1 00:02:12,300 --> 00:02:14,302 ANY CASE, I THINK I CAN JUST 2 00:02:14,302 --> 00:02:21,776 START BY SAYING, THIS MORNING A 3 00:02:21,776 --> 00:02:38,459 PLEASURE TO BE HERE. 4 00:02:38,459 --> 00:02:39,060 I'M FROM CENTER FOR BIOLOGICS EVALUATION 5 00:02:39,060 --> 00:02:39,761 AND RESEARCH. 6 00:02:39,761 --> 00:02:43,031 ALSO KNOWN AS CBER. 7 00:02:43,031 --> 00:02:46,768 I ALSO WANT TO APOLOGIZE 8 00:02:46,768 --> 00:02:51,406 BECAUSE I'M STILL STRUGGLING 9 00:02:51,406 --> 00:02:54,576 WITH A COUGH [OFF MIC] 10 00:02:54,576 --> 00:03:00,315 EARLIER INFECTION WITH COVID. 11 00:03:00,315 --> 00:03:04,385 SO ANYHOW, IN REGULATING THE 12 00:03:04,385 --> 00:03:05,086 PHARMACEUTICAL MANUFACTURING 13 00:03:05,086 --> 00:03:06,955 SECTOR, AND ALSO MORE RECENTLY 14 00:03:06,955 --> 00:03:11,960 WITH THE RAPID DEVELOPMENT, 15 00:03:11,960 --> 00:03:13,394 ACCELERATED DEVELOPMENT, 16 00:03:13,394 --> 00:03:14,262 COMMERCIALLY VIABLE GENE 17 00:03:14,262 --> 00:03:14,996 THERAPIES. 18 00:03:14,996 --> 00:03:17,131 BUT ALSO IN COORDINATING A 19 00:03:17,131 --> 00:03:19,968 RAPID RESPONSE DURING THE 20 00:03:19,968 --> 00:03:22,837 COVID-19 PANDEMIC, CBER 21 00:03:22,837 --> 00:03:25,907 REALIZES THE NEED FOR MAXIMALLY 22 00:03:25,907 --> 00:03:29,310 FLEXIBLE AND EFFICIENT AND 23 00:03:29,310 --> 00:03:31,412 AGILE BIO PHARMACEUTICAL 24 00:03:31,412 --> 00:03:33,281 MANUFACTURING SECTOR. 25 00:03:33,281 --> 00:03:36,818 TO RELIABLY AND ALSO TIMELY 26 00:03:36,818 --> 00:03:39,921 SUPPLY AND PRODUCE HIGH-QUALITY 27 00:03:39,921 --> 00:03:40,889 BIOLOGICS. 28 00:03:40,889 --> 00:03:43,725 TO ACHIEVE THIS VISION, CBER IS 29 00:03:43,725 --> 00:03:47,295 WORKING ACTIVELY TO ENCOURAGE 30 00:03:47,295 --> 00:03:49,264 THE DEVELOPMENT OF TECHNOLOGIES 31 00:03:49,264 --> 00:03:53,001 TO MODERNIZE A WAY WE 32 00:03:53,001 --> 00:03:54,702 MANUFACTURE QUALITY BIOLOGICS. 33 00:03:54,702 --> 00:03:58,573 AND SO IN TODAY'S PRESENTATION, 34 00:03:58,573 --> 00:04:02,010 WHEN MY SLIDES COME UP, I WILL 35 00:04:02,010 --> 00:04:04,112 TALK ABOUT SOME OF THE 36 00:04:04,112 --> 00:04:08,283 INITIATIVES UNDER OUR PROGRAM, 37 00:04:08,283 --> 00:04:09,951 CBER, ADVANCED TECHNOLOGIES 38 00:04:09,951 --> 00:04:11,586 PROGRAM TO REALLY PROMOTE THE 39 00:04:11,586 --> 00:04:15,990 DEVELOP MENT AND ALSO ADOPTION 40 00:04:15,990 --> 00:04:18,860 OF ADVANCED MANUFACTURING 41 00:04:18,860 --> 00:04:24,265 TECHNOLOGIES TO REALLY, FOR THE 42 00:04:24,265 --> 00:04:29,470 CBER REGULATED PRODUCTS. 43 00:04:29,470 --> 00:04:30,705 I DON'T KNOW, SHOULD I WAIT FOR 44 00:04:30,705 --> 00:04:40,915 THE SLIDES? 45 00:05:14,849 --> 00:05:21,856 ALSO YESTERDAY, DR. SALLOW 46 00:05:21,856 --> 00:05:23,491 SALOMON IN HER TALK, SHOULD 47 00:05:23,491 --> 00:05:25,259 ENGINEER WITH THE END IN MIND. 48 00:05:25,259 --> 00:05:27,028 [OFF MIC] 49 00:05:27,028 --> 00:05:29,330 OH, SORRY. 50 00:05:29,330 --> 00:05:33,434 I WAS JUST SAYING, I THINK 51 00:05:33,434 --> 00:05:35,803 YESTERDAY, DR. SALOMON IN HER 52 00:05:35,803 --> 00:05:38,239 PRESENTATION, SHE MENTIONED 53 00:05:38,239 --> 00:05:39,173 THAT DEVELOPMENT SHOULD 54 00:05:39,173 --> 00:05:40,641 ENGINEER WITH THE END IN MIND. 55 00:05:40,641 --> 00:05:42,543 I THOUGHT THAT WAS A GREAT 56 00:05:42,543 --> 00:05:42,744 POINT. 57 00:05:42,744 --> 00:05:46,247 BECAUSE ESPECIALLY IN OUR 58 00:05:46,247 --> 00:05:47,648 EXPERIENCE EVALUATING 59 00:05:47,648 --> 00:05:51,152 BIOLOGICAL PRODUCTS WE SEE THE 60 00:05:51,152 --> 00:05:53,488 DIFFERENT PHASES HOW THE 61 00:05:53,488 --> 00:05:57,125 MANUFACTURERS STRUGGLE, RIGHT? 62 00:05:57,125 --> 00:05:59,360 WHEN THEY REALIZE, SO INTENT, 63 00:05:59,360 --> 00:06:01,496 FOCUSED ON CURRENT STAGE OF 64 00:06:01,496 --> 00:06:02,830 DEVELOPMENT, SOMETIMES -- 65 00:06:02,830 --> 00:06:04,699 THERE'S ALSO MANY FACTORS TO 66 00:06:04,699 --> 00:06:06,801 PUSH YOU TO ACCELERATE AND 67 00:06:06,801 --> 00:06:08,202 ACCELERATE AND SPEED UP. 68 00:06:08,202 --> 00:06:10,772 SO YOU DON'T ALWAYS THINK AHEAD 69 00:06:10,772 --> 00:06:13,341 ABOUT THE COMMERCIAL NEEDS, OR 70 00:06:13,341 --> 00:06:14,642 COMMERCIAL VIABILITY OF YOUR 71 00:06:14,642 --> 00:06:16,144 DEVELOPMENT APPROACH. 72 00:06:16,144 --> 00:06:18,179 AND VERY OFTEN IT ALSO COMES IN 73 00:06:18,179 --> 00:06:22,316 MANUFACTURING. 74 00:06:22,316 --> 00:06:24,385 SO THAT, WHEN YOU SHIFT YOUR 75 00:06:24,385 --> 00:06:26,020 STRATEGY LATER ON, IN THE LATER 76 00:06:26,020 --> 00:06:28,990 PHASE OF DEVELOPMENT, THAT JUST 77 00:06:28,990 --> 00:06:31,359 CREATES A TREMENDOUS AMOUNT OF 78 00:06:31,359 --> 00:06:32,060 CHALLENGES, SOMETIMES EVEN AT 79 00:06:32,060 --> 00:06:35,063 THE COST OF REPEATING SOME OF 80 00:06:35,063 --> 00:06:36,431 YOUR NON-CLINICAL OR CLINICAL 81 00:06:36,431 --> 00:06:39,100 STUDIES. 82 00:06:39,100 --> 00:06:40,902 THAT COULD ACTUALLY INTRODUCE 83 00:06:40,902 --> 00:06:42,370 SIGNIFICANT DELAY IN YOUR 84 00:06:42,370 --> 00:06:43,738 PROCESS AND PRODUCT DEVELOPMENT 85 00:06:43,738 --> 00:06:45,706 TIMELINE, RIGHT? 86 00:06:45,706 --> 00:06:48,643 AND SOMETIMES IT COULD BE AS 87 00:06:48,643 --> 00:06:50,511 SMALL AS, OH, YOU KNOW, 88 00:06:50,511 --> 00:06:56,884 SOMETHING WORKS MAYBE WITH 89 00:06:56,884 --> 00:06:57,218 MICROFLUIDICS. 90 00:06:57,218 --> 00:06:58,986 IF I HAVE TO SCALE UP, WHAT 91 00:06:58,986 --> 00:07:01,088 KIND OF SCALE DO I NEED TO HAVE 92 00:07:01,088 --> 00:07:02,523 FOR PILOT AND FOR PRODUCTION. 93 00:07:02,523 --> 00:07:04,358 AND WHAT KIND OF PATIENT 94 00:07:04,358 --> 00:07:05,860 DEMANDS DO I HAVE THERE TO MAKE 95 00:07:05,860 --> 00:07:08,729 THAT HAPPEN? 96 00:07:08,729 --> 00:07:10,131 AND MY CURRENT APPROACH THAT 97 00:07:10,131 --> 00:07:12,300 WORKS FOR THE LABORATORY, FOR 98 00:07:12,300 --> 00:07:22,777 EXAMPLE, CENTRIFICATION OR 99 00:07:27,615 --> 00:07:30,017 FLUIDICS. 100 00:07:30,017 --> 00:07:30,952 LIKE GENE THERAPIES, BECAUSE WE 101 00:07:30,952 --> 00:07:33,020 DON'T HAVE A LOT OF PRODUCT 102 00:07:33,020 --> 00:07:33,588 KNOWLEDGE OR MANUFACTURING 103 00:07:33,588 --> 00:07:34,655 EXPERIENCE. 104 00:07:34,655 --> 00:07:35,823 HOWEVER, THE CLINICAL 105 00:07:35,823 --> 00:07:37,492 DEVELOPMENT IS ACTUALLY 106 00:07:37,492 --> 00:07:39,193 ACCELERATED COMPARED TO 107 00:07:39,193 --> 00:07:40,461 CONVENTIONAL PRODUCTS. 108 00:07:40,461 --> 00:07:42,163 SO VERY OFTEN, YOU KNOW, THE 109 00:07:42,163 --> 00:07:44,499 PROCESS DEVELOPMENT AND ALSO 110 00:07:44,499 --> 00:07:45,566 ANALYTICAL DEVELOPMENT ACTUALLY 111 00:07:45,566 --> 00:07:46,501 LAGS BEHIND. 112 00:07:46,501 --> 00:07:48,469 AND THEN YOU HAVE THIS PUSH AT 113 00:07:48,469 --> 00:07:50,104 THE END THAT DOESN'T ALWAYS 114 00:07:50,104 --> 00:07:51,372 WORK OUT AS SMOOTHLY AS IT 115 00:07:51,372 --> 00:07:58,145 SHOULD BE. 116 00:07:58,145 --> 00:08:03,551 DO YOU THINK I SHOULD GIVE A 117 00:08:03,551 --> 00:08:13,961 -- VERSION OF MY TALK? 118 00:08:41,756 --> 00:08:46,127 [OFF MIC] 119 00:08:46,127 --> 00:08:47,895 I WILL TRY MY BEST TO ANSWER 120 00:08:47,895 --> 00:08:58,139 ANY QUESTIONS. 121 00:09:10,751 --> 00:09:20,861 [OFF MIC] 122 00:09:48,256 --> 00:09:49,724 >> ALL RIGHT, SO THIS WAS JUST 123 00:09:49,724 --> 00:09:50,558 A TEST. 124 00:09:50,558 --> 00:09:51,993 IT DIDN'T WORK OUT. 125 00:09:51,993 --> 00:09:58,032 SO WE WILL HAVE LIGHTNING TALK 126 00:09:58,032 --> 00:09:59,900 INSTEAD OF -- 127 00:09:59,900 --> 00:10:06,507 WE HAVE VLAHOS COMING FROM 128 00:10:06,507 --> 00:10:07,375 STANFORD UNIVERSITY. 129 00:10:07,375 --> 00:10:14,148 HE WILL BE TELLING US ABOUT 130 00:10:14,148 --> 00:10:14,782 "COMPACT PROGRAMABLE CONTROL OF 131 00:10:14,782 --> 00:10:15,549 PROTEIN SECRETION IN MAMMALIAN 132 00:10:15,549 --> 00:10:16,717 CELLS". 133 00:10:16,717 --> 00:10:22,657 SO, PLEASE. 134 00:10:22,657 --> 00:10:23,658 >> Alexander Vlahos: PERFECT, 135 00:10:23,658 --> 00:10:26,294 THANK YOU SO MUCH FOR THE KIND 136 00:10:26,294 --> 00:10:26,627 INTRODUCTION. 137 00:10:26,627 --> 00:10:27,928 I SEE MY SLIDES. 138 00:10:27,928 --> 00:10:34,502 SWITCH? 139 00:10:34,502 --> 00:10:35,803 HE IS SWITCHING. 140 00:10:35,803 --> 00:10:38,205 OKAY, I WILL HAVE A BRIEF 141 00:10:38,205 --> 00:10:39,373 15-MINUTE CHAT HERE ABOUT A 142 00:10:39,373 --> 00:10:43,010 SLIDE WE HAVE BEEN WORKING ON 143 00:10:43,010 --> 00:10:43,611 LABELED "COMPACT PROGRAMABLE 144 00:10:43,611 --> 00:10:44,278 CONTROL OF PROTEIN SECRETION IN 145 00:10:44,278 --> 00:10:45,946 MAMMALIAN CELLS". 146 00:10:45,946 --> 00:10:50,084 SO WHEN WE THINK ABOUT ANY SORT 147 00:10:50,084 --> 00:10:52,219 OF CELL THERAPIES OR IN 148 00:10:52,219 --> 00:10:54,288 GENERAL, CELLS IN THE HUMAN 149 00:10:54,288 --> 00:10:58,325 BODY ARE REALLY GOVERNED BY 150 00:10:58,325 --> 00:10:59,193 INTRACELLULAR SIGNALS. 151 00:10:59,193 --> 00:11:09,570 IT'S REALLY A CAREFUL 152 00:11:10,938 --> 00:11:12,039 HOMEOSTATIC RELATIONSHIP, THAT 153 00:11:12,039 --> 00:11:13,207 GOVERN THE IMMUNE CELL. 154 00:11:13,207 --> 00:11:15,109 SO WHEN IT COMES TO THE 155 00:11:15,109 --> 00:11:18,913 COMMUNICATION, THESE ARE ALL 156 00:11:18,913 --> 00:11:20,114 GOVERNED BY INTERCELLULAR 157 00:11:20,114 --> 00:11:21,749 SIGNALS AND ANY KIND OF CELL 158 00:11:21,749 --> 00:11:25,219 THERAPY WE PLAN TO DELIVERY, 159 00:11:25,219 --> 00:11:26,854 EITHER SOMETHING FOR PILOT 160 00:11:26,854 --> 00:11:28,589 TRANSPORTATION, YOU ARE 161 00:11:28,589 --> 00:11:35,363 ESSENTIALLY DISRUPTING THAT 162 00:11:35,363 --> 00:11:36,397 HOMEOSTASIS. 163 00:11:36,397 --> 00:11:38,499 THE FIELD OF SYNTHETIC BIOLOGY 164 00:11:38,499 --> 00:11:41,068 HAS REALLY BEEN FOCUSING ON 165 00:11:41,068 --> 00:11:44,605 USING THESE ENGINEERED CELLS 166 00:11:44,605 --> 00:11:46,907 THAT CAN SENSE PROCESS AND 167 00:11:46,907 --> 00:11:52,813 RESPOND TO ENDOGENOUS INPUTS 168 00:11:52,813 --> 00:11:57,385 AND HAVE VARIOUS RESPONSE. 169 00:11:57,385 --> 00:12:03,991 THE FIELD MAMMALIAN SYN-BIO, 170 00:12:03,991 --> 00:12:05,526 ONLY IN THE PAST FIVE YEARS 171 00:12:05,526 --> 00:12:08,229 THERE'S BEEN A PUSH TO USING 172 00:12:08,229 --> 00:12:10,231 PROTEIN-BASED CIRCUIT. 173 00:12:10,231 --> 00:12:12,099 SO SYNTHETIC PROTEIN BASED 174 00:12:12,099 --> 00:12:14,235 CIRCUIT HAVE SOME ADVANTAGES, 175 00:12:14,235 --> 00:12:16,737 THEY FUNCTION A ENTIRELY AT THE 176 00:12:16,737 --> 00:12:17,905 POST TRANSLATIONAL LEVEL. 177 00:12:17,905 --> 00:12:19,874 THEY ARE RELATIVELY COMPACT. 178 00:12:19,874 --> 00:12:21,409 BEING ABLE TO BE ENCODED ALSO 179 00:12:21,409 --> 00:12:23,444 UNDER THE CONTROL OF A SINGLE 180 00:12:23,444 --> 00:12:24,678 PROMOTER. 181 00:12:24,678 --> 00:12:25,880 AND MORE IMPORTANTLY, THEY 182 00:12:25,880 --> 00:12:28,516 ACTUALLY CAN BE DELIVERED VIA 183 00:12:28,516 --> 00:12:29,450 mRNA. 184 00:12:29,450 --> 00:12:31,786 WHICH NOWADAYS IS A PRETTY 185 00:12:31,786 --> 00:12:34,221 STANDARD THING WITH ALL THE 186 00:12:34,221 --> 00:12:35,122 COVID VACCINE. 187 00:12:35,122 --> 00:12:38,859 WHEN IT COMES TO THE CIRCUIT, 188 00:12:38,859 --> 00:12:41,462 THE PROTEASE HAS BEEN THE 189 00:12:41,462 --> 00:12:42,863 COMMON CURRENCY THAT'S ALLOWED 190 00:12:42,863 --> 00:12:45,199 US TO DESIGN THESE COMPLEX 191 00:12:45,199 --> 00:12:45,466 BEHAVIORS. 192 00:12:45,466 --> 00:12:48,269 SO WHEN WE THINK OF THE INPUT 193 00:12:48,269 --> 00:12:50,638 PROCESS AND OUTPUT SCHEME, THE 194 00:12:50,638 --> 00:12:54,909 INPUTS REALLY CAN BE ANY SORT 195 00:12:54,909 --> 00:12:57,711 OF DIMERIZATION EVENT THAT CAN 196 00:12:57,711 --> 00:13:02,249 CONSTITUTE A PROTEASE AND 197 00:13:02,249 --> 00:13:02,616 FUNCTIONAL. 198 00:13:02,616 --> 00:13:03,984 CHOMP SOMETHING DEVELOPED IN 199 00:13:03,984 --> 00:13:06,120 OUR GROUP IS THE PROCESSING 200 00:13:06,120 --> 00:13:10,724 MODULE THAT ALLOWS US TO DO 201 00:13:10,724 --> 00:13:13,327 ORTHOGONAL PROTEASE FOR THESE 202 00:13:13,327 --> 00:13:14,962 COMPLEX BEHAVIORS AND ONLY 203 00:13:14,962 --> 00:13:18,299 RECENTLY WE PUBLISHED A 204 00:13:18,299 --> 00:13:23,270 PLATFORM CALLED RELEASE TO 205 00:13:23,270 --> 00:13:25,506 CONTROL INTERCELLULAR SIGNALS. 206 00:13:25,506 --> 00:13:26,106 BEFORE ANY ENGINEERING THAT 207 00:13:26,106 --> 00:13:27,475 WOULD BE DONE WOULD BE DONE IN 208 00:13:27,475 --> 00:13:29,076 THE CELL ITSELF AND WOULDN'T BE 209 00:13:29,076 --> 00:13:30,711 ABLE TO COMMUNICATE WITH ANY 210 00:13:30,711 --> 00:13:32,813 CELLS ON THE EXTERIOR. 211 00:13:32,813 --> 00:13:35,149 SO JUST BRIEFLY THE WAY RELEASE 212 00:13:35,149 --> 00:13:39,820 WORKS, IT REALLY HARNESSES 213 00:13:39,820 --> 00:13:41,222 NATIVE ENDOGENOUS SIGNALING 214 00:13:41,222 --> 00:13:43,524 MOTIFS, WE CAN TAG A PROTEIN OF 215 00:13:43,524 --> 00:13:47,261 INTEREST, SHOWN HERE, WITH THIS 216 00:13:47,261 --> 00:13:48,429 ER RETENTION MOTIF. 217 00:13:48,429 --> 00:13:52,733 WHAT HAPPENS IS WHEN YOU TAG 218 00:13:52,733 --> 00:13:56,637 THIS ER RETENTION MOTIF, IT'S 219 00:13:56,637 --> 00:13:58,405 ACTIVELY TRANSPORTED BACK TO 220 00:13:58,405 --> 00:13:58,973 THE ER. 221 00:13:58,973 --> 00:14:01,308 AND THEY ARE IN THE CYTOSOL. 222 00:14:01,308 --> 00:14:03,544 BECAUSE YOU HAVE SECRETION OF 223 00:14:03,544 --> 00:14:05,646 THE PROTEINS VIA THE ER, THIS 224 00:14:05,646 --> 00:14:07,715 SORT OF ALLOWS US TO CONTROL 225 00:14:07,715 --> 00:14:09,683 THE SECRETION IN RESPONSE TO 226 00:14:09,683 --> 00:14:11,485 PROTEASE ACTIVITY. 227 00:14:11,485 --> 00:14:14,555 SO WHEN THERE'S NO PROTEASE 228 00:14:14,555 --> 00:14:16,390 ACTIVITY OR YOU HAVE NO INPUT 229 00:14:16,390 --> 00:14:19,960 ON, YOU END UP GETTING A 230 00:14:19,960 --> 00:14:21,362 RETROGRADE TRANSPORT OF THE 231 00:14:21,362 --> 00:14:22,429 PROTEIN OF INTEREST. 232 00:14:22,429 --> 00:14:24,598 ONLY WHEN YOU HAVE ACTIVATION 233 00:14:24,598 --> 00:14:27,735 OF THE PROTEASE YOU GET REMOVAL 234 00:14:27,735 --> 00:14:30,304 OF THE MOTIF, IT GETS 235 00:14:30,304 --> 00:14:32,172 TRANSPORTED THROUGH THE 236 00:14:32,172 --> 00:14:32,573 SECONDARY PATHWAY. 237 00:14:32,573 --> 00:14:39,914 AND OUR CASE WE ATTACHED A CURE 238 00:14:39,914 --> 00:14:41,582 CUT CYTOMEMBRANE BOUND AND 239 00:14:41,582 --> 00:14:44,652 PROCESS IT IN ITS SOLUBLE FORM. 240 00:14:44,652 --> 00:14:47,655 THAT WAS AN EXAMPLE OF 241 00:14:47,655 --> 00:14:50,190 ACTIVATING PROTEIN SECRETION IN 242 00:14:50,190 --> 00:14:53,127 RESPONSE TO PROTEASE ACTIVITY. 243 00:14:53,127 --> 00:14:55,696 SOMETHING IS TO TURN OFF 244 00:14:55,696 --> 00:14:57,498 PROTEIN SECRETION IN RESPONSE. 245 00:14:57,498 --> 00:15:01,869 THINK OF IT IS AS AN OFF-SWITCH. 246 00:15:01,869 --> 00:15:03,270 INITIALLY WHEN WE WERE LOOKING 247 00:15:03,270 --> 00:15:06,607 TO USE THE RELEASE PLATFORM FOR 248 00:15:06,607 --> 00:15:12,846 THIS PROTEOLYTIC REPRESSION, 249 00:15:12,846 --> 00:15:14,014 WE WOULD HAVE SOMETHING TO TURN 250 00:15:14,014 --> 00:15:17,551 ON THE THING, YOU REQUIRE 251 00:15:17,551 --> 00:15:18,886 MULTIPLE PROTEASES TO HAVE THIS 252 00:15:18,886 --> 00:15:19,186 BEHAVIOR. 253 00:15:19,186 --> 00:15:19,653 . 254 00:15:19,653 --> 00:15:21,522 . 255 00:15:21,522 --> 00:15:28,095 SO WHAT ENDS UP HAPPENING IS 256 00:15:28,095 --> 00:15:30,831 YOU CAN HAVE AN INTERMEDIATE 257 00:15:30,831 --> 00:15:33,400 THAT ACTS AS A PROCESSING SO 258 00:15:33,400 --> 00:15:35,069 THE INPUT SUPPRESSES THAT, 259 00:15:35,069 --> 00:15:36,303 EFFECTIVELY TURNING OFF THE 260 00:15:36,303 --> 00:15:36,971 RELEASE SYSTEM. 261 00:15:36,971 --> 00:15:38,505 BUT WHAT I WOULD LIKE TO SORT 262 00:15:38,505 --> 00:15:41,909 OF SHOW IS THE FACT THAT EVEN 263 00:15:41,909 --> 00:15:43,844 IN THIS TWO-PROTEASE SYSTEM, AS 264 00:15:43,844 --> 00:15:45,479 YOU INCREASE THE AMOUNT OF 265 00:15:45,479 --> 00:15:56,023 INPUT PROTEAS, YOU DON'T GET 266 00:15:58,092 --> 00:16:00,294 A TURN OFF OF THE SYSTEM. 267 00:16:00,294 --> 00:16:03,230 WE ARE LOWERING THE AMOUNT OF 268 00:16:03,230 --> 00:16:06,233 PROTEASE FOR MORE COMPLEX 269 00:16:06,233 --> 00:16:06,500 BEHAVIORS. 270 00:16:06,500 --> 00:16:07,935 THE COMPONENTS NEED TO BE 271 00:16:07,935 --> 00:16:09,103 REALLY FINALLY TUNED. 272 00:16:09,103 --> 00:16:13,707 EVEN IN THIS IN VITRO SET UP WE 273 00:16:13,707 --> 00:16:14,808 DON'T TURN OFF PROTEIN 274 00:16:14,808 --> 00:16:16,010 SECRETION. 275 00:16:16,010 --> 00:16:16,710 MORE IMPORTANTLY, AND AT THE 276 00:16:16,710 --> 00:16:19,279 END OF THE DAY WE ACTUALLY 277 00:16:19,279 --> 00:16:20,247 INCREASE THE OVERALL SIZE OF 278 00:16:20,247 --> 00:16:21,148 THE TRANSCRIPT. 279 00:16:21,148 --> 00:16:23,884 WHEN WE ARE THINKING OF 280 00:16:23,884 --> 00:16:25,552 STREAMLINING THESE PROTEIN 281 00:16:25,552 --> 00:16:27,187 CIRCUIT AND HARNESSES THE 282 00:16:27,187 --> 00:16:28,122 ADVANTAGE OF COMPACTNESS, WE 283 00:16:28,122 --> 00:16:29,757 WANT TO REDUCE THE SIZE OF OUR 284 00:16:29,757 --> 00:16:32,059 TRANSCRIPT AS MUCH AS POSSIBLE. 285 00:16:32,059 --> 00:16:34,128 SO WE REALIZE THAT SINCE WE ARE 286 00:16:34,128 --> 00:16:36,663 FUNCTIONING ALL AT THE 287 00:16:36,663 --> 00:16:37,598 POST-TRANSLATIONAL LEVEL, THERE 288 00:16:37,598 --> 00:16:41,301 ARE ALSO ADDITIONAL OTHER 289 00:16:41,301 --> 00:16:42,002 POST-TRANSLATIONAL THAT CELLS 290 00:16:42,002 --> 00:16:44,204 USE TO CONTROL SURFACE 291 00:16:44,204 --> 00:16:44,805 EXPRESSION NORMALLY. 292 00:16:44,805 --> 00:16:46,640 SO ONE REALLY INTERESTING ONE 293 00:16:46,640 --> 00:16:54,014 IS ACTUALLY THE INTERACTION 294 00:16:54,014 --> 00:16:59,586 BETWEEN PHOSPHOROLATED PEP 295 00:16:59,586 --> 00:17:03,590 TIDES AND THEIR ABILITY TO 296 00:17:03,590 --> 00:17:09,463 RECRUIT IN THESE 14-3-3 297 00:17:09,463 --> 00:17:10,597 SCAFFOLDING PROTEINS. 298 00:17:10,597 --> 00:17:13,901 THEY CAN BLOCK THE MOTIFS BY 299 00:17:13,901 --> 00:17:16,437 BLOCKING REACTIONS WITH THE 300 00:17:16,437 --> 00:17:19,373 RETROGRADE MACHINERY. 301 00:17:19,373 --> 00:17:21,742 EFFECTIVELY IN RESPONSE TO 302 00:17:21,742 --> 00:17:23,177 PHOSPHORYLATION THERE ARE 303 00:17:23,177 --> 00:17:24,111 RECEPTOR PROTEINS THAT ARE 304 00:17:24,111 --> 00:17:25,312 EXPRESSED ON THE SURFACE. 305 00:17:25,312 --> 00:17:27,047 THAT'S HOW THEY CONTROL THEIR 306 00:17:27,047 --> 00:17:27,648 SURFACE EXPRESSION. 307 00:17:27,648 --> 00:17:30,918 WE HAD A HYPOTHESIS WHAT IF WE 308 00:17:30,918 --> 00:17:34,388 COULD HARNESS THESE 14-3-3 309 00:17:34,388 --> 00:17:35,556 INTERACTIONS TO TUNE PROTEIN 310 00:17:35,556 --> 00:17:36,223 SECRETION. 311 00:17:36,223 --> 00:17:39,727 SO WHAT WE USED IS, INSTEAD OF 312 00:17:39,727 --> 00:17:43,197 FOCUSING ON PHOSPHORYLATION WE 313 00:17:43,197 --> 00:17:47,935 SIMPLY ATTACHED A 14-3-3 314 00:17:47,935 --> 00:17:49,837 ANTAGONIST TO THE RELEASE 315 00:17:49,837 --> 00:17:51,905 CONSTRUCT AND WE HAD ANOTHER 316 00:17:51,905 --> 00:17:54,308 MUTANT VERSION IN WHICH THE 317 00:17:54,308 --> 00:17:56,577 PEPTIDES INVOLVED WITH 318 00:17:56,577 --> 00:17:57,811 RECRUITMENT WERE MUTATED OUT. 319 00:17:57,811 --> 00:17:59,780 WHAT I'M SHOWING YOU HERE IS 320 00:17:59,780 --> 00:18:02,616 EXAMPLE OF A PROTEIN THAT IS 321 00:18:02,616 --> 00:18:04,017 NORMALLY SECRETED BUT WHEN IT'S 322 00:18:04,017 --> 00:18:05,185 TAGGED WITH THE RELEASE COME 323 00:18:05,185 --> 00:18:07,988 PRINCE GEORGE-VALEMOUNT -- 324 00:18:07,988 --> 00:18:12,059 COMPOUND THAT HAS A MUTANT 325 00:18:12,059 --> 00:18:16,196 14-3-3, IT'S NOT SECRETED. 326 00:18:16,196 --> 00:18:18,098 YOU GET BLOCK OF THE RETENTION 327 00:18:18,098 --> 00:18:19,733 CAPABILITIES OF THE RELEASE AND 328 00:18:19,733 --> 00:18:22,503 SECRETION OF YOUR PROTEIN OF 329 00:18:22,503 --> 00:18:29,710 INTEREST. 330 00:18:29,710 --> 00:18:31,812 WE CAN NOW DEVELOP A STRATEGY 331 00:18:31,812 --> 00:18:34,014 WE CAN TURN OFF PROTEIN 332 00:18:34,014 --> 00:18:35,816 SECRETION IN RESPONSE TO 333 00:18:35,816 --> 00:18:36,483 PROTEASE ACTIVITY. 334 00:18:36,483 --> 00:18:41,522 WITHOUT THE IMMEDIATE -- 335 00:18:41,522 --> 00:18:45,659 NEED OF AN INTERMEDIATE. 336 00:18:45,659 --> 00:18:53,467 YOU HAVE ACTIVATION OF INPUT 337 00:18:53,467 --> 00:18:55,068 PROTEASE. 338 00:18:55,068 --> 00:18:55,903 IT'S RESTORED. 339 00:18:55,903 --> 00:18:57,137 THIS IS AN EXAMPLE OF THE 340 00:18:57,137 --> 00:18:59,439 CURVES WE HAVE BEEN SEEING. 341 00:18:59,439 --> 00:19:02,009 WE ARE EFFECTIVELY GETTING 342 00:19:02,009 --> 00:19:02,876 PROTEIN SECRETION COMPLETELY 343 00:19:02,876 --> 00:19:03,443 TURNED OFF. 344 00:19:03,443 --> 00:19:06,013 SO NOW WITH THE ABILITY TO DO 345 00:19:06,013 --> 00:19:08,348 ON AND OFF, WE HAVE PREVIOUSLY 346 00:19:08,348 --> 00:19:14,054 SHOWED YOU CAN DO AND OROGATE, 347 00:19:14,054 --> 00:19:19,126 SINCE THIS IS A SYNTHETIC 348 00:19:19,126 --> 00:19:21,228 CONSORTIUM IT WOULD BE WRONG IF 349 00:19:21,228 --> 00:19:25,132 I DIDN'T SHOW ALL WE CAN DO. 350 00:19:25,132 --> 00:19:26,500 SOME ARE MORE USEFUL THAN 351 00:19:26,500 --> 00:19:27,935 OTHERS. 352 00:19:27,935 --> 00:19:30,470 WE DON'T REQUIRE INTERMEDIATE 353 00:19:30,470 --> 00:19:30,971 PROCESSING PROTEASES. 354 00:19:30,971 --> 00:19:33,507 ONE THAT I REALLY ACTUALLY 355 00:19:33,507 --> 00:19:35,142 THINK IS USEFUL, AT LEAST FOR 356 00:19:35,142 --> 00:19:40,781 OUR CASE AND LONG-TERM GOALS IS 357 00:19:40,781 --> 00:19:42,149 THIS NIMPLY GATE. 358 00:19:42,149 --> 00:19:44,117 YOU HAVE AN ENGINEER CELL YOU 359 00:19:44,117 --> 00:19:45,752 CO DELIVERED WITH THE 360 00:19:45,752 --> 00:19:47,154 THERAPEUTIC CELL AND YOU 361 00:19:47,154 --> 00:19:48,689 ESSENTIALLY WANT TO BE ABLE TO 362 00:19:48,689 --> 00:19:52,359 ONLY SENSE A SPECIFIC CELL TYPE. 363 00:19:52,359 --> 00:19:53,660 AN INPUT FROM A SPECIFIC CELL 364 00:19:53,660 --> 00:19:54,127 TYPE. 365 00:19:54,127 --> 00:19:57,631 SO IN THE TOP CASE THERE'S A 366 00:19:57,631 --> 00:20:03,403 PRO-INFLAMMATORY MACROPHAGE. 367 00:20:03,403 --> 00:20:07,774 YOU WANT TO TURN ON AN 368 00:20:07,774 --> 00:20:08,742 ANTIINFLAMMATORY CYTOKINE IN 369 00:20:08,742 --> 00:20:10,143 THAT SITUATION, BUT THERE MIGHT 370 00:20:10,143 --> 00:20:11,545 BE ANOTHER SITUATION YOU HAVE 371 00:20:11,545 --> 00:20:12,813 AN ADDITIONAL CELL AND 372 00:20:12,813 --> 00:20:13,981 ADDITIONAL INPUT. 373 00:20:13,981 --> 00:20:15,816 IN THAT SITUATION YOU WANT IT 374 00:20:15,816 --> 00:20:16,850 TO TURN OFF. 375 00:20:16,850 --> 00:20:20,387 THIS IS A PERFECT EXAMPLE OF 376 00:20:20,387 --> 00:20:21,955 THE NIMPLY GATE ACTIVATION. 377 00:20:21,955 --> 00:20:24,091 WHAT I WILL DO IS QUICKLY TAKE 378 00:20:24,091 --> 00:20:25,225 THROUGH HOW THIS WHOLE GATE 379 00:20:25,225 --> 00:20:25,993 WORKS. 380 00:20:25,993 --> 00:20:28,328 IN THE FIRST CASE WE HAVE NO 381 00:20:28,328 --> 00:20:28,562 INPUTS. 382 00:20:28,562 --> 00:20:33,567 WHAT WE HAVE IS THE PROTEIN 383 00:20:33,567 --> 00:20:35,235 RETAINED, AT THE END TERMINUS 384 00:20:35,235 --> 00:20:38,071 WE HAVE AN ADDITIONAL MOTIF 385 00:20:38,071 --> 00:20:39,406 FUNCTIONAL. 386 00:20:39,406 --> 00:20:42,042 THE C-TERMINUS IS INHIBITED BY 387 00:20:42,042 --> 00:20:42,909 THE PEPTIDE. 388 00:20:42,909 --> 00:20:44,344 WHEN YOU HAVE INPUT OF INTEREST 389 00:20:44,344 --> 00:20:46,747 YOU WANT TO TURN OFF, BY 390 00:20:46,747 --> 00:20:49,383 REMOVING THE END TERMINAL 391 00:20:49,383 --> 00:20:50,951 RETENTION MOTIF, THE SECOND IS 392 00:20:50,951 --> 00:20:52,853 BLOCK YOU HAVE PROTEIN OF 393 00:20:52,853 --> 00:20:53,787 INTEREST BEING SECRETED. 394 00:20:53,787 --> 00:20:56,123 IN THE OTHER CASE REPRESENTED 395 00:20:56,123 --> 00:20:59,192 BY THE OTHER PROTEASE, YOU ARE 396 00:20:59,192 --> 00:21:00,360 REMOVING THE INHIBITOR, SO THE 397 00:21:00,360 --> 00:21:02,696 PROTEIN OF INTEREST IS RETAINED. 398 00:21:02,696 --> 00:21:04,564 FINALLY WHEN BOTH INPUTS ARE 399 00:21:04,564 --> 00:21:06,633 PRESENT, EVEN THOUGH YOU REMOVE 400 00:21:06,633 --> 00:21:08,302 THIS END TERMINAL MOTIF, YOU 401 00:21:08,302 --> 00:21:09,937 HAVE A RESTORATION OF ACTIVITY 402 00:21:09,937 --> 00:21:11,838 IN THAT SECOND MOTIF. 403 00:21:11,838 --> 00:21:13,206 SO THE PROTEIN OF INTEREST IS 404 00:21:13,206 --> 00:21:13,707 RETAINED. 405 00:21:13,707 --> 00:21:16,009 HERE IS JUST AN EXAMPLE OF SORT 406 00:21:16,009 --> 00:21:19,780 OF WHAT WE END UP SEEING WITH 407 00:21:19,780 --> 00:21:23,417 THIS NIMPLY GATE. 408 00:21:23,417 --> 00:21:24,918 IT'S FOR THIS RESPONSE TO 409 00:21:24,918 --> 00:21:25,786 SPECIFIC INPUTS. 410 00:21:25,786 --> 00:21:28,221 IN ADDITION TO BEING ABLE TO 411 00:21:28,221 --> 00:21:30,524 SORT OF SENSE MULTIPLE INPUTS, 412 00:21:30,524 --> 00:21:33,560 ANOTHER USEFUL POTENTIAL 413 00:21:33,560 --> 00:21:36,196 ABILITY WOULD BE TO HAVE THIS 414 00:21:36,196 --> 00:21:36,897 QUANTITATIVE PROCESSING OF 415 00:21:36,897 --> 00:21:37,564 INPUTS. 416 00:21:37,564 --> 00:21:40,233 WHAT I MEAN HERE IS THE ABILITY 417 00:21:40,233 --> 00:21:42,169 TO SENSE CONCENTRATION OF A 418 00:21:42,169 --> 00:21:45,272 GIVEN INPUT AND CONTROL PROTEIN 419 00:21:45,272 --> 00:21:46,673 SECRETION IN RESPONSE TO THAT. 420 00:21:46,673 --> 00:21:49,009 ONE NICE THING ABOUT PROTEASES 421 00:21:49,009 --> 00:21:50,877 YOU CAN ACTUALLY TUNE THE 422 00:21:50,877 --> 00:21:52,946 CUTTING EFFICIENCY OF A 423 00:21:52,946 --> 00:21:55,482 PROTEASE BY SIMPLY CHANGING THE 424 00:21:55,482 --> 00:21:59,486 AMINO ACID SEQUENCE, COMPONENTS 425 00:21:59,486 --> 00:22:02,789 OF THE AMINO ACID SEQUENCES. 426 00:22:02,789 --> 00:22:04,391 WHAT I'M SEEING HERE IN BOTH 427 00:22:04,391 --> 00:22:07,494 THE ON AND OFF CASE OF THE 428 00:22:07,494 --> 00:22:10,464 RELEASE AND RELEASE-NOT BY 429 00:22:10,464 --> 00:22:13,500 CHANGING THE TUFT SITE, YOU CAN 430 00:22:13,500 --> 00:22:15,168 CHANGE THE EFFICIENCIES AND 431 00:22:15,168 --> 00:22:16,303 CONCENTRATIONS AT WHICH YOU 432 00:22:16,303 --> 00:22:19,006 WILL GET A SUFFICIENT CUTTING 433 00:22:19,006 --> 00:22:20,574 AND RELEASE OF YOUR PROTEIN OF 434 00:22:20,574 --> 00:22:22,242 INTEREST. 435 00:22:22,242 --> 00:22:26,780 AND SO, ONE EXAMPLE OF THIS 436 00:22:26,780 --> 00:22:30,283 SORT OF CONDITIONAL PROTEIN 437 00:22:30,283 --> 00:22:31,918 SECRETION IS EXAMPLE OF THE 438 00:22:31,918 --> 00:22:33,720 ANALOG OR BAND PASS FILTER. 439 00:22:33,720 --> 00:22:35,756 WHAT THIS MEANS IS ONLY WITHIN 440 00:22:35,756 --> 00:22:37,858 A GIVEN RANG OF A CONCENTRATION 441 00:22:37,858 --> 00:22:40,660 OF A GIVEN INPUT WOULD YOU GET 442 00:22:40,660 --> 00:22:42,162 YOUR RELEASE CONSTRUCT BEING 443 00:22:42,162 --> 00:22:43,230 RELEASED AND THEN FROM THERE 444 00:22:43,230 --> 00:22:45,098 YOU WOULD BE ABLE TO HAVE YOUR 445 00:22:45,098 --> 00:22:48,468 PROTEIN OF INTEREST BEING 446 00:22:48,468 --> 00:22:48,735 SECRETED. 447 00:22:48,735 --> 00:22:52,105 WHAT WE HAVE DONE IS MODIFIED 448 00:22:52,105 --> 00:22:54,374 THE NIMPLY GATE, TO HAVE TWO OF 449 00:22:54,374 --> 00:22:56,476 THE SAME PROTEASE CUT SITES BUT 450 00:22:56,476 --> 00:22:59,479 WE MADE IT SO THE SECOND CUT 451 00:22:59,479 --> 00:23:01,615 SITE SHOWN HERE IS LESS 452 00:23:01,615 --> 00:23:02,482 EFFICIENT THAN THE FIRST CUT 453 00:23:02,482 --> 00:23:03,250 SITE. 454 00:23:03,250 --> 00:23:04,951 WHAT THIS MEANS IS AS YOU 455 00:23:04,951 --> 00:23:07,220 INCREASE THE AMOUNT OF INPUT 456 00:23:07,220 --> 00:23:07,788 CONCENTRATIONS, WHAT WILL 457 00:23:07,788 --> 00:23:09,790 HAPPEN IS YOU WILL FIRST GET 458 00:23:09,790 --> 00:23:12,125 REMOVAL OF THIS FIRST CUT SITE 459 00:23:12,125 --> 00:23:13,493 TURNING ON PROTEIN SECRETION. 460 00:23:13,493 --> 00:23:16,063 AND ONLY ONCE YOU HAVE REACHED, 461 00:23:16,063 --> 00:23:19,099 THEN AS YOU INCREASE THE AMOUNT 462 00:23:19,099 --> 00:23:20,734 OF PROTEASE, YOU WILL GET 463 00:23:20,734 --> 00:23:22,569 REMOVAL OF BOTH AND THEN 464 00:23:22,569 --> 00:23:24,938 TURNING OFF OF PROTEIN 465 00:23:24,938 --> 00:23:25,205 SECRETION. 466 00:23:25,205 --> 00:23:26,339 INDEED, WHAT WE HAVE SHOWN IS 467 00:23:26,339 --> 00:23:28,175 WE HAVE THIS BAND PASS ACTIVITY 468 00:23:28,175 --> 00:23:30,710 IN RESPONSE TO INCREASING THE 469 00:23:30,710 --> 00:23:33,980 AMOUNT OF PROTEASE INPUT. 470 00:23:33,980 --> 00:23:35,582 AND FINALLY, ONE THING THAT WE 471 00:23:35,582 --> 00:23:37,217 HAVE ALSO REALLY SORT OF 472 00:23:37,217 --> 00:23:39,352 FOCUSED ON IS, OKAY, SO WE 473 00:23:39,352 --> 00:23:40,520 REALLY WANT TO LEVERAGE THE 474 00:23:40,520 --> 00:23:43,924 FACT THAT WE ARE USING 475 00:23:43,924 --> 00:23:46,359 POST-TRANSLATIONAL CIRCUIT. 476 00:23:46,359 --> 00:23:48,228 AND SO ONE THING WE ARE REALLY 477 00:23:48,228 --> 00:23:50,330 INTERESTED IN IS POTENTIALLY 478 00:23:50,330 --> 00:23:53,834 USING mRNA TO DELIVER 479 00:23:53,834 --> 00:23:54,534 PROTEIN-TAGGED PAYLOADS WITH 480 00:23:54,534 --> 00:23:55,268 RELEASE. 481 00:23:55,268 --> 00:23:58,271 SO THE IDEA HERE IS, LET'S SAY 482 00:23:58,271 --> 00:24:00,373 YOU TRANSPLANT CO-DELIVER ANT 483 00:24:00,373 --> 00:24:02,209 ENGINEERED CELL WITH YOUR 484 00:24:02,209 --> 00:24:03,276 THERAPEUTIC CELL AND FOUR 485 00:24:03,276 --> 00:24:04,578 MONTHS DOWN THE LINE YOU WANT 486 00:24:04,578 --> 00:24:08,081 TO CHANGE THE OUTPUT OF WHAT 487 00:24:08,081 --> 00:24:10,484 YOUR ENGINEERED CELLS ARE 488 00:24:10,484 --> 00:24:10,784 CONTROLLING. 489 00:24:10,784 --> 00:24:13,053 ONE THING WE ENVISIONED IS YOU 490 00:24:13,053 --> 00:24:14,855 CAN ACTUALLY ENCODE A PROTEIN 491 00:24:14,855 --> 00:24:15,522 TAG TO RELEASE. 492 00:24:15,522 --> 00:24:17,824 IN THIS CASE WE ARE USING AN 493 00:24:17,824 --> 00:24:18,492 IGG PROTEIN. 494 00:24:18,492 --> 00:24:20,427 ALL UNDER THE CONTROL OF AN 495 00:24:20,427 --> 00:24:21,061 mRNA. 496 00:24:21,061 --> 00:24:27,434 AND IF WE WERE TO DELIVER IT 497 00:24:27,434 --> 00:24:28,835 INDISCRIMINATELY TO THE SITE IT 498 00:24:28,835 --> 00:24:29,936 WOULD GO EVERYWHERE. 499 00:24:29,936 --> 00:24:31,404 BUT THE NICE THING ABOUT THE 500 00:24:31,404 --> 00:24:33,273 RELEASE PLATFORM, IN THE HOST 501 00:24:33,273 --> 00:24:34,941 CELLS OR WILD TYPE CELLS THEY 502 00:24:34,941 --> 00:24:37,110 WOULD TAKE UP THE mRNA BUT THE 503 00:24:37,110 --> 00:24:38,211 PROTEIN OF INTEREST WOULD BE 504 00:24:38,211 --> 00:24:40,080 CONTAINED IN THE ER BECAUSE 505 00:24:40,080 --> 00:24:42,516 THEY LACK MACHINERY TO RELEASE 506 00:24:42,516 --> 00:24:45,619 THE CONSTRUCT. 507 00:24:45,619 --> 00:24:48,655 COMPARISON THE CELLS THAT HAVE 508 00:24:48,655 --> 00:24:51,925 THE PROTEASE CIRCUIT, THIS CASE 509 00:24:51,925 --> 00:24:53,593 SMALL MOLECULE INDUCIBLE 510 00:24:53,593 --> 00:24:54,661 PROTEASE SHOWN HERE, YOU WOULD 511 00:24:54,661 --> 00:24:56,162 HAVE THE ABILITY TO ACTUALLY 512 00:24:56,162 --> 00:24:57,097 USE THAT PAYLOAD. 513 00:24:57,097 --> 00:25:00,133 WHAT WE DID, THIS HAS ALL BEEN 514 00:25:00,133 --> 00:25:02,002 DONE IN VITRO BUT WE HAD A 515 00:25:02,002 --> 00:25:04,204 MIXTURE OF THESE WILD TYPE AND 516 00:25:04,204 --> 00:25:09,242 ENGINEERED CELLS AND WE 517 00:25:09,242 --> 00:25:10,877 DELIVERED THE IGG CONSTRUCT VIA 518 00:25:10,877 --> 00:25:11,912 mRNA. 519 00:25:11,912 --> 00:25:13,680 WHAT I'M SHOWING HERE IN THIS 520 00:25:13,680 --> 00:25:17,384 MIXTURE OF CELLS WHEN WE 521 00:25:17,384 --> 00:25:19,719 SUSTAINED AND RAN FLOW 522 00:25:19,719 --> 00:25:21,888 CYTOMETRY, THEY WERE ABLE TO 523 00:25:21,888 --> 00:25:26,159 USE THE PAYLOADS AS EXPECTED. 524 00:25:26,159 --> 00:25:27,494 THERE WAS NO EXPRESSION ON THE 525 00:25:27,494 --> 00:25:29,930 SURFACE. 526 00:25:29,930 --> 00:25:31,531 COMPARISON THE ENGINEERED CELLS 527 00:25:31,531 --> 00:25:33,700 WERE ABLE TO NICELY PROCESS THE 528 00:25:33,700 --> 00:25:34,768 CONSTRUCT AND EXPRESS IT ON THE 529 00:25:34,768 --> 00:25:36,503 SURFACE. 530 00:25:36,503 --> 00:25:39,105 AND SO TO SORT OF SUMMARIZE, WE 531 00:25:39,105 --> 00:25:42,676 REALLY TRIED TO EXPAND THE 532 00:25:42,676 --> 00:25:43,643 WHOLE RELEASE PLATFORM AND 533 00:25:43,643 --> 00:25:46,012 THINK OF IT MORE AS A 534 00:25:46,012 --> 00:25:47,881 PROCESSING OUTPUT AND OUTPUT 535 00:25:47,881 --> 00:25:50,116 MODULE IN THESE PROTEASE-BASED 536 00:25:50,116 --> 00:25:50,483 CIRCUIT. 537 00:25:50,483 --> 00:25:52,953 WE HAVE SHOWN WE CAN IMPLEMENT 538 00:25:52,953 --> 00:25:55,355 NEGATIVE REGULATION OF PROTEIN 539 00:25:55,355 --> 00:25:57,991 SECRETION BY HARNESSING THE 540 00:25:57,991 --> 00:25:59,292 ENDOGENOUS INTERACTIONS. 541 00:25:59,292 --> 00:26:01,861 AND SHOWN THE DIFFERENT LOGIC 542 00:26:01,861 --> 00:26:03,496 GATES AND QUANTITATIVE 543 00:26:03,496 --> 00:26:07,701 PROCESSING WITHOUT REQUIRING 544 00:26:07,701 --> 00:26:08,635 INTERMEDIATE PROTEASES, COMPACT 545 00:26:08,635 --> 00:26:10,103 FYING AND STREAMLINING THE 546 00:26:10,103 --> 00:26:11,871 ENTIRE CIRCUIT. 547 00:26:11,871 --> 00:26:15,809 FINALLY WE SHOWED POTENTIAL OF 548 00:26:15,809 --> 00:26:18,111 USING mRNA FOR THESE PROTEIN 549 00:26:18,111 --> 00:26:20,480 CIRCUIT FOR FUTURE THERAPEUTICS. 550 00:26:20,480 --> 00:26:22,849 AND WITH THAT I WOULD LIKE TO 551 00:26:22,849 --> 00:26:24,918 THANK THE GAO LAB AS WELL AS 552 00:26:24,918 --> 00:26:26,052 OUR FUNDING AGENCIES. 553 00:26:26,052 --> 00:26:27,787 AND I'M HAPPY TO TAKE ANY 554 00:26:27,787 --> 00:26:28,054 QUESTIONS. 555 00:26:28,054 --> 00:26:29,089 THANK YOU SO MUCH. 556 00:26:29,089 --> 00:26:39,299 [ APPLAUSE ] 557 00:26:47,307 --> 00:26:48,708 >> HI. 558 00:26:48,708 --> 00:26:50,310 I WAS WONDERING ABOUT HOW YOU 559 00:26:50,310 --> 00:26:51,711 ARE TUNING THE PROTEASE 560 00:26:51,711 --> 00:26:52,679 ACTIVITY. 561 00:26:52,679 --> 00:26:55,649 IT SEEMED LIKE BASICALLY, 562 00:26:55,649 --> 00:26:58,051 WHENEVER YOU MADE IT A LITTLE 563 00:26:58,051 --> 00:27:00,220 BIT WORSE THAT'S THE MAIN WAY 564 00:27:00,220 --> 00:27:01,454 OF TUNING IT, SO THAT IT 565 00:27:01,454 --> 00:27:02,956 DOESN'T WORK. 566 00:27:02,956 --> 00:27:06,426 DO YOU HAVE FINER CONTROL OVER 567 00:27:06,426 --> 00:27:07,560 THAT? 568 00:27:07,560 --> 00:27:08,962 >> Alexander Vlahos: IF I 569 00:27:08,962 --> 00:27:09,896 UNDERSTAND CORRECTLY, ARE YOU 570 00:27:09,896 --> 00:27:12,432 REFERRING TO THE PROTEASE CUT 571 00:27:12,432 --> 00:27:14,367 SITE OR THE PROTEASE ITSELF? 572 00:27:14,367 --> 00:27:15,969 >> IF YOU GO BACK ON THE SLIDE, 573 00:27:15,969 --> 00:27:17,504 YOU HAVE THAT SLIDE THAT HAS 574 00:27:17,504 --> 00:27:17,671 -- 575 00:27:17,671 --> 00:27:19,039 >> Alexander Vlahos: THIS ONE? 576 00:27:19,039 --> 00:27:20,640 >> NO, FURTHER BACK. 577 00:27:20,640 --> 00:27:21,374 THAT'S THE ONE. 578 00:27:21,374 --> 00:27:22,308 YES. 579 00:27:22,308 --> 00:27:24,110 I'M REFERRING TO THE CUT SITE. 580 00:27:24,110 --> 00:27:26,546 >> Alexander Vlahos: YEAH, SO 581 00:27:26,546 --> 00:27:30,483 WE ARE, WE CAN TUNE IT TO BE 582 00:27:30,483 --> 00:27:30,684 WORSE. 583 00:27:30,684 --> 00:27:32,118 I DON'T, WE HAVEN'T TRIED TO 584 00:27:32,118 --> 00:27:33,053 MAKE IT BETTER. 585 00:27:33,053 --> 00:27:35,155 WHAT WE HAVE DONE ON THE BETTER 586 00:27:35,155 --> 00:27:37,223 END IS ACTUALLY TRYING TO USE 587 00:27:37,223 --> 00:27:42,462 DIFFERENT TYPES OF MUTATED TEVS 588 00:27:42,462 --> 00:27:44,564 OR OTHER PROTEASES WHICH ARE 589 00:27:44,564 --> 00:27:46,132 MORE CATALYTICKLY ACTIVE. 590 00:27:46,132 --> 00:27:47,267 THAT'S HOW WE HAVE GONE IN THE 591 00:27:47,267 --> 00:27:48,101 OPPOSITE DIRECTION. 592 00:27:48,101 --> 00:27:50,470 BUT FOR US TO TUNE THESE 593 00:27:50,470 --> 00:27:52,172 CAPABILITIES WE ESSENTIALLY 594 00:27:52,172 --> 00:27:54,240 FOCUS ON THE PROTEASE CUT SITE. 595 00:27:54,240 --> 00:27:54,708 >> OKAY. 596 00:27:54,708 --> 00:27:55,408 ALL RIGHT. 597 00:27:55,408 --> 00:27:59,312 THANKS. 598 00:27:59,312 --> 00:28:01,414 >> I WAS WONDERING IF YOU 599 00:28:01,414 --> 00:28:02,816 LOOKED INTO ANY KIND OF SYSTEM 600 00:28:02,816 --> 00:28:04,884 WHERE YOU COULD HAVE MORE THAN 601 00:28:04,884 --> 00:28:08,021 TWO INPUTS TO FACILITATE GATES? 602 00:28:08,021 --> 00:28:12,792 SO LIKE A THREE INPUT END GATE 603 00:28:12,792 --> 00:28:14,894 OR FOUR INPUT END GATE OR 604 00:28:14,894 --> 00:28:15,595 SOMETHING ALONG THOSE LINES? 605 00:28:15,595 --> 00:28:16,996 >> Alexander Vlahos: WE HAVEN'T 606 00:28:16,996 --> 00:28:18,531 LOOKED INTO THE THREE OR FOUR 607 00:28:18,531 --> 00:28:19,599 INPUT GATES. 608 00:28:19,599 --> 00:28:21,935 I THINK, BECAUSE THE MOD 609 00:28:21,935 --> 00:28:24,304 LAIRITY OF SORT OF PROTEINS IN 610 00:28:24,304 --> 00:28:25,705 GENERAL, I THINK IT COULD BE 611 00:28:25,705 --> 00:28:27,107 FEASIBLE, BUT I HAVE TO DRAW IT 612 00:28:27,107 --> 00:28:30,376 OUT AND SEE IF WE CAN FIND 613 00:28:30,376 --> 00:28:31,311 ENOUGH RETENTION MOTIFS. 614 00:28:31,311 --> 00:28:33,913 ONE NICE THING ABOUT -- SO 615 00:28:33,913 --> 00:28:35,782 THE INITIAL RETENTION MOTIF WE 616 00:28:35,782 --> 00:28:41,087 USED AND PUBLISHED ON IS A 617 00:28:41,087 --> 00:28:42,522 DELEISING MOTIF BUT HAS TO BE 618 00:28:42,522 --> 00:28:44,858 PRESENT AT THE C-TERMINUS, BUT 619 00:28:44,858 --> 00:28:46,760 IT COULD BE FOUND IN LOOPS. 620 00:28:46,760 --> 00:28:49,095 IN THEORY, YOU COULD, IN A WAY, 621 00:28:49,095 --> 00:28:52,298 DESIGN AN END GATE WHERE YOU 622 00:28:52,298 --> 00:28:54,434 HAVE MULTIPLE RXR MOTIFS WITH 623 00:28:54,434 --> 00:28:55,602 PROTEASE CUT SITES IN BETWEEN 624 00:28:55,602 --> 00:29:05,378 THEM TO HAVE THIS MULTI-END PUT. 625 00:29:05,378 --> 00:29:08,681 >> AND A QUESTION ABOUT THE 626 00:29:08,681 --> 00:29:11,684 LOGIC CIRCUIT BIOLOGY 627 00:29:11,684 --> 00:29:13,853 ENGINEERING IN GENERAL. 628 00:29:13,853 --> 00:29:15,288 FIRST END BIO. 629 00:29:15,288 --> 00:29:20,426 I WAS WONDERING, DO YOU KNOW, I 630 00:29:20,426 --> 00:29:23,463 THINK MARTIN FOSENEGER? 631 00:29:23,463 --> 00:29:24,631 (?) LAB HAS DONE THIS. 632 00:29:24,631 --> 00:29:26,933 DO YOU KNOW MORE COMPLICATED 633 00:29:26,933 --> 00:29:27,901 CIRCUIT BUILT. 634 00:29:27,901 --> 00:29:30,036 STARTING WITH GATES AND MAYBE 635 00:29:30,036 --> 00:29:32,372 MOVING TO HALF ATERS OR FULL 636 00:29:32,372 --> 00:29:34,073 ATERS OR ANYTHING LIKE THAT. 637 00:29:34,073 --> 00:29:35,341 IF SO, HOW FAR PEOPLE ARE 638 00:29:35,341 --> 00:29:36,109 TAKING IT. 639 00:29:36,109 --> 00:29:38,011 AND WHAT YOUR PERSPECTIVE IS 640 00:29:38,011 --> 00:29:43,116 ON, COULD WE HAVE LIKE A 641 00:29:43,116 --> 00:29:44,884 BIOLOGICAL MICRO PROCESSOR AT 642 00:29:44,884 --> 00:29:45,885 SOME POINT? 643 00:29:45,885 --> 00:29:47,153 >> Alexander Vlahos: I THINK 644 00:29:47,153 --> 00:29:48,588 THAT'S A REALLY GOOD POINT. 645 00:29:48,588 --> 00:29:52,325 I THINK ONE THING THAT IS A BIT 646 00:29:52,325 --> 00:29:53,726 TRICKY, AT LEAST IN OUR HANDS 647 00:29:53,726 --> 00:29:56,529 THAT WE HAVE SEEN, IS WHEN YOU 648 00:29:56,529 --> 00:29:59,065 TRY TO COMPLEX, OR MAKE THE 649 00:29:59,065 --> 00:30:00,433 CIRCUIT MORE COMPLEX, THERE'S 650 00:30:00,433 --> 00:30:01,868 ALWAYS A CHANCE THAT MORE 651 00:30:01,868 --> 00:30:03,269 THINGS CAN GO WRONG. 652 00:30:03,269 --> 00:30:06,339 LIKE IF A COMPONENT OF YOUR 653 00:30:06,339 --> 00:30:12,512 CIRCUIT, LET'S SAY USING 654 00:30:12,512 --> 00:30:13,179 TRADITIONAL TRANSCRIPTIONAL 655 00:30:13,179 --> 00:30:15,648 CIRCUIT, THE ENTIRE THING COULD 656 00:30:15,648 --> 00:30:17,183 GET MESSED UP. 657 00:30:17,183 --> 00:30:18,818 OUR FOCUS HAS BEEN ON 658 00:30:18,818 --> 00:30:19,719 SIMPLIFYING IT AS MUCH AS 659 00:30:19,719 --> 00:30:20,453 POSSIBLE. 660 00:30:20,453 --> 00:30:22,789 AT LEAST, YOU KNOW, INSTEAD OF 661 00:30:22,789 --> 00:30:25,925 HAVING A SINGLE INPUT, SINGLE 662 00:30:25,925 --> 00:30:26,159 OUTPUT. 663 00:30:26,159 --> 00:30:27,927 BUT I THINK DEPENDING ON HOW 664 00:30:27,927 --> 00:30:29,662 YOU ARE GOING TO ENGINEER YOUR 665 00:30:29,662 --> 00:30:31,898 SYSTEM, YOU CAN ALSO THINK OF 666 00:30:31,898 --> 00:30:33,499 DELIVERING MULTIPLE CELLS WITH 667 00:30:33,499 --> 00:30:35,435 DIFFERENT OUTPUTS AND DIFFERENT 668 00:30:35,435 --> 00:30:37,036 BEHAVIORS RATHER THAN HAVING A 669 00:30:37,036 --> 00:30:37,871 SINGLE CELL THAT CAN DO 670 00:30:37,871 --> 00:30:38,705 EVERYTHING. 671 00:30:38,705 --> 00:30:40,173 I DON'T KNOW WHICH ONE IS THE 672 00:30:40,173 --> 00:30:41,474 BETTER WAY TO GO. 673 00:30:41,474 --> 00:30:44,110 I THINK BOTH HAVE THE POTENTIAL 674 00:30:44,110 --> 00:30:44,344 TO WORK. 675 00:30:44,344 --> 00:30:44,944 BUT YEAH, THAT'S SORT OF MY 676 00:30:44,944 --> 00:30:46,212 VISION. 677 00:30:46,212 --> 00:30:47,380 SOMETIMES SIMPLER IS BETTER 678 00:30:47,380 --> 00:30:49,449 WITH THESE TYPES OF THINGS. 679 00:30:49,449 --> 00:30:51,351 ESPECIALLY IF YOUR GOAL IS TO 680 00:30:51,351 --> 00:30:52,552 EVENTUALLY TRANSLATE IT. 681 00:30:52,552 --> 00:30:54,621 >> SURE, SURE. 682 00:30:54,621 --> 00:30:55,421 THAT TOTALLY MAKES SENSE. 683 00:30:55,421 --> 00:30:56,723 THANK YOU. 684 00:30:56,723 --> 00:30:59,025 >> SURE, REALLY COOL EXTENSION 685 00:30:59,025 --> 00:31:00,426 OF CHOMP, I LIKE ALL THE THINGS 686 00:31:00,426 --> 00:31:02,795 YOU ARE DOING WITH SECRETION. 687 00:31:02,795 --> 00:31:03,930 REAL QUICK, ONE OF THE 688 00:31:03,930 --> 00:31:06,065 ADVANTAGES FOR THESE 689 00:31:06,065 --> 00:31:07,767 PROTEIN-BASED CIRCUIT IS SPEED. 690 00:31:07,767 --> 00:31:10,270 I DIDN'T SEE SPEED UP THERE TOO 691 00:31:10,270 --> 00:31:10,937 TERRIBLY MUCH. 692 00:31:10,937 --> 00:31:12,238 YOU ARE ADDING A LOT TO THE 693 00:31:12,238 --> 00:31:13,273 SYSTEM. 694 00:31:13,273 --> 00:31:15,174 IS IT STILL FAST? 695 00:31:15,174 --> 00:31:16,776 >> Alexander Vlahos: IN THIS 696 00:31:16,776 --> 00:31:18,211 CASE WE HAVEN'T SPECIFICALLY 697 00:31:18,211 --> 00:31:20,346 LOOKED AT THE DYNAMICS OF THE 698 00:31:20,346 --> 00:31:20,780 SYSTEM. 699 00:31:20,780 --> 00:31:21,514 OTHERS HAVE LOOKED. 700 00:31:21,514 --> 00:31:24,517 THEY ARE ABLE TO GET MEASURABLE 701 00:31:24,517 --> 00:31:26,119 PROTEIN SECRETION WITHIN AN 702 00:31:26,119 --> 00:31:27,320 HOUR TO TWO HOURS. 703 00:31:27,320 --> 00:31:28,955 IN OUR HANDS IT'S BEEN ABOUT 704 00:31:28,955 --> 00:31:31,524 TWO HOURS YOU CAN BEGIN TO SEE 705 00:31:31,524 --> 00:31:32,392 PROTEIN SECRETION FROM THE 706 00:31:32,392 --> 00:31:33,326 CELLS. 707 00:31:33,326 --> 00:31:35,528 I THINK THERE ARE WAYS TO MAKE 708 00:31:35,528 --> 00:31:37,030 IT FASTER. 709 00:31:37,030 --> 00:31:39,599 THERE ARE SOME ER EXPORT MOTIFS 710 00:31:39,599 --> 00:31:42,402 THAT MIGHT BE ABLE TO 711 00:31:42,402 --> 00:31:47,206 FACILITATE TRANSPORT THROUGH 712 00:31:47,206 --> 00:31:48,808 THE SECOND PATHWAY. 713 00:31:48,808 --> 00:31:51,544 CAN WE HAVE THIS THING WORK? 714 00:31:51,544 --> 00:31:52,779 BUT IT'S DEFINITELY SOMETHING 715 00:31:52,779 --> 00:31:54,581 WE ARE INTERESTED IN DOING. 716 00:31:54,581 --> 00:31:55,348 >> COOL, THANK YOU. 717 00:31:55,348 --> 00:31:56,549 >> Alexander Vlahos: THANK YOU. 718 00:31:56,549 --> 00:32:06,759 [ APPLAUSE ] 719 00:32:07,393 --> 00:32:09,462 >> NOW WE WILL SWITCH GEARS. 720 00:32:09,462 --> 00:32:11,764 WE HAVE TWO SPEAKERS COMING 721 00:32:11,764 --> 00:32:22,308 FROM DARPA, DR. SHANNON GREENE 722 00:32:26,813 --> 00:32:30,116 AND DR. MICHAEL. 723 00:32:30,116 --> 00:32:40,193 DR. 724 00:32:43,963 --> 00:32:46,466 DR. FEASEL, BIOCHEMIST AT 725 00:32:46,466 --> 00:32:48,768 UNIVERSITY OF TEXAS, AUSTIN. 726 00:32:48,768 --> 00:32:50,603 SO PLEASE, WITHOUT ANY FURTHER 727 00:32:50,603 --> 00:32:54,374 ADO, I BELIEVE DR. GREENE WILL 728 00:32:54,374 --> 00:32:55,775 GO FIRST, FEASEL AND THEN THERE 729 00:32:55,775 --> 00:32:57,010 WILL BE A DANCE BETWEEN THE TWO 730 00:32:57,010 --> 00:32:57,410 OF THEM. 731 00:32:57,410 --> 00:33:03,850 THANK YOU. 732 00:33:03,850 --> 00:33:04,817 >> Shannon Greene: GOOD 733 00:33:04,817 --> 00:33:05,652 MORNING, EVERYONE. 734 00:33:05,652 --> 00:33:07,754 THANK YOU FOR THE INTRODUCTION. 735 00:33:07,754 --> 00:33:10,823 THIS TALK WILL PIVOT FROM THE 736 00:33:10,823 --> 00:33:11,991 PREVIOUS PRESENTATION, I WILL 737 00:33:11,991 --> 00:33:13,593 TALK ABOUT PLATFORM DEVELOPMENT 738 00:33:13,593 --> 00:33:16,229 THAT WILL ENABLE THESE 739 00:33:16,229 --> 00:33:20,033 SYNTHETIC BIOLOGY APPLICATIONS. 740 00:33:20,033 --> 00:33:22,835 I'M A PROGRAM MANAGER IN 741 00:33:22,835 --> 00:33:24,070 DARPA'S TECHNOLOGY OFFICE. 742 00:33:24,070 --> 00:33:27,540 I WILL TALK ABOUT THE NUCLEIC 743 00:33:27,540 --> 00:33:35,381 ACIDS WORLDWIDE OR NAW PROGRAM. 744 00:33:35,381 --> 00:33:40,353 AT ITS BROAD LEVEL, NAW AIMS TO 745 00:33:40,353 --> 00:33:41,554 DEVELOP INTEGRATED PLATFORM 746 00:33:41,554 --> 00:33:50,229 THAT'S CAN SIN THEY SYNTHESIZE. 747 00:33:50,229 --> 00:33:52,832 WE RELY ON OUTDATED CENTRALIZED 748 00:33:52,832 --> 00:33:59,105 AND MOST CRITICALLY CELL-BASED 749 00:33:59,105 --> 00:34:02,108 MANUFACTURING AND PRODUCTION 750 00:34:02,108 --> 00:34:03,976 PARADIGM THAT RAPIDLY LIMITS 751 00:34:03,976 --> 00:34:05,778 OUR ACCESS TO mRNA. 752 00:34:05,778 --> 00:34:08,648 IF YOU WERE TO ORDER A HIGH 753 00:34:08,648 --> 00:34:09,849 QUALITY DNA SEQUENCE FOR 754 00:34:09,849 --> 00:34:12,018 EXPERIMENT THIS MIGHT TAKE 755 00:34:12,018 --> 00:34:12,418 POTENTIALLY WEEKS. 756 00:34:12,418 --> 00:34:14,353 IF WE ARE TALKING ABOUT 757 00:34:14,353 --> 00:34:15,755 CLINICAL GRADE MATERIAL THAT GO 758 00:34:15,755 --> 00:34:17,423 INTO HUMANS YOU ARE GETTING 759 00:34:17,423 --> 00:34:20,426 DELAYS ON THE ORDER OF MONTHS. 760 00:34:20,426 --> 00:34:22,295 AND MOST CRITICALLY ONE OF OUR 761 00:34:22,295 --> 00:34:23,930 KEY LIMITATIONS IN GETTING 762 00:34:23,930 --> 00:34:27,200 ACCESS TO HIGH QUALITY DNA AND 763 00:34:27,200 --> 00:34:30,636 RNA THEY ARE PRODUCED USING 764 00:34:30,636 --> 00:34:31,904 CELL-BASED METHODS. 765 00:34:31,904 --> 00:34:33,573 CELLS ARE MESSY. 766 00:34:33,573 --> 00:34:35,608 IF WE PURIFY FROM THE CELLULAR 767 00:34:35,608 --> 00:34:38,478 MATERIAL, THIS IS A VERY 768 00:34:38,478 --> 00:34:40,780 RESOURCE-INTENSIVE AND VERY 769 00:34:40,780 --> 00:34:41,714 SKILL-INTENSIVE PROCESS, WHICH 770 00:34:41,714 --> 00:34:43,649 DOES NOT LEND ITSELF TO 771 00:34:43,649 --> 00:34:47,420 DISTRIBUTED MANUFACTURING. 772 00:34:47,420 --> 00:34:49,288 SO TO REDUCE THESE BURDENS AND 773 00:34:49,288 --> 00:34:52,592 GET AWAY FROM THE MESSY 774 00:34:52,592 --> 00:34:57,663 CELL-BASED PROCESSES N.O.W. HAS 775 00:34:57,663 --> 00:34:59,699 DIFFERENT MODALITIES FOR THE 776 00:34:59,699 --> 00:35:01,567 DISTRIBUTED MANUFACTURING OF 777 00:35:01,567 --> 00:35:03,436 BOTH RNA AND DNA. 778 00:35:03,436 --> 00:35:04,137 THE MANUFACTURING PLATFORMS 779 00:35:04,137 --> 00:35:08,474 WILL GO ALL THE WAY FROM 780 00:35:08,474 --> 00:35:11,477 INSILKO SEQUENCE THROUGH THE 781 00:35:11,477 --> 00:35:12,845 NUCLEOTIDE SYNTHESIS, STITCHING 782 00:35:12,845 --> 00:35:15,648 TOGETHER INTO FULL LENGTH GENE 783 00:35:15,648 --> 00:35:16,816 TEMPLATE PURIFYING THEM ALSO 784 00:35:16,816 --> 00:35:18,718 WITH REAL-TIME ANALYTICS AND 785 00:35:18,718 --> 00:35:23,322 QUALITY CONTROL CHECKS. 786 00:35:23,322 --> 00:35:25,391 WHEN THE N.O.W. PROGRAM WAS 787 00:35:25,391 --> 00:35:27,960 FIRST CONCEIVED IN 2019, AS I 788 00:35:27,960 --> 00:35:29,595 MENTIONED, OUR CURRENT 789 00:35:29,595 --> 00:35:32,431 CAPABILITIES FOR ACCESSING HIGH 790 00:35:32,431 --> 00:35:36,669 QUALITY NUCLEIC ACIDS WERE 791 00:35:36,669 --> 00:35:39,472 LIMITED TO THESE FACILITIES. 792 00:35:39,472 --> 00:35:41,541 HOWEVER, DOD IS WORLDWIDE AND 793 00:35:41,541 --> 00:35:43,810 WAR FIGHTERS ARE OFTEN EXPOSED 794 00:35:43,810 --> 00:35:44,777 TO DISEASES WHERE THEY ARE 795 00:35:44,777 --> 00:35:45,578 DEPLOY. 796 00:35:45,578 --> 00:35:48,314 THEY CAN DEPLOY FOR 797 00:35:48,314 --> 00:35:49,982 HUMANITARIAN ASSISTANCE, 798 00:35:49,982 --> 00:35:51,184 DISASTER RELIEF MISSIONS WHERE 799 00:35:51,184 --> 00:35:53,052 THEY ARE PROVIDING MEDICAL CARE 800 00:35:53,052 --> 00:35:54,487 FOR LOCAL POPULATIONS. 801 00:35:54,487 --> 00:35:56,556 IN THESE CASES, BEING ABLE TO 802 00:35:56,556 --> 00:35:59,826 HAVE ACCESS TO RNA AND DNA 803 00:35:59,826 --> 00:36:01,160 BASED MEDICAL COUNTERMEASURES 804 00:36:01,160 --> 00:36:04,063 AT POINT OF NEED WHICH SHORTEN 805 00:36:04,063 --> 00:36:05,231 THE LOGISTICAL SUPPLY CHAIN. 806 00:36:05,231 --> 00:36:06,365 SO THE SOLUTION WE NEED IS 807 00:36:06,365 --> 00:36:07,800 SOMETHING THAT IS VERY FAST. 808 00:36:07,800 --> 00:36:09,902 SOMETHING THAT IS DISTRIBUTED. 809 00:36:09,902 --> 00:36:12,438 IT'S FLEXIBLE AND ADAPTABLE TO 810 00:36:12,438 --> 00:36:14,774 PIVOT TO RAPIDLY MAKING NEW 811 00:36:14,774 --> 00:36:17,143 SEQUENCES OF NEED AND MAKE A 812 00:36:17,143 --> 00:36:18,311 SYSTEM FULLY DEPLOYABLE. 813 00:36:18,311 --> 00:36:20,479 THE CONCEPT IS THAT IF WE CAN 814 00:36:20,479 --> 00:36:23,416 BEGIN TO RESPOND TO INFECTIOUS 815 00:36:23,416 --> 00:36:25,618 DISEASE OUTBREAKS AT A VERY 816 00:36:25,618 --> 00:36:27,386 EARLY SCALE AT THE POINT OF 817 00:36:27,386 --> 00:36:30,289 NEED WE MIGHT HOPEFULLY OBVIATE 818 00:36:30,289 --> 00:36:32,992 THE NEED TO MAKE MILLIONS OF 819 00:36:32,992 --> 00:36:34,861 DOSES OF AN OUTBREAK IF WE CAN 820 00:36:34,861 --> 00:36:39,131 NIP IT IN THE BUD VERY QUICKLY. 821 00:36:39,131 --> 00:36:43,102 SO IN ADDITION TO RNA AND DNA 822 00:36:43,102 --> 00:36:45,872 BASED MODALITYITIES FOR 823 00:36:45,872 --> 00:36:46,806 COUNTERMEASURES THEMSELVES 824 00:36:46,806 --> 00:36:48,741 OBVIOUSLY RNA AND DNA ARE 825 00:36:48,741 --> 00:36:53,746 CRITICAL FOR A LOT OF DOD NEEDS. 826 00:36:53,746 --> 00:36:54,447 THE MEDICAL COUNTERMEASURES 827 00:36:54,447 --> 00:37:04,657 THEMSELVES. 828 00:37:07,727 --> 00:37:10,263 PRECLINICAL TESTING. 829 00:37:10,263 --> 00:37:15,668 DNA AND RNA ARE NEEDED FOR 830 00:37:15,668 --> 00:37:16,969 BIOMANUFACTURING. 831 00:37:16,969 --> 00:37:17,970 THE COVID-19 PANDEMIC 832 00:37:17,970 --> 00:37:20,039 HIGHLIGHTED THE CRITICAL 833 00:37:20,039 --> 00:37:22,608 RESOURCE AND OUR LACK OF EASY 834 00:37:22,608 --> 00:37:24,944 ACCESS, AS MANUFACTURING SITES 835 00:37:24,944 --> 00:37:26,579 WERE OVERWHELMED AND TIMELINES 836 00:37:26,579 --> 00:37:28,681 WERE ORDERING THIS CRITICAL 837 00:37:28,681 --> 00:37:31,851 RESOURCE WERE EXTENDED. 838 00:37:31,851 --> 00:37:34,220 SO NOW, HOW DOES THE N.O.W. 839 00:37:34,220 --> 00:37:35,121 PROGRAM AIM TO SOLVE THIS 840 00:37:35,121 --> 00:37:36,322 PROGRAM. 841 00:37:36,322 --> 00:37:37,757 THEY HAVE TWO TECHNICAL AREAS 842 00:37:37,757 --> 00:37:39,392 ON THE LEFT. 843 00:37:39,392 --> 00:37:40,960 TECHNICAL AREA ONE, ADVANCING 844 00:37:40,960 --> 00:37:43,596 THE STATE-OF-THE-ART FOR 845 00:37:43,596 --> 00:37:47,867 UPSTREAM, THIS IS ENZYMATIC, WE 846 00:37:47,867 --> 00:37:50,603 ARE CHALLENGING OUR PERFORMERS 847 00:37:50,603 --> 00:37:52,004 TO SYNTHESIZE GENE LENGTH 848 00:37:52,004 --> 00:37:55,775 CONSTRUCTS UP TO FOUR KILOBASES. 849 00:37:55,775 --> 00:37:58,110 AND SYNTHESIZE HIGH QUALITY DNA 850 00:37:58,110 --> 00:38:00,446 OR RNA THAT IS ERROR-FREE. 851 00:38:00,446 --> 00:38:03,716 HIGHLY CRITICAL TO HAVE A 852 00:38:03,716 --> 00:38:04,917 MEDICAL COUNTERMEASURE GOING 853 00:38:04,917 --> 00:38:08,120 INTO HUMANS AND USE SIMPLIFIED 854 00:38:08,120 --> 00:38:08,888 STARTING MATERIALS. 855 00:38:08,888 --> 00:38:12,124 SO WE WANTED THIS TO BE AN 856 00:38:12,124 --> 00:38:15,428 ENZYMATIC PROCESS AND IDEALLY 857 00:38:15,428 --> 00:38:16,562 CHALLENGE THE COMMUNITY TO 858 00:38:16,562 --> 00:38:19,999 DEVELOP SOLUTIONS THAT COULD BE 859 00:38:19,999 --> 00:38:21,634 EASILY FREEZE DRIED SO YOU 860 00:38:21,634 --> 00:38:23,469 COULD HAVE REACTION WHERE YOU 861 00:38:23,469 --> 00:38:26,405 COULD ALMOST HAVE A "JUST ADD 862 00:38:26,405 --> 00:38:27,506 WATER" SOLUTION. 863 00:38:27,506 --> 00:38:29,375 ON THE RIGHT-HAND SIDE, 864 00:38:29,375 --> 00:38:30,509 TECHNICAL AREA 2, THIS IS WHERE 865 00:38:30,509 --> 00:38:32,645 WE PUT OUR ENGINEERS TO WORK 866 00:38:32,645 --> 00:38:33,813 WITH THE DOWNSTREAM PROCESS. 867 00:38:33,813 --> 00:38:36,415 SO AS I MENTIONED WE ARE MOVING 868 00:38:36,415 --> 00:38:37,116 AWAY FROM CELL-BASED 869 00:38:37,116 --> 00:38:39,952 MANUFACTURING IN THIS PROGRAM 870 00:38:39,952 --> 00:38:42,755 TOWARD ENZYMATIC SYNTHESIS OF 871 00:38:42,755 --> 00:38:44,657 DNA AND RNA BUT THERE ARE OTHER 872 00:38:44,657 --> 00:38:46,292 COMPONENTS OF THE THAT WOULD 873 00:38:46,292 --> 00:38:51,097 NEED TO BE PURIFIED AND NEED TO 874 00:38:51,097 --> 00:38:55,835 BE ABLE TO EMPLOY -- BEFORE 875 00:38:55,835 --> 00:38:58,437 IT COULD BE DEPLOYED AS A 876 00:38:58,437 --> 00:39:00,573 COUNTERMEASURE. 877 00:39:00,573 --> 00:39:03,142 WE SET CHALLENGING METRICS THEY 878 00:39:03,142 --> 00:39:06,345 HAD TO PRODUCE 500 DOSES IN A 879 00:39:06,345 --> 00:39:08,681 FULLY AUTOMATED AND INTEGRATED 880 00:39:08,681 --> 00:39:11,584 FASHION IN UNDER THREE DAYS. 881 00:39:11,584 --> 00:39:13,686 NOW WE DON'T EXPECT OUR 882 00:39:13,686 --> 00:39:15,554 PERFORMERS IN THESE PROGRAMS TO 883 00:39:15,554 --> 00:39:17,923 GET TO THESE FINAL METRICS 884 00:39:17,923 --> 00:39:20,026 OVERNIGHT, IT'S SET UP AS A 885 00:39:20,026 --> 00:39:20,960 FIVE-YEAR EFFORT, EACH YEAR 886 00:39:20,960 --> 00:39:23,095 THEY WOULD BE CHALLENGED WITH 887 00:39:23,095 --> 00:39:24,063 CAPABILITY DEMONSTRATIONS THAT 888 00:39:24,063 --> 00:39:30,336 WOULD FORCE THEM TO BE ABLE TO 889 00:39:30,336 --> 00:39:32,538 SYNTHESIZE NUCLEIC ACIDS AT 890 00:39:32,538 --> 00:39:34,573 GREATER LENGTH. 891 00:39:34,573 --> 00:39:36,475 INCREASING THE QUALITY OF 892 00:39:36,475 --> 00:39:38,144 SEQUENCE IDENTITY. 893 00:39:38,144 --> 00:39:39,612 INCREASING PURITY. 894 00:39:39,612 --> 00:39:41,047 DECREASING THE AMOUNT OF TIME 895 00:39:41,047 --> 00:39:43,816 THEY WOULD NEED TO SYNTHESIZE 896 00:39:43,816 --> 00:39:44,984 THESE MOLECULES. 897 00:39:44,984 --> 00:39:47,520 WE ALSO SET METRICS FOR 898 00:39:47,520 --> 00:39:48,487 INTEGRATION AND AUTOMATION. 899 00:39:48,487 --> 00:39:49,889 WHERE IN THE BEGINNING OF THE 900 00:39:49,889 --> 00:39:52,892 PROGRAM THE TEAMS WERE ABLE TO 901 00:39:52,892 --> 00:39:55,694 USE VERY AIR-GAPED MODULES BUT 902 00:39:55,694 --> 00:39:58,264 HAD TO MODULATE TOGETHER 903 00:39:58,264 --> 00:39:59,265 THROUGH PURIFICATION AND 904 00:39:59,265 --> 00:40:01,901 FORMULATION AT THE END. 905 00:40:01,901 --> 00:40:03,102 SO RIGHT NOW I WILL SPEAK TO 906 00:40:03,102 --> 00:40:04,937 THE FACT WE ARE ABOUT MIDWAY 907 00:40:04,937 --> 00:40:06,105 THROUGH THIS PROGRAM. 908 00:40:06,105 --> 00:40:09,542 THE A FIVE-YEAR EFFORT AND WE 909 00:40:09,542 --> 00:40:12,078 ARE IN YEAR THREE. 910 00:40:12,078 --> 00:40:17,716 THE N.O.W. PROGRAM HAS TWO 911 00:40:17,716 --> 00:40:22,188 TEAMS, NG, MONTH MODERNA MAKING 912 00:40:22,188 --> 00:40:24,523 MEDICAL COUNTERMEASURES AND GE 913 00:40:24,523 --> 00:40:26,859 HEALTHCARE IS OUR DNA TEAM. 914 00:40:26,859 --> 00:40:28,661 THE GE TEAM IS MAKING TWO 915 00:40:28,661 --> 00:40:29,628 DEVICES. 916 00:40:29,628 --> 00:40:31,931 ONE SYSTEM THAT WOULD MAKE A 917 00:40:31,931 --> 00:40:34,300 SINGLE SEQUENCE OF DNA FOR 918 00:40:34,300 --> 00:40:35,234 MEDICAL COUNTERMEASURE. 919 00:40:35,234 --> 00:40:37,803 BUT IN PARALLEL THEY ARE MAKING 920 00:40:37,803 --> 00:40:39,905 ANOTHER DEVICE THAT WOULD MAKE 921 00:40:39,905 --> 00:40:47,913 LOWER QUANTITIES OF THAT 922 00:40:47,913 --> 00:40:50,349 NUCLEIC MATERIAL FOR DNA 923 00:40:50,349 --> 00:40:50,749 CAPABILITIES. 924 00:40:50,749 --> 00:40:52,618 MY LAST MINUTES I WILL WALK 925 00:40:52,618 --> 00:40:54,019 THROUGH HIGHLIGHTS FROM THE 926 00:40:54,019 --> 00:40:56,489 PERFORMER TEAMS THE LAST COUPLE 927 00:40:56,489 --> 00:40:56,789 YEARS. 928 00:40:56,789 --> 00:41:01,193 END OF YEAR TWO MODERNA WAS 929 00:41:01,193 --> 00:41:03,496 CHALLENGED WITH DEMONSTRATION 930 00:41:03,496 --> 00:41:06,031 TO MANUFACTURE AND FORMULATE 931 00:41:06,031 --> 00:41:06,765 DOSES OF RNA-BASED VACCINE. 932 00:41:06,765 --> 00:41:11,904 THEY WERE ABLE TO MAKE OVER 933 00:41:11,904 --> 00:41:14,273 800 DOSES USING MOSTLY 934 00:41:14,273 --> 00:41:14,707 AUTOMATED PROCESSES. 935 00:41:14,707 --> 00:41:18,043 ABOUT TWO OF THE 41 STEPS IN 936 00:41:18,043 --> 00:41:19,311 THEIR PROCESS REQUIRE SOME 937 00:41:19,311 --> 00:41:20,312 MANUAL INPUT. 938 00:41:20,312 --> 00:41:25,818 BUT THEY MET OR EXCEEDED THE 939 00:41:25,818 --> 00:41:27,720 DIFFERENT QUALITY METRICS THAT 940 00:41:27,720 --> 00:41:30,456 WERE REQUIRED FOR THIS 941 00:41:30,456 --> 00:41:31,257 CAPABILITY DEMONSTRATION. 942 00:41:31,257 --> 00:41:33,592 AND IN THE FINAL YEARS OF THE 943 00:41:33,592 --> 00:41:34,760 PROGRAM THEY WILL WORK TO 944 00:41:34,760 --> 00:41:37,997 CONTINUE TO PHASE OUT ANY OF 945 00:41:37,997 --> 00:41:41,333 THOSE MANUAL INTERVENTION STEPS 946 00:41:41,333 --> 00:41:42,368 AND CONTINUE AUTOMATION OF THE 947 00:41:42,368 --> 00:41:43,636 PLATFORM. 948 00:41:43,636 --> 00:41:45,504 ON THE DNA SIDE OF THE HOUSE, 949 00:41:45,504 --> 00:41:47,873 THE GE TEAM HAS A UNIQUE 950 00:41:47,873 --> 00:41:48,807 CHALLENGE, THE DNA THAT COMES 951 00:41:48,807 --> 00:41:51,377 OUT OF THE SYSTEM IS NOT WHAT 952 00:41:51,377 --> 00:41:52,611 IS TRADITIONALLY USED FOR 953 00:41:52,611 --> 00:41:55,114 COUNTERMEASURES. 954 00:41:55,114 --> 00:41:56,782 NORMALLY DURING CELL-BASED 955 00:41:56,782 --> 00:41:59,885 PROCESSES CELLS ARE MODIFYING 956 00:41:59,885 --> 00:42:02,421 GENE BASE AND THIS HAS GONE 957 00:42:02,421 --> 00:42:04,990 INTO HUMANS FOR CLINICAL TRIALS 958 00:42:04,990 --> 00:42:07,326 FOR DNA-BASED VACCINES. 959 00:42:07,326 --> 00:42:09,762 HOWEVER, GE ARE USING ROLLING 960 00:42:09,762 --> 00:42:11,630 CIRCLE AMPLIFICATION TO 961 00:42:11,630 --> 00:42:13,732 MODIFIED THE NUMBER OF DOSES. 962 00:42:13,732 --> 00:42:17,136 AND IT'S A VERY HIGHLY BRANCHED 963 00:42:17,136 --> 00:42:19,672 HIGHLY CAT M&R RISED STRUCTURE 964 00:42:19,672 --> 00:42:22,241 AND RESULTS IN MATERIAL THAT IS 965 00:42:22,241 --> 00:42:23,642 ALSO VERY VISCOUS. 966 00:42:23,642 --> 00:42:25,744 SO THIS ROLLING CIRCLE 967 00:42:25,744 --> 00:42:27,646 AMPLIFIED DNA HAS NOT YET BEEN 968 00:42:27,646 --> 00:42:30,182 IN HUMANS SO THE QUESTION THE 969 00:42:30,182 --> 00:42:32,518 GE TEAM HAS POSED NOT ONLY DO 970 00:42:32,518 --> 00:42:35,588 WE MAKE THIS IN AN AUTOMATED 971 00:42:35,588 --> 00:42:37,456 FASHION BUT WILL IT PERFORM THE 972 00:42:37,456 --> 00:42:39,558 SAME IN ANIMAL MODELS. 973 00:42:39,558 --> 00:42:41,427 WHAT I'M SHOWING ON THIS SLIDE 974 00:42:41,427 --> 00:42:44,697 IS GE SYNTHESIZED INFLUENZA 975 00:42:44,697 --> 00:42:46,131 VACCINE USING THE PROCESS ON 976 00:42:46,131 --> 00:42:51,370 THE LEFTMENT TAKING OUR INPUT, 977 00:42:51,370 --> 00:42:53,239 AND ENZYMES USING NUCLEOTIDES, 978 00:42:53,239 --> 00:42:56,508 LIE GATING THEM TOGETHER INTO 979 00:42:56,508 --> 00:42:58,410 BLOCKS, USING ENZYMATIC ERROR 980 00:42:58,410 --> 00:42:59,612 CORRECTION TO REMOVE ERRORS 981 00:42:59,612 --> 00:43:00,779 INTO THE SEQUENCE AND 982 00:43:00,779 --> 00:43:02,915 SIMULATING IN THE FULL-LENGTH 983 00:43:02,915 --> 00:43:03,315 SEQUENCE. 984 00:43:03,315 --> 00:43:07,853 THEY WERE ABLE TO DO THE 985 00:43:07,853 --> 00:43:09,021 IDENTITY WE CHALLENGED THE TEAM 986 00:43:09,021 --> 00:43:11,824 WITH AND MADE IT IN ONLY FIVE 987 00:43:11,824 --> 00:43:13,192 DAYS WHEN TECHNICALLY THEY HAD 988 00:43:13,192 --> 00:43:18,430 A TIME PERIOD OF THREE WEEKS. 989 00:43:18,430 --> 00:43:19,865 THE TECHNOLOGY TO PIGS AND WE 990 00:43:19,865 --> 00:43:23,202 WERE ABLE TO DEMONSTRATE 991 00:43:23,202 --> 00:43:25,070 COMPARABLE IMMUNE RESPONSE 992 00:43:25,070 --> 00:43:27,172 ROLLING CIRCLE AMPLIFIED DNA 993 00:43:27,172 --> 00:43:29,742 VERSUS THE N.O.W. PROCESS, AS 994 00:43:29,742 --> 00:43:30,876 OPPOSED TO PLASMA 995 00:43:30,876 --> 00:43:32,177 STATE-OF-THE-ART KERL. 996 00:43:32,177 --> 00:43:34,280 THIS IS ONE VACCINE IN ONE 997 00:43:34,280 --> 00:43:35,147 ANIMAL MODEL. 998 00:43:35,147 --> 00:43:37,716 WE WILL TEST DIFFERENT TYPES OF 999 00:43:37,716 --> 00:43:40,052 DNA VACCINES OR MEDICAL 1000 00:43:40,052 --> 00:43:40,753 COUNTERMEASURES THROUGHOUT THE 1001 00:43:40,753 --> 00:43:42,354 REST OF THE PROGRAM. 1002 00:43:42,354 --> 00:43:44,023 BUT THESE RESULTS ARE REALLY 1003 00:43:44,023 --> 00:43:45,224 ENCOURAGING AND POINT TO A 1004 00:43:45,224 --> 00:43:49,628 FUTURE FOR FULLY AUTOMATED 1005 00:43:49,628 --> 00:43:50,896 SYNTHESIS FOR MEDICAL 1006 00:43:50,896 --> 00:43:51,930 COUNTERMEASURES. 1007 00:43:51,930 --> 00:43:55,901 I WILL PIVOT TO MY COLLEAGUE 1008 00:43:55,901 --> 00:43:58,270 MIKE FEASEL, WHO WILL TALK 1009 00:43:58,270 --> 00:44:08,747 ABOUT SYNTHESIS OF PROTEINS. 1010 00:44:13,585 --> 00:44:15,387 HOW DO I GET OUT? 1011 00:44:15,387 --> 00:44:16,655 NEVER MIND, I WON'T TOUCH 1012 00:44:16,655 --> 00:44:19,124 ANYTHING THEN. 1013 00:44:19,124 --> 00:44:20,492 >> Michael Feasel: AWESOME, 1014 00:44:20,492 --> 00:44:22,294 THANK YOU VERY MUCH. 1015 00:44:22,294 --> 00:44:29,802 AN SHANNON SAID, I'M MIKE 1016 00:44:29,802 --> 00:44:31,437 FEASEL IN DARPA OFFICE. 1017 00:44:31,437 --> 00:44:33,105 I'M HAPPY TO SHOW YOU THE 1018 00:44:33,105 --> 00:44:34,773 PROTEIN MANUFACTURING PROGRAM. 1019 00:44:34,773 --> 00:44:36,275 QUITE A BIT YOU WILL NOTICE 1020 00:44:36,275 --> 00:44:38,944 LOOKS SIMILAR TO THE PROBLEM 1021 00:44:38,944 --> 00:44:41,080 SET SHANNON POSED FOR HER 1022 00:44:41,080 --> 00:44:41,380 PROGRAM NOW. 1023 00:44:41,380 --> 00:44:43,382 WE RELY ON VERY MUCH A HUB AND 1024 00:44:43,382 --> 00:44:46,018 SPOKE MODEL FOR DISTRIBUTION OF 1025 00:44:46,018 --> 00:44:46,685 PROTEIN PRODUCTS ACROSS THE 1026 00:44:46,685 --> 00:44:48,087 WORLD. 1027 00:44:48,087 --> 00:44:50,923 THAT MEANS PROTEIN PRODUCTION 1028 00:44:50,923 --> 00:44:53,759 IS HIGHLY CENTRALIZED, RELIANT 1029 00:44:53,759 --> 00:44:56,061 ON COLD CHAIN LOGISTICS AND 1030 00:44:56,061 --> 00:44:58,630 RELY HEAVILY ON 1031 00:44:58,630 --> 00:44:59,331 FOREIGN-SUPPLIED CELL SYSTEMS. 1032 00:44:59,331 --> 00:45:02,101 AND IN THE BIGGEST CHALLENGE WE 1033 00:45:02,101 --> 00:45:03,702 HAVE, I THINK IN PROTEIN 1034 00:45:03,702 --> 00:45:05,371 PRODUCTION IS THE AMOUNT OF 1035 00:45:05,371 --> 00:45:06,238 LEAD TIME REQUIRED. 1036 00:45:06,238 --> 00:45:08,674 ONCE YOU KNOW WHAT YOU WANT TO 1037 00:45:08,674 --> 00:45:10,142 MAKE, TO SOURCE THE CELLS TO 1038 00:45:10,142 --> 00:45:12,010 MAKE IT, TO ENGINEER THEM TO 1039 00:45:12,010 --> 00:45:13,479 MAKE THE THING YOU WANT AND 1040 00:45:13,479 --> 00:45:14,780 BRING THAT TO THE SCALE NEEDED 1041 00:45:14,780 --> 00:45:17,616 IN THIS HUB AND SPOKE MODEL IN 1042 00:45:17,616 --> 00:45:19,251 YOUR 20,000 LITER REACTORS, 1043 00:45:19,251 --> 00:45:21,854 THAT IS NOT A RAPID RESPONSE 1044 00:45:21,854 --> 00:45:24,623 WAY TO GO ABOUT RAPID 1045 00:45:24,623 --> 00:45:24,957 DISTRIBUTION. 1046 00:45:24,957 --> 00:45:27,659 WHAT WE ARE AIMING FOR OF 1047 00:45:27,659 --> 00:45:30,496 COURSE LIKE N.O.W. IS 1048 00:45:30,496 --> 00:45:31,397 DISTRIBUTED CAPABILITY THAT'S 1049 00:45:31,397 --> 00:45:34,466 COULD BE MORE TACTICAL PLACE TO 1050 00:45:34,466 --> 00:45:36,602 SUPPORT MORE DoD OPERATIONS TO 1051 00:45:36,602 --> 00:45:39,838 PROVIDE FOR BIOLOGIC SOLUTIONS, 1052 00:45:39,838 --> 00:45:41,473 WHETHER PRODUCTION ENZYMES FOR 1053 00:45:41,473 --> 00:45:43,809 THINGS LIKE N.O.W., BIOLOGIC 1054 00:45:43,809 --> 00:45:45,911 PRODUCTS THEMSELVES LIKE 1055 00:45:45,911 --> 00:45:47,346 INSULIN, CLOTTING FACTORS OR 1056 00:45:47,346 --> 00:45:50,115 OTHER PRODUCTION OR THERAPEUTIC 1057 00:45:50,115 --> 00:45:51,517 PROTEINS AS DoD NEEDS. 1058 00:45:51,517 --> 00:45:56,221 SO THE GOAL OF THE PROGRAM IS 1059 00:45:56,221 --> 00:46:00,425 TO -- LET ME TAKE A STEP BACK. 1060 00:46:00,425 --> 00:46:01,794 UNLIKE N.O.W. RPM IS NOT TRYING 1061 00:46:01,794 --> 00:46:03,896 TO BUILD A BIG BOX THAT DOES 1062 00:46:03,896 --> 00:46:05,063 ALL THE MANUFACTURING FOR US. 1063 00:46:05,063 --> 00:46:07,666 WHAT WE ARE TRYING TO DO IS 1064 00:46:07,666 --> 00:46:09,268 DE-RISK AND DEVELOP THE 1065 00:46:09,268 --> 00:46:11,170 TECHNOLOGIES THAT UNDER LIE 1066 00:46:11,170 --> 00:46:13,806 SUCH A BOX THAT COULD BE USED 1067 00:46:13,806 --> 00:46:15,407 IN THE FUTURE. 1068 00:46:15,407 --> 00:46:18,076 WE ARE FOCUSING ON INCREASING 1069 00:46:18,076 --> 00:46:19,678 PRODUCTION YIELD AND DECREASING 1070 00:46:19,678 --> 00:46:20,612 THE TIME REQUIRED. 1071 00:46:20,612 --> 00:46:21,814 UNDERSTANDING WHAT YOU WANT TO 1072 00:46:21,814 --> 00:46:23,448 MAKE TO ACTUALLY MAKING THE 1073 00:46:23,448 --> 00:46:23,649 STUFF. 1074 00:46:23,649 --> 00:46:25,350 WE WANT TO GET THAT FROM MONTHS 1075 00:46:25,350 --> 00:46:27,486 AND YEARS DOWN TO DAYS. 1076 00:46:27,486 --> 00:46:29,421 THE SECOND TECHNICAL AREA IS 1077 00:46:29,421 --> 00:46:31,223 THE FUNCTIONALITY OF THE 1078 00:46:31,223 --> 00:46:33,292 PROTEINS WE ARE PRODUCING. 1079 00:46:33,292 --> 00:46:35,194 SO THAT MEANS, APPROPRIATE 1080 00:46:35,194 --> 00:46:37,062 FOLDING OF THE PEPTIDES AND 1081 00:46:37,062 --> 00:46:37,763 PROTEINS. 1082 00:46:37,763 --> 00:46:40,499 AS WELL AS POST TRANSLATIONAL 1083 00:46:40,499 --> 00:46:42,134 MODIFICATIONS THAT OUR FIRST 1084 00:46:42,134 --> 00:46:43,368 SPEAKER TOUCHED ON QUITE A BIT 1085 00:46:43,368 --> 00:46:45,504 WHICH WAS A REALLY GOOD SEGUE 1086 00:46:45,504 --> 00:46:47,005 INTO THIS. 1087 00:46:47,005 --> 00:46:57,516 WE ARE LOOKING AT PRIMARILY N 1088 00:46:58,250 --> 00:47:00,486 AND O-LINKED GLYCOSYLATION. 1089 00:47:00,486 --> 00:47:04,223 THE PERFORMERS FOR TA-1, FOR 1090 00:47:04,223 --> 00:47:05,858 THE PROTEIN SIDE PRODUCTION, 1091 00:47:05,858 --> 00:47:08,794 PURITY AND LEAD TIME FOCUS, WE 1092 00:47:08,794 --> 00:47:11,396 ARE LOOKING AT OPTIMIZING OF 1093 00:47:11,396 --> 00:47:12,764 COURSE REACTION CONDITIONS. 1094 00:47:12,764 --> 00:47:17,469 WE ARE LOOKING AT MODIFYING DNA 1095 00:47:17,469 --> 00:47:20,372 AND RNA TEMPLATES. 1096 00:47:20,372 --> 00:47:23,175 DESIGNING BIO REACTORS AND 1097 00:47:23,175 --> 00:47:24,109 SUPPLEMENTING WITH ORGANELLES 1098 00:47:24,109 --> 00:47:26,178 FOR THINGS THAT CELL-PHORESIS 1099 00:47:26,178 --> 00:47:28,046 STEMS DON'T DO CURRENTLY. 1100 00:47:28,046 --> 00:47:32,885 THE SECOND AREA, WE ARE LOOKING 1101 00:47:32,885 --> 00:47:34,620 AT ADDING ENDOGENOUS ENZYMES. 1102 00:47:34,620 --> 00:47:35,454 WHAT IF YOUR SYSTEM DOESN'T 1103 00:47:35,454 --> 00:47:38,457 HAVE THE THING YOU NEED FOR THE 1104 00:47:38,457 --> 00:47:38,957 POST TRANSLATIONAL 1105 00:47:38,957 --> 00:47:41,493 MODIFICATION, FOR THE CHAPERON 1106 00:47:41,493 --> 00:47:44,363 FOLDING OF YOUR PEPTIDE OR 1107 00:47:44,363 --> 00:47:47,866 PROTEIN OF INTEREST, WE ARE 1108 00:47:47,866 --> 00:47:49,668 ADDING EXOGENOUS WHERE THEY CAN 1109 00:47:49,668 --> 00:47:51,570 AUGMENT THE PRODUCTIVE PROCESS. 1110 00:47:51,570 --> 00:47:53,939 OF COURSE ITEMS TWO AND THREE 1111 00:47:53,939 --> 00:47:56,074 ARE CHEMICAL MODIFICATIONS AND 1112 00:47:56,074 --> 00:47:58,610 LEVERAGING AND ENCODING FOR 1113 00:47:58,610 --> 00:48:00,012 THOSE EXOGENOUS PROTEINS IN THE 1114 00:48:00,012 --> 00:48:03,081 CELL SYSTEMS WE ARE TALKING 1115 00:48:03,081 --> 00:48:05,183 ABOUT TAKING LYSATES FROM. 1116 00:48:05,183 --> 00:48:07,753 THE LAST SLIDE, I PROMISE, 1117 00:48:07,753 --> 00:48:09,087 OVERVIEW OF PROGRAM SCHEDULE 1118 00:48:09,087 --> 00:48:10,322 AND METRICS. 1119 00:48:10,322 --> 00:48:12,457 THIS IS A FOUR-YEAR PROGRAM. 1120 00:48:12,457 --> 00:48:14,560 WE ARE COMING UP ON 11 MONTHS. 1121 00:48:14,560 --> 00:48:16,995 SO WE ARE ALMOST TO OUR FIRST 1122 00:48:16,995 --> 00:48:18,297 CAPABILITY DEMONSTRATION WHERE 1123 00:48:18,297 --> 00:48:19,698 THE PERFORMERS WILL HAVE TO 1124 00:48:19,698 --> 00:48:22,267 DEMONSTRATE THEY CAN MAKE A 1125 00:48:22,267 --> 00:48:32,811 PROTEIN OF SIZE GREATER THAN 5 1126 00:48:35,547 --> 00:48:35,781 KILODALTONS. 1127 00:48:35,781 --> 00:48:37,382 TALKING ABOUT LEAD TIME LESS 1128 00:48:37,382 --> 00:48:38,584 THAN TWO WEEKS. 1129 00:48:38,584 --> 00:48:41,586 PURITY GREATER THAN 80% AND 1130 00:48:41,586 --> 00:48:44,156 REACTOR SIZE GREATER THAN ONE 1131 00:48:44,156 --> 00:48:46,325 MIL. 1132 00:48:46,325 --> 00:48:46,959 O-LINKED GLYCANSES AT THIS 1133 00:48:46,959 --> 00:48:47,960 POINT. 1134 00:48:47,960 --> 00:48:50,329 AS YOU MOVE ACROSS THE TIMELINE 1135 00:48:50,329 --> 00:48:51,697 ALL THESE METRICS GET MORE 1136 00:48:51,697 --> 00:48:53,432 DIFFICULT AND MOVE TOWARD THE 1137 00:48:53,432 --> 00:48:55,934 END GOAL OF BEING ABLE TO 1138 00:48:55,934 --> 00:48:57,836 RAPIDLY PRODUCE LARGE PROTEINS 1139 00:48:57,836 --> 00:49:00,205 COMPLEX IN NATURE. 1140 00:49:00,205 --> 00:49:10,716 THEY ARE FOLDED APPROPRIATELY 1141 00:49:16,321 --> 00:49:18,423 AS GLYCOSOLATED. 1142 00:49:18,423 --> 00:49:19,992 PERFORMERS SHOW THEY ARE ABLE 1143 00:49:19,992 --> 00:49:22,461 TO OPTIMIZE THE ENHANCER 1144 00:49:22,461 --> 00:49:24,763 SEQUENCE FOR LARGER PRODUCTION 1145 00:49:24,763 --> 00:49:26,565 AMOUNTS OF THE PROTEIN. 1146 00:49:26,565 --> 00:49:27,799 IN THIS BLOT YOU CAN SEE 1147 00:49:27,799 --> 00:49:29,468 COMPARED TO THE BASELINE ON THE 1148 00:49:29,468 --> 00:49:31,536 FAR LEFT SIDE, A COUPLE 1149 00:49:31,536 --> 00:49:33,171 ENHANCER ELEMENTS THAT ARE MORE 1150 00:49:33,171 --> 00:49:34,406 OPTIMAL FOR THE PRODUCTION OF 1151 00:49:34,406 --> 00:49:35,774 THIS PROTEIN. 1152 00:49:35,774 --> 00:49:42,614 AND IT'S THE SARS-COV-2 BINDER 1153 00:49:42,614 --> 00:49:44,349 RECEPTOR DOMAIN. 1154 00:49:44,349 --> 00:49:47,352 BOTH HAVE ABOVE BASELINE LEVELS 1155 00:49:47,352 --> 00:49:49,454 OF PRODUCTION OF THIS PROTEIN. 1156 00:49:49,454 --> 00:49:52,624 ON THE RIGHT SIDE, THE 1157 00:49:52,624 --> 00:49:54,960 PERFORMERS IS DEMONSTRATING HOW 1158 00:49:54,960 --> 00:49:57,529 SELL PRODUCTION USING HOLLOW 1159 00:49:57,529 --> 00:49:59,398 FIBER BIO REACTOR IS NOT ONLY 1160 00:49:59,398 --> 00:50:01,767 MORE ADVANTAGEOUS HOW MUCH 1161 00:50:01,767 --> 00:50:05,003 STUFF IT COULD MAKE IN A GIVEN 1162 00:50:05,003 --> 00:50:06,638 TIME, IT'S SCALABLE. 1163 00:50:06,638 --> 00:50:09,608 THEY WENT FROM 20 MILLIONS TO 1164 00:50:09,608 --> 00:50:12,144 40 AND SIGNIFICANT INCREASES 1165 00:50:12,144 --> 00:50:13,578 OVER BATCH-STYLE REACTION WHICH 1166 00:50:13,578 --> 00:50:14,513 IS REALLY ENCOURAGING. 1167 00:50:14,513 --> 00:50:16,381 THE METRIC FOR THE FIRST 1168 00:50:16,381 --> 00:50:20,419 CAPABILITY DEMONSTRATION IS 100 1169 00:50:20,419 --> 00:50:22,387 MILLIGRAMS OF PROTEIN A WEEK. 1170 00:50:22,387 --> 00:50:28,126 IN THE 40 MIL HOLLOW FIBER 1171 00:50:28,126 --> 00:50:29,528 REACTOR THEY DEMONSTRATED THEY 1172 00:50:29,528 --> 00:50:30,996 HAVE REASONABLY IF THEY RUN 1173 00:50:30,996 --> 00:50:32,798 THIS THING FOR MORE THAN THE 1174 00:50:32,798 --> 00:50:34,666 TWO HOUR SINGLE BATCH IT CAN 1175 00:50:34,666 --> 00:50:36,568 CURRENTLY DO, IF THEY RUN IT 1176 00:50:36,568 --> 00:50:37,836 LONGER THEY CAN EASILY ACHIEVE 1177 00:50:37,836 --> 00:50:39,838 THAT GOAL. 1178 00:50:39,838 --> 00:50:41,940 WHAT WE ARE DEMONSTRATING HERE, 1179 00:50:41,940 --> 00:50:44,576 WHAT THE PERFORMERS ARE 1180 00:50:44,576 --> 00:50:45,944 DEMONSTRATING HERE AND WHAT I'M 1181 00:50:45,944 --> 00:50:47,145 TELLING YOU ABOUT BECAUSE I 1182 00:50:47,145 --> 00:50:48,780 DIDN'T DO THIS WORK PERSONALLY, 1183 00:50:48,780 --> 00:50:51,383 THEY ARE RIGHT ON TRACK TO 1184 00:50:51,383 --> 00:50:52,551 ACHIEVE PURITY METRICS 1185 00:50:52,551 --> 00:51:03,095 PRODUCING IN THIS CASE, T7 RNA 1186 00:51:03,361 --> 00:51:05,030 POLYMERASE. 1187 00:51:05,030 --> 00:51:07,833 IT ACHIEVES GREATER THAN 80% 1188 00:51:07,833 --> 00:51:08,633 PURITY. 1189 00:51:08,633 --> 00:51:12,370 ON THE RIGHT SIDE WHEN WE TALK 1190 00:51:12,370 --> 00:51:19,611 ABOUT FUNCTIONALITY, THIS IS AN 1191 00:51:19,611 --> 00:51:23,415 INDICATION THE SELF-REPRODUCED, 1192 00:51:23,415 --> 00:51:25,750 T7 RNA POLYMERASE IT IS 1193 00:51:25,750 --> 00:51:27,252 PRODUCIBLE IN THOSE GOLD 1194 00:51:27,252 --> 00:51:28,720 STANDARD SYSTEMS. 1195 00:51:28,720 --> 00:51:30,222 THAT'S ENCOURAGING AS WELL. 1196 00:51:30,222 --> 00:51:32,758 MY LAST DATA SLIDE, THIS IS THE 1197 00:51:32,758 --> 00:51:35,060 HEAVIEST WORK AND VERY RECENT 1198 00:51:35,060 --> 00:51:37,162 WORK DONE ON POST TRANSLATIONAL 1199 00:51:37,162 --> 00:51:37,963 MODIFICATION SIDE OF THE 1200 00:51:37,963 --> 00:51:39,231 PROGRAM. 1201 00:51:39,231 --> 00:51:42,734 WHERE LOOKING AT THE PERFORMERS 1202 00:51:42,734 --> 00:51:51,476 LOOKING AT SOLUBILIZING OR 1203 00:51:51,476 --> 00:52:01,887 GENERATING SOLUBILIZED 1204 00:52:02,354 --> 00:52:03,922 GLYCOSYLTRANSFERASES. 1205 00:52:03,922 --> 00:52:06,558 IN HUMANS THEY ARE ALL 1206 00:52:06,558 --> 00:52:07,192 MEMBRANE-BOUND PROTEINS. 1207 00:52:07,192 --> 00:52:14,166 ON THE RIGHT SIDE YOU CAN SEE 1208 00:52:14,166 --> 00:52:16,735 GLIOKOS LATED INCREASE IN 1209 00:52:16,735 --> 00:52:17,769 PRODUCTION CONCENTRATION AS YOU 1210 00:52:17,769 --> 00:52:27,312 INCREASE THE AMOUNT OF 1211 00:52:27,312 --> 00:52:28,680 GLYCOSILATED. 1212 00:52:28,680 --> 00:52:39,224 THEY ARE WORK AT INCREASING THE 1213 00:52:43,862 --> 00:52:46,364 AMOUNT OF GLYCOSYLATED. 1214 00:52:46,364 --> 00:52:48,233 WITH THAT, THAT ENDS MY 1215 00:52:48,233 --> 00:52:50,535 PRESENTATION AND I WILL INVITE 1216 00:52:50,535 --> 00:52:52,170 SHANNON BACK UP ON STAGE TO 1217 00:52:52,170 --> 00:52:54,005 ANSWER ANY QUESTIONS FOR EITHER 1218 00:52:54,005 --> 00:52:54,773 OF US. 1219 00:52:54,773 --> 00:53:04,983 [ APPLAUSE ] 1220 00:53:07,285 --> 00:53:09,754 >> SHANNON, IT WAS PRETTY 1221 00:53:09,754 --> 00:53:10,922 IMPRESSIVE, THEY ALREADY 1222 00:53:10,922 --> 00:53:12,791 KNOCKED OUT 3 OF THE 41 STEPS, 1223 00:53:12,791 --> 00:53:14,226 STUFF LIKE THAT. 1224 00:53:14,226 --> 00:53:17,062 WHAT ARE THE REMAINING 1225 00:53:17,062 --> 00:53:17,696 CHALLENGES, REMAINING 1226 00:53:17,696 --> 00:53:18,930 OPERATIONS, THAT TAKE A LITTLE 1227 00:53:18,930 --> 00:53:21,399 BIT MORE TO GET RID OF? 1228 00:53:21,399 --> 00:53:22,133 >> Shannon Greene: GREAT 1229 00:53:22,133 --> 00:53:23,435 QUESTION. 1230 00:53:23,435 --> 00:53:25,036 A COUPLE MANUAL STEPS THAT ARE 1231 00:53:25,036 --> 00:53:28,707 STILL WORKING ON BEING 1232 00:53:28,707 --> 00:53:30,408 AUTOMATED ARE INTEGRATING OX 1233 00:53:30,408 --> 00:53:33,311 -- SEQUENCING. 1234 00:53:33,311 --> 00:53:35,647 THAT COULD BE DONE AUTOMATED 1235 00:53:35,647 --> 00:53:39,618 BUT THEY DID STILL DO OFFLINE 1236 00:53:39,618 --> 00:53:41,086 SINGER SEQUENCING AS 1237 00:53:41,086 --> 00:53:42,420 INTERMEDIATE COMPARISON SO THE 1238 00:53:42,420 --> 00:53:44,990 REACTION WAS PAUSED AND THEN 1239 00:53:44,990 --> 00:53:45,657 RESUMED AUTOMATION DOWNSTREAM 1240 00:53:45,657 --> 00:53:46,891 OF THAT. 1241 00:53:46,891 --> 00:53:49,327 AND ONE OF THE OTHER TRICKY 1242 00:53:49,327 --> 00:53:51,596 STEPS IS STILL SOME OF THE 1243 00:53:51,596 --> 00:53:53,698 LIQUID HANDLING AT VERY, VERY 1244 00:53:53,698 --> 00:53:55,333 LOW VOLUMES FOR DOING THE 1245 00:53:55,333 --> 00:53:57,469 INITIAL BLOCK ASSEMBLY PRIOR TO 1246 00:53:57,469 --> 00:54:00,272 GOING TO FULL GENE LENGTH 1247 00:54:00,272 --> 00:54:01,239 ASSEMBLY AND THAT'S SOMETHING 1248 00:54:01,239 --> 00:54:03,475 WE ARE WORKING ONTO DE-RISK. 1249 00:54:03,475 --> 00:54:10,548 >> COOL, THANKS. 1250 00:54:10,548 --> 00:54:13,785 >> [OFF MIC] 1251 00:54:13,785 --> 00:54:21,259 YOU MENTIONED, MIKE, ALL GLYNIC 1252 00:54:21,259 --> 00:54:23,361 (?) ENZYMES BUT ARE YOU GOING 1253 00:54:23,361 --> 00:54:26,231 TO EXPAND TO OTHER 1254 00:54:26,231 --> 00:54:28,133 GLYCOLIZATIONS? 1255 00:54:28,133 --> 00:54:30,502 >> Michael Feasel: YES, END OF 1256 00:54:30,502 --> 00:54:32,637 PROGRAM GOALS, IF YOU GO BACK, 1257 00:54:32,637 --> 00:54:34,572 I THOUGHT THEY WERE INCLUDED IN 1258 00:54:34,572 --> 00:54:35,440 THIS SLIDE. 1259 00:54:35,440 --> 00:54:38,710 WE DO TALK ABOUT O AND N, 1260 00:54:38,710 --> 00:54:40,578 PHOSPHORYLATION IS ANOTHER ONE 1261 00:54:40,578 --> 00:54:41,479 MENTIONED EARLIER TODAY. 1262 00:54:41,479 --> 00:54:42,681 I THINK THOSE ARE THE MAJOR 1263 00:54:42,681 --> 00:54:45,917 ONES WE ARE LOOKING AT. 1264 00:54:45,917 --> 00:54:48,820 LIPIDATION OPTIONS BUT REALLY 1265 00:54:48,820 --> 00:54:50,722 THE OTHER POST TRANSLATIONAL 1266 00:54:50,722 --> 00:54:51,656 MODIFICATIONS ARE VERY MUCH 1267 00:54:51,656 --> 00:54:53,892 GOING TO BE PERFORMER DIRECTED. 1268 00:54:53,892 --> 00:54:55,460 SO AS WE NEED THEM, BASED ON 1269 00:54:55,460 --> 00:54:56,861 THE PROTEIN WE ARE TRYING TO 1270 00:54:56,861 --> 00:54:58,897 MAKE, THAT'S WHEN THEY WILL BE 1271 00:54:58,897 --> 00:54:59,998 INTRODUCED IN THE PROCESS THIS 1272 00:54:59,998 --> 00:55:00,565 YEAR. 1273 00:55:00,565 --> 00:55:02,400 I IMAGINE BY THE END OF THIS 1274 00:55:02,400 --> 00:55:04,703 PROGRAM THERE WILL BE MUCH MORE 1275 00:55:04,703 --> 00:55:08,006 THAN IS ACTUALLY DEPICTED HERE, 1276 00:55:08,006 --> 00:55:09,407 MORE SPECIFIC ONES, RATHER. 1277 00:55:09,407 --> 00:55:10,608 >> SURE, SURE. 1278 00:55:10,608 --> 00:55:11,242 LOOKS IMPRESSIVE. 1279 00:55:11,242 --> 00:55:12,043 THANK YOU. 1280 00:55:12,043 --> 00:55:15,747 >> Michael Feasel: THANK YOU. 1281 00:55:15,747 --> 00:55:17,415 >> ANY OTHER QUESTIONS? 1282 00:55:17,415 --> 00:55:18,550 IF NOT, THANK YOU VERY MUCH, 1283 00:55:18,550 --> 00:55:20,385 AND THANK YOU FOR KEEPING US ON 1284 00:55:20,385 --> 00:55:21,086 TIME. 1285 00:55:21,086 --> 00:55:21,886 THIS IS REALLY GREAT. 1286 00:55:21,886 --> 00:55:22,954 THANK YOU. 1287 00:55:22,954 --> 00:55:33,164 [ APPLAUSE ] 1288 00:56:45,069 --> 00:56:46,171 >> Miljan Simonovic: ALL RIGHT, 1289 00:56:46,171 --> 00:56:47,739 NOW WE ARE BACK TO THE FIRST 1290 00:56:47,739 --> 00:56:50,809 PRESENTER. 1291 00:56:50,809 --> 00:56:53,411 DR. KOO WILL NOW PRESENT HER 1292 00:56:53,411 --> 00:56:55,547 WORK FROM FDA. 1293 00:56:55,547 --> 00:56:56,414 PLEASE, DR. KOO, IF YOU COULD 1294 00:56:56,414 --> 00:56:56,948 COME UP. 1295 00:56:56,948 --> 00:57:04,255 THANK YOU. 1296 00:57:04,255 --> 00:57:12,964 AND I APOLOGIZE FOR THE GLITCH. 1297 00:57:12,964 --> 00:57:23,241 YEAH, THANK YOU. 1298 00:57:25,009 --> 00:57:26,311 >> Lily Koo: HI, WELL, THANK 1299 00:57:26,311 --> 00:57:28,480 YOU VERY MUCH. 1300 00:57:28,480 --> 00:57:31,116 THANK YOU, MILJAN AND JAMAL FOR 1301 00:57:31,116 --> 00:57:32,250 FINDING MY SLIDES AGAIN. 1302 00:57:32,250 --> 00:57:33,685 AGAIN, AS I SAID, IT'S A 1303 00:57:33,685 --> 00:57:34,552 PLEASURE TO BE HERE THIS 1304 00:57:34,552 --> 00:57:35,320 MORNING. 1305 00:57:35,320 --> 00:57:39,958 JUST TO TELL YOU A LITTLE BIT 1306 00:57:39,958 --> 00:57:43,261 MORE ABOUT CBER, AS I MENTIONED 1307 00:57:43,261 --> 00:57:45,597 EARLIER, AT CBER WE REVIEW AND 1308 00:57:45,597 --> 00:57:46,764 EVALUATE THE SAFETY AND 1309 00:57:46,764 --> 00:57:49,100 EFFECTIVENESS OF A LARGE 1310 00:57:49,100 --> 00:57:50,802 VARIETY OF BIOLOGICAL PRODUCTS 1311 00:57:50,802 --> 00:57:52,470 I WILL MENTION A LITTLE BIT ON 1312 00:57:52,470 --> 00:57:53,605 A LATER SLIDE. 1313 00:57:53,605 --> 00:57:54,772 AND YOU KNOW, AFTER GOING 1314 00:57:54,772 --> 00:57:57,108 THROUGH THE PANDEMIC AND 1315 00:57:57,108 --> 00:57:59,377 SUPPORTING THE COMMERCIAL 1316 00:57:59,377 --> 00:58:06,117 LAUNCH OF NOW QUITE A NUMBER OF 1317 00:58:06,117 --> 00:58:07,719 GENE PRODUCTS WITNESSING THE 1318 00:58:07,719 --> 00:58:09,354 EFFECTIVE TREATMENT IT BROUGHT 1319 00:58:09,354 --> 00:58:11,789 TO OUR PATIENTS, IT'S EXCITING. 1320 00:58:11,789 --> 00:58:13,691 BUT WE ALSO REALIZE OUR 1321 00:58:13,691 --> 00:58:15,627 LIMITATIONS ESPECIALLY IN THE 1322 00:58:15,627 --> 00:58:16,794 AREA OF BIOMANUFACTURING. 1323 00:58:16,794 --> 00:58:20,532 AND THERE ARE WAYS TO IMPROVE 1324 00:58:20,532 --> 00:58:20,865 EFFICIENCY. 1325 00:58:20,865 --> 00:58:23,368 AND ALSO AGILITY SO THAT WE CAN 1326 00:58:23,368 --> 00:58:25,003 BRING THE MEDICINE TO PATIENTS 1327 00:58:25,003 --> 00:58:26,971 FASTER. 1328 00:58:26,971 --> 00:58:28,573 AND CAN ALSO RESPOND MORE 1329 00:58:28,573 --> 00:58:30,642 RAPIDLY TO A HEALTHCARE 1330 00:58:30,642 --> 00:58:30,942 EMERGENCY. 1331 00:58:30,942 --> 00:58:33,044 AND SO THIS IS WHERE TODAY I 1332 00:58:33,044 --> 00:58:34,445 WOULD LIKE TO IN MY 1333 00:58:34,445 --> 00:58:35,380 PRESENTATION TODAY I WOULD LIKE 1334 00:58:35,380 --> 00:58:37,949 TO TELL YOU A LITTLE BIT MORE 1335 00:58:37,949 --> 00:58:40,084 ABOUT WHAT CBER IS DOING, JUST 1336 00:58:40,084 --> 00:58:42,387 TO PROMOTE DEVELOPMENT AND ALSO 1337 00:58:42,387 --> 00:58:43,488 ADOPTION OF ADVANCED 1338 00:58:43,488 --> 00:58:45,190 MANUFACTURING TECHNOLOGIES. 1339 00:58:45,190 --> 00:58:47,458 AND THAT IS UNDER SOME OF THE 1340 00:58:47,458 --> 00:58:51,763 INITIATIVE UNDER THE CBER 1341 00:58:51,763 --> 00:58:54,732 ADVANCED TECHNOLOGIES PROGRAM. 1342 00:58:54,732 --> 00:58:55,233 [COUGH] 1343 00:58:55,233 --> 00:59:03,007 SORRY. 1344 00:59:03,007 --> 00:59:04,876 I UNDERSTAND, IT DOESN'T 1345 00:59:04,876 --> 00:59:06,244 ADVANCE ON THIS SCREEN. 1346 00:59:06,244 --> 00:59:07,445 OKAY. 1347 00:59:07,445 --> 00:59:10,481 I JUST NEED TO GET A THING FOR 1348 00:59:10,481 --> 00:59:13,918 THIS. 1349 00:59:13,918 --> 00:59:16,454 YEAH, SO, CBER, WE HAVE A LARGE 1350 00:59:16,454 --> 00:59:17,121 PORTFOLIO OF BIOLOGICAL 1351 00:59:17,121 --> 00:59:18,823 PRODUCTS. 1352 00:59:18,823 --> 00:59:25,663 AND YOU MAY NOT BE AWARE OF. 1353 00:59:25,663 --> 00:59:28,967 WE REGULATE GENICS FOR 1354 00:59:28,967 --> 00:59:30,568 DIAGNOSIS OF DISEASES. 1355 00:59:30,568 --> 00:59:33,137 WE REGULATE BLOOD AND BLOOD 1356 00:59:33,137 --> 00:59:35,673 COMPONENTS FOR BLOOD 1357 00:59:35,673 --> 00:59:37,742 TRANSFUSION, BLOOD DERIVED 1358 00:59:37,742 --> 00:59:39,143 THERAPEUTIC PROTEINS, GENE 1359 00:59:39,143 --> 00:59:41,279 THERAPIES, MANY OF YOU ARE VERY 1360 00:59:41,279 --> 00:59:43,615 MUCH AWARE WHAT WE CAN DO 1361 00:59:43,615 --> 00:59:51,522 THERE, BOTH ANTOLOGIST. 1362 00:59:51,522 --> 00:59:54,592 INVIVO OR EX VIVO. 1363 00:59:54,592 --> 00:59:57,395 PREVENTIVE AND THERAPEUTIC. 1364 00:59:57,395 --> 01:00:01,699 LIVE BIO THERAPEUTIC PRODUCTS 1365 01:00:01,699 --> 01:00:08,206 INCLUDING FECAL BOWEL MICRO 1366 01:00:08,206 --> 01:00:18,316 BIOTA. 1367 01:00:20,952 --> 01:00:23,688 XENOTRANSPLANTATIONAL PRODUCTS. 1368 01:00:23,688 --> 01:00:27,425 TWO PATIENTS RECEIVE TWO PIG 1369 01:00:27,425 --> 01:00:28,826 HEART TRANSPLANTS GENETICALLY 1370 01:00:28,826 --> 01:00:31,396 MODIFIED TO REDUCE REJECTION BY 1371 01:00:31,396 --> 01:00:32,463 THE BODY. 1372 01:00:32,463 --> 01:00:34,932 AND EVEN THOUGH I THINK THEY 1373 01:00:34,932 --> 01:00:37,001 LASTED ABOUT 30-40 DAYS BUT 1374 01:00:37,001 --> 01:00:38,603 THAT'S A REALLY A CRAZY BREAK 1375 01:00:38,603 --> 01:00:39,137 THROUGH. 1376 01:00:39,137 --> 01:00:40,738 AND WE ARE CONTINUING TO WORK 1377 01:00:40,738 --> 01:00:43,741 ON THAT TO IMPROVE THIS KIND OF 1378 01:00:43,741 --> 01:00:45,310 PRODUCTS TO ADDRESS SHORTAGE OF 1379 01:00:45,310 --> 01:00:47,512 TRANSPLANTS. 1380 01:00:47,512 --> 01:00:50,581 WE ACTUALLY ALSO REGULATE 1381 01:00:50,581 --> 01:00:50,815 DEVICES. 1382 01:00:50,815 --> 01:00:53,885 ESPECIALLY THOSE DEVICES USED 1383 01:00:53,885 --> 01:00:55,286 FOR SCREENING, TESTING, 1384 01:00:55,286 --> 01:00:56,954 ISOLATION PROCESSING AND ALSO 1385 01:00:56,954 --> 01:01:00,692 DELIVERY OF BIOLOGICAL PRODUCTS. 1386 01:01:00,692 --> 01:01:01,893 AND CERTAIN COMBINATION 1387 01:01:01,893 --> 01:01:03,995 PRODUCTS THAT THE PRIMARY MODE 1388 01:01:03,995 --> 01:01:05,663 OF ACTION WOULD BE ATTRIBUTABLE 1389 01:01:05,663 --> 01:01:08,132 TO THE BIOLOGICAL COMPONENT. 1390 01:01:08,132 --> 01:01:11,536 AS YOU CAN SEE, MANY OF THESE 1391 01:01:11,536 --> 01:01:13,638 PRODUCTS REALLY ARE ENABLED AND 1392 01:01:13,638 --> 01:01:15,073 BENEFITED FROM SYNTHETIC 1393 01:01:15,073 --> 01:01:16,841 BIOLOGY TECHNOLOGIES AND TOOLS. 1394 01:01:16,841 --> 01:01:18,342 AND I BELIEVE THE WORK WE ARE 1395 01:01:18,342 --> 01:01:20,478 DOING HERE IS REALLY IMPORTANT 1396 01:01:20,478 --> 01:01:23,948 BECAUSE WHAT THAT DOES, WE ARE 1397 01:01:23,948 --> 01:01:26,584 PROVIDING BETTER QUALITY 1398 01:01:26,584 --> 01:01:28,353 PRODUCTS THAT ARE MORE POTENT. 1399 01:01:28,353 --> 01:01:30,054 THEY ARE MORE PRECISE AND THEY 1400 01:01:30,054 --> 01:01:32,090 ARE SAFER FOR THE PATIENTS. 1401 01:01:32,090 --> 01:01:33,357 SO PLEASE CONTINUE THE GREAT 1402 01:01:33,357 --> 01:01:34,992 WORK YOU ARE DOING. 1403 01:01:34,992 --> 01:01:36,627 AND THE REST OF THE SLIDES I'M 1404 01:01:36,627 --> 01:01:40,365 GOING TO TELL YOU A LITTLE BIT 1405 01:01:40,365 --> 01:01:42,734 MORE WHAT CBER IS DOING TO 1406 01:01:42,734 --> 01:01:43,735 SUPPORT THESE ADVANCED 1407 01:01:43,735 --> 01:01:46,938 TECHNOLOGIES, ESPECIALLY IN THE 1408 01:01:46,938 --> 01:01:47,572 BIOMANUFACTURING SECTOR, SINCE 1409 01:01:47,572 --> 01:01:50,108 THIS IS THE TOPIC OF THIS 1410 01:01:50,108 --> 01:01:50,708 WEEK'S MEETING. 1411 01:01:50,708 --> 01:01:53,277 I THOUGHT THE FOCUS ABOUT 1412 01:01:53,277 --> 01:01:55,613 MANUFACTURING FOR THIS YEAR'S 1413 01:01:55,613 --> 01:01:56,581 MEETING IS ACTUALLY REALLY 1414 01:01:56,581 --> 01:01:57,014 TIMELY. 1415 01:01:57,014 --> 01:01:59,384 BECAUSE WE ARE FACING MANY 1416 01:01:59,384 --> 01:02:02,620 CHALLENGES IN THIS SPACE. 1417 01:02:02,620 --> 01:02:04,489 THE REASON, THIS RE OBVIOUS 1418 01:02:04,489 --> 01:02:06,357 SOMETIMES AND NOT SO OBVIOUS. 1419 01:02:06,357 --> 01:02:08,259 PART IS BECAUSE BIOLOGICAL 1420 01:02:08,259 --> 01:02:10,661 PRODUCTS ARE JUST VERY COMPLEX. 1421 01:02:10,661 --> 01:02:12,296 THEY HAVE VERY COMPLEX 1422 01:02:12,296 --> 01:02:12,897 STRUCTURES, COMPLEX MODE OF 1423 01:02:12,897 --> 01:02:13,898 ACTIONS. 1424 01:02:13,898 --> 01:02:16,634 THEY ARE NOT EASY TO 1425 01:02:16,634 --> 01:02:16,968 CHARACTERIZE. 1426 01:02:16,968 --> 01:02:19,203 SO IT IS DIFFICULT TO ESTABLISH 1427 01:02:19,203 --> 01:02:24,342 YOUR CRITICAL QUALITY 1428 01:02:24,342 --> 01:02:26,444 ATTRIBUTES OR THE IMPURITY 1429 01:02:26,444 --> 01:02:26,944 PROFILE. 1430 01:02:26,944 --> 01:02:28,813 AND ALSO DIFFICULT TO IDENTIFY, 1431 01:02:28,813 --> 01:02:33,117 YOU KNOW, OR DEVELOP THE 1432 01:02:33,117 --> 01:02:35,019 RELEASE SPECIFICATIONS AND ALSO 1433 01:02:35,019 --> 01:02:36,687 THE ASSAYS USED TO SUPPORT THEM. 1434 01:02:36,687 --> 01:02:39,056 AND ALL THESE ARE VERY CRITICAL 1435 01:02:39,056 --> 01:02:41,392 ASPECTS OF FORMING A VERY 1436 01:02:41,392 --> 01:02:42,794 ROBUST CONTROL STRATEGY FOR A 1437 01:02:42,794 --> 01:02:44,829 MANUFACTURING PROCESS. 1438 01:02:44,829 --> 01:02:48,366 AND OF COURSE, MOST OF OUR 1439 01:02:48,366 --> 01:02:50,668 PRODUCTS ARE DERIVED FROM 1440 01:02:50,668 --> 01:02:52,537 LIVING CELLS, TISSUES AND 1441 01:02:52,537 --> 01:02:55,139 ORGANIZISMS WITH VERY VARIABLE, 1442 01:02:55,139 --> 01:02:55,907 VERY VARIABLE STARTING 1443 01:02:55,907 --> 01:02:57,041 MATERIALS. 1444 01:02:57,041 --> 01:02:58,643 SO THAT INTRODUCES ADDITIONAL 1445 01:02:58,643 --> 01:02:59,944 VARIABILITY TO OUR FINAL 1446 01:02:59,944 --> 01:03:00,745 PRODUCT. 1447 01:03:00,745 --> 01:03:04,415 IN ADDITION TO THE PROCESS OR 1448 01:03:04,415 --> 01:03:06,651 MANUFACTURING VARIABILITIES. 1449 01:03:06,651 --> 01:03:07,952 AND OF COURSE, BECAUSE THEY ARE 1450 01:03:07,952 --> 01:03:10,388 LIVING, WE HAVE TO ALWAYS 1451 01:03:10,388 --> 01:03:11,355 CONSIDER THEIR VIABILITY AND 1452 01:03:11,355 --> 01:03:14,125 HOW TO MAINTAIN THE DESIRED 1453 01:03:14,125 --> 01:03:15,326 PHENOTYPE THROUGH OUR 1454 01:03:15,326 --> 01:03:16,627 PROCESSING AND DURING STORAGE. 1455 01:03:16,627 --> 01:03:20,364 SO THAT'S ALWAYS A CONCERN. 1456 01:03:20,364 --> 01:03:23,401 AND MANY OF OUR PRODUCTS, 1457 01:03:23,401 --> 01:03:24,569 DEPENDING HOW THEY ARE SOURCED 1458 01:03:24,569 --> 01:03:26,471 AND SOME OF THE RAW MATERIAL 1459 01:03:26,471 --> 01:03:27,638 INTRODUCED IN THE MANUFACTURING 1460 01:03:27,638 --> 01:03:29,507 STREAM ARE SUBJECT TO 1461 01:03:29,507 --> 01:03:32,477 CONTAMINATION, WITH 1462 01:03:32,477 --> 01:03:35,313 ADVANTAGEOUS REAGENTS. 1463 01:03:35,313 --> 01:03:38,149 AND THERE NEEDS TO BE A CONTROL 1464 01:03:38,149 --> 01:03:40,918 TO PREVENT, DETECT AND ALSO 1465 01:03:40,918 --> 01:03:42,320 REMOVE THESE HARMFUL AGENTS 1466 01:03:42,320 --> 01:03:44,188 FROM THE FINAL PRODUCT. 1467 01:03:44,188 --> 01:03:54,699 THAT'S ALSO ANOTHER THING TO 1468 01:03:58,569 --> 01:03:59,570 CONSIDER. 1469 01:03:59,570 --> 01:04:03,474 THERE WILL BE RELIABILITY ON 1470 01:04:03,474 --> 01:04:04,642 PROCESSING, THE GMP 1471 01:04:04,642 --> 01:04:08,679 REQUIREMENTS THAT COMES WITH 1472 01:04:08,679 --> 01:04:09,614 ASEPTIC PROCESSING AND 1473 01:04:09,614 --> 01:04:12,149 OPERATORS AND ALL THESE 1474 01:04:12,149 --> 01:04:13,551 COMPONENTS INCREASE PRODUCTION 1475 01:04:13,551 --> 01:04:16,120 COST AND COMPLEXITY. 1476 01:04:16,120 --> 01:04:19,790 VERY OFTEN WHEN WE INTRODUCE A 1477 01:04:19,790 --> 01:04:21,459 NOVEL THERAPEUTIC MODALITY, FOR 1478 01:04:21,459 --> 01:04:23,761 EXAMPLE, SOME OF OUR GENE 1479 01:04:23,761 --> 01:04:27,265 THERAPY PRODUCTS, THE NOVELTY 1480 01:04:27,265 --> 01:04:29,100 OF IT PRESENTS UNIQUE 1481 01:04:29,100 --> 01:04:30,268 CHALLENGES AS WELL, RIGHT? 1482 01:04:30,268 --> 01:04:32,203 BECAUSE WE DON'T HAVE A LOT OF 1483 01:04:32,203 --> 01:04:33,104 PRODUCT UNDERSTANDING AND WE 1484 01:04:33,104 --> 01:04:34,305 DON'T HAVE A LOT OF 1485 01:04:34,305 --> 01:04:36,107 MANUFACTURING EXPERIENCE. 1486 01:04:36,107 --> 01:04:39,176 SOMETIMES THESE PRODUCTS 1487 01:04:39,176 --> 01:04:49,654 ESPECIALLY FOR ENTOLOGOUS 1488 01:04:52,356 --> 01:04:53,724 PRODUCTS -- DEVELOP 1489 01:04:53,724 --> 01:04:54,725 APPROPRIATE CONTROL STRATEGY. 1490 01:04:54,725 --> 01:04:57,161 SO THESE ARE VERY UNIQUE 1491 01:04:57,161 --> 01:04:58,129 CHALLENGES ASSOCIATED WITH 1492 01:04:58,129 --> 01:05:00,665 COMPLEX BIOLOGICS. 1493 01:05:00,665 --> 01:05:04,402 AND ALSO IN TERMS OF SCALING, 1494 01:05:04,402 --> 01:05:08,606 CURRENTLY THERE ARE TWO 1495 01:05:08,606 --> 01:05:10,942 DIFFERENT APPROACHES. 1496 01:05:10,942 --> 01:05:14,512 THEY ARE NOT COMMONLY EMPLOYED 1497 01:05:14,512 --> 01:05:16,047 TO INCREASE MANUFACTURING 1498 01:05:16,047 --> 01:05:20,518 SCALING. 1499 01:05:20,518 --> 01:05:23,020 ONE IS SCALE UP, WHICH WE ARE 1500 01:05:23,020 --> 01:05:24,655 ALL VERY FAMILIAR WHEN WE ARE 1501 01:05:24,655 --> 01:05:26,023 MOVING OUR PRODUCT DEVELOPMENT 1502 01:05:26,023 --> 01:05:29,594 PHASE FROM LABORATORY SCALE TO 1503 01:05:29,594 --> 01:05:31,028 INTERMEDIATE SCALE AND THEN TO 1504 01:05:31,028 --> 01:05:31,896 COMMERCIAL SCALE. 1505 01:05:31,896 --> 01:05:34,198 THAT IS JUST SIMPLY INCREASE 1506 01:05:34,198 --> 01:05:38,269 THE PROCESS VOLUME, RIGHT? 1507 01:05:38,269 --> 01:05:40,905 IT'S EASIER SAID THAN DONE. 1508 01:05:40,905 --> 01:05:42,673 MORE RECENTLY THERE'S ANOTHER 1509 01:05:42,673 --> 01:05:44,375 MODALITY AND APPROACH WHICH IS 1510 01:05:44,375 --> 01:05:48,145 TO SCALE OUT. 1511 01:05:48,145 --> 01:05:52,283 ESPECIALLY RELEVANT FOR 1512 01:05:52,283 --> 01:05:56,587 ANTOLOGIST. 1513 01:05:56,587 --> 01:05:59,857 WE SEE THAT TODAY WITH A LOT OF 1514 01:05:59,857 --> 01:06:01,692 THE TEAM MANUFACTURING, WE CAN 1515 01:06:01,692 --> 01:06:03,694 DO TO BIG COMPANIES, THEY HAVE 1516 01:06:03,694 --> 01:06:07,531 REALLY GREAT FACILITIES, YOU 1517 01:06:07,531 --> 01:06:08,466 KNOW, GMP COMPLIANT, BUT WHEN 1518 01:06:08,466 --> 01:06:10,801 YOU WALK IN IT REMINDS YOU OF 1519 01:06:10,801 --> 01:06:12,903 GOING BACK TO GRADUATE SCHOOL. 1520 01:06:12,903 --> 01:06:16,440 YOU SEE UNITS AND UNITS OF BIO 1521 01:06:16,440 --> 01:06:16,807 SAFETY CABINETS. 1522 01:06:16,807 --> 01:06:17,842 THERE'S A LOT OF CONSIDERATION 1523 01:06:17,842 --> 01:06:19,243 WHEN IT COMES TO SCALE OUT, 1524 01:06:19,243 --> 01:06:20,878 BECAUSE YOU WANT TO MAKE SURE 1525 01:06:20,878 --> 01:06:22,613 THERE IS CONSISTENCY IN EACH 1526 01:06:22,613 --> 01:06:24,882 LOT. 1527 01:06:24,882 --> 01:06:26,517 BECAUSE VERY OFTEN THEY ARE 1528 01:06:26,517 --> 01:06:27,885 VERY MANUAL, RIGHT? 1529 01:06:27,885 --> 01:06:30,955 HOW DO YOU BRING CONSISTENCY TO 1530 01:06:30,955 --> 01:06:33,557 HUMAN INTERVENTIONS AND HUMAN 1531 01:06:33,557 --> 01:06:34,992 MANIPULATIONS, THERE'S A LOT OF 1532 01:06:34,992 --> 01:06:39,930 TRAINING INVOLVED AND RETAIN 1533 01:06:39,930 --> 01:06:40,898 THE ASEPTIC CONDITIONS. 1534 01:06:40,898 --> 01:06:44,168 ALSO, IF YOU WANT TO INCREASE 1535 01:06:44,168 --> 01:06:44,869 PRODUCTION, ENCOURAGE 1536 01:06:44,869 --> 01:06:45,503 CONCURRENT MANUFACTURING, THERE 1537 01:06:45,503 --> 01:06:47,171 YOU HAVE TO WORRY ABOUT THE 1538 01:06:47,171 --> 01:06:49,040 RISK OF CROSS CONTAMINATION 1539 01:06:49,040 --> 01:06:51,108 WHEN YOU WORK IN THAT SPACE. 1540 01:06:51,108 --> 01:06:53,377 SO THIS IS UNIQUE. 1541 01:06:53,377 --> 01:06:56,480 BUT ON TOP OF THAT, I ALSO WANT 1542 01:06:56,480 --> 01:06:59,116 TO THINK ABOUT THE DIFFERENT 1543 01:06:59,116 --> 01:07:00,985 VARIETIES OF BIOLOGICAL 1544 01:07:00,985 --> 01:07:02,386 PRODUCTS THAT WE HAVE. 1545 01:07:02,386 --> 01:07:04,755 SO THE TWO APPROACHES I JUST 1546 01:07:04,755 --> 01:07:06,924 MENTIONED, THEY HAVE THEIR OWN 1547 01:07:06,924 --> 01:07:10,461 UNIQUE LIMITATIONS. 1548 01:07:10,461 --> 01:07:12,096 AND LOGISTICAL COMPLEXITIES AS 1549 01:07:12,096 --> 01:07:13,964 I MENTIONED EARLIER, BUT 1550 01:07:13,964 --> 01:07:15,599 NEITHER OF THEM REALLY FULLY 1551 01:07:15,599 --> 01:07:18,402 ADDRESS THE POTENTIAL 1552 01:07:18,402 --> 01:07:19,804 MANUFACTURING CAPACITY 1553 01:07:19,804 --> 01:07:21,872 BOTTLENECK THAT ARISES DURING A 1554 01:07:21,872 --> 01:07:23,708 SICH FOR DEMAND. 1555 01:07:23,708 --> 01:07:26,644 SO SEARCH FOR DEMAND. 1556 01:07:26,644 --> 01:07:28,446 SO FOR EXAMPLE, DURING COVID-19 1557 01:07:28,446 --> 01:07:30,314 WE REQUIRE LARGE QUANTITY OF 1558 01:07:30,314 --> 01:07:32,683 VACCINES TO BE MANUFACTURED 1559 01:07:32,683 --> 01:07:34,752 VERY RAPIDLY. 1560 01:07:34,752 --> 01:07:36,620 AND FACE MANY CAPACITY 1561 01:07:36,620 --> 01:07:38,022 BOTTLENECK THAT WE ARE VERY 1562 01:07:38,022 --> 01:07:38,723 WELL AWARE OF. 1563 01:07:38,723 --> 01:07:41,759 AND ON THE OTHER END OF THE 1564 01:07:41,759 --> 01:07:44,295 SPECTRUM, WE ALSO HAVE 1565 01:07:44,295 --> 01:07:46,664 BIOLOGICS INDICATOR FOR VERY 1566 01:07:46,664 --> 01:07:49,166 SMALL PATIENT POPULATION. 1567 01:07:49,166 --> 01:07:51,168 AS IN THE CASE OF RARE DISEASES. 1568 01:07:51,168 --> 01:07:55,239 AND ALSO FOR PERSONALIZED 1569 01:07:55,239 --> 01:07:56,874 MEDICINE WHERE, YOU MAY NEED TO 1570 01:07:56,874 --> 01:08:01,412 HAVE JUST A FEW LOTS, OR SMALL 1571 01:08:01,412 --> 01:08:02,046 LOT SIZE. 1572 01:08:02,046 --> 01:08:08,185 AND I HAVE TO ADDRESS MORE 1573 01:08:08,185 --> 01:08:10,755 INTERMEDIATE FREQUENCY. 1574 01:08:10,755 --> 01:08:13,524 SO I THINK, HOW DID THAT HAPPEN? 1575 01:08:13,524 --> 01:08:15,659 DID I PRESS IT BY MISTAKE? 1576 01:08:15,659 --> 01:08:18,429 I'M PRETTY SURE I DIDN'T PRESS 1577 01:08:18,429 --> 01:08:18,696 ANYTHING. 1578 01:08:18,696 --> 01:08:21,899 SO, ADDING FLEXIBILITY TO 1579 01:08:21,899 --> 01:08:24,535 SCALABILITY, I THINK THAT'S A 1580 01:08:24,535 --> 01:08:25,736 VERY CRITICAL CONSIDERATION IN 1581 01:08:25,736 --> 01:08:27,838 HOW WE CAN MAKE OUR PROCESS 1582 01:08:27,838 --> 01:08:30,174 MORE EFFICIENT. 1583 01:08:30,174 --> 01:08:34,411 SO HOW TO ADDRESS THESE 1584 01:08:34,411 --> 01:08:36,814 CHALLENGES? 1585 01:08:36,814 --> 01:08:38,682 AND CBER BELIEVE ONE CRITICAL 1586 01:08:38,682 --> 01:08:40,151 SOLUTION IS APPLICATION OF 1587 01:08:40,151 --> 01:08:43,854 EVENTS MANUFACTURING. 1588 01:08:43,854 --> 01:08:46,157 WHAT ADVANCED MANUFACTURING? 1589 01:08:46,157 --> 01:08:48,492 THAT'S COLLECTIVELY TERM FOR 1590 01:08:48,492 --> 01:08:51,061 INNOVATIVELY APPLIED AND NEW 1591 01:08:51,061 --> 01:08:51,562 MEDICINE MANUFACTURING 1592 01:08:51,562 --> 01:08:53,130 APPROACHES. 1593 01:08:53,130 --> 01:08:57,368 AND THE INTENT IS THAT BY USING 1594 01:08:57,368 --> 01:08:57,868 ADVANCED MANUFACTURING 1595 01:08:57,868 --> 01:08:59,603 TECHNOLOGIES, WE CAN PRODUCE 1596 01:08:59,603 --> 01:09:09,880 BETTER PRODUCT. 1597 01:09:11,749 --> 01:09:14,018 WE CAN SPEED TIME TO MARKET. 1598 01:09:14,018 --> 01:09:16,620 SORRY, I'M REALLY STRUGGLING 1599 01:09:16,620 --> 01:09:16,887 WITH THIS. 1600 01:09:16,887 --> 01:09:20,891 AND THERE ARE SEVERAL 1601 01:09:20,891 --> 01:09:22,960 CHARACTERISTICS THAT CAN 1602 01:09:22,960 --> 01:09:24,595 DESCRIBE A.M. OR HOW IT'S BEING 1603 01:09:24,595 --> 01:09:25,796 APPLIED. 1604 01:09:25,796 --> 01:09:29,233 THAT INCLUDES INTEGRATING NOVEL 1605 01:09:29,233 --> 01:09:29,900 TECHNOLOGICAL APPROACHES TO A 1606 01:09:29,900 --> 01:09:33,837 PROCESS. 1607 01:09:33,837 --> 01:09:34,605 ALSO USING ESTABLISHED 1608 01:09:34,605 --> 01:09:36,674 TECHNIQUE BUT IN A VERY 1609 01:09:36,674 --> 01:09:40,044 INNOVATIVE WAY, OR A NEW WAY. 1610 01:09:40,044 --> 01:09:42,112 AND ALSO APPLYING PRODUCTION 1611 01:09:42,112 --> 01:09:44,248 METHODS IN A NEW DOMAIN WHERE 1612 01:09:44,248 --> 01:09:47,051 WE JUST DON'T HAVE A LOT OF 1613 01:09:47,051 --> 01:09:50,454 EXPERIENCE OR DEFINED BEST 1614 01:09:50,454 --> 01:09:51,055 PRACTICE. 1615 01:09:51,055 --> 01:09:54,792 SO I THINK YOU CAN SEE NOVEL 1616 01:09:54,792 --> 01:09:56,794 IS A THEME THAT RUNS THROUGH 1617 01:09:56,794 --> 01:09:59,630 A.M. 1618 01:09:59,630 --> 01:10:01,031 AND EXAMPLES OF ADVANCED 1619 01:10:01,031 --> 01:10:03,234 MANUFACTURING, I CAN START WITH 1620 01:10:03,234 --> 01:10:04,101 SMART MANUFACTURING. 1621 01:10:04,101 --> 01:10:08,505 SO THIS IS A TERM THAT IS USED, 1622 01:10:08,505 --> 01:10:12,576 APPLIED TO THE USE OR 1623 01:10:12,576 --> 01:10:13,510 UTILIZATION OF ADVANCED 1624 01:10:13,510 --> 01:10:16,347 TECHNOLOGY SUCH AS AUTOMATION, 1625 01:10:16,347 --> 01:10:18,782 INTERNET OF THINGS. 1626 01:10:18,782 --> 01:10:20,885 ARTIFICIAL INTELLIGENCE, BIG 1627 01:10:20,885 --> 01:10:22,486 DATA ANALYTICS, TO OPTIMIZE 1628 01:10:22,486 --> 01:10:25,689 PROCESS CONTROL. 1629 01:10:25,689 --> 01:10:27,791 AND THAT IS THROUGH DIGITAL 1630 01:10:27,791 --> 01:10:30,995 CONNECTION AND DIGITAL 1631 01:10:30,995 --> 01:10:31,695 COMMUNICATION AMONG 1632 01:10:31,695 --> 01:10:32,630 MANUFACTURING SYSTEMS THAT USED 1633 01:10:32,630 --> 01:10:34,498 TO WORK IN SILO. 1634 01:10:34,498 --> 01:10:36,100 SO ANOTHER EXAMPLE OF SMART 1635 01:10:36,100 --> 01:10:37,268 MANUFACTURING I CAN GIVE YOU IS 1636 01:10:37,268 --> 01:10:40,371 THE CREATION OF A DIGITAL TWIN. 1637 01:10:40,371 --> 01:10:43,474 WHICH IS A MODEL BASED VIRTUAL 1638 01:10:43,474 --> 01:10:45,042 REPRESENTATION OF THE PHYSICAL 1639 01:10:45,042 --> 01:10:47,378 PROCESS, RIGHT? 1640 01:10:47,378 --> 01:10:49,613 AND THAT IS, AS A CLOSED LOOP 1641 01:10:49,613 --> 01:10:50,681 PROCESS CONTROL. 1642 01:10:50,681 --> 01:10:52,549 AND IT HAS INTERACTIVE 1643 01:10:52,549 --> 01:10:54,184 COMMUNICATION WITH THE PHYSICAL 1644 01:10:54,184 --> 01:10:56,954 PROCESS THROUGH DATA LINK. 1645 01:10:56,954 --> 01:10:58,389 THAT'S A REAL-TIME 1646 01:10:58,389 --> 01:11:00,024 COMMUNICATION THROUGH THE USE 1647 01:11:00,024 --> 01:11:07,398 OF ONLINE AND INLINE SENSORS, 1648 01:11:07,398 --> 01:11:11,001 PROCESS ANALYTICAL TECHNOLOGIES. 1649 01:11:11,001 --> 01:11:16,273 AND THAT ENABLE THAT TWING TO 1650 01:11:16,273 --> 01:11:17,074 MAKE REAL-TIME PREDICTIONS OR 1651 01:11:17,074 --> 01:11:18,375 DECISIONS FOR THE PROCESS. 1652 01:11:18,375 --> 01:11:21,211 AND THROUGH THAT WE CAN MAKE 1653 01:11:21,211 --> 01:11:21,812 OPTIMIZATION, ONLINE 1654 01:11:21,812 --> 01:11:27,818 OPTIMIZATION. 1655 01:11:27,818 --> 01:11:29,253 CONTINUOUS OR SEMI-CONTINUOUS 1656 01:11:29,253 --> 01:11:31,121 MANUFACTURING IS ANOTHER NEW 1657 01:11:31,121 --> 01:11:34,258 MANUFACTURING PARADIGM. 1658 01:11:34,258 --> 01:11:36,794 AND THAT IS, WHAT IT DOES, THAT 1659 01:11:36,794 --> 01:11:38,395 INTEGRATES THE UNIT OPERATIONS, 1660 01:11:38,395 --> 01:11:40,030 RIGHT? 1661 01:11:40,030 --> 01:11:43,467 AND IT HAS CONTINUOUS INPUT OF 1662 01:11:43,467 --> 01:11:46,437 THE RAW MATERIALS AND 1663 01:11:46,437 --> 01:11:48,439 CONTINUOUS OUTPUT OF THE DRUG 1664 01:11:48,439 --> 01:11:49,740 SUBSTANCE OR DRUG PRODUCT. 1665 01:11:49,740 --> 01:11:51,942 WHEN IT IS APPROPRIATELY 1666 01:11:51,942 --> 01:11:52,409 APPLIED, CONTINUOUS 1667 01:11:52,409 --> 01:11:53,677 MANUFACTURING COULD BE VERY 1668 01:11:53,677 --> 01:11:54,511 EFFICIENT. 1669 01:11:54,511 --> 01:11:57,881 BECAUSE IT HAS LITTLE DOWN TIME. 1670 01:11:57,881 --> 01:12:00,684 AND IT PRODUCES BETTER QUALITY 1671 01:12:00,684 --> 01:12:02,786 BIOLOGICS OR PRODUCTS BECAUSE 1672 01:12:02,786 --> 01:12:04,955 PRODUCTION IS ALWAYS HAPPENING 1673 01:12:04,955 --> 01:12:06,857 AT A STEADY STATE. 1674 01:12:06,857 --> 01:12:08,959 THE DYNAMIC FOR STARTING UP THE 1675 01:12:08,959 --> 01:12:11,962 SYSTEM IS NOT THERE. 1676 01:12:11,962 --> 01:12:13,163 AND IT'S CONTINUOUS, SO THAT'S 1677 01:12:13,163 --> 01:12:14,565 REALLY IMPORTANT FOR THE 1678 01:12:14,565 --> 01:12:18,569 CONSISTENCY OF THE QUALITY OF A 1679 01:12:18,569 --> 01:12:23,040 PRODUCT THAT MANUFACTURES. 1680 01:12:23,040 --> 01:12:25,376 AND ALSO HAS REAL-TIME PROCESS 1681 01:12:25,376 --> 01:12:27,244 CORRECTION AND OPTIMIZATION. 1682 01:12:27,244 --> 01:12:32,082 THAT ALSO MAKES THE PRODUCT 1683 01:12:32,082 --> 01:12:37,521 MORE ROBUST AND CONTROLS THE 1684 01:12:37,521 --> 01:12:42,826 FINAL DRUG PRODUCT QUALITY. 1685 01:12:42,826 --> 01:12:43,660 ADDITIVE MANUFACTURING, ALSO 1686 01:12:43,660 --> 01:12:46,397 KNOWN TO MANY OF US AS 3D 1687 01:12:46,397 --> 01:12:48,265 PRINTING, THAT'S ANOTHER MOVEL 1688 01:12:48,265 --> 01:12:52,169 MANUFACTURING MODALITY THAT 1689 01:12:52,169 --> 01:12:53,303 PROVIDES PERSONALIZATION AND 1690 01:12:53,303 --> 01:12:56,273 FLEXIBILITY TO THE WAY WE 1691 01:12:56,273 --> 01:12:57,674 MANUFACTURE BIOLOGICS. 1692 01:12:57,674 --> 01:12:59,777 AND MENTIONED QUITE OFTEN AT 1693 01:12:59,777 --> 01:13:00,844 YESTERDAY'S AND TODAY'S 1694 01:13:00,844 --> 01:13:02,579 MEETING, IT WAS A GREAT 1695 01:13:02,579 --> 01:13:06,750 PRESENTATION, VERY EXCITING IS 1696 01:13:06,750 --> 01:13:07,351 DISTRIBUTED OR POINT-OF-CARE 1697 01:13:07,351 --> 01:13:08,919 MANUFACTURING. 1698 01:13:08,919 --> 01:13:11,021 AND THIS IS, THE GOAL IS REALLY 1699 01:13:11,021 --> 01:13:15,659 TO BRING THE MEDICINE CLOSER TO 1700 01:13:15,659 --> 01:13:16,927 THE PATIENTS. 1701 01:13:16,927 --> 01:13:18,429 SO THAT CAN ENSURE SUPPLY, 1702 01:13:18,429 --> 01:13:19,063 RIGHT? 1703 01:13:19,063 --> 01:13:20,864 AS OUR PREVIOUS SPEAKER 1704 01:13:20,864 --> 01:13:23,033 MENTIONED. 1705 01:13:23,033 --> 01:13:26,303 AND ALSO TO REDUCE TIME TO 1706 01:13:26,303 --> 01:13:28,172 ADMINISTRATION, MANY BIOLOGICAL 1707 01:13:28,172 --> 01:13:29,773 PRODUCTS HAVE LIMITED SHELF 1708 01:13:29,773 --> 01:13:29,973 LIFE. 1709 01:13:29,973 --> 01:13:31,442 SOME OF THEM REALLY HAVE TO BE 1710 01:13:31,442 --> 01:13:36,380 DELIVERED TO THE PATIENT FOR 1711 01:13:36,380 --> 01:13:37,748 IMPLANTATION OR USE QUITE 1712 01:13:37,748 --> 01:13:39,183 SHORTLY AFTER PRODUCT RELEASE. 1713 01:13:39,183 --> 01:13:42,853 AND SOME OF THEM REQUIRE ULTRA 1714 01:13:42,853 --> 01:13:44,488 COLD STORAGE WHICH CREATES A 1715 01:13:44,488 --> 01:13:48,926 LOT OF LOGISTICAL CHALLENGES. 1716 01:13:48,926 --> 01:13:51,261 SO WHAT WE ARE REALLY LOOKING 1717 01:13:51,261 --> 01:13:54,331 FOR, FOR THESE POINT-OF-CARE OR 1718 01:13:54,331 --> 01:13:56,433 DISTRIBUTED MANUFACTURING IS 1719 01:13:56,433 --> 01:13:56,900 REALLY AVAILABILITY, 1720 01:13:56,900 --> 01:13:57,968 ACCESSIBILITY AND ALSO 1721 01:13:57,968 --> 01:14:08,345 AFFORDABILITY, RIGHT? 1722 01:14:09,079 --> 01:14:09,880 NOT MOVING. 1723 01:14:09,880 --> 01:14:19,990 OKAY. 1724 01:14:30,400 --> 01:14:32,202 IT'S MOVING HERE, BUT NOT THERE. 1725 01:14:32,202 --> 01:14:33,604 SORRY, I'M A LITTLE CONFUSED 1726 01:14:33,604 --> 01:14:35,772 WHICH DIRECTION I SHOULD BE 1727 01:14:35,772 --> 01:14:36,039 POINTING. 1728 01:14:36,039 --> 01:14:38,842 MUST BE ME, I'M HAVING A LOT OF 1729 01:14:38,842 --> 01:14:40,377 I.T. PROBLEMS THIS MORNING. 1730 01:14:40,377 --> 01:14:42,513 WHAT ARE SOME OF THE BENEFITS? 1731 01:14:42,513 --> 01:14:44,982 SOME ARE ALREADY MENTIONED. 1732 01:14:44,982 --> 01:14:46,083 ADVANCED MANUFACTURING WE THINK 1733 01:14:46,083 --> 01:14:49,653 IT WILL PRODUCE BETTER-QUALITY 1734 01:14:49,653 --> 01:14:49,920 MEDICINE. 1735 01:14:49,920 --> 01:14:51,054 BECAUSE THE MANUFACTURING IS 1736 01:14:51,054 --> 01:14:54,424 MORE CONTROLLED AND LESS 1737 01:14:54,424 --> 01:14:55,125 ERROR-PRONE. 1738 01:14:55,125 --> 01:14:57,661 WE KNOW WHEN YOU HAVE A LOT OF 1739 01:14:57,661 --> 01:14:59,096 HUMAN INTERACTIONS OR 1740 01:14:59,096 --> 01:15:01,431 INTERVENTIONS, WE ARE HUMAN, WE 1741 01:15:01,431 --> 01:15:03,066 MAKE MISTAKES AND CAN INTRODUCE 1742 01:15:03,066 --> 01:15:08,739 A LOT OF ERROR ALONG THE WAY. 1743 01:15:08,739 --> 01:15:11,041 AND WE ALSO EXPECT THAT THE 1744 01:15:11,041 --> 01:15:13,844 MANUFACTURING COSTS WILL BE 1745 01:15:13,844 --> 01:15:19,616 REDUCED SIGNIFICANTLY, DUE TO 1746 01:15:19,616 --> 01:15:20,984 SMALLER FOOTPRINT, 1747 01:15:20,984 --> 01:15:21,952 MANUFACTURING FOOTPRINT. 1748 01:15:21,952 --> 01:15:26,590 AND ALSO MORE EFFICIENT PROCESS. 1749 01:15:26,590 --> 01:15:30,027 AND ALL THESE THINGS. 1750 01:15:30,027 --> 01:15:32,229 AND ALSO MORE ROBUST PROCESS 1751 01:15:32,229 --> 01:15:33,664 MONITORING AND CONTROL. 1752 01:15:33,664 --> 01:15:36,867 THIS WILL LEAD TO LESS 1753 01:15:36,867 --> 01:15:39,169 DEFECTIVE PRODUCTS AND LESS 1754 01:15:39,169 --> 01:15:40,237 REJECTED BATCHES, RIGHT. 1755 01:15:40,237 --> 01:15:43,473 IT WILL HELP TO DEVELOP AND 1756 01:15:43,473 --> 01:15:44,841 ALSO MANUFACTURE MEDICINE MORE 1757 01:15:44,841 --> 01:15:45,976 RAPIDLY. 1758 01:15:45,976 --> 01:15:48,812 AND IT WOULD PREVENT OR REDUCE 1759 01:15:48,812 --> 01:15:51,815 AT LEAST SHORTAGES OF NEEDED 1760 01:15:51,815 --> 01:15:54,184 MEDICINE BECAUSE THE PROCESS IS 1761 01:15:54,184 --> 01:15:56,987 MORE CONTROLLED, IS MORE ROBUST. 1762 01:15:56,987 --> 01:16:00,090 AND TODAY, I THINK, MORE THAN 1763 01:16:00,090 --> 01:16:02,392 50% OF OUR DRUG SHORTAGES ARE 1764 01:16:02,392 --> 01:16:05,729 ACTUALLY DUE TO QUALITY-RELATED 1765 01:16:05,729 --> 01:16:06,630 MANUFACTURING ISSUES. 1766 01:16:06,630 --> 01:16:08,031 WE REALIZE THIS IS AN AREA, 1767 01:16:08,031 --> 01:16:09,733 THERE'S A LOT OF ROOM TO 1768 01:16:09,733 --> 01:16:11,635 IMPROVE TO MAKE IT MORE 1769 01:16:11,635 --> 01:16:12,836 EFFICIENT AND MAKE IT MORE 1770 01:16:12,836 --> 01:16:14,771 ROBUST. 1771 01:16:14,771 --> 01:16:17,174 AND IT WOULD IMPROVE EMERGENCY 1772 01:16:17,174 --> 01:16:19,243 PREPAREDNESS, AS IT PROVIDES 1773 01:16:19,243 --> 01:16:20,010 ADDITIONAL FLEXIBILITY AND 1774 01:16:20,010 --> 01:16:22,980 AGILITY TO THE WAY WE PIVOT AND 1775 01:16:22,980 --> 01:16:24,615 RESPOND TO PUBLIC HEALTH 1776 01:16:24,615 --> 01:16:32,222 EMERGENCIES. 1777 01:16:32,222 --> 01:16:36,293 BUT DESPITE ALL THESE BENEFITS, 1778 01:16:36,293 --> 01:16:37,995 INNOVATION, UP TAKE OF 1779 01:16:37,995 --> 01:16:38,829 INNOVATIVE APPROACHES 1780 01:16:38,829 --> 01:16:40,230 ESPECIALLY IN A REGULATED 1781 01:16:40,230 --> 01:16:44,935 SETTING COULD BE SLOW. 1782 01:16:44,935 --> 01:16:47,037 AND CBER RECOGNIZES THAT AND WE 1783 01:16:47,037 --> 01:16:48,472 UNDERSTAND IMPLEMENTATION OF 1784 01:16:48,472 --> 01:16:51,475 EMERGING TECHNOLOGIES TO 1785 01:16:51,475 --> 01:16:55,312 MANUFACTURE HIGH-QUALITY 1786 01:16:55,312 --> 01:16:56,246 COMPLEX BIOLOGICS PRESENTS A 1787 01:16:56,246 --> 01:17:00,083 LARGE VARIETY OF, A BIG VARIETY 1788 01:17:00,083 --> 01:17:00,851 OF CHALLENGES. 1789 01:17:00,851 --> 01:17:03,920 NOT ONLY TO THE INDUSTRY BUT TO 1790 01:17:03,920 --> 01:17:04,988 CBER AS WELL. 1791 01:17:04,988 --> 01:17:07,691 SO TO RESPOND TO THAT, WE 1792 01:17:07,691 --> 01:17:10,394 ESTABLISHED THE CBER ADVANCED 1793 01:17:10,394 --> 01:17:13,297 TECHNOLOGIES PROGRAM. 1794 01:17:13,297 --> 01:17:15,032 AND THE PROGRAM HAS THREE 1795 01:17:15,032 --> 01:17:17,834 PILLARS. 1796 01:17:17,834 --> 01:17:20,837 WE FUND RESEARCH AND 1797 01:17:20,837 --> 01:17:23,740 DEVELOPMENT PROJECTS TO SUPPORT 1798 01:17:23,740 --> 01:17:26,443 OUR REGULATORY SCIENCE BUT ALSO 1799 01:17:26,443 --> 01:17:26,777 INNOVATION. 1800 01:17:26,777 --> 01:17:28,645 WE BUILD INTERNAL SCIENTIFIC 1801 01:17:28,645 --> 01:17:29,813 AND REGULATORY EXPERTISE 1802 01:17:29,813 --> 01:17:31,315 BECAUSE WE REALIZE WE HAVE TO 1803 01:17:31,315 --> 01:17:32,215 KEEP PACE. 1804 01:17:32,215 --> 01:17:34,518 WE HAVE TO HAVE OUR OWN 1805 01:17:34,518 --> 01:17:36,553 SCIENTIFIC KNOWLEDGE AND 1806 01:17:36,553 --> 01:17:38,622 EXPERTISE IN-HOUSE IN ORDER TO 1807 01:17:38,622 --> 01:17:39,790 EVALUATE THE EFFECTIVENESS AND 1808 01:17:39,790 --> 01:17:41,458 SAFETY OF THESE PRODUCTS. 1809 01:17:41,458 --> 01:17:46,596 AND ALSO TO UNDERSTAND THE MORE 1810 01:17:46,596 --> 01:17:50,767 INNOVATIVE WAY OF ENGINEERING 1811 01:17:50,767 --> 01:17:52,903 AND DOING, TO MODERNIZE THE WAY 1812 01:17:52,903 --> 01:17:54,604 WE ENGINEER OUR PRODUCTS. 1813 01:17:54,604 --> 01:17:57,808 AND WE ALSO CREATED THE CBER 1814 01:17:57,808 --> 01:17:58,508 ADVANCED TECHNOLOGIES TEAM, 1815 01:17:58,508 --> 01:18:00,711 WHICH I WILL DESCRIBE A LITTLE 1816 01:18:00,711 --> 01:18:04,214 LATER ON A LATER SLIDE. 1817 01:18:04,214 --> 01:18:06,316 SO, FIRST, TALKING ABOUT THE 1818 01:18:06,316 --> 01:18:07,150 EXTRAMURAL RESEARCH THAT WE 1819 01:18:07,150 --> 01:18:10,320 SUPPORT. 1820 01:18:10,320 --> 01:18:14,124 SINCE 2018, CBER HAS ALREADY 1821 01:18:14,124 --> 01:18:17,260 AWARDED OVER 20 GRANTS AND 1822 01:18:17,260 --> 01:18:20,564 CONTRACTS TO SUPPORT RESEARCH 1823 01:18:20,564 --> 01:18:21,765 PROJECTS ADDRESS KNOWLEDGE AND 1824 01:18:21,765 --> 01:18:23,867 EXPERIENCE GAPS THAT WE HAVE 1825 01:18:23,867 --> 01:18:25,535 IDENTIFIED FOR EMERGING 1826 01:18:25,535 --> 01:18:28,638 MANUFACTURING AND TESTING 1827 01:18:28,638 --> 01:18:28,972 TECHNOLOGIES. 1828 01:18:28,972 --> 01:18:30,741 TO SUPPORT THE DEVELOPMENT AND 1829 01:18:30,741 --> 01:18:32,175 ADOPTION OF THESE ADVANCED 1830 01:18:32,175 --> 01:18:32,676 TECHNOLOGIES. 1831 01:18:32,676 --> 01:18:34,978 SO EACH YEAR WE IDENTIFY AREAS 1832 01:18:34,978 --> 01:18:39,182 OF NEEDS IN THE ADVANCED 1833 01:18:39,182 --> 01:18:41,051 MANUFACTURING TECHNOLOGY AREA 1834 01:18:41,051 --> 01:18:43,120 AND SOLICIT APPLICATIONS 1835 01:18:43,120 --> 01:18:44,988 THROUGH FDA BROAD AGENCY 1836 01:18:44,988 --> 01:18:46,857 ANNOUNCEMENT AND ALSO THROUGH 1837 01:18:46,857 --> 01:18:48,024 THE NIH GRANT AND FUNDING 1838 01:18:48,024 --> 01:18:50,660 PORTAL. 1839 01:18:50,660 --> 01:18:52,295 SO I REALLY ENCOURAGE EVERYONE 1840 01:18:52,295 --> 01:18:54,364 TO CHECK IT OUT AND SEE IF 1841 01:18:54,364 --> 01:18:57,033 THERE ARE AREAS OF INTEREST AND 1842 01:18:57,033 --> 01:19:00,737 TO YOU AND TO THE FDA TO CBER 1843 01:19:00,737 --> 01:19:02,539 AND PLEASE SUBMIT YOUR 1844 01:19:02,539 --> 01:19:03,273 APPLICATIONS. 1845 01:19:03,273 --> 01:19:05,175 WE REALLY WOULD BE VERY HAPPY 1846 01:19:05,175 --> 01:19:07,911 TO SEE MORE WORK-RELATED TO 1847 01:19:07,911 --> 01:19:09,746 SYNTHETIC BIOLOGY AND HOW THAT 1848 01:19:09,746 --> 01:19:11,448 CAN IMPROVE OUR 1849 01:19:11,448 --> 01:19:21,925 BIOMANUFACTURING STRATEGIES. 1850 01:19:27,097 --> 01:19:28,432 OKAY, THAT IS TOO FAR. 1851 01:19:28,432 --> 01:19:38,308 MAYBE I JUST NEED TO BE PATIENT. 1852 01:19:38,308 --> 01:19:39,743 GOOD. 1853 01:19:39,743 --> 01:19:41,645 SOME EXAMPLES OF THE PROJECTS 1854 01:19:41,645 --> 01:19:44,681 WE SUPPORT, WE SUPPORT 3D 1855 01:19:44,681 --> 01:19:48,985 PRINTING PROJECTS, INCLUDING 1856 01:19:48,985 --> 01:19:51,188 BIO PRINTING OF TISSUE AND 1857 01:19:51,188 --> 01:19:52,055 VACCINE FORMULATIONS. 1858 01:19:52,055 --> 01:19:53,657 WE HAVE SOME REALLY COOL 1859 01:19:53,657 --> 01:19:56,026 PROJECTS. 1860 01:19:56,026 --> 01:19:57,194 NOVEL MANUFACTURING MODALITIES 1861 01:19:57,194 --> 01:20:02,165 AND APPROACHES FOR CELL AND 1862 01:20:02,165 --> 01:20:04,534 GENE THERAPY PRODUCTS. 1863 01:20:04,534 --> 01:20:07,337 SOME INCLUDE USE OF AUTOMATION 1864 01:20:07,337 --> 01:20:08,738 AND ALSO DOWNSTREAM 1865 01:20:08,738 --> 01:20:10,207 PURIFICATION PROCESS. 1866 01:20:10,207 --> 01:20:13,210 AND ALSO RELATED TO CRITICAL 1867 01:20:13,210 --> 01:20:15,378 QUALITY ATTRIBUTIONS, DISCOVERY 1868 01:20:15,378 --> 01:20:18,782 AND IDENTIFICATION USING 1869 01:20:18,782 --> 01:20:20,317 MULTI-NOMIC ANALYSIS APPROACHES. 1870 01:20:20,317 --> 01:20:22,953 WE HAVE SEVERAL PRODUCTS, 1871 01:20:22,953 --> 01:20:24,120 CONTINUOUS MANUFACTURING OF 1872 01:20:24,120 --> 01:20:25,956 DIFFERENT TYPES OF PRODUCTS. 1873 01:20:25,956 --> 01:20:29,693 AND IN FACT, LAST YEAR, WE 1874 01:20:29,693 --> 01:20:31,528 AWARDED A VERY LARGE SUM 1875 01:20:31,528 --> 01:20:34,197 CONTRACT TO A TEAM LED BY 1876 01:20:34,197 --> 01:20:37,667 M.I.T. TO WORK OUT A REALLY 1877 01:20:37,667 --> 01:20:39,069 G.M.P. PILOT SCALE 1878 01:20:39,069 --> 01:20:43,607 DEMONSTRATION UNIT THAT CAN 1879 01:20:43,607 --> 01:20:44,574 MANUFACTURE VACCINE, mRNA-BASED 1880 01:20:44,574 --> 01:20:46,176 VACCINES IN A CONTINUOUS 1881 01:20:46,176 --> 01:20:49,646 FASHION. 1882 01:20:49,646 --> 01:20:52,716 WE HAVE SUPPORTED ADVANCED 1883 01:20:52,716 --> 01:20:53,850 MANUFACTURING OF SYNTHETIC 1884 01:20:53,850 --> 01:20:59,189 SCAFFOLDS THAT WILL MIMIC CELL 1885 01:20:59,189 --> 01:21:00,824 OR EXTRA CELLULAR MATRIX 1886 01:21:00,824 --> 01:21:04,528 PROPERTIES. 1887 01:21:04,528 --> 01:21:04,995 WORK PROCESS 1888 01:21:04,995 --> 01:21:06,696 MODELING/SIMULATION AND ALSO 1889 01:21:06,696 --> 01:21:07,797 ANALYTICAL TECHNOLOGIES. 1890 01:21:07,797 --> 01:21:10,333 HE 1891 01:21:10,333 --> 01:21:12,469 ESPECIALLY INTERESTING ARE NON 1892 01:21:12,469 --> 01:21:15,472 DESTRUCTIVE TECHNOLOGIES OR 1893 01:21:15,472 --> 01:21:17,107 REAL-TIME SENSORS THAT CAN HELP 1894 01:21:17,107 --> 01:21:20,744 WITH THE ADVANCEMENT OF 1895 01:21:20,744 --> 01:21:23,780 BIOMANUFACTURING. 1896 01:21:23,780 --> 01:21:25,248 THERE IS A WEBSITE YOU CAN 1897 01:21:25,248 --> 01:21:34,357 CHECK IT OUT. 1898 01:21:34,357 --> 01:21:37,427 IN SUPPORTING THESE EXTRAMURAL 1899 01:21:37,427 --> 01:21:39,062 PROJECTS CBER IS LEARNING ABOUT 1900 01:21:39,062 --> 01:21:40,697 THESE CUTTING EDGE RESEARCH AND 1901 01:21:40,697 --> 01:21:44,167 TECHNOLOGIES AS WELL BECAUSE WE 1902 01:21:44,167 --> 01:21:50,073 DON'T HOLD A MINI SYMPOSIUM, WE 1903 01:21:50,073 --> 01:21:51,174 INVITE OUR RECIPIENTS OF OUR 1904 01:21:51,174 --> 01:21:53,877 FUNDING. 1905 01:21:53,877 --> 01:21:58,582 AND WE ALSO ORGANIZE 1906 01:21:58,582 --> 01:22:01,985 EDUCATIONAL SEMINAR SERIES AND 1907 01:22:01,985 --> 01:22:04,287 VERY, MOST RECENTLY, THIS FALL, 1908 01:22:04,287 --> 01:22:07,390 WE LAUNCHED OUR NEW CBER 1909 01:22:07,390 --> 01:22:08,191 ADVANCED MANUFACTURING SEMINAR 1910 01:22:08,191 --> 01:22:11,695 SERIES. 1911 01:22:11,695 --> 01:22:13,597 THAT INCLUDES, FEATURES 1912 01:22:13,597 --> 01:22:15,932 SPEAKERS FROM OUR PAST AND 1913 01:22:15,932 --> 01:22:18,068 PRESENT RECIPIENTS FROM OUR 1914 01:22:18,068 --> 01:22:18,301 FUNDING. 1915 01:22:18,301 --> 01:22:20,570 AND ALSO LEADING EXPERTS FROM 1916 01:22:20,570 --> 01:22:22,305 ACADEMIA AND INDUSTRY AND ALSO 1917 01:22:22,305 --> 01:22:23,907 GOVERNMENT SECTORS. 1918 01:22:23,907 --> 01:22:26,242 IF YOU ARE INTERESTED, YOU CAN 1919 01:22:26,242 --> 01:22:28,311 DEFINITELY LET ME KNOW, THIS IS 1920 01:22:28,311 --> 01:22:29,980 A PUBLIC MEETING, SEMINAR AND 1921 01:22:29,980 --> 01:22:32,082 WE CAN INCLUDE SOME OF THE 1922 01:22:32,082 --> 01:22:38,989 FOLKS WHO ARE INTERESTED HERE. 1923 01:22:38,989 --> 01:22:43,460 SO NOW I WILL MOVE TO THE CBER 1924 01:22:43,460 --> 01:22:44,394 ADVANCED TECHNOLOGIES TEAM, 1925 01:22:44,394 --> 01:22:47,230 ALSO KNOWN AS CATT. 1926 01:22:47,230 --> 01:22:48,598 CATT WAS ESTABLISHD IN 2019, 1927 01:22:48,598 --> 01:22:52,102 THAT IS TO PROMOTE THE 1928 01:22:52,102 --> 01:22:56,139 DIALOGUE, EDUCATION AND INPUT 1929 01:22:56,139 --> 01:22:58,441 AMONGST CBER AND ALSO BETWEEN 1930 01:22:58,441 --> 01:23:01,277 CBER AND TECHNOLOGY DEVELOPERS 1931 01:23:01,277 --> 01:23:02,679 FOR ADVANCED MANUFACTURING 1932 01:23:02,679 --> 01:23:03,013 TECHNOLOGIES. 1933 01:23:03,013 --> 01:23:04,814 THAT IS REALLY TO ENCOURAGE 1934 01:23:04,814 --> 01:23:06,750 THEIR ADOPTION, THEIR 1935 01:23:06,750 --> 01:23:10,120 IMPLEMENTATION. 1936 01:23:10,120 --> 01:23:12,756 AND PEOPLE WHO PARTICIPATE IN 1937 01:23:12,756 --> 01:23:18,561 THE CATT TEAM IS A CROSS 1938 01:23:18,561 --> 01:23:21,798 FUNCTIONAL GROUP CBER 1939 01:23:21,798 --> 01:23:23,667 LEADERSHIP AND SUBJECT MATTER 1940 01:23:23,667 --> 01:23:25,035 EXPERTS COMING FROM OUR REVIEW 1941 01:23:25,035 --> 01:23:25,802 OFFICES. 1942 01:23:25,802 --> 01:23:27,170 SO THE OFFICE REPRESENTED 1943 01:23:27,170 --> 01:23:29,039 INCLUDING OFFICE OF DIRECTOR, 1944 01:23:29,039 --> 01:23:33,009 OFFICE OF VACCINE, OFFICE OF 1945 01:23:33,009 --> 01:23:35,345 BLOOD AND ALSO OFFICE OF 1946 01:23:35,345 --> 01:23:37,280 THERAPEUTIC PRODUCTS, AS WELL 1947 01:23:37,280 --> 01:23:40,050 AS OFFICE OF COMPLIANT AND 1948 01:23:40,050 --> 01:23:44,454 BIOLOGICAL QUALITY GROUP. 1949 01:23:44,454 --> 01:23:47,023 AND THE CATT IS REALLY INTENT 1950 01:23:47,023 --> 01:23:49,526 TO PROVIDE ACCESS TO EARLY 1951 01:23:49,526 --> 01:23:50,093 INTERACTION. 1952 01:23:50,093 --> 01:23:52,862 I WILL LET YOU IN A MOMENT HOW 1953 01:23:52,862 --> 01:23:55,432 EARLY WITH CBER, THAT'S IN THE 1954 01:23:55,432 --> 01:23:56,566 PRE-SUBMISSION SPACE AND 1955 01:23:56,566 --> 01:23:58,268 DISCUSS TECHNICAL AND 1956 01:23:58,268 --> 01:23:59,369 REGULATORY ISSUES. 1957 01:23:59,369 --> 01:24:01,971 SOMETIMES IT COULD BE PERCEIVED 1958 01:24:01,971 --> 01:24:05,475 REGULATORY ISSUES RELATED TO 1959 01:24:05,475 --> 01:24:07,444 THE IMPLEMENTATION OF THESE 1960 01:24:07,444 --> 01:24:17,854 INNOVATIVE TECHNOLOGIES. 1961 01:24:21,191 --> 01:24:23,693 SO WHEN SHOULD YOU COME IN WITH 1962 01:24:23,693 --> 01:24:25,228 A CATT MEETING? 1963 01:24:25,228 --> 01:24:30,300 WHEN IS A CATT MEETING 1964 01:24:30,300 --> 01:24:30,600 APPROPRIATE? 1965 01:24:30,600 --> 01:24:31,468 I'M TRYING TO FOCUS ON THIS 1966 01:24:31,468 --> 01:24:31,835 AREA. 1967 01:24:31,835 --> 01:24:32,535 YES. 1968 01:24:32,535 --> 01:24:34,471 SO HERE IS SOMETHING YOU ARE 1969 01:24:34,471 --> 01:24:35,872 PROBABLY ALL VERY FAMILIAR WITH. 1970 01:24:35,872 --> 01:24:39,109 THAT IS DRUG EVALUATION PROCESS 1971 01:24:39,109 --> 01:24:41,044 USED BY FDA. 1972 01:24:41,044 --> 01:24:46,216 TO EVALUATE THE SAFETY AND 1973 01:24:46,216 --> 01:24:50,453 EFFECTIVENESS OF A DRUG IN 1974 01:24:50,453 --> 01:24:50,720 BIOLOGICS. 1975 01:24:50,720 --> 01:24:54,824 AS YOU CAN SEE FDA OFFERS 1976 01:24:54,824 --> 01:24:56,059 PHASE-APPROPRIATE MEETINGS TO 1977 01:24:56,059 --> 01:24:57,227 PROVIDE BINDING REGULATORY 1978 01:24:57,227 --> 01:24:58,294 ADVICE. 1979 01:24:58,294 --> 01:25:00,396 TO HELP THE MANUFACTURER TO 1980 01:25:00,396 --> 01:25:05,535 MOVE ALONG THE PIPELINE. 1981 01:25:05,535 --> 01:25:06,970 UP TO THE POINT WHERE YOU ARE 1982 01:25:06,970 --> 01:25:08,972 READY TO SUBMIT A COMMERCIAL 1983 01:25:08,972 --> 01:25:16,713 APPLICATION. 1984 01:25:16,713 --> 01:25:18,148 [COUGHS] 1985 01:25:18,148 --> 01:25:21,417 SORRY. 1986 01:25:21,417 --> 01:25:25,388 BUT DURING THAT PROCESS, FDA 1987 01:25:25,388 --> 01:25:27,690 AND ESPECIALLY CBER RECOGNIZE 1988 01:25:27,690 --> 01:25:30,293 THAT FOR SOME INNOVATIVE CLASS 1989 01:25:30,293 --> 01:25:32,362 OF PRODUCTS, THEY REPRESENT 1990 01:25:32,362 --> 01:25:35,865 VERY UNIQUE CHALLENGES, RIGHT? 1991 01:25:35,865 --> 01:25:38,268 SO FOR EXAMPLE, THEY MAY BE 1992 01:25:38,268 --> 01:25:40,570 ASSOCIATED WITH UNKNOWN SAFETY 1993 01:25:40,570 --> 01:25:40,837 PROFILES. 1994 01:25:40,837 --> 01:25:43,273 THEY HAVE VERY COMPLEX 1995 01:25:43,273 --> 01:25:46,242 MANUFACTURING PROCESS AND THEY 1996 01:25:46,242 --> 01:25:49,979 HAVE THE NEED TO USE INNOVATIVE 1997 01:25:49,979 --> 01:25:51,347 MANUFACTURING OR TESTING 1998 01:25:51,347 --> 01:25:55,118 TECHNOLOGIES. 1999 01:25:55,118 --> 01:25:57,453 SO EARLY INPUT AT A PHASE 2000 01:25:57,453 --> 01:25:59,522 BEFORE, PHASE 1 COULD BE VERY 2001 01:25:59,522 --> 01:26:02,425 BENEFICIAL FOR THE 2002 01:26:02,425 --> 01:26:03,026 MANUFACTURERS. 2003 01:26:03,026 --> 01:26:05,361 PRODUCT DEVELOPERS. 2004 01:26:05,361 --> 01:26:15,905 SO THIS IS WHEN CBER INTRODUCED 2005 01:26:27,617 --> 01:26:29,452 INTERACT INITIAL TARGETED 2006 01:26:29,452 --> 01:26:32,422 REGULATORY ADVICE FOR CBER 2007 01:26:32,422 --> 01:26:33,189 PRODUCTS. 2008 01:26:33,189 --> 01:26:34,857 AND THAT MEETING IS DISCUSSED 2009 01:26:34,857 --> 01:26:38,294 IN THE CONTEXT OF A SPECIFIC 2010 01:26:38,294 --> 01:26:39,262 INVESTIGATIVE PRODUCT. 2011 01:26:39,262 --> 01:26:43,466 AND THE TIMING IS USUALLY 2012 01:26:43,466 --> 01:26:45,768 BEFORE YOU HAVE DEVELOPED A 2013 01:26:45,768 --> 01:26:47,270 MANUFACTURING PROCESS FOR YOUR 2014 01:26:47,270 --> 01:26:48,338 CLINICAL STUDIES. 2015 01:26:48,338 --> 01:26:52,875 AND BEFORE YOU HAVE DEVELOPED 2016 01:26:52,875 --> 01:26:55,678 ALSO LET'S SAY A PRELIMINARY 2017 01:26:55,678 --> 01:26:58,514 RELEASE, NOT RELEASE CRITERIA. 2018 01:26:58,514 --> 01:27:08,725 AND ASSAYS. 2019 01:27:11,261 --> 01:27:13,062 RIGHT, THIS IS QUITE EARLY BUT 2020 01:27:13,062 --> 01:27:15,598 YOU SHOULD HAVE PRELIMINARY 2021 01:27:15,598 --> 01:27:16,532 CRITICAL PILOT DATA FOR 2022 01:27:16,532 --> 01:27:17,901 DISCUSSION WITH THE AGENCY. 2023 01:27:17,901 --> 01:27:20,036 SO THIS IS INTERACT MEETING. 2024 01:27:20,036 --> 01:27:22,872 AND THEN WE INTRODUCE A CATT 2025 01:27:22,872 --> 01:27:24,540 MEETING THAT ACTUALLY COMES 2026 01:27:24,540 --> 01:27:26,409 EVEN EARLIER THAN THE INTERACT 2027 01:27:26,409 --> 01:27:27,944 MEETING IN TERMS OF PRODUCT 2028 01:27:27,944 --> 01:27:29,445 DEVELOPMENT PHASE. 2029 01:27:29,445 --> 01:27:32,815 SO THE CATT MEETING IS REALLY A 2030 01:27:32,815 --> 01:27:35,852 WAY TO ENCOURAGE EARLY 2031 01:27:35,852 --> 01:27:37,253 ENGAGEMENT FOR TECHNOLOGY 2032 01:27:37,253 --> 01:27:38,421 DEVELOPERS, OKAY. 2033 01:27:38,421 --> 01:27:41,891 AND ALSO FOR APPLICANTS LOOKING 2034 01:27:41,891 --> 01:27:43,293 TO IMPLEMENT NOVEL TECHNOLOGY 2035 01:27:43,293 --> 01:27:45,862 IN THEIR DEVELOPMENT PROGRAM. 2036 01:27:45,862 --> 01:27:50,867 TO SPEAK TO CBER EARLY AND TO 2037 01:27:50,867 --> 01:27:52,902 DISCUSS THE DIFFERENT POTENTIAL 2038 01:27:52,902 --> 01:27:56,873 TECHNICAL AND ALSO REGULATORY 2039 01:27:56,873 --> 01:28:00,777 CHALLENGES OR HURDLES THAT YOU 2040 01:28:00,777 --> 01:28:02,812 MAY THINK THAT WILL BE DOWN THE 2041 01:28:02,812 --> 01:28:05,415 LINE IN THE IMPLEMENTATION OF 2042 01:28:05,415 --> 01:28:06,249 THE TECHNOLOGY. 2043 01:28:06,249 --> 01:28:09,319 THE PURPOSE OF CATT IS ALSO TO 2044 01:28:09,319 --> 01:28:10,720 BRING AWARENESS TO CBER TO 2045 01:28:10,720 --> 01:28:13,022 UNDERSTAND THE TYPE OF 2046 01:28:13,022 --> 01:28:14,057 INNOVATIVE PRODUCTS OR 2047 01:28:14,057 --> 01:28:18,428 TECHNOLOGY THAT IS COMING OUR 2048 01:28:18,428 --> 01:28:22,598 WAY. 2049 01:28:22,598 --> 01:28:24,667 BUT BECAUSE THE ENGAGEMENT IS 2050 01:28:24,667 --> 01:28:26,069 IN AN EARLY PHASE OF 2051 01:28:26,069 --> 01:28:28,671 DEVELOPMENT, THE REGULATORY 2052 01:28:28,671 --> 01:28:31,908 ADVICE PROVIDED BY CATT AND 2053 01:28:31,908 --> 01:28:32,875 INTERACT ARE CONSIDERED 2054 01:28:32,875 --> 01:28:40,550 NON-BINDING. 2055 01:28:40,550 --> 01:28:43,086 SO WHAT IS THE SCOPE OF CATT 2056 01:28:43,086 --> 01:28:44,554 MEETING, I THINK SOME WE 2057 01:28:44,554 --> 01:28:45,655 MENTIONED EARLIER. 2058 01:28:45,655 --> 01:28:47,056 THE TECHNOLOGY SHOULD BE NOVEL 2059 01:28:47,056 --> 01:28:49,125 AND THEY SHOULD HAVE 2060 01:28:49,125 --> 01:28:51,527 SIGNIFICANT IMPACT ON PRODUCT 2061 01:28:51,527 --> 01:28:52,595 DEVELOPMENT, MANUFACTURING 2062 01:28:52,595 --> 01:28:54,731 PROCESS AND ALSO IN THE 2063 01:28:54,731 --> 01:28:56,833 MANUFACTURING CONTROL 2064 01:28:56,833 --> 01:28:59,802 STRATEGIES. 2065 01:28:59,802 --> 01:29:01,671 THERE CAN BE MANUFACTURING AND 2066 01:29:01,671 --> 01:29:03,072 TESTING METHODS WHICH CBER 2067 01:29:03,072 --> 01:29:03,673 DOESN'T HAVE A LOT OF 2068 01:29:03,673 --> 01:29:04,240 EXPERIENCE. 2069 01:29:04,240 --> 01:29:08,444 SO WE WOULD LIKE TO BE AWARE 2070 01:29:08,444 --> 01:29:09,512 AND UNDERSTAND. 2071 01:29:09,512 --> 01:29:12,548 AS I MENTIONED EARLIER THEY ARE 2072 01:29:12,548 --> 01:29:13,116 NOT FOR PRODUCT-SPECIFIC 2073 01:29:13,116 --> 01:29:13,483 DISCUSSIONS. 2074 01:29:13,483 --> 01:29:14,617 WHEN YOU WANT TO BRING 2075 01:29:14,617 --> 01:29:17,653 DISCUSSION IN THE CONTEXT OF A 2076 01:29:17,653 --> 01:29:21,157 PRODUCT, THEN INTERACT OR 2077 01:29:21,157 --> 01:29:22,358 PRE-IND SUBMISSION MEETINGS MAY 2078 01:29:22,358 --> 01:29:23,292 BE MORE APPROPRIATE. 2079 01:29:23,292 --> 01:29:25,862 THEY ARE NOT MEANT FOR HIGHLY 2080 01:29:25,862 --> 01:29:26,629 TECHNICAL DISCUSSIONS BECAUSE 2081 01:29:26,629 --> 01:29:30,433 OF HOW EARLY THE DEVELOPMENT 2082 01:29:30,433 --> 01:29:33,603 PHASE IS. 2083 01:29:33,603 --> 01:29:35,471 THIS IS WHAT WE REQUEST IN 2084 01:29:35,471 --> 01:29:37,807 TERMS OF WHAT SHOULD BE PART OF 2085 01:29:37,807 --> 01:29:42,678 YOUR MEETING REQUEST PACKAGE. 2086 01:29:42,678 --> 01:29:45,181 WE USUALLY ASK FOR A TWO-PAGER. 2087 01:29:45,181 --> 01:29:47,083 THAT IS TO INCLUDE BACKGROUND 2088 01:29:47,083 --> 01:29:51,654 INFORMATION TO DESCRIBE THE 2089 01:29:51,654 --> 01:29:53,523 TECHNOLOGY AND TO TELL US WHY 2090 01:29:53,523 --> 01:29:56,659 THE TECHNOLOGY AND PRODUCT IS 2091 01:29:56,659 --> 01:29:59,729 NOVEL AND UNIQUE AND WHAT'S THE 2092 01:29:59,729 --> 01:30:05,201 IMPACT ON TECHNOLOGY OR ON A 2093 01:30:05,201 --> 01:30:05,902 PARTICULAR PRODUCT CLASS. 2094 01:30:05,902 --> 01:30:07,937 WE WOULD LIKE A SUMMARY OF 2095 01:30:07,937 --> 01:30:09,305 MANUFACTURING OR DEVELOPMENT 2096 01:30:09,305 --> 01:30:13,076 PLAN, BECAUSE IF YOU DON'T HAVE 2097 01:30:13,076 --> 01:30:14,677 A PLAN THEN MAYBE IT'S NOT 2098 01:30:14,677 --> 01:30:16,779 READY FOR A CATT MEETING 2099 01:30:16,779 --> 01:30:17,947 DISCUSSION YET. 2100 01:30:17,947 --> 01:30:19,782 BUT IF YOUR PLAN IS TO ADVANCE 2101 01:30:19,782 --> 01:30:22,852 YOU MAY WANT TO CONSIDER 2102 01:30:22,852 --> 01:30:23,419 INTERACT OR PRE-SUBMISSION 2103 01:30:23,419 --> 01:30:24,253 MEETING. 2104 01:30:24,253 --> 01:30:25,888 WE ALSO ASK FOR YOU TO INCLUDE 2105 01:30:25,888 --> 01:30:28,458 THE QUESTION REGARDING THE 2106 01:30:28,458 --> 01:30:29,859 REGULATORY, TECHNICAL OR OTHER 2107 01:30:29,859 --> 01:30:34,797 ISSUES THAT YOU SEE POTENTIALLY 2108 01:30:34,797 --> 01:30:36,666 COULD IMPACT THE IMPLEMENTATION 2109 01:30:36,666 --> 01:30:46,909 IN THE FUTURE. 2110 01:30:47,877 --> 01:30:53,916 SO BRIEFLY, THE REVIEW PROCESS. 2111 01:30:53,916 --> 01:30:55,318 THE EVALUATION INITIALLY IS 2112 01:30:55,318 --> 01:31:01,424 TRIAGED BY OUR CATT 2113 01:31:01,424 --> 01:31:02,792 COORDINATORS. 2114 01:31:02,792 --> 01:31:06,496 THEY WILL LOOK AT WHERE THE 2115 01:31:06,496 --> 01:31:08,364 TECHNOLOGY BELONGS TO, OR 2116 01:31:08,364 --> 01:31:09,732 SOMETIMES CROSS DISCIPLINARY 2117 01:31:09,732 --> 01:31:11,868 AND WE WILL ASSIGN TO THE 2118 01:31:11,868 --> 01:31:16,572 DEVELOP -- RELEVANT REVIEW 2119 01:31:16,572 --> 01:31:16,806 OFFICES. 2120 01:31:16,806 --> 01:31:18,674 THEY WILL REVIEW IT AND 2121 01:31:18,674 --> 01:31:20,309 RECOMMEND THE CATT COORDINATOR 2122 01:31:20,309 --> 01:31:22,678 IF THE MEETING SHOULD BE 2123 01:31:22,678 --> 01:31:23,546 GRANTED OR DECLINED. 2124 01:31:23,546 --> 01:31:25,915 AND THEY CAN ALSO SAY, HEY, WE 2125 01:31:25,915 --> 01:31:27,550 ARE REALLY INTERESTED IN THE 2126 01:31:27,550 --> 01:31:28,684 TECHNOLOGY, WE WOULD LIKE TO 2127 01:31:28,684 --> 01:31:30,786 LEARN MORE ABOUT IT. 2128 01:31:30,786 --> 01:31:32,421 SO WE WANT TO HAVE A 2129 01:31:32,421 --> 01:31:34,757 DISCUSSION, WANT TO SEE MORE 2130 01:31:34,757 --> 01:31:36,592 INFORMATION, WE MAY ASK FOR 2131 01:31:36,592 --> 01:31:37,793 ADDITIONAL INFORMATION AND ASK 2132 01:31:37,793 --> 01:31:39,629 FOR THE MEETING SLIDES. 2133 01:31:39,629 --> 01:31:42,165 BUT SOMETIMES THEY MAY SAY HEY, 2134 01:31:42,165 --> 01:31:43,533 THIS IS SOMETHING THAT WE HAVE 2135 01:31:43,533 --> 01:31:46,169 ALREADY SEEN IN A PREVIOUS CATT 2136 01:31:46,169 --> 01:31:47,503 MEETING SO WRITTEN RESPONSE IN 2137 01:31:47,503 --> 01:31:49,138 THIS CASE SHOULD BE SUFFICIENT. 2138 01:31:49,138 --> 01:31:50,306 SOMETIMES WE ALSO RECOMMEND 2139 01:31:50,306 --> 01:31:54,110 THAT MAYBE THERE'S ANOTHER MORE 2140 01:31:54,110 --> 01:31:56,045 APPROPRIATE REGULATORY FORMAT 2141 01:31:56,045 --> 01:32:02,451 OR MEETING TO SUPPORT A 2142 01:32:02,451 --> 01:32:03,319 DISCUSSION. 2143 01:32:03,319 --> 01:32:06,322 SOME EXAMPLES OF TECHNOLOGIES 2144 01:32:06,322 --> 01:32:07,623 DISCUSSED INCLUDE CONTINUOUS 2145 01:32:07,623 --> 01:32:09,859 MANUFACTURING. 2146 01:32:09,859 --> 01:32:10,793 IT'S A RECURRING THEME. 2147 01:32:10,793 --> 01:32:13,829 WE ALSO HAVE SEEN THE 2148 01:32:13,829 --> 01:32:15,665 DEVELOPMENT AND SOME ARE REALLY 2149 01:32:15,665 --> 01:32:19,168 NEAT, OF SOME FULLY-ENCLOSED 2150 01:32:19,168 --> 01:32:20,570 AUTOMATED AND SCALABLE SYSTEMS 2151 01:32:20,570 --> 01:32:23,272 FOR THE MANUFACTURING OF CELL 2152 01:32:23,272 --> 01:32:25,541 THERAPY PRODUCTS. 2153 01:32:25,541 --> 01:32:28,477 AND REALLY IN THE FASHION YOU 2154 01:32:28,477 --> 01:32:29,145 CAN IMAGINE, CONCURRENT 2155 01:32:29,145 --> 01:32:31,981 MANUFACTURING AND HOW THEY CAN 2156 01:32:31,981 --> 01:32:34,050 ENABLE MAYBE DISTRIBUTED 2157 01:32:34,050 --> 01:32:34,684 MANUFACTURING OR POINT-OF-CARE 2158 01:32:34,684 --> 01:32:35,251 MANUFACTURING. 2159 01:32:35,251 --> 01:32:37,587 WE ALSO HAVE PROJECTS WORKED 2160 01:32:37,587 --> 01:32:39,488 OUT, OR MEETING REQUESTS THAT 2161 01:32:39,488 --> 01:32:43,693 WORK ON IMPROVE CELL LINE FOR 2162 01:32:43,693 --> 01:32:45,227 BOTH AAV VECTOR MANUFACTURING 2163 01:32:45,227 --> 01:32:46,128 AND VACCINE DEVELOPMENT. 2164 01:32:46,128 --> 01:32:49,198 WE HAVE SEEN A LOT OF USE OF 2165 01:32:49,198 --> 01:32:51,968 A.I. ESPECIALLY IN THE AREA OF 2166 01:32:51,968 --> 01:32:54,537 ADVANCED IMAGING TECHNOLOGIES. 2167 01:32:54,537 --> 01:32:57,540 AND THAT IS FOR EXAMPLE, VISUAL 2168 01:32:57,540 --> 01:32:58,641 INSPECTION FOR REAL-TIME 2169 01:32:58,641 --> 01:33:01,577 QUALITY ASSESSMENT. 2170 01:33:01,577 --> 01:33:04,180 AND WE ACTUALLY ALSO SEE A LOT 2171 01:33:04,180 --> 01:33:05,615 OF FACILITY DESIGN, 2172 01:33:05,615 --> 01:33:06,515 MULTI-PRODUCT MANUFACTURING TO 2173 01:33:06,515 --> 01:33:10,253 MAKE IT MORE EFFICIENT, THAT WE 2174 01:33:10,253 --> 01:33:11,187 CAN ALLOW CONCURRENT 2175 01:33:11,187 --> 01:33:12,388 MANUFACTURING AND A LOT OF 2176 01:33:12,388 --> 01:33:14,890 TIMES THEY USE MODULAR-TYPE OF 2177 01:33:14,890 --> 01:33:15,658 TECHNOLOGIES. 2178 01:33:15,658 --> 01:33:19,161 WE HAVE SEEN TECHNOLOGY 2179 01:33:19,161 --> 01:33:26,869 SUPPORTING GENE EDITING AND 2180 01:33:26,869 --> 01:33:28,404 ALSO INFORMATIC MENTIONED 2181 01:33:28,404 --> 01:33:31,340 EARLIER IN THE TALK AND 2182 01:33:31,340 --> 01:33:35,177 SCALABLE OF OTHER CELLULAR 2183 01:33:35,177 --> 01:33:36,312 VESSELS ANOTHER INTERESTING 2184 01:33:36,312 --> 01:33:37,747 MODALITY. 2185 01:33:37,747 --> 01:33:40,783 AND HERE I JUST WANT TO MENTION 2186 01:33:40,783 --> 01:33:43,119 THAT CBER ALSO PARTICIPATED IN 2187 01:33:43,119 --> 01:33:48,924 THE DEVELOPMENT AND PUBLICATION 2188 01:33:48,924 --> 01:33:50,960 OF ISHQ13 WHICH IS CONTINUOUS 2189 01:33:50,960 --> 01:33:52,361 MANUFACTURING OF DRUG SUBSTANCE 2190 01:33:52,361 --> 01:33:53,963 AND DRUG PRODUCT. 2191 01:33:53,963 --> 01:33:57,833 AND UNDER THE PURPOSE OF ICHQ13 2192 01:33:57,833 --> 01:34:05,308 IS TO PROVIDE HARMONIZED 2193 01:34:05,308 --> 01:34:06,676 GUIDANCE OF IMPLEMENTATION HOW 2194 01:34:06,676 --> 01:34:09,245 WE ARE USING CONTINUOUS 2195 01:34:09,245 --> 01:34:10,413 MANUFACTURING TECHNOLOGIES TO 2196 01:34:10,413 --> 01:34:13,949 MAKE OUR DRUG SUBSTANCES AND 2197 01:34:13,949 --> 01:34:14,283 DRUG PRODUCTS. 2198 01:34:14,283 --> 01:34:15,584 AND THE SCOPE AT THE MOMENT, I 2199 01:34:15,584 --> 01:34:17,687 THINK THEY APPLY TO CHEMICAL 2200 01:34:17,687 --> 01:34:20,856 ENTITIES AND THERAPEUTIC 2201 01:34:20,856 --> 01:34:21,123 PROTEINS. 2202 01:34:21,123 --> 01:34:23,893 AND ALSO, YOU KNOW, THE 2203 01:34:23,893 --> 01:34:25,594 CONVERSION FROM BATCH 2204 01:34:25,594 --> 01:34:28,364 MANUFACTURING PART OF EXISTING 2205 01:34:28,364 --> 01:34:30,666 TECHNOLOGY OR EXISTING WAY OF 2206 01:34:30,666 --> 01:34:32,301 MANUFACTURING AND CONVERTING 2207 01:34:32,301 --> 01:34:34,603 THAT TO C.M. 2208 01:34:34,603 --> 01:34:36,706 IN OUR EXPERIENCE WE HAVEN'T 2209 01:34:36,706 --> 01:34:38,074 SEEN A CONTINUOUS MANUFACTURING 2210 01:34:38,074 --> 01:34:40,643 APPLIED TO THE PRODUCT THAT 2211 01:34:40,643 --> 01:34:43,079 CBER REGULATES BUT WE BELIEVE, 2212 01:34:43,079 --> 01:34:45,014 YOU KNOW, THE PRINCIPLES SHOULD 2213 01:34:45,014 --> 01:34:45,214 APPLY. 2214 01:34:45,214 --> 01:34:48,617 AND THIS IS WHERE WE ARE HOPING 2215 01:34:48,617 --> 01:34:51,187 ALSO TO LEARN VERY MUCH ABOUT 2216 01:34:51,187 --> 01:34:54,223 C.M. THROUGH A CONTRACT THAT WE 2217 01:34:54,223 --> 01:34:55,691 AWARDED TO M.I.T. THAT I 2218 01:34:55,691 --> 01:35:03,132 MENTIONED EARLIER. 2219 01:35:03,132 --> 01:35:05,735 SO IN SUMMARY WE ARE WORKING 2220 01:35:05,735 --> 01:35:06,902 ACTIVELY TO ACCELERATE THE 2221 01:35:06,902 --> 01:35:09,505 DEVELOPMENT, ALSO ADOPTION OF 2222 01:35:09,505 --> 01:35:10,005 ADVANCED MANUFACTURING 2223 01:35:10,005 --> 01:35:14,176 TECHNOLOGIES. 2224 01:35:14,176 --> 01:35:17,179 AND WE WE ENCOURAGE THE 2225 01:35:17,179 --> 01:35:18,347 DEVELOPMENT OF INNOVATION AND 2226 01:35:18,347 --> 01:35:20,216 WE WANT TO HAVE PEOPLE TO COME 2227 01:35:20,216 --> 01:35:22,017 TO US AND ENGAGE IN DIALOGUE 2228 01:35:22,017 --> 01:35:24,854 EARLY ON. 2229 01:35:24,854 --> 01:35:27,656 I KNOW A LOT OF PEOPLE, I 2230 01:35:27,656 --> 01:35:29,759 JOINED FDA ALMOST 10 YEARS AGO. 2231 01:35:29,759 --> 01:35:32,428 I REALIZE THAT A LOT OF THE 2232 01:35:32,428 --> 01:35:34,096 MANUFACTURERS OUT THERE AND 2233 01:35:34,096 --> 01:35:35,698 TECHNOLOGY DEVELOPER, THEY ARE 2234 01:35:35,698 --> 01:35:38,033 ACTUALLY SCARED OF COMING TO 2235 01:35:38,033 --> 01:35:39,468 FDA AND TALKING TO US. 2236 01:35:39,468 --> 01:35:43,839 BUT WE ARE ACTUALLY, WE ARE 2237 01:35:43,839 --> 01:35:45,040 VERY REASONABLE, I THINK. 2238 01:35:45,040 --> 01:35:46,942 I THINK. 2239 01:35:46,942 --> 01:35:48,978 AND IN A WAY, FLEXIBLE. 2240 01:35:48,978 --> 01:35:50,679 AND THERE'S A REASON WHY VERY 2241 01:35:50,679 --> 01:35:57,386 OFTEN WE SAY OH SOME 2242 01:35:57,386 --> 01:35:58,587 CONSIDERATIONS ARE CASE-BY-CASE. 2243 01:35:58,587 --> 01:35:59,989 BECAUSE WE DO CONSIDER YOUR 2244 01:35:59,989 --> 01:36:02,691 PRODUCT AND HOW YOU MANUFACTURE 2245 01:36:02,691 --> 01:36:04,326 THEM AND PROVIDE TAILORED 2246 01:36:04,326 --> 01:36:06,762 RESPONSE TO HELP YOU TO MOVE 2247 01:36:06,762 --> 01:36:08,397 ALONG THIS PROCESS FROM 2248 01:36:08,397 --> 01:36:09,432 DEVELOPMENT ALL THE WAY TO 2249 01:36:09,432 --> 01:36:15,805 COMMERCIALIZATION. 2250 01:36:15,805 --> 01:36:17,440 AND WE ARE ACTUALLY DOING A LOT 2251 01:36:17,440 --> 01:36:19,775 OF WORK TO COLLABORATE 2252 01:36:19,775 --> 01:36:23,145 INTERNALLY WITH OUR SISTER 2253 01:36:23,145 --> 01:36:26,916 AGENCY, CDER, THEY HAVE 2254 01:36:26,916 --> 01:36:27,616 EMERGING TECHNOLOGY PROGRAM 2255 01:36:27,616 --> 01:36:29,018 THAT WE WORK CLOSELY WITH THEM 2256 01:36:29,018 --> 01:36:32,688 TO DEVELOP A LOT OF REGULATORY 2257 01:36:32,688 --> 01:36:34,056 APPROACHES AND FRAMEWORKS. 2258 01:36:34,056 --> 01:36:36,859 AND WE ALSO ARE WORKING 2259 01:36:36,859 --> 01:36:41,730 COORDINATING WITH OUR 2260 01:36:41,730 --> 01:36:42,665 INTERNATIONAL REGULATORY 2261 01:36:42,665 --> 01:36:45,034 PARTNERS TO PROMOTE GLOBAL 2262 01:36:45,034 --> 01:36:45,701 ADOPTION OF ADVANCED 2263 01:36:45,701 --> 01:36:46,435 TECHNOLOGIES. 2264 01:36:46,435 --> 01:36:49,505 BUT ALSO TO TRY TO LOOK FOR 2265 01:36:49,505 --> 01:36:51,140 WAYS TO HARMONIZE THE 2266 01:36:51,140 --> 01:36:53,242 REGULATORY APPROACHES FOR THESE 2267 01:36:53,242 --> 01:36:54,410 FUTURE PRODUCTS AND 2268 01:36:54,410 --> 01:37:01,951 TECHNOLOGIES. 2269 01:37:01,951 --> 01:37:03,853 BEFORE I END MY PRESENTATION, I 2270 01:37:03,853 --> 01:37:06,188 WANT TO TELL YOU A LITTLE BIT 2271 01:37:06,188 --> 01:37:10,459 ABOUT TWO ACTIVITIES, OR TWO 2272 01:37:10,459 --> 01:37:12,795 OUTREACH ACTIVITIES AT CBER 2273 01:37:12,795 --> 01:37:14,196 THAT IS CURRENTLY ONGOING. 2274 01:37:14,196 --> 01:37:16,732 THE FIRST ONE IS WE ACTUALLY 2275 01:37:16,732 --> 01:37:19,401 PUSHED OUT A PILOT CROWD 2276 01:37:19,401 --> 01:37:20,703 SOURCING ACTIVITY. 2277 01:37:20,703 --> 01:37:22,404 IT JUST STARTED THIS WEEK, I 2278 01:37:22,404 --> 01:37:23,506 BELIEVE. 2279 01:37:23,506 --> 01:37:24,907 IT IS CALLED ENVISIONING THE 2280 01:37:24,907 --> 01:37:27,710 FUTURE FOR BIOLOGICAL PRODUCTS. 2281 01:37:27,710 --> 01:37:32,414 AND THIS IS PART OF CBER'S GOAL 2282 01:37:32,414 --> 01:37:36,252 TO KEEP PACE WITH THE RAPID 2283 01:37:36,252 --> 01:37:39,388 ADVANCEMENT IN MANY OF OUR 2284 01:37:39,388 --> 01:37:41,090 PRODUCT AREAS IN 2285 01:37:41,090 --> 01:37:41,490 BIOMANUFACTURING. 2286 01:37:41,490 --> 01:37:43,592 BUT ALSO TO KEEP PACE WITH THE 2287 01:37:43,592 --> 01:37:46,595 TECHNICAL AND SCIENTIFIC ISSUES 2288 01:37:46,595 --> 01:37:49,031 THAT IMPACTS THE PRODUCTS THAT 2289 01:37:49,031 --> 01:37:50,032 WE REGULATE. 2290 01:37:50,032 --> 01:37:54,103 SO WE WANT TO INVITE OUR 2291 01:37:54,103 --> 01:37:56,672 STAKEHOLDERS AND YOU ARE AMONG 2292 01:37:56,672 --> 01:37:59,241 THEM TO BRING YOUR INSIGHTS AND 2293 01:37:59,241 --> 01:38:02,344 TO GIVE YOUR IDEA AND VISION 2294 01:38:02,344 --> 01:38:05,281 FOR THE FUTURE OF BIOLOGICS. 2295 01:38:05,281 --> 01:38:08,517 WHERE IS THIS GOING? 2296 01:38:08,517 --> 01:38:15,424 WHERE IS THE LANDSCAPE OF 2297 01:38:15,424 --> 01:38:16,592 BIOMANUFACTURING IN THE NEXT 2298 01:38:16,592 --> 01:38:17,560 TEN YEARS. 2299 01:38:17,560 --> 01:38:19,795 SO PLEASE, CHECK IT OUT. 2300 01:38:19,795 --> 01:38:21,163 AND SUBMIT IDEAS. 2301 01:38:21,163 --> 01:38:23,098 BECAUSE IDEAS YOU SUBMIT WILL 2302 01:38:23,098 --> 01:38:25,601 HELP INFORM CBER FOR OUR FUTURE 2303 01:38:25,601 --> 01:38:26,168 PLANNING ACTIVITIES. 2304 01:38:26,168 --> 01:38:29,238 AND IT COULD BE THE PLANNING OF 2305 01:38:29,238 --> 01:38:33,409 WORKSHOPS, HOW TO BUILD UP AND 2306 01:38:33,409 --> 01:38:38,847 CREATING MAYBE MORE INTRA CBER 2307 01:38:38,847 --> 01:38:41,550 INTERNAL RESEARCH INITIATIVES. 2308 01:38:41,550 --> 01:38:45,087 AND OTHER STRATEGIC PLANNING 2309 01:38:45,087 --> 01:38:49,058 ACTIVITIES. 2310 01:38:49,058 --> 01:38:51,126 SO THAT ENDS IN TWO WEEKS. 2311 01:38:51,126 --> 01:38:53,228 SO IF YOU HAVE A GREAT IDEA, 2312 01:38:53,228 --> 01:38:56,532 PLEASE SHARE WITH US. 2313 01:38:56,532 --> 01:38:58,400 ANOTHER ONE IS A REQUEST FOR 2314 01:38:58,400 --> 01:38:59,802 INFORMATION POSTED BY OUR 2315 01:38:59,802 --> 01:39:02,371 OFFICE OF THERAPEUTIC PRODUCT. 2316 01:39:02,371 --> 01:39:03,739 AND THERE, THEY WOULD LIKE TO 2317 01:39:03,739 --> 01:39:05,708 LEARN WHAT YOU THINK ARE THE 2318 01:39:05,708 --> 01:39:07,042 SCIENTIFIC CHALLENGES. 2319 01:39:07,042 --> 01:39:08,911 AND ALSO OPPORTUNITIES TO 2320 01:39:08,911 --> 01:39:13,849 ADVANCE THE DEVELOPMENT OF 2321 01:39:13,849 --> 01:39:17,286 INDIVIDUALIZED CELLULAR AND 2322 01:39:17,286 --> 01:39:18,954 GENE THERAPY PRODUCTS. 2323 01:39:18,954 --> 01:39:21,490 IT COULD INCLUDE MANUFACTURING, 2324 01:39:21,490 --> 01:39:22,057 NON-CLINICAL AND CLINICAL 2325 01:39:22,057 --> 01:39:22,691 DEVELOPMENT. 2326 01:39:22,691 --> 01:39:24,994 HERE IS A LINK, CHECK IT OUT 2327 01:39:24,994 --> 01:39:26,795 AND JUST PROVIDE YOUR PUBLIC 2328 01:39:26,795 --> 01:39:29,431 COMMENTS. 2329 01:39:29,431 --> 01:39:31,967 AND IF THERE IS A FOLLOW-UP 2330 01:39:31,967 --> 01:39:33,369 WORKSHOP, JUST FOLLOW THE 2331 01:39:33,369 --> 01:39:34,570 ANNOUNCEMENTS AND WE WOULD LOVE 2332 01:39:34,570 --> 01:39:37,373 TO HEAR YOUR INPUT. 2333 01:39:37,373 --> 01:39:40,576 SO WITH THAT, I WILL CONCLUDE 2334 01:39:40,576 --> 01:39:42,011 MY PRESENTATION THIS MORNING. 2335 01:39:42,011 --> 01:39:45,714 THANK YOU VERY MUCH FOR YOUR 2336 01:39:45,714 --> 01:39:47,149 ATTENTION AND IF THERE'S ANY 2337 01:39:47,149 --> 01:39:49,218 QUESTION ABOUT THE PROGRAM I 2338 01:39:49,218 --> 01:39:50,486 TALKED ABOUT, JUST FEEL FREE TO 2339 01:39:50,486 --> 01:39:51,587 SEND ME AN EMAIL. 2340 01:39:51,587 --> 01:39:59,285 THANK YOU VERY MUCH. 2341 01:39:59,285 --> 01:40:00,620 ALRIGHT WE ARE 2342 01:40:00,620 --> 01:40:02,021 BACK, BACK IN POWER. 2343 01:40:02,021 --> 01:40:03,456 NOW WE WILL DO SOMETHING A 2344 01:40:03,456 --> 01:40:04,290 LITTLE DIFFERENT. 2345 01:40:04,290 --> 01:40:05,558 WE WILL HAVE A PANEL. 2346 01:40:05,558 --> 01:40:08,928 I THINK IT'S ACTUALLY TOP-NOTCH 2347 01:40:08,928 --> 01:40:10,863 PANEL THAT IS HERE. 2348 01:40:10,863 --> 01:40:21,374 STARTING WITH DAVID BORHANI, 2349 01:40:30,083 --> 01:40:34,721 LILY KOO, SUZIE PUN, RACHELLE 2350 01:40:34,721 --> 01:40:36,956 SALOMON, PAUL SHEEHAN AND ARIEL 2351 01:40:36,956 --> 01:40:37,991 WEINBERGER. 2352 01:40:37,991 --> 01:40:40,193 I WILL ASK THE PANEL TO 2353 01:40:40,193 --> 01:40:41,494 INTRODUCE THEMSELVES. 2354 01:40:41,494 --> 01:40:43,129 PLEASE, YOU CAN START FROM 2355 01:40:43,129 --> 01:40:44,130 DAVID, LET'S GO. 2356 01:40:44,130 --> 01:40:47,066 >> David Borhani: OKAY, DAVID 2357 01:40:47,066 --> 01:40:49,902 BORHANI AT GINGKO BIO WORKS. 2358 01:40:49,902 --> 01:40:51,170 THANKS FOR INVITING US TO THIS 2359 01:40:51,170 --> 01:40:51,771 PANEL. 2360 01:40:51,771 --> 01:40:54,073 SO I AM ON THE BUSINESS 2361 01:40:54,073 --> 01:40:55,241 DEVELOPMENT SIDE, FOCUSED ON 2362 01:40:55,241 --> 01:40:57,644 GOVERNMENT IN THE PHARMA AREA. 2363 01:40:57,644 --> 01:41:01,381 MY TRAINING IS IN DRUG 2364 01:41:01,381 --> 01:41:02,482 DISCOVERY, CHEMISTRY, 2365 01:41:02,482 --> 01:41:04,250 STRUCTURAL BIOLOGY. 2366 01:41:04,250 --> 01:41:05,318 BEFORE JOINING GINGKO ABOUT 2367 01:41:05,318 --> 01:41:09,756 FIVE YEARS AGO, I WAS AT DEHR 2368 01:41:09,756 --> 01:41:12,091 RESEARCH DOING COMPUTATIONAL 2369 01:41:12,091 --> 01:41:15,428 DRUG DISCOVERY ABOUT TEN YEARS, 2370 01:41:15,428 --> 01:41:17,096 BEFORE THAT STRUCTURAL AT 2371 01:41:17,096 --> 01:41:21,901 ABBOTT IN WESTERN MASS, WORKED 2372 01:41:21,901 --> 01:41:23,503 ON IMMUNOLOGY, ONCOLOGY, SMALL 2373 01:41:23,503 --> 01:41:24,671 AND LARGE MOLECULE. 2374 01:41:24,671 --> 01:41:27,006 WAY BACK IN ANCIENT HISTORY, I 2375 01:41:27,006 --> 01:41:29,842 RAN MY OWN LAB, STRUCTURE-BASED 2376 01:41:29,842 --> 01:41:32,412 DRUG DESIGN, TRAINED AT HARVARD 2377 01:41:32,412 --> 01:41:34,514 IN STRUCTURAL BIOLOGY AND IN 2378 01:41:34,514 --> 01:41:40,019 CHEMISTRY AT M.I.T. 2379 01:41:40,019 --> 01:41:43,423 >> Lily Koo: HI, MY NAME IS 2380 01:41:43,423 --> 01:41:45,558 LILY KOO, THE PAST TEN YEARS 2381 01:41:45,558 --> 01:41:49,328 WORKING AT FDA, STARTED AS LEAD 2382 01:41:49,328 --> 01:41:50,730 REVIEWING OF RESPIRATORY 2383 01:41:50,730 --> 01:41:53,299 DEVICES IN THE CENTER FOR 2384 01:41:53,299 --> 01:41:53,533 DEVICES. 2385 01:41:53,533 --> 01:41:55,935 AN THEN I MOVED OVER TO CBER 2386 01:41:55,935 --> 01:41:58,204 AND THERE I WAS WORKING AS A 2387 01:41:58,204 --> 01:42:00,773 REVIEWER, ALSO AS G.M.P. 2388 01:42:00,773 --> 01:42:04,110 INSPECTOR FOR A LOT OF THE 2389 01:42:04,110 --> 01:42:06,112 BIOLOGICAL PRODUCTS. 2390 01:42:06,112 --> 01:42:09,716 MORE RECENTLY I BECOME INVOLVED 2391 01:42:09,716 --> 01:42:12,819 WITH THE PROGRAM CBER PROGRAM 2392 01:42:12,819 --> 01:42:13,720 FOR ADVANCED TECHNOLOGIES. 2393 01:42:13,720 --> 01:42:16,089 BECAUSE I THINK JUST DURING ALL 2394 01:42:16,089 --> 01:42:17,957 THE REVIEW AND INSPECTION I 2395 01:42:17,957 --> 01:42:21,094 STARTED TO SEE THE NEED BUT 2396 01:42:21,094 --> 01:42:23,896 ALSO THE ACTUAL IMPLEMENTATION 2397 01:42:23,896 --> 01:42:26,999 AND GROWTH IN MORE OF THE 2398 01:42:26,999 --> 01:42:27,700 APPLICATION IN ADVANCED 2399 01:42:27,700 --> 01:42:28,901 TECHNOLOGY AND I THINK THIS IS 2400 01:42:28,901 --> 01:42:33,439 THE FUTURE TO COME TO REALLY 2401 01:42:33,439 --> 01:42:35,541 MOVE THE SECTOR, THE 2402 01:42:35,541 --> 01:42:38,044 BIOMANUFACTURING SPACE AND ALSO 2403 01:42:38,044 --> 01:42:38,511 DEVELOPMENT, PRODUCT 2404 01:42:38,511 --> 01:42:41,180 DEVELOPMENT FORWARD IN GIANT 2405 01:42:41,180 --> 01:42:42,915 LEAPS IN THE FUTURE. 2406 01:42:42,915 --> 01:42:45,017 AND PRIOR TO THAT, I WAS 2407 01:42:45,017 --> 01:42:47,153 ACTUALLY AT THE N.I.H. FOR 2408 01:42:47,153 --> 01:42:48,321 ALMOST TEN YEARS. 2409 01:42:48,321 --> 01:42:53,760 I DID MY POST DOC WITH DR. 2410 01:42:53,760 --> 01:42:55,862 ROGER JERMAINE, LOOKING AT CELL 2411 01:42:55,862 --> 01:43:01,334 TRAFFICKING AND DEVELOPING 2412 01:43:01,334 --> 01:43:03,469 TECHNIQUES FOR IMAGING 2413 01:43:03,469 --> 01:43:13,946 TECHNIQUES AND NIAD, WORKED 2414 01:43:14,547 --> 01:43:15,248 WITH RESEARCH TECHNOLOGY AND 2415 01:43:15,248 --> 01:43:17,683 PROGRAM. 2416 01:43:17,683 --> 01:43:19,318 ANYHOW, THIS IS MY BACKGROUND 2417 01:43:19,318 --> 01:43:21,687 AND I HAVE AN ENGINEERING 2418 01:43:21,687 --> 01:43:23,856 BACKGROUND. 2419 01:43:23,856 --> 01:43:25,291 YEP, THIS IS IT. 2420 01:43:25,291 --> 01:43:35,468 THANK YOU. 2421 01:43:40,406 --> 01:43:45,711 >> MY NAME IS SUZIE PUN, DRUG 2422 01:43:45,711 --> 01:43:48,481 DELIVERY APPLICATIONS AND IN 2423 01:43:48,481 --> 01:43:50,149 THE LAST, I GUESS EIGHT YEARS 2424 01:43:50,149 --> 01:43:52,451 OR SO, WE HAVE BEEN DEVELOPING 2425 01:43:52,451 --> 01:43:54,887 MATERIALS FOR CELL 2426 01:43:54,887 --> 01:44:00,293 MANUFACTURING. 2427 01:44:00,293 --> 01:44:04,931 >> GOOD MORNING, MY NAME IS 2428 01:44:04,931 --> 01:44:06,566 RACHELLE SALOMON, PROGRAM 2429 01:44:06,566 --> 01:44:08,434 DIRECTOR AT NCI IN THE DIVISION 2430 01:44:08,434 --> 01:44:09,869 OF CANCER TREATMENT AND 2431 01:44:09,869 --> 01:44:12,171 DIAGNOSIS. 2432 01:44:12,171 --> 01:44:13,573 DCTD. 2433 01:44:13,573 --> 01:44:17,310 WE OVERSEE A CONTRACT AT THE 2434 01:44:17,310 --> 01:44:18,511 FREDERICK NATIONAL LABS, WHICH 2435 01:44:18,511 --> 01:44:21,581 IS FOR THE BIO PHARMACEUTICAL 2436 01:44:21,581 --> 01:44:22,481 DEVELOPMENT PROGRAM. 2437 01:44:22,481 --> 01:44:25,952 AND AT THIS FACILITY WE DO 2438 01:44:25,952 --> 01:44:28,955 G.M.P. MANUFACTURING OF 2439 01:44:28,955 --> 01:44:31,757 BIOLOGICS FOR PHASE I AND PHASE 2440 01:44:31,757 --> 01:44:34,193 II CLINICAL TRIALS. 2441 01:44:34,193 --> 01:44:39,565 I'M EXCITED TO BE HERE TODAY. 2442 01:44:39,565 --> 01:44:41,901 MY BACKGROUND IS AS AN 2443 01:44:41,901 --> 01:44:44,737 IMMUNOLOGIST I'VE BEEN AT NCI 2444 01:44:44,737 --> 01:44:50,109 FOR MANY YEARS. 2445 01:44:50,109 --> 01:44:54,747 BEFORE THAT I WAS AT NIAID AS A 2446 01:44:54,747 --> 01:44:57,383 PROGRAM DIRECTOR FOR INFLUENZA 2447 01:44:57,383 --> 01:44:58,084 VACCINE RESEARCH AND 2448 01:44:58,084 --> 01:44:59,018 DEVELOPMENT. 2449 01:44:59,018 --> 01:45:02,154 AND THAT REALLY CAME OUT OF MY 2450 01:45:02,154 --> 01:45:05,191 LOVE FOR LOOKING AT IMMUNE 2451 01:45:05,191 --> 01:45:09,228 RESPONSES AND THE INTERACTIONS 2452 01:45:09,228 --> 01:45:09,695 WITH VIRUSES. 2453 01:45:09,695 --> 01:45:12,265 I WAS A FELLOW WITH ROBERT 2454 01:45:12,265 --> 01:45:14,634 WEBSTER AT SAINT JUDE 2455 01:45:14,634 --> 01:45:16,469 CHILDREN'S RESEARCH HOSPITAL IN 2456 01:45:16,469 --> 01:45:20,106 MEMPHIS, TENNESSEE. 2457 01:45:20,106 --> 01:45:22,675 AND BEFORE THAT, WHAT SPARKED 2458 01:45:22,675 --> 01:45:27,346 MY INTEREST IN IMMUNOLOGY AND 2459 01:45:27,346 --> 01:45:30,216 UNDERSTANDING THE HOST RESPONSE 2460 01:45:30,216 --> 01:45:33,986 TO DISEASES AND PATHOGENS WAS 2461 01:45:33,986 --> 01:45:37,256 WORKING IN THE LABORATORY OF 2462 01:45:37,256 --> 01:45:38,925 CHRISTINE BYRON AT BROWN 2463 01:45:38,925 --> 01:45:42,728 UNIVERSITY WHERE I DID MY Ph.D.. 2464 01:45:42,728 --> 01:45:46,832 SO I'M REALLY EXCITED TO BE 2465 01:45:46,832 --> 01:45:48,467 HERE AND SHARE SOME THOUGHTS 2466 01:45:48,467 --> 01:45:49,001 WITH THIS PANEL. 2467 01:45:49,001 --> 01:45:52,505 THANK YOU. 2468 01:45:52,505 --> 01:45:56,509 >> Paul Sheehan: HELLO, 2469 01:45:56,509 --> 01:45:58,444 EVERYONE, PAUL SHEEHAN, ARPA-H, 2470 01:45:58,444 --> 01:46:00,947 WE ARE NOW UP TO 12 FOLKS 2471 01:46:00,947 --> 01:46:03,316 TRYING TO COVER EVERYTHING THE 2472 01:46:03,316 --> 01:46:05,017 NIH IS TRYING TO DO, IT'S QUITE 2473 01:46:05,017 --> 01:46:06,686 A STRETCH. 2474 01:46:06,686 --> 01:46:10,823 BEFORE COMING TO DARPA-H, I WAS 2475 01:46:10,823 --> 01:46:13,359 DARPA IN THE BIOTECHNOLOGY 2476 01:46:13,359 --> 01:46:14,760 OFFICE, BTO. 2477 01:46:14,760 --> 01:46:16,629 I'M INTERESTED IN THE 2478 01:46:16,629 --> 01:46:19,198 INTERSECTION OF BIO 2479 01:46:19,198 --> 01:46:21,267 ELECTRONICS, SYNTHETIC BIOLOGY 2480 01:46:21,267 --> 01:46:22,535 AND SYNTHETIC ECOLOGY ALL 2481 01:46:22,535 --> 01:46:24,337 PULLED TOGETHER TO CREATE 2482 01:46:24,337 --> 01:46:28,140 CONTROL SYSTEMS FOR BIOLOGICAL 2483 01:46:28,140 --> 01:46:29,008 NETWORKS. 2484 01:46:29,008 --> 01:46:32,712 >> I'M ARIEL WEINBERGER, CEO 2485 01:46:32,712 --> 01:46:35,314 FOR -- WHAT WE FOCUS ON AS A 2486 01:46:35,314 --> 01:46:36,983 COMPANY IS DEVELOPING NEW 2487 01:46:36,983 --> 01:46:39,819 CLASSES OF RNA NOVEL MOLECULAR 2488 01:46:39,819 --> 01:46:41,654 CIRCUIT, IF YOU WOULD LIKE. 2489 01:46:41,654 --> 01:46:45,958 OR USING SYNTHETIC BIOLOGY TO 2490 01:46:45,958 --> 01:46:47,593 BUILD NUCLEIC ACIDS TO BUILD 2491 01:46:47,593 --> 01:46:50,162 WHERE AND WHEN THERAPEUTIC 2492 01:46:50,162 --> 01:46:51,097 PROTEINS ARE TRANSLATED. 2493 01:46:51,097 --> 01:46:52,965 WE ARE INTERESTED IN PRECISION 2494 01:46:52,965 --> 01:46:55,301 MEDICINES, WHAT WE CALL 2495 01:46:55,301 --> 01:46:56,702 AUTONOMOUS MEDICINES THAT CAN 2496 01:46:56,702 --> 01:46:58,604 DECIDE WHETHER TO MAKE PROTEIN, 2497 01:46:58,604 --> 01:47:00,706 WHETHER IT'S A DISEASE CELL AND 2498 01:47:00,706 --> 01:47:03,943 CONTROL THE OUTPUTS OF OUR 2499 01:47:03,943 --> 01:47:05,111 NUCLEIC ACID TECHNOLOGIES. 2500 01:47:05,111 --> 01:47:07,446 BEFORE THAT, BACKGROUND IS 2501 01:47:07,446 --> 01:47:08,614 EVOLUTIONARY BIOLOGIES BUT 2502 01:47:08,614 --> 01:47:10,149 THESE DAYS SYNTHETIC BIOLOGIES 2503 01:47:10,149 --> 01:47:11,384 AND MUCH OF WHAT YOU GUYS WORK 2504 01:47:11,384 --> 01:47:12,685 ON. 2505 01:47:12,685 --> 01:47:13,586 >> Miljan Simonovic: THAT'S 2506 01:47:13,586 --> 01:47:14,320 GREAT. 2507 01:47:14,320 --> 01:47:15,521 HOW WE WERE THINKING ABOUT 2508 01:47:15,521 --> 01:47:17,189 THIS, I WILL START OFF WITH A 2509 01:47:17,189 --> 01:47:18,724 FEW QUESTIONS. 2510 01:47:18,724 --> 01:47:20,126 I WOULD ENCOURAGE THE AUDIENCE 2511 01:47:20,126 --> 01:47:22,294 TO PARTICIPATE. 2512 01:47:22,294 --> 01:47:23,462 BUT ALSO AS THE DISCUSSION 2513 01:47:23,462 --> 01:47:25,231 GOES, WE WILL SEE HOW IT WILL 2514 01:47:25,231 --> 01:47:26,499 FLOW AND MAYBE ADDITIONAL 2515 01:47:26,499 --> 01:47:36,842 QUESTIONS WILL POP. 2516 01:47:39,945 --> 01:47:41,347 I WILL ASK TWO QUESTIONS, YOU 2517 01:47:41,347 --> 01:47:43,149 CAN PICK WHETHER YOU WANT TO 2518 01:47:43,149 --> 01:47:44,316 ANSWER BOTH OR JUST ONE. 2519 01:47:44,316 --> 01:47:47,153 WHAT ARE THE MAJOR CHALLENGES 2520 01:47:47,153 --> 01:47:48,788 IN BIOMANUFACTURING IN YOUR 2521 01:47:48,788 --> 01:47:49,955 AREA OF RESEARCH, OR WHATEVER 2522 01:47:49,955 --> 01:47:52,525 YOU ARE DOING AS MAYBE A 2523 01:47:52,525 --> 01:47:53,926 PROGRAM MANAGER, WHAT YOU ARE 2524 01:47:53,926 --> 01:47:55,795 COVERING WITHIN YOUR PORTFOLIO, 2525 01:47:55,795 --> 01:47:56,962 AS SOMEBODY RUNNING COMPANY, 2526 01:47:56,962 --> 01:47:58,297 WHAT WOULD BE THE MAIN 2527 01:47:58,297 --> 01:47:59,098 CHALLENGES. 2528 01:47:59,098 --> 01:48:01,934 AND THE SECOND WOULD BE, MAYBE 2529 01:48:01,934 --> 01:48:04,203 THIS IS PERTAINING TO 2530 01:48:04,203 --> 01:48:05,137 RESEARCHERS. 2531 01:48:05,137 --> 01:48:07,039 WHEN DO THEY HAVE TO START 2532 01:48:07,039 --> 01:48:08,174 THINKING ABOUT BIOMANUFACTURING. 2533 01:48:08,174 --> 01:48:09,842 AND WHAT WOULD BE THE 2534 01:48:09,842 --> 01:48:10,776 CONSIDERATIONS AND ISSUES THEY 2535 01:48:10,776 --> 01:48:13,446 HAVE TO TAKE INTO ACCOUNT? 2536 01:48:13,446 --> 01:48:15,514 BECAUSE IT IS DIFFERENT FROM, 2537 01:48:15,514 --> 01:48:17,616 AS I WAS CHATTING WITH DARPA 2538 01:48:17,616 --> 01:48:22,388 PEOPLE, DIFFERENT TO MAKE 2539 01:48:22,388 --> 01:48:24,290 POLYMERASE FOR TRANSCRIBING RNA 2540 01:48:24,290 --> 01:48:26,692 THAN FOR A LARGE SCALE 2541 01:48:26,692 --> 01:48:28,661 BIOMANUFACTURING PROGRAM. 2542 01:48:28,661 --> 01:48:30,763 SO, IF WE CAN START FROM ARIEL, 2543 01:48:30,763 --> 01:48:31,931 AND THE OTHER WAY AROUND. 2544 01:48:31,931 --> 01:48:34,967 THANK YOU. 2545 01:48:34,967 --> 01:48:36,602 >> ARIEL WEINBERGER: ABSOLUTELY. 2546 01:48:36,602 --> 01:48:38,137 THOSE QUESTIONS ARE KIND OF 2547 01:48:38,137 --> 01:48:38,737 INTERTWINED. 2548 01:48:38,737 --> 01:48:41,073 I WILL TRY TO ANSWER BOTH 2549 01:48:41,073 --> 01:48:42,508 TOGETHER, TO YOUR SECOND 2550 01:48:42,508 --> 01:48:43,676 QUESTION, CERTAINLY RUNNING A 2551 01:48:43,676 --> 01:48:45,744 COMPANY, THE GOAL IS TO MAKE 2552 01:48:45,744 --> 01:48:47,847 PRODUCTS, THAT MEANS TO GO 2553 01:48:47,847 --> 01:48:50,583 THROUGH FDA, THE FULL MONTY, 2554 01:48:50,583 --> 01:48:52,051 THE FULL GAMUT ON THAT. 2555 01:48:52,051 --> 01:48:56,956 IF WE RR ARE NOT ABLE TO 2556 01:48:56,956 --> 01:48:59,024 MANUFACTURE, OR THAT PRODUCT 2557 01:48:59,024 --> 01:49:00,693 SND AMENABLE TO SCAPABILITY, 2558 01:49:00,693 --> 01:49:02,128 IT'S PROBABLY A POOR INVESTMENT 2559 01:49:02,128 --> 01:49:02,895 FOR US. 2560 01:49:02,895 --> 01:49:04,730 AS A COMPANY IT'S PART AND 2561 01:49:04,730 --> 01:49:06,866 PARCEL WHAT YOU START WITH AT 2562 01:49:06,866 --> 01:49:09,001 THE OUTSET, AT LEAST A 2563 01:49:09,001 --> 01:49:11,036 PRINCIPLE VIEW WHETHER OR NOT 2564 01:49:11,036 --> 01:49:12,037 SOMETHING IS MANUFACTURERABLE 2565 01:49:12,037 --> 01:49:14,573 IN A WAY THAT IS AMENABLE TO 2566 01:49:14,573 --> 01:49:17,877 CLINICAL STUDIES AND ULTIMATELY 2567 01:49:17,877 --> 01:49:18,811 TO COMMERCIAL USE. 2568 01:49:18,811 --> 01:49:21,847 IN TERMS OF YOUR FIRST 2569 01:49:21,847 --> 01:49:23,282 QUESTION, OUR PARTICULAR AREA, 2570 01:49:23,282 --> 01:49:24,683 THE CHALLENGES THAT EMERGE IN 2571 01:49:24,683 --> 01:49:28,721 THE AREA WE WORK IN, OUR 2572 01:49:28,721 --> 01:49:36,662 COMPANY FOCUSES REALLY ON 2573 01:49:36,662 --> 01:49:38,531 NUCLEIC ACID THERAPEUTICS, THEY 2574 01:49:38,531 --> 01:49:39,832 ARE PROTEIN COATING. 2575 01:49:39,832 --> 01:49:42,301 WHEN YOU GET INTO THE DOMAIN OF 2576 01:49:42,301 --> 01:49:44,170 THERAPEUTICS AS OPPOSED TO 2577 01:49:44,170 --> 01:49:45,938 VACCINES, OBVIOUSLY THERE'S 2578 01:49:45,938 --> 01:49:49,375 BEEN A LOT OF WORK AND SUCCESS 2579 01:49:49,375 --> 01:49:54,947 IN VACCINES AND NUCLEIC 2580 01:49:54,947 --> 01:49:56,048 VACCINES. 2581 01:49:56,048 --> 01:49:58,217 THE SUCCESS IN THE DOSES OF 2582 01:49:58,217 --> 01:49:59,752 HUNDREDS OF MILLIONS OF 2583 01:49:59,752 --> 01:50:01,220 PATIENTS. 2584 01:50:01,220 --> 01:50:04,990 THERE ARE NO APPROVED mRNA 2585 01:50:04,990 --> 01:50:05,324 THERAPEUTICS. 2586 01:50:05,324 --> 01:50:08,460 THERE ARE A LOT OF INNATE OR 2587 01:50:08,460 --> 01:50:09,662 INTRINSIC CHALLENGES THAT 2588 01:50:09,662 --> 01:50:12,464 EMERGE IN THE THERAPEUTIC SPACE 2589 01:50:12,464 --> 01:50:14,200 THAT AREN'T OF THE SAME 2590 01:50:14,200 --> 01:50:15,367 MAGNITUDE IN TERMS OF THE 2591 01:50:15,367 --> 01:50:17,703 PROBLEM IN THE VACCINE SPACE. 2592 01:50:17,703 --> 01:50:19,772 A FEW OF THEM, AS MENTIONED 2593 01:50:19,772 --> 01:50:21,640 YESTERDAY YOU HAVE TO GIVE A 2594 01:50:21,640 --> 01:50:23,976 MUCH HIGHER DOSE WHEN GIVING 2595 01:50:23,976 --> 01:50:25,844 THERAPEUTICS, IT'S ABOUT 1,000 2596 01:50:25,844 --> 01:50:29,515 X HIGHER IN DOSE FOR 2597 01:50:29,515 --> 01:50:30,216 THERAPEUTIC VERSUS VACCINE. 2598 01:50:30,216 --> 01:50:32,585 IF YOU ARE JUST LOOKING AT A 2599 01:50:32,585 --> 01:50:34,620 META REVIEW OF THE LITERATURE. 2600 01:50:34,620 --> 01:50:37,523 THE IMMUNE SYSTEM FOR VACCINE 2601 01:50:37,523 --> 01:50:39,091 IS DOSE AMPLIFIER. 2602 01:50:39,091 --> 01:50:41,160 ANTIGEN YOU GET A LOT OF IMMUNE 2603 01:50:41,160 --> 01:50:42,094 CELLS BEING MADE. 2604 01:50:42,094 --> 01:50:43,862 YOU DON'T HAVE THAT FOR A 2605 01:50:43,862 --> 01:50:45,264 THERAPEUTIC WHERE YOU MAY HAVE 2606 01:50:45,264 --> 01:50:47,199 TO TREAT EVERY DISEASED CELL. 2607 01:50:47,199 --> 01:50:49,435 YOU HAVE ISSUES OF STABILITY, 2608 01:50:49,435 --> 01:50:52,705 YOU NEED THE THERAPEUTIC TO 2609 01:50:52,705 --> 01:50:55,074 STICK AROUND, WITH SNEENG 2610 01:50:55,074 --> 01:50:57,176 VACCINE YOU HAVE IMMUNE MEMORY. 2611 01:50:57,176 --> 01:51:02,014 IF YOU ARE TAKING LMP TO A 2612 01:51:02,014 --> 01:51:04,316 CELL, YOU CAN IMAGINE THE 2613 01:51:04,316 --> 01:51:05,351 DANGER SIGNAL THAT SENDS TO A 2614 01:51:05,351 --> 01:51:06,418 CELL. 2615 01:51:06,418 --> 01:51:07,553 THE CELL KNOWS WHAT THAT LOOKS 2616 01:51:07,553 --> 01:51:08,954 LIKE. 2617 01:51:08,954 --> 01:51:15,261 TO AN EXTENT IT'S REACTIVEGENIC. 2618 01:51:15,261 --> 01:51:18,631 FOR VACCINE THAT 12-HOUR EFFECT 2619 01:51:18,631 --> 01:51:21,000 WE FEEL AFTER WE GET VACCINES 2620 01:51:21,000 --> 01:51:23,168 IS A SIGN YOUR IMMUNE SYSTEM IS 2621 01:51:23,168 --> 01:51:26,839 KICKING IN. 2622 01:51:26,839 --> 01:51:28,774 YOU ARE KICKING OUT THE 2623 01:51:28,774 --> 01:51:29,875 THERAPEUTIC PAYLOAD AND YOU 2624 01:51:29,875 --> 01:51:31,977 AREN'T HAVING THE DESIRED 2625 01:51:31,977 --> 01:51:34,280 EFFECT BECAUSE DELIVERY IS CUT 2626 01:51:34,280 --> 01:51:34,446 OFF. 2627 01:51:34,446 --> 01:51:37,383 YOU HAVE THESE INTRINSIC 2628 01:51:37,383 --> 01:51:39,251 CHALLENGES IN THE THERAPEUTIC 2629 01:51:39,251 --> 01:51:43,289 SPACE YOU DON'T HAVE? 2630 01:51:43,289 --> 01:51:47,660 -- IN THE VACCINE SPACE. 2631 01:51:47,660 --> 01:51:50,362 YOU COULD EASILY MODIFY OR WE 2632 01:51:50,362 --> 01:51:51,030 NOW SCIENCE FICTIONFULLY, 2633 01:51:51,030 --> 01:51:57,369 THERE'S SCIENTIFICALLY, YOU 2634 01:51:57,369 --> 01:51:59,905 CAN'T DO WITH mRNAS WHERE 2635 01:51:59,905 --> 01:52:02,808 CHEMICALLY MANUFACTURING A 2636 01:52:02,808 --> 01:52:05,878 MULTI-KB mRNA OR PROTEIN-CODING 2637 01:52:05,878 --> 01:52:07,713 SEQUENCE IS A REAL CHALLENGE. 2638 01:52:07,713 --> 01:52:08,881 WE'RE NOT THERE. 2639 01:52:08,881 --> 01:52:14,186 SO NOW YOU HAVE TO RELY ON T7 2640 01:52:14,186 --> 01:52:16,021 PROTEASE, IT COULD INCORPORATE, 2641 01:52:16,021 --> 01:52:18,157 AND EVEN IF YOU COULD FIND A 2642 01:52:18,157 --> 01:52:20,893 WAY TO CHEMICALLY MODIFY THESE 2643 01:52:20,893 --> 01:52:28,434 LONG RNA'S, IT'S NOT CLEAR YOU 2644 01:52:28,434 --> 01:52:30,035 COULD TRANSCRIBE. 2645 01:52:30,035 --> 01:52:32,604 IT COULD BE LESS DEGRADABLE AND 2646 01:52:32,604 --> 01:52:34,940 IT WOULD BE LESS TRANSLATABLE. 2647 01:52:34,940 --> 01:52:38,444 SO THERE ARE A LOT OF PROBLEMS. 2648 01:52:38,444 --> 01:52:40,512 >> Miljan Simonovic: OKAY. 2649 01:52:40,512 --> 01:52:44,917 YOU SHOULD FOLLOW-UP ON THIS. 2650 01:52:44,917 --> 01:52:50,189 >> I THINK THAT'S EXHAUSTIVE. 2651 01:52:50,189 --> 01:52:52,491 OUR RESPONSE TO RPH THEY SHOULD 2652 01:52:52,491 --> 01:52:55,794 COME TO US AND WHEN THEY SHOULD 2653 01:52:55,794 --> 01:52:56,962 THINK ABOUT MANUFACTURING, MY 2654 01:52:56,962 --> 01:53:01,033 RESPONSE IS YOU HAVEN'T ALREADY 2655 01:53:01,033 --> 01:53:02,468 THOUGHT OF MANUFACTURING. 2656 01:53:02,468 --> 01:53:03,602 WE ARE HIGHLY FOCUSED ON 2657 01:53:03,602 --> 01:53:05,037 TRANSLATION. 2658 01:53:05,037 --> 01:53:09,541 WE AREN'T REALLY THERE FOR 2659 01:53:09,541 --> 01:53:12,845 DISCOVERY YOU NEED AN INITIAL 2660 01:53:12,845 --> 01:53:14,012 STRATEGY, EVEN EFFORT THAT'S 2661 01:53:14,012 --> 01:53:15,748 ARE A LITTLE BIT MORE 2662 01:53:15,748 --> 01:53:17,783 EXPLORATORY. 2663 01:53:17,783 --> 01:53:19,385 I WILL MENTION, THEY ARE TRYING 2664 01:53:19,385 --> 01:53:22,388 TO PRINT A HUMAN HEART IN UNDER 2665 01:53:22,388 --> 01:53:24,490 AN HOUR, THAT REQUIRES BILLIONS 2666 01:53:24,490 --> 01:53:25,891 OF CELLS, MASSIVE 2667 01:53:25,891 --> 01:53:27,526 DIFFERENTIATION AND SCALE-UP. 2668 01:53:27,526 --> 01:53:29,862 I THINK ALWAYS SCALE UP, HOW IS 2669 01:53:29,862 --> 01:53:31,964 THIS GOING TO MAKE ITS WAY 2670 01:53:31,964 --> 01:53:35,734 THROUGH, HOW IS IT GOING TO BE 2671 01:53:35,734 --> 01:53:36,835 MUTUALLY VIABLE. 2672 01:53:36,835 --> 01:53:40,706 WE HAVE LOTS OF DIFFERENT NEEDS. 2673 01:53:40,706 --> 01:53:43,008 IMMEDIATE NEED RIGHT NOW FOR 2674 01:53:43,008 --> 01:53:46,011 SOME PROGRAMS, HOW DO WE 2675 01:53:46,011 --> 01:53:47,446 EFFICIENTLY GENERATE CELLS WITH 2676 01:53:47,446 --> 01:53:50,015 THE MINIMUM OF ENGINEERING. 2677 01:53:50,015 --> 01:53:52,017 COULD RESPOND TO EXTERNAL STIM 2678 01:53:52,017 --> 01:53:55,654 LIE STIMULI. 2679 01:53:55,654 --> 01:53:58,457 WHAT SIGNALS CAN WE PUT IN TO 2680 01:53:58,457 --> 01:54:00,092 GENERATE EFFECTIVE PRODUCTION 2681 01:54:00,092 --> 01:54:04,129 IN VIVO, AS I WILL EXPLAIN 2682 01:54:04,129 --> 01:54:06,365 LATER. 2683 01:54:06,365 --> 01:54:08,133 >> I THINK PAUL'S RESPONSE WAS 2684 01:54:08,133 --> 01:54:09,568 EXCELLENT. 2685 01:54:09,568 --> 01:54:11,036 IT'S NEVER TOO EARLY TO START 2686 01:54:11,036 --> 01:54:13,872 THINKING ABOUT THE TRANSLATION 2687 01:54:13,872 --> 01:54:16,408 TO BIOMANUFACTURING. 2688 01:54:16,408 --> 01:54:20,546 I THINK LILY SHOWED THERE'S 2689 01:54:20,546 --> 01:54:22,414 EARLY, THE FDA UNDERSTANDS THIS 2690 01:54:22,414 --> 01:54:24,249 AND THERE'S EARLIER WAYS TO 2691 01:54:24,249 --> 01:54:25,884 INTERACT AND START HAVING THOSE 2692 01:54:25,884 --> 01:54:26,819 DISCUSSIONS WITH THEM. 2693 01:54:26,819 --> 01:54:30,022 BUT AGAIN, YOU KNOW, THIS IS A 2694 01:54:30,022 --> 01:54:31,190 SPACE WHERE YOU ARE WORKING 2695 01:54:31,190 --> 01:54:32,391 WITH THE END IN MIND. 2696 01:54:32,391 --> 01:54:36,829 THIS IS AN ENGINEERING TYPE OF 2697 01:54:36,829 --> 01:54:39,131 PARADIGM SO IT'S VERY DIFFERENT 2698 01:54:39,131 --> 01:54:41,767 THAN MAYBE ACADEMIC RESEARCHERS 2699 01:54:41,767 --> 01:54:48,874 ARE DOING AT THE BENCH. 2700 01:54:48,874 --> 01:54:51,610 WE PUT HIS TAGS ON A PROTEIN TO 2701 01:54:51,610 --> 01:54:53,512 HELP EASE WITH PURIFICATION. 2702 01:54:53,512 --> 01:54:55,380 BUT YOU CAN'T DO THAT, YOU'RE 2703 01:54:55,380 --> 01:54:57,950 NOT GOING TO PUT A PROTEIN THAT 2704 01:54:57,950 --> 01:54:59,818 DOESN'T NEED TO BE IN A PATIENT 2705 01:54:59,818 --> 01:55:00,752 IN A PATIENT. 2706 01:55:00,752 --> 01:55:03,655 SO START WITH THE END IN MIND. 2707 01:55:03,655 --> 01:55:07,025 ALWAYS THINK HOW DO I GET THIS 2708 01:55:07,025 --> 01:55:08,260 TO THE CLINIC. 2709 01:55:08,260 --> 01:55:18,704 AND THAT'S VERY IMPORTANT. 2710 01:55:20,172 --> 01:55:21,840 SOME CHALLENGES THAT OCCUR WITH 2711 01:55:21,840 --> 01:55:23,141 CELL MANUFACTURING, WE HAVE HAD 2712 01:55:23,141 --> 01:55:26,011 TO REALLY CHANGE OUR 2713 01:55:26,011 --> 01:55:29,147 UNDERSTANDING OF HOW TO OPERATE 2714 01:55:29,147 --> 01:55:39,525 AS A BIO MANUFACTURER. 2715 01:55:42,227 --> 01:55:44,062 WHEN THE DRUG GOES OFF IN 2716 01:55:44,062 --> 01:55:47,566 CLINICAL TRIALS FOR YEARS. 2717 01:55:47,566 --> 01:55:51,670 BUT IN THE PARADIGM YOU ARE 2718 01:55:51,670 --> 01:55:53,071 MANUFACTURING, GENETICALLY 2719 01:55:53,071 --> 01:55:54,473 ENGINEERING PATIENT CELL TO 2720 01:55:54,473 --> 01:55:57,609 GIVE BACK TO THAT PATIENT, IT'S 2721 01:55:57,609 --> 01:55:57,843 COMPLEX. 2722 01:55:57,843 --> 01:56:00,178 THERE ARE SO MANY MANY 2723 01:56:00,178 --> 01:56:02,180 LOGISTICAL CHALLENGES BEYOND 2724 01:56:02,180 --> 01:56:04,216 THE SCIENTIFIC AND SYNTHETIC 2725 01:56:04,216 --> 01:56:05,250 BIOLOGY CHALLENGES. 2726 01:56:05,250 --> 01:56:07,185 THERE'S THINGS THAT WE DIDN'T 2727 01:56:07,185 --> 01:56:09,488 FULLY APPRECIATE. 2728 01:56:09,488 --> 01:56:11,356 WHERE THE PATIENTS THEMSELVES 2729 01:56:11,356 --> 01:56:13,525 MAY NOT BE IN THE BEST OF 2730 01:56:13,525 --> 01:56:15,527 HEALTH AND THEY ARE JOINING 2731 01:56:15,527 --> 01:56:16,662 THIS CLINICAL TRIAL. 2732 01:56:16,662 --> 01:56:19,097 SO THEY NEED THIS THERAPY AS 2733 01:56:19,097 --> 01:56:23,435 SOON AS POSSIBLE. 2734 01:56:23,435 --> 01:56:25,737 SO YOU ARE SCHEDULING YOUR 2735 01:56:25,737 --> 01:56:28,574 MANUFACTURING TO FIT IN WITH 2736 01:56:28,574 --> 01:56:30,442 ALSO THE CLINICAL LOGISTICS. 2737 01:56:30,442 --> 01:56:32,044 WHEN CAN THEY GET THE PATIENT 2738 01:56:32,044 --> 01:56:33,011 THERE? 2739 01:56:33,011 --> 01:56:37,683 WHEN CAN THEY GET THE BLOOD AND 2740 01:56:37,683 --> 01:56:38,584 TRANSPORTATION LOGISTICS, BUT 2741 01:56:38,584 --> 01:56:42,454 ALSO IN ORDER TO ACCEPT THE 2742 01:56:42,454 --> 01:56:44,089 CELL THERAPY, MANY OF THE 2743 01:56:44,089 --> 01:56:48,126 PATIENTS HAVE TO BE LYMPHO 2744 01:56:48,126 --> 01:56:50,228 DEPLETED OR SOMETHING LIKE THAT. 2745 01:56:50,228 --> 01:56:52,631 BUT THEN THAT'S ANOTHER RISK. 2746 01:56:52,631 --> 01:56:55,500 WE DON'T WANT AN ALREADY-SICK 2747 01:56:55,500 --> 01:56:58,270 PATIENT TO BE LYMPHO DEPLETED 2748 01:56:58,270 --> 01:57:04,009 IF WE AREN'T ABLE TO 2749 01:57:04,009 --> 01:57:04,676 SUCCESSFULLY DELIVER THE 2750 01:57:04,676 --> 01:57:05,210 PRODUCT. 2751 01:57:05,210 --> 01:57:09,214 THERE ARE A LOT OF COMPLEXITIES 2752 01:57:09,214 --> 01:57:10,248 WE ARE DEALING WITH. 2753 01:57:10,248 --> 01:57:11,617 BUT THESE ARE CHALLENGES WE CAN 2754 01:57:11,617 --> 01:57:12,684 DEAL WITH. 2755 01:57:12,684 --> 01:57:15,020 LIKE HOW CAN WE GET ASSAYS THAT 2756 01:57:15,020 --> 01:57:18,523 CAN GIVE US THE RESULTS MORE 2757 01:57:18,523 --> 01:57:24,162 QUICKLY FOR STER RILLITY. 2758 01:57:24,162 --> 01:57:26,598 OTHER THINGS THAT CAN HELP WITH 2759 01:57:26,598 --> 01:57:29,635 RAPID RELEASE, WE WERE IN 2760 01:57:29,635 --> 01:57:31,003 PARADIGMS WE DIDN'T HAVE TO 2761 01:57:31,003 --> 01:57:32,204 RESPOND SO QUICKLY. 2762 01:57:32,204 --> 01:57:33,538 HOW DOES THAT WORK OUT. 2763 01:57:33,538 --> 01:57:35,040 I THINK THAT WENT WELL WITH THE 2764 01:57:35,040 --> 01:57:36,274 DISCUSSION THIS MORNING FROM 2765 01:57:36,274 --> 01:57:37,109 THE DoD. 2766 01:57:37,109 --> 01:57:39,444 IT'S JUST A DIFFERENT PARADIGM 2767 01:57:39,444 --> 01:57:41,279 OF MANUFACTURING TO CONSIDER. 2768 01:57:41,279 --> 01:57:50,756 SO, THANK YOU. 2769 01:57:50,756 --> 01:57:55,794 >> I WILL FOLLOW-UP ON RACHELLE. 2770 01:57:55,794 --> 01:57:56,328 ESPECIALLY COMPLEXITY OF 2771 01:57:56,328 --> 01:57:56,962 MANUFACTURING. 2772 01:57:56,962 --> 01:57:58,830 TWO THINGS WE THINK A LOT 2773 01:57:58,830 --> 01:58:01,199 ABOUT, IS FIRST HOW CAN WE TRY 2774 01:58:01,199 --> 01:58:02,834 TO TRANSFORM CELL MANUFACTURING 2775 01:58:02,834 --> 01:58:04,736 INTO A CLOSED SYSTEM. 2776 01:58:04,736 --> 01:58:06,838 SO THAT'S A LOT OF WHAT, I 2777 01:58:06,838 --> 01:58:08,006 THINK THE DARPA PEOPLE WERE 2778 01:58:08,006 --> 01:58:10,609 TALKING ABOUT FOR THE NUCLEIC 2779 01:58:10,609 --> 01:58:12,010 ACID AND PROTEINOTHERAPIES SO 2780 01:58:12,010 --> 01:58:14,212 CAN WE DO THAT ALSO FOR 2781 01:58:14,212 --> 01:58:15,547 CELL-BASED THERAPIES. 2782 01:58:15,547 --> 01:58:16,848 REDUCING THE RISK OF 2783 01:58:16,848 --> 01:58:17,449 CONTAMINATION. 2784 01:58:17,449 --> 01:58:19,985 AND THEN THE OTHER ONE IS CAN 2785 01:58:19,985 --> 01:58:23,488 WE SWITCH TO NOT HAVING TO USE 2786 01:58:23,488 --> 01:58:25,157 BIOLOGICS TO MAKE THIS BIOLOGIC. 2787 01:58:25,157 --> 01:58:27,059 AS YOU KNOW WITH CELL THERAPIES 2788 01:58:27,059 --> 01:58:30,562 IT RELIES A LOT OF ANTIBODIES, 2789 01:58:30,562 --> 01:58:32,864 VIRUSES, IT'S A VERY COSTLY 2790 01:58:32,864 --> 01:58:35,200 PROJECT BECAUSE YOU ARE USING 2791 01:58:35,200 --> 01:58:36,668 COSTLY REAGENTS JUST TO 2792 01:58:36,668 --> 01:58:37,502 MANUFACTURE. 2793 01:58:37,502 --> 01:58:39,805 WE ARE TRYING TO THINK OF WAYS 2794 01:58:39,805 --> 01:58:42,407 TO ELIMINATE OR REPLACE 2795 01:58:42,407 --> 01:58:44,476 BIOLOGICS WITH SYNTHETIC, 2796 01:58:44,476 --> 01:58:47,446 CHEAPER MATERIALS. 2797 01:58:47,446 --> 01:58:49,715 >> Lily Koo: GREAT POINTS AS 2798 01:58:49,715 --> 01:58:51,983 ALREADY MENTIONED BY PREVIOUS 2799 01:58:51,983 --> 01:58:52,250 PANELISTS. 2800 01:58:52,250 --> 01:58:55,687 I JUST WANT TO ADD, I THINK, I 2801 01:58:55,687 --> 01:58:57,322 COMPLETELY AGREE THAT WHEN YOU 2802 01:58:57,322 --> 01:58:58,990 START DEVELOPING A PRODUCT -- 2803 01:58:58,990 --> 01:59:00,425 >> Miljan Simonovic: CLOSER TO 2804 01:59:00,425 --> 01:59:01,326 THE MIC. 2805 01:59:01,326 --> 01:59:03,829 >> Mike 2806 01:59:07,099 --> 01:59:08,033 >> Lily Koo: SORRY, IS THAT 2807 01:59:08,033 --> 01:59:10,535 BETTER? 2808 01:59:10,535 --> 01:59:11,470 RACHELLE MENTIONED YOU SHOULD 2809 01:59:11,470 --> 01:59:13,538 HAVE THE END IN MIND. 2810 01:59:13,538 --> 01:59:14,239 CONSIDERATION AS MENTIONED 2811 01:59:14,239 --> 01:59:16,208 EARLIER IN THE TALK AS WELL, 2812 01:59:16,208 --> 01:59:19,244 SCALING UP AND ALSO YOUR CELL 2813 01:59:19,244 --> 01:59:21,947 BANK, HOW DO YOU RENEW A CELL 2814 01:59:21,947 --> 01:59:23,515 BANK? 2815 01:59:23,515 --> 01:59:27,552 WHEN IT'S DEPLETED IT'S GOING 2816 01:59:27,552 --> 01:59:28,954 TO BE, IF YOU DON'T HAVE 2817 01:59:28,954 --> 01:59:34,226 SOMETHING AS A BACK UP OR 2818 01:59:34,226 --> 01:59:35,861 RENEWABLE SOURCE THAT WILL 2819 01:59:35,861 --> 01:59:40,766 PROVIDE CHALLENGES WHEN THERE 2820 01:59:40,766 --> 01:59:41,933 ARE COMPARABILITY STUDIES AS 2821 01:59:41,933 --> 01:59:44,136 YOU MOVE FORWARD IN A CLINICAL 2822 01:59:44,136 --> 01:59:46,638 BASIS. 2823 01:59:46,638 --> 01:59:49,441 THINK OF ANALYTICAL DEVELOPMENT 2824 01:59:49,441 --> 01:59:51,643 THAT IS IN PACE WITH YOUR 2825 01:59:51,643 --> 02:00:02,020 PRODUCT UNDERSTANDING. 2826 02:00:07,425 --> 02:00:08,994 AS YOU MOVE FORWARD IN A 2827 02:00:08,994 --> 02:00:11,129 PROCESS YOU MAY REALIZE SOME OF 2828 02:00:11,129 --> 02:00:13,331 THE ASSAYS AREN'T THE BEST 2829 02:00:13,331 --> 02:00:14,699 SUITABLE, RIGHT? 2830 02:00:14,699 --> 02:00:16,001 AND SOME OTHER CONSIDERATION IS 2831 02:00:16,001 --> 02:00:18,136 REALLY HOW TO MINIMIZE THE NEED 2832 02:00:18,136 --> 02:00:23,008 TO CHANGE YOUR MANUFACTURING 2833 02:00:23,008 --> 02:00:24,242 PROCESS FROM EARLY ONTO THE 2834 02:00:24,242 --> 02:00:25,377 LATER PHASES. 2835 02:00:25,377 --> 02:00:26,745 EVERY CHANGE YOU HAVE TO 2836 02:00:26,745 --> 02:00:27,879 DEMONSTRATE THAT A PROCESS 2837 02:00:27,879 --> 02:00:31,149 CHANGE HAS NO IMPACT ON PRODUCT 2838 02:00:31,149 --> 02:00:33,251 QUALITY AND EFFECTIVENESS. 2839 02:00:33,251 --> 02:00:35,587 ANOTHER CONSIDERATION IS 2840 02:00:35,587 --> 02:00:38,223 ESTABLISHING IMPURITY PROFILE. 2841 02:00:38,223 --> 02:00:40,559 WHICH CAN BE RELATED TO THE 2842 02:00:40,559 --> 02:00:41,693 PRODUCT AS WELL AS PROCESS 2843 02:00:41,693 --> 02:00:42,227 ITSELF. 2844 02:00:42,227 --> 02:00:43,895 WHEN YOU CHANGE THE PROCESS TOO 2845 02:00:43,895 --> 02:00:46,698 MUCH YOU MAY HAVE TO RECONSIDER 2846 02:00:46,698 --> 02:00:48,633 WHAT KIND OF IMPURITY PROFILE 2847 02:00:48,633 --> 02:00:49,267 YOU HAVE. 2848 02:00:49,267 --> 02:00:51,369 I THINK FROM THE FDA 2849 02:00:51,369 --> 02:00:52,604 PERSPECTIVE AND LOOKING FORWARD 2850 02:00:52,604 --> 02:00:54,005 INTO THE FUTURE, I THINK THE 2851 02:00:54,005 --> 02:00:55,874 CHALLENGE IS REALLY IN THE 2852 02:00:55,874 --> 02:00:59,311 IMPLEMENTATION OF MANY ADVANCED 2853 02:00:59,311 --> 02:01:00,345 TECHNOLOGIES. 2854 02:01:00,345 --> 02:01:02,447 AS I MENTIONED EARLIER, WE ARE 2855 02:01:02,447 --> 02:01:05,317 SEEING THE INCORPORATION OF 2856 02:01:05,317 --> 02:01:08,820 A.I., LET'S SAY. 2857 02:01:08,820 --> 02:01:10,222 OR DATA-DRIVEN MODELS. 2858 02:01:10,222 --> 02:01:12,090 IN BOTH THE DEVELOPMENT 2859 02:01:12,090 --> 02:01:13,024 OPTIMIZATION, BUT ALSO IN THE 2860 02:01:13,024 --> 02:01:16,061 CONTROL OF THE PROCESS ITSELF, 2861 02:01:16,061 --> 02:01:16,261 RIGHT? 2862 02:01:16,261 --> 02:01:18,597 SO THIS IS A DIFFERENT WAY TO 2863 02:01:18,597 --> 02:01:20,532 THINK ABOUT CONTROL STRATEGY. 2864 02:01:20,532 --> 02:01:23,301 AND WE NEED TO UNDERSTAND HOW 2865 02:01:23,301 --> 02:01:24,102 THIS IS DONE. 2866 02:01:24,102 --> 02:01:26,538 AND WE ALSO HAVE TO UNDERSTAND 2867 02:01:26,538 --> 02:01:28,640 IF OUR EXISTING REGULATION 2868 02:01:28,640 --> 02:01:31,209 COULD ACCOMMODATE SOME OF THESE 2869 02:01:31,209 --> 02:01:32,811 ADVANCED TECHNOLOGIES OR 2870 02:01:32,811 --> 02:01:34,212 DIFFERENT MODALITIES FOR 2871 02:01:34,212 --> 02:01:37,048 MANUFACTURING, FOR EXAMPLE, 2872 02:01:37,048 --> 02:01:38,750 DISTRIBUTED MANUFACTURING OR 2873 02:01:38,750 --> 02:01:39,651 POINT-OF-CARE MANUFACTURING. 2874 02:01:39,651 --> 02:01:46,358 I THINK THE EARLIER TALK ABOUT 2875 02:01:46,358 --> 02:01:47,592 THE CENTRALIZED HUB AND 2876 02:01:47,592 --> 02:01:48,793 SATELLITE SITES. 2877 02:01:48,793 --> 02:01:51,129 WHAT DO WE DO WITH 2878 02:01:51,129 --> 02:01:52,097 ESTABLISHMENT, REGISTRATION, 2879 02:01:52,097 --> 02:01:52,297 RIGHT? 2880 02:01:52,297 --> 02:01:57,669 WHAT DO WE DO WITH INSPECTION? 2881 02:01:57,669 --> 02:02:00,272 AND HOW DO WE STREAMLINE FOR 2882 02:02:00,272 --> 02:02:02,874 EACH UNIT ASSUMING THEY ARE 2883 02:02:02,874 --> 02:02:03,808 REALLY EQUIVALENT? 2884 02:02:03,808 --> 02:02:05,944 SO THESE ARE THE THINGS WE HAVE 2885 02:02:05,944 --> 02:02:07,979 TO CONSIDER AS AN AGENCY. 2886 02:02:07,979 --> 02:02:10,048 SO I WILL STOP HERE OTHERWISE 2887 02:02:10,048 --> 02:02:17,856 THE LIST CAN GO ON. 2888 02:02:17,856 --> 02:02:19,758 >> David Borhani: THIS IS GREAT. 2889 02:02:19,758 --> 02:02:20,759 IN BROAD AGREEMENT WITH 2890 02:02:20,759 --> 02:02:23,762 EVERYTHING SAID. 2891 02:02:23,762 --> 02:02:25,664 BECAUSE GINGKO DOESN'T 2892 02:02:25,664 --> 02:02:27,565 MANUFACTURE ANYTHING, WE HAVE 2893 02:02:27,565 --> 02:02:29,000 MAYBE SLIGHTLY A DIFFERENT 2894 02:02:29,000 --> 02:02:30,502 VIEWPOINT WE CAN BRING TO THIS. 2895 02:02:30,502 --> 02:02:32,270 WE ARE HELPING OUR PARTNERS TO 2896 02:02:32,270 --> 02:02:34,372 ADDRESS ALL OF THESE ISSUES, 2897 02:02:34,372 --> 02:02:35,573 HOPEFULLY BEFORE THEY GET 2898 02:02:35,573 --> 02:02:37,208 THERE, OR WHEN THEY ARE 2899 02:02:37,208 --> 02:02:38,910 ACTUALLY IN MANUFACTURING TO 2900 02:02:38,910 --> 02:02:40,278 IMPROVE THINGS. 2901 02:02:40,278 --> 02:02:42,147 SO AGAIN, ECHOING THE THEME, 2902 02:02:42,147 --> 02:02:43,682 START WITH WHAT YOUR END IS IN 2903 02:02:43,682 --> 02:02:48,053 MIND. 2904 02:02:48,053 --> 02:02:51,556 DESIGN THE THERAPEUTIC, NEW 2905 02:02:51,556 --> 02:02:52,958 BIOLOGICAL ENTITY SO IT 2906 02:02:52,958 --> 02:02:54,592 INCREASES THE EFFICACY AND 2907 02:02:54,592 --> 02:02:57,228 SAFETY YOU NEED BUT ALSO 2908 02:02:57,228 --> 02:02:59,864 DESIGNED WITH THE VIEW, IT MUST 2909 02:02:59,864 --> 02:03:01,166 BE MANUFACTURERABLE. 2910 02:03:01,166 --> 02:03:03,268 AS YOU ARE WORKING WITH 2911 02:03:03,268 --> 02:03:05,637 SOMEBODY LIKE GINGKO OR ANOTHER 2912 02:03:05,637 --> 02:03:07,472 PARTNER OR INTERNALLY, REALLY 2913 02:03:07,472 --> 02:03:12,677 BRING THOSE SORTS OF PROCESSES 2914 02:03:12,677 --> 02:03:14,813 AND DESIGN STEPS TO WHAT YOU 2915 02:03:14,813 --> 02:03:16,681 ARE ULTIMATELY DELIVERING AS 2916 02:03:16,681 --> 02:03:20,285 THE THERAPEUTIC CANDIDATE. 2917 02:03:20,285 --> 02:03:27,292 MAYBE TO BRING SOME REALLY 2918 02:03:27,292 --> 02:03:29,461 PROZEIC EXAMPLES TO MIND, WITH 2919 02:03:29,461 --> 02:03:33,665 COVID-19 WE WORKED WITH RRN AND 2920 02:03:33,665 --> 02:03:35,066 DNA VACCINE MANUFACTURERS TO 2921 02:03:35,066 --> 02:03:37,435 INCREASE THE YIELD OF PLASMA 2922 02:03:37,435 --> 02:03:39,437 DNA NEEDED FOR THESE PRODUCTS 2923 02:03:39,437 --> 02:03:40,972 AND PROCESSES. 2924 02:03:40,972 --> 02:03:42,307 AND THAT EFFECTIVELY DOUBLES 2925 02:03:42,307 --> 02:03:44,476 THE NUMBER OF DOSES OR 2926 02:03:44,476 --> 02:03:45,944 QUADRUPLES THE NUMBER OF DOSES. 2927 02:03:45,944 --> 02:03:48,880 IF YOU CAN BRING THOSE KIND OF 2928 02:03:48,880 --> 02:03:50,315 MANUFACTURING IMPROVEMENTS, 2929 02:03:50,315 --> 02:03:53,184 SOMETHING THAT WAS PERHAPS A 2930 02:03:53,184 --> 02:03:57,088 DIFFICULT PROCESS TO EXECUTE 2931 02:03:57,088 --> 02:03:58,957 SUDDENLY BECAME MAYBE FOUR 2932 02:03:58,957 --> 02:03:59,924 TIMES EASIER BECAUSE YOU DON'T 2933 02:03:59,924 --> 02:04:01,793 HAVE TO MAKE AS MUCH. 2934 02:04:01,793 --> 02:04:04,095 IT KIND OF ECHOES WHAT ARIEL 2935 02:04:04,095 --> 02:04:06,598 HAS BEEN SAYING AS WELL. 2936 02:04:06,598 --> 02:04:08,066 AND JUST ONE OTHER TRIVIAL 2937 02:04:08,066 --> 02:04:10,168 EXAMPLE FROM THE SAME TIME, WE 2938 02:04:10,168 --> 02:04:16,574 WERE ABLE TO IMPROVE PRODUCTION 2939 02:04:16,574 --> 02:04:21,713 OF VACCINE BY TEN FOLD IN WEEKS. 2940 02:04:21,713 --> 02:04:23,348 THAT ADDRESSED KEY REAGENT 2941 02:04:23,348 --> 02:04:24,115 ISSUE. 2942 02:04:24,115 --> 02:04:25,984 THERE MAY BE BIAS IN THE FIELD 2943 02:04:25,984 --> 02:04:27,852 SOME OF THESE THINGS HAVE BEEN 2944 02:04:27,852 --> 02:04:30,555 WORKED ON FOR SO LONG LIKE 2945 02:04:30,555 --> 02:04:31,156 PLASMA DNA. 2946 02:04:31,156 --> 02:04:34,025 WHO WOULD HAVE THOUGHT YOU 2947 02:04:34,025 --> 02:04:38,797 COULD JUST QUADRUPLE DNA IN 2948 02:04:38,797 --> 02:04:39,831 JUST TEN WEEKS. 2949 02:04:39,831 --> 02:04:41,332 THE OTHER THING THAT MAYBE IS 2950 02:04:41,332 --> 02:04:43,201 OUTSIDE OF WHAT HAS BEEN SAID 2951 02:04:43,201 --> 02:04:48,073 HERE IS CAN WE DO QUALITY BY 2952 02:04:48,073 --> 02:04:50,475 DESIGN? 2953 02:04:50,475 --> 02:04:51,409 SO SOMETHING THAT I HAVE 2954 02:04:51,409 --> 02:04:54,012 CHATTED WITH A FEW FOLKS ABOUT, 2955 02:04:54,012 --> 02:04:55,647 ESPECIALLY IN REGARDS TO CELL 2956 02:04:55,647 --> 02:05:02,353 THERAPIES IS HOW CAN WE I GUESS 2957 02:05:02,353 --> 02:05:03,755 MODIFY OR BREAK THIS PROCESS 2958 02:05:03,755 --> 02:05:05,857 WHERE WE HAVE ONE SET OF PEOPLE 2959 02:05:05,857 --> 02:05:07,058 DOING THE WORK, ANOTHER SET 2960 02:05:07,058 --> 02:05:07,892 CHECKING THE QUALITY OF WHAT 2961 02:05:07,892 --> 02:05:09,127 WAS DONE. 2962 02:05:09,127 --> 02:05:11,296 WAS EVERY STEP OF THIS COMPLEX 2963 02:05:11,296 --> 02:05:12,397 PROCESS DONE CORRECTLY? 2964 02:05:12,397 --> 02:05:13,998 WE WANT TO KNOW IT WAS DONE 2965 02:05:13,998 --> 02:05:15,233 CORRECTLY. 2966 02:05:15,233 --> 02:05:17,569 CAN WE DESIGN THE CELLS SO THAT 2967 02:05:17,569 --> 02:05:20,905 THEY TELL US THEMSELVES, YEP, 2968 02:05:20,905 --> 02:05:22,674 I'M CORRECT. 2969 02:05:22,674 --> 02:05:26,344 IF I'M NOT CORRECT, I DIE. 2970 02:05:26,344 --> 02:05:28,880 SO THIS IS LIKE PAINTING A 2971 02:05:28,880 --> 02:05:30,048 VISION, SCIENCE FICTION, BUT 2972 02:05:30,048 --> 02:05:31,683 MAYBE IN TEN YEARS WITH A 2973 02:05:31,683 --> 02:05:35,587 LITTLE BIT OF HELP FROM 2974 02:05:35,587 --> 02:05:36,788 DARPA-H, WE CAN BE THERE. 2975 02:05:36,788 --> 02:05:40,291 >> Miljan Simonovic: ALMOST 2976 02:05:40,291 --> 02:05:42,360 LIKE SELF-REPORTING TOOL OR 2977 02:05:42,360 --> 02:05:42,627 PLATFORM. 2978 02:05:42,627 --> 02:05:43,328 >> David Borhani: EXACTLY. 2979 02:05:43,328 --> 02:05:44,195 >> Miljan Simonovic: THIS IS 2980 02:05:44,195 --> 02:05:44,729 NICE. 2981 02:05:44,729 --> 02:05:47,499 YOU KIND OF SEGUE, I WANTED TO 2982 02:05:47,499 --> 02:05:49,200 FOLLOW-UP WITH A QUESTION AND I 2983 02:05:49,200 --> 02:05:50,702 HOPE THE CROWD WILL START 2984 02:05:50,702 --> 02:05:53,872 ASKING. 2985 02:05:53,872 --> 02:05:58,143 WE CAN GO TO YOU, DAVID, NOW. 2986 02:05:58,143 --> 02:06:00,211 IN YOUR EXPERIENCE IS THERE A 2987 02:06:00,211 --> 02:06:02,747 DIFFICULT PATH IN 2988 02:06:02,747 --> 02:06:04,549 BIOMANUFACTURING, FROM LET'S 2989 02:06:04,549 --> 02:06:06,417 SAY DISCOVERING LAB AT 2990 02:06:06,417 --> 02:06:07,285 UNIVERSITY TO FULL SCALE 2991 02:06:07,285 --> 02:06:08,019 PRODUCTION. 2992 02:06:08,019 --> 02:06:10,522 IS THERE A TYPICAL STANDARD 2993 02:06:10,522 --> 02:06:12,190 OPERATING PROCEDURE? 2994 02:06:12,190 --> 02:06:14,926 OR EVERY, WE USED TO SAY IN THE 2995 02:06:14,926 --> 02:06:17,428 LAB EVERY PROTEIN IS ITS OWN 2996 02:06:17,428 --> 02:06:18,930 TALE. 2997 02:06:18,930 --> 02:06:21,065 EVERY PROTEIN IS CRYSTALLIZED 2998 02:06:21,065 --> 02:06:21,900 DIFFERENTLY, YOU KNOW WHAT I 2999 02:06:21,900 --> 02:06:22,934 MEAN? 3000 02:06:22,934 --> 02:06:26,171 IS IT ALWAYS UNIQUE OR IS THERE 3001 02:06:26,171 --> 02:06:29,507 SOMETHING THAT STANDS OUT AS A 3002 02:06:29,507 --> 02:06:31,543 COMMON THREAD? 3003 02:06:31,543 --> 02:06:33,411 >> David Borhani: I WOULD SAY 3004 02:06:33,411 --> 02:06:34,879 UNIQUENESS IS UNFORTUNATELY THE 3005 02:06:34,879 --> 02:06:37,148 PROBLEM. 3006 02:06:37,148 --> 02:06:43,388 WHAT IS THE OPENING LINE OF ANA 3007 02:06:43,388 --> 02:06:45,190 CARINDARA? 3008 02:06:45,190 --> 02:06:47,125 (?) EVERY PROTEIN IS DIFFERENT 3009 02:06:47,125 --> 02:06:49,494 IN ITS OWN UNFORTUNATE WAY. 3010 02:06:49,494 --> 02:06:56,534 THAT'S THE PROMISE OF NUCLEIC 3011 02:06:56,534 --> 02:06:58,169 ACID THERAPIES, IN THEORY THEY 3012 02:06:58,169 --> 02:06:59,904 ARE ALL GOING TO BE THE SAME. 3013 02:06:59,904 --> 02:07:01,906 I WAS CHATTING WITH SHANNON 3014 02:07:01,906 --> 02:07:05,410 ABOUT THIS, AS DARPA NOW 3015 02:07:05,410 --> 02:07:07,946 EXPANDS INTO BROADER TYPES OF 3016 02:07:07,946 --> 02:07:09,914 DNA AND RNA THAT IT WANTS TO 3017 02:07:09,914 --> 02:07:12,383 MAKE AND THIS IS SHANNON'S, 3018 02:07:12,383 --> 02:07:14,586 WHAT SHE SHARED WITH ME, THAT'S 3019 02:07:14,586 --> 02:07:16,688 WHERE THEY ARE KIND OF HEADED, 3020 02:07:16,688 --> 02:07:18,523 WHAT KINDS OF CHALLENGES ARE 3021 02:07:18,523 --> 02:07:21,125 GOING TO ARISE? 3022 02:07:21,125 --> 02:07:22,327 ESPECIALLY WITH RNA. 3023 02:07:22,327 --> 02:07:23,962 IS YOUR MANUFACTURING PROCESS 3024 02:07:23,962 --> 02:07:25,597 ROBUST TO THE SECONDARY 3025 02:07:25,597 --> 02:07:27,465 STRUCTURE? 3026 02:07:27,465 --> 02:07:28,633 WITH PROTEINS, JUST TAKE THAT 3027 02:07:28,633 --> 02:07:31,402 AND PUT IT ON STEROIDS AND IS 3028 02:07:31,402 --> 02:07:33,338 THERE A SOLUTION TO THAT? 3029 02:07:33,338 --> 02:07:34,839 I'M NOT SURE. 3030 02:07:34,839 --> 02:07:35,840 OTHER THAN GETTING INVOLVED 3031 02:07:35,840 --> 02:07:46,050 VERY EARLY. 3032 02:07:47,885 --> 02:07:50,054 >> Lily Koo: I GUESS ONE THING 3033 02:07:50,054 --> 02:07:53,324 I CAN THINK OF, SOME OF OUR 3034 02:07:53,324 --> 02:07:56,127 THERAPEUTIC MODALITIES AND THE 3035 02:07:56,127 --> 02:07:58,896 WAY THE MATERIAL, THERAPEUTIC 3036 02:07:58,896 --> 02:08:00,298 MATERIAL IS DELIVERED REALLY 3037 02:08:00,298 --> 02:08:03,601 CREATE OPPORTUNITY FOR PLATFORM 3038 02:08:03,601 --> 02:08:04,035 TECHNOLOGIES, RIGHT? 3039 02:08:04,035 --> 02:08:05,236 AND I THINK THAT COULD BE ONE 3040 02:08:05,236 --> 02:08:08,906 WAY TO SPEED UP THE TRANSLATION 3041 02:08:08,906 --> 02:08:10,541 FROM LABORATORY TO 3042 02:08:10,541 --> 02:08:12,844 COMMERCIALIZATION. 3043 02:08:12,844 --> 02:08:14,712 THERE IS NO NEED TO REINVENT 3044 02:08:14,712 --> 02:08:16,347 THE WHEEL, RIGHT? 3045 02:08:16,347 --> 02:08:18,716 FOR EXAMPLE, DEVELOPMENT OF AAV 3046 02:08:18,716 --> 02:08:22,754 VECTORS FOR GENE THERAPY AND 3047 02:08:22,754 --> 02:08:24,155 ESPECIALLY WITH mRNA-BASED 3048 02:08:24,155 --> 02:08:25,990 THERAPEUTICS OR VACCINE 3049 02:08:25,990 --> 02:08:27,191 MANUFACTURING, WE CAN REALLY 3050 02:08:27,191 --> 02:08:30,895 LOOK AT SOME OF THE COMMON 3051 02:08:30,895 --> 02:08:32,530 OPERATIONS AND UNDERSTAND HOW 3052 02:08:32,530 --> 02:08:34,165 THEY CAN BE OPTIMIZED. 3053 02:08:34,165 --> 02:08:36,768 AND WITH YOU GUYS WORKING ON 3054 02:08:36,768 --> 02:08:37,969 SYNTHETIC BIOLOGY CAN DO YOUR 3055 02:08:37,969 --> 02:08:39,804 TWEAK FOR WHAT IS NEEDED AS AN 3056 02:08:39,804 --> 02:08:40,672 INPUT. 3057 02:08:40,672 --> 02:08:43,708 AND THEN WE CAN JUST RUN 3058 02:08:43,708 --> 02:08:45,310 THROUGH A PLATFORM TECHNOLOGY 3059 02:08:45,310 --> 02:08:47,245 AND TURN OUT THE DESIRED 3060 02:08:47,245 --> 02:08:49,147 THERAPEUTIC, IN AN IDEAL SCENE 3061 02:08:49,147 --> 02:08:51,582 NAIR YO. 3062 02:08:51,582 --> 02:08:52,283 SCENARIO. 3063 02:08:52,283 --> 02:08:54,118 ANOTHER THING I THINK OF, IS 3064 02:08:54,118 --> 02:08:56,721 WHEN I WAS A GRADUATE STUDENT 3065 02:08:56,721 --> 02:08:59,057 WORKING THE LAP, THERE IS 3066 02:08:59,057 --> 02:09:01,826 S.O.P. IN THE LAB, YOU DO YOUR 3067 02:09:01,826 --> 02:09:03,528 PIPETTING UNDER THE HOOD. 3068 02:09:03,528 --> 02:09:07,865 THERE IS NOT AS MUCH AWARENESS 3069 02:09:07,865 --> 02:09:10,034 OF BIOTECHNOLOGY AND 3070 02:09:10,034 --> 02:09:10,435 BIOMANUFACTURING. 3071 02:09:10,435 --> 02:09:11,836 I THINK WHEN WE CAN INTRODUCE 3072 02:09:11,836 --> 02:09:14,639 EARLY ON IN OUR EDUCATION ABOUT 3073 02:09:14,639 --> 02:09:16,774 REGULATORY SCIENCE, ABOUT 3074 02:09:16,774 --> 02:09:18,176 G.M.P. COMPLIANCE AND ABOUT 3075 02:09:18,176 --> 02:09:20,778 WHAT'S REQUIRED FOR A 3076 02:09:20,778 --> 02:09:22,480 COMMERCIALLY-VIABLE PRODUCT, 3077 02:09:22,480 --> 02:09:25,083 AND I THINK THEN WE COULD START 3078 02:09:25,083 --> 02:09:26,684 OUR RESEARCH WITH THESE THINGS, 3079 02:09:26,684 --> 02:09:27,652 REQUIREMENTS IN MIND AND I 3080 02:09:27,652 --> 02:09:29,554 THINK THAT WILL HELP AS WELL. 3081 02:09:29,554 --> 02:09:32,056 >> Miljan Simonovic: THAT IS 3082 02:09:32,056 --> 02:09:36,861 GOOD, I SPECIALIZE IN -- TOO, 3083 02:09:36,861 --> 02:09:38,529 MAYBE I SHOULD INVITE YOU TO 3084 02:09:38,529 --> 02:09:40,031 SEE WHAT NEEDS TO BE DONE ON 3085 02:09:40,031 --> 02:09:41,899 THAT FRONT. 3086 02:09:41,899 --> 02:09:43,234 >> Lily Koo: START EARLY. 3087 02:09:43,234 --> 02:09:45,570 YOU DON'T HAVE TO GET YOUR 3088 02:09:45,570 --> 02:09:47,672 FIRST JOB IN A PHARMACEUTICAL 3089 02:09:47,672 --> 02:09:49,507 COMPANY AND LEARN THE -- 3090 02:09:49,507 --> 02:09:51,109 >> I'M HERE LEARNING THE SAME 3091 02:09:51,109 --> 02:09:52,276 THINGS, SO I DON'T HAVE 3092 02:09:52,276 --> 02:09:53,411 ANYTHING TO COMMENT ON. 3093 02:09:53,411 --> 02:09:58,950 >> Miljan Simonovic: OKAY, GOOD. 3094 02:09:58,950 --> 02:10:03,354 >> I DON'T HAVE ANYTHING 3095 02:10:03,354 --> 02:10:04,288 ADDITIONAL TO ADD. 3096 02:10:04,288 --> 02:10:05,923 >> I COULD ALWAYS TALK. 3097 02:10:05,923 --> 02:10:07,625 THERE'S ALWAYS A TENSION FOR 3098 02:10:07,625 --> 02:10:09,894 THINGS WE WANT TO FUND. 3099 02:10:09,894 --> 02:10:11,295 OFTEN WE JUST WANT TO SHOW IT 3100 02:10:11,295 --> 02:10:12,697 CAN BE DONE. 3101 02:10:12,697 --> 02:10:15,433 MANY TIMES IT COULD BE DONE BY 3102 02:10:15,433 --> 02:10:16,134 HOOK OR CROOK. 3103 02:10:16,134 --> 02:10:17,668 AND THEN YOU HAVE TO WORRY 3104 02:10:17,668 --> 02:10:21,472 ABOUT MANUFACTURING. 3105 02:10:21,472 --> 02:10:23,241 THIS IS COMMON. 3106 02:10:23,241 --> 02:10:25,276 HAVING WORKED ANOTHER LAB, A 3107 02:10:25,276 --> 02:10:27,612 SCIENTIST COMES UP WITH BIT OF 3108 02:10:27,612 --> 02:10:30,047 ELECTRONICS, RIGHT, THEY GO TO 3109 02:10:30,047 --> 02:10:32,583 THE E.E. AND THE DOUBLE-E IS 3110 02:10:32,583 --> 02:10:34,919 LIKE YEAH I KNOW WHAT YOU ARE 3111 02:10:34,919 --> 02:10:36,654 TALKING ABOUT, JUST STORE YOUR 3112 02:10:36,654 --> 02:10:38,423 VERSION THERE IN THE CORNER, ON 3113 02:10:38,423 --> 02:10:39,791 THE TRASH CAN. 3114 02:10:39,791 --> 02:10:41,926 RIGHT NEXT TO IT, YOU DON'T 3115 02:10:41,926 --> 02:10:44,028 HAVE TO ACTUALLY PUT IT IN, I 3116 02:10:44,028 --> 02:10:46,030 WILL DO IT LATER. 3117 02:10:46,030 --> 02:10:47,064 IT'S POORLY ENGINEERED SO 3118 02:10:47,064 --> 02:10:49,901 THERE'S ALWAYS THAT TENSION. 3119 02:10:49,901 --> 02:10:52,003 YOU WANT PEOPLE TO WORK HARD ON 3120 02:10:52,003 --> 02:10:53,404 SHOWING ITS POSSIBLE. 3121 02:10:53,404 --> 02:10:55,706 AT THE EARLIEST MOMENT START 3122 02:10:55,706 --> 02:10:57,575 BOTHERING WITH HOW ARE YOU 3123 02:10:57,575 --> 02:10:58,609 GOING TO ACTUALLY START 3124 02:10:58,609 --> 02:10:59,877 MANUFACTURING THIS? 3125 02:10:59,877 --> 02:11:02,213 THAT'S SOMETHING, IN THE DARPA 3126 02:11:02,213 --> 02:11:04,315 PROGRAM START MOVING IN, I WANT 3127 02:11:04,315 --> 02:11:07,652 YOU TO PROVE SOMETHING IS 3128 02:11:07,652 --> 02:11:09,720 POSSIBLE BUT AFTER YEAR ONE 3129 02:11:09,720 --> 02:11:11,823 ONCE YOU GET GOING, WE START 3130 02:11:11,823 --> 02:11:14,892 DOING THINGS, WHAT IS THE 3131 02:11:14,892 --> 02:11:16,994 DESIGN MODULAR, THIS CONSTRUCT, 3132 02:11:16,994 --> 02:11:20,031 EVERYTHING HAS TO WORK SO, OR 3133 02:11:20,031 --> 02:11:23,301 RUGGEDNESS THAT, YOU DO NEED TO 3134 02:11:23,301 --> 02:11:24,936 START THINKING ABOUT IT, MAYBE 3135 02:11:24,936 --> 02:11:27,472 NOT DAY ONE BUT AS SOON AS 3136 02:11:27,472 --> 02:11:30,641 THINGS START WORKING, LET'S 3137 02:11:30,641 --> 02:11:35,279 START ENSURING THAT IT HAS A 3138 02:11:35,279 --> 02:11:36,113 MANUFACTURING FUTURE. 3139 02:11:36,113 --> 02:11:38,049 >> I THINK I STRONGLY AGREE 3140 02:11:38,049 --> 02:11:38,883 WITH THAT POINT. 3141 02:11:38,883 --> 02:11:40,651 TO ANSWER YOUR QUESTION, I 3142 02:11:40,651 --> 02:11:42,086 WOULD SAY THAT, YOU KNOW, IF 3143 02:11:42,086 --> 02:11:44,655 YOU ARE DEVELOPING A NOVEL 3144 02:11:44,655 --> 02:11:45,590 TECHNOLOGY, THERE'S OBVIOUSLY, 3145 02:11:45,590 --> 02:11:48,125 I THINK BY CONSTRUCTION, BY 3146 02:11:48,125 --> 02:11:49,560 NECESSITY THERE ISN'T A TRIED 3147 02:11:49,560 --> 02:11:51,429 AND TRUE PATH BECAUSE YOU ARE 3148 02:11:51,429 --> 02:11:53,264 TRYING TO PAVE A NEW PATH. 3149 02:11:53,264 --> 02:11:54,699 THERE WILL BE KIND OF 3150 02:11:54,699 --> 02:11:55,867 DEVELOPING NEW APPROACHES TO 3151 02:11:55,867 --> 02:11:58,035 MAKE IT WORK, TO MANUFACTURE 3152 02:11:58,035 --> 02:12:00,137 IT, BUT AS PAUL SAID, EARLY ON, 3153 02:12:00,137 --> 02:12:04,342 AS THEY SAY IN COMPUTER 3154 02:12:04,342 --> 02:12:05,510 SCIENCE, PRE-OPTIMIZATION ISN'T 3155 02:12:05,510 --> 02:12:06,444 A GOOD IDEA. 3156 02:12:06,444 --> 02:12:08,279 YOU HAVE TO CHOOSE YOUR BATTLE 3157 02:12:08,279 --> 02:12:11,315 AND THE FIRST IS TO SHOW 3158 02:12:11,315 --> 02:12:12,149 FEASIBILITY BEFORE 3159 02:12:12,149 --> 02:12:12,917 MANUFACTURING. 3160 02:12:12,917 --> 02:12:16,521 AND TO ADD ONCE A TECHNOLOGY 3161 02:12:16,521 --> 02:12:18,155 mRNA EXAMPLE, WELL DEVELOPED 3162 02:12:18,155 --> 02:12:19,757 AND WELL SCALED YOU MIGHT MAKE 3163 02:12:19,757 --> 02:12:21,859 THE ARGUMENT THAT POST-MATURE 3164 02:12:21,859 --> 02:12:23,327 OPTIMIZATION IS JUST A WASTE OF 3165 02:12:23,327 --> 02:12:25,162 TIME AND MONEY. 3166 02:12:25,162 --> 02:12:26,330 IT SOUNDS TERRIBLE BUT IF YOU 3167 02:12:26,330 --> 02:12:28,366 ARE A COMPANY AND ACTUALLY 3168 02:12:28,366 --> 02:12:29,634 DEVELOPING THINGS AND THINKING 3169 02:12:29,634 --> 02:12:31,502 ABOUT GOING BACK THROUGH FDA ON 3170 02:12:31,502 --> 02:12:33,371 SOMETHING THAT IS ALREADY GOOD 3171 02:12:33,371 --> 02:12:34,505 ENOUGH, IT'S NOT ALWAYS CLEAR 3172 02:12:34,505 --> 02:12:36,007 THE PAY OFF IS THERE. 3173 02:12:36,007 --> 02:12:37,808 ON THE EARLY END YOU HAVE TO 3174 02:12:37,808 --> 02:12:40,111 SOMETIMES PURSUE AN APPROACH 3175 02:12:40,111 --> 02:12:41,979 THAT ISN'T SCALABLE ON THE 3176 02:12:41,979 --> 02:12:44,315 LATE-STAGE END IF SOMETHING HAS 3177 02:12:44,315 --> 02:12:45,483 ALREADY BEEN VALIDATED EVEN IF 3178 02:12:45,483 --> 02:12:47,818 THERE MAY BE A BETTER APPROACH, 3179 02:12:47,818 --> 02:12:49,720 BECAUSE THERE'S ALWAYS A WAY TO 3180 02:12:49,720 --> 02:12:52,089 OPTIMIZE SOMETHING, IT MAY NOT 3181 02:12:52,089 --> 02:12:53,658 BE THE BEST USE OF RESOURCES. 3182 02:12:53,658 --> 02:12:54,825 >> Miljan Simonovic: THANKS. 3183 02:12:54,825 --> 02:12:59,697 >> IF I COULD ADD ONE THOUGHT, 3184 02:12:59,697 --> 02:13:02,066 MAYBE TAKING A HISTORICAL 3185 02:13:02,066 --> 02:13:03,267 PERSPECTIVE, BECAUSE I'M MAYBE 3186 02:13:03,267 --> 02:13:04,268 OLDER THAN I LOOK. 3187 02:13:04,268 --> 02:13:05,836 WHEN I STARTED IN THIS 3188 02:13:05,836 --> 02:13:12,677 BUSINESS, IN 1990, IT WAS 3189 02:13:12,677 --> 02:13:17,348 REALLY COMMON IN THE SMALL 3190 02:13:17,348 --> 02:13:19,884 MOLECULE ARENA TO HAVE SMALL 3191 02:13:19,884 --> 02:13:21,352 GROUP FROM DEVELOPMENT, 3192 02:13:21,352 --> 02:13:24,622 DEVELOPMENT THOSE WHO WORKED ON 3193 02:13:24,622 --> 02:13:26,724 THINGS, LIKE FORMULATION AND 3194 02:13:26,724 --> 02:13:27,291 TOXICITY ASSESSMENT AND SO 3195 02:13:27,291 --> 02:13:28,125 FORTH. 3196 02:13:28,125 --> 02:13:30,061 I'M NOT EVEN TALKING CLINICAL 3197 02:13:30,061 --> 02:13:31,629 DEVELOPMENT. 3198 02:13:31,629 --> 02:13:33,230 AND CHEMISTS WOULD THROW 3199 02:13:33,230 --> 02:13:35,366 MOLECULES OVER THE VERITIABLE 3200 02:13:35,366 --> 02:13:36,000 WALL. 3201 02:13:36,000 --> 02:13:39,103 AND IT'S LIKE WE DID OUR JOB. 3202 02:13:39,103 --> 02:13:42,306 IT'S NOT OUR PROBLEM THE 3203 02:13:42,306 --> 02:13:43,975 COMPOUND IS BRICK DUST. 3204 02:13:43,975 --> 02:13:46,377 THAT HAS CHANGED DRAMATICALLY. 3205 02:13:46,377 --> 02:13:49,213 AND ALL OF THESE SORT OF 3206 02:13:49,213 --> 02:13:50,381 DEVELOPMENTAL ATTRIBUTES HAVE 3207 02:13:50,381 --> 02:13:51,282 BEEN BROUGHT EARLIER AND 3208 02:13:51,282 --> 02:13:52,416 EARLIER IN THE DISCOVERY 3209 02:13:52,416 --> 02:13:54,085 PROCESS. 3210 02:13:54,085 --> 02:13:58,656 AND SIMILARLY, FOR SYNTHESIS, 3211 02:13:58,656 --> 02:14:00,024 THOUGH PERHAPS A LITTLE LESS 3212 02:14:00,024 --> 02:14:01,425 SO, THE INTERNATIONAL ACTIONS 3213 02:14:01,425 --> 02:14:03,294 WITH THE PROCESS CHEMISTS HAVE 3214 02:14:03,294 --> 02:14:07,164 BEEN HAPPENING EARLIER AND 3215 02:14:07,164 --> 02:14:07,531 EARLIER. 3216 02:14:07,531 --> 02:14:10,301 OH YOU THINK YOU HAVE ONE IN 3217 02:14:10,301 --> 02:14:11,202 FIVE CANDIDATES LET'S GET 3218 02:14:11,202 --> 02:14:11,969 INVOLVED. 3219 02:14:11,969 --> 02:14:13,804 WE HAVE TO MAKE A TON OF IT. 3220 02:14:13,804 --> 02:14:16,874 YOU ONLY HAD TO MAKE 50 3221 02:14:16,874 --> 02:14:18,275 MILLIGRAMS ASAP BECAUSE YOU ARE 3222 02:14:18,275 --> 02:14:21,078 IN A DISCOVERY PROGRAM, WE ARE 3223 02:14:21,078 --> 02:14:22,046 OPERATING UNDER DIFFERENT 3224 02:14:22,046 --> 02:14:22,747 CONSTRAINTS. 3225 02:14:22,747 --> 02:14:27,351 I DON'T THINK THIS KIND OF MIND 3226 02:14:27,351 --> 02:14:30,354 SET IS REALLY THAT OPERATIVE IN 3227 02:14:30,354 --> 02:14:36,227 THE BIOLOGICAL REALM , SURE. 3228 02:14:36,227 --> 02:14:36,861 THERE'S DEVELOPMENTAL ASSAYS, 3229 02:14:36,861 --> 02:14:39,430 IS THERE A GOOD ANTIBODY OR NOT? 3230 02:14:39,430 --> 02:14:42,233 WILL IT CRASH OUT A SOLUTION OR 3231 02:14:42,233 --> 02:14:42,400 NOT? 3232 02:14:42,400 --> 02:14:43,901 BUT WHEN YOU GET TO THE MORE 3233 02:14:43,901 --> 02:14:47,371 AND MORE COMPLEX AND POWERFUL 3234 02:14:47,371 --> 02:14:48,773 TECHNOLOGIES, IT'S HARD TO 3235 02:14:48,773 --> 02:14:52,343 BRING THIS KIND OF END THINKING 3236 02:14:52,343 --> 02:14:53,177 EARLIER AND EARLIER. 3237 02:14:53,177 --> 02:14:55,413 BUT I THINK WE NEED TO TRY. 3238 02:14:55,413 --> 02:14:58,182 >> Miljan Simonovic: SO MORE 3239 02:14:58,182 --> 02:14:59,417 SYNERGY, MORE INTEGRATION EARLY 3240 02:14:59,417 --> 02:15:00,051 ON? 3241 02:15:00,051 --> 02:15:01,719 >> David Borhani: ABSOLUTELY. 3242 02:15:01,719 --> 02:15:03,587 AND TO BRING ON PLATFORMS AS 3243 02:15:03,587 --> 02:15:05,589 MUCH AS POSSIBLE. 3244 02:15:05,589 --> 02:15:07,725 >> Miljan Simonovic: HM. 3245 02:15:07,725 --> 02:15:08,993 ARE THERE ANY QUESTIONS FROM 3246 02:15:08,993 --> 02:15:10,461 THE AUDIENCE? 3247 02:15:10,461 --> 02:15:11,962 WE CAN OPEN TO THE FLOOR IF YOU 3248 02:15:11,962 --> 02:15:18,169 GUYS HAVE ANY QUESTIONS. 3249 02:15:18,169 --> 02:15:19,136 DON'T BE SHY. 3250 02:15:19,136 --> 02:15:21,072 OR MAYBE YOU ARE AFRAID BECAUSE 3251 02:15:21,072 --> 02:15:27,745 FDA IS HERE. 3252 02:15:27,745 --> 02:15:30,414 >> David Borhani: LILY IS 3253 02:15:30,414 --> 02:15:31,348 ABSOLUTELY TERRIFYING. 3254 02:15:31,348 --> 02:15:34,719 >> WHAT IS AUTOMATION DOING IN 3255 02:15:34,719 --> 02:15:36,153 BIOMANUFACTURING? 3256 02:15:36,153 --> 02:15:37,188 THAT IS SOMETHING I'VE BEEN 3257 02:15:37,188 --> 02:15:38,055 THINKING ABOUT. 3258 02:15:38,055 --> 02:15:39,790 SO THOSE OF YOU THAT HAVE A 3259 02:15:39,790 --> 02:15:49,934 COMMENT. 3260 02:15:51,602 --> 02:15:54,138 >> Miljan Simonovic: GINGKO'S 3261 02:15:54,138 --> 02:15:58,342 LAB IS ALL ROBOT. 3262 02:15:58,342 --> 02:16:01,579 >> WE USE AUTOMATION TO 3263 02:16:01,579 --> 02:16:02,513 DRAMATICALLY EXPAND THE SEARCH 3264 02:16:02,513 --> 02:16:04,381 SPACE SO WE CAN FIND THE BEST 3265 02:16:04,381 --> 02:16:06,050 ANSWER FOR MANUFACTURING. 3266 02:16:06,050 --> 02:16:06,684 BUT THAT'S, I DON'T THINK 3267 02:16:06,684 --> 02:16:07,852 THAT'S WHAT YOU ARE REALLY 3268 02:16:07,852 --> 02:16:10,054 ASKING. 3269 02:16:10,054 --> 02:16:13,057 I THINK THIS IS COMING TO WHAT 3270 02:16:13,057 --> 02:16:14,692 LILY WAS TALKING ABOUT. 3271 02:16:14,692 --> 02:16:18,229 REALLY BRINGING IN PROCESS 3272 02:16:18,229 --> 02:16:18,496 CONTROLS. 3273 02:16:18,496 --> 02:16:20,131 AND I MEAN, THIS IS NOT AN AREA 3274 02:16:20,131 --> 02:16:22,733 I KNOW ABOUT, SO THIS IS A WILD 3275 02:16:22,733 --> 02:16:25,503 GUESS, SOME COMBINATION OF 3276 02:16:25,503 --> 02:16:26,637 MECHANICAL COMPUTER AUTOMATION. 3277 02:16:26,637 --> 02:16:30,141 BUT CAN WE GET THE MATERIAL 3278 02:16:30,141 --> 02:16:34,111 ITSELF TO BE SOMEWHAT 3279 02:16:34,111 --> 02:16:35,713 SELF-AUTOMATING, BUT MAYBE LILY 3280 02:16:35,713 --> 02:16:36,514 CAN JUMP IN. 3281 02:16:36,514 --> 02:16:38,783 >> Lily Koo: I THINK 3282 02:16:38,783 --> 02:16:40,985 AUTOMATION, I THINK IT'S ALWAYS 3283 02:16:40,985 --> 02:16:41,786 INTERESTING, RIGHT? 3284 02:16:41,786 --> 02:16:44,121 WHEN WE LOOK AT A DOSSIER AND 3285 02:16:44,121 --> 02:16:49,026 WE LOOK AT PROCESS VALIDATION. 3286 02:16:49,026 --> 02:16:51,629 WE ALWAYS SAY YOU CAN ALWAYS 3287 02:16:51,629 --> 02:16:53,264 VALIDATE A PROCESS BUT YOU 3288 02:16:53,264 --> 02:16:54,899 CAN'T VALIDATE A HUMAN BEING, 3289 02:16:54,899 --> 02:16:56,534 YOU CAN QUALIFY A HUMAN BEING 3290 02:16:56,534 --> 02:16:57,701 BASED ON THEIR TRAINING AND 3291 02:16:57,701 --> 02:16:59,570 SORT OF THEIR PERFORMANCE. 3292 02:16:59,570 --> 02:17:02,973 AND I THINK THAT'S WHERE 3293 02:17:02,973 --> 02:17:04,408 AUTOMATION IS TRYING TO NOT 3294 02:17:04,408 --> 02:17:06,977 ONLY MAKE THE PROCESS EFFICIENT 3295 02:17:06,977 --> 02:17:09,146 BECAUSE THE MACHINE CAN RUN 3296 02:17:09,146 --> 02:17:10,114 MAYBE 24/7. 3297 02:17:10,114 --> 02:17:11,982 BUT ALSO TO MAKE IT MORE 3298 02:17:11,982 --> 02:17:12,583 CONSISTENT, RIGHT? 3299 02:17:12,583 --> 02:17:15,820 TO MAKE IT MORE ROBUST. 3300 02:17:15,820 --> 02:17:17,755 AND THERE ARE ALSO AREAS FOR 3301 02:17:17,755 --> 02:17:20,691 EXAMPLE, WHEN YOU THINK OF 3302 02:17:20,691 --> 02:17:22,092 ASEPTIC PROCESSES, A HUMAN IS 3303 02:17:22,092 --> 02:17:27,198 REALLY THE MAJOR SOURCE OF 3304 02:17:27,198 --> 02:17:27,531 CONTAMINATION. 3305 02:17:27,531 --> 02:17:29,633 YOU WALK IN AND START SHEDDING 3306 02:17:29,633 --> 02:17:30,501 EVERYWHERE. 3307 02:17:30,501 --> 02:17:33,604 YOU WALK INTO A G.M.P. 3308 02:17:33,604 --> 02:17:35,439 ENVIRONMENT YOU DON'T SEE 3309 02:17:35,439 --> 02:17:37,107 HUMANS STANDING IN ISO5 3310 02:17:37,107 --> 02:17:37,741 ENVIRONMENT. 3311 02:17:37,741 --> 02:17:40,444 YOU WILL HAVE YOUR BIOLOGICAL 3312 02:17:40,444 --> 02:17:42,146 SAFETY CABINET. 3313 02:17:42,146 --> 02:17:43,514 YOUR ISOLATOR AND HUMAN WORKS 3314 02:17:43,514 --> 02:17:44,348 AROUND IT. 3315 02:17:44,348 --> 02:17:46,684 WHEN I FIRST JOINED CBER, FIRST 3316 02:17:46,684 --> 02:17:48,786 THING I LEARNED IS THE CONCEPT 3317 02:17:48,786 --> 02:17:50,521 OF FIRST AIR. 3318 02:17:50,521 --> 02:17:53,057 WHICH IS THAT HEPA FILTERED 3319 02:17:53,057 --> 02:17:54,358 CLEAN AIR THAT HAS TO REACH THE 3320 02:17:54,358 --> 02:17:55,593 PRODUCT. 3321 02:17:55,593 --> 02:17:57,261 YOU CANNOT STICK YOUR HAND OR 3322 02:17:57,261 --> 02:17:59,029 ANYTHING IN THAT PATH. 3323 02:17:59,029 --> 02:18:01,432 SO I THINK AUTOMATION ALSO 3324 02:18:01,432 --> 02:18:03,067 INTRODUCE POSSIBILITY FOR THAT, 3325 02:18:03,067 --> 02:18:05,870 AND THAT'S I THINK SUZIE TALK 3326 02:18:05,870 --> 02:18:07,438 ABOUT HOW TO MAKE EVERYTHING 3327 02:18:07,438 --> 02:18:08,672 CLOSED SYSTEM. 3328 02:18:08,672 --> 02:18:11,008 CLOSED SYSTEM IS TO PREVENT, 3329 02:18:11,008 --> 02:18:13,344 REALLY TO SEGREGATE THE PRODUCT 3330 02:18:13,344 --> 02:18:15,045 AND THE PROCESS STREAM FROM THE 3331 02:18:15,045 --> 02:18:15,980 EXTERNAL ENVIRONMENT. 3332 02:18:15,980 --> 02:18:20,918 AND THAT INCLUDES US. 3333 02:18:20,918 --> 02:18:24,421 I THINK THIS IS, YEAH, SOME OF 3334 02:18:24,421 --> 02:18:25,823 THE MAIN POINTS WITH AUTOMATION. 3335 02:18:25,823 --> 02:18:36,000 THANK YOU. 3336 02:18:37,735 --> 02:18:41,572 >> I WILL ADD, IT'S A POINT OF 3337 02:18:41,572 --> 02:18:42,973 AUTOMATION WITH US, WANT TO 3338 02:18:42,973 --> 02:18:47,811 TALK WITH LILY HOW TO ENSURE 3339 02:18:47,811 --> 02:18:48,913 CONSTRUCTS, HOW DO YOU PULL 3340 02:18:48,913 --> 02:18:50,848 PEOPLE OUT OF THE MANIPULATION 3341 02:18:50,848 --> 02:18:52,483 BUT STILL ALLOW THE FLEXIBILITY 3342 02:18:52,483 --> 02:18:54,818 TO DO NEW THINGS, INSTEAD OF 3343 02:18:54,818 --> 02:18:56,487 HAVING SET UP ONCE AND 3344 02:18:56,487 --> 02:19:00,024 VALIDATE, HOW DO YOU HAVE THE 3345 02:19:00,024 --> 02:19:00,958 AUTOMATION BUT IN A FLEXIBLE 3346 02:19:00,958 --> 02:19:02,092 WAY. 3347 02:19:02,092 --> 02:19:03,761 USING A.I. AND THESE OTHER 3348 02:19:03,761 --> 02:19:09,166 SYSTEMS THAT DEAL WITH DIE 3349 02:19:09,166 --> 02:19:10,768 DIMENSIONAL. 3350 02:19:10,768 --> 02:19:14,538 VERY INTERESTED IN HE MERGING 3351 02:19:14,538 --> 02:19:17,107 ARTIFICIAL INTELLIGENCE WITH 3352 02:19:17,107 --> 02:19:18,142 THESE SELF-DRIVEN LABS PEOPLE 3353 02:19:18,142 --> 02:19:21,645 HAVE BUILT. 3354 02:19:21,645 --> 02:19:22,680 >> Miljan Simonovic: NOTHING 3355 02:19:22,680 --> 02:19:24,715 ELSE? 3356 02:19:24,715 --> 02:19:27,551 I MEAN, IT'S NICE THAT YOU 3357 02:19:27,551 --> 02:19:28,118 MENTIONED ARTIFICIAL 3358 02:19:28,118 --> 02:19:28,886 INTELLIGENCE. 3359 02:19:28,886 --> 02:19:31,355 HOW MUCH DO YOU SEE OUT THERE 3360 02:19:31,355 --> 02:19:32,623 BEING USED? 3361 02:19:32,623 --> 02:19:36,160 I'VE SEEN IT, OBVIOUSLY IN 3362 02:19:36,160 --> 02:19:40,698 PROJECTS THAT RELY ON 3363 02:19:40,698 --> 02:19:42,599 ENGINEERING ENZYMES, 3364 02:19:42,599 --> 02:19:43,067 ENGINEERING PROTEINS. 3365 02:19:43,067 --> 02:19:44,702 A LOT OF PEOPLE RELY ON A.I. 3366 02:19:44,702 --> 02:19:45,736 MACHINE LEARNING. 3367 02:19:45,736 --> 02:19:48,806 BUT WHAT OTHER AREAS DO YOU SEE 3368 02:19:48,806 --> 02:19:50,674 WITHIN THE BRANCH THAT YOU ARE 3369 02:19:50,674 --> 02:19:53,243 WORKING IN, THAT A.I. IS 3370 02:19:53,243 --> 02:19:56,347 POWERING UP OR FACILITATING OR 3371 02:19:56,347 --> 02:19:58,716 DO YOU FORESEE MAYBE BEING MORE 3372 02:19:58,716 --> 02:20:03,087 USED? 3373 02:20:03,087 --> 02:20:06,190 I DON'T KNOW IF YOU USE -- 3374 02:20:06,190 --> 02:20:07,324 BIOLOGICS OR YOU ARE STILL 3375 02:20:07,324 --> 02:20:07,891 WAITING TO SEE? 3376 02:20:07,891 --> 02:20:08,959 >> Ariel Weinberger: THAT'S A 3377 02:20:08,959 --> 02:20:09,660 FAIR QUESTION. 3378 02:20:09,660 --> 02:20:12,863 I MAY BE AN OUTLIER ON THIS ONE. 3379 02:20:12,863 --> 02:20:15,432 THERE ARE THOSE WHO ARE VERY, 3380 02:20:15,432 --> 02:20:17,101 VERY ENTHUSIASTIC ABOUT USING 3381 02:20:17,101 --> 02:20:19,436 A.I. TO DEVELOP NOVEL DRUGS AND 3382 02:20:19,436 --> 02:20:21,972 THERE ARE THOSE WHO ARE A BIT 3383 02:20:21,972 --> 02:20:24,074 MORE SKEPTICAL, FOR ME, TO BE 3384 02:20:24,074 --> 02:20:28,345 FRANK, MAY BE SKEPTICAL ON A.I. 3385 02:20:28,345 --> 02:20:32,149 BUT BRING UP PROTEIN DESIGN AND 3386 02:20:32,149 --> 02:20:35,386 SUCH, ONE BUT CAN'T ACKNOWLEDGE 3387 02:20:35,386 --> 02:20:36,553 INCREDIBLE SUCCESSES THERE. 3388 02:20:36,553 --> 02:20:37,888 THERE ARE DEFINITELY PEOPLE 3389 02:20:37,888 --> 02:20:40,858 USING A.I. IN THE SPACE I'M IN. 3390 02:20:40,858 --> 02:20:42,926 WHETHER SORT OF PREDICTING 3391 02:20:42,926 --> 02:20:44,161 NOVEL ANTIGENS IF YOU ARE 3392 02:20:44,161 --> 02:20:45,029 MAKING VACCINES. 3393 02:20:45,029 --> 02:20:48,065 AND THERE ARE MANY AREAS, WHAT 3394 02:20:48,065 --> 02:20:49,767 PAUL WAS TALKING ABOUT 3395 02:20:49,767 --> 02:20:51,168 OBVIOUSLY IS INTEREST, YOU CAN 3396 02:20:51,168 --> 02:20:53,470 THINK ABOUT IT, GREAT USES FOR 3397 02:20:53,470 --> 02:20:56,306 IT IN MANUFACTURING, IN CLOSED 3398 02:20:56,306 --> 02:20:57,741 LOOP MANUFACTURING, AS WE 3399 02:20:57,741 --> 02:20:58,509 MENTIONED EARLIER. 3400 02:20:58,509 --> 02:21:00,978 YOU CAN THINK OF NOVEL WAYS FOR 3401 02:21:00,978 --> 02:21:07,951 ERROR CHECKING AND HIGH 3402 02:21:07,951 --> 02:21:10,087 DIMENSIONAL BIO ANALYSIS. 3403 02:21:10,087 --> 02:21:12,656 THERE ARE CERTAIN CASES, YOU 3404 02:21:12,656 --> 02:21:19,730 MENTION PROTEIN DESIGN, BUT 3405 02:21:19,730 --> 02:21:21,165 GENOTYPE TO PHENOTYPE, WHETHER 3406 02:21:21,165 --> 02:21:22,800 IT'S AMENABLE TO A.I., THE 3407 02:21:22,800 --> 02:21:24,468 TRAINING DATA AND WHETHER WE 3408 02:21:24,468 --> 02:21:26,070 HAVE THE RELIABILITY TO KIND OF 3409 02:21:26,070 --> 02:21:28,872 PUT THAT ALGORITHM INTO USING 3410 02:21:28,872 --> 02:21:30,040 BUILDING NOVEL DRUGS. 3411 02:21:30,040 --> 02:21:32,176 >> Miljan Simonovic: HM. 3412 02:21:32,176 --> 02:21:35,312 FAIR POINT. 3413 02:21:35,312 --> 02:21:36,947 >> David Borhani: YOU ASKED HOW 3414 02:21:36,947 --> 02:21:38,248 OFTEN I HEAR A.I.? 3415 02:21:38,248 --> 02:21:39,083 ALL THE TIME. 3416 02:21:39,083 --> 02:21:40,317 >> Miljan Simonovic: IS IT TO 3417 02:21:40,317 --> 02:21:40,918 USE? 3418 02:21:40,918 --> 02:21:43,053 YOU KNOW WHAT I MEAN, I CAN SAY 3419 02:21:43,053 --> 02:21:45,589 IT, BUT IS IT SOMETHING THAT 3420 02:21:45,589 --> 02:21:48,659 -- 3421 02:21:48,659 --> 02:21:50,994 >> Paul Sheehan: I WOULD SAY IT 3422 02:21:50,994 --> 02:21:51,995 DEPENDS WHAT PEOPLE WANT TO USE 3423 02:21:51,995 --> 02:21:55,265 IT FOR. 3424 02:21:55,265 --> 02:21:57,401 GLORIFIED FITTING AND MAGIC. 3425 02:21:57,401 --> 02:21:58,902 DEPENDS ON WHO IS DOING IT AND 3426 02:21:58,902 --> 02:22:08,979 WHY. 3427 02:22:15,252 --> 02:22:17,154 -- PEOPLE DO HAVE CLEAR IDEAS 3428 02:22:17,154 --> 02:22:18,856 HOW THEY ARE USING A.I., THE 3429 02:22:18,856 --> 02:22:20,924 WAY THEY ARE USING IT, I WILL 3430 02:22:20,924 --> 02:22:23,760 GO BACK TO TALK A LITTLE BIT. 3431 02:22:23,760 --> 02:22:25,762 NOT TALK ABOUT NOT RUNNING 3432 02:22:25,762 --> 02:22:27,030 THESE PROGRAMS BUT THINGS DO 3433 02:22:27,030 --> 02:22:28,365 POP OUT. 3434 02:22:28,365 --> 02:22:30,467 WE HAD THIS EFFORT FOR CLOSED 3435 02:22:30,467 --> 02:22:32,136 LOOP COWN TROLL OVER WOUND 3436 02:22:32,136 --> 02:22:32,736 HEALING. 3437 02:22:32,736 --> 02:22:35,072 WE WERE BUILDING THIS SUPER 3438 02:22:35,072 --> 02:22:36,440 SMART BANDAGE, COULD PUT 3439 02:22:36,440 --> 02:22:38,108 INFORMATION BACK ON AND PART OF 3440 02:22:38,108 --> 02:22:40,677 THAT IS BUILDING WHAT IS GOING 3441 02:22:40,677 --> 02:22:42,513 ON IN WOUND HEALING. 3442 02:22:42,513 --> 02:22:44,948 ALL THE DIFFERENT COMPONENTS OF 3443 02:22:44,948 --> 02:22:49,253 THE CELLS IN THE WOUNDS AND PUT 3444 02:22:49,253 --> 02:22:50,687 DEEPER INFIRSTMENT LEARNING AND 3445 02:22:50,687 --> 02:22:52,723 IT PLAYED THE GAME OF WOUND 3446 02:22:52,723 --> 02:22:53,257 HEALING. 3447 02:22:53,257 --> 02:23:03,800 THE OUTCOME, NEW MARKERS, NEW 3448 02:23:05,035 --> 02:23:06,103 PATHWAYS THAT STARTED POPPING 3449 02:23:06,103 --> 02:23:08,205 UP AS IMPORTANT AND WOUND 3450 02:23:08,205 --> 02:23:09,806 HEALING WITHOUT SCARRING, RIGHT? 3451 02:23:09,806 --> 02:23:12,409 SO ULTIMATELY THAT CHANGED 3452 02:23:12,409 --> 02:23:15,479 CLINICAL STUDIES AT WALTER REED. 3453 02:23:15,479 --> 02:23:16,480 A SIDE EFFECT. 3454 02:23:16,480 --> 02:23:18,982 I THINK THAT'S A VERY 3455 02:23:18,982 --> 02:23:19,416 COMPLICATED SYSTEM. 3456 02:23:19,416 --> 02:23:22,686 EACH ONE OF THESE SIMULATIONS 3457 02:23:22,686 --> 02:23:26,056 TOOK 6-8 HOURS, MILLIONS OF 3458 02:23:26,056 --> 02:23:27,891 CELLS, 30-50 CELL TYPES. 3459 02:23:27,891 --> 02:23:29,793 SOMETHING A HUMAN, IT WAS VERY 3460 02:23:29,793 --> 02:23:30,928 CHALLENGING TO RUN DIFFERENT 3461 02:23:30,928 --> 02:23:33,230 EXPERIMENTS LIKE THAT. 3462 02:23:33,230 --> 02:23:34,865 BUT THAT A.I. WAS PATIENT, 3463 02:23:34,865 --> 02:23:36,700 COULD RUN THROUGH ALL THOSE 3464 02:23:36,700 --> 02:23:37,601 THINGS AND IDENTIFY THINGS LIKE 3465 02:23:37,601 --> 02:23:38,368 THAT. 3466 02:23:38,368 --> 02:23:44,641 I DO THINK CLEVER APPROACHES, 3467 02:23:44,641 --> 02:23:47,177 USING A.I. CAN SOLVE REAL 3468 02:23:47,177 --> 02:23:48,779 PROBLEMS IN BIOLOGY THAT IT'S 3469 02:23:48,779 --> 02:23:50,480 HARD FOR THE HUMAN BRAIN TO 3470 02:23:50,480 --> 02:23:51,348 COMPREHEND. 3471 02:23:51,348 --> 02:23:53,250 I WANT TO GO BACK TO SOMETHING 3472 02:23:53,250 --> 02:23:54,184 YOU MENTIONED, THE TRAINING 3473 02:23:54,184 --> 02:23:54,918 DATA. 3474 02:23:54,918 --> 02:23:57,020 FOR PEOPLE WHO COME TO ME, I 3475 02:23:57,020 --> 02:23:58,388 DON'T ACTUALLY ASK SO MUCH 3476 02:23:58,388 --> 02:24:00,724 ABOUT WHAT YOUR A.I. SOLUTION 3477 02:24:00,724 --> 02:24:01,391 IS, BECAUSE HONESTLY BY THE 3478 02:24:01,391 --> 02:24:04,194 TIME YOU START IN SIX WEEKS 3479 02:24:04,194 --> 02:24:06,330 SOMEONE WILL PUBLISH A PAPER 3480 02:24:06,330 --> 02:24:07,331 AND SAY NO, I'M GOING TO DO 3481 02:24:07,331 --> 02:24:08,398 THIS. 3482 02:24:08,398 --> 02:24:11,668 LOTS OF HIGH QUALITY DATA, LOTS 3483 02:24:11,668 --> 02:24:12,869 OF REPRODUCIBLE DATA AND WHERE 3484 02:24:12,869 --> 02:24:13,570 IT'S COMING FROM. 3485 02:24:13,570 --> 02:24:15,539 IF YOU HAVE NOVEL SET OF DATA, 3486 02:24:15,539 --> 02:24:17,507 THEN WE CAN TALK ABOUT A.I. 3487 02:24:17,507 --> 02:24:19,376 >> Miljan Simonovic: FAIR 3488 02:24:19,376 --> 02:24:20,978 POINT, FAIR POINT. 3489 02:24:20,978 --> 02:24:24,281 >> IF I CAN JUMP IN TOO, DATA. 3490 02:24:24,281 --> 02:24:26,617 DATA IS WHAT IT'S ALL ABOUT. 3491 02:24:26,617 --> 02:24:28,218 THE ALGORITHMS AND CAPABILITIES 3492 02:24:28,218 --> 02:24:30,621 ARE JUST MOVING SO FAST. 3493 02:24:30,621 --> 02:24:32,322 ONE OF THE, ACTUALLY A COUPLE 3494 02:24:32,322 --> 02:24:34,057 IDEAS WE HAVE BEEN TALKING 3495 02:24:34,057 --> 02:24:35,158 ABOUT AT GINGKO, HOW WOULD YOU 3496 02:24:35,158 --> 02:24:35,826 DO THIS. 3497 02:24:35,826 --> 02:24:37,995 IF YOU THINK ABOUT SMALL 3498 02:24:37,995 --> 02:24:40,030 MOLECULES THAT ARE COMPLEX 3499 02:24:40,030 --> 02:24:41,298 NATURAL PRODUCTS, HOW DO THEY 3500 02:24:41,298 --> 02:24:43,300 GET MADE? 3501 02:24:43,300 --> 02:24:45,168 THERE ARE MASSIVE ENZYMES THE 3502 02:24:45,168 --> 02:24:50,607 SPOKE CREATE THESE THINGS. 3503 02:24:50,607 --> 02:24:52,476 WE DON'T UNDERSTAND, IF YOU 3504 02:24:52,476 --> 02:24:54,678 WILL, THE LANGUAGE THEY ARE 3505 02:24:54,678 --> 02:24:58,849 SPEAKING, WE KNOW THEY ARE 3506 02:24:58,849 --> 02:24:59,783 AMINO ACID SEQUENCES BUT IT 3507 02:24:59,783 --> 02:25:01,418 DOESN'T TELL US WHAT MOLECULE 3508 02:25:01,418 --> 02:25:02,586 THEY WILL MAKE. 3509 02:25:02,586 --> 02:25:04,221 CAN WE USE A.I. TO UNDERSTAND 3510 02:25:04,221 --> 02:25:06,556 THAT AND USE A.I. TO UNDERSTAND 3511 02:25:06,556 --> 02:25:08,425 THE REVERSE PROCESS, I HAVE 3512 02:25:08,425 --> 02:25:10,761 THIS MOLECULE, WHAT SEQUENCE OF 3513 02:25:10,761 --> 02:25:11,895 AMINO ACIDS DO I NEED TO MAKE 3514 02:25:11,895 --> 02:25:14,598 IT? 3515 02:25:14,598 --> 02:25:16,900 SO I THINK WE WILL GET THERE, 3516 02:25:16,900 --> 02:25:19,703 THIS IS A TACKLABLE PROBLEM. 3517 02:25:19,703 --> 02:25:21,605 BUT IN THIS ONE IN PARTICULAR, 3518 02:25:21,605 --> 02:25:25,108 WE ARE THINKING, OKAY, HOW MANY 3519 02:25:25,108 --> 02:25:26,710 NRPS'S DO WE NEED TO MAKE OF 3520 02:25:26,710 --> 02:25:29,279 WHAT KIND OF MUTATION ALCOVE 3521 02:25:29,279 --> 02:25:31,782 RAJ TO EVEN COLLECT THE DATA 3522 02:25:31,782 --> 02:25:35,285 THAT WILL TRAIN THOSE MODELS. 3523 02:25:35,285 --> 02:25:36,653 IT'S A HUGE ISSUE. 3524 02:25:36,653 --> 02:25:37,621 >> Miljan Simonovic: I BELIEVE 3525 02:25:37,621 --> 02:25:38,555 WE HAVE A QUESTION. 3526 02:25:38,555 --> 02:25:42,693 >> JUST A QUICK QUESTION. 3527 02:25:42,693 --> 02:25:48,765 WE HAVE A PRETTY DIVERSE PANEL, 3528 02:25:48,765 --> 02:25:55,272 REGULATORY AGENCIES, FUNDING 3529 02:25:55,272 --> 02:25:58,008 AGENCIES, THESE TEND TO CLASH. 3530 02:25:58,008 --> 02:26:00,610 MY QUESTION IS, DO YOU THINK 3531 02:26:00,610 --> 02:26:07,050 THERE ARE REDUNDANCIES IN PLACE 3532 02:26:07,050 --> 02:26:08,652 INHIBITING BIOMANUFACTURING OR 3533 02:26:08,652 --> 02:26:11,521 ARE THERE PITFALL THAT'S NEED 3534 02:26:11,521 --> 02:26:13,390 TO BE ADDRESSED? 3535 02:26:13,390 --> 02:26:14,891 MAYBE COMBINATION OF BOTH. 3536 02:26:14,891 --> 02:26:17,594 SUCH A MIX OF PEOPLE HERE. 3537 02:26:17,594 --> 02:26:20,931 SO VERY OPEN-ENDED QUESTION. 3538 02:26:20,931 --> 02:26:23,033 >> Miljan Simonovic: I CAN SAY 3539 02:26:23,033 --> 02:26:24,434 YOU'RE NOT CLASHING. 3540 02:26:24,434 --> 02:26:32,809 >> WE ARE PARTNERS. 3541 02:26:32,809 --> 02:26:33,844 REDUNDANCY SOMETIMES IS GOOD. 3542 02:26:33,844 --> 02:26:36,646 I APPRECIATE FOR EXAMPLE, WE 3543 02:26:36,646 --> 02:26:38,081 HAVE AN FDA THAT IS TRYING TO 3544 02:26:38,081 --> 02:26:41,385 MAKE SURE WE HAVE THE SAFEST 3545 02:26:41,385 --> 02:26:43,153 AND BEST MEDICINES AVAILABLE. 3546 02:26:43,153 --> 02:26:48,425 BUT I LOOK AT IT IS EARLY AND 3547 02:26:48,425 --> 02:26:49,059 OFTEN ENGAGEMENT THAT IS THE 3548 02:26:49,059 --> 02:26:53,764 KEY. 3549 02:26:53,764 --> 02:26:55,332 >> Lily Koo: I WOULD ALSO LIKE 3550 02:26:55,332 --> 02:26:58,702 TO ADD, I DO SEE IT AS A VERY 3551 02:26:58,702 --> 02:27:01,004 COLLABORATIVE PROCESS. 3552 02:27:01,004 --> 02:27:02,406 AND I TOTALLY UNDERSTAND WHERE 3553 02:27:02,406 --> 02:27:04,040 YOU ARE COMING FROM, YOU AREN'T 3554 02:27:04,040 --> 02:27:06,610 THE ONLY ONE WHO THINKS THAT 3555 02:27:06,610 --> 02:27:11,348 FDA IS RESPONSIBLE FOR 3556 02:27:11,348 --> 02:27:12,349 DETERRING IMPLEMENTATION OF 3557 02:27:12,349 --> 02:27:13,283 ANYTHING NEW. 3558 02:27:13,283 --> 02:27:14,918 MAYBE THERE WAS A TIME IT WAS 3559 02:27:14,918 --> 02:27:15,552 LIKE THAT. 3560 02:27:15,552 --> 02:27:19,289 I THINK RIGHT NOW, THE AGENCY 3561 02:27:19,289 --> 02:27:22,125 IS, WE ARE VERY OPEN TO, 3562 02:27:22,125 --> 02:27:25,529 BECAUSE WE REALIZE THE FIELD IS 3563 02:27:25,529 --> 02:27:26,897 MOVING QUICKLY AND THERE ARE A 3564 02:27:26,897 --> 02:27:27,798 LOT OF THINGS WE DON'T 3565 02:27:27,798 --> 02:27:28,565 UNDERSTAND. 3566 02:27:28,565 --> 02:27:30,400 IN MANY WAYS WE ARE ALSO 3567 02:27:30,400 --> 02:27:32,135 LEARNING FROM YOU, AND THIS IS 3568 02:27:32,135 --> 02:27:34,104 WHY WE ARE INTRODUCING 3569 02:27:34,104 --> 02:27:36,773 ENGAGEMENT WITH THE PEOPLE 3570 02:27:36,773 --> 02:27:41,711 INVOLVED, EVEN TECHNOLOGY 3571 02:27:41,711 --> 02:27:43,213 DEVELOPER AT AN EARLIER AND 3572 02:27:43,213 --> 02:27:46,950 EARLIER PHASE. 3573 02:27:46,950 --> 02:27:49,319 I THINK IT WOULD BE A MISTAKE 3574 02:27:49,319 --> 02:27:52,122 TO BE HESITANT TO TAKE 3575 02:27:52,122 --> 02:27:53,089 ADVANTAGE OF THE MEETINGS WE 3576 02:27:53,089 --> 02:27:54,291 OFFER. 3577 02:27:54,291 --> 02:27:57,060 THERE ARE DESIGNATIONS FOR 3578 02:27:57,060 --> 02:27:59,095 CERTAIN PRODUCTS WHETHER THEY 3579 02:27:59,095 --> 02:28:00,464 ARE BREAK THROUGH. 3580 02:28:00,464 --> 02:28:01,865 IF THE PRODUCT IS APPROPRIATE 3581 02:28:01,865 --> 02:28:03,133 FOR THAT DESIGNATION, YOU 3582 02:28:03,133 --> 02:28:03,767 SHOULD APPLY. 3583 02:28:03,767 --> 02:28:06,369 PART OF THE ADVANTAGE IS THERE 3584 02:28:06,369 --> 02:28:08,271 IS ADDITIONAL INTERACTION 3585 02:28:08,271 --> 02:28:09,873 IMPLEMENTED IN THAT PROCESS, 3586 02:28:09,873 --> 02:28:12,008 YOU CAN INTERACT WITH AGENCY 3587 02:28:12,008 --> 02:28:13,410 AND ACQUIRE ADDITIONAL FEEDBACK. 3588 02:28:13,410 --> 02:28:15,946 I THINK THAT BACK AND FORTH 3589 02:28:15,946 --> 02:28:17,347 THROUGHOUT DEVELOPMENT PHASE IS 3590 02:28:17,347 --> 02:28:18,315 ACTUALLY VERY, VERY IMPORTANT. 3591 02:28:18,315 --> 02:28:20,851 SO BEFORE YOU GO TOO FAR IN THE 3592 02:28:20,851 --> 02:28:22,786 WRONG DIRECTION, WE CAN, YOU 3593 02:28:22,786 --> 02:28:25,188 KNOW, ASK FOR CORRECTION AND WE 3594 02:28:25,188 --> 02:28:27,290 CAN POINT OUT TO YOU, HEY, 3595 02:28:27,290 --> 02:28:28,959 LOOK, THIS IS A CONCERN. 3596 02:28:28,959 --> 02:28:31,027 BEFORE, IF YOU ARE TOO FAR IN 3597 02:28:31,027 --> 02:28:31,962 THE OTHER DIRECTION. 3598 02:28:31,962 --> 02:28:39,870 SO THIS IS WHERE SOMETIMES 3599 02:28:39,870 --> 02:28:41,037 CLASHES IS INEVITABLE BUT WE 3600 02:28:41,037 --> 02:28:43,306 ALSO HAVE TO LEARN TO AGREE TO 3601 02:28:43,306 --> 02:28:44,074 DISAGREE. 3602 02:28:44,074 --> 02:28:46,409 BUT OF COURSE IN THE END WHAT 3603 02:28:46,409 --> 02:28:48,745 SHOWS IS DOES YOUR PRODUCT GET 3604 02:28:48,745 --> 02:28:50,413 IMPROVED OR NOT BASED ON THE 3605 02:28:50,413 --> 02:28:51,581 PRODUCT YOU DEMONSTRATE. 3606 02:28:51,581 --> 02:28:53,917 BUT OVERALL, I THINK IT'S A 3607 02:28:53,917 --> 02:28:57,053 VERY COLLABORATIVE PROCESS. 3608 02:28:57,053 --> 02:28:58,889 >> THAT CLASH WAS A HARSH WORD 3609 02:28:58,889 --> 02:29:00,624 TO SEE. 3610 02:29:00,624 --> 02:29:02,425 >> Lily Koo: CLASH ISN'T ALWAYS 3611 02:29:02,425 --> 02:29:04,327 A BAD THING, IT BRINGS OUT 3612 02:29:04,327 --> 02:29:05,462 DIFFERENT OPINIONS WE HAVE TO 3613 02:29:05,462 --> 02:29:07,130 LEARN TO RESPECT EACH OTHER AND 3614 02:29:07,130 --> 02:29:08,999 WORK TOGETHER, OUR GOAL IS THE 3615 02:29:08,999 --> 02:29:10,934 SAME THING, PATIENT SAFETY AND 3616 02:29:10,934 --> 02:29:12,269 PATIENT BENEFIT. 3617 02:29:12,269 --> 02:29:14,337 >> I ACTUALLY WANT TO THANK YOU 3618 02:29:14,337 --> 02:29:16,206 FOR THAT BRAVE QUESTION. 3619 02:29:16,206 --> 02:29:19,409 BECAUSE SOMETIMES WE DON'T 3620 02:29:19,409 --> 02:29:20,844 DISCUSS THE ELEPHANT IN THE 3621 02:29:20,844 --> 02:29:22,412 ROOM OR THINGS LIKE THAT. 3622 02:29:22,412 --> 02:29:24,047 BUT IT IS VERY IMPORTANT. 3623 02:29:24,047 --> 02:29:26,016 AND I THINK MEETINGS LIKE THIS 3624 02:29:26,016 --> 02:29:31,388 ARE SO IMPORTANT WHERE WE ALL 3625 02:29:31,388 --> 02:29:32,923 GET TO INTERACT AND HEAR WHAT'S 3626 02:29:32,923 --> 02:29:34,691 GOING ON IN THE DIFFERENT 3627 02:29:34,691 --> 02:29:36,059 GROUPS AND EXCHANGE INFORMATION. 3628 02:29:36,059 --> 02:29:43,600 AND I THINK THAT ALWAYS IS 3629 02:29:43,600 --> 02:29:45,902 HELPFUL, TRANSPARENCY AND 3630 02:29:45,902 --> 02:29:47,237 ABILITY TO EXCHANGE IDEAS AND 3631 02:29:47,237 --> 02:29:47,837 INFORMATION. 3632 02:29:47,837 --> 02:29:49,806 WE ARE ALL STAKEHOLDERS BUT YOU 3633 02:29:49,806 --> 02:29:52,242 ARE RIGHT, WE HAVE DIFFERENT 3634 02:29:52,242 --> 02:29:52,442 GOALS. 3635 02:29:52,442 --> 02:29:53,243 A LITTLE BIT DIFFERENT. 3636 02:29:53,243 --> 02:30:01,918 AND SO IT IS HELPFUL TO HELP 3637 02:30:01,918 --> 02:30:03,353 EACH OTHER UNDERSTAND WHAT IS 3638 02:30:03,353 --> 02:30:04,721 IMPORTANT, OR THE EXPERTISE OR 3639 02:30:04,721 --> 02:30:05,455 FOCUS. 3640 02:30:05,455 --> 02:30:05,922 IT'S HELPFUL. 3641 02:30:05,922 --> 02:30:08,024 SO THANK YOU FOR YOUR QUESTION. 3642 02:30:08,024 --> 02:30:10,193 >> SORRY, I KIND OF WANT TO 3643 02:30:10,193 --> 02:30:12,162 BUILD ON WHAT YOU ARE SAYING. 3644 02:30:12,162 --> 02:30:13,263 FROM ONE VIEW IT COULD BE 3645 02:30:13,263 --> 02:30:13,930 CLASH, RIGHT? 3646 02:30:13,930 --> 02:30:15,799 I WOULD SAY ANOTHER WAY TO 3647 02:30:15,799 --> 02:30:17,233 THINK, EVERYONE IS PAID TO LOOK 3648 02:30:17,233 --> 02:30:18,535 AT A PROBLEM IN A DIFFERENT 3649 02:30:18,535 --> 02:30:19,369 WAY, RIGHT? 3650 02:30:19,369 --> 02:30:21,905 SO THERE ARE JUST DIFFERENT 3651 02:30:21,905 --> 02:30:22,138 LENSES. 3652 02:30:22,138 --> 02:30:24,240 IT'S A CHALLENGE BACK WHEN YOU 3653 02:30:24,240 --> 02:30:25,842 ARE RESEARCH AND SAY THIS 3654 02:30:25,842 --> 02:30:30,380 TECHNOLOGY IS COOL, RIGHT? 3655 02:30:30,380 --> 02:30:32,115 LOOK WHAT IS HAPPENING AND THE 3656 02:30:32,115 --> 02:30:38,288 DATA, RIGHT? 3657 02:30:38,288 --> 02:30:40,357 ALL THE WAY TO YOU MAKING A 3658 02:30:40,357 --> 02:30:42,258 DIFFERENCE IN A PATIENCE'S LIFE. 3659 02:30:42,258 --> 02:30:44,160 ONE STEP IS YOU WANT TO MAKE A 3660 02:30:44,160 --> 02:30:45,395 COMPANY, RIGHT? 3661 02:30:45,395 --> 02:30:47,397 THEY DON'T CARE AS MUCH ABOUT 3662 02:30:47,397 --> 02:30:48,798 THE COOL TECHNOLOGY, CAN WE 3663 02:30:48,798 --> 02:30:50,433 MAKE MONEY, RIGHT? 3664 02:30:50,433 --> 02:30:51,334 ULTIMATELY BECAUSE IT DOESN'T 3665 02:30:51,334 --> 02:30:52,535 EXIST. 3666 02:30:52,535 --> 02:30:54,938 THE FDA, THEY ARE PAID, IS IT 3667 02:30:54,938 --> 02:30:56,473 SAFE, RIGHT? 3668 02:30:56,473 --> 02:30:58,408 IT'S SAFE AND EFFICACIOUS BUT 3669 02:30:58,408 --> 02:31:00,944 IF I HAVE TO INJECT MYSELF FIVE 3670 02:31:00,944 --> 02:31:02,646 TIMES A DAY, MY LIFE ISN'T 3671 02:31:02,646 --> 02:31:03,513 BETTER, RIGHT? 3672 02:31:03,513 --> 02:31:05,815 SO ALL OF THESE ARE VALID 3673 02:31:05,815 --> 02:31:06,850 VIEWPOINTS ON LOOKING AT A 3674 02:31:06,850 --> 02:31:17,060 TECHNOLOGY. 3675 02:31:20,597 --> 02:31:22,365 WHERE YOU RUN INTO TROUBLE, 3676 02:31:22,365 --> 02:31:23,633 RUNNING FULL STEAM AND YOU 3677 02:31:23,633 --> 02:31:26,269 NEVER CONSIDER THAT THE OTHER 3678 02:31:26,269 --> 02:31:28,805 PEOPLE GATE KEEPERS ALL ALONG 3679 02:31:28,805 --> 02:31:31,341 THE WAY THAT DON'T LOOK AT IT 3680 02:31:31,341 --> 02:31:32,509 FROM A DIFFERENT VIEWPOINT OR 3681 02:31:32,509 --> 02:31:33,943 YOU DIDN'T LOOK AT THE LANGUAGE 3682 02:31:33,943 --> 02:31:34,844 OR THE EXPERIMENT TO TALK TO 3683 02:31:34,844 --> 02:31:35,578 THEM. 3684 02:31:35,578 --> 02:31:38,381 SO THE EARLIER YOU CAN START TO 3685 02:31:38,381 --> 02:31:42,819 TALK TO THEM TO THINK ABOUT 3686 02:31:42,819 --> 02:31:43,753 THEIR FRAMEWORK, THE BETTER OFF 3687 02:31:43,753 --> 02:31:44,587 YOU ARE. 3688 02:31:44,587 --> 02:31:46,256 >> I AGREE WITH THAT, IF YOU 3689 02:31:46,256 --> 02:31:47,857 HAVE A NOVEL TECHNOLOGY AND YOU 3690 02:31:47,857 --> 02:31:53,163 WERE TO EARLY ON PITCH IT TO A 3691 02:31:53,163 --> 02:31:55,365 QUALITY PERSON OR REGULATORY, 3692 02:31:55,365 --> 02:31:58,902 FDA ESPECIALLY CBER HAS BEEN 3693 02:31:58,902 --> 02:32:00,236 WELCOMING TECHNOLOGIES AT THEIR 3694 02:32:00,236 --> 02:32:01,471 INCEPTION POINTS. 3695 02:32:01,471 --> 02:32:02,939 BUT TRADITIONALLY IF YOU DO 3696 02:32:02,939 --> 02:32:13,450 THAT, YOU MIGHT GET A LOT OF 3697 02:32:15,685 --> 02:32:16,519 CONCERN, IT'S HELPFUL. 3698 02:32:16,519 --> 02:32:18,421 THE CLASH IS GREAT JUST AN 3699 02:32:18,421 --> 02:32:19,556 EARLY WARNING OF WHAT YOU WILL 3700 02:32:19,556 --> 02:32:20,490 FACE DOWN THE ROAD. 3701 02:32:20,490 --> 02:32:21,725 >> THANK YOU. 3702 02:32:21,725 --> 02:32:28,798 >> Miljan Simonovic: THANK YOU. 3703 02:32:28,798 --> 02:32:30,700 >> Lily Koo: ONE POINT ON A.I.? 3704 02:32:30,700 --> 02:32:33,837 I WANT YOU TO BE AWARE LAST 3705 02:32:33,837 --> 02:32:35,505 MONTH FDA ACTUALLY HAD A 3706 02:32:35,505 --> 02:32:37,340 WORKSHOP DISCUSSING THE 3707 02:32:37,340 --> 02:32:39,242 APPLICATION OF A.I. AND MACHINE 3708 02:32:39,242 --> 02:32:40,143 LEARNING IN MANUFACTURING, 3709 02:32:40,143 --> 02:32:40,410 RIGHT? 3710 02:32:40,410 --> 02:32:44,948 SO THIS IS SOMETHING I THINK 3711 02:32:44,948 --> 02:32:48,485 MAYBE IS COLLABORATIVE EFFORT 3712 02:32:48,485 --> 02:32:52,789 BETWEEN PQRA AND CBER. 3713 02:32:52,789 --> 02:32:54,224 I THINK IT'S VERY INTERESTING 3714 02:32:54,224 --> 02:32:55,592 WITH APPLICATION OF A.I., THIS 3715 02:32:55,592 --> 02:32:57,026 IS SOMETHING WE DON'T HAVE A 3716 02:32:57,026 --> 02:32:58,661 LOT OF EXPERIENCE YET, 3717 02:32:58,661 --> 02:33:01,931 ESPECIALLY IN MANUFACTURING. 3718 02:33:01,931 --> 02:33:03,800 BUT BASED ON PUBLIC COMMENT WE 3719 02:33:03,800 --> 02:33:05,201 HAVE IDENTIFIED SOME AREAS 3720 02:33:05,201 --> 02:33:09,372 WHERE AT LEAST THE INDUSTRY IS 3721 02:33:09,372 --> 02:33:12,142 THINKING HOW A.I. CAN BE 3722 02:33:12,142 --> 02:33:22,285 APPLIED. 3723 02:33:24,854 --> 02:33:27,557 YES, PEOPLE ARE THINKING ABOUT 3724 02:33:27,557 --> 02:33:31,694 USING A.I. AND MACHINE LEARNING 3725 02:33:31,694 --> 02:33:34,264 OR HYBRID MODEL TO APPLY FOR 3726 02:33:34,264 --> 02:33:36,366 PROCESS CONTROL POTENTIALLY OR 3727 02:33:36,366 --> 02:33:37,433 SOMETIMES JUST PROCESS 3728 02:33:37,433 --> 02:33:47,744 MONITORING, RIGHT? 3729 02:33:49,646 --> 02:33:51,214 TO INFORM YOU IF SOMETHING IS 3730 02:33:51,214 --> 02:33:52,148 DEVIATING. 3731 02:33:52,148 --> 02:33:54,484 A.I. COULD BE VERY COMPLICATED, 3732 02:33:54,484 --> 02:33:57,120 WHAT DO WE NEED TO TELL YOU, 3733 02:33:57,120 --> 02:33:58,688 FDA, RITE? 3734 02:33:58,688 --> 02:33:59,689 -- RIGHT? 3735 02:33:59,689 --> 02:34:00,890 THIS IS SOMETHING WE ARE STILL 3736 02:34:00,890 --> 02:34:01,491 WORKING OUT. 3737 02:34:01,491 --> 02:34:04,327 BUT WE THINK IT SHOULD BE A 3738 02:34:04,327 --> 02:34:14,404 RISK-BASED ASSESSMENT, RIGHT? 3739 02:34:14,404 --> 02:34:16,472 HOW YOUR ALGORITHM IS BUILT, 3740 02:34:16,472 --> 02:34:18,141 WHAT IT IS INTENDED FOR AND 3741 02:34:18,141 --> 02:34:19,108 WHAT KIND OF DECISION IT COULD 3742 02:34:19,108 --> 02:34:19,976 MAKE. 3743 02:34:19,976 --> 02:34:22,078 BUT MAYBE LOWER RISK, MAYBE WE 3744 02:34:22,078 --> 02:34:24,180 DON'T NEED AS MUCH INFORMATION. 3745 02:34:24,180 --> 02:34:26,015 WHEN IF YOU ARE A.I. AND 3746 02:34:26,015 --> 02:34:27,217 MACHINE LEARNING MODEL IS PUT 3747 02:34:27,217 --> 02:34:30,553 IN A PROCESS CONTROL AND IT 3748 02:34:30,553 --> 02:34:33,356 COULD ACTUALLY ACTIVELY MAKE 3749 02:34:33,356 --> 02:34:34,524 MANUFACTURING DECISIONS THIS IS 3750 02:34:34,524 --> 02:34:38,161 WHERE THERE WILL BE GREATER 3751 02:34:38,161 --> 02:34:39,429 SCRUTINY. 3752 02:34:39,429 --> 02:34:42,532 DATA IS SO CRITICAL, RIGHT? 3753 02:34:42,532 --> 02:34:46,002 OTHERWISE PEOPLE SAY GARBAGE 3754 02:34:46,002 --> 02:34:46,703 IN, GARBAGE OUT. 3755 02:34:46,703 --> 02:34:48,838 WE WANT TO MAKE SURE THE DATA 3756 02:34:48,838 --> 02:34:50,673 IS GOOD AND THE MODEL DOESN'T 3757 02:34:50,673 --> 02:34:52,108 SHIFT OVER TIME. 3758 02:34:52,108 --> 02:34:54,210 HE IS SPSHLLY A.I. MACHINE 3759 02:34:54,210 --> 02:34:56,145 LEARNING, THE MODEL IS BEG 3760 02:34:56,145 --> 02:34:57,247 CONTINUOUSLY UPDATED. 3761 02:34:57,247 --> 02:35:00,316 HOW ARE WE GOING TO MONITOR ITS 3762 02:35:00,316 --> 02:35:01,684 PERFORMANCE AND WHAT KIND OF 3763 02:35:01,684 --> 02:35:04,387 POST APPROVAL CHANGE WILL BE 3764 02:35:04,387 --> 02:35:05,588 REQUIRED FOR FDA TO CONSIDER. 3765 02:35:05,588 --> 02:35:07,457 THESE ARE THINGS WE DON'T HAVE 3766 02:35:07,457 --> 02:35:08,825 ANSWERS YET BUT WE ARE THINKING 3767 02:35:08,825 --> 02:35:10,727 ABOUT IT AND BASED ON A LOT OF 3768 02:35:10,727 --> 02:35:11,794 FEEDBACK FROM THE PUBLIC. 3769 02:35:11,794 --> 02:35:13,796 IF YOU DIDN'T ATTEND A 3770 02:35:13,796 --> 02:35:14,864 WORKSHOP, I DEFINITELY WELCOME 3771 02:35:14,864 --> 02:35:16,199 YOU TO CHECK IT OUT. 3772 02:35:16,199 --> 02:35:17,600 >> Miljan Simonovic: THAT'S 3773 02:35:17,600 --> 02:35:18,201 GREAT, YEAH. 3774 02:35:18,201 --> 02:35:20,403 >> IF I CAN JUST JUMP ONTO THAT 3775 02:35:20,403 --> 02:35:21,804 AS WELL. 3776 02:35:21,804 --> 02:35:23,139 SOMETHING THAT GINGKO HAS BEEN 3777 02:35:23,139 --> 02:35:25,675 THINKING ABOUT THROUGH OUR 3778 02:35:25,675 --> 02:35:27,510 CONCENTRIC BIO SECURITY ARM IS 3779 02:35:27,510 --> 02:35:31,314 USE AND MISUSE OF A.I. MODELS 3780 02:35:31,314 --> 02:35:33,449 LIKE CHATGPT. 3781 02:35:33,449 --> 02:35:38,454 CAN SOMEBODY REQUEST IN SOME 3782 02:35:38,454 --> 02:35:40,556 SEEMINGLY BENIGN WAY FOR 3783 02:35:40,556 --> 02:35:41,724 CHATGPT TO GIVE THEM 3784 02:35:41,724 --> 02:35:43,359 INFORMATION THAT IS ACTUALLY 3785 02:35:43,359 --> 02:35:53,770 NOT BENIGN INFORMATION. 3786 02:35:56,139 --> 02:35:58,207 WE NEED TO KNOW THE DATA THAT 3787 02:35:58,207 --> 02:36:00,977 GOES IN, BUT THE DATA THAT 3788 02:36:00,977 --> 02:36:05,882 COMES OUT, IS INSCRUTABLE. 3789 02:36:05,882 --> 02:36:07,750 HOW DO YOU VALIDATE THAT. 3790 02:36:07,750 --> 02:36:10,520 SOMETHING ELSE IS CALLED RED 3791 02:36:10,520 --> 02:36:10,753 TEAMING. 3792 02:36:10,753 --> 02:36:13,156 SO PRESENT THE MODEL WITH ALL 3793 02:36:13,156 --> 02:36:15,258 KINDS OF SCENARIOS AND SEE HOW 3794 02:36:15,258 --> 02:36:16,592 IT RESPONDS. 3795 02:36:16,592 --> 02:36:18,494 SO LIKE HOW WOULD YOU READ TEAM 3796 02:36:18,494 --> 02:36:21,264 TO DEATH A MANUFACTURING 3797 02:36:21,264 --> 02:36:22,432 ALGORITHM SO THAT EVEN THOUGH 3798 02:36:22,432 --> 02:36:24,067 YOU DON'T UNDERSTAND REALLY 3799 02:36:24,067 --> 02:36:25,969 WHAT THAT ALGORITHM IS, YOU 3800 02:36:25,969 --> 02:36:28,071 KNOW HOW IT WILL RESPOND UNDER 3801 02:36:28,071 --> 02:36:29,105 ALL THE SITUATIONS YOU CARE 3802 02:36:29,105 --> 02:36:30,540 ABOUT. 3803 02:36:30,540 --> 02:36:31,874 >> Miljan Simonovic: SO TRUST, 3804 02:36:31,874 --> 02:36:33,509 BUT VALIDATE. 3805 02:36:33,509 --> 02:36:34,444 >> David Borhani: YEAH. 3806 02:36:34,444 --> 02:36:35,545 >> Miljan Simonovic: THAT'S 3807 02:36:35,545 --> 02:36:36,179 VERY GOOD. 3808 02:36:36,179 --> 02:36:40,116 I THINK WE CAN GO ON AND ON AND 3809 02:36:40,116 --> 02:36:42,452 ON. 3810 02:36:42,452 --> 02:36:44,520 THERE IS A LIST OF QUESTIONS I 3811 02:36:44,520 --> 02:36:46,856 MAY BE ASKING, BUT LILY 3812 02:36:46,856 --> 02:36:48,124 ACTUALLY BROUGHT A VERY GOOD 3813 02:36:48,124 --> 02:36:50,360 POINT TO ALL OF YOU, IS TO GO 3814 02:36:50,360 --> 02:36:51,828 OUT ON THE WEBSITES AND SEEK 3815 02:36:51,828 --> 02:36:53,830 INFORMATION. 3816 02:36:53,830 --> 02:36:55,898 FEDERAL AGENCIES HAVE ALWAYS 3817 02:36:55,898 --> 02:36:57,867 ANNOUNCEMENTS ABOUT FUNDING 3818 02:36:57,867 --> 02:36:58,701 MECHANISMS, OPPORTUNITIES. 3819 02:36:58,701 --> 02:37:00,670 SO YOU CAN ACTUALLY SEEK 3820 02:37:00,670 --> 02:37:03,306 INFORMATION, GO TO WORKSHOPS 3821 02:37:03,306 --> 02:37:13,683 AND EDUCATE YOURSELF. 3822 02:37:14,183 --> 02:37:19,589 WHAT FUNDING AGENCIES, WITHIN 3823 02:37:19,589 --> 02:37:23,926 NIH THERE IS A GAZILLION 3824 02:37:23,926 --> 02:37:26,229 INSTITUTES, ACTUALLY IT'S A 3825 02:37:26,229 --> 02:37:31,634 LIMITED NUMBER OF INSTITUTES. 3826 02:37:31,634 --> 02:37:33,469 NIBIB IS DIFFERENT. 3827 02:37:33,469 --> 02:37:34,670 GOOGLE MAY BE YOUR FRIEND IN 3828 02:37:34,670 --> 02:37:36,239 THAT CASE. 3829 02:37:36,239 --> 02:37:37,807 AT ANY RATE, AT THIS POINT, I 3830 02:37:37,807 --> 02:37:39,442 THINK MANY OF YOU ARE PROBABLY 3831 02:37:39,442 --> 02:37:40,209 HUNGRY AT THIS POINT. 3832 02:37:40,209 --> 02:37:42,945 I WOULD LIKE TO THANK THE 3833 02:37:42,945 --> 02:37:43,913 PANELISTS FOR AN AMAZING 3834 02:37:43,913 --> 02:37:44,414 DISCUSSION. 3835 02:37:44,414 --> 02:37:46,015 AND I WOULD LIKE TO THANK YOU 3836 02:37:46,015 --> 02:37:47,216 FOR YOUR PATIENCE AND ATTENTION. 3837 02:37:47,216 --> 02:37:48,117 THANK YOU. 3838 02:37:48,117 --> 02:37:53,331 [ APPLAUSE ] 3839 02:37:56,146 --> 02:37:58,248 WELCOME, THIS IS THE FRIDAY AFTERNOON SESSION 3840 02:37:58,248 --> 02:38:01,819 FOR THIS WONDERFUL SYNTHETIC 3841 02:38:01,819 --> 02:38:05,723 BIOLOGY MEETING HOSTED BY NIBIB. 3842 02:38:05,723 --> 02:38:10,527 MY NAME IS RAHUL THAKAR. 3843 02:38:10,527 --> 02:38:13,530 I WILL BE THE MODERATOR THIS 3844 02:38:13,530 --> 02:38:13,797 AFTERNOON. 3845 02:38:13,797 --> 02:38:17,634 THE CHALLENGE FOR THE SESSIONS 3846 02:38:17,634 --> 02:38:20,971 IN THE AFTERNOON WILL BE 3847 02:38:20,971 --> 02:38:24,775 GETTING EVERYBODY EXCITED BUT 3848 02:38:24,775 --> 02:38:25,809 AS EVERYBODY IS THINKING ABOUT 3849 02:38:25,809 --> 02:38:26,410 THE WEEKEND. 3850 02:38:26,410 --> 02:38:28,078 BUT I THINK THIS WILL BE 3851 02:38:28,078 --> 02:38:28,345 DIFFERENT. 3852 02:38:28,345 --> 02:38:29,947 WE HAVE A LOT OF GOOD SPEAKERS 3853 02:38:29,947 --> 02:38:30,814 AND THESE SORTS OF 3854 02:38:30,814 --> 02:38:31,815 COLLABORATIONS. 3855 02:38:31,815 --> 02:38:39,890 OUR FIRST SPEAKER IS DR. SUZIE 3856 02:38:39,890 --> 02:38:41,558 PUN AT UNIVERSITY OF 3857 02:38:41,558 --> 02:38:43,193 WASHINGTON, DIRECTOR OF 3858 02:38:43,193 --> 02:38:44,895 MOLECULAR ENGINEERING AND 3859 02:38:44,895 --> 02:38:45,696 SCIENCE INSTITUTE. 3860 02:38:45,696 --> 02:38:47,364 AND SHE IS THE ASSOCIATE 3861 02:38:47,364 --> 02:38:50,367 DIRECTOR OF THE RESUSCITATION 3862 02:38:50,367 --> 02:38:53,537 ENGINEERING SCIENCE UNIT, OR 3863 02:38:53,537 --> 02:38:54,938 RESCU. 3864 02:38:54,938 --> 02:38:58,876 BEFORE SHE GOT TO WASHINGTON, 3865 02:38:58,876 --> 02:39:00,744 SHE RECEIVED HER Ph.D. AT CAL 3866 02:39:00,744 --> 02:39:03,547 TECH AND SHE DID OUR 3867 02:39:03,547 --> 02:39:06,316 UNDERGRADUATE WORK IN CHEMICAL 3868 02:39:06,316 --> 02:39:07,251 ENGINEERING AT STANFORD. 3869 02:39:07,251 --> 02:39:10,554 SHE HAS AN INCREDIBLE BODY OF 3870 02:39:10,554 --> 02:39:11,255 RESEARCH, INCREDIBLE 3871 02:39:11,255 --> 02:39:13,590 DISCOVERIES, DEVELOPMENTS AND 3872 02:39:13,590 --> 02:39:14,758 AN INCREDIBLE FOCUS ON 3873 02:39:14,758 --> 02:39:15,692 MENTORSHIP AS WELL. 3874 02:39:15,692 --> 02:39:17,561 HER TALK WILL COVER WHAT SHE 3875 02:39:17,561 --> 02:39:20,697 HAS DEVELOPED WITH RESPECT TO 3876 02:39:20,697 --> 02:39:23,267 POLYMERIC DRUG DELIVERY AND 3877 02:39:23,267 --> 02:39:24,935 COMBINING WITH DRUG DELIVERY 3878 02:39:24,935 --> 02:39:28,605 FOR CELL AND GENE THERAPY AND 3879 02:39:28,605 --> 02:39:30,607 REGENERATIVE THERAPY IN GENERAL. 3880 02:39:30,607 --> 02:39:40,751 DR. PUN? 3881 02:39:43,387 --> 02:39:44,955 >> Suzie Pun: HI, EVERYONE. 3882 02:39:44,955 --> 02:39:47,991 IT'S A PLEASURE TO SPEAK TO YOU 3883 02:39:47,991 --> 02:39:49,660 ABOUT THE RESEARCH WE ARE DOING 3884 02:39:49,660 --> 02:39:51,962 AT UNIVERSITY OF WASHINGTON. 3885 02:39:51,962 --> 02:39:54,064 LET ME JUST GET MY SLIDES UP. 3886 02:39:54,064 --> 02:39:56,300 IT'S STRANGE TO SEE MY GIANT 3887 02:39:56,300 --> 02:39:57,367 FACE UP THERE. 3888 02:39:57,367 --> 02:40:02,673 OKAY, ALL RIGHT. 3889 02:40:02,673 --> 02:40:04,975 SO TODAY I WILL TELL YOU ABOUT 3890 02:40:04,975 --> 02:40:09,246 WHAT WE ARE DEVELOPING FOR CELL 3891 02:40:09,246 --> 02:40:11,515 DELIVERING MANUFACTURING. 3892 02:40:11,515 --> 02:40:15,152 SO JUST A QUICK OVERVIEW OF THE 3893 02:40:15,152 --> 02:40:18,522 CONCEPT OF CAR T-CELL THERAPY. 3894 02:40:18,522 --> 02:40:23,227 THE BASIC PREMISE IS THAT WE 3895 02:40:23,227 --> 02:40:24,628 HARVEST THE WHITE BLOOD CELLS 3896 02:40:24,628 --> 02:40:27,764 FROM THE PATIENT, ISOLATE 3897 02:40:27,764 --> 02:40:29,399 T-CELLS AND ENGINEER THE 3898 02:40:29,399 --> 02:40:31,001 T-CELLS SO THEY CAN RECOGNIZE 3899 02:40:31,001 --> 02:40:33,403 AND FIGHT THE TUMOR AND 3900 02:40:33,403 --> 02:40:34,872 REINTRODUCE THESE INTO THE 3901 02:40:34,872 --> 02:40:35,139 PATIENTS. 3902 02:40:35,139 --> 02:40:36,940 THERE HAVE BEEN GREAT SUCCESSES 3903 02:40:36,940 --> 02:40:39,977 IN CERTAIN TYPES OF CANCERS 3904 02:40:39,977 --> 02:40:43,413 USING CAR T-CELL THERAPIES AND 3905 02:40:43,413 --> 02:40:47,618 CURRENTLY THERE ARE SIX FDA 3906 02:40:47,618 --> 02:40:49,153 APPROVED CAR T-CELL THERAPY 3907 02:40:49,153 --> 02:40:50,187 PRODUCTS ON THE MARKET. 3908 02:40:50,187 --> 02:40:52,789 TODAY I WILL TELL YOU ABOUT THE 3909 02:40:52,789 --> 02:41:02,599 MANUFACTURING PROCESS FOR 3910 02:41:02,599 --> 02:41:05,302 BREYANZI, WHICH IS THE BRISTOL 3911 02:41:05,302 --> 02:41:07,938 MYERS. 3912 02:41:07,938 --> 02:41:10,807 FOR BREYANZI, THE PATIENT UNDER 3913 02:41:10,807 --> 02:41:20,884 GOES A LEUKO PARESIS PROCESS 3914 02:41:20,884 --> 02:41:22,886 WHICH SEPARATES THE WHITE BLOOD 3915 02:41:22,886 --> 02:41:23,921 CELLS. 3916 02:41:23,921 --> 02:41:28,158 AMONG THE APPROVED T-CELL 3917 02:41:28,158 --> 02:41:31,228 PRODUCTS, BREYANZI USES DEFINED 3918 02:41:31,228 --> 02:41:33,397 RATIO OF CD4 AND T-CELLS IN THE 3919 02:41:33,397 --> 02:41:34,865 FINAL PRODUCT. 3920 02:41:34,865 --> 02:41:37,067 THE FINAL STEP AFTER THIS IS TO 3921 02:41:37,067 --> 02:41:38,669 ACTIVATE THE T-CELLS SO THEY 3922 02:41:38,669 --> 02:41:40,070 ARE PROLIFERATING WHICH ALLOWS 3923 02:41:40,070 --> 02:41:45,609 THEM TO BE TRANSDEUCED USING 3924 02:41:45,609 --> 02:41:47,110 RETRO VIRAL VECTORS. 3925 02:41:47,110 --> 02:41:54,451 AND THE ENGINEER CELLS 3926 02:41:54,451 --> 02:41:56,220 TRANSDUCED TO RECEPTORS, THESE 3927 02:41:56,220 --> 02:41:58,188 T CELLS ARE REINJECTED BACK 3928 02:41:58,188 --> 02:41:59,856 INTO THE PATIENT. 3929 02:41:59,856 --> 02:42:04,261 NOW ALL OF THE SIX FDA-APPROVED 3930 02:42:04,261 --> 02:42:07,264 T CELL PRODUCTS COST SOMEWHERE 3931 02:42:07,264 --> 02:42:09,967 BETWEEN $350,000 AND $500,000 3932 02:42:09,967 --> 02:42:10,534 PER PATIENT. 3933 02:42:10,534 --> 02:42:13,303 IT IS QUITE A TIME INTENSIVE 3934 02:42:13,303 --> 02:42:14,571 MANUFACTURING PROCESS AS WELL. 3935 02:42:14,571 --> 02:42:19,042 SO IT'S HIGH COST AND ALSO AN 3936 02:42:19,042 --> 02:42:20,143 EXPENSIVE PROCESS. 3937 02:42:20,143 --> 02:42:21,745 SO WHEN WE CAME INTO THIS FIELD 3938 02:42:21,745 --> 02:42:23,614 WE WANTED TO SEE IF THERE WERE 3939 02:42:23,614 --> 02:42:25,249 WAYS WE COULD IMPROVE 3940 02:42:25,249 --> 02:42:26,883 MANUFACTURING AND MAKE THE 3941 02:42:26,883 --> 02:42:28,118 PRODUCT MORE ACCESSIBLE FOR 3942 02:42:28,118 --> 02:42:36,193 MORE PEOPLE. 3943 02:42:36,193 --> 02:42:39,229 THE STATUS QUO IS THE FIRST TWO 3944 02:42:39,229 --> 02:42:41,331 STEPS FOR ISOLATION, AS WELL AS 3945 02:42:41,331 --> 02:42:42,866 FOR ACTIVATION, BOTH USE 3946 02:42:42,866 --> 02:42:44,368 ANTIBODIES. 3947 02:42:44,368 --> 02:42:46,737 SO YOU USE ANTIBODIES TO SELECT 3948 02:42:46,737 --> 02:42:50,774 THE CELLS AND ANTIBODIES TO 3949 02:42:50,774 --> 02:42:53,710 ACTIVATE THE CELLS AND THIRD 3950 02:42:53,710 --> 02:42:56,013 PROCESS USES VIRAL VECTORS. 3951 02:42:56,013 --> 02:42:58,448 ALL ARE EXPENSIVE REAGENTS. 3952 02:42:58,448 --> 02:43:00,450 TODAY I WILL FOCUS ON THIS VERY 3953 02:43:00,450 --> 02:43:01,918 FIRST STEP, WHICH IS THE 3954 02:43:01,918 --> 02:43:09,860 ISOLATION STEP. 3955 02:43:09,860 --> 02:43:14,564 IT USES ANTIBODIES MOBILIZED ON 3956 02:43:14,564 --> 02:43:18,502 MAGNETIC BEADS AND MAGNET IS 3957 02:43:18,502 --> 02:43:19,536 INTRODUCED TO SELECT THE CELLS 3958 02:43:19,536 --> 02:43:20,871 OF INTEREST. 3959 02:43:20,871 --> 02:43:23,640 WHEN THE MAGNET IS REMOVED, 3960 02:43:23,640 --> 02:43:25,142 THEY ARE STILL ASSOCIATED WITH 3961 02:43:25,142 --> 02:43:28,178 THE CELLS. 3962 02:43:28,178 --> 02:43:34,651 THEY HAVE MAGNETIC IRON OXIDE 3963 02:43:34,651 --> 02:43:34,851 BEADS. 3964 02:43:34,851 --> 02:43:38,622 THEY ARE ALREADY MARK WITH THE 3965 02:43:38,622 --> 02:43:39,189 MAGNETIC BEADS. 3966 02:43:39,189 --> 02:43:42,492 WE SAW THERE WAS A NEED FOR A 3967 02:43:42,492 --> 02:43:44,594 LOW-COST, TRACELESS AND 3968 02:43:44,594 --> 02:43:45,228 POTENTIALLY FASTER METHOD OF 3969 02:43:45,228 --> 02:43:45,996 SELECTION. 3970 02:43:45,996 --> 02:43:47,397 SO THAT'S WHAT I WANT TO TALK 3971 02:43:47,397 --> 02:43:48,532 TO YOU ABOUT TODAY. 3972 02:43:48,532 --> 02:43:49,966 THIS IS IN THE CONTEXT OF SOME 3973 02:43:49,966 --> 02:43:52,102 OF THE WORK WE HAVE BEEN DOING 3974 02:43:52,102 --> 02:43:53,003 IN MY LAB. 3975 02:43:53,003 --> 02:43:55,372 AS YOU WILL SEE THIS IS THE 3976 02:43:55,372 --> 02:43:57,541 THREE DIFFERENT PROCESSES, 3977 02:43:57,541 --> 02:43:58,342 ISOLATION, SELECTION, AND 3978 02:43:58,342 --> 02:43:59,209 GENETIC MODIFICATION. 3979 02:43:59,209 --> 02:44:04,147 WE PUT A REVIEW ARTICLE ON THE 3980 02:44:04,147 --> 02:44:05,315 DIFFERENT SYNTHETIC MATERIALS 3981 02:44:05,315 --> 02:44:06,750 MY LAB HAS BEEN DEVELOPING FOR 3982 02:44:06,750 --> 02:44:09,052 EACH STEP. 3983 02:44:09,052 --> 02:44:10,320 FOR TODAY'S PURPOSES WE WILL 3984 02:44:10,320 --> 02:44:11,455 JUST TALK ABOUT THE ISOLATION 3985 02:44:11,455 --> 02:44:18,962 STEP. 3986 02:44:18,962 --> 02:44:28,372 I WILL TALK ABOUT AN APTEMER 3987 02:44:28,372 --> 02:44:32,509 PROCESS AND DERIVATIVE TO USE 3988 02:44:32,509 --> 02:44:33,977 APTAMER BASED TRACELESS T-CELL 3989 02:44:33,977 --> 02:44:35,112 FOR SELECTION OF THE PRODUCT. 3990 02:44:35,112 --> 02:44:38,148 I WILL TELL YOU ABOUT 3991 02:44:38,148 --> 02:44:39,516 MULTIPLEXED METHOD, WE BELIEVE 3992 02:44:39,516 --> 02:44:41,418 WE CAN IMPROVE EFFICACY. 3993 02:44:41,418 --> 02:44:43,553 AND I WILL TALK A LITTLE ABOUT 3994 02:44:43,553 --> 02:44:44,888 OUR EYE TOWARD MANUFACTURING 3995 02:44:44,888 --> 02:44:46,390 AND ADAPTING THIS METHOD FOR 3996 02:44:46,390 --> 02:44:52,596 MANUFACTURING PROCESS. 3997 02:44:52,596 --> 02:44:53,730 WHAT ARE APTAMERS? 3998 02:44:53,730 --> 02:44:56,133 HOW MANY IN THE AUDIENCE KNOW 3999 02:44:56,133 --> 02:44:57,033 WHAT APTAMERS ARE? 4000 02:44:57,033 --> 02:44:59,169 IF YOU COULD RAISE YOUR HAND. 4001 02:44:59,169 --> 02:45:00,804 IT'S A LARGE PERCENTAGE. 4002 02:45:00,804 --> 02:45:02,339 I'M SO PLEASED. 4003 02:45:02,339 --> 02:45:06,777 SO APTAMERS ARE BASICALLY 4004 02:45:06,777 --> 02:45:09,179 SEQUENCE OF OLIGO NUCLEOTIDE 4005 02:45:09,179 --> 02:45:11,448 THAT CAN FOLD THEMSELVES ON A 4006 02:45:11,448 --> 02:45:12,582 SECONDARY STRUCTURE. 4007 02:45:12,582 --> 02:45:15,152 WHAT REALLY CAUGHT OUR 4008 02:45:15,152 --> 02:45:16,553 INTEREST, THEY HAVE HIGH 4009 02:45:16,553 --> 02:45:18,922 AFFINITY FOR THEIR TARGET. 4010 02:45:18,922 --> 02:45:22,259 THEY HAVE NANO MOW LAR BINDING, 4011 02:45:22,259 --> 02:45:24,895 SIMILAR TO ANTIBODIES BUT 4012 02:45:24,895 --> 02:45:30,767 CONTRAST TO ANTIBODIES WHICH 4013 02:45:30,767 --> 02:45:32,202 ARE NATURALLY MADE, APTAMERS 4014 02:45:32,202 --> 02:45:33,370 ARE SYNTHETIC. 4015 02:45:33,370 --> 02:45:42,813 ON A MOLAR THEY ARE HALF THE 4016 02:45:42,813 --> 02:45:44,915 COST, THEY CAN BE HIGHLY STABLE 4017 02:45:44,915 --> 02:45:46,550 AND ALSO VERY, VERY UNIFORM. 4018 02:45:46,550 --> 02:45:48,752 THEY AREN'T GOING TO VARY 4019 02:45:48,752 --> 02:45:50,086 BETWEEN BATCHES. 4020 02:45:50,086 --> 02:45:53,056 SO OUR HYPOTHESIS IS WE CAN 4021 02:45:53,056 --> 02:45:54,491 REPLACE ANTIBODIES USED IN THE 4022 02:45:54,491 --> 02:45:56,626 MANUFACTURING PROCESS WITH 4023 02:45:56,626 --> 02:45:57,727 THESE SYNTHETIC MOLECULES 4024 02:45:57,727 --> 02:45:58,261 CALLED APTAMERS. 4025 02:45:58,261 --> 02:46:01,064 NOW IN ORDER TO DO THIS WE HAVE 4026 02:46:01,064 --> 02:46:03,166 TO FIND APTAMERS THAT WILL BE 4027 02:46:03,166 --> 02:46:04,568 RELEVANT FOR T CELL 4028 02:46:04,568 --> 02:46:04,901 MANUFACTURING. 4029 02:46:04,901 --> 02:46:06,203 SO WHEN WE STARTED THIS PROJECT 4030 02:46:06,203 --> 02:46:08,038 WE STARTED TO IDENTIFY APTAMERS 4031 02:46:08,038 --> 02:46:10,440 THAT WOULD BIND TO HUMAN T 4032 02:46:10,440 --> 02:46:10,640 CELLS. 4033 02:46:10,640 --> 02:46:12,542 THE WAY TO IDENTIFY IS USUALLY 4034 02:46:12,542 --> 02:46:13,777 THROUGH A LIBRARY SELECTION 4035 02:46:13,777 --> 02:46:14,644 APPROACH. 4036 02:46:14,644 --> 02:46:18,048 SO WE ADAPTED AN APPROACH 4037 02:46:18,048 --> 02:46:20,650 DIRECTED BY WAYWARD TAN CALLED 4038 02:46:20,650 --> 02:46:21,518 HOME SELECTS. 4039 02:46:21,518 --> 02:46:24,120 WE TAKE LIBRARIES OF 10 TO THE 4040 02:46:24,120 --> 02:46:25,288 16th DIVERSITY. 4041 02:46:25,288 --> 02:46:28,058 AND THEN WE LOOK FOR APTAMERS 4042 02:46:28,058 --> 02:46:29,226 THAT BIND TO OUR CELLS OF 4043 02:46:29,226 --> 02:46:30,160 INTEREST. 4044 02:46:30,160 --> 02:46:33,063 AND WE REMOVE APTAMERS THAT 4045 02:46:33,063 --> 02:46:33,897 BIND NON-SPECIFICALLY. 4046 02:46:33,897 --> 02:46:35,999 WE DO THIS AS AN ITERATIVE 4047 02:46:35,999 --> 02:46:38,568 PROCESS. 4048 02:46:38,568 --> 02:46:39,503 OVER AND OVER. 4049 02:46:39,503 --> 02:46:41,505 SO IN OUR CASE, WE DID FIVE 4050 02:46:41,505 --> 02:46:42,739 ROUNDS. 4051 02:46:42,739 --> 02:46:44,875 I WILL TELL YOU THAT WE 4052 02:46:44,875 --> 02:46:46,376 ACTUALLY HAD TO DO THIS 4053 02:46:46,376 --> 02:46:47,711 MULTIPLE TIMES. 4054 02:46:47,711 --> 02:46:49,779 OUR FIRST ROUNDS OF SELECTIONS 4055 02:46:49,779 --> 02:46:50,981 WERE UNSUCCESSFUL. 4056 02:46:50,981 --> 02:46:53,083 AND WHAT ACTUALLY MADE THE 4057 02:46:53,083 --> 02:46:54,684 SELECTION SUCCESSFUL WAS A KEY 4058 02:46:54,684 --> 02:46:57,053 CHANGE IN THIS STEP RIGHT HERE 4059 02:46:57,053 --> 02:46:58,922 FOR OUR POSITIVE SELECTION. 4060 02:46:58,922 --> 02:47:00,757 WE HAD TO DO COMPETITIVE 4061 02:47:00,757 --> 02:47:02,626 BINDING WHERE WE PUT OUR WHOLE 4062 02:47:02,626 --> 02:47:04,227 LIBRARY WITH ALL WHITE BLOOD 4063 02:47:04,227 --> 02:47:05,629 CELLS SO THERE WAS COMPETITION 4064 02:47:05,629 --> 02:47:06,596 FOR BINDING. 4065 02:47:06,596 --> 02:47:09,633 AND THEN WE REMOVED ONLY THE T 4066 02:47:09,633 --> 02:47:11,268 CELLS AND FOUND APTAMERS THAT 4067 02:47:11,268 --> 02:47:13,837 BOUND TO THOSE T CELLS. 4068 02:47:13,837 --> 02:47:16,740 ALL RIGHT, SO WHAT YOU CAN SEE 4069 02:47:16,740 --> 02:47:22,779 HERE OUR LIBRARY IS 4070 02:47:22,779 --> 02:47:25,549 FLUORESCENTLY LABELED SO WE CAN 4071 02:47:25,549 --> 02:47:27,617 TRACK THE SELECTION PROCESS. 4072 02:47:27,617 --> 02:47:29,486 THIS IS OUR DIFFERENT ROUNDS OF 4073 02:47:29,486 --> 02:47:29,753 SELECTION. 4074 02:47:29,753 --> 02:47:31,121 WE ARE LOOKING AT BINDING TO 4075 02:47:31,121 --> 02:47:32,188 OUR T CELLS. 4076 02:47:32,188 --> 02:47:35,091 YOU CAN SEE BY ROUND 3 AND 4 WE 4077 02:47:35,091 --> 02:47:36,459 START TO GET A POPULATION 4078 02:47:36,459 --> 02:47:38,562 BINDING TO THE APTAMER LIBRARY. 4079 02:47:38,562 --> 02:47:41,598 WHEN WE GET TO ROUND 5, IF WE 4080 02:47:41,598 --> 02:47:43,700 LOOK IN OUR CONTROL CELLS THESE 4081 02:47:43,700 --> 02:47:45,969 DON'T EXPRESS A LOT OF T-CELL 4082 02:47:45,969 --> 02:47:47,003 RECEPTORS. 4083 02:47:47,003 --> 02:47:49,472 WE SEE BINDING TO OUR CONTROL 4084 02:47:49,472 --> 02:47:49,673 CELLS. 4085 02:47:49,673 --> 02:47:51,207 THIS TELLS US FIVE ROUNDS OF 4086 02:47:51,207 --> 02:47:53,877 SELECTION WE ARE GETTING 4087 02:47:53,877 --> 02:47:55,278 AMPLIFIED NON-SPECIFIC BINDERS. 4088 02:47:55,278 --> 02:47:58,315 INDEED WHEN WE DID SEQUENCING 4089 02:47:58,315 --> 02:47:59,015 AND TESTED SEQUENCERS THAT'S 4090 02:47:59,015 --> 02:48:04,120 WHAT WE FOUND. 4091 02:48:04,120 --> 02:48:08,892 ROUND FOUR SEQUENCE HAD QUITE A 4092 02:48:08,892 --> 02:48:11,528 FEW SPECIFIC. 4093 02:48:11,528 --> 02:48:13,630 AND THEN NON SPECIFIC. 4094 02:48:13,630 --> 02:48:15,999 I WILL SKIP OVER SOME OF THE 4095 02:48:15,999 --> 02:48:18,335 APTAMERS WE TESTED BUT ONE 4096 02:48:18,335 --> 02:48:19,502 ENDED UP BEING INTERESTING, 4097 02:48:19,502 --> 02:48:21,838 WHEN WE SYNTHESIZED AND LOOKED 4098 02:48:21,838 --> 02:48:23,673 FOR BINDING WE FOUND THIS 4099 02:48:23,673 --> 02:48:26,710 APTAMER FOUND ALL OF THE CD8 4100 02:48:26,710 --> 02:48:27,010 POPULATION. 4101 02:48:27,010 --> 02:48:33,617 THIS IS CD8 LABELING ON THE Y 4102 02:48:33,617 --> 02:48:37,120 AXIS, CD4 AND IT FOUND NONE OF 4103 02:48:37,120 --> 02:48:40,624 THE CD4 CELLS. 4104 02:48:40,624 --> 02:48:42,125 IT FOUND CD8 CELLS. 4105 02:48:42,125 --> 02:48:49,699 IF WE LOOK AT BINDING, 2 4106 02:48:49,699 --> 02:48:50,433 NANOMOLAR. 4107 02:48:50,433 --> 02:48:58,341 WE CAN FIND IT INDEED BINDS, WE 4108 02:48:58,341 --> 02:48:59,509 ELIMINATE THE APTAMER BINDING. 4109 02:48:59,509 --> 02:49:01,344 IF WE TAKE OUR CONTROL CELL 4110 02:49:01,344 --> 02:49:04,147 LINE THAT DOESN'T EXPRESS CD8 4111 02:49:04,147 --> 02:49:06,716 AND TRANSDUCE IT WITH CAN 4112 02:49:06,716 --> 02:49:07,651 INTRODUCE APTAMER BINDING. 4113 02:49:07,651 --> 02:49:10,387 IF WE COME WITH ANTIBODY 4114 02:49:10,387 --> 02:49:12,088 AGAINST CDLE WE CAN COMPETE 4115 02:49:12,088 --> 02:49:14,624 WITH THE APTAMER FOR BINDING. 4116 02:49:14,624 --> 02:49:15,792 BUT MOST CONVINCINGLY FOR ME, 4117 02:49:15,792 --> 02:49:19,796 IF WE TAKE THE RECOMBINANT CD8 4118 02:49:19,796 --> 02:49:21,631 WE CAN INTRODUCE BINDING TO 4119 02:49:21,631 --> 02:49:23,967 THIS PROTEIN, WE CAN CONFIRM 4120 02:49:23,967 --> 02:49:32,308 THIS IS HIGH AFFINITY NANO 4121 02:49:32,308 --> 02:49:33,476 MOLAR. 4122 02:49:33,476 --> 02:49:37,814 THEY ARE SWITCHABLE, UNLIKE 4123 02:49:37,814 --> 02:49:38,114 ANTIBODIES. 4124 02:49:38,114 --> 02:49:39,416 THEY BIND WITH ANTIBODY 4125 02:49:39,416 --> 02:49:40,850 AFFINITY BUT YOU CAN SWITCH THE 4126 02:49:40,850 --> 02:49:42,986 BINDING ON AND OFF BECAUSE THE 4127 02:49:42,986 --> 02:49:44,220 BINDING IS DEPENDENT ON THE 4128 02:49:44,220 --> 02:49:46,222 SECONDARY STRUCTURE OF THE 4129 02:49:46,222 --> 02:49:46,456 APTAMER. 4130 02:49:46,456 --> 02:49:48,658 WHAT I'M SHOWING IS THE 4131 02:49:48,658 --> 02:49:50,593 PREDICTED SECONDARY STRUCTURE. 4132 02:49:50,593 --> 02:49:52,629 THE APTAMER HAS CERTAIN 4133 02:49:52,629 --> 02:49:54,164 STRUCTURE WHICH FORMS THESE 4134 02:49:54,164 --> 02:49:57,100 SECONDARY STRUCTURES. 4135 02:49:57,100 --> 02:49:59,235 WHAT WE DID IS WE TOOK OUR 4136 02:49:59,235 --> 02:50:01,137 APTAMER AND WE EXTENDED THE 4137 02:50:01,137 --> 02:50:04,140 BOTTOM LOOP HERE, THOSE OF YOU 4138 02:50:04,140 --> 02:50:05,308 IN SYNTHETIC BIOLOGY ARE 4139 02:50:05,308 --> 02:50:07,444 FAMILIAR, THIS IS A TOE HOLD 4140 02:50:07,444 --> 02:50:08,445 SEQUENCE. 4141 02:50:08,445 --> 02:50:10,380 THAT ALLOWS US TO COME IN WITH 4142 02:50:10,380 --> 02:50:13,783 A SEQUENCE THAT IS COMPLETELY 4143 02:50:13,783 --> 02:50:16,586 COMPLIMENTARY SO IT WILL HAVE 4144 02:50:16,586 --> 02:50:17,787 HIGHER AFFINITY THAN THE 4145 02:50:17,787 --> 02:50:18,688 APTAMER ITSELF. 4146 02:50:18,688 --> 02:50:20,557 IF WE HAVE A REVERSAL AGENT 4147 02:50:20,557 --> 02:50:22,459 THAT WILL CHANGE THE SECONDARY 4148 02:50:22,459 --> 02:50:24,094 STRUCTURE OF THE APTAMER AND 4149 02:50:24,094 --> 02:50:25,895 SWITCH OFF ITS BINDING. 4150 02:50:25,895 --> 02:50:28,064 THIS HAPPENS VERY FAST. 4151 02:50:28,064 --> 02:50:32,268 SO WE JUST ADDED IN, LOOKED A 4152 02:50:32,268 --> 02:50:34,370 COUPLE SECONDS LATER, APTAMER 4153 02:50:34,370 --> 02:50:35,538 COMPLETELY LOSES ITS BINDING. 4154 02:50:35,538 --> 02:50:37,173 NOW YOU CAN IMAGINE FOR A 4155 02:50:37,173 --> 02:50:38,575 SELECTION AGENT, WE CAN HAVE 4156 02:50:38,575 --> 02:50:39,976 SOMETHING THAT BINDS TO OUR 4157 02:50:39,976 --> 02:50:41,644 CELLS OF INTEREST, BUT THEN WE 4158 02:50:41,644 --> 02:50:43,747 CAN ALSO SWITCH OFF BINDING AND 4159 02:50:43,747 --> 02:50:45,115 RELEASE THE CELLS WITHOUT 4160 02:50:45,115 --> 02:50:46,282 HAVING ANY SELECTION AGENT. 4161 02:50:46,282 --> 02:50:49,519 SO THIS IS A SCHEMATIC OF HOW 4162 02:50:49,519 --> 02:50:53,256 WE EMPLOY THESE APTAMERS. 4163 02:50:53,256 --> 02:50:57,293 WE IMMOBILIZE THEM ON MAGNETIC 4164 02:50:57,293 --> 02:50:57,827 BEADS. 4165 02:50:57,827 --> 02:51:01,898 THIS IS AN EXAMPLE OF THE LEUKO 4166 02:51:01,898 --> 02:51:03,199 PARESIS PRODUCT. 4167 02:51:03,199 --> 02:51:07,237 WE APPLY TO MAGNET, WE RETAIN 4168 02:51:07,237 --> 02:51:08,705 THE CD8 CELLS, ALL OF THIS IS 4169 02:51:08,705 --> 02:51:09,572 BEING DONE NOW. 4170 02:51:09,572 --> 02:51:10,740 THE DIFFERENCE IS NOW WE CAN 4171 02:51:10,740 --> 02:51:12,842 COME IN WITH A REVERSAL AGENT 4172 02:51:12,842 --> 02:51:14,711 THAT CHANGES THE CONFIRMATION 4173 02:51:14,711 --> 02:51:16,813 OF THE APTAMER AND THEN THE 4174 02:51:16,813 --> 02:51:19,682 CELLS ARE RELEASED TRACELESSLY, 4175 02:51:19,682 --> 02:51:22,952 WITHOUT ANY SELECTION AGENT. 4176 02:51:22,952 --> 02:51:25,522 SO WE ARE REALLY EXCITED ABOUT 4177 02:51:25,522 --> 02:51:27,624 THIS BECAUSE, NUMBER ONE WE 4178 02:51:27,624 --> 02:51:29,292 COULD POTENTIALLY MOVE TO A 4179 02:51:29,292 --> 02:51:35,431 COMPLETE LY SYNTHETIC SYSTEM. 4180 02:51:35,431 --> 02:51:41,004 WE HAVE NO CONTAMINATION, THESE 4181 02:51:41,004 --> 02:51:43,106 ARE COMING OFF UNTOUCHED THE 4182 02:51:43,106 --> 02:51:44,741 REASON THIS IS IMPORTANT YOU 4183 02:51:44,741 --> 02:51:46,409 CAN THEN DO SUBSEQUENT 4184 02:51:46,409 --> 02:51:47,811 SELECTION WITH THE CELLS. 4185 02:51:47,811 --> 02:51:50,580 WE CAN DO SERIAL SELECTIONS A. 4186 02:51:50,580 --> 02:51:52,715 THE END OF MY TALK I WILL GIVE 4187 02:51:52,715 --> 02:51:54,884 YOU AN EXAMPLE HOW WE HAVE DONE 4188 02:51:54,884 --> 02:51:55,285 THAT. 4189 02:51:55,285 --> 02:51:56,719 SO THE NEXT COUPLE OF SLIDES 4190 02:51:56,719 --> 02:51:59,923 ARE JUST TO SHOW YOU THAT THE 4191 02:51:59,923 --> 02:52:01,124 APTAMER SELECTED PRODUCT IS THE 4192 02:52:01,124 --> 02:52:03,993 SAME AS THE ANTIBODY-SELECTED 4193 02:52:03,993 --> 02:52:04,327 PRODUCT. 4194 02:52:04,327 --> 02:52:05,495 OKAY? 4195 02:52:05,495 --> 02:52:08,998 THIS IS FOR EXAMPLE, PB & M 4196 02:52:08,998 --> 02:52:14,571 FROM A HUMAN DONOR, ANTIBODY 4197 02:52:14,571 --> 02:52:16,439 SELECTION FOR CD8, A HIGH 4198 02:52:16,439 --> 02:52:18,041 POPULATION OF PURE CELLS SAME 4199 02:52:18,041 --> 02:52:20,009 AS WHEN WE DO APTAMER-BASED 4200 02:52:20,009 --> 02:52:20,443 SELECTION. 4201 02:52:20,443 --> 02:52:23,479 IF WE LOOK AT PURITY, WE HAVE 4202 02:52:23,479 --> 02:52:25,114 ABOUT 99% PURITY USING THIS 4203 02:52:25,114 --> 02:52:27,851 METHOD JUST LIKE WITH ANTIBODY 4204 02:52:27,851 --> 02:52:28,384 BASED SELECTION. 4205 02:52:28,384 --> 02:52:30,720 THE CELLS WE HAVE ANALYZED 4206 02:52:30,720 --> 02:52:33,957 EXTENSIVELY AND THEY ARE 4207 02:52:33,957 --> 02:52:35,458 INDISTINGUISHABLE FROM 4208 02:52:35,458 --> 02:52:36,259 ANTIBODY-BASED SELECTION. 4209 02:52:36,259 --> 02:52:38,628 IF WE LOOK AT PHENOTYPE THE 4210 02:52:38,628 --> 02:52:42,232 DISTRIBUTION IS THE SAME. 4211 02:52:42,232 --> 02:52:44,767 WE DID NANO STRING ANALYSIS ON 4212 02:52:44,767 --> 02:52:46,269 ALMOST 300 DIFFERENT RNA 4213 02:52:46,269 --> 02:52:47,570 TRANSCRIPTS AND WE SEE NO 4214 02:52:47,570 --> 02:52:50,139 DIFFERENCE AT ALL IN ANY OF THE 4215 02:52:50,139 --> 02:52:51,074 GENE EXPRESSION PROFILES. 4216 02:52:51,074 --> 02:52:53,409 AS FAR AS WE KNOW, THESE CELLS 4217 02:52:53,409 --> 02:52:55,979 FROM EITHER ANTIBODY OR 4218 02:52:55,979 --> 02:52:56,613 APTAMER-BASED SELECTION, THEY 4219 02:52:56,613 --> 02:52:57,847 ARE THE SAME. 4220 02:52:57,847 --> 02:53:00,416 AND WE FURTHER VALIDATED THIS 4221 02:53:00,416 --> 02:53:03,253 BY GENERATING CAR T CELLS FROM 4222 02:53:03,253 --> 02:53:05,321 BOTH ANTIBODY AND APTAMER 4223 02:53:05,321 --> 02:53:07,657 SELECTED CELLS AND TESTED IT IN 4224 02:53:07,657 --> 02:53:09,459 AN ANIMAL MODEL THAT WAS 4225 02:53:09,459 --> 02:53:10,226 NON-CURATED. 4226 02:53:10,226 --> 02:53:13,796 WE PICKED A NON-CURATED MODEL 4227 02:53:13,796 --> 02:53:16,266 TO SEE IF THERE WERE ANY 4228 02:53:16,266 --> 02:53:17,333 DIFFERENCES IN TUMOR GROWTH 4229 02:53:17,333 --> 02:53:19,535 RATE AS WELL AS SURVIVAL. 4230 02:53:19,535 --> 02:53:21,237 THE ANSWER IS, NOT 4231 02:53:21,237 --> 02:53:22,705 SURPRISINGLY, NONE. 4232 02:53:22,705 --> 02:53:25,842 SO THE ORANGE LINES ARE 4233 02:53:25,842 --> 02:53:28,244 TRIPLICATE HUMAN DONORS WITH 4234 02:53:28,244 --> 02:53:31,047 CAR T CELLS THAT WERE ISOLATED 4235 02:53:31,047 --> 02:53:32,949 EITHER ORIGINALLY BY APTAMER OR 4236 02:53:32,949 --> 02:53:35,718 ANTIBODY. 4237 02:53:35,718 --> 02:53:36,986 ANTIBODY IN ORANGE, APTAMER IN 4238 02:53:36,986 --> 02:53:37,353 BLUE. 4239 02:53:37,353 --> 02:53:39,455 WHAT YOU ARE SEEING IS THEY 4240 02:53:39,455 --> 02:53:41,057 BEHAVE ALMOST THE SAME. 4241 02:53:41,057 --> 02:53:43,860 AND IF WE LOOK IN THE MOUSE 4242 02:53:43,860 --> 02:53:46,930 MODEL, THE EFFICACY OF THESE 4243 02:53:46,930 --> 02:53:47,997 GENERATED CAR T CELLS IS ALSO 4244 02:53:47,997 --> 02:53:50,500 THE SAME. 4245 02:53:50,500 --> 02:53:52,135 SO OUR CONCLUSION FROM THIS 4246 02:53:52,135 --> 02:53:55,838 FIRST SECTION IS THAT WE CAN 4247 02:53:55,838 --> 02:53:56,706 NOW EMPLOY APTAMER-BASED 4248 02:53:56,706 --> 02:53:57,006 SELECTION. 4249 02:53:57,006 --> 02:53:59,342 THIS GIVES US A TRACELESS 4250 02:53:59,342 --> 02:54:01,444 PRODUCT AND ENGINEER CAR T 4251 02:54:01,444 --> 02:54:03,179 CELLS USING THIS APTAMER-BASED 4252 02:54:03,179 --> 02:54:07,116 APPROACH. 4253 02:54:07,116 --> 02:54:09,719 OKAY, I WILL MOVE ONTO ANOTHER 4254 02:54:09,719 --> 02:54:10,753 EXAMPLE USING APTAMERS, IN THIS 4255 02:54:10,753 --> 02:54:12,555 CASE TRYING TO IMPROVE THE 4256 02:54:12,555 --> 02:54:14,991 SAFETY OF THE FINAL CAR T CELL 4257 02:54:14,991 --> 02:54:16,526 PRODUCT. 4258 02:54:16,526 --> 02:54:18,394 I MENTIONED, VERY BRIEFLY, THAT 4259 02:54:18,394 --> 02:54:23,933 WE TRIED SEVERAL TIMES TO GET 4260 02:54:23,933 --> 02:54:26,970 THAT CD8 T CELL APTAMER WITHOUT 4261 02:54:26,970 --> 02:54:28,571 SUCCESS BEFORE WE FINALLY 4262 02:54:28,571 --> 02:54:29,539 FIGURED THE BEST METHOD FOR 4263 02:54:29,539 --> 02:54:30,473 SELECTION. 4264 02:54:30,473 --> 02:54:34,243 IN THE PROCESS OF DOING THAT WE 4265 02:54:34,243 --> 02:54:38,915 INITIALLY USED CULTURE CELLS WE 4266 02:54:38,915 --> 02:54:42,652 HAD JURKAT CELLS AND MUTANT 4267 02:54:42,652 --> 02:54:44,721 JURKAT MUTANT CELL LINE WHICH 4268 02:54:44,721 --> 02:54:46,656 IS NEGATIVE FOR MOST OF THE 4269 02:54:46,656 --> 02:54:47,523 T-CELL RECEPTORS. 4270 02:54:47,523 --> 02:54:49,459 WE ACTUALLY THOUGHT THIS WAS AN 4271 02:54:49,459 --> 02:54:50,860 UNSUCCESSFUL SELECTION. 4272 02:54:50,860 --> 02:54:53,096 BECAUSE AS WE MOVED ALONG THE 4273 02:54:53,096 --> 02:54:55,932 SELECTION PROCESS WE GOTTEN 4274 02:54:55,932 --> 02:54:57,400 RICHMENT IN BINDING TO BOTH 4275 02:54:57,400 --> 02:54:59,836 CELL TYPES. 4276 02:54:59,836 --> 02:55:02,905 WE DISGUARDED THIS AND MOVED ON 4277 02:55:02,905 --> 02:55:03,973 THE CD8 STUDY. 4278 02:55:03,973 --> 02:55:05,908 WE CAME BACK BECAUSE HE WITH 4279 02:55:05,908 --> 02:55:07,043 WERE GETTING BINDING APTAMERS 4280 02:55:07,043 --> 02:55:07,577 HERE. 4281 02:55:07,577 --> 02:55:09,645 WE WANTED TO SEE WHAT ACTUALLY 4282 02:55:09,645 --> 02:55:14,083 WAS BINDING? 4283 02:55:14,083 --> 02:55:16,419 WE TOOK OUT THE TOP APTAMERS 4284 02:55:16,419 --> 02:55:18,521 FROM SEQUENCING AND LOOKED AT 4285 02:55:18,521 --> 02:55:19,722 BINDING AND SAW THEY WERE 4286 02:55:19,722 --> 02:55:21,357 BINDING TO BOTH OUR POSITIVE 4287 02:55:21,357 --> 02:55:25,028 AND NEGATIVE CELL LINE. 4288 02:55:25,028 --> 02:55:26,529 AND IT BINDS WITH VERY HIGH 4289 02:55:26,529 --> 02:55:27,363 AFFINITY. 4290 02:55:27,363 --> 02:55:29,899 SO THE AFFINITY AGAIN HERE IS 4291 02:55:29,899 --> 02:55:34,871 ON THE ORDER OF SINGLE 4292 02:55:34,871 --> 02:55:35,204 NANOMOLAR. 4293 02:55:35,204 --> 02:55:38,708 WE ACTUALLY TRUNCATED TO 91 4294 02:55:38,708 --> 02:55:40,576 NUCLEOTIDES, IT DISPLAYS THE 4295 02:55:40,576 --> 02:55:42,412 SAME BINDING A FINITE BUT 4296 02:55:42,412 --> 02:55:44,247 SMALLER APTAMER TO WORK WITH. 4297 02:55:44,247 --> 02:55:46,382 SO WE ENDED UP IDENTIFYING THE 4298 02:55:46,382 --> 02:55:49,452 RECEPTOR USING A PULL-DOWN 4299 02:55:49,452 --> 02:55:51,154 ASSAY, WE REMOBILIZED THE 4300 02:55:51,154 --> 02:55:53,923 APTAMER, EXPOSED IT TO CELL, 4301 02:55:53,923 --> 02:55:59,829 AND RAN IT BY MASS SPEC. 4302 02:55:59,829 --> 02:56:04,000 THE RESULTS SHOWED WE WERE 4303 02:56:04,000 --> 02:56:06,269 ENRICHING TRANSCRIPTOR 1, ALSO 4304 02:56:06,269 --> 02:56:07,670 KNOWN AS CD71. 4305 02:56:07,670 --> 02:56:08,571 AGAIN WE WENT THROUGH THE 4306 02:56:08,571 --> 02:56:09,305 VALIDATION. 4307 02:56:09,305 --> 02:56:11,641 I WILL GO THROUGH THIS QUICKLY. 4308 02:56:11,641 --> 02:56:13,076 THIS IS VERY CHARACTERISTIC 4309 02:56:13,076 --> 02:56:14,844 WHEN WE KNOW OUR RECEPTOR THAT 4310 02:56:14,844 --> 02:56:17,013 THE STAINING OF THE RECEPTOR, 4311 02:56:17,013 --> 02:56:19,682 VERSUS STAINING OF THE ANTIBODY 4312 02:56:19,682 --> 02:56:21,984 ON CELLS WILL CORRELATE WITH 4313 02:56:21,984 --> 02:56:24,854 DIAGONAL, THE HIGHER THE 4314 02:56:24,854 --> 02:56:26,656 RECEPTOR THE HIGHER THE BINDING 4315 02:56:26,656 --> 02:56:27,356 OF THE APTAMER. 4316 02:56:27,356 --> 02:56:30,159 WE CAN SEE IF WE KNOCK DOWN THE 4317 02:56:30,159 --> 02:56:32,728 RECEPTOR, WE KNOCK DOWN APTAMER 4318 02:56:32,728 --> 02:56:35,832 BINDING AND WE CAN DIRECTLY 4319 02:56:35,832 --> 02:56:37,800 MEASURE BINDING USING 4320 02:56:37,800 --> 02:56:38,868 RECOMBINANT PROTEIN. 4321 02:56:38,868 --> 02:56:40,503 I LOVE TO SHOW THIS SLIDE 4322 02:56:40,503 --> 02:56:43,573 BECAUSE I THINK THIS IS THE 4323 02:56:43,573 --> 02:56:47,176 VERY FIRST CRYOIAIN IMAGE OF 4324 02:56:47,176 --> 02:56:49,045 APTAMER BOUND TO ITS TARGET. 4325 02:56:49,045 --> 02:56:53,649 THIS WAS DONE BY UNIVERSITY OF 4326 02:56:53,649 --> 02:56:55,718 NEW YORK, TONG WANG IS THE LEAD 4327 02:56:55,718 --> 02:56:57,153 OF THE TEAM. 4328 02:56:57,153 --> 02:56:59,222 THIS IS THE RECEPTOR AND 4329 02:56:59,222 --> 02:57:01,991 APTAMER IS SHOWN IN YELLOW. 4330 02:57:01,991 --> 02:57:06,896 AND THE COOLEST THING WAS HARSH 4331 02:57:06,896 --> 02:57:10,333 BANSIA A POST DOC WAS ABLE TO 4332 02:57:10,333 --> 02:57:13,136 MODEL THE APTAMER AND DETERMINE 4333 02:57:13,136 --> 02:57:14,537 EXACTLY WHICH NUCLEOTIDES IN 4334 02:57:14,537 --> 02:57:18,241 THE APTAMER ARE BINDING TO 4335 02:57:18,241 --> 02:57:20,877 WHICH AMINO ACID RESIDUES. 4336 02:57:20,877 --> 02:57:22,745 WE LOVE THIS BECAUSE IT ALLOWS 4337 02:57:22,745 --> 02:57:24,380 US TO BETTER ENGINEER THESE 4338 02:57:24,380 --> 02:57:24,814 APTAMERS. 4339 02:57:24,814 --> 02:57:26,782 WE HAVE BEEN DOING THIS WITH 4340 02:57:26,782 --> 02:57:27,984 ALMOST ALL THE APTAMERS WE 4341 02:57:27,984 --> 02:57:28,651 DISCOVER. 4342 02:57:28,651 --> 02:57:30,186 I JUST WANTED TO PUT THAT AS AN 4343 02:57:30,186 --> 02:57:31,020 ASIDE. 4344 02:57:31,020 --> 02:57:34,290 GOING BACK TO CELL THERAPY. 4345 02:57:34,290 --> 02:57:36,592 TURNS OUT CD71 IS OVER 4346 02:57:36,592 --> 02:57:38,461 EXPRESSED IN ALMOST ALL TYPES 4347 02:57:38,461 --> 02:57:39,662 OF CANCER CELLS. 4348 02:57:39,662 --> 02:57:40,596 IT'S RESPONSIBLE FOR BRINGING 4349 02:57:40,596 --> 02:57:43,132 IRON IN THE CELLS. 4350 02:57:43,132 --> 02:57:45,001 THESE CELLS RAPIDLY DIVIDING 4351 02:57:45,001 --> 02:57:47,103 NEED MORE RESOURCES SO THEY UP 4352 02:57:47,103 --> 02:57:48,738 REGULATE THIS TO GET MORE IRON. 4353 02:57:48,738 --> 02:57:52,708 YOU CAN SEE ACROSS THESE CELL 4354 02:57:52,708 --> 02:57:53,976 TYPES THAT CD71 IS OVER 4355 02:57:53,976 --> 02:57:55,011 EXPRESSED. 4356 02:57:55,011 --> 02:58:00,449 THIS IS RELEVANT BECAUSE IN 4357 02:58:00,449 --> 02:58:02,518 REIMAGINING OF CAR T CELLS IT'S 4358 02:58:02,518 --> 02:58:04,487 CRITICAL THERE ARE NO BLOOD 4359 02:58:04,487 --> 02:58:05,855 CANCER CELLS THAT MAKE IT IN 4360 02:58:05,855 --> 02:58:06,889 THE MANUFACTURING PROCESS. 4361 02:58:06,889 --> 02:58:09,158 THIS IS AN EXAMPLE REPORTED IN 4362 02:58:09,158 --> 02:58:11,460 NATURE MEDICINE OF ONE CAR T 4363 02:58:11,460 --> 02:58:14,263 CELL PATIENT WHO ENDED UP 4364 02:58:14,263 --> 02:58:15,731 HAVING A RELAPSE BECAUSE HE HAD 4365 02:58:15,731 --> 02:58:19,035 A LEUKEMIA CELL THAT MADE IT 4366 02:58:19,035 --> 02:58:20,803 INTO THE MANUFACTURING PROCESS. 4367 02:58:20,803 --> 02:58:23,940 AND THAT LEUKEMIA CELL WAS 4368 02:58:23,940 --> 02:58:26,642 TRANSDUCED WITH A CAR RECEPTOR. 4369 02:58:26,642 --> 02:58:30,213 THE CAR RECEPTOR MASKED THE CD 4370 02:58:30,213 --> 02:58:32,014 17 EPITOPE. 4371 02:58:32,014 --> 02:58:33,416 THE PATIENT UNDERGOS REMISSION 4372 02:58:33,416 --> 02:58:35,551 AND MANY DAYS LATER, ALMOST A 4373 02:58:35,551 --> 02:58:38,287 DAY LATER HE GETS LEUKEMIA 4374 02:58:38,287 --> 02:58:40,423 AGAIN AND THE CAUSE OF A 4375 02:58:40,423 --> 02:58:42,391 LEUKEMIA WAS A LEUKEMIA CELL 4376 02:58:42,391 --> 02:58:45,728 THAT MADE IT IN THIS T-CELL 4377 02:58:45,728 --> 02:58:46,495 MANUFACTURING PROCESS AND 4378 02:58:46,495 --> 02:58:52,568 TRANCE TRANSDUCED WITH THE CAR 4379 02:58:52,568 --> 02:58:53,903 T-CELL RECEPTOR. 4380 02:58:53,903 --> 02:58:56,505 IT'S QUITE AN ISSUE, THESE MUST 4381 02:58:56,505 --> 02:58:59,508 BE REMOVED DURING THE CAR 4382 02:58:59,508 --> 02:59:01,277 T-CELL MANUFACTURING PROCESS. 4383 02:59:01,277 --> 02:59:04,447 TURNS OUT THOSE HAVE HIGH 4384 02:59:04,447 --> 02:59:06,315 EXPRESSION OF THIS RECEPTOR. 4385 02:59:06,315 --> 02:59:08,217 SO WHAT WE PROPOSE, WE CAN 4386 02:59:08,217 --> 02:59:10,786 INCLUDE A STEP IN THE ISOLATION 4387 02:59:10,786 --> 02:59:14,056 PROCESS TO SPECIFICALLY REMOVE 4388 02:59:14,056 --> 02:59:16,826 LEUKEMIA CELLS BEFORE ENTERING 4389 02:59:16,826 --> 02:59:18,694 THE CAR T CELL PROCESS. 4390 02:59:18,694 --> 02:59:22,398 SO AS PROOF OF CONCEPT WE 4391 02:59:22,398 --> 02:59:25,635 SIMPLY APPLIED MAGNETIC BEADS 4392 02:59:25,635 --> 02:59:27,536 WITH OUR CD71 APTAMER, AND WE 4393 02:59:27,536 --> 02:59:30,406 SHOWED THAT WE CAN TAKE 4394 02:59:30,406 --> 02:59:32,041 MIXTURES OF CELLS, SO WE DOPED 4395 02:59:32,041 --> 02:59:36,779 IN LIEU -- LEUKEMIA CELLS 4396 02:59:36,779 --> 02:59:39,715 HERE AT 10%, IF WE MOVE IT 4397 02:59:39,715 --> 02:59:41,784 THROUGH THE COLUMN WITH CAN 4398 02:59:41,784 --> 02:59:43,886 REMOVE ALMOST ALL CELLS, THIS 4399 02:59:43,886 --> 02:59:45,388 SIGNIFICANTLY REDUCES ANY RISK 4400 02:59:45,388 --> 02:59:46,455 OF CONTAMINATION. 4401 02:59:46,455 --> 02:59:47,857 THIS WE CAN DO WITHOUT 4402 02:59:47,857 --> 02:59:50,660 IMPACTING AT ALL THE 4403 02:59:50,660 --> 02:59:52,728 LYMPHOCYTES THAT ARE NEEDED FOR 4404 02:59:52,728 --> 02:59:56,666 CAR T CELL MANUFACTURING. 4405 02:59:56,666 --> 02:59:59,468 YOU MAY WONDERING CAN WE 4406 02:59:59,468 --> 03:00:01,337 DEPLETE EVEN SMALL AMOUNTS OF 4407 03:00:01,337 --> 03:00:02,938 CONTAMINATION, THE ANSWER IS 4408 03:00:02,938 --> 03:00:04,440 YES. 4409 03:00:04,440 --> 03:00:05,808 WE TESTED DIFFERENT PERCENTAGES 4410 03:00:05,808 --> 03:00:11,180 AND WE CAN GET VERY HIGH 4411 03:00:11,180 --> 03:00:12,348 DEPLETION AT ALL THE 4412 03:00:12,348 --> 03:00:13,049 PERCENTAGES WE TESTED. 4413 03:00:13,049 --> 03:00:16,552 I TOLD YOU ABOUT THE CONCEPT OF 4414 03:00:16,552 --> 03:00:19,355 USING APTAMERS TO SELECT T 4415 03:00:19,355 --> 03:00:23,592 CELLS USING APTAMERS TO DEPLETE 4416 03:00:23,592 --> 03:00:26,062 T CELLS TO IMPROVE SAFETY. 4417 03:00:26,062 --> 03:00:27,363 AND NEXT EXAMPLE, THIS IS 4418 03:00:27,363 --> 03:00:29,298 SOMETHING NEW FROM OUR LAB, WE 4419 03:00:29,298 --> 03:00:31,167 ARE TRYING TO IMPROVE THE 4420 03:00:31,167 --> 03:00:34,136 EFFICACY OF SOME OF THESE CAR T 4421 03:00:34,136 --> 03:00:35,037 CELL THERAPIES. 4422 03:00:35,037 --> 03:00:37,606 SO IT IS NOW KNOWN THAT CERTAIN 4423 03:00:37,606 --> 03:00:40,409 SUBSETS OF T CELLS CAN ACTUALLY 4424 03:00:40,409 --> 03:00:42,311 GENERATE BETTER PERFORMING CAR 4425 03:00:42,311 --> 03:00:43,012 T CELL PRODUCTS. 4426 03:00:43,012 --> 03:00:44,914 BUT ONE OF THE CHALLENGES HAS 4427 03:00:44,914 --> 03:00:46,515 BEEN IN THE MANUFACTURING. 4428 03:00:46,515 --> 03:00:48,384 THAT'S BECAUSE IN TRYING TO 4429 03:00:48,384 --> 03:00:50,252 SELECT FOR MULTIPLE MARKERS, IF 4430 03:00:50,252 --> 03:00:53,322 YOU USE THE MAGNETIC APPROACH, 4431 03:00:53,322 --> 03:00:54,724 AGAINST ONCE THE CELLS ARE 4432 03:00:54,724 --> 03:00:56,625 MARKED WITH THE BEADS YOU CAN'T 4433 03:00:56,625 --> 03:00:59,061 DO ANY SUBSEQUENT SELECTIONS. 4434 03:00:59,061 --> 03:01:00,796 SO WHAT NORMALLY HAS TO BE DONE 4435 03:01:00,796 --> 03:01:02,231 IS A COMBINATION OF NEGATIVE 4436 03:01:02,231 --> 03:01:03,466 SELECTION, WHERE YOU REMOVE ALL 4437 03:01:03,466 --> 03:01:05,267 THE CELLS THAT YOU DON'T WANT 4438 03:01:05,267 --> 03:01:07,136 AND THEN POSITIVE SECTION. 4439 03:01:07,136 --> 03:01:10,139 AND THIS IS EVEN HIGHER IN COST 4440 03:01:10,139 --> 03:01:11,974 BECAUSE THE NEGATIVE SELECTION 4441 03:01:11,974 --> 03:01:13,843 STEP COMBINES A MIXTURE OF 4442 03:01:13,843 --> 03:01:15,745 ANTIBODIES NOW AND ALSO THE 4443 03:01:15,745 --> 03:01:21,217 EFFICIENCY AND YIELD IS LOWER. 4444 03:01:21,217 --> 03:01:22,918 SO WE THINK APTAMERS CAN 4445 03:01:22,918 --> 03:01:24,754 ADDRESS A LOT OF THESE ISSUES 4446 03:01:24,754 --> 03:01:26,122 WITH THE NEED FOR SERIAL 4447 03:01:26,122 --> 03:01:26,856 SELECTION. 4448 03:01:26,856 --> 03:01:28,758 I WILL MENTION THIS BRIEFLY, WE 4449 03:01:28,758 --> 03:01:30,860 HAVE BEEN ABLE TO TAKE TWO CELL 4450 03:01:30,860 --> 03:01:34,163 TYPE THAT'S HAVE COMPLETELY 4451 03:01:34,163 --> 03:01:35,564 ORTHOGONAL RECEPTORS AND APPLY 4452 03:01:35,564 --> 03:01:36,932 APTAMER AGAINST BOTH OF THESE 4453 03:01:36,932 --> 03:01:37,700 RECEPTORS. 4454 03:01:37,700 --> 03:01:39,368 WE CAN ISOLATE THE CELLS 4455 03:01:39,368 --> 03:01:40,302 TOGETHER ONTO A COLUMN. 4456 03:01:40,302 --> 03:01:43,606 AND THEN WE CAN SPECIFICALLY 4457 03:01:43,606 --> 03:01:45,207 ELUTE ONE CELL VERSUS THE 4458 03:01:45,207 --> 03:01:48,477 SECOND CELL BY APPLYING THE 4459 03:01:48,477 --> 03:01:49,578 REVERSAL AGENT SPECIFIC TO THAT 4460 03:01:49,578 --> 03:01:50,346 APTAMER. 4461 03:01:50,346 --> 03:01:52,681 IN ONE SECTION WE CAN ISOLATE 4462 03:01:52,681 --> 03:01:53,649 TWO DIFFERENT POPULATIONS OF 4463 03:01:53,649 --> 03:01:54,750 CELLS. 4464 03:01:54,750 --> 03:01:55,684 THAT'S ONE POSSIBLE 4465 03:01:55,684 --> 03:01:56,419 CONFIGURATION. 4466 03:01:56,419 --> 03:01:58,254 BUT THE ONE I WILL TALK TO YOU 4467 03:01:58,254 --> 03:02:00,122 ABOUT TODAY IS GETTING INTO 4468 03:02:00,122 --> 03:02:02,458 SUBSETS OF CELLS WHERE WE WANT 4469 03:02:02,458 --> 03:02:05,027 TO ISOLATE CELLS THAT HAVE 4470 03:02:05,027 --> 03:02:06,896 EXPRESSED TWO RECEPTORS ON THE 4471 03:02:06,896 --> 03:02:07,363 SAME CELL. 4472 03:02:07,363 --> 03:02:13,669 OUR INTEREST IN THIS IS DUE TO 4473 03:02:13,669 --> 03:02:15,604 ANI NAIVE AND MEMORY T CELLS 4474 03:02:15,604 --> 03:02:17,373 WHICH HAVE SHOWN TO BE MORE 4475 03:02:17,373 --> 03:02:20,776 POTENT IN TERMS OF CAR T CELL 4476 03:02:20,776 --> 03:02:23,712 EFFICACY. 4477 03:02:23,712 --> 03:02:25,548 THESE T-CELLS START OFF NAIVE 4478 03:02:25,548 --> 03:02:29,485 AND THEN THEY WILL START TO 4479 03:02:29,485 --> 03:02:29,819 DIFFERENTIATE. 4480 03:02:29,819 --> 03:02:31,787 OVER TIME INTO BECOMING 4481 03:02:31,787 --> 03:02:33,722 EFFECTOR CELLS. 4482 03:02:33,722 --> 03:02:35,124 THESE EFFECTOR CELLS ARE GOOD 4483 03:02:35,124 --> 03:02:38,127 AT KILLING BUT ALSO GENERATE 4484 03:02:38,127 --> 03:02:39,995 HIGHER CYTOKINE RESPONSE AND 4485 03:02:39,995 --> 03:02:41,397 THEY DON'T PROLIFERATE AS MUCH, 4486 03:02:41,397 --> 03:02:42,465 THEY HAVE LESS MEMORY. 4487 03:02:42,465 --> 03:02:46,135 WHAT I WILL SHOW YOU NEXT, THE 4488 03:02:46,135 --> 03:02:46,869 CELLS INTERMEDIATE HERE TURN 4489 03:02:46,869 --> 03:02:49,271 OUT TO BE BETTER FOR CAR T CELL 4490 03:02:49,271 --> 03:02:50,573 PRODUCTS. 4491 03:02:50,573 --> 03:02:51,974 THESE CELLS HERE, IF YOU LOOK 4492 03:02:51,974 --> 03:02:53,843 AT THEIR MARKERS ARE GOING TO 4493 03:02:53,843 --> 03:02:57,546 BE POSITIVE FOR CD4 AND CD8 BUT 4494 03:02:57,546 --> 03:03:00,449 THEN ALSO FOR CD62L, WHICH IS L 4495 03:03:00,449 --> 03:03:01,750 SELECTED. 4496 03:03:01,750 --> 03:03:05,488 SO WHAT WE REALLY WANT IS TO 4497 03:03:05,488 --> 03:03:09,358 HAVE T-CELLS CD8 POSITIVE BUT 4498 03:03:09,358 --> 03:03:10,292 ALSO CD62L POSITIVE. 4499 03:03:10,292 --> 03:03:11,560 THIS IS SOME EXAMPLE. 4500 03:03:11,560 --> 03:03:14,396 THIS WAS ACTUALLY A STUDY THAT 4501 03:03:14,396 --> 03:03:23,906 ENTERED INTO HUMAN STUDIES. 4502 03:03:23,906 --> 03:03:26,475 WHAT YOU CAN SEE HERE IS IF YOU 4503 03:03:26,475 --> 03:03:28,344 TAKE THE BULK T-CELL 4504 03:03:28,344 --> 03:03:30,446 POPULATION, SHOWN IN BLUE, 4505 03:03:30,446 --> 03:03:33,015 VERSUS THE T CELL POPULATION 4506 03:03:33,015 --> 03:03:35,584 GENERATED FROM NAIVE AND MEMORY 4507 03:03:35,584 --> 03:03:38,220 STEM CELLS, THAT'S SHOWN IN 4508 03:03:38,220 --> 03:03:41,657 RED, THAT THE RED POPULATION 4509 03:03:41,657 --> 03:03:43,759 WILL HAVE BETTER EFFICACY, 4510 03:03:43,759 --> 03:03:46,562 BETTER SURVIVAL AND MORE SAFETY 4511 03:03:46,562 --> 03:03:48,197 PROFILE, LESS CYTOKINE SYNDROME 4512 03:03:48,197 --> 03:03:49,532 THAT IS OBSERVED. 4513 03:03:49,532 --> 03:03:51,534 THIS WAS CARRIED OUT IN HUMAN 4514 03:03:51,534 --> 03:03:52,401 CLINICAL TRIALS. 4515 03:03:52,401 --> 03:03:53,769 I WILL JUST SUMMARIZE THE 4516 03:03:53,769 --> 03:03:57,439 FINDING HERE. 4517 03:03:57,439 --> 03:04:00,242 THEY SAID IT'S VERY EFFICACIOUS 4518 03:04:00,242 --> 03:04:02,545 BUT THE DEVELOPMENT OF CELL 4519 03:04:02,545 --> 03:04:04,947 ISOLATION TECHNOLOGIES THAT 4520 03:04:04,947 --> 03:04:07,249 UTILIZE CELL SORTING OR CELL 4521 03:04:07,249 --> 03:04:09,552 SERIAL COLUMN BASED SELECTIONS 4522 03:04:09,552 --> 03:04:10,953 WITH REVERSALLY BINDING AGENTS 4523 03:04:10,953 --> 03:04:12,555 MAY FURTHER REFINE THE 4524 03:04:12,555 --> 03:04:13,556 SELECTION OF T-CELLS. 4525 03:04:13,556 --> 03:04:14,924 SO I SPOKE WITH THE FIRST 4526 03:04:14,924 --> 03:04:16,292 AUTHOR OF THIS PAPER. 4527 03:04:16,292 --> 03:04:18,160 WHAT HE TOLD ME WAS THEY HAD A 4528 03:04:18,160 --> 03:04:19,562 SIGNIFICANT FRACTION OF 4529 03:04:19,562 --> 03:04:20,729 PATIENTS THEY COULDN'T TREAT AT 4530 03:04:20,729 --> 03:04:22,231 ALL BECAUSE THE YIELD WAS TOO 4531 03:04:22,231 --> 03:04:22,865 LOW. 4532 03:04:22,865 --> 03:04:25,801 THEY HAVE TO DO DOUBLE 4533 03:04:25,801 --> 03:04:26,769 SELECTION OF NEGATIVE AND 4534 03:04:26,769 --> 03:04:27,736 POSITIVE SELECTION. 4535 03:04:27,736 --> 03:04:30,005 WHILE THIS COULD BE MORE 4536 03:04:30,005 --> 03:04:31,840 EFFICACIOUS, THEY COULDN'T 4537 03:04:31,840 --> 03:04:33,709 GENERATE ENOUGH PRODUCT FOR A 4538 03:04:33,709 --> 03:04:34,343 SIGNIFICANT PERCENTAGE OF THE 4539 03:04:34,343 --> 03:04:39,481 PATIENTS. 4540 03:04:39,481 --> 03:04:41,383 I HAVE SHOWN IDENTIFICATION OF 4541 03:04:41,383 --> 03:04:42,851 TWO DIFFERENT APTAMERS. 4542 03:04:42,851 --> 03:04:45,120 I WILL SKIP THAT AND SAY WE 4543 03:04:45,120 --> 03:04:47,456 IDENTIFIED THE CD62 APTAMER 4544 03:04:47,456 --> 03:04:49,792 THAT HAS HIGH-BINDING AFFINITY. 4545 03:04:49,792 --> 03:04:50,926 HOPEFULLY THESE CURVES LOOK 4546 03:04:50,926 --> 03:04:51,894 VERY FAMILIAR TO YOU. 4547 03:04:51,894 --> 03:04:53,762 THIS ONE IS REALLY HIGH BINDING 4548 03:04:53,762 --> 03:04:54,897 AFFINITY. 4549 03:04:54,897 --> 03:05:00,302 LESS THAN ONE NM BINDING 4550 03:05:00,302 --> 03:05:00,569 AFFINITY. 4551 03:05:00,569 --> 03:05:04,073 WE CAN DEFINE BY CHARACTERISTIC 4552 03:05:04,073 --> 03:05:06,875 DIAGONAL OF APTAMER BINDING 4553 03:05:06,875 --> 03:05:09,178 VERSUS CD62L. 4554 03:05:09,178 --> 03:05:11,113 AND CONFIRM USING RECOMBINANT 4555 03:05:11,113 --> 03:05:11,981 PROTEIN. 4556 03:05:11,981 --> 03:05:14,116 WHAT WE CAN DO SINCE WE HAVE 4557 03:05:14,116 --> 03:05:15,517 THE TWO APTAMERS WE CAN USE 4558 03:05:15,517 --> 03:05:16,185 THEM TOGETHER. 4559 03:05:16,185 --> 03:05:19,655 WE CAN TAKE OUR PBMC'S, WE CAN 4560 03:05:19,655 --> 03:05:21,056 ADD IN BOTH APTAMERS. 4561 03:05:21,056 --> 03:05:23,659 WE CAN ADD IN, SORRY, APTAMER 4562 03:05:23,659 --> 03:05:26,495 FOR CD8 AND THEN ISOLATE OUR 4563 03:05:26,495 --> 03:05:31,400 CD8 POSITIVE CELLS. 4564 03:05:31,400 --> 03:05:34,403 SO THAT'S ISOLATION OF OUR CD8 4565 03:05:34,403 --> 03:05:37,439 POSITIVE CELLS AND TAKE THE CD8 4566 03:05:37,439 --> 03:05:40,509 POSITIVE CELLS SINCE THEY ARE 4567 03:05:40,509 --> 03:05:41,210 TRACELESSLY SELECTED, THEY 4568 03:05:41,210 --> 03:05:43,946 DON'T COME OFF WITH MAGNETIC 4569 03:05:43,946 --> 03:05:46,615 BEADS, AND PUT THEM BACK FOR 4570 03:05:46,615 --> 03:05:47,149 SECOND SELECTION, SERIAL 4571 03:05:47,149 --> 03:05:48,784 SELECTION. 4572 03:05:48,784 --> 03:05:52,688 WE INCUBATE WITH CD62 APTAMERS 4573 03:05:52,688 --> 03:05:56,558 AND WE CAN CAPTURE THE CELLS 4574 03:05:56,558 --> 03:05:58,661 ALSO USING TRACELESS SELECTION. 4575 03:05:58,661 --> 03:06:00,062 WE GET DOUBLE TRACELESS 4576 03:06:00,062 --> 03:06:00,496 SELECTION. 4577 03:06:00,496 --> 03:06:02,898 AND WE GET OUR PURE POPULATION 4578 03:06:02,898 --> 03:06:03,098 HERE. 4579 03:06:03,098 --> 03:06:09,638 THIS IS NOW CD8 POSITIVE AND 4580 03:06:09,638 --> 03:06:10,639 CD62 POSITIVE CELLS. 4581 03:06:10,639 --> 03:06:12,641 THE PURITY OF THE CELLS, USING 4582 03:06:12,641 --> 03:06:14,510 OUR DOUBLE APTAMER VERSUS 4583 03:06:14,510 --> 03:06:17,146 ANTIBODY SELECTION IS THE SAME. 4584 03:06:17,146 --> 03:06:18,247 BUT THE BIG DIFFERENCE IS IN 4585 03:06:18,247 --> 03:06:20,582 YIELD. 4586 03:06:20,582 --> 03:06:23,385 SO WE DOUBLE THE YIELD OF OUR 4587 03:06:23,385 --> 03:06:26,488 PRODUCT BY USING THIS TRACELESS 4588 03:06:26,488 --> 03:06:26,989 APTAMER-BASED SELECTION 4589 03:06:26,989 --> 03:06:28,223 APPROACH. 4590 03:06:28,223 --> 03:06:31,593 AND SO YOU CAN SEE HERE IF WE 4591 03:06:31,593 --> 03:06:33,696 ANALYZE THE PHENOTYPE OF THE 4592 03:06:33,696 --> 03:06:36,298 CD8 CELLS COMING OUT, WE START 4593 03:06:36,298 --> 03:06:38,801 OUT WITH ONLY THREE AND A HALF 4594 03:06:38,801 --> 03:06:41,170 PERCENT OF NAIVE T-CELLS. 4595 03:06:41,170 --> 03:06:43,772 IF WE ONLY DO CD8 SELECTION, 4596 03:06:43,772 --> 03:06:44,940 THE RELEVANT CELLS HERE ARE 4597 03:06:44,940 --> 03:06:46,141 JUST ABOUT A LITTLE BIT UNDER 4598 03:06:46,141 --> 03:06:46,542 HALF. 4599 03:06:46,542 --> 03:06:50,979 IF WE DO A COMBINATION OF CD8 4600 03:06:50,979 --> 03:06:53,749 AND CD62L SELECTION, THEN WE 4601 03:06:53,749 --> 03:06:56,685 ARE GETTING 70-80% OF OUR CELLS 4602 03:06:56,685 --> 03:06:59,254 BEING THESE NAIVE AND MEMORY 4603 03:06:59,254 --> 03:07:02,324 STEM CELL PHENOTYPES. 4604 03:07:02,324 --> 03:07:04,593 OKAY. 4605 03:07:04,593 --> 03:07:06,695 SO I'VE BEEN ABLE TO TELL YOU 4606 03:07:06,695 --> 03:07:07,663 ABOUT DIFFERENT APPLICATIONS OF 4607 03:07:07,663 --> 03:07:08,664 APTAMERS. 4608 03:07:08,664 --> 03:07:10,966 I JUST WANTED TO END WITH ONE 4609 03:07:10,966 --> 03:07:11,266 THING. 4610 03:07:11,266 --> 03:07:14,436 WE REALLY WANTED TO MOVE TO 4611 03:07:14,436 --> 03:07:15,704 MANUFACTURERABLE SYSTEMS. 4612 03:07:15,704 --> 03:07:17,706 AS I MENTIONED DURING THE PANEL 4613 03:07:17,706 --> 03:07:19,775 DISCUSSION, WE WANTED TO MOVE 4614 03:07:19,775 --> 03:07:21,143 TO SYNTHETIC REAGENTS. 4615 03:07:21,143 --> 03:07:22,678 SO HOPEFULLY I HAVE TOLD YOU 4616 03:07:22,678 --> 03:07:25,147 ABOUT APTAMERS WHICH ARE 4617 03:07:25,147 --> 03:07:26,882 SYNTHETIC ANTIBODIES FOR THIS 4618 03:07:26,882 --> 03:07:27,182 APPLICATION. 4619 03:07:27,182 --> 03:07:28,684 AND SECONDLY WE ARE INTERESTED 4620 03:07:28,684 --> 03:07:31,053 IN MOVING TO CLOSED SYSTEM. 4621 03:07:31,053 --> 03:07:33,655 INSTEAD OF USING MAGNETIC BEADS 4622 03:07:33,655 --> 03:07:35,557 AND REMOVAL OF MAGNETIC BEADS 4623 03:07:35,557 --> 03:07:37,526 WE WANTED TO SEE IF WE COULD 4624 03:07:37,526 --> 03:07:41,563 USE RESIN SO WE COULD HAVE 4625 03:07:41,563 --> 03:07:42,164 CHROMOTOGRAPHY-LIKE RECEPTION 4626 03:07:42,164 --> 03:07:42,831 OF CELLS. 4627 03:07:42,831 --> 03:07:44,233 THE ANSWER TO THAT IS YES. 4628 03:07:44,233 --> 03:07:47,903 WE HAVE BEEN ABLE TO COUPLE 4629 03:07:47,903 --> 03:07:52,274 THESE APTAMERS TO RESIN BEADS, 4630 03:07:52,274 --> 03:07:55,310 WE USE POLYSTYRENE BECAUSE IT 4631 03:07:55,310 --> 03:07:56,612 COULD BE EASILY STERILIZED. 4632 03:07:56,612 --> 03:07:58,580 WE HAVE BEEN ABLE TO USE THIS 4633 03:07:58,580 --> 03:07:59,515 FOR CELL DEPLETION. 4634 03:07:59,515 --> 03:08:01,183 I DIDN'T TALK ABOUT IT BUT WE 4635 03:08:01,183 --> 03:08:03,085 HAVE A HUMAN MONOCYTE BINDING 4636 03:08:03,085 --> 03:08:03,519 APTAMER. 4637 03:08:03,519 --> 03:08:05,521 WE CAN USE THIS FOR DEPLETION 4638 03:08:05,521 --> 03:08:07,389 OF CELLS THAT YOU DON'T WANT. 4639 03:08:07,389 --> 03:08:11,326 WE HAVE ALSO BEEN ABLE TO DO 4640 03:08:11,326 --> 03:08:14,196 THIS TYPE OF COLUMN-BASED 4641 03:08:14,196 --> 03:08:16,098 SELECTION FOR CD8 POSITIVE T 4642 03:08:16,098 --> 03:08:20,202 CELLS SO THIS WAS REPORTED IN 4643 03:08:20,202 --> 03:08:22,704 ACA BIO MATERIALS SCIENCE AND 4644 03:08:22,704 --> 03:08:23,005 ENGINEERING. 4645 03:08:23,005 --> 03:08:25,440 WE ARE EXCITED ABOUT THIS 4646 03:08:25,440 --> 03:08:25,974 APTAMER-BASED TECHNOLOGY. 4647 03:08:25,974 --> 03:08:27,009 THE ONE THING I DIDN'T MENTION 4648 03:08:27,009 --> 03:08:27,976 WAS THE PRICE. 4649 03:08:27,976 --> 03:08:33,448 SO FOR US, THE COST TO DO THE 4650 03:08:33,448 --> 03:08:35,217 MAGNETIC BASED SELECTION WITH 4651 03:08:35,217 --> 03:08:38,787 ANTIBODIES IS ABOUT $5,000 IN 4652 03:08:38,787 --> 03:08:39,121 THE REAGENTS. 4653 03:08:39,121 --> 03:08:41,423 THE APTAMERS WE USE FOR THE 4654 03:08:41,423 --> 03:08:42,825 APTAMER AND REVERSAL AGENT IS 4655 03:08:42,825 --> 03:08:44,726 LESS THAN $10. 4656 03:08:44,726 --> 03:08:47,696 THE APTAMERS BECAUSE WE USE LOW 4657 03:08:47,696 --> 03:08:48,864 CONCENTRATION AND BECAUSE 4658 03:08:48,864 --> 03:08:50,799 APTAMERS ARE SO CHEAP TO 4659 03:08:50,799 --> 03:08:51,200 PRODUCE. 4660 03:08:51,200 --> 03:08:53,202 WE ARE EXCITED ABOUT IT BECAUSE 4661 03:08:53,202 --> 03:08:54,903 WE THINK THE ABILITY TO REVERSE 4662 03:08:54,903 --> 03:08:56,238 THE SWITCHING OF THE APTAMER 4663 03:08:56,238 --> 03:08:58,841 MAKE IT'S VERY POWERFUL FOR 4664 03:08:58,841 --> 03:09:00,008 DOING ADVANCED SELECTION AND 4665 03:09:00,008 --> 03:09:02,578 COMBINED WITH THE CHEAPLESS OF 4666 03:09:02,578 --> 03:09:03,745 THIS APTAMER-BASED APPROACH WE 4667 03:09:03,745 --> 03:09:05,981 THINK IT COULD MAKE AN IMPACT 4668 03:09:05,981 --> 03:09:08,851 IN TERMS OF THE COST OF 4669 03:09:08,851 --> 03:09:09,184 MANUFACTURING. 4670 03:09:09,184 --> 03:09:11,453 ALL RIGHT, SO JUST TO SUMMARIZE 4671 03:09:11,453 --> 03:09:12,588 FOR THESE SECTIONS, IF THE 4672 03:09:12,588 --> 03:09:14,122 FIRST SECTION I TALKED ABOUT 4673 03:09:14,122 --> 03:09:16,191 CONCEPT OF USING APTAMERS. 4674 03:09:16,191 --> 03:09:18,093 THE MAIN POINT IS THE APTAMERS 4675 03:09:18,093 --> 03:09:20,562 ARE SWITCHABLE AND WE CAN GET 4676 03:09:20,562 --> 03:09:21,563 TRACELESS SELECTED CELLS. 4677 03:09:21,563 --> 03:09:23,332 THE SECOND SECTION I SHOWED WE 4678 03:09:23,332 --> 03:09:25,968 CAN ALSO USE THIS TO IMPROVE 4679 03:09:25,968 --> 03:09:30,472 SAFETY BY REMOVING CANCER CELLS. 4680 03:09:30,472 --> 03:09:32,241 THE THIRD SECTION I SHOWED WE 4681 03:09:32,241 --> 03:09:34,843 CAN ACTUALLY POTENTIALLY MAKE A 4682 03:09:34,843 --> 03:09:36,712 METHOD THAT WAS NOT 4683 03:09:36,712 --> 03:09:38,413 TRANSLATABLE BECAUSE OF POOR 4684 03:09:38,413 --> 03:09:41,149 YIELD INTO A POTENTIALLY 4685 03:09:41,149 --> 03:09:42,217 TRANSLATABLE PRODUCT. 4686 03:09:42,217 --> 03:09:43,919 WITH APTAMERS WE CAN GET ABOUT 4687 03:09:43,919 --> 03:09:45,821 DOUBLE THE YIELD FOR THE SERIAL 4688 03:09:45,821 --> 03:09:46,755 SELECTIONS. 4689 03:09:46,755 --> 03:09:48,123 FINALLY WE HAVE BEEN ABLE TO 4690 03:09:48,123 --> 03:09:52,194 SHOW WE CAN CHEMICALLY MODIFY 4691 03:09:52,194 --> 03:09:58,467 RESINS, AND USE CHROMATOGRAPHIC. 4692 03:09:58,467 --> 03:10:02,371 FOR THOSE WHO ARE GRADUATE 4693 03:10:02,371 --> 03:10:03,272 STUDENTS, SOMETIMES FAILED 4694 03:10:03,272 --> 03:10:05,741 EXPERIMENTS CAN STILL BE USEFUL. 4695 03:10:05,741 --> 03:10:08,076 THIS WORK WAS DONE IN CLOSE 4696 03:10:08,076 --> 03:10:09,678 COLLABORATION WITH MICHAEL 4697 03:10:09,678 --> 03:10:11,680 JENSEN AT SEATTLE CHILDREN'S, 4698 03:10:11,680 --> 03:10:14,650 HE IS THE FIZZ IKS I PHYSICIAN 4699 03:10:14,650 --> 03:10:16,184 I HAVE THE GREAT PRIVILEGE OF 4700 03:10:16,184 --> 03:10:17,920 WORKING. 4701 03:10:17,920 --> 03:10:25,260 THE CD8 WORK, BY NATALY 4702 03:10:25,260 --> 03:10:33,869 KACHEROVSKY. 4703 03:10:33,869 --> 03:10:38,607 EMMELINE CHENG. 4704 03:10:38,607 --> 03:10:41,476 MELISSA YANG DID HARD WORK. 4705 03:10:41,476 --> 03:10:44,246 ABE WU HAS BEEN PIONEERING THE 4706 03:10:44,246 --> 03:10:45,781 MEMORY STEM CELL POPULATION 4707 03:10:45,781 --> 03:10:46,782 ISOLATION. 4708 03:10:46,782 --> 03:10:50,485 THIS IS OUR LAB IN SUNNY 4709 03:10:50,485 --> 03:10:51,954 SEATTLE IN THE SUMMER. 4710 03:10:51,954 --> 03:10:54,489 WE ARE VERY GRATEFUL FOR OUR 4711 03:10:54,489 --> 03:10:54,723 FUNDING. 4712 03:10:54,723 --> 03:10:58,160 THIS WORK WAS STARTED BY 4713 03:10:58,160 --> 03:11:00,662 FUNDING FROM JUNE NO 4714 03:11:00,662 --> 03:11:10,205 THERAPEUTICS AND NOW NIH NIBIB. 4715 03:11:10,205 --> 03:11:11,606 VERY GRATEFUL. 4716 03:11:11,606 --> 03:11:13,942 I WOULD BE HAPPY TO ANSWER ANY 4717 03:11:13,942 --> 03:11:24,453 QUESTIONS THAT YOU MIGHT HAVE. 4718 03:11:24,786 --> 03:11:26,822 >> Rahul Thakar: SUZIE, THAT 4719 03:11:26,822 --> 03:11:27,756 WAS BEAUTIFUL WORK. 4720 03:11:27,756 --> 03:11:29,658 ONE QUESTION ABOUT THE TRANSFER 4721 03:11:29,658 --> 03:11:31,293 AND RECEPTOR, WHICH IS NEAR AND 4722 03:11:31,293 --> 03:11:39,001 DEAR TO MY HEART. 4723 03:11:39,001 --> 03:11:41,370 I WAS UNDER THE IMPRESSION 4724 03:11:41,370 --> 03:11:43,271 EVERY CELL HAS TRANSFER AND 4725 03:11:43,271 --> 03:11:46,341 RECEPTOR, HOW DO YOU GET NOT 4726 03:11:46,341 --> 03:11:48,443 LOSING THE CELLS YOU WANT WHEN 4727 03:11:48,443 --> 03:11:51,179 USING THAT COUNTER SELECTION? 4728 03:11:51,179 --> 03:11:53,281 >> Suzie Pun: YES, BECAUSE 4729 03:11:53,281 --> 03:11:55,117 TRANSFER AND RECEPTOR IS UP 4730 03:11:55,117 --> 03:11:56,985 REGULATED SO MUCH MORE, AND 4731 03:11:56,985 --> 03:12:04,092 BUEZ BECAUSE WE ARE USING 4732 03:12:04,092 --> 03:12:06,461 MAGNETIC, WE CAN'T RECOVER THE 4733 03:12:06,461 --> 03:12:08,263 CELLS WELL BECAUSE YOU DON'T 4734 03:12:08,263 --> 03:12:09,731 HAVE ENOUGH BEAD, SO IT TURNS 4735 03:12:09,731 --> 03:12:11,500 OUT TO BE A VERY SIMPLE 4736 03:12:11,500 --> 03:12:13,635 SELECTION. 4737 03:12:13,635 --> 03:12:14,936 IT'S BECAUSE OF THE LEVEL OF 4738 03:12:14,936 --> 03:12:15,637 DIFFERENCE. 4739 03:12:15,637 --> 03:12:22,878 >> COOL, THANK YOU. 4740 03:12:22,878 --> 03:12:24,513 >> VERY NICE WORK. 4741 03:12:24,513 --> 03:12:26,615 VERY BEAUTIFUL DATA. 4742 03:12:26,615 --> 03:12:30,786 I'M JUST CURIOUS WHEN YOU SAY 4743 03:12:30,786 --> 03:12:33,622 TEMPERATURE DEPENDENCE, SORTING 4744 03:12:33,622 --> 03:12:37,626 DEFICIENCIES, I'M CURIOUS ABOUT 4745 03:12:37,626 --> 03:12:39,528 THE SECONDARY STRUCTURE OF THE 4746 03:12:39,528 --> 03:12:45,100 APTAMERS AND IF YOU NEED TO 4747 03:12:45,100 --> 03:12:47,035 ANIL (?) AT DIFFERENT 4748 03:12:47,035 --> 03:12:47,669 TEMPERATURES? 4749 03:12:47,669 --> 03:12:49,771 >> Suzie Pun: THAT'S A GOOD 4750 03:12:49,771 --> 03:12:51,940 QUESTION, SOME APTAMERS CAN BE 4751 03:12:51,940 --> 03:12:52,841 TEMPERATURE SENSITIVE. 4752 03:12:52,841 --> 03:12:54,709 IN THIS CASE WE DIDN'T HAVE ANY 4753 03:12:54,709 --> 03:12:56,344 TROUBLE WITH THAT, WE DO OUR 4754 03:12:56,344 --> 03:12:59,581 SELECTIONS AT ROOM TEMPERATURE. 4755 03:12:59,581 --> 03:13:02,918 WE DO HAVE AN APTAMER THAT I 4756 03:13:02,918 --> 03:13:05,053 DIDN'T TALK ABOUT HERE THAT WE 4757 03:13:05,053 --> 03:13:07,622 WANTED TO USE IN VIVO AND THAT 4758 03:13:07,622 --> 03:13:10,625 APTAMER WHEN WE GET TO 37° 4759 03:13:10,625 --> 03:13:12,727 LOSES ABOUT HALF OFITY BINDING. 4760 03:13:12,727 --> 03:13:14,362 YOU ARE RIGHT THAT TEMPERATURE 4761 03:13:14,362 --> 03:13:17,399 SENSITIVITY CAN BE AN ISSUE. 4762 03:13:17,399 --> 03:13:19,267 SOME APTAMERS ARE STABLE ENOUGH. 4763 03:13:19,267 --> 03:13:21,103 I THINK THE OTHER THING WE CAN 4764 03:13:21,103 --> 03:13:24,706 DO IS TO INCREASE THE STEM 4765 03:13:24,706 --> 03:13:27,776 REGION OR SWITCH IN FOR 4766 03:13:27,776 --> 03:13:29,811 EXAMPLE, CG COMPLEXES TO TRY TO 4767 03:13:29,811 --> 03:13:31,113 INCREASE THE THERMAL STABILITY 4768 03:13:31,113 --> 03:13:33,115 AND ALSO DO THE SELECTION AT 4769 03:13:33,115 --> 03:13:35,917 THE TEMPERATURE THAT WOULD BE 4770 03:13:35,917 --> 03:13:37,085 RELEVANT, THE SELECTION OF THE 4771 03:13:37,085 --> 03:13:37,319 APTAMER. 4772 03:13:37,319 --> 03:13:39,221 IF YOU DO THE SELECTS PROCEDURE 4773 03:13:39,221 --> 03:13:42,023 AT A HIGHER TEMPERATURE, YOU 4774 03:13:42,023 --> 03:13:43,925 WILL SELECT APTAMERS THAT ARE 4775 03:13:43,925 --> 03:13:45,994 MORE STABLE AT THAT TEMPERATURE. 4776 03:13:45,994 --> 03:13:47,629 >> MAYBE A FOLLOW-UP QUESTION, 4777 03:13:47,629 --> 03:13:49,998 THE PRESENCE OF THE CELLS WITH 4778 03:13:49,998 --> 03:13:51,633 POTENTIAL RELEASE OF DNA OR 4779 03:13:51,633 --> 03:13:53,301 THINGS LIKE THAT, HAVE YOU SEEN 4780 03:13:53,301 --> 03:13:56,071 ANY EFFECT ON THE CELL SORTING 4781 03:13:56,071 --> 03:13:57,706 EFFICIENCY, BASED OFF HOW 4782 03:13:57,706 --> 03:13:59,107 CLEAN, FOR EXAMPLE, THE 4783 03:13:59,107 --> 03:14:06,615 STARTING PRODUCT IS? 4784 03:14:06,615 --> 03:14:08,250 >> Suzie Pun: WE HAVE IN A 4785 03:14:08,250 --> 03:14:10,585 SENSE, IF WE HAVE A LOT OF DEAD 4786 03:14:10,585 --> 03:14:14,156 CELLS THEY WILL SOMETIMES STICK 4787 03:14:14,156 --> 03:14:15,557 NON SPECIFICALLY TO THE RESIN 4788 03:14:15,557 --> 03:14:17,325 AND IT WILL GUM UP THE RESIN. 4789 03:14:17,325 --> 03:14:21,429 THAT WAS A PROBLEM WITH OUR 4790 03:14:21,429 --> 03:14:23,732 CHROMOTOGRAPHY ONES WITH WERE 4791 03:14:23,732 --> 03:14:25,233 RELYING ON GRAVITY FLOW. 4792 03:14:25,233 --> 03:14:28,603 IN THAT CASE WE HAD TO HAVE A 4793 03:14:28,603 --> 03:14:31,239 PRE-COLUMN TO REMOVE STICKY AND 4794 03:14:31,239 --> 03:14:34,876 DEAD CELLS IN THE 4795 03:14:34,876 --> 03:14:35,343 CHROMOTOGRAPHY METHOD. 4796 03:14:35,343 --> 03:14:38,580 WE HAVE TRIED FRESH CELLS AND 4797 03:14:38,580 --> 03:14:40,916 THAWED CELLS AND CELLS FROM 4798 03:14:40,916 --> 03:14:42,284 DIFFERENT DONORS AND HAVEN'T 4799 03:14:42,284 --> 03:14:46,221 SEEN A HUGE ISSUE WITH THAT. 4800 03:14:46,221 --> 03:14:47,055 >> REALLY GREAT TALK. 4801 03:14:47,055 --> 03:14:50,158 I ESPECIALLY REALLY ENJOYED 4802 03:14:50,158 --> 03:14:51,560 SEEING THE CHROMOTOGRAPHY WORK 4803 03:14:51,560 --> 03:14:53,795 WITH THE RESIN YOU HAVE DONE. 4804 03:14:53,795 --> 03:14:59,935 ONE QUESTION I THINK COMES UP 4805 03:14:59,935 --> 03:15:05,974 WITH RESIN REUSE, IT'S MAYBE 4806 03:15:05,974 --> 03:15:08,610 FINANCIALLY INCENTIVE TO REUSE. 4807 03:15:08,610 --> 03:15:10,512 THE APTAMERS YOU ARE USING TO 4808 03:15:10,512 --> 03:15:12,681 RELEASE EITHER THE CD8 CELLS OR 4809 03:15:12,681 --> 03:15:13,615 WHATEVER CELLS YOU ARE 4810 03:15:13,615 --> 03:15:16,151 SELECTING FOR. 4811 03:15:16,151 --> 03:15:17,786 IS REUSABILITY STILL POSSIBLE 4812 03:15:17,786 --> 03:15:18,019 WITH IT? 4813 03:15:18,019 --> 03:15:23,491 ONE THOUGHT IS HOW DO YOU 4814 03:15:23,491 --> 03:15:24,593 SEPARATE THAT CHANGED STRUCTURE 4815 03:15:24,593 --> 03:15:26,528 AFTER YOU ADD THE SECOND PIECE. 4816 03:15:26,528 --> 03:15:28,430 >> Suzie Pun: GREAT QUESTION. 4817 03:15:28,430 --> 03:15:31,199 THEE ARE THICALLY IT WOULD BE 4818 03:15:31,199 --> 03:15:32,400 TOTALLY REUSABLE BECAUSE WHEN 4819 03:15:32,400 --> 03:15:34,736 YOU REHEAT YOU CAN SEPARATE 4820 03:15:34,736 --> 03:15:37,038 THAT REVERSAL STRAND. 4821 03:15:37,038 --> 03:15:41,042 LIKE GABE WAS ELUDING TO, WHEN 4822 03:15:41,042 --> 03:15:43,411 IT COOLS IT WILL FOLD BACK IN 4823 03:15:43,411 --> 03:15:45,113 ITS SECONDARY STRUCTURE. 4824 03:15:45,113 --> 03:15:45,981 WE HAVEN'T EXPLORED THAT 4825 03:15:45,981 --> 03:15:47,849 BECAUSE THE APTAMERS ARE JUST 4826 03:15:47,849 --> 03:15:50,051 SO CHEAP. 4827 03:15:50,051 --> 03:15:51,920 THE $5 WORTH OF APTAMERS. 4828 03:15:51,920 --> 03:15:54,990 IS IT WORTH IT TO RESTERILIZE 4829 03:15:54,990 --> 03:15:57,125 IF THE COST OF YOUR REAGENT IS 4830 03:15:57,125 --> 03:15:58,693 SO LOW. 4831 03:15:58,693 --> 03:15:59,861 I CAN'T ANSWER THAT. 4832 03:15:59,861 --> 03:16:01,663 OKAY, THANK YOU. 4833 03:16:01,663 --> 03:16:03,698 ALL RIGHT, THANK 4834 03:16:03,698 --> 03:16:03,865 YOU. 4835 03:16:03,865 --> 03:16:14,075 [ APPLAUSE ] 4836 03:17:01,990 --> 03:17:04,225 Rahul Thakar: HELLO, AGAIN. 4837 03:17:04,225 --> 03:17:06,594 IT'S MY PRIVILEGE TO INTRODUCE 4838 03:17:06,594 --> 03:17:09,831 OUR NEXT SPEAKER, DR. PAUL 4839 03:17:09,831 --> 03:17:10,765 SHEEHAN FROM ARPA-H. 4840 03:17:10,765 --> 03:17:12,167 HE IS GOING TO GIVE YOU A 4841 03:17:12,167 --> 03:17:14,069 LITTLE BIT OF AN IDEA OF WHAT'S 4842 03:17:14,069 --> 03:17:15,937 GOING ON BETWEEN THE 4843 03:17:15,937 --> 03:17:17,572 INTERSECTION BETWEEN BIO 4844 03:17:17,572 --> 03:17:18,740 ELECTRONICS AND SYNTHETIC 4845 03:17:18,740 --> 03:17:20,175 BIOLOGY. 4846 03:17:20,175 --> 03:17:23,712 BEFORE HE WAS AT ARPA-H HE 4847 03:17:23,712 --> 03:17:27,449 RECEIVED A Ph.D. IN CHEMICAL 4848 03:17:27,449 --> 03:17:28,416 PHYSICS FROM HARVARD AND USED 4849 03:17:28,416 --> 03:17:31,219 THAT KNOWLEDGE AS A BASIS TO 4850 03:17:31,219 --> 03:17:33,088 PUSH FORWARD NANO SCALE 4851 03:17:33,088 --> 03:17:35,657 MECHANICS AND WHAT NOT AT 4852 03:17:35,657 --> 03:17:38,226 N.R.L. AND DARPA. 4853 03:17:38,226 --> 03:17:39,394 TAKING THOSE INFLUENCES AND 4854 03:17:39,394 --> 03:17:41,529 PIECES OF KNOWLEDGE HE HAS COME 4855 03:17:41,529 --> 03:17:42,697 TO ARPA-H IN FEBRUARY. 4856 03:17:42,697 --> 03:17:44,966 AND HE HAS ALREADY INITIATED 4857 03:17:44,966 --> 03:17:45,734 FOUR PROGRAMS. 4858 03:17:45,734 --> 03:17:46,801 ONE OF WHICH HE WILL TELL US 4859 03:17:46,801 --> 03:17:47,369 ABOUT. 4860 03:17:47,369 --> 03:17:53,508 THANK YOU. 4861 03:17:53,508 --> 03:17:56,177 >> Paul Sheehan: THANK YOU SO 4862 03:17:56,177 --> 03:17:57,812 MUCH JERMONT AND COMPANY, FOR 4863 03:17:57,812 --> 03:17:59,214 THE INVITATION. 4864 03:17:59,214 --> 03:18:03,418 GREAT. 4865 03:18:03,418 --> 03:18:05,487 AS RAHUL NOTED TODAY MY PLAN IS 4866 03:18:05,487 --> 03:18:07,589 TO TALK A LITTLE ABOUT THE 4867 03:18:07,589 --> 03:18:08,990 AGENCY, TO LET PEOPLE KNOW, I 4868 03:18:08,990 --> 03:18:09,824 HAVE AN IDEA. 4869 03:18:09,824 --> 03:18:12,293 IS IT A RIGHT FIT, A GOOD FIT 4870 03:18:12,293 --> 03:18:12,961 FOR ARPA-H. 4871 03:18:12,961 --> 03:18:14,162 AT THE END I WILL TALK ABOUT 4872 03:18:14,162 --> 03:18:15,897 SOME OF THE PROGRAMS WE HAVE 4873 03:18:15,897 --> 03:18:16,931 ANNOUNCED. 4874 03:18:16,931 --> 03:18:19,501 SOME OF WHICH TAKE ADVANTAGE OF 4875 03:18:19,501 --> 03:18:20,902 SYNTHETIC BIOLOGY SO YOU GET A 4876 03:18:20,902 --> 03:18:22,804 FEEL FOR THE KINDS OF THINGS WE 4877 03:18:22,804 --> 03:18:23,972 ARE LOOKING FOR. 4878 03:18:23,972 --> 03:18:26,975 FOR THOSE OF YOU WHO ARE 4879 03:18:26,975 --> 03:18:28,410 UNFAMILIAR, ARPA-H WAS SET UP A 4880 03:18:28,410 --> 03:18:32,914 YEAR AND A HALF AGO IN MARCH OF 4881 03:18:32,914 --> 03:18:34,282 2022. 4882 03:18:34,282 --> 03:18:36,384 THE INSPIRATION FOR IT WAS FROM 4883 03:18:36,384 --> 03:18:39,621 DARPA, THE AGENCY I CAME FROM 4884 03:18:39,621 --> 03:18:40,722 BEFORE ARPA-H. 4885 03:18:40,722 --> 03:18:43,057 IS EVERYONE FAMILIAR WITH DARPA? 4886 03:18:43,057 --> 03:18:44,259 SHOW OF HANDS? 4887 03:18:44,259 --> 03:18:46,261 GREAT. 4888 03:18:46,261 --> 03:18:49,030 THE CONCEPT BEHIND DARPA IS IT 4889 03:18:49,030 --> 03:18:55,603 IS AN AGENCY THAT UNDERTAKES 4890 03:18:55,603 --> 03:18:56,538 HIGH-RISK, HIGH-REWARD EFFORTS. 4891 03:18:56,538 --> 03:18:58,173 WE ARE A RISK MITIGATION 4892 03:18:58,173 --> 03:18:59,541 AGENCIMENT WE TAKE YOUR CRAZY 4893 03:18:59,541 --> 03:19:00,275 IDEA. 4894 03:19:00,275 --> 03:19:03,545 WE MEET WITH YOU MONTHLY, THINK 4895 03:19:03,545 --> 03:19:06,147 OF ANYWAY IT CAN GO WRONG, COME 4896 03:19:06,147 --> 03:19:08,450 UP WITH A BACK UP PLAN, TRY TO 4897 03:19:08,450 --> 03:19:10,318 FUND PEOPLE AS FULLY AS 4898 03:19:10,318 --> 03:19:11,519 POSSIBLE, EACH AND EVERY MONTH, 4899 03:19:11,519 --> 03:19:13,154 I HAVE TALKED TO SOME PEOPLE ON 4900 03:19:13,154 --> 03:19:15,023 THE PHONE CALLS EACH AND EVERY 4901 03:19:15,023 --> 03:19:16,324 MONTH TRYING TO TRACK WHAT'S 4902 03:19:16,324 --> 03:19:17,826 GOING ON. 4903 03:19:17,826 --> 03:19:19,928 THAT'S THE GLOBAL CONCEPT. 4904 03:19:19,928 --> 03:19:21,696 AND THAT IS A SOLUTION, 4905 03:19:21,696 --> 03:19:23,665 PROBABLY ONE OF THE BETTER 4906 03:19:23,665 --> 03:19:24,599 SOLUTIONS FOR ADDRESSING THESE 4907 03:19:24,599 --> 03:19:26,601 SORT OF WILD IDEAS. 4908 03:19:26,601 --> 03:19:29,404 IS IT EVEN POSSIBLE. 4909 03:19:29,404 --> 03:19:31,039 WE ARE REPRESENTING THE 4910 03:19:31,039 --> 03:19:32,240 COMMENTS FROM PRESIDENT BIDEN 4911 03:19:32,240 --> 03:19:34,409 WHEN HE ANNOUNCED IT. 4912 03:19:34,409 --> 03:19:36,511 SOME IDEAS ARE SO AUDACIOUS 4913 03:19:36,511 --> 03:19:38,146 SOME SAY IT WILL WORK ONLY IF 4914 03:19:38,146 --> 03:19:39,747 WE CAN TRY IT IN A BIG WAY, 4915 03:19:39,747 --> 03:19:41,683 RIGHT? 4916 03:19:41,683 --> 03:19:43,785 SO THE OTHER THING ABOUT 4917 03:19:43,785 --> 03:19:45,687 ARPA-H, THE WAY IT 4918 03:19:45,687 --> 03:19:46,488 DIFFERENTIATES FROM DARPA IS 4919 03:19:46,488 --> 03:19:49,257 THAT WE ARE REALLY, REALLY 4920 03:19:49,257 --> 03:19:57,298 FOCUSED ON ACCELERATING BETH 4921 03:19:57,298 --> 03:19:58,933 -- BETTER HEALTH OUT COMES FOR 4922 03:19:58,933 --> 03:19:59,200 EVERYONE. 4923 03:19:59,200 --> 03:20:01,269 FOR ME THE A UNIQUE OPPORTUNITY. 4924 03:20:01,269 --> 03:20:02,770 WE WERE TALKING ABOUT LUNCH 4925 03:20:02,770 --> 03:20:04,272 ABOUT ONE OF THE DIFFERENCES. 4926 03:20:04,272 --> 03:20:06,407 ONE OF THE DIFFERENCES FOR 4927 03:20:06,407 --> 03:20:10,445 DARPA WHEN I'M TRYING TO DO 4928 03:20:10,445 --> 03:20:12,547 BIOMEDICAL RESEARCH AT DARPA 4929 03:20:12,547 --> 03:20:14,382 IT'S FOR YOUNG HEALTHY WAR 4930 03:20:14,382 --> 03:20:16,885 FIGHTERS WHO GO THROUGH TRAUMA. 4931 03:20:16,885 --> 03:20:19,053 IT TENDS TO BE A SUBSET. 4932 03:20:19,053 --> 03:20:20,054 OFTEN THOSE APPLICATIONS ARE 4933 03:20:20,054 --> 03:20:21,623 FAIRLY NARROW. 4934 03:20:21,623 --> 03:20:23,491 SO I'M ALWAYS SEARCHING FOR 4935 03:20:23,491 --> 03:20:26,561 SOMETHING RELATED THAT COULD BE 4936 03:20:26,561 --> 03:20:36,471 SUFFICIENTLY, YOU KNOW, 4937 03:20:36,471 --> 03:20:39,140 REMUENER TIVE, PROFITABLE. 4938 03:20:39,140 --> 03:20:41,643 THERE IS BLAST INJURIES BUT 4939 03:20:41,643 --> 03:20:43,745 THAT'S ADJACENT TO DIABETIC -- 4940 03:20:43,745 --> 03:20:45,980 WHICH IS A $20 BILLION A YEAR 4941 03:20:45,980 --> 03:20:47,282 PROBLEM. 4942 03:20:47,282 --> 03:20:52,220 I WOULD DEVELOP THIS 4943 03:20:52,220 --> 03:20:53,154 TECHNOLOGY, HIGH-TECH BANDAGE 4944 03:20:53,154 --> 03:20:55,023 FOR BURN AND BLAST INJURY, THE 4945 03:20:55,023 --> 03:20:58,026 COMPANY WOULD TAKE IT THROUGH 4946 03:20:58,026 --> 03:20:59,861 FDA FOR DIABETIC -- WE WOULD 4947 03:20:59,861 --> 03:21:02,864 TRY TO BRING IT BACK FOR BLAST 4948 03:21:02,864 --> 03:21:04,632 INJURIES. 4949 03:21:04,632 --> 03:21:06,501 HERE I DON'T HAVE TO DO THAT, I 4950 03:21:06,501 --> 03:21:07,869 CAN GO DIRECTLY AFTER THESE 4951 03:21:07,869 --> 03:21:08,603 PROBLEMS. 4952 03:21:08,603 --> 03:21:09,437 HOWEVER, THERE'S ALSO A WEIGHT 4953 03:21:09,437 --> 03:21:10,238 ON ME. 4954 03:21:10,238 --> 03:21:11,773 I HAVE TO TAKE INTO 4955 03:21:11,773 --> 03:21:12,674 CONSIDERATION ALL THE OTHER 4956 03:21:12,674 --> 03:21:14,075 THINGS AT THE BEGINNING, WHAT 4957 03:21:14,075 --> 03:21:17,145 IS THE PATIENT GOING TO 4958 03:21:17,145 --> 03:21:18,379 EXPERIENCE, HOW IS THEIR LIFE 4959 03:21:18,379 --> 03:21:20,848 GOING TO BE BETTER WITH THIS 4960 03:21:20,848 --> 03:21:21,349 TECHNOLOGY. 4961 03:21:21,349 --> 03:21:25,553 THE WAY IT'S SET UP, 4962 03:21:25,553 --> 03:21:28,790 GOVERNMENTLY, WE ARE WITH NIH 4963 03:21:28,790 --> 03:21:34,963 BUT THE ARPA-H DIRECTOR REPORTS 4964 03:21:34,963 --> 03:21:42,537 DIRECTLY TO SECRETARY BECERRA. 4965 03:21:42,537 --> 03:21:44,739 THE VAST EXPERTISE IS 4966 03:21:44,739 --> 03:21:46,941 INCREDIBLY VIABLE TO US AT 4967 03:21:46,941 --> 03:21:47,542 ARPA-H. 4968 03:21:47,542 --> 03:21:49,911 BE ABLE TO HIT YOU UP WITH 4969 03:21:49,911 --> 03:21:51,279 DIFFERENT INSIGHTS, DIFFERENT 4970 03:21:51,279 --> 03:21:52,880 THOUGHTS, HELP US IMPROVE 4971 03:21:52,880 --> 03:21:53,615 PROGRAMS. 4972 03:21:53,615 --> 03:21:55,249 BUT WE ARE INDEPENDENT SO WE 4973 03:21:55,249 --> 03:21:58,052 CAN GO OUR OWN WAY, PROPOSE OUR 4974 03:21:58,052 --> 03:21:59,887 OWN RULES, WORK IN THE SORT OF 4975 03:21:59,887 --> 03:22:04,859 FAST AND FLEXIBLE WAY THAT 4976 03:22:04,859 --> 03:22:05,960 ENABLES OUR PROGRAMS. 4977 03:22:05,960 --> 03:22:08,129 THE OTHER THING TO NOTE, WHEN I 4978 03:22:08,129 --> 03:22:10,932 WAS AT DARPA AND HAVEN'T 4979 03:22:10,932 --> 03:22:12,100 RECEIVED YET, HEY I WOULD LIKE 4980 03:22:12,100 --> 03:22:14,702 TO WORK IN YOUR RESEARCH LABS. 4981 03:22:14,702 --> 03:22:16,104 WE DON'T HAVE ANY LABS. 4982 03:22:16,104 --> 03:22:17,939 WE TAKE THE MONEY AND HAND IT 4983 03:22:17,939 --> 03:22:19,273 TO OTHER PEOPLE TO DO THE GOOD 4984 03:22:19,273 --> 03:22:20,041 RESEARCH. 4985 03:22:20,041 --> 03:22:26,581 SO FAR WE HAVE $2.5 BILLION FOR 4986 03:22:26,581 --> 03:22:27,982 INITIAL APPROPRIATION. 4987 03:22:27,982 --> 03:22:29,784 THESE ARE GENERALLY CONTRACTS, 4988 03:22:29,784 --> 03:22:30,518 NOT GRANTS. 4989 03:22:30,518 --> 03:22:34,489 THAT GOES BACK TO THE CONSTANT 4990 03:22:34,489 --> 03:22:36,557 INTERACTION WITH THE PERFORMER. 4991 03:22:36,557 --> 03:22:38,660 WE DON'T HAND YOU MONEY AND ASK 4992 03:22:38,660 --> 03:22:40,428 YOU TO REPORT BACK IN A YEAR OR 4993 03:22:40,428 --> 03:22:41,195 TWO. 4994 03:22:41,195 --> 03:22:43,297 WE ARE THERE EVERY STEP OF THE 4995 03:22:43,297 --> 03:22:44,899 WAY, HOW ARE THINGS 4996 03:22:44,899 --> 03:22:45,900 PROGRESSING, RIGHT. 4997 03:22:45,900 --> 03:22:47,935 THE OTHER THING WE HAVE WHAT WE 4998 03:22:47,935 --> 03:22:50,304 CALL A SUPER POWER, WE CAN PAY 4999 03:22:50,304 --> 03:22:52,874 OTHER AGENCIES, SUCH AS THE FDA 5000 03:22:52,874 --> 03:22:54,509 TO ENGAGE ON CERTAIN PROBLEMS. 5001 03:22:54,509 --> 03:22:56,377 WE ARE STILL FIGURING OUT HOW 5002 03:22:56,377 --> 03:22:59,881 THAT WORKS IN PRACTICE, BUT WE 5003 03:22:59,881 --> 03:23:02,350 ARE EXCITED TO PURSUE THAT 5004 03:23:02,350 --> 03:23:03,151 CAPABILITY, FLEXIBILITY. 5005 03:23:03,151 --> 03:23:06,621 ONE OF THE KEY FEATURES OF 5006 03:23:06,621 --> 03:23:07,155 ARPA-H. 5007 03:23:07,155 --> 03:23:10,825 ONE IS THAT THE AGENCY REVOLVES 5008 03:23:10,825 --> 03:23:14,662 AROUND PROGRAM MANAGERS, SUCH 5009 03:23:14,662 --> 03:23:14,929 AS MYSELF. 5010 03:23:14,929 --> 03:23:18,866 OFTEN PEOPLE GO WHAT IS ARPA-H 5011 03:23:18,866 --> 03:23:19,200 INTERESTED IN. 5012 03:23:19,200 --> 03:23:21,202 WHAT ARPA-H IS INTERESTED IS 5013 03:23:21,202 --> 03:23:23,071 WHATEVER THE PROGRAM MANAGERS 5014 03:23:23,071 --> 03:23:24,706 AT THIS TIME ARE INTERESTED IN. 5015 03:23:24,706 --> 03:23:26,974 I COMPARE IT TO THE PACIFIC 5016 03:23:26,974 --> 03:23:27,675 OCEAN. 5017 03:23:27,675 --> 03:23:30,244 WE CAN GO ANYWHERE, MOST OF THE 5018 03:23:30,244 --> 03:23:32,346 SPACE IS EMPTY, WE HAVE 5019 03:23:32,346 --> 03:23:34,248 VOLCANOS HERE AND THERE WE ARE 5020 03:23:34,248 --> 03:23:35,883 TRYING TO GENERATE A NEW ISLAND. 5021 03:23:35,883 --> 03:23:40,555 TRYING TO FIND IN THE GIGANTIC 5022 03:23:40,555 --> 03:23:41,756 SPACE, FOCUS INVESTMENT WILL 5023 03:23:41,756 --> 03:23:44,058 REALLY MAKE A DIFFERENCE. 5024 03:23:44,058 --> 03:23:49,797 WE HAVE HUGE AUTO -- 5025 03:23:49,797 --> 03:23:51,099 AUTONOMY IN THIS TO DO WHATEVER 5026 03:23:51,099 --> 03:23:51,632 WE WANT. 5027 03:23:51,632 --> 03:23:53,768 I COME UP WITH AN IDEA, THERE'S 5028 03:23:53,768 --> 03:23:55,403 FEEDBACK IN THE OFFICE, I GO 5029 03:23:55,403 --> 03:23:59,107 STRAIGHT TO THE DIRECTOR, THE 5030 03:23:59,107 --> 03:24:01,209 DIRECTOR SAYS YES OR NO I CAN 5031 03:24:01,209 --> 03:24:03,311 PURSUE THIS PROGRAM. 5032 03:24:03,311 --> 03:24:09,183 THEY CHECK ON ME TWICE A YEAR, 5033 03:24:09,183 --> 03:24:12,220 BUT THEN I CAN HIRE, FIRE, 5034 03:24:12,220 --> 03:24:13,855 WHATEVER TO REPORT BACK TO THE 5035 03:24:13,855 --> 03:24:14,122 DIRECTOR. 5036 03:24:14,122 --> 03:24:17,158 WE WANT TO BE FAST, SO WE HAVE 5037 03:24:17,158 --> 03:24:17,925 VERY FAST CONTRACTING 5038 03:24:17,925 --> 03:24:18,559 MECHANISMS. 5039 03:24:18,559 --> 03:24:23,865 I CAN SAY WE, IN MARCH THIS 5040 03:24:23,865 --> 03:24:27,101 YEAR, THAT WE PUT OUT THIS OPEN 5041 03:24:27,101 --> 03:24:28,503 B.A., BEFORE THE END OF THE 5042 03:24:28,503 --> 03:24:32,373 FISCAL YEAR WE USED UP OUR 5043 03:24:32,373 --> 03:24:34,041 FIRST YEAR APPROPRIATION WHICH 5044 03:24:34,041 --> 03:24:35,009 WAS $1 BILLION. 5045 03:24:35,009 --> 03:24:36,611 WE MOVED A LOT OF RESEARCH IN 5046 03:24:36,611 --> 03:24:39,814 THE FIRST YEAR BECAUSE WE MOVE 5047 03:24:39,814 --> 03:24:42,116 QUICKLY AND NIMBLY. 5048 03:24:42,116 --> 03:24:42,850 FLEXIBILITY IN HIRING. 5049 03:24:42,850 --> 03:24:44,952 WE LOOK FOR PROGRAM MANAGERS 5050 03:24:44,952 --> 03:24:47,054 AND THAT'S ONE OF THE CALLS FOR 5051 03:24:47,054 --> 03:24:48,422 EVERYONE HERE, IF YOU OR 5052 03:24:48,422 --> 03:24:49,824 SOMEONE YOU KNOW WOULD BE 5053 03:24:49,824 --> 03:24:51,692 INTERESTED IN A PROJECT MANAGER 5054 03:24:51,692 --> 03:24:53,861 WE ARE ALWAYS LOOKING FOR 5055 03:24:53,861 --> 03:24:54,095 PEOPLE. 5056 03:24:54,095 --> 03:24:56,864 WE HIRE FROM GOVERNMENT, 5057 03:24:56,864 --> 03:24:58,499 ACADEMIA, FROM HMO'S, 5058 03:24:58,499 --> 03:24:59,867 CLINICIANS, ACROSS-THE-BOARD. 5059 03:24:59,867 --> 03:25:02,904 ANYONE WHO HAS AN IDEA AND 5060 03:25:02,904 --> 03:25:04,505 WANTS TO MAKE IT A REALITY IS 5061 03:25:04,505 --> 03:25:08,609 WELCOME. 5062 03:25:08,609 --> 03:25:10,244 PART OF THE JOB AND I THINK 5063 03:25:10,244 --> 03:25:12,580 THIS CAME OUT EARLIER IN THE 5064 03:25:12,580 --> 03:25:15,116 DISCUSSION, IS ADDRESSING ALL 5065 03:25:15,116 --> 03:25:17,351 OF THESE DIFFERENT CUSTOMERS, 5066 03:25:17,351 --> 03:25:19,654 EACH ONE OF THESE GROUPS HAS 5067 03:25:19,654 --> 03:25:21,289 THEIR OWN LENSES AND WE ARE 5068 03:25:21,289 --> 03:25:23,124 TRYING TO ADDRESS ALL THOSE 5069 03:25:23,124 --> 03:25:25,693 LENSES TO SOLVE A PROBLEM FOR 5070 03:25:25,693 --> 03:25:27,161 THIS ENTIRE COMMUNITY, RIGHT? 5071 03:25:27,161 --> 03:25:28,262 CUSTOMERS. 5072 03:25:28,262 --> 03:25:30,131 PATIENT GROUPS. 5073 03:25:30,131 --> 03:25:31,299 WE ENGAGE WITH THEM. 5074 03:25:31,299 --> 03:25:33,000 WHAT DO THEY WANT TO SEE IN 5075 03:25:33,000 --> 03:25:34,001 THEIR LIVES. 5076 03:25:34,001 --> 03:25:37,672 HOW CAN WE IMPROVE THEIR 5077 03:25:37,672 --> 03:25:38,139 DAY-TO-DAY EXPERIENCE. 5078 03:25:38,139 --> 03:25:38,806 HEALTHCARE PROVIDERS, IT WON'T 5079 03:25:38,806 --> 03:25:41,375 GET TO THE PATIENTS IF THE 5080 03:25:41,375 --> 03:25:42,777 CLINICIANS DON'T BUY INTO USING 5081 03:25:42,777 --> 03:25:45,546 T. THE PUBLIC AT LARGE WANT TO 5082 03:25:45,546 --> 03:25:47,415 SEE VALUE OUT OF THE MONEY THEY 5083 03:25:47,415 --> 03:25:50,685 ARE GIVING TO ARPA-H. 5084 03:25:50,685 --> 03:25:52,887 NIH, WE TRY TO PLUG IN. 5085 03:25:52,887 --> 03:25:54,455 THE TECHNOLOGY IS, YOU COME TO 5086 03:25:54,455 --> 03:25:56,357 US, IT'S AMAZING TECHNOLOGY, IT 5087 03:25:56,357 --> 03:26:00,061 NEEDS A LITTLE OOMPH BEHIND IT, 5088 03:26:00,061 --> 03:26:01,329 USE THE FLEXIBILITY TO GET THAT 5089 03:26:01,329 --> 03:26:02,530 OUT THERE. 5090 03:26:02,530 --> 03:26:09,403 LOTS OF OTHER FEDERAL PARTNERS, 5091 03:26:09,403 --> 03:26:12,073 FDA, CMS. 5092 03:26:12,073 --> 03:26:13,941 ACADEMIA, INDUSTRY, NGO'S, ALSO 5093 03:26:13,941 --> 03:26:15,576 PRIVATE INVESTORS TRYING TO 5094 03:26:15,576 --> 03:26:17,845 PULL ALL THESE COMMUNITIES IN. 5095 03:26:17,845 --> 03:26:18,512 THAT'S THE LABOR BUT THE 5096 03:26:18,512 --> 03:26:19,146 EXCITEMENT. 5097 03:26:19,146 --> 03:26:20,982 YOU HAVE A NEW TECHNOLOGY AND 5098 03:26:20,982 --> 03:26:22,617 YOU ARE TRYING TO GET IT ALL 5099 03:26:22,617 --> 03:26:24,785 THE WAY FROM SOMEONE'S GLIMMER 5100 03:26:24,785 --> 03:26:29,090 IN THE EYE, ALL THE WAY TO CMS 5101 03:26:29,090 --> 03:26:31,425 GIVING A CODE SO SOMEONE CAN 5102 03:26:31,425 --> 03:26:33,327 GET PAID FOR PROVIDING THIS 5103 03:26:33,327 --> 03:26:33,794 CAPABILITY. 5104 03:26:33,794 --> 03:26:39,133 SO SOME OF THE ORGANIZATIONAL 5105 03:26:39,133 --> 03:26:39,967 ATTRIBUTE THAT'S CAN SUPPORT 5106 03:26:39,967 --> 03:26:42,770 THE MISSION. 5107 03:26:42,770 --> 03:26:43,271 PROBLEM-FOCUSED PROGRAM 5108 03:26:43,271 --> 03:26:43,537 MANAGERS. 5109 03:26:43,537 --> 03:26:47,108 I DO NOT HAVE, I'M NOT DOING 5110 03:26:47,108 --> 03:26:48,843 RESEARCH IN GENERAL AND CANCER. 5111 03:26:48,843 --> 03:26:50,611 I HAVE A PARTICULAR PROBLEM 5112 03:26:50,611 --> 03:26:52,480 THAT I'M TRYING TO SOLVE AND I 5113 03:26:52,480 --> 03:26:55,049 WORK BACK TO A SET OF SOLUTIONS 5114 03:26:55,049 --> 03:26:56,450 AND THEY PUSH ALL THE WAY 5115 03:26:56,450 --> 03:26:58,085 THROUGH THOSE, RIGHT? 5116 03:26:58,085 --> 03:27:00,454 SO IT'S REALLY THAT FOCUS ON 5117 03:27:00,454 --> 03:27:03,057 THE PROBLEM AND I THINK OF 5118 03:27:03,057 --> 03:27:06,861 MYSELF AS A CONCIERGE FOR THE 5119 03:27:06,861 --> 03:27:07,161 PERFORMERS. 5120 03:27:07,161 --> 03:27:08,763 THE OTHER WAY TO DESCRIBE IT TO 5121 03:27:08,763 --> 03:27:10,865 PEOPLE, IT'S LIKE THE CANADIAN 5122 03:27:10,865 --> 03:27:11,666 GAME CURLING. 5123 03:27:11,666 --> 03:27:14,435 SO WE ARE BACK THERE WITH THE 5124 03:27:14,435 --> 03:27:15,803 PERFORMERS, WE THROW THE ROCK 5125 03:27:15,803 --> 03:27:18,139 AND I AND MY WHOLE TIME JUMP 5126 03:27:18,139 --> 03:27:20,875 OUT IN FRONT OF THE STONE AND 5127 03:27:20,875 --> 03:27:22,710 WE ARE THERE WITH THE BROOM, 5128 03:27:22,710 --> 03:27:24,345 RIGHT? 5129 03:27:24,345 --> 03:27:26,881 TRYING TO MAKE SURE IT GETS ON 5130 03:27:26,881 --> 03:27:27,581 TARGET. 5131 03:27:27,581 --> 03:27:29,483 THAT MEANS ANYTHING THEY MIGHT 5132 03:27:29,483 --> 03:27:31,852 NEED, IF THEY NEED TO TALK TO 5133 03:27:31,852 --> 03:27:33,955 THE FDA, TRYING TO FACILITATE 5134 03:27:33,955 --> 03:27:34,622 THAT IF NEEDED. 5135 03:27:34,622 --> 03:27:36,524 IF THEY NEED TO TALK TO 5136 03:27:36,524 --> 03:27:38,259 INVESTORS WE LINE THAT UP. 5137 03:27:38,259 --> 03:27:39,827 IF THEY NEED AN EXPERT IN 5138 03:27:39,827 --> 03:27:41,896 RESIDENCE TO COME UP WITH AN IP 5139 03:27:41,896 --> 03:27:44,231 FOR THE COMPANY. 5140 03:27:44,231 --> 03:27:46,400 ANY CONNECTION THEY MIGHT NEED 5141 03:27:46,400 --> 03:27:48,869 WE TRY TO FACILITATE THOSE 5142 03:27:48,869 --> 03:27:51,706 INTERACTIONS, RIGHT? 5143 03:27:51,706 --> 03:27:53,140 SO DEEP SUPPORT FROM ACROSS THE 5144 03:27:53,140 --> 03:28:01,549 AGENCY FOR ME. 5145 03:28:01,549 --> 03:28:04,352 WE LOOK FOR RADICAL CHANGE. 5146 03:28:04,352 --> 03:28:07,154 IF SOMEONE COMES TO US AND IT'S 5147 03:28:07,154 --> 03:28:09,056 SOMETHING ELSE SOMEONE ELSE 5148 03:28:09,056 --> 03:28:11,158 COULD OR SHOULD FUND THAT ISN'T 5149 03:28:11,158 --> 03:28:15,629 THAT RISKY, I SAY 4-5 TIMES A 5150 03:28:15,629 --> 03:28:17,498 DAY, YOUR IDEA IS GREAT, IT 5151 03:28:17,498 --> 03:28:19,500 SHOULD BE DONE, IT DOESN'T 5152 03:28:19,500 --> 03:28:20,334 REALLY FIT WITH US. 5153 03:28:20,334 --> 03:28:21,969 OTHER PEOPLE CAN DO THIS, IT'S 5154 03:28:21,969 --> 03:28:25,873 NOT A REALLY RISKY PROPOSITION. 5155 03:28:25,873 --> 03:28:26,941 YOU ARE DOING SOMETHING SMART 5156 03:28:26,941 --> 03:28:28,242 AND GOOD. 5157 03:28:28,242 --> 03:28:32,446 SO WE ARE REALLY LOOKING FOR 5158 03:28:32,446 --> 03:28:34,548 THESE HIGH-RISK, HIGH IMPACT 5159 03:28:34,548 --> 03:28:36,917 PROPOSALS THAT CAN REALLY WORK 5160 03:28:36,917 --> 03:28:39,153 ONLY AT SCALE. 5161 03:28:39,153 --> 03:28:43,224 LOTS OF AUTONOMY, AS NOTED. 5162 03:28:43,224 --> 03:28:45,393 I'M REALLY ONLY RESPONSIBLE TO 5163 03:28:45,393 --> 03:28:46,694 THE DIRECTOR. 5164 03:28:46,694 --> 03:28:50,231 ULTIMATELY AT THE END OF THE 5165 03:28:50,231 --> 03:28:51,799 DAY, THE AGENCIES, WHEN WE 5166 03:28:51,799 --> 03:28:55,636 FULLY STAFF WILL HAVE MAYBE 5167 03:28:55,636 --> 03:28:56,370 100-120 PROGRAM MANAGERS. 5168 03:28:56,370 --> 03:28:58,939 I IMAGINE THE SAME AT DARPA, 5169 03:28:58,939 --> 03:29:00,574 THE DIRECTOR KNOWS EVERY SINGLE 5170 03:29:00,574 --> 03:29:01,742 PROGRAM MANAGER BY NAME, ANY 5171 03:29:01,742 --> 03:29:03,477 TIME I CAN GO AND TALK TO THE 5172 03:29:03,477 --> 03:29:04,812 DIRECTOR ABOUT WHAT I WANT TO 5173 03:29:04,812 --> 03:29:06,480 GET DONE, RIGHT? 5174 03:29:06,480 --> 03:29:08,783 SO HIGHLY EMPOWER ERRED. 5175 03:29:08,783 --> 03:29:11,585 ER -- EMPOWERED. 5176 03:29:11,585 --> 03:29:12,286 THEN TERM LIMITS. 5177 03:29:12,286 --> 03:29:13,921 I HAVE TO SAY, I THINK IT'S ONE 5178 03:29:13,921 --> 03:29:15,189 OF THE BEST JOBS IN THE 5179 03:29:15,189 --> 03:29:19,093 GOVERNMENT, THEY GIVE YOU A LOT 5180 03:29:19,093 --> 03:29:20,261 OF AUTONOMY, MONEY, SUPPORT, 5181 03:29:20,261 --> 03:29:23,097 YOU GET TO WORK WITH AMAZING 5182 03:29:23,097 --> 03:29:24,165 PEOPLE AND THEN THEY KICK YOU 5183 03:29:24,165 --> 03:29:24,932 OUT. 5184 03:29:24,932 --> 03:29:26,600 YOU ONLY HAVE A SHORT AMOUNT OF 5185 03:29:26,600 --> 03:29:27,868 TIME TO GET THINGS DONE. 5186 03:29:27,868 --> 03:29:38,312 THEY CALL IT THE FLYWHEEL. 5187 03:29:39,013 --> 03:29:42,883 FEELS LIKE A TORE TORNADO WHEN 5188 03:29:42,883 --> 03:29:44,285 ARE YOU GOING THROUGH IT. 5189 03:29:44,285 --> 03:29:46,020 YOU GET THREE YEARS AND MAYBE 5190 03:29:46,020 --> 03:29:47,888 CAN GET AN ADDITIONAL THREE 5191 03:29:47,888 --> 03:29:49,690 YEARS. 5192 03:29:49,690 --> 03:29:51,525 IF SOMEONE GIVES YOU TEN YEARS, 5193 03:29:51,525 --> 03:29:53,427 YOU ARE LIKELY TO TAKE TEN 5194 03:29:53,427 --> 03:29:54,728 YEARS TO GET IT DONE. 5195 03:29:54,728 --> 03:29:56,263 IF YOU KNOW YOU HAVE THREE 5196 03:29:56,263 --> 03:29:57,932 YEARS YOU WILL PUSH DAY AND 5197 03:29:57,932 --> 03:30:00,701 NIGHT AND ON WEEKENDS TRYING TO 5198 03:30:00,701 --> 03:30:02,336 SEE SOME CHANGE WHILE YOU ARE 5199 03:30:02,336 --> 03:30:04,238 STILL THERE, RIGHT? 5200 03:30:04,238 --> 03:30:06,040 THIS MEANS PEOPLE COME AND GO. 5201 03:30:06,040 --> 03:30:07,608 THAT MEANS WE ARE ALWAYS 5202 03:30:07,608 --> 03:30:08,876 LOOKING FOR PROGRAM MANAGERS. 5203 03:30:08,876 --> 03:30:10,845 AGAIN, YOU WILL HEAR THIS 5204 03:30:10,845 --> 03:30:12,012 MULTIPLE TIMES, IF YOU KNOW 5205 03:30:12,012 --> 03:30:13,914 ANYBODY, IF YOU WANT TO BE A 5206 03:30:13,914 --> 03:30:15,282 PROGRAM MANAGER WE ARE ALWAYS 5207 03:30:15,282 --> 03:30:16,717 LOOKING FOR NEW CANDIDATES TO 5208 03:30:16,717 --> 03:30:18,652 COME IN AND TAKE IT OVER. 5209 03:30:18,652 --> 03:30:20,187 THE OTHER IMPACTS OF THIS, I'M 5210 03:30:20,187 --> 03:30:21,889 NOT THERE AT THE END OF MY 5211 03:30:21,889 --> 03:30:22,790 PROGRAM, RIGHT? 5212 03:30:22,790 --> 03:30:24,558 I COME AND PITCH A PROGRAM. 5213 03:30:24,558 --> 03:30:27,695 I MAY HAVE A FIVE-YEAR PROGRAM 5214 03:30:27,695 --> 03:30:29,363 AND I'M UNLIKELY TO BE THERE AT 5215 03:30:29,363 --> 03:30:30,131 THE VERY END. 5216 03:30:30,131 --> 03:30:32,066 YOU HAVE TO HAVE MULTIPLE EYES 5217 03:30:32,066 --> 03:30:33,834 ON IT, IT HAS TO BE CONVINCING 5218 03:30:33,834 --> 03:30:36,604 TO A LOT OF PEOPLE, NOT JUST MY 5219 03:30:36,604 --> 03:30:38,506 BUDDIES, MY PALS, NOT ACCUSING 5220 03:30:38,506 --> 03:30:40,174 ANYONE OF THAT, BUT IT HAS TO 5221 03:30:40,174 --> 03:30:41,842 BE CONVINCING TO LOTS OF FOLKS 5222 03:30:41,842 --> 03:30:51,886 TO MAKE THAT HAPPEN. 5223 03:30:51,886 --> 03:30:53,954 THERE ARE LOTS OF PHENOTYPES. 5224 03:30:53,954 --> 03:30:56,590 DO I HAVE TO COME FROM NIH OR 5225 03:30:56,590 --> 03:30:58,459 BE AN ACADEMIC. 5226 03:30:58,459 --> 03:31:00,327 THERE ARE LOTS OF FOLKS THAT 5227 03:31:00,327 --> 03:31:02,663 COME ALL OVER, THE RESEARCH 5228 03:31:02,663 --> 03:31:03,397 COMMUNITY, THE HEALTHCARE 5229 03:31:03,397 --> 03:31:03,831 COMMUNITY. 5230 03:31:03,831 --> 03:31:06,167 WHAT WE ARE REALLY LOOKING FOR 5231 03:31:06,167 --> 03:31:08,502 IS SOMEONE WHO WANTS TO TAKE 5232 03:31:08,502 --> 03:31:10,838 OWNERSHIP, THEY THINK LIKE A 5233 03:31:10,838 --> 03:31:13,174 CEO FOR EACH OF THESE EFFORTS. 5234 03:31:13,174 --> 03:31:14,842 YOU NEED NOT ONLY TO HAVE THAT 5235 03:31:14,842 --> 03:31:16,544 EXPERTISE, YOU NEED THE 5236 03:31:16,544 --> 03:31:16,810 CURIOSITY. 5237 03:31:16,810 --> 03:31:18,012 YOU NEED TO HEAR WHEN PEOPLE 5238 03:31:18,012 --> 03:31:19,580 COME IN, YOU ACTUALLY TALK TO 5239 03:31:19,580 --> 03:31:22,750 ME MORE ABOUT THAT, THAT SOUNDS 5240 03:31:22,750 --> 03:31:25,119 CRAZY BUT MAYBE THAT'S A THING, 5241 03:31:25,119 --> 03:31:26,987 I KNOW SOMEBODY WHO CAN MAYBE 5242 03:31:26,987 --> 03:31:27,821 SOLVE THAT PROBLEM. 5243 03:31:27,821 --> 03:31:30,124 YOU NEED TO BE ABLE TO LISTEN 5244 03:31:30,124 --> 03:31:31,158 ACROSS FIELDS. 5245 03:31:31,158 --> 03:31:33,227 OFTEN TIMES YOU WILL NEED TO 5246 03:31:33,227 --> 03:31:35,563 DEVELOP A TECHNOLOGY ACROSS 5247 03:31:35,563 --> 03:31:37,464 MULTIPLE DIFFERENT AREAS. 5248 03:31:37,464 --> 03:31:45,873 AS MENTIONED EARLIER, SOMETIMES 5249 03:31:45,873 --> 03:31:46,574 IT'S BIOELECTRONICS, SYNBIO. 5250 03:31:46,574 --> 03:31:48,209 YOU NEED TO BE OPEN TO MULTIPLE 5251 03:31:48,209 --> 03:31:48,943 FIELDS. 5252 03:31:48,943 --> 03:31:50,611 I WILL PUT IN A POINT ONE OF 5253 03:31:50,611 --> 03:31:54,481 THE NICE THINGS THEY DO FOR US, 5254 03:31:54,481 --> 03:31:57,017 THEY PROVIDE SCIENCE ENGINEER 5255 03:31:57,017 --> 03:31:58,419 TECHNICAL ADVISORS, SMART 5256 03:31:58,419 --> 03:32:00,254 PEOPLE Ph.D.'S WHO HELP US 5257 03:32:00,254 --> 03:32:01,188 THINK ABOUT PROBLEMS. 5258 03:32:01,188 --> 03:32:03,090 I OCCUR NTLY HAVE SEVEN PEOPLE 5259 03:32:03,090 --> 03:32:06,093 ON MY TEAM TO THINK OF 5260 03:32:06,093 --> 03:32:07,962 BIOMANUFACTURING TO CANCER, TO 5261 03:32:07,962 --> 03:32:09,563 CELL PRINTING, TO HELP ME THINK 5262 03:32:09,563 --> 03:32:11,298 ABOUT AND RUN ALL THESE 5263 03:32:11,298 --> 03:32:12,700 EFFORTS, RIGHT? 5264 03:32:12,700 --> 03:32:15,869 YOU AT LEAST HAVE TO BE OPEN TO 5265 03:32:15,869 --> 03:32:17,004 CONCEPTS OUTSIDE OF YOUR NARROW 5266 03:32:17,004 --> 03:32:17,738 LANE. 5267 03:32:17,738 --> 03:32:19,607 DECISIVE. 5268 03:32:19,607 --> 03:32:22,910 YOU CUT PEOPLE, RIGHT? 5269 03:32:22,910 --> 03:32:24,278 SOMETIMES THINGS DON'T WORK. 5270 03:32:24,278 --> 03:32:26,413 SO YOU HAVE TO MAKE SURE THAT 5271 03:32:26,413 --> 03:32:28,482 IF IT'S NOT WORKING, YOU CUT 5272 03:32:28,482 --> 03:32:29,917 THEM AND TAKE THOSE RESOURCES 5273 03:32:29,917 --> 03:32:31,518 AND YOU PUT THEM WHERE THEY ARE 5274 03:32:31,518 --> 03:32:32,353 GOING TO WORK. 5275 03:32:32,353 --> 03:32:33,621 DRIVE. 5276 03:32:33,621 --> 03:32:35,256 NO FEAR OF FAILURE. 5277 03:32:35,256 --> 03:32:36,890 THINGS CAN BLOWUP. 5278 03:32:36,890 --> 03:32:38,792 I GENERALLY, THE NEW PROGRAM 5279 03:32:38,792 --> 03:32:39,994 MANAGERS WHO ARE COMING IN, 5280 03:32:39,994 --> 03:32:41,362 LIKE HOW DO I KNOW? 5281 03:32:41,362 --> 03:32:44,632 WELL, IF YOU ARE WORRIED IT 5282 03:32:44,632 --> 03:32:46,100 WILL BLOW UP IN YOUR FACE YOU 5283 03:32:46,100 --> 03:32:48,902 ARE PROBABLY ON THE RIGHT TRACK. 5284 03:32:48,902 --> 03:32:54,675 THAT'S WHY WE ARE HERE, IT'S A 5285 03:32:54,675 --> 03:32:55,609 HIGH-RISK, HIGH-REWARD EFFORT. 5286 03:32:55,609 --> 03:32:58,412 YOU ARE HERE TO MAKE SURE IT 5287 03:32:58,412 --> 03:33:00,180 WILL WORK, IF NOT THAT'S OKAY. 5288 03:33:00,180 --> 03:33:02,850 I HAVE CUT EFFORTS BUT I HAVE 5289 03:33:02,850 --> 03:33:04,251 LEARNED FROM WHAT MOTHER NATURE 5290 03:33:04,251 --> 03:33:07,054 SAID YOU COULDN'T DO, SO THAT'S 5291 03:33:07,054 --> 03:33:10,024 USEFUL IN ITS OWN SELF-. 5292 03:33:10,024 --> 03:33:11,992 BE HONEST AND CUSTOMER CENTRIC. 5293 03:33:11,992 --> 03:33:13,661 I NEED TO KNOW WHO MY 5294 03:33:13,661 --> 03:33:14,695 STAKEHOLDERS ARE. 5295 03:33:14,695 --> 03:33:16,096 WHO I'M GOING TO DELIVER 5296 03:33:16,096 --> 03:33:17,331 TECHNOLOGY TO AND I NEED TO 5297 03:33:17,331 --> 03:33:18,932 MAKE SURE I CAN HAND THAT OFF 5298 03:33:18,932 --> 03:33:20,534 AT THE END OF THE PROGRAM. 5299 03:33:20,534 --> 03:33:22,169 FOR THE SIMPLE REASON THAT 5300 03:33:22,169 --> 03:33:23,804 AGAIN, THE PROGRAM STARTS, YOU 5301 03:33:23,804 --> 03:33:26,373 HAVE FOUR OR FIVE YEARS, RIGHT? 5302 03:33:26,373 --> 03:33:28,909 AND THEN IT HAS TO LIVE 5303 03:33:28,909 --> 03:33:29,743 SOMEWHERE ELSE. 5304 03:33:29,743 --> 03:33:31,412 WE ARE GONE. 5305 03:33:31,412 --> 03:33:34,214 WE ARE A VOLCANO, WE START, WE 5306 03:33:34,214 --> 03:33:35,649 STOP AND SOMEONE HAS TO PICK IT 5307 03:33:35,649 --> 03:33:38,152 UP AND SAY THIS IS WORTHWHILE. 5308 03:33:38,152 --> 03:33:42,323 ROSS WAS A NAVY SURGEON, 5309 03:33:42,323 --> 03:33:44,625 DARSHACK WAS THE CMO FOR UNITED 5310 03:33:44,625 --> 03:33:46,760 HEALTH. 5311 03:33:46,760 --> 03:33:48,629 ANDY WAS PART OF OPERATION WARP 5312 03:33:48,629 --> 03:33:49,797 SPEED. 5313 03:33:49,797 --> 03:33:52,333 YOU GET THE FEEL, FROM ALL OVER 5314 03:33:52,333 --> 03:34:01,208 FROM GOVERNMENT, FROM ACADEMIA, 5315 03:34:01,208 --> 03:34:04,912 ALANNA WAS IN ACADEMIA A BIT. 5316 03:34:04,912 --> 03:34:06,513 ALL ACROSS-THE-BOARD. 5317 03:34:06,513 --> 03:34:13,253 OKAY, SO ONE OF THE THINGS WE 5318 03:34:13,253 --> 03:34:21,462 ALWAYS PUSH IS SOMETHING CALLED 5319 03:34:21,462 --> 03:34:24,365 THE HEILMEIER QUESTIONS. 5320 03:34:24,365 --> 03:34:25,499 STOLEN FROM DARPA. 5321 03:34:25,499 --> 03:34:27,634 YOU KIND OF READ THE QUESTION. 5322 03:34:27,634 --> 03:34:29,703 NEVER QUITE GOT IT MYSELF. 5323 03:34:29,703 --> 03:34:30,471 THESE ARE PRETTY BASIC 5324 03:34:30,471 --> 03:34:32,339 QUESTIONS. 5325 03:34:32,339 --> 03:34:33,273 MOST PEOPLE WOPT KNOW THE 5326 03:34:33,273 --> 03:34:35,109 ANSWERS IF YOU LOOK AT IT. 5327 03:34:35,109 --> 03:34:37,211 HONESTLY I THINK A HIGH SCHOOL 5328 03:34:37,211 --> 03:34:38,846 DEBATE TEAM COULD COME UP WITH 5329 03:34:38,846 --> 03:34:41,014 THE QUESTIONS, BUT AT DARPA 5330 03:34:41,014 --> 03:34:42,416 THEY SAY IT'S MAGICAL. 5331 03:34:42,416 --> 03:34:44,284 I WILL SAY WITH EXPERIENCE THEY 5332 03:34:44,284 --> 03:34:45,252 ARE USEFUL, RIGHT? 5333 03:34:45,252 --> 03:34:47,121 MANY PEOPLE COME TO US AND THEY 5334 03:34:47,121 --> 03:34:47,988 ARE EXCITED ABOUT THE 5335 03:34:47,988 --> 03:34:48,756 CAPABILITY. 5336 03:34:48,756 --> 03:34:50,557 AND YOU START STEPPING INTO THE 5337 03:34:50,557 --> 03:34:51,325 QUESTION. 5338 03:34:51,325 --> 03:34:53,227 BEFORE YOU COME TALK TO US, 5339 03:34:53,227 --> 03:34:54,428 TAKE A LOOK, RIGHT? 5340 03:34:54,428 --> 03:34:55,896 THESE ARE SIMPLE QUESTIONS. 5341 03:34:55,896 --> 03:34:57,164 CAN YOU ANSWER THEM SUPER 5342 03:34:57,164 --> 03:34:57,898 QUICKLY? 5343 03:34:57,898 --> 03:35:00,234 WHAT ARE YOU TRYING TO DO, TELL 5344 03:35:00,234 --> 03:35:02,803 ME IN 30 SECONDS, NO JARGON, 5345 03:35:02,803 --> 03:35:05,406 HOW DO I CONVINCE OTHER PEOPLE, 5346 03:35:05,406 --> 03:35:07,007 GOOD IDEAS DON'T NEED A LOT OF 5347 03:35:07,007 --> 03:35:11,478 SALES MAN SHIP OR ADD VERTISING. 5348 03:35:11,478 --> 03:35:14,014 I WILL PRINT HUMAN HEARTS IN AN 5349 03:35:14,014 --> 03:35:16,116 HOUR BECAUSE PEOPLE ARE DYING 5350 03:35:16,116 --> 03:35:17,251 WAITING FOR HUMAN HEARTS. 5351 03:35:17,251 --> 03:35:19,386 AND THEN YOU EXPLAIN THE REST 5352 03:35:19,386 --> 03:35:20,988 OF YOUR TIME EXPLAINING HOW IT 5353 03:35:20,988 --> 03:35:22,156 COULD BE POSSIBLE. 5354 03:35:22,156 --> 03:35:23,323 WHAT'S HAPPENING RIGHT NOW. 5355 03:35:23,323 --> 03:35:25,192 NOT JUST WHAT'S IN THE CLINIC. 5356 03:35:25,192 --> 03:35:26,827 BUT WHAT'S ON THE RESEARCH 5357 03:35:26,827 --> 03:35:29,296 BENCH THAT IS NOT MAKING IT? 5358 03:35:29,296 --> 03:35:30,764 HOW IS YOUR TECHNOLOGY ANY 5359 03:35:30,764 --> 03:35:31,198 DIFFERENT? 5360 03:35:31,198 --> 03:35:32,666 WHAT'S NEW? 5361 03:35:32,666 --> 03:35:35,002 WHAT IS YOUR SECRET SAUCE, 5362 03:35:35,002 --> 03:35:35,602 RIGHT? 5363 03:35:35,602 --> 03:35:38,205 IF I HEAR ANOTHER ONE, I WILL 5364 03:35:38,205 --> 03:35:42,943 DO OMICS AND APPLY AI, AS IS 5365 03:35:42,943 --> 03:35:43,210 EVERYONE. 5366 03:35:43,210 --> 03:35:44,278 TELL ME HOW, PARTICULAR 5367 03:35:44,278 --> 03:35:46,880 APPROACH IS GOING TO MAKE A 5368 03:35:46,880 --> 03:35:48,081 DIFFERENCE. 5369 03:35:48,081 --> 03:35:51,819 NUMBER FOUR IS AMAZING. 5370 03:35:51,819 --> 03:35:53,854 MANY PEOPLE CAN'T ANSWER THIS, 5371 03:35:53,854 --> 03:35:54,621 IT'S STUNNING. 5372 03:35:54,621 --> 03:35:55,789 IT'S REALLY NEAT. 5373 03:35:55,789 --> 03:35:57,391 IT IS REALLY NEAT, BUT WHO 5374 03:35:57,391 --> 03:35:58,158 CARES. 5375 03:35:58,158 --> 03:35:58,959 I AGREE. 5376 03:35:58,959 --> 03:36:00,360 THIS IS ALL GOING TO WORK. 5377 03:36:00,360 --> 03:36:02,162 BUT AT THE END OF THE DAY, HOW 5378 03:36:02,162 --> 03:36:03,330 DOES THIS CHANGE THE WORLD? 5379 03:36:03,330 --> 03:36:05,032 AND A LOT OF PEOPLE DON'T HAVE 5380 03:36:05,032 --> 03:36:06,834 AN ANSWER TO IT, RIGHT? 5381 03:36:06,834 --> 03:36:08,302 I WOULD SAY THAT'S THE HEART OF 5382 03:36:08,302 --> 03:36:09,169 IT, RIGHT? 5383 03:36:09,169 --> 03:36:11,972 IF YOU CAN GET THROUGH THREE 5384 03:36:11,972 --> 03:36:13,974 AND FOUR, WHAT DOES IT MATTER, 5385 03:36:13,974 --> 03:36:15,008 WHO CARES? 5386 03:36:15,008 --> 03:36:16,877 HOW WILL THIS CHANGE THE WORLD, 5387 03:36:16,877 --> 03:36:18,579 YOU ARE OVER THE HUMP, RIGHT. 5388 03:36:18,579 --> 03:36:20,414 THE REST OF THE QUESTIONS, WHAT 5389 03:36:20,414 --> 03:36:21,348 ARE THE RISKS? 5390 03:36:21,348 --> 03:36:22,549 WE ARE THE RISK MANAGEMENT 5391 03:36:22,549 --> 03:36:23,684 AGENCY. 5392 03:36:23,684 --> 03:36:25,552 CAN WE MITIGATE THESE RISKS? 5393 03:36:25,552 --> 03:36:27,187 WHAT KEEPS YOU UP AT NIGHT. 5394 03:36:27,187 --> 03:36:28,856 WHEN WE FORM OUR PROGRAMS THIS 5395 03:36:28,856 --> 03:36:31,391 IS WHAT WE CALL TECHNICAL AREAS. 5396 03:36:31,391 --> 03:36:33,160 WE FIND THE HARDEST THINGS WE 5397 03:36:33,160 --> 03:36:34,495 HAVE TO DO AND WE FOCUS ON 5398 03:36:34,495 --> 03:36:35,295 THOSE. 5399 03:36:35,295 --> 03:36:37,130 SO WE KNOW SPECIFICALLY WHAT'S 5400 03:36:37,130 --> 03:36:38,065 GOING TO HAPPEN. 5401 03:36:38,065 --> 03:36:40,167 AND THE REST IS LIKE, HOW LONG 5402 03:36:40,167 --> 03:36:41,768 IS THIS GOING TO TAKE? 5403 03:36:41,768 --> 03:36:44,638 CAN WE GET THIS DONE IN 3-4 5404 03:36:44,638 --> 03:36:44,838 YEARS? 5405 03:36:44,838 --> 03:36:46,440 HOW MUCH WILL IT COST? 5406 03:36:46,440 --> 03:36:47,541 WHAT ARE MIDTERM AND FINAL 5407 03:36:47,541 --> 03:36:49,209 CHECKS? 5408 03:36:49,209 --> 03:36:52,246 JUST MILESTONES, WE ARE 5409 03:36:52,246 --> 03:36:53,180 MILESTONE DRIVEN, WHERE WILL 5410 03:36:53,180 --> 03:36:55,983 YOU BE IN ONE YEAR, TWO YEARS 5411 03:36:55,983 --> 03:36:57,484 AND FIVE YEARS, THAT KEEPS 5412 03:36:57,484 --> 03:36:58,585 PEOPLE HONEST. 5413 03:36:58,585 --> 03:36:59,987 TO KEEP THINGS ON TRACK. 5414 03:36:59,987 --> 03:37:03,323 THE LAST TWO THINGS, I THINK 5415 03:37:03,323 --> 03:37:06,493 DARPA YOU WOULD CONSIDER THIS 5416 03:37:06,493 --> 03:37:07,694 SACRILEGE TO ADD IN QUESTIONS 5417 03:37:07,694 --> 03:37:09,296 BUT I THINK IT'S APPROPRIATE 5418 03:37:09,296 --> 03:37:10,964 FOR OUR PAGE. 5419 03:37:10,964 --> 03:37:12,032 TO ENSURE EQUITABLE ACCESS TO 5420 03:37:12,032 --> 03:37:12,866 ALL PEOPLE. 5421 03:37:12,866 --> 03:37:15,435 HOW IS THE COST, ACCESSIBILITY, 5422 03:37:15,435 --> 03:37:17,104 USER EXPERIENCE GOING TO BE 5423 03:37:17,104 --> 03:37:17,371 ADDRESSED. 5424 03:37:17,371 --> 03:37:21,508 I WILL SAY FOR MYSELF, IF CAR T 5425 03:37:21,508 --> 03:37:25,045 THERAPIES ARE AMAZING, A 5426 03:37:25,045 --> 03:37:28,315 MIRACLE BUT ALSO A HALF MILLION. 5427 03:37:28,315 --> 03:37:29,917 I'M SURE YOU WILL BRING COSTS 5428 03:37:29,917 --> 03:37:31,118 DOWN. 5429 03:37:31,118 --> 03:37:33,921 I FEEL IF WE COME UP WITH 5430 03:37:33,921 --> 03:37:34,821 ANOTHER MILLION-DOLLAR SOLUTION 5431 03:37:34,821 --> 03:37:36,256 WE HAVE KIND OF FAILED. 5432 03:37:36,256 --> 03:37:39,293 THAT'S REALLY LIMITING ACCESS 5433 03:37:39,293 --> 03:37:40,260 TO THE PUBLIC. 5434 03:37:40,260 --> 03:37:42,663 HOW CAN WE MANUFACTURE THIS TO 5435 03:37:42,663 --> 03:37:44,965 BE CHEAP AND SUCCESSFUL. 5436 03:37:44,965 --> 03:37:48,201 HOW MIGHT THIS PROGRAM BE 5437 03:37:48,201 --> 03:37:49,369 MISPERCEIVED AND MISUSED. 5438 03:37:49,369 --> 03:37:53,407 WE WANT TO CREATE TRUST 5439 03:37:53,407 --> 03:37:54,841 PARTICULARLY WHERE PEOPLE DON'T 5440 03:37:54,841 --> 03:37:56,243 TRUST THE MEDICAL SYSTEM, WE 5441 03:37:56,243 --> 03:37:59,880 WANT TO BRING THEM INTO THE 5442 03:37:59,880 --> 03:38:02,683 HEALTHCARE SYSTEM. 5443 03:38:02,683 --> 03:38:04,818 SO HOW DOES IT WORK. 5444 03:38:04,818 --> 03:38:07,721 I AM STILL TRYING TO CONVINCE 5445 03:38:07,721 --> 03:38:10,490 PEOPLE TO APPLY TO BE A PROGRAM 5446 03:38:10,490 --> 03:38:10,724 MANAGER. 5447 03:38:10,724 --> 03:38:12,626 HOW DOES IT WORK? 5448 03:38:12,626 --> 03:38:14,695 A PROGRAM MANAGER COMES IN, YOU 5449 03:38:14,695 --> 03:38:16,096 PITCH THIS IDEA, WE ALL BEAT 5450 03:38:16,096 --> 03:38:20,233 YOU UP IN A NICE WAYMENT. 5451 03:38:20,233 --> 03:38:22,336 SAY YOU GET THE JOB. 5452 03:38:22,336 --> 03:38:25,405 YOU COME IN, HELP TO FIND THIS 5453 03:38:25,405 --> 03:38:27,307 CHALLENGE WITH YOUR CDA'S. 5454 03:38:27,307 --> 03:38:30,577 IT SHOULDN'T BE EASILY SOLVABLE 5455 03:38:30,577 --> 03:38:32,446 BY OTHER METHODS. 5456 03:38:32,446 --> 03:38:33,847 THE PROGRAM LAUNCH. 5457 03:38:33,847 --> 03:38:36,650 OFTEN TIMES YOU HAVE 2-3 5458 03:38:36,650 --> 03:38:37,317 PERFORMERS, SOMETIMES PEOPLE 5459 03:38:37,317 --> 03:38:40,120 PICK UP A FEW MORE PERFORMERS 5460 03:38:40,120 --> 03:38:41,722 AND THEY GO, RIGHT? 5461 03:38:41,722 --> 03:38:44,291 SO THIS, YOU KNOW, TYPICALLY 5462 03:38:44,291 --> 03:38:46,660 YOU SELL YOUR PROGRAM IN THE 5463 03:38:46,660 --> 03:38:48,495 FIRST COUPLE MONTHS. 5464 03:38:48,495 --> 03:38:49,830 THE B.A. GOES OUT. 5465 03:38:49,830 --> 03:38:52,299 WITHIN YOUR FIRST YEAR OR LESS, 5466 03:38:52,299 --> 03:38:54,167 NINE TO TEN MONTHS YOU WILL 5467 03:38:54,167 --> 03:38:55,602 HAVE KICKED OFF YOUR PROGRAM 5468 03:38:55,602 --> 03:38:57,738 AND THINGS WILL BE UNDER WAY. 5469 03:38:57,738 --> 03:39:01,908 FROM THEN, YOU HAVE YOUR 5470 03:39:01,908 --> 03:39:02,976 MULTIPLE PERFORMERS, LIKE I 5471 03:39:02,976 --> 03:39:04,478 SAID YOU WILL MEET WITH THEM 5472 03:39:04,478 --> 03:39:06,947 EVERY MONTH, NOT EVERYONE MAKES 5473 03:39:06,947 --> 03:39:09,950 IT, THAT'S OKAY, YOU TRY CRAZY 5474 03:39:09,950 --> 03:39:11,585 THINGS, OFTEN TIMES THERE WILL 5475 03:39:11,585 --> 03:39:13,253 BE SPIN OFFS BUT ONE WILL MAKE 5476 03:39:13,253 --> 03:39:16,957 IT TO THE END STATE. 5477 03:39:16,957 --> 03:39:19,760 AT THAT POINT YOU HAVE A 5478 03:39:19,760 --> 03:39:22,596 TRANSITION AND THAT TRANSITION 5479 03:39:22,596 --> 03:39:24,097 GOES OUT BROADLY ACROSS THE 5480 03:39:24,097 --> 03:39:25,465 U.S. PUBLIC. 5481 03:39:25,465 --> 03:39:28,035 AND I WILL TALK, I THINK THE 5482 03:39:28,035 --> 03:39:35,042 NEXT SLIDE SHOULD BE GREAT. 5483 03:39:35,042 --> 03:39:37,377 AS NOTED WE ARE HERE TO MAKE A 5484 03:39:37,377 --> 03:39:39,713 DIFFERENCE FOR THE U.S. PUBLIC, 5485 03:39:39,713 --> 03:39:40,747 FOR THE HEALTHCARE SYSTEM, 5486 03:39:40,747 --> 03:39:41,348 RIGHT? 5487 03:39:41,348 --> 03:39:45,052 ONE OF THE COOL THINGS THAT 5488 03:39:45,052 --> 03:39:47,587 ARPA-H HAS DONE IS SET UP THIS 5489 03:39:47,587 --> 03:39:49,923 PATIO OFFICE, THE PROJECT 5490 03:39:49,923 --> 03:39:50,891 SELLER TRANSITION INNOVATION 5491 03:39:50,891 --> 03:39:53,060 OFFICE. 5492 03:39:53,060 --> 03:39:55,629 HELP FOR YOUR NEW P.M., YOU 5493 03:39:55,629 --> 03:39:58,699 NEED TO COME WITH IDEA, 5494 03:39:58,699 --> 03:40:00,600 LANDSCAPE ANALYSIS, THOSE BITS 5495 03:40:00,600 --> 03:40:01,768 OF SUPPORT, THAT'S HELPFUL. 5496 03:40:01,768 --> 03:40:04,104 I THINK THE LATTER HALF OF THIS 5497 03:40:04,104 --> 03:40:05,772 IS WHAT'S REALLY AMAZING. 5498 03:40:05,772 --> 03:40:07,607 I HAVE SOME PERFORMERS, THEY 5499 03:40:07,607 --> 03:40:09,676 ARE DOING SOME COOL TECHNOLOGY. 5500 03:40:09,676 --> 03:40:12,245 PATIO IS THERE TO PROVIDE 5501 03:40:12,245 --> 03:40:14,114 BASICALLY THE MENU OF ALL THE 5502 03:40:14,114 --> 03:40:15,015 OTHER CAPABILITIES I CAN ORDER 5503 03:40:15,015 --> 03:40:16,450 FOR THEM. 5504 03:40:16,450 --> 03:40:18,785 THESE INCLUDE, OKAY I'VE GOT A 5505 03:40:18,785 --> 03:40:20,654 COMPANY, I NEED TO HAVE 5506 03:40:20,654 --> 03:40:22,122 SOMEBODY WHO KNOWS THE 5507 03:40:22,122 --> 03:40:26,193 LANDSCAPE SO I CAN COME UP WITH 5508 03:40:26,193 --> 03:40:28,528 AN APPROPRIATE IP STRATEGY. 5509 03:40:28,528 --> 03:40:36,503 OR THERE'S ELSIE, ETHICAL LEGAL 5510 03:40:36,503 --> 03:40:37,671 SCIENTIFIC IMPLICATIONS. 5511 03:40:37,671 --> 03:40:39,973 HELP ME WORK THROUGH OR WE WILL 5512 03:40:39,973 --> 03:40:41,641 BRING THAT RESOURCE. 5513 03:40:41,641 --> 03:40:43,710 ALSO CONNECTING TO VENTURE 5514 03:40:43,710 --> 03:40:44,945 CAPITALISTS WHO MAY WANT TO 5515 03:40:44,945 --> 03:40:47,814 INVEST IN THE TECHNOLOGY. 5516 03:40:47,814 --> 03:40:50,250 PEOPLE WHO ARE FAMILIAR WITH 5517 03:40:50,250 --> 03:40:51,752 REGULATORY ENGAGEMENT. 5518 03:40:51,752 --> 03:40:54,287 HELP ME THINK HOW I MIGHT 5519 03:40:54,287 --> 03:40:55,756 ENGAGE MOST EFFECTIVELY WITH 5520 03:40:55,756 --> 03:40:57,357 THE FDA, WE PROVIDE THAT 5521 03:40:57,357 --> 03:40:58,058 CAPABILITY. 5522 03:40:58,058 --> 03:40:59,960 THIS GOES BACK TO THE ROLE, 5523 03:40:59,960 --> 03:41:01,595 IT'S NOT JUST HANDING OUT THE 5524 03:41:01,595 --> 03:41:03,430 BRIEF CASE WITH THE CASH, BUT 5525 03:41:03,430 --> 03:41:05,732 DOING WHATEVER IS POSSIBLE TO 5526 03:41:05,732 --> 03:41:06,733 MAKE THOSE PERFORMERS 5527 03:41:06,733 --> 03:41:07,634 SUCCESSFUL. 5528 03:41:07,634 --> 03:41:10,237 SO AT THE END OF THE DAY, IF 5529 03:41:10,237 --> 03:41:11,838 THEY FAILED THAT'S BECAUSE THEY 5530 03:41:11,838 --> 03:41:14,141 DIDN'T WORK HARD ENOUGH, WHICH 5531 03:41:14,141 --> 03:41:15,342 SHOULDN'T HAPPEN, BECAUSE YOU 5532 03:41:15,342 --> 03:41:17,310 ARE THERE EVERY MONTH AND PICK 5533 03:41:17,310 --> 03:41:18,512 MOTIVATED PEOPLE. 5534 03:41:18,512 --> 03:41:19,780 OR MOTHER NATURE SAID NO. 5535 03:41:19,780 --> 03:41:22,849 OR YOU ARE TRYING TO LAY THIS 5536 03:41:22,849 --> 03:41:24,251 GROUNDWORK. 5537 03:41:24,251 --> 03:41:25,385 FANTASTIC ADDITIONAL CAPABILITY 5538 03:41:25,385 --> 03:41:27,020 FROM THE PATIO OFFICE. 5539 03:41:27,020 --> 03:41:27,954 ALL RIGHT. 5540 03:41:27,954 --> 03:41:30,590 SO THERE ARE LOTS OF DIFFERENT 5541 03:41:30,590 --> 03:41:34,561 WAYS TO PARTNER, AS NOTED. 5542 03:41:34,561 --> 03:41:35,762 BECOME A PROGRAM MANAGER. 5543 03:41:35,762 --> 03:41:36,830 WE ARE ALWAYS LOOKING FOR NEW 5544 03:41:36,830 --> 03:41:38,131 PEOPLE. 5545 03:41:38,131 --> 03:41:40,367 THE OPEN B.A. FOR PEOPLE, FOR 5546 03:41:40,367 --> 03:41:44,171 PEOPLE WHO WANT TO SEND IN 5547 03:41:44,171 --> 03:41:45,772 THEIR CRAZY IDEAS. 5548 03:41:45,772 --> 03:41:48,375 THE OPEN BAA IS ALWAYS OPEN. 5549 03:41:48,375 --> 03:41:49,476 HENCE THE NAME. 5550 03:41:49,476 --> 03:41:51,645 THIS ONE CLOSES IN MARCH, A NEW 5551 03:41:51,645 --> 03:41:53,480 ONE WILL OPEN THE NEXT DAY. 5552 03:41:53,480 --> 03:41:55,182 A THING TO KNOW FOR THE FIRST 5553 03:41:55,182 --> 03:41:56,817 COUPLE YEARS A LOT OF MONEY IS 5554 03:41:56,817 --> 03:41:59,853 GOING OUT THROUGH THE OPEN BAA, 5555 03:41:59,853 --> 03:42:01,721 YOU COME IN WITH YOUR CRAZY 5556 03:42:01,721 --> 03:42:03,590 IDEA, YOU SEND IN YOUR 5557 03:42:03,590 --> 03:42:06,626 ABSTRACT, WE EITHER SAY EH, OR 5558 03:42:06,626 --> 03:42:07,527 YEAH THAT'S INTERESTING, SEND 5559 03:42:07,527 --> 03:42:09,396 US A FULL PROPOSAL. 5560 03:42:09,396 --> 03:42:14,568 YOU SEND US A FULL PROPOSAL AND 5561 03:42:14,568 --> 03:42:16,203 WE WILL SEND OUT A NOTICE TO 5562 03:42:16,203 --> 03:42:17,304 FUND OR NOT FUND. 5563 03:42:17,304 --> 03:42:18,471 QUITE A FEW HAVE BEEN FUNDED 5564 03:42:18,471 --> 03:42:19,272 THIS YEAR. 5565 03:42:19,272 --> 03:42:22,075 NEXT YEAR IT WILL GO DOWN, THE 5566 03:42:22,075 --> 03:42:23,443 NUMBER OF PROPOSALS WE FUND OUT 5567 03:42:23,443 --> 03:42:26,913 OF THE OPEN BAA, THE REASON IS 5568 03:42:26,913 --> 03:42:29,482 NUMBER OF PROGRAMS WILL GO UP, 5569 03:42:29,482 --> 03:42:32,285 SO THE MONEY WILL SHIFT OVER. 5570 03:42:32,285 --> 03:42:35,655 THIS WILL ALWAYS BE AN OPEN 5571 03:42:35,655 --> 03:42:37,424 BAA, YOU CAN STILL DREAM REALLY 5572 03:42:37,424 --> 03:42:39,459 BIG FOR THE OPEN BAA. 5573 03:42:39,459 --> 03:42:42,562 BECOME A PROGRAM MANAGER. 5574 03:42:42,562 --> 03:42:43,897 THE OTHERS, FOR FOLKS WHO ARE 5575 03:42:43,897 --> 03:42:47,400 IN INDUSTRY WE HAVE A COOL 5576 03:42:47,400 --> 03:42:49,269 SYSTEM CALLED HUB AND SPOKE. 5577 03:42:49,269 --> 03:42:51,771 WE HAVE TWO HUBS, ONE IN BOSTON 5578 03:42:51,771 --> 03:42:53,006 AND DALLAS. 5579 03:42:53,006 --> 03:42:55,108 BOSTON IS ABOUT THE INVESTMENT 5580 03:42:55,108 --> 03:42:58,912 COMMUNITY TRYING TO BRING THEIR 5581 03:42:58,912 --> 03:43:01,448 TECHNICAL EXPERTISE TO 5582 03:43:01,448 --> 03:43:01,882 ACCELERATE PROGRAMS. 5583 03:43:01,882 --> 03:43:03,516 THE DALLAS THEY ARE USING THE 5584 03:43:03,516 --> 03:43:04,451 USER EXPERIENCE, RIGHT. 5585 03:43:04,451 --> 03:43:06,586 SO THERE ARE NO REQUIREMENTS IF 5586 03:43:06,586 --> 03:43:10,323 YOU RUN A TRIAL, FDA, IT HAS TO 5587 03:43:10,323 --> 03:43:11,258 REPLICATE THE POPULATION OF THE 5588 03:43:11,258 --> 03:43:12,859 UNITED STATES WHO SUFFERS FROM 5589 03:43:12,859 --> 03:43:14,261 THAT DISEASE, RIGHT? 5590 03:43:14,261 --> 03:43:18,164 THAT COULD BE A CHALLENGE. 5591 03:43:18,164 --> 03:43:23,069 THAT HUB IS THERE TO NORMALLY 5592 03:43:23,069 --> 03:43:25,839 EXPEDITE THE CLINICAL TRIALS 5593 03:43:25,839 --> 03:43:27,240 BUT ALSO DISTRIBUTE CLINICAL 5594 03:43:27,240 --> 03:43:29,009 TRIALS PEOPLE LIVING IN REMOTE 5595 03:43:29,009 --> 03:43:30,243 LOCATIONS CAN PARTICIPATE. 5596 03:43:30,243 --> 03:43:32,779 ALSO WORK ON USER ENGAGEMENT. 5597 03:43:32,779 --> 03:43:34,681 AGAIN HERE IS USER TECHNOLOGY, 5598 03:43:34,681 --> 03:43:36,983 HOW IS A PATIENT GOING TO LIVE 5599 03:43:36,983 --> 03:43:38,418 WITH THIS TECHNOLOGY. 5600 03:43:38,418 --> 03:43:39,786 CAN WE PROVIDE FEEDBACK AS 5601 03:43:39,786 --> 03:43:41,688 EARLY AS POSSIBLE TO SHAKE THAT 5602 03:43:41,688 --> 03:43:41,988 TECHNOLOGY. 5603 03:43:41,988 --> 03:43:45,158 IF YOU ARE ON THE COMMERCIAL 5604 03:43:45,158 --> 03:43:46,593 SIDE AND INTERESTING THERE IS 5605 03:43:46,593 --> 03:43:47,294 AN APPLICATION PROCESS. 5606 03:43:47,294 --> 03:43:48,929 WHAT HAPPENS WITH THE HUB AND 5607 03:43:48,929 --> 03:43:51,464 SPOKE, IF I NEED A CAPABILITY, 5608 03:43:51,464 --> 03:43:53,166 I CAN TAB INTO THE HUB AND 5609 03:43:53,166 --> 03:43:53,366 SPOKE. 5610 03:43:53,366 --> 03:43:54,567 I WOULD LIKE TO TALK TO 5611 03:43:54,567 --> 03:43:55,936 SOMEBODY IN THIS PARTICULAR 5612 03:43:55,936 --> 03:43:57,337 AREA WHO KNOWS THIS PARTICULAR 5613 03:43:57,337 --> 03:43:58,972 THING SO THAT THEY CAN HELP ME 5614 03:43:58,972 --> 03:44:00,373 WITH THE EFFORT AND LINEUP THE 5615 03:44:00,373 --> 03:44:02,509 PERFORMER. 5616 03:44:02,509 --> 03:44:05,879 OKAY, SO RIGHT NOW THERE ARE 5617 03:44:05,879 --> 03:44:09,316 FOUR INITIAL FOCUS AREAS. 5618 03:44:09,316 --> 03:44:11,151 HEALTH SCIENCE FUTURES, THEY 5619 03:44:11,151 --> 03:44:14,020 TEND TO DO THE MORE FAR OUT 5620 03:44:14,020 --> 03:44:15,121 THERE CONCEPTS. 5621 03:44:15,121 --> 03:44:16,990 LIKE WHAT MIGHT BE POSSIBLE. 5622 03:44:16,990 --> 03:44:18,825 STILL TRYING TO DELIVER 5623 03:44:18,825 --> 03:44:20,493 THERAPIES BUT THEY DO TRY TO 5624 03:44:20,493 --> 03:44:22,128 PUSH FOR IT. 5625 03:44:22,128 --> 03:44:24,030 SCALABLE SOLUTIONS IS TRYING TO 5626 03:44:24,030 --> 03:44:24,931 REACH EVERYONE QUICKLY. 5627 03:44:24,931 --> 03:44:27,133 WE HAVE TALKED A LOT ABOUT 5628 03:44:27,133 --> 03:44:28,335 MANUFACTURING TODAY. 5629 03:44:28,335 --> 03:44:29,869 THIS IS REALLY ONE THAT IS 5630 03:44:29,869 --> 03:44:33,406 TRYING TO PUSH ON MANUFACTURING 5631 03:44:33,406 --> 03:44:35,942 DISTRIBUTION OF BOTH THE 5632 03:44:35,942 --> 03:44:38,278 THERAPY ITSELF BUT ALSO DATA, 5633 03:44:38,278 --> 03:44:40,146 PUSHES AS BROADLY AS POSSIBLE. 5634 03:44:40,146 --> 03:44:41,448 PROACTIVE HEALTH. 5635 03:44:41,448 --> 03:44:43,283 LET'S TRY TO KEEP PEOPLE FROM 5636 03:44:43,283 --> 03:44:44,584 BECOMING PATIENTS. 5637 03:44:44,584 --> 03:44:46,686 LET'S GET THE U.S. POPULATION 5638 03:44:46,686 --> 03:44:49,723 TO BE AS HEALTHY AS POSSIBLE. 5639 03:44:49,723 --> 03:44:50,890 RESILIENT SYSTEMS TRYING TO 5640 03:44:50,890 --> 03:44:52,792 BUILD AN INTEGRATED HEALTHCARE 5641 03:44:52,792 --> 03:44:55,862 SYSTEM, WE HAVE A LOT OF 5642 03:44:55,862 --> 03:44:59,199 INFORMATION FLOATING AROUND 5643 03:44:59,199 --> 03:45:00,400 ELECTRONIC HEALTHCARE RECORDS. 5644 03:45:00,400 --> 03:45:03,203 HOW DO WE GIVE PEOPLE ACCESS IN 5645 03:45:03,203 --> 03:45:04,938 A USABLE FORM AND GET THE MOST 5646 03:45:04,938 --> 03:45:06,039 UTILITY OUT OF IT. 5647 03:45:06,039 --> 03:45:07,707 LOOK AT OUR HEALTHCARE SYSTEM 5648 03:45:07,707 --> 03:45:10,944 AND MAKE SURE IT'S RESILIENT 5649 03:45:10,944 --> 03:45:13,313 AGAINST ANY SORT OF 5650 03:45:13,313 --> 03:45:16,316 DISRUPTIONS, SUCH AS A PANDEMIC. 5651 03:45:16,316 --> 03:45:18,418 OKAY, SO THAT GIVES YOU AN 5652 03:45:18,418 --> 03:45:19,352 OVERVIEW OF THE OFFICE. 5653 03:45:19,352 --> 03:45:21,688 I WAS GOING TO TAKE A FEW MORE 5654 03:45:21,688 --> 03:45:23,556 MINUTES TO TALK ABOUT THE 5655 03:45:23,556 --> 03:45:25,392 PROJECTS I'VE FUNDED TO DATE. 5656 03:45:25,392 --> 03:45:26,760 HAPPY TO ANSWER ANY QUESTIONS 5657 03:45:26,760 --> 03:45:27,527 ABOUT THEM. 5658 03:45:27,527 --> 03:45:29,629 AND ALSO ABOUT A RECENT 5659 03:45:29,629 --> 03:45:30,997 ANNOUNCEMENT FOR A FIRST FULL 5660 03:45:30,997 --> 03:45:31,731 PROGRAM. 5661 03:45:31,731 --> 03:45:33,433 THIS IS TO GIVE YOU A FEEL FOR 5662 03:45:33,433 --> 03:45:35,935 THE SCOPE, I WILL TRY TO LEAVE 5663 03:45:35,935 --> 03:45:37,804 TEN MINUTES FOR QUESTIONS, IF 5664 03:45:37,804 --> 03:45:38,738 THAT'S ALL RIGHT. 5665 03:45:38,738 --> 03:45:41,207 HERE ARE SOME FUNDED PROJECTS. 5666 03:45:41,207 --> 03:45:42,475 THE FIRST ONE IS CALLED HEART. 5667 03:45:42,475 --> 03:45:44,377 THIS IS THE ONE I MIGHT HAVE 5668 03:45:44,377 --> 03:45:45,578 MENTIONED A FEW TIMES. 5669 03:45:45,578 --> 03:45:47,881 THIS IS TRYING TO PRINT A HUMAN 5670 03:45:47,881 --> 03:45:49,949 HEART IN UNDER ONE HOUR. 5671 03:45:49,949 --> 03:46:00,393 THIS IS TAKING A SAMPLE, 5672 03:46:03,029 --> 03:46:04,831 MASSIVE STEM CELLS. 5673 03:46:04,831 --> 03:46:06,066 YOU NEED BILLIONS OF 5674 03:46:06,066 --> 03:46:07,567 APPROPRIATE CELLS. 5675 03:46:07,567 --> 03:46:10,136 TAKE THE CELLS, STEM CELLS, 5676 03:46:10,136 --> 03:46:13,840 DIFFERENTIATING THEM IN THE 5677 03:46:13,840 --> 03:46:14,974 RIGHT QUANTITIES AND RIGHT 5678 03:46:14,974 --> 03:46:15,742 VOLUMES. 5679 03:46:15,742 --> 03:46:18,044 YOU HAVE MASSIVE QUANTITIES OF 5680 03:46:18,044 --> 03:46:20,146 CELLS AND YOU DON'T DO IT 5681 03:46:20,146 --> 03:46:21,614 QUICKLY THEY ARE ALL GOING TO 5682 03:46:21,614 --> 03:46:22,348 DIE, RIGHT? 5683 03:46:22,348 --> 03:46:24,350 YOU HAVE ONE HOUR, ROUGHLY, TO 5684 03:46:24,350 --> 03:46:25,985 PRINT ALL OF THESE CELLS SO 5685 03:46:25,985 --> 03:46:30,890 COME UP WITH VERY HIGH-SPEED 5686 03:46:30,890 --> 03:46:32,559 PRINTERS THAT BASICALLY NEEDLES 5687 03:46:32,559 --> 03:46:34,427 COMING IN FROM ALL SIDES AT THE 5688 03:46:34,427 --> 03:46:37,363 SAME TIME PRINTING THE HUMAN 5689 03:46:37,363 --> 03:46:37,564 HEART. 5690 03:46:37,564 --> 03:46:40,567 IT'S A VERY SCI-FI-LOOKING WAY. 5691 03:46:40,567 --> 03:46:41,601 AMAZING TEAM OUT THERE. 5692 03:46:41,601 --> 03:46:43,536 YOU CAN IMAGINE, THANKS TO THE 5693 03:46:43,536 --> 03:46:46,406 NEED, CELL ENGINEERING, MASSIVE 5694 03:46:46,406 --> 03:46:49,476 SCALABILITY, THESE 3D PRINTING 5695 03:46:49,476 --> 03:46:50,677 TECHNOLOGIES THEY HAVE WORLD 5696 03:46:50,677 --> 03:46:52,545 LEADERS ON THAT. 5697 03:46:52,545 --> 03:46:53,813 VASCULAR PRINTING, THE CELLS 5698 03:46:53,813 --> 03:46:56,716 WILL DIE IF YOU DON'T HAVE THE 5699 03:46:56,716 --> 03:46:59,018 VASCULATURE IS THERE AND 5700 03:46:59,018 --> 03:47:00,820 OPERATIONAL QUICKLY. 5701 03:47:00,820 --> 03:47:03,156 AND LASTLY ORGAN MATURATION. 5702 03:47:03,156 --> 03:47:05,058 YOU PRINT THIS IN AN HOUR, IT 5703 03:47:05,058 --> 03:47:06,292 DOESN'T MEAN IT'S READY TO GO, 5704 03:47:06,292 --> 03:47:08,228 YOU HAVE TO TAKE TIME TO MATURE 5705 03:47:08,228 --> 03:47:12,065 THE CELLS SO IT OPERATES AS AN 5706 03:47:12,065 --> 03:47:15,602 ORGAN. 5707 03:47:15,602 --> 03:47:18,638 SO THOR, HE NAMES EVERY PROGRAM 5708 03:47:18,638 --> 03:47:25,578 AFTER SOMETHING FROM MARVEL. 5709 03:47:25,578 --> 03:47:26,212 ANYWAY, FANTASTICALLY A CLEVER 5710 03:47:26,212 --> 03:47:26,980 GUY. 5711 03:47:26,980 --> 03:47:37,423 THIS IS A TARGETED HYBRID 5712 03:47:41,828 --> 03:47:42,328 ONCOTHERAPEUTIC REGULATION. 5713 03:47:42,328 --> 03:47:52,872 HE IS TRYING TO IMPLANT DEVICE 5714 03:47:55,808 --> 03:47:57,010 FOR CANCER. 5715 03:47:57,010 --> 03:47:59,078 A CONTROL SYSTEM THAT CAN 5716 03:47:59,078 --> 03:48:01,981 MODULATE THE LOCAL AND SYSTEMIC 5717 03:48:01,981 --> 03:48:04,317 IMMUNE SYSTEM OF A PATIENT, 5718 03:48:04,317 --> 03:48:06,853 EXTERNALLY, SO YOU CAN TUNE IT 5719 03:48:06,853 --> 03:48:09,722 UP AND TUNE DOWN AND A WEARABLE 5720 03:48:09,722 --> 03:48:11,324 THAT TRACKS THE PATIENT. 5721 03:48:11,324 --> 03:48:13,660 GOING AFTER REAL BIOLOGICAL 5722 03:48:13,660 --> 03:48:15,595 INFORMATION, USING A VARIETY OF 5723 03:48:15,595 --> 03:48:18,131 TECHNIQUES TO TRACK THE STATUS 5724 03:48:18,131 --> 03:48:19,566 OF THE IMMUNE SYSTEM. 5725 03:48:19,566 --> 03:48:22,569 CONCEPT IS NOT ONLY TO PROVIDE 5726 03:48:22,569 --> 03:48:28,107 BETTER THERAPY FOR CANCERS OF 5727 03:48:28,107 --> 03:48:29,709 THE PERITONEUM. 5728 03:48:29,709 --> 03:48:33,880 BUT ALSO PATIENTS WHO LIVE IN 5729 03:48:33,880 --> 03:48:35,548 LOWER SOCIOECONOMIC STATUS, OR 5730 03:48:35,548 --> 03:48:37,617 RURAL AREA, THEY CAN'T GO IN AS 5731 03:48:37,617 --> 03:48:40,687 EASILY, THEY CAN GO HOME, THE 5732 03:48:40,687 --> 03:48:42,322 CLINICIAN CAN ADJUST IT UP OR 5733 03:48:42,322 --> 03:48:43,489 TOWN, TRACKED WITH A WEARABLE 5734 03:48:43,489 --> 03:48:44,824 AND GIVE A WARNING. 5735 03:48:44,824 --> 03:48:47,427 IF THEY ARE STARTING TO 5736 03:48:47,427 --> 03:48:51,664 INITIATE, EXPERIENCE A CYTOKINE 5737 03:48:51,664 --> 03:48:53,733 RELEASE SYNDROME, A FLAG CAN GO 5738 03:48:53,733 --> 03:48:55,335 UP, THEY CAN GET IN THE CAR, 5739 03:48:55,335 --> 03:48:57,103 GET ON I A PLANE TO GET BACK TO 5740 03:48:57,103 --> 03:48:57,737 THE CLINIC. 5741 03:48:57,737 --> 03:48:59,839 A LOT OF FOCUSING ON HOW THE 5742 03:48:59,839 --> 03:49:02,408 BEST SITE OF CYTOKINES TO GO 5743 03:49:02,408 --> 03:49:05,111 AFTER SOLID TUMORS. 5744 03:49:05,111 --> 03:49:08,014 CELL FACTOR THAT'S ARE STABLE 5745 03:49:08,014 --> 03:49:12,752 AND HIGHLY PRODUCTIVE. 5746 03:49:12,752 --> 03:49:16,689 BIOCHEMICAL SENSORS. 5747 03:49:16,689 --> 03:49:17,423 DART. 5748 03:49:17,423 --> 03:49:21,427 THIS IS A LARGE ANNOUNCEMENT WE 5749 03:49:21,427 --> 03:49:27,000 RELEASED OUT OF HARVARD MEDICAL 5750 03:49:27,000 --> 03:49:27,967 SCHOOL. 5751 03:49:27,967 --> 03:49:29,836 DEFEATING ANTIBIOTIC RESISTANCE 5752 03:49:29,836 --> 03:49:30,336 THROUGH TRANSFORMATIVE 5753 03:49:30,336 --> 03:49:36,509 SOLUTIONS. 5754 03:49:36,509 --> 03:49:39,779 BASED ON A WEATHER MACHINE. 5755 03:49:39,779 --> 03:49:44,684 THIS IS GOING AFTER ANTIBIOTIC 5756 03:49:44,684 --> 03:49:45,785 RESISTANT. 5757 03:49:45,785 --> 03:49:49,422 EVERYONE IS FAMILIAR WITH PETRI 5758 03:49:49,422 --> 03:49:50,390 DISHES. 5759 03:49:50,390 --> 03:49:53,192 HE HAS A SYSTEM WITH TWO 5760 03:49:53,192 --> 03:49:57,163 MILLION KHAL -- CHANNELS AND 5761 03:49:57,163 --> 03:50:00,633 HE CAN CAPTURE A DIFFERENT 5762 03:50:00,633 --> 03:50:04,437 BACTERIUM IN EVERYONE, HE CAN 5763 03:50:04,437 --> 03:50:12,145 FISH OR HYPERSPECTRAL IMAGING 5764 03:50:12,145 --> 03:50:13,346 WITHOUT 96-98% ACCURACY. 5765 03:50:13,346 --> 03:50:15,415 EACH DAY HE LOOKS AT BILLIONS 5766 03:50:15,415 --> 03:50:17,550 OF CELLS WHICH PROVIDES 5767 03:50:17,550 --> 03:50:18,985 INCREDIBLE THROUGHPUT OF DATA. 5768 03:50:18,985 --> 03:50:21,020 AND WITH THIS, THEY CAN DO 5769 03:50:21,020 --> 03:50:23,790 THINGS LIKE UNDERSTAND THE 5770 03:50:23,790 --> 03:50:26,793 BASIS FOR ANTIBIOTIC 5771 03:50:26,793 --> 03:50:27,160 SUSCEPTIBILITY. 5772 03:50:27,160 --> 03:50:29,796 WHAT ARE THE PERSISTORS? 5773 03:50:29,796 --> 03:50:31,264 WHAT ARE THE SURVIVORS? 5774 03:50:31,264 --> 03:50:33,466 ONLY ONE IN 50,000, ONE IN 5775 03:50:33,466 --> 03:50:34,734 100,000. 5776 03:50:34,734 --> 03:50:38,037 HE HAS ENOUGH TRENCHES TO 5777 03:50:38,037 --> 03:50:40,606 IDENTIFY, NOT TO BUILDING TO A 5778 03:50:40,606 --> 03:50:42,442 COLONY AND LOSE THE PHENOTYPE, 5779 03:50:42,442 --> 03:50:43,576 BUT WHAT MAKES IT A SURVIVE R 5780 03:50:43,576 --> 03:50:44,344 YO. 5781 03:50:44,344 --> 03:50:46,179 EVEN IN THE PAST FEW WEEKS HE 5782 03:50:46,179 --> 03:50:49,449 HAS COME UP, IDENTIFIED NEW 5783 03:50:49,449 --> 03:50:50,883 GENES THAT MAY BE RESPONSIBLE 5784 03:50:50,883 --> 03:50:54,087 FOR THE PERSISTENCE. 5785 03:50:54,087 --> 03:50:56,222 HE IS ALSO COMING UP WITH A 5786 03:50:56,222 --> 03:51:00,960 SYSTEM TO MASSIVELY SCREEN FOR 5787 03:51:00,960 --> 03:51:02,562 NEW ANTIBIOTIC PEPTIDES. 5788 03:51:02,562 --> 03:51:04,464 HE CAN SCREEN, PRODUCER CELLS 5789 03:51:04,464 --> 03:51:06,766 NEXT TO THE TARGET PATHOGENS 5790 03:51:06,766 --> 03:51:10,036 AND LOOK AT WHICH ONES KILL OFF 5791 03:51:10,036 --> 03:51:12,538 THE PATHOGENS, SCREENING 5792 03:51:12,538 --> 03:51:13,706 MILLIONS OF DIFFERENT STRAINS 5793 03:51:13,706 --> 03:51:14,941 AT THE SAME TIME. 5794 03:51:14,941 --> 03:51:16,309 ONCE THAT IS DONE HE IS 5795 03:51:16,309 --> 03:51:17,276 OPTIMIZE IT. 5796 03:51:17,276 --> 03:51:20,446 THIS IS SOMETHING HE DID BEFORE 5797 03:51:20,446 --> 03:51:21,848 WITH SYNTHETIC BIOLOGY CIRCUIT 5798 03:51:21,848 --> 03:51:23,249 BUT YOU CAN CHANGE EVERYTHING. 5799 03:51:23,249 --> 03:51:24,450 YOU CAN SCREEN MASSIVE 5800 03:51:24,450 --> 03:51:26,085 LIBRARIES AT THE SAME TIME. 5801 03:51:26,085 --> 03:51:27,487 MILLIONS OF VARIANTS ALL RUN AT 5802 03:51:27,487 --> 03:51:29,889 THE SAME TIME TO LOOK FOR AN 5803 03:51:29,889 --> 03:51:32,358 OPTIMAL SOLUTION. 5804 03:51:32,358 --> 03:51:33,960 LASTLY, ANTIBIOTIC 5805 03:51:33,960 --> 03:51:35,161 SUSCEPTIBILITY TESTING. 5806 03:51:35,161 --> 03:51:37,029 THIS SYSTEM IS SO PRECISE IT 5807 03:51:37,029 --> 03:51:39,665 CAN LOOK AT DOUBLING TIMES, IT 5808 03:51:39,665 --> 03:51:41,434 CAN PREDICT DOUBLING TIMES EVEN 5809 03:51:41,434 --> 03:51:43,803 BEFORE THE BACTERIUM HAS 5810 03:51:43,803 --> 03:51:45,405 FINISHED DOUBLING. 5811 03:51:45,405 --> 03:51:47,240 IT HAS PRECISION IN DOUBLING 5812 03:51:47,240 --> 03:51:51,411 TIMES IN MILLISECONDS. 5813 03:51:51,411 --> 03:51:54,514 HOW THIS IS BEING IMPACTED, 5814 03:51:54,514 --> 03:51:56,582 AGAIN ALL SCREENED AT THE SAME 5815 03:51:56,582 --> 03:51:56,783 TIME. 5816 03:51:56,783 --> 03:51:59,385 THE CONCEPT YOU MAY HAVE SEPSIS 5817 03:51:59,385 --> 03:52:01,487 UTI, IN LESS THAN AN HOUR IT 5818 03:52:01,487 --> 03:52:04,357 WILL TELL YOU WHICH ANTIBIOTIC 5819 03:52:04,357 --> 03:52:06,993 YOU SHOULD BE GETTING. 5820 03:52:06,993 --> 03:52:08,394 THESE ARE PROGRAMS THAT HAVE 5821 03:52:08,394 --> 03:52:10,029 ALREADY BEEN FUNDED. 5822 03:52:10,029 --> 03:52:20,540 RECENTLY WE ANNOUNCED REACT, 5823 03:52:25,545 --> 03:52:27,547 RESILIENT EXTENDED AND 5824 03:52:27,547 --> 03:52:29,048 AUTOMATED CELLULAR THERAPIES. 5825 03:52:29,048 --> 03:52:31,517 A CARRIER THAT CAN CONTROL THE 5826 03:52:31,517 --> 03:52:33,152 RELEASE OF THERAPIES FROM 5827 03:52:33,152 --> 03:52:37,290 ENGINEERED CELLS, RIGHT? 5828 03:52:37,290 --> 03:52:40,026 YOU ARE FAMILIAR -- DID SOME 5829 03:52:40,026 --> 03:52:41,894 WORK, BOB LINGER RECENTLY, THE 5830 03:52:41,894 --> 03:52:45,498 CONCEPT YOU HAVE A DEVICE, IT'S 5831 03:52:45,498 --> 03:52:46,866 IMPLANTED FROM YOUR SMARTPHONE. 5832 03:52:46,866 --> 03:52:49,001 YOU CAN SEND A SIGNAL, THAT 5833 03:52:49,001 --> 03:52:51,337 SIGNAL TELLS THE BIO ELECTRONIC 5834 03:52:51,337 --> 03:52:55,074 DEVICE TO SHINE A LIGHT ON OR A 5835 03:52:55,074 --> 03:52:57,944 MAGNETIC FIELD OR ELECTRICALLY 5836 03:52:57,944 --> 03:52:59,145 STIMULATE CELLS. 5837 03:52:59,145 --> 03:53:01,214 ONCE STIMULATED THEY ARE 5838 03:53:01,214 --> 03:53:03,082 ENGINEERED TO RELEASE A THERAPY. 5839 03:53:03,082 --> 03:53:05,151 THAT'S CALLED A LIVING PHARMACY. 5840 03:53:05,151 --> 03:53:06,953 YOU CAN ALSO THINK OF THE 5841 03:53:06,953 --> 03:53:09,689 REVERSE. 5842 03:53:09,689 --> 03:53:15,161 I KNOW WENDELL LIM WAS HERE. 5843 03:53:15,161 --> 03:53:20,399 MANY HAVE BUILT TRANCE DEUSSERS. 5844 03:53:20,399 --> 03:53:23,970 WHEN IT DETECTS A HORMONE OR 5845 03:53:23,970 --> 03:53:27,406 CYTOKINE, IT GENERATES A 5846 03:53:27,406 --> 03:53:28,574 RESPONSE, BUBBLES, CHANGE IN 5847 03:53:28,574 --> 03:53:30,343 THE MEMBRANE POTENTIAL THEN 5848 03:53:30,343 --> 03:53:33,012 PICKED UP BY THE BIO ELECTRONIC 5849 03:53:33,012 --> 03:53:33,846 DEVICE AND REPORTED TO THE 5850 03:53:33,846 --> 03:53:34,680 SMARTPHONE. 5851 03:53:34,680 --> 03:53:36,582 THE CONCEPT IS YOU HAVE A NEW 5852 03:53:36,582 --> 03:53:38,050 INTERFACE INTO THE BODY. 5853 03:53:38,050 --> 03:53:43,122 YOU CAN ARBITRARILY CONTROL 5854 03:53:43,122 --> 03:53:44,524 CYTOKINES OR HORMONES OR TRACK 5855 03:53:44,524 --> 03:53:45,625 THE SAME COMING OUT OF THE 5856 03:53:45,625 --> 03:53:46,893 SYSTEM. 5857 03:53:46,893 --> 03:53:49,228 PROPOSERS DAY IS IN A FEW WEEKS 5858 03:53:49,228 --> 03:53:51,664 OUT IN DENVER AND ABSTRACTS ARE 5859 03:53:51,664 --> 03:53:54,233 DUE AT THE END OF THE MONTH. 5860 03:53:54,233 --> 03:53:56,602 LOOKING FOR ANY AND ALL TAKERS 5861 03:53:56,602 --> 03:53:58,704 FOR THE REACT PROGRAM. 5862 03:53:58,704 --> 03:54:01,974 ALL RIGHT, SO, I THINK THIS IS, 5863 03:54:01,974 --> 03:54:04,544 SHOULD BE MY LAST SLIDE. 5864 03:54:04,544 --> 03:54:06,379 TECHNICAL AREAS IN HERE. 5865 03:54:06,379 --> 03:54:09,282 ALMOST ALL OF THESE HINGE ON 5866 03:54:09,282 --> 03:54:11,117 SYNTHETIC BIOLOGY. 5867 03:54:11,117 --> 03:54:12,718 LONG-TERM MAINTENANCE OF CELLS 5868 03:54:12,718 --> 03:54:13,653 IN VIVO, RIGHT? 5869 03:54:13,653 --> 03:54:15,288 YOU ARE TAKING SOME CELLS AND 5870 03:54:15,288 --> 03:54:17,390 MAYBE THEY ARE NOT FROM THAT 5871 03:54:17,390 --> 03:54:20,159 AREA OF THE BODY. 5872 03:54:20,159 --> 03:54:23,262 MAYBE THEY ARE PLANTED SUB 5873 03:54:23,262 --> 03:54:26,766 CUTANEOUSLY, HOW DO YOU 5874 03:54:26,766 --> 03:54:28,100 MAINTAIN THE VIABILITY IN THAT 5875 03:54:28,100 --> 03:54:29,302 NEW ENVIRONMENT. 5876 03:54:29,302 --> 03:54:30,803 SOME MAY BE MODIFICATIONS TO 5877 03:54:30,803 --> 03:54:31,938 THE CARRIER. 5878 03:54:31,938 --> 03:54:34,840 SOME MAY BE INCLUSION OF HELPER 5879 03:54:34,840 --> 03:54:38,678 CELLS BUT ALSO SYNBIO HAS A 5880 03:54:38,678 --> 03:54:40,913 ROLE. 5881 03:54:40,913 --> 03:54:41,847 MANUFACTURER OF STANDARDIZED 5882 03:54:41,847 --> 03:54:44,617 CELL LINES. 5883 03:54:44,617 --> 03:54:53,159 WE NEED HOME HOMOGENEIC CELL 5884 03:54:53,159 --> 03:54:53,359 LINES. 5885 03:54:53,359 --> 03:54:54,927 HOW DO WE MAKE THAT MODULAR. 5886 03:54:54,927 --> 03:54:56,596 IF I SPEND MILLIONS AND 5887 03:54:56,596 --> 03:54:58,898 MILLIONS TO PRODUCE A CELL LINE 5888 03:54:58,898 --> 03:55:01,233 THAT WHEN ELECTRICALLY 5889 03:55:01,233 --> 03:55:03,603 STIMULATED WILL RELEASE ONE 5890 03:55:03,603 --> 03:55:04,770 PEPTIDE HORMONE AND NOW I WANT 5891 03:55:04,770 --> 03:55:06,939 TO MAKE THE NEXT, DO I HAVE TO 5892 03:55:06,939 --> 03:55:08,274 GO BACK TO SUB ZERO? 5893 03:55:08,274 --> 03:55:11,510 I THINK I HAVE A ROBUST CHASSI, 5894 03:55:11,510 --> 03:55:14,113 CAN I JUST WALK IN THE GENE TO 5895 03:55:14,113 --> 03:55:16,882 GENERATE THE DIFFERENT PEPTIDE. 5896 03:55:16,882 --> 03:55:18,317 IMPLANTABLE DEVICE THAT'S 5897 03:55:18,317 --> 03:55:19,719 COMMUNICATES WITH THE PATIENT, 5898 03:55:19,719 --> 03:55:22,288 THIS IS PROBABLY MORE FOR 5899 03:55:22,288 --> 03:55:24,557 DOUBLE E'S BUT ROBUST POWER 5900 03:55:24,557 --> 03:55:28,961 MANAGEMENT. 5901 03:55:28,961 --> 03:55:30,763 TWO MAIN TRACKS, LIVING THERAPY. 5902 03:55:30,763 --> 03:55:32,465 WHAT IS THE BEST WAY TO 5903 03:55:32,465 --> 03:55:34,133 STIMULATE A CELL TO RELEASE THE 5904 03:55:34,133 --> 03:55:34,834 THERAPY, RIGHT? 5905 03:55:34,834 --> 03:55:41,374 ELECTRICAL? 5906 03:55:41,374 --> 03:55:43,709 MAKE THE CHOICE, JUSTIFY IT, 5907 03:55:43,709 --> 03:55:45,111 AND ENGINEERING FOR THE CELL 5908 03:55:45,111 --> 03:55:47,713 AND DEVICE WORK BACK FROM THERE. 5909 03:55:47,713 --> 03:55:49,815 SIMILARLY FOR THE LIVING 5910 03:55:49,815 --> 03:55:50,116 SENTINEL. 5911 03:55:50,116 --> 03:55:51,017 ALL RIGHT. 5912 03:55:51,017 --> 03:55:52,918 AND I JUST WANT TO GIVE OUT A 5913 03:55:52,918 --> 03:55:53,819 QUICK SHOUT. 5914 03:55:53,819 --> 03:55:56,656 I KNOW THERE'S TALK ABOUT 5915 03:55:56,656 --> 03:55:59,325 VIRUSES EARLIER. 5916 03:55:59,325 --> 03:56:00,493 ANOTHER PROGRAM PROPOSERS DAY, 5917 03:56:00,493 --> 03:56:03,029 WE ARE TAG TEAMING IN DENVER, 5918 03:56:03,029 --> 03:56:07,433 THIS IS ANDY KILLIANSKI NEW 5919 03:56:07,433 --> 03:56:09,535 TECHNIQUES A.I. COMING UP WITH 5920 03:56:09,535 --> 03:56:11,637 BETTER VACCINES FOR PATHOGENS, 5921 03:56:11,637 --> 03:56:20,079 INSTEAD OF ONESIES, TWOSIES, 5922 03:56:20,079 --> 03:56:21,113 GOING AFTER MULTIPLE AT ONE 5923 03:56:21,113 --> 03:56:22,448 TIME. 5924 03:56:22,448 --> 03:56:24,750 THIS USED TO BE THE 5925 03:56:24,750 --> 03:56:25,685 UNIMAGINABLE FUTURE, WE ARE 5926 03:56:25,685 --> 03:56:28,754 HOPING FOR YOU TO BRING US YOUR 5927 03:56:28,754 --> 03:56:30,956 IDEAS, WHAT IS THE UNIMAGINABLE 5928 03:56:30,956 --> 03:56:31,791 FUTURE. 5929 03:56:31,791 --> 03:56:33,793 COME WORK WITH US AS A PROGRAM 5930 03:56:33,793 --> 03:56:35,027 MANAGER AND HELP US BUILD THAT 5931 03:56:35,027 --> 03:56:35,528 FUTURE. 5932 03:56:35,528 --> 03:56:36,195 THANK YOU. 5933 03:56:36,195 --> 03:56:46,405 [ APPLAUSE ] 5934 03:56:51,844 --> 03:56:53,412 >> THANK YOU, VERY ENGAGING 5935 03:56:53,412 --> 03:56:54,113 PRESENTATION. 5936 03:56:54,113 --> 03:56:55,981 I WAS WONDERING ABOUT THE TYPES 5937 03:56:55,981 --> 03:56:58,684 OF PROJECTS FUNDED BY ARPA-H, 5938 03:56:58,684 --> 03:57:00,786 DOES IT HAVE TO BE DIRECTLY 5939 03:57:00,786 --> 03:57:03,322 SOMETHING WITH A DIRECT 5940 03:57:03,322 --> 03:57:04,990 CLINICAL ENDPOINT OR TECHNOLOGY 5941 03:57:04,990 --> 03:57:07,960 THAT ENABLES THE BASIC SCIENCES 5942 03:57:07,960 --> 03:57:13,265 TO STUDY SOMETHING WITH PO -- 5943 03:57:13,265 --> 03:57:19,004 POTENTIAL CLINICAL USE, HUMAN 5944 03:57:19,004 --> 03:57:21,340 CELL TYPE ATLAS. 5945 03:57:21,340 --> 03:57:26,812 I'M NOT SAYING I DID THAT, BUT. 5946 03:57:26,812 --> 03:57:31,550 >> Paul Sheehan: YOU ZIGGED AT 5947 03:57:31,550 --> 03:57:32,918 THE END THERE. 5948 03:57:32,918 --> 03:57:35,988 I WAS ABOUT TO SAY NO. 5949 03:57:35,988 --> 03:57:37,890 BECAUSE WE COME AND GO, WE WILL 5950 03:57:37,890 --> 03:57:39,191 NEVER BE AN AGENCY TO BUILD A 5951 03:57:39,191 --> 03:57:39,992 DATABASE. 5952 03:57:39,992 --> 03:57:41,393 BECAUSE WHO IS GOING TO RUN 5953 03:57:41,393 --> 03:57:43,362 THAT IN FIVE YEARS WHEN WE ARE 5954 03:57:43,362 --> 03:57:45,131 GONE. 5955 03:57:45,131 --> 03:57:47,199 HOWEVER, IF THERE IS SOME NEW 5956 03:57:47,199 --> 03:57:48,801 TECHNOLOGY THAT CAN INFORM 5957 03:57:48,801 --> 03:57:50,870 THOSE DATABASES WE ARE HAPPY TO 5958 03:57:50,870 --> 03:57:52,138 BUILD THAT. 5959 03:57:52,138 --> 03:57:54,673 IN THIS CASE PEOPLE BUILDUP 5960 03:57:54,673 --> 03:57:55,841 PATHOGEN DATABASES, SO THESE 5961 03:57:55,841 --> 03:57:58,410 TOOLS WE ARE BUILDING WILL 5962 03:57:58,410 --> 03:57:59,645 VASTLY HELP POPULATE THOSE 5963 03:57:59,645 --> 03:58:01,147 DATABASES, RIGHT? 5964 03:58:01,147 --> 03:58:03,949 THAT SAID, IN GENERAL WE DON'T, 5965 03:58:03,949 --> 03:58:05,584 WE'RE NOT REALLY A DISCOVERY 5966 03:58:05,584 --> 03:58:08,888 AGENCY, WE ARE A CAPABILITY. 5967 03:58:08,888 --> 03:58:12,691 NIH AND OTHERS DO A FANTASTIC 5968 03:58:12,691 --> 03:58:14,093 JOB WITH DISCOVERY, NEW 5969 03:58:14,093 --> 03:58:14,560 INSIGHTS. 5970 03:58:14,560 --> 03:58:17,096 WE WANT TO TAKE THAT AND PUSH 5971 03:58:17,096 --> 03:58:18,764 TO A CAPABILITY. 5972 03:58:18,764 --> 03:58:21,333 THAT CAPABILITY THEN OPENS UP 5973 03:58:21,333 --> 03:58:22,768 NEW FRONTIERS, DOES THAT MAKE 5974 03:58:22,768 --> 03:58:22,968 SENSE? 5975 03:58:22,968 --> 03:58:25,337 >> I THINK SO, IT STILL SOUNDS 5976 03:58:25,337 --> 03:58:26,939 IT'S A LITTLE ON THE EDGE WITH 5977 03:58:26,939 --> 03:58:30,910 REGARDS TO WHAT I'M ASKING. 5978 03:58:30,910 --> 03:58:32,645 TECHNOLOGIES TO ENABLE 5979 03:58:32,645 --> 03:58:33,879 DISCOVERY ARE STILL -- 5980 03:58:33,879 --> 03:58:35,681 >> Paul Sheehan: IF AT THE END 5981 03:58:35,681 --> 03:58:38,484 OF THIS, YOU ARE LIKE OH THIS 5982 03:58:38,484 --> 03:58:41,320 IS A GREAT TOOL FOR LEARNING 5983 03:58:41,320 --> 03:58:41,587 MORE, NO. 5984 03:58:41,587 --> 03:58:43,222 THAT'S NOT REALLY US. 5985 03:58:43,222 --> 03:58:46,492 IF THIS TOOL IS OKAY, THIS TOOL 5986 03:58:46,492 --> 03:58:49,028 SOLVES THE PROBLEM OF SEPSIS 5987 03:58:49,028 --> 03:58:50,162 AND ALSO GENERATES INFORMATION 5988 03:58:50,162 --> 03:58:53,199 THAT WOULD BE GOING INTO A 5989 03:58:53,199 --> 03:58:53,566 DATABASE, SURE. 5990 03:58:53,566 --> 03:58:54,466 >> I SEE, I SEE. 5991 03:58:54,466 --> 03:58:55,067 THANK YOU. 5992 03:58:55,067 --> 03:58:57,169 I DID HAVE ONE MORE QUESTION 5993 03:58:57,169 --> 03:58:59,505 WHICH WAS, MY APOLOGIES, MAYBE 5994 03:58:59,505 --> 03:59:01,373 I MISSED THIS BECAUSE I WAS IN 5995 03:59:01,373 --> 03:59:03,008 THE RESTROOM AT THE BEGINNING 5996 03:59:03,008 --> 03:59:03,709 OF YOUR TALK. 5997 03:59:03,709 --> 03:59:06,879 DO YOU TAKE PROPOSALS FROM 5998 03:59:06,879 --> 03:59:07,279 ACADEMIC LABS? 5999 03:59:07,279 --> 03:59:10,115 >> Paul Sheehan: YEAH. 6000 03:59:10,115 --> 03:59:12,218 ABSOLUTELY. 6001 03:59:12,218 --> 03:59:16,455 ACADEMIC LABS. 6002 03:59:16,455 --> 03:59:17,189 BUSINESSES, INTERNATIONAL. 6003 03:59:17,189 --> 03:59:19,992 IF YOU ARE FROM NORTH KOREA, I 6004 03:59:19,992 --> 03:59:21,160 DON'T THINK SO, THAT WILL 6005 03:59:21,160 --> 03:59:23,062 PROBABLY BE A CHALLENGE. 6006 03:59:23,062 --> 03:59:24,597 BUT YEAH, FROM MOST PLACES AND 6007 03:59:24,597 --> 03:59:25,931 MOST PEOPLE. 6008 03:59:25,931 --> 03:59:26,665 >> GOT IT. 6009 03:59:26,665 --> 03:59:29,235 THANK YOU VERY MUCH. 6010 03:59:29,235 --> 03:59:30,970 >> SO ONE OF THE FOCUS AREAS 6011 03:59:30,970 --> 03:59:33,205 YOU SAID WILL BE PROACTIVE 6012 03:59:33,205 --> 03:59:34,506 HEALTH. 6013 03:59:34,506 --> 03:59:36,609 SO I'M CURIOUS HOW MUCH YOU SEE 6014 03:59:36,609 --> 03:59:38,477 PUBLIC HEALTH AS BEING A 6015 03:59:38,477 --> 03:59:40,346 COMPONENT OF THE ARPA-H 6016 03:59:40,346 --> 03:59:41,847 PROGRAMS? 6017 03:59:41,847 --> 03:59:43,716 >> Paul Sheehan: ALSO, I'M A 6018 03:59:43,716 --> 03:59:45,384 PROGRAM MANAGER, I DO MY THING. 6019 03:59:45,384 --> 03:59:49,488 THE HEAD OF PROACTIVE HEALTH 6020 03:59:49,488 --> 03:59:50,422 HASN'T BEEN ANNOUNCED, THEY 6021 03:59:50,422 --> 03:59:51,590 HAVE BEEN HIRED. 6022 03:59:51,590 --> 03:59:53,592 THAT IS, I MEAN, WE ARE TRYING 6023 03:59:53,592 --> 03:59:56,228 TO THINK OF THE HEALTHCARE 6024 03:59:56,228 --> 03:59:58,097 SYSTEM AT LARGE. 6025 03:59:58,097 --> 03:59:59,732 IN MANY WAYS. 6026 03:59:59,732 --> 04:00:01,100 SO TECHNOLOGIES AND 6027 04:00:01,100 --> 04:00:02,735 CAPABILITIES THAT WOULD IMPROVE 6028 04:00:02,735 --> 04:00:06,171 HOW THAT FUNCTION ARE ALWAYS 6029 04:00:06,171 --> 04:00:06,405 WELCOME. 6030 04:00:06,405 --> 04:00:08,507 AND ALSO, WE OFTEN THINK, 6031 04:00:08,507 --> 04:00:10,609 ESPECIALLY WITH DARPA LIKE THE 6032 04:00:10,609 --> 04:00:13,212 TECHNOLOGY, SO WOULD THE P.M.'S 6033 04:00:13,212 --> 04:00:16,916 THAT SHOWED UP LIKE DARSHUNK 6034 04:00:16,916 --> 04:00:18,651 AND BARPU, THEY ARE AT THE END, 6035 04:00:18,651 --> 04:00:20,920 TRYING TO THINK OF NEW MODELS 6036 04:00:20,920 --> 04:00:23,022 FOR PEOPLE TO GET REIMBURSED 6037 04:00:23,022 --> 04:00:24,723 FOR RURAL HEALTH. 6038 04:00:24,723 --> 04:00:27,526 OR HOW DO WE DO MATERNAL 6039 04:00:27,526 --> 04:00:29,595 HEALTH, HOW DO WE BRING 6040 04:00:29,595 --> 04:00:30,996 CAPABILITIES TO A RURAL SETTING 6041 04:00:30,996 --> 04:00:33,332 TO DO MATERNAL HEALTH WELL. 6042 04:00:33,332 --> 04:00:35,668 NOT JUST HERE IS SOME CRAZY 6043 04:00:35,668 --> 04:00:37,503 TECHNOLOGY WE AREN'T SURE THAT 6044 04:00:37,503 --> 04:00:37,770 WILL WORK. 6045 04:00:37,770 --> 04:00:40,539 WE'RE NOT SURE IF THIS POLICY 6046 04:00:40,539 --> 04:00:41,974 WILL WORK, WE ARE TRYING TO 6047 04:00:41,974 --> 04:00:43,809 FIGURE OUT FAR DOWN THE FIELD. 6048 04:00:43,809 --> 04:00:45,711 THEY MAY STILL HAVE WEIRD A.I. 6049 04:00:45,711 --> 04:00:49,481 OR OTHER COMPONENTS BUT IT'S 6050 04:00:49,481 --> 04:00:51,016 REALLY FARTHER DOWNSTREAM. 6051 04:00:51,016 --> 04:00:52,985 TO YOUR APPOINT, I HOPE 6052 04:00:52,985 --> 04:00:54,153 IMADDRESSING, IF YOU ARE 6053 04:00:54,153 --> 04:00:55,821 THINKING OF THE PUBLIC HEALTH 6054 04:00:55,821 --> 04:00:58,857 SYSTEM AND HOW TO DO BETTER AND 6055 04:00:58,857 --> 04:01:00,059 REARRANGE SOME THINGS THEY ARE 6056 04:01:00,059 --> 04:01:00,993 THINKING THROUGH THAT. 6057 04:01:00,993 --> 04:01:03,796 NONE OF THAT HAS BEEN ANNOUNCED. 6058 04:01:03,796 --> 04:01:08,600 >> GOOD TO KNOW, THANK YOU. 6059 04:01:08,600 --> 04:01:10,703 >> HELLO, THE CONTRAST WITH THE 6060 04:01:10,703 --> 04:01:11,904 DARPA PRESENTERS EARLIER WHEN 6061 04:01:11,904 --> 04:01:14,907 THEY WERE MAKING NUCLEIC ACIDS 6062 04:01:14,907 --> 04:01:16,775 OR PROTEINS FOR MILITARY 6063 04:01:16,775 --> 04:01:18,143 PURPOSE. 6064 04:01:18,143 --> 04:01:21,280 YOU HAVE THIS MAYBE BUYER,-END 6065 04:01:21,280 --> 04:01:22,715 USER READY TO GO WITH THE 6066 04:01:22,715 --> 04:01:24,249 MILITARY DEFENSE. 6067 04:01:24,249 --> 04:01:26,585 SO HOW EARLY, AND WHAT HAPPENS 6068 04:01:26,585 --> 04:01:29,388 WITH THE DOWNSTREAM USERS AND 6069 04:01:29,388 --> 04:01:31,457 INVESTMENTS, ARE THERE 6070 04:01:31,457 --> 04:01:33,325 MILESTONES IN THEIR PROJECTS TO 6071 04:01:33,325 --> 04:01:35,694 ENSURE YOU ARE GETTING BUY-IN 6072 04:01:35,694 --> 04:01:38,030 TO TAKE THIS TO THE NEXT STEP. 6073 04:01:38,030 --> 04:01:38,864 IT'S SO COMPLICATED IN THE 6074 04:01:38,864 --> 04:01:39,665 SPACE. 6075 04:01:39,665 --> 04:01:42,267 >> Paul Sheehan: IT'S SO 6076 04:01:42,267 --> 04:01:42,568 COMPLICATED. 6077 04:01:42,568 --> 04:01:43,969 HONESTLY THIS IS WHAT WE ARE 6078 04:01:43,969 --> 04:01:46,005 WORKING OUT RIGHT NOW. 6079 04:01:46,005 --> 04:01:48,507 YOU PUT YOUR FINGER RIGHT ON IT. 6080 04:01:48,507 --> 04:01:50,542 THE NICE THING ABOUT WORKING 6081 04:01:50,542 --> 04:01:52,678 FOR DARPA IS IF YOU ARE 6082 04:01:52,678 --> 04:01:54,980 BUILDING A HYPER SONIC MISSILE, 6083 04:01:54,980 --> 04:01:56,615 YOU KNOW WHO WILL BUILD IT AND 6084 04:01:56,615 --> 04:01:57,583 WHO WILL BUY IT. 6085 04:01:57,583 --> 04:01:59,385 NOT SO IN THE AMERICAN 6086 04:01:59,385 --> 04:02:00,753 HEALTHCARE SYSTEM. 6087 04:02:00,753 --> 04:02:03,155 YOU HAVE TO FIGURE ALL THAT OUT. 6088 04:02:03,155 --> 04:02:04,790 I CAN ANSWER FOR MYSELF, 6089 04:02:04,790 --> 04:02:06,158 THERE'S A NATURAL TENSION 6090 04:02:06,158 --> 04:02:08,794 THERE, IN THAT IF I'M TRYING TO 6091 04:02:08,794 --> 04:02:12,197 DO SOMETHING CRAZY ON THE 6092 04:02:12,197 --> 04:02:13,365 TECHNOLOGY SIDE I DON'T 6093 04:02:13,365 --> 04:02:15,534 NECESSARILY WANT TO BOTHER THE 6094 04:02:15,534 --> 04:02:17,569 PERFORMERS DO YOU HAVE A CMS 6095 04:02:17,569 --> 04:02:18,771 CODE IN THE FIRST YEAR? 6096 04:02:18,771 --> 04:02:21,140 HOW DO I INTRODUCE THAT? 6097 04:02:21,140 --> 04:02:22,741 AT THE SAME TIME WE CAN'T GET 6098 04:02:22,741 --> 04:02:24,810 TO YEAR FIVE AND SAY, HEY, DO 6099 04:02:24,810 --> 04:02:25,911 YOU THINK PATIENTS WILL WANT 6100 04:02:25,911 --> 04:02:26,879 THIS? 6101 04:02:26,879 --> 04:02:30,549 I TRY TO MAINTAIN A COGNITIVE 6102 04:02:30,549 --> 04:02:32,885 LOAD, AT THE RIGHT TIME, LET'S 6103 04:02:32,885 --> 04:02:34,987 START THINKING ABOUT IT. 6104 04:02:34,987 --> 04:02:36,388 AND SOME THINGS, IF YOU ARE 6105 04:02:36,388 --> 04:02:38,557 GOING TO ENGAGE WITH THE FDA, 6106 04:02:38,557 --> 04:02:40,392 RIGHT, YOU HAVE TO THINK ABOUT 6107 04:02:40,392 --> 04:02:42,061 IN YEAR ONE, THAT'S NOT A YEAR 6108 04:02:42,061 --> 04:02:42,728 TWO OR THREE. 6109 04:02:42,728 --> 04:02:45,330 SO PART OF MY JOB IS, YOU KNOW, 6110 04:02:45,330 --> 04:02:46,732 BRINGING UP THOSE ISSUES, 6111 04:02:46,732 --> 04:02:47,900 MAKING SURE THEY ARE TALKED 6112 04:02:47,900 --> 04:02:51,270 THROUGH AT THE RIGHT TIME. 6113 04:02:51,270 --> 04:02:52,938 >> ONE QUICK QUESTION, MICHELLE 6114 04:02:52,938 --> 04:02:54,540 TOOK THE FIRST PART OF IT FOR 6115 04:02:54,540 --> 04:02:56,642 ME, SO IT SAVES US SOME TIME. 6116 04:02:56,642 --> 04:02:58,210 IT HAD TO DO WITH THE DIAGRAM 6117 04:02:58,210 --> 04:03:01,313 OR THE FIGURE YOU SHOWED. 6118 04:03:01,313 --> 04:03:03,916 IT HAD THREE OF THE PERFORMERS. 6119 04:03:03,916 --> 04:03:05,984 TWO OF THEM NOT SUCCEEDING OR 6120 04:03:05,984 --> 04:03:07,386 WASHING OUT AT DIFFERENT POINTS 6121 04:03:07,386 --> 04:03:09,321 AND ONE MAKING IT TO THE FINISH 6122 04:03:09,321 --> 04:03:10,189 LINE. 6123 04:03:10,189 --> 04:03:12,558 DOES A MECHANISM EXIST FOR A 6124 04:03:12,558 --> 04:03:13,959 PERFORMER WHO DOES WASH OUT, 6125 04:03:13,959 --> 04:03:15,360 DOESN'T MAKE IT TO THE FINISH 6126 04:03:15,360 --> 04:03:17,496 LINE FOR WHATEVER REASON, DOES 6127 04:03:17,496 --> 04:03:19,832 A MECHANISM EXIST FOR YOU TO 6128 04:03:19,832 --> 04:03:22,134 FILTER THAT, SAY TO ONE OF THE 6129 04:03:22,134 --> 04:03:24,503 IC'S HERE AT NIH, THEY AREN'T 6130 04:03:24,503 --> 04:03:26,138 GOING TO MEET YOUR TIMELINES 6131 04:03:26,138 --> 04:03:28,707 BUT SAY UNDER AN EXTENDED 6132 04:03:28,707 --> 04:03:30,075 TIMELINE, FURTHER FUNDING, MORE 6133 04:03:30,075 --> 04:03:30,375 FLEXIBILITY? 6134 04:03:30,375 --> 04:03:31,710 >> Paul Sheehan: I HAVE 6135 04:03:31,710 --> 04:03:33,445 CERTAINLY SENT PEOPLE OVER. 6136 04:03:33,445 --> 04:03:34,880 ESPECIALLY IF THERE'S LIKE A 6137 04:03:34,880 --> 04:03:35,481 SUBSET. 6138 04:03:35,481 --> 04:03:40,552 HEY YOU REALLY SHOULD GO TALK 6139 04:03:40,552 --> 04:03:41,753 TO NIBIB, THEY WILL LIKE THIS 6140 04:03:41,753 --> 04:03:43,088 PART OF IT. 6141 04:03:43,088 --> 04:03:44,990 THERE HAVE ALSO BEEN ONES WHERE 6142 04:03:44,990 --> 04:03:46,158 THIS DOESN'T WORK, BUT THIS 6143 04:03:46,158 --> 04:03:48,026 PART OF YOUR EFFORT, WE ARE 6144 04:03:48,026 --> 04:03:49,995 GOING TO FORM A COMPANY. 6145 04:03:49,995 --> 04:03:52,197 WE ACTUALLY WILL PAY FOR AN 6146 04:03:52,197 --> 04:03:55,234 ENTREPRENEUR TO PAY FOR THAT 6147 04:03:55,234 --> 04:03:57,536 $250K, WE WILL PAY FOR THAT 6148 04:03:57,536 --> 04:03:58,937 ENTREPRENEUR TO PICK UP THAT 6149 04:03:58,937 --> 04:03:59,571 TECHNOLOGY AND DOING THE SAME 6150 04:03:59,571 --> 04:04:00,772 HERE. 6151 04:04:00,772 --> 04:04:02,241 EVEN THOUGH WE CUT PEOPLE, WE 6152 04:04:02,241 --> 04:04:05,477 TAKE CARE OF THE STUDENTS. 6153 04:04:05,477 --> 04:04:06,979 WE DON'T WANT ANYBODY TO GET 6154 04:04:06,979 --> 04:04:07,980 BURNED. 6155 04:04:07,980 --> 04:04:10,816 IF WE CUT THEM, THE STUDENTS 6156 04:04:10,816 --> 04:04:12,918 ARE STILL TAKEN CARE OF, WE 6157 04:04:12,918 --> 04:04:14,253 NEGOTIATE HOW LONG. 6158 04:04:14,253 --> 04:04:15,654 I HAVE CERTAINLY CUT PEOPLE, 6159 04:04:15,654 --> 04:04:17,890 BUT I DON'T THINK ANYONE HAS 6160 04:04:17,890 --> 04:04:20,392 EVER BEEN SURPRISED. 6161 04:04:20,392 --> 04:04:22,794 I THOUGHT IT WAS A GOOD IDEA, 6162 04:04:22,794 --> 04:04:25,364 YOU THOUGHT IT WAS A GOOD IDEA, 6163 04:04:25,364 --> 04:04:27,199 BUT IT'S NOT WORKING. 6164 04:04:27,199 --> 04:04:29,768 WE WILL END IT, OFFRAMP. 6165 04:04:29,768 --> 04:04:31,837 BUT IF THEY WORKED HARD, THEY 6166 04:04:31,837 --> 04:04:34,173 CAN COME TO ME THE NEXT DAY AND 6167 04:04:34,173 --> 04:04:35,073 CONSIDER THEIR IDEAS. 6168 04:04:35,073 --> 04:04:37,442 I THOUGHT IT WAS A GOOD IDEA 6169 04:04:37,442 --> 04:04:39,044 TOO, IT'S JUST NOT WORKING. 6170 04:04:39,044 --> 04:04:40,712 >> THAT WAS THE INTERESTING 6171 04:04:40,712 --> 04:04:44,883 PART FOR RISK MITIGATION, YOU 6172 04:04:44,883 --> 04:04:46,251 AREN'T SACRIFICING THEIR 6173 04:04:46,251 --> 04:04:47,419 FUTURES FOR WHATEVER IS NEEDED 6174 04:04:47,419 --> 04:04:48,353 IN THE FUTURE. 6175 04:04:48,353 --> 04:04:50,022 >> Paul Sheehan: WE TRY TO GET 6176 04:04:50,022 --> 04:04:53,292 TO AT LEAST THE NEXT PAPER, THE 6177 04:04:53,292 --> 04:04:54,026 NEXT SEMESTER, WHATEVER MAKES 6178 04:04:54,026 --> 04:04:55,961 SENSE. 6179 04:04:55,961 --> 04:04:57,329 HAVE I ANSWERED ALL QUESTIONS? 6180 04:04:57,329 --> 04:04:57,829 ALL RIGHT. 6181 04:04:57,829 --> 04:04:59,198 THANK YOU. 6182 04:04:59,198 --> 04:05:09,408 [ APPLAUSE ] 6183 04:05:13,346 --> 04:05:16,849 LET'S GET IT GOING. 6184 04:05:16,849 --> 04:05:18,184 OUR LAST SESSION HERE, IT 6185 04:05:18,184 --> 04:05:20,653 STARTS OFF WITH A WONDERFUL 6186 04:05:20,653 --> 04:05:30,696 TALK ABOUT DR. MANU PLATT. 6187 04:05:30,696 --> 04:05:32,932 CURRENTLY DIRECTOR FOR THE BETA 6188 04:05:32,932 --> 04:05:33,166 CENTER. 6189 04:05:33,166 --> 04:05:40,006 HE COMES TO US BY WAY OF 6190 04:05:40,006 --> 04:05:45,044 BACHELOR'S IN BIOLOGY FROM MORE 6191 04:05:45,044 --> 04:05:54,120 HOUSE AND POST DOC, HE IS A 6192 04:05:54,120 --> 04:05:56,889 REALLY COOL GUY AND NATIONALLY 6193 04:05:56,889 --> 04:06:00,393 RECOGNIZED LETTER IN DEIA AND 6194 04:06:00,393 --> 04:06:01,928 IMPLEMENTING IT IN STEM. 6195 04:06:01,928 --> 04:06:04,397 I WILL STOP AND LET MANU TALK 6196 04:06:04,397 --> 04:06:09,368 ABOUT THE BETA CENTER. 6197 04:06:09,368 --> 04:06:10,536 >> Manu Platt: THANKS FOR 6198 04:06:10,536 --> 04:06:14,073 HAVING ME AT THE END OF YOUR 6199 04:06:14,073 --> 04:06:15,508 SYNTHETIC BIOLOGY MEETING. 6200 04:06:15,508 --> 04:06:25,551 I WAS UP IN 2023 THEN HERE. 6201 04:06:25,551 --> 04:06:27,853 WHEN WE TALK ABOUT NIH WE THINK 6202 04:06:27,853 --> 04:06:30,756 ABOUT THE MONEY WE GIGANTE -- 6203 04:06:30,756 --> 04:06:34,560 GIVE TO THE OUTSIDE WORLD BUT 6204 04:06:34,560 --> 04:06:36,162 THERE ARE MANY -- I'M HERE TO 6205 04:06:36,162 --> 04:06:38,564 TALK ABOUT THE BETA CENTER, 6206 04:06:38,564 --> 04:06:48,174 CENTER FOR BIO ENGINEERING 6207 04:06:48,174 --> 04:06:53,479 TECHNICAL ASSOCIATION. 6208 04:06:53,479 --> 04:07:01,687 -- TECHNOLOGY ACCELERATOR. 6209 04:07:01,687 --> 04:07:02,855 THERE ARE GREAT OPPORTUNITIES 6210 04:07:02,855 --> 04:07:06,592 HERE WITH THE INTRAMURAL 6211 04:07:06,592 --> 04:07:08,961 RESEARCH PROGRAM AND ONE OF MY 6212 04:07:08,961 --> 04:07:10,129 COLLEAGUES HAVE JOINED US IN 6213 04:07:10,129 --> 04:07:13,633 THE AUDIENCE WE WILL USE HIM 6214 04:07:13,633 --> 04:07:16,736 FOR RADIO LABELING. 6215 04:07:16,736 --> 04:07:25,011 THE I IN NIH IS PLURAL, THE 6216 04:07:25,011 --> 04:07:28,481 NATIONAL INSTITUTES OF HEALTH. 6217 04:07:28,481 --> 04:07:32,418 MOST OF THOSE CENTERS DO HAVE 6218 04:07:32,418 --> 04:07:34,287 INTRAMURAL RESEARCHERS HERE ON 6219 04:07:34,287 --> 04:07:43,596 THE BETH BETHESDA CAMPUS. 6220 04:07:43,596 --> 04:07:47,066 WE TRAIN POST DOCS, POST 6221 04:07:47,066 --> 04:07:48,334 BACCALAUREATE AND POST GRAD 6222 04:07:48,334 --> 04:07:49,402 STUDENTS AS WELL. 6223 04:07:49,402 --> 04:07:51,971 I AM IN NIBIB, A LITTLE MORE 6224 04:07:51,971 --> 04:07:52,805 THAN 20 YEARS. 6225 04:07:52,805 --> 04:07:55,741 WE ARE THE NATIONAL INSTITUTE 6226 04:07:55,741 --> 04:07:56,976 OF BIOMEDICAL ENGINEERING AND 6227 04:07:56,976 --> 04:08:03,983 BIO ENGINEERING. 6228 04:08:03,983 --> 04:08:04,950 UNDER BRUCE TROMBERG. 6229 04:08:04,950 --> 04:08:07,787 BEFORE I GOT HERE, HE SAID WE 6230 04:08:07,787 --> 04:08:09,622 SHOULD BRING TOGETHER ON CAMPUS 6231 04:08:09,622 --> 04:08:12,291 TO CREATE A COMMUNITY OF 6232 04:08:12,291 --> 04:08:14,026 BIOMEDICAL ENGINEERS. 6233 04:08:14,026 --> 04:08:15,227 FIRST THERE'S GREAT WORK WE CAN 6234 04:08:15,227 --> 04:08:16,629 DO TO CROSS COLLABORATE AND 6235 04:08:16,629 --> 04:08:18,230 CONNECT WITH EACH OTHER. 6236 04:08:18,230 --> 04:08:20,566 BUT ALSO THE NIH HAS A 6237 04:08:20,566 --> 04:08:21,534 WONDERFUL CLINICAL CENTER ON 6238 04:08:21,534 --> 04:08:23,369 THE CUTTING EDGE OF MEDICAL 6239 04:08:23,369 --> 04:08:24,804 TECHNOLOGY AND MEDICAL BREAK 6240 04:08:24,804 --> 04:08:26,939 THROUGHS AND ALSO DEVELOPING 6241 04:08:26,939 --> 04:08:34,246 EQUIPMENT, ASSAYS ET CETERA BUT 6242 04:08:34,246 --> 04:08:38,651 IN THE INTRAMURAL WE ARE NOT 6243 04:08:38,651 --> 04:08:39,585 LIKE YOUR UNIVERSITIES. 6244 04:08:39,585 --> 04:08:42,722 I'M SURE YOU DON'T HAVE SILOED. 6245 04:08:42,722 --> 04:08:45,858 WE ARE TRYING TO BUILD CROSS 6246 04:08:45,858 --> 04:08:47,493 CONNECTIONS AMONG THE DIFFERENT 6247 04:08:47,493 --> 04:08:49,128 INSTITUTES ON CAMPUS. 6248 04:08:49,128 --> 04:08:52,131 TO BUILD THIS MODEL FOR 6249 04:08:52,131 --> 04:08:53,332 DISCIPLINE ENGINEERING RESEARCH 6250 04:08:53,332 --> 04:08:54,700 AND CLINICAL TRANSLATION. 6251 04:08:54,700 --> 04:08:57,303 THERE'S A NUMBER OF DIFFERENT 6252 04:08:57,303 --> 04:08:59,171 TOPICS THAT ARE HAPPENING ON 6253 04:08:59,171 --> 04:09:00,272 CAMPUS THAT WE LIKE TO BRING 6254 04:09:00,272 --> 04:09:01,474 TOGETHER. 6255 04:09:01,474 --> 04:09:06,846 PLUS SOME NEW ENGINEERING 6256 04:09:06,846 --> 04:09:09,048 TOPICS BY BRINGING NEW HIRES 6257 04:09:09,048 --> 04:09:11,984 AND BRINGING FROM THE OUTSIDE. 6258 04:09:11,984 --> 04:09:14,720 CENTRAL TO THE BETA COMMISSION, 6259 04:09:14,720 --> 04:09:16,422 IS EXPANDING DIVERSITY, EQUITY 6260 04:09:16,422 --> 04:09:20,593 AND INCLUSION IN THE NIH'S 6261 04:09:20,593 --> 04:09:21,026 INTRAMURAL PROGRAM. 6262 04:09:21,026 --> 04:09:22,695 WE ARE TRYING TO BUILD A 6263 04:09:22,695 --> 04:09:25,531 COMMUNITY OF ENGINEERS AND 6264 04:09:25,531 --> 04:09:26,699 BIOMEDICAL ENGINEERS ON CAMPUS. 6265 04:09:26,699 --> 04:09:29,869 SO FAR WE HAVE GOTTEN 80 6266 04:09:29,869 --> 04:09:30,202 INTERESTED. 6267 04:09:30,202 --> 04:09:32,772 WE ARE CUTTING ACROSS 16 6268 04:09:32,772 --> 04:09:34,039 DIFFERENT INSTITUTES SO FAR. 6269 04:09:34,039 --> 04:09:34,707 WE ARE GETTING EVERYBODY 6270 04:09:34,707 --> 04:09:35,107 TOGETHER. 6271 04:09:35,107 --> 04:09:38,377 SO WE HAVE BEEN HAVING A SERIES 6272 04:09:38,377 --> 04:09:39,478 OF MEET AND GREETS AND OTHER 6273 04:09:39,478 --> 04:09:40,479 THINGS. 6274 04:09:40,479 --> 04:09:42,782 WHEN WE ASK WHAT ARE THE CORE 6275 04:09:42,782 --> 04:09:44,183 CAPABILITIES THEY PROVIDE IN 6276 04:09:44,183 --> 04:09:46,385 THEIR LAB THEY WOULD BE WILLING 6277 04:09:46,385 --> 04:09:47,853 TO SHARE OR WORK WITH OTHER 6278 04:09:47,853 --> 04:09:49,188 INVESTIGATORS I WAS SURPRISED 6279 04:09:49,188 --> 04:09:50,923 BY THE AMOUNT OF DIFFERENT 6280 04:09:50,923 --> 04:09:52,091 TOOLS THEY WERE WILLING TO 6281 04:09:52,091 --> 04:09:53,526 SHARE AND ALREADY BEEN 6282 04:09:53,526 --> 04:09:54,894 GENERATING AND USING. 6283 04:09:54,894 --> 04:09:56,529 BEYOND THAT I LEARNED ABOUT THE 6284 04:09:56,529 --> 04:09:58,164 NUMBER OF INVESTIGATORS WORKING 6285 04:09:58,164 --> 04:10:00,466 IN SIMILAR SPACES WHO HAVE NOT 6286 04:10:00,466 --> 04:10:02,802 YET MET EACH OTHER. 6287 04:10:02,802 --> 04:10:13,312 AGAIN, IT'S ALL ABOUT MEETING 6288 04:10:14,780 --> 04:10:15,414 INVESTIGATORS TO COLLABORATE. 6289 04:10:15,414 --> 04:10:18,384 THESE ARE THE MORE TRADITIONAL 6290 04:10:18,384 --> 04:10:25,424 TOOLS, PEOPLE ARE DEVELOPING 3* 6291 04:10:25,424 --> 04:10:27,793 D ORGANOTYPEIC TUMOR. 6292 04:10:27,793 --> 04:10:29,161 ENERGY METABOLISM. 6293 04:10:29,161 --> 04:10:31,497 AIR THEY BREATHE, CO THEY CAN 6294 04:10:31,497 --> 04:10:34,500 DO ALL THAT OVER A 24-48 HOUR 6295 04:10:34,500 --> 04:10:35,701 PERIOD AND EVEN LONGER IF NEED 6296 04:10:35,701 --> 04:10:37,069 BE. 6297 04:10:37,069 --> 04:10:40,639 WHO DOESN'T WANT ACCESS IF YOU 6298 04:10:40,639 --> 04:10:43,776 DO METABOLIC STUDIES. 6299 04:10:43,776 --> 04:10:44,743 THERE'S STRONG NEURO 6300 04:10:44,743 --> 04:10:47,313 CAPABILITIES ON THE OUTSIDE WE 6301 04:10:47,313 --> 04:10:48,514 HAVE THOSE IN HERE. 6302 04:10:48,514 --> 04:10:50,382 THERE ARE PEOPLE DEVELOPING AND 6303 04:10:50,382 --> 04:10:52,017 IMPROVING THEIR MACHINE 6304 04:10:52,017 --> 04:10:53,486 LEARNING, COMPUTER VISION AND 6305 04:10:53,486 --> 04:10:54,353 DEEP LEARNING. 6306 04:10:54,353 --> 04:10:55,754 BUT THERE'S A STRONG POOL TO 6307 04:10:55,754 --> 04:10:57,156 BRING MORE OF THESE INDIVIDUALS 6308 04:10:57,156 --> 04:10:57,890 TO CAMPUS. 6309 04:10:57,890 --> 04:10:59,758 TO THE TRAINEES LISTENING OR IN 6310 04:10:59,758 --> 04:11:00,926 THE AUDIENCE IF YOU ARE 6311 04:11:00,926 --> 04:11:02,328 INTERESTED IN COMING TO AN 6312 04:11:02,328 --> 04:11:05,130 EXCITING PLACE TO DO YOUR POST 6313 04:11:05,130 --> 04:11:07,466 DOC, THE NIH IS A GREAT PLACE 6314 04:11:07,466 --> 04:11:09,301 AND COMPLETELY COVER YOUR 6315 04:11:09,301 --> 04:11:11,203 HEALTHCARE WHILE A FELLOW AND 6316 04:11:11,203 --> 04:11:12,137 TRAINEE. 6317 04:11:12,137 --> 04:11:13,772 SELF-PITCH. 6318 04:11:13,772 --> 04:11:15,875 WE ARE IN THE IMAGING INSTITUTE. 6319 04:11:15,875 --> 04:11:18,210 THERE ARE A NUMBER OF DIFFERENT 6320 04:11:18,210 --> 04:11:22,748 IMAGING MODALITIS. 6321 04:11:22,748 --> 04:11:26,585 MR PET, PT CT SCANS. 6322 04:11:26,585 --> 04:11:29,488 OTHER WAYS TO TRACK THEM 6323 04:11:29,488 --> 04:11:30,456 THROUGH SMALL ANIMALS AND 6324 04:11:30,456 --> 04:11:31,857 PEOPLE ARE GETTING HUMAN 6325 04:11:31,857 --> 04:11:32,591 PROTOCOLS AS WELL. 6326 04:11:32,591 --> 04:11:34,660 I THINK THAT'S THE BIGGEST DRAW 6327 04:11:34,660 --> 04:11:36,295 AND MOST EXCITING THING IS THE 6328 04:11:36,295 --> 04:11:38,230 CLINICAL CENTER AT NIH. 6329 04:11:38,230 --> 04:11:39,598 IT'S LARGE, BUILDING 10, YOU 6330 04:11:39,598 --> 04:11:41,233 WILL BUMP INTO IT ON THE WAY 6331 04:11:41,233 --> 04:11:41,400 OUT. 6332 04:11:41,400 --> 04:11:42,668 THERE ARE LOTS OF CLINICAL 6333 04:11:42,668 --> 04:11:44,503 TRIALS AND WAYS TO TRANSLATE 6334 04:11:44,503 --> 04:11:50,476 YOUR WORK HERE ON CAMPUS. 6335 04:11:50,476 --> 04:11:53,612 WE ALSO NEED TO BE RECRUITING 6336 04:11:53,612 --> 04:11:54,647 AND TRAINING STUDENTS, WE WANT 6337 04:11:54,647 --> 04:11:57,583 YOUR STUDENTS. 6338 04:11:57,583 --> 04:11:59,885 THERE'S THESE WONDERFUL SUMMER 6339 04:11:59,885 --> 04:12:00,953 INTERN PROGRAMS IF YOU WOULD 6340 04:12:00,953 --> 04:12:02,955 LIKE TO SEND TO MEET A 6341 04:12:02,955 --> 04:12:03,889 PROFESSOR AND ESTABLISH 6342 04:12:03,889 --> 04:12:04,823 COLLABORATION WHEN THEY GO 6343 04:12:04,823 --> 04:12:07,026 BACK, WE HAVE OUR SUMMER 6344 04:12:07,026 --> 04:12:09,929 INTERNSHIP PROGRAM. 6345 04:12:09,929 --> 04:12:14,833 NIBIB SPECIFICALLY SPONSORS THE 6346 04:12:14,833 --> 04:12:18,037 BIOMEDICAL ENGINEERING SUMMER 6347 04:12:18,037 --> 04:12:19,838 INTERNSHIP UNDER THE BETA 6348 04:12:19,838 --> 04:12:21,907 CENTER. 6349 04:12:21,907 --> 04:12:23,309 FOR THOSE STUDENTS WHO 6350 04:12:23,309 --> 04:12:24,743 GRADUATED WHO WANT MORE 6351 04:12:24,743 --> 04:12:28,047 TRAINING BEFORE THEY DO AN 6352 04:12:28,047 --> 04:12:31,050 Ph.D., MD OR MD Ph.D.. 6353 04:12:31,050 --> 04:12:34,186 ONE OR TWO YEARS, HEALTHCARE IS 6354 04:12:34,186 --> 04:12:35,220 COVERED WHILE WORKING HERE ON 6355 04:12:35,220 --> 04:12:36,021 CAMPUS. 6356 04:12:36,021 --> 04:12:37,890 THESE ARE GREAT OPPORTUNITIES 6357 04:12:37,890 --> 04:12:41,393 NIH'S OFFICE OF INTRAMURAL 6358 04:12:41,393 --> 04:12:45,197 TRAINING HELP STUDENTS PREPARE 6359 04:12:45,197 --> 04:12:46,165 APPLICATION, PREPARE M-CAT, 6360 04:12:46,165 --> 04:12:48,467 PREPARE AS LIFE AS A STUDENT 6361 04:12:48,467 --> 04:12:51,270 THOSE ARE ALL FREE TO STUDENTS. 6362 04:12:51,270 --> 04:12:52,705 NSF IS A GOOD FRIEND OF OURS, 6363 04:12:52,705 --> 04:12:53,839 AS YOU CAN IMAGINE. 6364 04:12:53,839 --> 04:12:55,341 THEY HAVE A WONDERFUL INTERN 6365 04:12:55,341 --> 04:12:56,442 PROGRAM. 6366 04:12:56,442 --> 04:12:57,610 FOR THOSE INTERESTED 6367 04:12:57,610 --> 04:12:58,811 PARTICULARLY IN BIO ENGINEERING 6368 04:12:58,811 --> 04:13:02,047 WORK, IF YOU ARE A GRAD STUDENT 6369 04:13:02,047 --> 04:13:03,649 FINISHING, OR NOT EVEN 6370 04:13:03,649 --> 04:13:05,985 FINISHING, BUT THERE'S A PLACE 6371 04:13:05,985 --> 04:13:08,554 IN YOUR PROJECT YOU CAN SPEND 6372 04:13:08,554 --> 04:13:10,656 3-6 WEEKS WORKING IN A LAB ON 6373 04:13:10,656 --> 04:13:12,091 THE NIH CAMPUS, IT'S A GREAT 6374 04:13:12,091 --> 04:13:14,026 WAY TO UNDERSTAND WHAT THE 6375 04:13:14,026 --> 04:13:15,027 INTRAMURAL PROGRAM HERE. 6376 04:13:15,027 --> 04:13:15,961 WE HAVE INVESTIGATORS HERE 6377 04:13:15,961 --> 04:13:17,096 LOOKING FOR PEOPLE WITH THE 6378 04:13:17,096 --> 04:13:19,832 SKILL SETS THAT YOU HAVE, OKAY? 6379 04:13:19,832 --> 04:13:22,401 WE ARE ALSO LOOKING, I'M HIRING 6380 04:13:22,401 --> 04:13:24,036 POST DOC FELLOWS FOR OTHERS AND 6381 04:13:24,036 --> 04:13:26,138 LOOKING FOR WAYS FACULTY 6382 04:13:26,138 --> 04:13:27,973 INTERESTED IN DOING SABBATICALS 6383 04:13:27,973 --> 04:13:31,510 TO ALSO COME ALONG ON CAMPUS, 6384 04:13:31,510 --> 04:13:34,980 MAKE FRIENDS, ESTABLISH 6385 04:13:34,980 --> 04:13:35,347 COLLABORATIONS. 6386 04:13:35,347 --> 04:13:36,849 WE ARE GREAT TO WORK WITH YOU, 6387 04:13:36,849 --> 04:13:38,517 WE CAN COLLABORATE WITH YOU ON 6388 04:13:38,517 --> 04:13:40,919 YOUR GRANT BUT WE DON'T TAKE 6389 04:13:40,919 --> 04:13:43,288 MONEY FROM YOU FROM YOUR GRANT, 6390 04:13:43,288 --> 04:13:44,657 AREN'T WE GREAT PEOPLE? 6391 04:13:44,657 --> 04:13:47,259 I CARE A LOT ABOUT DEIA. 6392 04:13:47,259 --> 04:13:48,661 STARTED IN LATE FEBRUARY BUT WE 6393 04:13:48,661 --> 04:13:50,529 STILL PUT TOGETHER A SUMMER 6394 04:13:50,529 --> 04:13:53,532 RESEARCH PROGRAM, WE HAD SIX 6395 04:13:53,532 --> 04:13:57,503 STUDENTS FROM HBCU'S, DEAF 6396 04:13:57,503 --> 04:13:59,138 SERVING INSTITUTION AT 6397 04:13:59,138 --> 04:14:00,873 GALLAUDET. 6398 04:14:00,873 --> 04:14:03,642 WE ARE ABOUT EXPANDING 6399 04:14:03,642 --> 04:14:05,077 BIOMEDICAL ENGINEERING. 6400 04:14:05,077 --> 04:14:06,578 BRING OTHERS TO IT FROM ALL THE 6401 04:14:06,578 --> 04:14:08,647 OTHER DISCIPLINES THEY COULD BE 6402 04:14:08,647 --> 04:14:10,049 BIOMEDICAL ENGINEERS AS WELL. 6403 04:14:10,049 --> 04:14:14,153 AND THEY PLAYED WITH THE LONG 6404 04:14:14,153 --> 04:14:15,354 RUNNING BCIP PROGRAM. 6405 04:14:15,354 --> 04:14:19,358 THERE'S A PICTURE OF OUR 6406 04:14:19,358 --> 04:14:20,993 FEARLESS LEADER, BRUCE 6407 04:14:20,993 --> 04:14:23,762 TROMBERG, TALLER THAN ME, STILL 6408 04:14:23,762 --> 04:14:25,164 HUMBLING MYSELF OVER THAT EVERY 6409 04:14:25,164 --> 04:14:28,300 DAY WE HAVE A MEETING. 6410 04:14:28,300 --> 04:14:31,570 AND OUR WONDERFUL DIRECTOR, 6411 04:14:31,570 --> 04:14:36,175 NICHOLE MORE BEGAN. 6412 04:14:36,175 --> 04:14:37,509 -- MORGAN. 6413 04:14:37,509 --> 04:14:39,211 I'VE BEEN BUSY ALL OF OCTOBER 6414 04:14:39,211 --> 04:14:41,747 AS YOU CAN SEE, I'M IN TOWN FOR 6415 04:14:41,747 --> 04:14:42,981 A WEEK. 6416 04:14:42,981 --> 04:14:44,850 WE ARE RECRUITING FROM DIVERSE 6417 04:14:44,850 --> 04:14:47,419 POPULATIONS, THE LAST ONE IS 6418 04:14:47,419 --> 04:14:49,154 SBRCMS IN NOVEMBER. 6419 04:14:49,154 --> 04:14:50,789 I'M TELLING YOU ALL TO TELL 6420 04:14:50,789 --> 04:14:53,325 YOUR FRIENDS THAT WE ARE HERE. 6421 04:14:53,325 --> 04:14:55,094 BUT IN THE FUTURE, WE ALSO 6422 04:14:55,094 --> 04:14:58,497 AGAIN, TRYING TO GET THE IRP, 6423 04:14:58,497 --> 04:14:59,998 INTRAMURAL RESEARCH PROGRAM TO 6424 04:14:59,998 --> 04:15:02,067 BIO ENGINEERS IN THE COMMUNITY. 6425 04:15:02,067 --> 04:15:06,105 NEXT YEAR THE ANNUAL MEETING IS 6426 04:15:06,105 --> 04:15:07,272 HELD IN BALTIMORE, MARYLAND 6427 04:15:07,272 --> 04:15:08,440 RIGHT UP THE WAY. 6428 04:15:08,440 --> 04:15:09,408 BEFORE THAT MEETING WE WILL 6429 04:15:09,408 --> 04:15:11,510 HAVE ON THE TUESDAY BEFORE THE 6430 04:15:11,510 --> 04:15:12,244 CONFERENCE STARTS, PEOPLE 6431 04:15:12,244 --> 04:15:14,546 BROUGHT TO CAMPUS AND WE WILL 6432 04:15:14,546 --> 04:15:17,816 HAVE SESSIONS ON THE NIH CAMPUS 6433 04:15:17,816 --> 04:15:19,718 FOR PROFESSORS AND GRAD 6434 04:15:19,718 --> 04:15:24,623 STUDENTS AND POST DOCS, COME 6435 04:15:24,623 --> 04:15:26,992 TO CAMPUS, SEE WHAT WE ARE 6436 04:15:26,992 --> 04:15:27,926 DOING, ESTABLISH CONNECTIONS, 6437 04:15:27,926 --> 04:15:29,728 WE WILL HAVE TALKS AND 6438 04:15:29,728 --> 04:15:31,196 INTERACTIONS. 6439 04:15:31,196 --> 04:15:33,265 COME ONE DAY EARLY AND YOU CAN 6440 04:15:33,265 --> 04:15:34,800 COME ON CAMPUS. 6441 04:15:34,800 --> 04:15:37,536 WE WILL ALSO BRING OTHER AGENCY 6442 04:15:37,536 --> 04:15:39,371 PARTNERS, FDA, I KNOW, IS 6443 04:15:39,371 --> 04:15:40,773 INTERESTED AND OTHER PEOPLE. 6444 04:15:40,773 --> 04:15:45,911 GETTING THE WORD OUT NOW, IN A 6445 04:15:45,911 --> 04:15:46,111 YEAR. 6446 04:15:46,111 --> 04:15:46,812 SEVERAL INSTITUTES ARE LOOKING 6447 04:15:46,812 --> 04:15:47,746 TO BE INVOLVED. 6448 04:15:47,746 --> 04:15:49,148 PLEASE, THINK ABOUT THAT FOR 6449 04:15:49,148 --> 04:15:51,450 YOU AND ALSO FOR YOUR TRAINEES. 6450 04:15:51,450 --> 04:15:53,318 BUT WHAT ELSE WE ARE OFFERING 6451 04:15:53,318 --> 04:15:55,220 TO OUR INTRAMURAL RESEARCH 6452 04:15:55,220 --> 04:15:57,990 PROGRAM, WE WANT TO LOWER THE 6453 04:15:57,990 --> 04:16:00,425 BARRIER TO ENTRY INTO USING 6454 04:16:00,425 --> 04:16:01,326 ENGINEERING PRINCIPLES AND 6455 04:16:01,326 --> 04:16:02,661 PRACTICES IN THEIR RESEARCH. 6456 04:16:02,661 --> 04:16:04,596 THEY CAN READ A PAPER AND SEE 6457 04:16:04,596 --> 04:16:06,932 SOMEONE MADE THIS NANO PARTICLE 6458 04:16:06,932 --> 04:16:08,367 WITH THE DELIVERY THING, I 6459 04:16:08,367 --> 04:16:09,668 DON'T KNOW, I DON'T KNOW HOW TO 6460 04:16:09,668 --> 04:16:13,338 MAKE THAT. 6461 04:16:13,338 --> 04:16:17,042 WE WILL OFFER CONCIERGE SERVICE 6462 04:16:17,042 --> 04:16:18,677 FOR BETA SERVICE AFFILIATES TO 6463 04:16:18,677 --> 04:16:20,312 MEET WITH THE TEAM WHERE THE 6464 04:16:20,312 --> 04:16:21,246 INVESTIGATOR WILL SAY WHAT 6465 04:16:21,246 --> 04:16:23,115 THEIR NEEDS MIGHT BE AND WE CAN 6466 04:16:23,115 --> 04:16:25,017 HELP THEM NARROW THE PROBLEM TO 6467 04:16:25,017 --> 04:16:26,652 A WORKABLE PLACE AND HELP THEM 6468 04:16:26,652 --> 04:16:28,020 GET STARTED GOING DOWN THOSE 6469 04:16:28,020 --> 04:16:29,922 DIRECTIONS. 6470 04:16:29,922 --> 04:16:38,297 NIBIB ALSO HAS THREE NIH-SHARED 6471 04:16:38,297 --> 04:16:41,600 RESOURCES. 6472 04:16:41,600 --> 04:16:42,734 IDEAS GROUP. 6473 04:16:42,734 --> 04:16:46,038 THEY CAN MAKE BOXES THAT WATCH 6474 04:16:46,038 --> 04:16:47,606 YOUR MOUTH AND CONTROL -- 6475 04:16:47,606 --> 04:16:49,241 FANTASTIC. 6476 04:16:49,241 --> 04:16:58,483 ADVANCED IMAGING AND MICROSCOPY 6477 04:16:58,483 --> 04:16:59,618 RESOURCE. 6478 04:16:59,618 --> 04:17:01,253 THEY ARE AMAZING, AS WELL AS 6479 04:17:01,253 --> 04:17:02,654 WITH THE PROCESSING OF YOUR 6480 04:17:02,654 --> 04:17:05,958 SAMPLES AND THE A.I. AND DATA 6481 04:17:05,958 --> 04:17:07,192 GENERATION. 6482 04:17:07,192 --> 04:17:09,761 MY DEPUTY DIRECTOR NICHOLE 6483 04:17:09,761 --> 04:17:13,432 MORGAN RUNS THE BIOMEDICAL AND 6484 04:17:13,432 --> 04:17:15,367 ENGINEERING PHYSICAL SCIENCE. 6485 04:17:15,367 --> 04:17:16,235 SOME SOFTER MATERIALS AND HELP 6486 04:17:16,235 --> 04:17:24,409 WITH ALL OF THOSE THINGS AND 6487 04:17:24,409 --> 04:17:26,778 AGAIN MY GOOD BUDDY DALE IS 6488 04:17:26,778 --> 04:17:30,549 RADIO CHEMIST, YOU CAN RUN 6489 04:17:30,549 --> 04:17:32,417 MODELS LIVE IN STUDIES. 6490 04:17:32,417 --> 04:17:37,155 WE HIRED COMPUTATIONAL 6491 04:17:37,155 --> 04:17:37,956 BIOLOGIST. 6492 04:17:37,956 --> 04:17:39,758 WE ARE TRYING TO PROVIDE TOOLS 6493 04:17:39,758 --> 04:17:42,094 AND SKILL SETS TO LOWER THOSE 6494 04:17:42,094 --> 04:17:44,863 BARS TO MAKE EVERYBODY HERE 6495 04:17:44,863 --> 04:17:46,899 LOVE BIOMEDICAL ENGINEERING AND 6496 04:17:46,899 --> 04:17:48,066 BRING YOUR FRIENDS AS WELL. 6497 04:17:48,066 --> 04:17:50,969 M COULDING IN -- COMING IN 6498 04:17:50,969 --> 04:17:53,005 THE FUTURE WE WILL HAVE A MAKER 6499 04:17:53,005 --> 04:17:54,206 SPACE ON CAMPUS, THE FIRST EVER. 6500 04:17:54,206 --> 04:17:56,541 WE HAVE A FEW SPACES THAT 6501 04:17:56,541 --> 04:17:59,344 ALREADY HAVE THE MACHINERY AND 6502 04:17:59,344 --> 04:18:00,279 OTHER PLACES APPLY. 6503 04:18:00,279 --> 04:18:01,947 THE DIFFERENCE WITH THE MAKER 6504 04:18:01,947 --> 04:18:03,782 SPACE, WE WOULD TRAIN THE 6505 04:18:03,782 --> 04:18:04,983 RESEARCHERS IN YOUR GROUP ON 6506 04:18:04,983 --> 04:18:06,385 HOW TO USE A PIECE OF EQUIPMENT 6507 04:18:06,385 --> 04:18:07,619 AND THEY WOULD COME IN AND 6508 04:18:07,619 --> 04:18:09,221 CONTINUE TO MAKE THE 6509 04:18:09,221 --> 04:18:11,223 MODIFICATIONS AND DEVELOP THE 6510 04:18:11,223 --> 04:18:11,523 TECHNOLOGY. 6511 04:18:11,523 --> 04:18:14,459 SO REALLY EXCITED ABOUT THIS. 6512 04:18:14,459 --> 04:18:15,894 THIS IS ALL THE THINGS 6513 04:18:15,894 --> 04:18:18,163 HAPPENING IN THE BETA CENTER. 6514 04:18:18,163 --> 04:18:20,999 A MENU TO CLOSE OUT WITH WHAT I 6515 04:18:20,999 --> 04:18:21,333 TALKED ABOUT. 6516 04:18:21,333 --> 04:18:23,101 FIRST AND FOREMOST BUILDING 6517 04:18:23,101 --> 04:18:25,203 THIS IMAGING AND ENGINEERING 6518 04:18:25,203 --> 04:18:26,138 COMMUNITY ON CAMPUS. 6519 04:18:26,138 --> 04:18:29,174 IF ENGE ENGINEERS ARE OUT 6520 04:18:29,174 --> 04:18:30,409 THERE AND WANT TO COME, YOU 6521 04:18:30,409 --> 04:18:32,678 WILL NOT BE ALONE. 6522 04:18:32,678 --> 04:18:35,514 RELYING ON OUR EXTRAMURAL 6523 04:18:35,514 --> 04:18:40,686 PARTNERS, SEND YOUR STUDENTS, 6524 04:18:40,686 --> 04:18:42,321 POST DOCS, PROFESSORS. 6525 04:18:42,321 --> 04:18:43,288 BUILDING COLLABORATION, SOON WE 6526 04:18:43,288 --> 04:18:45,157 WILL HAVE OUR MAKER SPACE. 6527 04:18:45,157 --> 04:18:46,325 YOU CAN DO THAT HERE. 6528 04:18:46,325 --> 04:18:47,960 THANK YOU VERY MUCH FOR THIS 6529 04:18:47,960 --> 04:18:50,062 TIME TO SHARE. 6530 04:18:50,062 --> 04:18:51,463 IF THERE'S TIME FOR QUESTIONS I 6531 04:18:51,463 --> 04:18:53,565 WILL TAKE ONE OR TWO OTHERWISE 6532 04:18:53,565 --> 04:18:54,800 YOU CAN CATCH ME WHEN THIS IS 6533 04:18:54,800 --> 04:18:55,200 ALL OVER. 6534 04:18:55,200 --> 04:18:56,335 THANK YOU. 6535 04:18:56,335 --> 04:19:06,545 [ APPLAUSE ] 6536 04:19:18,724 --> 04:19:20,525 >> ONE QUICK ADMINISTRATIVE 6537 04:19:20,525 --> 04:19:23,762 NOTE, I WAS TOLD ANY POSTERS 6538 04:19:23,762 --> 04:19:25,597 THAT ARE STILL UP, THEY SHOULD 6539 04:19:25,597 --> 04:19:26,999 PROBABLY BE TAKEN DOWN, 6540 04:19:26,999 --> 04:19:28,300 PROBABLY AFTER THE NEXT COUPLE 6541 04:19:28,300 --> 04:19:29,334 OF TALKS. 6542 04:19:29,334 --> 04:19:30,936 SO PLEASE DON'T LEAVE THEM 6543 04:19:30,936 --> 04:19:32,537 HERE, TAKE THEM HOME WITH YOU. 6544 04:19:32,537 --> 04:19:37,242 WHAT WE HAVE ON DOCKET HERE IS 6545 04:19:37,242 --> 04:19:38,443 TWO FINAL LIGHTNING TALKS. 6546 04:19:38,443 --> 04:19:42,614 THE FIRST IS BY DR. SARA 6547 04:19:42,614 --> 04:19:44,516 MOLINARI, ASSISTANT PROFESSOR 6548 04:19:44,516 --> 04:19:47,219 AT UNIVERSITY OF MARYLAND, 6549 04:19:47,219 --> 04:19:50,055 COLLEGE PARK. 6550 04:19:50,055 --> 04:19:50,655 WILL TALK ABOUT "DE NOVO 6551 04:19:50,655 --> 04:19:51,456 ENGINEERED LIVING MATERIALS 6552 04:19:51,456 --> 04:19:52,891 FROM BACTERIA" 6553 04:19:52,891 --> 04:19:53,658 SARA? 6554 04:19:53,658 --> 04:19:58,730 [ APPLAUSE ] 6555 04:19:58,730 --> 04:20:00,665 >> Sara Molinari: HI, EVERYONE. 6556 04:20:00,665 --> 04:20:02,167 THANK YOU FOR STICKING AROUND, 6557 04:20:02,167 --> 04:20:04,736 YOU ARE THE BRAVE FOR STAYING 6558 04:20:04,736 --> 04:20:06,171 FOR THE LAST TALKS. 6559 04:20:06,171 --> 04:20:08,807 I JUST STARTED IN MY LAB AT 6560 04:20:08,807 --> 04:20:10,308 UNIVERSITY OF MARYLAND IN JULY. 6561 04:20:10,308 --> 04:20:11,410 MY RESEARCH IS BRAND NEW. 6562 04:20:11,410 --> 04:20:12,778 MOST OF WHAT I WILL TALK ABOUT 6563 04:20:12,778 --> 04:20:14,913 IS PART OF POSTDOCTORAL WORK, I 6564 04:20:14,913 --> 04:20:17,282 WILL GIVE YOU INSIGHT WHAT I 6565 04:20:17,282 --> 04:20:17,983 WILL DO NEXT. 6566 04:20:17,983 --> 04:20:19,618 THIS IS PROBABLY A LITTLE 6567 04:20:19,618 --> 04:20:21,453 DIFFERENT OF THE TALK THAT YOU 6568 04:20:21,453 --> 04:20:23,121 HEARD UNTIL NOW, BECAUSE WE ARE 6569 04:20:23,121 --> 04:20:24,489 MOSTLY GOING TO TALK ABOUT 6570 04:20:24,489 --> 04:20:25,424 BACTERIA. 6571 04:20:25,424 --> 04:20:27,759 AND I HOPE THAT BY THE END OF 6572 04:20:27,759 --> 04:20:30,295 THIS PRESENTATION, YOU ARE AS 6573 04:20:30,295 --> 04:20:33,165 CONVINCED AS I AM BACTERIA IS 6574 04:20:33,165 --> 04:20:35,700 SUPER COOL THAT HAS LOTS OF 6575 04:20:35,700 --> 04:20:36,701 POTENTIAL FOR BIOMEDICAL 6576 04:20:36,701 --> 04:20:37,602 APPLICATION. 6577 04:20:37,602 --> 04:20:40,405 OF COURSE THIS AUDIENCE NEEDS 6578 04:20:40,405 --> 04:20:41,573 NO INTRODUCTION WHY BIO 6579 04:20:41,573 --> 04:20:44,142 MATERIAL ARE SO INCREDIBLY 6580 04:20:44,142 --> 04:20:45,777 USEFUL FOR BIO MEDICINE, THEY 6581 04:20:45,777 --> 04:20:46,912 COVER A VAST ARRAY OF 6582 04:20:46,912 --> 04:20:47,446 APPLICATION. 6583 04:20:47,446 --> 04:20:48,847 BECAUSE OF THIS NEW MATERIAL 6584 04:20:48,847 --> 04:20:51,716 THAT WE CAN ACTUALLY DELIVER A 6585 04:20:51,716 --> 04:20:55,253 LOT OF NEW AND NOVEL 6586 04:20:55,253 --> 04:20:57,122 THERAPEUTICS LIKE DRUG 6587 04:20:57,122 --> 04:20:58,824 DELIVERY, MEDICAL IMPLANTS. 6588 04:20:58,824 --> 04:21:00,392 WOUND HEALING, BUT ALSO NEW 6589 04:21:00,392 --> 04:21:02,027 SURFACES THAT PREVENT THE 6590 04:21:02,027 --> 04:21:04,863 FORMATION OF BIO FILM TISSUE, 6591 04:21:04,863 --> 04:21:08,333 SCAFFOLD THAT WILL ALLOW THE 6592 04:21:08,333 --> 04:21:09,167 FORMATION OF ORGANOIDS AND SO 6593 04:21:09,167 --> 04:21:11,103 FORTH. 6594 04:21:11,103 --> 04:21:13,038 DESPITE THE GREAT ADVANCES IN 6595 04:21:13,038 --> 04:21:16,007 THIS FIELD, IN THE LAST DECADE 6596 04:21:16,007 --> 04:21:16,908 REALLY EXPLODED, THERE'S STILL 6597 04:21:16,908 --> 04:21:21,113 ONE THING WE ARE NOT REALLY 6598 04:21:21,113 --> 04:21:21,346 GOOD AT. 6599 04:21:21,346 --> 04:21:22,547 HAVING A MATERIAL THAT DOES A 6600 04:21:22,547 --> 04:21:24,683 LOT OF THINGS AT THE SAME TIME. 6601 04:21:24,683 --> 04:21:26,318 USUALLY BIO MATERIAL ARE 6602 04:21:26,318 --> 04:21:27,486 ENGINEERED FOR ONE PURPOSE AND 6603 04:21:27,486 --> 04:21:28,987 THEY ARE REALLY GOOD AT THAT 6604 04:21:28,987 --> 04:21:30,021 ONE THING. 6605 04:21:30,021 --> 04:21:33,225 THEY HAVE EXCELLENT MECHANICAL 6606 04:21:33,225 --> 04:21:35,160 PROPERTIES, BIO COMPATIBILITY 6607 04:21:35,160 --> 04:21:36,328 BUT IT'S VERY DIFFICULT THAT 6608 04:21:36,328 --> 04:21:38,196 ONE MATERIAL CAN COVER A BUNCH 6609 04:21:38,196 --> 04:21:40,031 OF DIFFERENT FUNCTIONS. 6610 04:21:40,031 --> 04:21:42,868 TO GIVE YOU AN EXAMPLE OF HOW 6611 04:21:42,868 --> 04:21:45,370 REALLY TRICKY THIS PROPERTY IS, 6612 04:21:45,370 --> 04:21:47,506 THINK ABOUT WOUND DRESSING. 6613 04:21:47,506 --> 04:21:49,608 THIS AN ACTIVE FIELD. 6614 04:21:49,608 --> 04:21:51,476 IMAGINE IF YOU HAVE WOUND 6615 04:21:51,476 --> 04:21:53,578 DRESSING THAT DOESN'T ONLY 6616 04:21:53,578 --> 04:21:57,149 MECHANICALLY PROTECT THE WOUND 6617 04:21:57,149 --> 04:22:01,086 BUT PREVENTS FORMATION OF 6618 04:22:01,086 --> 04:22:03,255 BIOGENIC BIO FILM, PREVENTING 6619 04:22:03,255 --> 04:22:05,056 SCARRING. 6620 04:22:05,056 --> 04:22:06,458 THIS IS EXTREMELY ACTIVE 6621 04:22:06,458 --> 04:22:07,626 RESEARCH AND THERE'S STILL NOT 6622 04:22:07,626 --> 04:22:08,960 A FINAL SOLUTION FOR THIS 6623 04:22:08,960 --> 04:22:13,532 PROBLEM. 6624 04:22:13,532 --> 04:22:14,933 IN THE SAME LINE OF THOUGHT 6625 04:22:14,933 --> 04:22:17,836 IMAGINE YOU COULD HAVE 6626 04:22:17,836 --> 04:22:19,604 PACKAGING THAT TELLS IF THERE'S 6627 04:22:19,604 --> 04:22:22,507 TOXIN IN THE FOOD OR CLOTHES IN 6628 04:22:22,507 --> 04:22:23,375 THE PHYSIOLOGY OF THE HUMAN 6629 04:22:23,375 --> 04:22:25,544 BEING. 6630 04:22:25,544 --> 04:22:26,745 MULTI-FUNCTIONALITY CAN OPEN A 6631 04:22:26,745 --> 04:22:27,879 LOT OF DIFFERENT POSSIBILITY, A 6632 04:22:27,879 --> 04:22:29,014 LOT OF DIFFERENT APPLICATION IN 6633 04:22:29,014 --> 04:22:30,916 THE FIELD OF BIO MEDICINE. 6634 04:22:30,916 --> 04:22:34,586 OF COURSE THE REASON WE STILL 6635 04:22:34,586 --> 04:22:36,888 DON'T HAVE A LOT OF 6636 04:22:36,888 --> 04:22:38,056 MULTI-FUNCTIONAL MATERIAL, IT'S 6637 04:22:38,056 --> 04:22:39,925 REALLY NOT EASY TO ENGINEER. 6638 04:22:39,925 --> 04:22:42,294 WE ARE LOOKING FOR A NEW 6639 04:22:42,294 --> 04:22:45,530 METHOD, NEW IDEAS TO ACTUALLY 6640 04:22:45,530 --> 04:22:46,798 ENGINEER MULTIPLE FUNCTION IN 6641 04:22:46,798 --> 04:22:47,399 BIO MATERIAL. 6642 04:22:47,399 --> 04:22:50,802 IF YOU ARE LOOKING AROUND, 6643 04:22:50,802 --> 04:22:53,138 MATERIAL THAT ARE ALREADY 6644 04:22:53,138 --> 04:22:53,905 MULTI-FUNCTIONAL YOU REALLY 6645 04:22:53,905 --> 04:22:56,107 DON'T NEED TO LOOK FAR BECAUSE 6646 04:22:56,107 --> 04:22:57,509 LIVING MATERIAL ARE ALREADY 6647 04:22:57,509 --> 04:22:59,611 HAVE A VAST ARRAY OF BIOLOGICAL 6648 04:22:59,611 --> 04:23:00,545 FUNCTION. 6649 04:23:00,545 --> 04:23:02,214 THEY CAN PROCESS MULTIPLE 6650 04:23:02,214 --> 04:23:03,615 INPUTS WITH MULTIPLE OUTPUTS AT 6651 04:23:03,615 --> 04:23:04,783 THE SAME TIME. 6652 04:23:04,783 --> 04:23:06,384 AND THEY ALSO HAVE A 6653 04:23:06,384 --> 04:23:08,053 COMBINATION OF PHYSICAL AND 6654 04:23:08,053 --> 04:23:08,987 MECHANICAL PROPERTIES THAT 6655 04:23:08,987 --> 04:23:12,290 SUPPORT THEIR FINAL PURPOSE. 6656 04:23:12,290 --> 04:23:13,959 MORE OF THAT, LIVING MATERIAL 6657 04:23:13,959 --> 04:23:16,761 THEY GROW WITH MINIMAL ENERGY 6658 04:23:16,761 --> 04:23:16,962 INPUT. 6659 04:23:16,962 --> 04:23:19,064 THEY JUST GROW FROM CELLULAR 6660 04:23:19,064 --> 04:23:22,334 CELLS, THEY DON'T NEED HARSH 6661 04:23:22,334 --> 04:23:23,735 CHEMICAL OR SPECIALIZED 6662 04:23:23,735 --> 04:23:24,569 FACILITY OR PRESSURE, NOTHING 6663 04:23:24,569 --> 04:23:28,707 LIKE THAT. 6664 04:23:28,707 --> 04:23:30,575 AND ALSO BECAUSE OF THEIR 6665 04:23:30,575 --> 04:23:33,411 ABILITY OF SELF-ASSEMBLING THEY 6666 04:23:33,411 --> 04:23:35,046 ALSO SELF-REPAIR, HIGH 6667 04:23:35,046 --> 04:23:36,514 LONGEVITY AND VERY LOW 6668 04:23:36,514 --> 04:23:37,616 MAINTENANCE COSTS. 6669 04:23:37,616 --> 04:23:39,951 SO DESPITE THE BROAD VARIETY OF 6670 04:23:39,951 --> 04:23:41,319 LIVING MATERIAL, LIKE FOR 6671 04:23:41,319 --> 04:23:45,657 EXAMPLE, THE HUMAN BODY, 6672 04:23:45,657 --> 04:23:50,161 ORGANS, PLANTS, SOIL, THEY ALL 6673 04:23:50,161 --> 04:23:54,165 SHARE A VERY SIMILAR STRUCTURE. 6674 04:23:54,165 --> 04:23:58,570 THEY ARE SELF-AMENDED IN BIO 6675 04:23:58,570 --> 04:24:01,239 LOGICAL MATRIX. 6676 04:24:01,239 --> 04:24:04,342 THE SELF-PRODUCED BIO MOLECULAR 6677 04:24:04,342 --> 04:24:05,510 MATRIX CONTROLS THE FINAL 6678 04:24:05,510 --> 04:24:07,245 PHYSICAL AND MECHANICAL 6679 04:24:07,245 --> 04:24:08,280 PROPERTIES. 6680 04:24:08,280 --> 04:24:11,316 SO WHAT I'VE DONE, I'M TRYING 6681 04:24:11,316 --> 04:24:13,518 TO REENGINEER THIS PROCESS. 6682 04:24:13,518 --> 04:24:15,820 LIKE FROM SCRATCH IN A CELL, 6683 04:24:15,820 --> 04:24:19,357 WHERE THE CELL HAS A 6684 04:24:19,357 --> 04:24:21,059 GENETICALLY ENCODED SYNTHETIC 6685 04:24:21,059 --> 04:24:22,694 MATRIX, BUT AT THE SAME TIME 6686 04:24:22,694 --> 04:24:24,996 ALLOWS THE CELLS TO REACH THE 6687 04:24:24,996 --> 04:24:27,799 MARKER CELL, SO ORGANIZE 6688 04:24:27,799 --> 04:24:28,733 HIERARCHICAL AGGREGATION OF 6689 04:24:28,733 --> 04:24:30,368 CELLS AND ALSO CONTROL THE 6690 04:24:30,368 --> 04:24:32,604 FINAL PROPERTIES OF THIS 6691 04:24:32,604 --> 04:24:34,139 MICROSCOPIC AGGREGATE. 6692 04:24:34,139 --> 04:24:43,715 SO I STARTED FROM A VERY 6693 04:24:43,715 --> 04:24:45,383 PECULIAR BACTERIA, THE PRESENCE 6694 04:24:45,383 --> 04:24:47,452 OF A SURFACE LAYER THAT 6695 04:24:47,452 --> 04:24:49,988 SURROUNDS THE ENTIRE OUTER 6696 04:24:49,988 --> 04:24:51,623 SURFACE OF THE CELL. 6697 04:24:51,623 --> 04:24:54,726 THIS SURFACE LAYER IS MADE OF 6698 04:24:54,726 --> 04:25:05,170 ONE SINGLE CALLED THE RSA. 6699 04:25:05,170 --> 04:25:06,304 (CAULOBACTER CRESCENTUS) 6700 04:25:06,304 --> 04:25:09,708 IT MAKES SURE IT DOESN'T FLY 6701 04:25:09,708 --> 04:25:09,908 AWAY. 6702 04:25:09,908 --> 04:25:12,043 DOMAIN THAT GIVES THE FINAL 6703 04:25:12,043 --> 04:25:14,379 THREE DIMENSIONAL SHAPE AND 6704 04:25:14,379 --> 04:25:14,713 SECRETION TAG. 6705 04:25:14,713 --> 04:25:21,853 SO THE SECRETION TAG WAS 6706 04:25:21,853 --> 04:25:24,589 PREVIOUSLY IDENTIFIED AS 6707 04:25:24,589 --> 04:25:25,423 SELF-AGGREGATING DOMAIN. 6708 04:25:25,423 --> 04:25:27,325 IN ORDER FOR THIS AGGREGATION 6709 04:25:27,325 --> 04:25:28,927 TO HAPPEN, IT HAS TO BE FREE 6710 04:25:28,927 --> 04:25:32,597 FROM THE SECONDARY STRUCTURE 6711 04:25:32,597 --> 04:25:33,998 THAT IT REACHES AT THE END. 6712 04:25:33,998 --> 04:25:36,568 WHAT WE DID WITH A SINGLE 6713 04:25:36,568 --> 04:25:38,937 GENETIC MODIFICATION, WE INSERT 6714 04:25:38,937 --> 04:25:45,543 NON STRUCTURAL DOMAIN, THIS IS 6715 04:25:45,543 --> 04:25:50,682 AN ELASTIC POLY PEPTIDE DOMAIN. 6716 04:25:50,682 --> 04:25:54,085 WE COMPLETELY UNFOLDED ON THE 6717 04:25:54,085 --> 04:25:59,991 PROCESS OF THE CELL. 6718 04:25:59,991 --> 04:26:02,527 WE EXPOSE, WE COVER EVERY CELL 6719 04:26:02,527 --> 04:26:04,996 WITH A STICKY LAYER, RIGHT? 6720 04:26:04,996 --> 04:26:07,132 THE CELLS BECOME STICKY. 6721 04:26:07,132 --> 04:26:11,503 SO THE RESULTS OF THE 6722 04:26:11,503 --> 04:26:12,937 STICKINESS IS THAT WHEN WE GROW 6723 04:26:12,937 --> 04:26:19,244 THE CELL, THE STATE OF GROWING 6724 04:26:19,244 --> 04:26:20,745 ITSELF AGGREGATES INTO 6725 04:26:20,745 --> 04:26:22,781 MICROSCOPIC MATERIALS. 6726 04:26:22,781 --> 04:26:27,152 THIS IS A TYPICAL FLASK, EVEN 6727 04:26:27,152 --> 04:26:32,791 BOWL IS ABOUT HALF A CENTIMETER. 6728 04:26:32,791 --> 04:26:35,360 THIS IS THE BIGGEST AGGREGATION 6729 04:26:35,360 --> 04:26:37,395 OF BACTERIA EVER ACHIEVED. 6730 04:26:37,395 --> 04:26:39,097 AND WE ACTUALLY IMAGE ALL THE 6731 04:26:39,097 --> 04:26:40,532 STRUCTURE OF THIS MATERIAL, 6732 04:26:40,532 --> 04:26:46,204 LIKE IN BLUE YOU SEE THE POLY 6733 04:26:46,204 --> 04:26:48,273 CELLULAR MATRIX, IN YELLOW YOU 6734 04:26:48,273 --> 04:26:50,875 SEE THE CELL, THIS MATRIX 6735 04:26:50,875 --> 04:26:52,043 PERMEATES THE ENTIRE STRUCTURE 6736 04:26:52,043 --> 04:26:53,912 OF THE LIVING MATERIAL THAT 6737 04:26:53,912 --> 04:26:55,780 GOES FROM SURROUNDING EVERY 6738 04:26:55,780 --> 04:26:58,850 SINGLE CELL TO PERMEATING THE 6739 04:26:58,850 --> 04:27:00,218 ENTIRE MICROSCOPIC STRUCTURE. 6740 04:27:00,218 --> 04:27:06,291 WE ALSO OBSERVE VERY PECULIAR 6741 04:27:06,291 --> 04:27:13,031 HOMOGENEITY AND INTERMEDIARY 6742 04:27:13,031 --> 04:27:16,167 MICROFICATION LEVEL. 6743 04:27:16,167 --> 04:27:19,003 I WILL BE HAPPY TO COMMENT MORE. 6744 04:27:19,003 --> 04:27:20,638 A SINGLE GENETIC MODIFICATION 6745 04:27:20,638 --> 04:27:23,641 IS ABLE TO ORGANIZE CELLS OVER 6746 04:27:23,641 --> 04:27:27,245 FOUR ORDERS OF MAGNITUDE SO WE 6747 04:27:27,245 --> 04:27:30,348 REACH THE -- OF SCALE. 6748 04:27:30,348 --> 04:27:31,382 VERY INTERESTINGLY BECAUSE THIS 6749 04:27:31,382 --> 04:27:32,684 IS EVERYWHERE IN THE STRUCTURE 6750 04:27:32,684 --> 04:27:37,489 LIKE WE SEE HERE, WHAT WE 6751 04:27:37,489 --> 04:27:38,389 HYPOTHESIZE BY CHANGING WE 6752 04:27:38,389 --> 04:27:40,291 SHOULD BE ABLE TO SIGNIFICANTLY 6753 04:27:40,291 --> 04:27:41,059 EFFECT THE FINAL PROPERTY OF 6754 04:27:41,059 --> 04:27:43,027 THE MATERIAL. 6755 04:27:43,027 --> 04:27:45,163 AND IN FACT, IF YOU LOOK AT 6756 04:27:45,163 --> 04:27:46,564 HERE, WE CREATED THREE 6757 04:27:46,564 --> 04:27:48,066 DIFFERENT VERSION OF THIS 6758 04:27:48,066 --> 04:27:50,401 MATRIX. 6759 04:27:50,401 --> 04:27:53,238 I DON'T KNOW IF IT'S OBVIOUS 6760 04:27:53,238 --> 04:27:55,807 FROM THIS PICTURE, BELIEVE ME 6761 04:27:55,807 --> 04:27:57,675 THIS PICTURE, THEY LOOK VERY 6762 04:27:57,675 --> 04:27:59,177 DIFFERENT FROM EACH OTHER. 6763 04:27:59,177 --> 04:28:00,178 YOU CAN TELL THERE'S A 6764 04:28:00,178 --> 04:28:00,478 DIFFERENCE. 6765 04:28:00,478 --> 04:28:02,347 ONE OF THE MAJOR DIFFERENCE FOR 6766 04:28:02,347 --> 04:28:07,185 EXAMPLE, IF YOU REMOVE THE 6767 04:28:07,185 --> 04:28:09,754 ANCHOR AND THE PROTEIN GETS 6768 04:28:09,754 --> 04:28:11,122 SECRETED FROM THE CELL, YOU 6769 04:28:11,122 --> 04:28:12,624 DON'T SEE HIGH DENSITY OF THE 6770 04:28:12,624 --> 04:28:14,125 CELLS YOU SEE IN OTHER TWO 6771 04:28:14,125 --> 04:28:15,593 MATERIALS. 6772 04:28:15,593 --> 04:28:19,664 SO WE UNDER UNDERSTOOD MUCH 6773 04:28:19,664 --> 04:28:21,566 BETTER WAY THAN SECRETION TO 6774 04:28:21,566 --> 04:28:24,168 CREATE MATERIAL THAT HAVE A 6775 04:28:24,168 --> 04:28:25,537 HIGH DENSITY OF CELLS. 6776 04:28:25,537 --> 04:28:26,738 MORE IMPORTANTLY, WHEN YOU 6777 04:28:26,738 --> 04:28:28,406 MEASURE THE MECHANICAL PROPERTY 6778 04:28:28,406 --> 04:28:30,542 OF THIS MATERIAL, WE SHOW THAT 6779 04:28:30,542 --> 04:28:31,609 THE MODULATION IS PRETTY 6780 04:28:31,609 --> 04:28:32,610 SIGNIFICANT. 6781 04:28:32,610 --> 04:28:39,150 WE HAVE OVER 25 FOLD DIFFERENCE. 6782 04:28:39,150 --> 04:28:41,686 THAT IS THE BIGGEST DIFFERENCE 6783 04:28:41,686 --> 04:28:43,121 THAT HAVEN'T BEEN ACHIEVED IN 6784 04:28:43,121 --> 04:28:44,689 THE FIELD. 6785 04:28:44,689 --> 04:28:46,758 ONLY ACHIEVED THROUGH GENETIC 6786 04:28:46,758 --> 04:28:48,493 MODIFICATION, THERE'S NO 6787 04:28:48,493 --> 04:28:49,794 MANIPULATION OF THE MATERIAL 6788 04:28:49,794 --> 04:28:51,529 WHATSOEVER. 6789 04:28:51,529 --> 04:28:54,198 ONCE WE WERE DONE, WE PLAYED 6790 04:28:54,198 --> 04:28:56,267 QUITE A BIT WITH THEM TO SHOW 6791 04:28:56,267 --> 04:28:59,337 WHAT THEIR POTENTIAL REALLY IS. 6792 04:28:59,337 --> 04:29:01,205 WE SHOW THAT WE COULD ACTUALLY 6793 04:29:01,205 --> 04:29:04,509 TAKE THEM OUT FROM THE LIQUID, 6794 04:29:04,509 --> 04:29:07,378 LIVE WITH NO ANTIBIOTIC AND PUT 6795 04:29:07,378 --> 04:29:09,614 IT BACK IN MEDIA AND GROW NEW 6796 04:29:09,614 --> 04:29:11,082 MATERIAL. 6797 04:29:11,082 --> 04:29:13,184 THIS IS VERY SIGNIFICANT ONLY 6798 04:29:13,184 --> 04:29:15,053 BECAUSE WE HAD FUN DOING THAT, 6799 04:29:15,053 --> 04:29:17,121 BUT BECAUSE IMAGINE IF YOU CAN 6800 04:29:17,121 --> 04:29:19,223 TURN THIS MATERIAL INTO 6801 04:29:19,223 --> 04:29:20,158 THERAPEUTICS, THE 6802 04:29:20,158 --> 04:29:21,326 TRANSPORTATION AND STORAGE OF 6803 04:29:21,326 --> 04:29:24,329 THE MATERIAL WILL NOT REQUIRE 6804 04:29:24,329 --> 04:29:26,297 ANY REFRIGERATION WHATSOEVER OR 6805 04:29:26,297 --> 04:29:27,398 ANY PARTICULAR FACILITY. 6806 04:29:27,398 --> 04:29:29,701 SO THEY CAN BE STORED AT ROOM 6807 04:29:29,701 --> 04:29:31,803 TEMPERATURE AND THIS MATRIX 6808 04:29:31,803 --> 04:29:33,972 PROTECTS THE CELL FROM 6809 04:29:33,972 --> 04:29:36,808 DESICCATION SO WHEN YOU 6810 04:29:36,808 --> 04:29:47,251 REINKNOCK IO RANCHO -- 6811 04:29:48,186 --> 04:29:49,787 RE-INOCULATE AND SELF-ASSEMBLE. 6812 04:29:49,787 --> 04:29:52,190 THIS COULD BE SOMETHING LIKE 6813 04:29:52,190 --> 04:29:53,625 TOOTHPASTE, JUST TO GIVE YOU AN 6814 04:29:53,625 --> 04:29:53,958 IDEA. 6815 04:29:53,958 --> 04:29:55,627 AND ONE OF THE THINGS THAT WE 6816 04:29:55,627 --> 04:30:00,198 HAVE SEEN IS THAT WE CAN 6817 04:30:00,198 --> 04:30:03,534 ACTUALLY INCORPORATE INORGANIC 6818 04:30:03,534 --> 04:30:04,235 POWDER, GLASS POWDER IN THE 6819 04:30:04,235 --> 04:30:06,104 FORM OF A VERY STRONG STRUCTURE. 6820 04:30:06,104 --> 04:30:08,172 OF COURSE AFTER A MONTH THE 6821 04:30:08,172 --> 04:30:09,841 CELLS ARE WELL DEAD INSIDE THE 6822 04:30:09,841 --> 04:30:11,476 MATERIAL, SO THE MATERIAL ISN'T 6823 04:30:11,476 --> 04:30:13,811 LIVING ANY MORE, BUT THIS IS 6824 04:30:13,811 --> 04:30:15,213 LIKE A SELF-PRODUCING CEMENTING 6825 04:30:15,213 --> 04:30:17,248 AGENT THAT CAN REPRODUCE 6826 04:30:17,248 --> 04:30:19,917 ANYWHERE WITH NO NEED FOR 6827 04:30:19,917 --> 04:30:30,294 SPECIALIZED EQUIPMENT. 6828 04:30:39,671 --> 04:30:42,407 THERE ARE TWO THINGS THAT CAN 6829 04:30:42,407 --> 04:30:43,307 BE ACHIEVED. 6830 04:30:43,307 --> 04:30:45,910 WHEN WE TALK ABOUT BIOLOGIC 6831 04:30:45,910 --> 04:30:46,944 PROPERTY, WE AREN'T JUST 6832 04:30:46,944 --> 04:30:48,312 TALKING ABOUT WHAT WE CAN 6833 04:30:48,312 --> 04:30:50,448 ENGINEERING BUT WE CAN CHOOSE 6834 04:30:50,448 --> 04:30:51,382 BACTERIA THAT ALREADY DO 6835 04:30:51,382 --> 04:30:53,251 SOMETHING WE ARE INTERESTED IN, 6836 04:30:53,251 --> 04:30:55,119 FOR EXAMPLE, IN BIO MEDICINE WE 6837 04:30:55,119 --> 04:30:59,657 CAN THINK ABOUT PROBIOTICKS. 6838 04:30:59,657 --> 04:31:01,826 OR USE TO ENCODE NATURAL 6839 04:31:01,826 --> 04:31:11,202 FUNCTION THAT WOULD ALLOW TO 6840 04:31:11,202 --> 04:31:14,939 POTENTIATE. 6841 04:31:14,939 --> 04:31:17,308 WE CAN MODULATE THE PHYSICAL 6842 04:31:17,308 --> 04:31:18,276 AND MECHANICAL PROPERTY, NOT 6843 04:31:18,276 --> 04:31:21,446 ONLY WHAT WE ALREADY SHOW SO WE 6844 04:31:21,446 --> 04:31:28,286 CAN MODULATE VISCOSITY BUT 6845 04:31:28,286 --> 04:31:30,922 SURFACE ADHESION OR -- AND 6846 04:31:30,922 --> 04:31:32,123 ELECTRICAL CONDUCK TIVITY. 6847 04:31:32,123 --> 04:31:35,193 SO WHY, IN SUMMARY, ARE THE 6848 04:31:35,193 --> 04:31:36,594 NOVEL ELM'S SO TRANSFORMATIVE 6849 04:31:36,594 --> 04:31:38,162 AND WHICH ARE THE APPLICATION 6850 04:31:38,162 --> 04:31:41,399 WHERE THEY COULD BE MORE 6851 04:31:41,399 --> 04:31:41,666 RELEVANT. 6852 04:31:41,666 --> 04:31:43,301 FOR ONCE THEY INCREASE THE 6853 04:31:43,301 --> 04:31:44,936 LOCAL CONCENTRATION OF CELLS 6854 04:31:44,936 --> 04:31:46,871 BECAUSE THIS MATERIAL ARE 6855 04:31:46,871 --> 04:31:47,939 EXTREMELY CELL-DENSE. 6856 04:31:47,939 --> 04:31:49,373 THEY ALSO INCREASE THE PER SIS 6857 04:31:49,373 --> 04:31:57,448 STEN PERSISTENCY. 6858 04:31:57,448 --> 04:32:04,122 THEY CAN ADHERE TO TISSUE, THEY 6859 04:32:04,122 --> 04:32:05,323 SELF-REGENERATE AND SELF-REPAIR. 6860 04:32:05,323 --> 04:32:09,494 SOME IS FOR EXAMPLE TO USE THEM 6861 04:32:09,494 --> 04:32:13,731 AS PROBIOTICS WE KNOW ONE 6862 04:32:13,731 --> 04:32:15,099 OBSTACLE USING PROBIOTICS IS 6863 04:32:15,099 --> 04:32:18,136 THEY HAVE SCARCE AND 6864 04:32:18,136 --> 04:32:20,705 UNPREDICTABLE -- OF THE 6865 04:32:20,705 --> 04:32:20,972 INTESTINE. 6866 04:32:20,972 --> 04:32:26,144 IF YOU CAN ENGINEER BETTER 6867 04:32:26,144 --> 04:32:28,913 PERSISTENCY AND HIGHER -- OF 6868 04:32:28,913 --> 04:32:32,950 CELLS IT COULD BE POTENTIATED. 6869 04:32:32,950 --> 04:32:34,819 IT'S ALSO DIFFICULT TO STUDY 6870 04:32:34,819 --> 04:32:37,388 WHAT THESE PROBUY OTICS DO. 6871 04:32:37,388 --> 04:32:40,224 WE ARE AVERAGING PEOPLE TO HAVE 6872 04:32:40,224 --> 04:32:41,025 A MASSIVELY-DIFFERENT 6873 04:32:41,025 --> 04:32:41,459 COLONIZATION LEVEL. 6874 04:32:41,459 --> 04:32:45,196 SO WHAT WE SEE IS ON AVERAGE 6875 04:32:45,196 --> 04:32:46,531 WITH HIGH STANDARD DEVIATION. 6876 04:32:46,531 --> 04:32:48,232 SO THIS COULD ALSO BECOME A 6877 04:32:48,232 --> 04:32:53,237 TOOL TO STUDY WHAT ACTUALLY 6878 04:32:53,237 --> 04:32:54,705 PROBIOTICS DO IN THE HUMAN BODY. 6879 04:32:54,705 --> 04:32:58,009 IN THE SAME WAY, THESE TOOLS 6880 04:32:58,009 --> 04:33:01,546 CAN BE USED IN AGRICULTURE TO 6881 04:33:01,546 --> 04:33:04,348 FAVOR THE INTERACTION WITH 6882 04:33:04,348 --> 04:33:06,217 ENGINEERED CELLS AND PLANTS 6883 04:33:06,217 --> 04:33:07,618 WHICH IS CURRENTLY A MAJOR 6884 04:33:07,618 --> 04:33:10,188 LIMITATION IN THE APPLICATION 6885 04:33:10,188 --> 04:33:12,156 OF SYNTHETIC BIOLOGY IN 6886 04:33:12,156 --> 04:33:12,523 AGRICULTURE. 6887 04:33:12,523 --> 04:33:17,461 EVEN IF WE ENGINEER SYMBIOTIC 6888 04:33:17,461 --> 04:33:18,062 RELATIONSHIP IT'S PHYSICALLY 6889 04:33:18,062 --> 04:33:19,764 HARD TO KEEP THE BACTERIA NEXT 6890 04:33:19,764 --> 04:33:21,599 TO THE PLANT. 6891 04:33:21,599 --> 04:33:23,034 WITH THOSE IDEAS IN MIND, I 6892 04:33:23,034 --> 04:33:24,869 THANK YOU FOR YOUR ATTENTION 6893 04:33:24,869 --> 04:33:27,405 AND I WELCOME ANY QUESTIONS. 6894 04:33:27,405 --> 04:33:37,615 [ APPLAUSE ] 6895 04:33:38,149 --> 04:33:40,918 >> FOR THE PROBIOTIC 6896 04:33:40,918 --> 04:33:41,619 APPLICATION, I'M CURIOUS, DO 6897 04:33:41,619 --> 04:33:43,020 YOU KNOW WHETHER THE AGOCATION 6898 04:33:43,020 --> 04:33:45,590 OF THESE BACTERIA COULD, OR 6899 04:33:45,590 --> 04:33:50,027 DOES ENHANCE BACTERIAL 6900 04:33:50,027 --> 04:33:51,762 CONJUGATION DELIVERY METHODS? 6901 04:33:51,762 --> 04:33:53,397 >> Sara Molinari: THERE'S NONE, 6902 04:33:53,397 --> 04:33:55,266 THAT I KNOW OF. 6903 04:33:55,266 --> 04:33:57,101 THIS HAS NOT EVER BEEN OBSERVED. 6904 04:33:57,101 --> 04:33:59,871 IT IS KNOWN THAT BACTERIA 6905 04:33:59,871 --> 04:34:03,174 AGGREGATION ENHANCE THE 6906 04:34:03,174 --> 04:34:05,276 PROBIOTIC POTENTIAL. 6907 04:34:05,276 --> 04:34:07,111 THEY ARE USUALLY BETTER BECAUSE 6908 04:34:07,111 --> 04:34:10,348 THEY STICK LONGER IN THE 6909 04:34:10,348 --> 04:34:14,552 INTESTINE AND BY AGGREGATING 6910 04:34:14,552 --> 04:34:18,289 THEY CAN BE PERSISTENT IN THE 6911 04:34:18,289 --> 04:34:19,156 INTESTINAL TRACK. 6912 04:34:19,156 --> 04:34:29,600 >> I WAS WONDERING WHEN 6913 04:34:35,907 --> 04:34:37,141 CAULOBACTER -- 6914 04:34:37,141 --> 04:34:38,609 >> Sara Molinari: THEY DIE 6915 04:34:38,609 --> 04:34:41,345 QUICKLY BUT IN THE MASS SPEC WE 6916 04:34:41,345 --> 04:34:43,214 HAVE SEEN THEY CAN SURVIVE UP 6917 04:34:43,214 --> 04:34:43,681 TO THREE WEEKS. 6918 04:34:43,681 --> 04:34:44,382 >> WOW. 6919 04:34:44,382 --> 04:34:45,549 THANKS. 6920 04:34:45,549 --> 04:34:46,984 >> VERY INTERESTING TALK, YOU 6921 04:34:46,984 --> 04:34:49,086 CAN SEE ME ENJOYING IT. 6922 04:34:49,086 --> 04:34:55,459 QUESTION, IS THIS MATRIX IS 6923 04:34:55,459 --> 04:34:56,560 SUSCEPTIBLE. 6924 04:34:56,560 --> 04:34:58,062 DO YOU KNOW WHICH COULD BREAK 6925 04:34:58,062 --> 04:34:58,429 IT DOWN? 6926 04:34:58,429 --> 04:35:00,064 >> Sara Molinari: NO, I WOULD 6927 04:35:00,064 --> 04:35:01,232 BE HAVE INTERESTED TO FIND THAT 6928 04:35:01,232 --> 04:35:02,166 OUT. 6929 04:35:02,166 --> 04:35:04,035 WHAT MY LAB WILL DO IS 6930 04:35:04,035 --> 04:35:05,503 IDENTIFYING THE DESIGN RULE FOR 6931 04:35:05,503 --> 04:35:07,071 THE APPLICATION OF THE 6932 04:35:07,071 --> 04:35:09,607 MATRIXES, SO WE WILL TEST 6933 04:35:09,607 --> 04:35:10,975 VARIETY OF DIFFERENT GENETIC 6934 04:35:10,975 --> 04:35:13,311 PARTS THAT CAN CONTRIBUTE TO 6935 04:35:13,311 --> 04:35:14,245 GIVE DIFFERENT FUNCTION. 6936 04:35:14,245 --> 04:35:16,647 THIS IS A VERY NICE SPACE TO 6937 04:35:16,647 --> 04:35:20,484 LOOK INTO. 6938 04:35:20,484 --> 04:35:22,520 >> JUST A QUICK QUESTION. 6939 04:35:22,520 --> 04:35:25,389 WHAT IS THE MINIMUM DIAMETER 6940 04:35:25,389 --> 04:35:28,359 THAT YOU CAN EXTRUDE THIS 6941 04:35:28,359 --> 04:35:30,127 MATERIAL THROUGH? 6942 04:35:30,127 --> 04:35:31,662 >> Sara Molinari: SORRY, THE 6943 04:35:31,662 --> 04:35:32,830 MINIMUM DIAMETER? 6944 04:35:32,830 --> 04:35:36,267 >> YEAH, I THINK YOU SAW 6945 04:35:36,267 --> 04:35:37,201 EXTRUSION THROUGH SYRINGE, WHAT 6946 04:35:37,201 --> 04:35:39,303 IS THE MINIMUM DIAMETER YOU ARE 6947 04:35:39,303 --> 04:35:42,940 USING, OR CAN YOU GO TO? 6948 04:35:42,940 --> 04:35:44,375 >> Sara Molinari: UNFORTUNATELY 6949 04:35:44,375 --> 04:35:46,510 I DON'T HAVE A QUANTITATIVE 6950 04:35:46,510 --> 04:35:47,878 ANSWER. 6951 04:35:47,878 --> 04:35:52,483 WE ALSO EXTRUDE SYRINGE WITH A 6952 04:35:52,483 --> 04:35:56,821 NEEDLE, I WOULD SAY A 6953 04:35:56,821 --> 04:35:59,657 MILLIMETER. 6954 04:35:59,657 --> 04:36:01,892 WE CAN CENTRIFUGE THIS MATERIAL 6955 04:36:01,892 --> 04:36:06,163 TO EXTRUDE SOME OF THE LIQUID 6956 04:36:06,163 --> 04:36:07,999 SO THAT CHANGES HOW VISCOUS IS 6957 04:36:07,999 --> 04:36:10,568 THE MATERIAL AND WHAT IS THE 6958 04:36:10,568 --> 04:36:11,268 EXTRUDABILITY LOOK LIKE. 6959 04:36:11,268 --> 04:36:15,206 >> THANK YOU. 6960 04:36:15,206 --> 04:36:16,874 >> THANK YOU FOR A GREAT TALK. 6961 04:36:16,874 --> 04:36:19,143 I HAVE A QUICK QUESTION TOO, DO 6962 04:36:19,143 --> 04:36:21,846 THE PROPERTIES OF THE MATERIAL 6963 04:36:21,846 --> 04:36:23,314 CHANGE MUCH LIVING IN DEAD 6964 04:36:23,314 --> 04:36:24,482 CELLS? 6965 04:36:24,482 --> 04:36:26,317 >> Sara Molinari: WE DIDN'T 6966 04:36:26,317 --> 04:36:30,788 LOOK A LOT INTO OCOLINGA? 6967 04:36:30,788 --> 04:36:34,325 (?) CELLS, THE STRENGTH IS IT 6968 04:36:34,325 --> 04:36:35,726 CONTAINS LIVING CELLS, THEY DO. 6969 04:36:35,726 --> 04:36:37,595 THE MASS IS STRONGLY REDUCED IF 6970 04:36:37,595 --> 04:36:39,864 YOU KILL THE CELL. 6971 04:36:39,864 --> 04:36:47,204 >> THANK YOU. 6972 04:36:47,204 --> 04:36:57,415 [ APPLAUSE ] 6973 04:37:09,593 --> 04:37:11,629 >> Rahul Thakar: NOW OUR FINAL 6974 04:37:11,629 --> 04:37:22,139 TALK OF THE DAY BY XINLING LI. 6975 04:37:29,346 --> 04:37:29,847 "MATHEMATICAL MODEL OF AND 6976 04:37:29,847 --> 04:37:30,414 GATED SYNTHETIC BIOMARKERS 6977 04:37:30,414 --> 04:37:30,981 PREDICTS TUNABLE SIGNAL TO 6978 04:37:30,981 --> 04:37:32,149 NOISE AND COOPERATIVE BEHAVIOR." 6979 04:37:32,149 --> 04:37:33,918 >> Xinling Li: HI, EVERYONE, 6980 04:37:33,918 --> 04:37:35,252 THANK YOU FOR STAYING UNTIL THE 6981 04:37:35,252 --> 04:37:41,959 END. 6982 04:37:41,959 --> 04:37:43,594 I'M XINLING LI. 6983 04:37:43,594 --> 04:37:45,429 WE THOUGHT TO SWITCH IT UP A 6984 04:37:45,429 --> 04:37:47,998 LITTLE BIT TODAY AND IN THIS 6985 04:37:47,998 --> 04:37:48,899 HIGHLY COLLABORATIVE MEETING WE 6986 04:37:48,899 --> 04:37:58,309 ARE GOING TO EXPLORE THE FLOOR 6987 04:37:58,309 --> 04:37:59,910 (AMRUDT) 6988 04:37:59,910 --> 04:38:03,581 AS EVERYONE KNOW THEY ARE A 6989 04:38:03,581 --> 04:38:04,115 LARGE IMPORTANT ENZYMES 6990 04:38:04,115 --> 04:38:06,750 INVOLVED IN A LOT OF 6991 04:38:06,750 --> 04:38:08,319 PHYSIOLOGICAL PROCESSES WHEN 6992 04:38:08,319 --> 04:38:10,421 THEY GET DYSREGULATED THEY CAN 6993 04:38:10,421 --> 04:38:11,388 BE PROGRESSORS OF DISEASE. 6994 04:38:11,388 --> 04:38:13,657 WE ARE STARTING TO SCRATCH THE 6995 04:38:13,657 --> 04:38:15,493 SURFACE AND LEARN MORE ABOUT 6996 04:38:15,493 --> 04:38:16,227 PROTEASES. 6997 04:38:16,227 --> 04:38:18,596 IN THE FIELD OF DIAGNOSTICS WE 6998 04:38:18,596 --> 04:38:20,531 KNOW THERE ARE DIFFERENT 6999 04:38:20,531 --> 04:38:22,800 PROTEASE DISEASE PROFILES 7000 04:38:22,800 --> 04:38:24,168 ACROSS DISEASE STAGES. 7001 04:38:24,168 --> 04:38:26,237 AS WELL AS DURING DRUG 7002 04:38:26,237 --> 04:38:27,338 RESPONSES TO THERAPY. 7003 04:38:27,338 --> 04:38:30,274 SHOWN HERE WITH CANCER IMMUNO 7004 04:38:30,274 --> 04:38:31,175 THERAPY. 7005 04:38:31,175 --> 04:38:33,511 AS SUCH PROTEASES ARE BEING 7006 04:38:33,511 --> 04:38:37,114 INCREASINGLY UTILIZED AS 7007 04:38:37,114 --> 04:38:40,484 ACTIVATION MECHANISM SUCH AS 7008 04:38:40,484 --> 04:38:42,853 MASS CYTOKINES, ACTIVATABLE 7009 04:38:42,853 --> 04:38:45,222 ENGINE PROBES. 7010 04:38:45,222 --> 04:38:46,390 AND SYNTHETIC BIOMARKERSING 7011 04:38:46,390 --> 04:38:48,492 SOMETHING OUR LABS HAVE 7012 04:38:48,492 --> 04:38:50,161 EXPERTISE, BIO ENGINEER SENSORS 7013 04:38:50,161 --> 04:38:54,131 THAT CAN CREATE DISEASE AND 7014 04:38:54,131 --> 04:38:55,199 RELEASE SYNTHETIC -- IN THE 7015 04:38:55,199 --> 04:38:56,534 URINE. 7016 04:38:56,534 --> 04:38:58,435 AS BIO ENGINEERS WE ARE DEEPLY 7017 04:38:58,435 --> 04:39:00,137 INTERESTED IN HOW CAN WE 7018 04:39:00,137 --> 04:39:01,539 GENERATE A QUANTITATIVE 7019 04:39:01,539 --> 04:39:02,473 UNDERSTANDING HOW THESE SYSTEMS 7020 04:39:02,473 --> 04:39:03,407 WORK. 7021 04:39:03,407 --> 04:39:06,677 AND HOW CAN WE USE THIS TO 7022 04:39:06,677 --> 04:39:07,845 DERIVE DESIGN GUIDELINES. 7023 04:39:07,845 --> 04:39:14,084 OUR LABS ARE USING ON THE 7024 04:39:14,084 --> 04:39:15,252 INTERFACE MATHEMATICAL MODELS 7025 04:39:15,252 --> 04:39:20,691 TO PREDICT THE BEHAVIOR OF 7026 04:39:20,691 --> 04:39:21,992 PROTEASE-ACTIVATABLE SYSTEMS. 7027 04:39:21,992 --> 04:39:24,361 HOW CAN WE MAP THE INSIGHTS WE 7028 04:39:24,361 --> 04:39:26,263 GAIN THROUGH EXPERIMENTS INTO 7029 04:39:26,263 --> 04:39:27,865 DIFFERENT MODEL SYSTEMS, MODEL 7030 04:39:27,865 --> 04:39:29,967 ORGANISMS AND POTENTIALLY 7031 04:39:29,967 --> 04:39:30,834 THINKING TOWARD TRANSLATION 7032 04:39:30,834 --> 04:39:31,602 INTO HUMANS. 7033 04:39:31,602 --> 04:39:33,938 SO ONE WAY WE FOUND WE CAN DO 7034 04:39:33,938 --> 04:39:36,540 THIS IS BY EXTRACTING 7035 04:39:36,540 --> 04:39:38,008 DIMENSIONS FROM MATHEMATICAL 7036 04:39:38,008 --> 04:39:38,876 MODELS. 7037 04:39:38,876 --> 04:39:40,844 THE SECOND TOPIC IS RELATED TO 7038 04:39:40,844 --> 04:39:43,214 TACKLING THE ISSUE OF SUBSTRATE 7039 04:39:43,214 --> 04:39:43,480 SELECTION. 7040 04:39:43,480 --> 04:39:45,916 JUST TO GIVE YOU A LITTLE 7041 04:39:45,916 --> 04:39:47,117 PERSPECTIVE, TYPICALLY WHEN WE 7042 04:39:47,117 --> 04:39:49,253 LOOK AT PROTEASES WE ARE 7043 04:39:49,253 --> 04:39:51,088 LOOKING AT 4-6 AMINO ACID 7044 04:39:51,088 --> 04:39:52,823 SEQUENCES. 7045 04:39:52,823 --> 04:39:55,226 DESIGN SPACE OF MILLIONS OF 7046 04:39:55,226 --> 04:39:57,094 SUBSTRATE WE CAN CHOOSE FROM. 7047 04:39:57,094 --> 04:39:59,363 CAN WE DESIGN COMPUTATIONAL 7048 04:39:59,363 --> 04:40:00,864 TOOLS TO SELECT THE BEST 7049 04:40:00,864 --> 04:40:03,400 SUBSTRATES FOR THE JOB AT HAND? 7050 04:40:03,400 --> 04:40:06,971 WHAT WE LEARNED IS TYPICALLY 7051 04:40:06,971 --> 04:40:08,606 THE PROMISCUOUS SUBSTRATES WE 7052 04:40:08,606 --> 04:40:09,840 THROW OUT BUT THEY MIGHT 7053 04:40:09,840 --> 04:40:11,208 CONTAIN A LOT OF USEFUL 7054 04:40:11,208 --> 04:40:12,843 INFORMATION. 7055 04:40:12,843 --> 04:40:16,614 FINALLY, CAN WE APPLY A 7056 04:40:16,614 --> 04:40:18,949 COMPUTATIONAL TOOLKIT FOR MORE 7057 04:40:18,949 --> 04:40:19,850 SENSITIVE AND EFFECTIVE 7058 04:40:19,850 --> 04:40:20,618 DIAGNOSTICS. 7059 04:40:20,618 --> 04:40:24,955 ONE WAY IS BY TAKING PRINCIPLES 7060 04:40:24,955 --> 04:40:27,458 OF COOPERATIVITY WE HAVE 7061 04:40:27,458 --> 04:40:29,493 LEARNED AND APPLY TO BETTER 7062 04:40:29,493 --> 04:40:30,394 DESIGN SENSORS. 7063 04:40:30,394 --> 04:40:33,831 WE ARE ASKING HERE CAN WE 7064 04:40:33,831 --> 04:40:34,431 DEVELOP MATHEMATICAL MODEL 7065 04:40:34,431 --> 04:40:37,801 THAT'S CAN HELP US DESIGN 7066 04:40:37,801 --> 04:40:39,103 BETTER COOPERATIVE SENSORS? 7067 04:40:39,103 --> 04:40:41,639 FOR THE FIRST TOPIC, HOW CAN WE 7068 04:40:41,639 --> 04:40:42,273 PREDICT SCALE. 7069 04:40:42,273 --> 04:40:46,010 WHAT I MEAN BY THIS, FROM IN 7070 04:40:46,010 --> 04:40:48,779 VITRO TO INVIVO OR FROM TUMOR 7071 04:40:48,779 --> 04:40:52,516 TYPE TO TUMOR TYPE OR FROM MICE 7072 04:40:52,516 --> 04:40:52,783 TO HUMANS. 7073 04:40:52,783 --> 04:40:55,786 THEY ARE DIFFICULT TO PREDICT 7074 04:40:55,786 --> 04:41:00,224 THE EFFECTS ON THESE SYSTEMS. 7075 04:41:00,224 --> 04:41:05,763 WE TOOK EXAMPLES FROM REYNOLDS 7076 04:41:05,763 --> 04:41:06,897 NUMBER CAN STRATIFY FLOW 7077 04:41:06,897 --> 04:41:08,098 REGIMES. 7078 04:41:08,098 --> 04:41:09,967 IT'S AGO NOTIC TO THE 7079 04:41:09,967 --> 04:41:13,504 CONDITIONS, IT SCALES WELL WITH 7080 04:41:13,504 --> 04:41:14,638 GEOMETRY, TEMPERATURE, FLUID. 7081 04:41:14,638 --> 04:41:17,441 WE WANTED TO APPLY THIS SIMILAR 7082 04:41:17,441 --> 04:41:18,676 PRINCIPLE TO A BIOLOGICAL 7083 04:41:18,676 --> 04:41:19,576 SYSTEM. 7084 04:41:19,576 --> 04:41:24,381 HERE IS AN EXAMPLE WITH A 7085 04:41:24,381 --> 04:41:27,251 MICROBIAL PROJECT ACTIVATED BY 7086 04:41:27,251 --> 04:41:33,357 MICROBIAL PROTEASE AND LEADS 7087 04:41:33,357 --> 04:41:38,028 TO CELL DEATH. 7088 04:41:38,028 --> 04:41:41,832 WE PERFORMED AND, BACTERIAL 7089 04:41:41,832 --> 04:41:44,134 ADVANTAGE, WHAT IS HELPFUL IS 7090 04:41:44,134 --> 04:41:46,337 THIS COULD PREDICT PROJECT 7091 04:41:46,337 --> 04:41:51,375 SUCCESS VERSUS ESCAPE WITH THIS 7092 04:41:51,375 --> 04:41:53,077 CLEAN STEP FUNCTION BASED ON 7093 04:41:53,077 --> 04:41:54,211 OUR MODEL. 7094 04:41:54,211 --> 04:41:56,747 WE WERE EXCITED AND WE STRESS 7095 04:41:56,747 --> 04:41:58,148 TESTED AGAINST NINE MODELS. 7096 04:41:58,148 --> 04:42:00,017 YOU CAN SEE WHAT IT PREDICTS 7097 04:42:00,017 --> 04:42:02,119 AND WHEN WE PERFORM AN 7098 04:42:02,119 --> 04:42:04,455 EXPERIMENT IT AGREES VERY WELL 7099 04:42:04,455 --> 04:42:06,557 SHOWING THE MODEL IS PREDICTIVE. 7100 04:42:06,557 --> 04:42:08,659 THIS IS POWERFUL AND SHOWS WE 7101 04:42:08,659 --> 04:42:11,428 CAN USE MATHEMATICAL MODELING 7102 04:42:11,428 --> 04:42:12,896 TO EXTRACT -- FOR SCALING. 7103 04:42:12,896 --> 04:42:15,966 I WILL TALK ABOUT SUBSTRATE 7104 04:42:15,966 --> 04:42:16,633 SELECTION. 7105 04:42:16,633 --> 04:42:18,736 THE WAY THE FIELD THINKS OF 7106 04:42:18,736 --> 04:42:22,940 THIS CHALLENGE IS THROUGH LONG 7107 04:42:22,940 --> 04:42:25,042 PIPELINE, GENERATING A LIST OF 7108 04:42:25,042 --> 04:42:26,443 CANDIDATE SUBSTRATES FOR 7109 04:42:26,443 --> 04:42:29,880 LITERATURE FOR THESE PROTEASES 7110 04:42:29,880 --> 04:42:31,815 AND SYNTHESIZING SUBSTRATES, A 7111 04:42:31,815 --> 04:42:33,384 SCREEN, AND THEN PERFORMING 7112 04:42:33,384 --> 04:42:34,151 WINNER SELECTION. 7113 04:42:34,151 --> 04:42:36,253 WE WILL FOCUS ON THE LAST 7114 04:42:36,253 --> 04:42:38,122 ARROW, THE WINNER SELECTION 7115 04:42:38,122 --> 04:42:38,322 ARROW. 7116 04:42:38,322 --> 04:42:39,656 TYPICALLY WHAT THE FIELD DOES, 7117 04:42:39,656 --> 04:42:43,293 WE LOOK FOR THE MOST ORTHOGONAL 7118 04:42:43,293 --> 04:42:45,863 SET OF SUBSTRATES POSSIBLE. 7119 04:42:45,863 --> 04:42:47,331 IDEALLY ONE SUBSTRATE FOR A 7120 04:42:47,331 --> 04:42:48,665 GIVEN PROTEASE. 7121 04:42:48,665 --> 04:42:51,301 BUT THIS IS AGAINST THE BIOLOGY 7122 04:42:51,301 --> 04:42:53,137 OR EVOLUTION OF PROTEASE WHICH 7123 04:42:53,137 --> 04:42:55,239 ARE EVOLVED TO BE VERY 7124 04:42:55,239 --> 04:42:56,407 PROMISCUOUS. 7125 04:42:56,407 --> 04:42:58,308 THERE ARE ADVANTAGES, IT 7126 04:42:58,308 --> 04:42:59,710 PROVIDES ALTERNATIVE 7127 04:42:59,710 --> 04:43:03,981 EVOLUTIONARY MECHANISMS AND 7128 04:43:03,981 --> 04:43:05,349 MORE BIOLOGICAL PROCESSES WHERE 7129 04:43:05,349 --> 04:43:06,617 IT COULD PERFORM MULTIPLE 7130 04:43:06,617 --> 04:43:07,484 FUNCTIONS. 7131 04:43:07,484 --> 04:43:10,788 WE ASKED CAN WE USE 7132 04:43:10,788 --> 04:43:13,290 MATHEMATICAL MODELS TO USE 7133 04:43:13,290 --> 04:43:13,924 PROMISCUOUS SUBSTRATES TO OUR 7134 04:43:13,924 --> 04:43:17,027 ADVANTAGE. 7135 04:43:17,027 --> 04:43:18,629 WE DERIVED THIS COMPRESSION 7136 04:43:18,629 --> 04:43:20,431 SCORE, THE NUMBER OF PROTEASES 7137 04:43:20,431 --> 04:43:22,633 BEING COVERED. 7138 04:43:22,633 --> 04:43:24,034 WE HYPOTHESIZED IT COULD LEAD 7139 04:43:24,034 --> 04:43:26,570 TO A MORE PROMISCUOUS SMALLER 7140 04:43:26,570 --> 04:43:28,572 LIBRARY THAT COULD PERFORM 7141 04:43:28,572 --> 04:43:31,375 DIAGNOSTIC ACCURACY. 7142 04:43:31,375 --> 04:43:32,976 WE TESTED USING TWO COMPRESSION 7143 04:43:32,976 --> 04:43:34,578 SCORES. 7144 04:43:34,578 --> 04:43:37,281 COMPLEX MIXTURE WITH PLASMA 7145 04:43:37,281 --> 04:43:40,384 FROM MICE. 7146 04:43:40,384 --> 04:43:42,719 IN THIS MIXTURE IT CAN'T 7147 04:43:42,719 --> 04:43:46,723 DIFFERENTIATE THE DOTS, BUT NOW 7148 04:43:46,723 --> 04:43:54,031 WITH HIGH COMPRESSION. 7149 04:43:54,031 --> 04:43:55,933 WITH MATHEMATICAL MODELING WE 7150 04:43:55,933 --> 04:43:57,301 CAN TAKE ADVANTAGE OF THE 7151 04:43:57,301 --> 04:43:58,168 PROPERTIES TO PERFORM 7152 04:43:58,168 --> 04:43:59,203 DIAGNOSTICS. 7153 04:43:59,203 --> 04:44:00,604 LASTLY, WE WILL TALK ABOUT HOW 7154 04:44:00,604 --> 04:44:03,607 WE CAN APPLY COOPERATIVITY TO 7155 04:44:03,607 --> 04:44:05,642 THE SITE OF EARLY DETECTION. 7156 04:44:05,642 --> 04:44:07,845 WHEN WE THINK OF EARLY CANCER 7157 04:44:07,845 --> 04:44:10,247 DETECTION IT'S A NEEDLE IN A 7158 04:44:10,247 --> 04:44:11,882 HEY STACK CHALLENGE. 7159 04:44:11,882 --> 04:44:16,787 TUMORS ON THE ORDER OF 7160 04:44:16,787 --> 04:44:18,188 MILLIMETERS TO CENTIMETERS, 7161 04:44:18,188 --> 04:44:21,225 THERE IS NOISE THAT CAN 7162 04:44:21,225 --> 04:44:22,759 COMPOUND ACCURACY. 7163 04:44:22,759 --> 04:44:25,395 WE COULD HAVE OFF TARGET NOISE 7164 04:44:25,395 --> 04:44:29,433 FROM CIRCULATING PROTEASES IN 7165 04:44:29,433 --> 04:44:29,633 BLOOD. 7166 04:44:29,633 --> 04:44:32,169 BLOOD VOLUME IS 4-5 ORDERS OF 7167 04:44:32,169 --> 04:44:34,872 MAGNITUDE LARGER THAN THE EXTRA 7168 04:44:34,872 --> 04:44:36,406 CELLULAR SPACE. 7169 04:44:36,406 --> 04:44:37,608 THIS COULD CONTRIBUTE. 7170 04:44:37,608 --> 04:44:41,178 AND THIS IDEA OF OFF TARGET ON 7171 04:44:41,178 --> 04:44:45,349 TUMOR NOISE, THERE AREN'T 7172 04:44:45,349 --> 04:44:46,283 TUMOR-SPECIFIC PROTEASES. 7173 04:44:46,283 --> 04:44:49,786 WHAT WE USE AS ACTIVATION 7174 04:44:49,786 --> 04:44:51,655 MECHANISMS ARE ALSO EXPRESSED 7175 04:44:51,655 --> 04:44:53,290 IN PROCESSES LIKE WOUND HEALING. 7176 04:44:53,290 --> 04:44:56,293 THERE ARE SEVERAL WAYS TO GO 7177 04:44:56,293 --> 04:44:57,461 ABOUT ADDRESSING THESE ISSUES. 7178 04:44:57,461 --> 04:45:01,265 ONE WAY IS TO DESIGN SENSORS 7179 04:45:01,265 --> 04:45:06,503 THAT REQUIRE CLEAVAGE BY TWO 7180 04:45:06,503 --> 04:45:07,137 PROTEASES. 7181 04:45:07,137 --> 04:45:09,273 WE HAVE A LARGE BODY OF WORK, 7182 04:45:09,273 --> 04:45:14,011 BUT I WILL HAND IT OVER TO 7183 04:45:14,011 --> 04:45:18,115 XINLING HERE TO TALK. 7184 04:45:18,115 --> 04:45:21,084 >> Xinling Li: WE STARTED 7185 04:45:21,084 --> 04:45:23,253 MODELING TWO ARMS WERE 7186 04:45:23,253 --> 04:45:23,520 IDENTICAL. 7187 04:45:23,520 --> 04:45:25,722 THE TWO ARMS COULD BE CUT 7188 04:45:25,722 --> 04:45:27,824 SEQUENTIALLY BY THE TARGET 7189 04:45:27,824 --> 04:45:29,226 PROTEASE TO FORM PRODUCT. 7190 04:45:29,226 --> 04:45:33,664 AT THE SAME TIME NOISE IS 7191 04:45:33,664 --> 04:45:38,669 COMBINED AND -- 2-ARM. 7192 04:45:38,669 --> 04:45:42,172 CONTRAST, WORK HAS CONTROL ONLY 7193 04:45:42,172 --> 04:45:46,476 HAS ONE ARM EITHER BY TARGET OR 7194 04:45:46,476 --> 04:45:48,745 NOISE PROTEASE. 7195 04:45:48,745 --> 04:45:50,380 THE 2-ARM AND GATED SENSOR AND 7196 04:45:50,380 --> 04:45:53,517 IT WILL BE MORE COMPLEX. 7197 04:45:53,517 --> 04:45:56,787 WE TAKE THE DIFFERENCES ACROSS 7198 04:45:56,787 --> 04:45:57,387 BIOLOGICAL COMPARTMENTS INTO 7199 04:45:57,387 --> 04:45:59,790 CONSIDERATION. 7200 04:45:59,790 --> 04:46:02,726 TUMOR PROTEASES EXIST WITH 7201 04:46:02,726 --> 04:46:03,794 LOWER CONCENTRATION OF THE 7202 04:46:03,794 --> 04:46:05,295 TUMOR. 7203 04:46:05,295 --> 04:46:07,230 PROTEASES IN TUMOR HAVE HIGH 7204 04:46:07,230 --> 04:46:10,300 REACTIVITY. 7205 04:46:10,300 --> 04:46:14,271 BLOOD HAS LARGE CIRCLE 7206 04:46:14,271 --> 04:46:16,640 PROTEASES OFF TARGET NOISE, 7207 04:46:16,640 --> 04:46:23,413 SINCE MOST ARE INACTIVE BY 7208 04:46:23,413 --> 04:46:26,183 INHIBITORS THEIR NOISE IS LOW. 7209 04:46:26,183 --> 04:46:28,352 THE MODEL WITH THE BIOLOGICAL 7210 04:46:28,352 --> 04:46:29,252 REACTION. 7211 04:46:29,252 --> 04:46:32,356 IN THIS CASE, THE PROJECT 7212 04:46:32,356 --> 04:46:37,761 PROTEASE IS TUMOR, AND NOISE IS 7213 04:46:37,761 --> 04:46:42,165 BLOOD, AND KM TARGET PROTEASE 7214 04:46:42,165 --> 04:46:44,201 IS 1-10. 7215 04:46:44,201 --> 04:46:46,870 TO COMPARE AND GATE SENSOR WE 7216 04:46:46,870 --> 04:46:48,438 USE THIS. 7217 04:46:48,438 --> 04:46:53,543 YOU CAN SEE, ON THE RIGHT SHOWS 7218 04:46:53,543 --> 04:46:59,116 SENSOR AND ON THE LEFT -- 7219 04:46:59,116 --> 04:47:00,250 SIGNAL INPUT. 7220 04:47:00,250 --> 04:47:05,088 BECAUSE WE KNOW RESULTS CAN BE 7221 04:47:05,088 --> 04:47:07,658 NON INTUITIVE WE NEED 7222 04:47:07,658 --> 04:47:09,559 EXPERIMENTAL DATA TO MAKE SURE 7223 04:47:09,559 --> 04:47:11,328 OR MODEL IS DOING SOMETHING 7224 04:47:11,328 --> 04:47:12,863 RIGHT. 7225 04:47:12,863 --> 04:47:18,168 WE DESIGNED EXPERIMENT WE USE 7226 04:47:18,168 --> 04:47:20,237 -- 7227 04:47:20,237 --> 04:47:22,372 FOR BOTH INPUT SINGLE SENSOR ON 7228 04:47:22,372 --> 04:47:26,343 THE LEFT AND 2-ARM AND GATED 7229 04:47:26,343 --> 04:47:27,411 SENSOR ON THE RIGHT. 7230 04:47:27,411 --> 04:47:31,214 WE CAN SEE FOR AND-GATED 7231 04:47:31,214 --> 04:47:32,683 SENSOR, THE NOISE IS HIGHER 7232 04:47:32,683 --> 04:47:34,284 THAN THE SINGLE INPUT AND THE 7233 04:47:34,284 --> 04:47:36,153 DIFFERENCE IS SIGNIFICANT. 7234 04:47:36,153 --> 04:47:37,521 THEREFORE THIS VALIDATES OUR 7235 04:47:37,521 --> 04:47:39,356 RESULTS FOR THE COMPUTATION 7236 04:47:39,356 --> 04:47:41,692 PART ON THE LEFT, INDICATING 7237 04:47:41,692 --> 04:47:45,462 OUR COMPUTATION PART IS RIGHT. 7238 04:47:45,462 --> 04:47:48,565 AND NEXT WE PICK A CONDITION 7239 04:47:48,565 --> 04:47:50,667 WHICH HIGH NOISE TO INTERROGATE 7240 04:47:50,667 --> 04:47:53,537 WHETHER MORE ARMS PROVIDE 7241 04:47:53,537 --> 04:47:57,107 CAPABILITY TO DISTINGUISH 7242 04:47:57,107 --> 04:47:57,841 SIGNAL TO NOISE. 7243 04:47:57,841 --> 04:47:59,910 WE CAN SEE THAT AS THE NUMBER 7244 04:47:59,910 --> 04:48:03,513 OF ARM INCREASES THE SENSOR 7245 04:48:03,513 --> 04:48:05,148 BECOMES MORE COOPERATIVE. 7246 04:48:05,148 --> 04:48:10,754 THE NEXT COULD BE RELATED TO 7247 04:48:10,754 --> 04:48:11,054 SPECIFICITY. 7248 04:48:11,054 --> 04:48:13,090 IT INCREASES MONATOMICKLY. 7249 04:48:13,090 --> 04:48:14,458 HOWEVER FROM OUR MODELING 7250 04:48:14,458 --> 04:48:15,625 RESULTS THAT'S NOT THE CASE. 7251 04:48:15,625 --> 04:48:18,161 WHEN WE FIX THE TIME POINT TO 7252 04:48:18,161 --> 04:48:23,934 30 MINUTES AND 90 MINUTES AND 7253 04:48:23,934 --> 04:48:25,602 SIGNALING MINUS NOISE WE CAN 7254 04:48:25,602 --> 04:48:29,339 SEE FOR 30 MINUTES ON THE TOP, 7255 04:48:29,339 --> 04:48:30,774 THE THREE-ARM SENSOR PERFORMED 7256 04:48:30,774 --> 04:48:32,609 BEST, WHICH HAS THE HIGHEST 7257 04:48:32,609 --> 04:48:34,277 SIGNAL AMOUNT OF NOISE. 7258 04:48:34,277 --> 04:48:38,248 WHERE AS FOR 90 MINUTES, THE 7259 04:48:38,248 --> 04:48:47,057 7-ARM SENSOR HAS THE HIGHEST 7260 04:48:47,057 --> 04:48:47,290 SIGNAL. 7261 04:48:47,290 --> 04:48:49,426 -- CAN INCREASE SPECIFICITY OF 7262 04:48:49,426 --> 04:48:50,427 THE SENSOR. 7263 04:48:50,427 --> 04:48:54,297 AND THEN NEXT WE START WITH OUR 7264 04:48:54,297 --> 04:48:55,699 TWO-ARM AND GATED SENSOR, THE 7265 04:48:55,699 --> 04:48:59,236 QUESTION WE WILL ASK ARE THEY 7266 04:48:59,236 --> 04:49:00,470 SENSITIVE TO CONCENTRATION IN 7267 04:49:00,470 --> 04:49:01,371 TUMORS. 7268 04:49:01,371 --> 04:49:03,640 BECAUSE WE KNOW THAT TUMOR 7269 04:49:03,640 --> 04:49:05,509 PROTEASE CONCENTRATION CAN BE 7270 04:49:05,509 --> 04:49:08,645 2-10 FOLD HIGHER THAN THE 7271 04:49:08,645 --> 04:49:10,247 HOUSING ORGAN. 7272 04:49:10,247 --> 04:49:15,352 ON THE LEFT, ONE AXIS IS SINGLE 7273 04:49:15,352 --> 04:49:19,623 INPUT SENSOR, THE Y AXIS IS 7274 04:49:19,623 --> 04:49:21,792 PARAMETER PROTEASE 7275 04:49:21,792 --> 04:49:23,260 CONCENTRATION DIVIDED BY -- 7276 04:49:23,260 --> 04:49:26,930 AND THE DASH LINE IN THE PLOT 7277 04:49:26,930 --> 04:49:29,232 SHOWING TWO-ARM THE SAME AS ONE 7278 04:49:29,232 --> 04:49:29,399 ARM. 7279 04:49:29,399 --> 04:49:31,535 BUT WE CAN SEE THAT SINCE THE 7280 04:49:31,535 --> 04:49:33,937 BLUE CURVE IS ALWAYS ABOVE THE 7281 04:49:33,937 --> 04:49:36,273 DASH LINE, INDICATING THAT OUR 7282 04:49:36,273 --> 04:49:38,542 AND GATED SENSOR CAN ALWAYS 7283 04:49:38,542 --> 04:49:41,144 DETECT THE TUMOR WITH MUCH 7284 04:49:41,144 --> 04:49:42,746 HIGHER SPECIFICITY THAN THE 7285 04:49:42,746 --> 04:49:44,381 SINGLE INPUT SENSOR. 7286 04:49:44,381 --> 04:49:50,987 THEREFORE THEY ARE SENSITIVE TO 7287 04:49:50,987 --> 04:49:51,755 PROTEASES CONCENTRATION IN 7288 04:49:51,755 --> 04:49:53,990 TUMORS. 7289 04:49:53,990 --> 04:49:56,359 THE OTHER QUESTION, WE KNOW FOR 7290 04:49:56,359 --> 04:50:01,565 CANCER PATIENTS MANY ARE IN 7291 04:50:01,565 --> 04:50:02,966 HYPER COAGULATABLE STATE. 7292 04:50:02,966 --> 04:50:06,903 OUR SENSOR CAN STILL DETECT 7293 04:50:06,903 --> 04:50:09,472 TUMOR IN THOSE PATIENTS THAN 7294 04:50:09,472 --> 04:50:10,841 WITH SINGLE SENSOR. 7295 04:50:10,841 --> 04:50:12,442 LAST BUT NOT LEAST WE WANT TO 7296 04:50:12,442 --> 04:50:18,481 ASK HOW DO PROTEASE SUBSTRATE 7297 04:50:18,481 --> 04:50:21,084 -- WE ASK BETWEEN THE TARGET 7298 04:50:21,084 --> 04:50:22,485 PROTEASE AND SUBSTRATE 7299 04:50:22,485 --> 04:50:26,423 INCREASES THE SPECIFICITY OF 7300 04:50:26,423 --> 04:50:29,226 THE T2-ARM SENSE SORE INCREASES 7301 04:50:29,226 --> 04:50:31,328 MORE THAN SINGLE SENSOR, WE 7302 04:50:31,328 --> 04:50:33,430 WANT TO SELECT SUBSTRATE THAT 7303 04:50:33,430 --> 04:50:34,865 HAS HIGHER BINDING AFFINITY 7304 04:50:34,865 --> 04:50:36,733 WITH THE TARGET PROTEASE, TO 7305 04:50:36,733 --> 04:50:40,003 MAXIMIZE THE SPECIFICITY OF THE 7306 04:50:40,003 --> 04:50:41,805 SENSOR FOR TUMOR DETECTION. 7307 04:50:41,805 --> 04:50:47,244 AND ALSO IN SUMMARY, WE CAN USE 7308 04:50:47,244 --> 04:50:49,112 DIMENSIONAL SUSPECTER FOR 7309 04:50:49,112 --> 04:50:51,248 SCALING AND CONTAINS USEFUL 7310 04:50:51,248 --> 04:50:52,182 INFORMATION AND THIRD 7311 04:50:52,182 --> 04:50:55,418 INCREASING THE NUMBER OF ARMS 7312 04:50:55,418 --> 04:50:56,353 INCREASES CONNECTIVITY AND 7313 04:50:56,353 --> 04:50:58,321 SPECIFICITY OF THE SENSOR AND 7314 04:50:58,321 --> 04:51:00,690 LAST BUT NOT LEAST WE CAN 7315 04:51:00,690 --> 04:51:05,161 OPTIMIZE PARAMETERS TO INCREASE 7316 04:51:05,161 --> 04:51:06,296 SENSITIVITY FOR DETECTION OF 7317 04:51:06,296 --> 04:51:08,598 TUMOR. 7318 04:51:08,598 --> 04:51:11,668 WE CAN APPLY FOR 7319 04:51:11,668 --> 04:51:12,602 DIFFERENTIATING ANTI-TUMOR 7320 04:51:12,602 --> 04:51:14,738 RESPONSE FROM VIRAL INFECTION 7321 04:51:14,738 --> 04:51:25,282 AND DIFFERENTIATING METASTASIS 7322 04:51:25,482 --> 04:51:34,691 FROM LONG METASTASIS. 7323 04:51:34,691 --> 04:51:37,227 THANK YOU FOR LISTENING AND WE 7324 04:51:37,227 --> 04:51:47,704 ARE HAPPY TO TAKE QUESTIONS. 7325 04:51:58,548 --> 04:52:04,287 ) ANIRUDH SIVAKUMAR) 7326 04:52:04,287 --> 04:52:06,389 THIS IS MORE OF A NITTY-GRITTY 7327 04:52:06,389 --> 04:52:08,024 QUESTION BUT I'M CURIOUS AS 7328 04:52:08,024 --> 04:52:09,859 SOMEONE WHO WOULD LIKE TO 7329 04:52:09,859 --> 04:52:13,196 IMPROVE MY OWN COMPUTATIONAL 7330 04:52:13,196 --> 04:52:14,831 MODELING SKILLS, I WONDER WHAT 7331 04:52:14,831 --> 04:52:16,733 SOFTWARE YOU USED FOR MAKING 7332 04:52:16,733 --> 04:52:18,234 THE MODELS OR WHAT PROGRAM. 7333 04:52:18,234 --> 04:52:23,206 >> Xinling Li: WE WERE USING MY 7334 04:52:23,206 --> 04:52:24,441 LAB, MAX ACTION MODELS. 7335 04:52:24,441 --> 04:52:26,209 >> VERY NICE, VERY NICE, THANK 7336 04:52:26,209 --> 04:52:27,277 YOU, THAT'S GREAT. 7337 04:52:27,277 --> 04:52:37,587 MUCH APPRECIATED. 7338 04:52:43,760 --> 04:52:44,861 ANY MORE QUESTIONS? 7339 04:52:44,861 --> 04:52:46,896 >> I LOVE PROTEASE QUESTIONS. 7340 04:52:46,896 --> 04:52:49,032 I DIDN'T WANT TO ASK TOO HARD 7341 04:52:49,032 --> 04:52:50,633 CORE OF A QUESTION. 7342 04:52:50,633 --> 04:52:52,802 QUESTION, ARE YOU THINKING OF 7343 04:52:52,802 --> 04:52:55,205 INCORPORATING WAYS SO DIFFERENT 7344 04:52:55,205 --> 04:52:56,606 PROTEASES WORK IN DIFFERENT 7345 04:52:56,606 --> 04:52:58,508 ENVIRONMENTS, ARE YOU THINKING 7346 04:52:58,508 --> 04:53:05,482 OF INCORPORATING DIFFERENT PH. 7347 04:53:05,482 --> 04:53:07,984 I LOVE THE IDEA OF THE NOISE, 7348 04:53:07,984 --> 04:53:10,854 BUT ARE YOU THINKING OF 7349 04:53:10,854 --> 04:53:12,288 CHANGING THE ENVIRONMENT. 7350 04:53:12,288 --> 04:53:15,658 >> YOU MEAN IN CONTEXT OF 7351 04:53:15,658 --> 04:53:16,126 COMPUTATIONAL MODEL. 7352 04:53:16,126 --> 04:53:18,161 OF COURSE THE REAL THING TOO. 7353 04:53:18,161 --> 04:53:19,829 BUT IT MIGHT AFFECT THE SYSTEM 7354 04:53:19,829 --> 04:53:21,364 THAT IS GIVING YOU THE 7355 04:53:21,364 --> 04:53:22,399 READ-OUTS. 7356 04:53:22,399 --> 04:53:24,267 >> YEAH, I WOULD ANSWER THAT IN 7357 04:53:24,267 --> 04:53:25,602 TWO DIFFERENT WAYS. 7358 04:53:25,602 --> 04:53:27,437 FOR THE MATHEMATICAL MODEL NOW 7359 04:53:27,437 --> 04:53:30,440 WE ARE THINKING OF THIS AS A 7360 04:53:30,440 --> 04:53:31,775 SINGLE COMPARTMENT. 7361 04:53:31,775 --> 04:53:33,877 TREATING IT IT WOULD BE TOUGH 7362 04:53:33,877 --> 04:53:35,278 IN THE CURRENT INSTANCE TO 7363 04:53:35,278 --> 04:53:36,246 THINK OF DIFFERENT 7364 04:53:36,246 --> 04:53:37,614 ENVIRONMENTAL CONDITIONS BUT 7365 04:53:37,614 --> 04:53:39,783 THAT IS CERTAINLY SOMETHING WE 7366 04:53:39,783 --> 04:53:43,319 ARE THINKING ABOUT, DIFFERENT 7367 04:53:43,319 --> 04:53:45,855 COMPARTMENTS WITH DIFFERENT 7368 04:53:45,855 --> 04:53:51,494 CONDITIONS, TUMOR COMPARTMENTS 7369 04:53:51,494 --> 04:53:52,929 AND BLOOD COMPARTMENTS. 7370 04:53:52,929 --> 04:53:54,097 THE OTHER WAY TO ANSWER THAT 7371 04:53:54,097 --> 04:53:55,965 QUESTION, WE ARE REALLY 7372 04:53:55,965 --> 04:53:57,801 INTERESTED HOW CAN WE FIND 7373 04:53:57,801 --> 04:53:59,202 SUBSTRATE THAT'S PERFORM BETTER 7374 04:53:59,202 --> 04:54:01,805 IN DIFFERENT PHYSIOLOGICAL 7375 04:54:01,805 --> 04:54:03,673 ENVIRONMENTS, SO WE ARE WORKING 7376 04:54:03,673 --> 04:54:05,508 ON DIFFERENT SCREENING 7377 04:54:05,508 --> 04:54:07,844 PLATFORMS, WITH MICE, WHAT 7378 04:54:07,844 --> 04:54:09,479 SUBSTRATES WILL PERFORM BETTER. 7379 04:54:09,479 --> 04:54:11,314 HOPEFULLY WE CAN CAPTURE THE 7380 04:54:11,314 --> 04:54:13,583 REAL PH CHANGES IN DIFFERENT 7381 04:54:13,583 --> 04:54:15,085 ENVIRONMENTAL CONDITIONS. 7382 04:54:15,085 --> 04:54:15,952 Xinling Li: THANKS. 7383 04:54:15,952 --> 04:54:26,162 [ APPLAUSE ] 7384 04:54:31,668 --> 04:54:33,570 >> Rahul Thakar: JUST TO ADD 7385 04:54:33,570 --> 04:54:35,839 MORE INFORMATION ABOUT THE 7386 04:54:35,839 --> 04:54:37,907 BALCONY POSTERS, THERE IS MORE 7387 04:54:37,907 --> 04:54:38,975 IN C. 7388 04:54:38,975 --> 04:54:42,045 I THINK I HAVE HEARD SO MANY 7389 04:54:42,045 --> 04:54:42,479 GOOD CONVERSATIONS. 7390 04:54:42,479 --> 04:54:43,413 WHAT I WOULD LIKE TO DO IS 7391 04:54:43,413 --> 04:54:46,015 THANK ALL THE PARTICIPANTS, THE 7392 04:54:46,015 --> 04:54:50,787 MODERATORS, THE SPEAKERS, THE 7393 04:54:50,787 --> 04:54:53,356 POSTER SESSION FOLKS, SYNTHETIC 7394 04:54:53,356 --> 04:54:54,791 BIOLOGY CONSORTIUM AND ALL THE 7395 04:54:54,791 --> 04:54:56,626 PEOPLE WHO SUPPORTED THIS EVENT. 7396 04:54:56,626 --> 04:54:58,761 I WISH YOU A SAFE TRIP BACK 7397 04:54:58,761 --> 04:55:00,163 HOME AND LOOK FORWARD TO SEEING 7398 04:55:00,163 --> 04:55:03,666 YOU HERE NEXT YEAR FOR THE 7399 04:55:03,666 --> 04:55:07,437 FIFTH ANNUAL SYNTHETIC BIOLOGY CONSORTIUM. 7400 04:55:07,437 --> 04:55:13,376 THANK YOU VERY MUCH. AND TAKE CARE CH. 7401 04:55:13,376 --> 04:55:14,244 [ APPLAUSE ]