTERACTION BETWEEN THE 1055 00:38:15,756 --> 00:38:19,026 SPIKE OF THE VIRUS WITH THE 1056 00:38:19,026 --> 00:38:21,528 RECEPTOR, IT A KEY DETERMINANT 1057 00:38:21,528 --> 00:38:24,598 OF THE TROPISM AND HOST RANGE OF 1058 00:38:24,598 --> 00:38:25,165 THIS VIRUS. 1059 00:38:25,165 --> 00:38:28,235 SO AGAIN, OUR FOCUS WAS ON 1060 00:38:28,235 --> 00:38:29,703 IDENTIFYING AND WORKING SPECIES 1061 00:38:29,703 --> 00:38:31,405 THAT WERE NATURALLY SUSCEPTIBLE 1062 00:38:31,405 --> 00:38:33,907 TO THE VIRUS. 1063 00:38:33,907 --> 00:38:35,242 INITIALLY, WE LOOKED AT THE 1064 00:38:35,242 --> 00:38:37,978 LITERATURE TO SEE WHAT WAS KNOWN 1065 00:38:37,978 --> 00:38:40,647 ABOUT U. SUSCEPTIBILITY OF THESE 1066 00:38:40,647 --> 00:38:42,115 ANIMALS TO CORONAVIRUS, AND 1067 00:38:42,115 --> 00:38:44,718 THERE WAS A PAPER PUBLISHED IN 1068 00:38:44,718 --> 00:38:47,721 2008 THAT ACTUALLY CHARACTERIZED 1069 00:38:47,721 --> 00:38:48,822 THE SUSCEPTIBILITY OF BOTH 1070 00:38:48,822 --> 00:38:52,459 FERRET AND CATS TO SARS 1, AND 1071 00:38:52,459 --> 00:38:55,662 THEY KE DEMONSTRATED REPLICATIOF 1072 00:38:55,662 --> 00:38:57,931 THE VIRUS IN THE LUNG. 1073 00:38:57,931 --> 00:39:00,467 FERRETS IN THE UPPER AND LOWER 1074 00:39:00,467 --> 00:39:02,035 RESPIRATORY TRACT OF CATS, THEY 1075 00:39:02,035 --> 00:39:03,236 ALSO CHARACTERIZE EXPRESSION OF 1076 00:39:03,236 --> 00:39:05,372 THE ACE 2 RECEPTOR THROUGHOUT 1077 00:39:05,372 --> 00:39:10,177 THE RESPIRATORY TRACT. 1078 00:39:10,177 --> 00:39:11,845 AND THE DISTRIBUTION OF ACE 1079 00:39:11,845 --> 00:39:13,280 2 EXPRESSION IN THOSE SPECIES IS 1080 00:39:13,280 --> 00:39:16,016 VERY SIMILAR TO THAT WHAT IS 1081 00:39:16,016 --> 00:39:17,250 FOUND IN HUMANS. 1082 00:39:17,250 --> 00:39:19,853 THERE'S A MORE RECENT PAPER THAT 1083 00:39:19,853 --> 00:39:22,389 PUBLISHED AND DEMONSTRATED 1084 00:39:22,389 --> 00:39:23,457 EXPRESSION ALSO IN THE 1085 00:39:23,457 --> 00:39:25,359 RESPIRATORY MUCOSA AND THE 1086 00:39:25,359 --> 00:39:28,395 OLFACTORY MUCOSA OF BOTH 1087 00:39:28,395 --> 00:39:28,929 SPECIES. 1088 00:39:28,929 --> 00:39:30,397 SO VERY SIMILAR ACE DISTRIBUTION 1089 00:39:30,397 --> 00:39:33,000 TO THAT WHAT IS FOUND IN HUMANS. 1090 00:39:33,000 --> 00:39:34,334 THE OTHER ASPECT THAT WE LOOKED 1091 00:39:34,334 --> 00:39:43,610 AT IS THE PRECE THE RECEPTOR DIS 1092 00:39:43,610 --> 00:39:44,011 HIGHLIGHTED HERE. 1093 00:39:44,011 --> 00:39:51,651 WHEN COMPARED TO THE HUMAN, TH 1094 00:39:51,651 --> 00:39:54,488 THE -- THE CAT HAS FOUR AMINO 1095 00:39:54,488 --> 00:39:56,723 ACID DIFFERENCES, THE ONES 1096 00:39:56,723 --> 00:39:58,392 HIGHLIGHTED IN YELLOW ARE SHARED 1097 00:39:58,392 --> 00:39:59,593 BY BOTH SPECIES. 1098 00:39:59,593 --> 00:40:01,795 IT'S NOT THE PERFECT MATCH WHEN 1099 00:40:01,795 --> 00:40:04,531 COMPARED TO THE HAMSTER, GOLDEN 1100 00:40:04,531 --> 00:40:06,800 HAMSTER HAS ONLY TWO MUTATION -- 1101 00:40:06,800 --> 00:40:09,169 TWO DIFFERENCES. 1102 00:40:09,169 --> 00:40:09,836 WHEN COMPARED TO 1103 00:40:09,836 --> 00:40:11,338 THE HUMAN. 1104 00:40:11,338 --> 00:40:12,305 SO ONE OF THE FIRST STUDIES THAT 1105 00:40:12,305 --> 00:40:14,574 WE DID WAS TO BASICALLY 1106 00:40:14,574 --> 00:40:17,110 ESTABLISH THE FERRET MODEL IN 1107 00:40:17,110 --> 00:40:18,211 THE LAB. 1108 00:40:18,211 --> 00:40:23,817 WE DID AN INFECTIOUS DOSE STUDY 1109 00:40:23,817 --> 00:40:25,786 AND ALSO COMPARED SUSCEPTIBILITY 1110 00:40:25,786 --> 00:40:27,888 OF TWO DIFFERENT AGE GROUPS OF 1111 00:40:27,888 --> 00:40:28,422 FERRETS. 1112 00:40:28,422 --> 00:40:31,925 WE USED 6 MONTH OLD ANIMALS 1113 00:40:31,925 --> 00:40:34,528 WHICH WE CALLED YOUNG FERRETS 1114 00:40:34,528 --> 00:40:37,964 AND THEN WE ALSO HAD AGED 1115 00:40:37,964 --> 00:40:41,435 ANIMALS THAT WERE BETWEEN 18 AND 1116 00:40:41,435 --> 00:40:44,504 36 MONTHS OF AGE. 1117 00:40:44,504 --> 00:40:46,473 DIVIDED THESE ANIMALS IN FIVE 1118 00:40:46,473 --> 00:40:47,707 GROUPS, CONTROL ANIMALS, AND 1119 00:40:47,707 --> 00:40:50,877 THEN ANIMALS THAT WERE 1120 00:40:50,877 --> 00:40:53,280 INOCULATED WITH DIFFERENT 1121 00:40:53,280 --> 00:40:58,618 INFECTIOUS DOSES FROM 10 TO 1 TO 1122 00:40:58,618 --> 00:40:59,953 10 TO THE 6. 1123 00:40:59,953 --> 00:41:02,189 WE MONITORED THESE ANIMALS BY 1124 00:41:02,189 --> 00:41:03,290 COLLECTING CLINICALLY AND 1125 00:41:03,290 --> 00:41:05,092 COLLECTING SAMPLES FOR 1126 00:41:05,092 --> 00:41:06,560 VIROLOGICAL ASSESSMENTS AS WELL. 1127 00:41:06,560 --> 00:41:11,398 AS SHOWN HERE, WE ONLY DETECTED 1128 00:41:11,398 --> 00:41:12,799 REPLICATION AND SHEDDING OF 1129 00:41:12,799 --> 00:41:16,636 INFECTIOUS VIRUS OF THOSE 10 TO 1130 00:41:16,636 --> 00:41:16,970 THE 2. 1131 00:41:16,970 --> 00:41:19,573 WITH AGED ANIMALS PRESENTING 1132 00:41:19,573 --> 00:41:26,146 SLIGHT LEHIGLY HIGHER REPLICATIN 1133 00:41:26,146 --> 00:41:27,681 THE UPPER RESPIRATORY TRACT, AND 1134 00:41:27,681 --> 00:41:29,082 THAT WAS CONSISTENT THROUGHOUT 1135 00:41:29,082 --> 00:41:31,318 THE DOSES THAT WE USED, AND THAT 1136 00:41:31,318 --> 00:41:36,490 WAS ALSO CONFIRMED BY 1137 00:41:36,490 --> 00:41:37,624 SEROCONVERSION SO ONLY ANIMALS 1138 00:41:37,624 --> 00:41:41,428 THAT WERE INOCULATED TENDED TO 1139 00:41:41,428 --> 00:41:44,331 BE -- HIGHER FREQUENCY OF AGED 1140 00:41:44,331 --> 00:41:46,500 ANIMALS ACTUALLY CONVERTING TO 1141 00:41:46,500 --> 00:41:46,800 INFECTION. 1142 00:41:46,800 --> 00:41:48,335 SO WITH THOSE RESULTS, WE 1143 00:41:48,335 --> 00:41:50,637 DETERMINED THE INFECTIOUS DOSE 1144 00:41:50,637 --> 00:41:52,873 IN BOTH AGE GROUPS. 1145 00:41:52,873 --> 00:41:57,310 AND AS SHOWN HERE, THE YOUNGER 1146 00:41:57,310 --> 00:41:59,846 ANIMALS REQUIRED THREE FOLD 1147 00:41:59,846 --> 00:42:02,415 HIGHER DOSE TO ACTUALLY BECOME 1148 00:42:02,415 --> 00:42:05,085 INFECTED WITH SARS-COV-2. 1149 00:42:05,085 --> 00:42:08,321 THAN THE AGED ANIMALS. 1150 00:42:08,321 --> 00:42:13,426 WE LOOKED AT POTENTIAL CAUSES 1151 00:42:13,426 --> 00:42:14,628 FOR THIS AGE DIFFERENCE AND ONE 1152 00:42:14,628 --> 00:42:17,397 THING THAT WE OBSERVED IN THIS 1153 00:42:17,397 --> 00:42:19,566 STUDY IS THAT AGED ANIMALS 1154 00:42:19,566 --> 00:42:23,203 EXPRESSED USING QPCR, AGED 1155 00:42:23,203 --> 00:42:24,070 ANIMALS EXPRESSED HIGHER LEVELS 1156 00:42:24,070 --> 00:42:28,675 OF ACE 2 AND TMPRSS2 IN THE 1157 00:42:28,675 --> 00:42:29,242 NASAL MUCOSA. 1158 00:42:29,242 --> 00:42:31,511 THERE WERE NO DIFFERENCES IN 1159 00:42:31,511 --> 00:42:32,979 EXPRESSION OF THOSE TWO 1160 00:42:32,979 --> 00:42:34,314 MOLECULES IN THE LUNG. 1161 00:42:34,314 --> 00:42:37,784 SO WE THINK THAT THIS COULD 1162 00:42:37,784 --> 00:42:39,119 POTENTIALLY AT LEAST PARTIALLY 1163 00:42:39,119 --> 00:42:40,120 EXPLAIN THIS AGE DIFFERENCE. 1164 00:42:40,120 --> 00:42:43,156 OBVIOUSLY WE HAVE NOT ASSESSED 1165 00:42:43,156 --> 00:42:44,591 IMMUNOLOGICAL FACTORS THAT ARE 1166 00:42:44,591 --> 00:42:48,328 ALSO LIKELY DIFFERENT BETWEEN 1167 00:42:48,328 --> 00:42:54,067 AGED AND YOUNG FERRETS. 1168 00:42:54,067 --> 00:42:56,336 SO THE NEXT STUDY WE CONDUCTED 1169 00:42:56,336 --> 00:42:58,305 WAS TO COMPARE THE PATHOGENESIS 1170 00:42:58,305 --> 00:43:01,675 OF B1 OR D614G VARIANTS WITH THE 1171 00:43:01,675 --> 00:43:02,943 ALPHA VARIANT AS SOON AS THE 1172 00:43:02,943 --> 00:43:05,245 VARIANT ACTUALLY EMERGED. 1173 00:43:05,245 --> 00:43:06,046 IN THE 1174 00:43:06,046 --> 00:43:08,848 U.S., SO WE DESIGNED AN 1175 00:43:08,848 --> 00:43:10,283 EXPERIMENT WITH THREE GROUPS, 1176 00:43:10,283 --> 00:43:12,719 CONTROL ANIMALS, ANIMALS THAT 1177 00:43:12,719 --> 00:43:14,888 WERE INOCULATED WITH B1 AND THEN 1178 00:43:14,888 --> 00:43:16,223 WITH THE ALPHA VARIANT. 1179 00:43:16,223 --> 00:43:20,293 WE EUTHANIZED ANIMALS O ON DAYS 1180 00:43:20,293 --> 00:43:22,262 3 AND 5 TO MONITOR VIRUS 1181 00:43:22,262 --> 00:43:24,364 REPLICATION AND TISSUES AND 1182 00:43:24,364 --> 00:43:25,932 AGAIN COLLECTED RESPIRATORY 1183 00:43:25,932 --> 00:43:27,867 SAMPLES TO MONITOR VIRUS 1184 00:43:27,867 --> 00:43:29,736 REPLICATION AND SHEDDING. 1185 00:43:29,736 --> 00:43:31,972 WE ALSO MONITORED THESE ANIMALS 1186 00:43:31,972 --> 00:43:33,807 CLINICALLY AND AS YOU CAN SEE 1187 00:43:33,807 --> 00:43:36,209 HERE, WE HAVE NOT OBSERVED ANY 1188 00:43:36,209 --> 00:43:38,445 CLINICAL SIGNS AND I THINK THAT 1189 00:43:38,445 --> 00:43:40,413 THIS IS A FEATURE OF THE FERRET 1190 00:43:40,413 --> 00:43:41,815 MODEL. 1191 00:43:41,815 --> 00:43:43,583 THEY DON'T DEVELOP FEVER, THEY 1192 00:43:43,583 --> 00:43:47,921 ALSO DON'T LOSE WEIGHT AFTER 1193 00:43:47,921 --> 00:43:49,723 INFECTION, SO IT'S A SUBCLINICAL 1194 00:43:49,723 --> 00:43:52,559 INFECTION IN THE FERRET MODEL. 1195 00:43:52,559 --> 00:43:55,629 WE LOOKED AT REPLICATION OF THE 1196 00:43:55,629 --> 00:43:59,532 VIRUS IN THE UPPER RESPIRATORY 1197 00:43:59,532 --> 00:44:01,468 TRACT PCR RESULTS SHOWING ON THE 1198 00:44:01,468 --> 00:44:07,941 LEFT HERE. 1199 00:44:07,941 --> 00:44:10,110 VIRUS TITRATIONS ON THE RIGHT. 1200 00:44:10,110 --> 00:44:11,311 WE DID NOT SEE DIFFERENCES IN 1201 00:44:11,311 --> 00:44:12,646 THE LEVELS OF RNA THAT WE 1202 00:44:12,646 --> 00:44:13,446 DETECTED THROUGHOUT THE COURSE 1203 00:44:13,446 --> 00:44:15,048 OF THE EXPERIMENT. 1204 00:44:15,048 --> 00:44:20,453 THERE WAS A SLI SLIGHTLY HIGHERS 1205 00:44:20,453 --> 00:44:22,422 OF INFECTIOUS VIRUS IN THE NASAL 1206 00:44:22,422 --> 00:44:26,259 SWABS FOR THE D614G VIRUS BUT WE 1207 00:44:26,259 --> 00:44:27,927 HAVE NOT OBSERVED THE SAME 1208 00:44:27,927 --> 00:44:29,729 DIFFERENCE, THIS WAS NOT 1209 00:44:29,729 --> 00:44:31,264 SIGNIFICANT, WE DID NOT OBSERVE 1210 00:44:31,264 --> 00:44:32,866 DIFFERENCES IN VIRUS REPLICATION 1211 00:44:32,866 --> 00:44:34,634 IN THE OROPHARYNGEAL SWABS AS 1212 00:44:34,634 --> 00:44:34,968 WELL. 1213 00:44:34,968 --> 00:44:37,170 WHEN WE LOOKED AT TISSUES, WE 1214 00:44:37,170 --> 00:44:42,842 DID DETECT RNA IN THE UPPER AND 1215 00:44:42,842 --> 00:44:44,377 ALSO LOWER RESPIRATORY TRACT, 1216 00:44:44,377 --> 00:44:47,514 BUT WHEN WE PERFORMED VIRAL 1217 00:44:47,514 --> 00:44:48,581 TITRATIONS TO LOOK FOR 1218 00:44:48,581 --> 00:44:50,550 INFECTIOUS VIRUS, THAT WAS 1219 00:44:50,550 --> 00:44:52,085 BASICALLY RESTRIBTED TO THE 1220 00:44:52,085 --> 00:44:55,822 UPPER RESPIRATORY TRACT WHERE WE 1221 00:44:55,822 --> 00:44:57,691 OBSERVED HIGH LEVELS OF 1222 00:44:57,691 --> 00:44:59,292 REPLICATION IN THE NASAL 1223 00:44:59,292 --> 00:45:01,995 TURBINATES FOR BOTH VIRUSES AND 1224 00:45:01,995 --> 00:45:03,830 IN THE TONSIL WITH NO DETECTION 1225 00:45:03,830 --> 00:45:09,936 OF VIRUS ON DAY 3 OR DAY 5 IN 1226 00:45:09,936 --> 00:45:14,574 THE LOWER RESPIRATORY TRACT. 1227 00:45:14,574 --> 00:45:15,241 ANOTHER INTERESTING OUTCOME OF 1228 00:45:15,241 --> 00:45:17,310 THIS STUDY IS WHEN WE LOOKED AT 1229 00:45:17,310 --> 00:45:21,815 CHANGES IN THE VIRUS FOLLOWING 1230 00:45:21,815 --> 00:45:22,582 INOCULATION, WE OBSERVED THAT 1231 00:45:22,582 --> 00:45:24,351 THE VIRUS ACTUALLY CHANGED VERY 1232 00:45:24,351 --> 00:45:27,187 QUICKLY FOLLOWING INOCULATION OF 1233 00:45:27,187 --> 00:45:30,256 FERRETS AND THOSE CHANGES WERE 1234 00:45:30,256 --> 00:45:33,526 LOCATED IN THE RECEPTOR-BINDING 1235 00:45:33,526 --> 00:45:34,861 DOMAIN OF THIS SPIKE. 1236 00:45:34,861 --> 00:45:36,963 THIS HAS BEEN DESCRIBED BY OTHER 1237 00:45:36,963 --> 00:45:39,699 GROUPS, OUR FINDINGS BASICALLY 1238 00:45:39,699 --> 00:45:42,268 REINFORCED WHAT WAS SEEN, AND 1239 00:45:42,268 --> 00:45:48,041 ONE PARTICULAR MUTATION, THE 1240 00:45:48,041 --> 00:45:50,043 Y453 F MUTATION OCCURRED IN A 1241 00:45:50,043 --> 00:45:53,179 HIGHER FREQUENCY OF ANIMALS AS 1242 00:45:53,179 --> 00:45:55,882 EARLY AS DAY 3 POST INOCULATION. 1243 00:45:55,882 --> 00:45:59,552 SO INDICATING THAT THERE'S A 1244 00:45:59,552 --> 00:46:01,988 PRETTY HIGH PRESSURE ON THE 1245 00:46:01,988 --> 00:46:02,856 RECEPTOR-BINDING DOMAIN, MOST 1246 00:46:02,856 --> 00:46:04,624 LIKELY BECAUSE OF THAT 1247 00:46:04,624 --> 00:46:06,059 INCOMPATIBILITY OF THE SPIKE AND 1248 00:46:06,059 --> 00:46:08,061 THE RECEPTOR. 1249 00:46:08,061 --> 00:46:09,696 RECEPTOR-BINDING THE DOMAIN. 1250 00:46:09,696 --> 00:46:11,664 GIVEN THESE FINDINGS, WE DECIDED 1251 00:46:11,664 --> 00:46:16,169 THAT WE PROBABLY NEEDED A BETTER 1252 00:46:16,169 --> 00:46:18,037 MODEL TO STUDY PATHOGENESIS OF 1253 00:46:18,037 --> 00:46:19,672 SARS-COV-2 THAN THE FERRET 1254 00:46:19,672 --> 00:46:21,741 MODEL. 1255 00:46:21,741 --> 00:46:24,878 BECAUSE WE REALLY WANTED TO 1256 00:46:24,878 --> 00:46:27,180 ASSESS POTENTIAL TRANSMISSION 1257 00:46:27,180 --> 00:46:30,550 AND INFECT -- IDENTIFY VIRULENCE 1258 00:46:30,550 --> 00:46:31,451 DETERMINANTS AND DETERMINE THEIR 1259 00:46:31,451 --> 00:46:32,919 ROLE IN PATHOGENESIS. 1260 00:46:32,919 --> 00:46:35,422 IF THE VIRUS WOULD BE CHANGING 1261 00:46:35,422 --> 00:46:37,824 VERY EARLY ON AFTER INOCULATION 1262 00:46:37,824 --> 00:46:40,126 ON THESE ANIMALS, THAT COULD 1263 00:46:40,126 --> 00:46:43,763 POTENTIALLY MASK AND REALLY 1264 00:46:43,763 --> 00:46:44,497 COMPLICATE INTERPRETATION OF THE 1265 00:46:44,497 --> 00:46:46,599 RESULTS. 1266 00:46:46,599 --> 00:46:50,103 WHEN WE WERE FINISHING OUT THAT 1267 00:46:50,103 --> 00:46:52,972 PATHOGENESIS STUDY, I RECEIVED A 1268 00:46:52,972 --> 00:46:58,011 CASE OF A CAT WITH VERY SEVERE 1269 00:46:58,011 --> 00:46:59,846 SARS-COV-2 INFECTION IN THE 1270 00:46:59,846 --> 00:47:02,382 DIAGNOSTIC LAB AT CORNELL, WHERE 1271 00:47:02,382 --> 00:47:03,716 I AM DIRECTOR OF THE VIROLOGY 1272 00:47:03,716 --> 00:47:03,983 LAB. 1273 00:47:03,983 --> 00:47:05,952 AS YOU CAN SEE HERE, THIS IS THE 1274 00:47:05,952 --> 00:47:07,153 LUNG OF THE CAT REALLY SHOWING 1275 00:47:07,153 --> 00:47:10,990 PRETTY SEVERE COMPROMISE OR 1276 00:47:10,990 --> 00:47:13,827 PNEUMONIA ON THAT LUNG. 1277 00:47:13,827 --> 00:47:16,396 WHEN WE LOOKED AT THE HISTOLOGY 1278 00:47:16,396 --> 00:47:20,400 OF THE LUNG, IT WAS VERY 1279 00:47:20,400 --> 00:47:21,868 CHARACTERISTIC SARS-COV-2 1280 00:47:21,868 --> 00:47:24,671 INFECTION, RESEMBLING THE 1281 00:47:24,671 --> 00:47:26,372 PNEUMONIA THAT IS DESCRIBED IN 1282 00:47:26,372 --> 00:47:30,076 HUMANS WITH A DIFFUSE ALVEOLAR 1283 00:47:30,076 --> 00:47:33,346 DAMAGE, AND INFLAMMATORY 1284 00:47:33,346 --> 00:47:35,448 INFILTRATE, IN THIS CASE, MAINLY 1285 00:47:35,448 --> 00:47:37,083 CHARACTERIZED BY MACROPHAGES. 1286 00:47:37,083 --> 00:47:39,519 WE ALSO OBSERVED VERY ROBUST 1287 00:47:39,519 --> 00:47:41,087 REPLICATION OF THE VIRUS IN THE 1288 00:47:41,087 --> 00:47:45,892 LUNG IN THIS PARTICULAR CASE. 1289 00:47:45,892 --> 00:47:49,696 AS SHOWN HERE BY IN SITU 1290 00:47:49,696 --> 00:47:51,865 HYBRIDIZATION AND 1291 00:47:51,865 --> 00:47:54,868 HISTOCHEMISTRY, MAINLY IN 1292 00:47:54,868 --> 00:47:57,971 BRONCHIOLAR EPITHELIAL CELLS. 1293 00:47:57,971 --> 00:47:59,572 ONE INTERESTING FEATURE ABOUT 1294 00:47:59,572 --> 00:48:00,273 THIS PARTICULAR CAT, THIS CAT 1295 00:48:00,273 --> 00:48:03,343 WAS DIAGNOSED WITH A 1296 00:48:03,343 --> 00:48:09,282 HYPERTROPHIC -- WHICH IS A 1297 00:48:09,282 --> 00:48:12,719 CONDITION THAT HAS BEEN 1298 00:48:12,719 --> 00:48:15,255 DESCRIBED AS -- IN HUMANS 1299 00:48:15,255 --> 00:48:16,723 LEADING TO SEVERE DISEASE. 1300 00:48:16,723 --> 00:48:18,358 AND I THINK THERE'S A FEW OTHER 1301 00:48:18,358 --> 00:48:20,460 CASES IN CATS THAT DIED FROM 1302 00:48:20,460 --> 00:48:21,661 NATURAL INFECTION THAT ALSO 1303 00:48:21,661 --> 00:48:23,963 PRESENTED THE SAME HIRE TROPHIC 1304 00:48:23,963 --> 00:48:24,364 CARDIOMYOPATHY. 1305 00:48:24,364 --> 00:48:26,599 SO WITH THAT, WE DECIDED TO 1306 00:48:26,599 --> 00:48:28,301 INITIATE THE ESTABLISHMENT OF 1307 00:48:28,301 --> 00:48:34,240 THE FELINE MODEL IN THE LAB. 1308 00:48:34,240 --> 00:48:35,241 THE FIRST STUDY WE CONDUCTED WAS 1309 00:48:35,241 --> 00:48:37,644 A COMPARISON BETWEEN THREE 1310 00:48:37,644 --> 00:48:42,048 VARIANTS, D614G DELTA AND 1311 00:48:42,048 --> 00:48:42,615 OMICRON BA1. 1312 00:48:42,615 --> 00:48:45,151 AND IN THESE STUDIES, IN ALL 1313 00:48:45,151 --> 00:48:46,352 PARAMETERS THAT WE EVALUATED 1314 00:48:46,352 --> 00:48:49,956 WHAT WE OBSERVED IS THAT DELTA 1315 00:48:49,956 --> 00:48:53,860 IN D614G BEHAVED VERY SIMILAR 1316 00:48:53,860 --> 00:48:56,796 ALSO AS THE ANIMALS INOCULATED 1317 00:48:56,796 --> 00:48:58,197 WITH THOSE VIRUSES DEVELOPED 1318 00:48:58,197 --> 00:48:59,666 FEVER, THEY ALSO HAD A SLIGHT 1319 00:48:59,666 --> 00:49:01,568 DECREASE IN BODY WEIGHT, THEY 1320 00:49:01,568 --> 00:49:04,938 PRESENTED VERY HIGH VIRUS 1321 00:49:04,938 --> 00:49:06,172 REPLICATION IN THE UPPER 1322 00:49:06,172 --> 00:49:08,575 RESPIRATORY TRACT AND IN THE 1323 00:49:08,575 --> 00:49:10,009 LUNG, AND HIGH LEVELS OF VIRUS 1324 00:49:10,009 --> 00:49:10,910 SHEDDING. 1325 00:49:10,910 --> 00:49:13,646 AND BOTH OF THESE VARIANTS HAVE 1326 00:49:13,646 --> 00:49:16,149 MUCH HIGHER VIRUS REPLICATION 1327 00:49:16,149 --> 00:49:20,453 THAN THE OMICRON BA1 VARIANT. 1328 00:49:20,453 --> 00:49:24,357 THEY ALSO CAUSED MORE SEVERE 1329 00:49:24,357 --> 00:49:27,060 PATHOLOGY AND ALSO HIGHER 1330 00:49:27,060 --> 00:49:30,863 ANTIBODY RESPONSES. 1331 00:49:30,863 --> 00:49:32,298 SO THE QUESTION THAT CAME UP OF 1332 00:49:32,298 --> 00:49:33,433 THIS STUDY IS WHAT WAS THE ROLE 1333 00:49:33,433 --> 00:49:34,801 OF THE SPIKE ON THIS, THE 1334 00:49:34,801 --> 00:49:38,171 OMICRON BA1 HAD AT LEAST 35 1335 00:49:38,171 --> 00:49:39,772 MUTATIONS IN THE SPIKE PROTEIN 1336 00:49:39,772 --> 00:49:45,311 ALONE, SO WE COLLABORATED WITH 1337 00:49:45,311 --> 00:49:48,181 DR. MARTINEZ SOBRITO AND HE 1338 00:49:48,181 --> 00:49:51,818 PROVIDED US WITH THE INFECTIOUS 1339 00:49:51,818 --> 00:50:02,362 CLONE BASED ON THE WASHINGTON 1340 00:50:03,896 --> 00:50:05,465 D614G -- CONDUCTED THE STUDY IN 1341 00:50:05,465 --> 00:50:07,166 THE FELINE MODEL TO ASSESS THE 1342 00:50:07,166 --> 00:50:12,338 ROLE OF THE SPIKE ON VIRAL 1343 00:50:12,338 --> 00:50:12,972 PATHOGENESIS. 1344 00:50:12,972 --> 00:50:16,676 SO AT THREE -- TWO GROUPS WERE 1345 00:50:16,676 --> 00:50:20,346 INOCULATED WITH THE D614G OR 1346 00:50:20,346 --> 00:50:23,016 WITH THE OMICRON, AND THEN WE 1347 00:50:23,016 --> 00:50:25,485 EUTHANIZED ANIMALS ON DAYS 3, 1348 00:50:25,485 --> 00:50:27,120 5 OR 14, AND AGAIN MONITORED 1349 00:50:27,120 --> 00:50:30,356 CLINICAL SIGNS BY VIRAL 1350 00:50:30,356 --> 00:50:33,326 REPLICATION AND IN THE UPPER AND 1351 00:50:33,326 --> 00:50:35,928 LOWER RESPIRATORY TRACT AND -- 1352 00:50:35,928 --> 00:50:36,262 TISSUES. 1353 00:50:36,262 --> 00:50:39,732 YOU CAN SEE HERE, WE DID OBSERVE 1354 00:50:39,732 --> 00:50:44,404 CLINICAL DIFFERENCES BETWEEN THE 1355 00:50:44,404 --> 00:50:47,240 D614G AND THE OMICRON SPIKE 1356 00:50:47,240 --> 00:50:51,911 VIRUS WHERE THE ANIMALS 1357 00:50:51,911 --> 00:50:53,046 PRESENTED INCREASED TEMPERATURE 1358 00:50:53,046 --> 00:50:55,048 BETWEEN DAYS 1 AND 3 AND THEY 1359 00:50:55,048 --> 00:50:57,450 ALSO PRESENTED A SLIGHT DECREASE 1360 00:50:57,450 --> 00:50:59,485 IN BODY WEIGHT WHILE ALL THE 1361 00:50:59,485 --> 00:51:01,454 OMICRON INOCULATED CATS ACTUALLY 1362 00:51:01,454 --> 00:51:02,622 GAINED WEIGHT AND THIS IS 1363 00:51:02,622 --> 00:51:06,325 CONSISTENT WITH OUR FIRST STUDY 1364 00:51:06,325 --> 00:51:10,063 WHERE THESE ANIMALS DON'T 1365 00:51:10,063 --> 00:51:11,631 PRESENT CLINICAL SIGNS. 1366 00:51:11,631 --> 00:51:13,733 THIS WAS CONFIRMED WHEN WE 1367 00:51:13,733 --> 00:51:17,970 LOOKED AT VIRUS REPLICATION. 1368 00:51:17,970 --> 00:51:22,742 AS SHOWN HERE, WE DETECTED 1369 00:51:22,742 --> 00:51:24,177 SIGNIFICANTLY LOWER LEVELS OF 1370 00:51:24,177 --> 00:51:25,411 VARIABLE RNA AND INFECTIOUS 1371 00:51:25,411 --> 00:51:29,182 VIRUS IN NASAL SWABS AND OUR 1372 00:51:29,182 --> 00:51:31,050 PHARYNGEAL SWABS AND ALSO IN THE 1373 00:51:31,050 --> 00:51:35,421 LOWER RESPIRATORY TRACT AND 1374 00:51:35,421 --> 00:51:37,090 BRONCHIOLAR LAVAGE FLUIDS IN THE 1375 00:51:37,090 --> 00:51:38,391 CURRENT SPIKE INOCULATED 1376 00:51:38,391 --> 00:51:39,058 ANIMALS. 1377 00:51:39,058 --> 00:51:42,895 WHEN WE LOOKED AT REPLICATION IN 1378 00:51:42,895 --> 00:51:46,299 TISSUES, WE AGAIN OBSERVED MUCH 1379 00:51:46,299 --> 00:51:48,201 LOWER LEVELS OF REPLICATION OF 1380 00:51:48,201 --> 00:51:51,204 THE OMICRON SPIKE WHEN COMPARED 1381 00:51:51,204 --> 00:51:53,139 TO THE D614G. 1382 00:51:53,139 --> 00:51:56,642 IN BOTH THE UPPER AND LOWER 1383 00:51:56,642 --> 00:52:00,113 RESPIRATORY TRACT, SHOWING YOU 1384 00:52:00,113 --> 00:52:02,048 HERE REPLICATION IN THE NASAL 1385 00:52:02,048 --> 00:52:03,883 TURBINATES. 1386 00:52:03,883 --> 00:52:04,784 PRETTY STRIKING PHENOTYPIC 1387 00:52:04,784 --> 00:52:06,018 DIFFERENCE BETWEEN THE TWO 1388 00:52:06,018 --> 00:52:06,919 VIRUSES. 1389 00:52:06,919 --> 00:52:09,522 SO THIS IS A SUMMARY SLIDE AND 1390 00:52:09,522 --> 00:52:10,556 FOR SAKE OF TIME I DIDN'T HAVE 1391 00:52:10,556 --> 00:52:12,358 TIME TO SHOW YOU THE WORK THAT 1392 00:52:12,358 --> 00:52:14,527 WE DID IN VITRO, BUT WHAT WE 1393 00:52:14,527 --> 00:52:18,865 OBSERVED IS THAT THE SPIKE, THE 1394 00:52:18,865 --> 00:52:20,500 CHIMERA WITH THE OMICRON SPIKE 1395 00:52:20,500 --> 00:52:22,835 VIRUS IS ABLE TO INFECT CELLS 1396 00:52:22,835 --> 00:52:26,239 JUST AS EFFICIENTLY AS THE D614G 1397 00:52:26,239 --> 00:52:28,341 VIRUS, BUT THIS VIRUS IS REALLY 1398 00:52:28,341 --> 00:52:30,643 IMPAIRED IN ITS ABILITY TO 1399 00:52:30,643 --> 00:52:32,612 SPREAD FROM CELL-TO-CELL. 1400 00:52:32,612 --> 00:52:34,947 SO THIS SPIKE OF THE OMICRON HAS 1401 00:52:34,947 --> 00:52:39,452 A MUCH LOWER -- ABILITY WHEN 1402 00:52:39,452 --> 00:52:41,687 COMPARED TO THE D614G VIRUS. 1403 00:52:41,687 --> 00:52:47,226 WE KIND OF OBSERVED TH THE SAMEN 1404 00:52:47,226 --> 00:52:49,729 VIVO WHERE THERE WERE A FEW 1405 00:52:49,729 --> 00:52:51,264 CELLS INSPECTED WITH THE OMICRON 1406 00:52:51,264 --> 00:52:54,167 SPIKE BUT THE VIRUS DIDN'T SEEM 1407 00:52:54,167 --> 00:52:55,468 TO BE ABLE TO SPREAD 1408 00:52:55,468 --> 00:52:56,803 CELL-TO-CELL AS EFFICIENTLY AS 1409 00:52:56,803 --> 00:52:58,805 THE D614F VIRUS. 1410 00:52:58,805 --> 00:53:04,443 614G VIRUS.WE BELIEVE THIS IS OE 1411 00:53:04,443 --> 00:53:05,444 POTENTIAL MECHANISMS THAT 1412 00:53:05,444 --> 00:53:08,414 EXPLAIN THE DIFFERENCE IN 1413 00:53:08,414 --> 00:53:10,950 PATHOGENICITY WHEN COMPARED TO 1414 00:53:10,950 --> 00:53:12,852 THE D614G VIRUS. 1415 00:53:12,852 --> 00:53:14,754 SO THE LAST STORY THAT I WANT TO 1416 00:53:14,754 --> 00:53:15,988 TELL YOU, AND I NEED TO RUN 1417 00:53:15,988 --> 00:53:17,990 BECAUSE I'M RUNNING OUT OF TIME, 1418 00:53:17,990 --> 00:53:21,561 IS ON THE COMPARISON IN THE 1419 00:53:21,561 --> 00:53:23,796 EFFECT OF ORF3 ON THE 1420 00:53:23,796 --> 00:53:24,897 PATHOGENESIS OF THE VIRUS AGAIN 1421 00:53:24,897 --> 00:53:27,366 USING THE FELINE MODEL, WE 1422 00:53:27,366 --> 00:53:33,806 COMPARED A VIRUS -- 1423 00:53:33,806 --> 00:53:36,309 CONTAINING -- VIRUS IN WHICH THE 1424 00:53:36,309 --> 00:53:39,745 3A ACCESS REA GEN ACCESSORY GENN 1425 00:53:39,745 --> 00:53:40,313 DELETED. 1426 00:53:40,313 --> 00:53:43,683 WE DID NOT OBSERVE DIFFERENCES 1427 00:53:43,683 --> 00:53:44,684 IN BODY TEMPERATURE BETWEEN THE 1428 00:53:44,684 --> 00:53:48,120 TWO VIRUSES, HOWEVER, THE DELTA 1429 00:53:48,120 --> 00:53:49,789 RF3 VIRUS INOCULATED ANIMALS DID 1430 00:53:49,789 --> 00:53:51,357 NOT PRESENT REDUCTION IN THE 1431 00:53:51,357 --> 00:53:57,597 BODY WEIGHT WHILE THE WASHINGTON 1432 00:53:57,597 --> 00:53:58,698 1 INOCULATED ANIMALS PRESENTED 1433 00:53:58,698 --> 00:54:00,199 DECREASE IN BODY WEIGHT. 1434 00:54:00,199 --> 00:54:01,534 WHEN WE LACKED AT REPLICATION IN 1435 00:54:01,534 --> 00:54:03,803 THE UPPER AND LOWER RESPIRATORY 1436 00:54:03,803 --> 00:54:05,037 TRACT, AGAIN WE OBSERVED 1437 00:54:05,037 --> 00:54:06,873 SIGNIFICANT REDUCTION IN 1438 00:54:06,873 --> 00:54:09,775 REPLICATION OR SHEDDING LEVELS 1439 00:54:09,775 --> 00:54:12,378 OF THE DELTA R3 VIRUS WHEN 1440 00:54:12,378 --> 00:54:16,382 COMPARED TO THE WASHINGTON 1441 00:54:16,382 --> 00:54:18,851 1 BACKBONE IN THE UPPER AND THE 1442 00:54:18,851 --> 00:54:21,254 LOWER RESPIRATORY TRACT 1443 00:54:21,254 --> 00:54:22,488 SECRETIONS AS SHOWN IN THIS 1444 00:54:22,488 --> 00:54:24,590 GRAPH. 1445 00:54:24,590 --> 00:54:26,893 SIMILARLY WHEN WE LOOKED AT 1446 00:54:26,893 --> 00:54:32,598 TISSUES, BOTH DELTA ORF3 VIRUS 1447 00:54:32,598 --> 00:54:34,300 PRESENTED MUCH LOWER VIRAL LOADS 1448 00:54:34,300 --> 00:54:37,503 IN THE UPPER AND LOWER 1449 00:54:37,503 --> 00:54:39,739 RESPIRATORY TRACT WHEN COMPARED 1450 00:54:39,739 --> 00:54:46,612 TO THE D614G VIRUS THIS WAS 1451 00:54:46,612 --> 00:54:48,748 REFLECTED IN THE PATHOLOGY AS 1452 00:54:48,748 --> 00:54:51,250 WELL, DELTA R3 INOCULATED 1453 00:54:51,250 --> 00:54:53,019 ANIMALS PRESENTED LUNG HISTOLOGY 1454 00:54:53,019 --> 00:54:54,420 VERY SIMILAR TO OUR CONTROL 1455 00:54:54,420 --> 00:54:56,689 ANIMALS, WHEN THE WASHINGTON ONE 1456 00:54:56,689 --> 00:54:57,723 INOCULATED ANIMALS PRESENTED 1457 00:54:57,723 --> 00:55:01,560 MORE SEVERE LESIONS IN THE LUNG. 1458 00:55:01,560 --> 00:55:03,296 WE ALSO LOOKED AT GENE 1459 00:55:03,296 --> 00:55:08,801 EXPRESSION LEVELS BY RNA SEQ, 1460 00:55:08,801 --> 00:55:10,069 AND WHAT I WOULD LIKE TO POINT 1461 00:55:10,069 --> 00:55:11,470 OUT HERE IS THAT WHEN WE LOOKED 1462 00:55:11,470 --> 00:55:14,507 AT TRANSCRIPTION FACTORS THAT 1463 00:55:14,507 --> 00:55:16,042 COULD BE REGULATING THESE GENES 1464 00:55:16,042 --> 00:55:17,376 WITHOUT THEIR GENE EXPRESSION, 1465 00:55:17,376 --> 00:55:20,079 WHAT WE FOUND OUT IS THAT 1466 00:55:20,079 --> 00:55:21,080 SEVERAL OF THE TRANSCRIPTION 1467 00:55:21,080 --> 00:55:22,915 FACTORS THAT WERE IDENTIFIED, 1468 00:55:22,915 --> 00:55:27,553 THEY BELONGED TO THIS ZNF FAMILY 1469 00:55:27,553 --> 00:55:33,726 OF TRANSCRIPTION FACTORS O, ANDE 1470 00:55:33,726 --> 00:55:35,161 SEARCHED THE LITERATURE TO SEE 1471 00:55:35,161 --> 00:55:36,195 WHETHER THIS HAS BEEN DESCRIBED 1472 00:55:36,195 --> 00:55:37,363 BEFORE AND WE FOUND THIS PAPER 1473 00:55:37,363 --> 00:55:40,032 WHERE THEY CONDUCTED A PRETTY 1474 00:55:40,032 --> 00:55:42,768 LARGE PROTEOMICS SCREEN AND THEY 1475 00:55:42,768 --> 00:55:44,971 ACTUALLY HAD FOUND THROUGH THIS 1476 00:55:44,971 --> 00:55:49,809 SCREEN THAT ORF3 INTERACTS WITH 1477 00:55:49,809 --> 00:55:52,912 ZNF579 ON THAT LARGE SCREEN. 1478 00:55:52,912 --> 00:55:55,581 THEY HAVE NOT FOLLOWED UP ON THE 1479 00:55:55,581 --> 00:55:59,151 CHARACTERIZATION OF THIS, SO WE 1480 00:55:59,151 --> 00:56:03,456 CONFIRMED THAT INTERACTION OF 1481 00:56:03,456 --> 00:56:05,424 ORF3 WITH THE CATH ZNF ALPHA, 1482 00:56:05,424 --> 00:56:07,426 AND THIS IS SOMETHING WE'RE 1483 00:56:07,426 --> 00:56:08,594 CURRENTLY WORKING ON TO FURTHER 1484 00:56:08,594 --> 00:56:09,328 CHARACTERIZE THIS. 1485 00:56:09,328 --> 00:56:10,629 WE'RE LOOKING AT THIS 1486 00:56:10,629 --> 00:56:12,898 INTERACTION IN THE CONTEXT OF 1487 00:56:12,898 --> 00:56:15,201 VIRUS INFECTION AND ALSO LOOKING 1488 00:56:15,201 --> 00:56:16,802 AT CHARACTERIZING THE EFFECT OF 1489 00:56:16,802 --> 00:56:18,070 THIS INTERACTION IN GENE 1490 00:56:18,070 --> 00:56:23,009 TRANSCRIPTION USING -- STUDIES. 1491 00:56:23,009 --> 00:56:28,314 SO JUST A QUICK OVERVEUL OF THE 1492 00:56:28,314 --> 00:56:31,751 OVERVIEW OF THEMODELS WE DISCUS. 1493 00:56:31,751 --> 00:56:33,185 SO THE FERRET MODEL, THERE'S 1494 00:56:33,185 --> 00:56:35,021 RELATIVELY LOW VIRUS SHEDDING OR 1495 00:56:35,021 --> 00:56:35,921 VIRUS REPLICATION WHEN COMPARED 1496 00:56:35,921 --> 00:56:37,056 TO THE FELINE MODEL. 1497 00:56:37,056 --> 00:56:39,892 THE ANIMALS, FERRETS DO NOT 1498 00:56:39,892 --> 00:56:41,761 DEVELOP CLINICAL SIGNS FOLLOWING 1499 00:56:41,761 --> 00:56:43,262 INOCULATION. 1500 00:56:43,262 --> 00:56:45,398 AND VIRUS RE REPLICATION IS REAY 1501 00:56:45,398 --> 00:56:47,733 LIMITED TO THE UPPER RESPIRATORY 1502 00:56:47,733 --> 00:56:51,270 TRACT WITH QUESTIONABLE 1503 00:56:51,270 --> 00:56:52,938 REPLICATION IN THE LUNGS, WHICH 1504 00:56:52,938 --> 00:56:56,609 DOESN'T REALLY REPRESENT THE 1505 00:56:56,609 --> 00:57:01,080 PATHOLOGY THAT WE SEE IN HUMANS. 1506 00:57:01,080 --> 00:57:04,617 THE CATS, ON THE OTHER HAND, THE 1507 00:57:04,617 --> 00:57:07,820 VIRUS REPLICATES A LOT BETTER IN 1508 00:57:07,820 --> 00:57:09,588 BOTH THE UPPER AND LOWER 1509 00:57:09,588 --> 00:57:13,225 RESPIRATORY TRACT AND WE ALSO 1510 00:57:13,225 --> 00:57:15,528 OBSERVE PATHOLOGY THAT RESEMBLES 1511 00:57:15,528 --> 00:57:17,830 THE PATHOLOGY THAT IS OBSERVED 1512 00:57:17,830 --> 00:57:21,734 IN HUMANS. 1513 00:57:21,734 --> 00:57:23,069 SO STRENGTHS, LIMITATIONS AND 1514 00:57:23,069 --> 00:57:24,370 OPPORTUNITIES, THIS IS MY LAST 1515 00:57:24,370 --> 00:57:26,972 SLIDE, THE FELINE MODEL, IT DOES 1516 00:57:26,972 --> 00:57:28,941 PRESENT ADVANTAGES OVER THE 1517 00:57:28,941 --> 00:57:30,309 FERRET MODEL AS THE VIRUS 1518 00:57:30,309 --> 00:57:31,610 REPLICATES IN THE UPPER AND 1519 00:57:31,610 --> 00:57:33,813 LOWER RESPIRATORY TRACT. 1520 00:57:33,813 --> 00:57:35,314 OTHER GROUPS HAVE SHOWN THAT 1521 00:57:35,314 --> 00:57:39,085 IT'S ALSO A VERY USEFUL MODEL TO 1522 00:57:39,085 --> 00:57:41,720 ASSESS TRANSMISSION OF 1523 00:57:41,720 --> 00:57:42,488 SARS-COV-2. 1524 00:57:42,488 --> 00:57:44,457 LIMITATIONS IS OBVIOUSLY SIMILAR 1525 00:57:44,457 --> 00:57:46,792 TO THE HAMSTER MODEL, AND MAYBE 1526 00:57:46,792 --> 00:57:49,562 A LITTLE LESS SO. 1527 00:57:49,562 --> 00:57:51,263 WE HAVE A FEW IMMUNE REAGENTS 1528 00:57:51,263 --> 00:57:53,165 THAT ARE AVAILABLE BUT 1529 00:57:53,165 --> 00:57:54,633 DEFINITELY MORE IMMUNE REAGENTS 1530 00:57:54,633 --> 00:57:56,836 ARE NEEDED TO ACTUALLY LOOK AT 1531 00:57:56,836 --> 00:58:00,339 HOST IMMUNE RESPONSES AN HOST 1532 00:58:00,339 --> 00:58:01,407 FACTORS. 1533 00:58:01,407 --> 00:58:03,142 THE OTHER LIMITATION IS THAT 1534 00:58:03,142 --> 00:58:05,644 STUDYING HOST GENETICS IN A 1535 00:58:05,644 --> 00:58:07,279 LARGE SMALL ANIMAL MODEL AS THE 1536 00:58:07,279 --> 00:58:10,149 FELINE MODEL IS MUCH MORE COSTLY 1537 00:58:10,149 --> 00:58:10,816 AND COMPLICATED THAN IT IS IN 1538 00:58:10,816 --> 00:58:12,384 THE SMALLER MODELS. 1539 00:58:12,384 --> 00:58:17,256 SO THAT IS A SIGNIFICANT 1540 00:58:17,256 --> 00:58:18,057 LIMITATION. 1541 00:58:18,057 --> 00:58:21,193 THE OTHER THING ABOUT FELINE, A 1542 00:58:21,193 --> 00:58:25,164 FELINE MODEL IS THAT THEY CAN 1543 00:58:25,164 --> 00:58:26,832 POTENTIALLY SERVE AS MODELS FOR 1544 00:58:26,832 --> 00:58:30,136 OTHER RESPIRATORY TRY VUSES. 1545 00:58:30,136 --> 00:58:30,436 VIRUSES. 1546 00:58:30,436 --> 00:58:32,238 WE HAVE ALSO BEEN INVOLVED IN 1547 00:58:32,238 --> 00:58:34,440 ALSO THE DETECTION OF HIGHLY 1548 00:58:34,440 --> 00:58:35,107 PATHOGENIC INFLUENZA. 1549 00:58:35,107 --> 00:58:39,545 IN A FEW OF THESE FARMS WE 1550 00:58:39,545 --> 00:58:43,282 DETECTED THE VIRUS IN DAIRY 1551 00:58:43,282 --> 00:58:44,350 CATTLE. 1552 00:58:44,350 --> 00:58:52,791 -- WERE THE FIRST TO DIE FROM 1553 00:58:52,791 --> 00:58:54,560 H -- YOU CAN SEE VERY HEAVY 1554 00:58:54,560 --> 00:58:57,596 REPLICATION OF THE VIRUS IN THE 1555 00:58:57,596 --> 00:58:58,998 BRAIN OF INFECTED ANIMALS, WE 1556 00:58:58,998 --> 00:59:01,567 ALSO SEE REPLICATION IN THE 1557 00:59:01,567 --> 00:59:08,274 LUNG, LIVER, AND MODERATE T -- K 1558 00:59:08,274 --> 00:59:10,643 THE FELINE MODEL COULD REALLY 1559 00:59:10,643 --> 00:59:12,077 SERVE AS A VERY GOOD MODEL TO 1560 00:59:12,077 --> 00:59:15,114 UNDERSTAND THE NEUROTROPISM OF 1561 00:59:15,114 --> 00:59:17,850 H5N1 IN MAMMALIAN SPECIES, EVEN 1562 00:59:17,850 --> 00:59:21,220 WITH THE LIMITATIONS OF THE LACK 1563 00:59:21,220 --> 00:59:22,888 OF REAGENTS THAT WE HAVE. 1564 00:59:22,888 --> 00:59:24,390 WITH THAT, I WOULD LIKE TO THANK 1565 00:59:24,390 --> 00:59:27,293 MY LAB, ESPECIALLY MOHAMMAD, WHO 1566 00:59:27,293 --> 00:59:33,566 DID A LOT OF THE WORK ON THE 1567 00:59:33,566 --> 00:59:36,235 FELINE MODEL, MATHIAS WAS THE 1568 00:59:36,235 --> 00:59:37,436 PERSON WHO BASICALLY STARTED THE 1569 00:59:37,436 --> 00:59:38,571 WORK IN THE LAB. 1570 00:59:38,571 --> 00:59:40,005 HE'S CURRENTLY AT PENN STATE 1571 00:59:40,005 --> 00:59:40,573 UNIVERSITY. 1572 00:59:40,573 --> 00:59:43,576 AND OBVIOUSLY FUNDING FROM NIH 1573 00:59:43,576 --> 00:59:51,750 AND USDA. 1574 00:59:51,750 --> 00:59:52,751 >> YES, SEEMA. 1575 00:59:52,751 --> 00:59:54,019 >> I REALLY LIKE THAT, AND I 1576 00:59:54,019 --> 00:59:56,722 LOVE THE FELINE MODEL, AND I AM 1577 00:59:56,722 --> 00:59:58,190 CURIOUS, A COUPLE OF QUESTIONS 1578 00:59:58,190 --> 00:59:59,525 THAT KIND OF COME TO MIND 1579 00:59:59,525 --> 01:00:02,461 BECAUSE I THINK IT'S SUPER 1580 01:00:02,461 --> 01:00:05,431 FASCINATING. 1581 01:00:05,431 --> 01:00:07,533 ONE HAS ANYONE LOOKED AT OMICRON 1582 01:00:07,533 --> 01:00:10,069 TRANSMISSION IN CATS GIVEN THE 1583 01:00:10,069 --> 01:00:12,037 LACK OF TRANSMISSION PHENOTYPES 1584 01:00:12,037 --> 01:00:12,972 IN HAMSTERS? 1585 01:00:12,972 --> 01:00:14,773 MY SECOND, CAN I DO THAT 1586 01:00:14,773 --> 01:00:15,074 AFTERWARDS. 1587 01:00:15,074 --> 01:00:17,776 >> NOT THAT I KNOW. 1588 01:00:17,776 --> 01:00:19,445 WE HAVE NOT HAD A CHANCE TO LOOK 1589 01:00:19,445 --> 01:00:21,847 AT -- UNFORTUNATELY WE DON'T 1590 01:00:21,847 --> 01:00:24,650 HAVE THE RIGHT GAUGING SYSTEM TO 1591 01:00:24,650 --> 01:00:26,885 DO TRANSMISSION STUDIES IN CATS. 1592 01:00:26,885 --> 01:00:33,492 THAT'S THE COMPLICATION OF THIS. 1593 01:00:33,492 --> 01:00:34,693 I'M WORKING WITH ADMINISTRATION 1594 01:00:34,693 --> 01:00:36,328 RIGHT NOW TO ACTUALLY GET CAGES 1595 01:00:36,328 --> 01:00:37,630 THAT WOULD ALLOW US TO DO 1596 01:00:37,630 --> 01:00:40,532 TRANSMISSION STUDIES. 1597 01:00:40,532 --> 01:00:42,167 >> AND THEN MY OTHER PART WAS, 1598 01:00:42,167 --> 01:00:45,371 COULD YOU SPECULATE SORT OF ON 1599 01:00:45,371 --> 01:00:47,273 THE -- I THOUGHT IT REALLY 1600 01:00:47,273 --> 01:00:48,240 FASCINATING DURING THE COVID-19 1601 01:00:48,240 --> 01:00:49,441 PANDEMIC AND NOW OBVIOUSLY 1602 01:00:49,441 --> 01:00:51,510 DURING H5, WHERE DURING COVID-19 1603 01:00:51,510 --> 01:00:53,379 WE WERE SEEING BIG CATS GET 1604 01:00:53,379 --> 01:00:54,780 INFECTED AT ZOOS. 1605 01:00:54,780 --> 01:00:57,049 TIGRRS AND LIONS, AND THEY 1606 01:00:57,049 --> 01:00:58,717 CLEARLY DO NOT HAVE A LOT OF 1607 01:00:58,717 --> 01:01:02,588 CLOSE RANGE CONTACT WITH OTHER 1608 01:01:02,588 --> 01:01:05,090 ANIMALS OR HUMANS, THERE'S A LOT 1609 01:01:05,090 --> 01:01:05,524 OF DISTANCE. 1610 01:01:05,524 --> 01:01:07,192 SO I'M CURIOUS WHAT YOU THINK 1611 01:01:07,192 --> 01:01:09,561 SORT OF THE MECHANISMS THAT 1612 01:01:09,561 --> 01:01:10,863 MIGHT BE FOR TRANSMISSION IN 1613 01:01:10,863 --> 01:01:12,364 CATS AND WHAT DO YOU THINK IS 1614 01:01:12,364 --> 01:01:15,100 SORT OF HAPPENING IN THE CATS' 1615 01:01:15,100 --> 01:01:17,469 SPACE AS THE PANDEMIC SORT OF 1616 01:01:17,469 --> 01:01:20,572 CONTINUED? 1617 01:01:20,572 --> 01:01:21,740 >> AND YOU'RE ASKING THE 1618 01:01:21,740 --> 01:01:23,075 QUESTION SPECIFICALLY ABOUT 1619 01:01:23,075 --> 01:01:25,444 SARS-COV-2? 1620 01:01:25,444 --> 01:01:28,947 OKAY. 1621 01:01:28,947 --> 01:01:29,915 SO -- YEAH. 1622 01:01:29,915 --> 01:01:31,450 IF WE LOOK AT THE NUMBER OF 1623 01:01:31,450 --> 01:01:34,787 ANIMALS THAT WERE NATURALLY 1624 01:01:34,787 --> 01:01:35,888 INFECTED WITH SARS-COV-2, IT'S 1625 01:01:35,888 --> 01:01:37,890 VERY SMALL, RIGHT? 1626 01:01:37,890 --> 01:01:39,391 BUT IF YOU LOOK AT THE SPECIES 1627 01:01:39,391 --> 01:01:43,729 THAT WERE INFECTED, I THINK CATS 1628 01:01:43,729 --> 01:01:45,331 WERE SECOND AFTER WHITETAILED 1629 01:01:45,331 --> 01:01:45,531 DEER. 1630 01:01:45,531 --> 01:01:47,299 SO THEY ARE HIGHLY SUSCEPTIBLE 1631 01:01:47,299 --> 01:01:49,201 TO INFECTION. 1632 01:01:49,201 --> 01:01:50,869 THEY DO GET INFECTED. 1633 01:01:50,869 --> 01:01:53,172 I THINK THAT THE ROLLING 1634 01:01:53,172 --> 01:01:54,606 TRANSMISSION IS PROBABLY 1635 01:01:54,606 --> 01:01:55,374 MINIMAL. 1636 01:01:55,374 --> 01:01:58,811 I DON'T THINK THAT THEY 1637 01:01:58,811 --> 01:02:00,446 TRANSMITTED SARS-COV-2 COV-2. 1638 01:02:00,446 --> 01:02:04,049 WITH HPAI, I DON'T KNOW. 1639 01:02:04,049 --> 01:02:07,686 I THINK THAT THESE CATS COULD 1640 01:02:07,686 --> 01:02:08,954 POTENTIALLY BE SHEDDING ENOUGH 1641 01:02:08,954 --> 01:02:12,224 VIRUS THAT WOULD LEAD TO 1642 01:02:12,224 --> 01:02:16,161 TRANSMISSION TO OTHER CATS OR 1643 01:02:16,161 --> 01:02:18,097 POTENTIALLY OTHER ANIMALS. 1644 01:02:18,097 --> 01:02:19,832 I DON'T KNOW HOW QUICKLY THEY 1645 01:02:19,832 --> 01:02:21,467 DIE AFTER INFECTION TOO, SO 1646 01:02:21,467 --> 01:02:23,135 THAT'S ANOTHER QUESTION THAT 1647 01:02:23,135 --> 01:02:26,372 NEEDS TO BE ADDRESSED. 1648 01:02:26,372 --> 01:02:29,408 THESE ARE -- THE OTHER ANIMALS 1649 01:02:29,408 --> 01:02:31,410 WERE FOUND DEAD AND THAT'S HOW 1650 01:02:31,410 --> 01:02:32,177 WE TESTED THEM. 1651 01:02:32,177 --> 01:02:34,213 BUT I THINK THAT, YOU KNOW, 1652 01:02:34,213 --> 01:02:37,282 EXPERIMENTAL STUDIES ARE NEEDED 1653 01:02:37,282 --> 01:02:38,450 TO REALLY ANSWER SOME OF THESE 1654 01:02:38,450 --> 01:02:40,586 QUESTIONS. 1655 01:02:40,586 --> 01:02:42,154 >> I'M GOING TO TAKE LIBERTY AND 1656 01:02:42,154 --> 01:02:44,590 ASK A QUESTION AND THEN I THINK 1657 01:02:44,590 --> 01:02:49,561 WE'LL MOVE TO THE NEXT SPEAKER. 1658 01:02:49,561 --> 01:02:51,730 FOR TRANSMISSION, COULD YOU TAKE 1659 01:02:51,730 --> 01:02:53,866 THE VIRUSES THAT ARE BEING SHED 1660 01:02:53,866 --> 01:02:57,403 FROM THE CATS AND THEN AT LEAST 1661 01:02:57,403 --> 01:03:00,072 MAYBE IN A PRIMARY CELL CULTURE 1662 01:03:00,072 --> 01:03:05,344 SYSTEM LIKE HUMAN EPITHELIAL 1663 01:03:05,344 --> 01:03:06,845 CELLS LOOK AND SEE WHAT IT DOES 1664 01:03:06,845 --> 01:03:07,946 TO HUMAN CELLS? 1665 01:03:07,946 --> 01:03:11,350 DO VIRUSES THAT ARE SHED FROM 1666 01:03:11,350 --> 01:03:15,020 CATS HAVE THE POTENTIAL FOR 1667 01:03:15,020 --> 01:03:18,657 INFECTIVITY, CELL KILLING, YOU 1668 01:03:18,657 --> 01:03:19,057 KNOW? 1669 01:03:19,057 --> 01:03:20,325 BECAUSE I REALIZE YOU'RE NOT 1670 01:03:20,325 --> 01:03:21,794 GOING TO BE ABLE TO DO 1671 01:03:21,794 --> 01:03:22,895 TRANSMISSION TO HUMANS, BUT 1672 01:03:22,895 --> 01:03:25,197 COULD YOU MODEL TRANSMISSION? 1673 01:03:25,197 --> 01:03:26,999 >> I THINK MODELING TRANSMISSION 1674 01:03:26,999 --> 01:03:28,667 IN VITRO IS NEARLY IMPOSSIBLE, 1675 01:03:28,667 --> 01:03:30,369 RIGHT? 1676 01:03:30,369 --> 01:03:33,071 WHAT WE KNOW IS THAT WE ARE 1677 01:03:33,071 --> 01:03:35,240 DETECTING SIX LOGS OF VIRUS IN 1678 01:03:35,240 --> 01:03:41,280 NASAL SECRETIONS IN SARS-COV-2 1679 01:03:41,280 --> 01:03:42,581 FROM THESE ANIMALS. 1680 01:03:42,581 --> 01:03:44,450 THAT KEPT THE NATURALLY INFECTED 1681 01:03:44,450 --> 01:03:47,119 ANIMAL THAT I SHOWED, THAT GROSS 1682 01:03:47,119 --> 01:03:50,255 PATHOLOGY, WE DETECTED 1683 01:03:50,255 --> 01:03:52,157 POTENTIALLY EIGHT LOGS OF VIRUS 1684 01:03:52,157 --> 01:03:53,992 IN NASAL SECRETIONS AND IN 1685 01:03:53,992 --> 01:03:54,827 SEVERAL OF THE -- 1686 01:03:54,827 --> 01:03:56,962 >> BECAUSE I'M THINKING ABOUT 1687 01:03:56,962 --> 01:03:58,430 ONE HEALTH, YOU THINK ABOUT 1688 01:03:58,430 --> 01:04:00,399 THESE COMPANION ANIMALS, AND YOU 1689 01:04:00,399 --> 01:04:01,934 KNOW, MAYBE MORE SO ABOUT 1690 01:04:01,934 --> 01:04:03,869 TRANSMISSION TO HUMANS THAN TO 1691 01:04:03,869 --> 01:04:04,870 OTHER FELINE. 1692 01:04:04,870 --> 01:04:06,839 >> THERE ARE OTHER PLACES, I 1693 01:04:06,839 --> 01:04:10,542 MEAN, KANSAS STATE AND I THINK 1694 01:04:10,542 --> 01:04:11,844 THE -- GROUP IN WISCONSIN, THEY 1695 01:04:11,844 --> 01:04:13,145 DID TRANSMISSION STUDIES IN CATS 1696 01:04:13,145 --> 01:04:15,113 AND THEY TRANSMIT VERY 1697 01:04:15,113 --> 01:04:16,081 EFFICIENTLY. 1698 01:04:16,081 --> 01:04:19,117 I THINK -- SARS-COV-2. 1699 01:04:19,117 --> 01:04:22,087 >> THANK YOU. 1700 01:04:22,087 --> 01:04:22,754 >> ALL RIGHT. 1701 01:04:22,754 --> 01:04:26,258 I WOULD LIKE TO INVITE SEEMA 1702 01:04:26,258 --> 01:04:29,595 LAKDAWALA FROM EMORY UNIVERSITY 1703 01:04:29,595 --> 01:04:31,597 TO GIVE HER TALK ENTITLED 1704 01:04:31,597 --> 01:04:33,432 RE-THINKING THE FERRET MODEL TO 1705 01:04:33,432 --> 01:04:34,833 STUDY INFLUENZA VIRUS 1706 01:04:34,833 --> 01:04:37,503 TRANSMISSION. 1707 01:04:37,503 --> 01:04:38,871 >> THANK YOU, SABRA. 1708 01:04:38,871 --> 01:04:40,172 AND THANKS TO THE ORGANIZERS FOR 1709 01:04:40,172 --> 01:04:41,507 THIS REALLY GREAT MEETING. 1710 01:04:41,507 --> 01:04:42,741 I'M GLAD THAT I COULD BE HERE 1711 01:04:42,741 --> 01:04:43,842 AND THANKS FOR THE OPPORTUNITY 1712 01:04:43,842 --> 01:04:45,611 TO SPEAK. 1713 01:04:45,611 --> 01:04:50,315 I'LL WAIT FOR MY SLIDES. 1714 01:04:50,315 --> 01:04:52,251 I THINK WHAT I WANT TO TALK 1715 01:04:52,251 --> 01:04:53,352 ABOUT TODAY IS SORT OF LIKE 1716 01:04:53,352 --> 01:04:54,887 SOMETHING THAT WAS TOUCHED ON 1717 01:04:54,887 --> 01:04:57,222 YESTERDAY IN STACEY'S OVERVIEW 1718 01:04:57,222 --> 01:04:58,690 AND KIND OF I THINK THE REASON 1719 01:04:58,690 --> 01:05:01,760 WE'RE HERE IS TO UNDERSTAND AND 1720 01:05:01,760 --> 01:05:02,628 THINK ABOUT WHAT ARE THE 1721 01:05:02,628 --> 01:05:05,130 QUESTIONS WE'RE ASKING, AND HOW 1722 01:05:05,130 --> 01:05:08,166 CAN WE DESIGN THE EXPERIMENTS TO 1723 01:05:08,166 --> 01:05:10,135 REALLY TEST THE QUESTIONS THAT 1724 01:05:10,135 --> 01:05:11,236 WE ARE MOST INTERESTED IN 1725 01:05:11,236 --> 01:05:11,537 ASKING. 1726 01:05:11,537 --> 01:05:12,938 SO WE'RE GOING TO TALK ABOUT HOW 1727 01:05:12,938 --> 01:05:14,506 WE CAN RE-THINK TRANSMISSION. 1728 01:05:14,506 --> 01:05:15,073 THIS IS FINE. 1729 01:05:15,073 --> 01:05:21,680 I CAN DO THIS. 1730 01:05:21,680 --> 01:05:31,890 WE'RE GOOD. 1731 01:05:40,732 --> 01:05:42,000 SO I'VE BEEN STUDYING 1732 01:05:42,000 --> 01:05:43,101 TRANSMISSION SINCE THE 2009 1733 01:05:43,101 --> 01:05:45,003 PANDEMIC AND I WAS A POSTDOC. 1734 01:05:45,003 --> 01:05:47,739 SO I WROTE THIS REVIEW BACK IN 1735 01:05:47,739 --> 01:05:47,940 2012. 1736 01:05:47,940 --> 01:05:49,141 AND THIS IS HOW I USED TO THINK 1737 01:05:49,141 --> 01:05:51,209 ABOUT THIS PROBLEM, RIGHT, IS 1738 01:05:51,209 --> 01:05:52,077 THAT TRANSMISSION KIND OF WORKED 1739 01:05:52,077 --> 01:05:53,278 WITH THIS AND THERE WERE THREE 1740 01:05:53,278 --> 01:05:54,012 PARTS OF THE EQUATION. 1741 01:05:54,012 --> 01:05:56,081 I'M GOING TO KIND OF COME BACK 1742 01:05:56,081 --> 01:05:57,683 TO THIS WHICH IS WHERE MY MIND 1743 01:05:57,683 --> 01:05:59,318 HAS COME OVER A DECADE OF 1744 01:05:59,318 --> 01:06:00,085 STUDYING TRANSMISSION, IS WHAT 1745 01:06:00,085 --> 01:06:02,421 IS THE EQUATION OF TRANSMISSION, 1746 01:06:02,421 --> 01:06:03,155 RIGHT? 1747 01:06:03,155 --> 01:06:05,424 YOU GOT A DONOR, THE VIRUS HAS 1748 01:06:05,424 --> 01:06:09,695 TO REPLICATE IN A DONOR. 1749 01:06:09,695 --> 01:06:11,897 THAT VIRUS IS THEN EXPELLED INTO 1750 01:06:11,897 --> 01:06:13,832 A VARIETY OF AEROSOLS. 1751 01:06:13,832 --> 01:06:17,102 THERE'S LARGE DROPLET SPRAY, AIR 1752 01:06:17,102 --> 01:06:21,840 STOLES, FINE AIR SO SO AEROSOLS. 1753 01:06:21,840 --> 01:06:25,477 ONE OF THE THINGS VIROLOGISTS 1754 01:06:25,477 --> 01:06:26,578 DON'T DO ENOUGH IS ACTUALLY 1755 01:06:26,578 --> 01:06:27,813 THINK ABOUT THE VIRUS IN THE 1756 01:06:27,813 --> 01:06:29,181 VIERPT, HOW THE ENVIRONMENTAL 1757 01:06:29,181 --> 01:06:30,382 PARAMETERS ACTUALLY INFLUENCE 1758 01:06:30,382 --> 01:06:31,383 THE FATE OF THESE VIRUSES AND 1759 01:06:31,383 --> 01:06:33,218 HOW THAT THEN LEADS TO 1760 01:06:33,218 --> 01:06:33,986 SUCCESSFUL TRANSMISSION OR LACK 1761 01:06:33,986 --> 01:06:34,753 OF TRANSMISSION. 1762 01:06:34,753 --> 01:06:36,888 THEN THE THIRD PART OF THE 1763 01:06:36,888 --> 01:06:38,056 EQUATION IS SUSCEPTIBILITY OF 1764 01:06:38,056 --> 01:06:38,557 THE RECIPIENT. 1765 01:06:38,557 --> 01:06:39,858 WE TALKED ABOUT IMMUNITY 1766 01:06:39,858 --> 01:06:43,795 YESTERDAY AND VAX NAISE VACCIN. 1767 01:06:43,795 --> 01:06:46,264 WE ARE NOT IMMUNOLOGICALLY NAIVE 1768 01:06:46,264 --> 01:06:49,334 HOSTS AS WE WALK AROUND IN 1769 01:06:49,334 --> 01:06:50,736 SOCIETY AND OUR DAILY LIVES, SO 1770 01:06:50,736 --> 01:06:52,270 THINKING ABOUT WHAT THAT MEANS 1771 01:06:52,270 --> 01:06:52,604 IS IMPORTANT. 1772 01:06:52,604 --> 01:06:54,406 SO IN IS HOW I USED TO THINK 1773 01:06:54,406 --> 01:06:55,140 ABOUT THIS PROBLEM. 1774 01:06:55,140 --> 01:06:56,842 OH, IT'S VERY BINARY, RIGHT? 1775 01:06:56,842 --> 01:06:57,743 IT'S LIKE THERE'S A DONOR, 1776 01:06:57,743 --> 01:06:58,543 THERE'S THE ENVIRONMENT AND 1777 01:06:58,543 --> 01:07:00,579 THERE'S THE RECIPIENT. 1778 01:07:00,579 --> 01:07:03,148 BUT IN REALITY, AND I USED TO 1779 01:07:03,148 --> 01:07:07,653 ALWAYS SAY, THIS IS AN OLD 1780 01:07:07,653 --> 01:07:08,754 SLIDE, ANY OF THESE PARAMETERS 1781 01:07:08,754 --> 01:07:10,589 CAN CHANGE THE TRANSMISSION 1782 01:07:10,589 --> 01:07:10,889 DYNAMICS. 1783 01:07:10,889 --> 01:07:12,891 BUT AGAIN, THESE ARE THREE 1784 01:07:12,891 --> 01:07:14,192 EQUATIONS, THREE VARIABLES, YOU 1785 01:07:14,192 --> 01:07:15,027 MANIPULATE ANY OF THEM AND YOU 1786 01:07:15,027 --> 01:07:16,461 CAN SHIFT THE BALANCE OF 1787 01:07:16,461 --> 01:07:17,529 TRANSMISSION. 1788 01:07:17,529 --> 01:07:19,097 BUT ACTUALLY TRANSMISSION IS WAY 1789 01:07:19,097 --> 01:07:20,232 MORE COMPLICATED, RIGHT? 1790 01:07:20,232 --> 01:07:22,634 WE ARE NOT IN THESE ISOLATED 1791 01:07:22,634 --> 01:07:25,237 SCENARIOS OF A DONOR RECIPIENT 1792 01:07:25,237 --> 01:07:30,108 SINGLE INTERACTION. 1793 01:07:30,108 --> 01:07:30,942 WE LIVE IN COMPLEX SITUATIONS. 1794 01:07:30,942 --> 01:07:35,280 WE GO TO COMPLEK PL COMPLEX PLAE 1795 01:07:35,280 --> 01:07:35,714 DIFFERENT. 1796 01:07:35,714 --> 01:07:37,149 WE HAVE A VARIETY OF DIFFERENT 1797 01:07:37,149 --> 01:07:38,250 TYPES OF INTERACTIONS. 1798 01:07:38,250 --> 01:07:39,951 WE HAVE CLOSE RANGE CONTACTS, 1799 01:07:39,951 --> 01:07:41,386 THERE ARE LONG-RANGE CONTACTS, 1800 01:07:41,386 --> 01:07:43,221 WE SIT NEXT TO PEOPLE AT 1801 01:07:43,221 --> 01:07:44,523 SEMINARS, WE TALK TO PEOPLE 1802 01:07:44,523 --> 01:07:47,826 ACROSS TABLES AT BARS, RIGHT? 1803 01:07:47,826 --> 01:07:50,095 OR WE'RE SHARING A SUBWAY CAR 1804 01:07:50,095 --> 01:07:50,462 DISTANCES APART. 1805 01:07:50,462 --> 01:07:53,365 ALL OF THESE SPACES SORT OF 1806 01:07:53,365 --> 01:07:54,166 CHANGE TRANSMISSION DYNAMICS. 1807 01:07:54,166 --> 01:07:55,000 ONE OF THE THINGS I'M REALLY 1808 01:07:55,000 --> 01:07:56,301 GOING TO TALK ABOUT HERE IS THAT 1809 01:07:56,301 --> 01:07:57,636 AT CLOSE RANGE, ALL MODES OF 1810 01:07:57,636 --> 01:07:58,770 TRANSMISSION ARE POSSIBLE. 1811 01:07:58,770 --> 01:08:00,272 WE TALK ABOUT CONTACT TRAPS 1812 01:08:00,272 --> 01:08:02,507 MISTRANSMISSION AS THOUGH THIS S 1813 01:08:02,507 --> 01:08:03,942 LAKE A WAY OF ONLY LOOKING AT 1814 01:08:03,942 --> 01:08:05,143 TOUCHING PHYSICAL THINGS, BUT 1815 01:08:05,143 --> 01:08:08,380 ACTUALLY IN REALITY, CLOSE RANGE 1816 01:08:08,380 --> 01:08:09,147 TRANSMISSION MEANS THAT YOU ARE 1817 01:08:09,147 --> 01:08:10,882 BEING EXPELLED AND EXPOSED TO 1818 01:08:10,882 --> 01:08:12,684 ALL OF THE AIR THAT SOMEONE PUTS 1819 01:08:12,684 --> 01:08:12,918 OUT. 1820 01:08:12,918 --> 01:08:14,419 AND ALL OF THOSE SIZE RANGES 1821 01:08:14,419 --> 01:08:16,788 HAVE A MUCH MORE HIGHER 1822 01:08:16,788 --> 01:08:19,624 EFFICIENCY OF GETTING INTO YOUR 1823 01:08:19,624 --> 01:08:20,692 RESPIRATORY TRACT BECAUSE YOU'RE 1824 01:08:20,692 --> 01:08:21,860 BREATHING IN THAT PLUME 1825 01:08:21,860 --> 01:08:25,597 IMMEDIATELY FROM THAT SOURCE. 1826 01:08:25,597 --> 01:08:26,898 THEN OF COURSE LONG RANGE 1827 01:08:26,898 --> 01:08:31,269 TRANSMISSION K IS CAN VARY IN 1828 01:08:31,269 --> 01:08:34,306 TERMS OF WHAT TYPES OF -- 1829 01:08:34,306 --> 01:08:35,974 EVERYBODY IS STARTING TO GO BACK 1830 01:08:35,974 --> 01:08:37,375 TO AND REALLY PUSH FORWARD THE 1831 01:08:37,375 --> 01:08:39,010 MODES OF TRANSMISSION, I AM 1832 01:08:39,010 --> 01:08:40,312 MOVING AWAY FROM THAT BECAUSE I 1833 01:08:40,312 --> 01:08:41,947 THINK WE HAVE DONE OURS SEFS A 1834 01:08:41,947 --> 01:08:43,081 DISSERVICE OF THINKING ABOUT 1835 01:08:43,081 --> 01:08:44,249 INDIVIDUAL MODES OF 1836 01:08:44,249 --> 01:08:45,650 TRANSMISSION, ISOLATING THEM AND 1837 01:08:45,650 --> 01:08:47,452 THEN TRYING TO DEFINE THEIR 1838 01:08:47,452 --> 01:08:48,987 IMPORTANCE WHEN IN REALITY WE 1839 01:08:48,987 --> 01:08:51,423 LIVE IN A SPACE WHERE ALL MODES 1840 01:08:51,423 --> 01:08:52,424 ARE FEASIBLE. 1841 01:08:52,424 --> 01:08:54,726 SO THAT'S JUST MY SOAP BOX. 1842 01:08:54,726 --> 01:08:56,795 THIS GETS BACK TO WE ARE 1843 01:08:56,795 --> 01:08:57,996 COMPLEX, ALL AGE RANGES OF 1844 01:08:57,996 --> 01:08:58,897 INDIVIDUALS HAVE DIFFERENT TYPES 1845 01:08:58,897 --> 01:09:01,166 OF BEHAVIORS, DIFFERENT TYPES OF 1846 01:09:01,166 --> 01:09:02,501 PRE-EXISTING IMMUNITY, DIFFERENT 1847 01:09:02,501 --> 01:09:04,436 TYPES OF MICROBIAL COMMUNITIES, 1848 01:09:04,436 --> 01:09:05,837 DIFFERENT TYPES OF ENVIRONMENTAL 1849 01:09:05,837 --> 01:09:07,372 PARAMETERS THAT WE LIVE IN. 1850 01:09:07,372 --> 01:09:09,007 EVERYONE HAS MINGS MENGSED, I'M 1851 01:09:09,007 --> 01:09:11,143 GOING TO TALK ABOUT DAYCARES, I 1852 01:09:11,143 --> 01:09:12,177 PROMISE BUT START OFF BY SAYING 1853 01:09:12,177 --> 01:09:13,578 WE HAVE TO RE-THINK THE WHOLE 1854 01:09:13,578 --> 01:09:14,646 SYSTEM. 1855 01:09:14,646 --> 01:09:15,580 SO THIS IS WHAT I'VE ACTUALLY 1856 01:09:15,580 --> 01:09:17,349 BEEN DOING FOR THE PAST 10 1857 01:09:17,349 --> 01:09:19,951 YEARS, IS THINKING ABOUT WHEN I 1858 01:09:19,951 --> 01:09:21,553 STARTED IN 2009, THERE WERE A 1859 01:09:21,553 --> 01:09:22,988 HANDFUL OF OTHER GROUPS THAT DID 1860 01:09:22,988 --> 01:09:23,955 TRANSMISSION AND WE ALL WERE 1861 01:09:23,955 --> 01:09:25,257 DOING THEM THE SAME WAY. 1862 01:09:25,257 --> 01:09:26,992 AND WHEN I REALIZED IN 2015, I 1863 01:09:26,992 --> 01:09:29,194 WAS LIKE, WE CAN'T KEEP DOING IT 1864 01:09:29,194 --> 01:09:29,828 THE SAME WAY. 1865 01:09:29,828 --> 01:09:32,230 WE'VE GOT TO REALLY RETHINK HOW 1866 01:09:32,230 --> 01:09:33,999 WE AS HUMANS SPREAD VIRUSES TO 1867 01:09:33,999 --> 01:09:35,367 OTHER HUMANS, IF THAT'S OUR 1868 01:09:35,367 --> 01:09:36,268 QUESTION, IF THAT'S WHAT WE'RE 1869 01:09:36,268 --> 01:09:40,505 TRYING TO GET AT, THEN WITH WE E 1870 01:09:40,505 --> 01:09:42,607 TO DESIGN OUR MODEL SYSTEMS TO 1871 01:09:42,607 --> 01:09:43,475 RECAPITULATE THAT. 1872 01:09:43,475 --> 01:09:45,310 SOME OF THE THINGS MY LAB HAS 1873 01:09:45,310 --> 01:09:46,511 THOUGHT ABOUT ARE HERE. 1874 01:09:46,511 --> 01:09:48,947 PRE-EXISTING IMMUNITY, WE'RE NOT 1875 01:09:48,947 --> 01:09:49,881 IMMUNOLOGICALLY NIGH EE. WE'VE 1876 01:09:49,881 --> 01:09:50,982 WORKED ON MICROBIAL COMMUNITIES 1877 01:09:50,982 --> 01:09:53,084 WITH STACEY, WE WORK ON A 1878 01:09:53,084 --> 01:09:54,319 VARIETY OF ENVIRONMENTAL 1879 01:09:54,319 --> 01:09:55,487 PARAMETERS TRYING TO UNDERSTAND 1880 01:09:55,487 --> 01:09:56,555 HOW THAT INFLUENCES TRANSMISSION 1881 01:09:56,555 --> 01:09:59,858 DYNAMICS AND THEN BEHAVIORS OF 1882 01:09:59,858 --> 01:10:01,026 INDIVIDUALS AND PEOPLE AND HOW 1883 01:10:01,026 --> 01:10:05,163 THAT CAN BE INFLUENCED. 1884 01:10:05,163 --> 01:10:06,898 SO WE USED THE FERRET MODEL 1885 01:10:06,898 --> 01:10:09,534 SYSTEM, I'M TALK ABOUT WHY, 1886 01:10:09,534 --> 01:10:10,969 DIEGO INTRODUCED IT, IT'S BEEN 1887 01:10:10,969 --> 01:10:12,771 INTRODUCED BY OTHERS, I'LL TELL 1888 01:10:12,771 --> 01:10:13,905 YOU WHY I LIKE IT. 1889 01:10:13,905 --> 01:10:15,340 BUT I WILL SAY, THIS IS 1890 01:10:15,340 --> 01:10:16,208 SOMETHING STACEY BROUGHT UP IN 1891 01:10:16,208 --> 01:10:18,076 THE OPENING AND I TOTALLY AGREE, 1892 01:10:18,076 --> 01:10:19,911 IS THAT SOMETIMES THE PRIMARY 1893 01:10:19,911 --> 01:10:21,580 MODEL IS ACTUALLY HUMANS. 1894 01:10:21,580 --> 01:10:23,348 AND SO I WILL SAY IN THE LAST 1895 01:10:23,348 --> 01:10:25,183 FEW YEARS, THE THING THAT MY LAB 1896 01:10:25,183 --> 01:10:26,184 IS ALSO PUSHING FORWARD IS 1897 01:10:26,184 --> 01:10:27,819 ACTUALLY A HUMAN TRANSMISSION 1898 01:10:27,819 --> 01:10:30,522 MODEL, USING CONTROLLED HUMAN 1899 01:10:30,522 --> 01:10:31,857 INFECTIONS TO DETERMINE HOW 1900 01:10:31,857 --> 01:10:33,558 VIRUSES ACTUALLY SPREAD IN 1901 01:10:33,558 --> 01:10:33,892 HUMANS. 1902 01:10:33,892 --> 01:10:35,160 SO THAT WE CAN UNDERSTAND 1903 01:10:35,160 --> 01:10:36,628 WHETHER OUR MODEL SYSTEMS ARE 1904 01:10:36,628 --> 01:10:38,063 ACTUALLY ACCURATE. 1905 01:10:38,063 --> 01:10:40,098 WE SPEND SO MUCH MONEY, WE SPEND 1906 01:10:40,098 --> 01:10:42,067 SO MUCH TIME DOING TRANSMISSION 1907 01:10:42,067 --> 01:10:43,969 IN ANIMAL MODEL, AND IF THAT 1908 01:10:43,969 --> 01:10:45,904 DOES NOT ACTUALLY RECAPITULATE 1909 01:10:45,904 --> 01:10:49,374 WHAT IS HAPPENING IN HUMANS, 1910 01:10:49,374 --> 01:10:51,276 HAVE WE REALLY PUSHED FORWARD? 1911 01:10:51,276 --> 01:10:52,677 THAT'S REALLY IMPORTANT TO ME. 1912 01:10:52,677 --> 01:10:54,713 SO TRANSMISSION IN HUMANS, WHY 1913 01:10:54,713 --> 01:10:55,914 DO I LIKE THEM? 1914 01:10:55,914 --> 01:10:57,616 THEY'RE SUSCEPTIBLE TO HUMAN 1915 01:10:57,616 --> 01:10:59,818 INFLUENZA VIRUSES, I CAN TAKE A 1916 01:10:59,818 --> 01:11:01,920 CLINICAL ISOLATE, GIVE TO 1917 01:11:01,920 --> 01:11:03,355 FERRETS AND LOOK AT TRANSMISSION 1918 01:11:03,355 --> 01:11:03,688 PHENOTYPES. 1919 01:11:03,688 --> 01:11:05,290 IT HAS A SIMILAR RESPIRATORY 1920 01:11:05,290 --> 01:11:11,196 TRACT TO HUMANS, FIVE LUNG 1921 01:11:11,196 --> 01:11:19,738 CLOA --SIMILAR SIGNS, THEY SNEEY 1922 01:11:19,738 --> 01:11:20,138 LOSE WEIGHT. 1923 01:11:20,138 --> 01:11:22,674 WE HAVE A REALLY NICE REVISED 1924 01:11:22,674 --> 01:11:26,711 SCORING SYSTEM, WE HAVE A NICE 1925 01:11:26,711 --> 01:11:27,879 PAPER WE PUT TOGETHER WITH 1926 01:11:27,879 --> 01:11:32,484 STACEY ACTUALLY THAT REALLY 1927 01:11:32,484 --> 01:11:34,152 HIGHLIGHTS THIS, SO YOU CAN 1928 01:11:34,152 --> 01:11:35,520 ACTUALLY BREAK DOWN BASED ON THE 1929 01:11:35,520 --> 01:11:37,055 SEVERITY OF DIFFERENT SYMPTOMS 1930 01:11:37,055 --> 01:11:38,690 AND HAVE A REALLY NICE BAR GRAPH 1931 01:11:38,690 --> 01:11:40,558 TO LOOK AT THE TYPES OF 1932 01:11:40,558 --> 01:11:41,760 DIFFERENT DISEASES THAT ARE 1933 01:11:41,760 --> 01:11:43,261 ASSOCIATED WITH VIRAL INFECTIONS 1934 01:11:43,261 --> 01:11:45,797 IN FERRETS. 1935 01:11:45,797 --> 01:11:47,799 THEN THEY EXHALE INFECTIOUS 1936 01:11:47,799 --> 01:11:48,300 VIRUS INTO THE AIR. 1937 01:11:48,300 --> 01:11:49,868 SO WHAT WE CAN DO IN MY LAB, 1938 01:11:49,868 --> 01:11:50,969 BECAUSE I DO CARE A LOT ABOUT 1939 01:11:50,969 --> 01:11:52,771 THE VIRUS IN THE ENVIRONMENT, IS 1940 01:11:52,771 --> 01:11:54,606 THAT WE'VE SPENT A LOT OF TIME 1941 01:11:54,606 --> 01:11:56,374 FIGURING OUT WAYS TO ASSESS THE 1942 01:11:56,374 --> 01:11:57,242 VIRUS IN THE ENVIRONMENT. 1943 01:11:57,242 --> 01:11:58,843 SO HERE IS OUR FERRET, IT'S IN 1944 01:11:58,843 --> 01:12:03,682 ONE OF OUR CHAMBER BOXES. 1945 01:12:03,682 --> 01:12:05,550 THIS IS A TYPE OF AEROSOL 1946 01:12:05,550 --> 01:12:08,253 SAMPLER CALLED A BIOSPOT. 1947 01:12:08,253 --> 01:12:10,889 IT IS A LIQUID CONDENSED AEROSOL 1948 01:12:10,889 --> 01:12:11,957 SAMPLER, SO WHAT THAT MEANS IS 1949 01:12:11,957 --> 01:12:13,291 THIS IS PULLING IN -- THIS IS 1950 01:12:13,291 --> 01:12:16,594 NOT THE VIVUS BUT IT'S AN OLDER 1951 01:12:16,594 --> 01:12:19,698 VERSION PULLING IN AT 2 L 2-LITS 1952 01:12:19,698 --> 01:12:20,932 PER MINUTE, IT GOES INTO THIS 1953 01:12:20,932 --> 01:12:22,667 PORT HERE, IT'S CONNECTED TO 1954 01:12:22,667 --> 01:12:24,336 HERE, AND THEN THE LIQUID GETS 1955 01:12:24,336 --> 01:12:25,403 ADDED TO ALL THE DIFFERENT 1956 01:12:25,403 --> 01:12:26,738 AEROSOLS AND IT GETS COLLECTED 1957 01:12:26,738 --> 01:12:29,341 INTO LIQUID SO WE COLLECT FOR 1958 01:12:29,341 --> 01:12:32,744 JUST 10 MINUTES. 1959 01:12:32,744 --> 01:12:34,713 WE DO IT EVERY DAY BEFORE WE 1960 01:12:34,713 --> 01:12:35,613 NASAL-WASH THE FERRETS. 1961 01:12:35,613 --> 01:12:37,749 HERE I'M WATCHING THE INFECTIOUS 1962 01:12:37,749 --> 01:12:39,617 VIRUS TITER JUST FROM THE AIR OF 1963 01:12:39,617 --> 01:12:40,318 THESE ANIMALS. 1964 01:12:40,318 --> 01:12:43,121 THIS IS INFECTED WITH THE 1965 01:12:43,121 --> 01:12:45,623 H1N1 PANDEMIC MY VUS, THIS IS -- 1966 01:12:45,623 --> 01:12:48,026 PER TOTAL SAMPLE, WHICH IS ABOUT 1967 01:12:48,026 --> 01:12:48,493 750 MICRO LITERS. 1968 01:12:48,493 --> 01:12:49,894 WE HAVE A VARIETY OF OTHER 1969 01:12:49,894 --> 01:12:51,029 SYSTEMS THAT WE USE AND I'M 1970 01:12:51,029 --> 01:12:51,863 HAPPY TO TALK ABOUT THAT PPED A 1971 01:12:51,863 --> 01:12:53,631 I'LL TALK ABOUT THAT IN THE 1972 01:12:53,631 --> 01:12:55,166 DAYCARE SETTING TOO, BUT WE'RE 1973 01:12:55,166 --> 01:12:56,134 REALLY INTERESTED IN THIS 1974 01:12:56,134 --> 01:12:57,635 PROBLEM AND HAPPY TO HELP OTHERS 1975 01:12:57,635 --> 01:13:00,605 SORT OF FIGURE OUT WAYS TO 1976 01:13:00,605 --> 01:13:01,473 SAMPLE AIR IN THE ENVIRONMENT AS 1977 01:13:01,473 --> 01:13:01,940 WELL. 1978 01:13:01,940 --> 01:13:02,774 OKAY. 1979 01:13:02,774 --> 01:13:05,510 SO LET'S TALK ABOUT OUR 1980 01:13:05,510 --> 01:13:07,245 CLASSICAL TRANSMISSION MODELS 1981 01:13:07,245 --> 01:13:08,780 FOR FERRETS IS THIS SORT OF 1982 01:13:08,780 --> 01:13:10,015 DEVICE HERE WHERE THERE'S A 1983 01:13:10,015 --> 01:13:13,485 SINGLE DONOR, THERE'S A 1984 01:13:13,485 --> 01:13:14,819 RECIPIENT, YOU'LL SEE THIS IN MY 1985 01:13:14,819 --> 01:13:16,654 TALKS AS WELL, AND THERE ARE 1986 01:13:16,654 --> 01:13:17,756 PERFORATIONS THAT SORT OF 1987 01:13:17,756 --> 01:13:19,624 SEPARATE THESE ANIMALS SO THEY 1988 01:13:19,624 --> 01:13:20,392 DON'T HAVE ANY DIRECT COULD BE 1989 01:13:20,392 --> 01:13:22,794 TACT AND THERE IS DIRECTIONAL 1990 01:13:22,794 --> 01:13:23,261 AIR FLOW. 1991 01:13:23,261 --> 01:13:25,196 AT LEAST IN MY SYSTEM FROM THE 1992 01:13:25,196 --> 01:13:27,165 DONOR TO THE RECIPIENT. 1993 01:13:27,165 --> 01:13:28,066 TRADITIONALLY THESE HAVE BEEN 1994 01:13:28,066 --> 01:13:30,335 DONE FOR 14 CONSECUTIVE DAYS. 1995 01:13:30,335 --> 01:13:32,303 THIS IS A 2 BY 2 BOX. 1996 01:13:32,303 --> 01:13:35,607 WHEN I GIVE THESE TALKS, IMAGINE 1997 01:13:35,607 --> 01:13:38,009 A 2 BY 2 BOX AND IMAGINE YOU'RE 1998 01:13:38,009 --> 01:13:39,744 SITTING IN HALF OF THAT 2 BY 1999 01:13:39,744 --> 01:13:41,746 2 BOX FOR 14 DAYS AND 13 NIGHTS. 2000 01:13:41,746 --> 01:13:43,815 COULD YOU IMAGINE, WHO LIVES -- 2001 01:13:43,815 --> 01:13:45,216 ANYBODY WHO HAS ACTUALLY DONE 2002 01:13:45,216 --> 01:13:46,184 THAT AS LIKE A THOUGHT 2003 01:13:46,184 --> 01:13:47,919 EXPERIMENT OR HAS LIVED THAT 2004 01:13:47,919 --> 01:13:49,788 LIFE, RAISE YOUR HAND. 2005 01:13:49,788 --> 01:13:50,688 NO ONE, RIGHT? 2006 01:13:50,688 --> 01:13:52,323 WE DON'T -- THAT'S NOT HOW WE 2007 01:13:52,323 --> 01:13:52,724 LIVE. 2008 01:13:52,724 --> 01:13:54,225 SO THIS IS A REALLY ARTIFICIAL 2009 01:13:54,225 --> 01:13:57,662 SYSTEM. 2010 01:13:57,662 --> 01:14:00,598 WE ALSO USE IMMUNOLOGICALLY 2011 01:14:00,598 --> 01:14:01,266 NAIVE ANIMALS. 2012 01:14:01,266 --> 01:14:04,769 THIS IS ALL THE PANDEMIC 2013 01:14:04,769 --> 01:14:08,606 PREPAREDNESS -- USE IMEU 2014 01:14:08,606 --> 01:14:11,342 KNOWLEDGEICALLY IMMUNE ANIMALS. 2015 01:14:11,342 --> 01:14:13,178 THEN DIRECTIONAL AIR FLOW AT 2016 01:14:13,178 --> 01:14:18,049 HIGH AIR CHANGE RATES. 2017 01:14:18,049 --> 01:14:20,618 THEY ACTUALLY DID A CROSS 2018 01:14:20,618 --> 01:14:22,620 CENTER, CROSS LAB EXPERIMENT 2019 01:14:22,620 --> 01:14:24,456 USING I THINK IT WAS 11 2020 01:14:24,456 --> 01:14:26,524 DIFFERENT LABS THAT DO AEROSOL 2021 01:14:26,524 --> 01:14:28,393 TRANSMISSION EXPERIMENTS WITH 2022 01:14:28,393 --> 01:14:29,694 FERRETS THAT HAVE DIFFERENT 2023 01:14:29,694 --> 01:14:31,029 SETUPS TO SORT OF COMPARE ACROSS 2024 01:14:31,029 --> 01:14:32,897 THEM, AND THE AIR EXCHANGE RATES 2025 01:14:32,897 --> 01:14:36,067 RANGE FROM 11 TO 35. 2026 01:14:36,067 --> 01:14:37,035 SO THAT IS HUGE. 2027 01:14:37,035 --> 01:14:38,803 I WILL SAY IN A SPACE LIKE THIS, 2028 01:14:38,803 --> 01:14:40,004 GIVEN THE VAULTED CEILINGS, 2029 01:14:40,004 --> 01:14:41,773 WE'RE PROBABLY LOOKING AT AN AIR 2030 01:14:41,773 --> 01:14:42,841 EXCHANGE RATE OF ABOUT -- IF WE 2031 01:14:42,841 --> 01:14:45,110 WERE TO TRY TO MEASURE, ABOUT 5, 2032 01:14:45,110 --> 01:14:45,944 RIGHT? 2033 01:14:45,944 --> 01:14:47,645 SO THAT'S FIVE AIR CHANGES PER 2034 01:14:47,645 --> 01:14:47,846 HOUR. 2035 01:14:47,846 --> 01:14:49,948 THAT'S ABOUT REASONABLE, IT'S 2036 01:14:49,948 --> 01:14:51,382 ACTUALLY PRETTY HIGH FOR AN 2037 01:14:51,382 --> 01:14:51,916 OFFICE BUILDING. 2038 01:14:51,916 --> 01:14:52,917 THAT'S WHAT IT FEELS LIKE AT 2039 01:14:52,917 --> 01:14:54,219 LEAST WITH THE VOLUME OF AIR IN 2040 01:14:54,219 --> 01:14:55,753 THIS SPACE. 2041 01:14:55,753 --> 01:14:58,623 MOST DAYCARE CENTERS OR OFFICE 2042 01:14:58,623 --> 01:15:02,961 BUILD THATION AREBUILDINGS THATE 2043 01:15:02,961 --> 01:15:04,596 LESS THAN 1 AIR EXCHANGE PER 2044 01:15:04,596 --> 01:15:06,764 HOUR AND HOSPITALS RUN AT ABOUT 2045 01:15:06,764 --> 01:15:07,966 6 TO 11, RIGHT? 2046 01:15:07,966 --> 01:15:08,500 OSHA REQUIREMENTS. 2047 01:15:08,500 --> 01:15:10,168 JUST TO GIVE EVERYBODY A SETUP 2048 01:15:10,168 --> 01:15:10,802 OF WHERE WE ARE. 2049 01:15:10,802 --> 01:15:11,803 SO THE WAY WE'VE DONE THIS IS 2050 01:15:11,803 --> 01:15:13,538 THAT WE INFECT THE FERRET, THIS 2051 01:15:13,538 --> 01:15:14,873 IS SORT OF TRADITIONAL HERE, 2052 01:15:14,873 --> 01:15:17,408 RIGHT, YOU INFECT A FERRET ON 2053 01:15:17,408 --> 01:15:17,842 DAY ZERO. 2054 01:15:17,842 --> 01:15:21,779 24 DAYS LATER, YOU PUT THE NAIVE 2055 01:15:21,779 --> 01:15:23,047 RECIPIENT IN THE OTHER PART OF 2056 01:15:23,047 --> 01:15:23,314 THE CAGE. 2057 01:15:23,314 --> 01:15:25,717 YOU DO THE CLASSICAL EXPOSURE 2058 01:15:25,717 --> 01:15:26,618 FOR 14 DAYS. 2059 01:15:26,618 --> 01:15:28,453 EVERY OTHER DAY YOU PULL THEM 2060 01:15:28,453 --> 01:15:31,189 OUT, NASAL WASH THEM, WEIGH 2061 01:15:31,189 --> 01:15:33,391 THEM, AND DAY 14 YOU COLLECT 2062 01:15:33,391 --> 01:15:34,259 SERUM. 2063 01:15:34,259 --> 01:15:37,428 THIS WAS PUBLISHED IN A PAPER IN 2064 01:15:37,428 --> 01:15:40,932 2012 -- SORRY, 2021, OH GOSH, 2065 01:15:40,932 --> 01:15:42,567 THAT WE LOOKED AT THE DIFFERENT 2066 01:15:42,567 --> 01:15:44,169 TIMINGS OF EXPOSURE. 2067 01:15:44,169 --> 01:15:46,871 SO WE DID A 7-DAY -- WE THOUGHT 2068 01:15:46,871 --> 01:15:50,074 14 WAS RIDICULOUS, THEN WE DID A 2069 01:15:50,074 --> 01:15:51,209 TWO-DAY SHORT, WHICH I CONSIDER 2070 01:15:51,209 --> 01:15:53,778 BEING A WEEKEND. 2071 01:15:53,778 --> 01:15:57,682 SAY YOU'RE STUCK IN A 2-BEDROOM 2072 01:15:57,682 --> 01:15:58,583 CONDO WITH SOMEBODY FOR THE 2073 01:15:58,583 --> 01:15:59,017 WEEKEND. 2074 01:15:59,017 --> 01:16:00,418 I CALLED IT A SLEEPOVER, BUT 2075 01:16:00,418 --> 01:16:01,619 BASICALLY WE DID A SLEEPOVER, 2076 01:16:01,619 --> 01:16:03,021 BUT WE DID IT FOR FIVE NIGHTS. 2077 01:16:03,021 --> 01:16:04,222 WHAT WE WERE TRYING TO MIMIC 2078 01:16:04,222 --> 01:16:06,858 HERE WAS LIKE I GO TO WORK AND I 2079 01:16:06,858 --> 01:16:08,626 SHARE A SMALL OFFICE WITH 2080 01:16:08,626 --> 01:16:12,964 SOMEONE EVERY DAY FOR FIVE DAYS, 2081 01:16:12,964 --> 01:16:14,732 FROM MONDAY TO FRIDAY. 2082 01:16:14,732 --> 01:16:16,901 BUT SINCE FERRETS ARE NOCTURNAL, 2083 01:16:16,901 --> 01:16:18,336 WE DID IT AT NIGHT, SO THAT'S 2084 01:16:18,336 --> 01:16:21,105 WHY IT'S LIKE A SLEEPOVER. 2085 01:16:21,105 --> 01:16:25,577 WE DID THIS FOR THE SEASONAL 2086 01:16:25,577 --> 01:16:26,878 2009H1N1. 2087 01:16:26,878 --> 01:16:29,380 AND SEASONAL -- I'M JUST GOING 2088 01:16:29,380 --> 01:16:30,048 TO SUMMARIZE THIS HERE. 2089 01:16:30,048 --> 01:16:31,616 WHAT WE FOUND IS THAT IN THE 2090 01:16:31,616 --> 01:16:35,053 2009 PANDEMIC, ALL OF -- IN 2091 01:16:35,053 --> 01:16:35,954 EVERY SYSTEM WE TESTED THAT 2092 01:16:35,954 --> 01:16:38,156 VIRUS LOVES TO TRANSMIT, THIS IS 2093 01:16:38,156 --> 01:16:40,758 WHY FOR A VIRUS THIS IS 2094 01:16:40,758 --> 01:16:41,459 FANTASTIC IN FERRETS. 2095 01:16:41,459 --> 01:16:43,428 IT'S REALLY HARD TO GET THAT 2096 01:16:43,428 --> 01:16:46,064 VIRUS NOT TO TRANSMIT. 2097 01:16:46,064 --> 01:16:51,836 THEN THE SEASONAL -- ALSO HAD 2098 01:16:51,836 --> 01:16:52,937 REALLY HIGH EFFICIENT 2099 01:16:52,937 --> 01:16:53,471 TRANSMISSION. 2100 01:16:53,471 --> 01:16:55,873 I WILL SAY WE'VE MOVED TO TWO 2101 01:16:55,873 --> 01:16:58,409 DAYS SHORT BECAUSE I THINK IT 2102 01:16:58,409 --> 01:16:59,911 STREAMLINES EVERYTHING IN TERMS 2103 01:16:59,911 --> 01:17:02,914 OF HUSBANDRY, IN TERMS OF 2104 01:17:02,914 --> 01:17:04,849 PERSONNEL, SO WE'VE NOW MOVED TO 2105 01:17:04,849 --> 01:17:06,818 DOING TWO-DAY EXPOSURES FOR OUR 2106 01:17:06,818 --> 01:17:07,518 STUDIES, SO I'LL TALK ABOUT 2107 01:17:07,518 --> 01:17:08,486 THAT. 2108 01:17:08,486 --> 01:17:10,688 WE THINK THAT'S MAYBE NOT AS 2109 01:17:10,688 --> 01:17:12,290 GREAT AS WHERE WE ARE WHAT 2110 01:17:12,290 --> 01:17:14,826 HUMANS LIVE IN, BUT IT'S BETTER 2111 01:17:14,826 --> 01:17:15,126 THAN 14. 2112 01:17:15,126 --> 01:17:16,761 AND THEN THE OTHER THING I'LL 2113 01:17:16,761 --> 01:17:18,730 MOVE ON TO IS PRE-EXISTING 2114 01:17:18,730 --> 01:17:19,430 IMMUNITY. 2115 01:17:19,430 --> 01:17:20,932 THIS IS A PICTURE OF MY KIDS 2116 01:17:20,932 --> 01:17:22,834 AROUND THE AGE OF 5, SO WE KNOW 2117 01:17:22,834 --> 01:17:25,670 FROM REALLY NICE COHORT STUDIES 2118 01:17:25,670 --> 01:17:27,272 DONE BOTH IN EUROPE AND THE U.S. 2119 01:17:27,272 --> 01:17:29,340 THAT PREDOMINANTLY BY THE AGE OF 2120 01:17:29,340 --> 01:17:31,209 5, WE'VE ALL EXPERIENCED 2121 01:17:31,209 --> 01:17:32,377 INFLUENZA, EITHER FROM NATURAL 2122 01:17:32,377 --> 01:17:33,511 INFECTION OR FROM VACCINATION. 2123 01:17:33,511 --> 01:17:36,080 SO THIS WORK DONE BY KATIE 2124 01:17:36,080 --> 01:17:39,417 GOSTIC AND SARAH COBE AND JAMIE 2125 01:17:39,417 --> 01:17:40,852 LLOYD SMITH AND OTHERS REALLY 2126 01:17:40,852 --> 01:17:41,719 NICELY SORT OF GIVE THE 2127 01:17:41,719 --> 01:17:43,488 PROBABILITY BASED ON YOUR BIRTH 2128 01:17:43,488 --> 01:17:45,757 YEAR OF WHAT YOUR INITIAL VIRAL 2129 01:17:45,757 --> 01:17:47,959 INFECTION PO POTENTIALLY WAS. 2130 01:17:47,959 --> 01:17:49,227 SO I REALLY LIKE THIS BECAUSE IT 2131 01:17:49,227 --> 01:17:50,495 SORT OF HIGHLIGHTS THAT IF YOU 2132 01:17:50,495 --> 01:17:51,896 WERE LIKE ME AND YOU'RE BORN IN 2133 01:17:51,896 --> 01:17:55,400 THE 80s, YOU PREDOMINANTLY 2134 01:17:55,400 --> 01:17:57,935 HAVE AN H3N2 INITIAL PRIMING 2135 01:17:57,935 --> 01:18:00,338 IMMUNE RESPONSE VERSUS AN H1N1. 2136 01:18:00,338 --> 01:18:03,941 BUT IF YOU WERE BORN MAYBE IN 2137 01:18:03,941 --> 01:18:05,810 2009, THESE YOUNG ONES HERE, 2138 01:18:05,810 --> 01:18:07,445 THEY HAVE A MUCH MORE 2139 01:18:07,445 --> 01:18:09,414 PREDOMINANT AGE 1 PRIMARY 2140 01:18:09,414 --> 01:18:10,848 INFECTION VERSUS THE ELDERLY. 2141 01:18:10,848 --> 01:18:12,817 SO THIS IS IMPORTANT BECAUSE 2142 01:18:12,817 --> 01:18:13,985 TRANSMISSION OF BOTH SEASONAL 2143 01:18:13,985 --> 01:18:17,755 AND PANDEMIC INFLUENZA VIRUSES 2144 01:18:17,755 --> 01:18:19,057 OCCURS IN THE CONTEXT OF 2145 01:18:19,057 --> 01:18:20,458 PRE-EXISTING IMMUNITY FROM 2146 01:18:20,458 --> 01:18:21,793 SEASONAL VIRUSES, RIGHT? 2147 01:18:21,793 --> 01:18:25,263 LIKE THAT IS -- THAT SHOULD BE 2148 01:18:25,263 --> 01:18:27,365 OBVIOUS TO ESH. 2149 01:18:27,365 --> 01:18:27,799 EVERYBODY. 2150 01:18:27,799 --> 01:18:29,233 SO WHEN WE TALK ABOUT 2151 01:18:29,233 --> 01:18:30,568 TRANSMISSION FITNESSES OF BOTH 2152 01:18:30,568 --> 01:18:33,271 SEASONAL VIRUSES AND EMERGING 2153 01:18:33,271 --> 01:18:34,806 PANDEMIC THREATS, THEY SHOULD 2154 01:18:34,806 --> 01:18:36,507 ALWAYS BE DONE IN THE CONTEXT OF 2155 01:18:36,507 --> 01:18:37,041 PRE-EXISTING IMMUNITY. 2156 01:18:37,041 --> 01:18:39,510 SO WE STARTED WITH THIS IDEA OF 2157 01:18:39,510 --> 01:18:41,145 SEASONAL INFECTIONS, BECAUSE 2158 01:18:41,145 --> 01:18:44,215 OBVIOUSLY H3N2 STILL TRANSMITS 2159 01:18:44,215 --> 01:18:48,052 AND H1N1 STILL TRANSMITS EACH 2160 01:18:48,052 --> 01:18:50,788 YEAR IN ALL THIS PRE-EXISTING 2161 01:18:50,788 --> 01:18:51,756 IMMUNITY IN THE POPULATION. 2162 01:18:51,756 --> 01:18:53,858 SO WE DID THIS EXPERIMENT AGAIN 2163 01:18:53,858 --> 01:18:55,626 WHERE WE HAVE OUR TRANSMISSION 2164 01:18:55,626 --> 01:18:57,128 SETUP HERE, AND THIS IS WHAT OUR 2165 01:18:57,128 --> 01:18:59,464 CAGING SYSTEM LOOKS LIKE AND 2166 01:18:59,464 --> 01:19:00,765 I'LL SHOW YOU OUR STUDY DESIGN 2167 01:19:00,765 --> 01:19:03,167 IN A MINUTE, BUT WE HAVE THESE 2168 01:19:03,167 --> 01:19:05,536 NICE ALLENTOWN CAGES, I DESIGNED 2169 01:19:05,536 --> 01:19:07,071 THEM WHEN I WAS A POSTDOC AT THE 2170 01:19:07,071 --> 01:19:08,539 NIH AND WE STILL USE THEM NOW. 2171 01:19:08,539 --> 01:19:10,174 I MADE SOME MODIFICATIONS, BUT 2172 01:19:10,174 --> 01:19:13,845 THE PERFORATION BARRIERS ARE ONE 2173 01:19:13,845 --> 01:19:15,012 INCH APART AND THE PERFORATIONS 2174 01:19:15,012 --> 01:19:17,415 ARE OFFSET SO THAT THERE IS 2175 01:19:17,415 --> 01:19:18,516 REALLY WHAT WE'RE SHOWING HERE 2176 01:19:18,516 --> 01:19:20,585 IS LARGER AEROSOL DYNAMICS. 2177 01:19:20,585 --> 01:19:22,019 WE'VE HAD SOME AEROSOL 2178 01:19:22,019 --> 01:19:22,954 COLLABORATORS WORK WITH US TO 2179 01:19:22,954 --> 01:19:24,555 TRY TO FIGURE OUT WHAT THE 2180 01:19:24,555 --> 01:19:26,190 AEROSOL SIZE IS THAT REALLY GETS 2181 01:19:26,190 --> 01:19:27,325 ACROSS BUT IT PROBABLY ANYTHING 2182 01:19:27,325 --> 01:19:29,360 THAT'S SMALLER THAN 10 OR 2183 01:19:29,360 --> 01:19:36,567 15 MICRONS IS GETTING ACROSS. 2184 01:19:36,567 --> 01:19:38,236 SO WHAT WE DECIDED TO DO TO TEST 2185 01:19:38,236 --> 01:19:39,670 THE IMPACT OF PRE-EXISTING 2186 01:19:39,670 --> 01:19:41,305 IMMUNITY ON TRANSMISSION IS TO 2187 01:19:41,305 --> 01:19:44,809 LOOK AT -- TAKE DONOR AND 2188 01:19:44,809 --> 01:19:47,078 RECIPIENT ANIMALS AND GIVE THEM 2189 01:19:47,078 --> 01:19:48,079 A PRIMARY INFECTION. 2190 01:19:48,079 --> 01:19:50,381 SO AS STACEY MENTIONED, WE 2191 01:19:50,381 --> 01:19:52,350 PRESCREEN FERRETS TO MAKE SURE 2192 01:19:52,350 --> 01:19:57,021 THEY'RE SERONEGATIVE, AND THAT'S 2193 01:19:57,021 --> 01:19:58,589 BECAUSE I'D LOVE TO START BUYING 2194 01:19:58,589 --> 01:20:00,324 THE IMMUNE ONES THAT NOBODY ELSE 2195 01:20:00,324 --> 01:20:03,528 WANTS BUT I WANT TO KNOW THE 2196 01:20:03,528 --> 01:20:05,797 TIMING OF PRIMARY INFECTION TO 2197 01:20:05,797 --> 01:20:08,666 SECONDARY INFECTIONS CURRENTLY. 2198 01:20:08,666 --> 01:20:10,268 SO WE DO A PRIMARY INFECTION AND 2199 01:20:10,268 --> 01:20:12,170 THEN WE WAIT -- WE USED TO WAIT 2200 01:20:12,170 --> 01:20:14,372 60 DAYS, WE NOW WAIT UPWARDS OF 2201 01:20:14,372 --> 01:20:14,639 84 DAYS. 2202 01:20:14,639 --> 01:20:16,174 SO THIS IS THREE MONTHS. 2203 01:20:16,174 --> 01:20:19,744 THIS IS -- WE HAVE A FERRET 2204 01:20:19,744 --> 01:20:22,280 DAYCARE AS WELL AS A FERRET 2205 01:20:22,280 --> 01:20:26,517 STAYCATIO INSURE, A LITTLEN, A T 2206 01:20:26,517 --> 01:20:27,084 COMMITTEE WE'RE RUNNING. 2207 01:20:27,084 --> 01:20:28,586 SO WE HAVE THE ANIMAL, GIVE THEM 2208 01:20:28,586 --> 01:20:31,722 A PRIMARY INFORECAST, THREE INFE 2209 01:20:31,722 --> 01:20:32,924 MONTHS LATER, BRING THEM BACK 2210 01:20:32,924 --> 01:20:34,525 IN, GIVE THE DONOR A SECONDARY 2211 01:20:34,525 --> 01:20:35,960 INFECTION AND RECIPIENTS ARE 2212 01:20:35,960 --> 01:20:37,829 PLACED INTO A CAGE 24 LATER, AND 2213 01:20:37,829 --> 01:20:39,764 THEN WE DO A 2-DAY EXPOSURE. 2214 01:20:39,764 --> 01:20:42,667 WE STARTED OFF BY LOOKING -- 2215 01:20:42,667 --> 01:20:44,802 ASKING THIS QUESTION ABOUT 2216 01:20:44,802 --> 01:20:45,336 HETEROLOGOUS IMMUNITY. 2217 01:20:45,336 --> 01:20:47,638 IF YOU HAVE A PRIMARY 2218 01:20:47,638 --> 01:20:50,842 H1N1 INFECTION WHAT IS YOUR 2219 01:20:50,842 --> 01:20:53,878 SUSCEPTIBILITY TO 2220 01:20:53,878 --> 01:20:55,213 HDN2 TRANSMISSION AND VICE 2221 01:20:55,213 --> 01:20:56,414 VERSA. 2222 01:20:56,414 --> 01:21:00,751 SO THIS VIRUS IN 2009 EMERGED IN 2223 01:21:00,751 --> 01:21:04,355 THE CONTEXT OF BOTH PRE-EXISTING 2224 01:21:04,355 --> 01:21:07,191 H1N1 IMMUNITY FROM PRE2009 AND 2225 01:21:07,191 --> 01:21:07,658 H3N2 IMMUNITY. 2226 01:21:07,658 --> 01:21:08,759 SO I'M JUST GOING TO WALK 2227 01:21:08,759 --> 01:21:09,827 THROUGH SOME OF THE GRAPHS HERE. 2228 01:21:09,827 --> 01:21:11,762 SO THIS IS NO PRIOR IMMUNITIES 2229 01:21:11,762 --> 01:21:12,830 OF THE DONOR ANIMALS. 2230 01:21:12,830 --> 01:21:14,098 EACH BAR IS AN INDIVIDUAL 2231 01:21:14,098 --> 01:21:14,465 ANIMAL. 2232 01:21:14,465 --> 01:21:15,967 WE DID FOUR PAIRS. 2233 01:21:15,967 --> 01:21:17,435 AND HERE YOU'LL SEE THAT THIS 2234 01:21:17,435 --> 01:21:19,704 VIRUS TRANSMITS 100% -- SORRY, 2235 01:21:19,704 --> 01:21:22,874 THIS IS THREE PAIRS -- TO 100% 2236 01:21:22,874 --> 01:21:25,309 OF THE NAIVE RECIPIENTS AND EACH 2237 01:21:25,309 --> 01:21:29,146 LINE IN BLUE IS A RECIPIENT. 2238 01:21:29,146 --> 01:21:30,381 THEN THESE ANIMALS HERE ON THE 2239 01:21:30,381 --> 01:21:33,985 RIGHT-HAND SIDE HAVE A PRIOR 2240 01:21:33,985 --> 01:21:34,852 H3N2 IMMUNITY, BOTH THE DONORS 2241 01:21:34,852 --> 01:21:36,354 AND THE RECIPIENTS. 2242 01:21:36,354 --> 01:21:37,655 SO YOU'LL SEE FIRST THAT IF YOU 2243 01:21:37,655 --> 01:21:39,790 PUT A LOT OF VIRUS UP A FERRET 2244 01:21:39,790 --> 01:21:41,325 NOSE WITH PRE-EXISTING IMMUNITY, 2245 01:21:41,325 --> 01:21:43,261 THEY'LL SHED A LOT OF VIRUS 2246 01:21:43,261 --> 01:21:44,529 STILL FOR LOTS OF DAYS, BUT THEY 2247 01:21:44,529 --> 01:21:49,867 DO CLEAR THE VIRUS FASTER, VIRAL 2248 01:21:49,867 --> 01:21:52,303 CLEARANCE IS SHORTENED, THE 2249 01:21:52,303 --> 01:21:53,604 TIMING TO VIRAL CLEARANCE. 2250 01:21:53,604 --> 01:21:55,239 SO DAY 5, YOU'LL SEE THERE'S 2251 01:21:55,239 --> 01:21:57,074 LESS VIRUS IN PREIMMUNE FERRETS 2252 01:21:57,074 --> 01:21:57,942 COMPARED TO THOSE THAT DON'T 2253 01:21:57,942 --> 01:22:00,478 HAVE ANY PRE-EXISTING IMMUNITY. 2254 01:22:00,478 --> 01:22:01,679 AND THEN IN THIS EXPERIMENT THAT 2255 01:22:01,679 --> 01:22:03,915 WE'VE DONE, WE'VE DONE THIS MANY 2256 01:22:03,915 --> 01:22:05,116 TIMES AND TRANSMISSION 2257 01:22:05,116 --> 01:22:06,484 EFFICIENCIES HAVE ONLY GONE UP. 2258 01:22:06,484 --> 01:22:08,686 WE'VE GOT 2 OUT OF 3, IN 2259 01:22:08,686 --> 01:22:10,221 SUBSEQUENT ONES WE'VE GOT 3 OUT 2260 01:22:10,221 --> 01:22:10,555 OF 3. 2261 01:22:10,555 --> 01:22:12,089 BUT THIS IS CLASSIC REALLY 2262 01:22:12,089 --> 01:22:14,492 EFFICIENT TRANSMISSION. 2263 01:22:14,492 --> 01:22:17,128 SO H1N1 TRANSMITS IN THE CONTEXT 2264 01:22:17,128 --> 01:22:19,864 OF PRE-EXISTING IMMUNITY AGAIN 2265 01:22:19,864 --> 01:22:21,566 AFTER A TWO-DAY EXECUTIVE 2266 01:22:21,566 --> 01:22:22,199 EXPOSURE. 2267 01:22:22,199 --> 01:22:24,502 WHAT ABOUT H3N2? 2268 01:22:24,502 --> 01:22:27,638 SO HERE IS OUR NAIVE -- 2269 01:22:27,638 --> 01:22:29,106 IMMUNOLOGICALLY NAIVE FERRETS, 2270 01:22:29,106 --> 01:22:31,142 SO ALL OF THE DONOR ANIMALS SHED 2271 01:22:31,142 --> 01:22:32,810 VIRUS, ALL OF THE RECIPIENTS, WE 2272 01:22:32,810 --> 01:22:35,079 DID IN GROUPS OF 4, ALSO SHED 2273 01:22:35,079 --> 01:22:37,548 VIRUS AND WERE INFECTED. 2274 01:22:37,548 --> 01:22:39,283 AND THEN IF YOU HAVE 2275 01:22:39,283 --> 01:22:42,853 PRE-EXISTING H1N1 I ME1 IMMUNITH 2276 01:22:42,853 --> 01:22:44,488 IN THE DONORS AND RECIPIENTS, 2277 01:22:44,488 --> 01:22:47,491 YOU HAVE INCREASED CLEARANCE BY 2278 01:22:47,491 --> 01:22:48,859 DAY 5, YOU DO SHED A LOT OF 2279 01:22:48,859 --> 01:22:50,361 VIRUS IN THE DONORS BUT YOU HAVE 2280 01:22:50,361 --> 01:22:51,495 NO TRANSMISSION TO THE 2281 01:22:51,495 --> 01:22:53,297 RECIPIENTS. 2282 01:22:53,297 --> 01:22:54,432 IT'S REALLY FASCINATING. 2283 01:22:54,432 --> 01:22:57,168 THIS IS AIRBORNE TRANSMISSION. 2284 01:22:57,168 --> 01:22:58,736 SO WE ALSO THEN FURTHER MAP THIS 2285 01:22:58,736 --> 01:23:01,339 TO THE RECIPIENT IMMUNITY 2286 01:23:01,339 --> 01:23:01,672 SPECIFICALLY. 2287 01:23:01,672 --> 01:23:04,408 YOU COULD HAVE DONORS THAT ARE 2288 01:23:04,408 --> 01:23:06,811 IMMUNOLOGICALLY NAIVE AND THE 2289 01:23:06,811 --> 01:23:08,312 RECIPIENTS WERE THE ONES THAT 2290 01:23:08,312 --> 01:23:10,247 WERE CAUSING THIS GLOBAL 2291 01:23:10,247 --> 01:23:10,881 PROTECTION. 2292 01:23:10,881 --> 01:23:11,716 BUT YOU'RE THINKING IN YOUR 2293 01:23:11,716 --> 01:23:14,151 HEAD,S THAT INTERESTING BUT WE 2294 01:23:14,151 --> 01:23:16,253 GET H2N2, IT TRANSMITS ALL THE 2295 01:23:16,253 --> 01:23:18,556 TIME. 2296 01:23:18,556 --> 01:23:19,457 2017, 2018. 2297 01:23:19,457 --> 01:23:22,093 HUGE H3N2 SEASON, ALMOST 80,000 2298 01:23:22,093 --> 01:23:22,627 DEATHS THAT YEAR. 2299 01:23:22,627 --> 01:23:23,628 IT WAS A BAD YEAR. 2300 01:23:23,628 --> 01:23:25,129 SO WHAT HAPPENED? 2301 01:23:25,129 --> 01:23:26,464 SO LET'S THINK AGAIN ABOUT HOW 2302 01:23:26,464 --> 01:23:31,602 DO WE LIVE IN SPACES? 2303 01:23:31,602 --> 01:23:33,704 WE LIVE WITH COMPLEX BEHAVIORS, 2304 01:23:33,704 --> 01:23:35,673 WE LIVE IN COMPLEX ENVIRONMENTS. 2305 01:23:35,673 --> 01:23:37,408 SO AGAIN AT CLOSE RANGE, ALL 2306 01:23:37,408 --> 01:23:38,309 TRANSMISSION MODES ARE POSSIBLE. 2307 01:23:38,309 --> 01:23:40,478 SO WHAT WE DID WAS WE JUST DID 2308 01:23:40,478 --> 01:23:42,046 THE SAME EXPERIMENT BUT NOW 2309 01:23:42,046 --> 01:23:43,648 REMOVE THE BARRIER SO IT'S A 2310 01:23:43,648 --> 01:23:44,849 CONTACT TRANSMISSION EXPERIMENT, 2311 01:23:44,849 --> 01:23:47,284 TWO DAYS, YOU GET EFFICIENT 2312 01:23:47,284 --> 01:23:48,819 TRANSMISSION. 2313 01:23:48,819 --> 01:23:53,057 SO WHEN YOU HAVE ALL MODES OF 2314 01:23:53,057 --> 01:23:54,825 TRANSMISSION, THE BARRIER TO 2315 01:23:54,825 --> 01:23:55,693 INFECTION FROM PRE-EXISTING 2316 01:23:55,693 --> 01:24:00,197 IMMUNITY CAN BE OVERCOME. 2317 01:24:00,197 --> 01:24:02,066 YOU'RE GOING TO ASK ME IS IT A 2318 01:24:02,066 --> 01:24:03,834 DOSE ISSUE, IT'S NOT. 2319 01:24:03,834 --> 01:24:07,672 WE TRIED TO DO FD50 STUDIES AND 2320 01:24:07,672 --> 01:24:08,706 WE DON'T HAVE A BIG DIFFERENCE 2321 01:24:08,706 --> 01:24:11,709 IN TERMS OF THE INFECTIOUS DOSE 2322 01:24:11,709 --> 01:24:13,477 INTRANASALLY INOCULATED INTO AN 2323 01:24:13,477 --> 01:24:14,712 ANIMAL, BUT AGAIN, TRANSMISSION 2324 01:24:14,712 --> 01:24:19,183 IS NOT A BIG BOLUS OF VIRUS UP A 2325 01:24:19,183 --> 01:24:19,717 FERRET'S NOSE. 2326 01:24:19,717 --> 01:24:21,152 IT IS LOTS OF DIFFERENT AEROSOL 2327 01:24:21,152 --> 01:24:22,420 PARTICLES FALLING AT DIFFERENT 2328 01:24:22,420 --> 01:24:23,354 SITES WITHIN THE RESPIRATORY 2329 01:24:23,354 --> 01:24:24,689 TRACT AND INITIATING INFECTIONS 2330 01:24:24,689 --> 01:24:26,323 AND BEING SUCCESSFUL. 2331 01:24:26,323 --> 01:24:28,426 SO THERE'S A LOT OF COMPLEXITY 2332 01:24:28,426 --> 01:24:33,097 HERE. 2333 01:24:33,097 --> 01:24:34,765 SO BEFORE I MOVE ON TO THE 2334 01:24:34,765 --> 01:24:36,067 FERRET DAYCARE, WHAT THIS MEANS 2335 01:24:36,067 --> 01:24:37,268 I THINK THAT'S REALLY IMPORTANT 2336 01:24:37,268 --> 01:24:44,408 IS THAT SEASONAL VIRUSES HAVE 2337 01:24:44,408 --> 01:24:50,514 DIFFERENT AIRBORNE TRANSMISSION 2338 01:24:50,514 --> 01:24:51,949 IN DIFFERENT -- FORECASTING AND 2339 01:24:51,949 --> 01:24:53,150 PREDICTION MODELING AND ALL OF 2340 01:24:53,150 --> 01:24:54,785 THAT, WE SORT OF LUMP EVERYTHING 2341 01:24:54,785 --> 01:24:55,886 TOGETHER FOR INFLUENZA. 2342 01:24:55,886 --> 01:24:57,755 ALSO WE HAVE STARTED USING THIS 2343 01:24:57,755 --> 01:25:00,291 IN OUR NEW RISK ASSESSMENT 2344 01:25:00,291 --> 01:25:00,624 PIPELINE. 2345 01:25:00,624 --> 01:25:03,427 WE HAVE A NEW TRIAGE MANUSCRIPT 2346 01:25:03,427 --> 01:25:04,662 OUT FOR SWINE VIRUSES AND WE'VE 2347 01:25:04,662 --> 01:25:08,165 DONE IT NOW WITH H5s, IS 2348 01:25:08,165 --> 01:25:11,135 LOOKING AT THE ROLE OF THESE 2349 01:25:11,135 --> 01:25:12,903 PRE-EXISTING IMMUNITY IN THE 2350 01:25:12,903 --> 01:25:14,972 PATHOGENESIS AND TRANSMISSION OF 2351 01:25:14,972 --> 01:25:17,341 EMERGING PANDEMIC THREATS. 2352 01:25:17,341 --> 01:25:21,479 SO WE SEE DEFINITELY INFECTION 2353 01:25:21,479 --> 01:25:23,781 HAPPENS BUT REDUCED SEVERITY OF 2354 01:25:23,781 --> 01:25:24,915 DISEASE. 2355 01:25:24,915 --> 01:25:26,417 SO COMING BACK TO THIS, HOW DO 2356 01:25:26,417 --> 01:25:27,952 WE CHANGE THINGS? 2357 01:25:27,952 --> 01:25:29,620 WE'VE GOT TO CHANGE EXPOSURE 2358 01:25:29,620 --> 01:25:31,322 TIMES 100%, WE'VE GOT TO START 2359 01:25:31,322 --> 01:25:32,690 USING ANIMALS WITH PRE-EXISTING 2360 01:25:32,690 --> 01:25:34,625 IMMUNITY BECAUSE WE ARE NOT 2361 01:25:34,625 --> 01:25:35,259 IMMUNOLOGICALLY NAIVE. 2362 01:25:35,259 --> 01:25:36,827 MAYBE YOU COULD ARGUE THAT WE 2363 01:25:36,827 --> 01:25:39,163 WERE FOR SARS-COV-2, BUT WE ALSO 2364 01:25:39,163 --> 01:25:41,532 HAD SOME PRE-EXISTING 2365 01:25:41,532 --> 01:25:42,466 CORONAVIRUS IMMUNITY THAT I 2366 01:25:42,466 --> 01:25:43,300 THINK IS IMPORTANT TO IMPLEMENT 2367 01:25:43,300 --> 01:25:44,502 WHEN WE DO THESE SORT OF 2368 01:25:44,502 --> 01:25:45,136 STUDIES. 2369 01:25:45,136 --> 01:25:46,036 AND THEN LET'S TALK ABOUT AIR 2370 01:25:46,036 --> 01:25:46,904 FLOW. 2371 01:25:46,904 --> 01:25:47,738 I'M HOPING I'M ON TIME. 2372 01:25:47,738 --> 01:25:51,609 I ACTUALLY HAVE NO IDEA. 2373 01:25:51,609 --> 01:25:52,943 AM I REALLY? 2374 01:25:52,943 --> 01:25:54,912 I'M SO SORRY. 2375 01:25:54,912 --> 01:26:00,084 OH, IS THAT THE TIMER? 2376 01:26:00,084 --> 01:26:02,253 OKAY. 2377 01:26:02,253 --> 01:26:04,121 SO WE BUILT A FERRET PLAY PEN. 2378 01:26:04,121 --> 01:26:08,225 WE'VE GOT A ROBOT, AIR SAMPLING 2379 01:26:08,225 --> 01:26:09,593 AT THE SOURCE. 2380 01:26:09,593 --> 01:26:11,929 WHAT WE CAN DO IS HAVE REALISTIC 2381 01:26:11,929 --> 01:26:12,563 BEHAVIORS. 2382 01:26:12,563 --> 01:26:13,597 EVERYONE LOVES THIS, THE FERRETS 2383 01:26:13,597 --> 01:26:15,232 LOVE TO RIDE ON THESE ROBOTS. 2384 01:26:15,232 --> 01:26:16,767 WE'VE GOT AIR SAMPLERS AROUND 2385 01:26:16,767 --> 01:26:18,836 THE PERIMETER AND THEY HAVE 2386 01:26:18,836 --> 01:26:20,271 REALISTIC BEHAVIORS. 2387 01:26:20,271 --> 01:26:22,006 WHAT WE END UP DOING IS WE DO 2388 01:26:22,006 --> 01:26:24,875 ANYWHERE FROM ONE TO FOUR HOURS 2389 01:26:24,875 --> 01:26:26,210 OF EXPOSURE AND THEN WE 2390 01:26:26,210 --> 01:26:28,045 INDIVIDUALLY HOUSE FERRETS. 2391 01:26:28,045 --> 01:26:30,181 WE ARE LOOKING AGAIN AT THIS 2392 01:26:30,181 --> 01:26:31,382 EQUATION OF TRANSMISSION THAT'S 2393 01:26:31,382 --> 01:26:32,049 REALLY IMPORTANT TO ME. 2394 01:26:32,049 --> 01:26:33,551 SO WHAT WE'RE DOING IS NOW 2395 01:26:33,551 --> 01:26:35,419 BEHAVIOR TRACKING THESE ANIMALS 2396 01:26:35,419 --> 01:26:37,988 AND WE'RE USING BEHAVIOR THINGS 2397 01:26:37,988 --> 01:26:39,490 TO DEFINE WHAT ARE ALL THE 2398 01:26:39,490 --> 01:26:40,891 DIFFERENT INTERACTIONS THAT 2399 01:26:40,891 --> 01:26:43,427 FERRETS MAKE AND YOU WOULD 2400 01:26:43,427 --> 01:26:44,862 EXPECT THAT OF COURSE FERRETS 2401 01:26:44,862 --> 01:26:46,831 WOULD HAVE THE TOTAL DURATION OF 2402 01:26:46,831 --> 01:26:48,399 DONOR TOUCHING WOULD BE WHAT 2403 01:26:48,399 --> 01:26:51,235 WOULD LEAD TO SUCCESSFUL 2404 01:26:51,235 --> 01:26:52,369 TRANSMISSION EVENT, AND IN 2405 01:26:52,369 --> 01:26:54,138 REALITY IT'S NOT, SO THESE ARE 2406 01:26:54,138 --> 01:26:56,407 TWO RECIPIENT ANIMALS THAT GOT 2407 01:26:56,407 --> 01:26:57,508 INFECTED AND THEY HAVE THE 2408 01:26:57,508 --> 01:27:01,245 LOWEST NUMBER OF TOTAL DURATION 2409 01:27:01,245 --> 01:27:02,346 IN ONE OF OUR STUDIES. 2410 01:27:02,346 --> 01:27:04,748 WE ALSO CAN LOOK AT INFECTION IN 2411 01:27:04,748 --> 01:27:06,350 THE ENVIRONMENT, SO WE SWAB A 2412 01:27:06,350 --> 01:27:09,153 VARIETY OF SURFACES. 2413 01:27:09,153 --> 01:27:11,822 THIS IS ERNIE, OUR ROBOT 2414 01:27:11,822 --> 01:27:12,056 SAMPLER. 2415 01:27:12,056 --> 01:27:13,490 SO THESE ARE THINGS WE FOUND 2416 01:27:13,490 --> 01:27:16,427 INFECTIOUS VIRUS ON AND WE FOUND 2417 01:27:16,427 --> 01:27:19,263 MORE WITH RNA. 2418 01:27:19,263 --> 01:27:20,397 MY BIG THING IS THAT WE SHOULD 2419 01:27:20,397 --> 01:27:23,000 BE RE-THINKING ANIMAL MODELS, 2420 01:27:23,000 --> 01:27:25,169 AND WE'LL TALK ABOUT THAT MORE. 2421 01:27:25,169 --> 01:27:26,637 SO THIS IS LIKE WHERE WE SHOULD 2422 01:27:26,637 --> 01:27:28,172 BE FOCUSING ON THINGS THAT ARE 2423 01:27:28,172 --> 01:27:30,341 MORE REALISTIC IN TERMS OF 2424 01:27:30,341 --> 01:27:31,876 EXPOSURE TIMES, VENTILATION 2425 01:27:31,876 --> 01:27:34,011 RATES AND NETWORKS OF HOW PEOPLE 2426 01:27:34,011 --> 01:27:35,179 INTERACT. 2427 01:27:35,179 --> 01:27:37,615 AND THIS IS MY TEAM. 2428 01:27:37,615 --> 01:27:38,816 WE'RE REALLY FORTUNATE ALL OF 2429 01:27:38,816 --> 01:27:41,652 THE PLAY PEN STUFF WAS FUNDED BY 2430 01:27:41,652 --> 01:27:43,587 FLU LAB BECAUSE IT'S HARD TO GET 2431 01:27:43,587 --> 01:27:44,755 NIH FUNDING FOR THAT SORT OF 2432 01:27:44,755 --> 01:27:45,389 STUFF. 2433 01:27:45,389 --> 01:27:50,027 YEAH, THIS YEAR, OTHER FOLKS AND 2434 01:27:50,027 --> 01:27:50,694 MY TEAM. 2435 01:27:50,694 --> 01:27:51,362 THANKS. 2436 01:27:51,362 --> 01:27:57,635 I'M SORRY. 2437 01:27:57,635 --> 01:27:59,570 >> HI, SEEMA. 2438 01:27:59,570 --> 01:28:00,104 REALLY COOL TALK. 2439 01:28:00,104 --> 01:28:02,473 I REALLY LIKE WHAT YOU'RE DOING 2440 01:28:02,473 --> 01:28:04,308 WITH THE PRE-EXISTING MODEL. 2441 01:28:04,308 --> 01:28:05,609 I THINK IT'S SUPER IMPORTANT. 2442 01:28:05,609 --> 01:28:07,044 I HAVE TWO QUESTIONS RELATED TO 2443 01:28:07,044 --> 01:28:07,311 THAT. 2444 01:28:07,311 --> 01:28:09,079 DO YOU HAVE ANY UNDERSTANDING OF 2445 01:28:09,079 --> 01:28:11,749 THE CORRELATES FOR PROTECTION? 2446 01:28:11,749 --> 01:28:13,918 I KNOW YOU SAID IT'S SENTINEL 2447 01:28:13,918 --> 01:28:15,286 BUT DO YOU KNOW WHAT IS GOING ON 2448 01:28:15,286 --> 01:28:16,754 IN THIS ANIMAL? 2449 01:28:16,754 --> 01:28:17,421 SECONDLY, DO YOU THINK THAT YOUR 2450 01:28:17,421 --> 01:28:19,323 TIMING IS GOOD ENOUGH, LIKE, TO 2451 01:28:19,323 --> 01:28:21,358 84 DAYS, WOULD YOU -- FOR 2452 01:28:21,358 --> 01:28:22,559 EXAMPLE, IF YOU WAIT A YEAR, IS 2453 01:28:22,559 --> 01:28:24,194 THAT MORE LIKE WHAT WE SEE IN A 2454 01:28:24,194 --> 01:28:25,195 HUMAN POPULATION? 2455 01:28:25,195 --> 01:28:26,697 >> THOSE ARE BOTH GOOD 2456 01:28:26,697 --> 01:28:28,599 QUESTIONS. 2457 01:28:28,599 --> 01:28:30,034 THE FIRST ONE IS DO WE HAVE ANY 2458 01:28:30,034 --> 01:28:31,802 IDEA WHAT THE CORRELATIVE 2459 01:28:31,802 --> 01:28:32,303 PROTECTION IS? 2460 01:28:32,303 --> 01:28:34,738 WE KNOW IT IS NOT NEUTRALIZING 2461 01:28:34,738 --> 01:28:39,243 ANTIBODIES, WE KNOW IT'S NOT 2462 01:28:39,243 --> 01:28:40,244 NEUROMINIDACE AND BODIES, WE 2463 01:28:40,244 --> 01:28:41,779 DON'T THINK IT'S ANY SORT OF 2464 01:28:41,779 --> 01:28:44,181 ANTIBODIES AGAINST THE HUMAN 2465 01:28:44,181 --> 01:28:45,783 GLUTE NN, WE'RE DOING DIFFERENT 2466 01:28:45,783 --> 01:28:49,086 ROUTES OF INOCULATION FOR THE 2467 01:28:49,086 --> 01:28:50,721 VACCINES TO TEASE APART 2468 01:28:50,721 --> 01:28:52,456 IMMUNE -- THEORETICALLY TICKLING 2469 01:28:52,456 --> 01:28:55,826 OF IMMUNE RESPONSES, T CELLS 2470 01:28:55,826 --> 01:28:57,261 VERSUS B CELLS, GERNTION WE 2471 01:28:57,261 --> 01:28:59,296 DON'T HAVE THE REAGENTS FOR 2472 01:28:59,296 --> 01:29:01,031 FERRET TO REALLY TEASE THAT 2473 01:29:01,031 --> 01:29:02,700 APART AND I'M NOT AN 2474 01:29:02,700 --> 01:29:04,001 IMMUNOLOGIST SO EVEN IF WE DID, 2475 01:29:04,001 --> 01:29:05,536 I'D BE LOST. 2476 01:29:05,536 --> 01:29:09,506 SO WE HAVE FOUND THAT 2477 01:29:09,506 --> 01:29:12,309 INACTIVATED VACCINES 2478 01:29:12,309 --> 01:29:15,746 ADMINISTERED INTRANASALLY IS NOT 2479 01:29:15,746 --> 01:29:16,113 PROTECTIVE. 2480 01:29:16,113 --> 01:29:20,217 IF I CAN GIVE AN H1N1 INTRANASAL 2481 01:29:20,217 --> 01:29:22,152 MONOVALENT INACTIVATED VACCINE 2482 01:29:22,152 --> 01:29:24,088 WITH ADJUNCT IT DOES NOT PROTECT 2483 01:29:24,088 --> 01:29:27,458 AGAINST H2N2 NATURAL INFECTION. 2484 01:29:27,458 --> 01:29:28,459 SO TRANSMISSION NOT UP THEIR 2485 01:29:28,459 --> 01:29:29,927 NOSE BUT AS A RECIPIENT. 2486 01:29:29,927 --> 01:29:32,863 HOWEVER, IF WE GIVE LA IV, WE 2487 01:29:32,863 --> 01:29:34,298 ARE STARTING TO SEE PROTECTION. 2488 01:29:34,298 --> 01:29:35,499 SO WE DO THINK THAT'S SOMETHING 2489 01:29:35,499 --> 01:29:37,401 TO DO ABOUT THE REPLICATION AND 2490 01:29:37,401 --> 01:29:40,070 THAT INDUCING POTENTIALLY MORE 2491 01:29:40,070 --> 01:29:42,272 MUCOSAL T CELLS RATHER THAN 2492 01:29:42,272 --> 01:29:43,240 ANTIBODIES, BUT WE'RE TRYING TO 2493 01:29:43,240 --> 01:29:48,612 FIGURE ALL THAT OUT. 2494 01:29:48,612 --> 01:29:49,246 SO WE'RE WORKING ON THAT. 2495 01:29:49,246 --> 01:29:51,115 BECAUSE OF THE LACK REAGENTS, 2496 01:29:51,115 --> 01:29:52,783 WHAT WE'RE DOING WITH SCOTT 2497 01:29:52,783 --> 01:29:55,919 BOYD'S GROUP IS DOING SINGLE 2498 01:29:55,919 --> 01:29:57,187 CELL RNA SEQ WITH ALL OF THESE 2499 01:29:57,187 --> 01:29:58,589 STUDIES WITH PRE-EXISTING 2500 01:29:58,589 --> 01:30:01,992 IMMUNITY AFTER THE PRIMARY IB 2501 01:30:01,992 --> 01:30:03,494 INFECTION, AFTER THE SECONDARY 2502 01:30:03,494 --> 01:30:05,162 INFECTION TO SEE WHAT TYPE OF 2503 01:30:05,162 --> 01:30:06,897 RESPONSES WE GET. 2504 01:30:06,897 --> 01:30:07,531 THEN YOUR SECOND QUESTION ABOUT 2505 01:30:07,531 --> 01:30:08,599 TIMING, WE HAVE NOT WAITED A 2506 01:30:08,599 --> 01:30:11,802 YEAR BUT WE HAVE WAITED OUT TO 2507 01:30:11,802 --> 01:30:14,505 160 DAYS, I THINK IS THE LONGEST 2508 01:30:14,505 --> 01:30:16,673 WE'VE GONE, MOSTLY BECAUSE THESE 2509 01:30:16,673 --> 01:30:17,941 FERRETS, WE HANG THEM OUT, 2510 01:30:17,941 --> 01:30:18,776 REALLY IT'S A RETIREMENT 2511 01:30:18,776 --> 01:30:19,510 COMMUNITY THAT WE'VE BEEN 2512 01:30:19,510 --> 01:30:21,378 RUNNING UP AT PITTSBURGH AND 2513 01:30:21,378 --> 01:30:24,548 VALERIE IN MY GROUP AND -- ROCKY 2514 01:30:24,548 --> 01:30:25,716 DID A LOT OF THIS WORK THAT I 2515 01:30:25,716 --> 01:30:28,385 PRESENTED HAS REALLY BEEN 2516 01:30:28,385 --> 01:30:30,020 MAINTAINING THAT IN PITTSBURGH 2517 01:30:30,020 --> 01:30:31,588 AND SO YEAH, WE HAVEN'T GONE OUT 2518 01:30:31,588 --> 01:30:32,689 TO A YEAR, IT'S INTERESTING TO 2519 01:30:32,689 --> 01:30:33,123 THINK ABOUT. 2520 01:30:33,123 --> 01:30:34,892 WHAT WE HAVE DONE ARE THESE 2521 01:30:34,892 --> 01:30:36,527 TERTIARY INFECTIONS WHERE WE DO 2522 01:30:36,527 --> 01:30:39,730 A PRIMARY WITH ONE H1, SECONDARY 2523 01:30:39,730 --> 01:30:42,800 WITH AN H3N2 THROUGH NATURAL 2524 01:30:42,800 --> 01:30:43,901 INFECTION, THESE RECIPIENTS, AND 2525 01:30:43,901 --> 01:30:45,569 BRING THEM BACK IN FOR TERTIARY 2526 01:30:45,569 --> 01:30:48,338 TO SEE IF WE CAN GET ANOTHER 2527 01:30:48,338 --> 01:30:49,206 THIRD REPLICATION OR THIRD 2528 01:30:49,206 --> 01:30:52,509 INFECTION AND THROUGH NATURAL 2529 01:30:52,509 --> 01:30:54,211 ROUTES AS RECIPIENTS. 2530 01:30:54,211 --> 01:30:56,380 >> WE'LL TAKE ONE MORE. 2531 01:30:56,380 --> 01:30:58,782 >> I LOVE THE FERRET DAYCARE 2532 01:30:58,782 --> 01:31:04,121 PLAY PEN MODEL FOR TRANSMISSION. 2533 01:31:04,121 --> 01:31:05,756 IT'S SO MUCH MORE RELEVANT TO 2534 01:31:05,756 --> 01:31:06,190 HUMAN BEHAVIOR. 2535 01:31:06,190 --> 01:31:07,324 HAVE YOU EVER THOUGHT ABOUT HOW 2536 01:31:07,324 --> 01:31:09,326 THIS COULD BE POSSIBLY ADAPTED 2537 01:31:09,326 --> 01:31:12,996 OR SPOKEN WITH EHS OR OTHER 2538 01:31:12,996 --> 01:31:13,831 PEOPLE ABOUT LIKE IF YOU'RE 2539 01:31:13,831 --> 01:31:15,132 DEALING WITH A HIGHER 2540 01:31:15,132 --> 01:31:16,667 CONTAINMENT PATHOGEN, IS THERE 2541 01:31:16,667 --> 01:31:18,035 ANY WAY TO REPLICATE THAT? 2542 01:31:18,035 --> 01:31:21,105 >> THEY'RE OWE C OKAY WITH US D- 2543 01:31:21,105 --> 01:31:22,372 WE ALREADY HAVE PLANS IN PLACE 2544 01:31:22,372 --> 01:31:23,140 TO DO THIS. 2545 01:31:23,140 --> 01:31:24,374 WHAT WE HAVE DISCUSSED WITH 2546 01:31:24,374 --> 01:31:26,076 THEM, SO WE HAVE THE SYSTEM IS 2547 01:31:26,076 --> 01:31:29,213 SORT OF CONTAINED BUT ALSO WE 2548 01:31:29,213 --> 01:31:30,781 WEAR PPE AS THE INDIVIDUALS IN 2549 01:31:30,781 --> 01:31:33,584 THE ROOM TO PROTECT US FROM THE 2550 01:31:33,584 --> 01:31:35,819 EXPULSION OF THE AIR OF THE 2551 01:31:35,819 --> 01:31:38,489 ANIMALS WHEN THEY ARE OUT 2552 01:31:38,489 --> 01:31:40,324 PLAYING IN THAT SPACE. 2553 01:31:40,324 --> 01:31:41,825 AND SO IT'S THE SAME THING AS 2554 01:31:41,825 --> 01:31:43,827 LIKE MOVING AN ANIMAL OUTSIDE OF 2555 01:31:43,827 --> 01:31:45,929 THEIR CAGING BETWEEN, YOU KNOW, 2556 01:31:45,929 --> 01:31:47,564 I TAKING THEM OUT OF THE CAGE, 2557 01:31:47,564 --> 01:31:49,366 PUTTING THEM INTO A BOX IN THE 2558 01:31:49,366 --> 01:31:49,967 BIOSAFETY CABINET. 2559 01:31:49,967 --> 01:31:53,003 AND SO THEY SEEM TO BE OKAY WITH 2560 01:31:53,003 --> 01:31:54,404 US DOING THIS, AND AS LONG AS 2561 01:31:54,404 --> 01:31:56,206 LIKE NOBODY ELSE IS COMING INTO 2562 01:31:56,206 --> 01:31:57,241 THE ROOM. 2563 01:31:57,241 --> 01:31:59,209 THE ROOM IS NEGATIVE PRESSURED, 2564 01:31:59,209 --> 01:31:59,743 AS LONG AS EVERYTHING IS 2565 01:31:59,743 --> 01:32:04,281 CONTAINED IN THE ROOM, 2566 01:32:04,281 --> 01:32:05,249 PROTECTED, AND THERE'S OBVIOUSLY 2567 01:32:05,249 --> 01:32:06,483 A DWELL TIME BEFORE WE OPEN THE 2568 01:32:06,483 --> 01:32:08,852 DOOR SO THAT EVERYTHING CAN BE 2569 01:32:08,852 --> 01:32:10,087 EXCHANGED. 2570 01:32:10,087 --> 01:32:10,921 THEY SEEM TO BE ALL RIGHT WITH 2571 01:32:10,921 --> 01:32:11,522 THAT. 2572 01:32:11,522 --> 01:32:18,428 >> THAT'S AMAZING. 2573 01:32:18,428 --> 01:32:20,097 >> I'M GOING TO TURN TO MICHELLE 2574 01:32:20,097 --> 01:32:20,430 REALLY QUICK. 2575 01:32:20,430 --> 01:32:21,765 DO YOU WANT TO KEEP GOING WITH 2576 01:32:21,765 --> 01:32:22,566 QUESTIONS OR -- 2577 01:32:22,566 --> 01:32:24,101 >> WE HAVE TIME IN THE PANEL 2578 01:32:24,101 --> 01:32:25,035 DISCUSSION. 2579 01:32:25,035 --> 01:32:26,537 SO PLEASE SAVE YOUR QUESTIONS 2580 01:32:26,537 --> 01:32:28,138 AND BRING THEM UP THEN. 2581 01:32:28,138 --> 01:32:29,339 YEAH, LET'S JUST TAKE -- THANK 2582 01:32:29,339 --> 01:32:29,873 YOU, SEEMA. 2583 01:32:29,873 --> 01:32:30,340 >> THANK YOU. 2584 01:32:30,340 --> 01:32:35,279 [APPLAUSE] 2585 01:32:35,279 --> 01:32:39,650 YOU ANDAND WE HAVE A BREAK UNTI, 2586 01:32:39,650 --> 01:32:40,121 SO WE'LL RECONVENE AT 10:20. 2587 01:32:41,697 --> 01:32:42,398 >> I'M GOING TO ENCOURAGE 2588 01:32:42,398 --> 01:32:47,069 EVERYBODY TO GET SETTLED AS I 2589 01:32:47,069 --> 01:32:48,471 WELCOME PETER HALFMANN FROM THE 2590 01:32:48,471 --> 01:32:51,107 UNIVERSITY OF WISCONSIN TO THE 2591 01:32:51,107 --> 01:32:54,477 PODIUM TO GIVE A TALK ENTITLED 2592 01:32:54,477 --> 01:32:56,445 INFLUENZA VIRUS AND SARS-COV-2 2593 01:32:56,445 --> 01:32:57,480 TRANSMISSION IN SMALL ANIMAL 2594 01:32:57,480 --> 01:32:59,749 MODELS. 2595 01:32:59,749 --> 01:33:00,883 AN OVERVIEW. 2596 01:33:00,883 --> 01:33:06,255 >> THANKS FOR THE INTRODUCTION. 2597 01:33:06,255 --> 01:33:08,157 SO THE PURPOSE OF THE 2598 01:33:08,157 --> 01:33:09,458 PRESENTATION TODAY WAS TO TRY TO 2599 01:33:09,458 --> 01:33:13,629 GIVE A TRANSMISSION 101 TALK ON 2600 01:33:13,629 --> 01:33:16,065 INFLUENZA VIRUSES, WHAT SUBTYPES 2601 01:33:16,065 --> 01:33:17,500 TRANSMIT, WHAT SUBTYPES DON'T, 2602 01:33:17,500 --> 01:33:21,771 AND THEN ALSO ON SARS-COV-2 2603 01:33:21,771 --> 01:33:24,507 VARIANTS, OF WHICH VARIANTS DO 2604 01:33:24,507 --> 01:33:25,941 TRANSMIT AND DON'T. 2605 01:33:25,941 --> 01:33:30,980 AND THEN LOOKING AT DIFFERENT 2606 01:33:30,980 --> 01:33:33,315 ANIMAL MODELS, PARTICULARLY JUST 2607 01:33:33,315 --> 01:33:37,353 FOCUSING ON THE RODENT MODEL OF 2608 01:33:37,353 --> 01:33:39,021 TRANSMISSION, WHAT RODENT MODELS 2609 01:33:39,021 --> 01:33:41,223 SUPPORT TRANSMISSION AND ONES 2610 01:33:41,223 --> 01:33:42,091 THAT DON'T. 2611 01:33:42,091 --> 01:33:43,592 AND YES, WE'RE GOING TO TALK 2612 01:33:43,592 --> 01:33:47,663 ABOUT ROUTES OF TRANSMISSION, 2613 01:33:47,663 --> 01:33:50,666 AIRBORNE TRANSMISSION, DIRECT 2614 01:33:50,666 --> 01:33:52,067 CONTACT, AND ALSO LOOKING AT 2615 01:33:52,067 --> 01:34:02,445 VERTICAL TRANSMISSION. 2616 01:34:09,652 --> 01:34:10,786 HERE WE GO. 2617 01:34:10,786 --> 01:34:13,456 SO FOR CONSIDERATIONS WITH 2618 01:34:13,456 --> 01:34:15,524 TRANSMISSION, THERE'S A LOT TO 2619 01:34:15,524 --> 01:34:16,325 THINK ABOUT. 2620 01:34:16,325 --> 01:34:17,626 I'M ONLY GOING TO SCRATCH THE 2621 01:34:17,626 --> 01:34:20,863 SURFACE, BUT THE VIRUS TITERS, 2622 01:34:20,863 --> 01:34:22,598 THE AMOUNT OF SHEDDING YOU HAVE, 2623 01:34:22,598 --> 01:34:25,768 THE TIME LAPSE WHEN YOU ADD THE 2624 01:34:25,768 --> 01:34:28,971 CONTACT OF THE NAIVE WITH THE 2625 01:34:28,971 --> 01:34:29,572 INFECTED ANIMAL. 2626 01:34:29,572 --> 01:34:31,607 WHAT ARE YOUR READOUTS FOR 2627 01:34:31,607 --> 01:34:31,941 EXPOSURE? 2628 01:34:31,941 --> 01:34:34,510 ARE YOU LOOKING AT FOR AN 2629 01:34:34,510 --> 01:34:35,811 INFECTIOUS VIRUS, ARE YOU 2630 01:34:35,811 --> 01:34:37,680 LOOKING FOR VIRAL RNA, DO YOU 2631 01:34:37,680 --> 01:34:39,782 WAIT THE 21 DAYS, 28 DAYS AND 2632 01:34:39,782 --> 01:34:42,451 LOOK FOR SEROCONVERSION. 2633 01:34:42,451 --> 01:34:43,853 DURING THE BEGINNING OF THE 2634 01:34:43,853 --> 01:34:46,121 PANDEMIC, WE SPENT A LOT OF TIME 2635 01:34:46,121 --> 01:34:48,958 WORKING WITH OUR MECHANICAL SHOP 2636 01:34:48,958 --> 01:34:51,060 MAKING DIFFERENT CAGES FOR 2637 01:34:51,060 --> 01:34:51,861 TRANSMISSION STUDY. 2638 01:34:51,861 --> 01:34:53,395 EVERYONE HAS THEIR OWN CAGING 2639 01:34:53,395 --> 01:34:56,031 SYSTEM THAT'S NOT REALLY 2640 01:34:56,031 --> 01:34:58,367 UNIVERSAL. 2641 01:34:58,367 --> 01:35:01,003 AIR FLOW IS IMPORTANT FOR THE 2642 01:35:01,003 --> 01:35:01,437 ENVIRONMENT. 2643 01:35:01,437 --> 01:35:02,404 THERE'S WORK DONE THAT IF YOU 2644 01:35:02,404 --> 01:35:03,639 LOOK AT TRANSMISSION AT 2645 01:35:03,639 --> 01:35:05,241 5 DEGREES VERSUS 20 DEGREES, YOU 2646 01:35:05,241 --> 01:35:06,809 SEE DIFFERENCES, AND WHAT KIND 2647 01:35:06,809 --> 01:35:08,477 OF BEDDING ARE YOU USING IN THE 2648 01:35:08,477 --> 01:35:08,844 CAGES? 2649 01:35:08,844 --> 01:35:12,214 DO YOU HAVE AIR FLOW THAT'S 2650 01:35:12,214 --> 01:35:14,083 BLOWING YOUR CORN COULD BE 2651 01:35:14,083 --> 01:35:15,117 BEDDING ACROSS TO THE NEXT CAGE 2652 01:35:15,117 --> 01:35:16,952 AND YOU'RE LOOKING AT AIRBORNE 2653 01:35:16,952 --> 01:35:17,853 TRANSMISSION, YOU ARE REALLY 2654 01:35:17,853 --> 01:35:18,821 LOOKING AT AIRBORNE 2655 01:35:18,821 --> 01:35:19,221 TRANSMISSION? 2656 01:35:19,221 --> 01:35:20,723 THAT KIND OF GOES INTO THEN WHAT 2657 01:35:20,723 --> 01:35:22,591 IS BEING TRANSMITTED, YOU COULD 2658 01:35:22,591 --> 01:35:23,692 SPEND THE WHOLE AFTERNOON 2659 01:35:23,692 --> 01:35:25,594 TALKING ABOUT MECHANICS OF 2660 01:35:25,594 --> 01:35:30,699 TRANSMISSION SIZES, ARE YOU 2661 01:35:30,699 --> 01:35:32,067 LOOKING AT RESPIRATORY DROP 2662 01:35:32,067 --> 01:35:36,238 LEATHER DROPLEATHERS BEING TRAND 2663 01:35:36,238 --> 01:35:39,241 OR AEROSOL FOMITES THAT ARE 2664 01:35:39,241 --> 01:35:41,510 BEING TRANSMITTED. 2665 01:35:41,510 --> 01:35:42,845 SO TRANSMISSION AND THE USE OF 2666 01:35:42,845 --> 01:35:45,681 ANIMAL MODELS FOR INFLUENZA 2667 01:35:45,681 --> 01:35:49,451 STARTED BACK IN THE 1930s. 2668 01:35:49,451 --> 01:35:51,120 THEY LOOKED IN THE 1940s AT 2669 01:35:51,120 --> 01:35:53,622 TRANSMISSION OF FLU VIRUSES WITH 2670 01:35:53,622 --> 01:35:57,026 INFLUENZA VIRUS. 2671 01:35:57,026 --> 01:35:58,294 AND EVEN BACK THEN, THEY COULD 2672 01:35:58,294 --> 01:35:59,929 SEE AT A DISTANCE OF 3 FEET THAT 2673 01:35:59,929 --> 01:36:01,363 YOU COULD SEE TRANSMISSION 2674 01:36:01,363 --> 01:36:03,432 STRAIGHT DOWN THE CORRIDOR. 2675 01:36:03,432 --> 01:36:06,635 IF YOU HAVE LIKE A BEND IN YOUR 2676 01:36:06,635 --> 01:36:07,636 TRANSMISSION UNIT, YOU COULD 2677 01:36:07,636 --> 01:36:08,604 STILL SEE TRANSMISSION 2678 01:36:08,604 --> 01:36:09,038 HAPPENING. 2679 01:36:09,038 --> 01:36:12,041 THE SAD PART HERE IS THAT THIS 2680 01:36:12,041 --> 01:36:13,375 IS 80 YEARS AGO AND WE HAVEN'T 2681 01:36:13,375 --> 01:36:15,477 REALLY CHANGED MUCH LOOKING AT 2682 01:36:15,477 --> 01:36:18,514 TRANSMISSION UNFORTUNATELY. 2683 01:36:18,514 --> 01:36:22,284 THE TALK RIGHT BEFORE THE BREAK 2684 01:36:22,284 --> 01:36:23,352 IS EXCELLENT WAYS TO START 2685 01:36:23,352 --> 01:36:28,824 THINKING ABOUT HOW LOOKING AT 2686 01:36:28,824 --> 01:36:30,893 TRANSMISSION AGAIN. 2687 01:36:30,893 --> 01:36:34,263 HOWHAT COSTSAND HOW MANY LABS CY 2688 01:36:34,263 --> 01:36:35,664 DO THAT KIND OF TRANSMISSION 2689 01:36:35,664 --> 01:36:36,899 STUDY IS ANOTHER CONSIDERATION. 2690 01:36:36,899 --> 01:36:38,334 NOT EVERYONE CAN USE FERRETS FOR 2691 01:36:38,334 --> 01:36:39,535 TRANSMISSION, SO OF COURSE THERE 2692 01:36:39,535 --> 01:36:41,503 WAS EFFORTS IN THE 60s TO LOOK 2693 01:36:41,503 --> 01:36:45,908 AT CAN WE LOOK AT MACE FOR MICET 2694 01:36:45,908 --> 01:36:47,142 WAS ALLUDED YESTERDAY THAT MICE 2695 01:36:47,142 --> 01:36:48,577 ARE A POOR MODEL FOR 2696 01:36:48,577 --> 01:36:48,911 TRANSMISSION. 2697 01:36:48,911 --> 01:36:51,347 A GROUP DID LOOK AT 2698 01:36:51,347 --> 01:36:54,650 H2N2 VIRUSES, BOTH MOUSE-ADAPTED 2699 01:36:54,650 --> 01:36:57,286 VIRUSES AND NON-MOUSE ADAPTED 2700 01:36:57,286 --> 01:36:57,686 H2N2. 2701 01:36:57,686 --> 01:36:59,355 WITH MICE, YOU COULD SEE 50% 2702 01:36:59,355 --> 01:37:01,290 TRANSMISSION, THEY WERE USING 2703 01:37:01,290 --> 01:37:03,359 THE SWISS WEBSTER MICE. 2704 01:37:03,359 --> 01:37:06,428 THESE WERE MALES, THEY DID 2705 01:37:06,428 --> 01:37:07,229 24-HOUR CONTACT. 2706 01:37:07,229 --> 01:37:09,465 OF COURSE WE DON'T HAVE 2707 01:37:09,465 --> 01:37:11,300 H2N2 CIRCULATING IN HUMAN 2708 01:37:11,300 --> 01:37:13,068 POPULATION ANYMORE, AND 2709 01:37:13,068 --> 01:37:16,405 CURRENTLY NO OTHER SUBTYPES ARE 2710 01:37:16,405 --> 01:37:18,674 IDENTIFIED FOR TRANSMISSION WITH 2711 01:37:18,674 --> 01:37:23,278 MICE, ADULT MICE, I SHOULD SAY. 2712 01:37:23,278 --> 01:37:24,947 DIRECT CONTACT TRANSMISSION HAS 2713 01:37:24,947 --> 01:37:25,514 ITS MERITS. 2714 01:37:25,514 --> 01:37:28,384 OF COURSE THIS IS AGAIN 2715 01:37:28,384 --> 01:37:30,486 SUBTYPE-SPECIFIC. 2716 01:37:30,486 --> 01:37:33,656 A GROUP LOOKING AT H1 VERSUS 2717 01:37:33,656 --> 01:37:35,157 H3N2 VIRUSES SHOWED THAT WHEN 2718 01:37:35,157 --> 01:37:37,026 YOU LOOKED AT THE H1N1s 2719 01:37:37,026 --> 01:37:39,695 INCLUDING PRA, YOU DIDN'T SEE 2720 01:37:39,695 --> 01:37:45,734 ANY DIRECT CONTACT TRANSMISSION 2721 01:37:45,734 --> 01:37:46,502 INVOLVE -- C FEMALES. 2722 01:37:46,502 --> 01:37:50,239 BUT YOU DID SEE ISOLATE SPECIFIC 2723 01:37:50,239 --> 01:37:51,907 SUBTYPE SPECIFIC WITH 2724 01:37:51,907 --> 01:37:52,541 H2N2 VIRUSES. 2725 01:37:52,541 --> 01:37:54,109 THEY WENT ON TO SHOW THAT A 2726 01:37:54,109 --> 01:37:57,446 FACTOR THAT I BROUGHT UP OF THE 2727 01:37:57,446 --> 01:37:58,313 TIMING IN THE VIRAL LOAD IS 2728 01:37:58,313 --> 01:37:59,715 IMPORTANT WHEN YOU LOOK AT 2729 01:37:59,715 --> 01:38:02,351 TRANSMISSION FOR DIRECT CONTACT. 2730 01:38:02,351 --> 01:38:05,020 THIS LAG BETWEEN WHEN YOU PUT A 2731 01:38:05,020 --> 01:38:07,423 CONTACT MOUSE IN WITH THE 2732 01:38:07,423 --> 01:38:11,627 INFECTED MOUSE WILL SKEW OR WILL 2733 01:38:11,627 --> 01:38:14,129 CHANGE YOUR TRANSMISSION 2734 01:38:14,129 --> 01:38:14,697 PERCENTAGES. 2735 01:38:14,697 --> 01:38:19,234 AND THEY SHOWED THAT IF YOU LOOK 2736 01:38:19,234 --> 01:38:21,270 AS LATE AT 56 HOURS, YOU NEVER 2737 01:38:21,270 --> 01:38:22,471 SAW TRANSMISSION WHEN YOU PUT 2738 01:38:22,471 --> 01:38:24,440 THE NAIVE IN, AND THAT PEAKED AT 2739 01:38:24,440 --> 01:38:25,607 30 HOURS AFTER CONTACT TIME. 2740 01:38:25,607 --> 01:38:28,777 AND YOU COULD SEE SOME 2741 01:38:28,777 --> 01:38:31,180 TRANSMISSION WITHIN SIX HOURS, 2742 01:38:31,180 --> 01:38:35,317 PUTTING THE NAIVE CONTACT IN. 2743 01:38:35,317 --> 01:38:36,485 AND THEN THEY ACTUALLY WENT 2744 01:38:36,485 --> 01:38:38,987 FURTHER TO SHOW THAT THE HIGHER 2745 01:38:38,987 --> 01:38:43,158 THE VIRUS TITER IN THE I SALIVA, 2746 01:38:43,158 --> 01:38:46,929 THESE ARE THE H3N2s IN GREEN, 2747 01:38:46,929 --> 01:38:49,264 YOU HAD HIGHER PERCENTAGE OF 2748 01:38:49,264 --> 01:38:50,032 INFECTION IN THE CONTACTS. 2749 01:38:50,032 --> 01:38:51,567 THE VIRUSES THAT ARE IN THE 2750 01:38:51,567 --> 01:38:56,472 GREY, THE WSN, THE H1N1s AND 2751 01:38:56,472 --> 01:38:59,708 MEMPHIS HAD LOWER TITERS IN THE 2752 01:38:59,708 --> 01:39:01,543 SALIVA AND THESE WERE 2753 01:39:01,543 --> 01:39:05,881 NON-TRANSMISSIBLE. 2754 01:39:05,881 --> 01:39:08,283 WITH THE DISCOVERY OF H5N1 IN 2755 01:39:08,283 --> 01:39:10,452 COWS AND INFECTED COW MILK, WE 2756 01:39:10,452 --> 01:39:12,488 WERE INTERESTED IN KNOWING COULD 2757 01:39:12,488 --> 01:39:13,589 THE MOUSE MODEL BE USED TO LOOK 2758 01:39:13,589 --> 01:39:16,825 AT VERTICAL TRANSMISSION. 2759 01:39:16,825 --> 01:39:18,527 TRYING TO ANSWER BASIC QUESTIONS 2760 01:39:18,527 --> 01:39:21,130 OF DO YOU ACTUALLY FIND 2761 01:39:21,130 --> 01:39:22,364 INFECTIOUS VIRUS IN THE MILK OF 2762 01:39:22,364 --> 01:39:23,899 MICE LIKE YOU DO WITH COWS, AND 2763 01:39:23,899 --> 01:39:25,634 THEN CAN THAT BE TRANSMITTED TO 2764 01:39:25,634 --> 01:39:27,536 PUPS. 2765 01:39:27,536 --> 01:39:32,441 SO IN OUR STUDY, WE USED BALB 2766 01:39:32,441 --> 01:39:34,676 Cs, LACTATING FEMALES. 2767 01:39:34,676 --> 01:39:36,779 THEY GAVE BIRTH 5 TO 7 DAYS AND 2768 01:39:36,779 --> 01:39:40,482 THEN WE INFECTED THEM WITH 100 2769 01:39:40,482 --> 01:39:45,754 PFU OF BOVINE H5N1 VIRUS AND 2770 01:39:45,754 --> 01:39:48,590 THEN WE WAITED 7 OR 9 DAYS TO 2771 01:39:48,590 --> 01:39:50,159 LOOK AT EITHER FOR THE PUPS, DO 2772 01:39:50,159 --> 01:39:51,593 WE FIND INFECTIOUS VIRUS IN THE 2773 01:39:51,593 --> 01:39:54,363 TISSUES, AND WHEN WE ALLOWED THE 2774 01:39:54,363 --> 01:39:56,131 MOTHER TO TAKE CARE OF THE PUPS 2775 01:39:56,131 --> 01:39:58,233 FOR NINE DAYS, WE SAW AROUND 37% 2776 01:39:58,233 --> 01:40:02,070 TRANSMISSION TO THE PUPS, 2777 01:40:02,070 --> 01:40:04,840 LOOKING AS SOON AS FOUR DAYS 2778 01:40:04,840 --> 01:40:05,808 AFTER THE INFECTION OF THE 2779 01:40:05,808 --> 01:40:07,476 MOTHER TO THE PUPS, WE ACTUALLY 2780 01:40:07,476 --> 01:40:09,311 SAW NO TRANSMISSION. 2781 01:40:09,311 --> 01:40:12,381 AND THIS CORRELATED TO HAVING 2782 01:40:12,381 --> 01:40:14,116 VIRUS POSITIVE SAMPLES OF THE 2783 01:40:14,116 --> 01:40:16,985 MOUSE MILK, AND ALSO POSITIVE 2784 01:40:16,985 --> 01:40:19,922 MAMMARY GLANDS IN THESE MOTHERS. 2785 01:40:19,922 --> 01:40:22,691 WHEN WE DID THIS SAME EXACT 2786 01:40:22,691 --> 01:40:24,326 EXPERIMENT BUT INSTEAD OF 2787 01:40:24,326 --> 01:40:26,094 PUTTING -- HAVING THE PUPS STAY 2788 01:40:26,094 --> 01:40:30,065 IN THE CAGE, WE INTRODUCED ADULT 2789 01:40:30,065 --> 01:40:31,600 FEMALES, AND WAITED FOR THE 2790 01:40:31,600 --> 01:40:33,402 EXACT SAME DAYS. 2791 01:40:33,402 --> 01:40:35,637 WE SAW NO DIRECT CONTACT 2792 01:40:35,637 --> 01:40:39,107 TRANSMISSION IN THOSE ADULT GUY 2793 01:40:39,107 --> 01:40:40,008 FEMALES, SUGGESTING THAT IT'S 2794 01:40:40,008 --> 01:40:41,643 THE INFECTED MILK THAT WE SEE 2795 01:40:41,643 --> 01:40:43,445 THE TRANSMISSION AND NOT SOME 2796 01:40:43,445 --> 01:40:47,382 KIND OF FOMITES IN THE CAGE. 2797 01:40:47,382 --> 01:40:49,451 SO WITH A MOUSE MODEL, THAT'S 2798 01:40:49,451 --> 01:40:51,486 VERY SUBTYPE-SPECIFIC. 2799 01:40:51,486 --> 01:40:54,690 TIMING IN VIRAL LOADS CAN PLAY A 2800 01:40:54,690 --> 01:40:56,191 BIG FACTOR TO DIRECT 2801 01:40:56,191 --> 01:40:57,259 TRANSMISSION, ALONG WITH 2802 01:40:57,259 --> 01:40:58,894 ASSOCIATION WITH THE HA PROTEIN 2803 01:40:58,894 --> 01:41:01,129 FOR TRANSMISSION. 2804 01:41:01,129 --> 01:41:04,199 AND WITH H5, WE SUSPECT THAT 2805 01:41:04,199 --> 01:41:06,168 ANOTHER HIGH PATH AVIAN 2806 01:41:06,168 --> 01:41:09,004 INFLUENZA LIKE H7N9 COULD ALSO 2807 01:41:09,004 --> 01:41:10,272 BE TRANSMITTED BY VERTICAL 2808 01:41:10,272 --> 01:41:15,277 TRANSMISSION. 2809 01:41:15,277 --> 01:41:17,045 THE GREAT MODEL, INSTEAD OF 2810 01:41:17,045 --> 01:41:19,014 USING MICE, GUINEA PIGS HAVE 2811 01:41:19,014 --> 01:41:21,583 BEEN A GREAT MODEL OF 2812 01:41:21,583 --> 01:41:22,017 TRANSMISSION. 2813 01:41:22,017 --> 01:41:23,118 A GROUP HAS SHOWN THAT 2814 01:41:23,118 --> 01:41:24,019 TEMPERATURE IS A FACTOR WHEN YOU 2815 01:41:24,019 --> 01:41:27,155 LOOK AT TRANSMISSION. 2816 01:41:27,155 --> 01:41:28,857 WHEN THEY USED A B VIRUS TO LOOK 2817 01:41:28,857 --> 01:41:30,959 AT DIRECT TRANSMISSION BETWEEN 2818 01:41:30,959 --> 01:41:35,797 TWO GUINEA PIGS, THEY SAW 100% 2819 01:41:35,797 --> 01:41:43,171 TRANSMISSION FOUR PAIRS, SPI 2820 01:41:43,171 --> 01:41:44,573 SPIKE -- HOWEVER WHEN THEY 2821 01:41:44,573 --> 01:41:46,074 LOOKED AT AIRBORNE TRANSMISSION, 2822 01:41:46,074 --> 01:41:47,409 ONLY 50% OF THE PAIRS HAD 2823 01:41:47,409 --> 01:41:48,677 TRANSMISSION WHEN IT WAS 2824 01:41:48,677 --> 01:41:50,279 20 DEGREES AND 100% OF THE 2825 01:41:50,279 --> 01:41:51,280 ANIMALS TRANSMITTED AT 2826 01:41:51,280 --> 01:41:52,547 5 DEGREES. 2827 01:41:52,547 --> 01:41:53,615 YOU CAN ASSUME THIS CORRELATES 2828 01:41:53,615 --> 01:41:54,750 TO THE TRANSMISSION OF FLU 2829 01:41:54,750 --> 01:41:56,485 VIRUSES IN THE WINTERTIME. 2830 01:41:56,485 --> 01:41:58,820 THIS WAS AN N OF 4 BUT THEY ALSO 2831 01:41:58,820 --> 01:42:00,088 REPEATED IT WITH ANOTHER LINEAGE 2832 01:42:00,088 --> 01:42:03,892 OF B VIRUS AND ALSO SAW THE SAME 2833 01:42:03,892 --> 01:42:09,097 KIND OF TRANSMISSION KINETICS. 2834 01:42:09,097 --> 01:42:10,599 WITH GUINEA PIG, YOU CAN ALSO 2835 01:42:10,599 --> 01:42:13,902 LOOK AT MUGS PEL DIFF MULTIPLE F 2836 01:42:13,902 --> 01:42:15,704 INFLUENZA A VIRUS AND YOU CAN 2837 01:42:15,704 --> 01:42:18,240 ALSO START PULLING APART VIRAL 2838 01:42:18,240 --> 01:42:19,541 DETERMINANTS AND PROBABLY 2839 01:42:19,541 --> 01:42:21,243 MORPHISMS THAT CORRELATE TO 2840 01:42:21,243 --> 01:42:22,778 TRANSMISSION. 2841 01:42:22,778 --> 01:42:28,684 IN FEMALE GUINEA PIGS, FOR 2842 01:42:28,684 --> 01:42:31,119 DIRECT TRANSMISSION WITH H1N1, 2843 01:42:31,119 --> 01:42:33,121 WE SEE 100% TRANSMISSION. 2844 01:42:33,121 --> 01:42:34,323 SIMILARLY YOU SEE 100% 2845 01:42:34,323 --> 01:42:36,058 TRANSMISSION WITH THE AIRBORNE 2846 01:42:36,058 --> 01:42:36,792 TRANSMISSION MODEL. 2847 01:42:36,792 --> 01:42:38,860 THIS WAS DONE WITH THE 2848 01:42:38,860 --> 01:42:40,429 CALIFORNIA ZERO NINE BUT IT WAS 2849 01:42:40,429 --> 01:42:42,965 ALSO SIMILAR RESULTS WITH 2850 01:42:42,965 --> 01:42:47,703 ANOTHNETHERLANDS PANDEMIC VIRUS. 2851 01:42:47,703 --> 01:42:50,138 ALSO H3N2 VIRUSES CAN BE 2852 01:42:50,138 --> 01:42:52,474 TRANSMITTED IN GUINEA PIGS. 2853 01:42:52,474 --> 01:42:53,775 100% TRANSMISSION WITH THE 2854 01:42:53,775 --> 01:42:56,511 PANAMA VIRUS. 2855 01:42:56,511 --> 01:42:59,047 THE GROUP THEN LOOKED AT WOULD 2856 01:42:59,047 --> 01:43:01,049 THE ABILITY FOR THE VIRUS TO 2857 01:43:01,049 --> 01:43:02,918 REPLICATE AT HIGH EFFICIENCY DUE 2858 01:43:02,918 --> 01:43:05,120 TO THE PB2 AMINO ACIDS KIND OF 2859 01:43:05,120 --> 01:43:07,456 CHANGE THIS, SO IF YOU MUTATED 2860 01:43:07,456 --> 01:43:16,598 THE PB2 AMINO ACIDS AT 627 AND 2861 01:43:16,598 --> 01:43:21,770 701, PARTICULARLY AT 627 -- BACK 2862 01:43:21,770 --> 01:43:23,105 AGAIN CLOSE TO 100% WHEN YOU GO 2863 01:43:23,105 --> 01:43:25,707 IN WITH A MUTATION AT THE 2864 01:43:25,707 --> 01:43:26,208 709 POSITION. 2865 01:43:26,208 --> 01:43:29,811 THEY WERE ABLE TO SHOW THAT WITH 2866 01:43:29,811 --> 01:43:31,013 VIETNAM 1203, WHICH DOES NOT 2867 01:43:31,013 --> 01:43:33,281 HAVE AIRBORNE TRANSMISSION IN 2868 01:43:33,281 --> 01:43:35,017 GUINEA PIGS BUT THERE'S DIRECT 2869 01:43:35,017 --> 01:43:35,784 CONTACT. 2870 01:43:35,784 --> 01:43:38,887 THE SAME KIND OF AMINO ACID 2871 01:43:38,887 --> 01:43:40,756 POLYMORPHISMS WILL CHANGE THE 2872 01:43:40,756 --> 01:43:44,026 REPLICATION POTENTIAL. 2873 01:43:44,026 --> 01:43:45,794 LIKE JACCO MENTIONED EARLIER, 2874 01:43:45,794 --> 01:43:48,130 AIRBORNE TRANSMISSION IS ALSO IN 2875 01:43:48,130 --> 01:43:48,397 HAMSTERS. 2876 01:43:48,397 --> 01:43:52,734 THIS WAS DONE BY THE KIYOKO 2877 01:43:52,734 --> 01:43:53,735 GROUP IN JAPAN. 2878 01:43:53,735 --> 01:43:55,137 THEY LOOKED AT SYRIAN HAMSTERS 2879 01:43:55,137 --> 01:43:57,339 IN FEMALES, AND THEY SAW 100% 2880 01:43:57,339 --> 01:43:59,141 TRANSMISSION OR CLOSE TO IT WITH 2881 01:43:59,141 --> 01:44:02,844 THE H1N1 SUBTYPES. 2882 01:44:02,844 --> 01:44:05,580 THIS FALTERED WITH THE 2883 01:44:05,580 --> 01:44:06,648 H3N2 SUBTYPES AND THEY SAW NO 2884 01:44:06,648 --> 01:44:10,652 TRANSMISSION WITH THE B VIRUSES. 2885 01:44:10,652 --> 01:44:12,821 SO FOR THE RODENT MODELS FOR 2886 01:44:12,821 --> 01:44:15,657 AIRBORNE TRANSMISSION WITH FLU, 2887 01:44:15,657 --> 01:44:17,059 I WOULD SUGGEST THAT WE PUT OUR 2888 01:44:17,059 --> 01:44:18,593 EFFORTS INTO MAKING REAGENTS FOR 2889 01:44:18,593 --> 01:44:22,464 GUINEA PIGS SINCE THE H1s, THE 2890 01:44:22,464 --> 01:44:24,433 H3s TRANSMIT ALONG WITH THE B 2891 01:44:24,433 --> 01:44:25,100 VIRUSES. 2892 01:44:25,100 --> 01:44:26,501 IT'S STILL UNKNOWN ABOUT 2893 01:44:26,501 --> 01:44:29,004 MAMMALIAN TRANSMISSIBLE 2894 01:44:29,004 --> 01:44:32,808 H5 VIRUSES OR POTENTIAL H5N1s 2895 01:44:32,808 --> 01:44:37,079 FROM COW VIRUSES ARE BIGGER THAN 2896 01:44:37,079 --> 01:44:38,914 A TRANSMIT IN GUINEA PIGS. 2897 01:44:38,914 --> 01:44:40,882 SO THE REST OF THE TALK WILL BE 2898 01:44:40,882 --> 01:44:43,518 ABOUT TRANSMISSION OF 2899 01:44:43,518 --> 01:44:43,919 SARS-COV-2. 2900 01:44:43,919 --> 01:44:51,426 WHEN THE ORIGINAL SARS 2901 01:44:51,426 --> 01:44:52,761 COV1 OUTBREAK OCCURRED HAMSTERS 2902 01:44:52,761 --> 01:44:53,929 WERE KNOWN TO BE GREAT 2903 01:44:53,929 --> 01:44:54,896 TRANSMISSION MODEL FOR THAT 2904 01:44:54,896 --> 01:44:55,097 VIRUS. 2905 01:44:55,097 --> 01:44:56,998 WE PUT A LOT OF WORK INTO 2906 01:44:56,998 --> 01:44:59,201 SHOWING TRANSMISSION OF COV2 IN 2907 01:44:59,201 --> 01:45:01,369 HAMSTERS. 2908 01:45:01,369 --> 01:45:03,839 WE HAD TWO DIFFERENT SETUPS FOR 2909 01:45:03,839 --> 01:45:06,708 TRANSMISSION IN THE BEGINNING. 2910 01:45:06,708 --> 01:45:08,543 WE HAD ANIMALS THAT WERE IN THE 2911 01:45:08,543 --> 01:45:10,345 SAME CAGE TOGETHER WITH A WIRE 2912 01:45:10,345 --> 01:45:14,583 MESH SEB RATING SEPARATING THER 2913 01:45:14,583 --> 01:45:15,817 FLOW GOING FROM THE INFECTED TO 2914 01:45:15,817 --> 01:45:16,451 THE CONTACT. 2915 01:45:16,451 --> 01:45:18,453 WE ALSO HAD NON-DIRECTIONAL AIR 2916 01:45:18,453 --> 01:45:20,455 FLOW SETUPS TOO WHERE THE 2917 01:45:20,455 --> 01:45:21,490 ANIMALS WERE SIDE BY SIDE AND 2918 01:45:21,490 --> 01:45:23,425 AIR FLOW WAS GOING IN A 2919 01:45:23,425 --> 01:45:25,794 NON-DIRECTIONAL MANNER. 2920 01:45:25,794 --> 01:45:28,330 THESE ARE OUR SETUPS AT MADISON 2921 01:45:28,330 --> 01:45:28,730 FOR TRANSMISSION. 2922 01:45:28,730 --> 01:45:30,165 WE CAN EITHER PUT ONE CAGE IN 2923 01:45:30,165 --> 01:45:33,702 FOR THE DIRECTIONAL AIR FLOW AND 2924 01:45:33,702 --> 01:45:34,970 THE SIDE BY SIDE. 2925 01:45:34,970 --> 01:45:38,640 WE CAN PUT SIX PAIRS OF HAMSTERS 2926 01:45:38,640 --> 01:45:42,611 TO DO OUR STUDIES. 2927 01:45:42,611 --> 01:45:44,446 WE SAW RIGHT AWAY WHAT THE DELTA 2928 01:45:44,446 --> 01:45:45,447 VARIANT WAS, IT WAS DIFFICULT 2929 01:45:45,447 --> 01:45:46,314 NOT TO HAVE TRANSMISSION GOING 2930 01:45:46,314 --> 01:45:46,648 ON. 2931 01:45:46,648 --> 01:45:48,917 SO YOU COULD PAIR THESE ANIMALS 2932 01:45:48,917 --> 01:45:50,318 TOGETHER FOR 24 HOURS OR AS 2933 01:45:50,318 --> 01:45:55,457 SHORT AS 6 HOURS AND WE SAW 100% 2934 01:45:55,457 --> 01:45:57,125 TRANSMISSION IN OUR DIRECTIONAL 2935 01:45:57,125 --> 01:45:58,059 AIR FLOW SETUP. 2936 01:45:58,059 --> 01:45:59,361 SO TRIED TO MAKE THINGS A LITTLE 2937 01:45:59,361 --> 01:46:02,430 MORE STRINGENT, WE WENT AHEAD 2938 01:46:02,430 --> 01:46:03,632 AND TRIED NON-DIRECTIONAL AIR 2939 01:46:03,632 --> 01:46:04,065 FLOW. 2940 01:46:04,065 --> 01:46:07,335 AGAIN AT 24 HOURS, WE SAW 100% 2941 01:46:07,335 --> 01:46:10,639 TRANSMISSION, AND THAT STARTED 2942 01:46:10,639 --> 01:46:12,274 CREEPING DOWN TO NO TRANSMISSION 2943 01:46:12,274 --> 01:46:13,475 IF YOU DID JUST AN HOUR OF 2944 01:46:13,475 --> 01:46:18,146 CONTACT TIME. 2945 01:46:18,146 --> 01:46:18,880 AGAIN JACCO MENTIONED THIS 2946 01:46:18,880 --> 01:46:20,415 MORNING THIS ALL KIND OF CHANGED 2947 01:46:20,415 --> 01:46:24,553 WITH THE BA1 INTRODUCTION. 2948 01:46:24,553 --> 01:46:26,421 NON-DIRECTION OR DIRECTION AIR 2949 01:46:26,421 --> 01:46:27,622 FLOW DIDN'T MATTER, WE COULD 2950 01:46:27,622 --> 01:46:29,090 NEVER GET AIRBORNE TRANSMISSION 2951 01:46:29,090 --> 01:46:31,059 WITH BA1. 2952 01:46:31,059 --> 01:46:34,963 WE TRIED A COUPLE DIFFERENT 2953 01:46:34,963 --> 01:46:35,430 PARAMETERS CHANGING. 2954 01:46:35,430 --> 01:46:38,133 WE USED 72 HOURS FOR CONTACT 2955 01:46:38,133 --> 01:46:39,367 TIME BUT STILL NO TRANSMISSION. 2956 01:46:39,367 --> 01:46:42,504 WE ALSO INCREASED THE DOSE THAT 2957 01:46:42,504 --> 01:46:44,105 WE GAVE FROM 10 TO THE THIRD TO 2958 01:46:44,105 --> 01:46:45,540 10 TO THE FIFTH AND STILL SAW NO 2959 01:46:45,540 --> 01:46:47,375 TRANSMISSION IN THESE ANIMALS. 2960 01:46:47,375 --> 01:46:49,978 WE WORKED WITH ZONDA AND USED 2961 01:46:49,978 --> 01:46:51,913 THIS TRANSGENIC ACE 2 HAMSTERS 2962 01:46:51,913 --> 01:46:54,049 AND REALLY INCREASED THE CONTACT 2963 01:46:54,049 --> 01:46:57,752 TIME TO 96 HOURS. 2964 01:46:57,752 --> 01:46:58,720 BUT STILL SAW NO TRANSMISSION. 2965 01:46:58,720 --> 01:47:00,488 IT WAS ONLY WHEN WE DID DIRECT 2966 01:47:00,488 --> 01:47:02,357 CONTACT STUDIES WITH BA1 THAT WE 2967 01:47:02,357 --> 01:47:06,861 SAW THE TRANSMISSION. 2968 01:47:06,861 --> 01:47:10,599 OOSK TOF COURSE THE VIRUS HAS BN 2969 01:47:10,599 --> 01:47:12,067 MUTATING THROUGHOUT THESE LAST 2970 01:47:12,067 --> 01:47:13,602 FOUR YEARS. 2971 01:47:13,602 --> 01:47:17,572 WUHAN, DELTA, MU, WE ALWAYS SAW 2972 01:47:17,572 --> 01:47:18,340 100% TRANSMISSION. 2973 01:47:18,340 --> 01:47:22,444 WITH BA1 ON TO BA5, THERE WAS 2974 01:47:22,444 --> 01:47:23,712 NEVER ABLE TO SEE AIRBORNE 2975 01:47:23,712 --> 01:47:24,412 TRANSMISSION WITH THESE 2976 01:47:24,412 --> 01:47:24,679 VARIANTS. 2977 01:47:24,679 --> 01:47:28,316 IT WAS INTERESTING THAT WHEN A 2978 01:47:28,316 --> 01:47:30,418 NATURALLY OCCURRING RECOMBINANT 2979 01:47:30,418 --> 01:47:32,821 OF DELTA THAT POSSESSED THE 2980 01:47:32,821 --> 01:47:35,023 BA1 SPIKE EMERGED, WHICH WAS 2981 01:47:35,023 --> 01:47:39,027 CALLED XD, AGAIN WE SAW 100% 2982 01:47:39,027 --> 01:47:39,461 TRANSMISSION. 2983 01:47:39,461 --> 01:47:42,163 SO A SPIKE FROM BA1 THAT IS NOT 2984 01:47:42,163 --> 01:47:44,432 TRANSMISSIBLE PUT INTO THE DELTA 2985 01:47:44,432 --> 01:47:46,868 BACKGROUND DID RESULT IN A 2986 01:47:46,868 --> 01:47:51,573 TRANSMISSIBLE VIRUS THEN. 2987 01:47:51,573 --> 01:47:54,042 AS THE VIRUS KEPT EVOLVING, WE 2988 01:47:54,042 --> 01:47:56,411 GOT MORE MUTATIONS IN THE SPIKE 2989 01:47:56,411 --> 01:47:58,847 AND OTHER OPEN READING FRAMES, 2990 01:47:58,847 --> 01:48:00,548 WE DID SEE TRANSMISSION CREEP UP 2991 01:48:00,548 --> 01:48:04,919 FROM XBB.1.16 THAT WE SAW 50% 2992 01:48:04,919 --> 01:48:06,855 TRANSMISSION, AND THEN 50 AND 2993 01:48:06,855 --> 01:48:10,392 60% TRANSMISSION WITH 2994 01:48:10,392 --> 01:48:12,027 XBB.1.5 AND EG.5.1. 2995 01:48:12,027 --> 01:48:13,662 WE STARTED DOING VACCINATION 2996 01:48:13,662 --> 01:48:16,598 STUDIES TO SEE IF VACCINES WOULD 2997 01:48:16,598 --> 01:48:19,234 CHANGE TRANSMISSION KINETICS, 2998 01:48:19,234 --> 01:48:22,003 AND ALSO A NEW VARIANT CAME OUT, 2999 01:48:22,003 --> 01:48:24,239 JN.1, WHICH HAD ANOTHER 30 TO 40 3000 01:48:24,239 --> 01:48:25,540 AMINO ACID DIFFERENCES IN ITS 3001 01:48:25,540 --> 01:48:26,241 GENOME. 3002 01:48:26,241 --> 01:48:28,576 AND THAT VIRUS NOW WAS AGAIN 3003 01:48:28,576 --> 01:48:29,778 DEAD IN OUR AIRBORNE 3004 01:48:29,778 --> 01:48:33,581 TRANSMISSION STUDIES. 3005 01:48:33,581 --> 01:48:37,485 NOW WE WORKED TOGETHER TO LOOK 3006 01:48:37,485 --> 01:48:41,189 AT SOME CORONAVIRUS OF ENDEMIC 3007 01:48:41,189 --> 01:48:41,756 POTENTIAL. 3008 01:48:41,756 --> 01:48:47,228 THIS INCLUDED THE PENG LIN 3009 01:48:47,228 --> 01:48:48,496 CORONAVIRUS THAT WE SAW 17% 3010 01:48:48,496 --> 01:48:53,535 TRANSMISSION AND WIVSH014 AND 3011 01:48:53,535 --> 01:48:54,969 BANAL WHICH DON'T SHOW ANY 3012 01:48:54,969 --> 01:48:55,603 TRANSMISSION IN THE HAMSTER 3013 01:48:55,603 --> 01:48:57,839 MODEL. 3014 01:48:57,839 --> 01:49:00,942 WHICH OF COURSE IS GOOD SINCE 3015 01:49:00,942 --> 01:49:02,544 THESE DON'T TRANSMIT IN HUMANS 3016 01:49:02,544 --> 01:49:03,945 AND THERE NEEDS TO BE SOME KIND 3017 01:49:03,945 --> 01:49:04,846 OF BARRIER THAT NEEDS TO 3018 01:49:04,846 --> 01:49:06,314 OVERCOME FOR THESE VIRUSES TO 3019 01:49:06,314 --> 01:49:06,715 TRANSMIT. 3020 01:49:06,715 --> 01:49:08,683 SO WHAT ARE THE ALTERNATIVES 3021 01:49:08,683 --> 01:49:12,787 THAT WE HAVE? 3022 01:49:12,787 --> 01:49:15,090 SINCE IT'S PROBABLY NOT GREAT TO 3023 01:49:15,090 --> 01:49:16,324 PASSAGE ANY OF THESE VIRUSES TO 3024 01:49:16,324 --> 01:49:19,561 GET THEM TO TRANSMIT, LET MOTHER 3025 01:49:19,561 --> 01:49:21,529 NATURE DO THAT, WE'RE LOOKING AT 3026 01:49:21,529 --> 01:49:22,731 ALTERNATIVE ANIMAL MODELS. 3027 01:49:22,731 --> 01:49:24,032 WE THOUGHT FERRETS WOULD BE 3028 01:49:24,032 --> 01:49:24,799 GOOD. 3029 01:49:24,799 --> 01:49:29,938 SO WE INFECTED FEMALES 10 TO THE 3030 01:49:29,938 --> 01:49:38,747 6 PFU DELTA OR EG.5.1. 3031 01:49:38,747 --> 01:49:41,249 THE DELTA VARIANT GREW HIGH 3032 01:49:41,249 --> 01:49:45,720 TITERS IN THE NASAL TURBINATE 3033 01:49:45,720 --> 01:49:54,396 AND IN THE SOFT PA PAL L PALAT 3034 01:49:54,396 --> 01:49:55,330 LUNGS. 3035 01:49:55,330 --> 01:49:57,932 IF WE WANT TO STUDY GN1 OR OTHER 3036 01:49:57,932 --> 01:49:59,367 VARIANTS THAT DON'T TRANSMIT IN 3037 01:49:59,367 --> 01:50:00,335 HAMSTERS, THE FERRET MODEL DOES 3038 01:50:00,335 --> 01:50:01,736 NOT SEEM TO BE USEFUL HERE. 3039 01:50:01,736 --> 01:50:04,239 WE HAVE STARTED LOOKING AT DWARF 3040 01:50:04,239 --> 01:50:04,606 HAMSTERS. 3041 01:50:04,606 --> 01:50:06,040 THIS CAME AFTER A GERMAN 3042 01:50:06,040 --> 01:50:07,642 PUBLICATION THAT THESE DWARF 3043 01:50:07,642 --> 01:50:10,345 HAMSTERS ARE EXTREMELY 3044 01:50:10,345 --> 01:50:12,981 SUSCEPTIBLE TO COV-2. 3045 01:50:12,981 --> 01:50:15,383 THEY SHAKE, THEY LOSE WEIGHT, 3046 01:50:15,383 --> 01:50:18,186 THEY WILL DIE. 3047 01:50:18,186 --> 01:50:22,223 SO WE DECIDED TO INFECT THESE 3048 01:50:22,223 --> 01:50:23,892 DWARF HAMSTERS WITH A BUNCH OF 3049 01:50:23,892 --> 01:50:25,360 DIFFERENT OMICRON VARIANTS, AND 3050 01:50:25,360 --> 01:50:27,695 YOU CAN SEE ON THE LEFT-HAND 3051 01:50:27,695 --> 01:50:32,700 SIDE THE NASAL TURBINATE TITERS, 3052 01:50:32,700 --> 01:50:35,136 THIS VIRUS REPLICATES GREAT. 3053 01:50:35,136 --> 01:50:36,204 THIS IS DIFFERENT FROM WHAT WE 3054 01:50:36,204 --> 01:50:40,809 SAW WITH BA1 AND SYRIAN HAMENTS 3055 01:50:40,809 --> 01:50:42,977 TERSE, YOU SO YOU NO OR VERY 3056 01:50:42,977 --> 01:50:44,279 POOR NON-CONSISTENT REPLICATION 3057 01:50:44,279 --> 01:50:46,147 OF BSM A1 AND THE SYRIAN 3058 01:50:46,147 --> 01:50:50,018 HAMSTERS WITH LOW TITERS AND THE 3059 01:50:50,018 --> 01:50:51,252 NASAL TURBINATE TO ALMOST NO 3060 01:50:51,252 --> 01:50:52,987 DETECTABLE VIRUS TITERS IN THE 3061 01:50:52,987 --> 01:50:53,321 LUNG. 3062 01:50:53,321 --> 01:50:58,927 THIS EXTENDS FROM BA1 TO BA5 TO 3063 01:50:58,927 --> 01:50:59,294 XBB.1.16. 3064 01:50:59,294 --> 01:51:01,896 SO WE SET UP A PILOT STUDY JUST 3065 01:51:01,896 --> 01:51:03,331 LOOKING AT DIRECT TRANSMISSION 3066 01:51:03,331 --> 01:51:06,601 OF DELTA, DELTA WILL TRANSMIT 3067 01:51:06,601 --> 01:51:07,469 ALL THE TIME. 3068 01:51:07,469 --> 01:51:09,170 SO WE INFECTED THESE DWARFS WITH 3069 01:51:09,170 --> 01:51:12,173 10 TO THE THIRD PFU, WE DIDN'T 3070 01:51:12,173 --> 01:51:12,740 WANT TO KILL THEM. 3071 01:51:12,740 --> 01:51:15,777 WE WAITED 48 HOURS FOR 3072 01:51:15,777 --> 01:51:18,046 TRANSMISSION TO HOPEFULLY 3073 01:51:18,046 --> 01:51:19,514 HAPPEN, AND YOU CAN SEE FROM THE 3074 01:51:19,514 --> 01:51:21,216 INFECTED ANIMALS WE HAD GREAT 3075 01:51:21,216 --> 01:51:23,384 VIRUS REPLICATION IN THE NASAL 3076 01:51:23,384 --> 01:51:24,686 TURBINATES AND THE LUNGS, BUT WE 3077 01:51:24,686 --> 01:51:30,325 WERE NEVER ABLE TO DETECT DIRECT 3078 01:51:30,325 --> 01:51:32,660 CONTACT TRANSMISSION IN THE 3079 01:51:32,660 --> 01:51:33,294 DWARFS. 3080 01:51:33,294 --> 01:51:35,697 WE HAVE NOT GONE OUT TO 21, 28 3081 01:51:35,697 --> 01:51:39,434 DAYS TO LOOK AT SERO CONVERSION, 3082 01:51:39,434 --> 01:51:41,569 JUST BASING THIS ON NO 3083 01:51:41,569 --> 01:51:44,405 INFECTIOUS VIRUS ON DAY 3. 3084 01:51:44,405 --> 01:51:45,373 ANOTHER ALTERNATIVE IS WHAT WE 3085 01:51:45,373 --> 01:51:46,908 CALL THE BUBBLE BOY HAMSTERS. 3086 01:51:46,908 --> 01:51:50,078 THESE HAMSTERS LACK IL2 RECEPTOR 3087 01:51:50,078 --> 01:51:50,812 GAMMA. 3088 01:51:50,812 --> 01:51:51,713 IL2 IS IMPORTANT FOR YOU TO 3089 01:51:51,713 --> 01:51:55,183 DEVELOP T CELLS, B CELLS AND -- 3090 01:51:55,183 --> 01:51:55,617 CELLS. 3091 01:51:55,617 --> 01:51:57,352 AGAIN THESE ARE FROM ZONDA'S 3092 01:51:57,352 --> 01:51:59,954 LAB. 3093 01:51:59,954 --> 01:52:01,756 WE CAN TAKE THESE ANIMALS OUT TO 3094 01:52:01,756 --> 01:52:03,625 DAY 100 WHEN WE INFECT THEM WITH 3095 01:52:03,625 --> 01:52:05,960 10 TO THE FOURTH PFU SO IT'S A 3096 01:52:05,960 --> 01:52:09,330 PERSISTENT MODEL OF INFECTION. 3097 01:52:09,330 --> 01:52:11,199 WE ONLY SAW TETHER IN ONE ANIMAL 3098 01:52:11,199 --> 01:52:13,201 AROUND DAY 97. 3099 01:52:13,201 --> 01:52:14,235 DESPITE THE INCREASE IN WEIGHT 3100 01:52:14,235 --> 01:52:16,271 GAIN, YOU CAN SEE THAT FROM ORAL 3101 01:52:16,271 --> 01:52:19,140 SWABS, WE HAVE DECENT VIRUS 3102 01:52:19,140 --> 01:52:22,310 TITERS FOR THAT STUDY. 3103 01:52:22,310 --> 01:52:25,580 WE HAVE LOOKED AT VIRUS TITERS 3104 01:52:25,580 --> 01:52:26,614 ON DAY 100 AND YOU CAN SEE THAT 3105 01:52:26,614 --> 01:52:28,449 WE HAVE VERY NICE REPLICATION IN 3106 01:52:28,449 --> 01:52:30,518 THE LUPG AND NASAL TURBINATE, 3107 01:52:30,518 --> 01:52:32,287 AND NOW WHAT WE'RE WORKING ON 3108 01:52:32,287 --> 01:52:34,289 WITH ZONDA RIGHT NOW IS LOOKING 3109 01:52:34,289 --> 01:52:37,559 WOULD WE BE ABLE TO USE THESE LR 3110 01:52:37,559 --> 01:52:41,062 TRANSMISSION STUDIES. 3111 01:52:41,062 --> 01:52:42,530 MAYBE NOT TO LOOK AT EVERY 3112 01:52:42,530 --> 01:52:43,398 VARIANT THAT'S OUT THERE, BUT 3113 01:52:43,398 --> 01:52:44,866 LOOK AT TRANSMISSION DYNAMICS 3114 01:52:44,866 --> 01:52:46,401 AND MAYBE MORE IMPORTANTLY LOOK 3115 01:52:46,401 --> 01:52:47,635 AT VIRUS POPULATIONS. 3116 01:52:47,635 --> 01:52:48,870 WHAT'S THE VIRUS POPULATION IN 3117 01:52:48,870 --> 01:52:50,238 THE INFECTED ANIMAL VERSUS 3118 01:52:50,238 --> 01:52:51,506 WHAT'S THE VIRUS POPULATION IN 3119 01:52:51,506 --> 01:52:54,409 THE TRANSMITTED ANIMAL, IF THIS 3120 01:52:54,409 --> 01:52:56,511 VIRUS WILL TRANSMIT. 3121 01:52:56,511 --> 01:52:58,012 ALSO I DON'T THINK WE SHOULD 3122 01:52:58,012 --> 01:53:02,917 TURN OUR BACKS ON MERS. 3123 01:53:02,917 --> 01:53:04,452 THERE'S A PRE-PRINT OUT ON USING 3124 01:53:04,452 --> 01:53:08,156 THE TRANSGENIC HUMAN 3125 01:53:08,156 --> 01:53:09,324 DPP4 TRANSGENIC MICE. 3126 01:53:09,324 --> 01:53:12,060 THE MICE ARE POOR OR VERY 3127 01:53:12,060 --> 01:53:13,261 INEFFICIENT FOR TRANSMISSION. 3128 01:53:13,261 --> 01:53:17,432 THAT'S BOTH DIRECT AND AIRBORNE 3129 01:53:17,432 --> 01:53:17,765 TRANSMISSION. 3130 01:53:17,765 --> 01:53:20,268 WE WORKED WITH ZONDA TO DO SOME 3131 01:53:20,268 --> 01:53:23,571 PRELIMINARY STUDIES WITH 3132 01:53:23,571 --> 01:53:25,073 TRANSGENIC HAMSTERS NOW 3133 01:53:25,073 --> 01:53:26,307 INFECTING THEM WITH MERS AND 3134 01:53:26,307 --> 01:53:29,210 LOOKING AT DAY THREE, WE CAN SEE 3135 01:53:29,210 --> 01:53:31,846 VIRUS REPLICATION LOWER IN THE 3136 01:53:31,846 --> 01:53:35,650 LUPG LURNG AND HIGHER IN THE NAL 3137 01:53:35,650 --> 01:53:36,618 TURBINATES AND IN THE NEXT 3138 01:53:36,618 --> 01:53:37,952 COUPLE MONTHS WE'LL LOOB AT 3139 01:53:37,952 --> 01:53:39,153 TRANSMISSION WITH THESE ANIMALS. 3140 01:53:39,153 --> 01:53:40,888 SO IN SUMMARY, THE GUINEA PIG 3141 01:53:40,888 --> 01:53:42,457 WOULD BE MY VOTE FOR THE 3142 01:53:42,457 --> 01:53:45,893 TRANSMISSION MODEL FOR INFLUENZA 3143 01:53:45,893 --> 01:53:46,928 VIRUSES, IF WE'RE TALKING ABOUT 3144 01:53:46,928 --> 01:53:48,630 A RODENT MODEL, THERE'S BEEN 3145 01:53:48,630 --> 01:53:51,566 GREAT STUDIES TO LOOK AT VIRUS 3146 01:53:51,566 --> 01:53:52,533 DETERMINANTS OF INFECTION, 3147 01:53:52,533 --> 01:53:55,770 LOOKING AT AMINO ACIDS AND 3148 01:53:55,770 --> 01:53:58,139 PROTEINS THAT ARE ESSENTIAL FOR 3149 01:53:58,139 --> 01:54:00,074 TRANSMISSION. 3150 01:54:00,074 --> 01:54:01,776 WITH SARS-COV-2, HAMSTERS ARE 3151 01:54:01,776 --> 01:54:03,411 SUITABLE BUT WE'RE LACKING THE 3152 01:54:03,411 --> 01:54:04,145 AIRBORNE TRANSMISSION ROUTES IN 3153 01:54:04,145 --> 01:54:07,582 SOME OF THESE. 3154 01:54:07,582 --> 01:54:08,950 AND WE SHOULD START LEARNING 3155 01:54:08,950 --> 01:54:11,019 WHAT THE INFLUENZA GROUP HAS 3156 01:54:11,019 --> 01:54:12,687 DONE FOR TRANSMISSION STUDIES AS 3157 01:54:12,687 --> 01:54:18,092 WE START BRINGING THIS INTO 3158 01:54:18,092 --> 01:54:20,328 SARS, SARS-COV-2 TRANSMISSION 3159 01:54:20,328 --> 01:54:21,763 STUDIES, MAINLY LOOKING AT WHAT 3160 01:54:21,763 --> 01:54:23,131 ARE THE VIRAL DETERMINANTS THAT 3161 01:54:23,131 --> 01:54:26,734 WE'RE SEEING WITH THIS 3162 01:54:26,734 --> 01:54:28,803 DIFFERENCE BETWEEN PREOMICRON 3163 01:54:28,803 --> 01:54:30,238 AND POST OMICRON VARIANT AND OF 3164 01:54:30,238 --> 01:54:31,439 COURSE DOING LOSS OF FUNCTION 3165 01:54:31,439 --> 01:54:31,739 STUDIES. 3166 01:54:31,739 --> 01:54:36,144 FOR THAT, THNGS FOR YOUR TIME. 3167 01:54:36,144 --> 01:54:36,644 THANKS FOR YOUR TIME. 3168 01:54:36,644 --> 01:54:37,812 >> TIME FOR QUESTIONS. 3169 01:54:37,812 --> 01:54:40,682 >> THIS IS TONY WONG FROM FDA. 3170 01:54:40,682 --> 01:54:41,382 VERY BEAUTIFUL WORK. 3171 01:54:41,382 --> 01:54:44,686 I'M JUST WONDERING FOR THOSE 3172 01:54:44,686 --> 01:54:46,821 SOME OF THE OMICRONS THAT DO NOT 3173 01:54:46,821 --> 01:54:48,156 TRANSMIT VERY WELL IN HAMSTER 3174 01:54:48,156 --> 01:54:50,324 MODEL, DID YOU TRY TO CORRELATE 3175 01:54:50,324 --> 01:54:54,462 THE VIRAL LOAD IN THE NASAL 3176 01:54:54,462 --> 01:54:55,763 CAVITY VERSUS TRANSMISSIBILITY? 3177 01:54:55,763 --> 01:54:57,432 >> THIS IS A STUDY WE HAVE 3178 01:54:57,432 --> 01:54:58,766 PLANNED HERE, NOT ONLY 3179 01:54:58,766 --> 01:54:59,801 CORRELATION BETWEEN TITERS BUT 3180 01:54:59,801 --> 01:55:02,136 WE ALSO WANT TO SEE WHAT'S BEING 3181 01:55:02,136 --> 01:55:05,373 EXPELLED BY CATCHING VIRUSES ON 3182 01:55:05,373 --> 01:55:06,474 CELL CULTURE PLATES AND THEN 3183 01:55:06,474 --> 01:55:08,509 ALSO I THINK IT'S WORTH DOING 3184 01:55:08,509 --> 01:55:09,711 JUST DIRECT TRANSMISSION WITH 3185 01:55:09,711 --> 01:55:12,246 ALL OF THESE VARIANTS, AS MANY 3186 01:55:12,246 --> 01:55:13,981 AS WE CAN, TO SEE IF THERE'S ANY 3187 01:55:13,981 --> 01:55:14,515 DIFFERENCES THERE. 3188 01:55:14,515 --> 01:55:16,017 BUT YEAH, THAT'S A STUDY THAT 3189 01:55:16,017 --> 01:55:16,517 WE'RE LOOKING AT 3190 01:55:16,517 --> 01:55:18,853 >> DO YOU THINK THE REASON THAT 3191 01:55:18,853 --> 01:55:21,823 SOME OF THE OMICRON SUBVARIANTS 3192 01:55:21,823 --> 01:55:24,025 DO NOT TRANSMIT VERY WELL IN 3193 01:55:24,025 --> 01:55:26,194 HAMSTER MODEL IS BECAUSE THEY 3194 01:55:26,194 --> 01:55:27,295 JUST SIMPLY DON'T REPLICATE VERY 3195 01:55:27,295 --> 01:55:28,863 WELL IN NASAL CAVITY? 3196 01:55:28,863 --> 01:55:31,332 >> I WOULD SAY THE OMICRONS 3197 01:55:31,332 --> 01:55:33,835 REPLICATE BETTER IN THE NASAL 3198 01:55:33,835 --> 01:55:34,168 TURBINATES -- 3199 01:55:34,168 --> 01:55:35,703 >> EVEN IN HAMSTERS? 3200 01:55:35,703 --> 01:55:36,637 >> YEAH. 3201 01:55:36,637 --> 01:55:38,172 SO IT'S KIND OF ACTUALLY 3202 01:55:38,172 --> 01:55:39,540 DIFFERENT, SO WITH THE DELTA YOU 3203 01:55:39,540 --> 01:55:40,475 SEE HIGHER IN THE LUNG AND LOWER 3204 01:55:40,475 --> 01:55:44,779 IN THE NASAL TURBINATES WITH 3205 01:55:44,779 --> 01:55:45,880 OMICRONS AND AFTER, IT'S THE 3206 01:55:45,880 --> 01:55:46,547 OTHER WAY AROUND. 3207 01:55:46,547 --> 01:55:49,851 >> WE KIND OF -- I MEAN, THE 3208 01:55:49,851 --> 01:55:50,885 LITERATURE, MY RECOLLECTION, IS 3209 01:55:50,885 --> 01:55:53,187 SOME LABS SHOW THAT OMICRON 3210 01:55:53,187 --> 01:55:55,022 REPLICATES WELL IN NASAL 3211 01:55:55,022 --> 01:55:56,858 TURBINATES, BUT SOME LABS DON'T. 3212 01:55:56,858 --> 01:56:00,495 LIKE IN OUR OWN GROUP, OMICRON 3213 01:56:00,495 --> 01:56:02,163 SUBVARIANTS ALWAYS REPLICATE 3214 01:56:02,163 --> 01:56:03,865 WORSE THAN THE PREOMICRON EVEN 3215 01:56:03,865 --> 01:56:05,867 IN SYRIAN HAMSTERS. 3216 01:56:05,867 --> 01:56:07,268 >> MALES OR FEMALES? 3217 01:56:07,268 --> 01:56:08,002 >> ACTUALLY BOTH. 3218 01:56:08,002 --> 01:56:09,237 >> INTERESTING. 3219 01:56:09,237 --> 01:56:10,972 COULD BE VENDOR-SPECIFIC TOO. 3220 01:56:10,972 --> 01:56:11,606 >> SURE. 3221 01:56:11,606 --> 01:56:13,441 THANKS. 3222 01:56:13,441 --> 01:56:14,709 >> STANLEY. 3223 01:56:14,709 --> 01:56:18,045 >> SO ALONG THE SAME LINES, I 3224 01:56:18,045 --> 01:56:18,913 THOUGHT THE EXPERIMENT YOU 3225 01:56:18,913 --> 01:56:22,750 BRIEFLY MENTIONED BETWEEN THE XD 3226 01:56:22,750 --> 01:56:25,486 AND BA1 AND DELTA VARIANTS WAS 3227 01:56:25,486 --> 01:56:27,421 VERY INTERESTING BECAUSE YOU SAW 3228 01:56:27,421 --> 01:56:28,422 THAT TRANSMISSION BASICALLY 3229 01:56:28,422 --> 01:56:30,191 WASN'T DEPENDENT ON THE SPIKE 3230 01:56:30,191 --> 01:56:31,292 PROTEIN. 3231 01:56:31,292 --> 01:56:33,327 SO ARE YOU GOING TO BE 3232 01:56:33,327 --> 01:56:39,267 INVESTIGATING THOSE MORE? 3233 01:56:39,267 --> 01:56:43,671 >> WE'RE KIND OF FOLLOWING MATT 3234 01:56:43,671 --> 01:56:45,907 FRIEDMAN'S LEAD ON LOOKING AT 3235 01:56:45,907 --> 01:56:52,146 SOCK KNOCKOUTS, # OR 6. 3236 01:56:52,146 --> 01:56:55,950 MAYBE THINKING ABOUT AMINO ACID 3237 01:56:55,950 --> 01:56:57,585 CHANGES IN THE ORFs -- 3238 01:56:57,585 --> 01:57:01,088 >> WONDERING IF IT'S THE ORFs 3239 01:57:01,088 --> 01:57:02,156 OR MSPs OR -- 3240 01:57:02,156 --> 01:57:03,991 >> YEAH. 3241 01:57:03,991 --> 01:57:10,398 >> SO IN YOUR MODEL TO PUP 3242 01:57:10,398 --> 01:57:12,133 TRANSMISSION MODEL OF HN1 YOU 3243 01:57:12,133 --> 01:57:13,267 SAID SOME OF THEM WERE 3244 01:57:13,267 --> 01:57:13,634 SUCCESSFUL. 3245 01:57:13,634 --> 01:57:17,138 WHEN YOU LOOK AT THE LITTERS, IS 3246 01:57:17,138 --> 01:57:20,541 IT REALLY LITTER-SPECIFIC, LIKE 3247 01:57:20,541 --> 01:57:21,943 MOMS THAT TRANSMIT BETTER THAN 3248 01:57:21,943 --> 01:57:22,243 OTHER MOMS? 3249 01:57:22,243 --> 01:57:23,611 >> NO, THERE WAS NO CORRELATION. 3250 01:57:23,611 --> 01:57:25,046 SO WITH THE NUMBERS THAT WE DID, 3251 01:57:25,046 --> 01:57:27,849 YOU WOULD HAVE A LITTER OF FIVE 3252 01:57:27,849 --> 01:57:30,284 PUPS, ALL OF THEM WOULD BE 3253 01:57:30,284 --> 01:57:30,952 INFECTED. 3254 01:57:30,952 --> 01:57:32,220 SOMETIMES YOU'D HAVE ONE OR TWO. 3255 01:57:32,220 --> 01:57:33,688 IF YOU TRY TO CONSIDER LATE THAT 3256 01:57:33,688 --> 01:57:37,124 WITH WAS THE MAMMARY GLAND 3257 01:57:37,124 --> 01:57:38,659 POSITIVE FOR VIRUS, WE HAD SOME 3258 01:57:38,659 --> 01:57:41,629 MOMS THAT DID HAVE POSITIVE 3259 01:57:41,629 --> 01:57:44,999 MAMMARY GRANDZ BU GLANDS BUT NOT 3260 01:57:44,999 --> 01:57:45,666 WERE AFFECTED. 3261 01:57:45,666 --> 01:57:47,735 SO IT SEEMS TO BE A TIMING 3262 01:57:47,735 --> 01:57:49,604 THING, HOW WELL THE VIRUS CAN GO 3263 01:57:49,604 --> 01:57:50,605 FROM THE LUNGS TO THE REST OF 3264 01:57:50,605 --> 01:57:51,272 THE BODY. 3265 01:57:51,272 --> 01:57:53,341 NINE DATES IS AS FAR AS WE CAN 3266 01:57:53,341 --> 01:57:56,277 TAKE IT OUT BECAUSE OF THE 3267 01:57:56,277 --> 01:58:00,848 LETHALITY AT 100 PFI OF THAT 3268 01:58:00,848 --> 01:58:01,048 VIRUS. 3269 01:58:01,048 --> 01:58:05,019 >> THANK YOU. 3270 01:58:05,019 --> 01:58:15,563 I'D LIKE TO INVITE MILA ORTIGOZA 3271 01:58:19,834 --> 01:58:22,737 FROM NYU LANGONE HEALTH, SHE 3272 01:58:22,737 --> 01:58:24,372 WILL BE TALKING ABOUT THE INFANT 3273 01:58:24,372 --> 01:58:26,774 MOUSE MODEL TO STUDY INFLUENZA 3274 01:58:26,774 --> 01:58:27,541 VIRUS AND SARS-COV-2 3275 01:58:27,541 --> 01:58:27,975 TRANSMISSION. 3276 01:58:27,975 --> 01:58:29,844 >> I WANT TO THANK THE 3277 01:58:29,844 --> 01:58:30,845 ORGANIZERS FOR INVITING ME. 3278 01:58:30,845 --> 01:58:32,914 I'M REALLY EXCITED TO TALK ABOUT 3279 01:58:32,914 --> 01:58:34,015 THE MOUSE MODEL FOR 3280 01:58:34,015 --> 01:58:34,348 TRANSMISSION. 3281 01:58:34,348 --> 01:58:35,983 I THINK IN THE PAST 36 HOURS, 3282 01:58:35,983 --> 01:58:37,018 EVERY SLIDE I'VE SEEN, THERE IS 3283 01:58:37,018 --> 01:58:38,486 A LOT OF PEOPLE SAYING MICE 3284 01:58:38,486 --> 01:58:40,221 DON'T TRANSMIT, SO I HOPE THAT I 3285 01:58:40,221 --> 01:58:44,358 CAN CONVINCE YOU OTHERWISE. 3286 01:58:44,358 --> 01:58:45,826 AND WE'LL HAVE A DIALOGUE THAT 3287 01:58:45,826 --> 01:58:47,762 WE NEED DIVERSITY OF MODELS, 3288 01:58:47,762 --> 01:58:48,629 DEPENDING ON THE QUESTIONS WE 3289 01:58:48,629 --> 01:58:51,399 ASK, WE CAN LEARN A LOT ABOUT 3290 01:58:51,399 --> 01:59:01,642 TRANSMISSION. 3291 01:59:04,679 --> 01:59:06,647 SO IN OUR LAB, WE THINK OF 3292 01:59:06,647 --> 01:59:08,416 TRANSMISSION IN THREE DIFFERENT 3293 01:59:08,416 --> 01:59:08,649 STAGES. 3294 01:59:08,649 --> 01:59:10,384 STAGE I IS THE UPPER RESPIRATORY 3295 01:59:10,384 --> 01:59:11,719 TRACT REPLICATION OF THE VIRUS 3296 01:59:11,719 --> 01:59:14,655 AND THAT HOST IMMUNE RESPONSE TO 3297 01:59:14,655 --> 01:59:15,323 INFECTION. 3298 01:59:15,323 --> 01:59:16,724 STAGE II IS SHEDDING OF THAT 3299 01:59:16,724 --> 01:59:18,292 VIRUS INTO THE ENVIRONMENT. 3300 01:59:18,292 --> 01:59:19,694 AND STAGE III IS VIRUS 3301 01:59:19,694 --> 01:59:23,197 ACQUISITION OF A NAIVE HOST. 3302 01:59:23,197 --> 01:59:25,599 I DO ALSO WANT TO BRING UP STAGE 3303 01:59:25,599 --> 01:59:27,201 IV THAT'S OFTEN STUDIED IN 3304 01:59:27,201 --> 01:59:28,869 INFLUENZA VIRUSES, IT'S THE 3305 01:59:28,869 --> 01:59:30,871 STAGE OF PATHOGENESIS WHERE 3306 01:59:30,871 --> 01:59:32,707 VIRUS IN THE UPPER RESPIRATORY 3307 01:59:32,707 --> 01:59:34,542 TRACT TRANSITIONS TO THE LOWER 3308 01:59:34,542 --> 01:59:36,711 RESPIRATORY TRACT, CAUSING 3309 01:59:36,711 --> 01:59:39,513 INVASIVE DISEASE, IN THIS CASE, 3310 01:59:39,513 --> 01:59:41,449 PNEUMONIA. 3311 01:59:41,449 --> 01:59:42,950 THIS IS NOT THE FOCUS OF OUR 3312 01:59:42,950 --> 01:59:43,484 STUDY. 3313 01:59:43,484 --> 01:59:44,552 ALTHOUGH VERY IMPORTANT FOR 3314 01:59:44,552 --> 01:59:46,454 VACCINE WORK, WE KNOW THAT 3315 01:59:46,454 --> 01:59:49,256 VACCINES PROTECT HOSTS FROM 3316 01:59:49,256 --> 01:59:50,424 DISEASE, STAGE IV, BUT WE ALSO 3317 01:59:50,424 --> 01:59:52,460 KNOW THAT WE CAN DO BETTER 3318 01:59:52,460 --> 01:59:54,328 BECAUSE CURRENT VACCINES DO NOT 3319 01:59:54,328 --> 01:59:55,529 PROTECT AGAINST TRANSMISSION 3320 01:59:55,529 --> 01:59:58,366 BECAUSE THEY DON'T INDUCE A 3321 01:59:58,366 --> 02:00:00,101 POTENT MUCOSAL IMMUNITY IN THE 3322 02:00:00,101 --> 02:00:01,969 UPPER RESPIRATORY TRACT. 3323 02:00:01,969 --> 02:00:05,573 SO WE DO FOCUS ON STAGE I 3324 02:00:05,573 --> 02:00:08,042 THROUGH STAGE III, FOCUSED ON 3325 02:00:08,042 --> 02:00:09,610 THE ANATOMY OF THE UPPER 3326 02:00:09,610 --> 02:00:12,580 RESPIRATORY TRACT IN OUR STUD 3327 02:00:12,580 --> 02:00:13,781 STUDIES. 3328 02:00:13,781 --> 02:00:14,849 THE TWO FUNDAMENTAL QUESTIONS 3329 02:00:14,849 --> 02:00:16,183 THAT WE REALLY WANT TO ANSWER IS 3330 02:00:16,183 --> 02:00:17,985 WHAT DRIVES HOST INFECTIOUSNESS, 3331 02:00:17,985 --> 02:00:20,021 AND WHAT DRIVES HOST 3332 02:00:20,021 --> 02:00:21,122 SUSCEPTIBILITY TO VIRUS 3333 02:00:21,122 --> 02:00:23,557 INFECTION AFTER AN EXPOSURE, AND 3334 02:00:23,557 --> 02:00:25,393 THIS REQUIRES REALLY AN IN DEPTH 3335 02:00:25,393 --> 02:00:28,763 ANALYSIS OF STAGE I, II AND II 3336 02:00:28,763 --> 02:00:30,931 BOTH FROM THE VIRUS PERSPECTIVE 3337 02:00:30,931 --> 02:00:31,732 AS WELL AS FROM THE HOST 3338 02:00:31,732 --> 02:00:32,033 PERSPECTIVE. 3339 02:00:32,033 --> 02:00:34,668 WITH THAT, WE NEED TO CHOOSE AN 3340 02:00:34,668 --> 02:00:35,803 ADEQUATE ANIMAL MODEL THAT NOT 3341 02:00:35,803 --> 02:00:39,807 ONLY ALLOWS US TO STUDY VIRAL 3342 02:00:39,807 --> 02:00:40,808 BIOLOGY BUT ALSO HOST BIOLOGY. 3343 02:00:40,808 --> 02:00:42,543 I'M A PHYSICIAN. 3344 02:00:42,543 --> 02:00:43,677 THERE ISN'T ANYTHING THAT I WANT 3345 02:00:43,677 --> 02:00:45,513 TO DO WITH HUMANS. 3346 02:00:45,513 --> 02:00:46,747 HUMANS ARE THE PERFECT MODELS 3347 02:00:46,747 --> 02:00:49,150 FOR STUDYING TRANSMISSION, BUT 3348 02:00:49,150 --> 02:00:51,652 THEY'RE ALSO VERY CHALLENGING TO 3349 02:00:51,652 --> 02:00:52,953 STUDY THE HOST REQUIREMENTS FOR 3350 02:00:52,953 --> 02:00:53,621 TRANSMISSION. 3351 02:00:53,621 --> 02:00:55,489 SO ARE FERRETS AND GUINEA PIGS. 3352 02:00:55,489 --> 02:00:57,358 THEY'RE FANTASTIC MODELS. 3353 02:00:57,358 --> 02:00:58,859 YOU CAN USE CLINICAL ISOLATES 3354 02:00:58,859 --> 02:01:01,495 AND ASK QUESTIONS ABOUT VIRAL 3355 02:01:01,495 --> 02:01:02,329 TRANSMISSIBILITY VERY EASILY, 3356 02:01:02,329 --> 02:01:04,265 BUT THEY DO HAVE DRAW BACKS. 3357 02:01:04,265 --> 02:01:05,633 THEY'RE COMPLEX, THEY'RE 3358 02:01:05,633 --> 02:01:07,701 EXPENSIVE, THEY REQUIRE SPECIAL 3359 02:01:07,701 --> 02:01:08,602 HOUSING. 3360 02:01:08,602 --> 02:01:10,237 OFTEN TRANSMISSION STUDIES ARE 3361 02:01:10,237 --> 02:01:13,407 LARGELY UNDERPOWERED, AND MOST 3362 02:01:13,407 --> 02:01:16,177 IMPORTANTLY, RIGHT NOW I THINK 3363 02:01:16,177 --> 02:01:19,980 THE TOPIC OF THIS SESSION, 3364 02:01:19,980 --> 02:01:21,715 LIMITED REAGENTS, WE CAN DO MUCH 3365 02:01:21,715 --> 02:01:23,150 BETTER ABOUT REAGENTS IN THESE 3366 02:01:23,150 --> 02:01:23,384 MODELS. 3367 02:01:23,384 --> 02:01:25,352 ALL OF THESE DRAWBACKS IN THESE 3368 02:01:25,352 --> 02:01:26,420 COMPLEX MODELS ARE ACTUALLY 3369 02:01:26,420 --> 02:01:27,955 ADVANTAGES IN THE MOUSE MODEL, 3370 02:01:27,955 --> 02:01:29,290 BUT AS WE KNOW HISTORICALLY FOR 3371 02:01:29,290 --> 02:01:31,892 THE PAST 70 YEARS, ADULT MICE 3372 02:01:31,892 --> 02:01:34,195 HAVE DEMONSTRATED INCONSISTENT 3373 02:01:34,195 --> 02:01:36,263 TRANSMISSION AND WE WERE VERY 3374 02:01:36,263 --> 02:01:40,201 INTERESTED IN UNDERSTANDING WHY 3375 02:01:40,201 --> 02:01:41,102 ADULT MICE DON'T TRANSMIT 3376 02:01:41,102 --> 02:01:42,570 BECAUSE WE REALLY WANTED TO 3377 02:01:42,570 --> 02:01:43,938 STUDY HOST BIOLOGY AND HOST 3378 02:01:43,938 --> 02:01:44,738 DETERMINANTS OF TRANSMISSION. 3379 02:01:44,738 --> 02:01:46,707 SO FOR THE PAST SIX YEARS, WE'VE 3380 02:01:46,707 --> 02:01:49,877 BEEN OPTIMIZING AND VALIDATING 3381 02:01:49,877 --> 02:01:51,479 THE MOUSE MODEL, WE IDENTIFIED 3382 02:01:51,479 --> 02:01:54,315 INFANT MICE TO BE VERY RELIABLE, 3383 02:01:54,315 --> 02:01:55,616 VERY EFFICIENT, VERY ROBUST 3384 02:01:55,616 --> 02:01:58,719 MODEL TO STUDY FLU TRANSMISSION. 3385 02:01:58,719 --> 02:02:00,788 BUT NO MODEL IS PERFECT, AND THE 3386 02:02:00,788 --> 02:02:03,657 INFANT MOUSE MODEL IS NOT 3387 02:02:03,657 --> 02:02:03,958 UNIQUE. 3388 02:02:03,958 --> 02:02:05,826 ONE OF THE MAJOR DRAWBACKS IS 3389 02:02:05,826 --> 02:02:10,631 THAT THEY COME AS A UNIT, SO THE 3390 02:02:10,631 --> 02:02:11,966 MOTHERS IN THE CAGE, YOU CANNOT 3391 02:02:11,966 --> 02:02:12,833 SEPARATE THE PUPS FROM EACH 3392 02:02:12,833 --> 02:02:14,335 OTHER, YOU CANNOT SEPARATE THE 3393 02:02:14,335 --> 02:02:15,369 MOM FROM THE PUPS SO THAT LIMITS 3394 02:02:15,369 --> 02:02:17,671 THE KIND OF QUESTIONS WE CAN ASK 3395 02:02:17,671 --> 02:02:19,306 WITH THIS MODEL SUCH AS THE 3396 02:02:19,306 --> 02:02:20,374 MODES OF TRANSMISSION, AND LIKE 3397 02:02:20,374 --> 02:02:21,909 SEEMA MENTIONED PREVIOUSLY, WHEN 3398 02:02:21,909 --> 02:02:23,310 IT COMES TO LIKE A HOUSEHOLD 3399 02:02:23,310 --> 02:02:25,980 KIND OF MODEL TRANSMISSION, ALL 3400 02:02:25,980 --> 02:02:27,281 TRANSMISSION MODES ARE VALID. 3401 02:02:27,281 --> 02:02:29,450 SO THIS IS BASICALLY WE VIEW IT 3402 02:02:29,450 --> 02:02:33,087 AS A HOUSEHOLD KIND OF 3403 02:02:33,087 --> 02:02:35,923 TRANSMISSION, YOU KNOW, ASSAY. 3404 02:02:35,923 --> 02:02:38,058 WE CANNOT REALLY ASK QUESTIONS 3405 02:02:38,058 --> 02:02:39,393 ABOUT ROLE OF IMMUNITY BECAUSE 3406 02:02:39,393 --> 02:02:40,661 OBVIOUSLY WE CANNOT SEPARATE THE 3407 02:02:40,661 --> 02:02:44,331 PUPS FROM THE MOTHER. 3408 02:02:44,331 --> 02:02:45,900 THEY'RE CONSTANTLY FEEDING SO WE 3409 02:02:45,900 --> 02:02:46,767 CANNOT ISOLATE THE EFFECTS OF 3410 02:02:46,767 --> 02:02:49,970 THE IMMUNITY FROM THE MOTHER 3411 02:02:49,970 --> 02:02:51,038 BEING TRANSMITTED THROUGH THE 3412 02:02:51,038 --> 02:02:51,438 MILK. 3413 02:02:51,438 --> 02:02:54,842 AND MOST IMPORTANTLY, MICE ARE 3414 02:02:54,842 --> 02:02:56,977 STRAIN-DEPENDENT, SO THERE ARE A 3415 02:02:56,977 --> 02:02:59,847 LOT OF -- ISOLATES THAT JUST 3416 02:02:59,847 --> 02:03:00,714 DON'T AFFECT MICE. 3417 02:03:00,714 --> 02:03:01,549 OTHER THINGS ABOUT THIS MODEL I 3418 02:03:01,549 --> 02:03:02,950 WANT TO MENTION AND I GET THESE 3419 02:03:02,950 --> 02:03:04,585 QUESTIONS A LOT SO I WANT TO 3420 02:03:04,585 --> 02:03:05,553 JUST BRING IT FORTH, DOES THE 3421 02:03:05,553 --> 02:03:07,087 MOTHER GET INFECTED WHEN WE 3422 02:03:07,087 --> 02:03:08,789 INFECT THE PUPS, AND THE ANSWER 3423 02:03:08,789 --> 02:03:10,391 IS YES. 3424 02:03:10,391 --> 02:03:11,792 BUT THE PUPS TRANSMIT TO THE 3425 02:03:11,792 --> 02:03:13,594 MOTHER VERY INEFFICIENTLY, LESS 3426 02:03:13,594 --> 02:03:16,597 THAN 10% OF EXPOSURES. 3427 02:03:16,597 --> 02:03:17,932 OTHER QUESTIONS WE GET ASKED IS, 3428 02:03:17,932 --> 02:03:20,134 WELL, IS THIS A FOMITE KIND OF 3429 02:03:20,134 --> 02:03:22,536 MODE OF TRANSMISSION IN THIS 3430 02:03:22,536 --> 02:03:24,071 MODEL. 3431 02:03:24,071 --> 02:03:26,907 OBVIOUSLY THE INFANTS ARE 3432 02:03:26,907 --> 02:03:28,309 SUCKLING SAME NIPPLES AND THE 3433 02:03:28,309 --> 02:03:30,744 BEDDING IS CONSTANTLY THERE, BUT 3434 02:03:30,744 --> 02:03:33,347 WHEN WE DO CROSS DB EXPERIMENTS 3435 02:03:33,347 --> 02:03:34,882 OR CHANGE THE CAGES, 3436 02:03:34,882 --> 02:03:35,749 TRANSMISSION DOES OCCUR, BUT 3437 02:03:35,749 --> 02:03:37,184 AGAIN, VERY INEFFICIENT. 3438 02:03:37,184 --> 02:03:39,386 SO IN THIS MODEL, TRANSMISSION 3439 02:03:39,386 --> 02:03:41,722 IS DRIVEN FROM PUP TO PUP VIA 3440 02:03:41,722 --> 02:03:42,890 UPPER RESPIRATORY TRACT 3441 02:03:42,890 --> 02:03:43,224 SECRETIONS. 3442 02:03:43,224 --> 02:03:45,759 AND WE DEMONSTRATE THIS HERE IN 3443 02:03:45,759 --> 02:03:47,528 THIS GRAPH OF INFANT SHEDDING, 3444 02:03:47,528 --> 02:03:51,899 WHERE WE HAVE INFECTIOUS TITERS 3445 02:03:51,899 --> 02:03:55,502 OVER TIME, AND EACH DOT IS A 3446 02:03:55,502 --> 02:03:57,471 SHEDDING EVENT FROM A SINGLE 3447 02:03:57,471 --> 02:04:01,976 PUP, AND IN BLACK WE SEE TH THE 3448 02:04:01,976 --> 02:04:05,045 INDEX SHEDDING CORRESPONDS WITH 3449 02:04:05,045 --> 02:04:06,747 THE ACQUISITION OF SHEDDING 3450 02:04:06,747 --> 02:04:09,183 CONTACTS IN RED, AND YOU SEE THE 3451 02:04:09,183 --> 02:04:11,352 TIMING OF INDEX SHEDDING 3452 02:04:11,352 --> 02:04:12,286 CORRESPONDS WITH TRANSMISSION BY 3453 02:04:12,286 --> 02:04:13,220 THE CONTACTS. 3454 02:04:13,220 --> 02:04:15,089 HOW WE COLLECT SHEDDING IN THIS 3455 02:04:15,089 --> 02:04:17,324 ASSAY IS SIMPLY BY DIPPING THE 3456 02:04:17,324 --> 02:04:18,759 NOSTRILS AND ONLY THE NOSTRILS 3457 02:04:18,759 --> 02:04:21,128 OF THE PUPS IN VIRAL MEDIA, AND 3458 02:04:21,128 --> 02:04:23,430 WE CAN EASILY TRACK THE KINETICS 3459 02:04:23,430 --> 02:04:24,531 OF TRANSMISSION OVER TIME 3460 02:04:24,531 --> 02:04:27,268 WITHOUT THE NEED OF SACRIFICING 3461 02:04:27,268 --> 02:04:30,804 THE ANIMAL OR EUTHANIZING OR 3462 02:04:30,804 --> 02:04:32,006 USING ANESTHESIA. 3463 02:04:32,006 --> 02:04:34,808 BUT ALSO WE CAN SELECT DIFFERENT 3464 02:04:34,808 --> 02:04:36,143 TIME POINTS AND ASSESS FOR 3465 02:04:36,143 --> 02:04:37,645 REPLICATION IN THE UPPER 3466 02:04:37,645 --> 02:04:38,879 RESPIRATORY TRACT, AND ASSESS 3467 02:04:38,879 --> 02:04:40,547 FOR TRANSMISSION, AND THIS IS 3468 02:04:40,547 --> 02:04:41,849 HOW WE DEFINE TRANSMISSION. 3469 02:04:41,849 --> 02:04:44,351 SO FOR EXAMPLE, AT DAY # 4, WE 3470 02:04:44,351 --> 02:04:45,986 KNOW WE ACHIEVE 100% 3471 02:04:45,986 --> 02:04:47,821 TRANSMISSION ALREADY IN THIS 3472 02:04:47,821 --> 02:04:50,057 MODEL. 3473 02:04:50,057 --> 02:04:51,592 SO I DON'T WANT TO SPEND TOO 3474 02:04:51,592 --> 02:04:52,693 MUCH TIME TALKING ABOUT THE 3475 02:04:52,693 --> 02:04:56,430 MODEL ITSELF, BUT MORE ABOUT 3476 02:04:56,430 --> 02:04:57,531 WHAT WE'VE LEARNED FROM DOING 3477 02:04:57,531 --> 02:04:58,632 THESE ASSAYS, WHAT ARE THE 3478 02:04:58,632 --> 02:05:01,802 FACTORS THAT ARE IMPORTANT IN 3479 02:05:01,802 --> 02:05:02,569 INFLUENZA TRANSMISSION IN MICE. 3480 02:05:02,569 --> 02:05:03,804 SO WE'RE GOING TO TALK ABOUT 3481 02:05:03,804 --> 02:05:05,306 HOST AGE AND SEX, EXPOSURE 3482 02:05:05,306 --> 02:05:07,274 PERIOD, THE UPPER RESPIRATORY 3483 02:05:07,274 --> 02:05:08,942 TRACT ENVIRONMENT, WHICH 3484 02:05:08,942 --> 02:05:11,578 INCLUDES NOT ONLY SIALIC ACIDS 3485 02:05:11,578 --> 02:05:13,614 BUT THE MICROBIOTA, THE 3486 02:05:13,614 --> 02:05:14,548 INFLAMMATORY STATE AND OBVIOUSLY 3487 02:05:14,548 --> 02:05:15,482 WE'LL FINISH UP WITH OUR 3488 02:05:15,482 --> 02:05:18,986 FAVORITE TOPIC, WHICH IS VIRUS 3489 02:05:18,986 --> 02:05:21,622 STRAIN. 3490 02:05:21,622 --> 02:05:24,058 SO ONE OF THE FIRST THINGS WE 3491 02:05:24,058 --> 02:05:27,094 LEARNED WAS THAT TRANSMISSION 3492 02:05:27,094 --> 02:05:28,862 EFFICIENCY IS DEPENDENT ON HOST 3493 02:05:28,862 --> 02:05:29,563 AGE. 3494 02:05:29,563 --> 02:05:32,599 HERE AGAIN WILL SHOW VIRUS -- 3495 02:05:32,599 --> 02:05:33,967 EACH PANEL REPRESENTS EACH STAGE 3496 02:05:33,967 --> 02:05:35,602 OF TRANSMISSION, SO STAGE ONE 3497 02:05:35,602 --> 02:05:40,174 THE UPPER RESPIRATORY TRACT 3498 02:05:40,174 --> 02:05:41,809 REPLICATION, STAGE II, SHEDDING, 3499 02:05:41,809 --> 02:05:43,777 AND STAGE III, CONTACT 3500 02:05:43,777 --> 02:05:44,578 ACQUISITION. 3501 02:05:44,578 --> 02:05:45,546 AS WE CAN SEE COMPARED IN 3502 02:05:45,546 --> 02:05:47,281 INFANTS AND ADULTS, DESPITE 3503 02:05:47,281 --> 02:05:49,149 EQUAL REPLICATION IN THE UPPER 3504 02:05:49,149 --> 02:05:50,584 RESPIRATORY TRACT, WE SEE VERY 3505 02:05:50,584 --> 02:05:52,886 DIFFERENT KINETICS OF SHEDDING, 3506 02:05:52,886 --> 02:05:54,688 WHEREBY INFANTS SHED HIGHER AND 3507 02:05:54,688 --> 02:05:56,690 MORE EFFICIENTLY THAN ADULTS AND 3508 02:05:56,690 --> 02:05:57,558 CORE SPORINGLY, THEY TRANSMIT 3509 02:05:57,558 --> 02:05:59,026 BETTER COMPARED TO ADULTS. 3510 02:05:59,026 --> 02:06:00,761 AND ALSO INFANTS ARE MORE 3511 02:06:00,761 --> 02:06:02,730 SUSCEPTIBLE TO ADULTS IN 3512 02:06:02,730 --> 02:06:04,531 TRANSMISSION, SO THERE IS AN 3513 02:06:04,531 --> 02:06:06,900 ADVANTAGE TO STAGE TWO, WHERE 3514 02:06:06,900 --> 02:06:09,002 THEY'RE MORE INFECTIOUS, AND 3515 02:06:09,002 --> 02:06:11,839 THERE'S ALSO -- IN STAGE III 3516 02:06:11,839 --> 02:06:13,674 WHERE THEY'RE MORE SUSCEPTIBLE. 3517 02:06:13,674 --> 02:06:16,810 WHEN WI WE LOOK AT CORRELATION F 3518 02:06:16,810 --> 02:06:18,078 AGE COMPARED TO TRANSMISSION 3519 02:06:18,078 --> 02:06:19,513 EFFICIENCY, WE SEE THAT THE 3520 02:06:19,513 --> 02:06:21,181 YOUNGEST TRANSMIT MORE 3521 02:06:21,181 --> 02:06:22,483 EFFICIENTLY AND THE OLDEST 3522 02:06:22,483 --> 02:06:24,651 TRANSMIT VERY INEFFICIENT, SO 3523 02:06:24,651 --> 02:06:25,452 THERE'S A VERY BEAUTIFUL 3524 02:06:25,452 --> 02:06:28,489 CORRELATION WITH AGE. 3525 02:06:28,489 --> 02:06:29,423 OTHER THINGS THAT WE'RE STARTING 3526 02:06:29,423 --> 02:06:32,893 TO LOOK AT, YES, THE FANT MOUSE 3527 02:06:32,893 --> 02:06:34,862 MODEL IS BEAUTIFUL, BUT THERE IS 3528 02:06:34,862 --> 02:06:36,330 AN ADVANTAGE AT LOOKING AT ADULT 3529 02:06:36,330 --> 02:06:38,899 MICE WHERE THEY'RE NOT 3530 02:06:38,899 --> 02:06:42,903 SUSCEPTIBLE TO INFLUENZA VIRUS 3531 02:06:42,903 --> 02:06:44,938 TRANSMISSION, BUT WE DID LEARN 3532 02:06:44,938 --> 02:06:47,040 THAT SEX IS AN IMPORTANT 3533 02:06:47,040 --> 02:06:48,242 BIOLOGICAL VARIABLE THAT WE NEED 3534 02:06:48,242 --> 02:06:49,543 TO TAKE INTO ACCOUNT. 3535 02:06:49,543 --> 02:06:51,178 AND WHEN WE DID THAT IN HERE, 3536 02:06:51,178 --> 02:06:55,582 WE'RE USING ADULT ANIMALS THAT 3537 02:06:55,582 --> 02:06:57,985 MALES ARE MORE SUSCEPTIBLE TO 3538 02:06:57,985 --> 02:06:59,420 ACQUISITION OF INFLUENZA VIRUS 3539 02:06:59,420 --> 02:07:01,321 COMPARED TO FEMALES, SO NOW WE 3540 02:07:01,321 --> 02:07:02,923 NOT ONLY HAVE AN INFANT MOUSE 3541 02:07:02,923 --> 02:07:04,258 MODEL OF TRANSMISSION, WE ALSO 3542 02:07:04,258 --> 02:07:05,926 HAVE AN ADULT MODEL OF 3543 02:07:05,926 --> 02:07:08,962 TRANSMISSION IF WE USE THE RIGHT 3544 02:07:08,962 --> 02:07:09,730 HOST. 3545 02:07:09,730 --> 02:07:10,864 BUT ALSO NOT ONLY USING THE 3546 02:07:10,864 --> 02:07:12,266 RIGHT HOST, WE CAN USE RIGHT 3547 02:07:12,266 --> 02:07:13,233 CONDITIONS. 3548 02:07:13,233 --> 02:07:14,568 SO THINGS THAT WE'VE LEARNED 3549 02:07:14,568 --> 02:07:16,103 FROM HUMANS, WE'RE NOW TRYING TO 3550 02:07:16,103 --> 02:07:18,505 APPLY THIS IN OUR MODEL. 3551 02:07:18,505 --> 02:07:21,742 AGAIN, ADULT HERE SHEDDING, SO 3552 02:07:21,742 --> 02:07:22,776 INDEX SHEDDING IN BLACK CORE 3553 02:07:22,776 --> 02:07:28,816 SPONTS TCORRESPONDS TO ACQUISITF 3554 02:07:28,816 --> 02:07:30,884 THE VIRUS IN THE CONTACTS IN 3555 02:07:30,884 --> 02:07:31,118 RED. 3556 02:07:31,118 --> 02:07:32,319 AS YOU CAN SEE IF YOU REMEMBER 3557 02:07:32,319 --> 02:07:34,388 FROM THE INFANT GRAPH, THE ADULT 3558 02:07:34,388 --> 02:07:35,956 ACQUISITION IS A BIT DELAYED AND 3559 02:07:35,956 --> 02:07:37,057 IF WE SELECT DIFFERENT TIME 3560 02:07:37,057 --> 02:07:38,692 POINTS AND ASSESS FOR VARIABLE 3561 02:07:38,692 --> 02:07:39,893 REPLICATION IN THE UPPER 3562 02:07:39,893 --> 02:07:41,595 RESPIRATORY TRACT, WE SEE THAT 3563 02:07:41,595 --> 02:07:45,132 BY DAY FOUR, INEFFICIENT 3564 02:07:45,132 --> 02:07:46,133 TRANSMISSION BUT LET THEM HANG 3565 02:07:46,133 --> 02:07:48,035 OUT A LITTLE BIT TO FORM THAT 3566 02:07:48,035 --> 02:07:48,669 MEANINGFUL EXPOSURE. 3567 02:07:48,669 --> 02:07:51,738 WE SEE THAT TRANSMISSION IS 3568 02:07:51,738 --> 02:07:55,042 NEARLY 100% IN THE ADULT ANIMALS 3569 02:07:55,042 --> 02:07:57,277 BECAUSE WE ARE EXPOSING THEM FOR 3570 02:07:57,277 --> 02:08:00,280 A LONGER PERIOD OF TIME. 3571 02:08:00,280 --> 02:08:02,783 SO KIND OF LIKE CORRELATES WHEN 3572 02:08:02,783 --> 02:08:04,151 YOU'RE WALKING BY SOMEBODY IN 3573 02:08:04,151 --> 02:08:05,619 THE HALLWAY, THAT EXPOSURE IS 3574 02:08:05,619 --> 02:08:07,187 NOT VERY MEANINGFUL COMPARED TO 3575 02:08:07,187 --> 02:08:08,355 WHERE YOU LIVE WITH THAT PERSON 3576 02:08:08,355 --> 02:08:09,556 OR YOU'RE SITTING IN A CLOSED 3577 02:08:09,556 --> 02:08:09,957 OFFICE. 3578 02:08:09,957 --> 02:08:12,493 SO THE FACT THAT MICE DON'T 3579 02:08:12,493 --> 02:08:13,694 TRANSMIT, I THINK THAT NARRATIVE 3580 02:08:13,694 --> 02:08:16,563 WE NEED TO CHANGE THAT. 3581 02:08:16,563 --> 02:08:18,732 IT'S MORE ABOUT THE RIGHT HOST, 3582 02:08:18,732 --> 02:08:20,167 THE RIGHT VIRUS AND THE RIGHT 3583 02:08:20,167 --> 02:08:21,602 CONDITIONS. 3584 02:08:21,602 --> 02:08:24,438 OTHER THINGS I WANT TO MENTION 3585 02:08:24,438 --> 02:08:25,873 IS TRANSMISSION EFFICIENCY 3586 02:08:25,873 --> 02:08:27,307 DEPENDENT ON THE UPPER 3587 02:08:27,307 --> 02:08:29,042 RESPIRATORY TRACT ENVIRONMENT. 3588 02:08:29,042 --> 02:08:31,144 TWO POINTS I WANT TO MAKE HERE. 3589 02:08:31,144 --> 02:08:33,313 SO FIRST THAT THE INFLUENZA 3590 02:08:33,313 --> 02:08:34,982 RECEPTORS IS INDEED PRESENT IN 3591 02:08:34,982 --> 02:08:37,818 THE UPPER RESPIRATORY TRACT FOR 3592 02:08:37,818 --> 02:08:40,387 MICE AND WE LOOKED USING 3593 02:08:40,387 --> 02:08:41,922 IMMUNOHISTOCHEMISTRY OF THE 3594 02:08:41,922 --> 02:08:42,789 UPPER RESPIRATORY TRACT OF 3595 02:08:42,789 --> 02:08:45,959 INFANTS AND ADULTS, AND WE SEE 3596 02:08:45,959 --> 02:08:48,795 HERE BEAUTIFULLY TERMINAL ALPHA 3597 02:08:48,795 --> 02:08:55,235 26 AND ALPHA 2-3 LING -- IN THE 3598 02:08:55,235 --> 02:08:59,172 OLFACTORY AND THE RESPIRATORY 3599 02:08:59,172 --> 02:09:01,975 EPITHELIUM IN -- IN THE LUNGS AS 3600 02:09:01,975 --> 02:09:08,081 SHOWN BY PETER, HOWEVER THE ONE 3601 02:09:08,081 --> 02:09:09,550 DIFFERENCE BETWEEN MICE IS THEY 3602 02:09:09,550 --> 02:09:11,585 DON'T EXPRESS AL VA 2-6 IN THE 3603 02:09:11,585 --> 02:09:13,253 TRACHEA BUT THEY DO EXPRESS 3604 02:09:13,253 --> 02:09:13,921 ALPHA 2-3. 3605 02:09:13,921 --> 02:09:15,255 SO IF YOU'RE THINKING ABOUT 3606 02:09:15,255 --> 02:09:17,524 STUDIES WHERE YOU'RE LOOKING AT 3607 02:09:17,524 --> 02:09:19,092 TRANSITION OF VIRUS FROM THE 3608 02:09:19,092 --> 02:09:20,360 UPPER TO THE LOWER, YOU HAVE TO 3609 02:09:20,360 --> 02:09:22,963 TAKE INTO ACCOUNT VIRUSES THAT 3610 02:09:22,963 --> 02:09:26,099 REQUIRE OR PREFERENTIALLY BIND 3611 02:09:26,099 --> 02:09:31,238 TO 2-6 LENGTH SIALIC ACIDS 3612 02:09:31,238 --> 02:09:32,539 BECAUSE THEY -- THEY'RE NOT 3613 02:09:32,539 --> 02:09:34,775 EXPRESSED IN THE TRACHEA. 3614 02:09:34,775 --> 02:09:36,510 BUT LOOKING AT THE UPPER 3615 02:09:36,510 --> 02:09:37,177 RESPIRATORY TRACT THAT SEEMS TO 3616 02:09:37,177 --> 02:09:38,178 BE LESS OF A CONCERN. 3617 02:09:38,178 --> 02:09:39,046 THE SECOND THING I WANT TO 3618 02:09:39,046 --> 02:09:40,714 MENTION IS THESE RECEPTORS ARE 3619 02:09:40,714 --> 02:09:45,118 NOT ONLY EXPRESSED, THEY'RE NOT 3620 02:09:45,118 --> 02:09:46,153 FUNCTIONAL. 3621 02:09:46,153 --> 02:09:46,987 DOING A SIMPLE TRANSMISSION 3622 02:09:46,987 --> 02:09:49,389 ASSAY AND INOCULATED OR 3623 02:09:49,389 --> 02:09:51,792 INTRANASALLY ADMINISTERING 3624 02:09:51,792 --> 02:09:57,598 BROADLY ACTIVE NEURO -- WE USE 3625 02:09:57,598 --> 02:10:00,467 DAS181 WHICH EXPRESSES -- JUST 3626 02:10:00,467 --> 02:10:02,903 TO PROVE A POINT THAT IF WE 3627 02:10:02,903 --> 02:10:06,373 TREAT THESE ANIMALS WITH DISIGH 3628 02:10:06,373 --> 02:10:08,609 AL LATE IN VIVO WE SEE A DEFECT 3629 02:10:08,609 --> 02:10:11,678 IN SHEDDING AND ALSO A DEFECT IN 3630 02:10:11,678 --> 02:10:14,748 TRANSMISSION. 3631 02:10:14,748 --> 02:10:15,949 WHICH AGAIN PROVES A POINT THAT 3632 02:10:15,949 --> 02:10:19,152 THESE VIRUSES IN THE SYSTEM, 3633 02:10:19,152 --> 02:10:21,655 SIALIC ACIDS ARE REQUIRED TO 3634 02:10:21,655 --> 02:10:22,723 ESTABLISH A TRANSMISSION EVENT. 3635 02:10:22,723 --> 02:10:25,792 AND A SIDE NOTE, IF YOU WANT TO 3636 02:10:25,792 --> 02:10:29,029 TEST DIFFERENT THERAPEUTICS FOR 3637 02:10:29,029 --> 02:10:30,197 THEIR EFFECT ON TRANSMISSION, 3638 02:10:30,197 --> 02:10:31,732 THIS MODEL IS ALSO VERY 3639 02:10:31,732 --> 02:10:34,701 EFFICIENT FOR THAT. 3640 02:10:34,701 --> 02:10:36,703 WE CAN DO THE SAME THING USING A 3641 02:10:36,703 --> 02:10:38,005 COMPLETELY DIFFERENT ASSAY 3642 02:10:38,005 --> 02:10:40,540 ACHIEVING THE SAME RESULTS. 3643 02:10:40,540 --> 02:10:43,577 IT'S IMPORTANT TO ACKNOWLEDGE AS 3644 02:10:43,577 --> 02:10:44,177 MENTIONED PREVIOUSLY THAT 3645 02:10:44,177 --> 02:10:45,812 INFLUENZA VIRUS DOES NOT INFECT 3646 02:10:45,812 --> 02:10:47,848 A STERILE ENVIRONMENT. 3647 02:10:47,848 --> 02:10:49,616 SO WE WANTED TO ADD A LITTLE BIT 3648 02:10:49,616 --> 02:10:52,285 OF COMPLEXITY TO THIS MODEL BY 3649 02:10:52,285 --> 02:10:55,455 DOING COINFECTIONS. 3650 02:10:55,455 --> 02:10:58,725 AND WE KNOW FROM INFANTS THAT 3651 02:10:58,725 --> 02:10:59,960 ONE OF THE MAJOR COLONIZERS OF 3652 02:10:59,960 --> 02:11:02,596 THE UPPER RESPIRATORY TRACT IS 3653 02:11:02,596 --> 02:11:06,333 STREPTOCOCCUS PNEUMONIA, AND SO 3654 02:11:06,333 --> 02:11:07,801 WE ESTABLISH A COINFECTION MODEL 3655 02:11:07,801 --> 02:11:10,037 WHERE ALL OF THE LITTERS ARE 3656 02:11:10,037 --> 02:11:11,238 COLONIZED FIRST WITH STREPT 3657 02:11:11,238 --> 02:11:17,310 COCOST PNESTREPTOCOCCUS PNEUMONN 3658 02:11:17,310 --> 02:11:19,613 ASK HOW DOES COLONIZATION OF THE 3659 02:11:19,613 --> 02:11:21,214 BACTERIA AFFECT TRANSMISSIBILITY 3660 02:11:21,214 --> 02:11:22,416 OF INFLUENZA. 3661 02:11:22,416 --> 02:11:25,018 HERE WE'RE SPECIFICALLY 3662 02:11:25,018 --> 02:11:27,421 INTERESTED IN BACTERIAL 3663 02:11:27,421 --> 02:11:28,955 NORMALIZATION OF THOSE EFFECTS 3664 02:11:28,955 --> 02:11:33,260 AND WE COLONIZE ONE COHORT WITH 3665 02:11:33,260 --> 02:11:36,063 WILD TYPE BACTERIA WHICH 3666 02:11:36,063 --> 02:11:39,366 EXPRESSES -- AND A SECOND 3667 02:11:39,366 --> 02:11:40,734 BACTERIA THAT DOES NOT EXPRESS 3668 02:11:40,734 --> 02:11:41,468 UNDER THE SURFACE. 3669 02:11:41,468 --> 02:11:43,970 AS WE CAN SEE FROM THE RESULTS, 3670 02:11:43,970 --> 02:11:46,740 BOTH UPPER RESPIRATORY TRACT 3671 02:11:46,740 --> 02:11:49,276 REPLICATION AND SHEDDING ARE 3672 02:11:49,276 --> 02:11:50,744 CO-INFECT BID COLONIZATION OF 3673 02:11:50,744 --> 02:11:51,812 THE TWO STRAINS BUT THE DEFECT 3674 02:11:51,812 --> 02:11:53,246 IS HERE AT THE PART OF 3675 02:11:53,246 --> 02:11:55,849 ACQUISITION WHERE THE BACTERIA 3676 02:11:55,849 --> 02:11:59,519 THAT HAS -- EXPRESSED LIMITS THE 3677 02:11:59,519 --> 02:12:01,288 CONTACT ACQUISITION OF INFLUENZA 3678 02:12:01,288 --> 02:12:04,091 VIRUSES WHERE THAT IS NOT 3679 02:12:04,091 --> 02:12:05,492 PRESENT WHEN THEY'RE COLONIZED 3680 02:12:05,492 --> 02:12:08,061 WITH THE MUTANT BACTERIA. 3681 02:12:08,061 --> 02:12:14,434 AGAIN, PROVING THE POINT THAT 3682 02:12:14,434 --> 02:12:15,402 DESIALYLATING IN VIVO BLOCKS 3683 02:12:15,402 --> 02:12:18,505 TRANSMISSION BUT ALSO A BIGGER 3684 02:12:18,505 --> 02:12:20,240 PICTURE IS THAT YOUR 3685 02:12:20,240 --> 02:12:21,141 SUSCEPTIBILITY CAN CHANGE 3686 02:12:21,141 --> 02:12:22,676 DEPENDING ON WHAT YOU'RE 3687 02:12:22,676 --> 02:12:23,143 COLONIZED WITH. 3688 02:12:23,143 --> 02:12:26,179 SO WE'RE TRYING TO DO SIMILAR 3689 02:12:26,179 --> 02:12:28,915 EXPERIMENTS USING DIFFERENT 3690 02:12:28,915 --> 02:12:32,452 BACTERIA, PARTICULARLY STAPH 3691 02:12:32,452 --> 02:12:33,854 AUREUS AND SEEING IF WE SEE A 3692 02:12:33,854 --> 02:12:37,257 SIMILAR EFFECT. 3693 02:12:37,257 --> 02:12:38,358 LAST POINT I WANT TO MAKE IS 3694 02:12:38,358 --> 02:12:39,392 ABOUT VIRUS STRAIN. 3695 02:12:39,392 --> 02:12:40,694 SO I WAS ONLY ALLOTTED 15 3696 02:12:40,694 --> 02:12:41,661 MINUTES SO I'LL BE A COUPLE 3697 02:12:41,661 --> 02:12:45,866 MINUTES OVER. 3698 02:12:45,866 --> 02:12:47,434 VIRUS TRANSMISSION IN MICE IS 3699 02:12:47,434 --> 02:12:48,802 DEPENDENT ON VIRUS STRAIN. 3700 02:12:48,802 --> 02:12:51,004 THAT IS NOT NEW TO US, AND I 3701 02:12:51,004 --> 02:12:54,741 ONLY HAVE A FEW THAT I'VE TESTED 3702 02:12:54,741 --> 02:12:55,842 SO IF YOU HAVE YOUR FAVORITE 3703 02:12:55,842 --> 02:12:57,043 STRAIN AND YOU WANT TO TEST IT 3704 02:12:57,043 --> 02:12:58,678 IN THE SYSTEM, I'M HAPPY TO TAKE 3705 02:12:58,678 --> 02:13:02,449 IT AND TEST IT, BUT IN GENERAL, 3706 02:13:02,449 --> 02:13:05,152 H1N1 VIRUSES SHED LOWER THAN 3707 02:13:05,152 --> 02:13:06,520 H3N2 VIRUS AND CORRESPONDINGLY 3708 02:13:06,520 --> 02:13:07,821 THEY TRANSMIT TO A LOWER 3709 02:13:07,821 --> 02:13:11,758 EFFICIENCY COMPARED TO 3710 02:13:11,758 --> 02:13:13,627 H3N2 VIRUS WHICH IS INTERESTING 3711 02:13:13,627 --> 02:13:15,195 BUT IT ALSO GIVES US GOOD TOOLS 3712 02:13:15,195 --> 02:13:15,762 TO WORK WITH. 3713 02:13:15,762 --> 02:13:21,802 SO OUR FERRET VI FAVORITE VIRUSS 3714 02:13:21,802 --> 02:13:22,903 AN OPPORTUNITY TO STUDY BIOLOGY 3715 02:13:22,903 --> 02:13:25,539 OF THE HOST THROUGH VIROLOGY. 3716 02:13:25,539 --> 02:13:28,408 AND OBVIOUSLY THEY'RE ICEGENICS 3717 02:13:28,408 --> 02:13:33,480 OISOGENICSOF ONE ANOTHER SO WE E 3718 02:13:33,480 --> 02:13:38,919 DIFFERENT COMBINATIONS AND ASK 3719 02:13:38,919 --> 02:13:40,220 WHAT IS THE TRANSMISSION 3720 02:13:40,220 --> 02:13:41,121 EFFICIENCIES OF THESE DIFFERENT 3721 02:13:41,121 --> 02:13:41,354 CLONES. 3722 02:13:41,354 --> 02:13:42,989 SO WHEN WE TEST ALL OF THESE 3723 02:13:42,989 --> 02:13:45,425 VIRUSES, WE SEE THE UPPER 3724 02:13:45,425 --> 02:13:47,093 RESPIRATORY TRACT REPLICATION IS 3725 02:13:47,093 --> 02:13:49,262 SIMILAR ACROSS ALL OF THESE 3726 02:13:49,262 --> 02:13:51,131 STRAINGS. 3727 02:13:51,131 --> 02:13:51,565 STRAINS. 3728 02:13:51,565 --> 02:13:53,200 SHEDDING IS VERY DIFFERENT, SO 3729 02:13:53,200 --> 02:13:57,537 IF YOU HAVE VIRUS THAT CONTA 3730 02:13:57,537 --> 02:14:00,340 CONTAINS -- THAN H -- VIRUSES 3731 02:14:00,340 --> 02:14:02,676 CONTAINING H1s AND 3732 02:14:02,676 --> 02:14:03,977 CORRESPONDINGLY THEY TRANSMIT 3733 02:14:03,977 --> 02:14:05,278 MUCH EFFICIENTLY COMPARED TO 3734 02:14:05,278 --> 02:14:07,814 VIRUSES CONTAINING H1s. 3735 02:14:07,814 --> 02:14:09,482 CLEARLY THIS TYPE OF VIROLOGY, 3736 02:14:09,482 --> 02:14:11,051 YOU CAN DO IN GUINEA PIGS, 3737 02:14:11,051 --> 02:14:13,553 FERRETS, YOU CAN EVEN DO IN 3738 02:14:13,553 --> 02:14:14,421 HUMANS, BUT THIS WAS INTERESTING 3739 02:14:14,421 --> 02:14:16,056 TO US BECAUSE NOW WE HAVE TOOLS. 3740 02:14:16,056 --> 02:14:18,825 WE HAVE HIGHLY TRANSMISSIBLE 3741 02:14:18,825 --> 02:14:20,594 VIRUSES, WE HAVE LOW 3742 02:14:20,594 --> 02:14:21,661 TRANSMISSIBLE VIRUSES AND WE CAN 3743 02:14:21,661 --> 02:14:23,463 NOW APPLY THESE IN OUR SYSTEM 3744 02:14:23,463 --> 02:14:25,966 AND USE THE POWER OF THE MICE 3745 02:14:25,966 --> 02:14:28,168 UNDERSTAND HOST REQUIREMENTS FOR 3746 02:14:28,168 --> 02:14:29,035 TRANSMISSION. 3747 02:14:29,035 --> 02:14:30,237 SO THE ONE -- ONE OF THE 3748 02:14:30,237 --> 02:14:32,572 FUNDAMENTAL QUESTIONS WE WANTED 3749 02:14:32,572 --> 02:14:34,307 TO ASK IS WHAT MAKES A HOST 3750 02:14:34,307 --> 02:14:34,741 INFECTIOUS? 3751 02:14:34,741 --> 02:14:37,510 SO WHAT WE DID IS WE DID A 3752 02:14:37,510 --> 02:14:40,146 COMPREHENSIVE UPPER RESPIRATORY 3753 02:14:40,146 --> 02:14:42,015 PROFILING OF INDEX MICE AND FROM 3754 02:14:42,015 --> 02:14:46,519 THEIR SCREATIONS, WE DID SEVERAL 3755 02:14:46,519 --> 02:14:47,187 ANALYSES. 3756 02:14:47,187 --> 02:14:48,555 ONE OF THE THINGS WE LEARNED IS 3757 02:14:48,555 --> 02:14:50,357 THAT HIGHLY TRANSMISSIBLE 3758 02:14:50,357 --> 02:14:53,994 VIRUSES INDUCE A HIGHER 3759 02:14:53,994 --> 02:14:55,729 INFLAMMATORY CYTOKINE RESPONSE, 3760 02:14:55,729 --> 02:14:58,965 THEY INDUCE HIGHER JEAN 3761 02:14:58,965 --> 02:15:02,769 EXPRESSION, INFLAMMATORY GENE 3762 02:15:02,769 --> 02:15:03,436 EXPRESSION. 3763 02:15:03,436 --> 02:15:04,804 THEY RECRUIT ABUNDANCE OF 3764 02:15:04,804 --> 02:15:07,607 MACROPHAGE AND NEUTROPHILLING TO 3765 02:15:07,607 --> 02:15:09,910 THE UPPER RESPIRATORY TRACT AND 3766 02:15:09,910 --> 02:15:10,911 THEY PRODUCE MORE MUCUS. 3767 02:15:10,911 --> 02:15:13,213 SO IN FOUR DIFFERENT ASSAYS, WE 3768 02:15:13,213 --> 02:15:14,347 SEE A SIMILAR TREND. 3769 02:15:14,347 --> 02:15:17,384 THE SIMILAR TREND IS THAT 3770 02:15:17,384 --> 02:15:21,421 INFLUENZA TRANSMISSION IS MORE 3771 02:15:21,421 --> 02:15:22,656 EFFICIENT WHEN THE INDEX HOST 3772 02:15:22,656 --> 02:15:23,690 HAS A STRONG INFLAMMATORY 3773 02:15:23,690 --> 02:15:24,124 RESPONSE. 3774 02:15:24,124 --> 02:15:25,992 SO IF YOU ARE PUZZLED ABOUT WHAT 3775 02:15:25,992 --> 02:15:27,093 INFLAMMATION MEANS, SO IN 3776 02:15:27,093 --> 02:15:28,094 HUMANS, WHEN YOU'RE INFECTED 3777 02:15:28,094 --> 02:15:30,764 WITH A VIRUS, YOU CREATE A VERY 3778 02:15:30,764 --> 02:15:34,534 ROW WROBUST INFLAMMATORY RESPONE 3779 02:15:34,534 --> 02:15:34,901 AGAINST THAT. 3780 02:15:34,901 --> 02:15:36,169 YOU BECOME SYMPTOMATIC AND WE 3781 02:15:36,169 --> 02:15:37,971 KNOW FOR A FACT THAT WE ARE 3782 02:15:37,971 --> 02:15:39,105 HIGHLY INFECTIOUS AND MORE 3783 02:15:39,105 --> 02:15:40,206 TRANSMISSIBLE WHEN WE ARE 3784 02:15:40,206 --> 02:15:40,507 SYMPTOMATIC. 3785 02:15:40,507 --> 02:15:42,375 SO THIS IS HOW WE MEASURE 3786 02:15:42,375 --> 02:15:43,843 SYMPTOMS IN THE MICE, IT'S HARD 3787 02:15:43,843 --> 02:15:46,146 TO ASK THEM HOW THEY FEEL. 3788 02:15:46,146 --> 02:15:52,953 AN NOW WEAR TRYING T WE'RE TRYIA 3789 02:15:52,953 --> 02:15:54,354 LITTLE DEEPER WITH KNOCKOUT 3790 02:15:54,354 --> 02:15:56,122 MODELS AND THERAPEUTICS TO SEE 3791 02:15:56,122 --> 02:15:57,357 WHICH HOST PATHWAYS ARE 3792 02:15:57,357 --> 02:16:00,160 IMPORTANT FOR THE 3793 02:16:00,160 --> 02:16:02,295 TRANSMISSIBILITY OF FLIE. 3794 02:16:02,295 --> 02:16:03,363 FLU. 3795 02:16:03,363 --> 02:16:04,731 SO WITH THAT, I JUST WANT TO 3796 02:16:04,731 --> 02:16:06,433 SUMMARIZE THAT I HOPE I 3797 02:16:06,433 --> 02:16:08,268 CONVINCED YOU THAT MICE ARE AN 3798 02:16:08,268 --> 02:16:10,203 ALTERNATIVE MODEL TO STUDY HOST 3799 02:16:10,203 --> 02:16:13,173 BIOLOGY AND TRANSMISSION, 3800 02:16:13,173 --> 02:16:14,708 PARTICULARLY FACTORS THAT ARE 3801 02:16:14,708 --> 02:16:18,778 IMPORTANT FOR INFECTIOUSNESS AND 3802 02:16:18,778 --> 02:16:19,279 SUSCEPTIBILITY. 3803 02:16:19,279 --> 02:16:20,547 THERE ARE BIOLOGICAL FACTORS WE 3804 02:16:20,547 --> 02:16:22,282 NEED TO TAKE INTO ACCOUNT, 3805 02:16:22,282 --> 02:16:26,119 OBVIOUSLY AGE, SEX AND THE UPPER 3806 02:16:26,119 --> 02:16:28,688 RESPIRATORY TRACK ENVIRONMENT 3807 02:16:28,688 --> 02:16:30,090 AND VIRUS STRAINS MATTER. 3808 02:16:30,090 --> 02:16:31,658 AND IT AFFECTS HOW WE RESPOND TO 3809 02:16:31,658 --> 02:16:32,993 THE INFECTION AND HOW WE 3810 02:16:32,993 --> 02:16:34,627 TRANSMIT THE VIRUS. 3811 02:16:34,627 --> 02:16:36,930 SO THANK YOU FOR YOUR ATTENTION. 3812 02:16:36,930 --> 02:16:39,265 I WOULD LIKE TO THANK MY LAB. 3813 02:16:39,265 --> 02:16:45,939 WE'RE SMALL BUT WE'RE FEISTY, 3814 02:16:45,939 --> 02:16:47,107 AND OUR COLLABORATORS AND OUR 3815 02:16:47,107 --> 02:16:47,440 FUNDING. 3816 02:16:47,440 --> 02:16:48,308 >> OKAY. 3817 02:16:48,308 --> 02:16:50,610 WE'VE GONE A BIT OVER. 3818 02:16:50,610 --> 02:16:52,479 DOES ANYONE HAVE A BURNING 3819 02:16:52,479 --> 02:16:52,746 QUESTION? 3820 02:16:52,746 --> 02:16:55,248 BECAUSE I CANNOT LET A SPEAKER 3821 02:16:55,248 --> 02:16:55,782 GO WITHOUT -- 3822 02:16:55,782 --> 02:16:57,851 >> SO WHAT IS REALLY THE 3823 02:16:57,851 --> 02:17:00,053 DIFFERENCE BETWEEN IN YOUR MOUSE 3824 02:17:00,053 --> 02:17:04,491 MODEL APR8 AND X31, SINCE 3825 02:17:04,491 --> 02:17:06,693 X31 HAS THE APR8 INTERNAL GENES? 3826 02:17:06,693 --> 02:17:10,330 >> WELL, X31 IS PR8 WITH 3827 02:17:10,330 --> 02:17:13,066 EXCEPTION OF TWO SEGMENTS, THE 3828 02:17:13,066 --> 02:17:18,271 HEMAGGLUTININ AND NEUROMEN DAYS, 3829 02:17:18,271 --> 02:17:20,473 WHICH EYE RIFED FROM THE HONG 3830 02:17:20,473 --> 02:17:21,841 KONG 1968 PANDEMIC VIRUS. 3831 02:17:21,841 --> 02:17:25,178 SO THEY'RE ICEGENIC OF ONE 3832 02:17:25,178 --> 02:17:26,413 ANOTHER WITH THE EXCEPTION OF 3833 02:17:26,413 --> 02:17:26,746 TWO SEGMENTS. 3834 02:17:26,746 --> 02:17:31,317 >> SO WHERE IS THE TRANSMISSION 3835 02:17:31,317 --> 02:17:34,220 BLOCK REPLICATION FROM INTERNAL 3836 02:17:34,220 --> 02:17:37,457 GENES OR INNATE IMMUNE RESPONSE? 3837 02:17:37,457 --> 02:17:39,926 >> WE HAVE IT DOWN TO BEING THE 3838 02:17:39,926 --> 02:17:40,326 H3 COMPONENT. 3839 02:17:40,326 --> 02:17:45,298 WE HAD OUR MONEY ON THE NEUROMIN 3840 02:17:45,298 --> 02:17:47,267 DAYS COMPONENT, IT WAS 3841 02:17:47,267 --> 02:17:48,735 SURPRISING THAT H3 WAS A DRIVER 3842 02:17:48,735 --> 02:17:50,303 OF TRANSMISSION, SO WE'RE DOING 3843 02:17:50,303 --> 02:17:51,671 FOLLOW-UP STUDIES WITH WHAT 3844 02:17:51,671 --> 02:17:54,340 SECTION OF H3 DRIVES THAT, BUT 3845 02:17:54,340 --> 02:17:55,008 OBVIOUSLY THOSE ARE EXPERIMENTS 3846 02:17:55,008 --> 02:17:57,410 THAT YOU CAN DO BETTER WITH 3847 02:17:57,410 --> 02:17:59,646 OTHER MODEL SYSTEMS, BUT 3848 02:17:59,646 --> 02:18:01,514 OBVIOUSLY WE'RE DOING IT IN OUR 3849 02:18:01,514 --> 02:18:03,283 SYSTEM AS WELL. 3850 02:18:03,283 --> 02:18:05,185 BUT WE'RE USING THESE VIRUSES AS 3851 02:18:05,185 --> 02:18:06,820 TOOLS TO LEARN MORE ABOUT WHAT 3852 02:18:06,820 --> 02:18:12,826 OTHER SYSTEMS CAN ANSWER, WHICH 3853 02:18:12,826 --> 02:18:14,060 IS HOST BIOLOGY AND 3854 02:18:14,060 --> 02:18:14,394 INFLAMMATION. 3855 02:18:14,394 --> 02:18:14,727 >> ALL RIGHT. 3856 02:18:14,727 --> 02:18:15,728 WELL, I WOULD LOVE TO INVITE ALL 3857 02:18:15,728 --> 02:18:17,063 OF THE SPEAKERS, AND I ASSUME 3858 02:18:17,063 --> 02:18:19,032 WE'LL BE ABLE TO BRING JACCO UP 3859 02:18:19,032 --> 02:18:29,275 ON THE SCREEN. 3860 02:18:37,784 --> 02:18:42,755 I'M HOPING WE CAN -- 3861 02:18:42,755 --> 02:18:44,124 >> THIS IS AV. 3862 02:18:44,124 --> 02:18:45,592 IF YOU CAN UNMUTE YOUR 3863 02:18:45,592 --> 02:18:46,793 MICROPHONE AND TURN ON YOUR 3864 02:18:46,793 --> 02:18:47,026 CAMERA. 3865 02:18:47,026 --> 02:18:50,196 >> I DID. 3866 02:18:50,196 --> 02:18:51,097 CAN PEOPLE HEAR ME? 3867 02:18:51,097 --> 02:18:52,298 >> WE CAN SEE AND HEAR YOU. 3868 02:18:52,298 --> 02:19:02,475 THANK YOU. 3869 02:19:09,549 --> 02:19:10,216 >> ALL RIGHT. 3870 02:19:10,216 --> 02:19:13,853 WE ARE READY TO GO. 3871 02:19:13,853 --> 02:19:15,221 SO LET'S BEGIN OUR DISCUSSION 3872 02:19:15,221 --> 02:19:16,956 ABOUT THE UTILITY OF THESE 3873 02:19:16,956 --> 02:19:19,359 ANIMAL MODELS. 3874 02:19:19,359 --> 02:19:20,426 IS THERE ANYBODY WHO WOULD LIKE 3875 02:19:20,426 --> 02:19:21,761 TO START OFF WITH A BROAD 3876 02:19:21,761 --> 02:19:28,234 QUESTION? 3877 02:19:28,234 --> 02:19:30,470 >> SO WHEN YOU LOOK AT THESE 3878 02:19:30,470 --> 02:19:31,337 TRANSMISSION MODELS, HOW MUCH OF 3879 02:19:31,337 --> 02:19:33,072 THIS DO YOU BENCHMARK AGAINST 3880 02:19:33,072 --> 02:19:34,440 THESE HOUSEHOLD TRANSMISSION 3881 02:19:34,440 --> 02:19:37,410 STUDIES THAT PEOPLE HAVE DONE 3882 02:19:37,410 --> 02:19:39,212 AND TRIED TO CORRELATE OR 3883 02:19:39,212 --> 02:19:40,847 ASSOCIATE SOME OF THOSE FINDINGS 3884 02:19:40,847 --> 02:19:43,516 WITH SYMPTOMATIC VERSUS 3885 02:19:43,516 --> 02:19:48,721 ASYMPTOMATIC TRANSMISSION? 3886 02:19:48,721 --> 02:19:51,191 >> I CAN START WITH THAT. 3887 02:19:51,191 --> 02:19:52,525 I THINK FACING EVERYTHING IN 3888 02:19:52,525 --> 02:19:54,027 WHAT WE UNDERSTAND FROM HUMANS 3889 02:19:54,027 --> 02:19:56,829 IS REALLY IMPORTANT. 3890 02:19:56,829 --> 02:19:58,264 I THINK HOUSEHOLD TRANSMISSION 3891 02:19:58,264 --> 02:20:00,967 STUDYS ARE FASCINATING, BUT THEY 3892 02:20:00,967 --> 02:20:02,869 SORT OF LACK A LOT OF CLARITY, 3893 02:20:02,869 --> 02:20:04,537 WHICH YOU SORT OF NEED IN ORDER 3894 02:20:04,537 --> 02:20:09,709 TO BENCHMARK, SPECIFICALLY WHAT 3895 02:20:09,709 --> 02:20:13,246 WAS THE INITIAL INFECTION 3896 02:20:13,246 --> 02:20:14,414 INITIATION, WHAT WAS THE 3897 02:20:14,414 --> 02:20:14,881 EXPOSURE DURATIONS. 3898 02:20:14,881 --> 02:20:16,616 THERE'S A LOT OF COMPLEXITY IN 3899 02:20:16,616 --> 02:20:20,587 THE SYSTEM. 3900 02:20:20,587 --> 02:20:24,857 I THINK THAT -- SO I THINK WHAT 3901 02:20:24,857 --> 02:20:26,626 I HAVE REALIZED ABOUT 3902 02:20:26,626 --> 02:20:27,860 ASYMPTOMATIC INFECTIONS AND 3903 02:20:27,860 --> 02:20:29,295 POTENTIAL TRANSMISSION 3904 02:20:29,295 --> 02:20:30,430 EFFICIENCIES, AND SORT OF WHAT 3905 02:20:30,430 --> 02:20:33,933 THAT MEANS, HAS REALLY COME FROM 3906 02:20:33,933 --> 02:20:35,635 LOOKING AT TRANSMISSION FITNESS 3907 02:20:35,635 --> 02:20:37,103 IN ANIMALS THAT ARE 3908 02:20:37,103 --> 02:20:38,471 ASYMPTOMATIC. 3909 02:20:38,471 --> 02:20:43,443 AND YOU CAN CORRELATE VIRAL 3910 02:20:43,443 --> 02:20:45,245 LOADS TO EXPULSION TO WHAT'S 3911 02:20:45,245 --> 02:20:46,246 BEING RELEASED INTO THE AIR TO 3912 02:20:46,246 --> 02:20:49,415 THEN A FORWARD TRANSMISSION 3913 02:20:49,415 --> 02:20:50,917 EVENT, SO I THINK THAT'S WHAT'S 3914 02:20:50,917 --> 02:20:51,184 IMPORTANT. 3915 02:20:51,184 --> 02:20:53,820 BUT I THINK THAT IT'S A GREAT 3916 02:20:53,820 --> 02:20:54,687 QUESTION TO SORT OF CONTINUE TO 3917 02:20:54,687 --> 02:20:56,889 THINK ABOUT WHAT HAPPENS IN 3918 02:20:56,889 --> 02:20:58,391 HUMANS AND HOW YOU RELATE THAT 3919 02:20:58,391 --> 02:20:58,758 BACK. 3920 02:20:58,758 --> 02:21:00,093 THAT'S JUST MY TAKE. 3921 02:21:00,093 --> 02:21:04,297 >> I JUST WANTED TO ADD TO THAT. 3922 02:21:04,297 --> 02:21:06,266 WITH RETROSPECTIVE STUDIES IN 3923 02:21:06,266 --> 02:21:10,670 HUMANS HAVE DEMONSTRATED THAT 3924 02:21:10,670 --> 02:21:11,938 ASYMPTOMATIC OR PRESYMPTOMATIC 3925 02:21:11,938 --> 02:21:13,273 IS THOSE WHO DON'T YET 3926 02:21:13,273 --> 02:21:15,642 EXPERIENCE SYMPTOMS BUT GO ON TO 3927 02:21:15,642 --> 02:21:16,709 DEVELOP SYMPTOMS LATER. 3928 02:21:16,709 --> 02:21:19,145 THEY DO SHED VIRUS. 3929 02:21:19,145 --> 02:21:22,081 BUT THEY DON'T SHED VIRUS TO 3930 02:21:22,081 --> 02:21:24,117 HIGHER AMOUNTS COMPARED TO 3931 02:21:24,117 --> 02:21:24,450 SYMPTOMATIC. 3932 02:21:24,450 --> 02:21:25,618 SO THE POTENTIAL FOR 3933 02:21:25,618 --> 02:21:26,653 TRANSMISSION IS THERE, BUT AT 3934 02:21:26,653 --> 02:21:32,325 THE TIME, LA LIKE SEEMA SAID, IS 3935 02:21:32,325 --> 02:21:34,327 PRETTY UNCONTROLLED, YOU DON'T 3936 02:21:34,327 --> 02:21:35,662 HAVE SYMPTOMS, YOU DON'T HAVE 3937 02:21:35,662 --> 02:21:35,995 THOSE METRICS. 3938 02:21:35,995 --> 02:21:38,197 BUT WHAT WE KNOW FROM HUMAN 3939 02:21:38,197 --> 02:21:40,333 STUDIES IS THAT ONCE SYMPTOMS 3940 02:21:40,333 --> 02:21:42,568 ARE PRESENT, WHEN THE PATIENT 3941 02:21:42,568 --> 02:21:45,371 EXPERIENCES SYMPTOMS, THEY'RE 3942 02:21:45,371 --> 02:21:47,640 VERY INFECTIOUS. 3943 02:21:47,640 --> 02:21:52,545 >> THANK YOU. 3944 02:21:52,545 --> 02:21:52,812 ANYBODY -- 3945 02:21:52,812 --> 02:21:53,546 >> OVER HERE. 3946 02:21:53,546 --> 02:21:55,581 SO MY LAB, WE DO ANIMAL STUDIES 3947 02:21:55,581 --> 02:21:59,519 BUT WE WE ALSO DO STRUCTURAL 3948 02:21:59,519 --> 02:22:00,687 BIOLOGY AND CHEMISTRY. 3949 02:22:00,687 --> 02:22:02,555 SO AS FAR AS TRANSMISSION 3950 02:22:02,555 --> 02:22:05,825 STUDIES, IS THERE A ROLE FOR 3951 02:22:05,825 --> 02:22:09,829 NON-TRADITIONAL ANIMAL OR FLU 3952 02:22:09,829 --> 02:22:11,364 PEOPLE EITHER FROM STRUCTURAL 3953 02:22:11,364 --> 02:22:14,567 BIOLOGY, CHEMISTRY, ARTIFICIAL 3954 02:22:14,567 --> 02:22:15,335 INTELLIGENT MODELING? 3955 02:22:15,335 --> 02:22:17,337 WHERE ARE SOME OF THE GAPS THAT 3956 02:22:17,337 --> 02:22:19,172 PEOPLE WHO HAVE EXPERTISE IN 3957 02:22:19,172 --> 02:22:21,074 OTHER FIELDS CAN COME IN AND 3958 02:22:21,074 --> 02:22:21,374 HELP? 3959 02:22:21,374 --> 02:22:22,275 JUST A GENERAL QUESTION. 3960 02:22:22,275 --> 02:22:23,943 WHAT ARE SOME OF THE GAPS THAT 3961 02:22:23,943 --> 02:22:26,346 YOU GUYS NEED FROM OTHER PEOPLE 3962 02:22:26,346 --> 02:22:35,588 IN OTHER FIELDS THAT COULD HELP? 3963 02:22:35,588 --> 02:22:39,392 >> I THINK A.I. WILL BE HELPFUL. 3964 02:22:39,392 --> 02:22:42,562 HOW MANY MUTANT CORONAVIRUS DO 3965 02:22:42,562 --> 02:22:43,730 WE WANT TO MAKE TO START TEASING 3966 02:22:43,730 --> 02:22:45,064 APART WHY THE TRANSMISSION IS 3967 02:22:45,064 --> 02:22:46,899 NOT WORKING VERSUS WHY IT'S 3968 02:22:46,899 --> 02:22:48,167 WORKING? 3969 02:22:48,167 --> 02:22:51,437 AT LEAST IN THE HAMSTERS. 3970 02:22:51,437 --> 02:22:54,907 SO I DON'T KNOW IF WE HAVE 3971 02:22:54,907 --> 02:22:55,808 ENOUGH SEQUENCE INFORMATION WITH 3972 02:22:55,808 --> 02:22:57,443 THE DIFFERENT VARIANTS THAT WE 3973 02:22:57,443 --> 02:23:00,179 HAVE FOR COV-2, BUT ARTIFICIAL 3974 02:23:00,179 --> 02:23:01,614 INTELLIGENCE WOULD BE GREAT, 3975 02:23:01,614 --> 02:23:02,782 LARGE LANGUAGE LEARNING, TO 3976 02:23:02,782 --> 02:23:04,450 START DIVING DEEP INTO THESE. 3977 02:23:04,450 --> 02:23:05,318 IT DOESN'T HAVE TO BE 3978 02:23:05,318 --> 02:23:05,852 TRANSMISSION. 3979 02:23:05,852 --> 02:23:07,620 IT COULD BE ANY KIND OF 3980 02:23:07,620 --> 02:23:11,591 PHENOTIME THAT PHENOTYPE THAT WE 3981 02:23:11,591 --> 02:23:12,692 VIRUS IN A CERTAIN ANIMAL. 3982 02:23:12,692 --> 02:23:14,026 >> WOULD YOU LIKE TO ADD 3983 02:23:14,026 --> 02:23:14,794 ANYTHING ABOUT THE STRUCTURAL 3984 02:23:14,794 --> 02:23:17,230 BIOLOGY AND HOW YOU THINK THAT 3985 02:23:17,230 --> 02:23:19,665 MIGHT -- LIKE WHAT YOU WERE 3986 02:23:19,665 --> 02:23:20,099 THINKING. 3987 02:23:20,099 --> 02:23:25,671 >> WELL, PEOPLE WHO STUDY VIRAL 3988 02:23:25,671 --> 02:23:27,206 GLYCOPRETEENS OR STRUCTURAL 3989 02:23:27,206 --> 02:23:28,040 PROTEINS, PARTICULARLY WHEN 3990 02:23:28,040 --> 02:23:29,609 SEEMA WAS GIVING HER TALK RS I 3991 02:23:29,609 --> 02:23:31,444 WAS THINKING, OH, YOU SHOULD 3992 02:23:31,444 --> 02:23:33,212 SEND ME YOUR FLU VIRUSES SO WE 3993 02:23:33,212 --> 02:23:35,882 CAN LOOK AT THE MORPHOLOGY TO 3994 02:23:35,882 --> 02:23:37,083 SEE, YOU KNOW, WHAT YOU GAVE THE 3995 02:23:37,083 --> 02:23:38,818 FERRETS AND WHAT CAME OUT. 3996 02:23:38,818 --> 02:23:42,221 ARE THERE MORE FILAMENTOUS, HOW 3997 02:23:42,221 --> 02:23:45,758 IS MORPHOLOGY STRUCTURED, AND 3998 02:23:45,758 --> 02:23:47,293 WITH THE LOSS OF FUNCTION OR 3999 02:23:47,293 --> 02:23:49,095 GAIN OF FUNCTION WITH 4000 02:23:49,095 --> 02:23:51,030 CORONAVIRUS, DOES THE VIRUS HAVE 4001 02:23:51,030 --> 02:23:57,537 MORE HOST FUSION MORE POST FUSIR 4002 02:23:57,537 --> 02:23:59,705 PREFUSION SPIKES? 4003 02:23:59,705 --> 02:24:02,308 THAT'S JUST MY WORLD WHERE WE 4004 02:24:02,308 --> 02:24:02,508 LIVE? 4005 02:24:02,508 --> 02:24:03,709 >> I ALSO THINK THERE'S A ROLE 4006 02:24:03,709 --> 02:24:05,611 FOR MODELERS IN ALL OF THIS. 4007 02:24:05,611 --> 02:24:08,881 THERE IS SO MUCH DATA AND SO 4008 02:24:08,881 --> 02:24:10,416 MANY DIFFERENT ANIMAL MODELS AND 4009 02:24:10,416 --> 02:24:12,518 THE COMPLENGSITY AS SEEMA AND 4010 02:24:12,518 --> 02:24:16,122 OTHERS HAVE ALLUDED TO IS VERY 4011 02:24:16,122 --> 02:24:17,590 HIGH IN TERMS OF DURATION, WHEN 4012 02:24:17,590 --> 02:24:19,659 THE EXPOSURE, WITH OR WITHOUT 4013 02:24:19,659 --> 02:24:22,361 SYMPTOMS, PRE-EXISTING IMMUNITY. 4014 02:24:22,361 --> 02:24:27,266 I THINK HAVING MODELERS TAKE ALL 4015 02:24:27,266 --> 02:24:29,535 THE DATA, AI TAKE ALL THE DATA 4016 02:24:29,535 --> 02:24:31,037 THAT IS OUT THERE AND GENERATE 4017 02:24:31,037 --> 02:24:34,874 SOME TESTABLE HYPOTHESES, I 4018 02:24:34,874 --> 02:24:36,642 THINK WILL BE EXTREMELY HELPFUL 4019 02:24:36,642 --> 02:24:40,513 GOING FORWARD. 4020 02:24:40,513 --> 02:24:41,881 >> BRIAN, I SEE YOUR HAND UP. 4021 02:24:41,881 --> 02:24:42,915 >> YEAH, THAT'S GREAT. 4022 02:24:42,915 --> 02:24:44,717 THANK YOU, SABRA. 4023 02:24:44,717 --> 02:24:45,051 HI, EVERYBODY. 4024 02:24:45,051 --> 02:24:46,385 IT'S BEEN -- CAN EVERYONE HEAR 4025 02:24:46,385 --> 02:24:46,886 ME ALL RIGHT? 4026 02:24:46,886 --> 02:24:47,753 >> YES, VERY WELL. 4027 02:24:47,753 --> 02:24:48,855 >> OKAY. 4028 02:24:48,855 --> 02:24:50,122 IT'S HARD TO TELL ON THIS END. 4029 02:24:50,122 --> 02:24:51,958 THANK YOU, MICHELLE, FOR A 4030 02:24:51,958 --> 02:24:52,859 FANTASTIC WORKSHOP. 4031 02:24:52,859 --> 02:24:54,494 SO TRIED TO ASK A QUESTION 4032 02:24:54,494 --> 02:24:55,461 YESTERDAY WHEN THINKING ABOUT 4033 02:24:55,461 --> 02:24:56,829 MUCOSAL IMMUNITY, AND I THINK IT 4034 02:24:56,829 --> 02:24:58,464 GOES INTO THIS TRANSMISSION AS 4035 02:24:58,464 --> 02:25:00,032 WELL. 4036 02:25:00,032 --> 02:25:03,803 THINKING ABOUT SEEMA'S QUESTION 4037 02:25:03,803 --> 02:25:06,138 ABOUT PRE-EXISTING IMMUNITY IN 4038 02:25:06,138 --> 02:25:07,473 SOME OF THESE ANIMALS, HOW 4039 02:25:07,473 --> 02:25:10,810 THAT'S INFLUENCING TRANSMISSION. 4040 02:25:10,810 --> 02:25:12,044 SO I GUESS WHAT I WANT TO FORM 4041 02:25:12,044 --> 02:25:13,479 IS LIKE A HYPOTHESIS AND I WANT 4042 02:25:13,479 --> 02:25:15,414 TO SEE HOW THESE ANIMALS MODELS 4043 02:25:15,414 --> 02:25:17,350 ARE BEST CHALLENGING THIS, THAT 4044 02:25:17,350 --> 02:25:19,118 THE MUCOSAL IMMUNITY IN THE 4045 02:25:19,118 --> 02:25:20,686 UPPER RESPIRATORY TRACT, I THINK 4046 02:25:20,686 --> 02:25:22,655 WE KIND OF GOT TO YESTERDAY IN 4047 02:25:22,655 --> 02:25:26,259 THAT IT DOESN'T REALLY ALLOW 4048 02:25:26,259 --> 02:25:27,960 FOR, IT'S NOT EVOLVED FOR 4049 02:25:27,960 --> 02:25:28,294 STERILIZATION. 4050 02:25:28,294 --> 02:25:29,395 ITS GOAL IS NOT MEMORY. 4051 02:25:29,395 --> 02:25:30,663 THAT COULD JUST BE BECAUSE OF 4052 02:25:30,663 --> 02:25:33,833 THE EVOLUTION OF THE VIRUSES, 4053 02:25:33,833 --> 02:25:35,468 ITS ANTIGENIC EVOLUTION, BUT 4054 02:25:35,468 --> 02:25:36,903 BECAUSE OF CARRIAGE OF 4055 02:25:36,903 --> 02:25:39,272 COMMENSALS AND EVERYTHING ELSE 4056 02:25:39,272 --> 02:25:42,808 TOO, THAT WE'RE NOT HAVING A 4057 02:25:42,808 --> 02:25:44,677 LARGE IMPACT ON LIKE MEMORY. 4058 02:25:44,677 --> 02:25:46,646 SO DO WE REALLY FEEL LIKE WE CAN 4059 02:25:46,646 --> 02:25:48,481 TARGET TRANSMISSION IN A 4060 02:25:48,481 --> 02:25:53,819 VACCINATION SCHEME AND GETTING 4061 02:25:53,819 --> 02:25:57,223 AT THE HYPOTHESIS, WHERE IN OUR 4062 02:25:57,223 --> 02:25:58,658 ANIMAL MODELS DO WE REALLY HAVE 4063 02:25:58,658 --> 02:25:59,792 A CLEAR UNDERSTANDING OF WHERE 4064 02:25:59,792 --> 02:26:00,660 THAT PREVIOUS IMMUNITY IS GOING 4065 02:26:00,660 --> 02:26:02,361 TO REALLY HAVE AN IMPACT ON 4066 02:26:02,361 --> 02:26:03,429 TRANSMISSION AS OPPOSED TO 4067 02:26:03,429 --> 02:26:05,631 SETTING ASIDE THE ISSUE OF 4068 02:26:05,631 --> 02:26:06,299 SYSTEMIC MEMORY? 4069 02:26:06,299 --> 02:26:07,500 >> GREAT QUESTION. 4070 02:26:07,500 --> 02:26:08,768 ANYBODY WANT TO START TO ADDRESS 4071 02:26:08,768 --> 02:26:09,435 THAT? 4072 02:26:09,435 --> 02:26:11,837 >> SURE, I'LL TAKE A STAB. 4073 02:26:11,837 --> 02:26:16,609 ABSOLUTELY, I THINK WE CAN 4074 02:26:16,609 --> 02:26:17,476 ACHIEVE, FIRST OF ALL, 4075 02:26:17,476 --> 02:26:18,077 UNDERSTAND A LITTLE BIT MORE 4076 02:26:18,077 --> 02:26:20,179 ABOUT THE UPPER RESPIRATORY 4077 02:26:20,179 --> 02:26:20,513 TRACT. 4078 02:26:20,513 --> 02:26:23,215 A LOT OF THESE STUDIES 4079 02:26:23,215 --> 02:26:24,584 HISTORICALLY FROM RESPIRATORY 4080 02:26:24,584 --> 02:26:26,185 VIRUSES HAVE EMPHASIZED A LOT IN 4081 02:26:26,185 --> 02:26:28,421 THE LUNGS, INFLUENZA AS AN 4082 02:26:28,421 --> 02:26:29,956 EXAMPLE. 4083 02:26:29,956 --> 02:26:31,791 EVEN SARS-COV-2, WE HAVE SEVERAL 4084 02:26:31,791 --> 02:26:34,660 MOUSE MODELS, AND MOST OF THE 4085 02:26:34,660 --> 02:26:36,128 FIGURES AND PAPERS ARE ABOUT THE 4086 02:26:36,128 --> 02:26:37,563 LUNGS AND EVEN IN MIGRANTS, WHEN 4087 02:26:37,563 --> 02:26:39,398 I TALK ABOUT THE UPPER 4088 02:26:39,398 --> 02:26:41,834 RESPIRATORY TRACT, REVIEWERS ARE 4089 02:26:41,834 --> 02:26:45,071 YOU BE SED WITH THE LUNGS, WHICH 4090 02:26:45,071 --> 02:26:49,642 IS ABSOLUTELY IMPORTANT, IS A 4091 02:26:49,642 --> 02:26:51,043 MODEL OF PNEUMONIA BUT NOT A 4092 02:26:51,043 --> 02:26:52,778 MODEL OF TRANSMISSION. 4093 02:26:52,778 --> 02:26:53,879 SO WE KNOW ABSOLUTELY NOTHING 4094 02:26:53,879 --> 02:26:55,414 ABOUT THE UPPER RESPIRATORY 4095 02:26:55,414 --> 02:26:57,416 TRACT, SO I THINK THAT'S STEP 4096 02:26:57,416 --> 02:26:57,583 ONE. 4097 02:26:57,583 --> 02:26:58,618 LET'S FOCUS A LITTLE BIT MORE 4098 02:26:58,618 --> 02:27:01,120 ABOUT THE UPPER RESPIRATORY 4099 02:27:01,120 --> 02:27:02,388 TRACK SO WE CAN LEARN A LITTLE 4100 02:27:02,388 --> 02:27:03,289 MORE ABOUT THE STRUCTURE, THE 4101 02:27:03,289 --> 02:27:04,523 IMMUNITY, THE CELLS, HOW THEY 4102 02:27:04,523 --> 02:27:05,791 RESPOND TO VIRUSES AND THEN WE 4103 02:27:05,791 --> 02:27:07,360 CAN APPROACH THE HE QUESTION 4104 02:27:07,360 --> 02:27:10,262 ABOUT HOW TO DESIGN BETTER 4105 02:27:10,262 --> 02:27:13,265 THERAPEUTICS, BETTER VACCINES 4106 02:27:13,265 --> 02:27:14,800 THAT CAN INDUCE THAT LONG TERM 4107 02:27:14,800 --> 02:27:16,235 MUCOSAL IMMUNITY, ABSOLUTELY. 4108 02:27:16,235 --> 02:27:16,869 IT'S POSSIBLE. 4109 02:27:16,869 --> 02:27:18,237 WE JUST AS A GROUP NEED TO KIND 4110 02:27:18,237 --> 02:27:20,106 OF TAKE TO THE NEXT LEVEL WITH 4111 02:27:20,106 --> 02:27:24,510 INTENTION. 4112 02:27:24,510 --> 02:27:26,679 >> WOULD ANYONE ELSE LIKE TO ADD 4113 02:27:26,679 --> 02:27:26,946 ANYTHING? 4114 02:27:26,946 --> 02:27:28,614 >> I'D LIKE TO ADD IN SOMETHING. 4115 02:27:28,614 --> 02:27:30,783 I THINK SEVERAL GROUPS NOW HAVE 4116 02:27:30,783 --> 02:27:33,519 LOOKED AT MUCOSAL VERSUS 4117 02:27:33,519 --> 02:27:34,720 SYSTEMIC VACCINES AND ITS ROLE 4118 02:27:34,720 --> 02:27:37,089 ON PROTECTION AGAINST 4119 02:27:37,089 --> 02:27:40,459 TRANSMISSION AND EVEN ONWARDS 4120 02:27:40,459 --> 02:27:40,893 TRANSMISSION. 4121 02:27:40,893 --> 02:27:42,728 THERE'S A CLEAR PHENOTYPE THAT 4122 02:27:42,728 --> 02:27:45,798 MUCOSAL VACCINES AND PRIOR 4123 02:27:45,798 --> 02:27:48,134 INFECTION ARE VASTLY SUPERIOR IN 4124 02:27:48,134 --> 02:27:50,236 REDUCING UPPER AND LOWER AIRWAY 4125 02:27:50,236 --> 02:27:52,738 TITERS AS WELL AS PREVENTING 4126 02:27:52,738 --> 02:27:53,639 ONWARDS TRANSMISSION. 4127 02:27:53,639 --> 02:27:58,377 WHAT I THINK IS THE FUTURE HERE 4128 02:27:58,377 --> 02:28:00,846 IS UNDERSTANDING WHAT ARE THE 4129 02:28:00,846 --> 02:28:02,481 CORRELATES OF THAT PROTECTION? 4130 02:28:02,481 --> 02:28:06,318 IS IT T CELLS, IS IT SECRETORY 4131 02:28:06,318 --> 02:28:09,588 IGA, AND HOW DOES DRIFT PLAY IN 4132 02:28:09,588 --> 02:28:11,657 ALL OF THIS, BECAUSE WE 4133 02:28:11,657 --> 02:28:15,027 SHOULDN'T FORGET A LOT OF THE 4134 02:28:15,027 --> 02:28:18,197 REINFECTIONS AND ESPECIALLY FOR 4135 02:28:18,197 --> 02:28:20,599 FLU AND SARS-COV-2, A LOT OF THE 4136 02:28:20,599 --> 02:28:23,102 REINFECTION POTENTIAL ACTUALLY 4137 02:28:23,102 --> 02:28:24,804 COMES THROUGH EVASION OF 4138 02:28:24,804 --> 02:28:26,038 PRE-EXISTING IMMUNITY, 4139 02:28:26,038 --> 02:28:27,773 SPECIFICALLY NEUTRALIZING 4140 02:28:27,773 --> 02:28:28,741 ANTIBODIES. 4141 02:28:28,741 --> 02:28:32,044 SO YES, I AGREE THAT THE UPPER 4142 02:28:32,044 --> 02:28:34,180 HAIR WAY MAY NOT BE THERE TO 4143 02:28:34,180 --> 02:28:36,315 MAINTAIN STERILIZING IMMUNITY, 4144 02:28:36,315 --> 02:28:38,951 BUT IT'S STILL PRETTY GOOD AT 4145 02:28:38,951 --> 02:28:42,221 CONTROLLING THE VIRUS, AND EVEN 4146 02:28:42,221 --> 02:28:43,656 PREVENTING REINFECTION WITH 4147 02:28:43,656 --> 02:28:44,957 HOMOLOGOUS STRAIN. 4148 02:28:44,957 --> 02:28:46,826 SO THOSE ARE MY THOUGHTS ON THAT 4149 02:28:46,826 --> 02:28:47,960 TOPIC. 4150 02:28:47,960 --> 02:28:50,730 >> THANK YOU. 4151 02:28:50,730 --> 02:28:53,599 ANYONE ELSE? 4152 02:28:53,599 --> 02:28:55,534 >> I DON'T HAVE ANYTHING MORE TO 4153 02:28:55,534 --> 02:28:57,903 ADD ON MUCOSAL IMMUNITY, BRIAN, 4154 02:28:57,903 --> 02:28:59,171 BECAUSE IT'S REALLY HARD, BUT I 4155 02:28:59,171 --> 02:29:00,539 WANTED TO JUST ADD ON TO LIKE 4156 02:29:00,539 --> 02:29:02,575 WHAT I THINK IS MISSING, BECAUSE 4157 02:29:02,575 --> 02:29:03,776 REALLY I THINK IT'S SO 4158 02:29:03,776 --> 02:29:04,176 IMPORTANT. 4159 02:29:04,176 --> 02:29:06,412 YOU KNOW, WE'RE VIROLOGISTS AND 4160 02:29:06,412 --> 02:29:07,713 TALKING ABOUT ANIMAL MODELS AND 4161 02:29:07,713 --> 02:29:09,315 THERE'S A BIG INTEREST IN 4162 02:29:09,315 --> 02:29:10,950 IMMUNOLOGY, BUT WHAT WE ARE 4163 02:29:10,950 --> 02:29:12,084 LACKING AND WHAT WE REALLY NEED 4164 02:29:12,084 --> 02:29:14,854 TO DO IS BRING IN MORE 4165 02:29:14,854 --> 02:29:20,693 ENGINEERS, ESPECIALLY AEROSOL 4166 02:29:20,693 --> 02:29:22,661 SCIENTISTS AND PEOPLE WHO DO 4167 02:29:22,661 --> 02:29:23,763 DEVELOPMENT OF SPACES, TALKING 4168 02:29:23,763 --> 02:29:25,831 ABOUT CIVIL ENGINEERS. 4169 02:29:25,831 --> 02:29:28,567 WE DON'T HAVE AN APPRECIATION 4170 02:29:28,567 --> 02:29:30,102 FOR A LOT OF THESE THINGS FOR 4171 02:29:30,102 --> 02:29:32,571 DETECTION OF VIRUSES IN THE 4172 02:29:32,571 --> 02:29:34,206 ENVIRONMENT, FOR EXPULSION OF 4173 02:29:34,206 --> 02:29:37,910 VIRUSES, FROM ANIMAL MODELS AND 4174 02:29:37,910 --> 02:29:38,911 HUMANS, FROM THE ORAL CAVITY, 4175 02:29:38,911 --> 02:29:40,279 WE'RE TALKING ABOUT THE UPPER 4176 02:29:40,279 --> 02:29:41,447 RESPIRATORY TRACT, THE ORAL 4177 02:29:41,447 --> 02:29:43,149 CAVITY IS A REALLY BIG SITE HERE 4178 02:29:43,149 --> 02:29:47,019 TOO FOR EXPULSION IN ALL OF 4179 02:29:47,019 --> 02:29:47,820 THESE MODEL SYSTEMS. 4180 02:29:47,820 --> 02:29:49,755 I THINK THAT TO ME HAS ALWAYS 4181 02:29:49,755 --> 02:29:51,157 LACKED A LOT, AND I WOULD LIKE 4182 02:29:51,157 --> 02:29:52,658 FOR US TO BE MORE THOUGHTFUL 4183 02:29:52,658 --> 02:29:53,125 MOVING FORWARD. 4184 02:29:53,125 --> 02:29:57,463 >> THANK YOU FOR ADDING THAT. 4185 02:29:57,463 --> 02:29:59,532 SO I THINK WE'VE HEARD ABOUT 4186 02:29:59,532 --> 02:30:03,102 LOTS WONDERFUL MODELS FOR 4187 02:30:03,102 --> 02:30:05,404 TRANSMISSION, AND I WELCOME THE 4188 02:30:05,404 --> 02:30:10,242 PANEL DISCUSSING WITH US, DO WE 4189 02:30:10,242 --> 02:30:11,944 NEED ALL THESE MODELS, IS THAT 4190 02:30:11,944 --> 02:30:13,045 CONVERGING EVIDENCE, DOES THAT 4191 02:30:13,045 --> 02:30:13,879 GIVE STRENGTH? 4192 02:30:13,879 --> 02:30:16,916 ARE THERE AT TIMES SOME OF THESE 4193 02:30:16,916 --> 02:30:18,417 MODELS ARE BETTER THAN OTHERS, 4194 02:30:18,417 --> 02:30:20,853 AND YOU EACH KIND OF PRESENTED 4195 02:30:20,853 --> 02:30:23,055 ON YOUR UNIQUE MODELS AND GAVE 4196 02:30:23,055 --> 02:30:25,825 YOUR INDIVIDUAL OPINIONS, BUT 4197 02:30:25,825 --> 02:30:26,892 THAT DIDN'T RESULT NECESSARILY 4198 02:30:26,892 --> 02:30:32,298 IN SOME DEBATE AND DISCUSSION. 4199 02:30:32,298 --> 02:30:34,300 I LEFT EACH OF YOUR TALKS 4200 02:30:34,300 --> 02:30:35,868 THINKING IT'S HAMSTERS, NO, IT'S 4201 02:30:35,868 --> 02:30:37,736 GUINEA PIGS, NO, IT'S DEFINITELY 4202 02:30:37,736 --> 02:30:38,838 FERRETS, IT'S INFANT MICE. 4203 02:30:38,838 --> 02:30:42,441 SO I THINK IT COULD BE OF VALUE 4204 02:30:42,441 --> 02:30:43,409 AS A COMMUNITY TO HAVE A LITTLE 4205 02:30:43,409 --> 02:30:47,746 BIT OF A DEBATE AND DISCUSSION 4206 02:30:47,746 --> 02:30:49,215 ABOUT WHERE WE REALLY SEE SOME 4207 02:30:49,215 --> 02:30:50,115 OF THE STRENGTHS, WHERE MAYBE 4208 02:30:50,115 --> 02:30:53,953 EACH OF YOU AS EXPERTS IN THIS 4209 02:30:53,953 --> 02:30:55,254 AREA SAW SOME CONVERGING 4210 02:30:55,254 --> 02:30:56,522 EVIDENCE ACROSS YOUR MODELS OR 4211 02:30:56,522 --> 02:30:58,824 PLACES WHERE YOU'RE NOT SEEING 4212 02:30:58,824 --> 02:30:59,792 THESE THINGS SO WE CAN 4213 02:30:59,792 --> 02:31:00,893 APPRECIATE MAYBE SOME OF THE 4214 02:31:00,893 --> 02:31:02,595 LIMITATIONS. 4215 02:31:02,595 --> 02:31:04,563 AND I KNOW THAT'S A BIG ASK, BUT 4216 02:31:04,563 --> 02:31:05,798 I THINK THAT'S WHERE THIS PANEL 4217 02:31:05,798 --> 02:31:14,006 NEEDS TO GO. 4218 02:31:14,006 --> 02:31:15,674 >> ALL RIGHT. 4219 02:31:15,674 --> 02:31:17,676 SO EXCELLENT POINT, AND I HOPE 4220 02:31:17,676 --> 02:31:18,978 OTHERS WOULD JUMP IN AS WELL, 4221 02:31:18,978 --> 02:31:22,047 BUT MY TAKE ON THIS IS THE 4222 02:31:22,047 --> 02:31:23,682 QUESTIONS, RIGHT? 4223 02:31:23,682 --> 02:31:26,952 SO THE QUESTIONS YOU ASK, 4224 02:31:26,952 --> 02:31:28,020 WHATEVER YOU'RE INTERESTED IN, 4225 02:31:28,020 --> 02:31:29,121 WHATEVER YOU'RE PASSIONATE ABOUT 4226 02:31:29,121 --> 02:31:30,589 WILL DETERMINE WHAT MODEL YOU 4227 02:31:30,589 --> 02:31:31,624 USE. 4228 02:31:31,624 --> 02:31:34,693 IF YOU WANT TO STUDY THE 4229 02:31:34,693 --> 02:31:37,296 DYNAMICS OF TRANSMISSION AND 4230 02:31:37,296 --> 02:31:39,732 AEROSOL BIOLOGY, OBVIOUSLY YOU 4231 02:31:39,732 --> 02:31:40,933 HAVE TO CHOOSE A MODEL THAT 4232 02:31:40,933 --> 02:31:43,869 ALLOWS FOR THAT HUMANS, FERRETS, 4233 02:31:43,869 --> 02:31:46,305 FANTASTIC FOR THAT, EVEN GUINEA 4234 02:31:46,305 --> 02:31:46,872 PIG, I GUESS. 4235 02:31:46,872 --> 02:31:49,575 IF YOU WANT TO STUDY HOST 4236 02:31:49,575 --> 02:31:51,844 BIOLOGY, AND WE DON'T HAVE 4237 02:31:51,844 --> 02:31:52,745 ENOUGH REAGENTS IN THE FERRET 4238 02:31:52,745 --> 02:31:53,846 MODEL OR GUINEA PIGS THAT YOU 4239 02:31:53,846 --> 02:31:58,550 WANT TO USE, MICE ARE ADEAL FOR 4240 02:31:58,550 --> 02:32:00,486 THAT. 4241 02:32:00,486 --> 02:32:02,855 IF YOU WANT TO TEST PRE-EXISTING 4242 02:32:02,855 --> 02:32:06,892 IMMUNITY, WE CAN MODEL THAT IN 4243 02:32:06,892 --> 02:32:09,061 ANY OF THESE MODELS, BUT 4244 02:32:09,061 --> 02:32:09,929 ULTIMATELY IT WOULD BE THE HUMAN 4245 02:32:09,929 --> 02:32:11,463 MODEL THAT WOULD BE THE MOST 4246 02:32:11,463 --> 02:32:12,164 USEFUL FOR THAT. 4247 02:32:12,164 --> 02:32:18,003 SO THAT'S MY TAKE ON IT. 4248 02:32:18,003 --> 02:32:19,638 >> I WILL JUST ADD THAT I THINK 4249 02:32:19,638 --> 02:32:21,674 I HAVE NOT EVER BEEN AS HUMBLED 4250 02:32:21,674 --> 02:32:22,975 ABOUT TRANSMISSION AS I HAVE 4251 02:32:22,975 --> 02:32:24,109 BEEN WHEN I STARTED USING 4252 02:32:24,109 --> 02:32:24,743 HUMANS. 4253 02:32:24,743 --> 02:32:26,011 I'VE LEARNED MORE IN THE LAST 4254 02:32:26,011 --> 02:32:26,912 TWO YEARS ABOUT TRANSMISSION 4255 02:32:26,912 --> 02:32:28,647 THAN I HAVE IN OVER A DECADE OF 4256 02:32:28,647 --> 02:32:30,249 STUDYING IT AND READING 4257 02:32:30,249 --> 02:32:30,816 MANUSCRIPTS ON IT. 4258 02:32:30,816 --> 02:32:33,352 SO I THINK WHILE I DON'T HAVE AN 4259 02:32:33,352 --> 02:32:34,820 ANSWER, I MEAN, EVERY ANIMAL 4260 02:32:34,820 --> 02:32:37,556 MODEL IS FLAWED. 4261 02:32:37,556 --> 02:32:38,123 YOU KNOW? 4262 02:32:38,123 --> 02:32:39,858 FERRETS ARE FLAWED, MICE ARE 4263 02:32:39,858 --> 02:32:42,027 FLAWED, HAMSTERS ARE FLAWED, 4264 02:32:42,027 --> 02:32:44,196 GUINEA PIGS ARE FLAWED, CATS ARE 4265 02:32:44,196 --> 02:32:45,631 FLAWED, ALTHOUGH I REALLY LIKE 4266 02:32:45,631 --> 02:32:45,898 THE CATS. 4267 02:32:45,898 --> 02:32:48,667 I JUST THINK THAT, YOU KNOW, WE 4268 02:32:48,667 --> 02:32:49,802 ARE -- ANIMAL MODELS ARE FLAWED 4269 02:32:49,802 --> 02:32:56,442 AND WE REALLY DO, LIKE SAID AT 4270 02:32:56,442 --> 02:33:01,013 THE BEGINNING, WE SHOULD BE 4271 02:33:01,013 --> 02:33:02,514 CONSTANTLY THINKING ABOUT OUR 4272 02:33:02,514 --> 02:33:03,582 QUESTION, WHAT THAT IS, 4273 02:33:03,582 --> 02:33:04,450 ESPECIALLY FOR TRANSMISSION IN 4274 02:33:04,450 --> 02:33:06,819 TERMS OF HUMAN ASPECTS. 4275 02:33:06,819 --> 02:33:08,587 >> SEEMA, CAN I REALLY QUICKLY 4276 02:33:08,587 --> 02:33:09,021 EXPAND ON THAT? 4277 02:33:09,021 --> 02:33:12,424 ARE THERE FLAWS TO THE HUMAN -- 4278 02:33:12,424 --> 02:33:14,493 CONTROL HUMAN INFECTION STUDIES? 4279 02:33:14,493 --> 02:33:17,629 >> ABSOLUTELY THERE ARE FLAWS IN 4280 02:33:17,629 --> 02:33:20,299 CONTROLLED HUMAN INFECTION 4281 02:33:20,299 --> 02:33:23,302 MODELS, AS YOU KNOW, SOME OF THE 4282 02:33:23,302 --> 02:33:27,106 PUBLISHED DATA, AND HOURS -- 4283 02:33:27,106 --> 02:33:29,208 THERE IS LIMITED TRANSMISSION. 4284 02:33:29,208 --> 02:33:31,276 I JOKE AROUND A LOT, DOES FLU 4285 02:33:31,276 --> 02:33:32,144 ACTUALLY TRANSMIT? 4286 02:33:32,144 --> 02:33:34,179 LIKE I AM CONSTANTLY AMAZED WHEN 4287 02:33:34,179 --> 02:33:36,615 I SIT PEOPLE IN A TENT AND I 4288 02:33:36,615 --> 02:33:38,250 STARE AT THEM AND THEY DO CRAZY, 4289 02:33:38,250 --> 02:33:39,952 KREAS THINGS TO TRY TO GET 4290 02:33:39,952 --> 02:33:40,819 TRANSMISSION AND IT DOESN'T 4291 02:33:40,819 --> 02:33:42,154 WORK, IT IS ASTONISHING TO ME. 4292 02:33:42,154 --> 02:33:45,090 BUT I THINK WHAT I HAVE LEARNED 4293 02:33:45,090 --> 02:33:49,094 IS THAT THERE MAY BE A LOT OF 4294 02:33:49,094 --> 02:33:52,064 STOCHASTICITY IN HUMANS THAT WE 4295 02:33:52,064 --> 02:33:54,767 DO NOT RECAPITULATE IN HUMANS AT 4296 02:33:54,767 --> 02:33:56,201 ALL AND THAT WE REALLY NEED TO 4297 02:33:56,201 --> 02:33:57,836 UNDERSTAND A BIT MORE TO THEN 4298 02:33:57,836 --> 02:33:59,405 BUILD ANIMAL MODELS THAT ARE 4299 02:33:59,405 --> 02:34:01,073 MORE EFFICIENT AT HELPING US 4300 02:34:01,073 --> 02:34:02,741 STUDY IMPORTANT ASPECTS OF HUMAN 4301 02:34:02,741 --> 02:34:03,208 TRANSMISSION. 4302 02:34:03,208 --> 02:34:06,178 DOES THAT MAKE SENSE? 4303 02:34:06,178 --> 02:34:06,378 YEAH. 4304 02:34:06,378 --> 02:34:07,946 >> DIEGO, I KNOW YOU -- 4305 02:34:07,946 --> 02:34:09,481 >> I WAS JUST GOING TO ADD THAT 4306 02:34:09,481 --> 02:34:11,150 I'M THE ODD BALL HERE BECAUSE 4307 02:34:11,150 --> 02:34:12,418 I'VE DONE WORK ON TRANSMISSION 4308 02:34:12,418 --> 02:34:14,987 BUT IF WE THINK ABOUT 4309 02:34:14,987 --> 02:34:16,121 PATHOGENESIS, I DON'T THINK 4310 02:34:16,121 --> 02:34:17,489 THERE'S ONE ANIMAL MODEL THAT 4311 02:34:17,489 --> 02:34:18,757 FITS ALL AS WELL. 4312 02:34:18,757 --> 02:34:21,493 AND I DO THINK THAT WE DO NEED 4313 02:34:21,493 --> 02:34:24,897 TO COMPARE AND CONTRAST TO 4314 02:34:24,897 --> 02:34:28,233 REALLY DRAW RELEVANT CONCLUSIONS 4315 02:34:28,233 --> 02:34:29,301 ABOUT INFECTION BIOLOGY AND 4316 02:34:29,301 --> 02:34:33,138 VIRAL BIOLOGY IN GENERAL. 4317 02:34:33,138 --> 02:34:33,806 >> PETER. 4318 02:34:33,806 --> 02:34:35,741 >> I WAS JUST GOING TO SAY THAT 4319 02:34:35,741 --> 02:34:37,242 WE CAN TRY TO HUMANIZE THE 4320 02:34:37,242 --> 02:34:38,677 ANIMAL MODELS TO TRY TO MAKE 4321 02:34:38,677 --> 02:34:40,446 MORE TRANSGENICS, BUT IT MIGHT 4322 02:34:40,446 --> 02:34:42,181 COME DOWN TO THE FACT THAT THIS 4323 02:34:42,181 --> 02:34:44,983 IS WHAT THE HUMAN FACE, THE 4324 02:34:44,983 --> 02:34:48,487 HUMAN RESPIRATORY -- LOOKS LIKE 4325 02:34:48,487 --> 02:34:50,022 AND IT'S GOING TO DIFFER FROM A 4326 02:34:50,022 --> 02:34:51,090 GUINEA PIG, IT'S GOING TO DIFFER 4327 02:34:51,090 --> 02:34:52,624 FROM A HAMSTER, SO IT MIGHT HAVE 4328 02:34:52,624 --> 02:34:54,793 TO LEARN TO LIVE WITH SOME OF 4329 02:34:54,793 --> 02:34:56,762 THE ISSUES THAT WE'RE DEALING 4330 02:34:56,762 --> 02:34:57,963 WITH. 4331 02:34:57,963 --> 02:35:02,901 >> I AGREE. 4332 02:35:02,901 --> 02:35:04,503 >> ANOTHER QUESTION BUT THIS IS 4333 02:35:04,503 --> 02:35:05,104 VERY GRANULAR. 4334 02:35:05,104 --> 02:35:06,138 YESTERDAY WE SORT OF TALKED 4335 02:35:06,138 --> 02:35:08,774 ABOUT DIRTY MICE, THE SORT OF 4336 02:35:08,774 --> 02:35:10,042 RAISED A THOUGHT IN MY HEAD 4337 02:35:10,042 --> 02:35:11,477 ABOUT THE ROLE OF COMMENSAL 4338 02:35:11,477 --> 02:35:11,944 BACTERIA. 4339 02:35:11,944 --> 02:35:13,645 ONE OF THE THINGS THAT AT LEAST 4340 02:35:13,645 --> 02:35:15,380 WE'VE LEARNED FROM SARS-COV-2, 4341 02:35:15,380 --> 02:35:16,715 I'M SURE THIS HAS BEEN THERE FOR 4342 02:35:16,715 --> 02:35:18,350 FLU I'M JUST NOT AS FAMILIAR 4343 02:35:18,350 --> 02:35:19,785 WITH THE FIELD, IS THAT THERE'S 4344 02:35:19,785 --> 02:35:22,788 CLEARLY CHANGES IN THE NASAL 4345 02:35:22,788 --> 02:35:24,556 MICROBIOTA DURING SARS-COV-2 4346 02:35:24,556 --> 02:35:27,726 INFECTION. 4347 02:35:27,726 --> 02:35:29,628 WHEN YOU LOOK AT THESE AIRBORNE 4348 02:35:29,628 --> 02:35:32,731 DROPLETS OF TRANSMISSION, DO 4349 02:35:32,731 --> 02:35:34,666 THEY CONTAIN BACK T BACTERIA? 4350 02:35:34,666 --> 02:35:36,668 AND WHEN YOU THINK ABOUT YOUR 4351 02:35:36,668 --> 02:35:37,402 TRANSMISSION MODEL, HOW MUCH 4352 02:35:37,402 --> 02:35:41,673 DOES THAT POTENTIALLY INFLUENCE 4353 02:35:41,673 --> 02:35:43,442 THE SEEDING OF VIRUS IN ANOTHER 4354 02:35:43,442 --> 02:35:45,811 NASAL CAVITY AND POTENTIAL 4355 02:35:45,811 --> 02:35:46,812 INNATE IMMUNITY, INDUCTION AND 4356 02:35:46,812 --> 02:35:49,448 THOSE TYPES OF THINGS? 4357 02:35:49,448 --> 02:35:50,649 >> I WILL TOUCH ON THIS BECAUSE 4358 02:35:50,649 --> 02:35:52,151 I THINK IT'S REALLY IMPORTANT. 4359 02:35:52,151 --> 02:35:53,919 WE ARE NOW DEEP SEQUENCING AS 4360 02:35:53,919 --> 02:35:58,290 MUCH AS WE CAN THINGS THAT ARE 4361 02:35:58,290 --> 02:36:00,259 BEING EXPELLED FROM FERRETS AND 4362 02:36:00,259 --> 02:36:01,860 HUMANS, TO SAY THAT. 4363 02:36:01,860 --> 02:36:03,862 BUT WHEN WE HAVE COINFECTION 4364 02:36:03,862 --> 02:36:04,830 STUDIES AND WE'VE LOOKED 4365 02:36:04,830 --> 02:36:07,699 SPECIFICALLY FOR BACTERIA KIND 4366 02:36:07,699 --> 02:36:12,771 OF SIMILAR TO WHAT -- WE 4367 02:36:12,771 --> 02:36:15,707 DEFINITELY SEE IT IN THE AIR, 4368 02:36:15,707 --> 02:36:21,380 STREP PNEUMO AND FLU, THEY'RE 4369 02:36:21,380 --> 02:36:23,148 CONTAINED IF DIFFERENT SIZE 4370 02:36:23,148 --> 02:36:23,949 AEROSOL CONTAINMENTS. 4371 02:36:23,949 --> 02:36:25,951 SO YOU CAN FRACTIONATE THE AIR 4372 02:36:25,951 --> 02:36:28,353 USING SOME OF THESE NIOSH 4373 02:36:28,353 --> 02:36:33,492 SAMPLERS THAT CAN DO A 1 MICRON 4374 02:36:33,492 --> 02:36:34,526 4-MICRON SPLIT YOU COULD SEE 4375 02:36:34,526 --> 02:36:35,894 THAT BACTERIA AS YOU WOULD 4376 02:36:35,894 --> 02:36:37,429 EXPECT ARE IN THESE LARGER 4377 02:36:37,429 --> 02:36:38,864 AEROSOL FRAGMENTS THAN THOSE 4378 02:36:38,864 --> 02:36:40,799 SMALLER ONES. 4379 02:36:40,799 --> 02:36:41,867 SO WE'RE WORKING ON SOMETHING WE 4380 02:36:41,867 --> 02:36:44,303 CALL A PAYLOAD EXPERIMENT WHERE 4381 02:36:44,303 --> 02:36:45,837 DIFFERENT SIZE AEROSOLS TRY TO 4382 02:36:45,837 --> 02:36:47,472 UNDERSTAND HOW MANY VIRAL 4383 02:36:47,472 --> 02:36:49,174 PARTICLES AND POTENTIALLY OTHER 4384 02:36:49,174 --> 02:36:51,043 PATHOGENS ARE IN EACH AEROSOL OF 4385 02:36:51,043 --> 02:36:52,678 DIFFERENT SIZE RANGES, BECAUSE 4386 02:36:52,678 --> 02:36:55,380 WE CAN -- THIS IS AMAZING THINGS 4387 02:36:55,380 --> 02:36:56,915 YOU CAN DO WHEN YOU WORK WITH 4388 02:36:56,915 --> 02:36:57,916 ENGINEERS, ACTUALLY FIGURE OUT 4389 02:36:57,916 --> 02:37:01,386 WAYS TO TUNE AEROSOL DELIVERY 4390 02:37:01,386 --> 02:37:02,921 DEVICES AS SPECIFIC SIZE 4391 02:37:02,921 --> 02:37:03,889 FRACTIONS CAN BE MADE. 4392 02:37:03,889 --> 02:37:05,757 BUT THESE ARE IMPORTANT 4393 02:37:05,757 --> 02:37:06,091 QUESTIONS. 4394 02:37:06,091 --> 02:37:08,627 YOU DO FIND THEM. 4395 02:37:08,627 --> 02:37:09,795 >> SO THE SWAFER HAMSTERS AND 4396 02:37:09,795 --> 02:37:12,197 THE SYRIAN HAMSTERS, THE DWARFS 4397 02:37:12,197 --> 02:37:12,831 ARE DIRTY. 4398 02:37:12,831 --> 02:37:15,133 THEY'RE BASICALLY COMING FROM 4399 02:37:15,133 --> 02:37:16,568 WILD AND BEING COLLECTED. 4400 02:37:16,568 --> 02:37:20,939 SO YOU SEE WHAT THE DWARFS, YOU 4401 02:37:20,939 --> 02:37:23,275 SEE THE LETHALITY, YOU SEE THE 4402 02:37:23,275 --> 02:37:25,010 WEIGHT LOSS YOU DON'T SEE IN THE 4403 02:37:25,010 --> 02:37:25,677 SYRIANS. 4404 02:37:25,677 --> 02:37:26,612 YOU ALSO DON'T SEE TRANSMISSION. 4405 02:37:26,612 --> 02:37:28,680 SO IF WE COULD START TRYING TO 4406 02:37:28,680 --> 02:37:30,849 CLEAN UP THE DWARFS, HAVE 4407 02:37:30,849 --> 02:37:33,585 SEPARATE SETS THAT ARE DIRTY, 4408 02:37:33,585 --> 02:37:35,220 SEMI CLEAN OR CLEAN AND SEE IF 4409 02:37:35,220 --> 02:37:36,655 WE SEE CHANGES, IT WOULD BE 4410 02:37:36,655 --> 02:37:37,856 INTERESTING TO LOOK AT. 4411 02:37:37,856 --> 02:37:44,396 IF WE CAN CLEAN THEM UP. 4412 02:37:44,396 --> 02:37:46,198 >> MICHAEL. 4413 02:37:46,198 --> 02:37:48,200 >> TO PICK UP ON WHAT SEEMA 4414 02:37:48,200 --> 02:37:50,969 SAID, DEPENDING ON WHERE IN THE 4415 02:37:50,969 --> 02:37:52,471 RESPIRATORY TRACTS THAT THE 4416 02:37:52,471 --> 02:37:53,805 AEROSOL IS MADE, YOU WILL HAVE 4417 02:37:53,805 --> 02:37:54,740 DIFFERENT PARTICLE SIZE, RIGHT, 4418 02:37:54,740 --> 02:38:01,113 AND THIS WILL AFFECT AEROSOL 4419 02:38:01,113 --> 02:38:02,180 TRANSMISSION, SO IS THERE A 4420 02:38:02,180 --> 02:38:05,217 DIFFERENCE BETWEEN THE ANIMAL 4421 02:38:05,217 --> 02:38:06,852 MODELS, AND WHICH ONE IS 4422 02:38:06,852 --> 02:38:08,253 REFLECTING BEST WHAT HAPPENS IN 4423 02:38:08,253 --> 02:38:10,022 HUMANS, FOR EXAMPLE, AFTER 4424 02:38:10,022 --> 02:38:10,255 SNEEZE. 4425 02:38:10,255 --> 02:38:11,790 >> I WILL SAY ACTUALLY I THINK 4426 02:38:11,790 --> 02:38:12,658 THAT THIS IS WHERE WE THINK A 4427 02:38:12,658 --> 02:38:14,192 LITTLE BIT BINARY ABOUT 4428 02:38:14,192 --> 02:38:15,260 AEROSOLS, SO YOU'RE ABSOLUTELY 4429 02:38:15,260 --> 02:38:17,596 RIGHT THAT AEROSOLS CAN BE 4430 02:38:17,596 --> 02:38:19,097 GENERATED BOTH FROM THE ORAL AND 4431 02:38:19,097 --> 02:38:22,467 NASAL CAVITY DURING A VARIETY OF 4432 02:38:22,467 --> 02:38:22,768 EXPULSIONS. 4433 02:38:22,768 --> 02:38:25,203 HOWEVER, THERE IS REALLY POOR 4434 02:38:25,203 --> 02:38:27,706 DATA, EMPIRICAL DATA ON THE 4435 02:38:27,706 --> 02:38:30,242 DIFFERENT AEROSOL FRACTIONS THAT 4436 02:38:30,242 --> 02:38:31,877 EMERGE FROM THE ORAL VERSUS 4437 02:38:31,877 --> 02:38:32,411 NASAL CAVITY. 4438 02:38:32,411 --> 02:38:34,012 MOST OF IT IS DONE THROW 4439 02:38:34,012 --> 02:38:35,414 MODELING AND TRYING TO 4440 02:38:35,414 --> 02:38:37,282 UNDERSTAND HOW THESE THINGS ARE 4441 02:38:37,282 --> 02:38:38,717 POTENTIALLY BEING FORMED, WHICH 4442 02:38:38,717 --> 02:38:40,252 IS WHY PEOPLE SAY THAT YOU 4443 02:38:40,252 --> 02:38:41,420 GENERATE LARGER AEROSOLS FROM 4444 02:38:41,420 --> 02:38:45,223 THE ORAL CAVITY VERSUS THE NASAL 4445 02:38:45,223 --> 02:38:45,691 CAVITY. 4446 02:38:45,691 --> 02:38:46,992 I DON'T THINK THERE'S GOOD DATA 4447 02:38:46,992 --> 02:38:50,228 ON THAT IS WHAT I WILL SAY, LIKE 4448 02:38:50,228 --> 02:38:52,364 ACTUAL SHARE MENTAL DATA. 4449 02:38:52,364 --> 02:38:56,668 BUT THE OTHER THINK I THINK IS 4450 02:38:56,668 --> 02:38:57,769 REALLY IMPORTANT WE IG NOOR IS 4451 02:38:57,769 --> 02:38:59,104 THAT AEROSOL THAT GET EXPELLED 4452 02:38:59,104 --> 02:39:00,305 ARE NOT -- THEY ARE NOT -- 4453 02:39:00,305 --> 02:39:01,540 THEY'RE VERY DYNAMIC IN THE 4454 02:39:01,540 --> 02:39:04,876 ENVIRONMENT AS WELL, SOLID YA'S 4455 02:39:04,876 --> 02:39:06,411 GROUP AT MIT HAS DONE SOME 4456 02:39:06,411 --> 02:39:08,180 BEAUTIFUL WORK USING FLUID 4457 02:39:08,180 --> 02:39:10,015 DYNAMIC MODELS TO SHOW HOW 4458 02:39:10,015 --> 02:39:12,517 AEROSOLS ACTUALLY CHANGE SIZE 4459 02:39:12,517 --> 02:39:15,787 AND SHAPE IN THE AIR SO 4460 02:39:15,787 --> 02:39:17,589 DEPENDING UPON HUMIDITY AND 4461 02:39:17,589 --> 02:39:18,757 TEMPERATURE THEY CAN DESICCATE 4462 02:39:18,757 --> 02:39:19,758 AT FASTER RATES. 4463 02:39:19,758 --> 02:39:21,960 ALSO LARGER, SMALLER AEROSOLS 4464 02:39:21,960 --> 02:39:25,530 WILL COME OFF, THEY'RE NOT JUST 4465 02:39:25,530 --> 02:39:28,033 GOING TO STAY AT THAT ONE SIZE 4466 02:39:28,033 --> 02:39:29,034 RANGE WHEN IT GETS EXPELLED. 4467 02:39:29,034 --> 02:39:30,102 SO IT'S REALLY IMPORTANT TO 4468 02:39:30,102 --> 02:39:31,970 THINK ABOUT WHEN WE THINK ABOUT 4469 02:39:31,970 --> 02:39:34,573 AEROSOLS, IS THAT THEY ARE SUPER 4470 02:39:34,573 --> 02:39:37,008 DYNAMIC, AND OF COURSE THE 4471 02:39:37,008 --> 02:39:38,844 LARGER ISSUE IS WHEN A RECIPIENT 4472 02:39:38,844 --> 02:39:40,612 BREATHES THEM IN, DEPENDING UPON 4473 02:39:40,612 --> 02:39:43,148 THE SIZE AND WHAT ELSE IS IN 4474 02:39:43,148 --> 02:39:46,284 THEM, DEPOSIT AND BE SUCCESSFUL 4475 02:39:46,284 --> 02:39:47,786 SOMEWHERE ELSE IN THE 4476 02:39:47,786 --> 02:39:48,220 RESPIRATORY TRACT. 4477 02:39:48,220 --> 02:39:52,391 >> IS IT NORMAL -- A FERRET THAT 4478 02:39:52,391 --> 02:39:53,692 SNEEZES VERSUS A GUINEA PIG? 4479 02:39:53,692 --> 02:39:57,295 >> SO FERRETS ARE SIMILAR TO 4480 02:39:57,295 --> 02:40:00,365 HUMAN, IF YOU LOOK AT TOTAL 4481 02:40:00,365 --> 02:40:01,133 PARTICLE EXOWNTS, WHAT I CALL 4482 02:40:01,133 --> 02:40:02,534 THE DARK MATTER OF AEROSOL 4483 02:40:02,534 --> 02:40:03,735 BIOLOGY, IS THAT ALL OF OUR 4484 02:40:03,735 --> 02:40:06,438 DETECTION SYSTEMS THAT STUDY 4485 02:40:06,438 --> 02:40:08,340 AEROSOL SIZES IS REALLY GOOD AT 4486 02:40:08,340 --> 02:40:10,509 25 MICRONS AND SMALLER. 4487 02:40:10,509 --> 02:40:12,511 UNDERSTANDING AND QUANTIFYING 4488 02:40:12,511 --> 02:40:14,112 LARGER AEROSOLS GREATER THAN 4489 02:40:14,112 --> 02:40:17,716 25 MICRONS IS REALLY HARD. 4490 02:40:17,716 --> 02:40:20,018 IF YOU READ OLD AEROSOL PAPERS 4491 02:40:20,018 --> 02:40:21,887 TO UNDERSTAND HOW THEY DO THAT, 4492 02:40:21,887 --> 02:40:23,989 IT'S LIKE MAKE SOMEBODY BUT DYE 4493 02:40:23,989 --> 02:40:25,357 IN THEIR MOUTH AND SPLATTER IT 4494 02:40:25,357 --> 02:40:26,858 ON TO A PIECE OF PAPER AND LOOK 4495 02:40:26,858 --> 02:40:28,627 AT SIZE FRACTIONS FROM DIFFERENT 4496 02:40:28,627 --> 02:40:28,960 EXPULSIONS. 4497 02:40:28,960 --> 02:40:30,829 THAT IS LIKE SO CRUDE, IT IS 4498 02:40:30,829 --> 02:40:32,764 REALLY A CHALLENGE HERE TO STUDY 4499 02:40:32,764 --> 02:40:33,432 THINGS. 4500 02:40:33,432 --> 02:40:35,834 SO IF YOU LOOK AT -- THAT IS TO 4501 02:40:35,834 --> 02:40:37,436 SAY IF YOU LOOK AT THESE 4502 02:40:37,436 --> 02:40:39,638 PARTICLE COUNTERS THAT GO 4503 02:40:39,638 --> 02:40:40,839 25 MICRONS AND SMALLER, FERRETS 4504 02:40:40,839 --> 02:40:43,141 LIKE HUMANS, WE MAKE 4505 02:40:43,141 --> 02:40:43,875 PREDOMINANTLY REALLY SMALL 4506 02:40:43,875 --> 02:40:45,544 AEROSOLS, BUT A LOT OF THAT IS 4507 02:40:45,544 --> 02:40:47,279 CONTAMINATED STUFF FROM THE AIR. 4508 02:40:47,279 --> 02:40:48,914 YOU HAVE TO GET DOWN TO CLEAN 4509 02:40:48,914 --> 02:40:50,649 ROOM SIZES TO GET TO THAT, BUT 4510 02:40:50,649 --> 02:40:54,219 YOU STILL SEE A LOT OF SMALL 4511 02:40:54,219 --> 02:40:56,721 PARTICLES BEING GENERATED. 4512 02:40:56,721 --> 02:40:57,422 DOES THAT MAKE SENSE? 4513 02:40:57,422 --> 02:40:58,523 I DON'T KNOW IF ANYBODY ELSE 4514 02:40:58,523 --> 02:41:00,892 WANTS TO ADD ANYTHING TO THAT. 4515 02:41:00,892 --> 02:41:01,660 >> THANK YOU. 4516 02:41:01,660 --> 02:41:03,628 I WANT TO LET ZONDA HAVE A 4517 02:41:03,628 --> 02:41:04,863 MOMENT TO ASK A QUESTION. 4518 02:41:04,863 --> 02:41:10,669 >> YES, ON TRANSMISSION MODELS, 4519 02:41:10,669 --> 02:41:15,974 WE HAVE DISCUSSED A LOT ABOUT -- 4520 02:41:15,974 --> 02:41:18,810 INFECTION HISTORY, CLEAN AND 4521 02:41:18,810 --> 02:41:20,145 DIRTY MICE LIKE THAT, AND WE 4522 02:41:20,145 --> 02:41:23,515 ALSO TOUCH ON AGING, 4523 02:41:23,515 --> 02:41:24,149 AGE-DEPENDENT, ABOUT HOW ABOUT 4524 02:41:24,149 --> 02:41:26,651 OTHER CONDITIONS LIKE METABOLIC 4525 02:41:26,651 --> 02:41:30,489 CONDITIONS? 4526 02:41:30,489 --> 02:41:33,892 SHOULD WE ADDRESS THAT? 4527 02:41:33,892 --> 02:41:36,061 >> TBD, WE'RE DOING THOSE 4528 02:41:36,061 --> 02:41:36,928 EXPERIMENTS. 4529 02:41:36,928 --> 02:41:38,597 AT LEAST IN THE MOUSE MODEL. 4530 02:41:38,597 --> 02:41:39,331 ABSOLUTELY. 4531 02:41:39,331 --> 02:41:42,400 METABOLIC CONDITIONS, AT LEAST 4532 02:41:42,400 --> 02:41:44,035 IN HUMANS, PATIENTS WITH 4533 02:41:44,035 --> 02:41:46,238 DIABETES, AS WELL AS THOSE WITH 4534 02:41:46,238 --> 02:41:49,708 HEART DISEASE TEND TO BE MORE 4535 02:41:49,708 --> 02:41:51,042 SUSCEPTIBILITY TO FLU AND THEY 4536 02:41:51,042 --> 02:41:54,145 ALSO SHED FLU FOR PROLONGED 4537 02:41:54,145 --> 02:41:55,814 PERIOD OF TIME, 4538 02:41:55,814 --> 02:41:56,448 IMMUNOCOMPROMISED PATIENTS, SO 4539 02:41:56,448 --> 02:41:57,349 WE'RE TRYING TO MODEL ALL OF 4540 02:41:57,349 --> 02:42:00,619 THOSE IN MICE. 4541 02:42:00,619 --> 02:42:02,287 >> I KNOW YOU LIKE MICE BUT -- 4542 02:42:02,287 --> 02:42:03,221 >> FERRETS OVER HERE. 4543 02:42:03,221 --> 02:42:07,859 >> METABOLIC SYNDROMES, I REALLY 4544 02:42:07,859 --> 02:42:10,061 RECOMMEND YOU USE HAMSTERS. 4545 02:42:10,061 --> 02:42:12,030 TODAY I WOULD TALK A LITTLE BIT 4546 02:42:12,030 --> 02:42:13,298 ABOUT THE ADVANTAGE OF HAMSTER 4547 02:42:13,298 --> 02:42:17,435 IN TERMS OF MODELING METABOLIC 4548 02:42:17,435 --> 02:42:17,669 DISEASE. 4549 02:42:17,669 --> 02:42:18,503 >> SO IT WOULD BE GREAT TO SEE 4550 02:42:18,503 --> 02:42:20,372 YOUR HAMSTERS AND SEND THEM TO 4551 02:42:20,372 --> 02:42:22,073 WISCONSIN MAYBE. 4552 02:42:22,073 --> 02:42:23,441 >> I LOVE IT. 4553 02:42:23,441 --> 02:42:25,544 ARE THERE ANY QUESTIONS ONLINE 4554 02:42:25,544 --> 02:42:27,946 SINCE I KNOW I'VE BEEN REMISS 4555 02:42:27,946 --> 02:42:30,882 ASKING THAT? 4556 02:42:30,882 --> 02:42:32,517 ANY LAST BURNING QUESTION? 4557 02:42:32,517 --> 02:42:33,451 YES, STANLEY. 4558 02:42:33,451 --> 02:42:35,487 >> SO APOLOGIZE, THIS IS 4559 02:42:35,487 --> 02:42:36,788 PROBABLY NOT A BURNING QUESTION. 4560 02:42:36,788 --> 02:42:40,125 BUT WHEN YOU THINK ABOUT 4561 02:42:40,125 --> 02:42:41,259 TRANSMISSION, SO IF WE THINK 4562 02:42:41,259 --> 02:42:45,196 ABOUT THE PERSON WHO'S THE DONOR 4563 02:42:45,196 --> 02:42:46,831 AS IT WERE, DO WE THINK THAT 4564 02:42:46,831 --> 02:42:52,304 THAT PERSON HAS UNIFORM VIRAL 4565 02:42:52,304 --> 02:42:55,273 INFECTION ACROSS HIS OWN NASAL 4566 02:42:55,273 --> 02:42:56,575 CAVITY OR ARE WE THINKING 4567 02:42:56,575 --> 02:42:57,909 DIFFERENT PEOPLE, VIRUS MIGHT BE 4568 02:42:57,909 --> 02:42:59,544 IN ONE PLACE IN ONE PERSON, 4569 02:42:59,544 --> 02:43:01,313 DIFFERENT PLACE IN ANOTHER 4570 02:43:01,313 --> 02:43:03,381 PERSON AND THIS MIGHT CONFOUND 4571 02:43:03,381 --> 02:43:04,716 TRANSMISSION STUDIES BECAUSE 4572 02:43:04,716 --> 02:43:05,917 MAYBE ONE PART DOESN'T TRANSMIT 4573 02:43:05,917 --> 02:43:06,518 AS WELL? 4574 02:43:06,518 --> 02:43:08,153 >> I'M HAPPY TO TAKE THAT. 4575 02:43:08,153 --> 02:43:11,990 SO IF I'M USING CHIM STUDIES TO 4576 02:43:11,990 --> 02:43:14,726 JUST FLU H3 IN OUR CONTROLLED 4577 02:43:14,726 --> 02:43:16,595 HUMAN INFECTION MODELS WE SEE A 4578 02:43:16,595 --> 02:43:17,796 HUGE AMOUNT OF HETEROGENEITY IN 4579 02:43:17,796 --> 02:43:20,098 TERMS OF VIRAL LOAD IN THE NASAL 4580 02:43:20,098 --> 02:43:21,700 CAVITY VERSUS THE ORAL CAVITY. 4581 02:43:21,700 --> 02:43:26,204 SO WE SAMPLE THE NASOPHARYNGEAL 4582 02:43:26,204 --> 02:43:28,940 SITE, WE DO ORAL SWABS, SALIVA 4583 02:43:28,940 --> 02:43:30,442 COLLECTION THROUGH SPIT, WE DO 4584 02:43:30,442 --> 02:43:31,843 THROAT SWABS AND WE DO LIKE SORT 4585 02:43:31,843 --> 02:43:34,079 OF THE GCF TO SORT OF LIKE 4586 02:43:34,079 --> 02:43:36,247 BRUSHING YOUR TEETH, AND WE FIND 4587 02:43:36,247 --> 02:43:37,382 VARYING VIRAL LOADS IN ALL OF 4588 02:43:37,382 --> 02:43:38,416 THOSE SPACES. 4589 02:43:38,416 --> 02:43:42,020 IN FERRETS, WE SEE HIGH 4590 02:43:42,020 --> 02:43:43,488 CORRELATION BETWEEN NASAL TITERS 4591 02:43:43,488 --> 02:43:44,556 AND ORAL TITERS. 4592 02:43:44,556 --> 02:43:47,292 WE ALSO COLLECT SALIVA IN THE 4593 02:43:47,292 --> 02:43:49,060 FERRETS, I FORGOT TO MENTION 4594 02:43:49,060 --> 02:43:50,428 THAT, BUT I THINK IN HUMANS, 4595 02:43:50,428 --> 02:43:53,331 IT'S MUCH MORE HETEROGENEOUS. 4596 02:43:53,331 --> 02:43:54,633 >> WHAT ABOUT WITHIN EACH OF 4597 02:43:54,633 --> 02:43:56,835 THOSE AREAS, WITHIN THE NASAL OR 4598 02:43:56,835 --> 02:43:58,703 ORAL CAVITY, DO YOU THINK THAT'S 4599 02:43:58,703 --> 02:43:58,937 UNIFORM? 4600 02:43:58,937 --> 02:44:00,605 >> WE'RE ACTUALLY NOW DOING 4601 02:44:00,605 --> 02:44:02,807 SAMPLING TWO TIMES A DAY TO SEE 4602 02:44:02,807 --> 02:44:04,009 WHAT IS THE VAIR YITION OVER A 4603 02:44:04,009 --> 02:44:05,210 DAY WITHIN A SINGLE INDIVIDUAL. 4604 02:44:05,210 --> 02:44:06,411 I WILL TELL YOU WHAT I THINK IS 4605 02:44:06,411 --> 02:44:07,178 REALLY FASCINATING, THIS IS 4606 02:44:07,178 --> 02:44:09,914 WHERE I'M ALSO -- BEN CALLEN 4607 02:44:09,914 --> 02:44:12,517 TOLD ME THIS REALLY NIGHT TIDBIT 4608 02:44:12,517 --> 02:44:13,718 ONCE, IS THAT A SUPER SPREADER 4609 02:44:13,718 --> 02:44:15,453 IS ONLY A SUPER SPREADER ONCE, 4610 02:44:15,453 --> 02:44:15,720 RIGHT? 4611 02:44:15,720 --> 02:44:16,821 SO WHEN THEY'VE LOOKED AT HONG 4612 02:44:16,821 --> 02:44:18,089 KONG AND THEY'VE LOOKED AT THESE 4613 02:44:18,089 --> 02:44:20,725 SUPER SPREADERS AND I FIND 4614 02:44:20,725 --> 02:44:22,527 SOMEBODY SEEDED 200 INFECTIONS 4615 02:44:22,527 --> 02:44:26,631 AND THEN WENT TO ANOTHER SPACE 4616 02:44:26,631 --> 02:44:28,400 LATER THAT DAY, THEY DID NOT 4617 02:44:28,400 --> 02:44:32,003 SEED ANY FURTHER INFECTIONS SO. 4618 02:44:32,003 --> 02:44:35,073 STOCHASTICKITY IS SUPER 4619 02:44:35,073 --> 02:44:35,907 INTERESTING. 4620 02:44:35,907 --> 02:44:36,975 >> SO WE'VE ONLY GONE 2 MINUTES 4621 02:44:36,975 --> 02:44:38,510 OVER SO I THINK WE'VE HAD A 4622 02:44:38,510 --> 02:44:40,078 RATHER SUCCESSFUL SESSION. 4623 02:44:40,078 --> 02:44:41,813 PLEASE JOIN ME IN THANKING OUR 4624 02:44:41,813 --> 02:44:42,080 PANELISTS. 4625 02:44:42,080 --> 02:44:47,218 [APPLAUSE] 4626 02:44:47,218 --> 02:44:48,453 AND ACCORDING TO THE SCHEDULE, 4627 02:44:48,453 --> 02:44:53,358 WE NOW HAVE LUNCH UNTIL 12:45. 4628 02:44:53,358 --> 02:44:55,226 SO THAT'S TRUE FOR ALL OF OUR 4629 02:44:55,226 --> 02:44:55,994 ONLINE PARTICIPANTS. 4630 02:44:55,994 --> 02:45:01,825 THANK YOU. 4631 02:45:04,836 --> 02:45:06,705 >> I JUST WANT TO MAKE NOTE, I 4632 02:45:06,705 --> 02:45:08,006 THINK BECAUSE LUNCH IS A LITTLE 4633 02:45:08,006 --> 02:45:10,408 EARLIER TODAY, THEY'RE ON THEIR 4634 02:45:10,408 --> 02:45:13,878 WAY BUT IT'S NOT HERE IN THE 4635 02:45:13,878 --> 02:45:15,313 CAFETERIA THIS EXACT MOMENT, BUT 4636 02:45:15,313 --> 02:45:16,748 WE EXPECT THEM VERY SOON. THANKS. 4637 02:45:16,748 --> 02:45:26,891 4638 02:46:41,210 --> 02:46:42,645 IN THE INSTITUTE FOR ANTIVIRAL 4639 02:46:42,645 --> 02:46:45,147 RESEARCH, WE HAVE A GROUP OF 4640 02:46:45,147 --> 02:46:46,482 ABOUT 50 PEOPLE, AND REALLY 4641 02:46:46,482 --> 02:46:47,683 WE'VE HAD -- WE'VE BEEN SO 4642 02:46:47,683 --> 02:46:49,318 BLESSED WITH WORKING WITH THE 4643 02:46:49,318 --> 02:46:51,487 NIH, WE HAVE BEEN PART OF THE 4644 02:46:51,487 --> 02:46:52,788 COLLABORATIVE ANTIVIRAL TESTING 4645 02:46:52,788 --> 02:46:54,423 GROUP, REALLY FOR MORE THAN 25 4646 02:46:54,423 --> 02:46:56,759 YEARS. 4647 02:46:56,759 --> 02:46:59,361 WE APPRECIATE THE FUNDING ALL 4648 02:46:59,361 --> 02:47:01,330 THAT TIME FROM THE RESPIRATORY 4649 02:47:01,330 --> 02:47:03,299 DISEASES BRANCH, THE VIROLOGY 4650 02:47:03,299 --> 02:47:03,766 BRANCH. 4651 02:47:03,766 --> 02:47:06,135 WE DO BOTH IN VITRO EVALUATION, 4652 02:47:06,135 --> 02:47:08,237 SO IN VITRO SCREENING. 4653 02:47:08,237 --> 02:47:11,206 THIS IS A VALID ASSAY, WE JUST 4654 02:47:11,206 --> 02:47:12,374 CANNOT EVALUATE ALL THE 4655 02:47:12,374 --> 02:47:13,709 COMPOUNDS IN ANIMALS. 4656 02:47:13,709 --> 02:47:17,313 IT WOULD JUST BE TOO EXPENSIVE. 4657 02:47:17,313 --> 02:47:18,280 SO IN VITRO SCREENING STILL 4658 02:47:18,280 --> 02:47:19,915 PLAYS AN IMPORTANT PART. 4659 02:47:19,915 --> 02:47:22,017 15 YEARS AGO, WE WERE RUNNING 4660 02:47:22,017 --> 02:47:22,885 5,000 COMPOUNDS AGAINST 4661 02:47:22,885 --> 02:47:23,786 INFLUENZA EVERY YEAR. 4662 02:47:23,786 --> 02:47:25,287 THAT'S GREATLY DECREASED BUT WE 4663 02:47:25,287 --> 02:47:26,822 STILL ARE RUNNING THOUSANDS OF 4664 02:47:26,822 --> 02:47:27,489 COMPOUNDS EVERY YEAR. 4665 02:47:27,489 --> 02:47:29,858 THERE ARE ABOUT 40 DIFFERENT IN 4666 02:47:29,858 --> 02:47:30,659 VITRO ASSAYS THAT WE RUN. 4667 02:47:30,659 --> 02:47:32,394 WE ACTUALLY HAVE ANIMAL MODELS 4668 02:47:32,394 --> 02:47:35,130 FOR PROBABLY HALF OF THESE 4669 02:47:35,130 --> 02:47:38,634 VIRUSES. 4670 02:47:38,634 --> 02:47:39,735 DISTRIBUTED AMONG DIFFERENT 4671 02:47:39,735 --> 02:47:41,036 PIs, WE KIND OF DO SIMILAR 4672 02:47:41,036 --> 02:47:42,371 THINGS BUT WITH DIFFERENT 4673 02:47:42,371 --> 02:47:43,539 VIRUSES. 4674 02:47:43,539 --> 02:47:45,307 WE OFTEN HAVE SPONSORS, THESE 4675 02:47:45,307 --> 02:47:46,308 PEOPLE WHO HAVE HAD THEIR 4676 02:47:46,308 --> 02:47:47,276 COMPOUND APPROVED FOR TESTING TO 4677 02:47:47,276 --> 02:47:49,378 THE NIH. 4678 02:47:49,378 --> 02:47:52,548 IT'S THN GIV THEN GIVEN US TO. 4679 02:47:52,548 --> 02:47:53,616 THEY RECEIVE THE RESULTS, THEY 4680 02:47:53,616 --> 02:47:54,717 MAINTAIN ALL THE PROPRIETARY 4681 02:47:54,717 --> 02:47:57,987 RIGHTS AND THE NIH PAYS US. 4682 02:47:57,987 --> 02:48:01,924 A DEAL FOR ALL AROUND, ISN'T IT? 4683 02:48:01,924 --> 02:48:03,459 I'M OFTEN ASKED BY SPONSORS, 4684 02:48:03,459 --> 02:48:05,127 THEY HAVE A COMPOUND THAT'S VERY 4685 02:48:05,127 --> 02:48:05,861 EFFECTIVE IN VITRO AND IT FAILS 4686 02:48:05,861 --> 02:48:08,163 IN THE ANIMAL. 4687 02:48:08,163 --> 02:48:09,031 THEY'LL SAY, WHAT HAPPENED? 4688 02:48:09,031 --> 02:48:10,032 WHY DIDN'T THIS WORK? 4689 02:48:10,032 --> 02:48:11,567 AND I READ THIS LITTLE 4690 02:48:11,567 --> 02:48:13,202 STATEMENT, THE ONLY LATIN I 4691 02:48:13,202 --> 02:48:17,673 KNOW, OKAY, INSILICO -- IN VIVO 4692 02:48:17,673 --> 02:48:18,107 VERITAS. 4693 02:48:18,107 --> 02:48:19,441 I'VE ADDED IN VITRO IN THERE. 4694 02:48:19,441 --> 02:48:20,843 SO IN COMPUTERS AND CELL 4695 02:48:20,843 --> 02:48:22,811 CULTURE, WE MAKE PREDICTIONS. 4696 02:48:22,811 --> 02:48:23,912 IT'S IN THE ANIMAL WE LEARN THE 4697 02:48:23,912 --> 02:48:26,215 TRUTH. 4698 02:48:26,215 --> 02:48:27,650 THAT'S THE GOAL AND I HAVE TO 4699 02:48:27,650 --> 02:48:32,087 SAY THE TRUTH OFTEN FALSE FAR FR 4700 02:48:32,087 --> 02:48:33,055 SHORT OF THE GOAL. 4701 02:48:33,055 --> 02:48:36,992 I LOVE THIS QUOTE BY GEORGE BOX, 4702 02:48:36,992 --> 02:48:37,993 STATISTICIAN WHO SAYS ALL MODELS 4703 02:48:37,993 --> 02:48:40,162 ARE WRONG, SOME ARE USEFUL. 4704 02:48:40,162 --> 02:48:42,231 I THINK IS POINT IS WE SHOULD 4705 02:48:42,231 --> 02:48:44,333 FOCUS ON SOMETHING THAT CAN BE 4706 02:48:44,333 --> 02:48:46,402 APPLIED IN A USEFUL MANNER 4707 02:48:46,402 --> 02:48:47,836 RATHER THAN DEBATING IF IT'S 4708 02:48:47,836 --> 02:48:49,004 CORRECT IN ALL CASES. 4709 02:48:49,004 --> 02:48:51,306 AND REA PRODUCIBILITY, I THINK 4710 02:48:51,306 --> 02:48:52,207 IS ABSOLUTELY KEY. 4711 02:48:52,207 --> 02:48:53,375 I THINK ABOUT WHAT I CAN TALK 4712 02:48:53,375 --> 02:48:56,545 ABOUT IN THIS LITTLE SHORT 4713 02:48:56,545 --> 02:48:57,980 PRESENTATION TODAY, AND I'M 4714 02:48:57,980 --> 02:48:59,515 GOING TO TALK ABOUT LESSONS 4715 02:48:59,515 --> 02:49:00,616 LEARNED, OFTEN LESSONS LEARNED 4716 02:49:00,616 --> 02:49:03,218 THE HARD WAY IN MY LIFE, OKAY, 4717 02:49:03,218 --> 02:49:05,487 THAT REPRODUCIBILITY, ABSOLUTELY 4718 02:49:05,487 --> 02:49:06,622 KEY TO ALL THE MODELS THAT WE'RE 4719 02:49:06,622 --> 02:49:10,459 PRODUCING. 4720 02:49:10,459 --> 02:49:11,527 A LITTLE BIT OF A DIFFERENCE 4721 02:49:11,527 --> 02:49:13,829 BETWEEN A QUALIFICATION OR A 4722 02:49:13,829 --> 02:49:15,631 QUALIFIED ASSAY AND A VALIDATED 4723 02:49:15,631 --> 02:49:16,231 ASSAY. 4724 02:49:16,231 --> 02:49:19,134 WHEN I WORKED IN THE VACCINE 4725 02:49:19,134 --> 02:49:21,370 INDUSTRY, WE WOULD OFTEN DEVELOP 4726 02:49:21,370 --> 02:49:22,471 OR VALIDATE ASSAYS AS PART OF 4727 02:49:22,471 --> 02:49:23,672 THE LICENSING PROCESS. 4728 02:49:23,672 --> 02:49:26,108 VALIDATION IS A VERY HIGH 4729 02:49:26,108 --> 02:49:27,576 STANDARD. 4730 02:49:27,576 --> 02:49:28,277 QUALIFICATION MEANS IT PROVIDES 4731 02:49:28,277 --> 02:49:30,779 A HIGH DEGREE OF CONFIDENCE THAT 4732 02:49:30,779 --> 02:49:32,748 A PROCESS OR A MODEL IS 4733 02:49:32,748 --> 02:49:34,149 REPRODUCIBLE UNDER ANTICIPATED 4734 02:49:34,149 --> 02:49:38,454 VARIABLE RANGES. 4735 02:49:38,454 --> 02:49:40,022 ANTICIPATED BEING THE KEYWORD, 4736 02:49:40,022 --> 02:49:43,258 ANTICIPATED OR EXPECTED. 4737 02:49:43,258 --> 02:49:44,126 VALIDATION DESCRIBES PERFORMANCE 4738 02:49:44,126 --> 02:49:45,360 UNDER VERY HIGHLY CONTROLLED 4739 02:49:45,360 --> 02:49:45,961 CONDITIONS. 4740 02:49:45,961 --> 02:49:47,096 USUALLY BEYOND WHAT WE DO WITH 4741 02:49:47,096 --> 02:49:49,498 ANIMAL STUDIES. 4742 02:49:49,498 --> 02:49:50,933 IN PRE-CLINICAL TESTING FOR 4743 02:49:50,933 --> 02:49:52,334 ANTIVIRALS FOR VACCINES, WE 4744 02:49:52,334 --> 02:49:54,336 NORMALLY USE MODELS THAT ARE NOT 4745 02:49:54,336 --> 02:49:58,373 FULLY VALIDATED BUT QUALIFIED. 4746 02:49:58,373 --> 02:49:59,875 IT MEANS WE'VE DETERMINED WHERE 4747 02:49:59,875 --> 02:50:04,480 THE VARIABILITY IS FOUND. 4748 02:50:04,480 --> 02:50:08,884 SO LESSONS LEARNED, 25 YEARS A 4749 02:50:08,884 --> 02:50:12,888 AGO, HARD TO BELIEVE THAT, 1999, 4750 02:50:12,888 --> 02:50:13,789 HORSES IN NEW YORK WERE 4751 02:50:13,789 --> 02:50:18,260 DIAGNOSED WITH WEST NILE VIRUS, 4752 02:50:18,260 --> 02:50:19,795 A VIRUS THAT HAD NEVER BEFORE 4753 02:50:19,795 --> 02:50:21,897 BEEN IDENTIFIED IN THE WESTERN 4754 02:50:21,897 --> 02:50:22,297 HEMISPHERE. 4755 02:50:22,297 --> 02:50:23,398 PEOPLE DIDN'T BELIEVE IT AT THE 4756 02:50:23,398 --> 02:50:23,832 TIME, IT WAS TRUE. 4757 02:50:23,832 --> 02:50:25,167 SO LESSON LEARNED, WHAT IS 4758 02:50:25,167 --> 02:50:26,468 CONSIDERED A FOREIGN DISEASE 4759 02:50:26,468 --> 02:50:27,770 AGENT TODAY MAY BECOME AN 4760 02:50:27,770 --> 02:50:28,337 ENDEMIC AGENT TOMORROW. 4761 02:50:28,337 --> 02:50:30,773 YOU SEE, DUH, OBVIOUS. 4762 02:50:30,773 --> 02:50:34,376 AT THE TIME IT WAS NOT. 4763 02:50:34,376 --> 02:50:35,911 THIS WAS ASTONISHING. 4764 02:50:35,911 --> 02:50:38,213 IT TOOK FIVE YEARS FOR WEST NILE 4765 02:50:38,213 --> 02:50:42,084 TO GO FROM THE WEST V WEST COASE 4766 02:50:42,084 --> 02:50:44,653 EAST COAST. 4767 02:50:44,653 --> 02:50:45,254 MOSQUITO-BORNE. 4768 02:50:45,254 --> 02:50:48,824 THIS WAS ASTONISHING TO 4769 02:50:48,824 --> 02:50:50,192 BIOLOGISTS, EPIDEMIOLOGISTS, TO 4770 02:50:50,192 --> 02:50:50,793 PUBLIC HEALTH PEOPLE. 4771 02:50:50,793 --> 02:50:52,327 WE'D NEVER SEEN THIS BEFORE. 4772 02:50:52,327 --> 02:50:53,629 WITH REGARDS TO VACCINE 4773 02:50:53,629 --> 02:50:54,530 DEVELOPMENT, WE ALWAYS THINK 4774 02:50:54,530 --> 02:50:55,264 PROS AND CONS. 4775 02:50:55,264 --> 02:50:57,666 WE WANT TO BE FIRST. 4776 02:50:57,666 --> 02:50:59,101 FOR A NOVEL PRODUCT AT THAT 4777 02:50:59,101 --> 02:51:00,235 TIME, WE WERE DEVELOPING ONE OF 4778 02:51:00,235 --> 02:51:02,337 THE VERY FIRST RECOMBINANT 4779 02:51:02,337 --> 02:51:03,572 VACCINES FOR USE IN VETERINARY 4780 02:51:03,572 --> 02:51:03,872 MEDICINE. 4781 02:51:03,872 --> 02:51:06,208 SO THE PRO, WE CAN SET THE 4782 02:51:06,208 --> 02:51:08,076 STANDARD TO WHERE WE WANT TO BE. 4783 02:51:08,076 --> 02:51:09,912 CON, THE REGULATORY GUIDELINES 4784 02:51:09,912 --> 02:51:11,246 MAY NOT BE IN PLACE FOR 4785 02:51:11,246 --> 02:51:15,050 SOMETHING THAT NOVEL. 4786 02:51:15,050 --> 02:51:19,221 WE STITTED SUBMITTED AN ADDITIOL 4787 02:51:19,221 --> 02:51:20,322 DOSSIER FOR LICENSING THE 4788 02:51:20,322 --> 02:51:20,589 VACCINE. 4789 02:51:20,589 --> 02:51:23,392 IT TOOK THE USDA18 MONTHS TO 4790 02:51:23,392 --> 02:51:25,794 COME BACK TO US TO SAY THIS IS A 4791 02:51:25,794 --> 02:51:26,361 CHIMERIC VIRUS. 4792 02:51:26,361 --> 02:51:27,429 WE KNOW. 4793 02:51:27,429 --> 02:51:30,732 THEY DIDN'T HAVE THE EXPERTISE 4794 02:51:30,732 --> 02:51:32,968 AT THAT TIME. 4795 02:51:32,968 --> 02:51:35,270 SO I STARTED WORKING ON EQUINE 4796 02:51:35,270 --> 02:51:37,906 VACCINES, ACTUALLY DEVELOPED TWO 4797 02:51:37,906 --> 02:51:41,510 EQUINE VACCINES IN HORSES, A FEW 4798 02:51:41,510 --> 02:51:42,911 VACCINES, AND AT THAT TIME IN 4799 02:51:42,911 --> 02:51:46,081 2004, SO ABOUT 20 YEARS AGO, 4800 02:51:46,081 --> 02:51:48,183 EQUINE INFLUENZA JUMPED FROM 4801 02:51:48,183 --> 02:51:51,119 RACING HORSES TO RACING DOGS IN 4802 02:51:51,119 --> 02:51:55,824 FLORIDA. 4803 02:51:55,824 --> 02:51:57,359 THAT WAS KIND OF ASTONISHING, 4804 02:51:57,359 --> 02:51:57,993 LESSON LEARNED. 4805 02:51:57,993 --> 02:51:59,962 SO A DISEASE AGENT MAY JUMP FROM 4806 02:51:59,962 --> 02:52:01,630 ONE SPECIES TO ANOTHER. 4807 02:52:01,630 --> 02:52:03,198 AGAIN, DUH, OF COURSE. 4808 02:52:03,198 --> 02:52:04,600 SURPRISING AT THE TIME, NOT 4809 02:52:04,600 --> 02:52:07,302 EXPECTED 20 YEARS AGO. 4810 02:52:07,302 --> 02:52:09,071 AGAIN, WE DEVELOPED A NOVEL 4811 02:52:09,071 --> 02:52:10,272 PRODUCT, TRYING TO BE FIRST ON 4812 02:52:10,272 --> 02:52:11,807 THE MARKET, BEING FIRST, YOU CAN 4813 02:52:11,807 --> 02:52:15,844 SET THE STANDARD. 4814 02:52:15,844 --> 02:52:17,613 BUT IN THIS CASE THE CON, THE 4815 02:52:17,613 --> 02:52:18,247 REGULATORY AUTHORITIES, MAY NOT 4816 02:52:18,247 --> 02:52:23,051 HAVE THE SPEAR TE EXPERTISE, SON 4817 02:52:23,051 --> 02:52:24,386 TO OUTSIDE EXPERTS THAT MAY HAVE 4818 02:52:24,386 --> 02:52:25,254 INCORRECT BIASES. 4819 02:52:25,254 --> 02:52:26,889 WE SUBMITTED AN EMERGENCY USE 4820 02:52:26,889 --> 02:52:28,323 AUTHORIZATION DOSSIER. 4821 02:52:28,323 --> 02:52:30,092 THEY GOT IT, THEY SENT IT OUT TO 4822 02:52:30,092 --> 02:52:30,626 AN EXPERT. 4823 02:52:30,626 --> 02:52:32,160 THEY DIDN'T HAVE EXPERTISE IN 4824 02:52:32,160 --> 02:52:34,229 CANINE INFLUENZA. 4825 02:52:34,229 --> 02:52:36,198 THE EXPERT WAS AN EXPERT IN 4826 02:52:36,198 --> 02:52:37,399 BACTERIAL RESPIRATORY DISEASES 4827 02:52:37,399 --> 02:52:38,600 OF DOGS AND HE SAYS THIS IS 4828 02:52:38,600 --> 02:52:43,739 KENNEL COUGH. 4829 02:52:43,739 --> 02:52:45,140 WE SAID WE KNOW THIS IS NOT 4830 02:52:45,140 --> 02:52:47,009 KENNEL COUGH. 4831 02:52:47,009 --> 02:52:49,678 WE GOT HIM BACK, GOT ALL THE 4832 02:52:49,678 --> 02:52:51,280 TESTS, AGAIN SUBMITTED THE 4833 02:52:51,280 --> 02:52:54,716 DOSSIER AND YES, IT WAS LICEN 4834 02:52:54,716 --> 02:52:55,450 LICENSED. 4835 02:52:55,450 --> 02:52:59,721 SO LET ME GO TO THE MOUSE. 4836 02:52:59,721 --> 02:53:01,223 USU IN 2008. 4837 02:53:01,223 --> 02:53:04,893 IN 2009, ENDEMIC H1N1 HIT. 4838 02:53:04,893 --> 02:53:06,161 THAT WAS A PANDEMIC. 4839 02:53:06,161 --> 02:53:07,796 WE DODGED THE BULLET AT THAT 4840 02:53:07,796 --> 02:53:09,231 TIME, WE DID NOT LEARN THE 4841 02:53:09,231 --> 02:53:12,401 LESSON THAT WE NEEDED TO LEARN 4842 02:53:12,401 --> 02:53:17,639 FOR 2020, SARS-COV-2. 4843 02:53:17,639 --> 02:53:23,111 DON SNEAD AND MYSELF WERE 4844 02:53:23,111 --> 02:53:24,746 WORKING ON THE PANDEMIC FLU AT 4845 02:53:24,746 --> 02:53:26,615 THAT TIME AND HELPING RESPOND TO 4846 02:53:26,615 --> 02:53:28,483 THIS THREAT, THIS PANDEMIC. 4847 02:53:28,483 --> 02:53:29,718 WE REALLY DIDN'T HAVE TIME TO GO 4848 02:53:29,718 --> 02:53:32,854 THROUGH A LICENSURE PROCESS. 4849 02:53:32,854 --> 02:53:35,924 SO WHAT WE WERE FOCUSING ON WAS 4850 02:53:35,924 --> 02:53:37,326 COMBINATION DRUG STUDIES, TRYING 4851 02:53:37,326 --> 02:53:39,528 TO TAKE TWO LICENSED DRUGS, 4852 02:53:39,528 --> 02:53:41,063 SEEING IF WE COULD INCREASE THE 4853 02:53:41,063 --> 02:53:42,397 EFFICACY OF THE EXISTING 4854 02:53:42,397 --> 02:53:43,365 ANTIVIRAL DRUGS. 4855 02:53:43,365 --> 02:53:44,433 JUST KIND OF LOOKING HERE 4856 02:53:44,433 --> 02:53:45,734 QUICKLY AT THE MOUSE, WE HAVE 4857 02:53:45,734 --> 02:53:47,269 WEIGHT LOSS, KIND OF METRICS, I 4858 02:53:47,269 --> 02:53:48,470 LIKE TO CALL THEM. 4859 02:53:48,470 --> 02:53:49,638 THEY'RE PARAMETERS WE CAN 4860 02:53:49,638 --> 02:53:52,441 EVALUATE TO EVALUATE ANTIVIRAL 4861 02:53:52,441 --> 02:53:54,409 EFFICACY, VACCINE EFFICACY. 4862 02:53:54,409 --> 02:53:56,044 WEIGHT LOSS, MORTALITY ARE GOOD 4863 02:53:56,044 --> 02:53:56,378 METRICS. 4864 02:53:56,378 --> 02:53:57,579 PNEUMONIA, WE CAN LOOK AT LUNG 4865 02:53:57,579 --> 02:53:57,879 SCORE. 4866 02:53:57,879 --> 02:54:00,515 THIS IS SOMETHING VERY SIMPLE, 4867 02:54:00,515 --> 02:54:03,051 WORKING AT SAY FOUR QUADRANTS IN 4868 02:54:03,051 --> 02:54:04,820 THE LUNG, HOW MUCH OF THE LUNG 4869 02:54:04,820 --> 02:54:08,390 IS SHOWING A PURPLE COLOR 4870 02:54:08,390 --> 02:54:08,890 CONSOLIDATION? 4871 02:54:08,890 --> 02:54:10,792 WHITE ARE A GOOD NUMBER. 4872 02:54:10,792 --> 02:54:17,065 VIRUS TITERS, LUNG HI, STO. 4873 02:54:17,065 --> 02:54:18,033 CYTOKINE MEASUREMENTS, NOT 4874 02:54:18,033 --> 02:54:20,969 REALLY SO MUCH FOR ANTIVIRALS 4875 02:54:20,969 --> 02:54:22,404 BUT DEFINITELY FOR VACCINES. 4876 02:54:22,404 --> 02:54:24,906 SO A FEW LESSONS LEARNED, VIRUS 4877 02:54:24,906 --> 02:54:26,341 STRAIN DIFFERENCES. 4878 02:54:26,341 --> 02:54:27,676 SEASONAL INFLUENZA HAS BEEN 4879 02:54:27,676 --> 02:54:28,010 TALKED ABOUT. 4880 02:54:28,010 --> 02:54:29,511 IN FACT, THERE'S BEEN SO MANY 4881 02:54:29,511 --> 02:54:30,812 THINGS THAT HAVE BEEN DISCUSSED, 4882 02:54:30,812 --> 02:54:33,882 I CAN JUST STAND UP HERE AND SAY 4883 02:54:33,882 --> 02:54:37,052 DITTO AND GO BACK AND SIT DOWN. 4884 02:54:37,052 --> 02:54:40,655 SEASONAL INFLUENZA A REQUIRES 4885 02:54:40,655 --> 02:54:42,524 VIRUS ADAPTATION TO CAUSE 4886 02:54:42,524 --> 02:54:43,625 LETHALITY IN MICE. 4887 02:54:43,625 --> 02:54:46,128 THANK GOODNESS HIGHLY PATHOGENIC 4888 02:54:46,128 --> 02:54:47,896 AVIAN FLU DOES NOT REQUIRE 4889 02:54:47,896 --> 02:54:53,468 ADAPTATION. 4890 02:54:53,468 --> 02:54:55,103 SO DON'T HAVE TO DEAL WITH ADAP 4891 02:54:55,103 --> 02:54:57,639 TITION TO GAIN OF FUNCTION-TYPE 4892 02:54:57,639 --> 02:54:57,873 THINGS. 4893 02:54:57,873 --> 02:55:00,242 TALK ABOUT H3N2 VIRUSES, VERY 4894 02:55:00,242 --> 02:55:01,143 DIFFICULT TO ADAPT. 4895 02:55:01,143 --> 02:55:04,946 THEY ARE HEAVILY GLYCOSYLATED. 4896 02:55:04,946 --> 02:55:06,348 WHEREAS WE FIND WITH MOUSE 4897 02:55:06,348 --> 02:55:08,884 ADAPTATION OF FLU VIRUSES, IF 4898 02:55:08,884 --> 02:55:10,986 THEY ARE GLYCOSYLATED, THEY WILL 4899 02:55:10,986 --> 02:55:16,758 LOSE GL GLYCOSYLATION. 4900 02:55:16,758 --> 02:55:19,828 IT'S WHAT MAKING IT SO DIFFICULT 4901 02:55:19,828 --> 02:55:21,696 TO ADAPT. 4902 02:55:21,696 --> 02:55:24,066 2009, PANDEMIC H1 WAS JUST 4903 02:55:24,066 --> 02:55:27,636 DIFFERENT. 4904 02:55:27,636 --> 02:55:30,872 IT WAS JUST DIFFERENT. 4905 02:55:30,872 --> 02:55:32,174 THESE LITTLE CHARTS THAT COME 4906 02:55:32,174 --> 02:55:33,275 OUT OF THE WOR WORLD HEALTH 4907 02:55:33,275 --> 02:55:33,942 ORGANIZATION, THIS WAS FOR THE 4908 02:55:33,942 --> 02:55:34,609 END OF JUNE. 4909 02:55:34,609 --> 02:55:36,011 IF YOU'VE NOT LOOKED AT THESE, 4910 02:55:36,011 --> 02:55:38,080 THE LITTLE PIE CHART SHOWS 4911 02:55:38,080 --> 02:55:39,214 GEOGRAPHICAL AREAS AROUND THE 4912 02:55:39,214 --> 02:55:42,250 WORLD WHERE THEY'RE GETTING 4913 02:55:42,250 --> 02:55:43,218 SAMPLES OF DIFFERENT COLORS IN 4914 02:55:43,218 --> 02:55:44,786 THE LITTLE PIE CHART SHOWING 4915 02:55:44,786 --> 02:55:47,622 WHICH FLU SUBTYPES. 4916 02:55:47,622 --> 02:55:52,627 SO THE LIGHT GREEN IS H1. 4917 02:55:52,627 --> 02:55:54,696 MEDIUM COLORED GREEN IS JUST 4918 02:55:54,696 --> 02:55:56,231 INFLUENZA A, THEY'RE NOT 4919 02:55:56,231 --> 02:55:57,999 DISTINGUISHING BETWEEN H1 OR H3. 4920 02:55:57,999 --> 02:56:06,975 THE DARK GREEN IS NOW THE 4921 02:56:06,975 --> 02:56:08,276 COMBINATION, THE MIDDLE GREEN IS 4922 02:56:08,276 --> 02:56:08,710 H3. 4923 02:56:08,710 --> 02:56:10,278 THE RUST COLOR ORANGE, WHATEVER 4924 02:56:10,278 --> 02:56:11,680 COLOR YOU WANT TO CALL IT, 4925 02:56:11,680 --> 02:56:12,747 THAT'S INFLUENZA B. 4926 02:56:12,747 --> 02:56:14,182 WHAT WAS REMARKABLE IS LOOKING 4927 02:56:14,182 --> 02:56:16,051 AT THIS LITTLE CHART, AND IT 4928 02:56:16,051 --> 02:56:16,818 CHANGES, IT'S ALWAYS BEEN 4929 02:56:16,818 --> 02:56:18,120 INTERESTING TO ME HOW DIFFERENT 4930 02:56:18,120 --> 02:56:19,321 REGIONS OF THE WORLD, DIFFERENT 4931 02:56:19,321 --> 02:56:22,057 FLU VIRUS SUBTYPES ARE 4932 02:56:22,057 --> 02:56:22,724 CIRCULATING. 4933 02:56:22,724 --> 02:56:24,893 WHEN THE PANDEMIC CAME IN, 4934 02:56:24,893 --> 02:56:26,995 PANDEMIC H1 BACK IN 2009, IT 4935 02:56:26,995 --> 02:56:30,465 PUSHED EVERYTHING ELSE OUT. 4936 02:56:30,465 --> 02:56:33,001 ALL THESE PIE CHARTS WERE ONE 4937 02:56:33,001 --> 02:56:37,706 COLOR. 4938 02:56:37,706 --> 02:56:40,308 THE PANDEMIC, 2009, H1N1, WAS 4939 02:56:40,308 --> 02:56:40,976 DIFFERENT. 4940 02:56:40,976 --> 02:56:42,177 IT NEVER EXISTED IN THE WORLD 4941 02:56:42,177 --> 02:56:42,511 BEFORE. 4942 02:56:42,511 --> 02:56:45,580 SO JUST KIND OF A REMARKABLE 4943 02:56:45,580 --> 02:56:47,849 THING. 4944 02:56:47,849 --> 02:56:51,920 I DON'T WANT TO BO BEAT THIS TO 4945 02:56:51,920 --> 02:56:53,355 DEATH, IF I WORK FOR THE FDA AND 4946 02:56:53,355 --> 02:56:55,423 SOMEBODY CAME UP TO ME TO BRING 4947 02:56:55,423 --> 02:57:00,896 A DOSSIER SHOWING EFFICACY FOR 4948 02:57:00,896 --> 02:57:02,531 PR8, I WOULD SAY THIS IS VERY 4949 02:57:02,531 --> 02:57:04,933 NICE, NOW PLEASE DO IT IN A 4950 02:57:04,933 --> 02:57:06,468 CLINICALLY RELEVANT MODEL. 4951 02:57:06,468 --> 02:57:09,204 I WENT TO A KEYSTONE MEETING 4952 02:57:09,204 --> 02:57:10,305 HERE A COUPLE YEARS AGO ON 4953 02:57:10,305 --> 02:57:12,174 INJURY AND INFLAMMATION IN THE 4954 02:57:12,174 --> 02:57:12,474 LUNG. 4955 02:57:12,474 --> 02:57:15,110 SO THESE WERE NON-VIROLOGISTS. 4956 02:57:15,110 --> 02:57:17,078 THEY WERE USING PR8 AND I 4957 02:57:17,078 --> 02:57:18,280 THOUGHT, I LIKE IT. 4958 02:57:18,280 --> 02:57:21,883 THEY WERE USING PR8 AS THE 4959 02:57:21,883 --> 02:57:22,117 INSULT. 4960 02:57:22,117 --> 02:57:23,318 THAT WAS THE INJURY TO THE LUNG 4961 02:57:23,318 --> 02:57:25,187 TO LOOK AT INJURY AND 4962 02:57:25,187 --> 02:57:25,520 INFLAMMATION. 4963 02:57:25,520 --> 02:57:27,022 THEY WERE NOT VIROLOGISTS, THEY 4964 02:57:27,022 --> 02:57:29,758 DIDN'T CARE WHAT -- THEY COULD 4965 02:57:29,758 --> 02:57:30,625 BE ASSUMING ASBESTOS. 4966 02:57:30,625 --> 02:57:32,060 BUT I THOUGHT IN THAT SITUATION, 4967 02:57:32,060 --> 02:57:34,229 I THOUGHT THAT WAS A GREAT 4968 02:57:34,229 --> 02:57:37,866 MODEL. 4969 02:57:37,866 --> 02:57:41,136 SO I RECOGNIZE THERE ARE 4970 02:57:41,136 --> 02:57:41,970 DIFFERENT LOCATIONS WHERE THAT 4971 02:57:41,970 --> 02:57:44,839 COULD BE A GOOD M MODEL. 4972 02:57:44,839 --> 02:57:46,374 INFLUENZA B, THIS LITTLE CHART 4973 02:57:46,374 --> 02:57:47,475 HERE, IMAGINE IF IT WAS SARS, 4974 02:57:47,475 --> 02:57:49,344 BECAUSE WE WERE WEARING MASKS 4975 02:57:49,344 --> 02:57:50,979 AND OF COURSE NO ONE BELIEVES 4976 02:57:50,979 --> 02:57:52,147 MASKS WERE EFFECTIVEMENT WE KNOW 4977 02:57:52,147 --> 02:57:55,684 TEFFECTIVE.WE KNOW THAT THEY WE. 4978 02:57:55,684 --> 02:57:57,919 SO EFFECTIVE THAT IT'S PROBABLY 4979 02:57:57,919 --> 02:58:00,622 DRIVEN THE MAMAGATA VICTORIA 4980 02:58:00,622 --> 02:58:04,259 LINEAGES OF INFLUENZA B, 4981 02:58:04,259 --> 02:58:08,930 SPORADICALLY IDENTIFIED SINCE 4982 02:58:08,930 --> 02:58:10,932 SARS 22, IT'S BEEN PUSHED TO 4983 02:58:10,932 --> 02:58:11,366 EXTINCTION. 4984 02:58:11,366 --> 02:58:12,334 I BELIEVE, SOMEONE ELSE CAN 4985 02:58:12,334 --> 02:58:14,302 CORRECT ME, THAT THIS YEAR IT'S 4986 02:58:14,302 --> 02:58:17,138 NOT A QUADRA VALENT VACCINE. 4987 02:58:17,138 --> 02:58:23,311 PRIOR TO THIS WE'VE HAD H1H3, 4988 02:58:23,311 --> 02:58:24,913 INFLUENZA A, AND BOTH VICTORIA 4989 02:58:24,913 --> 02:58:28,383 AND A MAMAGATA FOR THE INFLUENZA 4990 02:58:28,383 --> 02:58:29,618 Bs, THIS YEAR THEY WENT BACK 4991 02:58:29,618 --> 02:58:33,221 TO H1, H3 AND VICTORIA. 4992 02:58:33,221 --> 02:58:36,958 THE YAMAGATA IS BEING PUSHED 4993 02:58:36,958 --> 02:58:37,292 OUT. 4994 02:58:37,292 --> 02:58:38,727 WHICH IS KIND OF INTERESTING. 4995 02:58:38,727 --> 02:58:39,561 OKAY. 4996 02:58:39,561 --> 02:58:40,295 VIRUS CHALLENGE DOSE. 4997 02:58:40,295 --> 02:58:43,498 WE WILL DO A 3XLD50 AS PART OF 4998 02:58:43,498 --> 02:58:48,436 OUR QUALIFIED ANTIVIRAL TESTING 4999 02:58:48,436 --> 02:58:50,972 MODELS. 5000 02:58:50,972 --> 02:58:54,576 IF YOU THINK A LOG SCALE PAPER, 5001 02:58:54,576 --> 02:58:55,910 HALF A LOG IS NOT HALFWAY 5002 02:58:55,910 --> 02:58:56,945 BETWEEN THE SCALES. 5003 02:58:56,945 --> 02:58:59,147 IT'S A THIRD OF THE WAY. 5004 02:58:59,147 --> 02:59:02,117 SO 3 IS ABOUT A HALF LOG. 5005 02:59:02,117 --> 02:59:07,689 SO L3XLD50 IS ABOUT A HALF LOG 5006 02:59:07,689 --> 02:59:10,191 HIGHER THAN LD50. 5007 02:59:10,191 --> 02:59:11,192 IT'S THEORETICALLY A LITTLE 5008 02:59:11,192 --> 02:59:12,927 HIGHER THAN LD90. 5009 02:59:12,927 --> 02:59:14,262 BUT WHAT WE'RE WANTING TO DO, 5010 02:59:14,262 --> 02:59:15,764 WE'RE WANTING TO CAUSE LETHALITY 5011 02:59:15,764 --> 02:59:19,501 IN ALMOST 100% OF THE MICE. 5012 02:59:19,501 --> 02:59:20,935 BUT WE DON'T WANT TO 5013 02:59:20,935 --> 02:59:22,003 OVERCHALLENGE BECAUSE WE WANT TO 5014 02:59:22,003 --> 02:59:26,708 GIVE THE ANTIVIRAL -- OF THE 5015 02:59:26,708 --> 02:59:28,476 VACCINE THE OPTIMAL CHANCE OF 5016 02:59:28,476 --> 02:59:28,910 SHOWING EFFICACY. 5017 02:59:28,910 --> 02:59:31,646 SO WE DON'T WANT TO 5018 02:59:31,646 --> 02:59:32,180 OVERCHALLENGE IT. 5019 02:59:32,180 --> 02:59:33,615 THE DOSE IS PART OF THE 5020 02:59:33,615 --> 02:59:34,783 QUALIFIED MODEL. 5021 02:59:34,783 --> 02:59:38,953 WHY I'M STRESSING THAT, I WILL 5022 02:59:38,953 --> 02:59:44,659 HAVE SPONSORED FROM THE NIH HAS 5023 02:59:44,659 --> 02:59:45,960 APPROVED, YES, WE'D LIKE TO MORE 5024 02:59:45,960 --> 02:59:47,696 OR LESS HOLD THE VACCINE DOSE 5025 02:59:47,696 --> 02:59:49,230 CONSTANT AND HAVE US CHANGE THE 5026 02:59:49,230 --> 02:59:50,031 VIRUS CHALLENGE DOSE. 5027 02:59:50,031 --> 02:59:51,866 AND I HAVE TO BE VERY TIP LOMA 5028 02:59:51,866 --> 02:59:59,841 TICK ADIPLOMATICAND TELL THEM T. 5029 02:59:59,841 --> 03:00:00,675 THE CHALLENGE DOSE IS PART OF 5030 03:00:00,675 --> 03:00:01,176 THE MODEL. 5031 03:00:01,176 --> 03:00:03,044 IF THE VACCINE DOESN'T WORK, I'M 5032 03:00:03,044 --> 03:00:04,446 SORRY, IT'S NOT EFFICACIOUS, BUT 5033 03:00:04,446 --> 03:00:07,515 THE MODEL STANDS. 5034 03:00:07,515 --> 03:00:09,050 SOMETHING ELSE I'VE LEARNED FROM 5035 03:00:09,050 --> 03:00:10,352 REALLY JUST INS TEUGAL MEMORY 5036 03:00:10,352 --> 03:00:12,120 WHEN I WORKED IN THE VACCINE 5037 03:00:12,120 --> 03:00:13,088 INDUSTRY, IT WAS A VERY GOOD 5038 03:00:13,088 --> 03:00:15,390 COMPANY, WE HAD A LOT OF 5039 03:00:15,390 --> 03:00:17,659 EXPERTISE. 5040 03:00:17,659 --> 03:00:19,861 I WILL HAVE SPONSORS COME TO US, 5041 03:00:19,861 --> 03:00:21,162 TWO, THREE, FOUR VACCINATIONS 5042 03:00:21,162 --> 03:00:25,567 FOR EFFICACY, AND WHAT I WAS 5043 03:00:25,567 --> 03:00:27,001 TAUGHT VERY EARLY ON, WE WANT TO 5044 03:00:27,001 --> 03:00:28,403 DO A SINGLE DOSE IN A 5045 03:00:28,403 --> 03:00:30,038 PRELIMINARY STUDY, THAT IF I'M 5046 03:00:30,038 --> 03:00:31,906 USING MORE THAN ONE DOSE OF 5047 03:00:31,906 --> 03:00:36,177 VACCINE, IT CAN MASK A VERY WEAK 5048 03:00:36,177 --> 03:00:37,045 IMMUNOGEN. 5049 03:00:37,045 --> 03:00:38,813 AND THE COMPANY I WAS WORKING 5050 03:00:38,813 --> 03:00:40,982 FOR, WE WANT TO KNOW IF IT'S A 5051 03:00:40,982 --> 03:00:42,083 PORE IMMUNOGEN BECAUSE WE WANT 5052 03:00:42,083 --> 03:00:43,385 TO CUT OUR LOSSES BEFORE WE GO 5053 03:00:43,385 --> 03:00:43,952 ON. 5054 03:00:43,952 --> 03:00:45,887 WHY KEEP CHASING, WE'RE KICKING 5055 03:00:45,887 --> 03:00:47,756 A DEAD COURSE AS THEY MIGHT SAY. 5056 03:00:47,756 --> 03:00:51,259 YOU WANT TO KEEP WORKING ON TH 5057 03:00:51,259 --> 03:00:52,260 THIS -- YOU DON'T WANT TO KEEP 5058 03:00:52,260 --> 03:00:53,361 WORKING ON THIS IF IT'S NOT 5059 03:00:53,361 --> 03:00:54,462 GOING TO BE EFFECTIVE. 5060 03:00:54,462 --> 03:00:56,398 FROM THERE, WE CAN GO ON TO DO 5061 03:00:56,398 --> 03:01:00,668 LOTS OF OTHER THINGS. 5062 03:01:00,668 --> 03:01:01,770 REGARDING ADJUVANT STUDY, 5063 03:01:01,770 --> 03:01:03,037 THERE'S A REASON I'M STARTING 5064 03:01:03,037 --> 03:01:03,505 WITH THIS. 5065 03:01:03,505 --> 03:01:05,273 I OFTEN WILL CALL THIS KIND OF 5066 03:01:05,273 --> 03:01:06,574 THREADING THE NEEDLE. 5067 03:01:06,574 --> 03:01:08,209 SO I WANT TO GET A SUBOPTIMAL 5068 03:01:08,209 --> 03:01:12,580 DOSE OF A VACCINE THAT DOES NOT 5069 03:01:12,580 --> 03:01:14,449 PRODUCE STATISTICALLY 5070 03:01:14,449 --> 03:01:16,518 SIGNIFICANT EFFICACY BY ITSELF, 5071 03:01:16,518 --> 03:01:18,953 BUT NOW THAT I HAVE AN ADJUVANT, 5072 03:01:18,953 --> 03:01:22,190 THEN I CAN SEE STATISTICAL 5073 03:01:22,190 --> 03:01:22,791 SIGNIFICANCE, AND IT'S SHOWING 5074 03:01:22,791 --> 03:01:27,128 ME THAT THE ADJUVANT IS WORKING. 5075 03:01:27,128 --> 03:01:28,363 KIND OF A CHALLENGE THERE. 5076 03:01:28,363 --> 03:01:30,632 VERY SIMILAR TO AN ANTIVIRAL 5077 03:01:30,632 --> 03:01:33,701 COMBINATION DRUG STUDY. 5078 03:01:33,701 --> 03:01:35,570 BUT YOU TAKE TWO EFFICACIOUS 5079 03:01:35,570 --> 03:01:37,071 DRUGS, PUT THEM TOGETHER, YOU 5080 03:01:37,071 --> 03:01:38,740 CAN'T SEE IF THERE'S SYNERGY OR 5081 03:01:38,740 --> 03:01:39,073 NOT. 5082 03:01:39,073 --> 03:01:41,676 SO WHAT WE'LL DO, WE DO A 5083 03:01:41,676 --> 03:01:42,877 SUBOPTIMAL DOSE OF BOTH, PUT 5084 03:01:42,877 --> 03:01:44,212 THEM TOGETHER AND THEN LOOK FOR 5085 03:01:44,212 --> 03:01:44,946 SIGNIFICANCE AND IT WILL TELL 5086 03:01:44,946 --> 03:01:48,817 YOU IF THERE'S SYNERGY OR NOT. 5087 03:01:48,817 --> 03:01:49,784 BREATHING ANTAGONISM. 5088 03:01:49,784 --> 03:01:52,320 SO MODEL TO EVALUATE AND DEVELOP 5089 03:01:52,320 --> 03:01:54,255 THERAPEUTICS LETHAL VERSUS 5090 03:01:54,255 --> 03:01:56,224 NON- LETHAL OBVIOUS QUESTION. 5091 03:01:56,224 --> 03:01:57,759 MANY TIMES I'VE BEEN CRITICIZED 5092 03:01:57,759 --> 03:01:59,761 FOR LETHAL MODELS, THEY SAY WHAT 5093 03:01:59,761 --> 03:02:01,162 POPULATION ARE YOU REALLY 5094 03:02:01,162 --> 03:02:01,596 MODELING? 5095 03:02:01,596 --> 03:02:03,364 WELL, PEOPLE THAT ARE SEVERELY 5096 03:02:03,364 --> 03:02:04,766 INFECTED IN HOSPITALS, THAT'S 5097 03:02:04,766 --> 03:02:05,767 PROBABLY NOT TOO BAD A 5098 03:02:05,767 --> 03:02:06,534 POPULATION. 5099 03:02:06,534 --> 03:02:07,735 IF WE CAN DEVELOP AN ANTIVIRAL 5100 03:02:07,735 --> 03:02:09,370 THAT WILL PROTECT THEM, IT WILL 5101 03:02:09,370 --> 03:02:10,004 DEFINITELY PROTECT SOMEONE AT 5102 03:02:10,004 --> 03:02:11,239 HOME. 5103 03:02:11,239 --> 03:02:13,508 BUT THIS IDEA OF THE NON-LETHAL 5104 03:02:13,508 --> 03:02:14,709 MODEL IS IMPORTANT AND I'M GOING 5105 03:02:14,709 --> 03:02:16,010 TO COME BACK TO THAT IN JUST A 5106 03:02:16,010 --> 03:02:17,011 MINUTE. 5107 03:02:17,011 --> 03:02:18,580 MORE GENERALLY, WHEN I THINK 5108 03:02:18,580 --> 03:02:21,483 ABOUT DEVELOPING A MODEL, I'M 5109 03:02:21,483 --> 03:02:23,818 DEVELOPING SOME NEW ONES RIGHT 5110 03:02:23,818 --> 03:02:28,356 NOW FOR HE COVIRUSES IN 5111 03:02:28,356 --> 03:02:29,824 CHILDREN, WHAT AM I WANTING TO 5112 03:02:29,824 --> 03:02:30,458 MODEL? 5113 03:02:30,458 --> 03:02:33,761 THE CLINICAL SIGNS IN THAT 5114 03:02:33,761 --> 03:02:34,929 POPULATION, YOUNG CHILDREN, AND 5115 03:02:34,929 --> 03:02:36,064 OFTENTIMES WE CAN'T MODEL IT, 5116 03:02:36,064 --> 03:02:38,132 BUT I SEE WHAT CAN WE PRODUCE, 5117 03:02:38,132 --> 03:02:39,434 WHAT CLINICAL SIGNS CAN WE 5118 03:02:39,434 --> 03:02:42,270 OBSERVE IN OUR MODEL IN THE 5119 03:02:42,270 --> 03:02:43,571 ANIMAL AS BEING OBSERVED IN THE 5120 03:02:43,571 --> 03:02:44,572 CLINIC, WITH THE IDEA OF COMING 5121 03:02:44,572 --> 03:02:45,773 UP WITH SOME KIND OF A METRIC, 5122 03:02:45,773 --> 03:02:47,108 BECAUSE I LIKE TO CALL IT A 5123 03:02:47,108 --> 03:02:48,343 PARAMETER THAT WE CAN EVALUATE 5124 03:02:48,343 --> 03:02:51,813 TO SEE IF THAT ANTIVIRAL DRUG IS 5125 03:02:51,813 --> 03:02:54,415 HELPING OR ALLEVIATING THAT 5126 03:02:54,415 --> 03:02:58,253 METRIC. 5127 03:02:58,253 --> 03:02:59,454 I FOUND GOOD POSITIVE CONTROL IS 5128 03:02:59,454 --> 03:02:59,888 SO IMPORTANT. 5129 03:02:59,888 --> 03:03:02,190 A FEW YEARS AGO WE DEVELOPED 5130 03:03:02,190 --> 03:03:03,925 ENTEROVIRUS MODELS FOR 5131 03:03:03,925 --> 03:03:05,460 ENTEROVIRUS 68 #, ENTEROVIRUS 5132 03:03:05,460 --> 03:03:06,127 71. 5133 03:03:06,127 --> 03:03:10,498 THE D68 WENT WELL, WE HAD A 5134 03:03:10,498 --> 03:03:11,699 GREAT POSITIVE CONTROL, WE WERE 5135 03:03:11,699 --> 03:03:14,669 HAPPY MOVING ON, JUST GO AHEAD, 5136 03:03:14,669 --> 03:03:15,870 WORK ON THE 71 MODEL. 5137 03:03:15,870 --> 03:03:17,939 GOT IT WAY DOWN THE LINE, NOW 5138 03:03:17,939 --> 03:03:20,341 STARTED WORKING LOOKING FOR 5139 03:03:20,341 --> 03:03:21,910 POSITIVE CONTROL, GOODNESS, 5140 03:03:21,910 --> 03:03:24,812 NOTHING WORKED. 5141 03:03:24,812 --> 03:03:26,848 SO I HAVE TO START LOOKING FOR 5142 03:03:26,848 --> 03:03:28,449 POSITIVE CONTROL VERY EARLY ON 5143 03:03:28,449 --> 03:03:30,084 BECAUSE IDENTIFYING THOSE 5144 03:03:30,084 --> 03:03:31,386 METRICS FOR EVALUATION, I CAN 5145 03:03:31,386 --> 03:03:32,720 SEE HOW THE POSITIVE CONTROL IS 5146 03:03:32,720 --> 03:03:34,122 WORKING IN THOSE CLINICAL 5147 03:03:34,122 --> 03:03:34,589 PARAMETERS. 5148 03:03:34,589 --> 03:03:36,958 IS IT REDUCING PARAMETERS IF 5149 03:03:36,958 --> 03:03:38,626 IT'S HIGH, IS IT INCREASING AND 5150 03:03:38,626 --> 03:03:40,895 IF IT'S LOW, IS IT A BENEFIT. 5151 03:03:40,895 --> 03:03:42,664 THANK YOU FOR THE INVITATION TO 5152 03:03:42,664 --> 03:03:43,197 COME AND TALK. 5153 03:03:43,197 --> 03:03:44,933 THIS IS SOMETHING I'VE BEEN 5154 03:03:44,933 --> 03:03:46,601 THINKING ABOUT, THIS MIDDLE 5155 03:03:46,601 --> 03:03:56,544 DIAMID LITLITTLEDIAGRAM, WHY H1, 5156 03:03:56,544 --> 03:03:56,978 SARS WAS DIFFERENT. 5157 03:03:56,978 --> 03:03:59,047 SO IT WAS KIND OF FUN TO PUT 5158 03:03:59,047 --> 03:03:59,514 THIS TOGETHER. 5159 03:03:59,514 --> 03:04:00,815 I'VE DRAWN THIS ON BOARDS, I'VE 5160 03:04:00,815 --> 03:04:02,250 NEVER ACTUALLY HAD IT IN A 5161 03:04:02,250 --> 03:04:02,750 POWERPOINT. 5162 03:04:02,750 --> 03:04:04,419 SO HERE WE HAVE AN INFECTION, 5163 03:04:04,419 --> 03:04:08,690 THIS IS FLU, DAY 3, DAY 6, IT'S 5164 03:04:08,690 --> 03:04:09,991 NOT EXACTLY PERFECT BUT IT'S 5165 03:04:09,991 --> 03:04:12,527 PRETTY CLOSE. 5166 03:04:12,527 --> 03:04:14,262 SO IF I DRAW A SECOND LINE, THIS 5167 03:04:14,262 --> 03:04:16,698 WOULD BE THE HISTOPATHOLOGY. 5168 03:04:16,698 --> 03:04:18,333 SO FIRST WE HAVE VIRUS TITERS 5169 03:04:18,333 --> 03:04:19,233 COMING UP. 5170 03:04:19,233 --> 03:04:25,873 THE VIRUS IS DEPI -- CYTOPATHIC 5171 03:04:25,873 --> 03:04:26,941 SPREAD WE'RE SEEING LESIONS IN 5172 03:04:26,941 --> 03:04:29,410 THE TISSUE, AS THE LESIONS IN 5173 03:04:29,410 --> 03:04:30,778 THE TISSUE COME UP, THEN WE 5174 03:04:30,778 --> 03:04:34,515 BEGIN TO SEE CLINICAL SIGNS. 5175 03:04:34,515 --> 03:04:37,118 AND JUST PARD3 MY MAKING A 5176 03:04:37,118 --> 03:04:38,653 COMPLEX VERY SIMPLE BUT IN MY 5177 03:04:38,653 --> 03:04:40,188 MIND I'M KIND OF SIMPLE, I'M 5178 03:04:40,188 --> 03:04:41,389 SEEING THESE THINGS COME UP AND 5179 03:04:41,389 --> 03:04:42,824 THEN THEY'RE GOING DOWN. 5180 03:04:42,824 --> 03:04:45,326 FIRST TITER GOES DOWN, HEALING 5181 03:04:45,326 --> 03:04:46,527 BEGINS, THE TISSUES ARE STARTING 5182 03:04:46,527 --> 03:04:47,528 TO HEAL. 5183 03:04:47,528 --> 03:04:48,796 CLINICAL SIGNS ARE THEN 5184 03:04:48,796 --> 03:04:50,798 FOLLOWING. 5185 03:04:50,798 --> 03:04:53,434 AND SO WE SEE THIS NICE PRETTY 5186 03:04:53,434 --> 03:04:57,138 PARALLEL LINES. 5187 03:04:57,138 --> 03:04:58,439 TIME TO MORBIDITY IS IMPORTANT 5188 03:04:58,439 --> 03:05:01,409 FOR A TREATMENT WINDOW, LOOKING 5189 03:05:01,409 --> 03:05:02,944 AT ANTIVIRAL DRUGS. 5190 03:05:02,944 --> 03:05:04,679 AGAIN, WE WILL HAVE A SPONSOR 5191 03:05:04,679 --> 03:05:07,348 COME AND THIS IS QUITE ROUTINE, 5192 03:05:07,348 --> 03:05:09,951 I WANT TO DOSE MICE TWICE A DAY 5193 03:05:09,951 --> 03:05:10,918 FOR 10 DAYS. 5194 03:05:10,918 --> 03:05:13,888 OKAY, LOOK AT MY TIMELINE HERE. 5195 03:05:13,888 --> 03:05:16,391 IF I'M DOSING CLEAR OUT HERE AT 5196 03:05:16,391 --> 03:05:17,825 10, I'LL PROBABLY START SEEING, 5197 03:05:17,825 --> 03:05:21,663 AGAIN, BASED UPON H1, H3, B, H5, 5198 03:05:21,663 --> 03:05:23,731 THAT TIME OF MORTALITY CAN SHIFT 5199 03:05:23,731 --> 03:05:25,933 A COUPLE DAYS, THEY'RE STILL 5200 03:05:25,933 --> 03:05:26,367 PRETTY CLOSE. 5201 03:05:26,367 --> 03:05:29,570 THEY'RE WANTING TO DOSE TO DAY 5202 03:05:29,570 --> 03:05:30,938 10 SOME OF THESE ANIMALS ARE 5203 03:05:30,938 --> 03:05:35,710 DYING. 5204 03:05:35,710 --> 03:05:36,444 BECAUSE THEY'RE ALREADY IN THE 5205 03:05:36,444 --> 03:05:38,446 PERIOD WHERE THERE'S SOME PRETTY 5206 03:05:38,446 --> 03:05:40,715 SEVERE CLINICAL SIGNS. 5207 03:05:40,715 --> 03:05:42,684 THIS TIME PERIOD BEFORE 5, I 5208 03:05:42,684 --> 03:05:46,087 WANT TO MAKE SURE TREATMENT IS 5209 03:05:46,087 --> 03:05:47,088 EXREETED BEFORE DAY 6. 5210 03:05:47,088 --> 03:05:50,358 I DON'T WANT TO HAVE A COFACTOR 5211 03:05:50,358 --> 03:05:52,894 OF THE SICKNESS OF THE ANIMAL 5212 03:05:52,894 --> 03:05:54,195 BEING INTERFERED WITH BY THE 5213 03:05:54,195 --> 03:05:56,297 DOSING OF THE DRUG. 5214 03:05:56,297 --> 03:05:57,498 SO I'LL COME BACK TO THAT IN 5215 03:05:57,498 --> 03:05:58,700 JUST A FEW MINUTES HERE. 5216 03:05:58,700 --> 03:06:00,101 THAT'S KIND OF INTERESTING. 5217 03:06:00,101 --> 03:06:01,602 THIS IS A ROUTE OF THERAPEUTIC 5218 03:06:01,602 --> 03:06:01,969 ADMINISTRATION. 5219 03:06:01,969 --> 03:06:03,838 THIS IS A VERY COMPLEX SLIDE BUT 5220 03:06:03,838 --> 03:06:05,373 I'M GOING TO MAKE IT VERY 5221 03:06:05,373 --> 03:06:06,140 SIMPLE. 5222 03:06:06,140 --> 03:06:07,341 OF MICE AND MEN, MICE ARE NOT 5223 03:06:07,341 --> 03:06:13,347 MEN. 5224 03:06:13,347 --> 03:06:14,782 THIS IS A LICENSED DRUG USED IN 5225 03:06:14,782 --> 03:06:15,450 THE CLINIC. 5226 03:06:15,450 --> 03:06:17,819 IT'S ADMINISTERED BY NEBULIZER 5227 03:06:17,819 --> 03:06:20,588 TO PEOPLE BECAUSE THE 5228 03:06:20,588 --> 03:06:22,957 PHARMACODYNAMICS WERE NOT GOOD 5229 03:06:22,957 --> 03:06:24,292 ENOUGH BY ORAL ROUTE OR ANY 5230 03:06:24,292 --> 03:06:25,293 OTHER MEASUREMENT SO IT WOULD 5231 03:06:25,293 --> 03:06:26,561 HAVE TO BE ADMINISTERED BY 5232 03:06:26,561 --> 03:06:27,128 NEBULIZER TO PEOPLE. 5233 03:06:27,128 --> 03:06:29,097 THIS IS SHOWING YOU MICE ARE NOT 5234 03:06:29,097 --> 03:06:29,964 MEN. 5235 03:06:29,964 --> 03:06:33,901 SO THIS NOW LOOKING SANAMOVIR, 5236 03:06:33,901 --> 03:06:34,802 10 MILLIGRAMS PER KILOGRAM PER 5237 03:06:34,802 --> 03:06:38,072 DAY FOR FIVE DAYS DOWN TO THREE, 5238 03:06:38,072 --> 03:06:41,909 1.3, THESE ARE THE DOSE RANGES, 5239 03:06:41,909 --> 03:06:45,713 INTRAPERITONEAL, INTRAMUSCULAR, 5240 03:06:45,713 --> 03:06:48,916 BY ORAL, AND WHICH MIMICS 5241 03:06:48,916 --> 03:06:49,217 NEBULIZER. 5242 03:06:49,217 --> 03:06:51,319 YOU CAN SEE THESE ARE ALL PRETTY 5243 03:06:51,319 --> 03:06:52,854 POTENT REGARDLESS OF THEIR ROUTE 5244 03:06:52,854 --> 03:06:55,223 OF ADMINISTRATION. 5245 03:06:55,223 --> 03:06:57,425 THIS IS NOT OBSERVED IN HUMANS. 5246 03:06:57,425 --> 03:06:59,460 SO I'LL HAVE SOMEONE COME TO ME 5247 03:06:59,460 --> 03:07:01,262 AND SAY WE WANT TO GO FOR NEB 5248 03:07:01,262 --> 03:07:02,997 LASER ROUTE, CAN YOU DO THAT? 5249 03:07:02,997 --> 03:07:06,734 I'LL SAY WE CAN, BUT IN A MOUSE, 5250 03:07:06,734 --> 03:07:07,969 WE CAN LOOK AT A DIFFERENT ROUTE 5251 03:07:07,969 --> 03:07:09,570 AND SEE IF IT'S GOING TO WORK. 5252 03:07:09,570 --> 03:07:11,539 AND I'LL COME BACK TO THAT IN A 5253 03:07:11,539 --> 03:07:12,206 MINUTE. 5254 03:07:12,206 --> 03:07:13,074 ANOTHER POINT HERE KIND OF 5255 03:07:13,074 --> 03:07:14,142 INTERESTING, SO IF YOU LOOK UP 5256 03:07:14,142 --> 03:07:17,445 HERE AT THIS HIGH DOSE, 10 MG 5257 03:07:17,445 --> 03:07:21,082 DOSE, THEY'RE 11 MOUSE OF EACH 5258 03:07:21,082 --> 03:07:22,817 OTHER ON A DIFFERENT ROUTE. 5259 03:07:22,817 --> 03:07:25,119 WHAT I FOUND, WHAT ALL OF US 5260 03:07:25,119 --> 03:07:27,288 HAVE FOUND OVER AND OVER, I 5261 03:07:27,288 --> 03:07:28,589 CONTEND TWO GROUPS OF MICE, 5262 03:07:28,589 --> 03:07:29,590 ORDERED THEM AT THE SAME TIME, 5263 03:07:29,590 --> 03:07:32,760 ARRIVED THE SAME TIME, I STARTED 5264 03:07:32,760 --> 03:07:34,495 ON TWO DIFFERENT DAYS, SAME 5265 03:07:34,495 --> 03:07:35,563 TECHNICIANS, SAME TECHNIQUE, 5266 03:07:35,563 --> 03:07:37,265 SAME DRUG, SAME VIRUS, AND THERE 5267 03:07:37,265 --> 03:07:38,766 CAN BE ONE MOUSE DIFFERENCE IN 5268 03:07:38,766 --> 03:07:40,635 THE GROUP OF 10 BETWEEN THOSE 5269 03:07:40,635 --> 03:07:47,308 TWO STUDIES. 5270 03:07:47,308 --> 03:07:49,043 SO THIS IS PRETTY GOOD HERE. 5271 03:07:49,043 --> 03:07:50,912 NOW IF WE GO DOWN TO THREE, 5272 03:07:50,912 --> 03:07:52,446 HOPEFULLY YOU CAN SEE THIS, THE 5273 03:07:52,446 --> 03:07:54,515 BLUE HIGHLIGHT, EFFICACY REALLY 5274 03:07:54,515 --> 03:07:57,151 DROPPED, AND NOT ONLY DOES THE 5275 03:07:57,151 --> 03:07:58,686 EFFICACY DROP, VARIABILITY IS 5276 03:07:58,686 --> 03:08:01,088 INCREASING. 5277 03:08:01,088 --> 03:08:03,157 IT'S FROM HAVING A SINGLE MOUSE, 5278 03:08:03,157 --> 03:08:04,025 NOW THERE'S TWO MICE. 5279 03:08:04,025 --> 03:08:06,460 IF I DROP AGAIN, NOW I'M DOWN TO 5280 03:08:06,460 --> 03:08:09,397 30% VARIABILITY. 5281 03:08:09,397 --> 03:08:10,598 I'VE NOT PUBLISHED THIS BUT THIS 5282 03:08:10,598 --> 03:08:12,033 IS SOMETHING I'VE FOUND FROM 5283 03:08:12,033 --> 03:08:13,801 MANY, MANY ANTIVIRAL STUDIES, I 5284 03:08:13,801 --> 03:08:19,807 SEE AIN CRE AN INCREASE IN VARIY 5285 03:08:19,807 --> 03:08:21,375 AT THE LOWER LEVEL OF ANTIVIRAL 5286 03:08:21,375 --> 03:08:21,909 EFFICACY. 5287 03:08:21,909 --> 03:08:23,945 IT DOESN'T MEAN THE DOSE. 5288 03:08:23,945 --> 03:08:24,812 SPONSOR COMES TO US, THEY HAVE 5289 03:08:24,812 --> 03:08:26,047 THE DRUG, VERY FIRST THING WE 5290 03:08:26,047 --> 03:08:28,316 DO, WE DO WHAT WE CALL A MAXIMUM 5291 03:08:28,316 --> 03:08:29,417 TOLERATED DOSE STUDY. 5292 03:08:29,417 --> 03:08:30,518 WE EVALUATE THE DOSE RANGE OF 5293 03:08:30,518 --> 03:08:32,453 THAT DRUG, NO VIRUS CHALLENGE, 5294 03:08:32,453 --> 03:08:35,323 WE LOOK FOR WEIGHT LOSS, 5295 03:08:35,323 --> 03:08:35,890 SEIZURE, TOXICITY. 5296 03:08:35,890 --> 03:08:37,625 I CAN GO WITH THE VERY HIGHEST 5297 03:08:37,625 --> 03:08:41,562 DOSE OF DRUG AND SEE VERY HIGH 5298 03:08:41,562 --> 03:08:42,563 VARIABILITY, AND THAT SUGGESTS 5299 03:08:42,563 --> 03:08:44,398 TO ME THAT THAT DRUG IS PROBABLY 5300 03:08:44,398 --> 03:08:47,802 AT ITS LOWEST LIMIT. 5301 03:08:47,802 --> 03:08:50,538 SO AGAIN THIS WAS KIND OF 5302 03:08:50,538 --> 03:08:55,209 INTERESTING. 5303 03:08:55,209 --> 03:08:57,545 THIS WAS A 5-DAY TREATMENT. 5304 03:08:57,545 --> 03:08:58,980 WE FOUND THAT WE WERE USING -- I 5305 03:08:58,980 --> 03:09:02,683 MUST HAVE STARTED LATE. 5306 03:09:02,683 --> 03:09:04,752 WE FOUND THAT THE INTRANASAL 5307 03:09:04,752 --> 03:09:06,387 SALINE TREATMENT OR INTRANASAL 5308 03:09:06,387 --> 03:09:08,789 ADMINISTRATION OF THE DRUG 5309 03:09:08,789 --> 03:09:11,392 EXACERBATED THE INFECTION. 5310 03:09:11,392 --> 03:09:12,960 SO WE WENT BACK AND EVALUATED 5311 03:09:12,960 --> 03:09:13,961 THIS. 5312 03:09:13,961 --> 03:09:16,230 HERE'S CALIFORNIA, HERE'S THE 5313 03:09:16,230 --> 03:09:18,332 PANDEMIC H1, HERE'S ACTUALLY A 5314 03:09:18,332 --> 03:09:20,501 RESISTANT H1, HERE'S A 5315 03:09:20,501 --> 03:09:22,570 HISTORICAL H1, KIND OF LIKE THE 5316 03:09:22,570 --> 03:09:23,971 PR8. 5317 03:09:23,971 --> 03:09:27,508 HERE'S VICTORIA H3N2, H5N1 LOW 5318 03:09:27,508 --> 03:09:28,709 PATH, AND THESE ARE NOW LOOKING 5319 03:09:28,709 --> 03:09:33,080 AT THE INTRANASALLY TREATED, AND 5320 03:09:33,080 --> 03:09:33,514 THE UNTREATED MICE. 5321 03:09:33,514 --> 03:09:35,149 I WANT TO PICK OUT THIS ONE IS 5322 03:09:35,149 --> 03:09:37,318 THE HIGHEST HERE. 5323 03:09:37,318 --> 03:09:40,288 THE MLD50 FOR THE TREATED MICE, 5324 03:09:40,288 --> 03:09:43,758 TREAT DADELY FOR FIVE DAYS, 1.5. 5325 03:09:43,758 --> 03:09:44,325 4.5 FOR UNTREATED. 5326 03:09:44,325 --> 03:09:46,227 AND AGAIN, THIS IS NOT A 5327 03:09:46,227 --> 03:09:47,728 THREE-FOLD INCREASE IN VIRUS. 5328 03:09:47,728 --> 03:09:49,363 THIS IS A THOUSAND FOLD INCREASE 5329 03:09:49,363 --> 03:09:52,466 IN VIRUS. 5330 03:09:52,466 --> 03:09:53,868 UP HERE YOU CAN SEE THAT LOW 5331 03:09:53,868 --> 03:09:58,005 DOSE VIRUS WITHOUT INTRANASAL 5332 03:09:58,005 --> 03:10:00,074 TREATMENT OF LIQUID, THEN WE ADD 5333 03:10:00,074 --> 03:10:01,709 THE SALINE TO IT, WE CAN SEE 5334 03:10:01,709 --> 03:10:03,945 THAT THAT LOW DOSE CHALLENGE IS 5335 03:10:03,945 --> 03:10:05,680 BEHAVING JUST LIKE A HIGHER 5336 03:10:05,680 --> 03:10:13,454 CONCENTRATION OF VIRUS. 5337 03:10:13,454 --> 03:10:15,289 I'M WAY OUT OF TIME, I'M SORRY. 5338 03:10:15,289 --> 03:10:19,660 THIS IS A COMBINATION DRUG STU 5339 03:10:19,660 --> 03:10:19,860 STUDY. 5340 03:10:19,860 --> 03:10:23,297 WE HAD STANDING ORDERS FOR 350 5341 03:10:23,297 --> 03:10:24,932 MICE PER WEEK AND WE WERE STILL 5342 03:10:24,932 --> 03:10:25,800 ORDERING MORE MICE. 5343 03:10:25,800 --> 03:10:27,868 THIS IS 28 GROUPS OF 10 MICE 5344 03:10:27,868 --> 03:10:30,271 EACH LOOKING AT A COMBINATION 5345 03:10:30,271 --> 03:10:31,839 DRUG STUDY. 5346 03:10:31,839 --> 03:10:33,774 WE WERE SEEING IF THERE WAS 5347 03:10:33,774 --> 03:10:34,875 SYNERGY BETWEEN TWO DRUGS IF 5348 03:10:34,875 --> 03:10:36,077 THEY COULD BE ADDED TOGETHER. 5349 03:10:36,077 --> 03:10:37,611 SO WE'RE ADDING SUBOPTIMAL 5350 03:10:37,611 --> 03:10:41,115 DOSES, THIS IS USING A SYNERGY 5351 03:10:41,115 --> 03:10:44,585 SOFTWARE DEVELOPED BY PRITCHARD 5352 03:10:44,585 --> 03:10:47,121 AND CHIPMAN AND THE DRUG-DRUG 5353 03:10:47,121 --> 03:10:49,657 INTERACTION THAT HAD BEEN REALLY 5354 03:10:49,657 --> 03:10:51,158 MODELED IN A GROUP AT SAINT 5355 03:10:51,158 --> 03:10:53,995 JUDE'S WHERE LESS THAN 25% IS 5356 03:10:53,995 --> 03:10:55,529 INSIGNIFICANT SYNERGY 5357 03:10:55,529 --> 03:10:57,932 ANTAGONISM, 25 TO 50 IS MINOR 5358 03:10:57,932 --> 03:10:59,800 SYNERGY, 50 TO 100 MODERATE, 5359 03:10:59,800 --> 03:11:00,568 STRONG SYNERGY. 5360 03:11:00,568 --> 03:11:03,304 THIS ACTUALLY IS MEASURING AREA 5361 03:11:03,304 --> 03:11:05,606 UNDER A CURVE DRUG DOSING 5362 03:11:05,606 --> 03:11:10,011 SHOWING DRUG-DRUG INTERACTIONS. 5363 03:11:10,011 --> 03:11:11,278 WHAT I'M GETTING TO, THIS IS A 5364 03:11:11,278 --> 03:11:12,947 CONCERN I HAVE IN THE FIELD OF 5365 03:11:12,947 --> 03:11:14,048 INFLUENZA. 5366 03:11:14,048 --> 03:11:16,384 THAT WE WILL SEE IN A PUBLISHED 5367 03:11:16,384 --> 03:11:18,185 WORK SOMEONE IS USING C57 BLACK 5368 03:11:18,185 --> 03:11:20,154 AND THEY'RE USING PR8 AND 5369 03:11:20,154 --> 03:11:21,355 THEY'RE TELLING YOU THEIR 5370 03:11:21,355 --> 03:11:22,556 MORTALITY BUT THEY'VE NOT TOLD 5371 03:11:22,556 --> 03:11:26,827 ME THEIR WEIGHT LOSS CUTOFF. 5372 03:11:26,827 --> 03:11:30,531 SOMEONE ELSE IS LOOKING AT 5373 03:11:30,531 --> 03:11:32,199 H3N2 BALB C AND USING A 5374 03:11:32,199 --> 03:11:33,267 DIFFERENT WEIGHT LOSS CUTOFF OR 5375 03:11:33,267 --> 03:11:35,469 DIFFERENT MORTALITY, HOW DO WE 5376 03:11:35,469 --> 03:11:36,804 COMPARE THESE THINGS? 5377 03:11:36,804 --> 03:11:38,305 IT'S SHOWING THE ROBUSTNESS IN 5378 03:11:38,305 --> 03:11:41,809 THE FIELD THAT THEY'RE WORKING, 5379 03:11:41,809 --> 03:11:43,778 BUT HOW DO WE COMPARE THEM? 5380 03:11:43,778 --> 03:11:45,379 THIS STUDY WAS DONE, THIS WAS 5381 03:11:45,379 --> 03:11:51,118 TRUE MORTALITY, AND WE FIND -- 5382 03:11:51,118 --> 03:11:52,853 THEY HAVE THE SAME MECHANISM OF 5383 03:11:52,853 --> 03:11:54,922 ACTION SO I WOULD KIND OF EXPECT 5384 03:11:54,922 --> 03:11:56,924 MINOR ANTAGONISM OR MINOR 5385 03:11:56,924 --> 03:12:03,230 SYNERGY AND FOR TRUE 5386 03:12:03,230 --> 03:12:04,899 MORTALITIES, MINOR ANTAGONISM. 5387 03:12:04,899 --> 03:12:07,368 THAT SAME SET OF WEIGHTS, WE'VE 5388 03:12:07,368 --> 03:12:10,104 NOW TAKEN UNDER 20%, 25%, 30% 5389 03:12:10,104 --> 03:12:13,307 WEIGHT LOSS, AND LOOK AT THE 5390 03:12:13,307 --> 03:12:14,608 DIFFERENCE. 5391 03:12:14,608 --> 03:12:18,879 AT 20% IS INSIGNIFICANT SYNERGY, 5392 03:12:18,879 --> 03:12:20,481 25% MODERN ANTAGONISM, 30% 5393 03:12:20,481 --> 03:12:23,951 WEIGHT LOSS, STRONG SYNERGY. 5394 03:12:23,951 --> 03:12:25,152 THIS IS A CONCERN TO ME, THAT 5395 03:12:25,152 --> 03:12:26,253 BASED UPON OUR WEIGHT LOSS, 5396 03:12:26,253 --> 03:12:29,857 WE'RE SEEING DIFFERENT EFFECTS. 5397 03:12:29,857 --> 03:12:33,694 TO ME, THAT'S A HUGE CONCERN. 5398 03:12:33,694 --> 03:12:42,303 AND I'M WAY OVER TIME. 5399 03:12:42,303 --> 03:12:44,171 SURE. 5400 03:12:44,171 --> 03:12:45,906 CAN I SHOW ONE MORE SLIDE? 5401 03:12:45,906 --> 03:12:48,542 IT'S THE CLINCHER. 5402 03:12:48,542 --> 03:12:52,813 OKAY? 5403 03:12:52,813 --> 03:12:54,014 I THOUGHT THIS WAS GOING TO BE 5404 03:12:54,014 --> 03:12:54,748 REALLY QUICK. 5405 03:12:54,748 --> 03:12:55,983 OKAY. 5406 03:12:55,983 --> 03:13:00,588 SO I SHOW YOU THIS GRAPH OF 5407 03:13:00,588 --> 03:13:06,260 INFLUENZA, HISTO COMES UP, WHAT 5408 03:13:06,260 --> 03:13:09,263 WAS ASTONISHING TO ME WAS IN 5409 03:13:09,263 --> 03:13:11,632 THESE HAMSTERS, TITERS GO UP, 5410 03:13:11,632 --> 03:13:15,436 THEY COME DOWN, CLINICAL SIGNS 5411 03:13:15,436 --> 03:13:16,237 CONTINUED, HISTOPATHOLOGY 5412 03:13:16,237 --> 03:13:17,238 CONTINUED. 5413 03:13:17,238 --> 03:13:21,375 I HAVE NEVER SEEN THIS BEFORE. 5414 03:13:21,375 --> 03:13:23,978 I'VE WORKED ON 30 DIFFERENT 5415 03:13:23,978 --> 03:13:24,879 VIRUSES, 15 DIFFERENT MODELS. 5416 03:13:24,879 --> 03:13:26,180 THIS WAS ASTONISHING TO ME. 5417 03:13:26,180 --> 03:13:28,449 THE VIRUS WAS DOWN, IS VIRUS 5418 03:13:28,449 --> 03:13:30,217 STILL THERE, IS IT PERSISTENT, 5419 03:13:30,217 --> 03:13:31,952 IS IT CHRONIC? 5420 03:13:31,952 --> 03:13:34,922 IS THERE SOMETHING -- KIND OF AN 5421 03:13:34,922 --> 03:13:36,090 OBSERVATION HYPOTHESIS, IS THE 5422 03:13:36,090 --> 03:13:39,527 VIRUS ACTUALLY LEADING TO A DOWN 5423 03:13:39,527 --> 03:13:40,928 REGULATION OF GENES THAT ARE 5424 03:13:40,928 --> 03:13:41,829 ALLOWING HEALING TO OCCUR? 5425 03:13:41,829 --> 03:13:43,030 A LOT OF THINGS GOING ON. 5426 03:13:43,030 --> 03:13:43,998 I THOUGHT THAT WAS KIND OF 5427 03:13:43,998 --> 03:13:46,400 INTERESTING. 5428 03:13:46,400 --> 03:13:47,168 OKAY. 5429 03:13:47,168 --> 03:13:50,337 SORRY. 5430 03:13:50,337 --> 03:13:54,675 [APPLAUSE] 5431 03:13:54,675 --> 03:13:57,344 >> I TOTALLY APPRECIATE -- ANY 5432 03:13:57,344 --> 03:13:59,246 ONE BURNING QUESTION BEFORE WE 5433 03:13:59,246 --> 03:14:00,114 MAYBE SAVE THE DISCUSSION FOR 5434 03:14:00,114 --> 03:14:04,852 THE PANEL M TIME? 5435 03:14:04,852 --> 03:14:05,686 ALL RIGHT. 5436 03:14:05,686 --> 03:14:06,487 WE'LL DEFINITELY COME BACK TO 5437 03:14:06,487 --> 03:14:06,654 YOU. 5438 03:14:06,654 --> 03:14:17,097 THANK YOU SO MUCH OUR NEXT 5439 03:14:23,938 --> 03:14:25,272 SPEAKER IS ZONDA WANG. 5440 03:14:25,272 --> 03:14:28,175 >> HELLO, EVERYONE. 5441 03:14:28,175 --> 03:14:30,978 I'M VERY HAPPY TO BE HERE, 5442 03:14:30,978 --> 03:14:38,285 BECAUSE I'M NEW BIOLOGIST BUT -- 5443 03:14:38,285 --> 03:14:40,721 TODAY I'M GOING TO SHARE WITH 5444 03:14:40,721 --> 03:14:43,991 YOU OUR EFFORT IN DEVELOPING 5445 03:14:43,991 --> 03:14:50,231 UNCONVENTIONAL ANIMAL MODELS, 5446 03:14:50,231 --> 03:14:51,665 UNCONVENTIONAL SPECIES MODELS. 5447 03:14:51,665 --> 03:14:53,234 THE DEFINITION OF UNCONVENTIONAL 5448 03:14:53,234 --> 03:14:54,935 IS VERY LOOSE. 5449 03:14:54,935 --> 03:14:59,206 BASICALLY FOR ME, IT CAN MEAN 5450 03:14:59,206 --> 03:15:03,611 ANYTHING NOT THE -- MOUSE OR 5451 03:15:03,611 --> 03:15:08,415 RAT, BUT STACEY GAVE ME A VERY 5452 03:15:08,415 --> 03:15:12,553 GOOD DEFINITION, FANCY MODEL, SO 5453 03:15:12,553 --> 03:15:13,954 I'LL USE THAT FANCY MODEL FROM 5454 03:15:13,954 --> 03:15:15,489 NOW ON. 5455 03:15:15,489 --> 03:15:18,792 SO MY EXPERTISE IS IN -- AS I 5456 03:15:18,792 --> 03:15:21,095 SAID I'M NOT AWARE OF IT, SO MY 5457 03:15:21,095 --> 03:15:24,798 EXPERTISE IS SO SPECIALIZED THAT 5458 03:15:24,798 --> 03:15:28,535 THAT -- ON THE ANIMAL GENOME IS 5459 03:15:28,535 --> 03:15:30,471 THE ONLY THING I KNOW, NOTHING 5460 03:15:30,471 --> 03:15:30,804 ELSE. 5461 03:15:30,804 --> 03:15:34,441 SO I COLLABORATE WITH -- FIRST I 5462 03:15:34,441 --> 03:15:35,409 THANK -- I DON'T KNOW WHY IT'S 5463 03:15:35,409 --> 03:15:42,983 NOT GOING FORWARD. 5464 03:15:42,983 --> 03:15:44,718 SO I HAVE A LOT OF PEOPLE TO 5465 03:15:44,718 --> 03:15:48,689 THANK BUT THESE ARE SOME OF TH 5466 03:15:48,689 --> 03:15:49,556 THEM. 5467 03:15:49,556 --> 03:15:50,724 INSTEAD OF READING THEIR NIAMS, 5468 03:15:50,724 --> 03:15:55,429 I WOULD LIKE YOU TO SEE BILL 5469 03:15:55,429 --> 03:15:57,398 WOLD AND -- AMONG THE FIRST TO 5470 03:15:57,398 --> 03:16:01,035 USE THE -- MODEL AND MANY 5471 03:16:01,035 --> 03:16:02,369 VIROLOGISTS REACHED OUT TO ME OR 5472 03:16:02,369 --> 03:16:04,071 I REACHED OUT TO THEM TO 5473 03:16:04,071 --> 03:16:05,406 COLLABORATE, AND SOME OF THEM 5474 03:16:05,406 --> 03:16:08,575 ARE IN THE AUDIENCE. 5475 03:16:08,575 --> 03:16:11,745 MY GOOD FRIEND, AND PETER AND 5476 03:16:11,745 --> 03:16:12,846 RYAN. 5477 03:16:12,846 --> 03:16:16,483 SO FUNNY THING IS THAT THIS 5478 03:16:16,483 --> 03:16:17,451 ISN'T MY FIRST TIME TO MEET 5479 03:16:17,451 --> 03:16:17,651 THEM. 5480 03:16:17,651 --> 03:16:19,286 WE HAVE BEEN COLLABORATING, HAVE 5481 03:16:19,286 --> 03:16:23,324 WORKED TOGETHER, PUBLISHED 5482 03:16:23,324 --> 03:16:25,526 TOGETHER FOR TIMES, BUT OF 5483 03:16:25,526 --> 03:16:26,694 COURSE BART IS MY COLLEAGUE, 5484 03:16:26,694 --> 03:16:27,494 I'VE MET HIM BEFORE. 5485 03:16:27,494 --> 03:16:30,331 SO THE PEOPLE ON THIS PANEL ARE 5486 03:16:30,331 --> 03:16:37,037 ONES THAT WORK WITH ME ON -- 5487 03:16:37,037 --> 03:16:38,906 HAMSTER MODELS AND THEN I 5488 03:16:38,906 --> 03:16:41,842 STARTED WORK WITH TWO 5489 03:16:41,842 --> 03:16:50,017 INDIVIDUAL, ALISTAIR MCGREGOR 5490 03:16:50,017 --> 03:16:54,955 AND DR. ANICE LOWEN, AND 5491 03:16:54,955 --> 03:16:59,126 RECENTLY WE ESTABLISHED A COLONY 5492 03:16:59,126 --> 03:17:01,962 AND ACTUALLY WE CAN HANDLE -- 5493 03:17:01,962 --> 03:17:05,432 PRETTY WELL, THAT'S IT, NOT 5494 03:17:05,432 --> 03:17:08,836 TOO -- I WOULD LIKE TO 5495 03:17:08,836 --> 03:17:13,340 ESPECIALLY THANK STANLEY FOR 5496 03:17:13,340 --> 03:17:15,109 PROVIDING ME -- ABOUT 10 YEARS 5497 03:17:15,109 --> 03:17:24,485 AGO, SO THAT'S HOW WE MADE -- 5498 03:17:24,485 --> 03:17:27,521 AND STEFAN FROM HAWAII, I HAVE 5499 03:17:27,521 --> 03:17:29,523 NOT MET HIM YET BUT HE PROVIDED 5500 03:17:29,523 --> 03:17:30,824 THE PIGGY BACK VECTOR. 5501 03:17:30,824 --> 03:17:37,698 AND THEN TONY SCHOUNZ SENT ME 5502 03:17:37,698 --> 03:17:41,869 MORE THAN 100 DEER MICE SO THANK 5503 03:17:41,869 --> 03:17:46,473 THEM AND I HAVE A -- A LOT OF 5504 03:17:46,473 --> 03:17:48,609 MONEY AT THE BEGINNING FROM THE 5505 03:17:48,609 --> 03:17:52,579 UNIVERSITY OF UTAH SCIENCE -- 5506 03:17:52,579 --> 03:17:56,417 RESEARCH, THAT'S THE PROGRAM -- 5507 03:17:56,417 --> 03:18:02,322 MOST MODEL I DEVELOP THROUGH 5508 03:18:02,322 --> 03:18:04,091 THAT -- ALL RIGHT. 5509 03:18:04,091 --> 03:18:06,360 SO MICE, WE'RE GOOD, WE'RE 5510 03:18:06,360 --> 03:18:08,629 POWERFUL, AND WHY I'M INTERESTED 5511 03:18:08,629 --> 03:18:09,963 IN THE FANCY MODELS. 5512 03:18:09,963 --> 03:18:16,336 AND I THINK -- IN THIS CASE I 5513 03:18:16,336 --> 03:18:20,707 THINK FAN SATISFY -- I SAID THAT 5514 03:18:20,707 --> 03:18:22,342 YESTERDAY I HAVE A ZOO AND I 5515 03:18:22,342 --> 03:18:24,545 WILL SHOW YOU AT THE END OF MY 5516 03:18:24,545 --> 03:18:25,979 TALK, I WANT TO MAKE A LIST BUT 5517 03:18:25,979 --> 03:18:29,049 TODAY I JUST ONLY SHOW YOU THE 5518 03:18:29,049 --> 03:18:30,551 HAMSTER. 5519 03:18:30,551 --> 03:18:32,986 WE TALK ABOUT HAMSTER -- AND 5520 03:18:32,986 --> 03:18:34,054 DRAWBACKS AND SO FORTH. 5521 03:18:34,054 --> 03:18:38,525 I JUST WANTED TO MENTION A 5522 03:18:38,525 --> 03:18:41,829 FEW -- WE HAVE NOT TOUCHED. 5523 03:18:41,829 --> 03:18:45,132 FIRST THE HUMAN ADENOVIRUS, THE 5524 03:18:45,132 --> 03:18:47,301 HAMSTER IS THE ONLY RODENT FOUND 5525 03:18:47,301 --> 03:18:53,207 TO BE PERMISSIVE FOR HUMAN 5526 03:18:53,207 --> 03:18:54,741 SPECIES, THE PARENTAL STRAIN FOR 5527 03:18:54,741 --> 03:18:57,377 MOST OF THE VECTORS USED TODAY. 5528 03:18:57,377 --> 03:19:01,415 SO IF YOU WANT AN -- VIRUS TO 5529 03:19:01,415 --> 03:19:03,050 CURE CHILDREN, YOU NEED TO USE 5530 03:19:03,050 --> 03:19:04,351 HAMSTER AS MODEL. 5531 03:19:04,351 --> 03:19:10,724 AND IF YOU WANT TO HAVE A -- 5532 03:19:10,724 --> 03:19:13,760 COMPETENT -- VECTOR -- HAMSTER 5533 03:19:13,760 --> 03:19:15,729 MODEL, BECAUSE IN MOUSE, IT JUST 5534 03:19:15,729 --> 03:19:16,730 DO NOT REPLICATE. 5535 03:19:16,730 --> 03:19:20,901 AND ANOTHER VIRUS -- IT'S 5536 03:19:20,901 --> 03:19:24,404 CONSIDERED AS THE ONLY ANIMAL 5537 03:19:24,404 --> 03:19:28,542 MODEL THAT RESEMBLES THE 5538 03:19:28,542 --> 03:19:30,744 HANTAVIRUS PULMONARY SYNDROME, 5539 03:19:30,744 --> 03:19:32,179 ESTABLISHED AS A MODEL FOR 5540 03:19:32,179 --> 03:19:36,884 HORIZONTAL TRANSMISSION OF THE 5541 03:19:36,884 --> 03:19:38,619 AND VIRUS. 5542 03:19:38,619 --> 03:19:44,958 MY COLLEAGUE JOHN MORREY -- 5543 03:19:44,958 --> 03:19:46,727 COLORADO STATE, THEY USE HAMSTER 5544 03:19:46,727 --> 03:19:48,595 FOR YEARS FOR WEST NILE, YELLOW 5545 03:19:48,595 --> 03:19:54,501 FEVER, AND TH RECENTLY EQUINE -- 5546 03:19:54,501 --> 03:19:57,905 VIRUS, ZIKA -- IN THE HAMSTER. 5547 03:19:57,905 --> 03:20:00,941 THE LAST TWO VIRUS, WE TALK A 5548 03:20:00,941 --> 03:20:04,778 LOT, AND BASICALLY AMONG MANY 5549 03:20:04,778 --> 03:20:09,816 THINGS, HAMSTERS -- STRAIN OF 5550 03:20:09,816 --> 03:20:13,987 INFLUENZA AND ALSO TO FEW 5551 03:20:13,987 --> 03:20:18,559 STRAINS OF EVEN -- AND AMONG THE 5552 03:20:18,559 --> 03:20:20,427 GOOD FEATURES ABOUT USING THE 5553 03:20:20,427 --> 03:20:26,533 HAMSTER AS A MODEL FOR SARS 2, 5554 03:20:26,533 --> 03:20:29,069 WE ALREADY TALK A LOT BUT 5555 03:20:29,069 --> 03:20:34,074 BASICALLY WHAT I WANT -- HERE IS 5556 03:20:34,074 --> 03:20:39,680 THAT TWO -- HUMAN CONTACT -- 5557 03:20:39,680 --> 03:20:44,051 DISTANCE -- TRANSMISSION, 5558 03:20:44,051 --> 03:20:47,988 PETER -- BUT THE ORIGINAL 5559 03:20:47,988 --> 03:20:48,522 STRAIN -- ALL RIGHT. 5560 03:20:48,522 --> 03:20:51,592 I WOULD LIKE TO MENTION TWO 5561 03:20:51,592 --> 03:20:52,693 KNOWN INFECTIOUS DISEASE THAT 5562 03:20:52,693 --> 03:20:54,661 HAMSTERS HAVE BEEN USED VERY 5563 03:20:54,661 --> 03:20:55,295 READILY. 5564 03:20:55,295 --> 03:20:57,397 ONE IS METABOLIC SYNDROME, 5565 03:20:57,397 --> 03:20:59,700 ANOTHER IS CIRCADIAN RHYTHM 5566 03:20:59,700 --> 03:21:00,133 DISORDER. 5567 03:21:00,133 --> 03:21:01,935 THE REASON I MENTION THESE TWO 5568 03:21:01,935 --> 03:21:03,837 DISORDERS, BECAUSE THEY ARE 5569 03:21:03,837 --> 03:21:06,673 HIGHLY RELEVANT TO -- INFECTIONS 5570 03:21:06,673 --> 03:21:08,108 BECAUSE FOR EXAMPLE FOR THE 5571 03:21:08,108 --> 03:21:13,780 METABOLIC SYNDROME, AND HAMST 5572 03:21:13,780 --> 03:21:17,284 HAMSTERS -- METABOLISM MIMIC -- 5573 03:21:17,284 --> 03:21:19,486 AND FEW THINGS. 5574 03:21:19,486 --> 03:21:23,090 NUMBER ONE, CETP, CLS TROLL 5575 03:21:23,090 --> 03:21:24,291 ESTER TRANSFER PROTEIN, WHICH IS 5576 03:21:24,291 --> 03:21:29,663 VERY KEY, VERY IMPORTANT PROTEIN 5577 03:21:29,663 --> 03:21:31,531 IN -- HUMAN HAS IT, HAMSTER HAS 5578 03:21:31,531 --> 03:21:33,934 IT, BUT NO MICE AND NO RAT HAVE 5579 03:21:33,934 --> 03:21:34,368 IT. 5580 03:21:34,368 --> 03:21:42,242 SO TOTALLY DIFFERENT, AND ALSO 5581 03:21:42,242 --> 03:21:46,179 HEPA -- AND IN MOUSE IS A B-48. 5582 03:21:46,179 --> 03:21:51,218 SO IF YOU WANT TO USE -- WANT TO 5583 03:21:51,218 --> 03:21:55,155 STUDY METABOLIC SYNDROME AS A 5584 03:21:55,155 --> 03:21:57,457 CO-MORBIDITY IN VARIABLE 5585 03:21:57,457 --> 03:21:59,960 INFECTION I THINK IT COMES AS A 5586 03:21:59,960 --> 03:22:01,495 VERY GOOD MODEL. 5587 03:22:01,495 --> 03:22:03,030 CIRCADIAN RHYTHM DISORDER, 5588 03:22:03,030 --> 03:22:04,131 HAMSTERS ARE AMAZING. 5589 03:22:04,131 --> 03:22:06,400 THEY HAVE VERY PRECISE CIRCADIAN 5590 03:22:06,400 --> 03:22:06,733 RHYTHM. 5591 03:22:06,733 --> 03:22:14,641 IF YOU HAVE HAMSTER FEMALE TODAY 5592 03:22:14,641 --> 03:22:16,910 AS CIRCLE ONE, 400 DAYS LATER -- 5593 03:22:16,910 --> 03:22:18,645 THEY ONLY RESPOND TO LIGHT, THEY 5594 03:22:18,645 --> 03:22:20,747 DO NOT RESPOND TO HORMONE. 5595 03:22:20,747 --> 03:22:23,183 VERY STRAIGHT, VERY NICE. 5596 03:22:23,183 --> 03:22:27,854 AND THEN I LIST -- OF THE 100 5597 03:22:27,854 --> 03:22:36,930 TOP SETTING -- DRUGS -- AND THEN 5598 03:22:36,930 --> 03:22:40,200 ABOUT 58% OF DRUGS ONLY HAVE A 5599 03:22:40,200 --> 03:22:41,301 HALF-LIFE SIX HOURS. 5600 03:22:41,301 --> 03:22:42,969 SO THIS BEGS THE QUESTION 5601 03:22:42,969 --> 03:22:45,472 WHEN -- WHEN YOU TEST DRUGS AND 5602 03:22:45,472 --> 03:22:52,345 ANIMAL MODELS -- AND ALSO 5603 03:22:52,345 --> 03:22:53,680 TRANSMISSION I WAS THINKING THIS 5604 03:22:53,680 --> 03:22:58,051 MORNING, WILL TRANSMISSION OCCUR 5605 03:22:58,051 --> 03:23:01,221 DIFFERENTLY AT A DIFFERENT -- 5606 03:23:01,221 --> 03:23:05,492 SIR CADECIRCADIAN CYCLE. 5607 03:23:05,492 --> 03:23:07,461 SO NO ONE HAS STUDIED THIS YET. 5608 03:23:07,461 --> 03:23:09,429 ALL RIGHT. 5609 03:23:09,429 --> 03:23:12,933 FINALLY, FUN FACT ABOUT HAMSTER, 5610 03:23:12,933 --> 03:23:15,669 TO BE USED AS AN ANIMAL MODEL, 5611 03:23:15,669 --> 03:23:17,838 YOU LIKE IT A LOT. 5612 03:23:17,838 --> 03:23:19,306 NUMBER ONE, THEY HAVE THE 5613 03:23:19,306 --> 03:23:22,342 SHORTEST GESTATION AMONG ALL 5614 03:23:22,342 --> 03:23:25,078 THE -- MAMMALS, 16 DAYS, AND 5615 03:23:25,078 --> 03:23:27,380 LARGE -- SIZE. 5616 03:23:27,380 --> 03:23:33,620 18, 20 PUPS PER LITTER. 5617 03:23:33,620 --> 03:23:35,822 FEMALE HAS SOME DIFFICULT RESULT 5618 03:23:35,822 --> 03:23:37,224 OF THEM, AND THEN THEY'RE VERY 5619 03:23:37,224 --> 03:23:38,992 EASY TO HANDLE. 5620 03:23:38,992 --> 03:23:41,161 IN THE PAST, MORE THAN 10 YEARS, 5621 03:23:41,161 --> 03:23:47,901 I THINK ONLY TWO INCIDENTS GET 5622 03:23:47,901 --> 03:23:49,803 BITTEN BY A HAMSTER. 5623 03:23:49,803 --> 03:23:51,638 I DON'T KNOW WHAT THEY DO, I 5624 03:23:51,638 --> 03:23:53,206 KEEP TELLING THEM THAT THEY DO 5625 03:23:53,206 --> 03:23:55,275 NOT BITE, YOU BITE THEM, THEY DO 5626 03:23:55,275 --> 03:23:58,779 NOT BITE YOU. 5627 03:23:58,779 --> 03:24:00,213 ALL RIGHT. 5628 03:24:00,213 --> 03:24:01,414 ANOTHER REASON, I DON'T HAVE 5629 03:24:01,414 --> 03:24:04,985 TIME TO TALK IN DETAIL IS THAT 5630 03:24:04,985 --> 03:24:08,155 CERTAIN HUMAN SET OF HANDS 5631 03:24:08,155 --> 03:24:09,823 WORKING THE -- IN A MOUSE. 5632 03:24:09,823 --> 03:24:12,092 THE REASON I MENTION THAT IS 5633 03:24:12,092 --> 03:24:13,426 BECAUSE WE HAVE AN ONGOING 5634 03:24:13,426 --> 03:24:16,596 EFFORT TO HUMANIZE THE -- 5635 03:24:16,596 --> 03:24:17,030 SYSTEM. 5636 03:24:17,030 --> 03:24:19,766 WE KNOW THAT HUMANIZED MOUSE 5637 03:24:19,766 --> 03:24:21,868 MODEL REALLY NOT WORKING. 5638 03:24:21,868 --> 03:24:27,140 THERE ARE NO -- NO GERMINAL 5639 03:24:27,140 --> 03:24:28,308 CENTER FORMATION AND THEN 5640 03:24:28,308 --> 03:24:29,709 SCIENTISTS HAVE BEEN PUTTING SO 5641 03:24:29,709 --> 03:24:32,679 MANY HUMAN GENES INTO THAT 5642 03:24:32,679 --> 03:24:33,880 MOUSE, IT'S STILL NOT WORKING 5643 03:24:33,880 --> 03:24:35,448 WELL. 5644 03:24:35,448 --> 03:24:38,051 AND THEN THESE FEW OF THESE 5645 03:24:38,051 --> 03:24:40,253 GENES I LISTED HERE ARE AMONG 5646 03:24:40,253 --> 03:24:43,523 THE GENES WE HAVE BEEN -- 5647 03:24:43,523 --> 03:24:46,293 SCIENTISTS HAVE BEEN TRYING TO 5648 03:24:46,293 --> 03:24:52,599 KNOCK INTO THE MOUSE GENOME. 5649 03:24:52,599 --> 03:24:53,366 HAMSTER LITERALLY HAVE THEM. 5650 03:24:53,366 --> 03:24:53,800 ALL RIGHT. 5651 03:24:53,800 --> 03:24:56,236 SO THERE ARE MANY GOOD REASONS 5652 03:24:56,236 --> 03:24:58,071 TO -- HAMS SISTERS, BUT AT THAT 5653 03:24:58,071 --> 03:25:00,607 TIME, THERE ARE NO GENERAL 5654 03:25:00,607 --> 03:25:02,142 MODIFICATION TECHNIQUES 5655 03:25:02,142 --> 03:25:04,544 AVAILABLE. 5656 03:25:04,544 --> 03:25:08,481 SO FIRST BUSINESS FOR US IS TO 5657 03:25:08,481 --> 03:25:10,450 ESTABLISH -- TECHNIQUES AND 5658 03:25:10,450 --> 03:25:12,752 LUCKILY CRISPR CAME ALONG AND WE 5659 03:25:12,752 --> 03:25:14,254 QUICKLY JUMPED ON TO IT AND I 5660 03:25:14,254 --> 03:25:15,722 THINK ALL OF YOU HAVE HEARD A 5661 03:25:15,722 --> 03:25:17,691 LOT AND KNOW A LOT ABOUT CRISPR 5662 03:25:17,691 --> 03:25:20,293 BUT I JUST SIMPLY SAVED THAT. 5663 03:25:20,293 --> 03:25:25,899 YOU CA DESIGN -- TARGET ANY GENE 5664 03:25:25,899 --> 03:25:27,968 YOU WANT AND BRING THE CASE LINE 5665 03:25:27,968 --> 03:25:30,937 INTO THE GENERAL LOCUS, YOU WANT 5666 03:25:30,937 --> 03:25:39,813 TO TARGET WE WILL INTRODUCE -- 5667 03:25:39,813 --> 03:25:42,249 DNA BREAKS AND THE CELL WILL 5668 03:25:42,249 --> 03:25:44,184 NORMALLY USE -- JOINING TO 5669 03:25:44,184 --> 03:25:46,586 REPAIR THE GENOME WHICH IS 5670 03:25:46,586 --> 03:25:48,355 ERROR-PRONE SO INTRODUCE THE 5671 03:25:48,355 --> 03:25:52,659 INSERTION THE DELETIONS -- AND 5672 03:25:52,659 --> 03:26:03,203 IF YOU WANT TO KNOW -- -- AND -- 5673 03:26:04,938 --> 03:26:15,115 SO WHEN WE -- 5674 03:26:25,859 --> 03:26:27,327 >> SO AT THAT TIME WHEN WE 5675 03:26:27,327 --> 03:26:28,528 STARTED WITH HAMSTERS AND CRISPR 5676 03:26:28,528 --> 03:26:31,598 ONLY WAS DEMONSTRATED TO BE 5677 03:26:31,598 --> 03:26:33,667 WORKING IN HUMAN AND THE MOUSE 5678 03:26:33,667 --> 03:26:36,069 CELLS, NOT OTHER SPECIES. 5679 03:26:36,069 --> 03:26:39,139 SO WE WILL NO IDEA, NOBODY HAD 5680 03:26:39,139 --> 03:26:41,775 NO IDEA, AND HE SAID OH, YOU 5681 03:26:41,775 --> 03:26:42,776 WANT TO TRY IN HAMSTER? 5682 03:26:42,776 --> 03:26:44,844 I DONE KNOW, MAY WORK, MAY NOT. 5683 03:26:44,844 --> 03:26:48,915 SO WE JUST USE KIDNEY HAMSTER 5684 03:26:48,915 --> 03:26:53,820 CELLS AND WE DESIGNED MULTIP 5685 03:26:53,820 --> 03:26:57,257 MULTIPLE -- AND DIFFERENT 5686 03:26:57,257 --> 03:27:01,294 DOMAINS, AND OTHER GENES AND 5687 03:27:01,294 --> 03:27:04,364 THEN WE BASICALLY TRANSVECT THE 5688 03:27:04,364 --> 03:27:10,270 PLASMA CARRYING THE -- THE NK 5689 03:27:10,270 --> 03:27:13,540 CELLS AND THEN WE DID THE SO 5690 03:27:13,540 --> 03:27:14,541 CALLED -- TERM BUT BASICALLY 5691 03:27:14,541 --> 03:27:19,679 WHAT WE DID IS THAT IF GENE 5692 03:27:19,679 --> 03:27:23,283 TARGETING HAPPENED, IN THIS CASE 5693 03:27:23,283 --> 03:27:27,287 FOR EXAMPLE -- WILL BE ABOLISHED 5694 03:27:27,287 --> 03:27:29,122 SO IT WILL BE PARTIALLY 5695 03:27:29,122 --> 03:27:34,461 RESISTANT TO THE -- THIS IS -- 5696 03:27:34,461 --> 03:27:38,965 IN THIS CASE, YOU HAVE SOME DCH 5697 03:27:38,965 --> 03:27:41,601 RESISTANT, BASED ON THAT -- 5698 03:27:41,601 --> 03:27:42,936 EFFICIENCY, SO WE WERE VERY, 5699 03:27:42,936 --> 03:27:48,174 VERY EXCITED BUT THERE'S A HUGE 5700 03:27:48,174 --> 03:27:49,275 PROBLEM BECAUSE WORKING WITH 5701 03:27:49,275 --> 03:27:53,013 HAMSTER IS DIFFERENT FROM OTHER 5702 03:27:53,013 --> 03:27:54,314 SPECIES. 5703 03:27:54,314 --> 03:27:58,351 NUMBER ONE, HAMSTERS -- ARE 5704 03:27:58,351 --> 03:27:59,552 EXTREMELY SENSITIVE TO 5705 03:27:59,552 --> 03:28:01,488 ENVIRONMENT EXPOSURE, 5706 03:28:01,488 --> 03:28:02,989 PARTICULARLY TO LIGHT. 5707 03:28:02,989 --> 03:28:06,059 THIS LIGHT WILL KEEP HAMSTER 5708 03:28:06,059 --> 03:28:08,128 EMBRYOS LIKE FAMILY, THEY STOP 5709 03:28:08,128 --> 03:28:08,461 DEVELOPING. 5710 03:28:08,461 --> 03:28:09,362 IT'S CRAZY. 5711 03:28:09,362 --> 03:28:14,167 AND NO COMMERCIAL EMBRYO 5712 03:28:14,167 --> 03:28:19,539 CULTURAL MEDIA WORKS FOR HAMS 5713 03:28:19,539 --> 03:28:19,773 HAMSTER. 5714 03:28:19,773 --> 03:28:21,441 SHEEP, GOAT, MOUSE, EQUINE, YOU 5715 03:28:21,441 --> 03:28:23,143 NAME IT, NONE OF THE MEDIA WORK 5716 03:28:23,143 --> 03:28:25,445 FOR HAMSTER EMBRYOS. 5717 03:28:25,445 --> 03:28:29,182 AND THEN THERE ARE NO -- 5718 03:28:29,182 --> 03:28:30,717 INJECTION OR -- INJECTION 5719 03:28:30,717 --> 03:28:31,284 TECHNIQUE AVAILABLE. 5720 03:28:31,284 --> 03:28:33,787 BECAUSE WE NEED THESE TECHNIQUES 5721 03:28:33,787 --> 03:28:36,523 TO INTRODUCE CRISPR INTO HAMSTER 5722 03:28:36,523 --> 03:28:37,524 EMBRY YOES. 5723 03:28:37,524 --> 03:28:41,795 SO BIG CHALLENGE, BUT WE WORKED 5724 03:28:41,795 --> 03:28:45,432 ON IT AND THIS ONE TABLE 5725 03:28:45,432 --> 03:28:49,936 SUMMARIZES ABOUT ONE YEAR'S 5726 03:28:49,936 --> 03:28:52,305 EFFORT. 5727 03:28:52,305 --> 03:28:53,840 WE DID -- WHEN WE SHOULD COLLECT 5728 03:28:53,840 --> 03:28:58,778 THE EMBRY YOES, WHEN TO DO THE 5729 03:28:58,778 --> 03:29:00,980 INJECTION, HOW MUCH TIME WE CAN 5730 03:29:00,980 --> 03:29:06,653 KEEP ON THIS -- BY THE WAY WE 5731 03:29:06,653 --> 03:29:08,421 WERE -- HOW MUCH WE INJECT IS 5732 03:29:08,421 --> 03:29:11,257 VERY, VERY CHALLENGING, BUT WE 5733 03:29:11,257 --> 03:29:11,825 GOT IT DONE. 5734 03:29:11,825 --> 03:29:13,359 SO WE HAVE THE TECHNOLOGY 5735 03:29:13,359 --> 03:29:16,663 AVAILABLE AND THEN WE JUST 5736 03:29:16,663 --> 03:29:18,832 IMMEDIATELY APPLY TECHNOLOGY TO 5737 03:29:18,832 --> 03:29:20,366 HAMSTER EMBRYOS, AND THIS JUST 5738 03:29:20,366 --> 03:29:25,205 SHOWS YOU THAT ONE LITER OF THE 5739 03:29:25,205 --> 03:29:28,041 PUPS BORN AND THE YELLOW -- 5740 03:29:28,041 --> 03:29:31,311 INJECT EMBRY YOES, THE BLACK -- 5741 03:29:31,311 --> 03:29:34,714 MOTHER WHO ARE -- PRODUCED 5742 03:29:34,714 --> 03:29:38,451 BECAUSE HAMSTERS ARE TOO 5743 03:29:38,451 --> 03:29:39,686 SENSITIVE TO ANY MANIPULATION. 5744 03:29:39,686 --> 03:29:42,889 IF YOU USE A SO YOU DOUGH 5745 03:29:42,889 --> 03:29:45,525 PREGNANT FEMALES, WHEN YOU 5746 03:29:45,525 --> 03:29:47,794 CREATE EMBRY YOE WILL NOT BE 5747 03:29:47,794 --> 03:29:49,028 ABLE TO INITIATE PREGNANCY. 5748 03:29:49,028 --> 03:29:50,363 AT THAT TIME WE IMPROVED 5749 03:29:50,363 --> 03:29:55,702 CONDITION, NOW WE CAN USE A -- 5750 03:29:55,702 --> 03:29:56,903 SOME OF THE PREGNANT FEMALES. 5751 03:29:56,903 --> 03:29:58,571 SO I JUST WANT TO SHOW YOU, THIS 5752 03:29:58,571 --> 03:30:01,641 ONE LITTER AND THESE TWO PUPS, 5753 03:30:01,641 --> 03:30:10,083 C5, C6 -- WE KNOW THEY CARRY I 5754 03:30:10,083 --> 03:30:13,019 IN -- REMEMBER IT'S JULY 10TH, 5755 03:30:13,019 --> 03:30:16,623 2013, ONLY A FEW -- YOU KNOW, A 5756 03:30:16,623 --> 03:30:17,991 FEW MONTHS AFTER THE CRISPR WAS 5757 03:30:17,991 --> 03:30:18,625 REPORTED. 5758 03:30:18,625 --> 03:30:27,167 THEN WE USE C6 FEMALE BECAUSE OF 5759 03:30:27,167 --> 03:30:29,569 CARRIER -- WHICH GENERATE A 5760 03:30:29,569 --> 03:30:36,809 KNOCKOUT -- ALSO KNOCKOUT SO 5761 03:30:36,809 --> 03:30:39,879 THEN WE BRED FEMALE WITH -- WE 5762 03:30:39,879 --> 03:30:43,583 FOUND ALL THE ALLELES CARRIED 5763 03:30:43,583 --> 03:30:44,684 ALLELE -- GERMLINE, WERE GOOD, 5764 03:30:44,684 --> 03:30:48,087 AND THEN WE JUST USE A RATHER -- 5765 03:30:48,087 --> 03:30:49,522 SEPARATING THAT PRODUCE -- AND 5766 03:30:49,522 --> 03:30:53,593 THE COLOR HAS BEEN USED A LOT. 5767 03:30:53,593 --> 03:30:55,528 ALL RIGHT. 5768 03:30:55,528 --> 03:30:56,629 SO IN THE NEXT FEW SLIDES, I 5769 03:30:56,629 --> 03:30:58,932 JUST WANT TO SHOW YOU WHAT WE 5770 03:30:58,932 --> 03:30:59,933 CAN DO IN THE HAMSTER. 5771 03:30:59,933 --> 03:31:02,769 NOW I SHOW KNOCKOUT. 5772 03:31:02,769 --> 03:31:05,838 AS AN EXAMPLE, THIS EXAMPLE IS 5773 03:31:05,838 --> 03:31:09,242 THAT YOU'RE KNOCKING IN LARGE 5774 03:31:09,242 --> 03:31:11,544 PIECE OF DNA INTO THE JEA NOME. 5775 03:31:11,544 --> 03:31:17,817 IN THIS CASE LO LUCIFERASE, INTO 5776 03:31:17,817 --> 03:31:22,889 PEER -- WE JUST SAID -- IN 5777 03:31:22,889 --> 03:31:23,923 THE -- GENE RIGHT BEFORE THE 5778 03:31:23,923 --> 03:31:27,860 LAST STOP CODON, PEPTIDE -- AS 5779 03:31:27,860 --> 03:31:33,032 VIROLOGISTS YOU -- SO THE -- 5780 03:31:33,032 --> 03:31:34,801 2 GENE AND REPORTER GENE WILL BE 5781 03:31:34,801 --> 03:31:41,641 EXPRESSED AS A SINGLE MRA DND SO 5782 03:31:41,641 --> 03:31:45,011 ANY GENE OF INTEREST CAN BE 5783 03:31:45,011 --> 03:31:49,616 ALMOST ANY LOCI IN THE GENOME, 5784 03:31:49,616 --> 03:31:53,253 AND 2A PEP TAID OR ERRORS 5785 03:31:53,253 --> 03:31:54,554 SEQUENCE, CAN YOU MAKE THE TRANS 5786 03:31:54,554 --> 03:31:58,491 GENE AND TOTAL CONTROL OF THE -- 5787 03:31:58,491 --> 03:32:01,227 SEQUENCE. 5788 03:32:01,227 --> 03:32:03,730 SO WE MADE THIS AND WE MADE A 5789 03:32:03,730 --> 03:32:04,497 FEW OTHERS TOO. 5790 03:32:04,497 --> 03:32:08,234 IN A MOMENT I'M GOING TO SHOW 5791 03:32:08,234 --> 03:32:11,204 YOU -- HUMAN RECEPTOR INTO THE 5792 03:32:11,204 --> 03:32:11,437 HAMSTER. 5793 03:32:11,437 --> 03:32:13,906 AND THEN GENE EDITING, THERE WAS 5794 03:32:13,906 --> 03:32:17,343 A VERY FAMOUS TALL HAMSTER 5795 03:32:17,343 --> 03:32:18,978 DISCOVERED IN 1988. 5796 03:32:18,978 --> 03:32:21,314 ONE OF THE FIRST MAMMALIAN 5797 03:32:21,314 --> 03:32:24,150 MUTATION GENE MUTATION FOUND TO 5798 03:32:24,150 --> 03:32:29,622 BE INVOLVED IN CIRCADIAN RHYTHM. 5799 03:32:29,622 --> 03:32:30,757 VERY FAMOUS HAMSTER. 5800 03:32:30,757 --> 03:32:31,958 BUT WE LOST IT. 5801 03:32:31,958 --> 03:32:34,360 NOBODY COULD FIND IT. 5802 03:32:34,360 --> 03:32:39,499 SO THEN -- WE WORKED TOGETHER 5803 03:32:39,499 --> 03:32:45,772 AND SUBMITTED A PROPOSAL -- 5804 03:32:45,772 --> 03:32:46,339 REGENERATED. 5805 03:32:46,339 --> 03:32:48,941 SO GENE EDITING, AND THEN WE 5806 03:32:48,941 --> 03:32:52,779 ALSO USE PIGGY BACK -- TRANS 5807 03:32:52,779 --> 03:32:58,351 GENESIS AND PRODUCE THE HACE 2. 5808 03:32:58,351 --> 03:33:01,854 PIGGY BACK -- IT CAN INTEGRATE 5809 03:33:01,854 --> 03:33:06,492 THE TRANS GENE WITH A LARGE 5810 03:33:06,492 --> 03:33:08,861 SLICE, MUCH LARGER THAN THE 5811 03:33:08,861 --> 03:33:11,064 REGULAR KNOCKINS, AND IF YOU 5812 03:33:11,064 --> 03:33:12,165 DON'T LIKE THE TRANS GENE FOR 5813 03:33:12,165 --> 03:33:13,533 SOME REASON, YOU WANT TO TAKE IT 5814 03:33:13,533 --> 03:33:15,668 OUT LATER, YOU CAN TRANSPOSE TO 5815 03:33:15,668 --> 03:33:19,172 REMOVE IT AND LEAVING NO SCARS, 5816 03:33:19,172 --> 03:33:25,078 SO IT'S GREAT. 5817 03:33:25,078 --> 03:33:31,150 ANOTHER THING ABOUT PIGGYBAC, I 5818 03:33:31,150 --> 03:33:36,289 WAS USING -- IN THE EARLY YEA 5819 03:33:36,289 --> 03:33:37,390 YEARS, -- THROUGH LIKE A 5820 03:33:37,390 --> 03:33:38,558 CRASHING, YOU KNOW, WITHOUT 5821 03:33:38,558 --> 03:33:42,695 KNOWING HOW TO GET INTO IT. 5822 03:33:42,695 --> 03:33:44,864 MOST CASES THE TRANS GENE COULD 5823 03:33:44,864 --> 03:33:47,934 BE DISRUPTED, AND YOU ALSO -- 5824 03:33:47,934 --> 03:33:51,270 STANLEY SHOWED YOU HAVE THAT -- 5825 03:33:51,270 --> 03:33:53,973 EIGHT COPIES, AND WE HAVE EIGHT 5826 03:33:53,973 --> 03:33:56,909 COPIES SOMETIMES CAUSE GENOMIC 5827 03:33:56,909 --> 03:33:57,677 INSTABILITY. 5828 03:33:57,677 --> 03:34:00,780 SO IF WE BREATHE ANIMALS, SOME 5829 03:34:00,780 --> 03:34:08,121 ANIMAL MAY LOSE SOME -- SO CAL 5830 03:34:08,121 --> 03:34:12,191 CALLED EPIGENOMIC SILENCING, BUT 5831 03:34:12,191 --> 03:34:14,894 MAMMALIAN CELLS AND THEY WOULD 5832 03:34:14,894 --> 03:34:17,530 BE -- SILENCED, BUT THE PIG 5833 03:34:17,530 --> 03:34:19,298 PIGGYBAC HAS THE SO-CALLED 5834 03:34:19,298 --> 03:34:22,235 GENOMIC INSULATOR FOR WHEN THE 5835 03:34:22,235 --> 03:34:25,972 TRANS GENE FORM -- AND ALSO 5836 03:34:25,972 --> 03:34:29,809 PREVENTED THAT SO CALLED 5837 03:34:29,809 --> 03:34:33,880 POSITIONAL EECT, SO WE LIKE PIG 5838 03:34:33,880 --> 03:34:34,414 PIGGYBAC A LOT. 5839 03:34:34,414 --> 03:34:36,048 SO THESE TECHNIQUES, THESE 5840 03:34:36,048 --> 03:34:37,183 HAMSTER MODELS WE PRODUCE. 5841 03:34:37,183 --> 03:34:39,919 BUT THIS IS ONLY HALF OF THEM. 5842 03:34:39,919 --> 03:34:41,120 A LOT. 5843 03:34:41,120 --> 03:34:45,725 ALL RIGHT. 5844 03:34:45,725 --> 03:34:47,326 THEN I JUST WANT TO USE THREE OR 5845 03:34:47,326 --> 03:34:52,231 FOUR EXAMPLES TO SHOW THE USE 5846 03:34:52,231 --> 03:34:53,633 USEFULNESS OF THE ENGINEERED 5847 03:34:53,633 --> 03:34:55,501 HAMSTER MODELS. 5848 03:34:55,501 --> 03:34:57,703 THIS ONE WE USED FOR SARS 2 AND 5849 03:34:57,703 --> 03:34:59,672 1 INTERESTING THING IS THAT THIS 5850 03:34:59,672 --> 03:35:04,811 IS VERY DRAMATIC, WE COMPARE T 5851 03:35:04,811 --> 03:35:07,246 THE -- VERSUS WILD TYPE 5852 03:35:07,246 --> 03:35:09,449 HAMSTERS, THEY'RE VERY LOW, 5853 03:35:09,449 --> 03:35:12,618 THOUSAND TIMES IN THIS CASE 5854 03:35:12,618 --> 03:35:14,587 100,000 TIMES. 5855 03:35:14,587 --> 03:35:18,758 SO THIS TELLS YOU THAT STAT 2 IS 5856 03:35:18,758 --> 03:35:20,326 VERY IMPORTANT. 5857 03:35:20,326 --> 03:35:26,432 BUT SURPRISINGLY, IF YOU HAVE SO 5858 03:35:26,432 --> 03:35:27,967 MUCH -- HAMSTER, YOU DON'T HAVE 5859 03:35:27,967 --> 03:35:28,968 PATHOLOGY. 5860 03:35:28,968 --> 03:35:34,106 SO IT'S A DOUBLE EDGED SWORD. 5861 03:35:34,106 --> 03:35:36,742 -- BY -- BY THE WAY I SEND THE 5862 03:35:36,742 --> 03:35:39,512 HAMSTER ALL OVER THE WORLD. 5863 03:35:39,512 --> 03:35:44,550 BELGIUM AND OTHER COUNTRIES TOO. 5864 03:35:44,550 --> 03:35:50,690 SO ANOTHER EXAMPLE, THEY USED TO 5865 03:35:50,690 --> 03:35:54,193 USE -- AS IMMUNOSUPPRESSANT 5866 03:35:54,193 --> 03:35:56,162 WHICH IS -- SO THEY REACH OUT TO 5867 03:35:56,162 --> 03:36:00,700 ME ASKING WHETHER WE CAN -- AND 5868 03:36:00,700 --> 03:36:05,838 WE SEND THE RAG 2 HAMSTER -- AND 5869 03:36:05,838 --> 03:36:09,108 AT THAT TIME WE DID NOT HAVE THE 5870 03:36:09,108 --> 03:36:11,577 HACE2 HAMSTER YET. 5871 03:36:11,577 --> 03:36:14,981 -- MORE LETHAL BUT -- SO WE 5872 03:36:14,981 --> 03:36:16,482 DEVELOPED A DIFFERENT MODEL AND 5873 03:36:16,482 --> 03:36:18,718 ALSO I WOULD LIKE TO POINT OUT 5874 03:36:18,718 --> 03:36:23,956 THAT IT'S NOT HERE BUT THEY 5875 03:36:23,956 --> 03:36:29,996 FOUND NEURAL INFECTIONS, 5876 03:36:29,996 --> 03:36:30,897 CARDIOVASCULAR INFECTIONS AND AT 5877 03:36:30,897 --> 03:36:32,965 THAT TIME WE THOUGHT MAYBE IT'S 5878 03:36:32,965 --> 03:36:35,401 ARTIFACT BUT LATER ON WE'RE 5879 03:36:35,401 --> 03:36:39,238 REALIZING THAT A LOT OF PATIENTS 5880 03:36:39,238 --> 03:36:40,439 GOT -- INFECTIONS AND HEART 5881 03:36:40,439 --> 03:36:41,007 INFORECASTS. 5882 03:36:41,007 --> 03:36:45,478 PETER SHOWED THIS, THE -- 5883 03:36:45,478 --> 03:36:51,984 KNOCKOUT HAMSTER ABSENT OF NKK 5884 03:36:51,984 --> 03:36:54,287 CELLS AND B CELLS T CELLS 5885 03:36:54,287 --> 03:36:55,121 COMPROMISE. 5886 03:36:55,121 --> 03:36:57,490 THEY BEHAVE FROM SURVEYS JUST 5887 03:36:57,490 --> 03:36:59,759 LIKE WILD HAMSTERS, MEANING THEY 5888 03:36:59,759 --> 03:37:01,294 LOST WEIGHT AND THEY'RE JUST 5889 03:37:01,294 --> 03:37:02,194 SITTING THERE. 5890 03:37:02,194 --> 03:37:05,298 SO THIS WAS DONE IN THE ROCKY 5891 03:37:05,298 --> 03:37:09,001 MOUNTAIN LION, THEY THOUGHT OK 5892 03:37:09,001 --> 03:37:13,606 OKAY, THIS -- THE HAMSTER THERE 5893 03:37:13,606 --> 03:37:15,408 AND -- EUTHANIZE THE HAMSTER 5894 03:37:15,408 --> 03:37:17,944 AND -- VIRUS STILL THERE. 5895 03:37:17,944 --> 03:37:18,511 CRAZY. 5896 03:37:18,511 --> 03:37:20,479 AND RECENTLY, PETER DID AN 5897 03:37:20,479 --> 03:37:24,283 EXPERIMENT AS HE SHOW THAT UP TO 5898 03:37:24,283 --> 03:37:26,619 100 DAY, VIRUS STILL THERE, AND 5899 03:37:26,619 --> 03:37:28,688 ANIMAL CAN GAIN WEIGHT -- IN 5900 03:37:28,688 --> 03:37:30,957 THAT CASE, SO HEALTHY. 5901 03:37:30,957 --> 03:37:31,524 CRAZY. 5902 03:37:31,524 --> 03:37:34,827 SO NK CELLS, VERY IMPORTANT FOR 5903 03:37:34,827 --> 03:37:37,697 CLEARING THE VIRUS. 5904 03:37:37,697 --> 03:37:41,767 THEN THIS IS A RESPIRATORY 5905 03:37:41,767 --> 03:37:47,340 VIRUS, JUNIN VIRUS, USE TRF1 AS 5906 03:37:47,340 --> 03:37:49,108 RECEPTOR AND -- JUST CANNOT BE 5907 03:37:49,108 --> 03:37:49,575 AFFECTED. 5908 03:37:49,575 --> 03:37:55,047 SO WE KNOCKED IN THROUGH THIS 5909 03:37:55,047 --> 03:37:56,882 KNOCK-IN CRISPR MEDIAN KNOCK-IN, 5910 03:37:56,882 --> 03:38:04,690 WE PUT THE HUMAN -- SO -- IT 5911 03:38:04,690 --> 03:38:10,730 GOOD, AND SO THAT WHEN WE INFECT 5912 03:38:10,730 --> 03:38:13,366 THE HAMSTER YOU SEE MODEL 33% 5913 03:38:13,366 --> 03:38:17,837 AND MIMICKING HUMAN MORTALITY, 5914 03:38:17,837 --> 03:38:21,907 AND ALSO WE SEE DIFFERENT -- 5915 03:38:21,907 --> 03:38:24,176 NEUROPATHOLOGY IS ON THE -- AND 5916 03:38:24,176 --> 03:38:25,311 ALSO TREMORS. 5917 03:38:25,311 --> 03:38:27,813 I HAVE REALLY WHAT I -- BECAUSE 5918 03:38:27,813 --> 03:38:29,782 I WAS AFRAID IT WON'T WORK. 5919 03:38:29,782 --> 03:38:30,549 ALL RIGHT. 5920 03:38:30,549 --> 03:38:32,785 ANOTHER EXAMPLE OF A JEAN -- I'M 5921 03:38:32,785 --> 03:38:34,754 SORRY. 5922 03:38:34,754 --> 03:38:42,328 THIS IS A -- FOR HAMSTER -- FO 5923 03:38:42,328 --> 03:38:45,831 FOR -- LAB AND HIS LAB -- ALL 5924 03:38:45,831 --> 03:38:52,738 ABOUT CHEMISTRY, PCPHY AS 5925 03:38:52,738 --> 03:38:53,839 RECEPTOR, CONFIRM -- AND HAMSTER 5926 03:38:53,839 --> 03:38:57,677 IS ONLY A RODENT FOUND TO BE 5927 03:38:57,677 --> 03:39:00,413 SUSCEPTIBLE TO HANTAVIRUS. 5928 03:39:00,413 --> 03:39:02,081 AND WE WORKED TOGETHER, NUMBER 5929 03:39:02,081 --> 03:39:05,151 ONE, WE DELETE A DOMAIN THEY 5930 03:39:05,151 --> 03:39:06,452 BELIEVE IS -- CHEMISTRY THAT 5931 03:39:06,452 --> 03:39:11,190 THIS DOMAIN IS IMPORTANT FOR 5932 03:39:11,190 --> 03:39:12,825 HANTAVIRUS ATTACHMENT TO THE 5933 03:39:12,825 --> 03:39:13,492 CELL. 5934 03:39:13,492 --> 03:39:15,361 WHEN WE LOOKED AT THIS DOMAIN, 5935 03:39:15,361 --> 03:39:17,563 BOOM, TURN OUT THAT THE HAMSTER 5936 03:39:17,563 --> 03:39:20,633 100% PROTECTED FOR HANTAVIRUS 5937 03:39:20,633 --> 03:39:21,867 INFECTION AND THEY ALSO NARROWED 5938 03:39:21,867 --> 03:39:27,773 DOWN THE TWO IMMUNOASSAY -- 5939 03:39:27,773 --> 03:39:30,643 BOOM, AND HEMISPHERES WERE 5940 03:39:30,643 --> 03:39:33,379 LARGELY PROTECTED. 5941 03:39:33,379 --> 03:39:40,252 MEANING THAT THESE TWO -- FOR 5942 03:39:40,252 --> 03:39:41,120 HANTAVIRUS INFECTION. 5943 03:39:41,120 --> 03:39:47,059 ALL RIGHT, HACE2 HAMSTERS -- 5944 03:39:47,059 --> 03:39:49,261 ALSO -- I JUST WANTED TO SHOW 5945 03:39:49,261 --> 03:39:51,430 THAT. 5946 03:39:51,430 --> 03:39:59,205 TURN OUT TO BE A LETHAL MODEL. 5947 03:39:59,205 --> 03:40:01,440 BUT -- PUBLICLY INFORMED OVER -- 5948 03:40:01,440 --> 03:40:03,275 A FEW MONTHS LATER. 5949 03:40:03,275 --> 03:40:04,043 ALL RIGHT. 5950 03:40:04,043 --> 03:40:07,880 SO WITH UNDUE -- ONE OF GENES, 5951 03:40:07,880 --> 03:40:09,548 WHAT ARE WE UP TO. 5952 03:40:09,548 --> 03:40:14,386 SO I THINK THE FIRST THING -- 5953 03:40:14,386 --> 03:40:19,625 KNOCKOUT -- GENES, WHEN WE -- 5954 03:40:19,625 --> 03:40:30,136 GENES, -- IMPORTANT FOR -- AND 5955 03:40:31,103 --> 03:40:37,610 ALSO GENE ESPECIALLY FOR CERT 5956 03:40:37,610 --> 03:40:45,351 CERTAIN -- CELL, LYMPHOID -- I 5957 03:40:45,351 --> 03:40:50,723 SHOULD -- AND OTHER GENE 5958 03:40:50,723 --> 03:40:54,059 IMPORTANT FOR USING HAMSTER AS A 5959 03:40:54,059 --> 03:40:59,799 HOST FOR HUMAN HEMATOPOIETIC -- 5960 03:40:59,799 --> 03:41:03,669 BIG PROJECT ONGOING. 5961 03:41:03,669 --> 03:41:05,871 AND OTHER TYPES OF GENOME 5962 03:41:05,871 --> 03:41:07,306 MODIFICATION IN ADDITION TO 5963 03:41:07,306 --> 03:41:09,842 KNOCK IN, KNOCKOUT EDITING, WE 5964 03:41:09,842 --> 03:41:20,252 WANT TO -- SPECIFIC AND 5965 03:41:21,987 --> 03:41:23,122 SEX-SPECIFIC, I THINK HUMAN 5966 03:41:23,122 --> 03:41:29,428 GENOME IS ABOUT 5, 6% GENES 5967 03:41:29,428 --> 03:41:38,704 SEX-BIAS AND -- ALSO REPORTER -- 5968 03:41:38,704 --> 03:41:44,043 AND THEN WOULD LIKE TO PRODUCE 5969 03:41:44,043 --> 03:41:50,416 ANTIBODS, THIS IS A WISH LIST. 5970 03:41:50,416 --> 03:41:53,853 I SURVEYED -- BUYOLOGIST AND WE 5971 03:41:53,853 --> 03:41:56,922 CAME UP WITH A LONG LIST OF THE 5972 03:41:56,922 --> 03:41:59,658 ANTIBODY GENES AND WE SUBMIT A 5973 03:41:59,658 --> 03:42:02,561 PROPOSAL BUT IT WAS REJECTED 5974 03:42:02,561 --> 03:42:06,498 BECAUSE THE -- DON'T THINK 5975 03:42:06,498 --> 03:42:08,133 HAMSTER -- IS THAT CRITICAL 5976 03:42:08,133 --> 03:42:09,335 BECAUSE -- MICE FANTASTIC. 5977 03:42:09,335 --> 03:42:10,703 SO ANYWAY, WE HAVE NOT DONE THAT 5978 03:42:10,703 --> 03:42:10,870 YET. 5979 03:42:10,870 --> 03:42:14,940 BUT I CAN SAY THAT I HOPE IN A 5980 03:42:14,940 --> 03:42:18,277 YEAR OR TWO EVEN, WE SHOULD NOT 5981 03:42:18,277 --> 03:42:22,014 TALK ABOUT -- MENTION REAGENT IS 5982 03:42:22,014 --> 03:42:23,115 A LIMITATION BECAUSE IT'S NOT A 5983 03:42:23,115 --> 03:42:24,750 BIG DEAL. 5984 03:42:24,750 --> 03:42:25,951 -- SUPPORT THE RESEARCH, I 5985 03:42:25,951 --> 03:42:28,921 THINK A COUPLE OF R24, PROBLEM 5986 03:42:28,921 --> 03:42:29,288 SOLVED. 5987 03:42:29,288 --> 03:42:35,594 WHEN I DID MY PH.D., I MADE A 5988 03:42:35,594 --> 03:42:39,798 HUNDRED -- AND I MANUALLY 5989 03:42:39,798 --> 03:42:41,233 SEQUENCED -- I DON'T KNOW HOW 5990 03:42:41,233 --> 03:42:45,271 MANY SEQUENCES, RIGHT, BIG FIGHT 5991 03:42:45,271 --> 03:42:46,739 TO INCLUDE. 5992 03:42:46,739 --> 03:42:47,172 SO ALL RIGHT. 5993 03:42:47,172 --> 03:42:48,741 I SAID I HAVE A ZOO, AND I WANT 5994 03:42:48,741 --> 03:42:55,614 TO SHOW YOU THE OTHERS. 5995 03:42:55,614 --> 03:43:01,553 -- DMI, WHITE FOOT MICE, 5996 03:43:01,553 --> 03:43:02,888 PRODUCE -- MODELS AND HERE'S THE 5997 03:43:02,888 --> 03:43:03,188 LIST. 5998 03:43:03,188 --> 03:43:06,926 SOME OF THEM HAVE BEEN USED. 5999 03:43:06,926 --> 03:43:10,129 AND THEN THE OTHER SPECIES I'M 6000 03:43:10,129 --> 03:43:11,997 TRYING TO WORK ON. 6001 03:43:11,997 --> 03:43:13,632 NO, I'M WORKING ON, SORRY. 6002 03:43:13,632 --> 03:43:16,802 URBAN I HAVE ABOUT 300 NAKED 6003 03:43:16,802 --> 03:43:18,470 MOLE RATS IN MY LAB. 6004 03:43:18,470 --> 03:43:20,372 VERY CUTE ANIMALS. 6005 03:43:20,372 --> 03:43:22,608 ACTUALLY THEY CAN BE UP TO 6006 03:43:22,608 --> 03:43:25,778 30-SOME YEARS. 6007 03:43:25,778 --> 03:43:29,615 THEY NEVER DEVELOP -- THAT'S 6008 03:43:29,615 --> 03:43:33,986 VERY INTERESTING. 6009 03:43:33,986 --> 03:43:36,522 NO OXYGEN, MICE, 32ND, GET 6010 03:43:36,522 --> 03:43:37,756 KILLED. 6011 03:43:37,756 --> 03:43:39,091 BUT THIS -- AMAZING HOW THEY DO 6012 03:43:39,091 --> 03:43:39,458 THAT. 6013 03:43:39,458 --> 03:43:41,260 IF YOU WANT TO STUDY STROKE, HOW 6014 03:43:41,260 --> 03:43:46,565 TO PROTECT A PATIENT FROM 6015 03:43:46,565 --> 03:43:48,934 ACCIDENT -- DAMAGE, GOOD ONE. 6016 03:43:48,934 --> 03:43:53,105 SO CALIFORNIA MICE, THEY ARE 6017 03:43:53,105 --> 03:43:55,341 NATURAL HOSTS FOR HANTAVIRUS AND 6018 03:43:55,341 --> 03:43:57,743 ALSO OTHER -- MANY OTHER 6019 03:43:57,743 --> 03:43:58,944 ZOONOTIC PATHOGENS. 6020 03:43:58,944 --> 03:44:03,983 AND THEY HAVE VERY INTERESTING 6021 03:44:03,983 --> 03:44:06,719 SOCIAL PAIR BONDING. 6022 03:44:06,719 --> 03:44:08,954 THEY ARE MONOGAMOUS TOGETHER. 6023 03:44:08,954 --> 03:44:10,489 YOU CANNOT SEPARATE THEM, THEY 6024 03:44:10,489 --> 03:44:12,624 WILL NOT ACCEPT A NEW PARTNER AT 6025 03:44:12,624 --> 03:44:13,826 ALL. 6026 03:44:13,826 --> 03:44:16,228 COTTON RAT, RECENTLY WE GOT 6027 03:44:16,228 --> 03:44:16,762 THEM. 6028 03:44:16,762 --> 03:44:18,964 GOOD MODEL FOR RSV, WE ALL HEARD 6029 03:44:18,964 --> 03:44:21,633 ABOUT THAT, MEASLES, HERPES 6030 03:44:21,633 --> 03:44:24,136 SIMPLEX VIRUS, AND PARTICULARLY 6031 03:44:24,136 --> 03:44:25,771 A THING WE WOULD LIKE TO WORK ON 6032 03:44:25,771 --> 03:44:28,774 IS THE CONNECTION BETWEEN 6033 03:44:28,774 --> 03:44:32,478 DEMENTIA ESPECIALLY, AND VIRAL 6034 03:44:32,478 --> 03:44:32,945 INFECTION. 6035 03:44:32,945 --> 03:44:35,347 THERE IS SO APPLICATION, WE HAVE 6036 03:44:35,347 --> 03:44:37,016 HAD INDICATION, SO WE WOULD LIKE 6037 03:44:37,016 --> 03:44:39,651 TO INTRODUCE SOME OF THE HUMAN 6038 03:44:39,651 --> 03:44:42,621 ALLELES WHICH MAKE IT SO THE 6039 03:44:42,621 --> 03:44:49,294 POPULATION TO DEVELOP -- DISEASE 6040 03:44:49,294 --> 03:44:50,195 TO 80 AGE, SOMETHING LIKE THAT. 6041 03:44:50,195 --> 03:44:52,731 SO WE ARE WORKING ON THAT. 6042 03:44:52,731 --> 03:44:57,536 AGAIN, WE LIKE -- DON'T BE 6043 03:44:57,536 --> 03:45:03,275 AGGRESSIVE BUT -- THESE THINK 6044 03:45:03,275 --> 03:45:07,746 ABOUT AND ALREADY IN DISCUSSIONS 6045 03:45:07,746 --> 03:45:11,016 LIKE -- FROM COLORADO STATE FOR 6046 03:45:11,016 --> 03:45:12,017 TWO OR THREE YEARS. 6047 03:45:12,017 --> 03:45:17,556 HE HAS -- HE SA SENT TO ME -- AD 6048 03:45:17,556 --> 03:45:18,957 WE DID SOME OTHER THINGS. 6049 03:45:18,957 --> 03:45:21,293 I ALSO TEAM UP WITH A HUSBAND 6050 03:45:21,293 --> 03:45:23,362 AND WIFE TEAM FROM MY 6051 03:45:23,362 --> 03:45:24,897 UNIVERSITY, THEY DO FIELD 6052 03:45:24,897 --> 03:45:25,264 STUDIES. 6053 03:45:25,264 --> 03:45:26,598 THEY ARE VERY EXCITED, THEY ARE 6054 03:45:26,598 --> 03:45:28,901 GOING TO HAVE ME TRAP 6055 03:45:28,901 --> 03:45:31,537 WHITETAILED ANTELOPE GROUND 6056 03:45:31,537 --> 03:45:33,172 SQUIRRELS. 6057 03:45:33,172 --> 03:45:34,873 WHAT KIND OF PATHOGEN THEY 6058 03:45:34,873 --> 03:45:37,810 CARRY, WE DON'T KNOW YET. 6059 03:45:37,810 --> 03:45:42,781 BUT THEY ARE DIURNAL, AS I 6060 03:45:42,781 --> 03:45:44,550 MENTIONED CIRCADIAN RHYTHM VERY 6061 03:45:44,550 --> 03:45:45,951 IMPORTANT IN TERMS OF VIRAL 6062 03:45:45,951 --> 03:45:46,285 INFECTION. 6063 03:45:46,285 --> 03:45:51,223 YOU KNOW, MAYBE IT'S GOOD MODEL 6064 03:45:51,223 --> 03:45:55,761 FOR VIRAL INFECTION TOO. 6065 03:45:55,761 --> 03:45:59,231 JUMPING MICE, THEY ARE 6066 03:45:59,231 --> 03:46:02,634 SEROPOSITIVE FOR SNV AND THEY 6067 03:46:02,634 --> 03:46:03,335 HIBERNATE. 6068 03:46:03,335 --> 03:46:12,711 I TALK WITH -- THEY HAVE THE 6069 03:46:12,711 --> 03:46:14,680 ANIMALS, AND ANOTHER SPECIES, 6070 03:46:14,680 --> 03:46:17,015 SPECIES X, I HOPE YOU GUYS CAN 6071 03:46:17,015 --> 03:46:22,621 GIVE ME SOME CLUE. 6072 03:46:22,621 --> 03:46:30,162 SO PRESENT -- THAT WORKING WITH 6073 03:46:30,162 --> 03:46:34,900 THTHE FANCY -- THEY DON'T HAVE - 6074 03:46:34,900 --> 03:46:37,436 ES OR IPS CELLS, ALSO LACK OF 6075 03:46:37,436 --> 03:46:40,639 ANIMAL HOUSING CAPABILITIES, 6076 03:46:40,639 --> 03:46:42,941 STANLEY, THIS WAS 10 YEARS AGO, 6077 03:46:42,941 --> 03:46:47,846 YOU DON'T HAVE CAPACITY TO HOUSE 6078 03:46:47,846 --> 03:46:49,615 HAMSTERS. 6079 03:46:49,615 --> 03:46:53,919 AND THEN RESEARCH A LOT OF MICE 6080 03:46:53,919 --> 03:46:55,354 AND -- DO NOT WANT TO GET INTO 6081 03:46:55,354 --> 03:47:00,159 TOO MUCH -- FOR THE PROPOSAL I 6082 03:47:00,159 --> 03:47:05,264 SAW NEW STUDY SECTIONS -- NO. 6083 03:47:05,264 --> 03:47:09,735 SO I THINK THAT JUST SHOW THE 6084 03:47:09,735 --> 03:47:15,007 FUNDING MECHANISM AS A - BATON O 6085 03:47:15,007 --> 03:47:15,474 DIRECT THIS. 6086 03:47:15,474 --> 03:47:16,475 SO I HOPE THAT WILL HAPPEN. 6087 03:47:16,475 --> 03:47:17,442 ALL RIGHT. 6088 03:47:17,442 --> 03:47:18,577 A SUMMARY. 6089 03:47:18,577 --> 03:47:19,978 YOU CAN READ IT. 6090 03:47:19,978 --> 03:47:21,113 IT'S VERY SIMPLE. 6091 03:47:21,113 --> 03:47:22,548 ALL RIGHT. 6092 03:47:22,548 --> 03:47:23,315 THAT'S ALL FOR ME. 6093 03:47:23,315 --> 03:47:31,123 ALL RIGHT. 6094 03:47:31,123 --> 03:47:32,291 >> THAT WAS REALLY GREAT. 6095 03:47:32,291 --> 03:47:33,725 MAYBE WE'LL GO STRAIGHT TO THE 6096 03:47:33,725 --> 03:47:35,494 PANEL DISCUSSION AND THEN IF 6097 03:47:35,494 --> 03:47:36,562 PEOPLE -- BART, IF YOU WANT TO 6098 03:47:36,562 --> 03:47:38,230 COME UP, WE'LL JUST DO THE PANEL 6099 03:47:38,230 --> 03:47:39,998 DISCUSSION NOW. 6100 03:47:39,998 --> 03:47:42,334 SO TO ANSWER BROADER QUESTIONS 6101 03:47:42,334 --> 03:47:44,102 IF ANYBODY HAS ONE, PLEASE GO 6102 03:47:44,102 --> 03:47:44,303 AHEAD. 6103 03:47:44,303 --> 03:47:46,438 >> I JUST HAVE A COMMENT FOR 6104 03:47:46,438 --> 03:47:46,905 ZONDA. 6105 03:47:46,905 --> 03:47:49,741 YOU HAD ON YOUR LIST FOR GUINEA 6106 03:47:49,741 --> 03:47:51,843 BIG REAGENTS FOR TGF BETA. 6107 03:47:51,843 --> 03:47:54,079 IF YOU'RE LOOKING AT TGF BETA, 6108 03:47:54,079 --> 03:47:58,984 THE ACTIVE FORM OF IT, THE 6109 03:47:58,984 --> 03:48:00,319 HUMAN -- AND REAGENTS WILL WORK 6110 03:48:00,319 --> 03:48:02,120 TBEUT BUTTEFULLY BECAUSE IT'S 6111 03:48:02,120 --> 03:48:03,655 ABOUT 99% CONSERVED ACROSS ALL 6112 03:48:03,655 --> 03:48:05,224 THE SPECIES, SO I WOULD GIVE 6113 03:48:05,224 --> 03:48:06,992 THEM A TRY, THAT'S WORKED REALLY 6114 03:48:06,992 --> 03:48:11,163 WELL FOR US AND EVERYTHING. 6115 03:48:11,163 --> 03:48:12,998 >> ANY QUESTIONS? I'M HAPPY TO 6116 03:48:12,998 --> 03:48:13,498 START. 6117 03:48:13,498 --> 03:48:15,801 I THINK AGAIN, YOU BOTH HAVE 6118 03:48:15,801 --> 03:48:17,536 REALLY UNIQUE PERSPECTIVES ON 6119 03:48:17,536 --> 03:48:19,571 SMALL ANIMAL MODELS, AND I WAS 6120 03:48:19,571 --> 03:48:21,106 WONDERING IF YOU BOTH WANTED TO 6121 03:48:21,106 --> 03:48:22,507 SORT OF ADDRESS KIND OF GAPS 6122 03:48:22,507 --> 03:48:25,277 THAT YOU ZIEBART IN TERMS OF 6123 03:48:25,277 --> 03:48:26,845 WHAT -- AS NEW PATHOGENS EMERGE 6124 03:48:26,845 --> 03:48:30,882 AND THE DEVELOPMENT OF ANIMAL 6125 03:48:30,882 --> 03:48:32,017 MODELS NEEDS TO HAPPEN IN TERMS 6126 03:48:32,017 --> 03:48:34,219 OF THE REGULATORY SPACE IN 6127 03:48:34,219 --> 03:48:35,420 GETTING LICENSURE OF VACCINES 6128 03:48:35,420 --> 03:48:37,823 AND SMALL DRUG TARGETS, HOW THAT 6129 03:48:37,823 --> 03:48:38,991 IS PERCEIVED WHEN YOU DON'T HAVE 6130 03:48:38,991 --> 03:48:40,826 A WEALTH OF INFORMATION. 6131 03:48:40,826 --> 03:48:42,794 AND THEN ZONDA, WHEN THE NEW 6132 03:48:42,794 --> 03:48:45,163 PATHOGEN EMERGES, HOW DO YOU 6133 03:48:45,163 --> 03:48:45,931 PICK A MODEL SYSTEM? 6134 03:48:45,931 --> 03:48:47,266 IT WAS REALLY GREAT IF YOU CAN 6135 03:48:47,266 --> 03:48:48,734 TOUCH ON THOSE TOPICS A LITTLE 6136 03:48:48,734 --> 03:48:54,906 BIT. 6137 03:48:54,906 --> 03:48:59,144 >> FOR ME TO CHOOSE AN ANIMAL 6138 03:48:59,144 --> 03:49:01,680 MODEL, THERE'S A DISEASE AND 6139 03:49:01,680 --> 03:49:04,116 CERTAIN VIRUS -- WORKING WITH 6140 03:49:04,116 --> 03:49:05,450 THAT SPECIES AND THEY HAVE A 6141 03:49:05,450 --> 03:49:07,519 NEED TO KNOW WHAT THE CAUSE 6142 03:49:07,519 --> 03:49:08,186 EFFECTS ARE IMPORTANT. 6143 03:49:08,186 --> 03:49:11,623 SO THEN WE WORK TOGETHER. 6144 03:49:11,623 --> 03:49:14,026 THE GENE AND -- IN TERMS OF 6145 03:49:14,026 --> 03:49:17,562 WHICH MODEL TO CHOOSE FOR 6146 03:49:17,562 --> 03:49:19,865 RESEARCH VIRUS, I HAVE NO IDEA. 6147 03:49:19,865 --> 03:49:25,037 I JUST RELY ON YOU GUYS. 6148 03:49:25,037 --> 03:49:28,073 >> MY GOODNESS. 6149 03:49:28,073 --> 03:49:35,580 WE'RE JUST LUCKY. 6150 03:49:35,580 --> 03:49:36,448 JUST FROM PREVIOUS EXPERIENCE 6151 03:49:36,448 --> 03:49:37,749 REALLY JUST LOOKING WHAT'S OUT 6152 03:49:37,749 --> 03:49:38,083 THERE. 6153 03:49:38,083 --> 03:49:44,589 I KNOW I HAD A GRADUATE STUDENT 6154 03:49:44,589 --> 03:49:45,791 PROBABLY THREE YEARS BEFORE WE 6155 03:49:45,791 --> 03:49:53,899 HAD FUNDING FROM THE NIH, ON -- 6156 03:49:53,899 --> 03:49:55,434 ALREADY COMING UP IN THE 6157 03:49:55,434 --> 03:49:56,401 LITERATURE, JUST WATCHING SOME 6158 03:49:56,401 --> 03:50:02,708 OF THE EMERGING INFECTION -- 6159 03:50:02,708 --> 03:50:04,109 SOCIAL MEDIA IDENTIFYING WHAT IS 6160 03:50:04,109 --> 03:50:06,311 OUT THERE UNDER UNIQUE DISEASES, 6161 03:50:06,311 --> 03:50:08,013 DISEASES WE DON'T UNDERSTAND, 6162 03:50:08,013 --> 03:50:17,255 AND JUST KIND OF -- 6163 03:50:17,255 --> 03:50:18,957 >> BART, YOU KIND OF TOUCHED ON 6164 03:50:18,957 --> 03:50:20,125 THIS AND IT'S SOMETHING ACTUALLY 6165 03:50:20,125 --> 03:50:21,493 WE HAVE NOT TALKED ABOUT IN THIS 6166 03:50:21,493 --> 03:50:24,096 WORKSHOP, AND THAT'S THE 6167 03:50:24,096 --> 03:50:25,197 IMPORTANCE OF THOROUGHLY AND 6168 03:50:25,197 --> 03:50:26,064 PROPERLY DESCRIBING THE 6169 03:50:26,064 --> 03:50:30,202 TECHNIQUES THAT YOU USED IN YOUR 6170 03:50:30,202 --> 03:50:30,769 PUBLICATION, RIGHT? 6171 03:50:30,769 --> 03:50:32,170 SO WOULD YOU JUST EXPAND ON THAT 6172 03:50:32,170 --> 03:50:32,938 A LITTLE BIT? 6173 03:50:32,938 --> 03:50:35,073 A LOT OF TIMES I THINK PEOPLE 6174 03:50:35,073 --> 03:50:36,608 SAY REFER TO PRIOR PAPER OR 6175 03:50:36,608 --> 03:50:38,143 SOMETHING ELSE. 6176 03:50:38,143 --> 03:50:39,077 AND THE INFORMATION IS NOT 6177 03:50:39,077 --> 03:50:39,544 THERE. 6178 03:50:39,544 --> 03:50:40,712 SO DO YOU HAVE RECOMMENDATIONS 6179 03:50:40,712 --> 03:50:44,649 FOR HOW TO APPROACH THAT FOR 6180 03:50:44,649 --> 03:50:45,550 EVERYBODY? 6181 03:50:45,550 --> 03:50:48,153 >> THE WHOLE IDEA OF SHOWING THE 6182 03:50:48,153 --> 03:50:49,354 COMBINATION DRUG STUDIES AND THE 6183 03:50:49,354 --> 03:50:50,956 WEIGH LOSS CUTOFF, I'M NOT 6184 03:50:50,956 --> 03:50:52,391 AGAINST ANIMAL WELFARE, REALLY, 6185 03:50:52,391 --> 03:50:54,726 I'M FOR ANIMAL WELFARE. 6186 03:50:54,726 --> 03:50:56,495 BUT I ALSO THINK WE NEED TO MAKE 6187 03:50:56,495 --> 03:51:00,932 SAWYER THAT THSURE THAT THE DATE 6188 03:51:00,932 --> 03:51:02,000 GENERATING IS GOOD DATA. 6189 03:51:02,000 --> 03:51:04,770 EARLY ON IN THE PANDEMIC, WE HAD 6190 03:51:04,770 --> 03:51:08,173 A DISCUSSION, RESPIRATORY 6191 03:51:08,173 --> 03:51:12,978 DISEASE BRANCH PROJECT OFFICER, 6192 03:51:12,978 --> 03:51:16,381 ST. JEUDZ -- WISCONSIN, AND WE 6193 03:51:16,381 --> 03:51:17,549 WERE TALKING ABOUT REALLY 6194 03:51:17,549 --> 03:51:19,184 AGREEING ON THE MODEL AND REALLY 6195 03:51:19,184 --> 03:51:21,286 JUST A WEIGHT LOSS CUTOFF, AND 6196 03:51:21,286 --> 03:51:23,288 EVEN THAT WAS A LITTLE BIT OF A 6197 03:51:23,288 --> 03:51:25,490 CHALLENGE, BECAUSE ST. JEUDZ 6198 03:51:25,490 --> 03:51:28,093 SAID THEIR -- WOULD NOT LET HIM 6199 03:51:28,093 --> 03:51:29,861 GO ANY HIGHER THAN A 20% WEIGHT 6200 03:51:29,861 --> 03:51:31,663 LOSS. 6201 03:51:31,663 --> 03:51:32,764 SO IT KIND OF A CHALLENGE. 6202 03:51:32,764 --> 03:51:36,368 THESE ARE UNREGULATED SPECIES, 6203 03:51:36,368 --> 03:51:37,636 THAT DOESN'T MEAN I DON'T CARE 6204 03:51:37,636 --> 03:51:38,737 ABOUT THEM. 6205 03:51:38,737 --> 03:51:40,372 I DO CARE ABOUT THEM. 6206 03:51:40,372 --> 03:51:41,673 I'VE NEVER SEEN ANIMALS 6207 03:51:41,673 --> 03:51:43,208 MISTREATED IN THE LAB, THANK 6208 03:51:43,208 --> 03:51:45,043 GOODNESS, AND I DON'T THINK WE 6209 03:51:45,043 --> 03:51:45,677 SHOULD. 6210 03:51:45,677 --> 03:51:46,912 PEOPLE PAT US ON THE BACK THAT 6211 03:51:46,912 --> 03:51:48,313 WE GET SO MUCH INFORMATION OUT 6212 03:51:48,313 --> 03:51:52,551 OF A STUDY THAT WE RUN, ANY 6213 03:51:52,551 --> 03:51:54,286 INFORMATION WE CAN GET FROM AN 6214 03:51:54,286 --> 03:51:55,554 ANIMAL STUDY, BUT I THINK THERE 6215 03:51:55,554 --> 03:51:58,056 NEEDS TO BE SOME AGREEMENT AS TO 6216 03:51:58,056 --> 03:52:00,292 KIND OF A STANDARD STUDY. 6217 03:52:00,292 --> 03:52:01,526 I GUESS WHEN I SAY THAT, I DON'T 6218 03:52:01,526 --> 03:52:03,161 WANT TO BE THE ONE MAKING THE 6219 03:52:03,161 --> 03:52:04,496 RULES BECAUSE I THINK EVERYBODY 6220 03:52:04,496 --> 03:52:05,530 NEEDS TO BE ABLE TO HAVE THE 6221 03:52:05,530 --> 03:52:06,531 FREEDOM TO TRY SOMETHING 6222 03:52:06,531 --> 03:52:10,001 DIFFERENT. 6223 03:52:10,001 --> 03:52:14,840 BUT THE PEOPLE OVER IN ICUC 6224 03:52:14,840 --> 03:52:15,974 COMMITTEE, ARE THEY TELLING THE 6225 03:52:15,974 --> 03:52:16,875 SCIENTISTS HOW THEY SHOULD BE 6226 03:52:16,875 --> 03:52:19,377 DOING THE STUDY? 6227 03:52:19,377 --> 03:52:22,714 I WOULD DISAGREE WITH THAT. 6228 03:52:22,714 --> 03:52:23,815 DOES THAT MAKE SENSE? 6229 03:52:23,815 --> 03:52:26,117 IT BEEN A HUGE CONCERN FOR ME 6230 03:52:26,117 --> 03:52:27,285 FOR -- ACTUALLY WHEN I FIRST 6231 03:52:27,285 --> 03:52:30,021 CAME TO USU FOR 15 YEARS, JUST 6232 03:52:30,021 --> 03:52:31,122 THIS IDEA THAT I WILL READ A 6233 03:52:31,122 --> 03:52:34,593 PAPER ON INFLUENZA AND IT'S A 6234 03:52:34,593 --> 03:52:35,660 DIFFERENT MOUSE STRAIN AND A 6235 03:52:35,660 --> 03:52:36,528 DIFFERENCE VIRUS AND THEY'RE 6236 03:52:36,528 --> 03:52:39,698 SAYING MORTALITY AND THEY DON'T 6237 03:52:39,698 --> 03:52:40,699 DESCRIBE WEIGHT LOSS CUTOFF. 6238 03:52:40,699 --> 03:52:41,933 THAT SHOULD BE JUST BASIC 6239 03:52:41,933 --> 03:52:42,400 INFORMATION IN THERE. 6240 03:52:42,400 --> 03:52:44,736 THEN I CAN IS A YOU'RE USING A 6241 03:52:44,736 --> 03:52:45,136 20%. 6242 03:52:45,136 --> 03:52:46,304 I UNDERSTAND THAT. 6243 03:52:46,304 --> 03:52:48,139 AND SO IT'S ALMOST -- WE CAN'T 6244 03:52:48,139 --> 03:52:51,443 FORCE PEOPLE DO THAT KIND OF AN 6245 03:52:51,443 --> 03:52:52,310 AGREEMENT. 6246 03:52:52,310 --> 03:52:54,613 I GUESS I WAS TRAINED LONG AGO, 6247 03:52:54,613 --> 03:52:57,516 BUT IF I'M PUBLISHING A METHOD, 6248 03:52:57,516 --> 03:52:58,717 I SHOULD PUBLISH THAT METHOD SO 6249 03:52:58,717 --> 03:53:01,520 YOU CAN REPRODUCE WHAT I'VE JUST 6250 03:53:01,520 --> 03:53:02,721 DONE, AND I'VE GIVEN YOU ALL THE 6251 03:53:02,721 --> 03:53:03,955 DETAILS. 6252 03:53:03,955 --> 03:53:05,357 AND IT'S ONE OF THOSE I GUESS 6253 03:53:05,357 --> 03:53:07,292 GOES WITHOUT ASKING, AND IF I'M 6254 03:53:07,292 --> 03:53:10,128 USING A REAGENT, BY PUBLISHING, 6255 03:53:10,128 --> 03:53:12,297 I'M SAYING I WILL PROVIDE THAT 6256 03:53:12,297 --> 03:53:14,466 REAGENT TO YOU SO THAT YOU CAN 6257 03:53:14,466 --> 03:53:16,201 REPRODUCE WHAT I'VE JUST DONE. 6258 03:53:16,201 --> 03:53:17,736 MAYBE THIS NEEDS TO BE REVIEWED 6259 03:53:17,736 --> 03:53:19,104 FOR YOUNGER SCIENTISTS. 6260 03:53:19,104 --> 03:53:19,771 I DON'T KNOW. 6261 03:53:19,771 --> 03:53:21,306 AND THAT CAN BE CHALLENGING. 6262 03:53:21,306 --> 03:53:24,142 IF IT'S AN EXPENSIVE MONOCLONAL, 6263 03:53:24,142 --> 03:53:26,511 WE CAN'T -- YOU KNOW, BUT DOES 6264 03:53:26,511 --> 03:53:27,512 THAT MAKE SENSE? 6265 03:53:27,512 --> 03:53:28,947 SOMEONE ELSE PLEASE TALK. 6266 03:53:28,947 --> 03:53:32,651 >> SO YOUR COMMENT ABOUT WHEN 6267 03:53:32,651 --> 03:53:34,019 YOU PUBLISH THOSE REAGENTS, 6268 03:53:34,019 --> 03:53:35,320 YOU'RE SAYING THOSE REAGENTS ARE 6269 03:53:35,320 --> 03:53:36,187 AVAILABLE, AND THAT'S PART OF 6270 03:53:36,187 --> 03:53:38,523 THAT AGREEMENT, RIGHT? 6271 03:53:38,523 --> 03:53:39,991 AND IT DOESN'T ALWAYS HAPPEN. 6272 03:53:39,991 --> 03:53:41,760 WE ALL KNOW THAT, RIGHT? 6273 03:53:41,760 --> 03:53:43,495 OR YOU REACH OUT AND THE 6274 03:53:43,495 --> 03:53:44,796 REAGENTS ARE NOT WHAT THEY SAID 6275 03:53:44,796 --> 03:53:47,933 THEY WERE AND I CAN SAY AT LEAST 6276 03:53:47,933 --> 03:53:49,801 FROM GENERAL VIROLOGY AND ASM 6277 03:53:49,801 --> 03:53:52,971 THAT THE PUBLISHERS ARE REALLY 6278 03:53:52,971 --> 03:53:55,006 PUSHING BACK ON THIS. 6279 03:53:55,006 --> 03:53:57,075 SO IF WE GET AN EMAIL, WE JUST 6280 03:53:57,075 --> 03:53:58,410 GOT ONE FROM A GRADUATE STUDENT 6281 03:53:58,410 --> 03:54:00,645 SOMEWHERE THAT WAS TRYING TO GET 6282 03:54:00,645 --> 03:54:01,413 ACCESS TO SOMETHING THAT SHOULD 6283 03:54:01,413 --> 03:54:02,747 HAVE BEEN AVAILABLE AND THE 6284 03:54:02,747 --> 03:54:04,015 AUTHORS JUST COMPLETELY IGNORED 6285 03:54:04,015 --> 03:54:05,884 THEM, AND ASM SENT THE ETHICS 6286 03:54:05,884 --> 03:54:07,085 TEAM AFTER THEM AND WHEN THEY 6287 03:54:07,085 --> 03:54:08,486 WOULDN'T COMPLY, THEY CONTACTED 6288 03:54:08,486 --> 03:54:10,188 NIH BECAUSE IT WAS NIH-FUNDED 6289 03:54:10,188 --> 03:54:11,056 STUDY. 6290 03:54:11,056 --> 03:54:13,024 SO THESE THINGS ARE BEING TAKEN 6291 03:54:13,024 --> 03:54:13,358 SERIOUSLY. 6292 03:54:13,358 --> 03:54:14,659 WHEN YOU PUBLISH AND YOU SAY 6293 03:54:14,659 --> 03:54:18,163 THAT OPEN ACCESS AND OPEN 6294 03:54:18,163 --> 03:54:19,130 RESOURCES, THEY'RE GOING TO HOLD 6295 03:54:19,130 --> 03:54:20,699 YOU TO IT, WHICH I THINK IS 6296 03:54:20,699 --> 03:54:23,301 GOOD. 6297 03:54:23,301 --> 03:54:25,337 >> RYAN? 6298 03:54:25,337 --> 03:54:26,871 >> ZONDA, GREAT TALK. 6299 03:54:26,871 --> 03:54:28,173 CAN I ASK A QUESTION ABOUT -- 6300 03:54:28,173 --> 03:54:29,441 THESE MODELS ARE BEAUTIFUL AND I 6301 03:54:29,441 --> 03:54:30,275 THINK THEY'RE SUPER IMPORTANT. 6302 03:54:30,275 --> 03:54:32,711 A LOT OF THESE ARE OUTBRED AND 6303 03:54:32,711 --> 03:54:33,812 THEY'RE WILD ANIMALS. 6304 03:54:33,812 --> 03:54:36,615 WHAT KIND OF ADDITIONAL TOOLS 6305 03:54:36,615 --> 03:54:37,515 AND STANDARDIZATIONS WOULD YOU 6306 03:54:37,515 --> 03:54:38,683 LIKE TO SEE FOR ALL OF THESE? 6307 03:54:38,683 --> 03:54:41,052 I MEAN, THEY'RE PROBABLY NOT 6308 03:54:41,052 --> 03:54:42,687 INBRED ALL OF THESE, LIKE YOUR 6309 03:54:42,687 --> 03:54:45,657 WESTERN JUMPING MICE WON'T BE 6310 03:54:45,657 --> 03:54:46,358 INBRED RIGHT AWAY. 6311 03:54:46,358 --> 03:54:47,792 ARE THERE HIGH QUALITY GENOMES 6312 03:54:47,792 --> 03:54:48,760 FOR THESE THINGS AVAILABLE? 6313 03:54:48,760 --> 03:54:50,962 DO WE NEED TO EVALUATE 6314 03:54:50,962 --> 03:54:51,997 MICROBIOME CHANGES THAT EXIST 6315 03:54:51,997 --> 03:54:53,965 ACROSS THESE DIFFERENT ANIMALS 6316 03:54:53,965 --> 03:54:55,600 AND SORT OF WHAT HELP DO YOU 6317 03:54:55,600 --> 03:54:56,968 NEED DO THAT OR WHAT THINGS DO 6318 03:54:56,968 --> 03:54:58,003 YOU THINK ARE NECESSARY AS 6319 03:54:58,003 --> 03:54:59,304 YOU'RE DEVELOPING THESE MODELS 6320 03:54:59,304 --> 03:55:00,438 TO STUDY A DISEASE? 6321 03:55:00,438 --> 03:55:01,039 >> GREAT QUESTION. 6322 03:55:01,039 --> 03:55:03,208 I THINK A LOT NEEDS TO BE DONE. 6323 03:55:03,208 --> 03:55:07,045 AT THIS MOMENT, WHEN WE GET 6324 03:55:07,045 --> 03:55:08,146 ABOUT -- CAUGHT ANIMAL, WE JUST 6325 03:55:08,146 --> 03:55:12,584 DO A PANEL OF PATHOGENS, WHICH 6326 03:55:12,584 --> 03:55:15,754 ARE THE CONCERN OF THE VET, NOT 6327 03:55:15,754 --> 03:55:16,721 MY CONCERN ACTUALLY. 6328 03:55:16,721 --> 03:55:19,624 AND THEN WE SAY OKAY, WE IMPORT 6329 03:55:19,624 --> 03:55:23,361 THEM, BUT IN TERMS OF THEIR 6330 03:55:23,361 --> 03:55:25,997 GENOME, I THINK THE -- RIGHT NOW 6331 03:55:25,997 --> 03:55:29,434 IS OF A RARE GENE, WE GOT THAT 6332 03:55:29,434 --> 03:55:30,568 DOWN PRETTY QUICKLY. 6333 03:55:30,568 --> 03:55:32,837 ALSO WHETHER WE WANT TO KEEP 6334 03:55:32,837 --> 03:55:35,340 INBRED OR OUTBRED. 6335 03:55:35,340 --> 03:55:38,209 SO FOR US WHAT DO WE TRY TO DO 6336 03:55:38,209 --> 03:55:39,711 THAT, EVEN THE HAMSTER. 6337 03:55:39,711 --> 03:55:43,081 WHEN YOU PRODUCE A FOUNDER LINE, 6338 03:55:43,081 --> 03:55:44,949 YOU JUST USE THAT FOUNDER LINE, 6339 03:55:44,949 --> 03:55:46,151 IT WILL BECOME INBRED. 6340 03:55:46,151 --> 03:55:47,519 THIS COULD BE A GOOD THING OR A 6341 03:55:47,519 --> 03:55:49,254 BAD THING, WE DON'T KNOW. 6342 03:55:49,254 --> 03:55:51,122 SO WE TEND TO HAVE MODEL 6343 03:55:51,122 --> 03:55:54,592 FOUNDERS AND THEN PERIODICALLY 6344 03:55:54,592 --> 03:55:58,229 BREED WITH FRESH -- RIGHT NOW WE 6345 03:55:58,229 --> 03:56:04,135 ARE TRYING TO KEEP THEM AS -- AS 6346 03:56:04,135 --> 03:56:07,472 POSSIBLE, WE HAVE NOT TRIED TO 6347 03:56:07,472 --> 03:56:08,440 PRODUCE AN -- 6348 03:56:08,440 --> 03:56:10,341 >> JUST QUICKLY TO THE GENOME. 6349 03:56:10,341 --> 03:56:12,911 SO WHEN YOU HAVE A TOTALLY NEW 6350 03:56:12,911 --> 03:56:15,113 ONE LIKE THE WESTERN JUMPING 6351 03:56:15,113 --> 03:56:17,082 MICE OR ANTELOPE SQUIRRELS, DO 6352 03:56:17,082 --> 03:56:18,883 YOU AN TATE THE GENOME -- 6353 03:56:18,883 --> 03:56:19,484 >> NO. 6354 03:56:19,484 --> 03:56:23,655 FOR US, WE JUST DESIGN -- 6355 03:56:23,655 --> 03:56:23,955 PARAMETERS. 6356 03:56:23,955 --> 03:56:27,158 FIRST WE JUST LOOK AT -- GENE -- 6357 03:56:27,158 --> 03:56:30,528 FOR EXAMPLE AND LOOK AT -- 6358 03:56:30,528 --> 03:56:32,497 WHATEVER YOU HAVE IT, WE COMPARE 6359 03:56:32,497 --> 03:56:34,332 IT. 6360 03:56:34,332 --> 03:56:36,101 IF -- SEQUENCE -- WE SEQUENCE 6361 03:56:36,101 --> 03:56:38,570 IT, MAKE SURE THAT THERE ARE NO 6362 03:56:38,570 --> 03:56:41,206 POLYMORPHISM, SO TO GET OUR -- 6363 03:56:41,206 --> 03:56:47,612 WE DESIGN TARGET THE SEQUENCE, 6364 03:56:47,612 --> 03:56:51,983 AND -- WE JUST -- AMPLIFY THE 6365 03:56:51,983 --> 03:56:53,051 SEQUENCE LIKE THAT. 6366 03:56:53,051 --> 03:56:54,486 >> YOU KNOW, BECAUSE THERE'S A 6367 03:56:54,486 --> 03:56:56,955 FEW OF THESE CONSORTIA THAT ARE 6368 03:56:56,955 --> 03:56:59,290 OUT THERE LIKE THE VERTEBRA GENE 6369 03:56:59,290 --> 03:57:01,960 PROJECT AND SONOMIA, I WONDER IF 6370 03:57:01,960 --> 03:57:05,396 YOU KNOW IF NID OR NIH OR A 6371 03:57:05,396 --> 03:57:06,364 FUNDING AGENCY WOULD BE WILLING 6372 03:57:06,364 --> 03:57:07,665 TO HELP COVER THE COST OF 6373 03:57:07,665 --> 03:57:09,400 DEVELOPING ALL THESE MODELS AND 6374 03:57:09,400 --> 03:57:10,735 GETTING JOE NOMES DONE. 6375 03:57:10,735 --> 03:57:14,105 I THINK THE SEQUENCING IS NOT 6376 03:57:14,105 --> 03:57:17,008 TERRIBLY EXPENSIVE BUT THE 6377 03:57:17,008 --> 03:57:18,576 BIOINFORMATICS IS QUITE 6378 03:57:18,576 --> 03:57:20,311 TIME-CONSUMING ESPECIALLY FOR 6379 03:57:20,311 --> 03:57:21,613 TRULY NOVEL GENOME. 6380 03:57:21,613 --> 03:57:26,184 SO I THINK HAVING A PIPE LOIN TO 6381 03:57:26,184 --> 03:57:29,154 DO THIS, IT WOULD BE GREAT -- 6382 03:57:29,154 --> 03:57:35,093 THEY CHARGE YOU FOR THEM, IT'S - 6383 03:57:35,093 --> 03:57:37,428 >> ABSOLUTELY. 6384 03:57:37,428 --> 03:57:40,365 YOU'RE LUCKY -- 6385 03:57:40,365 --> 03:57:43,334 >> FANTASTIC. 6386 03:57:43,334 --> 03:57:43,802 I'LL ALLOW IT. 6387 03:57:43,802 --> 03:57:47,806 >> SO I HAVE A QUESTION FOR 6388 03:57:47,806 --> 03:57:48,339 ZONDA AS WELL. 6389 03:57:48,339 --> 03:57:51,509 I THINK YOU BRIEFLY TOUCHED UPON 6390 03:57:51,509 --> 03:57:53,011 HOW SENSITIVE, THE SYRIAN 6391 03:57:53,011 --> 03:57:54,212 HAMSTERS ARE TOO LIGHT. 6392 03:57:54,212 --> 03:57:55,947 MOST OF US PERFORM EXPERIMENTS 6393 03:57:55,947 --> 03:57:58,349 DURING DAY TIME, AND I'M KIND OF 6394 03:57:58,349 --> 03:58:01,085 CURIOUS HOW DO YOU THINK THAT 6395 03:58:01,085 --> 03:58:03,888 MAY POTENTIALLY AFFECT THE 6396 03:58:03,888 --> 03:58:06,891 OUTCOME OF THE EXPERIMENT? 6397 03:58:06,891 --> 03:58:09,460 >> THE EMBRYOS ARE SENSITIVE. 6398 03:58:09,460 --> 03:58:10,695 THE ANIMALS ARE NOT. 6399 03:58:10,695 --> 03:58:13,264 BUT THEY ARE SENSITIVE TO PHOTO 6400 03:58:13,264 --> 03:58:16,968 PERIOD, MEANING THAT THEIR SIR 6401 03:58:16,968 --> 03:58:21,372 CADDIAN RHYTHM -- WE HAVE FEW 6402 03:58:21,372 --> 03:58:23,942 OCCASION -- SOMEHOW THE LIGHT 6403 03:58:23,942 --> 03:58:25,710 JUST DOES NOT TURN OFF OR TURN 6404 03:58:25,710 --> 03:58:30,081 ON AND THEN PULL -- THE EXTRA 6405 03:58:30,081 --> 03:58:31,349 CYCLE AND TAKE AT LEAST ABOUT A 6406 03:58:31,349 --> 03:58:34,953 MONTH FOR FEMALE TO RECOVER. 6407 03:58:34,953 --> 03:58:39,858 SPO FSO FOR ADULT ANIMALS -- BUI 6408 03:58:39,858 --> 03:58:41,960 THINK THE CIRCADIAN RHYTHM WOULD 6409 03:58:41,960 --> 03:58:44,562 REALLY PROVIDE A VERY UNIQUE WAY 6410 03:58:44,562 --> 03:58:52,303 FOR US TO TETHER VACCINE -- AT 6411 03:58:52,303 --> 03:58:54,272 WHAT STATE OF CIRCADIAN RHYTHM 6412 03:58:54,272 --> 03:58:55,473 IS IMPORTANT OR NOT IMPORTANT AT 6413 03:58:55,473 --> 03:59:00,845 ALL. 6414 03:59:00,845 --> 03:59:02,180 >> ARE THERE ANY QUESTIONS 6415 03:59:02,180 --> 03:59:03,882 ONLINE OR IN THE CHAT ROOM? 6416 03:59:03,882 --> 03:59:04,782 GO AHEAD, MICHELLE. 6417 03:59:04,782 --> 03:59:08,987 >> I HAVE TWO HAMSTER QUESTIONS. 6418 03:59:08,987 --> 03:59:11,723 THE FIRST IS IF WE'RE DEVELOPING 6419 03:59:11,723 --> 03:59:12,824 REAGENTS AGAINST SYRIAN 6420 03:59:12,824 --> 03:59:13,925 HAMSTERS, IS THERE ANY 6421 03:59:13,925 --> 03:59:16,961 EXPECTATION THAT THOSE WILL BE 6422 03:59:16,961 --> 03:59:19,697 CROSS-REACTIVE IN OTHER HAMSTER 6423 03:59:19,697 --> 03:59:19,931 SPECIES? 6424 03:59:19,931 --> 03:59:21,666 >> NOT EXACTLY. 6425 03:59:21,666 --> 03:59:22,967 BECAUSE THEY ARE QUITE 6426 03:59:22,967 --> 03:59:27,906 DIFFERENT, HAMSTER AND -- MANY 6427 03:59:27,906 --> 03:59:28,339 YEARS. 6428 03:59:28,339 --> 03:59:31,175 WE HAVE TO TEST -- 6429 03:59:31,175 --> 03:59:34,646 >> WHEN WE WERE WORKING ON THE 6430 03:59:34,646 --> 03:59:41,386 SARS 2 MODEL IN THE HA 6431 03:59:41,386 --> 03:59:43,454 HACE2 HAMSTER I THINK WE 6432 03:59:43,454 --> 03:59:44,489 EVALUATED EVERY CYTOKINE KIT 6433 03:59:44,489 --> 03:59:46,958 THAT WAS AVAILABLE ON THE MARKET 6434 03:59:46,958 --> 03:59:48,593 FOR HAMSTER TO SEE IF IT WOULD 6435 03:59:48,593 --> 03:59:48,793 WORK. 6436 03:59:48,793 --> 03:59:49,761 NONE OF THEM DID. 6437 03:59:49,761 --> 03:59:50,528 NONE OF THEM DID. 6438 03:59:50,528 --> 03:59:53,898 >> THAT'S POSH INFORMATION. 6439 03:59:53,898 --> 03:59:54,766 THAT'S IMPORTANT INFORMATION. 6440 03:59:54,766 --> 03:59:55,533 MY SECOND QUESTION IS, 6441 03:59:55,533 --> 03:59:56,734 THROUGHOUT THE DAY TODAY, I'VE 6442 03:59:56,734 --> 03:59:57,835 HEARD SOME PEOPLE SAY THAT 6443 03:59:57,835 --> 03:59:59,103 HAMSTERS ARE RELATIVELY CHEAP 6444 03:59:59,103 --> 04:00:00,638 AND SOME PEOPLE SAY THAT THEY'RE 6445 04:00:00,638 --> 04:00:01,506 EXPENSIVE MODELS. 6446 04:00:01,506 --> 04:00:03,174 SO I KNOW THIS IS PROBABLY 6447 04:00:03,174 --> 04:00:04,676 SUBJECTIVE DEPENDING ON THE 6448 04:00:04,676 --> 04:00:07,178 PERSON, BUT SO HOW DO WE SORT OF 6449 04:00:07,178 --> 04:00:09,681 QUANTIFY THAT AND DECIDE, YOU 6450 04:00:09,681 --> 04:00:12,016 KNOW, THE EXPENSE? 6451 04:00:12,016 --> 04:00:16,587 >> WHEN YOU BUY A HAMSTER FROM 6452 04:00:16,587 --> 04:00:18,923 A -- THEY CHARGE MORE THAN MICE. 6453 04:00:18,923 --> 04:00:22,226 BUT HAMSTER REPRODUCE SO FAST, I 6454 04:00:22,226 --> 04:00:24,429 ANTICIPATE IF YOU HAVE A PAIR OF 6455 04:00:24,429 --> 04:00:28,166 HAMSTER, MALE/FEMALE AND A PAIR 6456 04:00:28,166 --> 04:00:30,835 OF MICE IN THE SAME ROOM, WITHIN 6457 04:00:30,835 --> 04:00:32,503 TWO YEARS, MORE THAN 95% OF THE 6458 04:00:32,503 --> 04:00:34,973 ANIMAL WILL BE HAMSTERS. 6459 04:00:34,973 --> 04:00:37,842 THEY REPRODUCE AT LIKE CRAZY, 6460 04:00:37,842 --> 04:00:39,911 RIGHT? 6461 04:00:39,911 --> 04:00:43,181 GESTATION TIME -- AND WHY 6462 04:00:43,181 --> 04:00:49,320 HAMSTER -- WE USE -- LARGER 6463 04:00:49,320 --> 04:00:52,890 CAGING, JUST -- IF I WANT TO 6464 04:00:52,890 --> 04:00:54,192 SELL PETS TO MAKE A LIVING, I 6465 04:00:54,192 --> 04:00:55,526 WOULD LIKE TO WORK WITH HAMSTER 6466 04:00:55,526 --> 04:00:56,694 THAN WORK WITH MICE. 6467 04:00:56,694 --> 04:00:59,764 SO IT SHOULD NOT BE THAT 6468 04:00:59,764 --> 04:01:00,331 EXPENSIVE. 6469 04:01:00,331 --> 04:01:04,469 IT'S THE MO NOP LI MONOPOLY, I . 6470 04:01:04,469 --> 04:01:08,072 BUT WE TRIED A LOT FOR HAMST 6471 04:01:08,072 --> 04:01:09,273 HAMSTER -- SO THAT'S WHY THE 6472 04:01:09,273 --> 04:01:14,512 HAMSTER I PRODUCE ARE 6473 04:01:14,512 --> 04:01:24,989 EXPENSIVE -- BUT IT'S OKAY. 6474 04:01:28,159 --> 04:01:31,029 >> THIS IS FOR BART. 6475 04:01:31,029 --> 04:01:32,330 I GO BACK TO IN MY PREVIOUS LIKE 6476 04:01:32,330 --> 04:01:35,800 I USED TO BE A STRUCTURE BASED 6477 04:01:35,800 --> 04:01:37,201 DRUG DESIGN PERSON SO I ASK YOU 6478 04:01:37,201 --> 04:01:38,703 ABOUT DRUGS. 6479 04:01:38,703 --> 04:01:41,005 SO ONE PROBLEM IN GOING FROM 6480 04:01:41,005 --> 04:01:43,074 ANIMALS TO HUMANS IN THE 6481 04:01:43,074 --> 04:01:44,275 PHARMACOKINETICS AND DYNAMICS 6482 04:01:44,275 --> 04:01:46,144 LIKE FOR SOME CANCER DRUGS, 6483 04:01:46,144 --> 04:01:47,879 HUMAN CELLS PUMPED THEM OUT, 6484 04:01:47,879 --> 04:01:50,281 WHERE THEY WAY WORK IN MICE. 6485 04:01:50,281 --> 04:01:52,350 SO IN YOUR FIELD OF LET'S SAY 6486 04:01:52,350 --> 04:01:54,118 ANTIVIRUS, IS THERE ANY LESSONS 6487 04:01:54,118 --> 04:01:56,954 LEARNED FROM THOSE THAT WORK IN 6488 04:01:56,954 --> 04:01:58,256 ANIMALS, WORK IN HUMANS, OR 6489 04:01:58,256 --> 04:01:59,891 DON'T WORK IN HUMANS BUT WORK IN 6490 04:01:59,891 --> 04:02:00,124 ANIMALS? 6491 04:02:00,124 --> 04:02:04,929 IS THERE SOME TYPE OF 6492 04:02:04,929 --> 04:02:09,167 PHARMOKINETIC DYNAMIC MAP, DOES 6493 04:02:09,167 --> 04:02:10,735 THIS PARTICULAR STRUCTURE -- IT 6494 04:02:10,735 --> 04:02:13,504 WILL BE GOOD BECAUSE THIS MOUSE 6495 04:02:13,504 --> 04:02:15,807 HAS THESE TRANSPORTERS OR THESE 6496 04:02:15,807 --> 04:02:16,174 SERUM PROTEINS. 6497 04:02:16,174 --> 04:02:17,675 IS THERE ANY WAY TO KIND OF 6498 04:02:17,675 --> 04:02:19,010 PREDICT AND PUT IN A COMPUTER IF 6499 04:02:19,010 --> 04:02:19,844 WE KNOW HOW DRUGS ARE 6500 04:02:19,844 --> 04:02:22,346 TRANSPORTED IN OR OUT OF SALES 6501 04:02:22,346 --> 04:02:24,415 OR TAKEN UP IN THE MUCOSA OR 6502 04:02:24,415 --> 04:02:25,316 THINGS LIKE THAT? 6503 04:02:25,316 --> 04:02:29,120 >> GOOD QUESTION. 6504 04:02:29,120 --> 04:02:30,755 THE TWO THINGS I SEE ARE GOING 6505 04:02:30,755 --> 04:02:33,925 TO KILL A DRU DRUG IN DEVELOPME, 6506 04:02:33,925 --> 04:02:34,992 TOXICITY, SOLUBILITY. 6507 04:02:34,992 --> 04:02:36,527 IS IT GOING TO BE TOXIC IN THE 6508 04:02:36,527 --> 04:02:37,829 HOST, AND IS IT SOLUBLE. 6509 04:02:37,829 --> 04:02:40,231 I THINK PROBABLY HALF OF THE 6510 04:02:40,231 --> 04:02:43,301 ANTIVIRALS THAT WE EVALUATE, 6511 04:02:43,301 --> 04:02:44,936 SPONSORS THROUGH THE ANTIVIRAL 6512 04:02:44,936 --> 04:02:47,472 TESTING PROGRAMMING, HAVE 6513 04:02:47,472 --> 04:02:48,973 SOLUBILITY ISSUES, AND WE HAVE 6514 04:02:48,973 --> 04:02:51,609 LITTLE TRICKS, DID I SAY -- DI 6515 04:02:51,609 --> 04:02:54,212 SAY THAT CORRECTLY? 6516 04:02:54,212 --> 04:02:55,546 HALF THE STUDIES FAILED. 6517 04:02:55,546 --> 04:02:59,050 AND I SAY THAT, ARE PROBABLY 6518 04:02:59,050 --> 04:02:59,817 SOLUBILITY ISSUES. 6519 04:02:59,817 --> 04:03:01,853 A LOT. 6520 04:03:01,853 --> 04:03:06,224 IN FACT, MY LAST -- 6521 04:03:06,224 --> 04:03:07,525 COMMUNICATION, WE HAVE A LOT OF 6522 04:03:07,525 --> 04:03:09,093 LIKE I SAID TIPS AND TRICKS. 6523 04:03:09,093 --> 04:03:12,430 SO A DRUG THAT IS NOT VERY 6524 04:03:12,430 --> 04:03:16,367 SOLUBLE, YOU CAN -- ORGANIC 6525 04:03:16,367 --> 04:03:21,606 SOLVENT AND TAKE THAT -- GO 10% 6526 04:03:21,606 --> 04:03:25,877 DMSO, SIZE THE DRUG, THEN GO 6527 04:03:25,877 --> 04:03:29,213 INTO -- I CAN TO THAT RAW TEE 6528 04:03:29,213 --> 04:03:31,315 TEENLY. 6529 04:03:31,315 --> 04:03:33,184 SONICATION HEAT, THESE ARE ALL 6530 04:03:33,184 --> 04:03:35,686 THINGS WE MIGHT -- CAN USE ON A 6531 04:03:35,686 --> 04:03:37,622 SMALL SCALE BUT NOW FOR 6532 04:03:37,622 --> 04:03:38,723 PHARMACEUTICAL DEVELOPMENT, 6533 04:03:38,723 --> 04:03:39,790 MANUFACTURING AND LICENSING. 6534 04:03:39,790 --> 04:03:42,760 SO SOLUBILITY IS JUST TOP. 6535 04:03:42,760 --> 04:03:45,429 GOING FROM AN ANIMAL TO HUMAN 6536 04:03:45,429 --> 04:03:47,765 DOSING, IT SOUNDS REALLY WEIRD. 6537 04:03:47,765 --> 04:03:49,534 THERE ACTUALLY ARE SOME METRICS 6538 04:03:49,534 --> 04:03:52,170 THAT ARE USED, SOME CONVERSIONS, 6539 04:03:52,170 --> 04:03:53,905 THEY GO BY SURFACE AREA. 6540 04:03:53,905 --> 04:03:55,439 SO THE SURFACE AREA -- THE SKIN 6541 04:03:55,439 --> 04:03:56,807 OF A MOUSE COMPARED TO THE SKIN 6542 04:03:56,807 --> 04:04:02,079 OF A HUMAN, AND THEY'VE KIND O 6543 04:04:02,079 --> 04:04:03,181 OF -- A LITTLE BIT OF NONSENSE 6544 04:04:03,181 --> 04:04:06,417 TO ME BUT THAT'S WHAT IT USED, 6545 04:04:06,417 --> 04:04:07,285 IS IT ACCURATE? 6546 04:04:07,285 --> 04:04:08,152 NOT ALWAYS. 6547 04:04:08,152 --> 04:04:15,126 I WILL HAVE A -- OR IT DID WORK 6548 04:04:15,126 --> 04:04:16,394 IN VITRO, WHY DIDN'T IT WORK IN 6549 04:04:16,394 --> 04:04:19,197 THE ANIMAL? 6550 04:04:19,197 --> 04:04:20,531 OFTEN -- HOW SOLUBLE IS IT, HOW 6551 04:04:20,531 --> 04:04:21,899 MANY MEMBRANES DOES IT NEED TO 6552 04:04:21,899 --> 04:04:22,233 CROSS? 6553 04:04:22,233 --> 04:04:23,201 BECAUSE THAT'S WHERE A DRUG WILL 6554 04:04:23,201 --> 04:04:25,736 NOT BE ABLE TO CAUSE THAT 6555 04:04:25,736 --> 04:04:28,005 MEMBRANE -- IT WILL JUST STOP, 6556 04:04:28,005 --> 04:04:28,773 OF ACTIVITY. 6557 04:04:28,773 --> 04:04:31,175 THINK ABOUT TAKING A PILL 6558 04:04:31,175 --> 04:04:32,510 THROUGH THE -- OF THE STOMACH, 6559 04:04:32,510 --> 04:04:34,779 GETS IN THE INTESTINE, HAS TO GO 6560 04:04:34,779 --> 04:04:35,913 THROUGH THE INTESTINAL WALL INTO 6561 04:04:35,913 --> 04:04:37,515 THE BLOOD, NOW I WANT TO GET TO 6562 04:04:37,515 --> 04:04:39,584 THE SURFACE OF THE LUNG, THAT'S 6563 04:04:39,584 --> 04:04:40,651 TOUGH. 6564 04:04:40,651 --> 04:04:45,556 NOW IT GOT TO COME BACK NA THE E 6565 04:04:45,556 --> 04:04:46,958 LUNG THROUGH THE LUNG-BLOOD 6566 04:04:46,958 --> 04:04:48,926 BARRIER, AND IN THE CASE OF 6567 04:04:48,926 --> 04:04:49,694 RESPIRATORY DISEASE WHERE 6568 04:04:49,694 --> 04:04:51,762 THERE'S INFLAMMATION, THERE'S 6569 04:04:51,762 --> 04:04:55,366 CONSOLIDATION, HOW DO IS THAT DG 6570 04:04:55,366 --> 04:04:58,402 GOING TO GET TO THE SURFACE WHEN 6571 04:04:58,402 --> 04:04:59,303 EVERYTHING IN THE LUNGS IS 6572 04:04:59,303 --> 04:05:00,071 FIGHTING AGAINST IT? 6573 04:05:00,071 --> 04:05:01,906 YOU CAN SAY NEBULIZER, BUT IF 6574 04:05:01,906 --> 04:05:04,976 YOU HAVE NEBULIZER, YOU'RE NOT 6575 04:05:04,976 --> 04:05:06,844 GOING TO GET IT EITHER. 6576 04:05:06,844 --> 04:05:08,279 SO THE LUNG IS A CHALLENGING 6577 04:05:08,279 --> 04:05:11,182 LOCATION TO TRY TO GET A DRUG -- 6578 04:05:11,182 --> 04:05:15,920 DID THAT MAKE SENSE? 6579 04:05:15,920 --> 04:05:18,956 >> SO QUESTION FROM ONLINE, THIS 6580 04:05:18,956 --> 04:05:19,924 IS FOR ZONDA. 6581 04:05:19,924 --> 04:05:21,792 HAVE YOU SEEN WHETHER THE ESTRUS 6582 04:05:21,792 --> 04:05:22,994 CYCLE IMPACT VIRAL INFECTION IN 6583 04:05:22,994 --> 04:05:25,796 YOUR MODELS LIKE THE INFLUENZA 6584 04:05:25,796 --> 04:05:26,430 VIRUS IN GUINEA PIGS? 6585 04:05:26,430 --> 04:05:29,967 >> THAT'S A GREAT QUESTION. 6586 04:05:29,967 --> 04:05:32,903 I HAVEN'T -- ANY ANIMALS, SO MY 6587 04:05:32,903 --> 04:05:33,671 COLLABORATORS, I HAVE IN 6588 04:05:33,671 --> 04:05:35,206 DISCUSSION WITH SOME OF THEM, 6589 04:05:35,206 --> 04:05:37,808 BUT THIS HAS NOT BEEN DONE YET. 6590 04:05:37,808 --> 04:05:41,412 I THINK VERY -- EFFECT AS CYCLE 6591 04:05:41,412 --> 04:05:42,613 ALSO CIRCADIAN RHYTHM WOULD BE 6592 04:05:42,613 --> 04:05:47,118 VERY IMPORTANT AND I HAVE A 6593 04:05:47,118 --> 04:05:48,986 REPORTER HAMSTER THAT WILL MAKE 6594 04:05:48,986 --> 04:05:53,190 THAT -- THE MODEL ALIGN VERY 6595 04:05:53,190 --> 04:05:54,725 CONVENIENT TO MONITOR THE 6596 04:05:54,725 --> 04:05:55,593 CIRCADIAN RHYTHM CHANGE. 6597 04:05:55,593 --> 04:06:03,501 GOOD QUESTION. 6598 04:06:03,501 --> 04:06:05,703 >> I WANTED TO ASK ONE MORE 6599 04:06:05,703 --> 04:06:06,804 QUESTION TOO ABOUT THAT DELIVERY 6600 04:06:06,804 --> 04:06:07,738 WERE YOU JUST MENTIONING AND I 6601 04:06:07,738 --> 04:06:08,606 THINK THIS IS REALLY 6602 04:06:08,606 --> 04:06:09,273 INTERESTING. 6603 04:06:09,273 --> 04:06:11,876 SO HOW DO YOU ENVISION OR HOW -- 6604 04:06:11,876 --> 04:06:13,844 WHAT HAVE YOU LEARNED MAYBE 6605 04:06:13,844 --> 04:06:15,913 LESSONS LEARNED ABOUT DIFFERENT 6606 04:06:15,913 --> 04:06:20,418 DELIVERY MODALITIES? 6607 04:06:20,418 --> 04:06:22,153 OBVIOUSLY NEB LIIZATION OF 6608 04:06:22,153 --> 04:06:23,020 STAGED THERAPY IS A BIG THING 6609 04:06:23,020 --> 04:06:25,189 NOW TO GET THEM TO THE LUNG, SO 6610 04:06:25,189 --> 04:06:27,158 TALKING ABOUT DELIVERY TO 6611 04:06:27,158 --> 04:06:27,591 MUCOSAL SITES. 6612 04:06:27,591 --> 04:06:29,794 THEN I THINK THIS DOVETAILS 6613 04:06:29,794 --> 04:06:31,862 MAYBE TO SORT OF -- ABOUT 6614 04:06:31,862 --> 04:06:36,901 MUCOSAL IMMUNITY, TARGETING -- 6615 04:06:36,901 --> 04:06:44,575 AND -- DRUGS TO MUCOSAL SITES? 6616 04:06:44,575 --> 04:06:50,681 >> IN ANIMALS, IN PEOPLE AS 6617 04:06:50,681 --> 04:06:52,717 WELL, THEY REALLY NEED TO BE 6618 04:06:52,717 --> 04:06:53,651 ADMINISTERED WITHIN 48 HOURS. 6619 04:06:53,651 --> 04:06:54,819 HOW MANY PEOPLE ARE GOING TO 6620 04:06:54,819 --> 04:06:56,754 KNOW THEY'RE INFECTED WITH FLU 6621 04:06:56,754 --> 04:06:57,955 WITHIN 48 HOURS OF BEING 6622 04:06:57,955 --> 04:06:58,289 INFECTED? 6623 04:06:58,289 --> 04:06:59,724 I'M GOING TO WAIT UNTIL I'M 6624 04:06:59,724 --> 04:07:00,958 REALLY SICK BUT I'M NOT GOING TO 6625 04:07:00,958 --> 04:07:04,295 GO TO THE DOCTOR. 6626 04:07:04,295 --> 04:07:05,396 SO IT'S A CHALLENGE WITH THE 6627 04:07:05,396 --> 04:07:05,830 LUNG. 6628 04:07:05,830 --> 04:07:08,232 IT'S ALMOST GOT TO BE THERE 6629 04:07:08,232 --> 04:07:09,667 EARLY. 6630 04:07:09,667 --> 04:07:11,102 SO IS THAT PROPHYLACTICALLY OR 6631 04:07:11,102 --> 04:07:13,137 IS IT VACCINATION? 6632 04:07:13,137 --> 04:07:15,172 I MEAN, THE VACCINE INDUSTRY, 6633 04:07:15,172 --> 04:07:16,774 THERE USED TO BE A HUGE -- I 6634 04:07:16,774 --> 04:07:19,143 REMEMBER IT WAS BLUE, A BOOK OF 6635 04:07:19,143 --> 04:07:19,810 MUCOSAL IMMUNOLOGY. 6636 04:07:19,810 --> 04:07:22,980 IT WAS PROBABLY THIS THICK. 6637 04:07:22,980 --> 04:07:24,715 THIS IS THE FUTURE! 6638 04:07:24,715 --> 04:07:26,250 YOU KNOW, THIS -- AND IT JUST -- 6639 04:07:26,250 --> 04:07:29,387 THE THINGS THAT WE'VE WORKED ON 6640 04:07:29,387 --> 04:07:30,388 FOR ABOUT 20 YEARS, IT REALLY 6641 04:07:30,388 --> 04:07:32,890 HASN'T WORKED OUT VERY WELL. 6642 04:07:32,890 --> 04:07:38,162 INTERESTING, THOUGH, ON VIRUS 6643 04:07:38,162 --> 04:07:39,964 SPREADING, ON THE VETERINARY 6644 04:07:39,964 --> 04:07:43,134 SIDE, WE WORKED ON A 6645 04:07:43,134 --> 04:07:44,902 BORDETELLA -- VACCINE FOR 6646 04:07:44,902 --> 04:07:46,670 PUPPIES, SO THERE'S THE 6647 04:07:46,670 --> 04:07:48,172 RESPIRATORY BACTERIAL DISEASE IN 6648 04:07:48,172 --> 04:07:50,474 DOGS, AND WE ACTUALLY DEVELOPED 6649 04:07:50,474 --> 04:07:52,877 A LICENSURE SO IT WAS ONSET OF 6650 04:07:52,877 --> 04:07:54,845 IMMUNITY IT WOULD BE LOOKED AT. 6651 04:07:54,845 --> 04:07:56,380 IF I KNOW THAT I HAVE TO TAKE -- 6652 04:07:56,380 --> 04:07:57,548 I'M GOING ON VACATION, I'M GOING 6653 04:07:57,548 --> 04:08:00,518 TO TAKE MY DOG TO THE KENNEL, IF 6654 04:08:00,518 --> 04:08:01,719 I VACCINATE IT AT 48 HOURS 6655 04:08:01,719 --> 04:08:03,587 BEFORE TAKING TO THE KENNEL, WE 6656 04:08:03,587 --> 04:08:05,856 SHOWED THAT THE VACCINE WAS 6657 04:08:05,856 --> 04:08:07,825 EFFICACIOUS IN PROTECTING THE 6658 04:08:07,825 --> 04:08:08,726 ANIMAL FROM GETTING THAT 6659 04:08:08,726 --> 04:08:11,662 INFECTION. 6660 04:08:11,662 --> 04:08:12,496 THINKING ABOUT THESE 6661 04:08:12,496 --> 04:08:13,130 TRANSMISSION STUDYS THAT HAVE 6662 04:08:13,130 --> 04:08:14,932 BEEN TALKED ABOUT, THAT'S KIND 6663 04:08:14,932 --> 04:08:16,534 OF COOL, BUT THERE WAS AN ONSET 6664 04:08:16,534 --> 04:08:18,202 OF IMMUNITY, WE HAD THE CLAIM, 6665 04:08:18,202 --> 04:08:18,536 48 HOURS. 6666 04:08:18,536 --> 04:08:20,638 SO THERE IS MUCOSAL ANTIBODY 6667 04:08:20,638 --> 04:08:23,808 COMING UP VERY RAPIDLY. 6668 04:08:23,808 --> 04:08:24,542 THAT'S IN A DOG. 6669 04:08:24,542 --> 04:08:26,644 I DON'T KNOW IF THEY'RE MAGIC. 6670 04:08:26,644 --> 04:08:28,379 I THINK WE COULD -- THAT'S 6671 04:08:28,379 --> 04:08:29,046 PROBABLY THE DIRECTION I WOULD 6672 04:08:29,046 --> 04:08:32,216 GO FOR HUMAN VACCINES. 6673 04:08:32,216 --> 04:08:33,517 KIND OF ONE MORE LITTLE TRIVIA 6674 04:08:33,517 --> 04:08:36,353 HERE, SO THINKING ABOUT OKAY, 6675 04:08:36,353 --> 04:08:38,322 THE FLUMIST VACCINE. 6676 04:08:38,322 --> 04:08:39,657 I WILL OFTEN TEACH WHEN I'M 6677 04:08:39,657 --> 04:08:41,826 TALKING ABOUT VACCINES, SAFETY, 6678 04:08:41,826 --> 04:08:44,228 EFFICACY, SAFETY, EFFICACY. 6679 04:08:44,228 --> 04:08:49,066 A KILL VACCINE, VERY SAFE. 6680 04:08:49,066 --> 04:08:51,502 -- ADMINISTERED, DEVELOPS 6681 04:08:51,502 --> 04:08:54,171 SOMETIMES LIFELONG SYSTEMIC 6682 04:08:54,171 --> 04:08:56,807 IMMUNITY, NOTHING AT THE MUCOSAL 6683 04:08:56,807 --> 04:08:57,708 SURFACE. 6684 04:08:57,708 --> 04:09:00,611 FLUMIST VACCINE, ADMINISTERED MU 6685 04:09:00,611 --> 04:09:04,648 KOMUCOSALLY, ADMINISTERS VERY GD 6686 04:09:04,648 --> 04:09:06,717 IGA TYPE MUCOSAL SURFACES, BUT 6687 04:09:06,717 --> 04:09:08,586 THE MUCOSAL IMMUNE SYSTEM IS 6688 04:09:08,586 --> 04:09:09,353 SHORT-LIVED. 6689 04:09:09,353 --> 04:09:13,290 YOU KNOW, SIX MONTHS A YEAR. 6690 04:09:13,290 --> 04:09:15,025 SO I'D HAVE TO KEEP GETTING 6691 04:09:15,025 --> 04:09:15,826 VACCINATED OVER AND OVER AGAIN 6692 04:09:15,826 --> 04:09:17,728 TO HAVE THAT MUCOSAL ANTIBODY 6693 04:09:17,728 --> 04:09:18,195 THERE. 6694 04:09:18,195 --> 04:09:20,264 SO WE GET SAFETY, EFFICACY. 6695 04:09:20,264 --> 04:09:21,832 I TEACH IN THE VET SCHOOL, I 6696 04:09:21,832 --> 04:09:25,069 TELL THE VETS, YOU NEED TO 6697 04:09:25,069 --> 04:09:25,936 TALK -- WHAT IS YOUR PATIENT 6698 04:09:25,936 --> 04:09:27,571 GOING TO NEED, SAFETY AND 6699 04:09:27,571 --> 04:09:28,973 EFFICACY, YOUNG ANIMALS, OLDER 6700 04:09:28,973 --> 04:09:30,407 ANIMALS. 6701 04:09:30,407 --> 04:09:31,775 I DON'T KNOW IF THAT ANSWERED 6702 04:09:31,775 --> 04:09:33,611 THE QUESTION, BUT -- 6703 04:09:33,611 --> 04:09:38,082 >> ANY OTHER QUESTIONS? 6704 04:09:38,082 --> 04:09:41,118 I THINK WE THEN ARE AT PERFECT 6705 04:09:41,118 --> 04:09:42,553 TIMING FOR A BREAK. 6706 04:09:42,553 --> 04:09:44,622 WAS IT 10 MINUTES, 20 MINUTES? 6707 04:09:44,622 --> 04:09:46,490 2:30. 6708 04:09:46,490 --> 04:09:47,691 IS THAT RIGHT? 6709 04:09:47,691 --> 04:09:48,559 OKAY, GREAT. 6710 04:09:48,559 --> 04:09:49,827 THANK YOU BOTH TO THE SPEAKERS. 6711 04:09:49,827 --> 04:09:50,561 THANK YOU. 6712 04:09:50,561 --> 04:09:53,745 [APPLAUSE] 6713 04:09:55,449 --> 04:09:56,917 >> WE'RE GOING TO GO AHEAD AND 6714 04:09:56,917 --> 04:09:59,553 GET STARTED ON OUR LAST SESSION 6715 04:09:59,553 --> 04:10:03,924 OR LAST PART OF THIS SESSION FOR 6716 04:10:03,924 --> 04:10:05,760 THE SMALL ANIMAL MODELS 6717 04:10:05,760 --> 04:10:06,027 WORKSHOP. 6718 04:10:06,027 --> 04:10:08,362 SO WE HAVE A PANEL DISCUSSION, 6719 04:10:08,362 --> 04:10:09,697 AND I'M GOING TO ASK EVERY 6720 04:10:09,697 --> 04:10:11,232 MEMBER OF THE PANEL TO FIRST 6721 04:10:11,232 --> 04:10:12,133 INTRODUCE THEMSELVES AND THEN I 6722 04:10:12,133 --> 04:10:15,303 KNOW A NUMBER OF THEM HAVE 6723 04:10:15,303 --> 04:10:18,172 SLIDES. 6724 04:10:18,172 --> 04:10:19,907 SO WE'LL GO DOWN THE ROW, 6725 04:10:19,907 --> 04:10:21,108 INTRODUCE, AND WE'LL START WITH 6726 04:10:21,108 --> 04:10:21,442 PRESENTATIONS. 6727 04:10:21,442 --> 04:10:23,644 THANK YOU. 6728 04:10:23,644 --> 04:10:24,945 >> GOOD AFTERNOON, EVERYONE. 6729 04:10:24,945 --> 04:10:26,580 MY NAME IS JOY LIU. 6730 04:10:26,580 --> 04:10:30,384 I'M A PROGRAM OFFICER FROM BASIC 6731 04:10:30,384 --> 04:10:31,452 IMMUNOLOGY BRANCH IN THE 6732 04:10:31,452 --> 04:10:33,454 DIVISION OF ALLERGY, IMMUNOLOGY 6733 04:10:33,454 --> 04:10:36,624 AND TRANSPLANTATION OF NIAID. 6734 04:10:36,624 --> 04:10:37,992 >> MY NAME IS MICHELLE ARNOLD. 6735 04:10:37,992 --> 04:10:39,627 I'M A PROGRAM OFFICER IN THE 6736 04:10:39,627 --> 04:10:42,630 DIVISION OF MICROBIOLOGY AND 6737 04:10:42,630 --> 04:10:45,499 INFECTIOUS DISEASES AT NIAID. 6738 04:10:45,499 --> 04:10:47,568 >> I'M ERIC STEMMY, I'M ALSO IN 6739 04:10:47,568 --> 04:10:49,070 THE DIVISION OF MICROBIOLOGY AND 6740 04:10:49,070 --> 04:10:50,438 INFECTIOUS DISEASES IN THE 6741 04:10:50,438 --> 04:10:51,639 RESPIRATORY DISEASES BRANCH, AND 6742 04:10:51,639 --> 04:10:52,840 I'M THE TEAM LEAD FOR THE 6743 04:10:52,840 --> 04:10:55,009 CENTERS OF EXCELLENCE FOR 6744 04:10:55,009 --> 04:10:56,177 INFLUENZA RESEARCH AND RESPONSE. 6745 04:10:56,177 --> 04:11:03,551 >> STACEY SCHULTZ-CHERRY, I AM 6746 04:11:03,551 --> 04:11:05,086 AT ST. JUDE CHILDREN'S RESEARCH 6747 04:11:05,086 --> 04:11:05,886 HOSPITAL. 6748 04:11:05,886 --> 04:11:10,758 >> SO FIRST I WOULD LIKE TO 6749 04:11:10,758 --> 04:11:13,627 INTRODUCE OUR SBIR REGION 6750 04:11:13,627 --> 04:11:14,095 DEVELOPMENT PROGRAM. 6751 04:11:14,095 --> 04:11:15,596 IF YOU CAN SEE THE SLIDES, IT'S 6752 04:11:15,596 --> 04:11:25,806 OVER THERE. 6753 04:11:28,776 --> 04:11:30,244 SO THIS PROGRAM ACTUALLY STARTED 6754 04:11:30,244 --> 04:11:30,778 IN 2018. 6755 04:11:30,778 --> 04:11:33,748 THE GOAL IS TO DEVELOP AND 6756 04:11:33,748 --> 04:11:37,585 VALIDATE RELIABLE ANTIBODIES FOR 6757 04:11:37,585 --> 04:11:39,653 TRACKING IMMUNE RESPONSE AND 6758 04:11:39,653 --> 04:11:43,057 IDENTIFY IMMUNE CELLS IN 6759 04:11:43,057 --> 04:11:44,992 UNDERREPRESENTED MAMMALIAN 6760 04:11:44,992 --> 04:11:50,364 MODELS AND NON-MAMMALIAN MODELS. 6761 04:11:50,364 --> 04:11:53,934 SO WHEN WE TALK ABOUT 6762 04:11:53,934 --> 04:11:56,070 NON-MAMMALIAN MODELS, WE MEAN 6763 04:11:56,070 --> 04:11:59,540 ARTHROPOD, AMPHIBIAN, FISH, 6764 04:11:59,540 --> 04:12:04,245 NEMATODE, MARINE ECHINOID, AND 6765 04:12:04,245 --> 04:12:06,013 BY UNDERREPRESENTED MAMMALIAN 6766 04:12:06,013 --> 04:12:08,649 MODELS WE MEAN GUINEA PIG, 6767 04:12:08,649 --> 04:12:10,851 FERRET, BAT, MINK, HAMSTER, 6768 04:12:10,851 --> 04:12:15,222 BIRD, COTTON RAT, CAT, RABBIT 6769 04:12:15,222 --> 04:12:17,191 AND MARMOSETS. 6770 04:12:17,191 --> 04:12:19,360 THIS PROGRAM HAS BEEN SUPPORTED 6771 04:12:19,360 --> 04:12:20,895 BY THE DIVISION OF ALLERGY, 6772 04:12:20,895 --> 04:12:22,296 IMMUNOLOGY AND TRANSPLANTATION, 6773 04:12:22,296 --> 04:12:24,498 THE NIAID, AND WE USE SBIR AS A 6774 04:12:24,498 --> 04:12:31,305 CONTRACT MECHANISM. 6775 04:12:31,305 --> 04:12:34,241 SO OVER THE YEARS WE HAVE FUNDED 6776 04:12:34,241 --> 04:12:35,443 220 PROJECTS. 6777 04:12:35,443 --> 04:12:41,148 YOU CAN SEE THE FUNDING 6778 04:12:41,148 --> 04:12:44,418 PROPOSALS ACCORDING TO THE 6779 04:12:44,418 --> 04:12:46,720 TARGETED SPECIES. 6780 04:12:46,720 --> 04:12:49,890 OVER THE YEARS WE HAVE HAD SIX 6781 04:12:49,890 --> 04:12:52,827 GUINEA PIG PROJECTS, ACTUALLY 6782 04:12:52,827 --> 04:12:57,097 THREE COMPLETED AND THREE 6783 04:12:57,097 --> 04:13:00,935 ONGOING, ANTIBODIES PRODUCED IN 6784 04:13:00,935 --> 04:13:04,772 THE RABBIT AND THE MOUSE AND 6785 04:13:04,772 --> 04:13:08,742 PENDING APPLICATIONS, ACTUALLY 6786 04:13:08,742 --> 04:13:11,445 IT'S A FLOW CYTOMETRY AND ALSO 6787 04:13:11,445 --> 04:13:14,949 YOU CAN ALSO SEE HAMSTER AND THE 6788 04:13:14,949 --> 04:13:18,018 FERRET ARE POPULAR SPECIES IN 6789 04:13:18,018 --> 04:13:18,519 OUR PROGRAM. 6790 04:13:18,519 --> 04:13:22,189 WE HAVE TWO COMPLETED PROJECTS 6791 04:13:22,189 --> 04:13:25,392 AND TWO ONGOING PROJECTS, THE 6792 04:13:25,392 --> 04:13:28,996 ANTIBODIES ALSO PRODUCE IN THE 6793 04:13:28,996 --> 04:13:32,066 IMMUNIZED MICE AND ALSO RABBITS. 6794 04:13:32,066 --> 04:13:36,237 WE ACTUALLY PLAN TO USE THESE 6795 04:13:36,237 --> 04:13:39,740 ANTIBODIES TO SUPPORT FLOW 6796 04:13:39,740 --> 04:13:42,343 CYTOMETRY EVEN THOUGH 6797 04:13:42,343 --> 04:13:46,514 FLUORESCENCE -- AND ALSO FOR THE 6798 04:13:46,514 --> 04:13:49,116 FERRETS PROJECTS, WE HAVE THREE 6799 04:13:49,116 --> 04:13:52,853 COMPLETED, ONCE WE USE THEM IN 6800 04:13:52,853 --> 04:13:56,457 THE SAME APPLICATIONS. 6801 04:13:56,457 --> 04:13:59,293 ADDITIONALLY, WE ALSO HAVE SOME 6802 04:13:59,293 --> 04:14:02,062 MIXED PROGRAMS, PROJECTS, ET 6803 04:14:02,062 --> 04:14:04,031 CETERA, FOR FERRET AND GUINEA 6804 04:14:04,031 --> 04:14:04,265 PIG. 6805 04:14:04,265 --> 04:14:08,636 WE ALSO HAVE ONE LIKE 6806 04:14:08,636 --> 04:14:13,440 NON-SPECIES IN THIS PROJECT -- 6807 04:14:13,440 --> 04:14:14,875 NINE SPECIES IN THIS PROJECT, 6808 04:14:14,875 --> 04:14:20,648 PEOPLE TRIED TO GENERATE -- 6809 04:14:20,648 --> 04:14:23,050 ANTIBODIES TO RECOGNIZE IMMUNE 6810 04:14:23,050 --> 04:14:23,851 CELLS IN DIFFERENT SPECIES. 6811 04:14:23,851 --> 04:14:26,687 YOU CAN ALSO SEE WE HAVE SOME 6812 04:14:26,687 --> 04:14:29,223 ANTIBODIES LIKE RABBIT, SWINE, 6813 04:14:29,223 --> 04:14:34,461 AND ZEBRAFISH OTHER SPECIES TOO. 6814 04:14:34,461 --> 04:14:39,700 SO THIS SLIDE SHOWS COMPLETED 6815 04:14:39,700 --> 04:14:42,336 ANTIBODIES FOR 26 FERRET 6816 04:14:42,336 --> 04:14:42,770 ANTIGENS. 6817 04:14:42,770 --> 04:14:48,676 WE HAVE CD3, CD11C, CD19, CD56. 6818 04:14:48,676 --> 04:14:52,012 THESE ANTIBODIES PRODUCED BY 6819 04:14:52,012 --> 04:14:53,247 SILVER LAKE RESEARCH CORPORATION 6820 04:14:53,247 --> 04:14:58,419 AND THE ANTIBODIES HAVE BEEN -- 6821 04:14:58,419 --> 04:15:01,488 BY FLOW CYTOMETRY AND 6822 04:15:01,488 --> 04:15:03,557 IMMUNOFLUORESCENCE USING THE 6823 04:15:03,557 --> 04:15:04,491 FERRET PBMCs. 6824 04:15:04,491 --> 04:15:08,295 WE ALSO HAVE LIKE CD ANTIBODIES 6825 04:15:08,295 --> 04:15:13,867 AGAINST CD56, CD64, CD86, AND 6826 04:15:13,867 --> 04:15:15,636 THEY ALSO HAVE BEEN TESTED BY 6827 04:15:15,636 --> 04:15:18,572 USING THE FERRET PBMC CELLS AND 6828 04:15:18,572 --> 04:15:21,742 THE COMPANY PRODUCING THE 6829 04:15:21,742 --> 04:15:25,045 ANTIBODIES IS THE AMPERSAND 6830 04:15:25,045 --> 04:15:26,113 BIOSCIENCES. 6831 04:15:26,113 --> 04:15:28,749 I ALREADY PUT THE NAMES OF THE 6832 04:15:28,749 --> 04:15:31,318 CONTACT PERSONS SO YOU CAN -- IF 6833 04:15:31,318 --> 04:15:33,153 YOU NEED, YOU CAN CONTACT THEM 6834 04:15:33,153 --> 04:15:34,355 DIRECTLY. 6835 04:15:34,355 --> 04:15:38,859 IN ADDITION TO THE SURFACE 6836 04:15:38,859 --> 04:15:41,128 MARKERS, WE ALSO HAVE 11 6837 04:15:41,128 --> 04:15:44,531 CYTOKINES PRODUCED -- THE 6838 04:15:44,531 --> 04:15:48,369 ANTIBODY AGAINST CYTOKINES BY 6839 04:15:48,369 --> 04:15:49,570 AMPERSAND. 6840 04:15:49,570 --> 04:15:52,840 SO THESE ANTIBODIES HAVE BEEN 6841 04:15:52,840 --> 04:16:01,715 TESTED IN -- USING THE -- FROM 6842 04:16:01,715 --> 04:16:04,918 STIMULATED FERRET PBMCs OR 6843 04:16:04,918 --> 04:16:05,419 WHOLE BLOOD CELLS. 6844 04:16:05,419 --> 04:16:10,691 IN THE PARALLEL AM P AMPERSAND 6845 04:16:10,691 --> 04:16:13,761 ALSO -- DIFFERENT CYTOKINE -- TO 6846 04:16:13,761 --> 04:16:18,132 DIFFERENT PANELS PRODUCED THEM 6847 04:16:18,132 --> 04:16:21,101 IN -- CAGE AND ALREADY TESTED 6848 04:16:21,101 --> 04:16:27,141 THEM USING THE NASAL -- FERRETS. 6849 04:16:27,141 --> 04:16:31,845 ADDITIONALLY WE ALSO HAVE 6850 04:16:31,845 --> 04:16:33,180 AVANGGEN, ANOTHER CONTRACTOR WE 6851 04:16:33,180 --> 04:16:34,148 ACTUALLY HAVE UNDER OUR PROGRAM 6852 04:16:34,148 --> 04:16:35,582 AND THEY ARE PRODUCING 6853 04:16:35,582 --> 04:16:37,584 ADDITIONAL ANTIBODIES FOR 6854 04:16:37,584 --> 04:16:44,892 CYTOKINES SUCH AS L1 BETA, L6, 6855 04:16:44,892 --> 04:16:49,897 L8, AND IT HAS BEEN TESTED USING 6856 04:16:49,897 --> 04:16:51,765 THE SUPER NATANT FROM STIMULATED 6857 04:16:51,765 --> 04:16:55,502 FERRET PBMCs. 6858 04:16:55,502 --> 04:16:58,372 AND AVANTGEN ALSO PRODUCED TWO 6859 04:16:58,372 --> 04:17:00,007 RECEPTOR ANTIBODIES FOR 6860 04:17:00,007 --> 04:17:04,144 L1 RECEPTOR AND THE TPNF AND 6861 04:17:04,144 --> 04:17:10,184 TESTED BY FL FLOW CYTOMETRY. 6862 04:17:10,184 --> 04:17:16,190 THEN WE ALSO HAVE FOUR COMPLETED 6863 04:17:16,190 --> 04:17:21,795 HAMSTER ANTIBODIES AGAINST CD16, 6864 04:17:21,795 --> 04:17:25,065 CD64, CD69 AND CD115. 6865 04:17:25,065 --> 04:17:28,869 AND THESE ANTIBODIES PRODUCED BY 6866 04:17:28,869 --> 04:17:29,770 SILVER LAKE RESEARCH 6867 04:17:29,770 --> 04:17:31,205 CORPORATION. 6868 04:17:31,205 --> 04:17:35,275 THEY TESTED THE FINDING OF THE 6869 04:17:35,275 --> 04:17:40,848 ANTIBODIES TO HAMSTER PBMCs. 6870 04:17:40,848 --> 04:17:43,584 WE HAVE ADDITIONAL ANTIBODIES IN 6871 04:17:43,584 --> 04:17:43,917 THE PIPELINE. 6872 04:17:43,917 --> 04:17:48,422 YOU CAN SEE WE HAVE ONE FERRET 6873 04:17:48,422 --> 04:17:50,924 ANTIGEN ANTIBODIES AGAINST 6874 04:17:50,924 --> 04:17:51,458 CD11C. 6875 04:17:51,458 --> 04:17:56,196 IT HAS BEEN TESTED BY USING THE 6876 04:17:56,196 --> 04:17:59,566 FLOW CYTOMETRY AND FLUORESCENCE 6877 04:17:59,566 --> 04:18:02,536 STAINING USING FERRET PBMCs 6878 04:18:02,536 --> 04:18:04,838 AND THE SILVER LAKE RESEARCH 6879 04:18:04,838 --> 04:18:08,008 CORPORATION IS PRODUCER, AND WE 6880 04:18:08,008 --> 04:18:12,179 HAVE 29 HAMSTER ANTIGEN 6881 04:18:12,179 --> 04:18:15,249 ANTIBODIES IN THE PIPELINE. 6882 04:18:15,249 --> 04:18:18,418 AND THE FOURTH ONE, FOURTH SET 6883 04:18:18,418 --> 04:18:21,688 ANTIBODIES INCLUDING -- 6884 04:18:21,688 --> 04:18:26,760 CYTOKINE -- GENES AND ALSO 6885 04:18:26,760 --> 04:18:28,595 FOUR -- MARKERS AND THESE 6886 04:18:28,595 --> 04:18:30,264 ANTIBODIES HAVE BEEN TESTED 6887 04:18:30,264 --> 04:18:35,969 USING LEUM NEXT, ELISA OR FLOW 6888 04:18:35,969 --> 04:18:37,271 CYTOMETRY IMMUNOFLUORESCENCE 6889 04:18:37,271 --> 04:18:41,441 STAINING VALIDATED BY USING THE 6890 04:18:41,441 --> 04:18:43,844 TRANSFECTED AND NON-TRANSFECTED 6891 04:18:43,844 --> 04:18:48,215 CELL LINES OR HAMSTER SERUM, 6892 04:18:48,215 --> 04:18:49,883 CELL AND TISSUE SAMPLES AFTER 6893 04:18:49,883 --> 04:18:56,023 STIMULATION OR INFECTION. 6894 04:18:56,023 --> 04:18:59,393 THESE ANTIBODIES ARE PRODUCED BY 6895 04:18:59,393 --> 04:19:01,395 AMPERSAND BIOSCIENCES. 6896 04:19:01,395 --> 04:19:03,130 AND WE HAVE ONE ADDITIONAL 6897 04:19:03,130 --> 04:19:05,766 ANTIBODIES PRODUCED BY SILVER 6898 04:19:05,766 --> 04:19:09,603 LAKE THAT'S CD32 AND HAS BEEN 6899 04:19:09,603 --> 04:19:11,805 VALIDATED BY IMMUNOFLUORESCENT 6900 04:19:11,805 --> 04:19:17,277 STAINING. 6901 04:19:17,277 --> 04:19:20,681 WE HAVE ANOTHER GROUP MA MAKING 6902 04:19:20,681 --> 04:19:25,252 SOME ADDITIONAL ANTIBO KEYS F AR 6903 04:19:25,252 --> 04:19:28,755 HAMSTERS SUCH AS CD8 ALPHA, 6904 04:19:28,755 --> 04:19:33,660 CD3E, IL-17, ISG15, CCL2, CCL3, 6905 04:19:33,660 --> 04:19:40,601 IL-6, IFNA RECEPTOR, LY6G, 6906 04:19:40,601 --> 04:19:46,506 CD169, TMEM119 AND CD16 AND 6907 04:19:46,506 --> 04:19:51,011 P2RY12, CX3CR1, AND THEY HAVE 6908 04:19:51,011 --> 04:19:52,846 TESTED THE FINDING OF THE 6909 04:19:52,846 --> 04:19:56,683 ANTIBODIES TO THE HAMSTER PBMC 6910 04:19:56,683 --> 04:19:58,986 TISSUE SERUM/PLASMA WITH OR 6911 04:19:58,986 --> 04:20:01,622 WITHOUT THE INFECTION BY USING 6912 04:20:01,622 --> 04:20:07,561 FLOW CYTOMETRY, OR ELISA OR IHC, 6913 04:20:07,561 --> 04:20:08,161 WESTERN BLOT. 6914 04:20:08,161 --> 04:20:12,866 THIS COMPANY IS CALLED QOOLABS. 6915 04:20:12,866 --> 04:20:14,735 I HAVE INCLUDED THEIR 6916 04:20:14,735 --> 04:20:16,904 INFORMATION THERE FOR YOU TO 6917 04:20:16,904 --> 04:20:22,175 CONTACT. 6918 04:20:22,175 --> 04:20:23,543 SO THAT'S ALL FOR ME. 6919 04:20:23,543 --> 04:20:28,982 I'D LIKE TO MENTION THAT WE 6920 04:20:28,982 --> 04:20:30,083 ACTUALLY GREATLY APPRECIATE IF 6921 04:20:30,083 --> 04:20:31,718 YOU COULD LET US KNOW WHAT KIND 6922 04:20:31,718 --> 04:20:34,588 OF ADDITIONAL TARGETS AND 6923 04:20:34,588 --> 04:20:38,191 SPECIES YOU NEED TO ADVANCE THE 6924 04:20:38,191 --> 04:20:38,525 FIELD. 6925 04:20:38,525 --> 04:20:40,627 IF YOU HAVE ANY QUESTIONS OR ANY 6926 04:20:40,627 --> 04:20:43,363 COMMENTS OR ANY SUGGESTIONS, 6927 04:20:43,363 --> 04:20:44,364 PLEASE CONTACT ME. 6928 04:20:44,364 --> 04:20:45,565 I LEAVE MY EMAIL THERE. 6929 04:20:45,565 --> 04:20:51,471 WITH THAT, THANK YOU SO MUCH. 6930 04:20:51,471 --> 04:20:55,309 >> THANK YOU. 6931 04:20:55,309 --> 04:20:56,243 SHOULD WE JUST GO THROUGH AND DO 6932 04:20:56,243 --> 04:20:57,611 ALL THE PRESENTATIONS FIRST? 6933 04:20:57,611 --> 04:20:58,345 MICHELLE, OR -- 6934 04:20:58,345 --> 04:20:58,812 >> YEAH. 6935 04:20:58,812 --> 04:21:00,580 SO I JUST WANTED TO MENTION THAT 6936 04:21:00,580 --> 04:21:01,782 THE DIVISION OF MICROBIOLOGY AND 6937 04:21:01,782 --> 04:21:03,550 IP FORECASTTIOUS DISEASES HAS 6938 04:21:03,550 --> 04:21:06,520 ITS OWN PROGRAM FOR GENERATING 6939 04:21:06,520 --> 04:21:10,557 REAGENTS FOR PRE-CLINICAL MODELS 6940 04:21:10,557 --> 04:21:12,092 OF INFECTIOUS DISEASES. 6941 04:21:12,092 --> 04:21:13,093 SO WE'RE USING A CONTRACT 6942 04:21:13,093 --> 04:21:14,962 MECHANISM TO DEVELOP MONOCLONAL 6943 04:21:14,962 --> 04:21:16,029 KNOCKOUT ANTIBODIES, AND I'VE 6944 04:21:16,029 --> 04:21:18,799 JUST MADE A LIST OF THE ONES 6945 04:21:18,799 --> 04:21:19,766 THAT WE HAVE ALREADY MADE THAT 6946 04:21:19,766 --> 04:21:22,536 VA BEEN DEPOSITED INTO BEI, SOME 6947 04:21:22,536 --> 04:21:24,504 OF WHICH ARE PENDING, WHICH 6948 04:21:24,504 --> 04:21:25,605 MEANS THE PAPERWORK HAS BEEN 6949 04:21:25,605 --> 04:21:26,139 SUBMITTED. 6950 04:21:26,139 --> 04:21:28,342 THEY WILL BE AVAILABLE SOON. 6951 04:21:28,342 --> 04:21:30,978 SO EACH OF THESE MONOCLONAL 6952 04:21:30,978 --> 04:21:31,645 ANTIBODIES HAS BEEN DEVELOPED 6953 04:21:31,645 --> 04:21:34,281 WITH A CORRESPONDING KNOCK-IN 6954 04:21:34,281 --> 04:21:37,217 AND KNOCK-OUT CELL LINE SO WE 6955 04:21:37,217 --> 04:21:38,986 CAN ENSURE THAT THE ANTIBODY IS 6956 04:21:38,986 --> 04:21:39,619 RECOGNIZING THE TARGET OF 6957 04:21:39,619 --> 04:21:41,054 INTEREST AND NEGATIVE IN A CELL 6958 04:21:41,054 --> 04:21:44,257 LINE OF INTEREST AS WELL. 6959 04:21:44,257 --> 04:21:45,392 AND THE CERTIFICATE OF ANALYSIS 6960 04:21:45,392 --> 04:21:46,893 FOR EACH OF THESE ANTIBODIES AS 6961 04:21:46,893 --> 04:21:50,297 WELL AS THE CELL LINES ARE ON 6962 04:21:50,297 --> 04:21:52,432 THE BEI WEBSITE OR ARE AVAILABLE 6963 04:21:52,432 --> 04:21:53,467 ON THE BEI WEBSITE. 6964 04:21:53,467 --> 04:21:55,569 SO WE'RE DOING THIS FOR BOTH 6965 04:21:55,569 --> 04:21:57,104 FERRET AND SYRIAN HAMSTER 6966 04:21:57,104 --> 04:21:57,804 REAGENTS. 6967 04:21:57,804 --> 04:21:59,306 WE ALSO HAVE SEVERAL THAT ARE 6968 04:21:59,306 --> 04:22:01,274 STILL UNDERGOING SYNTHESIS. 6969 04:22:01,274 --> 04:22:03,677 WE DON'T KNOW THE OUTCOME YET 6970 04:22:03,677 --> 04:22:04,678 BECAUSE WE HAVEN'T GONE THROUGH 6971 04:22:04,678 --> 04:22:06,079 ALL THE STAGES BUT WE DO HAVE A 6972 04:22:06,079 --> 04:22:07,748 COUPLE OF ADDITIONAL ONES IN 6973 04:22:07,748 --> 04:22:09,583 DEVELOPMENT, WHICH I'VE LISTED 6974 04:22:09,583 --> 04:22:09,983 HERE. 6975 04:22:09,983 --> 04:22:11,885 IN THE PAST, WE'VE USED REQUEST 6976 04:22:11,885 --> 04:22:14,788 FOR INFORMATION OR RFI TO ASK 6977 04:22:14,788 --> 04:22:15,622 FOR INPUT. 6978 04:22:15,622 --> 04:22:17,491 OUR RFI IS CLOSED BECAUSE THIS 6979 04:22:17,491 --> 04:22:19,993 WAS INITIATED FOUR YEARS AGO. 6980 04:22:19,993 --> 04:22:21,895 SO IN THE FUTURE, IF WE CHOOSE 6981 04:22:21,895 --> 04:22:25,766 TO DO THIS AGAIN, WE WILL LIKELY 6982 04:22:25,766 --> 04:22:29,369 PUT OUR ANOTHER RFI AND TRY TO 6983 04:22:29,369 --> 04:22:30,270 MAKE EVERYBODY AWARE OF IT SO 6984 04:22:30,270 --> 04:22:33,073 YOU CAN PROVIDE INPUT AS TO THE 6985 04:22:33,073 --> 04:22:34,641 MOST NEEDED REAGENTS RELEVANT TO 6986 04:22:34,641 --> 04:22:38,378 YOU. 6987 04:22:38,378 --> 04:22:39,746 >> SO I JUST WANTED TO PLUG 6988 04:22:39,746 --> 04:22:40,981 BRIEFLY THE REAGENTS THAT HAVE 6989 04:22:40,981 --> 04:22:46,153 BEEN CREATED THROUGH THE CEIRR 6990 04:22:46,153 --> 04:22:46,887 NETWORK AND THE PREVIOUS 6991 04:22:46,887 --> 04:22:47,220 GENERATION. 6992 04:22:47,220 --> 04:22:48,221 THESE ARE ALL AVAILABLE ON OUR 6993 04:22:48,221 --> 04:22:48,555 WEBSITE. 6994 04:22:48,555 --> 04:22:49,990 YOU SEE THE LINK THERE. 6995 04:22:49,990 --> 04:22:51,625 A VARIETY OF ANTIBODIES, BLOOD 6996 04:22:51,625 --> 04:22:55,929 MATERIALS, CELLS, PROTEIN, RES 6997 04:22:55,929 --> 04:22:57,798 PIER SAMPLES AND TISSUES AS WELL 6998 04:22:57,798 --> 04:22:59,633 AS FERRET REAGENTS AS WELL 6999 04:22:59,633 --> 04:23:01,301 MOSTLY PRODUCED BY STACEY THERE 7000 04:23:01,301 --> 04:23:04,905 AT ST. JUDE. 7001 04:23:04,905 --> 04:23:06,506 THOSE OF YOU THAT HAVE USED THE 7002 04:23:06,506 --> 04:23:07,574 WEBSITE, WE ARE GOING TO BE 7003 04:23:07,574 --> 04:23:09,743 GETTING READY TO UPDATE AND 7004 04:23:09,743 --> 04:23:15,248 REVAMP THE WEBSITE, SO ONE, IF 7005 04:23:15,248 --> 04:23:16,450 YOU SEE THINGS MISSING YOU WOULD 7006 04:23:16,450 --> 04:23:18,085 WANT TO SEE AND TWO, TO SAY IT 7007 04:23:18,085 --> 04:23:19,386 WOULD BE REALLY GREAT IF WE 7008 04:23:19,386 --> 04:23:20,720 COULD DO THIS WITH WHAT YOU 7009 04:23:20,720 --> 04:23:21,621 HAVE, PLEASE REACH OUT TO ME AND 7010 04:23:21,621 --> 04:23:23,023 WE CAN TRY AND GET THAT IN THE 7011 04:23:23,023 --> 04:23:24,491 PIPELINE AS WE REVISE THE 7012 04:23:24,491 --> 04:23:28,995 WEBSITE A LITTLE BIT. 7013 04:23:28,995 --> 04:23:29,863 >> GREAT, THANK YOU. 7014 04:23:29,863 --> 04:23:31,531 I THINK STACEY HAD A QUESTION. 7015 04:23:31,531 --> 04:23:36,336 >> MY QUESTION WAS FOR JOY. 7016 04:23:36,336 --> 04:23:37,671 IN TERMS OF VALIDATION, HOW WERE 7017 04:23:37,671 --> 04:23:38,738 THE VALIDATIONS DONE? 7018 04:23:38,738 --> 04:23:41,074 WAS IT JUST DOING FLOW CYTOMETRY 7019 04:23:41,074 --> 04:23:43,276 WITH FERRET, HAMSTER PBMCs AND 7020 04:23:43,276 --> 04:23:45,011 YOU GET A SHIFT SO YOU ASSUME 7021 04:23:45,011 --> 04:23:48,849 THAT YOU'RE ACTUALLY RECOGNIZING 7022 04:23:48,849 --> 04:23:49,950 THE TARGET OF INTEREST, OR IS IT 7023 04:23:49,950 --> 04:23:51,818 LIKE WHAT WE'RE DOING, WHICH IS 7024 04:23:51,818 --> 04:23:53,720 HAVING TO USE KNOCK-IN, 7025 04:23:53,720 --> 04:23:55,021 KNOCK-OUT CELL LINES TO ENSURE 7026 04:23:55,021 --> 04:23:56,490 THAT THE TARGET IS ACCURATE? 7027 04:23:56,490 --> 04:23:59,192 >> THAT'S A GREAT QUESTION. 7028 04:23:59,192 --> 04:24:02,496 THIS PROGRAM AS I SAID IS NOT 7029 04:24:02,496 --> 04:24:04,564 ESTABLISHED TOO LONG AGO, SO AT 7030 04:24:04,564 --> 04:24:08,301 VERY BEGINNING, WE HAVE LOW BARS 7031 04:24:08,301 --> 04:24:12,139 OF -- TO COME INTO THE PROGRAM. 7032 04:24:12,139 --> 04:24:14,774 WITH THE PROGRESS OF THE PROG 7033 04:24:14,774 --> 04:24:16,309 PROGRAM, OUR REQUIREMENT FOR 7034 04:24:16,309 --> 04:24:18,945 PHASE ONE STUDIES COME MORE AND 7035 04:24:18,945 --> 04:24:20,147 MORE STRINGENT. 7036 04:24:20,147 --> 04:24:22,015 WE ACTUALLY IN THE PAST, WE DO 7037 04:24:22,015 --> 04:24:26,319 ASK THEM TO SHOW THE SPECIFI 7038 04:24:26,319 --> 04:24:27,521 SPECIFICITY, BUT WE DID NOT ASK 7039 04:24:27,521 --> 04:24:31,358 THEM TO DO LIKE THE AFFINITY 7040 04:24:31,358 --> 04:24:35,629 ASSAYS, ESPECIALLY USING LIKE A 7041 04:24:35,629 --> 04:24:36,830 BELL SENSOR TO TEST THE 7042 04:24:36,830 --> 04:24:38,932 AFFINITY, NOW WE REQUEST THEY 7043 04:24:38,932 --> 04:24:40,767 HAVE TO DO THE AFFINITY ASSAYS. 7044 04:24:40,767 --> 04:24:46,406 WE ALSO ASK THEM TO DO KNOCK-IN, 7045 04:24:46,406 --> 04:24:47,674 KNOCK-OUT CELL LINES. 7046 04:24:47,674 --> 04:24:50,443 ADDITIONALLY, WE ASK THEM TO USE 7047 04:24:50,443 --> 04:24:52,512 THE COMPUTATION ASSAY USING 7048 04:24:52,512 --> 04:24:55,682 THEIR RECOMBINANT PROTEINS TO 7049 04:24:55,682 --> 04:24:58,885 BLOCK THE FUNDING OF THE 7050 04:24:58,885 --> 04:25:02,756 ANTIBODIES TO THE -- ANTIGENS. 7051 04:25:02,756 --> 04:25:05,892 SO WE REALIZE, YOU KNOW, IT 7052 04:25:05,892 --> 04:25:10,830 NEEDS TO BE MORE STRINGENT WHEN 7053 04:25:10,830 --> 04:25:15,335 WE MAKE SURE THE ANTIBODIES TO 7054 04:25:15,335 --> 04:25:18,638 BE MORE SPECIFIC, SO THAT'S WHY 7055 04:25:18,638 --> 04:25:21,374 WE HAVE ADDED NEW REQUIREMENTS 7056 04:25:21,374 --> 04:25:27,480 INTO THE PROGRAM. 7057 04:25:27,480 --> 04:25:29,049 I JUST WANT TO LET EVERYONE 7058 04:25:29,049 --> 04:25:35,789 KNOW, I PRINT SOME INFORMATION 7059 04:25:35,789 --> 04:25:37,224 HERE IF YOU WANT TO KNOW THE 7060 04:25:37,224 --> 04:25:38,425 ANTIBODY TARGETS WE HAVE, PLEASE 7061 04:25:38,425 --> 04:25:41,962 COME TO GET THE PAPER AFTER THE 7062 04:25:41,962 --> 04:25:46,866 SESSION. 7063 04:25:46,866 --> 04:25:49,336 >> THERE'S A COMMENT IN THE CHAT 7064 04:25:49,336 --> 04:25:56,476 BOX FROM LAURIE STEPHEN, WE HAVE 7065 04:25:56,476 --> 04:25:58,345 DONE WESTERNS ON THE EXPRESSED 7066 04:25:58,345 --> 04:25:59,479 PROTEINS AND CROSS REACTIVITY 7067 04:25:59,479 --> 04:26:01,648 WITH PROTEINS EXPRESSED IN THE 7068 04:26:01,648 --> 04:26:03,950 SAME CELL LINE, ALSO BETA TEST 7069 04:26:03,950 --> 04:26:05,252 WITH FERRETS THAT HAD THE FLU. 7070 04:26:05,252 --> 04:26:07,387 >> IS THIS RESPONSE TO THE ONE 7071 04:26:07,387 --> 04:26:08,455 WITH SBIR? 7072 04:26:08,455 --> 04:26:09,489 >> UH-HUH. 7073 04:26:09,489 --> 04:26:11,358 >> GO AHEAD. 7074 04:26:11,358 --> 04:26:13,660 >> SO ARE THERE ANY CENTRALIZED 7075 04:26:13,660 --> 04:26:15,395 EFFORTS TO SEE ANY CROSS 7076 04:26:15,395 --> 04:26:17,163 REACTIVITY WITH ANTIBODIES THAT 7077 04:26:17,163 --> 04:26:23,303 ARE ALREADY OUT THERE, LIKE 7078 04:26:23,303 --> 04:26:24,137 ANTIMOUSE, ANTIHAMSTER, ET 7079 04:26:24,137 --> 04:26:24,371 CETERA? 7080 04:26:24,371 --> 04:26:26,373 >> SO I CAN ADDRESS THAT. 7081 04:26:26,373 --> 04:26:27,507 WE'VE DONE -- AND I THINK 7082 04:26:27,507 --> 04:26:28,475 PROBABLY EVERYBODY IN THIS ROOM 7083 04:26:28,475 --> 04:26:29,909 HAS DONE A LOT OF THAT, IS ORDER 7084 04:26:29,909 --> 04:26:32,445 A COMMERCIAL ANTIBODY THAT'S 7085 04:26:32,445 --> 04:26:34,180 SUPPOSEDLY WORKS ACROSS MULTIPLE 7086 04:26:34,180 --> 04:26:35,715 SPECIES OR TO CONSERVE TARGET 7087 04:26:35,715 --> 04:26:40,420 AND YOU TEST IT. 7088 04:26:40,420 --> 04:26:41,187 MOST OF THE TIME IT DOESN'T 7089 04:26:41,187 --> 04:26:41,454 WORK. 7090 04:26:41,454 --> 04:26:44,057 I DON'T KNOW OF A CENTRALIZED 7091 04:26:44,057 --> 04:26:44,958 PLACE AND THAT'S SOMETHING WE 7092 04:26:44,958 --> 04:26:46,092 SHOULD THINK ABOUT WHERE YOU 7093 04:26:46,092 --> 04:26:47,060 ACTUALLY SHARE THAT DATA BECAUSE 7094 04:26:47,060 --> 04:26:48,295 YOU DON'T PUBLISH IT UNLESS 7095 04:26:48,295 --> 04:26:50,130 YOU'RE REALLY DOING AN ANTIBODY 7096 04:26:50,130 --> 04:26:51,164 VALIDATION PAPER. 7097 04:26:51,164 --> 04:26:54,334 BULL IT WOULD SAVE EVERYBODY, 7098 04:26:54,334 --> 04:26:55,535 THE COMMUNITY, SO MUCH TIME TO 7099 04:26:55,535 --> 04:26:56,970 HAVE ACCESS TO THAT INFORMATION 7100 04:26:56,970 --> 04:27:00,507 SO THAT YOU KNOW I TESTED THIS 7101 04:27:00,507 --> 04:27:02,242 USING THESE ASSAYS USING THESE 7102 04:27:02,242 --> 04:27:06,579 CELLS AND IN OUR HANDS, RIGHT? 7103 04:27:06,579 --> 04:27:09,382 BECAUSE THEN COW YOU COULD GO D 7104 04:27:09,382 --> 04:27:10,917 DO IT IN YOUR OWN HANDS OR SAY 7105 04:27:10,917 --> 04:27:12,052 THIS IS EXACTLY WHAT WE WANTED 7106 04:27:12,052 --> 04:27:14,020 TO DO AND THERE'S NO POINT. 7107 04:27:14,020 --> 04:27:15,989 TESTING SOME OF THESE ANTIBODIES 7108 04:27:15,989 --> 04:27:18,658 SPECIFICALLY DEVELOPING -- WHERE 7109 04:27:18,658 --> 04:27:19,759 DEVELOPING FOR FERRET, WE WILL 7110 04:27:19,759 --> 04:27:21,161 WANT TO SEE IF THEY CROSS REACT 7111 04:27:21,161 --> 04:27:22,495 WITH HAMSTER SO WE KNOW THAT UP 7112 04:27:22,495 --> 04:27:25,498 FRONT. 7113 04:27:25,498 --> 04:27:27,133 >> SO ONE OF THE THINGS WE'VE 7114 04:27:27,133 --> 04:27:28,768 RECENTLY LAUNCHED IS CALLED FLU 7115 04:27:28,768 --> 04:27:29,302 HUB. 7116 04:27:29,302 --> 04:27:30,637 IT'S INTENDED TO BE A WEBSITE 7117 04:27:30,637 --> 04:27:32,272 THAT SORT OF CENTRALIZES ALL OF 7118 04:27:32,272 --> 04:27:33,940 NIAID AS INFLUENZA RESOURCES AND 7119 04:27:33,940 --> 04:27:35,175 I THINK THIS MIGHT BE A NICE 7120 04:27:35,175 --> 04:27:36,576 PLACE FOR SOMETHING LIKE THAT TO 7121 04:27:36,576 --> 04:27:38,278 LIVE AS WE HAVE VERSION 1.0 NOW 7122 04:27:38,278 --> 04:27:39,913 AND AS WE MOVE ON, I THINK THIS 7123 04:27:39,913 --> 04:27:41,214 WOULD BE A GREAT RESOURCE WE CAN 7124 04:27:41,214 --> 04:27:42,749 START TO BUILD AND HAVE THAT 7125 04:27:42,749 --> 04:27:43,883 CONVERSATION AND BUILD UP A 7126 04:27:43,883 --> 04:27:47,921 DATABASE LIKE THAT. 7127 04:27:47,921 --> 04:27:49,656 >> I THINK FOR ME, WE WOULD NEED 7128 04:27:49,656 --> 04:27:51,091 TO UNDERSTAND ALL OF THE -- LIKE 7129 04:27:51,091 --> 04:27:52,125 ALL OF THE QUESTIONS WE WOULD 7130 04:27:52,125 --> 04:27:54,527 NEED TO ASK TO SORT OF 7131 04:27:54,527 --> 04:27:55,595 CATEGORIZE AND MAKE SURE ALL 7132 04:27:55,595 --> 04:27:56,830 THAT INFORMATION IS THERE, 7133 04:27:56,830 --> 04:28:01,000 RIGHT, SO THAT IS AS ERIC SAID A 7134 04:28:01,000 --> 04:28:02,102 DISCUSSION WE WOULD PROBABLY 7135 04:28:02,102 --> 04:28:03,303 NEED TO HAVE IN ORDER TO MAKE 7136 04:28:03,303 --> 04:28:05,405 SURE THAT THAT IS AS BROAD AS 7137 04:28:05,405 --> 04:28:08,241 POSSIBLE AND EFFECTIVE. 7138 04:28:08,241 --> 04:28:13,179 >> FOR ME, MY PROGRAM NOW IN 7139 04:28:13,179 --> 04:28:15,348 SOLICITATION WE REQUIRE THEM TO 7140 04:28:15,348 --> 04:28:18,118 DO THE MARKET ANALYSIS TO SHOW 7141 04:28:18,118 --> 04:28:20,987 THE ANTIBODIES ON THE MARKET 7142 04:28:20,987 --> 04:28:23,823 DOES NOT MEET THEIR NEED SO THAT 7143 04:28:23,823 --> 04:28:28,762 THAT CAN JUSTIFY THEIR PROPOSED 7144 04:28:28,762 --> 04:28:29,095 ANTIGEN. 7145 04:28:29,095 --> 04:28:31,631 AND ALSO WE REQUIRE THEM TO DO 7146 04:28:31,631 --> 04:28:34,300 THE CROSS REACTIVITY AT LEAST TO 7147 04:28:34,300 --> 04:28:37,170 THREE SPECIES IN THEIR PHASE TWO 7148 04:28:37,170 --> 04:28:38,338 STUDIES SO THAT WE CAN KNOW 7149 04:28:38,338 --> 04:28:41,307 WHETHER THE ANTIBODIES CAN BE 7150 04:28:41,307 --> 04:28:43,109 USED FOR OTHER SPECIES IN THE 7151 04:28:43,109 --> 04:28:43,643 FUTURE. 7152 04:28:43,643 --> 04:28:47,814 WE ALSO HAVE ONE PROJECT AS I 7153 04:28:47,814 --> 04:28:50,650 MENTIONED, THEY ARE PRODUCING 7154 04:28:50,650 --> 04:28:58,024 ANTIBODIES AGAINST -- LIKE -- 7155 04:28:58,024 --> 04:28:59,325 REACTIVE AGAINST NINE SPY SHE'S. 7156 04:28:59,325 --> 04:29:01,661 SO IN THAT CASE, ONE ANTIBODIES 7157 04:29:01,661 --> 04:29:03,930 CAN SERVE A LOT OF STUDY 7158 04:29:03,930 --> 04:29:09,436 RESEARCH NEED. 7159 04:29:09,436 --> 04:29:11,971 >> THESE ANTIBODIES BEING 7160 04:29:11,971 --> 04:29:13,273 GENERATED, IS THE PRIMARY 7161 04:29:13,273 --> 04:29:14,240 PURPOSE FOR DETECTION OF 7162 04:29:14,240 --> 04:29:19,546 PROTEINS BY, FOR EXAMPLE, ELI I, 7163 04:29:19,546 --> 04:29:25,151 LELUMINEX AND FLOW CYTOMETRY, 7164 04:29:25,151 --> 04:29:26,586 BECAUSE A LOT WERE IMMUNE CELLS. 7165 04:29:26,586 --> 04:29:28,455 BIGGER QUESTION I HAVE IS, DO US 7166 04:29:28,455 --> 04:29:30,990 AS INVESTIGATORS HAVE ACCESS TO 7167 04:29:30,990 --> 04:29:36,262 EITHER THE HYBRIDOMA OR MONL 7168 04:29:36,262 --> 04:29:37,530 CLONAL ANTIBODY SEQUENCE SO THAT 7169 04:29:37,530 --> 04:29:39,466 WE CAN ACTUALLY GENERATE IT AND 7170 04:29:39,466 --> 04:29:41,968 POTENTIALLY USE IT FOR DEPLETION 7171 04:29:41,968 --> 04:29:44,370 STUDIES? 7172 04:29:44,370 --> 04:29:46,005 OR BLOCKING STUDIES INA VERY VO? 7173 04:29:46,005 --> 04:29:47,373 >> THE ANSWER FOR OUR AGENTS IS 7174 04:29:47,373 --> 04:29:48,575 GOING TO BE ABSOLUTELY. 7175 04:29:48,575 --> 04:29:49,943 ANYTHING WE MAKE, WE VALIDATE, 7176 04:29:49,943 --> 04:29:51,578 WE'RE HAPPY WITH, WE'LL GET IT 7177 04:29:51,578 --> 04:29:53,112 SEQUENCED SO THAT WE CAN EVEN 7178 04:29:53,112 --> 04:29:57,116 MAKE -- SO IF WE LOSE A 7179 04:29:57,116 --> 04:29:58,751 HYBRIDOMA, YOU CAN MAKE 7180 04:29:58,751 --> 04:30:00,820 SYNTHETIC ANTIBODIES. 7181 04:30:00,820 --> 04:30:02,922 BUT THAT WAS OUR GOAL, WHAT 7182 04:30:02,922 --> 04:30:05,225 WOULD BE ACCESSIBLE IS PURIFIED 7183 04:30:05,225 --> 04:30:06,326 ANTIBODY, CERTIFICATE OF 7184 04:30:06,326 --> 04:30:07,727 ANALYSIS, KNOCK IN, KNOCK OUT 7185 04:30:07,727 --> 04:30:10,630 CELLS, AND THEN THE ACTUAL 7186 04:30:10,630 --> 04:30:11,364 HYBRIDOMA ITSELF. 7187 04:30:11,364 --> 04:30:13,032 BUT TO YOUR POINT, YEAH, A LOT 7188 04:30:13,032 --> 04:30:15,802 OF IT IS DETECTION AND 7189 04:30:15,802 --> 04:30:16,970 QUANTITATION, BUT WORKING -- 7190 04:30:16,970 --> 04:30:18,438 WE'RE DOING A LOT OF OUR WORK 7191 04:30:18,438 --> 04:30:20,540 WITH PAUL THOMAS, SO HE'S 7192 04:30:20,540 --> 04:30:21,741 SPECIFICALLY LOOKING FOR 7193 04:30:21,741 --> 04:30:22,609 DEPLETION ANTIBODIES. 7194 04:30:22,609 --> 04:30:27,380 AND HE HAS A CD TH CD8 THAT LOOE 7195 04:30:27,380 --> 04:30:31,084 A FAIRLY DECENT DEPLETER. 7196 04:30:31,084 --> 04:30:32,785 SO THAT'S WHERE I THINK FEEDBACK 7197 04:30:32,785 --> 04:30:33,853 FROM THE COMMUNITY IS REALLY 7198 04:30:33,853 --> 04:30:35,722 HELPFUL OF IS IT JUST SIMPLY YOU 7199 04:30:35,722 --> 04:30:37,156 WANT TO LACK AT THE NUMBER OF 7200 04:30:37,156 --> 04:30:38,291 IMMUNE CELLS FILTRATING IN, OR 7201 04:30:38,291 --> 04:30:39,392 DO YOU WANT TO KNOW THEIR 7202 04:30:39,392 --> 04:30:40,460 FUNCTION, DO YOU WANT TO GET RID 7203 04:30:40,460 --> 04:30:42,362 OF THEM, BASICALLY DO YOU WANT A 7204 04:30:42,362 --> 04:30:43,029 GIANT MOUSE, RIGHT? 7205 04:30:43,029 --> 04:30:44,097 SO THAT'S THE KIND OF 7206 04:30:44,097 --> 04:30:45,431 INFORMATION THAT'S REALLY 7207 04:30:45,431 --> 04:30:48,601 HELPFUL FROM US. 7208 04:30:48,601 --> 04:30:51,371 >> I WAS MORE INTERESTED FOR THE 7209 04:30:51,371 --> 04:30:53,339 COMPANIES THAT ARE PRODUCING 7210 04:30:53,339 --> 04:30:55,108 THESE, AND THE RELATIONSHIP WITH 7211 04:30:55,108 --> 04:30:57,977 THE NIH AN DO WE HAVE ACCESS TO 7212 04:30:57,977 --> 04:30:59,445 THE SOURCE MATERIAL TO GENERATE 7213 04:30:59,445 --> 04:31:00,713 IT OURSELVES. 7214 04:31:00,713 --> 04:31:03,149 TO PRODUCE IT OURSELVES AT A 7215 04:31:03,149 --> 04:31:05,451 QUANTITY THAT WOULD BE GREAT FOR 7216 04:31:05,451 --> 04:31:06,886 DEPLETION EXPERIMENTS. 7217 04:31:06,886 --> 04:31:09,289 OR WHEN YOU'RE DETECTING IMMUNE 7218 04:31:09,289 --> 04:31:15,995 CELLS, TO BE ABLE TO CO INSURING 7219 04:31:15,995 --> 04:31:17,764 JUGATE DIFFERENT FLUOROPHORES 7220 04:31:17,764 --> 04:31:17,997 READILY. 7221 04:31:17,997 --> 04:31:19,699 >> THAT'S FOR OUR PHASE TWO 7222 04:31:19,699 --> 04:31:24,571 STUDIES, WE ASK THEM NOT ONLY -- 7223 04:31:24,571 --> 04:31:26,005 FOR WILL VALIDATED ANTIBODIES 7224 04:31:26,005 --> 04:31:29,142 BUT ALSO WANT THEM TO MAKE READY 7225 04:31:29,142 --> 04:31:35,782 TO USE -- FORMS, OTHER KIND OF 7226 04:31:35,782 --> 04:31:38,284 MEASURE SO THAT THEY CAN SCALE 7227 04:31:38,284 --> 04:31:40,653 UP FOR PRODUCTION ALSO MARKETING 7228 04:31:40,653 --> 04:31:44,924 THE REAGENTS. 7229 04:31:44,924 --> 04:31:47,327 HOWEVER, FOR US -- I'M SO SORRY. 7230 04:31:47,327 --> 04:31:52,832 FOR US, THE PROGRAM IS FOR THE 7231 04:31:52,832 --> 04:31:54,133 SMALL -- I DON'T THINK WE CAN 7232 04:31:54,133 --> 04:31:55,702 JUST -- YOU KNOW, BECAUSE THE 7233 04:31:55,702 --> 04:31:56,869 PROPERTY STILL BELONGS TO THEM, 7234 04:31:56,869 --> 04:31:59,672 SO WE DON'T -- WE DON'T HAVE THE 7235 04:31:59,672 --> 04:32:02,642 AUTHORITY TO HAVE THE, YOU KNOW, 7236 04:32:02,642 --> 04:32:05,979 HAVE THEM TO PRODUCE ANTIBODIES 7237 04:32:05,979 --> 04:32:07,614 LIKE THE BIG QUANTITY. 7238 04:32:07,614 --> 04:32:10,350 THEY DON'T HAVE THE CAPACITY TO 7239 04:32:10,350 --> 04:32:14,287 DO THAT FOR -- STUDIES, BUT I 7240 04:32:14,287 --> 04:32:15,521 THINK IF YOU WANT, YOU CAN 7241 04:32:15,521 --> 04:32:17,790 EXPLORE THE POSSIBILITY WITH 7242 04:32:17,790 --> 04:32:18,358 THEM. 7243 04:32:18,358 --> 04:32:20,760 MOST OF THE ANTIBODIES ARE 7244 04:32:20,760 --> 04:32:22,228 RECOMBINANT ANTIBODIES, SO THEY 7245 04:32:22,228 --> 04:32:26,065 HAVE THE SEQUENCE ACTUALLY. 7246 04:32:26,065 --> 04:32:27,567 SO I THINK YOU CAN DIRECTLY TALK 7247 04:32:27,567 --> 04:32:29,902 TO THEM AND SEE WHAT'S THE 7248 04:32:29,902 --> 04:32:30,203 POSSIBILITY. 7249 04:32:30,203 --> 04:32:31,571 >> IT SOUNDS LIKE THOSE WOULD BE 7250 04:32:31,571 --> 04:32:32,572 MORE FOR PURCHASE. 7251 04:32:32,572 --> 04:32:34,607 THOSE ARE GOING TO BE ONES THAT 7252 04:32:34,607 --> 04:32:36,776 ARE GOING TO BE PURCHASED WHERE 7253 04:32:36,776 --> 04:32:38,077 OURS ARE GOING TO BE FREE TO THE 7254 04:32:38,077 --> 04:32:40,847 COMMUNITY. 7255 04:32:40,847 --> 04:32:46,052 >> YEAH, OUR CONTRACT, THEY 7256 04:32:46,052 --> 04:32:47,253 AGREE THAT AS LONG AS THERE'S A 7257 04:32:47,253 --> 04:32:49,822 NEED FROM NIAID SUPPORTED 7258 04:32:49,822 --> 04:32:53,092 RESEARCH INVESTIGATORS, THEY CAN 7259 04:32:53,092 --> 04:32:54,527 GIVE DISCOUNT, OR OTHERWISE YOU 7260 04:32:54,527 --> 04:32:57,096 CAN WORK WITH LIKE COLLABORATORS 7261 04:32:57,096 --> 04:32:59,932 TO HELP THEM TO VALIDATE THE 7262 04:32:59,932 --> 04:33:00,566 ANTIBODIES. 7263 04:33:00,566 --> 04:33:02,835 YOU CAN PROVIDE SOME FREE ONES, 7264 04:33:02,835 --> 04:33:05,471 FREE ANTIBODIES TO YOU. 7265 04:33:05,471 --> 04:33:07,206 >> STANLEY? 7266 04:33:07,206 --> 04:33:09,042 >> I WAS GOING TO ASK A QUESTION 7267 04:33:09,042 --> 04:33:11,611 ALONG THE SAME LINE. 7268 04:33:11,611 --> 04:33:14,914 SO WHEN DATA ARE AVAILABLE SHO 7269 04:33:14,914 --> 04:33:16,115 SHOWING HOW THEY VALIDATED, WILL 7270 04:33:16,115 --> 04:33:17,450 THE COMPANIES BE ABLE TO PUT THE 7271 04:33:17,450 --> 04:33:19,118 SAME AMOUNT OF DATA ON THE 7272 04:33:19,118 --> 04:33:21,954 WEBSITES AS THE NIAID ANTIBODIES 7273 04:33:21,954 --> 04:33:23,322 ARE GOING TO BE? 7274 04:33:23,322 --> 04:33:26,392 SO WE CAN SEE AS WAS MENTIONED 7275 04:33:26,392 --> 04:33:27,794 BY COMMERCIAL ANTIBODIES, WE 7276 04:33:27,794 --> 04:33:29,495 OFTEN GET THINGS THAT DON'T 7277 04:33:29,495 --> 04:33:31,130 WORK, BUT WITH THE COMPANIES, 7278 04:33:31,130 --> 04:33:32,565 WILL WE SEE DATA SHOWING THAT 7279 04:33:32,565 --> 04:33:33,900 THEY DO WORK? 7280 04:33:33,900 --> 04:33:38,905 WILL THAT BE AVAILABLE? 7281 04:33:38,905 --> 04:33:43,476 >> WE HAVE THE REPORT. 7282 04:33:43,476 --> 04:33:46,979 WE DO REVIEW THE REPORT, YOU 7283 04:33:46,979 --> 04:33:51,951 KNOW, IN T IN A TIMELY FASHION,I 7284 04:33:51,951 --> 04:33:53,619 DON'T THINK IT'S UP TO THE 7285 04:33:53,619 --> 04:33:54,787 COMPANY WHETHER THEY CAN SHARE 7286 04:33:54,787 --> 04:33:58,758 THE DATA OR NOT SH BU, BUT I DOK 7287 04:33:58,758 --> 04:34:00,093 AS LONG AS YOU ARE INTERESTED IN 7288 04:34:00,093 --> 04:34:01,227 THEIR ANTIBODIES, THEY ARE 7289 04:34:01,227 --> 04:34:02,328 WILLING TO SHARE THEIR DATA WITH 7290 04:34:02,328 --> 04:34:02,495 YOU. 7291 04:34:02,495 --> 04:34:05,631 >> SO IS THE DEAL TO DISTINGUISH 7292 04:34:05,631 --> 04:34:08,234 THIS FROM A USUAL COMMERCIAL 7293 04:34:08,234 --> 04:34:08,901 ANTIBODY, IS THE DIFFERENCE THAT 7294 04:34:08,901 --> 04:34:10,470 THE NIH IS PUTTING MORE MONEY 7295 04:34:10,470 --> 04:34:14,040 INTO IT OR WOU GETTING A REDUCED 7296 04:34:14,040 --> 04:34:14,540 PRICE? 7297 04:34:14,540 --> 04:34:15,775 WHAT'S THE ADVANTAGE OF GETTING 7298 04:34:15,775 --> 04:34:17,176 IT THROUGH THESE COMPANIES AS 7299 04:34:17,176 --> 04:34:18,644 OPPOSED TO A COMMERCIAL 7300 04:34:18,644 --> 04:34:18,911 ANTIBODY? 7301 04:34:18,911 --> 04:34:21,614 >> THIS IS A MECHANISM FROM HHS. 7302 04:34:21,614 --> 04:34:24,050 IT'S TO SUPPORT SMALL BUSINESS. 7303 04:34:24,050 --> 04:34:27,120 >> I THINK IF I CAN COMMENT, I 7304 04:34:27,120 --> 04:34:29,288 THINK THE NEED IS SO LARGE FROM 7305 04:34:29,288 --> 04:34:32,358 A VERY SMALL GROUP OF PEOPLE FOR 7306 04:34:32,358 --> 04:34:33,793 THESE REAGENTS, AND THAT THE 7307 04:34:33,793 --> 04:34:35,428 COST BENEFIT FOR A COMPANY IS 7308 04:34:35,428 --> 04:34:36,596 PROBABLY NOT THERE TO MAKE IT ON 7309 04:34:36,596 --> 04:34:38,097 THEIR OWN. 7310 04:34:38,097 --> 04:34:40,666 SO I THINK THE NIH IS TRYING TO 7311 04:34:40,666 --> 04:34:42,535 HELP FILL THAT GAP WHERE, LIKE, 7312 04:34:42,535 --> 04:34:46,139 YOU KNOW, THERE'S ONLY SO MUCH 7313 04:34:46,139 --> 04:34:48,207 THAT A COURSE CAN DO TO -- AT 7314 04:34:48,207 --> 04:34:49,275 LEAST THAT WAS MY UNDERSTANDING 7315 04:34:49,275 --> 04:34:50,877 OF THIS PROGRAM INITIALLY. 7316 04:34:50,877 --> 04:34:57,683 >> YEAH, THE -- IS NOT HUGE. 7317 04:34:57,683 --> 04:35:02,755 IT'S LIKE 600K FOR TWO YEARS FOR 7318 04:35:02,755 --> 04:35:03,422 AN AWARD. 7319 04:35:03,422 --> 04:35:08,995 FOR PHASE TWO, WE HAVE UP TO 7320 04:35:08,995 --> 04:35:12,765 $1.5 MILLION, BUT YOU'RE REALLY 7321 04:35:12,765 --> 04:35:15,501 ONLY -- THE SBIR IS ONLY 7322 04:35:15,501 --> 04:35:17,136 SUPPOSED TO BE FOR SMALL 7323 04:35:17,136 --> 04:35:17,403 BUSINESS. 7324 04:35:17,403 --> 04:35:18,971 >> AND THE LAST QUESTION, IS 7325 04:35:18,971 --> 04:35:20,273 THERE OVERLAP BETWEEN THE 7326 04:35:20,273 --> 04:35:22,241 ANTIBODIES THAT YOU HAVE AND 7327 04:35:22,241 --> 04:35:22,909 THAT NIAID HAD? 7328 04:35:22,909 --> 04:35:24,610 I COULDN'T TELL FROM THE LIST. 7329 04:35:24,610 --> 04:35:28,014 BUT IS THERE SOME OVERLAP THERE? 7330 04:35:28,014 --> 04:35:32,652 >> WE MAY HAVE SON OVER SOME OVP 7331 04:35:32,652 --> 04:35:33,119 ONES, YEAH. 7332 04:35:33,119 --> 04:35:33,519 >> SORRY. 7333 04:35:33,519 --> 04:35:37,623 I'M GOING TO I TAKE MY MODERATOR 7334 04:35:37,623 --> 04:35:39,125 POSITION HERE. 7335 04:35:39,125 --> 04:35:43,062 CURIOUS, YO ERIK YOU MENTIONED S 7336 04:35:43,062 --> 04:35:46,265 THING CALLED FLU HOME FOR 7337 04:35:46,265 --> 04:35:49,702 AGGREGAGGREGATING ALL OF THE THS 7338 04:35:49,702 --> 04:35:51,237 FLU-RELATED BECAUSE OBVIOUSLY 7339 04:35:51,237 --> 04:35:53,272 CEIRR HAS A VARIETY OF RESOURCES 7340 04:35:53,272 --> 04:36:00,479 DISTINCT FROM CBI AND IRR AND -- 7341 04:36:00,479 --> 04:36:03,115 COMPANIES I'M CURIOUS IF FLU 7342 04:36:03,115 --> 04:36:04,250 HOME IS GOING TO BE THE SITE 7343 04:36:04,250 --> 04:36:05,885 THAT ALLOWS ONE JUST LIKE A 7344 04:36:05,885 --> 04:36:07,553 CATALOG OF ALL OF THESE THINGS 7345 04:36:07,553 --> 04:36:13,392 THAT ARE COMMERCIAL, LIKE NIAID 7346 04:36:13,392 --> 04:36:15,361 FUNDED, CEIRR REAGENTS, AND ALSO 7347 04:36:15,361 --> 04:36:16,996 POTENTIALLY HAVE A SYSTEM 7348 04:36:16,996 --> 04:36:19,465 WHEREAS SOMEBODY ELSE MENTIONED, 7349 04:36:19,465 --> 04:36:20,566 INVESTIGATORS CAN WRITE IN AND 7350 04:36:20,566 --> 04:36:22,635 SAY, HEY, I TESTED THAT 7351 04:36:22,635 --> 04:36:24,003 ANTIBODY, AND THIS WAS THE FLOW 7352 04:36:24,003 --> 04:36:27,406 CHART I GOT FROM MY PBMCs. 7353 04:36:27,406 --> 04:36:29,508 LIKE, YOU KNOW WHAT I'M SAYING? 7354 04:36:29,508 --> 04:36:36,883 >> MA?MAYBE PART OF THAT IS USER 7355 04:36:36,883 --> 04:36:37,884 ERROR, BUT IS THAT A 7356 04:36:37,884 --> 04:36:38,184 POSSIBILITY? 7357 04:36:38,184 --> 04:36:40,019 >> YEAH, SO IT'S FLU HUB, NOT 7358 04:36:40,019 --> 04:36:41,787 HOME, SO SORRY IF IT DIDN'T COME 7359 04:36:41,787 --> 04:36:41,988 CLEAR. 7360 04:36:41,988 --> 04:36:46,626 SO FLUHUB. 7361 04:36:46,626 --> 04:36:48,160 WE'VE GOT A VERY FANCY LOGO AN 7362 04:36:48,160 --> 04:36:48,694 EVERYTHING. 7363 04:36:48,694 --> 04:36:51,430 SO RIGHT NOW IT MORE OF A LIST 7364 04:36:51,430 --> 04:36:53,132 OF INFLUENZA-RELATED PROGRAMS 7365 04:36:53,132 --> 04:36:55,768 LIKE CEIRR, LIKE CIVICS, LIKE 7366 04:36:55,768 --> 04:36:58,137 THE HIPCs, THINGS LIKE THAT 7367 04:36:58,137 --> 04:36:59,672 AND IT'S STARTING TO BUILD UP 7368 04:36:59,672 --> 04:37:02,241 THINGS LIKE COMPUTATIONAL 7369 04:37:02,241 --> 04:37:03,976 RESOURCES, DATABASES RELATIVE TO 7370 04:37:03,976 --> 04:37:04,977 INFLUENZA SORT OF LOOSELY MAPPED 7371 04:37:04,977 --> 04:37:07,213 TO OUR UNIVERSAL INFLUENZA 7372 04:37:07,213 --> 04:37:08,080 VACCINE STRATEGIC PLAN. 7373 04:37:08,080 --> 04:37:10,816 SO AS WE'RE BUILDING IT UP, WE 7374 04:37:10,816 --> 04:37:12,251 WANT TO DO THINGS AND FIGURE OUT 7375 04:37:12,251 --> 04:37:14,387 WHAT EATION USEFUL FOR THE 7376 04:37:14,387 --> 04:37:15,021 COMMUNITY. 7377 04:37:15,021 --> 04:37:17,456 SO I THINK LIKE MICHELLE SAID, 7378 04:37:17,456 --> 04:37:18,557 IT'S A DISCUSSION WE NEED TO 7379 04:37:18,557 --> 04:37:19,458 HAVE RIGHT NOW. 7380 04:37:19,458 --> 04:37:21,460 SO WHAT DOES SOMETHING LIKE THIS 7381 04:37:21,460 --> 04:37:22,428 LOOK LIKE? 7382 04:37:22,428 --> 04:37:28,167 IS IT FLOW POTTS L POTTS, SOME E 7383 04:37:28,167 --> 04:37:32,004 THAT'S FILTERABLE, SORT OF STAN 7384 04:37:32,004 --> 04:37:33,739 ARDIZED, THE WAYS WE CAN 7385 04:37:33,739 --> 04:37:34,573 REPRESENT THE WAY THINGS WERE 7386 04:37:34,573 --> 04:37:35,675 DONE AND WHAT WORKED AND DIDN'T 7387 04:37:35,675 --> 04:37:36,108 WORK. 7388 04:37:36,108 --> 04:37:37,209 WE DO AS THE U.S. GOVERNMENT 7389 04:37:37,209 --> 04:37:38,577 NEED TO BE A LITTLE BIT CAREFUL 7390 04:37:38,577 --> 04:37:40,413 ABOUT APPEARING TO ENDORSE ONE 7391 04:37:40,413 --> 04:37:42,081 PRODUCT OVER ANOTHER PRODUCT, SO 7392 04:37:42,081 --> 04:37:44,417 IT'S LESS OF US SAYING YES, THIS 7393 04:37:44,417 --> 04:37:45,751 COMPANY'S PRODUCT WORKS AND NO, 7394 04:37:45,751 --> 04:37:46,953 THIS COMPANY'S PRODUCT DOESN'T 7395 04:37:46,953 --> 04:37:49,188 WORK, SO IT'S A LITTLE BIT OF A 7396 04:37:49,188 --> 04:37:49,789 DISCLAIMER THERE, BUT I THINK 7397 04:37:49,789 --> 04:37:51,590 THAT'S SOMETHING WE CAN 7398 04:37:51,590 --> 04:37:51,857 NAVIGATE. 7399 04:37:51,857 --> 04:37:53,059 >> I LIKE THE TABLE FORMAT. 7400 04:37:53,059 --> 04:37:54,627 SO WE USE INTERNALLY, JUST 7401 04:37:54,627 --> 04:37:55,928 BECAUSE IT'S EASY AND THEN WE 7402 04:37:55,928 --> 04:37:57,964 CAN DO POWER VI TO SET UP 7403 04:37:57,964 --> 04:37:59,398 DATABASES WITH THAT. 7404 04:37:59,398 --> 04:38:00,366 ONE THING THAT WOULD BE HELPFUL 7405 04:38:00,366 --> 04:38:03,502 IF YOU'RE REQUESTING GOING TO T 7406 04:38:03,502 --> 04:38:04,937 WAY IS TO PUT THE CONTACT OF THE 7407 04:38:04,937 --> 04:38:08,441 PERSON, IF THEY AGREE, THAT DID 7408 04:38:08,441 --> 04:38:10,109 THE TESTING SO THAT IF YOU 7409 04:38:10,109 --> 04:38:11,344 WANTED TO REACH OUT TO ME 7410 04:38:11,344 --> 04:38:12,211 DIRECTLY AND SAY WHAT DID YOU 7411 04:38:12,211 --> 04:38:13,479 DO, CAN YOU SHARE THE DATA, YOU 7412 04:38:13,479 --> 04:38:14,780 CAN AT LEAST HAVE THOSE 7413 04:38:14,780 --> 04:38:16,782 CONVERSATIONS. 7414 04:38:16,782 --> 04:38:18,718 >> WE CAN LINK TO THE PROTOCOLS, 7415 04:38:18,718 --> 04:38:19,218 THINGS LIKE THAT. 7416 04:38:19,218 --> 04:38:20,519 WE CAN HAVE THOSE THINGS AND 7417 04:38:20,519 --> 04:38:21,721 LINKS THAT CAN BE PULLED UP FOR 7418 04:38:21,721 --> 04:38:23,589 PEOPLE TO SHARE AND TRY AND 7419 04:38:23,589 --> 04:38:29,261 REPRODUCE TOO. 7420 04:38:29,261 --> 04:38:30,963 >> CAN I ADD REALLY BRIEFLY, 7421 04:38:30,963 --> 04:38:32,431 IT'S LIKELY THAT, YOU KNOW, THE 7422 04:38:32,431 --> 04:38:33,666 RESULTS THAT ONE PERSON HAS IN 7423 04:38:33,666 --> 04:38:35,101 THEIR LAB MAY DIFFER FROM 7424 04:38:35,101 --> 04:38:36,202 ANOTHER, SO THERE SHOULD BE A 7425 04:38:36,202 --> 04:38:37,703 WAY TO CAPTURE THAT INSTEAD OF 7426 04:38:37,703 --> 04:38:39,739 JUST ONE PERSON HAVING THE SAY. 7427 04:38:39,739 --> 04:38:40,940 SO THESE ARE ALL THINGS THAT 7428 04:38:40,940 --> 04:38:43,576 WE'RE TRYING TO CONCEPTUALIZE 7429 04:38:43,576 --> 04:38:45,444 AND THAT'S PART OF THE OUTCOME 7430 04:38:45,444 --> 04:38:46,812 OF THIS WORKSHOP THAT MIGHT BE 7431 04:38:46,812 --> 04:38:50,249 REALLY BENEFICIAL. 7432 04:38:50,249 --> 04:38:51,784 >> THIS IS A QUESTION ABOUT THE 7433 04:38:51,784 --> 04:38:53,419 SMALL BUSINESS REAGENT PROGRAM. 7434 04:38:53,419 --> 04:38:55,087 IT WAS KIND OF UNCLEAR ABOUT THE 7435 04:38:55,087 --> 04:38:55,955 ANTIBODY. 7436 04:38:55,955 --> 04:38:58,457 SO ARE THEY MAKING THE -- WHEN 7437 04:38:58,457 --> 04:39:00,059 THEY HAVE THESE ANTIBODY 7438 04:39:00,059 --> 04:39:01,794 REAGENTS, ARE THEY MAKING THE 7439 04:39:01,794 --> 04:39:03,662 ANTIBODY SEQUENCES AVAILABLE? 7440 04:39:03,662 --> 04:39:05,264 IF THEY ARE NOT, I THINK THEY 7441 04:39:05,264 --> 04:39:09,301 SHOULD. 7442 04:39:09,301 --> 04:39:10,403 BECAUSE ONCE PEOPLE LIKE ME 7443 04:39:10,403 --> 04:39:11,937 START USING THESE ANTIBODIES, 7444 04:39:11,937 --> 04:39:14,573 THERE'S AN OPPORTUNITY THAT WE 7445 04:39:14,573 --> 04:39:16,075 COULD USE STRUCTURE BASE 7446 04:39:16,075 --> 04:39:17,943 ANTIBODY DESIGN TO MAKE THE 7447 04:39:17,943 --> 04:39:20,312 ANTIBODIES MORE SPECIFIC OR MAKE 7448 04:39:20,312 --> 04:39:21,781 THEM BROADER DEPENDING ON WHAT 7449 04:39:21,781 --> 04:39:23,883 THE COMMUNITY NEEDS. 7450 04:39:23,883 --> 04:39:25,951 SO I THINK IF THEY DON'T MAKE 7451 04:39:25,951 --> 04:39:27,386 THE ANTIBODY SEQUENCING 7452 04:39:27,386 --> 04:39:28,721 AVAILABLE, THEN THE NEXT 7453 04:39:28,721 --> 04:39:30,189 GENERATION OF IMPROVED 7454 04:39:30,189 --> 04:39:31,190 ANTIBODIES PROBABLY CAN'T BE 7455 04:39:31,190 --> 04:39:31,924 MADE. 7456 04:39:31,924 --> 04:39:34,593 SO THEY SHOULD REALLY BE MAKING 7457 04:39:34,593 --> 04:39:35,227 THE ANTIBODY SEQUENCES 7458 04:39:35,227 --> 04:39:39,665 AVAILABLE. 7459 04:39:39,665 --> 04:39:41,400 >> THANK YOU. 7460 04:39:41,400 --> 04:39:42,601 I WILL DISCUSS THIS WITH MY 7461 04:39:42,601 --> 04:39:43,702 SUPERVISOR AND MAYBE WE CAN ADD 7462 04:39:43,702 --> 04:39:47,306 THAT INTO OUR NEXT SOLICITATION. 7463 04:39:47,306 --> 04:39:52,178 >> JUST ANOTHER COMMENT FROM 7464 04:39:52,178 --> 04:39:59,018 LAURIE STEPHANS. 7465 04:39:59,018 --> 04:40:04,490 SHE JUST MENTIONED THAT ESV 7466 04:40:04,490 --> 04:40:05,658 CURRENTLY HAS ANTIBODIES FOR 7467 04:40:05,658 --> 04:40:06,158 SALE WITH DATA. 7468 04:40:06,158 --> 04:40:08,494 I DON'T KNOW IF THAT INCLUDES 7469 04:40:08,494 --> 04:40:09,095 SEQUENCING OR -- 7470 04:40:09,095 --> 04:40:10,129 >> ARE THEY ONLINE? 7471 04:40:10,129 --> 04:40:11,564 WOULD THEY LIKE TO UNMUTE AND 7472 04:40:11,564 --> 04:40:13,933 MAYBE JUST SPEAK TO THIS -- 7473 04:40:13,933 --> 04:40:16,669 MAYBE TO THIS TOPIC ON THE 7474 04:40:16,669 --> 04:40:17,303 SEQUENCE AVAILABILITY 7475 04:40:17,303 --> 04:40:18,971 SPECIFICALLY BECAUSE IT WAS 7476 04:40:18,971 --> 04:40:20,873 BROUGHT UP BY BOTH -- THAT WOULD 7477 04:40:20,873 --> 04:40:28,013 BE REALLY NICE. 7478 04:40:28,013 --> 04:40:28,981 IS ONE OF THE INDIVIDUALS 7479 04:40:28,981 --> 04:40:30,649 INVOLVED IN THE SBIR GRANT 7480 04:40:30,649 --> 04:40:33,519 ONLINE THAT WOULD LIKE TO YOU BE 7481 04:40:33,519 --> 04:40:39,325 UNMUTE? 7482 04:40:39,325 --> 04:40:40,459 IT WON'T LET THEM UNMUTE. 7483 04:40:40,459 --> 04:40:42,795 IS THERE A WAY WE CAN FIX THAT, 7484 04:40:42,795 --> 04:40:43,229 AV ISSUE? 7485 04:40:43,229 --> 04:40:44,630 BECAUSE THIS MIGHT BE THE MOST 7486 04:40:44,630 --> 04:40:55,040 DIRECT LINE OF COMMUNICATION. 7487 04:40:55,040 --> 04:40:57,409 >> PERHAPS YOU CAN GO TO THE 7488 04:40:57,409 --> 04:40:58,944 CHAT. 7489 04:40:58,944 --> 04:41:00,045 >> EXACTLY. 7490 04:41:00,045 --> 04:41:01,013 SPECIFICALLY ANSWER THE QUESTION 7491 04:41:01,013 --> 04:41:02,648 ABOUT WHETHER THE SEQUENCES FOR 7492 04:41:02,648 --> 04:41:05,017 THE ANTIBODIES THAT HAVE BEEN 7493 04:41:05,017 --> 04:41:06,552 CREATED BY AT LEAST YOUR COMPANY 7494 04:41:06,552 --> 04:41:08,420 THAT YOU ARE INVOLVED WITH WOULD 7495 04:41:08,420 --> 04:41:12,224 BE MADE AVAILABLE. 7496 04:41:12,224 --> 04:41:13,225 PRESUMABLY UPON REQUEST OR AS 7497 04:41:13,225 --> 04:41:17,830 PART OF THE DATA CERTIFICATE. 7498 04:41:17,830 --> 04:41:18,898 >> APOLOGIES. 7499 04:41:18,898 --> 04:41:21,167 THE MICROPHONES ON THE FAR END 7500 04:41:21,167 --> 04:41:22,234 THERE ARE UNMUTED. 7501 04:41:22,234 --> 04:41:23,636 THEY JUST HAVE TO OPEN THEIR 7502 04:41:23,636 --> 04:41:24,637 MICROPHONES BUT THEY ARE 7503 04:41:24,637 --> 04:41:24,970 UNMUTED. 7504 04:41:24,970 --> 04:41:29,575 SORRY. 7505 04:41:29,575 --> 04:41:32,144 >> WHILE I GUESS MAYBE WE WAIT 7506 04:41:32,144 --> 04:41:37,716 FOR THAT ANSWER TO COME THROUGH, 7507 04:41:37,716 --> 04:41:39,018 IS THERE ANYBODY ELSE ONLINE WHO 7508 04:41:39,018 --> 04:41:47,626 WANTED TO ASK A QUESTION? 7509 04:41:47,626 --> 04:41:49,595 CAN I COME BACK TO THE FLU HUB? 7510 04:41:49,595 --> 04:41:51,830 SO IS THIS -- THIS IS STARTING 7511 04:41:51,830 --> 04:41:53,566 TO SOUND A LITTLE BIT 7512 04:41:53,566 --> 04:41:56,635 REMINISCENT OF IRR BEFORE IT WAS 7513 04:41:56,635 --> 04:41:57,903 INTERNATIONAL REAGENT RESOURCE 7514 04:41:57,903 --> 04:42:00,206 AND IT WAS INFLUENZA REAGENT 7515 04:42:00,206 --> 04:42:00,472 RESOURCE? 7516 04:42:00,472 --> 04:42:01,674 OBVIOUSLY WHEN WE TALK ABOUT THE 7517 04:42:01,674 --> 04:42:03,509 VARIETY OF NIAID PROGRAMS AND 7518 04:42:03,509 --> 04:42:04,810 CIVICS, WHERE YOU ALSO HAVE NOW 7519 04:42:04,810 --> 04:42:07,980 CHIM OR CHALLENGE VIRUSES THERE, 7520 04:42:07,980 --> 04:42:09,481 AS PART OF CEIRR, WE'RE 7521 04:42:09,481 --> 04:42:11,951 DEVELOPING, YOU KNOW, RESCUE 7522 04:42:11,951 --> 04:42:17,957 SYSTEMS AND SERUM ASSAYS AND 7523 04:42:17,957 --> 04:42:18,624 LOTS OF THINGS. 7524 04:42:18,624 --> 04:42:23,562 SO I GUESS MAYBE CAN YOU -- 7525 04:42:23,562 --> 04:42:24,096 >> HI. 7526 04:42:24,096 --> 04:42:29,868 CAN YOU HEAR ME? 7527 04:42:29,868 --> 04:42:30,603 [ECHOING] 7528 04:42:30,603 --> 04:42:31,170 OH, MY GOD! 7529 04:42:31,170 --> 04:42:32,137 >> APOLOGIES. 7530 04:42:32,137 --> 04:42:33,339 >> IS THAT BETTER? 7531 04:42:33,339 --> 04:42:35,941 >> PLEASE MUTE YOUR SPEAKERS. 7532 04:42:35,941 --> 04:42:37,042 >> CAN YOU HEAR ME AT ALL? 7533 04:42:37,042 --> 04:42:38,210 >> THANK YOU. 7534 04:42:38,210 --> 04:42:39,878 WE CAN HEAR YOU BETTER NOW. 7535 04:42:39,878 --> 04:42:47,620 THANK YOU. 7536 04:42:47,620 --> 04:42:49,121 >> ONE MORE TRY, THEN I'LL LOG 7537 04:42:49,121 --> 04:42:49,288 OUT. 7538 04:42:49,288 --> 04:42:51,357 >> NO, LAURIE, WE CAN HEAR YOU. 7539 04:42:51,357 --> 04:42:52,157 >> OH, OKAY. 7540 04:42:52,157 --> 04:42:53,926 IT AN ECHO FOR ME SO I WASN'T -- 7541 04:42:53,926 --> 04:42:55,427 I WAS WORRIED THAT IT WAS ECHO 7542 04:42:55,427 --> 04:42:57,029 FOR YOU. 7543 04:42:57,029 --> 04:42:58,764 >> IT'S CLEARED UP NOW. 7544 04:42:58,764 --> 04:42:59,732 COW PLEASE -- THANK YOU FOR 7545 04:42:59,732 --> 04:43:00,232 UNMUTING. 7546 04:43:00,232 --> 04:43:01,767 WOULD YOU LIKE TO ANSWER THE 7547 04:43:01,767 --> 04:43:02,334 QUESTION ABOUT THE SEQUENCE 7548 04:43:02,334 --> 04:43:03,869 AVAILABILITY? 7549 04:43:03,869 --> 04:43:05,070 >> YEAH. 7550 04:43:05,070 --> 04:43:08,240 SO THE ISSUE WOULD BE THAT A 7551 04:43:08,240 --> 04:43:10,042 COMPETITOR COULD THEN JUST MAKE 7552 04:43:10,042 --> 04:43:11,277 THE ANTIBODY AND ALL THE EFFORT 7553 04:43:11,277 --> 04:43:16,081 THAT WE'VE PUT IN IS LOST. 7554 04:43:16,081 --> 04:43:16,282 SO -- 7555 04:43:16,282 --> 04:43:18,217 >> IS THERE A PATHWAY TO 7556 04:43:18,217 --> 04:43:19,752 POTENTIALLY MAKE IT AVAILABLE 7557 04:43:19,752 --> 04:43:22,054 FOR RESEARCH PURPOSES TO 7558 04:43:22,054 --> 04:43:25,524 SCIENTISTS? 7559 04:43:25,524 --> 04:43:28,193 >> I MEAN, WE'D HAVE TO ENTER 7560 04:43:28,193 --> 04:43:29,328 SOME KIND OF AGREEMENT 7561 04:43:29,328 --> 04:43:29,762 POTENTIALLY, YEAH. 7562 04:43:29,762 --> 04:43:31,997 I MEAN, WE HAVE SCALED UP A LOT 7563 04:43:31,997 --> 04:43:35,601 OF THE ANTIBODY SO WE CERTAINLY 7564 04:43:35,601 --> 04:43:36,769 CAN MAKE -- THOSE ARE AVAILABLE 7565 04:43:36,769 --> 04:43:39,338 FOR SALE AND WE CAN MAKE LARGE 7566 04:43:39,338 --> 04:43:40,105 QUANTITIES AVAILABLE. 7567 04:43:40,105 --> 04:43:41,607 BUT IN ORDER TO SEQUENCE IT AND 7568 04:43:41,607 --> 04:43:44,009 GIVE THAT OUT, THAT'S THE ONLY 7569 04:43:44,009 --> 04:43:45,077 CONCERN, IS THAT, YOU KNOW, THEN 7570 04:43:45,077 --> 04:43:47,012 ALL OF A SUDDEN EVERYBODY COULD 7571 04:43:47,012 --> 04:43:52,284 MAKE IT. 7572 04:43:52,284 --> 04:43:53,852 >> DID YOU HEAR THAT COMMENT? 7573 04:43:53,852 --> 04:43:55,220 >> I UNDERSTAND THAT CONCERN 7574 04:43:55,220 --> 04:43:56,121 FROM A SMALL BUSINESS, THAT 7575 04:43:56,121 --> 04:44:00,292 EVERYBODY CAN MAKE IT. 7576 04:44:00,292 --> 04:44:01,927 BUT TO BE BRUTALLY HONEST, IF 7577 04:44:01,927 --> 04:44:03,362 PEOPLE WANT TO MAKE ANTIBODY, 7578 04:44:03,362 --> 04:44:04,963 THEY CAN ORDER THE ANTIBODY AND 7579 04:44:04,963 --> 04:44:08,367 USE MASS SPEC TO SEQUENCE THE 7580 04:44:08,367 --> 04:44:09,468 ANTIBODY IF THEY REALLY WANT TO 7581 04:44:09,468 --> 04:44:10,169 MAKE IT. 7582 04:44:10,169 --> 04:44:11,837 SO I UNDERSTAND THAT ISSUE, BUT 7583 04:44:11,837 --> 04:44:13,472 THAT'S NOT REALLY -- SO IF WE 7584 04:44:13,472 --> 04:44:15,374 WANT TO MAKE ANTIBODY, WE COULD 7585 04:44:15,374 --> 04:44:19,912 ORDER IT FROM THE COMPANY, SPEND 7586 04:44:19,912 --> 04:44:21,413 $3,000, MASS SPEC AND REVERSE 7587 04:44:21,413 --> 04:44:22,514 ENGINEER IT AND PEOPLE HAVE DONE 7588 04:44:22,514 --> 04:44:23,582 THAT IN THE PAST. 7589 04:44:23,582 --> 04:44:24,917 I JUST WANT TO BRING THAT AS A 7590 04:44:24,917 --> 04:44:25,117 POINT. 7591 04:44:25,117 --> 04:44:26,418 >> NO, I UNDERSTAND THAT AND 7592 04:44:26,418 --> 04:44:28,120 THAT'S YOUR RIGHT, BUT IF WE PUT 7593 04:44:28,120 --> 04:44:32,057 ALL SEQUENCES ONLINE, THEN 7594 04:44:32,057 --> 04:44:33,258 OUR -- SYSTEMS COULD COME IN AND 7595 04:44:33,258 --> 04:44:34,493 JUST MAKE THEM ALL AND THEN WE 7596 04:44:34,493 --> 04:44:36,295 HAVE NOTHING. 7597 04:44:36,295 --> 04:44:37,796 AND PART OF THE REASON THAT WE 7598 04:44:37,796 --> 04:44:42,835 DID THIS IS YOU KNOW, BECAUSE IT 7599 04:44:42,835 --> 04:44:43,669 WAS A GOOD OPPORTUNITY TO GET 7600 04:44:43,669 --> 04:44:45,404 INTO SOMETHING NEW, BUT AS JOY 7601 04:44:45,404 --> 04:44:47,373 MENTIONED, IT'S NOT -- WE PUT A 7602 04:44:47,373 --> 04:44:48,974 LOT OF EXTRA TIME INTO IT. 7603 04:44:48,974 --> 04:44:51,276 IT'S NOT JUST ALL FUNDED. 7604 04:44:51,276 --> 04:44:53,812 AND YOU KNOW, WE ARE A SMALL 7605 04:44:53,812 --> 04:44:56,081 BUSINESS SO WE STILL -- A LOT OF 7606 04:44:56,081 --> 04:45:00,519 YOU GUYS ARE GETTING -- YOU'RE 7607 04:45:00,519 --> 04:45:01,620 GETTING -- YOUR LABS ARE PAID 7608 04:45:01,620 --> 04:45:02,921 FOR AND YOUR SALARIES ARE PAID 7609 04:45:02,921 --> 04:45:03,155 FOR. 7610 04:45:03,155 --> 04:45:04,857 I STILL HAVE TO PAY FOR MY 7611 04:45:04,857 --> 04:45:06,725 STUFF. 7612 04:45:06,725 --> 04:45:07,760 SO -- 7613 04:45:07,760 --> 04:45:08,894 >> THANK YOU, LAURIE. 7614 04:45:08,894 --> 04:45:10,662 I THINK WE UNDERSTAND THE 7615 04:45:10,662 --> 04:45:11,764 CONCERNS ON THE SMALL BUSINESS 7616 04:45:11,764 --> 04:45:11,964 SIDE. 7617 04:45:11,964 --> 04:45:14,666 I THINK MAYBE THERE ARE SOME 7618 04:45:14,666 --> 04:45:15,734 INTERNAL DISCUSSIONS ON YOUR END 7619 04:45:15,734 --> 04:45:17,202 AS WELL AS ON THE NIH SIDE TO 7620 04:45:17,202 --> 04:45:18,270 ESSENTIALLY THINK ABOUT PATHWAYS 7621 04:45:18,270 --> 04:45:18,704 FORWARD. 7622 04:45:18,704 --> 04:45:20,873 OBVIOUSLY MAYBE NOT MAKING THEM 7623 04:45:20,873 --> 04:45:22,107 FREELY AVAILABLE ON WEBSITES, 7624 04:45:22,107 --> 04:45:23,709 BUT MAYBE PATHWAYS FORWARD SUCH 7625 04:45:23,709 --> 04:45:26,845 THAT RESEARCH SCIENTISTS, YOU 7626 04:45:26,845 --> 04:45:28,447 KNOW, COULD WORK WITH COMPANIES 7627 04:45:28,447 --> 04:45:31,417 TO GET THE SEQUENCES TO DO 7628 04:45:31,417 --> 04:45:32,418 ADDITIONAL SCIENTIFIC INQUIRIES. 7629 04:45:32,418 --> 04:45:33,619 I THINK THAT'S WHAT WE'RE ASKING 7630 04:45:33,619 --> 04:45:33,919 FOR. 7631 04:45:33,919 --> 04:45:37,656 SO YEAH, MAYBE OFFLINE QUESTIONS 7632 04:45:37,656 --> 04:45:38,390 AND CONVERSATIONS ARE NEEDED 7633 04:45:38,390 --> 04:45:39,158 AROUND THAT. 7634 04:45:39,158 --> 04:45:42,428 THANK YOU. 7635 04:45:42,428 --> 04:45:45,164 ANY OTHER QUESTIONS ONLINE FROM 7636 04:45:45,164 --> 04:45:51,804 OUR AUDIENCE? 7637 04:45:51,804 --> 04:45:53,305 GO AHEAD, JOY. 7638 04:45:53,305 --> 04:45:57,709 >> AS A PROGRAM OFFICER 7639 04:45:57,709 --> 04:45:58,911 OVERSEEING THIS PROGRAM, 7640 04:45:58,911 --> 04:46:00,979 ACTUALLY WE HAVE EXPERIENCED A 7641 04:46:00,979 --> 04:46:03,482 LOT OF DIFFICULTY. 7642 04:46:03,482 --> 04:46:06,318 ONE DIFFICULTY IS WE DON'T KNOW 7643 04:46:06,318 --> 04:46:09,488 WHAT'S THE ANTIGEN LIST, 7644 04:46:09,488 --> 04:46:12,291 WHETHER -- WHICH ONE YOU LIKE, 7645 04:46:12,291 --> 04:46:16,028 YOU WANT, WHICH IS THE MOST 7646 04:46:16,028 --> 04:46:17,129 IMPORTANT ONES, PRIORITIES WE 7647 04:46:17,129 --> 04:46:19,731 WANT TO HAVE THE PRIORITIES FROM 7648 04:46:19,731 --> 04:46:22,668 THE -- YOU KNOW, THE FEW, WANT 7649 04:46:22,668 --> 04:46:23,535 TO MEET YOUR NEED. 7650 04:46:23,535 --> 04:46:25,404 SO IF WE CANNOT HEAR YOUR NEEDS, 7651 04:46:25,404 --> 04:46:28,841 WE DON'T KNOW WHICH ANTIBODIES, 7652 04:46:28,841 --> 04:46:30,843 YOU KNOW, WE SHOULD DEVELOP. 7653 04:46:30,843 --> 04:46:33,479 ANOTHER THING IS WE ACTUALLY 7654 04:46:33,479 --> 04:46:35,414 HAVE DIFFICULTIES TO FUND 7655 04:46:35,414 --> 04:46:39,985 COLLABORATORS TO VALIDATE OF OUR 7656 04:46:39,985 --> 04:46:41,220 ANTIBODIES, BECAUSE THERE'S A 7657 04:46:41,220 --> 04:46:43,889 DISCONNECTION BETWEEN THE END 7658 04:46:43,889 --> 04:46:47,860 USERS AND PRODUCERS, IT'S KIND 7659 04:46:47,860 --> 04:46:50,028 OF A DIFFICULTY FOR US TO MAKE 7660 04:46:50,028 --> 04:46:53,599 SURE THE ANTIBODIES ACTUALLY CAN 7661 04:46:53,599 --> 04:46:58,203 WORK WELL IN THE REALTIME 7662 04:46:58,203 --> 04:46:59,838 INFECTION MODELS OR SAMPLES. 7663 04:46:59,838 --> 04:47:01,607 SO IT WILL BE GREAT IF WE CAN 7664 04:47:01,607 --> 04:47:02,975 ESTABLISH SOME KIND OF 7665 04:47:02,975 --> 04:47:05,944 CONNECTION BETWEEN THE END USERS 7666 04:47:05,944 --> 04:47:09,014 AND THE PRODUCERS. 7667 04:47:09,014 --> 04:47:09,882 THAT'S MY COMMENT. 7668 04:47:09,882 --> 04:47:11,250 >> CAN I RESPOND TO THAT? 7669 04:47:11,250 --> 04:47:13,118 I KNOW PREVIOUSLY THERE WAS A 7670 04:47:13,118 --> 04:47:14,753 WORKING GROUP, I WAS A PART OF 7671 04:47:14,753 --> 04:47:16,288 IT, WE HAD MAYBE TWO CALLS, BUT 7672 04:47:16,288 --> 04:47:17,689 THERE WAS A FERRET REAGENT 7673 04:47:17,689 --> 04:47:19,658 WORKING GROUP AT LEAST, AND I 7674 04:47:19,658 --> 04:47:21,193 THINK WE CAN COME BACK TO THAT, 7675 04:47:21,193 --> 04:47:22,461 NOW THAT THERE'S BEEN SO MUCH 7676 04:47:22,461 --> 04:47:24,663 PROGRESS MADE. 7677 04:47:24,663 --> 04:47:26,865 AND SORT OF LIKE TO LOOK AT 7678 04:47:26,865 --> 04:47:28,267 REDUNDANCIES AND SORT OF I 7679 04:47:28,267 --> 04:47:29,535 AGREE, I THINK AS INVESTIGATORS, 7680 04:47:29,535 --> 04:47:31,436 WE WOULD LOVE TO HAVE A SEAT AT 7681 04:47:31,436 --> 04:47:34,606 THE TABLE TO TALK DIRECTLY TO 7682 04:47:34,606 --> 04:47:39,278 THOSE MAKING THE RESOURCES TO 7683 04:47:39,278 --> 04:47:39,878 FURTHER OUR SCIENCE. 7684 04:47:39,878 --> 04:47:41,680 >> AND IT SOUNDS LIKE THAT'S A 7685 04:47:41,680 --> 04:47:46,585 FERRET WORK GROUP, BUT MAYBE WE 7686 04:47:46,585 --> 04:47:48,754 PULL IN HAMSTERS AS WELL OR A 7687 04:47:48,754 --> 04:47:50,088 SEPARATE WORKSHOP FOR -- 7688 04:47:50,088 --> 04:47:51,523 >> I THINK TWO DIFFERENT WORKING 7689 04:47:51,523 --> 04:47:53,325 GROUPS WOULD BE IDEAL, JUST TO 7690 04:47:53,325 --> 04:48:01,433 ALSO SEE WHERE PROCESSES ARE. 7691 04:48:01,433 --> 04:48:02,334 MICHELLE, I'M GOING TO TURN IT 7692 04:48:02,334 --> 04:48:03,936 OVER TO YOU. 7693 04:48:03,936 --> 04:48:05,404 >> THANK YOU PANELISTS. 7694 04:48:05,404 --> 04:48:07,272 THANK YOU GUYS SO MUCH! 7695 04:48:07,272 --> 04:48:14,646 ALL RIGHT. 7696 04:48:14,646 --> 04:48:16,415 >> I'M JUST GOING TO MAKE A FEW 7697 04:48:16,415 --> 04:48:17,449 CLOSING REMARKS. 7698 04:48:17,449 --> 04:48:27,993 OH, I SHOULD PROBABLY BRING -- I 7699 04:48:28,560 --> 04:48:29,962 JUST WANTED TO DO A QUICK 7700 04:48:29,962 --> 04:48:30,796 SUMMARY TO CLOSE OUT THE 7701 04:48:30,796 --> 04:48:31,096 WORKSHOP. 7702 04:48:31,096 --> 04:48:32,831 BUT BEFORE I DO THAT, I JUST 7703 04:48:32,831 --> 04:48:35,467 WANT TO POINT OUT, I DO 7704 04:48:35,467 --> 04:48:36,468 APPRECIATE THE THANKS THAT 7705 04:48:36,468 --> 04:48:37,402 EVERYBODY HAS OFFERED IN MY 7706 04:48:37,402 --> 04:48:40,038 DIRECTION, BUT THIS IS NOT A 7707 04:48:40,038 --> 04:48:41,139 SINGLE PERSON CREATING THIS 7708 04:48:41,139 --> 04:48:41,607 MEETING. 7709 04:48:41,607 --> 04:48:43,875 IT REALLY TAKES AN ENTIRE TEAM 7710 04:48:43,875 --> 04:48:45,277 OF PEOPLE. 7711 04:48:45,277 --> 04:48:46,945 SO FIRST, OF COURSE, STEVEN 7712 04:48:46,945 --> 04:48:48,981 BLACK WHO IS ONE OF OUR PROJECT 7713 04:48:48,981 --> 04:48:50,749 COORDINATORS HAS DONE A 7714 04:48:50,749 --> 04:48:51,950 FANTASTIC JOB HELPING OUT AT 7715 04:48:51,950 --> 04:48:54,119 EVERY STEP OF THE WAY. 7716 04:48:54,119 --> 04:48:55,621 ALONGSIDE STEVEN, THERE HAS BEEN 7717 04:48:55,621 --> 04:48:58,023 AN ENTIRE TEAM OF PROGRAM 7718 04:48:58,023 --> 04:49:01,760 OFFICERS INCLUDING ERIK STEMMY, 7719 04:49:01,760 --> 04:49:06,298 KATE, LAUREN, JENNIFER GORT GORN 7720 04:49:06,298 --> 04:49:08,166 AND NITA ALL WHO HAVE CONTRIBUTE 7721 04:49:08,166 --> 04:49:09,701 TODAY DEVELOPING THIS PROGRAM, 7722 04:49:09,701 --> 04:49:11,670 SO WE ALL HAD EXTENSIVE 7723 04:49:11,670 --> 04:49:12,638 CONVERSATIONS ABOUT WHO TO 7724 04:49:12,638 --> 04:49:13,739 INVITE, WHAT WE HOPE TO 7725 04:49:13,739 --> 04:49:15,207 ACCOMPLISH, AND I THINK ALL 7726 04:49:15,207 --> 04:49:16,441 TOGETHER, YOU KNOW, WE PUT OUR 7727 04:49:16,441 --> 04:49:18,110 BEST IDEAS FORWARD IN ORDER TO 7728 04:49:18,110 --> 04:49:19,745 CREATE THIS WORKSHOP. 7729 04:49:19,745 --> 04:49:21,513 SO BEFORE WE CLAP FOR ALL OF 7730 04:49:21,513 --> 04:49:24,216 THESE PEOPLE, I JUST WANTED TO 7731 04:49:24,216 --> 04:49:28,387 ALSO ACKNOWLEDGE THE EXTERNAL 7732 04:49:28,387 --> 04:49:33,158 CONTRIBUTION OF MAHUL AND SEEMA 7733 04:49:33,158 --> 04:49:34,159 WHO ALSO MADE SUGGESTIONS FOR 7734 04:49:34,159 --> 04:49:36,261 PUTTING THIS WORKSHOP TOGETHER. 7735 04:49:36,261 --> 04:49:37,963 FINALLY OUR EXCELLENT MODERATORS 7736 04:49:37,963 --> 04:49:39,064 FOR EVERY SINGLE SESSION WHO 7737 04:49:39,064 --> 04:49:40,699 HAVE REALLY DONE A GREAT JOB ON 7738 04:49:40,699 --> 04:49:41,566 KEEPING EVERYBODY ON TIME AND 7739 04:49:41,566 --> 04:49:43,435 ALSO KEEPING THAT CONVERSATION 7740 04:49:43,435 --> 04:49:44,403 DRIVING FORWARD. 7741 04:49:44,403 --> 04:49:46,038 SO LET'S -- I GUESS WE'LL CLAP 7742 04:49:46,038 --> 04:49:51,309 FOR EVERYBODY, RIGHT? 7743 04:49:51,309 --> 04:49:52,711 SO JUST A COUPLE OF LESSONS THAT 7744 04:49:52,711 --> 04:49:54,346 THIS IS NOT A COMPREHENSIVE LIST 7745 04:49:54,346 --> 04:49:55,881 BUT A COUPLE OF LESSONS THAT 7746 04:49:55,881 --> 04:49:58,383 I'VE TAKEN AWAY FROM THIS 7747 04:49:58,383 --> 04:49:59,451 WORKSHOP. 7748 04:49:59,451 --> 04:50:00,619 AND THAT I'VE HEARD MULTIPLE 7749 04:50:00,619 --> 04:50:01,319 TIMES. 7750 04:50:01,319 --> 04:50:03,522 ALSO HAVING COLLATED YOUR 7751 04:50:03,522 --> 04:50:05,490 RESPONSES FROM THE CONFERENCE IO 7752 04:50:05,490 --> 04:50:06,892 APP, THE QR CODE QUIZ OR 7753 04:50:06,892 --> 04:50:09,728 QUESTIONS. 7754 04:50:09,728 --> 04:50:11,129 SO FIRST CHOOSING MODELS BASED 7755 04:50:11,129 --> 04:50:12,564 ON THE QUESTION THAT YOU'RE 7756 04:50:12,564 --> 04:50:14,633 SEEKING TO ANSWER CAME ACROSS 7757 04:50:14,633 --> 04:50:16,935 VERY LOUD AND CLEAR IN THE 7758 04:50:16,935 --> 04:50:17,903 WORKSHOP. 7759 04:50:17,903 --> 04:50:19,971 I ALSO THINK THAT CONSIDERATION 7760 04:50:19,971 --> 04:50:21,840 OF THE DEMOGRAPHICS AND THEN 7761 04:50:21,840 --> 04:50:23,375 OTHER HEALTH CONDITIONS REALLY 7762 04:50:23,375 --> 04:50:25,077 ADDS A LOT OF COMPLEXITY TO 7763 04:50:25,077 --> 04:50:25,911 THESE SYSTEMS. 7764 04:50:25,911 --> 04:50:27,312 AND IT IS UNLIKELY THAT WE WOULD 7765 04:50:27,312 --> 04:50:30,048 BE ABLE TO SORT OF ADDRESS EVERY 7766 04:50:30,048 --> 04:50:33,118 SINGLE CONDITION IN A SINGLE 7767 04:50:33,118 --> 04:50:34,686 SYSTEM, SO THEREIN THE DIVERSITY 7768 04:50:34,686 --> 04:50:36,188 OF THE ANIMAL MODELS THAT YOU 7769 04:50:36,188 --> 04:50:38,890 ARE ALL GENERATING REALLY WILL 7770 04:50:38,890 --> 04:50:41,493 BE ABLE TO PROVIDE NEW 7771 04:50:41,493 --> 04:50:42,928 INFORMATION, AND ADDITIONAL 7772 04:50:42,928 --> 04:50:45,097 EXPERIMENTAL SUPPORT TO 7773 04:50:45,097 --> 04:50:48,033 UNDERSTANDING THE PATHOGENESIS, 7774 04:50:48,033 --> 04:50:48,867 TRANSMISSION, IMMUNOLOGY AND 7775 04:50:48,867 --> 04:50:50,535 OTHER ASPECTS OF RESPIRATORY 7776 04:50:50,535 --> 04:50:53,839 VIRUS INFECTIONS. 7777 04:50:53,839 --> 04:50:54,706 WE'VE HAD A LOT OF PEOPLE 7778 04:50:54,706 --> 04:50:56,775 MENTION THAT THERE SHOULD BE 7779 04:50:56,775 --> 04:50:59,311 PROPER QUALIFICATION OR 7780 04:50:59,311 --> 04:50:59,611 VALIDATION. 7781 04:50:59,611 --> 04:51:00,879 THANK YOU, BART, TODAY FOR SORT 7782 04:51:00,879 --> 04:51:01,780 OF DISTINGUISHING THOSE TWO 7783 04:51:01,780 --> 04:51:02,247 THINGS. 7784 04:51:02,247 --> 04:51:05,083 WE DO USE THAT TERM VALIDATION, 7785 04:51:05,083 --> 04:51:06,451 WHEN PERHAPS WE REALLY ARE 7786 04:51:06,451 --> 04:51:07,152 TALKING MORE ABOUT QUALIFICATION 7787 04:51:07,152 --> 04:51:08,453 OF ALL THESE REAGENTS. 7788 04:51:08,453 --> 04:51:11,289 BUT IN ANY -- IN EITHER SENSE, 7789 04:51:11,289 --> 04:51:12,257 IT'S ESSENTIAL THAT WE MAKE SURE 7790 04:51:12,257 --> 04:51:15,127 THAT THE REAGENTS ARE USABLE. 7791 04:51:15,127 --> 04:51:16,528 SO THIS NOT ONLY INCLUDES WHAT 7792 04:51:16,528 --> 04:51:18,130 WE JUST DISCUSSED, WHICH ARE THE 7793 04:51:18,130 --> 04:51:19,564 COMMERCIAL AND SHARED ANTIBODY, 7794 04:51:19,564 --> 04:51:21,533 BUT ALSO SEQUENCING THE VIRUSES 7795 04:51:21,533 --> 04:51:23,168 AS YOU AMPLIFY THEM IN YOUR OWN 7796 04:51:23,168 --> 04:51:24,369 LABS TO MAKE SURE THAT YOU KNOW 7797 04:51:24,369 --> 04:51:28,306 WHAT YOU'RE WORKING WITH. 7798 04:51:28,306 --> 04:51:30,609 AND THEN THE WELL ANNOTATED 7799 04:51:30,609 --> 04:51:32,144 GENOMES WHICH BECAME MORE 7800 04:51:32,144 --> 04:51:32,844 APPARENT DURING THE DISCUSSIONS 7801 04:51:32,844 --> 04:51:33,311 TODAY. 7802 04:51:33,311 --> 04:51:34,112 THEN OF COURSE JUST TO SORT OF 7803 04:51:34,112 --> 04:51:36,515 BRING US BACK TO THE FIRST 7804 04:51:36,515 --> 04:51:37,682 SESSION OF THE FIRST DAY IS, YOU 7805 04:51:37,682 --> 04:51:40,418 KNOW, PUTTING IN SOME EFFORT 7806 04:51:40,418 --> 04:51:41,853 INTO LINKING THE STUDIES IN 7807 04:51:41,853 --> 04:51:44,422 SMALL ANIMALS TO STUDIES IN 7808 04:51:44,422 --> 04:51:44,756 HUMANS. 7809 04:51:44,756 --> 04:51:46,291 AND HOW ARE WE GOING TO BEST DO 7810 04:51:46,291 --> 04:51:49,594 THAT MOVING FORWARD. 7811 04:51:49,594 --> 04:51:53,298 SO A COUPLE OF THE NEEDS THAT 7812 04:51:53,298 --> 04:51:54,399 I'VE IDENTIFIED BASE ON THE 7813 04:51:54,399 --> 04:51:55,267 DISCUSSIONS HERE. 7814 04:51:55,267 --> 04:51:56,802 WE'VE JUST TALKED ABOUT THIS 7815 04:51:56,802 --> 04:51:57,335 COMPREHENSIVE DATABASE. 7816 04:51:57,335 --> 04:51:58,170 IT'S SOMETHING THAT HOPEFULLY 7817 04:51:58,170 --> 04:52:01,840 WE'LL BE ABLE TO FACILITATE AND 7818 04:52:01,840 --> 04:52:03,341 ENGAGE WITH ALL OF YOU IN ORDER 7819 04:52:03,341 --> 04:52:04,442 TO BUILD SOMETHING THAT'S USEFUL 7820 04:52:04,442 --> 04:52:05,744 FOR THE COMMUNITY. 7821 04:52:05,744 --> 04:52:07,946 AS WELL AS THE IMMUNOLOGICAL 7822 04:52:07,946 --> 04:52:11,216 REAGENTS AND I'VE SORT OF 7823 04:52:11,216 --> 04:52:12,484 CATEGORIZED THESE INTO SORT OF 7824 04:52:12,484 --> 04:52:14,719 DETECTION OF ANTIBODY SUBTYPES, 7825 04:52:14,719 --> 04:52:16,488 B CELLS, T CELLS AND MUCOSAL 7826 04:52:16,488 --> 04:52:16,922 TARGETS. 7827 04:52:16,922 --> 04:52:24,362 WHAT I HAVEN'T HEARD ARE ABOUT 7828 04:52:24,362 --> 04:52:25,964 NON-IMMUNOLOGICAL TARGETS, SORT 7829 04:52:25,964 --> 04:52:26,665 OF UNIDENTIFIED. 7830 04:52:26,665 --> 04:52:28,066 EVEN THOUGH A LOT OF THE TARGETS 7831 04:52:28,066 --> 04:52:29,367 THAT WE'RE TALKING ABOUT ARE 7832 04:52:29,367 --> 04:52:32,504 CALLING FOR NEEDS AND STUDIES OF 7833 04:52:32,504 --> 04:52:34,506 IMMUNOLOGY, PLEASE DON'T EXCLUDE 7834 04:52:34,506 --> 04:52:36,241 OTHER THINGS IF THOSE ARE THE 7835 04:52:36,241 --> 04:52:37,776 KIND OF ANTIBODIES OR THINGS 7836 04:52:37,776 --> 04:52:41,179 THAT YOU NEED TO DETECT. 7837 04:52:41,179 --> 04:52:46,184 SO I THINK WE ALSO NEED TO HAVE 7838 04:52:46,184 --> 04:52:47,919 GREAT ROBUST DISCUSSIONS ABOUT 7839 04:52:47,919 --> 04:52:51,089 APPROPRIATE EXPERIMENTAL USE OF 7840 04:52:51,089 --> 04:52:53,158 THE MOUSE ADAPTED STRAINS VERSUS 7841 04:52:53,158 --> 04:52:54,826 HUMAN STRAINS AND EXPERIMENTAL 7842 04:52:54,826 --> 04:52:55,160 SYSTEMS. 7843 04:52:55,160 --> 04:52:56,428 AND I'VE HEARD SEVERAL TIMES 7844 04:52:56,428 --> 04:52:57,662 ABOUT THE DEVELOPMENT OF UPDATED 7845 04:52:57,662 --> 04:52:58,730 MOUSE STRAINS, ESPECIALLY IN THE 7846 04:52:58,730 --> 04:53:01,132 CASE OF INFLUENZA, SO THIS IS 7847 04:53:01,132 --> 04:53:05,937 SOMETHING ALSO TO CONSIDER. 7848 04:53:05,937 --> 04:53:07,706 I'M REALLY GLAD THAT WE GOT TO 7849 04:53:07,706 --> 04:53:08,907 HEAR ABOUT THE COLLABORATIVE 7850 04:53:08,907 --> 04:53:10,542 CROSS MOUSE MODEL. 7851 04:53:10,542 --> 04:53:12,277 AND CERTAINLY THINK THAT THERE'S 7852 04:53:12,277 --> 04:53:15,547 A LOT OF REALLY INTERESTING AND 7853 04:53:15,547 --> 04:53:16,915 USEFUL POTENTIAL THINGS TO 7854 04:53:16,915 --> 04:53:19,918 HAPPEN THERE. 7855 04:53:19,918 --> 04:53:21,553 BUT I CAN ALSO SEE A NEED FOR 7856 04:53:21,553 --> 04:53:23,255 EXPANDING THAT MOUSE MODEL USE 7857 04:53:23,255 --> 04:53:24,823 AS WELL AS THE ASSOCIATED 7858 04:53:24,823 --> 04:53:26,057 EXPERTISE WITH THAT. 7859 04:53:26,057 --> 04:53:28,760 AND THEN FINALLY, SOME OF THE 7860 04:53:28,760 --> 04:53:29,961 BROADER COLLABORATIONS THAT 7861 04:53:29,961 --> 04:53:32,597 WE'RE ALWAYS LOOKING TO 7862 04:53:32,597 --> 04:53:34,099 ESTABLISH. 7863 04:53:34,099 --> 04:53:37,736 WITH ENGINEERS, INFORMATICIANS 7864 04:53:37,736 --> 04:53:39,237 AND OTHER UNIQUE VIEWPOINTS THAT 7865 04:53:39,237 --> 04:53:41,106 ARE REALLY GOING TO HELP DRIVE 7866 04:53:41,106 --> 04:53:43,375 OUR WORK AND YOUR WORK IN SMALL 7867 04:53:43,375 --> 04:53:43,875 ANIMAL MODELS FORWARD. 7868 04:53:43,875 --> 04:53:44,976 SO THOSE ARE THE TWO SUMMARIES 7869 04:53:44,976 --> 04:53:46,244 THAT I REALLY WANTED TO PROVIDE 7870 04:53:46,244 --> 04:53:48,046 FOR YOU JUST TO SORT OF WRAP UP 7871 04:53:48,046 --> 04:53:50,682 THE WORKSHOP AND BRING THINGS 7872 04:53:50,682 --> 04:53:51,316 TOGETHER. 7873 04:53:51,316 --> 04:53:53,084 IN THE CONFERENCES IO APP, WE 7874 04:53:53,084 --> 04:53:54,286 UNVEILED A LAST QUESTION WHICH 7875 04:53:54,286 --> 04:53:55,487 IS TO PROVIDE US WITH ANY 7876 04:53:55,487 --> 04:53:56,187 FEEDBACK OR THOUGHTS THAT YOU 7877 04:53:56,187 --> 04:53:57,656 MIGHT HAVE ON THE WORKSHOP OR 7878 04:53:57,656 --> 04:53:58,657 ANYTHING ELSE. 7879 04:53:58,657 --> 04:53:59,991 IF YOU DON'T WANT TO USE THAT 7880 04:53:59,991 --> 04:54:03,161 APP, FEEL FREE TO EMAIL ME OR 7881 04:54:03,161 --> 04:54:04,763 STEVEN BLACK. 7882 04:54:04,763 --> 04:54:06,531 IT HELPS IF YOU KNOW US BOTH, SO 7883 04:54:06,531 --> 04:54:08,066 WE CAN KEEP TRACK OF THINGS WITH 7884 04:54:08,066 --> 04:54:13,104 YOUR FEEDBACK. 7885 04:54:13,104 --> 04:54:14,639 HAVE I FORGOTTEN ANYTHING? 7886 04:54:14,639 --> 04:54:15,540 SO I GUESS WITH THAT, I'M GOING 7887 04:54:15,540 --> 04:54:16,608 TO SAY THANK YOU ALL VERY MUCH 7888 04:54:16,608 --> 04:54:18,376 FOR YOUR ENGAGEMENT AND 7889 04:54:18,376 --> 04:54:19,678 PARTICIPATION IN THIS MEETING. 7890 04:54:19,678 --> 04:54:22,514 I THINK IT WENT VERY WELL. 7891 04:54:22,514 --> 04:54:23,281 AND WE'LL CLOSE THE MEETING. 7892 04:54:23,281 --> 04:54:23,748 THANK YOU. 7893 04:54:23,748 --> 04:54:33,925 [APPLAUSE]